[ { "input_text": "IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase .", "target_text": { "IL-2 gene": "DNA", "NF-kappa B": "protein", "CD28": "protein", "5-lipoxygenase": "protein" } }, { "input_text": "Activation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 ( IL-2 ) and cell proliferation .", "target_text": { "CD28": "protein", "CD28 surface receptor": "protein", "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates ( ROIs ) which are required for CD28 -mediated activation of the NF-kappa B / CD28 -responsive complex and IL-2 expression .", "target_text": { "primary T lymphocytes": "cell_type", "CD28": "protein", "NF-kappa B": "protein", "CD28 -responsive complex": "protein", "IL-2": "protein" } }, { "input_text": "Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity , followed by the activation of phospholipase A2 and 5-lipoxygenase .", "target_text": { "CD28": "protein", "protein tyrosine kinase": "protein", "phospholipase A2": "protein", "5-lipoxygenase": "protein" } }, { "input_text": "Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-kappa B activation .", "target_text": { "lipoxygenase": "protein", "lipoxygenase metabolites": "protein", "IL-2": "protein", "NF-kappa B": "protein" } }, { "input_text": "These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway .", "target_text": { "CD28": "protein" } }, { "input_text": "The peri-kappa B site mediates human immunodeficiency virus type 2 enhancer activation in monocytes but not in T cells .", "target_text": { "peri-kappa B site": "DNA", "human immunodeficiency virus type 2 enhancer": "DNA", "monocytes": "cell_type", "T cells": "cell_type" } }, { "input_text": "Human immunodeficiency virus type 2 ( HIV-2 ) , like HIV-1 , causes AIDS and is associated with AIDS cases primarily in West Africa .", "target_text": {} }, { "input_text": "HIV-1 and HIV-2 display significant differences in nucleic acid sequence and in the natural history of clinical disease .", "target_text": { "nucleic acid sequence": "DNA" } }, { "input_text": "Consistent with these differences , we have previously demonstrated that the enhancer/promoter region of HIV-2 functions quite differently from that of HIV-1 .", "target_text": { "enhancer/promoter region": "DNA" } }, { "input_text": "Whereas activation of the HIV-1 enhancer following T-cell stimulation is mediated largely through binding of the transcription factor NF-kappa B to two adjacent kappa B sites in the HIV-1 long terminal repeat , activation of the HIV-2 enhancer in monocytes and T cells is dependent on four cis-acting elements : a single kappa B site , two purine-rich binding sites , PuB1 and PuB2 , and a pets site .", "target_text": { "HIV-1 enhancer": "DNA", "transcription factor": "protein", "NF-kappa B": "protein", "kappa B sites": "DNA", "HIV-1 long terminal repeat": "DNA", "HIV-2 enhancer": "DNA", "monocytes": "cell_type", "T cells": "cell_type", "cis-acting elements": "DNA", "kappa B site": "DNA", "purine-rich binding sites": "DNA", "PuB1": "DNA", "PuB2": "DNA", "pets site": "DNA" } }, { "input_text": "We have now identified a novel cis-acting element within the HIV-2 enhancer , immediately upstream of the kappa B site , designated peri-kappa B .", "target_text": { "cis-acting element": "DNA", "HIV-2 enhancer": "DNA", "kappa B site": "DNA", "peri-kappa B": "DNA" } }, { "input_text": "This site is conserved among isolates of HIV-2 and the closely related simian immunodeficiency virus , and transfection assays show this site to mediate HIV-2 enhancer activation following stimulation of monocytic but not T-cell lines .", "target_text": { "HIV-2 enhancer": "DNA", "monocytic": "cell_line", "T-cell lines": "cell_line" } }, { "input_text": "This is the first description of an HIV-2 enhancer element which displays such monocyte specificity , and no comparable enhancer element has been clearly defined for HIV-1 .", "target_text": { "HIV-2 enhancer element": "DNA", "enhancer element": "DNA" } }, { "input_text": "While a nuclear factor ( s ) from both peripheral blood monocytes and T cells binds the peri-kappa B site , electrophoretic mobility shift assays suggest that either a different protein binds to this site in monocytes versus T cells or that the protein recognizing this enhancer element undergoes differential modification in monocytes and T cells , thus supporting the transfection data .", "target_text": { "nuclear factor": "protein", "monocytes": "cell_type", "peripheral blood monocytes": "cell_type", "T cells": "cell_type", "peri-kappa B site": "DNA", "enhancer element": "DNA" } }, { "input_text": "Further , while specific constitutive binding to the peri-kappa B site is seen in monocytes , stimulation with phorbol esters induces additional , specific binding .", "target_text": { "peri-kappa B site": "DNA", "monocytes": "cell_type" } }, { "input_text": "Understanding the monocyte-specific function of the peri-kappa B factor may ultimately provide insight into the different role monocytes and T cells play in HIV pathogenesis .", "target_text": { "peri-kappa B factor": "protein", "monocytes": "cell_type", "T cells": "cell_type" } }, { "input_text": "E1A gene expression induces susceptibility to killing by NK cells following immortalization but not adenovirus infection of human cells .", "target_text": { "E1A gene": "DNA", "NK cells": "cell_type", "human cells": "cell_type" } }, { "input_text": "Adenovirus ( Ad ) infection and E1A transfection were used to model changes in susceptibility to NK cell killing caused by transient vs stable E1A expression in human cells .", "target_text": { "E1A": "protein", "human cells": "cell_type" } }, { "input_text": "Only stably transfected target cells exhibited cytolytic susceptibility , despite expression of equivalent levels of E1A proteins in Ad-infected targets .", "target_text": { "transfected target cells": "cell_line", "E1A proteins": "protein", "Ad-infected targets": "cell_line" } }, { "input_text": "The inability of E1A gene products to induce cytolytic susceptibility during infection was not explained by an inhibitory effect of viral infection on otherwise susceptible target cells or by viral gene effects on class I MHC antigen expression on target cells .", "target_text": { "E1A gene": "DNA", "target cells": "cell_type", "viral gene": "DNA", "class I MHC antigen": "protein" } }, { "input_text": "This differential effect of E1A expression on the cytolytic phenotypes of infected and stably transfected human cells suggests that human NK cells provide an effective immunologic barrier against the in vivo survival and neoplastic progression of E1A-immortalized cells that may emerge from the reservoir of persistently infected cells in the human host .", "target_text": { "E1A": "protein", "human cells": "cell_type", "NK cells": "cell_type", "human NK cells": "cell_type", "E1A-immortalized cells": "cell_line", "persistently infected cells": "cell_type" } }, { "input_text": "Distinct signaling properties identify functionally different CD4 epitopes .", "target_text": { "CD4 epitopes": "protein" } }, { "input_text": "The CD4 coreceptor interacts with non-polymorphic regions of major histocompatibility complex class II molecules on antigen-presenting cells and contributes to T cell activation .", "target_text": { "CD4 coreceptor": "protein", "non-polymorphic regions": "protein", "major histocompatibility complex class II molecules": "protein", "antigen-presenting cells": "cell_type" } }, { "input_text": "We have investigated the effect of CD4 triggering on T cell activating signals in a lymphoma model using monoclonal antibodies ( mAb ) which recognize different CD4 epitopes .", "target_text": { "CD4": "protein", "monoclonal antibodies": "protein", "mAb": "protein", "CD4 epitopes": "protein" } }, { "input_text": "We demonstrate that CD4 triggering delivers signals capable of activating the NF-AT transcription factor which is required for interleukin-2 gene expression .", "target_text": { "CD4": "protein", "NF-AT transcription factor": "protein", "interleukin-2": "protein" } }, { "input_text": "Whereas different anti-CD4 mAb or HIV-1 gp120 could all trigger activation of the protein tyrosine kinases p56lck and p59fyn and phosphorylation of the Shc adaptor protein , which mediates signals to Ras , they differed significantly in their ability to activate NF-AT .", "target_text": { "anti-CD4 mAb": "protein", "HIV-1 gp120": "protein", "protein tyrosine kinases": "protein", "p56lck": "protein", "p59fyn": "protein", "Shc adaptor protein": "protein", "Ras": "protein", "NF-AT": "protein" } }, { "input_text": "Lack of full activation of NF-AT could be correlated to a dramatically reduced capacity to induce calcium flux and could be complemented with a calcium ionophore .", "target_text": { "NF-AT": "protein" } }, { "input_text": "The results identify functionally distinct epitopes on the CD4 coreceptor involved in activation of the Ras /protein kinase C and calcium pathways .", "target_text": { "epitopes": "protein", "CD4 coreceptor": "protein", "Ras": "protein", "/protein kinase C": "protein", "Ras /protein kinase C": "protein" } }, { "input_text": "Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor .", "target_text": { "erythroid transcription factor": "protein", "GATA-1": "protein", "estrogen receptor": "protein" } }, { "input_text": "High-dose estrogen administration induces anemia in mammals .", "target_text": {} }, { "input_text": "In chickens , estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation .", "target_text": { "bone marrow-derived erythroid progenitor cells": "cell_type" } }, { "input_text": "This delay is associated with down-regulation of many erythroid cell-specific genes , including alpha- and beta- globin , band 3 , band 4.1 , and the erythroid cell-specific histone H5 .", "target_text": { "erythroid cell-specific genes": "DNA", "band 3": "DNA", "band 4.1": "DNA", "erythroid cell-specific histone": "protein", "H5": "protein" } }, { "input_text": "We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures .", "target_text": { "erythroid progenitor cells": "cell_type", "primary human bone marrow cultures": "cell_line" } }, { "input_text": "To address potential mechanisms by which estrogens suppress erythropoiesis , we have examined their effects on GATA-1 , an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes .", "target_text": { "GATA-1": "protein", "erythroid transcription factor": "protein", "erythroid cell-specific genes": "DNA", "erythrocytes": "cell_type" } }, { "input_text": "We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor ( ER ) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen .", "target_text": { "GATA-1": "protein", "estrogen receptor": "protein", "ER": "protein" } }, { "input_text": "ER -mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site , as well as in the context of an intact promoter which is normally regulated by GATA-1 .", "target_text": { "ER": "protein", "GATA-1": "protein", "artificial promoter": "DNA", "GATA-binding site": "DNA", "intact promoter": "DNA" } }, { "input_text": "GATA-1 and ER bind to each other in vitro in the absence of DNA .", "target_text": { "GATA-1": "protein", "ER": "protein" } }, { "input_text": "In coimmunoprecipitation experiments using transfected COS cells , GATA-1 and ER associate in a ligand-dependent manner .", "target_text": { "COS cells": "cell_line", "GATA-1": "protein", "ER": "protein" } }, { "input_text": "Mapping experiments indicate that GATA-1 and the ER form at least two contacts , which involve the finger region and the N-terminal activation domain of GATA-1 .", "target_text": { "GATA-1": "protein", "ER": "protein", "N-terminal activation domain": "protein" } }, { "input_text": "We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER .", "target_text": { "GATA-1": "protein", "ER": "protein" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "Mouse interleukin-2 receptor alpha gene expression .", "target_text": { "interleukin-2": "protein", "Mouse interleukin-2 receptor alpha gene": "DNA" } }, { "input_text": "Interleukin-1 and interleukin-2 control transcription via distinct cis-acting elements .", "target_text": { "Interleukin-1": "protein", "interleukin-2": "protein", "cis-acting elements": "DNA" } }, { "input_text": "We have shown that interleukin-1 ( IL-1 ) and IL-2 control IL-2 receptor alpha ( IL-2R alpha ) gene transcription in CD4-CD8- murine T lymphocyte precursors .", "target_text": { "interleukin-1": "protein", "IL-1": "protein", "IL-2": "protein", "IL-2 receptor alpha": "protein", "IL-2R alpha": "protein", "IL-2 receptor alpha ( IL-2R alpha ) gene": "DNA", "CD4-CD8- murine T lymphocyte precursors": "cell_line" } }, { "input_text": "Here we map the cis-acting elements that mediate interleukin responsiveness of the mouse IL-2R alpha gene using a thymic lymphoma-derived hybridoma ( PC60 ) .", "target_text": { "cis-acting elements": "DNA", "mouse IL-2R alpha": "protein", "mouse IL-2R alpha gene": "DNA", "thymic lymphoma-derived hybridoma": "cell_line", "PC60": "cell_line" } }, { "input_text": "The transcriptional response of the IL-2R alpha gene to stimulation by IL-1 + IL-2 is biphasic .", "target_text": { "IL-2R alpha gene": "DNA", "IL-1": "protein", "IL-2": "protein" } }, { "input_text": "IL-1 induces a rapid , protein synthesis-independent appearance of IL-2R alpha mRNA that is blocked by inhibitors of NF-kappa B activation .", "target_text": { "IL-1": "protein", "IL-2R alpha": "protein", "IL-2R alpha mRNA": "RNA", "NF-kappa B": "protein" } }, { "input_text": "It also primes cells to become IL-2 responsive and thereby prepares the second phase , in which IL-2 induces a 100-fold further increase in IL-2R alpha transcripts .", "target_text": { "IL-2": "protein", "IL-2R alpha": "protein", "IL-2R alpha transcripts": "RNA" } }, { "input_text": "Transient transfection experiments show that several elements in the promoter-proximal region of the IL-2R alpha gene contribute to IL-1 responsiveness , most importantly an NF-kappa B site conserved in the human and mouse gene .", "target_text": { "promoter-proximal region": "DNA", "IL-2R alpha": "protein", "IL-2R alpha gene": "DNA", "IL-1": "protein", "NF-kappa B": "protein", "NF-kappa B site": "DNA" } }, { "input_text": "IL-2 responsiveness , on the other hand , depends on a 78-nucleotide segment 1.3 kilobases upstream of the major transcription start site .", "target_text": { "IL-2": "protein", "78-nucleotide segment": "DNA", "major transcription start site": "DNA" } }, { "input_text": "This segment functions as an IL-2-inducible enhancer and lies within a region that becomes DNase I hypersensitive in normal T cells in which IL-2R alpha expression has been induced .", "target_text": { "IL-2-inducible enhancer": "DNA", "DNase I": "protein", "T cells": "cell_type", "IL-2R alpha": "protein" } }, { "input_text": "IL-2 responsiveness requires three distinct elements within the enhancer .", "target_text": { "IL-2": "protein", "elements": "DNA", "enhancer": "DNA" } }, { "input_text": "Two of these are potential binding sites for STAT proteins .", "target_text": { "STAT proteins": "protein" } }, { "input_text": "Hematopoietic lineage commitment : role of transcription factors .", "target_text": { "Hematopoietic lineage": "cell_type", "transcription factors": "protein" } }, { "input_text": "This review focuses on the roles of transcription factors in hematopoietic lineage commitment .", "target_text": { "transcription factors": "protein" } }, { "input_text": "A brief introduction to lineage commitment and asymmetric cell division is followed by a discussion of several methods used to identify transcription factors important in specifying hematopoietic cell types .", "target_text": { "transcription factors": "protein", "hematopoietic cell types": "cell_type" } }, { "input_text": "Next is presented a discussion of the use of embryonic stem cells in the analysis of hematopoietic gene expression and the use of targeted gene disruption to analyze the role of transcription factors in hematopoiesis .", "target_text": { "embryonic stem cells": "cell_type", "hematopoietic gene": "DNA", "transcription factors": "protein" } }, { "input_text": "Finally , the status of our current knowledge concerning the roles of transcription factors in the commitment to erythroid , myeloid and lymphoid cell types is summarized .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Epstein-Barr virus replicative gene transcription during de novo infection of human thymocytes : simultaneous early expression of BZLF-1 and its repressor RAZ .", "target_text": { "human thymocytes": "cell_type", "BZLF-1": "protein", "RAZ": "protein" } }, { "input_text": "Epstein-Barr virus ( EBV ) is known to infect B cells and epithelial cells .", "target_text": { "B cells": "cell_type", "epithelial cells": "cell_type" } }, { "input_text": "We and others have shown that EBV can also infect a subset of thymocytes .", "target_text": { "thymocytes": "cell_type" } }, { "input_text": "Infection of thymocytes was accompanied by the appearance of linear EBV genome within 8 hr of infection .", "target_text": { "thymocytes": "cell_type", "linear EBV genome": "DNA" } }, { "input_text": "Circularization of the EBV genome was not detected .", "target_text": { "EBV genome": "DNA" } }, { "input_text": "This is in contrast to the infection in B cells where the genome can circularize within 24 hr of infection .", "target_text": { "B cells": "cell_type" } }, { "input_text": "The appearance of the BamHI ZLF-1 gene product , ZEBRA , by RT-PCR , was observed within 8 hr of infection .", "target_text": { "BamHI ZLF-1 gene product": "protein", "ZEBRA": "protein" } }, { "input_text": "The appearance of a novel fusion transcript ( RAZ ) , which comprised regions of the BZLF-1 locus and the adjacent BRLF-1 locus , was detected by RT-PCR .", "target_text": { "fusion transcript": "protein", "RAZ": "protein", "BZLF-1": "protein", "BZLF-1 locus": "DNA", "BRLF-1 locus": "DNA" } }, { "input_text": "ZEBRA protein was also identified in infected thymocytes by immunoprecipitation .", "target_text": { "ZEBRA": "protein", "ZEBRA protein": "protein", "thymocytes": "cell_type" } }, { "input_text": "In addition , we demonstrated that the EBNA-1 gene in infected thymocytes was transcribed from the Fp promoter , rather than from the Cp/Wp promoter which is used in latently infected B cells .", "target_text": { "EBNA-1": "protein", "EBNA-1 gene": "DNA", "thymocytes": "cell_type", "Fp promoter": "DNA", "Cp/Wp promoter": "DNA", "B cells": "cell_type", "latently infected B cells": "cell_type" } }, { "input_text": "Transcripts encoding gp350/220 , the major coat protein of EBV , were identified , but we did not find any evidence of transcription from the LMP-2A or EBER-1 loci in infected thymocytes .", "target_text": { "gp350/220": "protein", "major coat protein": "protein", "LMP-2A": "DNA", "EBER-1 loci": "DNA", "thymocytes": "cell_type" } }, { "input_text": "These observations suggest that de novo EBV infection of thymocytes differs from infection of B cells .", "target_text": { "thymocytes": "cell_type", "B cells": "cell_type" } }, { "input_text": "The main difference is that with thymocytes , no evidence could be found that the virus ever circularizes .", "target_text": { "thymocytes": "cell_type" } }, { "input_text": "Rather , EBV remains in a linear configuration from which replicative genes are transcribed .", "target_text": { "replicative genes": "DNA" } }, { "input_text": "Identification and purification of human Stat proteins activated in response to interleukin-2 .", "target_text": { "human Stat proteins": "protein", "interleukin-2": "protein" } }, { "input_text": "A key cytokine induced during the immune response is IL-2 .", "target_text": { "cytokine": "protein", "IL-2": "protein" } }, { "input_text": "Following T cell activation , the genes encoding IL-2 and the various chains of its receptor are transcriptionally induced .", "target_text": { "IL-2": "protein" } }, { "input_text": "In turn , secreted IL-2 serves to stimulate the proliferation and differentiation of T lymphocytes .", "target_text": { "IL-2": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Several recent studies have implicated Jak kinases in the signaling pathway induced by IL-2 .", "target_text": { "IL-2": "protein" } }, { "input_text": "Following this lead , we set out to identify transcription factors induced in response to IL-2 .", "target_text": { "transcription factors": "protein", "IL-2": "protein" } }, { "input_text": "Human peripheral blood lymphocytes were observed to contain several IL-2 -inducible DNA binding activities .", "target_text": { "Human peripheral blood lymphocytes": "cell_type", "IL-2": "protein" } }, { "input_text": "Similar activities were also observed in a transformed human lymphocyte line , termed YT .", "target_text": { "transformed human lymphocyte line": "cell_line", "YT": "cell_line" } }, { "input_text": "We have purified these activities and found that the principal IL-2 -inducible component bears significant relatedness to a prolactin-induced transcription factor first identified in sheep mammary gland tissue .", "target_text": { "IL-2": "protein", "IL-2 -inducible component": "protein", "prolactin-induced transcription factor": "protein", "sheep mammary gland tissue": "cell_type" } }, { "input_text": "We hypothesize that activation of this protein , designated hStat5 , helps govern the biological effects of IL-2 during the immune response .", "target_text": { "hStat5": "protein", "IL-2": "protein" } }, { "input_text": "E2F-1 and a cyclin-like DNA repair enzyme , uracil-DNA glycosylase , provide evidence for an autoregulatory mechanism for transcription .", "target_text": { "E2F-1": "protein", "cyclin-like DNA repair enzyme": "protein", "uracil-DNA glycosylase": "protein" } }, { "input_text": "The cell cycle-dependent transcription factor , E2F-1 , regulates the cyclin -like species of the DNA repair enzyme uracil-DNA glycosylase ( UDG ) gene in human osteosarcoma ( Saos-2 ) cells .", "target_text": { "cell cycle-dependent transcription factor": "protein", "E2F-1": "protein", "cyclin": "protein", "DNA repair enzyme": "protein", "uracil-DNA glycosylase": "protein", "UDG": "protein", "uracil-DNA glycosylase ( UDG ) gene": "DNA", "Saos-2": "cell_line", "human osteosarcoma ( Saos-2 ) cells": "cell_line" } }, { "input_text": "We demonstrate , through the deletion of the human UDG promoter sequences , that expression of E2F-1 activates the UDG promoter through several E2F sites .", "target_text": { "UDG": "protein", "human UDG promoter sequences": "DNA", "E2F-1": "protein", "UDG promoter": "DNA", "E2F": "protein", "E2F sites": "DNA" } }, { "input_text": "The major putative downstream site for E2F , located in the first exon , serves as a target for E2F-1/DP1 complex binding in vitro .", "target_text": { "major putative downstream site": "DNA", "E2F": "protein", "first exon": "DNA", "E2F-1/DP1 complex": "protein" } }, { "input_text": "We also provide evidence for the functional relationship between the cyclin-like UDG gene product and E2F .", "target_text": { "UDG": "protein", "cyclin-like UDG gene product": "protein", "E2F": "protein" } }, { "input_text": "High levels of UDG expression in a transient transfection assay result in the down-regulation of transcriptional activity through elements specific for E2F -mediated transcription .", "target_text": { "UDG": "protein", "elements": "DNA", "E2F": "protein" } }, { "input_text": "Overexpression of UDG in Saos 2 cells was observed to delay growth late in G1 phase and transiently arrest these cells from progressing into the S phase .", "target_text": { "UDG": "protein", "Saos 2 cells": "cell_line" } }, { "input_text": "This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription , likely through E2F .", "target_text": { "E2F": "protein" } }, { "input_text": "This implicates E2F as a multifunctional target for proteins and enzymes , possibly , responsive to DNA damage through the negative effect of UDG on E2F -mediated transcriptional activity .", "target_text": { "E2F": "protein", "UDG": "protein" } }, { "input_text": "Cellular and molecular mechanisms of IFN-gamma production induced by IL-2 and IL-12 in a human NK cell line .", "target_text": { "IFN-gamma": "protein", "IL-2": "protein", "IL-12": "protein", "human NK cell line": "cell_line" } }, { "input_text": "Interferon-gamma ( IFN-gamma ) is an important immunoregulatory protein produced predominantly by T cells and large granular lymphocytes ( LGL ) in response to different extracellular signals .", "target_text": { "Interferon-gamma": "protein", "IFN-gamma": "protein", "immunoregulatory protein": "protein", "T cells": "cell_type", "large granular lymphocytes": "cell_type", "LGL": "cell_type" } }, { "input_text": "In particular , two interleukins ( ILs ) , IL-2 and IL-12 , have been shown to be potent inducers of IFN-gamma gene expression in both T cells and LGL .", "target_text": { "interleukins": "protein", "ILs": "protein", "IL-2": "protein", "IL-12": "protein", "IFN-gamma": "protein", "T cells": "cell_type", "LGL": "cell_type" } }, { "input_text": "Although it has been reported that there are some T cell lines that produce IFN-gamma in response to IL-2 and IL-12 stimulation , there has as yet been no report of a natural killer ( NK ) cell line that responds in a similar manner .", "target_text": { "T cell lines": "cell_line", "IFN-gamma": "protein", "natural killer ( NK ) cell line": "cell_line" } }, { "input_text": "In this report we present evidence that the cell line NK3.3 derived from human NK cells , responds to both IL-2 and IL-12 , as measured by increases in IFN-gamma and granulocyte-macrophage colony-stimulating factor ( GM-CSF ) cytoplasmic mRNA and protein expression .", "target_text": { "cell line NK3.3": "cell_line", "human NK cells": "cell_type", "IL-2": "protein", "IL-12": "protein", "IFN-gamma": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein" } }, { "input_text": "In addition , when used together IL-2 and IL-12 synergized in the induction of IFN-gamma and GM-CSF and this synergy was attributed to an increased accumulation and stability of the IFN-gamma and GM-CSF mRNAs .", "target_text": { "IL-2": "protein", "IL-12": "protein", "IFN-gamma": "protein", "GM-CSF": "protein", "GM-CSF mRNAs": "RNA", "IFN-gamma and GM-CSF mRNAs": "RNA" } }, { "input_text": "To investigate the signaling pathways involved in the gene induction , five inhibitors , cyclosporin A ( CsA ) , transforming growth factor-beta , cycloheximide , genistein , and staurosporine A , were used in analyzing the effects of IL-2 and IL-12 on NK3.3 cells .", "target_text": { "transforming growth factor-beta": "protein", "IL-2": "protein", "IL-12": "protein", "NK3.3 cells": "cell_line" } }, { "input_text": "The results suggest that activation of protein kinase C , but not new protein synthesis , is required for IL-2 induction of IFN-gamma and GM-CSF cytoplasmic mRNA .", "target_text": { "protein kinase C": "protein", "IL-2": "protein" } }, { "input_text": "In contrast , IL-12 induction of IFN-gamma cytoplasmic mRNA appears to only partially depend on activation of protein kinase C .", "target_text": { "IL-12": "protein", "IFN-gamma": "protein", "IFN-gamma cytoplasmic mRNA": "RNA", "protein kinase C": "protein" } }, { "input_text": "Furthermore , both transforming growth factor-beta and genistein , a tyrosine kinase inhibitor , could suppress IL-2 and IL-12 signaling but CsA was generally inactive .", "target_text": { "transforming growth factor-beta": "protein", "IL-2": "protein", "IL-12": "protein" } }, { "input_text": "It also was observed that suppression of cytokine gene expression by these agents was independent of the inhibition of proliferation .", "target_text": { "cytokine gene": "DNA" } }, { "input_text": "In addition , IL-2 but not IL-12 induced nuclear factors NF-kappa B and AP1 , and regulation of the nuclear levels of these two DNA binding protein complexes is correlated with IFN-gamma and GM-CSF gene expression .", "target_text": { "IL-2": "protein", "IL-12": "protein", "nuclear factors": "protein", "NF-kappa B": "protein", "AP1": "protein", "DNA binding protein complexes": "protein" } }, { "input_text": "These data indicate that IL-2 and IL-12 may have distinct signaling pathways leading to the induction of IFN-gamma and GM-CSF gene expression , and that the NK3.3 cell line may serve as a novel model for dissecting the biochemical and molecular events involved in these pathways .", "target_text": { "IL-2": "protein", "IL-12": "protein", "IFN-gamma": "protein", "GM-CSF": "protein", "NK3.3 cell line": "cell_line" } }, { "input_text": "A functional T-cell receptor signaling pathway is required for p95vav activity .", "target_text": { "T-cell receptor": "protein", "p95vav": "protein" } }, { "input_text": "Stimulation of the T-cell antigen receptor ( TCR ) induces activation of multiple tyrosine kinases , resulting in phosphorylation of numerous intracellular substrates .", "target_text": { "T-cell antigen receptor": "protein", "TCR": "protein", "tyrosine kinases": "protein" } }, { "input_text": "One substrate is p95vav , which is expressed exclusively in hematopoietic and trophoblast cells .", "target_text": { "p95vav": "protein" } }, { "input_text": "It contains a number of structural motifs , including Src homology 2 , Src homology 3 , and pleckstrin homology domains and a putative guanine nucleotide exchange domain .", "target_text": { "structural motifs": "protein", "Src homology 2": "protein", "Src homology 3": "protein", "pleckstrin homology domains": "protein", "Src homology 2 , Src homology 3 , and pleckstrin homology domains": "protein", "putative guanine nucleotide exchange domain": "protein" } }, { "input_text": "The role of p95vav in TCR -mediated signaling processes is unclear .", "target_text": { "p95vav": "protein", "TCR": "protein" } }, { "input_text": "Here , we show that overexpression of p95vav alone in Jurkat T cells leads to activation of the nuclear factors , including NFAT , involved in interleukin-2 expression .", "target_text": { "p95vav": "protein", "T cells": "cell_type", "nuclear factors": "protein", "NFAT": "protein", "interleukin-2": "protein" } }, { "input_text": "Furthermore , p95vav synergizes with TCR stimulation in inducing NFAT- and interleukin-2- dependent transcription .", "target_text": { "p95vav": "protein", "TCR": "protein" } }, { "input_text": "In contrast , NFAT activation by a G-protein-coupled receptor is not modulated by p95vav overexpression , suggesting that the effect is specific to the TCR signaling pathways .", "target_text": { "NFAT": "protein", "G-protein-coupled receptor": "protein", "p95vav": "protein", "TCR": "protein" } }, { "input_text": "Although removal of the first 67 amino acids of p95vav activates its transforming potential in NIH 3T3 cells , this region appears to be required for its function in T cells .", "target_text": { "first 67 amino acids": "protein", "p95vav": "protein", "NIH 3T3 cells": "cell_line", "T cells": "cell_type" } }, { "input_text": "We further demonstrate that the p95vav -induced NFAT activation is not mimicked by Ras activation , though its function is dependent upon Ras and Raf .", "target_text": { "p95vav": "protein", "NFAT": "protein", "Ras": "protein", "Raf": "protein" } }, { "input_text": "Furthermore , the activating function of p95vav is blocked by FK506 , suggesting that its activity also depends on calcineurin .", "target_text": { "p95vav": "protein", "calcineurin": "protein" } }, { "input_text": "To further dissect p95vav involvement in TCR signaling , we analyzed various Jurkat mutants deficient in TCR signaling function or TCR expression and showed that an intact TCR signaling pathway is required for p95vav to function .", "target_text": { "p95vav": "protein", "TCR": "protein", "Jurkat mutants": "cell_line" } }, { "input_text": "However , overexpression of p95vav does not appear to influence TCR -induced protein tyrosine phosphorylation or increases in cytoplasmic free calcium .", "target_text": { "p95vav": "protein", "TCR": "protein" } }, { "input_text": "Taken together , our data suggest that p95vav plays an important role at an yet unidentified proximal position in the TCR signaling cascade .", "target_text": { "p95vav": "protein", "TCR": "protein" } }, { "input_text": "Positive and negative regulation of granulocyte-macrophage colony-stimulating factor promoter activity by AML1-related transcription factor , PEBP2 .", "target_text": { "granulocyte-macrophage colony-stimulating factor": "protein", "AML1-related transcription factor": "protein", "PEBP2": "protein" } }, { "input_text": "The granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene promoter contains a consensus sequence for the polyomavirus enhancer binding-protein 2 ( PEBP2 ) transcription factor , which consists of alpha and beta subunits .", "target_text": { "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene promoter": "DNA", "polyomavirus enhancer binding-protein 2": "protein", "PEBP2": "protein", "polyomavirus enhancer binding-protein 2 ( PEBP2 ) transcription factor": "protein" } }, { "input_text": "There are at least two genes , alpha A and alpha B , encoding the alpha subunit .", "target_text": { "alpha A": "DNA", "alpha B": "DNA", "alpha subunit": "protein" } }, { "input_text": "alpha B is the mouse homologue of human AML1 gene detected at the breakpoints of t ( 8 ; 21 ) and t ( 3 ; 21 ) myeloid leukemias .", "target_text": { "alpha B": "DNA", "mouse homologue": "DNA", "human AML1 gene": "DNA" } }, { "input_text": "We examined alpha A1 ( an alpha A -gene product ) and alpha B1 and alpha B2 ( two alpha B -encoded isomers ) for their effects on the GM-CSF promoter .", "target_text": { "alpha A1": "protein", "alpha A": "DNA", "alpha A -gene product": "protein", "alpha B1": "protein", "alpha B2": "protein", "alpha B": "DNA", "alpha B -encoded isomers": "protein", "GM-CSF promoter": "DNA" } }, { "input_text": "PEBP2 alpha A1 , alpha B1 , and alpha B2 proteins bound the PEBP2 site within the mouse GM-CSF promoter .", "target_text": { "PEBP2": "protein", "alpha A1": "protein", "PEBP2 alpha A1": "protein", "alpha B1": "protein", "alpha B2 proteins": "protein", "PEBP2 site": "DNA", "GM-CSF": "protein", "mouse GM-CSF promoter": "DNA" } }, { "input_text": "PEBP2 alpha A1 and alpha B1 enhanced the expression of the GM-CSF promoter-driven reporter plasmid in unstimulated and 12-O-tetradecanoylphorbol 13-acetate/phytohemagglutinin-stimulated human Jurkat T cells .", "target_text": { "PEBP2": "protein", "alpha A1": "protein", "PEBP2 alpha A1": "protein", "alpha B1": "protein", "GM-CSF": "protein", "GM-CSF promoter-driven reporter plasmid": "DNA" } }, { "input_text": "In contrast , the promoter activity was suppressed by alpha B2 .", "target_text": { "alpha B2": "protein" } }, { "input_text": "Coexpression of alpha B1 and alpha B2 showed that the promoter activity could be determined by the alpha B1 /alpha B2 ratio .", "target_text": { "alpha B1": "protein", "alpha B2": "protein", "/alpha B2": "protein" } }, { "input_text": "Jurkat cell extract contained PEBP2 site-binding protein ( s ) that cross-reacted with antimouse alpha A1 antibodies .", "target_text": { "PEBP2": "protein", "PEBP2 site-binding protein": "protein", "alpha A1": "protein", "antimouse alpha A1 antibodies": "protein" } }, { "input_text": "Northern blot analysis indicated the expression of human PEBP2 alpha A , alpha B ( AML1 ) , and beta genes in Jurkat cells .", "target_text": { "PEBP2": "protein", "PEBP2 alpha A": "protein", "alpha B": "DNA", "AML1": "DNA", "beta genes": "DNA", "Jurkat cells": "cell_line" } }, { "input_text": "Although further studies are required to determine the precise role of PEBP2 in the GM-CSF promoter activity , the present findings suggested the importance of the relative ratio of different PEBP2 isoforms in regulating the levels of the promoter activity .", "target_text": { "PEBP2": "protein", "GM-CSF": "protein", "PEBP2 isoforms": "protein" } }, { "input_text": "IFN-gamma priming of monocytes enhances LPS -induced TNF production by augmenting both transcription and MRNA stability .", "target_text": { "IFN-gamma": "protein", "monocytes": "cell_type", "TNF": "protein" } }, { "input_text": "The induction of cytokine expression in monocytes / macrophages by bacterial endotoxin or lipopolysaccharide is a critical , highly regulated host defence response .", "target_text": { "cytokine": "protein", "monocytes": "cell_type", "macrophages": "cell_type", "bacterial endotoxin": "protein" } }, { "input_text": "The augmentation of LPS responses by interferon gamma ( IFN-gamma ) , referred to as priming , is well established .", "target_text": { "interferon gamma": "protein", "IFN-gamma": "protein" } }, { "input_text": "However , the mechanism ( s ) by which priming occurs is poorly defined .", "target_text": {} }, { "input_text": "Using tumour necrosis factor ( TNF ) induction as a model , experiments were designed to analyse in detail the priming effect on the LPS response in human monocytes .", "target_text": { "tumour necrosis factor": "protein", "TNF": "protein", "monocytes": "cell_type", "human monocytes": "cell_type" } }, { "input_text": "Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation .", "target_text": { "IFN-gamma": "protein", "TNF": "protein", "TNF mRNA": "RNA" } }, { "input_text": "IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response .", "target_text": { "IFN-gamma": "protein" } }, { "input_text": "Priming occurred after several hours of treatment , and the primed state was induced by either IFN-gamma or GM-CSF , but not M-CSF .", "target_text": { "IFN-gamma": "protein", "GM-CSF": "protein", "M-CSF": "protein" } }, { "input_text": "Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS .", "target_text": { "monocytes": "cell_type", "TNF": "protein", "TNF mRNA": "RNA" } }, { "input_text": "The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cells as determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide .", "target_text": { "nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "consensus NF-kappa B oligonucleotide": "DNA" } }, { "input_text": "An additional significant finding was than TNF mRNA induced in primed cells was much more stable than in unprimed cells ( T1/2 increased 6-8-fold ) .", "target_text": { "TNF": "protein", "TNF mRNA": "RNA", "primed cells": "cell_line", "unprimed cells": "cell_line" } }, { "input_text": "Consistent with the increased mRNA stability , the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes , in addition to being of greater magnitude .", "target_text": { "mRNA": "RNA", "monocytes": "cell_type" } }, { "input_text": "Finally , primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89 .", "target_text": {} }, { "input_text": "H-89 substantially suppressed LPS -induced TNF mRNA accumulation in unprimed cells , but had no effect on primed monocytes following LPS stimulation .", "target_text": { "TNF": "protein", "TNF mRNA": "RNA", "unprimed cells": "cell_line", "monocytes": "cell_type", "primed monocytes": "cell_line" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "A Myc-associated zinc finger protein binding site is one of four important functional regions in the CD4 promoter .", "target_text": { "Myc-associated zinc finger protein": "protein", "Myc-associated zinc finger protein binding site": "DNA", "functional regions": "DNA", "CD4": "protein", "CD4 promoter": "DNA" } }, { "input_text": "The CD4 promoter plays an important role in the developmental control of CD4 transcription .", "target_text": { "CD4": "protein", "CD4 promoter": "DNA" } }, { "input_text": "In this report , we show that the minimal CD4 promoter has four factor binding sites , each of which is required for full function .", "target_text": { "CD4": "protein", "CD4 promoter": "DNA", "factor binding sites": "DNA" } }, { "input_text": "Using biochemical and mutagenesis analyses , we determined that multiple nuclear factors bind to these independent sites .", "target_text": { "nuclear factors": "protein" } }, { "input_text": "We determined that an initiator-like sequence present at the cap site and an Ets consensus sequence are required for full promoter function .", "target_text": { "initiator-like sequence": "DNA", "cap site": "DNA", "Ets consensus sequence": "DNA", "promoter": "DNA" } }, { "input_text": "We also demonstrate that the Myc-associated zinc finger protein ( MAZ ) appears to be the predominant factor binding to one of these sites .", "target_text": { "zinc finger": "protein", "Myc-associated zinc finger protein": "protein", "MAZ": "protein", "predominant factor": "protein" } }, { "input_text": "This last site closely resembles the ME1a1 G3AG4AG3 motif previously shown to be a critical element in the P2 promoter of the c-myc gene .", "target_text": { "ME1a1 G3AG4AG3 motif": "DNA", "P2 promoter": "DNA", "c-myc gene": "DNA" } }, { "input_text": "We therefore believe that the MAZ transcription factor is also likely to play an important role in the control of developmental expression of the CD4 gene .", "target_text": { "MAZ": "protein", "MAZ transcription factor": "protein", "CD4": "protein", "CD4 gene": "DNA" } }, { "input_text": "Erythropoietin stimulates transcription of the TAL1/SCL gene and phosphorylation of its protein products .", "target_text": { "Erythropoietin": "protein", "TAL1/SCL gene": "DNA", "protein products": "protein" } }, { "input_text": "Activation of the TAL1 ( or SCL ) gene , originally identified through its involvement by a recurrent chromosomal translocation , is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia .", "target_text": { "TAL1 ( or SCL ) gene": "DNA", "molecular lesion": "DNA" } }, { "input_text": "The protein products of this gene contain the basic-helix-loop-helix motif characteristic of a large family of transcription factors that bind to the canonical DNA sequence CANNTG as protein heterodimers .", "target_text": { "protein products": "protein", "basic-helix-loop-helix motif": "protein", "transcription factors": "protein", "canonical DNA sequence CANNTG": "DNA", "protein heterodimers": "protein" } }, { "input_text": "TAL1 expression by erythroid cells in vivo and in chemical-induced erythroleukemia cell lines in vivo suggested the gene might regulate aspects of erythroid differentiation .", "target_text": { "TAL1": "protein", "erythroid cells": "cell_type", "chemical-induced erythroleukemia cell lines": "cell_line" } }, { "input_text": "Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin ( Epo ) , we investigated whether the expression or activity of the TAL1 gene and its protein products were affected by Epo in splenic erythroblasts from mice infected with an anemia-inducing strain of Friend virus ( FVA cells ) .", "target_text": { "glycoprotein hormone erythropoietin": "protein", "Epo": "protein", "TAL1": "protein", "TAL1 gene": "DNA", "protein products": "protein", "splenic erythroblasts": "cell_type" } }, { "input_text": "Epo elicited a rapid , dose-related increase in TAL1 mRNA by increasing transcription of the gene and stabilizing one of its mRNAs .", "target_text": { "Epo": "protein", "TAL1": "protein", "TAL1 mRNA": "RNA", "mRNAs": "RNA" } }, { "input_text": "An Epo -inducible TAL1 DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating mRNA and protein .", "target_text": { "Epo": "protein", "TAL1": "protein", "mRNA": "RNA", "protein": "protein" } }, { "input_text": "Induction of DNA binding activity was associated temporally with Epo -induced phosphorylation of nuclear TAL1 protein .", "target_text": { "Epo": "protein", "TAL1": "protein", "nuclear TAL1 protein": "protein" } }, { "input_text": "These results indicate that Epo acts at both transcriptional and posttranscriptional levels on the TAL1 locus in Friend virus -induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages .", "target_text": { "Epo": "protein", "TAL1": "protein", "Friend virus -induced erythroblasts": "cell_line", "transcription factors": "protein", "diverse cell lineages": "cell_type" } }, { "input_text": "Nonradioactive quantification of glucocorticoid receptor expression during differentiation of human monocytic cells ( U937 ) .", "target_text": { "glucocorticoid receptor": "protein", "monocytic cells": "cell_type", "U937": "cell_line" } }, { "input_text": "We describe a method for relative quantification of specific mRNA using a nonradioactive assay based on DNA strand competition between identical sequences of biotin- and fluorescein-labeled amplicon ( probe ) and unlabeled amplicon ( target ) during hybridization .", "target_text": { "mRNA": "RNA" } }, { "input_text": "As the target quantity increased , that of the double-labeled probe decreased in accordance with the mass action law .", "target_text": {} }, { "input_text": "This technique was successfully applied to evaluate differences in glucocorticoid receptor expression in U937 cells before and after the addition of potent differentiation inducers : 12-O-tetradecanoylphorbol 13-acetate ( TPA ) and a combination of all-trans retinoic acid ( RA ) and 1,25-dihydroxyvitamin D2 ( VD ) .", "target_text": { "glucocorticoid receptor": "protein", "U937 cells": "cell_line" } }, { "input_text": "We observed that TPA treatment was associated with an increase in specific binding of [3H]dexamethasone and up-regulation of GR mRNA while no enhanced GR expression was perceived with RA /VD treatment .", "target_text": { "GR": "protein", "GR mRNA": "RNA" } }, { "input_text": "Induction of Sp1 phosphorylation and NF-kappa B -independent HIV promoter domain activity in T lymphocytes stimulated by okadaic acid .", "target_text": { "Sp1": "protein", "NF-kappa B": "protein", "NF-kappa B -independent HIV promoter": "DNA", "T lymphocytes": "cell_type" } }, { "input_text": "In contrast to the purely enhancer-dependent effect of cytokines such as TNF on the activity of the HIV regulatory region ( LTR ) , we observed that okadaic acid ( OKA ) activates HIV transcription through both the enhancer , responding to the factor NF-kappa B , and the promoter domain of the LTR .", "target_text": { "cytokines": "protein", "TNF": "protein", "HIV regulatory region": "DNA", "LTR": "DNA", "NF-kappa B": "protein", "promoter domain": "DNA" } }, { "input_text": "The inducibility of HIV LTR -driven luciferase expression constructs in lymphoblastoid cells stimulated by OKA depended on both functional Sp1 binding elements and the ability of the TATA box to bind the protein TBP .", "target_text": { "HIV LTR": "DNA", "luciferase": "protein", "HIV LTR -driven luciferase expression constructs": "DNA", "lymphoblastoid cells": "cell_type", "Sp1": "protein", "functional Sp1 binding elements": "DNA", "TATA box": "DNA", "TBP": "protein" } }, { "input_text": "In both transformed and normal lymphocytes , OKA stimulation induced intense phosphorylation of the constitutively expressed Sp1 protein in the nucleus , a property of OKA not shared by TNF , phorbol ester , or PHA and interleukin 2 .", "target_text": { "Sp1": "protein", "Sp1 protein": "protein", "TNF": "protein", "PHA": "protein", "interleukin 2": "protein" } }, { "input_text": "Responsiveness of LTR constructs deleted of kappa B elements to HIV Tat expression was increased upon OKA but not TNF stimulation .", "target_text": { "LTR constructs": "DNA", "kappa B elements": "DNA", "HIV Tat": "protein", "TNF": "protein" } }, { "input_text": "Our results suggest that SP1 phosphorylation induced by OKA , a selective inhibitor of the serine-threonine phosphatase PP2A , facilitates the formation of a transcription complex involving general transcription factors , HIV Tat , and Sp1 proteins .", "target_text": { "SP1": "protein", "serine-threonine phosphatase": "protein", "PP2A": "protein", "transcription complex": "protein", "transcription factors": "protein", "HIV Tat": "protein", "Sp1": "protein", "Sp1 proteins": "protein" } }, { "input_text": "The formation of this complex would increase , independently of an in synergy with NF-kappa B , the low basal activity of the HIV LTR observed in normal T lymphocytes .", "target_text": { "NF-kappa B": "protein", "HIV LTR": "DNA", "T lymphocytes": "cell_type", "normal T lymphocytes": "cell_type" } }, { "input_text": "The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2 , IL-4 , IL-7 , IL-13 , and IL-15 .", "target_text": { "shared receptor motifs": "protein", "common Stat proteins": "protein", "cytokine": "protein", "IL-2": "protein", "IL-4": "protein", "IL-7": "protein", "IL-13": "protein", "IL-15": "protein" } }, { "input_text": "To understand the molecular bases for cytokine redundancy and pleiotropy , we have compared the Stat proteins activated in peripheral blood lymphocytes ( PBLs ) by cytokines with shared and distinct actions .", "target_text": { "Stat proteins": "protein", "peripheral blood lymphocytes": "cell_type", "PBLs": "cell_type", "cytokines": "protein" } }, { "input_text": "Interleukin-2 ( IL-2 ) rapidly activated Stat5 in fresh PBL , and Stat3 and Stat5 in preactivated PBL .", "target_text": { "Interleukin-2": "protein", "IL-2": "protein", "Stat5": "protein", "PBL": "cell_type", "Stat3": "protein", "preactivated PBL": "cell_type" } }, { "input_text": "IL-7 and IL-15 induced the same complexes as IL-2 , a feature explained by the existence of similar tyrosine -phosphorylated motifs in the cytoplasmic domains of IL-2R beta and IL-7R that can serve as docking sites for Stat proteins .", "target_text": { "IL-7": "protein", "IL-15": "protein", "IL-2": "protein", "tyrosine -phosphorylated motifs": "protein", "cytoplasmic domains": "protein", "IL-2R beta": "protein", "IL-7R": "protein", "Stat proteins": "protein" } }, { "input_text": "IL-13 Induced the same complexes as IL-4 , a finding explained by our studies implicating IL-4R as a shared component of the receptors .", "target_text": { "IL-13": "protein", "IL-4": "protein", "IL-4R": "protein", "receptors": "protein" } }, { "input_text": "These studies demonstrate that a single cytokine can activate different combinations of Stat proteins under different physiological conditions , and also indicate two mechanisms by which distinct cytokines can activate the same Stat protein .", "target_text": { "cytokine": "protein", "Stat proteins": "protein", "cytokines": "protein", "Stat protein": "protein" } }, { "input_text": "Control of I kappa B-alpha proteolysis by site-specific , signal-induced phosphorylation .", "target_text": { "I kappa B-alpha": "protein" } }, { "input_text": "I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm .", "target_text": { "I kappa B-alpha": "protein", "transcription factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "Various stimuli , typically those associated with stress or pathogens , rapidly inactivate I kappa B-alpha .", "target_text": { "I kappa B-alpha": "protein" } }, { "input_text": "This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism .", "target_text": { "NF-kappa B": "protein", "genes": "DNA" } }, { "input_text": "Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor .", "target_text": { "NF-kappa B": "protein", "I kappa B-alpha": "protein" } }, { "input_text": "When either serine-32 or serine-36 of I kappa B-alpha was mutated , the protein did not undergo signal-induced phosphorylation or degradation , and NF-kappa B could not be activated .", "target_text": { "I kappa B-alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs .", "target_text": { "human erythropoietin receptor gene": "DNA", "GATA-1": "DNA", "Sp1 motifs": "DNA", "GATA-1 and Sp1 motifs": "DNA" } }, { "input_text": "Erythropoietin ( Epo ) , the primary regulator of the production of erythroid cells , acts by binding to a cell surface receptor ( EpoR ) on erythroid progenitors .", "target_text": { "Erythropoietin": "protein", "Epo": "protein", "erythroid cells": "cell_type", "cell surface receptor": "protein", "EpoR": "protein", "erythroid progenitors": "cell_type" } }, { "input_text": "We used deletion analysis and transfection assays with reporter gene constructs to examine the transcription control elements in the 5' flanking region of the human EpoR gene .", "target_text": { "reporter gene constructs": "DNA", "transcription control elements": "DNA", "5' flanking region": "DNA", "EpoR": "protein", "human EpoR gene": "DNA" } }, { "input_text": "In erythroid cells most of the transcription activity was contained in a 150 bp promoter fragment with binding sites for transcription factors AP2 , Sp1 and the erythroid-specific GATA-1 .", "target_text": { "erythroid cells": "cell_type", "150 bp promoter": "DNA", "binding sites": "DNA", "transcription factors": "protein", "AP2": "protein", "Sp1": "protein", "erythroid-specific GATA-1": "protein" } }, { "input_text": "The 150 bp hEpoR promoter exhibited high and low activity in erythroid OCIM1 and K562 cells , respectively , reflecting the high and low levels of constitutive hEpoR expression .", "target_text": { "150 bp hEpoR promoter": "DNA", "OCIM1": "cell_line", "K562 cells": "cell_line", "hEpoR": "protein" } }, { "input_text": "The GATA-1 and Sp1 binding sites in this promoter lacking a TATA sequence were necessary for a high level of transcription activation .", "target_text": { "TATA sequence": "DNA" } }, { "input_text": "Protein-DNA binding studies suggested that Sp1 and two other CCGCCC binding proteins from erythroid and non-erythroid cells could bind to the Sp1 binding motif .", "target_text": { "Sp1": "protein", "CCGCCC binding proteins": "protein", "Sp1 binding motif": "DNA" } }, { "input_text": "By increasing GATA-1 levels via co-transfection , we were able to transactivate the hEpoR promoter in K562 cells and non-erythroid cells , but not in the highly active OCIM1 cells , although GATA-1 mRNA levels were comparable in OCIM1 and K562 .", "target_text": { "GATA-1": "protein", "hEpoR promoter": "DNA", "K562 cells": "cell_line", "non-erythroid cells": "cell_type", "OCIM1 cells": "cell_type", "GATA-1 mRNA": "RNA", "OCIM1": "cell_line", "K562": "cell_line" } }, { "input_text": "Interestingly , when we mutated the Sp1 site , resulting in a marked decrease in hEpoR promoter activity , we could restore transactivation by increasing GATA-1 levels in OCIM1 cells .", "target_text": { "Sp1": "protein", "Sp1 site": "DNA", "hEpoR promoter": "DNA", "GATA-1": "protein", "OCIM1 cells": "cell_type" } }, { "input_text": "These data suggest that while GATA-1 can transactivate the EpoR promoter , the level of hEpoR gene expression does not depend on GATA-1 alone .", "target_text": { "GATA-1": "protein", "EpoR": "protein", "EpoR promoter": "DNA", "hEpoR gene": "DNA" } }, { "input_text": "Rather , hEpoR transcription activity depends on coordination between Sp1 and GATA-1 with other cell-specific factors , including possibly other Sp1 -like binding proteins , to provide high level , tissue-specific expression .", "target_text": { "hEpoR": "protein", "Sp1": "protein", "GATA-1": "protein", "cell-specific factors": "protein", "Sp1 -like binding proteins": "protein" } }, { "input_text": "Overexpression of DR-nm23 , a protein encoded by a member of the nm23 gene family , inhibits granulocyte differentiation and induces apoptosis in 32Dc13 myeloid cells .", "target_text": { "DR-nm23": "protein", "nm23 gene family": "DNA", "granulocyte": "cell_type", "32Dc13 myeloid cells": "cell_line" } }, { "input_text": "Chronic myelogenous leukemia evolves in two clinically distinct stages : a chronic and a blast crisis phase .", "target_text": {} }, { "input_text": "The molecular changes associated with chronic phase to blast crisis transition are largely unknown .", "target_text": {} }, { "input_text": "We have identified a cDNA clone , DR-nm23 , differentially expressed in a blast-crisis cDNA library , which has approximately 70 % sequence similarity to the putative metastatic suppressor genes , nm23-H1 and nm23-H2 .", "target_text": { "cDNA clone": "DNA", "DR-nm23": "protein", "blast-crisis cDNA library ,": "DNA", "putative metastatic suppressor genes": "DNA", "nm23-H1": "DNA", "nm23-H2": "DNA" } }, { "input_text": "The deduced amino acid sequence similarity to the proteins encoded by these two latter genes is approximately 65 % and includes domains and amino acid residues ( the leucine zipper-like and the RGD domain , a serine and a histidine residue in the NH2- and in the COOH-terminal portion of the protein , respectively ) postulated to be important for nm23 function .", "target_text": { "amino acid sequence": "protein", "leucine zipper-like": "protein", "RGD domain": "protein", "NH2-": "protein", "COOH-terminal portion": "protein", "nm23": "protein" } }, { "input_text": "DR-nm23 mRNA is preferentially expressed at early stages of myeloid differentiation of highly purified CD34+ cells .", "target_text": { "DR-nm23": "protein", "DR-nm23 mRNA": "RNA", "highly purified CD34+ cells": "cell_line" } }, { "input_text": "Its constitutive expression in the myeloid precursor 32Dc13 cell line , which is growth-factor dependent for both proliferation and differentiation , results in inhibition of granulocytic differentiation induced by granulocyte colony-stimulating factor and causes apoptotic cell death .", "target_text": { "myeloid precursor 32Dc13 cell line": "cell_line", "granulocyte": "cell_type", "granulocyte colony-stimulating factor": "protein" } }, { "input_text": "These results are consistent with a role for DR-nm23 in normal hematopoiesis and raise the possibility that its overexpression contributes to differentiation arrest , a feature of blastic transformation in chronic myelogenous leukemia .", "target_text": { "DR-nm23": "protein" } }, { "input_text": "An interferon-gamma activation sequence mediates the transcriptional regulation of the IgG Fc receptor type IC gene by interferon-gamma .", "target_text": { "interferon-gamma activation sequence": "DNA", "IgG Fc receptor": "protein", "IgG Fc receptor type IC gene": "DNA", "interferon-gamma": "protein" } }, { "input_text": "Expression of the IgG Fc receptor type I ( Fc gamma RI ) on myeloid cells is dramatically increased by treatment with interferon-gamma ( IFN-gamma ) .", "target_text": { "IgG Fc receptor": "protein", "IgG Fc receptor type I": "protein", "Fc gamma RI": "protein", "myeloid cells": "cell_type", "interferon-gamma": "protein", "IFN-gamma": "protein" } }, { "input_text": "We observed that Fc gamma RI transcript levels in monoblast-like U937 cells were elevated within 3 hr and peaked 12 hr after exposure to IFN-gamma .", "target_text": { "Fc gamma RI": "protein", "monoblast-like U937 cells": "cell_line", "IFN-gamma": "protein" } }, { "input_text": "Treatment of U937 with IFN-gamma for 9 hr in the presence of cycloheximide led to super-induction of Fc gamma RI expression .", "target_text": { "U937": "cell_line", "IFN-gamma": "protein", "Fc gamma RI": "protein" } }, { "input_text": "Nuclear run-on analysis revealed that the rate of Fc gamma RI transcription was increased by IFN-gamma .", "target_text": { "Fc gamma RI": "protein", "IFN-gamma": "protein" } }, { "input_text": "Genomic sequence upstream of the Fc gamma RIC gene was cloned and subjected to primer extension analysis , which demonstrated a single transcription initiation site without a TATA box .", "target_text": { "Fc gamma RIC gene": "DNA", "transcription initiation site": "DNA", "TATA box": "DNA" } }, { "input_text": "Transient transfections of CAT reporter gene constructs containing various Fc gamma RIC promoter sequences into U937 cells revealed that a 20-bp region surrounding the transcription start site ( -7 to +13 ) was capable of mediating transcription initiation and that an IFN-gamma responsive element ( GIRE ) was present within 74 bp upstream of the transcription initiation site .", "target_text": { "reporter gene constructs": "DNA", "CAT reporter gene constructs": "DNA", "Fc gamma RIC promoter sequences": "DNA", "U937 cells": "cell_line", "20-bp region": "DNA", "transcription start site": "DNA", "IFN-gamma responsive element": "DNA", "GIRE": "DNA", "74 bp upstream": "DNA", "transcription initiation site": "DNA" } }, { "input_text": "A 17-bp sequence between positions -51 and -35 conferred IFN-gamma responsiveness on a heterologous promoter .", "target_text": { "17-bp sequence": "DNA", "IFN-gamma": "protein", "heterologous promoter": "DNA" } }, { "input_text": "Double-stranded GIRE sequence , but not a scrambled sequence , was specifically bound by nuclear proteins from IFN-gamma treated U937 cells .", "target_text": { "Double-stranded GIRE sequence": "DNA", "scrambled sequence": "DNA", "nuclear proteins": "protein", "IFN-gamma": "protein", "U937 cells": "cell_line", "IFN-gamma treated U937 cells": "cell_line" } }, { "input_text": "Gel shift experiments further showed that the STAT1 alpha protein bound to the Fc gamma RIC GIRE in response to IFN-gamma treatment of U937 cells .", "target_text": { "STAT1 alpha protein": "protein", "Fc gamma RIC GIRE": "DNA", "IFN-gamma": "protein", "U937 cells": "cell_line" } }, { "input_text": "The Fc gamma RIC GIRE is homologous to the IFN-gamma activation sequence ( GAS ) of the guanylate binding protein and to X box elements of class II MHC genes .", "target_text": { "Fc gamma RIC GIRE": "DNA", "IFN-gamma": "protein", "IFN-gamma activation sequence": "DNA", "GAS": "DNA", "guanylate binding protein": "protein", "X box elements": "DNA", "class II MHC genes": "DNA" } }, { "input_text": "Our results demonstrate that transcriptional regulation of the Fc gamma RIC gene by IFN-gamma involves the binding of STAT1 alpha to a 17-bp GAS homology in the proximal promoter .", "target_text": { "Fc gamma RIC gene": "DNA", "IFN-gamma": "protein", "STAT1 alpha": "protein", "17-bp GAS homology": "DNA", "proximal promoter": "DNA" } }, { "input_text": "Constitutively activated Jak -STAT pathway in T cells transformed with HTLV-I .", "target_text": { "Jak": "protein", "-STAT": "protein", "T cells": "cell_type" } }, { "input_text": "Human T cell lymphotropic virus I ( HTLV-I ) is the etiological agent for adult T cell leukemia and tropical spastic paraparesis ( also termed HTLV-I -associated myelopathy ) .", "target_text": {} }, { "input_text": "HTLV-I -infected peripheral blood T cells exhibit an initial phase of interleukin-2 ( IL-2 ) -dependent growth ; over time , by an unknown mechanism , the cells become IL-2 -independent .", "target_text": { "T cells": "cell_type", "HTLV-I -infected peripheral blood T cells": "cell_type", "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "Whereas the Jak kinases Jak1 and Jak3 and the signal transducer and activator of transcription proteins Stat3 and Stat5 are activated in normal T cells in response to IL-2 , this signaling pathway was constitutively activated in HTLV-I -transformed cells .", "target_text": { "Jak kinases": "protein", "Jak1": "protein", "Jak3": "protein", "transcription proteins": "protein", "Stat3": "protein", "Stat5": "protein", "T cells": "cell_type", "normal T cells": "cell_type", "IL-2": "protein", "HTLV-I -transformed cells": "cell_line" } }, { "input_text": "In HTLV-I -infected cord blood lymphocytes , the transition from IL-2 -dependent to IL-2 -independent growth correlated with the acquisition of a constitutively activated Jak -STAT pathway , which suggests that this pathway participates in HTLV-I -mediated T cell transformation .", "target_text": { "HTLV-I -infected cord blood lymphocytes": "cell_line", "IL-2": "protein", "Jak": "protein", "-STAT": "protein" } }, { "input_text": "Nitric oxide decreases cytokine -induced endothelial activation .", "target_text": { "cytokine": "protein" } }, { "input_text": "Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines .", "target_text": { "adhesion molecules": "protein", "proinflammatory cytokines": "protein" } }, { "input_text": "To test the hypothesis that nitric oxide ( NO ) limits endothelial activation , we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 ( VCAM-1 ) .", "target_text": { "cytokine-stimulated human saphenous vein endothelial cells": "cell_line", "vascular cell adhesion molecule-1": "protein", "VCAM-1": "protein" } }, { "input_text": "In a concentration-dependent manner , NO inhibited interleukin ( IL ) -1 alpha-stimulated VCAM-1 expression by 35-55 % as determined by cell surface enzyme immunoassays and flow cytometry .", "target_text": { "interleukin ( IL ) -1": "protein", "VCAM-1": "protein" } }, { "input_text": "This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays , was unaffected by cGMP analogues , and was quantitatively similar after stimulation by either IL-1 alpha , IL-1 beta , IL-4 , tumor necrosis factor ( TNF alpha ) , or bacterial lipopolysaccharide .", "target_text": { "IL-1 alpha": "protein", "IL-1 beta": "protein", "IL-4": "protein", "tumor necrosis factor": "protein", "TNF alpha": "protein" } }, { "input_text": "NO also decreased the endothelial expression of other leukocyte adhesion molecules ( E-selectin and to a lesser extent , intercellular adhesion molecule-1 ) and secretable cytokines ( IL-6 and IL-8 ) .", "target_text": { "adhesion molecules": "protein", "leukocyte adhesion molecules": "protein", "E-selectin": "protein", "intercellular adhesion molecule-1": "protein", "cytokines": "protein", "IL-6": "protein", "IL-8": "protein" } }, { "input_text": "Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1 , but did not augment cytokine-induced VCAM-1 expression .", "target_text": { "VCAM-1": "protein" } }, { "input_text": "Nuclear run-on assays , transfection studies using various VCAM-1 promoter reporter gene constructs , and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription , in part , by inhibiting NF-kappa B .", "target_text": { "VCAM-1": "protein", "reporter gene constructs": "DNA", "VCAM-1 promoter reporter gene constructs": "DNA", "NF-kappa B": "protein" } }, { "input_text": "We propose that NO 's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall .", "target_text": {} }, { "input_text": "MIP1 alpha nuclear protein ( MNP ) , a novel transcription factor expressed in hematopoietic cells that is crucial for transcription of the human MIP-1 alpha gene .", "target_text": { "MIP1 alpha nuclear protein": "protein", "MNP": "protein", "transcription factor": "protein", "human MIP-1 alpha gene": "DNA" } }, { "input_text": "Murine macrophage inflammatory protein 1 alpha ( MIP-1 alpha ) and its human equivalent ( GOS19 , LD78 , or AT464 ) are members of the -C-C family of low-molecular-weight chemokines .", "target_text": { "Murine macrophage inflammatory protein 1 alpha": "protein", "MIP-1 alpha": "protein", "human equivalent": "protein", "GOS19": "protein", "LD78": "protein", "AT464": "protein", "-C-C family": "protein", "low-molecular-weight chemokines": "protein" } }, { "input_text": "Secreted from activated T cells and macrophages , bone marrow-derived MIP-1 alpha /GOS19 inhibits primitive hematopoietic stem cells and appears to be involved in the homeostatic control of stem cell proliferation .", "target_text": { "T cells": "cell_type", "activated T cells": "cell_type", "macrophages": "cell_type", "MIP-1 alpha": "protein", "/GOS19": "protein", "marrow-derived MIP-1 alpha /GOS19": "protein", "primitive hematopoietic stem cells": "cell_type", "stem cell": "cell_type" } }, { "input_text": "It also induces chemotaxis and inflammatory responses in mature cell types .", "target_text": { "mature cell types": "cell_type" } }, { "input_text": "Therefore , it is important to understand the mechanisms which control the expression of MIP-1 alpha /GOS19 .", "target_text": { "MIP-1 alpha": "protein", "/GOS19": "protein" } }, { "input_text": "Previous work has shown that in Jurkat T cells , a set of widely expressed transcription factors ( the ICK-1 family ) affect the GOS19 promoter .", "target_text": { "T cells": "cell_type", "Jurkat T cells": "cell_line", "transcription factors": "protein", "ICK-1 family": "protein", "GOS19": "protein", "GOS19 promoter": "DNA" } }, { "input_text": "One member , ICK-1A , behaves as a strong negative regulator .", "target_text": { "ICK-1A": "protein", "strong negative regulator": "protein" } }, { "input_text": "In this communication , we provide evidence that the pathway of induction in the macrophage cell line U937 is different from that in Jurkat cells .", "target_text": { "macrophage cell line": "cell_line", "U937": "cell_line", "Jurkat cells": "cell_line" } }, { "input_text": "Furthermore , we show that the ICK-1 binding site does not confer negative regulation in U937 cells .", "target_text": { "ICK-1 binding site": "DNA", "U937 cells": "cell_line" } }, { "input_text": "We provide evidence for an additional binding site , the MIP-1 alpha nuclear protein ( MNP ) site , which overlaps the ICK-1 site .", "target_text": { "binding site": "DNA", "MIP-1 alpha": "protein", "MIP-1 alpha nuclear protein ( MNP ) site": "DNA", "ICK-1 site": "DNA" } }, { "input_text": "Interaction of nuclear extracts from various cell lines and tissue with the MNP site leads to the formation of fast-migrating protein-DNA complexes with similar but distinct electrophoretic mobilities .", "target_text": { "various cell lines": "cell_line", "MNP site": "DNA", "fast-migrating protein-DNA complexes": "protein" } }, { "input_text": "A mutation of the MNP site which does not abrogate ICK-1 binding inactivates the GOS19.1 promoter in U937 cells and reduces its activity by fourfold in Jurkat cells .", "target_text": { "MNP site": "DNA", "GOS19.1 promoter": "DNA", "U937 cells": "cell_line", "Jurkat cells": "cell_line" } }, { "input_text": "We propose that the MNP protein ( s ) binding at the MNP site constitutes a novel transcription factor ( s ) expressed in hematopoietic cells .", "target_text": { "MNP protein": "protein", "MNP site": "DNA", "transcription factor": "protein", "hematopoietic cells": "cell_type" } }, { "input_text": "The effect of Toremifene on the expression of some genes in human mononuclear cells .", "target_text": { "human mononuclear cells": "cell_type" } }, { "input_text": "Toremifene exerts multiple and varied effects on the gene expression of human peripheral mononuclear cells .", "target_text": { "human peripheral mononuclear cells": "cell_type" } }, { "input_text": "After short-term , in vitro exposure to therapeutical levels , distinct changes in P-glycoprotein , steroid receptors , p53 and Bcl-2 expression take place .", "target_text": {} }, { "input_text": "In view of the increasing use of antiestrogens in cancer therapy and prevention , there is obvious merit in long-term in vivo studies to be conducted .", "target_text": {} }, { "input_text": "The interleukin-5 /receptor interaction activates Lyn and Jak2 tyrosine kinases and propagates signals via the Ras-Raf-1-MAP kinase and the Jak -STAT pathways in eosinophils .", "target_text": { "interleukin-5": "protein", "Ras-Raf-1-MAP kinase": "protein", "Jak": "protein", "-STAT": "protein", "eosinophils": "cell_type" } }, { "input_text": "We have shown that the interaction of interleukin ( IL ) -5 with the receptor activates Lyn tyrosine kinase within 1 min and Jak2 tyrosine kinase within 1-3 min .", "target_text": { "interleukin ( IL ) -5": "protein", "Lyn tyrosine kinase": "protein", "Jak2 tyrosine kinase": "protein" } }, { "input_text": "IL-5 also stimulates GTP binding to p21ras .", "target_text": { "IL-5": "protein", "p21ras": "protein" } }, { "input_text": "The signal is subsequently propagated through the activation of Raf-1 , MEK , and MAP kinases as shown by their increased autophosphorylation in vitro and phosphorylation in situ .", "target_text": { "Raf-1": "protein", "MEK": "protein", "MAP kinases": "protein" } }, { "input_text": "Jak2 kinase has been shown to phosphorylate STAT nuclear proteins .", "target_text": { "Jak2 kinase": "protein", "nuclear proteins": "protein", "STAT nuclear proteins": "protein" } }, { "input_text": "The activation of STAT nuclear factors was studied by electrophoretic mobility shift assay using a gamma activation site ( GAS ) probe .", "target_text": { "STAT nuclear factors": "protein", "gamma activation site": "DNA", "GAS": "DNA" } }, { "input_text": "We found that IL-5 induces two GAS-binding proteins in eosinophils , one of which is STAT1 .", "target_text": { "IL-5": "protein", "GAS-binding proteins": "protein", "eosinophils": "cell_type", "STAT1": "protein" } }, { "input_text": "We conclude that IL-5 induced signals are propagated through two distinct pathways : ( 1 ) Lyn --> Ras --> Raf-1 --> MEK --> MAP kinase and ( 2 ) Jak2 --> STAT1 .", "target_text": { "IL-5": "protein", "Lyn": "protein", "Ras": "protein", "Raf-1": "protein", "MEK": "protein", "MAP kinase": "protein", "Jak2": "protein", "STAT1": "protein" } }, { "input_text": "The retinoblastoma gene product negatively regulates transcriptional activation mediated by the human cytomegalovirus IE2 protein .", "target_text": { "retinoblastoma gene product": "protein", "transcriptional activation": "protein", "human cytomegalovirus IE2 protein": "protein" } }, { "input_text": "The IE2 gene product of human cytomegalovirus ( HCMV ) is one of a few viral regulatory proteins expressed immediately upon infection of the host cell .", "target_text": { "IE2 gene product": "protein", "viral regulatory proteins": "protein", "host cell": "cell_type" } }, { "input_text": "It is a potent transcriptional activator of many viral and cellular promoters .", "target_text": { "transcriptional activator": "protein" } }, { "input_text": "We found that the retinoblastoma susceptibility gene product ( Rb ) dramatically suppressed this IE2 transactivation of various promoters .", "target_text": { "retinoblastoma susceptibility gene product": "protein", "Rb": "protein", "IE2": "protein", "various promoters": "DNA" } }, { "input_text": "However , unlike another tumor suppressor protein , p53 , Rb did not have any significant effect on basal levels of transcription , suggesting that Rb specifically interacts with IE2 rather than other cellular factors involved in the general transcription machinery .", "target_text": { "tumor suppressor protein": "protein", "p53": "protein", "Rb": "protein", "IE2": "protein", "cellular factors": "protein" } }, { "input_text": "We found by protein-affinity chromatography that Rb in nuclear extracts or produced by in vitro translation directly bound to IE2 .", "target_text": { "Rb": "protein", "IE2": "protein" } }, { "input_text": "Our results suggest that Rb may regulate the life cycle of HCMV , which is endemic in the human population .", "target_text": { "Rb": "protein" } }, { "input_text": "Furthermore , these data may provide new insights into the slow rate of HCMV DNA replication in cells and the possible involvement of HCMV in tumorigenesis .", "target_text": {} }, { "input_text": "Expression of the nucleoside diphosphate kinase in human skin cancers : an immunohistochemical study .", "target_text": { "nucleoside diphosphate kinase": "protein" } }, { "input_text": "Expression of nucleoside diphosphate ( NDP ) kinase , which is homologous to the nm23 gene product in a variety of species , has been found to be inversely associated with metastatic potential .", "target_text": { "nucleoside diphosphate ( NDP ) kinase": "protein", "nm23 gene": "DNA", "nm23 gene product": "protein" } }, { "input_text": "However , the relationship remains controversial according to the tumor cell types and experimental system , with conflicting results from different research groups .", "target_text": { "tumor cell types": "cell_type" } }, { "input_text": "In order to determine whether NDP kinase expression serves as a marker for metastatic potential in human skin cancer , we assessed the levels of NDP kinase expression in 9 keratoacanthomas ( KAs ) , 26 squamous cell carcinomas ( SCCs ) , and 25 basal cell carcinomas ( BCCs ) using immunohistochemistry .", "target_text": { "NDP kinase": "protein" } }, { "input_text": "The expression of NDP kinase was intense in KA and SCC compared with BCC .", "target_text": { "NDP kinase": "protein" } }, { "input_text": "However , the difference of NDP kinase expression between KA and SCC was not statistically significant .", "target_text": { "NDP kinase": "protein" } }, { "input_text": "And there was no statistically significant difference in NDP kinase expression between SCC with metastasis and SCC without metastasis .", "target_text": { "NDP kinase": "protein" } }, { "input_text": "Our results contradict the hypothesis concerning the possible role of nm23 gene as a metastatic suppressor gene in human skin cancer .", "target_text": { "nm23 gene": "DNA" } }, { "input_text": "The mechanism of overexpression in various tumor cell types and its biological significance in cutaneous carcinogenesis remain to be determined .", "target_text": { "tumor cell types": "cell_type" } }, { "input_text": "RB and a novel E2F-1 binding protein in MHC class II deficient B-cell lines and normal IFN-gamma induction of the class IL transactivator CIITA in class II non-inducible RB -defective tumor lines .", "target_text": { "RB": "protein", "E2F-1 binding protein": "protein", "MHC class II deficient B-cell lines": "cell_line", "IFN-gamma": "protein", "class IL transactivator": "DNA", "CIITA": "DNA", "class II non-inducible RB -defective tumor lines": "cell_line" } }, { "input_text": "The major histocompatibility ( MHC ) class II genes encode cell surface proteins that bind antigenic peptide for presentation to T-cells .", "target_text": { "major histocompatibility ( MHC ) class II genes": "DNA", "cell surface proteins": "protein", "T-cells": "cell_type" } }, { "input_text": "The class II proteins are expressed constitutively on B-cells and EBV- transformed B-cells , and are inducible by IFN-gamma on a wide variety of cell types .", "target_text": { "class II proteins": "protein", "B-cells": "cell_type", "EBV- transformed B-cells ,": "cell_line", "IFN-gamma": "protein", "cell types": "cell_type" } }, { "input_text": "Retinoblastoma protein ( RB ) is a tumor suppressor and functions as a transcriptional repressor by binding and inactivating the transactivator E2F-I .", "target_text": { "Retinoblastoma protein": "protein", "RB": "protein", "transcriptional repressor": "protein", "transactivator E2F-I": "DNA" } }, { "input_text": "RB -defective tumor lines are non-inducible for MHC class II by IFN-gamma , or very weakly inducible , but transfection of 2 different lines with RB expression vectors re-establishes or substantially enhances class II inducibility .", "target_text": { "RB": "protein", "RB -defective tumor lines": "cell_line", "MHC class II": "protein", "IFN-gamma": "protein", "RB expression vectors": "DNA" } }, { "input_text": "Therefore , we examined the RB status of a series of B-cell mutants that are defective in class II expression , generated either in vitro or derived from Bare Lymphocyte Syndrome ( BLS ) patients .", "target_text": { "RB": "protein" } }, { "input_text": "Nuclear matrix-bound RB was detectable in all cases , indicating that loss of RB is not responsible for decreased class II expression in these lines .", "target_text": { "RB": "protein" } }, { "input_text": "A second E2F-I binding protein , most likely DP-I , was also apparently normal in both class II-positive and -negative B-cell lines .", "target_text": {} }, { "input_text": "We also examined the IFN-gamma induction of CIITA in RB -defective lines .", "target_text": { "IFN-gamma": "protein", "CIITA": "DNA", "RB": "protein" } }, { "input_text": "CIITA is a class II gene transactivator known to be defective in one form of BLS and to be required for the induction of MHC class II by IFN-gamma .", "target_text": { "CIITA": "DNA", "class II gene transactivator": "DNA", "MHC class II": "protein", "IFN-gamma": "protein" } }, { "input_text": "CIITA mRNA is normally inducible by IFN-gamma in class II non-inducible , RB -defective lines , and in one line , re-expression of RB has no effect on CIITA mRNA induction levels .", "target_text": { "CIITA": "DNA", "CIITA mRNA": "RNA", "IFN-gamma": "protein", "RB": "protein", "class II non-inducible , RB -defective lines": "cell_line" } }, { "input_text": "Thus , the block in MHC class II inducibility in RB -defective cells is not due to a block in CIITA inducibility .", "target_text": { "RB": "protein", "RB -defective cells": "cell_line", "CIITA": "DNA" } }, { "input_text": "Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes .", "target_text": { "Interleukin 12": "protein", "STAT4": "protein", "human lymphocytes": "cell_type" } }, { "input_text": "Interleukin 12 ( IL-12 ) is an important immunoregulatory cytokine whose receptor is a member of the hematopoietin receptor superfamily .", "target_text": { "Interleukin 12": "protein", "IL-12": "protein", "immunoregulatory cytokine": "protein", "hematopoietin receptor superfamily": "protein" } }, { "input_text": "We have recently demonstrated that stimulation of human T and natural killer cells with IL-12 induces tyrosine phosphorylation of the Janus family tyrosine kinase JAK2 and Tyk2 , implicating these kinases in the immediate biochemical response to IL-12 .", "target_text": { "IL-12": "protein", "Janus family tyrosine kinase": "protein", "JAK2": "protein", "Tyk2": "protein", "kinases": "protein" } }, { "input_text": "Recently , transcription factors known as STATs ( signal transducers and activators of transcription ) have been shown to be tyrosine phosphorylated and activated in response to a number of cytokines that bind hematopoietin receptors and activate JAK kinases .", "target_text": { "transcription factors": "protein", "STATs": "protein", "signal transducers and activators of transcription": "protein", "cytokines": "protein", "hematopoietin receptors": "protein", "JAK kinases": "protein" } }, { "input_text": "In this report we demonstrate that IL-12 induces tyrosine phosphorylation of a recently identified STAT family member , STAT4 , and show that STAT4 expression is regulated by T-cell activation .", "target_text": { "IL-12": "protein", "STAT family member": "protein", "STAT4": "protein" } }, { "input_text": "Furthermore , we show that IL-12 stimulates formation of a DNA-binding complex that recognizes a DNA sequence previously shown to bind STAT proteins and that this complex contains STAT4 .", "target_text": { "IL-12": "protein", "DNA-binding complex": "protein", "STAT proteins": "protein", "STAT4": "protein" } }, { "input_text": "These data , and the recent demonstration of JAK phosphorylation by IL-12 , identify a rapid signal-transduction pathway likely to mediate IL-12 -induced gene expression .", "target_text": { "JAK": "protein", "IL-12": "protein" } }, { "input_text": "Temperature-induced down-regulation of the glucocorticoid receptor in peripheral blood mononuclear leucocyte in patients with sepsis or septic shock .", "target_text": { "glucocorticoid receptor": "protein", "peripheral blood mononuclear leucocyte": "cell_type" } }, { "input_text": "OBJECTIVE : Activation of the hypothalamic-pituitary-adrenal axis is of vital importance during critical illness .", "target_text": {} }, { "input_text": "We have studied the adaptive mechanisms which occur at the level of the glucocorticoid receptor in glucocorticoid target tissues in patients with sepsis or septic shock .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "DESIGN : The effects of hypercortisolaemia , hyperthermia and cellular composition on number of glucocorticoid receptors per cell and their affinity were evaluated , both in vitro and in vivo , in peripheral blood mononuclear leucocytes of control subjects and in patients with sepsis or septic shock .", "target_text": { "glucocorticoid receptors": "protein", "peripheral blood mononuclear leucocytes": "cell_type" } }, { "input_text": "SUBJECTS : Fifteen patients ( age 25-79 ) with sepsis or septic shock who were admitted to an intensive care unit were studied .", "target_text": {} }, { "input_text": "The control group consisted of 24 healthy laboratory employees .", "target_text": {} }, { "input_text": "MEASUREMENTS : The binding capacity and affinity of the glucocorticoid receptors were measured and compared to clinical data and the plasma cortisol concentrations .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "RESULTS : Hypercortisolaemia , in vitro , resulted in a decreased affinity and a decreased binding capacity of the glucocorticoid receptor .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "In vitro , hyperthermia as well as variations in the cellular composition did not influence the glucocorticoid receptor .", "target_text": {} }, { "input_text": "In vivo , there was no change in the number of receptors per cell in patients with sepsis or septic shock as compared to healthy controls .", "target_text": {} }, { "input_text": "However , a decreased affinity of the glucocorticoid receptor was observed .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "There was a weak but significant negative correlation between body temperature and the number of glucocorticoid receptors in the patient group .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "There was no relation between circulating cortisol concentrations and glucocorticoid receptor affinity and number .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "CONCLUSIONS : There is no obvious regulation of the number of glucocorticoid receptors by plasma cortisol concentrations in vivo .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "The decreased affinity of the glucocorticoid receptor together with the negative correlation between hyperthermia and the number of glucocorticoid receptors in patients with sepsis or septic shock suggest that hypothalamic-pituitary-adrenal axis activation during critical illness is accompanied by peripheral adaptation in glucocorticoid receptor number and affinity .", "target_text": { "glucocorticoid receptor": "protein", "glucocorticoid receptors": "protein" } }, { "input_text": "Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells .", "target_text": { "cytokine": "protein", "monocytic cells": "cell_type" } }, { "input_text": "A possible signaling role for the Syk tyrosine kinase .", "target_text": { "Syk tyrosine kinase": "protein" } }, { "input_text": "Activation of cytoplasmic tyrosine kinases is an important aspect of signal transduction mediated by integrins .", "target_text": { "cytoplasmic tyrosine kinases": "protein", "integrins": "protein" } }, { "input_text": "In the human monocytic cell line THP-1 , either integrin -dependent cell adhesion to fibronectin or ligation of beta 1 integrins with antibodies causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about 65-75 and 120-125 kDa .", "target_text": { "human monocytic cell line THP-1": "cell_line", "integrin": "protein", "fibronectin": "protein", "beta 1 integrins": "protein", "antibodies": "protein", "proteins": "protein" } }, { "input_text": "In addition , integrin ligation leads to nuclear translocation of the p50 and p65 subunits of the NF-kappa B transcription factor , to activation of a reporter gene driven by a promoter containing NF-kappa B sites , and to increased levels of mRNAs for immediate-early genes , including the cytokine interleukin ( IL ) -1 beta .", "target_text": { "integrin": "protein", "p50": "protein", "p65 subunits": "protein", "NF-kappa B transcription factor": "protein", "reporter gene": "DNA", "promoter": "DNA", "NF-kappa B sites": "DNA", "mRNAs": "RNA", "immediate-early genes": "DNA", "cytokine interleukin ( IL ) -1 beta": "protein" } }, { "input_text": "The tyrosine kinase inhibitors genistein and herbimycin A block both integrin -mediated tyrosine phosphorylation and increases in IL-1 beta message levels , indicating a causal relationship between the two events .", "target_text": { "integrin": "protein", "IL-1 beta": "protein" } }, { "input_text": "The components tyrosine phosphorylated subsequent to cell adhesion include paxillin , pp125FAK , and the SH2 domain containing tyrosine kinase Syk .", "target_text": { "paxillin": "protein", "pp125FAK": "protein", "SH2 domain": "protein", "SH2 domain containing tyrosine kinase Syk": "protein" } }, { "input_text": "In contrast , integrin ligation with antibodies induces tyrosine phosphorylation of Syk but not of FAK or paxillin .", "target_text": { "integrin": "protein", "antibodies": "protein", "Syk": "protein", "FAK": "protein", "paxillin": "protein" } }, { "input_text": "In adhering cells , pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of FAK and paxillin but not of Syk , while IL-1 beta message induction is unaffected .", "target_text": { "adhering cells": "cell_type", "FAK": "protein", "paxillin": "protein", "Syk": "protein", "IL-1 beta": "protein" } }, { "input_text": "These observations indicate that the Syk tyrosine kinase may be an important component of an integrin signaling pathway in monocytic cells , leading to activation of NF-kappa B and to increased levels of cytokine messages .", "target_text": { "Syk": "protein", "integrin": "protein", "monocytic cells": "cell_type", "NF-kappa B": "protein", "cytokine": "protein" } }, { "input_text": "Inhibition of dexamethasone binding to human glucocorticoid receptor by New World primate cell extracts .", "target_text": { "human glucocorticoid receptor": "protein" } }, { "input_text": "To determine if New World primates express an inhibitor that influences glucocorticoid receptor ( GR ) binding characteristics , we examined [3H]dexamethasone binding in cytosol prepared from B95-8 lymphoid cells , derived from the cotton top tamarin ( Saguinus oedipus ) , in combination with cytosol prepared from human or rat tissues .", "target_text": { "glucocorticoid receptor": "protein", "GR": "protein", "B95-8 lymphoid cells": "cell_line" } }, { "input_text": "B95-8 cytosol inhibited specific binding of [3H]dexamethasone ( P < 0.01 ) when mixed with cytosol prepared from either a human lymphoid cell line ( HL ) or rat thymus .", "target_text": { "human lymphoid cell line": "cell_line", "HL": "cell_line" } }, { "input_text": "The inhibitory activity was heat labile and trypsin sensitive .", "target_text": { "trypsin": "protein" } }, { "input_text": "Peak inhibitory activity was found in the 150-200 kd fractions after Sephacryl G-200 ultrafiltration .", "target_text": {} }, { "input_text": "Scatchard analysis of [3H]dexamethasone binding using mixed cytosol showed a diminished GR apparent binding affinity when compared to HL cytosol .", "target_text": { "GR": "protein" } }, { "input_text": "Kinetic studies using mixed cytosol indicated that B95-8 cytosol did not affect the apparent dissociation rate of [3H]dexamethasone .", "target_text": {} }, { "input_text": "These data demonstrate that B95-8 cells contain a competitive inhibitor that prevents binding of dexamethasone to its cognate receptor .", "target_text": { "B95-8 cells": "cell_type", "cognate receptor": "protein" } }, { "input_text": "Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals .", "target_text": { "GATA motif": "DNA", "Duffy gene promoter": "DNA", "erythroid gene": "DNA" } }, { "input_text": "The mRNA for the Duffy blood group antigen , the erythrocyte receptor for the Plasmodium vivax malaria parasite , has recently been cloned and shown to encode a widely expressed chemokine receptor .", "target_text": { "mRNA": "RNA", "Duffy blood group antigen": "protein", "erythrocyte receptor": "protein", "chemokine receptor": "protein" } }, { "input_text": "Here , we show that the Duffy antigen/chemokine receptor gene ( DARC ) is composed of a single exon and that most Duffy-negative blacks carry a silent FY*B allele with a single T to C substitution at nucleotide -46 .", "target_text": { "Duffy antigen/chemokine receptor": "protein", "Duffy antigen/chemokine receptor gene": "DNA", "DARC": "DNA", "exon": "DNA", "silent FY*B allele": "DNA" } }, { "input_text": "This mutation impairs the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor .", "target_text": { "erythroid cells": "cell_type", "binding site": "DNA", "GATA1 erythroid transcription factor": "protein" } }, { "input_text": "With the recent characterization of the FY*A and FY*B alleles , these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid-specific repression of the DARC gene in Duffy-negative individuals .", "target_text": { "DARC gene": "DNA" } }, { "input_text": "Activation of pp90rsk and early growth response-1 gene expression by pokeweed mitogen in human B cells .", "target_text": { "pp90rsk": "protein", "early growth response-1 gene": "DNA", "pokeweed mitogen": "protein", "human B cells": "cell_type" } }, { "input_text": "The present studies have examined the effects of pokeweed mitogen ( PWM ) on the induction of early growth response-1 gene ( EGR-1 ) in normal human B cells .", "target_text": { "pokeweed mitogen": "protein", "PWM": "protein", "early growth response-1 gene": "DNA", "EGR-1": "DNA", "human B cells": "cell_type", "normal human B cells": "cell_type" } }, { "input_text": "PWM regulates EGR-1 gene expression by both transcriptional and post-transcriptional mechanisms .", "target_text": { "PWM": "protein", "EGR-1": "DNA" } }, { "input_text": "Transient transfection assays with EGR-1 promoter fragments linked to the chloramphenicol acetyltransferase ( CAT ) gene demonstrated that PWM induced EGR-1 transcription is conferred by the CArG motif ( C C[AT]6GG ) in the EGR-1 promoter .", "target_text": { "EGR-1": "DNA", "EGR-1 promoter fragments": "DNA", "chloramphenicol acetyltransferase": "protein", "CAT": "protein", "chloramphenicol acetyltransferase ( CAT ) gene": "DNA", "PWM": "protein", "CArG motif": "DNA", "C C[AT]6GG": "DNA", "EGR-1 promoter": "DNA" } }, { "input_text": "The results further demonstrated the activation of S6 kinase ( pp90rsk ) , evidenced by phosphorylation of S6 and serum response factor ( SRF ) peptides , in PWM treated B cells .", "target_text": { "S6 kinase": "protein", "pp90rsk": "protein", "S6": "protein", "PWM": "protein", "PWM treated B cells": "cell_line" } }, { "input_text": "Taken together , these findings suggest that PWM is able to initiate an intracytoplasmic signalling cascade and EGR-1 induction in normal human B cells .", "target_text": { "PWM": "protein", "EGR-1": "DNA", "human B cells": "cell_type", "normal human B cells": "cell_type" } }, { "input_text": "A conserved motif in the promoters of several cytokines expressed by human Th2-type lymphocytes .", "target_text": { "conserved motif": "DNA", "promoters": "DNA", "cytokines": "protein", "human Th2-type lymphocytes": "cell_line" } }, { "input_text": "We have recently found a novel conserved motif in the promoters of several T-cell-expressed cytokines [ human interleukin -2 , -4 , -5 and -13 and human and mouse granulocyte/macrophage-colony stimulating factor ( GM-CSF ) ] .", "target_text": { "conserved motif": "DNA", "promoters": "DNA", "cytokines": "protein", "T-cell-expressed cytokines": "protein", "GM-CSF": "protein" } }, { "input_text": "It contains a core sequence CTTGG ... CCAAG which is present as part of larger palindromic sequences in each gene .", "target_text": { "core sequence": "DNA", "palindromic sequences": "DNA" } }, { "input_text": "This suggest that they may interact with a new family of trans-acting factors .", "target_text": { "trans-acting factors": "protein" } }, { "input_text": "In transfection assays , the human GM-CSF element has a strong positive effect on the expression of a reporter gene by the human T cell line Jurkat J6 upon stimulation .", "target_text": { "GM-CSF": "protein", "human GM-CSF element": "DNA", "reporter gene": "DNA", "human T cell line": "cell_line", "Jurkat J6": "cell_line" } }, { "input_text": "In DNA mobility shift assays , this sequence can give either six different specific bands which are competed out by different parts of the sequence or one specific band which is competed out by each of the inverted repeats , depending on the reconstitution conditions .", "target_text": {} }, { "input_text": "In different genes , the core sequences are separated by integer numbers of helical turns .", "target_text": { "genes": "DNA", "core sequences": "DNA", "helical turns": "DNA" } }, { "input_text": "Considering the strong positive regulatory effect of this element and its presence in several T-cell-expressed cytokine genes , it may be crucial to the coordinated expression of these cytokines in T helper cells .", "target_text": { "element": "DNA", "T-cell-expressed cytokine genes": "DNA", "cytokines": "protein", "T helper cells": "cell_type" } }, { "input_text": "cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line .", "target_text": { "cDNA": "DNA", "NGFI-B/nur77-related transcription factor": "protein", "apoptotic human T cell line": "cell_line" } }, { "input_text": "A human T lymphoid cell line , PEER , dies by apoptosis in the presence of PMA and calcium ionophore .", "target_text": { "human T lymphoid cell line": "cell_line", "PEER": "cell_line" } }, { "input_text": "A new gene , TINUR , was cloned from apoptotic PEER cells .", "target_text": { "gene": "DNA", "TINUR": "DNA", "apoptotic PEER cells": "cell_line" } }, { "input_text": "The expression of the TINUR gene is induced within 1 h after the cross-linking of the T cell Ag receptor complex .", "target_text": { "TINUR gene": "DNA", "T cell Ag receptor complex": "protein" } }, { "input_text": "TINUR belongs to the NGFI-B/nur77 family of the steroid receptor superfamily and is an orphan receptor .", "target_text": { "TINUR": "DNA", "NGFI-B/nur77 family": "protein", "steroid receptor superfamily": "protein", "orphan receptor": "protein" } }, { "input_text": "TINUR binds to the same DNA sequence as NGFI-B/nur77 .", "target_text": { "TINUR": "DNA", "DNA sequence": "DNA", "NGFI-B/nur77": "protein" } }, { "input_text": "We also propose that the NGFI-B/nur77 family can be classified into two subtypes .", "target_text": { "NGFI-B/nur77 family": "protein" } }, { "input_text": "Aspirin inhibits nuclear factor-kappa B mobilization and monocyte adhesion in stimulated human endothelial cells .", "target_text": { "nuclear factor-kappa B": "protein", "stimulated human endothelial cells": "cell_line" } }, { "input_text": "BACKGROUND : The induction of vascular cell adhesion molecule-1 ( VCAM-1 ) and E-selectin by tumor necrosis factor-alpha ( TNF ) is mediated by mobilization of the transcription factor nuclear factor-kappa B ( NF-kappa B ) .", "target_text": { "vascular cell adhesion molecule-1": "protein", "VCAM-1": "protein", "E-selectin": "protein", "tumor necrosis factor-alpha": "protein", "TNF": "protein", "transcription factor": "protein", "nuclear factor-kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "Since salicylates have been reported to inhibit NF-kappa B activation by preventing the degradation of its inhibitor I kappa B , we studied a potential inhibition of this pathway by acetylsalicylate ( aspirin ) in human umbilical vein endothelial cells ( HUVECs ) .", "target_text": { "NF-kappa B": "protein", "I kappa B": "protein", "human umbilical vein endothelial cells": "cell_line", "HUVECs": "cell_line" } }, { "input_text": "METHODS AND RESULTS : Gel-shift analyses demonstrated dose-dependent inhibition of TNF -induced NF-kappa B mobilization by aspirin at concentrations ranging from 1 to 10 mmol/L .", "target_text": { "TNF": "protein", "NF-kappa B": "protein" } }, { "input_text": "Induction of VCAM-1 and E-selectin surface expression by TNF was dose-dependently reduced by aspirin over the same range , while induction of intercellular adhesion molecule-1 ( ICAM-1 ) was hardly affected .", "target_text": { "VCAM-1": "protein", "E-selectin": "protein", "TNF": "protein", "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein" } }, { "input_text": "Aspirin appeared to prevent VCAM-1 transcription , since it dose-dependently inhibited induction of VCAM-1 mRNA by TNF .", "target_text": { "VCAM-1": "protein", "VCAM-1 mRNA": "RNA", "TNF": "protein" } }, { "input_text": "As a functional consequence , adhesion of U937 monocytes to TNF -stimulated HUVECs was markedly reduced by aspirin due to suppression of VCAM-1 and E-selectin upregulation .", "target_text": { "U937 monocytes": "cell_line", "TNF": "protein", "HUVECs": "cell_line", "TNF -stimulated HUVECs": "cell_line", "VCAM-1": "protein", "E-selectin": "protein" } }, { "input_text": "These effects of aspirin were not related to the inhibition of cyclooxygenase activity , since indomethacin was ineffective .", "target_text": { "cyclooxygenase": "protein" } }, { "input_text": "CONCLUSIONS : Our data suggest that aspirin inhibits NF-kappa B mobilization , induction of VCAM-1 and E-selectin , and subsequent monocyte adhesion in endothelial cells stimulated by TNF , thereby providing an additional mechanism for therapeutic effects of aspirin .", "target_text": { "NF-kappa B": "protein", "VCAM-1": "protein", "E-selectin": "protein", "endothelial cells": "cell_type", "TNF": "protein" } }, { "input_text": "Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites .", "target_text": { "NF-kappa B": "protein", "phosphatase": "protein", "I kappa B alpha": "protein", "phosphatase 2A-sensitive sites": "protein" } }, { "input_text": "Activation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor , I kappa B alpha , although the underlying mechanism remains unclear .", "target_text": { "NF-kappa B": "protein", "I kappa B alpha": "protein" } }, { "input_text": "In the present study , the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated .", "target_text": { "serine/threonine phosphatases": "protein", "I kappa B alpha": "protein" } }, { "input_text": "Our studies demonstrate that incubation of human T cells with low concentrations ( approximately 1-5 nM ) of calyculin A or okadaic acid , potent inhibitors of protein phosphatase type 1 ( PP-1 ) and type 2A ( PP-2A ) , induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus .", "target_text": { "human T cells": "cell_type", "PP-2A": "protein", "I kappa B alpha": "protein" } }, { "input_text": "This action of the phosphatase inhibitors , which is associated with the activation of the RelA.p50 NF-kappa B heterodimer , is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha ( TNF-alpha ) .", "target_text": { "NF-kappa B": "protein", "RelA.p50 NF-kappa B heterodimer": "protein", "I kappa B alpha": "protein", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "Furthermore , the phosphorylated I kappa B alpha from calyculin A -treated cells , but not that from TNF-alpha -stimulated cells , is sensitive to PP-2A in vitro , suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers .", "target_text": { "I kappa B alpha": "protein", "phosphorylated I kappa B alpha": "protein", "calyculin A -treated cells": "cell_line", "TNF-alpha": "protein", "TNF-alpha -stimulated cells": "cell_line", "PP-2A": "protein", "NF-kappa B": "protein" } }, { "input_text": "However , induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha .", "target_text": { "I kappa B alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor .", "target_text": {} }, { "input_text": "Together , these results suggest that phosphorylation of I kappa B alpha , mediated through both the TNF-alpha -inducible and the PP-2A -opposing kinases , may serve to target I kappa B alpha for proteasome -mediated degradation .", "target_text": { "I kappa B alpha": "protein", "TNF-alpha": "protein", "PP-2A": "protein", "PP-2A -opposing kinases": "protein", "proteasome": "protein" } }, { "input_text": "Sp1 functions in a chromatin -dependent manner to augment human alpha-globin promoter activity .", "target_text": { "Sp1": "protein", "chromatin": "DNA", "human alpha-globin promoter": "DNA" } }, { "input_text": "The 5' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site .", "target_text": { "5' flanking region": "DNA", "human alpha-globin gene": "DNA", "G + C rich": "DNA", "consensus sequence": "DNA", "Sp1": "protein", "Sp1 binding site": "DNA" } }, { "input_text": "We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer , HS-40 .", "target_text": { "G + C-rich region": "DNA", "alpha-globin promoter": "DNA", "far-upstream alpha-globin enhancer": "DNA", "HS-40": "DNA" } }, { "input_text": "We show that in transiently transfected erythroid cells , deletion of the alpha-globin G + C-rich 5' flanking region has no effect on alpha-globin promoter activity .", "target_text": { "transiently transfected erythroid cells": "cell_line", "alpha-globin G + C-rich 5' flanking region": "DNA", "alpha-globin promoter": "DNA" } }, { "input_text": "However , upon stable integration into chromatin , deletion of this region causes a nearly 90 % decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region .", "target_text": { "chromatin": "DNA", "alpha-globin promoter": "DNA" } }, { "input_text": "These results suggest that the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter activity in a chromatin -dependent manner .", "target_text": { "alpha-globin G + C-rich 5' flanking region": "DNA", "alpha-globin promoter": "DNA", "chromatin": "DNA" } }, { "input_text": "We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation .", "target_text": { "G + C-rich region": "DNA", "alpha-globin gene": "DNA" } }, { "input_text": "Finally , we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1 .", "target_text": { "G + C-rich region": "DNA", "alpha-globin promoter": "DNA", "alpha-globin gene": "DNA", "multiple binding sites": "DNA", "transcription factor": "protein", "Sp1": "protein" } }, { "input_text": "Costimulation of human CD4+ T cells with LFA-3 and B7 induce distinct effects on AP-1 and NF-kappa B transcription factors .", "target_text": { "human CD4+ T cells": "cell_line", "LFA-3": "protein", "B7": "protein", "AP-1": "protein", "NF-kappa B": "protein", "transcription factors": "protein" } }, { "input_text": "We have earlier shown that stimulation of human CD4+ T cells with SEA presented on Chinese hamster ovary ( CHO ) -DR transfectants coexpressing either B7 or LFA-3 resulted in distinct cytokine profiles .", "target_text": { "human CD4+ T cells": "cell_line", "Chinese hamster ovary ( CHO ) -DR transfectants": "cell_line", "B7": "protein", "LFA-3": "protein", "cytokine": "protein" } }, { "input_text": "We now demonstrate that B7 , but not LFA-3 , strongly costimulated IL-2 transcription and mRNA expression in CD4+ T cells .", "target_text": { "B7": "protein", "LFA-3": "protein", "IL-2": "protein", "CD4+ T cells": "cell_line" } }, { "input_text": "Maximal increase in IL-2 transcription was recorded with CHO-DR/ B7 / LFA-3 , suggesting a cooperative effect of B7 and LFA-3 at the transcriptional level .", "target_text": { "IL-2": "protein", "B7": "protein", "LFA-3": "protein", "CHO-DR/ B7 / LFA-3": "protein" } }, { "input_text": "Gel-shift analysis demonstrated that stimulation of CD4+ T cells with CHO-DR and staphylococcal enterotoxin A was sufficient to induce significant amounts of NF-kappa B binding proteins , whereas induction of AP-1 binding proteins required costimulation .", "target_text": { "CD4+ T cells": "cell_line", "CHO-DR": "protein", "NF-kappa B": "protein", "AP-1 binding proteins": "protein" } }, { "input_text": "LFA-3 induced moderate levels of AP-1 , but did not influence the levels of NF-kappa B , while B7 costimulation strongly induced both AP-1 and substantially enhanced NF-kappa B binding proteins .", "target_text": { "LFA-3": "protein", "AP-1": "protein", "NF-kappa B": "protein", "B7": "protein", "NF-kappa B binding proteins": "protein" } }, { "input_text": "The CHO-DR/ B7 / LFA-3 triple transfectant induced a further increase in AP-1 and NF-kappa B binding proteins compared with the double transfectants .", "target_text": { "B7": "protein", "LFA-3": "protein", "CHO-DR/ B7 / LFA-3 triple transfectant": "cell_line", "AP-1": "protein", "NF-kappa B": "protein", "binding proteins": "protein", "double transfectants": "cell_line" } }, { "input_text": "The level of Oct-1 binding proteins remained similar in all samples .", "target_text": { "Oct-1 binding proteins": "protein" } }, { "input_text": "Super-shift analysis revealed that the NF-kappa B complex of costimulated CD4+ T cells contained large amounts of p50 , substantial amounts of p65 , and marginal levels of c-Rel proteins .", "target_text": { "NF-kappa B": "protein", "NF-kappa B complex": "protein", "CD4+ T cells": "cell_line", "costimulated CD4+ T cells": "cell_line", "p50": "protein", "p65": "protein", "c-Rel proteins": "protein" } }, { "input_text": "The AP-1 binding proteins contained c-Jun , Jun-D , and Fra-1 , but marginal amounts of Jun-B and c-Fos .", "target_text": { "AP-1": "protein", "AP-1 binding proteins": "protein", "c-Jun": "protein", "Jun-D": "protein", "Fra-1": "protein", "Jun-B": "protein", "c-Fos": "protein" } }, { "input_text": "Our results indicate distinct effects of B7 and LFA-3 costimulation on the activity of AP-1 and NF-kappa B .", "target_text": { "B7": "protein", "LFA-3": "protein", "AP-1": "protein", "NF-kappa B": "protein" } }, { "input_text": "These may partly account for the differential effects of B7 and LFA-3 costimulation on IL-2 expression .", "target_text": { "B7": "protein", "LFA-3": "protein", "IL-2": "protein" } }, { "input_text": "The Ah receptor recognizes DNA binding sites for the B cell transcription factor , BSAP : a possible mechanism for dioxin-mediated alteration of CD19 gene expression in human B lymphocytes .", "target_text": { "Ah receptor": "protein", "DNA binding sites": "DNA", "transcription factor": "protein", "B cell transcription factor": "protein", "BSAP": "protein", "CD19 gene": "DNA", "human B lymphocytes": "cell_type" } }, { "input_text": "2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD ) inhibits murine and human B lymphocyte immunoglobulin production through an unknown mechanism .", "target_text": {} }, { "input_text": "This study investigated the effect of TCDD on expression of the CD19 gene in a human B lymphocyte cell line .", "target_text": { "CD19 gene": "DNA", "human B lymphocyte cell line": "cell_line" } }, { "input_text": "Northern blot analysis showed that TCDD treatment decreased steady state levels of CD19 mRNA by 67 % in the IM-9 cell line .", "target_text": { "CD19 mRNA": "RNA", "IM-9 cell line": "cell_line" } }, { "input_text": "Using a gel mobility shift assay , we identified a DNA-binding complex in IM-9 nuclear extracts that by several criteria appears to be the Ah receptor .", "target_text": { "DNA-binding complex": "protein", "Ah receptor": "protein" } }, { "input_text": "In addition , the Ah receptor complex recognized a DNA binding site for B cell lineage-specific activator protein ( BSAP ) in the promoter region of the human CD19 gene which is similar to the consensus Ah receptor DNA binding site .", "target_text": { "Ah receptor": "protein", "Ah receptor complex": "protein", "DNA binding site": "DNA", "B cell lineage-specific activator protein": "protein", "BSAP": "protein", "promoter region": "DNA", "CD19 gene": "DNA", "consensus Ah receptor DNA binding site": "DNA" } }, { "input_text": "These results suggest that the AhR could interfere with BSAP -stimulated CD19 gene transcription by competition for a common DNA binding site .", "target_text": { "AhR": "protein", "BSAP": "protein", "CD19 gene": "DNA", "DNA binding site": "DNA" } }, { "input_text": "Inhibitory action of nm23 proteins on induction of erythroid differentiation of human leukemia cells .", "target_text": { "nm23 proteins": "protein", "human leukemia cells": "cell_type" } }, { "input_text": "We recently identified a differentiation inhibitory factor ( I-factor ) in mouse myeloid leukemia M1 cells as a murine homolog of the human nm23-H2 gene product .", "target_text": { "differentiation inhibitory factor": "protein", "I-factor": "protein", "mouse myeloid leukemia M1 cells": "cell_line", "murine homolog": "protein", "human nm23-H2 gene product": "protein" } }, { "input_text": "nm23 genes encode proteins that participate in tumor metastasis regulation and in various fundamental cellular processes , although their mechanisms of action are still unknown .", "target_text": { "nm23 genes": "DNA" } }, { "input_text": "Although all nm23 proteins contain nucleoside diphosphate ( NDP ) kinase activity , it has not been established that the enzyme activity mediated the various functions of nm23 proteins .", "target_text": { "nm23 proteins": "protein", "nucleoside diphosphate ( NDP ) kinase": "protein" } }, { "input_text": "In the present experiment , we examined the effect of nm23 proteins on various differentiation induction systems of human leukemic cells including HL-60 , U937 , HEL/S , KU812F , K562 , and HEL cells .", "target_text": { "nm23 proteins": "protein", "human leukemic cells": "cell_type", "HL-60": "cell_line", "U937": "cell_line", "HEL/S": "cell_line", "KU812F": "cell_line", "K562": "cell_line", "HEL": "cell_line" } }, { "input_text": "Native human erythrocyte NDP kinase protein inhibited the induction of erythroid differentiation of HEL , KU812 and K562 cells , but not the induction of monocytic or granulocytic differentiation of HL-60 , U937 and HEL/S cells .", "target_text": { "Native human erythrocyte NDP kinase protein": "protein", "HL-60": "cell_line", "U937": "cell_line", "HEL/S": "cell_line" } }, { "input_text": "The erythroid differentiation of HEL cells was inhibited by recombinant human nm23 -H1 , -H2 , mouse nm23 -M1 , and -M2 proteins .", "target_text": { "HEL cells": "cell_line" } }, { "input_text": "Moreover , both the mutant nm23-H2His protein and truncated nm23-H2 protein containing N-terminal ( 1-60 ) peptide , which do not have NDP kinase activity , also inhibited erythroid differentiation of HEL cells .", "target_text": { "mutant nm23-H2His protein": "protein", "truncated nm23-H2 protein": "protein", "N-terminal ( 1-60 ) peptide": "protein", "NDP kinase": "protein", "HEL cells": "cell_line" } }, { "input_text": "These results suggest that ( 1 ) the differentiation inhibitory activity of I-factor /nm23 protein is not restricted to monocytic differentiation of M1 cells , ( 2 ) the inhibitory activity is exhibited without species specificity , and ( 3 ) the differentiation inhibitory activity of the nm23/NDP kinase protein is independent of its enzyme activity and requires the presence of N-terminal peptides .", "target_text": { "I-factor": "protein", "I-factor /nm23 protein": "protein", "M1 cells": "cell_line", "nm23/NDP kinase protein": "protein" } }, { "input_text": "Lipopolysaccharide -induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein .", "target_text": { "E-selectin": "protein", "bactericidal/permeability-increasing protein": "protein" } }, { "input_text": "Endothelial cells stimulated by LPS express E-selectin , which plays an important role in mediating neutrophil adhesion during inflammation .", "target_text": { "Endothelial cells": "cell_type", "E-selectin": "protein", "neutrophil": "cell_type" } }, { "input_text": "E-selectin is induced within 1-2 h , peaks at 4-6 h , and gradually returns to basal level by 24 h .", "target_text": { "E-selectin": "protein" } }, { "input_text": "rBPI21 , a recombinant N-terminal fragment of human bactericidal/permeability-increasing protein ( BPI ) , inhibited LPS -induced E-selectin expression when added at the same time as , and up to 6 h after , LPS .", "target_text": { "rBPI21": "protein", "recombinant N-terminal fragment": "protein", "human bactericidal/permeability-increasing protein": "protein", "BPI": "protein", "E-selectin": "protein" } }, { "input_text": "Delayed administration of rBPI21 also affected LPS -mediated activation of the nuclear factor , NF-kappa B .", "target_text": { "rBPI21": "protein", "nuclear factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "Two to 4 h following LPS addition to endothelial cells , when NF-kappa B was already activated , addition of rBPI21 resulted in marked reduction of NF-kappa B detectable at 4 or 6 h .", "target_text": { "endothelial cells": "cell_type", "NF-kappa B": "protein", "rBPI21": "protein" } }, { "input_text": "These results indicate that endothelial activation requires continuous presence of LPS , and rBPI21 acts to reverse LPS -mediated endothelial activation by interrupting the on-going LPS signal .", "target_text": { "rBPI21": "protein" } }, { "input_text": "GM-CSF and IL-2 share common control mechanisms in response to costimulatory signals in T cells .", "target_text": { "GM-CSF": "protein", "IL-2": "protein", "T cells": "cell_type" } }, { "input_text": "Antigen complexed with major histocompatibility complex class I or II molecules on the surface of antigen presenting cells interacts with the T cell receptor ( TCR ) on the surface of T cells and initiates an activation cascade .", "target_text": { "antigen presenting cells": "cell_type", "T cell receptor": "protein", "TCR": "protein", "T cells": "cell_type" } }, { "input_text": "So called costimulatory signals , mediated by other cell surface interactions or soluble cytokines produced by antigen presenting cells , are also required for complete T cell activation .", "target_text": { "soluble cytokines": "protein", "antigen presenting cells": "cell_type" } }, { "input_text": "High levels of cytokine gene expression in T cells also required both TCR and costimulatory signals .", "target_text": { "cytokine": "protein", "T cells": "cell_type", "TCR": "protein" } }, { "input_text": "The granulocyte-macrophage colony-stimulating factor requires sequences in the promoter as well as a powerful enhancer located 3kb upstream to respond to TCR -like signals .", "target_text": { "granulocyte-macrophage colony-stimulating factor": "protein", "promoter": "DNA", "enhancer": "DNA", "TCR": "protein" } }, { "input_text": "These promoter and enhancer regions are mainly activated by the transcription factor nuclear factor of activated T cells ( NFAT ) .", "target_text": { "promoter and enhancer regions": "DNA", "transcription factor": "protein", "nuclear factor": "protein", "T cells": "cell_type", "transcription factor nuclear factor of activated T cells": "protein", "NFAT": "protein" } }, { "input_text": "The activation of NFAT by TCR signals has been well described for interleukin-2 ( IL-2 ) and IL-4 gene transcription in T cells .", "target_text": { "NFAT": "protein", "TCR": "protein", "IL-2": "protein", "T cells": "cell_type" } }, { "input_text": "Costimulatory signals , such as activation of the CD28 cell surface molecule on T cells , lead to activation through a distinct region of the granulocyte-macrophage colony-stimulating factor ( GM-CSF ) promoter .", "target_text": { "CD28 cell surface molecule": "protein", "T cells": "cell_type", "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "granulocyte-macrophage colony-stimulating factor ( GM-CSF ) promoter": "DNA" } }, { "input_text": "This region is termed the CK-1 or CD28RE and appears to bind specific members of the NF-kappa B family of transcription factors .", "target_text": { "CK-1": "DNA", "CD28RE": "DNA", "NF-kappa B": "protein", "NF-kappa B family": "protein", "transcription factors": "protein" } }, { "input_text": "Human T leukemia virus type 1 ( HTLV-1 ) infects T cells and can lead to increase GM-CSF expression .", "target_text": { "T cells": "cell_type", "GM-CSF": "protein" } }, { "input_text": "We have found that the HTLV-1 transactivator protein , tax , acts as a costimulatory signal for GM-CSF and IL-2 gene transcription , in that it can cooperate with TCR signals to mediate high level gene expression .", "target_text": { "HTLV-1 transactivator protein": "protein", "tax": "protein", "TCR": "protein" } }, { "input_text": "Tax activates the GM-CSF promoter through the CK-1 /CD28RE region and also activates nuclear factor-kappa B binding to this region .", "target_text": { "GM-CSF": "protein", "GM-CSF promoter": "DNA", "CK-1": "DNA", "/CD28RE": "DNA", "nuclear factor-kappa B": "protein" } }, { "input_text": "However , other transcription factors or coactivators of NF-kappa B are required for tax activation but these remain to be identified .", "target_text": { "transcription factors": "protein", "NF-kappa B": "protein", "tax": "protein" } }, { "input_text": "The CK-1 /CD28RE of GM-CSF shows a high degree of similarity to the IL-2 CD28RE and the IL-3 gene also contains a related region .", "target_text": { "CK-1": "DNA", "/CD28RE": "DNA", "GM-CSF": "protein", "IL-2": "protein", "CD28RE": "DNA", "IL-3 gene": "DNA" } }, { "input_text": "This observation , together with the fact that both GM-CSF and IL-2 respond to TCR signals via NFAT , implies a high degree of conservation in the regulation of cytokine gene expression in T cells .", "target_text": { "GM-CSF": "protein", "IL-2": "protein", "TCR": "protein", "NFAT": "protein", "cytokine": "protein", "T cells": "cell_type" } }, { "input_text": "Danazol decreases transcription of estrogen receptor gene in human monocytes .", "target_text": { "estrogen receptor": "protein", "estrogen receptor gene": "DNA", "human monocytes": "cell_type" } }, { "input_text": "1. Administration of danazol for over one month reduced the levels of estrogen receptor ( ER ) and its mRNA to approximately 50 and 20 % , respectively in monocytes .", "target_text": { "estrogen receptor": "protein", "ER": "protein", "mRNA": "RNA", "monocytes": "cell_type" } }, { "input_text": "2. Danazol did not alter the degradation rate of ER mRNA in monocytes .", "target_text": { "ER": "protein", "ER mRNA": "RNA", "monocytes": "cell_type" } }, { "input_text": "3. Danazol decreased the transcription rate of ER gene to approximately 50 % in monocytes in a run-on assay .", "target_text": { "ER": "protein", "ER gene": "DNA", "monocytes": "cell_type" } }, { "input_text": "4. Danazol may release estrogen predominance via the reduction of transcription for ER gene , which leads to the reduction of ER mRNA and ER expressions in monocytes .", "target_text": { "ER": "protein", "ER gene": "DNA", "ER mRNA": "RNA", "monocytes": "cell_type" } }, { "input_text": "Functional characterization of novel IL-2 transcriptional inhibitors .", "target_text": { "IL-2": "protein" } }, { "input_text": "IL-2 -mediated T cell proliferation is a critical early event in the inflammatory process .", "target_text": { "IL-2": "protein", "T cell": "cell_type" } }, { "input_text": "Formation of the NFAT -1 transcriptional complex on the IL-2 promoter is essential for IL-2 transcription .", "target_text": { "NFAT": "protein", "NFAT -1 transcriptional complex": "protein", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Using a cell line that is stably transfected with a trimer of the NFAT -1 regulatory element linked to a lac-Z reporter gene , we screened for inhibitors of NFAT -1-mediated beta-galactosidase activity .", "target_text": { "NFAT": "protein", "NFAT -1 regulatory element": "DNA", "lac-Z reporter gene": "DNA", "beta-galactosidase": "protein" } }, { "input_text": "WIN 61058 and WIN 53071 were identified as microM inhibitors .", "target_text": {} }, { "input_text": "These compounds also inhibited beta-galactosidase mRNA levels .", "target_text": { "beta-galactosidase": "protein", "beta-galactosidase mRNA": "RNA" } }, { "input_text": "Similar inhibition of NFAT -1-mediated gene expression was observed in a second cell line , which is stably transfected with NFAT -1 regulatory elements linked to the reporter gene for sCD8 .", "target_text": { "NFAT": "protein", "cell line": "cell_line", "NFAT -1 regulatory elements": "DNA", "reporter gene for sCD8": "DNA" } }, { "input_text": "At 10 microM , both compounds inhibited IL-2 mRNA and protein levels in the NFAT -1-linked lac-Z transfectants , and in human lymphocytes .", "target_text": { "NFAT": "protein", "NFAT -1-linked lac-Z transfectants": "cell_line", "human lymphocytes": "cell_type" } }, { "input_text": "Both compounds inhibited the mixed lymphocyte reaction , and this inhibition was reversed by exogenous IL-2 .", "target_text": { "IL-2": "protein" } }, { "input_text": "WIN 53071 inhibited IL-2 production induced in the calcium-dependent PMA and ionomycin pathway .", "target_text": { "IL-2": "protein" } }, { "input_text": "Conversely , calcium-independent anti-CD28 Ab and PMA-induced IL-2 production was resistant .", "target_text": { "calcium-independent anti-CD28 Ab": "protein", "IL-2": "protein" } }, { "input_text": "Both compounds altered the NFAT -1 transcriptional complex , causing its retarded mobility on gels .", "target_text": { "NFAT": "protein", "NFAT -1 transcriptional complex": "protein" } }, { "input_text": "By these functional criteria , we believe we have identified two structurally distinct , novel inhibitors of NFAT -1-mediated transcription .", "target_text": { "NFAT": "protein" } }, { "input_text": "Transcriptional regulation of the vacuolar H(+)-ATPase B2 subunit gene in differentiating THP-1 cells .", "target_text": { "vacuolar H(+)-ATPase B2 subunit": "protein", "vacuolar H(+)-ATPase B2 subunit gene": "DNA", "differentiating THP-1 cells": "cell_line" } }, { "input_text": "Monocyte-macrophage differentiation was used as a model system for studying gene regulation of the human vacuolar H(+)-ATPase ( V-ATPase ) .", "target_text": { "human vacuolar H(+)-ATPase": "protein", "V-ATPase": "protein" } }, { "input_text": "We examined mRNA levels of various V-ATPase subunits during differentiation of both native monocytes and the cell line THP-1 , and found that transcriptional and post-transcriptional mechanisms could account for increases in cell V-ATPase content .", "target_text": { "mRNA": "RNA", "V-ATPase": "protein", "native monocytes": "cell_type", "cell line": "cell_line", "THP-1": "cell_line" } }, { "input_text": "From nuclear runoff experiments , we found that one subunit in particular , the B2 isoform ( Mr = 56,000 ) , was amplified primarily by transcriptional means .", "target_text": { "B2 isoform": "protein" } }, { "input_text": "We have begun to examine the structure of the B2 subunit promoter region .", "target_text": { "B2 subunit": "protein", "promoter region": "DNA", "B2 subunit promoter region": "DNA" } }, { "input_text": "Isolation and sequencing of the first exon and 5'-flanking region of this gene reveal a TATA-less promoter with a high G + C content .", "target_text": { "first exon": "DNA", "5'-flanking region": "DNA", "TATA-less promoter": "DNA" } }, { "input_text": "Primer extension and ribonuclease protection analyses indicate a single major transcriptional start site .", "target_text": { "ribonuclease": "protein", "major transcriptional start site": "DNA" } }, { "input_text": "We transfected promoter-luciferase reporter plasmids into THP-1 cells to define sequences that mediate transcriptional control during monocyte differentiation .", "target_text": { "promoter-luciferase reporter plasmids": "DNA", "THP-1 cells": "cell_line" } }, { "input_text": "We found that sequences downstream from the transcriptional start site were sufficient to confer increased expression during THP-1 differentiation .", "target_text": { "THP-1": "cell_line" } }, { "input_text": "DNase I footprinting and sequence analysis revealed the existence of multiple AP2 and Sp1 binding sites in the 5'-untranslated and proximal coding regions .", "target_text": { "DNase I": "protein" } }, { "input_text": "Synergy between signal transduction pathways is obligatory for expression of c-fos in B and T cell lines : implication for c-fos control via surface immunoglobulin and T cell antigen receptors .", "target_text": { "c-fos": "DNA", "surface immunoglobulin": "protein", "T cell antigen receptors": "protein" } }, { "input_text": "Expression of the protooncogene c-fos is controlled by three main regulatory pathways involving kinase C , cAMP , and calcium .", "target_text": { "c-fos": "DNA", "protooncogene c-fos": "DNA", "kinase C": "protein" } }, { "input_text": "Kinase C mediates its effects via phosphorylation of serum response factor ( SRF ) which interacts with the serum response element ( SRE ) ; cAMP and calcium mediate their effects via phosphorylation of CREB ( cAMP regulatory element binding protein ) presumably by activation of a protein kinase A or calmodulin-regulated kinase .", "target_text": { "Kinase C": "protein", "serum response factor": "protein", "SRF": "protein", "serum response element": "DNA", "SRE": "DNA", "CREB": "protein", "cAMP regulatory element binding protein": "protein", "protein kinase A": "protein", "calmodulin-regulated kinase": "protein" } }, { "input_text": "We have examined the function of these elements in Burkitt 's lymphoma cells ( Ramos and Daudi ) as well as a T lymphocytic cell line ( Jurkat ) .", "target_text": { "Burkitt 's lymphoma cells": "cell_line", "Ramos": "cell_line", "Daudi": "cell_line", "T lymphocytic cell line": "cell_line", "Jurkat": "cell_line" } }, { "input_text": "We have found that stimulation of any one of these pathways alone has little or no effect on c-fos induction .", "target_text": { "c-fos": "DNA" } }, { "input_text": "However , kinase C activation ( PMA stimulation ) combined with either cAMP ( forskolin plus MIX ) or calcium stimulation ( ionophore ) leads to greatly enhanced c-fos induction .", "target_text": { "kinase C": "protein", "c-fos": "DNA" } }, { "input_text": "By contrast , cAMP in the presence of calcium shows no synergy in c-fos induction .", "target_text": { "c-fos": "DNA" } }, { "input_text": "Okadaic acid augments PMA- as well as calcium- mediated activation of c-fos , and has little or no effect when combined with cAMP .", "target_text": { "c-fos": "DNA" } }, { "input_text": "The main difference between Ramos ( B cells ) and Jurkat ( T cells ) in the regulation of c-fos is that cAMP plus calcium is strongly synergistic in Jurkat and is without effect in Ramos .", "target_text": { "Ramos": "cell_line", "B cells": "cell_type", "Jurkat": "cell_line", "T cells": "cell_type", "c-fos": "DNA" } }, { "input_text": "Analysis of AP-1 activity using gel mobility shift assays confirms that the requirements for synergy in c-fos mRNA induction are paralleled by requirements for synergy in induction of AP-1 activity .", "target_text": { "AP-1": "protein", "c-fos": "DNA", "c-fos mRNA": "RNA" } }, { "input_text": "Signaling in B cells due to anti-Ig stimulation involves both kinase C activation and release of intracellular calcium , and results in c-fos mRNA induction .", "target_text": { "B cells": "cell_type", "anti-Ig": "protein", "kinase C": "protein", "c-fos": "DNA", "c-fos mRNA": "RNA" } }, { "input_text": "Our results indicate that synergy between the kinase C activation and calcium is needed for efficient c-fos induction since neither of these two alone induces c-fos well .", "target_text": { "kinase C": "protein", "c-fos": "DNA" } }, { "input_text": "That synergy of signaling pathways is relevant for the anti-Ig induction of c-fos is supported by the fact that cAMP -inducing agents and okadaic acid further enhance anti-Ig induction of c-fos .", "target_text": { "anti-Ig": "protein", "c-fos": "DNA" } }, { "input_text": "These results suggest that cell-specific patterns of synergy are an essential feature for c-fos induction and may be relevant for c-fos control through B and T cell antigen receptors .", "target_text": { "c-fos": "DNA" } }, { "input_text": "Multiple signals are required for function of the human granulocyte-macrophage colony-stimulating factor gene promoter in T cells .", "target_text": { "human granulocyte-macrophage colony-stimulating factor": "protein", "human granulocyte-macrophage colony-stimulating factor gene promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "The human granulocyte-macrophage CSF ( GM-CSF ) gene is expressed in T cells in response to TCR activation that can be mimicked by treatment of the cells with PMA and Ca2+ ionophore .", "target_text": { "human granulocyte-macrophage CSF": "protein", "GM-CSF": "protein", "human granulocyte-macrophage CSF ( GM-CSF ) gene": "DNA", "T cells": "cell_type", "TCR": "protein" } }, { "input_text": "The gene contains a proximal functional promoter region ( -620 to +34 ) , as well as a powerful enhancer located 3 kb upstream , both of which are involved in the response of the gene to TCR activation .", "target_text": { "proximal functional promoter region": "DNA", "-620 to +34": "DNA", "enhancer": "DNA", "TCR": "protein" } }, { "input_text": "The proximal promoter contains a region termed CLEO ( -54 to -31 ) that consists of a purine -rich element abutting an activator protein-1 ( AP-1 ) -like site , as well as an upstream nuclear factor-kappa B ( NF-kappa B ) site ( -85 to -76 ) and a CK-1 element ( -101 to -92 ) .", "target_text": { "proximal promoter": "DNA", "CLEO": "DNA", "-54 to -31": "DNA", "purine -rich element": "DNA", "activator protein-1": "protein", "AP-1": "protein", "activator protein-1 ( AP-1 ) -like site": "DNA", "nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "upstream nuclear factor-kappa B ( NF-kappa B ) site": "DNA", "-85 to -76": "DNA", "CK-1 element": "DNA", "-101 to -92": "DNA" } }, { "input_text": "We show in this work that mutations in either the purine -rich region of the CLEO element or the NF-kappa B site result in reduced PMA / Ca2+ activation of a 620-bp human GM-CSF promoter- luciferase reporter construct in Jurkat T cells by 65 % and 50 % , respectively .", "target_text": { "purine -rich region": "DNA", "CLEO": "DNA", "CLEO element": "DNA", "NF-kappa B": "protein", "NF-kappa B site": "DNA", "GM-CSF": "protein", "luciferase": "protein", "620-bp human GM-CSF promoter- luciferase reporter construct": "DNA", "T cells": "cell_type", "Jurkat T cells": "cell_line" } }, { "input_text": "The major inducible protein complex that binds to the human CLEO ( hCLEO ) element is an AP-1 -like complex that is inducible by PMA alone , but shows increased binding in response to PMA together with Ca2+ ionophore .", "target_text": { "inducible protein complex": "protein", "CLEO": "DNA", "hCLEO": "DNA", "human CLEO ( hCLEO ) element": "DNA", "AP-1": "protein", "AP-1 -like complex": "protein" } }, { "input_text": "Although the binding of this complex is not cyclosporin -sensitive , promoter induction is inhibited by cyclosporin treatment .", "target_text": {} }, { "input_text": "A second weak inducible complex resembling nuclear factor of activated T cells ( NF-AT ) was also observed binding to the hCLEO region .", "target_text": { "nuclear factor of activated T cells": "protein", "NF-AT": "protein", "hCLEO": "DNA", "hCLEO region": "DNA" } }, { "input_text": "By using recombinant proteins , we confirmed that AP-1 , NF-ATp , and a higher order NF-ATp / AP-1 complex could all form with the hCLEO element , and we have also defined the sequence requirements for binding of each of these complexes .", "target_text": { "recombinant proteins": "protein", "AP-1": "protein", "NF-ATp": "protein", "NF-ATp / AP-1 complex": "protein", "hCLEO": "DNA", "hCLEO element": "DNA" } }, { "input_text": "We found that expression of a constitutively active form of calcineurin could substitute for Ca2+ ionophore and synergize with PMA to activate the GM-CSF promoter , and conversely that mutant-activated Ras could substitute for PMA and cooperate with Ca2+ ionophore .", "target_text": { "calcineurin": "protein", "GM-CSF": "protein", "GM-CSF promoter": "DNA", "mutant-activated Ras": "protein" } }, { "input_text": "Co-expression of Ras and calcineurin , however , did not activate the GM-CSF promoter , but required the additional expression of NF-kappa B p65 .", "target_text": { "Ras": "protein", "calcineurin": "protein", "GM-CSF": "protein", "GM-CSF promoter": "DNA", "NF-kappa B": "protein", "NF-kappa B p65": "protein" } }, { "input_text": "These results imply that at least three signals are required to activate the GM-CSF proximal promoter , and that the signals impinge on distinct transcription factors that bind to the hCLEO and NF-kappa B regions of the promoter .", "target_text": { "GM-CSF": "protein", "proximal promoter": "DNA", "GM-CSF proximal promoter": "DNA", "transcription factors": "protein", "hCLEO": "DNA", "NF-kappa B": "protein", "NF-kappa B regions": "DNA", "hCLEO and NF-kappa B regions": "DNA", "promoter": "DNA" } }, { "input_text": "IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes .", "target_text": { "tyk2": "protein", "Jak1": "protein", "STAT1 alpha": "protein", "STAT3 complexes": "protein", "human T cells": "cell_type", "monocytes": "cell_type" } }, { "input_text": "IL-10 affects monocytes and T cells by driving the progression of immune responsiveness such that Th2 lymphocyte-mediated effects predominate .", "target_text": { "IL-10": "protein", "monocytes": "cell_type", "T cells": "cell_type" } }, { "input_text": "In this report , we show that in monocytes and T cells IL-10 stimulates tyrosine phosphorylation of the signal transducers and activators of transcription , STAT1 alpha and STAT3 , in a differential manner such that the relative formation of homo- and hetero dimers varies between the two cell types .", "target_text": { "monocytes": "cell_type", "T cells": "cell_type", "IL-10": "protein", "signal transducers": "protein", "activators of transcription": "protein", "STAT1 alpha": "protein", "STAT3": "protein" } }, { "input_text": "Moreover , monocytes express a novel IL-10 -stimulated STAT protein with an M(r) of 70 kDa that is recognized by the anti- STAT3 Ab but is not observed in T cells .", "target_text": { "monocytes": "cell_type", "IL-10": "protein", "IL-10 -stimulated STAT protein": "protein", "70 kDa": "protein", "STAT3": "protein", "anti- STAT3 Ab": "protein", "T cells": "cell_type" } }, { "input_text": "IL-10 treatment of both T cells and monocytes results in the ligand-induced tyrosine phosphorylation of tyk2 and Jak1 , but not Jak2 or Jak3 .", "target_text": { "IL-10": "protein", "T cells": "cell_type", "monocytes": "cell_type", "tyk2": "protein", "Jak1": "protein", "Jak2": "protein", "Jak3": "protein" } }, { "input_text": "Selective modulation of immune responsiveness by IL-10 in cells such as monocytes and T cells may result in part from the differential activation of STAT protein pairs .", "target_text": { "IL-10": "protein", "monocytes": "cell_type", "T cells": "cell_type", "STAT protein pairs": "protein" } }, { "input_text": "Use of new biologic markers in the ovulation induction .", "target_text": {} }, { "input_text": "Biological markers of ovulation , after a great in the past , have been fallen into disuse for the large diffusion of biochemical and biophysical ones .", "target_text": {} }, { "input_text": "However , the real effect of hormones involved in ovulation is expressed by biological modifications on target tissues .", "target_text": { "target tissues": "cell_type" } }, { "input_text": "To explore the modifications of not reproductive target tissues as ovulation markers we studied the behaviour of Albuminemia , Platelet Factor IV ( as indicator of Platelet Aggregation ) , Type II estrogenic receptors in 42 ovulation induced women , undergoing our observation .", "target_text": { "Platelet Factor IV": "protein", "Type II estrogenic receptors": "protein" } }, { "input_text": "33 of them had ovulation and 9 developed a LUF syndrome , constituting two biological models of an opposite situation for the three markers observed .", "target_text": {} }, { "input_text": "All the markers considered were sufficiently sensitive , but among them , Platelet Factor IV was the most reliable to the hormonal ovulatory situation .", "target_text": { "Platelet Factor IV": "protein" } }, { "input_text": "Abnormal regulation of the IL-2 promoter in lpr CD4-CD8- T lymphocytes results in constitutive expression of a novel nuclear factor of activated T cells -binding factor .", "target_text": { "IL-2": "protein", "IL-2 promoter": "DNA", "CD4-CD8- T lymphocytes": "cell_line", "T cells": "cell_type", "nuclear factor of activated T cells": "protein", "novel nuclear factor of activated T cells -binding factor": "protein" } }, { "input_text": "The inert quality of MRL-Ipr/Ipr ( Ipr ) peripheral CD4-CD8- ( CD4-8- ) T cells manifests primarily as an inability to proliferate or produce IL-2 in response to TCR or mitogenic stimulation .", "target_text": { "T cells": "cell_type", "MRL-Ipr/Ipr ( Ipr ) peripheral CD4-CD8- ( CD4-8- ) T cells": "cell_line", "IL-2": "protein", "TCR": "protein" } }, { "input_text": "Yet these same cells do initiate early TCR -mediated signaling events , such as generation of inositol phosphates and increased intracellular calcium .", "target_text": { "TCR": "protein" } }, { "input_text": "They also display constitutively high levels of p59fyn and CD3 zeta tyrosine phosphorylation .", "target_text": { "p59fyn": "protein", "CD3 zeta": "protein" } }, { "input_text": "The generation of second messengers in T cells normally leads to downstream signaling that results in transcriptional activation of the IL-2 gene .", "target_text": { "T cells": "cell_type", "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "We , therefore , compared the activation state of the IL-2 gene promoter region in freshly isolated and stimulated Ipr CD4-8- T cells with that of normal T lymphocytes .", "target_text": { "IL-2": "protein", "IL-2 gene promoter region": "DNA", "T cells": "cell_type", "Ipr CD4-8- T cells": "cell_line", "normal T lymphocytes": "cell_type" } }, { "input_text": "Levels of the octamer , NF-kappa B ( p50-p65 heterodimer ) , and AP-1 transcriptional factors are constitutively elevated in freshly isolated Ipr CD4-8- T cells , consistent with the activated phenotype of these cells .", "target_text": { "NF-kappa B": "protein", "p50-p65 heterodimer": "protein", "AP-1": "protein", "AP-1 transcriptional factors": "protein", "T cells": "cell_type", "Ipr CD4-8- T cells": "cell_line" } }, { "input_text": "Upon stimulation with mitogens , formation of the transactivating complex , nuclear factor of activated T cells ( NF-AT ) , occurs with normal kinetics in Ipr CD4-8- T cells .", "target_text": { "T cells": "cell_type", "nuclear factor of activated T cells": "protein", "NF-AT": "protein", "Ipr CD4-8- T cells": "cell_line" } }, { "input_text": "Yet , the levels of the activating NF-AT complex never reach those observed in similarly stimulated normal T cells .", "target_text": { "NF-AT complex": "protein", "T cells": "cell_type" } }, { "input_text": "Furthermore , nuclear extracts from Ipr CD4-8- T cells display high levels of a novel specific binding activity at the NF-AT site , which is present at much lower levels in freshly isolated normal T lymphocytes .", "target_text": { "T cells": "cell_type", "Ipr CD4-8- T cells": "cell_line", "NF-AT": "protein", "NF-AT site": "DNA", "normal T lymphocytes": "cell_type" } }, { "input_text": "Upon mitogenic stimulation , the binding activity of the novel NF-AT -binding factor is rapidly down-regulated in normal T cells , but persists at high levels in Ipr CD4-8- T cells .", "target_text": { "NF-AT": "protein", "NF-AT -binding factor": "protein", "T cells": "cell_type", "Ipr CD4-8- T cells": "cell_line" } }, { "input_text": "These two abnormalities at the NF-AT site provide a potential mechanism to account for the defect in IL-2 production from Ipr CD4-8- T cells .", "target_text": { "NF-AT": "protein", "NF-AT site": "DNA", "IL-2": "protein", "T cells": "cell_type", "Ipr CD4-8- T cells": "cell_line" } }, { "input_text": "Cross-linking of CD30 induces HIV expression in chronically infected T cells .", "target_text": { "CD30": "protein", "T cells": "cell_type" } }, { "input_text": "CD30 , a member of the tumor necrosis factor ( TNF ) receptor family , is expressed constitutively on the surface of the human T cell line ACH-2 , which is chronically infected with human immunodeficiency virus type-1 ( HIV ) -1 .", "target_text": { "CD30": "protein" } }, { "input_text": "We demonstrate that cross-linking CD30 with an anti- CD30 -specific monoclonal antibody , which mimics the described biological activities of the CD30 ligand ( CD30L ) , results in HIV expression .", "target_text": { "CD30": "protein", "CD30 ligand": "protein", "CD30L": "protein" } }, { "input_text": "CD30 cross-linking does not alter proliferation of ACH-2 cells and the induction of HIV expression is not mediated by endogenous TNF alpha/beta .", "target_text": { "CD30": "protein", "ACH-2 cells": "cell_line", "TNF alpha/beta": "protein" } }, { "input_text": "Furthermore , cross-linking of CD30 leads to NF-kappa B activation and enhanced HIV transcription .", "target_text": { "CD30": "protein", "NF-kappa B": "protein" } }, { "input_text": "Thus , CD30 -CD30L interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of TNF .", "target_text": { "CD30": "protein", "-CD30L": "protein", "TNF": "protein" } }, { "input_text": "This mechanism may be important in the activation of HIV expression from latently infected CD4+ T cells , especially in lymphoid organs where cell to cell contact is conducive to receptor-ligand interactions .", "target_text": { "T cells": "cell_type", "CD4+ T cells": "cell_line" } }, { "input_text": "Human MHC class II gene transcription directed by the carboxyl terminus of CIITA , one of the defective genes in type II MHC combined immune deficiency .", "target_text": { "MHC class II gene": "DNA", "carboxyl terminus": "protein", "CIITA": "DNA", "defective genes": "DNA", "MHC": "protein" } }, { "input_text": "Type II major histocompatibility complex combined immune deficiency ( type II MHC CID or bare lymphocyte syndrome ) is a congenital immunodeficiency disease characterized by absent MHC class II expression .", "target_text": { "Type II major histocompatibility complex": "protein", "MHC": "protein", "MHC class II": "protein" } }, { "input_text": "Four distinct complementation groups have been identified .", "target_text": {} }, { "input_text": "Recently , the defective gene in group II type II MHC CID has been isolated and termed CIITA .", "target_text": { "defective gene": "DNA", "MHC": "protein", "CIITA": "DNA" } }, { "input_text": "Here , we demonstrate that CIITA is an MHC class II gene-specific transcription activator .", "target_text": { "CIITA": "DNA", "MHC class II": "protein", "MHC class II gene-specific transcription activator": "DNA" } }, { "input_text": "The transcription activation function is provided by the N-terminal acidic domain ( amino acids 26-137 ) , which is experimentally exchangeable with a heterologous viral transcription-activating domain .", "target_text": { "N-terminal acidic domain": "protein", "amino acids 26-137": "protein", "heterologous viral transcription-activating domain": "protein" } }, { "input_text": "The specificity of CIITA for three major MHC class II genes , DR , DQ and DP , is mediated by its remaining C-terminal residues ( amino acids 317-1130 ) .", "target_text": { "CIITA": "protein", "MHC class II": "protein", "MHC class II genes": "DNA", "DR": "DNA", "DQ": "DNA", "DP": "DNA", "C-terminal residues": "protein", "amino acids 317-1130": "protein" } }, { "input_text": "The transactivation of multiple cis elements , especially S and X2 , of the DR alpha proximal promoter in group II CID cells is CIITA dependent .", "target_text": { "multiple cis elements": "DNA", "S": "DNA", "X2": "DNA", "proximal promoter": "DNA", "DR alpha proximal promoter": "DNA", "group II CID cells": "cell_line", "CIITA": "protein" } }, { "input_text": "Since CIITA overexpression in normal cells did not increase class II expression , we propose that initiation of CIITA expression serves as the on-off switch , while availability of downstream interactor ( s ) limits transcription .", "target_text": { "CIITA": "protein", "normal cells": "cell_type" } }, { "input_text": "Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion .", "target_text": { "P-selectin": "protein", "monocyte chemotactic protein-1": "protein", "tumor necrosis factor-alpha": "protein" } }, { "input_text": "Signal integration and NF-kappa B translocation [ see comments ]", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Adhesion molecules that tether circulating leukocytes to endothelial cells may also transduce or modulate outside-in signals for cellular activation , providing an initial regulatory point in the inflammatory response .", "target_text": { "Adhesion molecules": "protein", "circulating leukocytes": "cell_type", "endothelial cells": "cell_type" } }, { "input_text": "Adhesion of human monocytes to P-selectin , the most rapidly expressed endothelial tethering factor , increased the secretion of monocyte chemotactic protein-1 ( MCP-1 ) and tumor necrosis factor-alpha ( TNF-alpha ) by the leukocytes when they were stimulated with platelet-activating factor .", "target_text": { "monocytes": "cell_type", "human monocytes": "cell_type", "P-selectin": "protein", "endothelial tethering factor": "protein", "monocyte chemotactic protein-1": "protein", "MCP-1": "protein", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "leukocytes": "cell_type", "platelet-activating factor": "protein" } }, { "input_text": "Increased cytokine secretion was specifically inhibited by G1 , an anti- P-selectin mAb that prevents P-selectin from binding to its ligand ( P-selectin glycoprotein ligand-1 ) on myeloid cells .", "target_text": { "G1": "protein", "P-selectin": "protein", "anti- P-selectin mAb": "protein", "P-selectin glycoprotein ligand-1": "protein", "myeloid cells": "cell_type" } }, { "input_text": "Moreover , tethering by P-selectin specifically enhanced nuclear translocation of nuclear factor-kappa B ( NF-kappa B ) , a transcription factor required for expression of MCP-1 , TNF-alpha , and other immediate-early genes .", "target_text": { "P-selectin": "protein", "nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "transcription factor": "protein", "MCP-1": "protein", "TNF-alpha": "protein", "immediate-early genes": "DNA" } }, { "input_text": "These results demonstrate that P-selectin , through its ligands on monocytes , may locally regulate cytokine secretion in inflamed tissues .", "target_text": { "P-selectin": "protein", "monocytes": "cell_type", "cytokine": "protein" } }, { "input_text": "Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer .", "target_text": { "in vivo footprinted DNA motifs": "DNA", "alpha-globin enhancer": "DNA" } }, { "input_text": "Erythroid lineage and developmental stage specificities .", "target_text": {} }, { "input_text": "Transcriptional regulation of the human alpha-like globin genes , embryonic zeta 2 and adult alpha , during erythroid development is mediated by a distal enhancer , HS-40 .", "target_text": { "human alpha-like globin genes": "DNA", "embryonic zeta 2": "DNA", "adult alpha": "DNA", "distal enhancer": "DNA", "HS-40": "DNA" } }, { "input_text": "Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage- specific manner .", "target_text": { "HS-40": "DNA", "nuclear factor binding motifs": "DNA" } }, { "input_text": "We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures .", "target_text": { "factor binding motifs": "DNA", "HS-40": "DNA", "erythroid cell cultures": "cell_line" } }, { "input_text": "Three of these HS-40 enhancer motifs , 5'NF-E2/AP1 , GT II , and GATA-1(c) , positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha -globin promoter activity in adult erythroid MEL cells .", "target_text": { "HS-40": "DNA", "HS-40 enhancer motifs": "DNA", "5'NF-E2/AP1": "DNA", "GT II": "DNA", "GATA-1(c)": "DNA", "zeta 2-globin promoter": "DNA", "embryonic/fetal erythroid K562 cells": "cell_line", "adult alpha": "DNA", "adult alpha -globin promoter": "DNA", "adult erythroid MEL cells": "cell_line" } }, { "input_text": "On the other hand , the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells , and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor .", "target_text": { "3'NF-E2/AP1 motif": "DNA", "zeta 2-globin promoter": "DNA", "K562 cells": "cell_line", "ubiquitous AP1 factors": "protein", "erythroid-enriched NF-E2 factor": "protein" } }, { "input_text": "Mutation in the GATA-1(d) motif , which exhibits an adult erythroid-specific genomic footprint , decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells .", "target_text": { "GATA-1(d) motif": "DNA", "adult erythroid-specific genomic footprint": "DNA", "HS-40": "DNA", "HS-40 enhancer": "DNA", "dimethyl sulfoxide-induced MEL cells": "cell_line", "K562 cells": "cell_line" } }, { "input_text": "These studies have defined the regulatory roles of the different HS-40 motifs .", "target_text": { "HS-40": "DNA", "HS-40 motifs": "DNA" } }, { "input_text": "The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage- specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo .", "target_text": { "human alpha-like globin promoters": "DNA", "specific nuclear factors": "protein" } }, { "input_text": "Nitric oxide -stimulated guanine nucleotide exchange on p21ras .", "target_text": { "p21ras": "protein" } }, { "input_text": "The protooncogene p21ras , a monomeric G protein family member , plays a critical role in converting extracellular signals into intracellular biochemical events .", "target_text": { "protooncogene p21ras": "DNA", "monomeric G protein family member": "protein" } }, { "input_text": "Here , we report that nitric oxide ( NO ) activates p21ras in human T cells as evidenced by an increase in GTP -bound p21ras .", "target_text": { "p21ras": "DNA", "T cells": "cell_type", "human T cells": "cell_type", "GTP -bound p21ras": "protein" } }, { "input_text": "In vitro studies using pure recombinant p21ras demonstrate that the activation is direct and reversible .", "target_text": { "pure recombinant p21ras": "protein" } }, { "input_text": "Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP /GTP exchange .", "target_text": { "p21ras": "DNA" } }, { "input_text": "The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange .", "target_text": {} }, { "input_text": "Furthermore , we demonstrate that p21ras is essential for NO -induced downstream signaling , such as NF-kappa B activation , and that endogenous NO can activate p21ras in the same cell .", "target_text": { "p21ras": "protein", "NF-kappa B": "protein" } }, { "input_text": "These studies identify p21ras as a target of the same cell .", "target_text": { "p21ras": "DNA" } }, { "input_text": "These studies identify p21ras as a target of NO in T cells and suggest that NO activates p21ras by an action which mimics that of guanine nucleotide exchange factors .", "target_text": { "p21ras": "DNA", "T cells": "cell_type", "guanine nucleotide exchange factors": "protein" } }, { "input_text": "Interleukin-2 promoter activity in Epstein-Barr virus -transformed B lymphocytes is controlled by nuclear factor-chi B .", "target_text": { "Interleukin-2 promoter": "DNA", "Epstein-Barr virus -transformed B lymphocytes": "cell_line", "nuclear factor-chi B": "protein" } }, { "input_text": "The regulation of interleukin ( IL ) -2 gene expression has been investigated mainly in T lymphocytes , the predominant producers of IL-2 .", "target_text": { "interleukin ( IL ) -2 gene": "DNA", "T lymphocytes": "cell_type", "IL-2": "protein" } }, { "input_text": "However , B cells can also synthesize IL-2 .", "target_text": { "B cells": "cell_type", "IL-2": "protein" } }, { "input_text": "In the present study we analyzed the control of IL-2 promoter activity in Epstein-Barr virus ( EBV ) -transformed B cell clones which are capable of secreting IL-2 at a low level after stimulation with phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin .", "target_text": { "IL-2": "protein", "IL-2 promoter": "DNA", "Epstein-Barr virus ( EBV ) -transformed B cell clones": "cell_line" } }, { "input_text": "Transient transfections using reporter constructs with multiples of transcription factor binding sites from the IL-2 promoter [ distal nuclear factor ( NF ) -AT , proximal NF-AT , AP-1/Octamer ( UPS ) or NF-chi B ( TCEd ) sites ] were performed .", "target_text": { "reporter constructs": "DNA", "transcription factor binding sites": "DNA", "IL-2": "protein", "IL-2 promoter": "DNA", "distal nuclear factor ( NF ) -AT": "protein", "proximal NF-AT": "protein", "AP-1/Octamer": "protein", "UPS": "protein", "NF-chi B": "protein", "TCEd": "protein" } }, { "input_text": "In EBV-transformed B clones , the chi B site exerted the strongest inducible activity ; the NF-AT binding sites showed either no or only weak activity compared to Jurkat T cells .", "target_text": { "EBV-transformed B clones": "cell_line", "chi B site": "DNA", "NF-AT binding sites": "DNA", "Jurkat T cells": "cell_line" } }, { "input_text": "An IL-2 promoter bearing a defective NF- chi B site was completely inactive in EBV-transformed B cells , while it still had activity in Jurkat T cells .", "target_text": { "IL-2": "protein", "IL-2 promoter": "DNA", "chi B": "DNA", "NF- chi B": "protein", "NF- chi B site": "DNA", "B cells": "cell_type", "EBV-transformed B cells": "cell_line", "Jurkat T cells": "cell_line" } }, { "input_text": "In seven EBV-B cell clones or lines differing in their capacity to secrete IL-2 , the activity of the IL-2 promoter correlated well with the status of IL-2 secretion .", "target_text": { "EBV-B cell clones": "cell_line", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Similarly , a human immunodeficiency virus promoter , whose activity is controlled through chi B factors , was found to be active in the IL-2 producing EBV- B cells , but inactive in the non- IL-2 -producing cells .", "target_text": { "human immunodeficiency virus promoter": "DNA", "chi B factors": "protein", "IL-2": "protein", "B cells": "cell_type", "IL-2 producing EBV- B cells": "cell_line", "non- IL-2 -producing cells": "cell_line" } }, { "input_text": "Electrophoretic mobility shift assays using protein extracts from EBV- B cells and the IL-2 NF-chi B probe revealed the constitutive generation of chi B complexes in IL-2 -secreting cells consisting mainly of heterodimeric p50/p65 complexes .", "target_text": { "protein extracts": "protein", "B cells": "cell_type", "EBV- B cells": "cell_line", "IL-2": "protein", "NF-chi B": "protein", "chi B complexes": "protein", "IL-2 -secreting cells": "cell_line", "heterodimeric p50/p65 complexes": "protein" } }, { "input_text": "A weaker chi B complex formation and faster-migrating complexes were detected in non- IL-2 -secreting cells .", "target_text": { "chi B": "DNA", "IL-2": "protein", "non- IL-2 -secreting cells": "cell_line" } }, { "input_text": "These results demonstrate that the IL-2 NF-chi B site is indispensable for the activity of the IL-2 promoter in EBV-transformed B cells , whereas other transcription factors appear to be less important for IL-2 expression in these cells .", "target_text": { "IL-2": "protein", "NF-chi B": "protein", "IL-2 NF-chi B site": "DNA", "IL-2 promoter": "DNA", "B cells": "cell_type", "EBV-transformed B cells": "cell_line", "transcription factors": "protein" } }, { "input_text": "Latent membrane protein-1 induces cyclin D2 expression , pRb hyperphosphorylation , and loss of TGF-beta 1 -mediated growth inhibition in EBV-positive B cells .", "target_text": { "Latent membrane protein-1": "protein", "cyclin D2": "protein", "pRb": "protein", "TGF-beta 1": "protein", "B cells": "cell_type", "EBV-positive B cells": "cell_type" } }, { "input_text": "The normal cell cycle is regulated by several molecules , such as the tumor-suppressor protein pRb , the G1 cyclins , the cyclin-dependent kinases , and their inhibitors .", "target_text": { "pRb": "protein", "tumor-suppressor protein pRb": "protein", "G1 cyclins": "protein", "cyclin-dependent kinases": "protein" } }, { "input_text": "These regulators are targeted by negative growth regulatory signals , such as that provided by TGF-beta .", "target_text": { "TGF-beta": "protein" } }, { "input_text": "Here , we show that the presence of either wild-type EBV or its transforming latent membrane protein-1 ( LMP-1 ) results in the loss of TGF-beta 1 -mediated growth inhibition in human B cells .", "target_text": { "transforming latent membrane protein-1": "protein", "LMP-1": "protein", "TGF-beta": "protein", "TGF-beta 1": "protein", "B cells": "cell_type", "human B cells": "cell_type" } }, { "input_text": "Chemical cross-linking with 125I-labeled TGF-beta 1 showed an essentially normal TGF-beta receptor profile in EBV-positive and EBV-negative Burkitt 's lymphoma cell lines , and these receptors were shown to be functional in transducing signals , as evidenced by the TGF-beta 1 -mediated modulation of junB gene expression .", "target_text": { "TGF-beta": "protein", "TGF-beta 1": "protein", "125I-labeled TGF-beta 1": "protein", "TGF-beta receptor": "protein", "junB gene": "DNA" } }, { "input_text": "However , TGF-beta 1 did not induce dephosphorylation of pRb in EBV ( or LMP-1 ) -positive cells as opposed to EBV -negative cells , suggesting a dichotomy in the TGF-beta 1 signaling pathway leading to separable gene regulatory and growth inhibitory responses .", "target_text": { "TGF-beta 1": "protein", "pRb": "protein", "LMP-1": "protein", "EBV ( or LMP-1 ) -positive cells": "cell_line", "EBV -negative cells": "cell_line" } }, { "input_text": "Furthermore , LMP-1 was found to induce the expression of cyclin D2 ; normal B cells or EBV -negative Burkitt 's lymphoma cells do not express D-type cyclins .", "target_text": { "LMP-1": "protein", "cyclin D2": "protein", "B cells": "cell_type", "EBV -negative Burkitt 's lymphoma cells": "cell_line", "D-type cyclins": "protein" } }, { "input_text": "Taken together , these data point to a potential mechanism underlying EBV -mediated B cell transformation whereby constitutive induction of key cell cycle regulators by LMP-1 can lead to pRb hyperphosphorylation and uncontrolled cell proliferation .", "target_text": { "key cell cycle regulators": "protein", "LMP-1": "protein", "pRb": "protein" } }, { "input_text": "Does thyroidectomy , radioactive iodine therapy , or antithyroid drug treatment alter reactivity of patients ' T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases ?", "target_text": { "T cells": "cell_type", "thyrotropin receptor": "protein" } }, { "input_text": "The effect of treatment on thyroid antibody production and T cell reactivity to thyroid antigens was studied in 15 patients with Graves ' disease ( GD ) before and after thyroidectomy , 19 patients with GD before and after radioactive iodine ( RAI ) therapy , and 9 patients maintained euthyroid on antithyroid drugs ( ATD ) .", "target_text": {} }, { "input_text": "Twenty subjects matched for age and sex without known thyroid disease served as controls .", "target_text": {} }, { "input_text": "In GD patients , the responses of peripheral blood mononuclear cells ( PBMC ) and TSH receptor ( TSHR ) -specific T cell lines to recombinant human TSHR extracellular domain , thyroglobulin , and TSHR peptides were examined on the day of surgery or RAI therapy ( day 0 ) and also 6-8 weeks and 3-6 months thereafter .", "target_text": { "peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type", "TSH receptor": "protein", "TSHR": "protein", "TSH receptor ( TSHR ) -specific T cell lines": "cell_line", "recombinant human TSHR extracellular domain": "protein", "thyroglobulin": "protein" } }, { "input_text": "Reactivity to TSHR peptides before surgery was heterogeneous and spanned the entire extracellular domain .", "target_text": { "TSHR": "protein", "extracellular domain": "protein" } }, { "input_text": "Six to 8 weeks after subtotal thyroidectomy , the number of patients ' PBMC responding to any peptide and the average number of recognized peptides decreased .", "target_text": { "PBMC": "cell_type" } }, { "input_text": "A further decrease in the T cell reactivity to TSHR peptides was observed 3-6 months after surgery .", "target_text": { "TSHR": "protein" } }, { "input_text": "The responses of PBMC from Graves ' patients before RAI therapy were less than those in the presurgical group .", "target_text": { "PBMC": "cell_type" } }, { "input_text": "Six to 8 weeks after RAI therapy , the number of patients responding to any peptide and the average number of recognized peptides increased .", "target_text": {} }, { "input_text": "Three to 6 months after RAI , T cell responses to TSHR peptides were less than those 6-8 weeks after RAI therapy , but still higher than the values on day 0 .", "target_text": { "TSHR": "protein" } }, { "input_text": "Responses of PBMC from patients with GD , maintained euthyroid on ATD , were lower than those before surgery or RAI therapy .", "target_text": { "PBMC": "cell_type" } }, { "input_text": "The reactivity of T cell lines in different groups reflected a pattern similar to PBMC after treatment .", "target_text": { "T cell lines": "cell_line", "PBMC": "cell_type" } }, { "input_text": "TSHR antibody and microsomal antibody levels decreased after surgery , but increased after RAI therapy .", "target_text": { "TSHR": "protein", "TSHR antibody": "protein", "microsomal antibody": "protein" } }, { "input_text": "The difference in the number of recognized peptides by patients ' PBMC before RAI and surgery may reflect the effect of long term therapy with ATD in the patients before RAI vs. the shorter period in patients before surgery .", "target_text": { "PBMC": "cell_type" } }, { "input_text": "The decreased T cell reactivity to thyroid antigens after thyroidectomy could be the result of removal of a major part of the thyroid gland or redistribution of suppressor-inducer T cells .", "target_text": { "thyroid antigens": "protein", "T cells": "cell_type" } }, { "input_text": "The increased T cell response after RAI therapy is probably epitope specific , rather than a response to the whole TSHR molecule .", "target_text": { "TSHR": "protein" } }, { "input_text": "Synchronous recognition of peptides 158-176 and 248-263 is important for the development of GD , and the loss of recognition of one of these epitopes may be an early sign of immune remission and a predictor of euthyroidism .", "target_text": { "epitopes": "protein" } }, { "input_text": "Circumvention of tolerance for the nuclear T cell protein TCF-1 by immunization of TCF-1 knock-out mice .", "target_text": { "nuclear T cell protein": "protein", "TCF-1": "protein" } }, { "input_text": "Molecular events that underlie the well-defined phenotypic changes of the differentiating thymocyte are poorly understood .", "target_text": { "differentiating thymocyte": "cell_type" } }, { "input_text": "A candidate gene to control thymocyte differentiation , T cell factor-1 ( TCF-1 ) * encodes a DNA-binding protein .", "target_text": { "thymocyte": "cell_type", "T cell factor-1": "protein", "TCF-1": "protein", "DNA-binding protein": "protein" } }, { "input_text": "Its mRNA expression pattern is complex during embryogenesis , yet restricted to lymphocytes postnatally .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "Expression studies on TCF-1 protein have been hampered by the difficulty to raise antibodies due to extreme evolutionary conservation .", "target_text": { "TCF-1": "protein", "TCF-1 protein": "protein", "antibodies": "protein" } }, { "input_text": "TCF-1 knock-out mice , generated recently in our laboratory , have strongly decreased numbers of thymocytes , but are otherwise normal .", "target_text": { "TCF-1": "protein", "thymocytes": "cell_type" } }, { "input_text": "We have used these mice to generate anti- TCF-1 antibodies .", "target_text": { "TCF-1": "protein", "anti- TCF-1 antibodies": "protein" } }, { "input_text": "By immunization with a recombinant fusion protein , we show that TCF-1 knock-out mice readily yield antiserum titers against human and mouse TCF-1 protein .", "target_text": { "recombinant fusion protein": "protein", "TCF-1": "protein" } }, { "input_text": "Wild-type littermates remain unresponsive to TCF-1 while they mount a high-titer antibody response to the fusion protein , Maltose Binding Protein ( MBP ) .", "target_text": { "TCF-1": "protein", "fusion protein": "protein", "Maltose Binding Protein": "protein", "MBP": "protein" } }, { "input_text": "Subsequently , TCF-1 -specific hybridomas could be prepared from the spleens of immunized knock-out mice .", "target_text": { "TCF-1": "protein", "TCF-1 -specific hybridomas": "cell_line" } }, { "input_text": "This study illustrates the almost complete tolerance of mice for human TCF-1 and demonstrates that this tolerance is readily broken by gene knock-out .", "target_text": { "TCF-1": "protein", "human TCF-1": "protein" } }, { "input_text": "Furthermore , the usefulness of knock-out mice for the generation of monoclonal antibodies against the gene product of interest is underscored .", "target_text": { "monoclonal antibodies": "protein" } }, { "input_text": "The transcription factor , Nm23H2 , binds to and activates the translocated c-myc allele in Burkitt 's lymphoma .", "target_text": { "transcription factor": "protein", "Nm23H2": "protein", "c-myc allele": "DNA" } }, { "input_text": "We have identified an in vivo footprint over the PuF site on the translocated c-myc allele in Burkitt 's lymphoma cells .", "target_text": { "PuF site": "DNA", "c-myc allele": "DNA" } }, { "input_text": "The PuF site on the silent normal c-myc allele was unoccupied .", "target_text": { "PuF site": "DNA", "c-myc allele": "DNA", "silent normal c-myc allele": "DNA" } }, { "input_text": "We demonstrated by electrophoretic mobility shift assay , electrophoretic mobility shift assay with antibody , UV cross-linking followed by SDS-gel electrophoresis , and Western analysis that Nm23H2 in B cell nuclear extracts bound to the c-myc PuF site .", "target_text": { "Nm23H2": "protein", "PuF site": "DNA" } }, { "input_text": "Transfection experiments with c-myc promoter constructs in both DHL-9 and Raji cells revealed that the PuF site functioned as a positive regulatory element in B cells with a drop in activity with mutation of this site .", "target_text": { "c-myc promoter": "DNA", "c-myc promoter constructs": "DNA", "DHL-9": "cell_line", "Raji cells": "cell_line", "PuF site": "DNA", "positive regulatory element": "DNA", "B cells": "cell_type" } }, { "input_text": "Access to this site is blocked in the normal silent c-myc allele ; these data suggest that the Nm23H2 protein is involved in deregulation of the translocated c-myc allele in Burkitt 's lymphoma cells .", "target_text": { "c-myc allele": "DNA", "normal silent c-myc allele": "DNA", "Nm23H2": "protein", "Burkitt 's lymphoma cells": "cell_line" } }, { "input_text": "Identification of two novel regulatory elements within the 5'-untranslated region of the human A gamma-globin gene .", "target_text": { "regulatory elements": "DNA", "5'-untranslated region": "DNA", "human A gamma-globin gene": "DNA" } }, { "input_text": "Interaction between the stage selector element ( SSE ) in the proximal gamma-globin promoter and hypersensitivity site 2 in the locus control region partly mediates the competitive silencing of the beta-globin promoter in the fetal developmental stage .", "target_text": { "stage selector element": "DNA", "SSE": "DNA", "proximal gamma-globin promoter": "DNA", "hypersensitivity site 2": "DNA", "locus control region": "DNA", "beta-globin promoter": "DNA" } }, { "input_text": "We have now demonstrated that a second SSE-like element in the 5'-untranslated region of the gamma-gene also contributes to this competitive silencing of the beta-gene .", "target_text": { "SSE-like element": "DNA", "5'-untranslated region": "DNA", "gamma-gene": "DNA", "beta-gene": "DNA" } }, { "input_text": "Utilizing transient transfection assays in the fetal erythroid cell line , K562 , we have shown that the core enhancer of hypersensitivity site 2 can preferentially interact with the proximal gamma-promoter in the absence of the SSE , completely silencing a linked beta-promoter .", "target_text": { "fetal erythroid cell line": "cell_line", "K562": "cell_line", "core enhancer": "DNA", "hypersensitivity site 2": "DNA", "proximal gamma-promoter": "DNA", "SSE": "DNA", "linked beta-promoter": "DNA" } }, { "input_text": "Mutation of a 20-base pair sequence of the gamma-gene 5'-untranslated region ( UTR ) led to derepression of beta-promoter activity .", "target_text": { "gamma-gene 5'-untranslated region": "DNA", "UTR": "DNA", "beta-promoter": "DNA" } }, { "input_text": "A marked activation of gamma-promoter activity was also observed with this mutation , suggesting the presence of a repressor .", "target_text": { "gamma-promoter": "DNA" } }, { "input_text": "Fine mutagenesis dissected these activities to different regions of the 5'-UTR .", "target_text": { "5'-UTR": "DNA" } }, { "input_text": "The stage selector activity was localized to a region centered on nucleotides +13 to +15 .", "target_text": { "nucleotides +13 to +15": "DNA" } }, { "input_text": "Electromobility shift assays utilizing this sequence demonstrated binding of a fetal and erythroid -specific protein .", "target_text": {} }, { "input_text": "The repressor activity of the 5'-UTR was localized to tandem GATA-like sites , which appear to bind a complex of two proteins , one of which is the erythroid transcription factor GATA-1 .", "target_text": { "5'-UTR": "DNA", "GATA-like sites": "DNA", "transcription factor": "protein", "erythroid transcription factor": "protein", "GATA-1": "protein" } }, { "input_text": "These results indicate that the 5'-UTR of the gamma-gene contains sequences that may be important for its transcriptional and developmental regulation .", "target_text": { "5'-UTR": "DNA", "gamma-gene": "DNA" } }, { "input_text": "Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation .", "target_text": { "signal response domain": "protein", "I kappa B alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "The eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth .", "target_text": { "eukaryotic transcription factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha .", "target_text": { "NF-kappa B": "protein", "inhibitory subunit": "protein", "I kappa B alpha": "protein" } }, { "input_text": "This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B -inducing agents , including T-cell mitogens , proinflammatory cytokines , and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1 .", "target_text": { "NF-kappa B": "protein", "NF-kappa B -inducing agents": "protein", "T-cell mitogens ,": "protein", "proinflammatory cytokines": "protein", "viral transactivators": "protein", "Tax protein": "protein" } }, { "input_text": "To explore these I kappa B alpha -dependent mechanisms for NF-kappa B induction , we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes .", "target_text": { "I kappa B alpha": "protein", "NF-kappa B": "protein", "T lymphocytes": "cell_type", "human T lymphocytes": "cell_type" } }, { "input_text": "Specifically , removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm .", "target_text": { "N-terminal 36 amino acids": "protein", "I kappa B alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "However , this deletion mutation prevented the induced phosphorylation , degradative loss , and functional release of I kappa B alpha from NF-kappa B in Tax -expressing cells .", "target_text": { "I kappa B alpha": "protein", "NF-kappa B": "protein", "Tax": "protein", "Tax -expressing cells": "cell_line" } }, { "input_text": "Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax -induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction , including those initiated from antigen and cytokine receptors .", "target_text": { "N-terminal regulatory region": "protein", "I kappa B alpha": "protein", "Tax": "protein", "NF-kappa B": "protein" } }, { "input_text": "In contrast , introduction of a phosphoserine mimetic at these sites rectified this functional defect , a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor .", "target_text": { "cytoplasmic inhibitor": "protein" } }, { "input_text": "Together , these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli .", "target_text": { "I kappa B alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "Growth regulation and cellular changes during differentiation of human prostatic cancer LNCaP cells as induced by T lymphocyte -conditioned medium .", "target_text": { "LNCaP cells": "cell_line", "human prostatic cancer LNCaP cells": "cell_line" } }, { "input_text": "Human prostatic epithelial cells from an androgen-dependent LNCaP cell line were examined in response to conditioned medium ( CM ) derived from phytohemagglutinin ( PHA ) -stimulated lymphocytes .", "target_text": { "Human prostatic epithelial cells": "cell_line", "androgen-dependent LNCaP cell line": "cell_line", "phytohemagglutinin": "protein", "PHA": "protein", "lymphocytes": "cell_type", "phytohemagglutinin ( PHA ) -stimulated lymphocytes": "cell_line" } }, { "input_text": "Addition of CM caused a greater than 70 % reduction of cell proliferation by cell counting and cell cycle .", "target_text": {} }, { "input_text": "These cells showed G1 phase arrest and the clonogenicity was reduced .", "target_text": {} }, { "input_text": "The growth-modulating effect was dose-dependent and not due to cell lysis or apoptosis .", "target_text": {} }, { "input_text": "The binding of androgen to androgen receptor on these cells showed approximately 50 % reduction , underlining a proliferation reduction mechanism .", "target_text": { "androgen receptor": "protein" } }, { "input_text": "The prostate-specific antigen ( PSA ) was downregulated to approximately 75 % during the process .", "target_text": { "prostate-specific antigen": "protein", "PSA": "protein" } }, { "input_text": "Cell morphology showed dendritic processes extending from cytoplasm and other neuroendocrine cell characteristics .", "target_text": { "neuroendocrine cell": "cell_type" } }, { "input_text": "The expression of several cytoskeleton and intracellular proteins increased as determined by immunostaining on slides and by ELISA procedures .", "target_text": {} }, { "input_text": "These included vimentin , correlating to cell shape changes , cytokeratins 8 and 18 , associated with differentiated cell types of prostate epithelia , and neuron-specific enolase and serotonin , associated with neuroendocrine cells .", "target_text": { "vimentin": "protein", "differentiated cell types": "cell_type", "neuron-specific enolase": "protein", "neuroendocrine cells": "cell_type" } }, { "input_text": "From these cellular changes , we can infer that the cell growth was modulated along with induction of terminal differentiation .", "target_text": {} }, { "input_text": "Activated T cells were demonstrated to be important in providing the modulating activity .", "target_text": { "T cells": "cell_type" } }, { "input_text": "This growth modulator was semipurified and had an estimated molecular weight 13,000 to 24,000 Da .", "target_text": { "growth modulator": "protein" } }, { "input_text": "The activity was determined to be distinct from TGF , TNF , and some commonly known lymphokines .", "target_text": { "TGF": "protein", "TNF": "protein", "lymphokines": "protein" } }, { "input_text": "The interaction between lymphoid and prostatic cells in growth and development is described .", "target_text": {} }, { "input_text": "Platelet-activating factor stimulates transcription of the heparin-binding epidermal growth factor-like growth factor in monocytes .", "target_text": { "Platelet-activating factor": "protein", "heparin-binding epidermal growth factor-like growth factor": "protein", "monocytes": "cell_type" } }, { "input_text": "Correlation with an increased kappa B binding activity .", "target_text": {} }, { "input_text": "Human peripheral blood monocytes responded to stimulation of platelet-activating factor ( PAF ) with up-regulation of the transcript for heparin-binding epidermal growth factor-like growth factor ( HB-EGF ) , a potent mitogen for vascular smooth muscle cells .", "target_text": { "monocytes": "cell_type", "platelet-activating factor": "protein", "PAF": "protein", "heparin-binding epidermal growth factor-like growth factor": "protein", "HB-EGF": "protein", "potent mitogen": "protein", "vascular smooth muscle cells": "cell_type" } }, { "input_text": "This function of PAF was observed at nanomolar concentrations of the ligand , starting at 30 min after stimulation .", "target_text": { "PAF": "protein" } }, { "input_text": "The PAF -induced up-regulation of HB-EGF mRNA was accompanied by an increase in kappa B binding activity .", "target_text": { "PAF": "protein", "HB-EGF": "protein", "HB-EGF mRNA": "RNA" } }, { "input_text": "These functions of PAF appeared to be mediated through the cell surface PAF receptors , as two PAF receptor antagonists , WEB 2086 and L-659 , 989 , blocked both the up-regulation of HB-EGF mRNA and kappa B binding activity induced by PAF .", "target_text": { "PAF": "protein", "cell surface PAF receptors": "protein", "HB-EGF": "protein", "HB-EGF mRNA": "RNA" } }, { "input_text": "The antagonists , however , had no effect on phorbol ester -induced up-regulation of HB-EGF mRNA and kappa B binding activity .", "target_text": { "HB-EGF": "protein", "HB-EGF mRNA": "RNA" } }, { "input_text": "Pretreatment of monocytes with pertussis toxin inhibited these functions of PAF , whereas cholera toxin had no inhibitory effect .", "target_text": { "monocytes": "cell_type", "PAF": "protein" } }, { "input_text": "Pyrrolidine dithiocarbamate , an inhibitor for NF-kappa B activation , markedly reduced PAF -stimulated kappa B binding activity as well as up-regulation of HB-EGF mRNA .", "target_text": { "NF-kappa B": "protein", "PAF": "protein", "HB-EGF": "protein", "HB-EGF mRNA": "RNA" } }, { "input_text": "These results suggest a potential role of PAF in HB-EGF expression and provide evidence that this stimulation may occur through increased kappa B binding activity .", "target_text": { "PAF": "protein", "HB-EGF": "protein" } }, { "input_text": "Mapping of the interaction site of the defective transcription factor in the class II major histocompatibility complex mutant cell line clone-13 to the divergent X2-box .", "target_text": { "interaction site": "protein", "transcription factor": "protein", "defective transcription factor": "protein", "class II major histocompatibility complex mutant cell line clone-13": "cell_line", "divergent X2-box": "DNA" } }, { "input_text": "We have previously described a mutant B lymphoblastoid cell line , Clone-13 , that expresses HLA-DQ in the absence of HLA -DR and -DP .", "target_text": { "mutant B lymphoblastoid cell line": "cell_line", "Clone-13 ,": "cell_line", "HLA-DQ": "protein" } }, { "input_text": "Several criteria indicated that the defect in this cell line influences the activity of an isotype-specific transcription factor .", "target_text": { "isotype-specific transcription factor": "protein" } }, { "input_text": "Indeed , transient transfection of HLA-DRA and DQB reporter constructs indicated that the affected factor operates via cis-elements located between -141 base pairs and the transcription initiation site .", "target_text": { "cis-elements": "DNA", "-141 base pairs": "DNA", "transcription initiation site": "DNA" } }, { "input_text": "A series of hybrid DRA/DQB reporter constructs was generated to further map the relevant cis-elements in this system .", "target_text": { "reporter constructs": "DNA", "hybrid DRA/DQB reporter constructs": "DNA", "cis-elements": "DNA" } }, { "input_text": "Insertion of oligonucleotides spanning the DQB X-box ( but not the DQB-W region or the DQB Y-box ) upstream of -141 in a DRA reporter plasmid rescued expression to nearly wild-type levels .", "target_text": { "DQB X-box": "DNA", "DQB-W region": "DNA", "DQB Y-box": "DNA", "upstream of -141": "DNA", "DRA reporter plasmid": "DNA" } }, { "input_text": "Substitution promoters were then generated where the entire X-box , or only the X1- or X2- boxes of HLA-DRA were replaced with the analogous regions of HLA-DQB .", "target_text": { "X-box": "DNA", "HLA-DRA": "DNA", "HLA-DQB": "DNA" } }, { "input_text": "The DQB X2-box was able to restore expression to the silent DRA reporter construct .", "target_text": { "DQB X2-box": "DNA", "silent DRA reporter construct": "DNA" } }, { "input_text": "Moreover , replacement of the DQB X2-box with the DRA X2-box markedly diminished the activity of the DQB promoter in the mutant cell .", "target_text": { "DQB X2-box": "DNA", "DRA X2-box": "DNA", "DQB promoter": "DNA", "mutant cell": "cell_line" } }, { "input_text": "None of the hybrid reporter constructs were defective when transfected into the wild-type , HLA-DR/-DQ positive parental cell line , Jijoye .", "target_text": { "reporter constructs": "DNA", "hybrid reporter constructs": "DNA", "wild-type": "protein", "HLA-DR/-DQ positive parental cell line": "cell_line", "Jijoye": "cell_line" } }, { "input_text": "These studies suggest that the divergent X2-box of the class II major histocompatibility complex promoters plays an important role in influencing differential expression of the human class II isotypes .", "target_text": { "divergent X2-box": "DNA", "class II major histocompatibility complex": "protein", "class II major histocompatibility complex promoters": "DNA", "human class II isotypes": "DNA" } }, { "input_text": "Restoration of the Epstein-Barr virus ZEBRA protein 's capacity to disrupt latency by the addition of heterologous activation regions .", "target_text": { "Epstein-Barr virus ZEBRA protein": "protein", "heterologous activation regions": "protein" } }, { "input_text": "The ZEBRA protein has a unique biological function among herpesviral proteins .", "target_text": { "ZEBRA protein": "protein", "herpesviral proteins": "protein" } }, { "input_text": "It is responsible for the disruption of Epstein-Barr virus ( EBV ) latency and the induction of the lytic cycle .", "target_text": {} }, { "input_text": "ZEBRA is a bZIP transcriptional activator which binds as a dimer to 7-bp response elements within EBV promoters and is directly involved in the stimulation of virus replication at the EBV lytic origin .", "target_text": { "ZEBRA": "protein", "bZIP transcriptional activator": "protein", "7-bp response elements": "DNA", "EBV promoters": "DNA", "EBV lytic origin": "DNA" } }, { "input_text": "We have employed the ZEBRA /EBV biological system to test whether a heterologous activation domain can substitute for another activation domain ( the ZEBRA domain ) .", "target_text": { "ZEBRA": "protein", "heterologous activation domain": "protein", "ZEBRA domain": "protein" } }, { "input_text": "The ZEBRA activation region was replaced with the potent acid activation region from the herpes simplex virus VP16 protein or with the activation region of the EBV R protein .", "target_text": { "ZEBRA": "protein", "ZEBRA activation region": "protein", "acid activation region": "protein", "herpes simplex virus VP16 protein": "protein", "activation region": "protein", "EBV R protein": "protein" } }, { "input_text": "Both chimeras were found to transactivate model and native promoters at equivalent or better levels than ZEBRA itself .", "target_text": { "ZEBRA": "protein" } }, { "input_text": "Activation was not target- or cell-type dependent , nor was it dependent on the presence of virus .", "target_text": {} }, { "input_text": "These activation domains restored ZEBRA 's ability to induce early antigen and to stimulate origin replication to levels that were equal to or greater than those of wild type .", "target_text": { "ZEBRA": "protein", "early antigen": "protein" } }, { "input_text": "These studies suggest that the specificities of some of the known biological functions of ZEBRA are not dependent upon the nature of the activation domain present within ZEBRA .", "target_text": { "ZEBRA": "protein", "activation domain present": "protein" } }, { "input_text": "Interleukin 4 activates a signal transducer and activator of transcription ( Stat ) protein which interacts with an interferon-gamma activation site-like sequence upstream of the I epsilon exon in a human B cell line .", "target_text": { "Interleukin 4": "protein", "transcription ( Stat ) protein": "protein", "interferon-gamma activation site-like sequence": "DNA", "I epsilon exon": "DNA", "human B cell line": "cell_line" } }, { "input_text": "Evidence for the involvement of Janus kinase 3 and interleukin-4 Stat .", "target_text": { "Janus kinase 3": "protein", "interleukin-4 Stat": "protein" } }, { "input_text": "Germ line C transcripts can be induced by IL-4 in the human B cell line , BL-2 .", "target_text": { "Germ line C transcripts": "RNA", "IL-4": "protein", "human B cell line": "cell_line", "BL-2": "cell_line" } }, { "input_text": "Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon , we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells .", "target_text": { "IFN-gamma activation site-like DNA sequence element": "DNA", "I epsilon exon": "DNA", "IL-4": "protein", "BL-2 cells": "cell_line" } }, { "input_text": "This factor was designated IL-4 NAF ( IL-4 -induced nuclear-activating factors ) and was identified as a tyrosine phosphoprotein , which translocates from the cytosol to the nucleus upon IL-4 treatment .", "target_text": { "IL-4": "protein", "IL-4 NAF": "protein", "IL-4 -induced nuclear-activating factors": "protein", "tyrosine phosphoprotein": "protein" } }, { "input_text": "Because these are the characteristics of a signal transducer and activator of transcription ( Stat ) protein , we determined whether antibodies to Stat proteins will interfere with gel mobility shift and found that antibodies to IL-4 Stat , also known as Stat6 , but not antibodies to other Stat proteins , interfere with the formation of the IL-4 NAF complex .", "target_text": { "signal transducer and activator of transcription ( Stat ) protein": "protein", "antibodies to Stat proteins": "protein", "IL-4": "protein", "IL-4 Stat": "protein", "antibodies to IL-4 Stat": "protein", "Stat6": "protein", "antibodies": "protein", "Stat proteins": "protein", "IL-4 NAF complex": "protein" } }, { "input_text": "Congruous with the involvement of a Stat protein , IL-4 induced robust Janus kinase 3 ( JAK3 ) activity in BL-2 cells .", "target_text": { "Stat protein": "protein", "IL-4": "protein", "Janus kinase 3": "protein", "JAK3": "protein", "BL-2 cells": "cell_line" } }, { "input_text": "Cotransfection of JAK3 with IL-4 Stat into COS-7 cells produced an intracellular activity which bound the same IFN-gamma activation site-like sequence and comigrated with IL-4 NAF in electrophoretic mobility shift assay .", "target_text": { "JAK3": "protein", "IL-4": "protein", "IL-4 Stat": "protein", "COS-7 cells": "cell_line", "IFN-gamma activation site-like sequence": "DNA", "IL-4 NAF": "protein" } }, { "input_text": "These results show that IL-4 NAF is IL-4 Stat , which is activated by JAK3 in response to IL-4 receptor engagement .", "target_text": { "IL-4": "protein", "IL-4 NAF": "protein", "IL-4 Stat": "protein", "JAK3": "protein" } }, { "input_text": "Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia ? A pediatric oncology group study .", "target_text": { "TAL1 gene": "DNA" } }, { "input_text": "Almost 25 % of patients with T-cell acute lymphoblastic leukemia ( T-ALL ) have tumor-specific rearrangements of the TAL1 gene .", "target_text": { "TAL1 gene": "DNA" } }, { "input_text": "Although TAL1 expression has not been observed in normal lymphocytes , TAL1 gene products are readily detected in leukemic cells that harbor a rearranged TAL1 allele .", "target_text": { "TAL1": "protein", "normal lymphocytes": "cell_type", "TAL1 gene": "DNA", "TAL1 gene products": "protein", "leukemic cells": "cell_type", "rearranged TAL1 allele": "DNA" } }, { "input_text": "Hence , it has been proposed that ectopic expression of TAL1 promotes the development of T-ALL .", "target_text": { "TAL1": "protein" } }, { "input_text": "In this report , we show that TAL1 is expressed in the leukemic cells of most patients with T-ALL , including many that do not display an apparent TAL1 gene alteration .", "target_text": { "TAL1": "protein", "leukemic cells": "cell_type", "TAL1 gene": "DNA" } }, { "input_text": "A polymorphic dinucleotide repeat in the transcribed sequences of TAL1 was used to determine the allele specificity of TAL1 transcription in primary T-ALL cells .", "target_text": { "TAL1": "protein", "primary T-ALL cells": "cell_type" } }, { "input_text": "Monoallelic expression of TAL1 was observed in the leukemic cells of all patients ( 8 of 8 ) bearing a TAL1 gene rearrangement .", "target_text": { "TAL1": "protein", "leukemic cells": "cell_type", "TAL1 gene": "DNA" } }, { "input_text": "In the leukemic cells of patients without detectable TAL1 rearrangements , TAL1 transcription occurred in either a monoallelic ( 3 of 7 patients ) or a biallelic ( 4 of 7 patients ) fashion .", "target_text": { "leukemic cells": "cell_type", "TAL1": "protein" } }, { "input_text": "Thus , TAL1 activation in these patients may result from subtle alterations in cis-acting regulatory sequences ( affecting expression of a single TAL1 allele ) or changes in trans-acting factors that control TAL1 transcription ( affecting expression of both TAL1 alleles ) .", "target_text": { "TAL1": "protein", "cis-acting regulatory sequences": "DNA", "single TAL1 allele": "DNA", "TAL1 alleles": "DNA" } }, { "input_text": "Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down 's syndrome .", "target_text": { "erythroid-specific genes": "DNA" } }, { "input_text": "Acute megakaryoblastic leukaemia ( M7 ) and transient myeloproliferative disorder in Down 's syndrome ( TMD ) are characterized by rapid growth of abnormal blast cells which express megakaryocytic markers .", "target_text": { "abnormal blast cells": "cell_type", "megakaryocytic markers": "protein" } }, { "input_text": "To clarify properties of the blast cells in M7 and TMD cases , we examined erythroid markers expression in blasts from six cases with M7 and seven cases with TMD in this study .", "target_text": { "blast cells": "cell_type", "blasts": "cell_type" } }, { "input_text": "Erythroid-specific mRNAs encoding gamma-globin and erythroid delta-aminolevulinate synthase were found to be expressed in blasts from most of these cases , indicating that majorities of the blasts in M7 and TMD cases have erythroid and megakaryocytic phenotypes .", "target_text": { "Erythroid-specific mRNAs": "RNA", "gamma-globin": "protein", "erythroid delta-aminolevulinate synthase": "protein", "blasts": "cell_type" } }, { "input_text": "We also found that mRNAs encoding GATA-1 and GATA-2 are expressed in all these cases .", "target_text": { "mRNAs": "RNA", "GATA-1": "protein", "GATA-2": "protein" } }, { "input_text": "These results suggest that M7 blasts and TMD blasts correspond to the erythroid/megakaryocytic bipotential progenitor cells .", "target_text": { "M7 blasts": "cell_type", "TMD blasts": "cell_type", "erythroid/megakaryocytic bipotential progenitor cells": "cell_type" } }, { "input_text": "Expression of Ah receptor ( TCDD receptor ) during human monocytic differentiation .", "target_text": { "Ah receptor": "protein", "TCDD receptor": "protein" } }, { "input_text": "We have previously found a high expression of human Ah receptor ( TCDD receptor ) mRNA in peripheral blood cells of individuals .", "target_text": { "Ah receptor": "protein", "human Ah receptor": "protein", "TCDD receptor": "protein", "human Ah receptor ( TCDD receptor ) mRNA": "RNA", "peripheral blood cells": "cell_type" } }, { "input_text": "In this paper , the expression of this gene in blood cells was first investigated in fractions of nucleated cells , revealing predominant expression of the Ah receptor gene in the monocyte fraction .", "target_text": { "blood cells": "cell_type", "nucleated cells": "cell_type", "Ah receptor": "protein", "Ah receptor gene": "DNA", "monocyte fraction": "cell_type" } }, { "input_text": "Then the expression levels of AhR mRNA in various hematopoietic cell lines were examined together with those of Arnt and P450IA1 .", "target_text": { "AhR mRNA": "RNA", "hematopoietic cell lines": "cell_line", "Arnt": "protein", "P450IA1": "protein" } }, { "input_text": "AhR was expressed at high levels in monocytoid U937 , THP1 , and HEL/S cells , and at moderate levels in promyelocytic HL60 cells and erythroblastic HEL cells .", "target_text": { "AhR": "protein", "monocytoid U937": "cell_line", "THP1": "cell_line", "HEL/S cells": "cell_line", "promyelocytic HL60 cells": "cell_line", "erythroblastic HEL cells": "cell_line" } }, { "input_text": "However , it was not detected in lymphoid cells MOLT4 ( T cell ) and BALL1 ( B cell ) , nor in K562 erythroblasts .", "target_text": { "lymphoid cells": "cell_type", "MOLT4": "cell_line", "T cell": "cell_type", "BALL1": "cell_line", "B cell": "cell_type", "K562 erythroblasts": "cell_line" } }, { "input_text": "Furthermore , a specific induction of AhR during monocytic differentiation was investigated in HL60 and HEL cells .", "target_text": { "AhR": "protein", "HL60": "cell_line", "HEL cells": "cell_line" } }, { "input_text": "HL60 cells were induced to differentiate toward monocytes-macrophages by incubation with phorbol ester , showing a 5- to 2-fold increase of AhR mRNA .", "target_text": { "HL60 cells": "cell_line", "monocytes-macrophages": "cell_type", "AhR": "protein", "AhR mRNA": "RNA" } }, { "input_text": "The incubation with transforming growth factor beta 1 and 1 alpha,25-dihydroxyvitamin D3 resulted in a 5- to 7-fold increase of AhR mRNA .", "target_text": { "transforming growth factor beta 1": "protein", "AhR": "protein", "AhR mRNA": "RNA" } }, { "input_text": "The HEL cells also exhibited a similar elevation of AhR mRNA level , when they had differentiated toward monocyte-macrophage cells by these combined inducers , but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types .", "target_text": { "HEL cells": "cell_line", "AhR": "protein", "AhR mRNA": "RNA", "monocyte-macrophage cells": "cell_type" } }, { "input_text": "Treatment of the differentiated HL60 cells with 3-methylcholanthrene , a ligand of AhR , induced the expression of the P450IA1 gene .", "target_text": { "HL60": "cell_line", "differentiated HL60 cells": "cell_line", "AhR": "protein", "P450IA1": "protein" } }, { "input_text": "These results indicated that expression of AhR mRNA was significantly induced during monocytic differentiation and that the differentiated cells were responsive to xenobiotics .", "target_text": { "AhR": "protein", "AhR mRNA": "RNA", "differentiated cells": "cell_type" } }, { "input_text": "Our results suggest that AhR may play an important role in the function of monocytes and also in the eventual activation of environmental carcinogens .", "target_text": { "AhR": "protein", "monocytes": "cell_type" } }, { "input_text": "Neutrophils and monocytes express high levels of PU.1 ( Spi-1 ) but not Spi-B .", "target_text": { "Neutrophils": "cell_type", "monocytes": "cell_type", "PU.1": "protein", "Spi-1": "protein", "Spi-B": "protein" } }, { "input_text": "PU.1 ( the Spi-1 oncogene ) and Spi-B are closely related members of the ets transcription factor family , sharing similar DNA binding specificities mediated by similar DNA binding domains .", "target_text": { "PU.1": "protein", "Spi-1 oncogene": "DNA", "Spi-B": "protein", "ets transcription factor family": "protein", "DNA binding domains": "protein" } }, { "input_text": "PU.1 and Spi-B have been previously described as being predominantly expressed coordinately in macrophages and B cells , but their expression in early hematopoietic stages and during the course of myeloid differentiation to monocytes and macrophages or to neutrophils has not been extensively investigated .", "target_text": { "PU.1": "protein", "Spi-B": "protein", "macrophages": "cell_type", "B cells": "cell_type", "monocytes": "cell_type", "neutrophils": "cell_type" } }, { "input_text": "Here , we report that PU.1 mRNA is upregulated during myeloid differentiation of human purified CD34+ cells and murine multipotential FDCP-mix A4 cells , suggesting that PU.1 is upregulated as an early event during differentiation of multipotential progenitor cells .", "target_text": { "PU.1": "protein", "PU.1 mRNA": "RNA", "human purified CD34+ cells": "cell_line", "murine multipotential FDCP-mix A4 cells": "cell_line", "multipotential progenitor cells": "cell_type" } }, { "input_text": "PU.1 expression is maintained at stable levels during differentiation of myeloid cell lines U937 and HL-60 to monocytic and neutrophilic cells .", "target_text": { "PU.1": "protein", "myeloid cell lines": "cell_line", "U937": "cell_line", "HL-60": "cell_line" } }, { "input_text": "PU.1 is expressed at highest levels in mature human monocytes and human peripheral blood neutrophils .", "target_text": { "PU.1": "protein", "monocytes": "cell_type", "mature human monocytes": "cell_type", "neutrophils": "cell_type", "human peripheral blood neutrophils": "cell_type" } }, { "input_text": "In contrast to PU.1 , significant levels of Spi-B mRNA and protein are found only in some B-cell lines and spleen but are not found in myeloid cell lines , neutrophils , or macrophages .", "target_text": { "PU.1": "protein", "Spi-B": "protein", "Spi-B mRNA": "RNA", "B-cell lines": "cell_line", "myeloid cell lines": "cell_line", "neutrophils": "cell_type", "macrophages": "cell_type" } }, { "input_text": "In vitro translated Spi-B protein can bind to PU.1 binding sites in myeloid promoters and transactivate these promoters in nonmyeloid cells .", "target_text": { "Spi-B": "protein", "Spi-B protein": "protein", "PU.1": "protein", "PU.1 binding sites": "DNA", "myeloid promoters": "DNA", "promoters": "DNA", "nonmyeloid cells": "cell_type" } }, { "input_text": "Therefore , although PU.1 and Spi-B may bind to similar DNA control elements and have redundancy of transactivation function in vitro , the lack of significant levels of Spi-B in myeloid cells makes it unlikely that Spi-B plays a significant role in myeloid lineage development and gene expression .", "target_text": { "PU.1": "protein", "Spi-B": "protein", "myeloid cells": "cell_type" } }, { "input_text": "In contrast , PU.1 is expressed at high levels not only in monocytes and macrophages but also in neutrophils , indicating that PU.1 can activate gene expression in both major myeloid lineages .", "target_text": { "PU.1": "protein", "monocytes": "cell_type", "macrophages": "cell_type", "neutrophils": "cell_type", "major myeloid lineages": "cell_type" } }, { "input_text": "Identification of a major positive regulatory element located 5' to the human zeta-globin gene .", "target_text": { "positive regulatory element": "DNA", "human zeta-globin gene": "DNA" } }, { "input_text": "The function of the zeta-globin promoter was studied using a series of zeta-globin promoter deletion constructs to drive luciferase expression in transiently transfected human erythroleukemia cells .", "target_text": { "zeta-globin promoter": "DNA", "zeta-globin promoter deletion constructs": "DNA", "luciferase": "protein", "transiently transfected human erythroleukemia cells": "cell_line" } }, { "input_text": "The promoters were used without enhancers , or with enhancers derived from the beta-globin locus control region and the alpha-globin HS-40 enhancer .", "target_text": { "promoters": "DNA", "enhancers": "DNA", "beta-globin locus control region": "DNA", "alpha-globin HS-40 enhancer": "DNA" } }, { "input_text": "When transfected into K562 cells , which express zeta-globin , comparable amounts of activity were obtained from the -557 and -417 zeta- luciferase constructs and the alpha- luciferase constructs when no enhancers or the alpha-globin locus enhancers were used .", "target_text": { "K562 cells": "cell_line", "zeta-globin": "protein", "luciferase": "protein", "-557 and -417 zeta- luciferase constructs": "DNA", "alpha- luciferase constructs": "DNA", "enhancers": "DNA", "alpha-globin locus enhancers": "DNA" } }, { "input_text": "When the constructs were transfected into OCIM1 cells , which do not express zeta-globin , the zeta-globin promoters were at best 20 % as active as the alpha-globin promoters .", "target_text": { "OCIM1 cells": "cell_line", "zeta-globin": "protein", "zeta-globin promoters": "DNA", "promoters": "DNA", "alpha-globin promoters": "DNA" } }, { "input_text": "When sequences from -417 to -207 5' to the zeta-globin mRNA cap site were deleted , up to 95 % of the zeta-globin promoter activity was lost in K562 cells .", "target_text": { "sequences from -417 to -207 5'": "DNA", "zeta-globin mRNA": "RNA", "zeta-globin mRNA cap site": "RNA", "zeta-globin": "protein", "zeta-globin promoter": "DNA", "K562 cells": "cell_line" } }, { "input_text": "Reinsertion of these sequences into zeta- luciferase constructs missing the -417 to -207 region showed that the sequences lack classical enhancer activity .", "target_text": { "luciferase": "protein", "zeta- luciferase constructs": "DNA" } }, { "input_text": "Point mutation of a GATA-1 site at -230 reduced promoter activity by 37 % .", "target_text": { "GATA-1": "protein", "GATA-1 site": "DNA" } }, { "input_text": "Point mutation of a CCACC site at -240 had no effect .", "target_text": { "CCACC site": "DNA" } }, { "input_text": "Electrophoretic mobility shift assays indicated that the -230 GATA-1 site has a relatively low affinity for GATA-1 .", "target_text": { "GATA-1": "protein", "-230 GATA-1 site": "DNA" } }, { "input_text": "These experiments show the presence of a strong positive-acting element , located between -417 and -207 bp 5' to the zeta-globin mRNA cap site , is necessary for high-level promoter activity in K562 cells .", "target_text": { "positive-acting element": "DNA", "-417 and -207 bp 5'": "DNA", "zeta-globin": "protein", "zeta-globin mRNA": "RNA", "zeta-globin mRNA cap site": "DNA", "K562 cells": "cell_line" } }, { "input_text": "This element requires GATA-1 and additional unknown factors for maximal activity .", "target_text": { "GATA-1": "protein", "additional unknown factors": "protein" } }, { "input_text": "Analysis of the role of protein kinase C -alpha , -epsilon , and -zeta in T cell activation .", "target_text": {} }, { "input_text": "T cells express multiple isotypes of protein kinase C ( PKC ) and although it is well accepted that PKCs have an important role in T cell activation , little is known about the function of individual PKC isotypes .", "target_text": { "T cells": "cell_type", "protein kinase C": "protein", "PKC": "protein", "PKCs": "protein", "PKC isotypes": "protein" } }, { "input_text": "To address this issue , mutationally active PKC -alpha , -epsilon , or -zeta have been transfected into T cells and the consequences for T cell activation determined .", "target_text": { "T cells": "cell_type" } }, { "input_text": "p21ras plays an essential role in T cell activation .", "target_text": { "p21ras": "protein" } }, { "input_text": "Accordingly , the effects of the constitutively active PKCs were compared to the effects of mutationally activated p21ras .", "target_text": { "constitutively active PKCs": "protein", "p21ras": "protein" } }, { "input_text": "The data indicate that PKC-epsilon and , to a lesser extent PKC-alpha but not -zeta , can regulate the transcription factors AP-1 and nuclear factor of activated T cells ( NF-AT-1 ) .", "target_text": { "PKC-epsilon": "protein", "PKC-alpha": "protein", "-zeta": "protein", "transcription factors": "protein", "AP-1": "protein", "T cells": "cell_type", "factor of activated T cells": "protein", "NF-AT-1": "protein" } }, { "input_text": "The ability of PKC-epsilon to induce transactivation of NF-AT-1 and AP-1 was similar to the stimulatory effect of a constitutively activated p21ras .", "target_text": { "PKC-epsilon": "protein", "NF-AT-1": "protein", "AP-1": "protein", "p21ras": "protein", "constitutively activated p21ras": "protein" } }, { "input_text": "PKC-epsilon , but not PKC-alpha nor activated p21ras , was able to induce NF-KB activity .", "target_text": { "PKC-epsilon": "protein", "PKC-alpha": "protein", "p21ras": "protein", "NF-KB": "protein" } }, { "input_text": "Phorbol esters induce expression of CD69 whereas none of the activated PKC isotypes tested were able to have this effect .", "target_text": { "CD69": "protein", "PKC isotypes": "protein", "activated PKC isotypes": "protein" } }, { "input_text": "Activated Src and p21ras were able to induce CD69 expression .", "target_text": { "Src": "protein", "p21ras": "protein", "CD69": "protein" } }, { "input_text": "These results indicate selective functions for different PKC isotypes in T cells .", "target_text": { "PKC isotypes": "protein", "T cells": "cell_type" } }, { "input_text": "Moreover , the data comparing the effects of activated Ras and PKC mutants suggest that PKC-alpha , p21ras , and PKC-epsilon are not positioned linearly on a single signal transduction pathway .", "target_text": { "activated Ras": "protein", "PKC mutants": "protein", "PKC-alpha": "protein", "p21ras": "protein", "PKC-epsilon": "protein" } }, { "input_text": "Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Although glucocorticosteroids are a very effective treatment for asthma and other chronic inflammatory diseases , a small proportion of patients are resistant to their therapeutic effects .", "target_text": {} }, { "input_text": "The molecular mechanism for this steroid resistance is unclear .", "target_text": {} }, { "input_text": "Steroid resistance can not be explained by pharmacokinetic mechanisms , by a defect in the binding of steroids to glucocorticoid receptors , nor by defective nuclear translocation of this receptor , thereby suggesting that the molecular abnormality lies distal to nuclear translocation .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "We examined the ability of nuclear translocated glucocorticoid receptors to bind to their DNA binding sites ( GRE ) using electrophoretic mobility shift assays in PBMC from patients with steroid-sensitive and steroid-resistant asthma .", "target_text": { "glucocorticoid receptors": "protein", "DNA binding sites": "DNA", "GRE": "DNA", "PBMC": "cell_type" } }, { "input_text": "The binding of the glucocorticoid receptor to DNA in these patients was also studied using Scatchard analysis .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Dexamethasone induced a significant rapid and sustained twofold increase in GRE binding in PBMCs from steroid-sensitive asthmatic patients and nonasthmatic individuals , but this was markedly reduced in steroid-resistant asthmatic patients .", "target_text": { "GRE": "DNA", "PBMCs": "cell_type" } }, { "input_text": "Scatchard analysis of glucocorticoid receptor - GRE binding showed no change in binding affinity but did show a reduced number of receptors available for DNA binding in the steroid-resistant patients .", "target_text": { "glucocorticoid receptor": "protein", "GRE": "DNA", "receptors": "protein" } }, { "input_text": "These results suggest that the ability of the glucocorticoid receptor to bind to GRE is impaired in steroid-resistant patients because of a reduced number of receptors available for binding to DNA .", "target_text": { "glucocorticoid receptor": "protein", "GRE": "DNA", "receptors": "protein" } }, { "input_text": "Interleukin-5 signaling in human eosinophils involves JAK2 tyrosine kinase and Stat1 alpha .", "target_text": { "Interleukin-5": "protein", "human eosinophils": "cell_type", "JAK2": "protein", "JAK2 tyrosine kinase": "protein", "Stat1 alpha": "protein" } }, { "input_text": "Signaling by a wide variety of cytokines , including interferons , interleukins , and growth factors , involves activation of JAK kinases and Stat ( Signal transducers and activators of transcription ) proteins .", "target_text": { "cytokines": "protein", "interferons": "protein", "interleukins": "protein", "growth factors": "protein", "JAK kinases": "protein", "Stat": "protein", "Signal transducers and activators of transcription": "protein", "Stat ( Signal transducers and activators of transcription ) proteins": "protein" } }, { "input_text": "At present , not much is known about the molecular mechanisms by which interleukin-5 ( IL-5 ) exerts its diverse biologic effects .", "target_text": { "interleukin-5": "protein", "IL-5": "protein" } }, { "input_text": "Human eosinophils are one of the most important target cells for IL-5 and were used here to study IL-5 signaling in a primary human cell .", "target_text": { "Human eosinophils": "cell_type", "target cells": "cell_type", "IL-5": "protein", "primary human cell": "cell_type" } }, { "input_text": "IL-5 induced rapid and transient tyrosine phosphorylation of JAK2 .", "target_text": { "IL-5": "protein", "JAK2": "protein" } }, { "input_text": "Moreover , IL-5 induced at least two DNA-binding complexes , using nuclear extracts from normal human eosinophils and the IL-6/interferon-gamma response element of the ICAM-1 promoter ( ICAM-1 pIRE ) in an electromobility shift assay .", "target_text": { "IL-5": "protein", "DNA-binding complexes": "protein", "human eosinophils": "cell_type", "IL-6/interferon-gamma response element": "DNA", "ICAM-1 promoter": "DNA", "ICAM-1 pIRE": "DNA" } }, { "input_text": "From supershift experiments it was concluded that one DNA-binding complex contained Stat1 alpha , probably as a homodimer .", "target_text": { "DNA-binding complex": "protein", "Stat1 alpha": "protein" } }, { "input_text": "Both DNA-binding complexes were inhibited by a phosphotyrosine antibody ( 4G10 ) , suggesting that tyrosine phosphorylation is required for complex formation .", "target_text": { "DNA-binding complexes": "protein", "phosphotyrosine antibody": "protein", "4G10": "protein" } }, { "input_text": "IL-3 and granulocyte-macrophage colony-stimulating factor induced , similar to IL-5 , two DNA-binding complexes in human eosinophils , including Stat1 alpha .", "target_text": { "IL-3": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "IL-5": "protein", "DNA-binding complexes": "protein", "human eosinophils": "cell_type", "Stat1 alpha": "protein" } }, { "input_text": "These data show for the first time that molecular mechanisms of IL-5 signaling in human eosinophils involve members of the JAK kinase family as well as members of the Stat family .", "target_text": { "IL-5": "protein", "human eosinophils": "cell_type", "JAK kinase family": "protein", "Stat family": "protein" } }, { "input_text": "Infection and replication of Tat- human immunodeficiency viruses : genetic analyses of LTR and tat mutations in primary and long-term human lymphoid cells .", "target_text": { "LTR": "DNA", "tat mutations": "protein" } }, { "input_text": "Tat is an essential regulatory protein for the replication of human immunodeficiency virus ( HIV ) .", "target_text": { "Tat": "protein", "regulatory protein": "protein" } }, { "input_text": "Mutations in the tat gene have been shown to block HIV replication in human T cells .", "target_text": { "tat gene": "DNA", "human T cells": "cell_type" } }, { "input_text": "Several studies have established that Tat releases an elongation block to the transcription of HIV long terminal repeat ( LTR ) ; however , it is not known whether this mechanism alone is sufficient to explain the block to HIV replication in human T cells when Tat is absent .", "target_text": { "Tat": "protein", "elongation block": "protein", "HIV long terminal repeat": "DNA", "LTR": "DNA", "human T cells": "cell_type" } }, { "input_text": "It is possible that Tat is also needed for other functions during HIV replication .", "target_text": { "Tat": "protein" } }, { "input_text": "To test these hypotheses , we studied several tat mutants , including two stop codon mutants and one deletion mutant using replication-competent HIV-1 constructs carrying wild-type or mutant LTRs with modifications in the NF-kappa B and/or Sp1 binding sites .", "target_text": { "tat mutants": "protein", "stop codon mutants": "protein", "deletion mutant": "protein", "replication-competent HIV-1 constructs": "DNA" } }, { "input_text": "In this study , we show that Tat- HIV-1 with wild-type LTRs can replicate in HeLa cells , and the virus produced from HeLa cells can infect primary peripheral blood lymphocytes and macrophages .", "target_text": { "wild-type LTRs": "DNA", "HeLa cells": "cell_line", "peripheral blood lymphocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "It was found that the propagation of the Tat mutants containing wild-type LTRs was less efficient than that of the LTR-modified Tat mutants .", "target_text": { "Tat": "protein", "Tat mutants": "protein", "wild-type LTRs": "DNA", "LTR-modified Tat mutants": "protein" } }, { "input_text": "Large amounts of viral RNA and particles were synthesized in infections established using the tat mutants that contain modified LTRs .", "target_text": { "viral RNA": "RNA", "tat mutants": "protein", "modified LTRs": "DNA" } }, { "input_text": "However , this efficient propagation of the LTR-modified tat mutants was restricted to some lymphoid cell lines that have been transformed with other viruses .", "target_text": { "tat mutants": "protein", "LTR-modified tat mutants": "protein", "lymphoid cell lines": "cell_line" } }, { "input_text": "Thus , despite its essential role for releasing an elongation block , Tat is not otherwise absolutely required for synthesis of full-length HIV transcripts and assembly of virus particles .", "target_text": { "elongation block": "protein", "Tat": "protein", "full-length HIV transcripts": "RNA" } }, { "input_text": "Direct sequencing of the viral genomes and reinfection kinetics showed no evidence of wild-type reversion even after prolonged infection with the Tat -virus .", "target_text": { "viral genomes": "DNA", "Tat": "protein" } }, { "input_text": "The implications for in vivo HIV-1 replication and potential application of this system to the study of alternative Tat function are discussed .", "target_text": { "Tat": "protein" } }, { "input_text": "Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression .", "target_text": { "Oct-2A": "protein", "transcription factor Oct-2A": "protein", "high mobility group protein": "protein", "I/Y": "protein", "HLA-DRA gene": "DNA" } }, { "input_text": "The class II major histocompatibility complex gene HLA-DRA is expressed in B cells , activated T lymphocytes , and in antigen-presenting cells .", "target_text": { "class II major histocompatibility complex": "protein", "class II major histocompatibility complex gene": "DNA", "HLA-DRA": "DNA", "B cells": "cell_type", "T lymphocytes": "cell_type", "antigen-presenting cells": "cell_type" } }, { "input_text": "In addition , HLA-DRA gene expression is inducible in a variety of cell types by interferon-gamma ( IFN-gamma ) .", "target_text": { "HLA-DRA gene": "DNA", "interferon-gamma": "protein", "IFN-gamma": "protein" } }, { "input_text": "Here we show that the lymphoid-specific transcription factor Oct-2A plays a critical role in HLA-DRA gene expression in class II-positive B cell lines , and that the high mobility group protein ( HMG ) I/Y binds to multiple sites within the DRA promoter , including the Oct-2A binding site .", "target_text": { "lymphoid-specific transcription factor": "protein", "Oct-2A": "protein", "lymphoid-specific transcription factor Oct-2A": "protein", "HLA-DRA gene": "DNA", "class II-positive B cell lines": "cell_line", "high mobility group protein": "protein", "HMG": "protein", "I/Y": "protein", "DRA promoter": "DNA", "Oct-2A binding site": "DNA" } }, { "input_text": "Coexpression of HMG I/Y and Oct-2 in cell lines lacking Oct-2 results in high levels of HLA-DRA gene expression , and in vitro DNA-binding studies reveal that HMG I/Y stimulates Oct-2A binding to the HLA-DRA promoter .", "target_text": { "I/Y": "protein", "HMG I/Y": "protein", "Oct-2": "protein", "cell lines": "cell_line", "HLA-DRA gene": "DNA", "Oct-2A": "protein", "HLA-DRA promoter": "DNA" } }, { "input_text": "Thus , Oct-2A and HMG I/Y may synergize to activate HLA-DRA expression in B cells .", "target_text": { "Oct-2A": "protein", "I/Y": "protein", "HMG I/Y": "protein", "HLA-DRA": "DNA", "B cells": "cell_type" } }, { "input_text": "By contrast , Oct-2A is not involved in the IFN-gamma induction of the HLA-DRA gene in HeLa cells , but antisense HMG I/Y dramatically decreases the level of induction .", "target_text": { "Oct-2A": "protein", "IFN-gamma": "protein", "HLA-DRA gene": "DNA", "HeLa cells": "cell_line", "I/Y": "protein", "HMG I/Y": "protein", "antisense HMG I/Y": "DNA" } }, { "input_text": "We conclude that distinct sets of transcription factors are involved in the two modes of HLA-DRA expression , and that HMG I/Y may be important for B cell-specific expression , and is essential for IFN-gamma induction .", "target_text": { "transcription factors": "protein", "HLA-DRA": "DNA", "HMG I/Y": "protein", "IFN-gamma": "protein" } }, { "input_text": "Heterogeneous expression of Epstein-Barr virus latent proteins in endemic Burkitt 's lymphoma .", "target_text": { "Epstein-Barr virus latent proteins": "protein" } }, { "input_text": "Epstein-Barr virus ( EBV ) -infected cells may sustain three distinct forms of virus latency .", "target_text": { "Epstein-Barr virus ( EBV ) -infected cells": "cell_type" } }, { "input_text": "In lymphoblastoid cell lines , six EBV-encoded nuclear antigens ( EBNA 1 , 2 , 3A , 3B , 3C , -LP ) , three latent membrane proteins ( LMP1 , 2A , 2B ) , and two nuclear RNAs ( EBERs ) are expressed .", "target_text": { "lymphoblastoid cell lines": "cell_line", "EBV-encoded nuclear antigens": "protein", "latent membrane proteins": "protein", "LMP1": "protein", "2A": "protein", "2B": "protein", "nuclear RNAs": "RNA", "EBERs": "RNA" } }, { "input_text": "This form of latency , termed latency III , is also encountered in some posttransplant lymphoproliferative disorders .", "target_text": {} }, { "input_text": "In EBV-positive cases of Hodgkin 's disease , the EBERs , EBNA1 , and the LMPs are expressed ( latency II ) , whereas in Burkitt 's lymphoma ( BL ) only the EBERs and EBNA1 have been detected ( latency I ) .", "target_text": { "EBERs": "RNA", "EBNA1": "protein", "LMPs": "protein" } }, { "input_text": "We have studied the expression of EBV proteins in 17 cases of EBV-positive endemic BL by immunohistology .", "target_text": { "EBV proteins": "protein" } }, { "input_text": "Expression of LMP1 was seen in variable proportions of tumor cells in two cases and EBNA2 was detected in some tumor cells in three other cases .", "target_text": { "LMP1": "protein", "tumor cells": "cell_type", "EBNA2": "protein" } }, { "input_text": "Also , the BZLF1 trans-activator protein was expressed in a few tumor cells in 6 cases , indicating entry into the lytic cycle .", "target_text": { "BZLF1 trans-activator protein": "protein", "tumor cells": "cell_type" } }, { "input_text": "A phenotypic drift from latency I to latency III has been observed previously in some BL cell lines .", "target_text": { "BL cell lines": "cell_line" } }, { "input_text": "Our results suggest that a similar phenomenon may occur in BL in vivo and indicate that the operational definition of EBV latencies is not easily applied to human tumors .", "target_text": {} }, { "input_text": "The activation of the Jak -STAT 1 signaling pathway by IL-5 in eosinophils .", "target_text": { "Jak": "protein", "-STAT 1": "protein", "IL-5": "protein", "eosinophils": "cell_type" } }, { "input_text": "The intracellular signal transduction of IL-5 in eosinophils is unknown .", "target_text": { "IL-5": "protein", "eosinophils": "cell_type" } }, { "input_text": "The objective of this study was to investigate the involvement of the newly discovered Jak -STAT pathway in the IL-5 signal transduction mechanism .", "target_text": { "Jak": "protein", "-STAT": "protein", "IL-5": "protein" } }, { "input_text": "Eosinophils were purified from peripheral blood by discontinuous Percoll gradients and stimulated with IL-5 .", "target_text": { "Eosinophils": "cell_type", "IL-5": "protein" } }, { "input_text": "The involvement of Jak 2 was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation .", "target_text": { "Jak 2": "protein" } }, { "input_text": "The activation of Jak 2 was studied by autophosphorylation of the immunoprecipitated kinase .", "target_text": { "Jak 2": "protein", "immunoprecipitated kinase": "protein" } }, { "input_text": "Jak 2 was tyrosine phosphorylated within 1 to 3 min after stimulation of eosinophils with IL-5 .", "target_text": { "Jak 2": "protein", "eosinophils": "cell_type", "IL-5": "protein" } }, { "input_text": "Further , the immunoprecipitated Jak 2 obtained from IL-5 -stimulated cells underwent autophosphorylation .", "target_text": { "Jak 2": "protein", "immunoprecipitated Jak 2": "protein", "IL-5": "protein", "IL-5 -stimulated cells": "cell_line" } }, { "input_text": "Jak 2 coprecipitated with the beta-subunit of the IL-5 receptor , suggesting a physical association of the kinase with the receptor .", "target_text": { "Jak 2": "protein", "IL-5": "protein", "IL-5 receptor": "protein", "kinase": "protein" } }, { "input_text": "The nuclear factor STAT-1 ( p91 ) was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation .", "target_text": { "nuclear factor STAT-1": "protein", "p91": "protein" } }, { "input_text": "STAT-1 was tyrosine phosphorylated within 15 min of IL-5 stimulation .", "target_text": { "STAT-1": "protein", "IL-5": "protein" } }, { "input_text": "The presence of STAT-1 in the nuclear extract was studied by electrophoretic mobility shift assay .", "target_text": { "STAT-1": "protein" } }, { "input_text": "IL-5 induced two proteins that bound to the gamma-activating sequence .", "target_text": { "IL-5": "protein", "gamma-activating sequence": "DNA" } }, { "input_text": "In the presence of an anti- STAT-1 Ab , the band was supershifted .", "target_text": { "STAT-1": "protein", "anti- STAT-1 Ab": "protein" } }, { "input_text": "Thus , we demonstrated that IL-5 activated the Jak 2 -STAT 1 signaling pathway in eosinophils .", "target_text": { "IL-5": "protein", "Jak 2": "protein", "-STAT 1": "protein", "eosinophils": "cell_type" } }, { "input_text": "We speculate that the Jak 2 -STAT 1 pathway may be involved in the activation of IL-5 -inducible genes in eosinophils .", "target_text": { "Jak 2": "protein", "-STAT 1": "protein", "IL-5": "protein", "IL-5 -inducible genes": "DNA", "eosinophils": "cell_type" } }, { "input_text": "Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer : a prospective longitudinal study .", "target_text": { "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Immunosuppression has been often associated with the course of malignant diseases .", "target_text": {} }, { "input_text": "In the present study , the proliferation of peripheral blood mononuclear cells ( PBMCs ) in response to mitogenic stimulation with phytohaemagglutinin ( PHA ) was assessed prospectively in 90 patients with stage I-III breast cancer .", "target_text": { "peripheral blood mononuclear cells": "cell_type", "PBMCs": "cell_type", "phytohaemagglutinin": "protein", "PHA": "protein" } }, { "input_text": "Whereas PHA -induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals ( P < 0.001 ) , the degree of the defect in PHA -induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement ( P < 0.003 in each case ) .", "target_text": { "PHA": "protein", "PBMCs": "cell_type" } }, { "input_text": "PHA -induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide , methotrexate and fluorouracil ( CMF ) after an observation period of 6 months ( P < 0.01 ) , but not in patients under adjuvant treatment with tamoxifen only .", "target_text": { "PHA": "protein", "PBMCs": "cell_type" } }, { "input_text": "After an additional 6 months ( i.e. 12 months after surgery ) , PHA -induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment ( P > 0.1 ) , but in all patients still significantly decreased as compared with healthy controls ( P < 0.001 ) .", "target_text": { "PHA": "protein", "PBMCs": "cell_type" } }, { "input_text": "When data obtained preoperatively and after 12 months were compared , it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA -induced proliferation , 14 ( 61 % ) had developed metastatic disease within the subsequent 24 months ( i.e. 36 months after surgery ) .", "target_text": { "PBMCs": "cell_type", "PHA": "protein" } }, { "input_text": "In contrast , out of 59 patients whose PBMCs showed an increase in their PHA -induced proliferation within the first 12 months after surgery , only one ( 2 % ) presented with disease progression .", "target_text": { "PBMCs": "cell_type", "PHA": "protein" } }, { "input_text": "We thus conclude that PHA -induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease .", "target_text": { "PHA": "protein", "PBMCs": "cell_type" } }, { "input_text": "Activation of transcription by binding of NF-E1 ( YY1 ) to a newly identified element in the first exon of the human DR alpha gene .", "target_text": { "NF-E1": "protein", "YY1": "protein", "human DR alpha gene": "DNA" } }, { "input_text": "A previously unrecognized element , located downstream of the start site of transcription in the first exon of the DR alpha gene , has been defined that enhances promoter activity up to eightfold in a position-dependent manner .", "target_text": { "start site of transcription": "DNA", "exon": "DNA", "DR alpha gene": "DNA" } }, { "input_text": "Mutations in this DNA-binding site abolished binding of a nuclear factor in human B cell nuclear extract and decreased the activity of the DR alpha promoter to a basal level .", "target_text": { "DNA-binding site": "DNA", "nuclear factor": "protein", "DR alpha promoter": "DNA" } }, { "input_text": "Significant sequence homology of this element was found in the DNA of the DR beta , DP alpha and -beta , and DQ alpha genes , always located downstream of the transcriptional start site .", "target_text": { "element": "DNA", "transcriptional start site": "DNA" } }, { "input_text": "The nuclear factor binds to the DR alpha and DP alpha element but not to the element in the DQ alpha gene .", "target_text": { "DQ alpha gene": "DNA" } }, { "input_text": "It was identified as NF-E1 ( YY1 ) .", "target_text": { "NF-E1": "protein", "YY1": "protein" } }, { "input_text": "This protein , previously identified by its binding to the Ig kappa 3' enhancer and the Ig heavy chain mu E1 site , thus also appears to be quite important in the regulation of MHC class II gene expression .", "target_text": { "Ig kappa 3' enhancer": "DNA", "Ig heavy chain": "protein", "Ig heavy chain mu E1 site": "DNA", "MHC class II gene": "DNA" } }, { "input_text": "Transcriptional activity of core binding factor- alpha ( AML1 ) and beta subunits on murine leukemia virus enhancer cores .", "target_text": { "murine leukemia virus enhancer cores": "DNA" } }, { "input_text": "Core binding factor ( CBF ) , also known as polyomavirus enhancer-binding protein 2 and SL3 enhancer factor 1 , is a mammalian transcription factor that binds to an element termed the core within the enhancers of the murine leukemia virus family of retroviruses .", "target_text": { "Core binding factor": "protein", "CBF": "protein", "polyomavirus enhancer-binding protein 2": "protein", "SL3 enhancer factor 1": "protein", "mammalian transcription factor": "protein", "enhancers": "DNA" } }, { "input_text": "The core elements of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the viral long terminal repeat in T lymphocytes .", "target_text": { "core elements": "DNA", "viral long terminal repeat": "DNA", "T lymphocytes": "cell_type" } }, { "input_text": "CBF consists of two subunits , a DNA binding subunit , CBF alpha , and a second subunit , CBF beta , that stimulates the DNA binding activity of CBF alpha .", "target_text": { "CBF": "protein", "DNA binding subunit": "protein", "CBF alpha": "protein", "CBF beta": "protein" } }, { "input_text": "One of the genes that encodes a CBF alpha subunit is AML1 , also called Cbf alpha 2 .", "target_text": { "CBF alpha": "protein", "CBF alpha subunit": "protein", "AML1": "protein", "Cbf alpha 2": "protein" } }, { "input_text": "This locus is rearranged by chromosomal translocations in human myeloproliferative disorders and leukemias .", "target_text": {} }, { "input_text": "An exogenously expressed Cbf alpha 2 -encoded subunit ( CBF alpha 2-451 ) stimulated transcription from the SL3 enhancer in P19 and HeLa cells .", "target_text": { "Cbf alpha 2": "protein", "Cbf alpha 2 -encoded subunit": "protein", "CBF alpha": "protein", "CBF alpha 2-451": "protein", "SL3 enhancer": "DNA", "P19": "protein", "HeLa cells": "cell_line" } }, { "input_text": "Activity was mediated through the core elements .", "target_text": { "core elements": "DNA" } }, { "input_text": "Three different isoforms of CBF beta were also tested for transcriptional activity on the SL3 enhancer .", "target_text": { "CBF beta": "protein", "SL3 enhancer": "DNA" } }, { "input_text": "The longest form , CBF beta -187 , increased the transcriptional stimulation by CBF alpha 2-451 twofold in HeLa cells , although it had no effect in P19 cells .", "target_text": { "CBF beta": "protein", "CBF beta -187": "protein", "CBF alpha": "protein", "CBF alpha 2-451": "protein", "HeLa cells": "cell_line", "P19": "protein", "P19 cells": "cell_line" } }, { "input_text": "Transcriptional activation by CBF beta required binding to the CBF alpha subunit , as a form of CBF beta that lacked binding ability , CBF beta -148 , failed to increase activity .", "target_text": { "CBF beta": "protein", "CBF alpha": "protein", "CBF alpha subunit": "protein", "CBF beta -148": "protein" } }, { "input_text": "These results indicated that at least in certain cell types , the maximum activity of CBF required both subunits .", "target_text": { "CBF": "protein" } }, { "input_text": "They also provided support for the hypothesis that CBF is a factor in T lymphocytes that is responsible for recognition of the SL3 cores .", "target_text": { "CBF": "protein", "T lymphocytes": "cell_type", "SL3 cores": "DNA" } }, { "input_text": "We also examined whether CBF could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus , Akv .", "target_text": { "CBF": "protein", "enhancer core of SL3": "DNA" } }, { "input_text": "This difference strongly affects transcription in T cells and leukemogenicity of SL3 .", "target_text": { "SL3": "DNA" } }, { "input_text": "However , no combination of CBF alpha and CBF beta subunits that we tested was able to distinguish the 1-bp difference in transcription assays .", "target_text": { "CBF alpha": "protein", "CBF beta": "protein" } }, { "input_text": "Thus , a complete understanding of how T cells recognize the SL3 core remains to be elucidated .", "target_text": { "T cells": "cell_type", "SL3 core": "DNA" } }, { "input_text": "Interleukin ( IL ) -10 inhibits nuclear factor kappa B ( NF kappa B ) activation in human monocytes .", "target_text": { "Interleukin ( IL ) -10": "protein", "nuclear factor kappa B": "protein", "NF kappa B": "protein", "human monocytes": "cell_type" } }, { "input_text": "IL-10 and IL-4 suppress cytokine synthesis by different mechanisms .", "target_text": { "IL-10": "protein", "IL-4": "protein", "cytokine": "protein" } }, { "input_text": "Our previous studies in human monocytes have demonstrated that interleukin ( IL ) -10 inhibits lipopolysaccharide ( LPS ) -stimulated production of inflammatory cytokines , IL-1 beta , IL-6 , IL-8 , and tumor necrosis factor ( TNF ) -alpha by blocking gene transcription .", "target_text": { "human monocytes": "cell_type", "interleukin ( IL ) -10": "protein", "inflammatory cytokines": "protein", "IL-1 beta": "protein", "IL-6": "protein", "IL-8": "protein", "tumor necrosis factor ( TNF ) -alpha": "protein" } }, { "input_text": "Using electrophoretic mobility shift assays ( EMSA ) , we now show that , in monocytes stimulated with LPS or TNF alpha , IL-10 inhibits nuclear stimulation of nuclear factor kappa B ( NF kappa B ) , a transcription factor involved in the expression of inflammatory cytokine genes . Several other transcription factors including NF- IL-6 , AP-1 , AP-2 , GR , CREB , Oct-1 , and Sp-1 are not affected by IL-10 .", "target_text": { "TNF alpha": "protein", "IL-10": "protein", "nuclear factor kappa B": "protein", "NF kappa B": "protein", "transcription factor": "protein", "inflammatory cytokine genes": "DNA", "transcription factors": "protein", "IL-6": "protein", "AP-1": "protein", "AP-2": "protein", "GR": "protein", "CREB": "protein", "Oct-1": "protein", "Sp-1": "protein" } }, { "input_text": "This selective inhibition by IL-10 of NF kappa B activation occurs rapidly and in a dose-dependent manner and correlates well with IL-10 's cytokine synthesis inhibitory activity in terms of both kinetics and dose responsiveness .", "target_text": { "IL-10": "protein", "NF kappa B": "protein", "cytokine": "protein" } }, { "input_text": "Furthermore , compounds such as tosylphenylalanyl chloromethyl ketone and pyrrolidinedithiocarbamate that are known to selectively inhibit NF kappa B activation block cytokine gene transcription in LPS -stimulated monocytes .", "target_text": { "NF kappa B": "protein", "LPS -stimulated monocytes": "cell_line" } }, { "input_text": "Taken together , these results suggest that inhibition of NF kappa B activation may be an important mechanism for IL-10 suppression of cytokine gene transcription in human monocytes .", "target_text": { "NF kappa B": "protein", "IL-10": "protein", "human monocytes": "cell_type" } }, { "input_text": "IL-4 , another cytokine that inhibits cytokine mRNA accumulation in monocytes , shows little inhibitory effect on LPS -induced NF kappa B activation .", "target_text": { "IL-4": "protein", "cytokine": "protein", "cytokine mRNA": "RNA", "monocytes": "cell_type", "NF kappa B": "protein" } }, { "input_text": "Further examination reveals that , unlike IL-10 , IL-4 enhances mRNA degradation and does not suppress cytokine gene transcription .", "target_text": { "IL-10": "protein", "IL-4": "protein", "mRNA": "RNA" } }, { "input_text": "These data indicate that IL-10 and IL-4 inhibit cytokine production by different mechanisms .", "target_text": { "IL-10": "protein", "IL-4": "protein", "cytokine": "protein" } }, { "input_text": "LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha .", "target_text": { "LMP-1": "protein", "NF-kappa B": "protein", "I kappa B alpha": "protein", "inhibitory molecule I kappa B alpha": "protein" } }, { "input_text": "LMP-1 , an Epstein-Barr virus membrane protein expressed during latent infection , has oncogenic properties , as judged from its ability to transform B lymphocytes and rodent fibroblasts .", "target_text": { "LMP-1": "protein", "Epstein-Barr virus membrane protein": "protein", "lymphocytes": "cell_type", "rodent fibroblasts": "cell_type" } }, { "input_text": "LMP-1 induces the expression of bcl2 , an oncogene which protects cells from apoptosis , as well as of genes encoding other proteins involved in cell regulation and growth control .", "target_text": { "LMP-1": "protein", "bcl2": "DNA", "oncogene": "DNA" } }, { "input_text": "The mechanisms by which LMP-1 upregulates these proteins is unknown , but it is plausible that LMP-1 modifies signal transduction pathways that result in the activation of one or more transcription factors that ultimately regulate transcription of oncogenic genes .", "target_text": { "LMP-1": "protein", "transcription factors": "protein", "oncogenic genes": "DNA" } }, { "input_text": "NF-kappa B , a transcription factor controlling the expression of genes involved in cell activation and growth control , has been shown to be activated by LMP-1 .", "target_text": { "NF-kappa B": "protein", "transcription factor": "protein", "genes": "DNA", "LMP-1": "protein" } }, { "input_text": "The mechanism ( s ) regulating this activation remains unknown .", "target_text": {} }, { "input_text": "Our data indicate that increased NF-kappa B DNA binding and functional activity are present in B-lymphoid cells stably or transiently expressing LMP-1 .", "target_text": { "NF-kappa B": "protein", "B-lymphoid cells": "cell_type", "LMP-1": "protein" } }, { "input_text": "I kappa B alpha is selectively modified in LMP-1 -expressing B cells .", "target_text": { "I kappa B alpha": "protein", "LMP-1": "protein", "B cells": "cell_type", "LMP-1 -expressing B cells": "cell_line" } }, { "input_text": "A phosphorylated form of I kappa B alpha and increased protein turnover-degradation correlate with increased NF-kappa B nuclear translocation .", "target_text": { "I kappa B alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "This results in increased transcription of NF-kappa B -dependent-genes , including those encoding p105 and I kappa B alpha ( MAD3 ) .", "target_text": { "NF-kappa B": "protein", "NF-kappa B -dependent-genes": "DNA", "p105": "protein", "I kappa B alpha": "protein", "MAD3": "DNA" } }, { "input_text": "These results indicate that LMP-1 activates NF-kappa B in B-cell lines by targeting I kappa B alpha .", "target_text": { "LMP-1": "protein", "NF-kappa B": "protein", "B-cell lines": "cell_line", "I kappa B alpha": "protein" } }, { "input_text": "Identification of the pathways activated by LMP-1 to result in posttranslational modifications of I kappa B alpha will aid in determining the role of this virus-host cell protein interaction in Epstein-Barr virus -mediated oncogenesis .", "target_text": { "LMP-1": "protein", "I kappa B alpha": "protein" } }, { "input_text": "Identification of human TR2 orphan receptor response element in the transcriptional initiation site of the simian virus 40 major late promoter [ published erratum appears in J Biol Chem 1995 Nov 3 ; 270 ( 44 ) : 26721 ]", "target_text": { "human TR2 orphan receptor": "protein", "human TR2 orphan receptor response element": "DNA", "transcriptional initiation site": "DNA", "simian virus 40 major late promoter": "DNA" } }, { "input_text": "A DNA response element ( TR2RE-SV40 ) for the TR2 orphan receptor , a member of the steroid-thyroid hormone receptor superfamily , has been identified in the simian virus 40 ( SV40 ) +55 region ( nucleotide numbers 368-389 , 5'-GTTAAGGTTCGTAGGTCATGGA-3' ) .", "target_text": { "DNA response element": "DNA", "TR2RE-SV40": "DNA", "TR2 orphan receptor": "protein", "steroid-thyroid hormone receptor superfamily": "protein", "simian virus 40 ( SV40 ) +55 region": "DNA", "nucleotide numbers 368-389": "DNA" } }, { "input_text": "Electrophoretic mobility shift assay , using in vitro translated TR2 orphan receptor with a molecular mass of 67 kilodaltons , showed a specific binding with high affinity ( dissociation constant = 9 nM ) for this DNA sequence .", "target_text": { "TR2 orphan receptor": "protein", "67 kilodaltons": "protein", "DNA sequence": "DNA" } }, { "input_text": "DNA-swap experiments using chloramphenicol acetyl-transferase assay demonstrated that androgen can suppress the transcriptional activities of SV40 early promoter via the interaction between this TR2RE- SV40 and the chimeric receptor AR/TR2/AR with the DNA-binding domain of the TR2 orphan receptor flanked by the N-terminal and androgen-binding domains of the androgen receptor .", "target_text": { "chloramphenicol acetyl-transferase": "protein", "SV40 early promoter": "DNA", "TR2RE- SV40": "DNA", "chimeric receptor AR/TR2/AR": "protein", "DNA-binding domain": "protein", "TR2 orphan receptor": "protein", "androgen receptor": "protein" } }, { "input_text": "In addition , this TR2RE- SV40 can function as a repressor to suppress the transcriptional activities of both SV40 early and late promoters .", "target_text": { "TR2RE- SV40": "DNA" } }, { "input_text": "Together , these data suggest the TR2RE- SV40 may represent the first identified natural DNA response element for the TR2 orphan receptor that may function as a repressor for the SV40 gene expression .", "target_text": { "TR2RE- SV40": "DNA", "DNA response element": "DNA", "TR2 orphan receptor": "protein" } }, { "input_text": "Detection of the chromosome 16 CBF beta-MYH11 fusion transcript in myelomonocytic leukemias .", "target_text": { "chromosome 16": "DNA", "chromosome 16 CBF beta-MYH11 fusion transcript": "RNA" } }, { "input_text": "Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult .", "target_text": {} }, { "input_text": "Characterization of the two genes involved in the inv(16)(p13q22) , CBF beta and MYH11 , has allowed the detection of fusion transcripts by reverse-transcriptase polymerase chain reaction ( RT-PCR ) .", "target_text": { "CBF beta": "DNA", "MYH11": "DNA", "fusion transcripts": "RNA" } }, { "input_text": "We have analyzed CBF beta -MYH11 fusion transcripts by RT-PCR in myelomonocytic leukemias , with or without eosinophilia , to determine whether their presence correlates with morphology .", "target_text": { "CBF beta": "DNA", "-MYH11": "DNA", "CBF beta -MYH11 fusion transcripts": "RNA" } }, { "input_text": "Fifty-three cases ( 11 AML M4Eo ; 1 AML M4 with atypical abnormal eosinophils ( AML M4 \" Eo \" ) ; 29 AML M4 ; 8 AML M5 ; 3 CMML ; and 1 AML M2 with eosinophilia ) were analyzed .", "target_text": { "atypical abnormal eosinophils": "cell_type" } }, { "input_text": "All 11 typical AML M4Eo were CBF beta -MYH11 positive .", "target_text": { "CBF beta": "DNA", "-MYH11": "DNA" } }, { "input_text": "The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype , RT-PCR and fluorescent in situ hybridization ( FISH ) .", "target_text": {} }, { "input_text": "Three of 29 ( 10 % ) AML M4 without abnormal eosinophils were CBF beta -MYH11 positive , 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis ( 2 not tested ) .", "target_text": { "abnormal eosinophils": "cell_type", "CBF beta": "DNA", "-MYH11": "DNA", "chromosome 16": "DNA" } }, { "input_text": "Both cases tested also showed MYH11 genomic rearrangement .", "target_text": { "MYH11": "DNA" } }, { "input_text": "None of the other leukemias were RT-PCR positive .", "target_text": {} }, { "input_text": "Follow-up of three patient showed residual positivity in apparent complete remission .", "target_text": {} }, { "input_text": "These data show that CBF beta -MYH11 fusion transcripts occur not only in the vast majority of typical AML M4Eo , but also in approximately 10 % of AML M4 without eosinophilic abnormalities , a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would suggest .", "target_text": { "CBF beta": "DNA", "-MYH11": "DNA", "CBF beta -MYH11 fusion transcripts": "RNA", "chromosome 16": "DNA" } }, { "input_text": "Taken together with the detection of CBF beta - MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical banding techniques , these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4 , regardless of morphologic features , to allow accurate evaluation of the prognostic importance of this fusion transcript .", "target_text": { "CBF beta": "DNA", "MYH11": "DNA", "MYH11 transcripts": "RNA", "chromosome 16": "DNA", "fusion transcript": "RNA" } }, { "input_text": "HIV-1 Tat potentiates TNF -induced NF-kappa B activation and cytotoxicity by altering the cellular redox state .", "target_text": { "HIV-1 Tat": "protein", "TNF": "protein", "NF-kappa B": "protein" } }, { "input_text": "This study demonstrates that human immunodeficiency virus type 1 ( HIV-1 ) Tat protein amplifies the activity of tumor necrosis factor ( TNF ) , a cytokine that stimulates HIV-1 replication through activation of NF-kappa B .", "target_text": { "human immunodeficiency virus type 1 ( HIV-1 ) Tat protein": "protein", "tumor necrosis factor": "protein", "TNF": "protein", "NF-kappa B": "protein" } }, { "input_text": "In HeLa cells stably transfected with the HIV-1 tat gene ( HeLa-tat cells ) , expression of the Tat protein enhanced both TNF -induced activation of NF-kappa B and TNF -mediated cytotoxicity .", "target_text": { "HeLa cells": "cell_line", "HIV-1 tat gene": "DNA", "HeLa-tat cells": "cell_line", "Tat protein": "protein", "TNF": "protein", "NF-kappa B": "protein" } }, { "input_text": "A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein .", "target_text": { "TNF": "protein", "HeLa cells": "cell_line", "Tat protein": "protein" } }, { "input_text": "TNF -mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates .", "target_text": { "TNF": "protein", "NF-kappa B": "protein" } }, { "input_text": "Therefore , Tat -mediated effects on the cellular redox state were analyzed .", "target_text": { "Tat": "protein" } }, { "input_text": "In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase ( Mn-SOD ) , a mitochondrial enzyme that is part of the cellular defense system against oxidative stress .", "target_text": { "T cells": "cell_type", "HeLa cells": "cell_line", "HIV-1 Tat": "protein", "Mn-dependent superoxide dismutase": "protein", "Mn-SOD": "protein", "mitochondrial enzyme": "protein" } }, { "input_text": "Thus , Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat .", "target_text": { "Mn-SOD": "protein", "Tat": "protein" } }, { "input_text": "Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced : oxidized glutathione .", "target_text": { "Mn-SOD": "protein" } }, { "input_text": "A truncated Tat protein ( Tat1-72 ) , known to transactivate the HIV-1 long terminal repeat ( LTR ) , no longer affected Mn-SOD expression , the cellular redox state or TNF -mediated cytotoxicity .", "target_text": { "Tat": "protein", "Tat protein": "protein", "Tat1-72": "protein", "HIV-1 long terminal repeat": "DNA", "LTR": "DNA", "Mn-SOD": "protein", "TNF": "protein" } }, { "input_text": "Thus , our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione ( GSH ) and the GSH : oxidized GSH ( GSSG ) ratio .", "target_text": { "C-terminal region": "protein", "Tat": "protein", "HIV-1 Tat": "protein", "Mn-SOD": "protein", "GSH": "protein" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "The use of glucocorticoids in acute lymphoblastic leukemia of childhood .", "target_text": {} }, { "input_text": "Molecular , cellular , and clinical considerations .", "target_text": {} }, { "input_text": "Glucocorticoids have been included in almost all treatment regimens for childhood acute lymphoblastic leukemia for decades .", "target_text": {} }, { "input_text": "However , optimal agents , doses , and/or schedules have yet to be defined despite extensive clinical application .", "target_text": {} }, { "input_text": "New data on the pharmacokinetics , pharmacodynamics , and molecular mechanisms of action of glucocorticoids have suggested alternative approaches in ALL .", "target_text": {} }, { "input_text": "These suggest that prolonged , i.e. 28 day , glucocorticoid therapy may be unnecessary as exposure to glucocorticoid induces down-regulation of glucocorticoid receptors .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "Dexamethasone may be superior to prednisone in conventional equi-effective doses .", "target_text": {} }, { "input_text": "Blast sensitivity to glucocorticoids correlates closely with sensitivity to other , putatively non-cross-resisting agents and with outcome after multi-agent therapy , suggesting overlapping mechanisms of action , and focusing attention on the determinants of the threshold for apoptosis .", "target_text": {} }, { "input_text": "Increasing success in the treatment of childhood acute lymphoblastic leukemia has led to increasing awareness of avascular necrosis of bone as a potentially disabling sequela of glucocorticoid therapy , especially in adolescent and young adult patients .", "target_text": {} }, { "input_text": "Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU.1 .", "target_text": { "Epstein-Barr virus nuclear protein 2": "protein", "latent membrane protein 1 promoter": "DNA", "J kappa": "protein", "PU.1": "protein" } }, { "input_text": "Expression of the Epstein-Barr virus ( EBV ) latent membrane protein 1 ( LMP-1 ) oncogene is regulated by the EBV nuclear protein 2 ( EBNA-2 ) transactivator .", "target_text": { "latent membrane protein 1": "protein", "LMP-1": "protein", "Epstein-Barr virus ( EBV ) latent membrane protein 1 ( LMP-1 ) oncogene": "DNA", "EBNA-2": "protein", "EBV nuclear protein 2 ( EBNA-2 ) transactivator": "protein" } }, { "input_text": "EBNA-2 is known to interact with the cellular DNA-binding protein J kappa and is recruited to promoters containing the GTGGGAA J kappa recognition sequence .", "target_text": { "EBNA-2": "protein", "cellular DNA-binding protein": "protein", "J kappa": "protein", "promoters": "DNA", "J kappa recognition sequence": "DNA" } }, { "input_text": "The minimal EBNA-2 -responsive LMP-1 promoter includes one J kappa -binding site , and we now show that mutation of that site , such that J kappa can not bind , reduces EBNA-2 responsiveness by 60 % .", "target_text": { "EBNA-2": "protein", "minimal EBNA-2 -responsive LMP-1 promoter": "DNA", "J kappa": "protein", "J kappa -binding site": "DNA" } }, { "input_text": "To identify other factors which interact with the LMP-1 EBNA-2 response element ( E2RE ) , a -236/-145 minimal E2RE was used as a probe in an electrophoretic mobility shift assay .", "target_text": { "EBNA-2": "protein", "LMP-1 EBNA-2 response element": "DNA", "E2RE": "DNA", "-236/-145 minimal E2RE": "DNA" } }, { "input_text": "The previously characterized factors J kappa , PU.1 , and AML1 bind to the LMP-1 E2RE , along with six other unidentified factors ( LBF2 to LBF7 ) .", "target_text": { "J kappa": "protein", "PU.1": "protein", "AML1": "protein", "LMP-1 E2RE": "DNA", "LBF2": "protein", "LBF7": "protein" } }, { "input_text": "Binding sites were mapped for each factor .", "target_text": {} }, { "input_text": "LBF4 is B- and T-cell specific and recognizes the PU.1 GGAA core sequence as shown by methylation interference .", "target_text": { "LBF4": "protein", "PU.1": "protein", "PU.1 GGAA core sequence": "DNA" } }, { "input_text": "LBF4 has a molecular mass of 105 kDa and is probably unrelated to PU.1 .", "target_text": { "LBF4": "protein", "PU.1": "protein" } }, { "input_text": "LBF2 was found only in epithelial cell lines , whereas LBF3 , LBF5 , LBF6 , and LBF7 were not cell type specific .", "target_text": { "LBF2": "protein", "epithelial cell lines": "cell_line", "LBF3": "protein", "LBF5": "protein", "LBF6": "protein", "LBF7": "protein" } }, { "input_text": "Mutations of the AML1- or LBF4- binding sites had no effect on EBNA-2 transactivation , whereas mutation of the PU.1 -binding site completely eliminated EBNA-2 responses .", "target_text": { "EBNA-2": "protein", "PU.1": "protein", "PU.1 -binding site": "DNA" } }, { "input_text": "A gst- EBNA-2 fusion protein specifically depleted PU.1 from nuclear extracts and bound in vitro translated PU.1 , providing biochemical evidence for a direct EBNA-2 -PU.1 interaction .", "target_text": { "EBNA-2": "protein", "gst- EBNA-2 fusion protein": "protein", "PU.1": "protein", "-PU.1": "protein" } }, { "input_text": "Thus , EBNA-2 transactivation of the LMP-1 promoter is dependent on interaction with at least two distinct sequence-specific DNA-binding proteins , J kappa and PU.1 .", "target_text": { "EBNA-2": "protein", "LMP-1 promoter": "DNA", "DNA-binding proteins": "protein", "J kappa": "protein", "PU.1": "protein" } }, { "input_text": "LBF3 , LBF5 , LBF6 , or LBF7 may also be involved , since their binding sites also contribute to EBNA-2 responsiveness .", "target_text": { "LBF3": "protein", "LBF5": "protein", "LBF6": "protein", "LBF7": "protein", "EBNA-2": "protein" } }, { "input_text": "Lymphocyte glucocorticoid receptor : predictor of sertraline response in adolescent major depressive disorder ( MDD ) .", "target_text": { "Lymphocyte glucocorticoid receptor": "protein" } }, { "input_text": "Major depressive disorder ( MDD ) in adolescents demonstrates resistance to tricyclic antidepressants and absence of hypercortisolemia .", "target_text": {} }, { "input_text": "The efficacy of serotonin reuptake inhibitors ( SRIs ) is uncertain , and response predictors are unavailable .", "target_text": {} }, { "input_text": "Abnormal fast feedback and negative feedback of the hypothalamic-pituitary-adrenal axis implicates a dampened limbic-hippocampal glucocorticoid type II receptor ( GCII ) .", "target_text": { "limbic-hippocampal glucocorticoid type II receptor": "protein", "GCII": "protein" } }, { "input_text": "We hypothesized that lymphocyte GCII is altered in adolescent MDD and could serve as a marker for response to SRIs .", "target_text": { "GCII": "protein", "lymphocyte GCII": "protein" } }, { "input_text": "In an open-label study , adolescents ( n = 20 ) meeting DSM-III-R criteria for MDD showed baseline lymphocyte GCII sites per cell ( sites/cell ) values of 793 +/- 106 versus 2 , 563 +/- 499 ( +/- SEM ) for matched controls ( n = 18 ) ( t = 3.5 ; df = 36 ; p < .001 ) .", "target_text": { "GCII": "protein", "lymphocyte GCII sites": "protein" } }, { "input_text": "GCII was bimodally distributed , with SRI responders differing from nonresponders ( t = 3.9 ; df = 14 ; p < .001 ) .", "target_text": { "GCII": "protein" } }, { "input_text": "GCII accurately classified 90 percent of sertraline responders and 80 percent of nonresponders .", "target_text": { "GCII": "protein" } }, { "input_text": "Only SRI responders showed GCII sites/cell upregulated after 6 weeks of treatment ( t = 2.1 , df = 10 ; p < .05 ) .", "target_text": { "GCII": "protein" } }, { "input_text": "The role of NFATp in cyclosporin A-sensitive tumor necrosis factor -alpha gene transcription .", "target_text": { "NFATp": "protein", "cyclosporin A-sensitive tumor necrosis factor": "protein", "cyclosporin A-sensitive tumor necrosis factor -alpha gene": "DNA" } }, { "input_text": "The tumor necrosis factor-alpha ( TNF alpha ) gene is an immediate early gene in activated T cells , in that it is rapidly induced without a requirement for protein synthesis .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF": "protein", "tumor necrosis factor-alpha ( TNF alpha ) gene": "DNA", "T cells": "cell_type" } }, { "input_text": "Maximal induction of TNF alpha mRNA can be induced by treatment of T cells with calcium ionophores alone , via a calcineurin -dependent process that is blocked by cyclosporin A .", "target_text": { "TNF": "protein", "TNF alpha mRNA": "RNA", "T cells": "cell_type", "calcineurin": "protein" } }, { "input_text": "We have previously identified a promoter element , kappa 3 , that is required for calcium-stimulated , cyclosporin A -sensitive induction of the TNF alpha gene in activated T cells .", "target_text": { "promoter element": "DNA", "kappa 3": "DNA", "TNF": "protein", "TNF alpha gene": "DNA", "T cells": "cell_type" } }, { "input_text": "Here , we demonstrate that the kappa 3 binding factor contains NFATp , a cyclosporin-sensitive DNA-binding protein required for interleukin-2 gene transcription .", "target_text": { "kappa 3": "DNA", "kappa 3 binding factor": "protein", "NFATp": "protein", "cyclosporin-sensitive DNA-binding protein": "protein", "interleukin-2 gene": "DNA" } }, { "input_text": "NFATp binds to two sites within the kappa 3 element , and occupancy of both sites is required for TNF alpha gene induction .", "target_text": { "NFATp": "protein", "kappa 3": "DNA", "kappa 3 element": "DNA", "TNF": "protein" } }, { "input_text": "Thus , although the kappa 3 element has little sequence similarity to other NFATp -binding sites , it appears to function as a cyclosporin-sensitive promoter element in T cells by virtue of its ability to bind NFATp .", "target_text": { "kappa 3": "DNA", "kappa 3 element": "DNA", "NFATp": "protein", "NFATp -binding sites": "DNA", "promoter element": "DNA", "cyclosporin-sensitive promoter element": "DNA", "T cells": "cell_type" } }, { "input_text": "The involvement of NFATp in transcriptional activation of both the interleukin-2 and TNF alpha genes suggests that this factor plays an important role in the coordinate induction of multiple cytokine genes , starting at the earliest stages of T cell activation .", "target_text": { "NFATp": "protein", "interleukin-2": "protein", "TNF alpha": "protein", "TNF alpha genes": "DNA", "cytokine genes": "DNA" } }, { "input_text": "Regulation and specificity of MNDA expression in monocytes , macrophages , and leukemia/B lymphoma cell lines .", "target_text": { "MNDA": "protein", "monocytes": "cell_type", "macrophages": "cell_type", "leukemia/B lymphoma cell lines": "cell_line" } }, { "input_text": "The expression of the human myeloid cell nuclear differentiation antigen ( MNDA ) was observed specifically in cells of the granulocyte-macrophage lineage in our earlier reports .", "target_text": { "human myeloid cell nuclear differentiation antigen": "protein", "MNDA": "protein" } }, { "input_text": "The specificity of MNDA expression for cells in the granulocyte-macrophage lineage was reexamined in cell lines established from patients with Philadelphia chromosome-positive chronic myeloid leukemia .", "target_text": { "MNDA": "protein", "cell lines": "cell_line" } }, { "input_text": "Cell lines that expressed MNDA exhibited myeloid cell features and granulocyte or monocyte differentiation could be induced in vitro , while cell lines exhibiting properties of very early stage cells or multipotential cells did not express MNDA .", "target_text": { "MNDA": "protein", "multipotential cells": "cell_type" } }, { "input_text": "Cells originating from cases of Burkitt 's lymphoma were negative .", "target_text": {} }, { "input_text": "By contrast , three lymphoblastoid cell lines ( immortalized in vitro with Epstein-Barr virus ) were weakly positive and MNDA was up-regulated by interferon-alpha ( IFN-alpha ) treatment .", "target_text": { "lymphoblastoid cell lines": "cell_line", "MNDA": "protein", "interferon-alpha": "protein", "IFN-alpha": "protein" } }, { "input_text": "As we reported previously , MNDA mRNA level in adherent monocytes is elevated by IFN-alpha ; in this study , we further assessed MNDA expression in in vitro monocyte-derived macrophages .", "target_text": { "MNDA": "protein", "MNDA mRNA": "RNA", "monocytes": "cell_type", "IFN-alpha": "protein", "macrophages": "cell_type" } }, { "input_text": "Three additional agents ( endotoxin , phytohemagglutinin , and phorbol ester ) and other conditions that affect function , cytokine production , differentiation , and/or growth of monocytes were examined for their ability to alter MNDA expression .", "target_text": { "phytohemagglutinin": "protein", "cytokine": "protein", "monocytes": "cell_type", "MNDA": "protein" } }, { "input_text": "The results varied with the agent , cell type , and stage of differentiation .", "target_text": {} }, { "input_text": "Changes in MNDA expression occurred slowly ( hours to days ) , suggesting that MNDA could mediate changes realized over a long period .", "target_text": { "MNDA": "protein" } }, { "input_text": "The results also reveal a discordance in certain MNDA positive cells between steady-state levels or changes in levels of protein and mRNA indicating that the regulation of MNDA expression occurs at more than one point .", "target_text": { "MNDA": "protein", "MNDA positive cells": "cell_line", "mRNA": "RNA" } }, { "input_text": "Changes in MNDA expression are consistent with a role in opposing macrophage differentiation and activation of monocytes /macrophages .", "target_text": { "MNDA": "protein", "monocytes": "cell_type", "/macrophages": "cell_type" } }, { "input_text": "DNA-binding studies of the Epstein-Barr virus nuclear antigen 2 ( EBNA-2 ) : evidence for complex formation by latent membrane protein gene promoter-binding proteins in EBNA-2 -positive cell lines .", "target_text": { "Epstein-Barr virus nuclear antigen 2": "protein", "EBNA-2": "protein", "latent membrane protein gene promoter-binding proteins": "protein", "EBNA-2 -positive cell lines": "cell_line" } }, { "input_text": "The Epstein-Barr virus ( EBV ) nuclear antigen 2 ( EBNA-2 ) protein is essential for the immortalization of human primary B cells by EBV .", "target_text": { "Epstein-Barr virus ( EBV ) nuclear antigen 2": "protein", "EBNA-2": "protein", "human primary B cells": "cell_type" } }, { "input_text": "EBNA-2 trans-activates cellular and viral genes like CD23 , c-fgr , latent membrane protein 1 ( LMP1 ) and terminal protein 1 ( TP1 ) .", "target_text": { "EBNA-2": "protein", "CD23": "DNA", "c-fgr": "DNA", "latent membrane protein 1": "protein", "LMP1": "protein", "terminal protein 1": "protein", "TP1": "protein" } }, { "input_text": "Trans-activation of the TP1 promoter and of the BamHI C promoter has already been investigated in detail and appears to be mediated via protein-protein interactions and not by direct binding of EBNA-2 type A ( of EBV type 1 ) to the DNA .", "target_text": { "TP1 promoter": "DNA", "BamHI C promoter": "DNA", "EBNA-2": "protein", "EBNA-2 type A": "protein" } }, { "input_text": "EBNA-2 is able to trans-activate the expression of the LMP gene in several cell lines .", "target_text": { "EBNA-2": "protein", "LMP gene": "DNA" } }, { "input_text": "Various reports have delineated the cis-acting elements of the LMP promoter through which EBNA-2 mediates trans-activation .", "target_text": { "cis-acting elements": "DNA", "LMP promoter": "DNA", "EBNA-2": "protein" } }, { "input_text": "To determine whether EBNA-2 also trans-activates the LMP promoter by protein-protein interactions , we performed a series of gel retardation assays and competition experiments with LMP promoter fragments of different sizes .", "target_text": { "EBNA-2": "protein", "LMP promoter": "DNA", "LMP promoter fragments": "DNA" } }, { "input_text": "We determined that the protein-binding region on the LMP promoter was within a 42 bp fragment encompassing nucleotides -135 to -176 relative to the LMP transcriptional start site .", "target_text": { "protein-binding region": "DNA", "LMP promoter": "DNA", "42 bp fragment": "DNA", "nucleotides -135 to -176": "DNA", "LMP transcriptional start site": "DNA" } }, { "input_text": "None of the DNA fragments investigated indicated interaction of EBNA-2 with the DNA via protein-protein interactions .", "target_text": { "EBNA-2": "protein" } }, { "input_text": "No significant differences between EBNA-2 -positive and EBNA-2 -negative nuclear extracts could be seen in the gel retardation assay under conditions that clearly showed binding of EBNA-2A to the TP1 promoter .", "target_text": { "EBNA-2": "protein", "EBNA-2A": "protein", "TP1 promoter": "DNA" } }, { "input_text": "However , analysis of sucrose gradient fractions in the gel retardation assay provided evidence that the LMP promoter -binding proteins form a complex of higher M(r) in EBNA-2 -positive cell extracts .", "target_text": { "LMP promoter": "DNA", "LMP promoter -binding proteins": "protein", "EBNA-2": "protein", "EBNA-2 -positive cell": "cell_type" } }, { "input_text": "These complexes were destroyed by detergent .", "target_text": {} }, { "input_text": "We deduce from these results that EBNA-2 -positive cells might indeed contain specific complexes bound to the LMP promoter which are , however , too labile to be detected in a standard gel retardation assay .", "target_text": { "EBNA-2": "protein", "EBNA-2 -positive cells": "cell_line", "specific complexes": "protein", "LMP promoter": "DNA" } }, { "input_text": "Simultaneous activation of Ig and Oct-2 synthesis and reduction of surface MHC class II expression by IL-6 .", "target_text": { "Ig": "protein", "Oct-2": "protein", "MHC class II": "protein", "IL-6": "protein" } }, { "input_text": "Terminal differentiation of B cells to plasma cells in vivo is characterized by secretion of Ig and extinction of MHC class II expression on the cell surface .", "target_text": { "B cells": "cell_type", "plasma cells": "cell_type", "Ig": "protein", "MHC class II": "protein" } }, { "input_text": "We show that IL-6 signaling leads to marked increases in the synthesis and secretion of Ig in clonal human B cell lines and newly isolated polyclonal B lymphocytes in vitro .", "target_text": { "IL-6": "protein", "Ig": "protein", "clonal human B cell lines": "cell_line", "isolated polyclonal B lymphocytes": "cell_type" } }, { "input_text": "The IL-6-induced cells resemble plasma cells in ultrastructure and in reduced expression of surface MHC class II .", "target_text": { "IL-6-induced cells": "cell_line", "plasma cells": "cell_type", "surface MHC class II": "protein" } }, { "input_text": "Enhanced Ig synthesis is a result of coordinated transcriptional activation of Ig genes without promoter or isotype specificity , and differential accumulation of the mRNA encoding the secreted form of Ig heavy chain .", "target_text": { "Ig": "protein", "Ig genes": "DNA", "mRNA": "RNA", "Ig heavy chain": "protein" } }, { "input_text": "It is saturable and subject to negative control when IL-6 stimulation is prolonged .", "target_text": { "IL-6": "protein" } }, { "input_text": "Coordinate with temporal changes in Ig synthesis , the DNA-binding activity and the synthesis of the B cell-enriched transcription factor Oct-2 are regulated .", "target_text": { "Ig": "protein", "B cell-enriched transcription factor": "protein", "Oct-2": "protein" } }, { "input_text": "Thus , differentiation of B cells with IL-6 in vitro recapitulates the hallmarks of terminal B differentiation in vivo ; Oct-2 may have a role in this process .", "target_text": { "B cells": "cell_type", "IL-6": "protein", "Oct-2": "protein" } }, { "input_text": "T-cell functional regions of the human IL-3 proximal promoter .", "target_text": { "T-cell functional regions": "DNA", "human IL-3 proximal promoter": "DNA" } }, { "input_text": "The human interleukin-3 ( IL-3 ) gene is expressed almost exclusively in activated T cells .", "target_text": { "IL-3": "protein", "human interleukin-3 ( IL-3 ) gene": "DNA", "T cells": "cell_type" } }, { "input_text": "Its expression is regulated at both the transcriptional and post-transcriptional level .", "target_text": {} }, { "input_text": "We have previously shown that treatment of Jurkat T cells with phytohemaglutinin ( PHA ) and the phorbol ester , PMA , activated transcription initiation from the IL-3 gene .", "target_text": { "T cells": "cell_type", "Jurkat T cells": "cell_line", "phytohemaglutinin": "protein", "PHA": "protein", "IL-3 gene": "DNA" } }, { "input_text": "To define the regions of the gene required for transcription activation , we generated a series of reporter constructs containing different regions of the IL-3 gene 5' and 3' flanking sequences .", "target_text": { "IL-3 gene": "DNA", "IL-3 gene 5' and 3' flanking sequences": "DNA" } }, { "input_text": "Both positive and negative regulatory elements were identified in the proximal 5' flanking region of the IL-3 gene .", "target_text": { "proximal 5' flanking region": "DNA", "IL-3 gene": "DNA" } }, { "input_text": "The promoter region between -173 and -60 contained the strongest activating elements .", "target_text": { "promoter region": "DNA", "-173 and -60": "DNA", "activating elements": "DNA" } }, { "input_text": "The transcription factor AP-1 could bind to this positive activator region of the promoter .", "target_text": { "transcription factor": "protein", "AP-1": "protein" } }, { "input_text": "We also examined the function of the IL-3 CK-1/CK-2 elements that are present in many cytokine genes and found that they acted as a repressor of basal level expression when cloned upstream of a heterologous promoter but were also inducible by PMA /PHA .", "target_text": { "IL-3 CK-1/CK-2 elements": "DNA", "cytokine genes": "DNA", "heterologous promoter": "DNA", "/PHA": "protein" } }, { "input_text": "Expression of the Runt domain -encoding PEBP2 alpha genes in T cells during thymic development .", "target_text": { "Runt domain": "protein", "Runt domain -encoding PEBP2 alpha genes": "DNA", "T cells": "cell_type" } }, { "input_text": "The PEBP2 alpha A and PEBP2 alpha B genes encode the DNA-binding subunit of a murine transcription factor , PEBP2 , which is implicated as a T-cell-specific transcriptional regulator .", "target_text": { "DNA-binding subunit": "protein", "murine transcription factor": "protein", "PEBP2": "protein", "T-cell-specific transcriptional regulator": "protein" } }, { "input_text": "These two related genes share the evolutionarily conserved region encoding the Runt domain .", "target_text": { "Runt domain": "protein" } }, { "input_text": "PEBP2 alpha B is the murine counterpart of human AML1 , which is located at the breakpoints of the 8;21 and 3;21 chromosome translocations associated with acute myeloid leukemia .", "target_text": { "PEBP2": "protein", "PEBP2 alpha B": "protein", "murine counterpart": "protein", "human AML1": "protein" } }, { "input_text": "Northern ( RNA ) blots of various adult mouse tissues revealed that the levels of expression of both genes were most prominent in the thymus .", "target_text": {} }, { "input_text": "Furthermore , transcripts of PEBP2 alpha A and mouse AML1/ PEBP2 alpha B were detected in T lymphocytes in the thymuses from day 16 embryos and newborns , as well as 4-week-old adult mice , by in situ hybridization .", "target_text": { "PEBP2": "protein", "PEBP2 alpha A": "protein", "mouse AML1/ PEBP2 alpha B": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "The expression of the genes persisted in peripheral lymph nodes of adult mice .", "target_text": {} }, { "input_text": "The transcripts were detected in all the CD4- CD8- , CD4+ CD8+ , CD4+ CD8- , and CD4- CD8+ cell populations .", "target_text": {} }, { "input_text": "The results indicated that both genes are expressed in T cells throughout their development , supporting the notion that PEBP2 is a T-cell-specific transcription factor .", "target_text": { "T cells": "cell_type", "PEBP2": "protein", "T-cell-specific transcription factor": "protein" } }, { "input_text": "Transcripts of mouse AML1/ PEBP2 alpha B were also detected in day 12 fetal hematopoietic liver and in the bone marrow cells of newborn mice .", "target_text": { "PEBP2": "protein", "mouse AML1/ PEBP2 alpha B": "protein", "bone marrow cells": "cell_type" } }, { "input_text": "The implication of mouse AML1/ PEBP2 alpha B expression in hematopoietic cells other than those of T-cell lineage is discussed in relation to myeloid leukemogenesis .", "target_text": { "PEBP2": "protein", "AML1/ PEBP2 alpha B": "protein", "hematopoietic cells": "cell_type", "T-cell lineage": "cell_type" } }, { "input_text": "Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells .", "target_text": { "human peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Glucocorticoids have an inhibitory effect on inflammatory and immune responses , and this may be through the modulation of transcription factor binding to DNA .", "target_text": { "transcription factor": "protein" } }, { "input_text": "The interaction of the transcription factors , activator protein-1 ( AP-1 ) , nuclear factor kappa B ( NF kappa B ) , and cAMP-responsive element binding protein ( CREB ) with DNA and glucocorticoid receptors ( GR ) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays .", "target_text": { "transcription factors": "protein", "activator protein-1": "protein", "AP-1": "protein", "nuclear factor kappa B": "protein", "NF kappa B": "protein", "cAMP-responsive element binding protein": "protein", "CREB": "protein", "glucocorticoid receptors": "protein", "GR": "protein", "human peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "TNF-alpha , IL-1 beta and phorbol myristate acetate ( PMA ) treatment increased AP-1 and NF kappa B DNA binding by up to 200 % but decreased CREB binding ( 38 % ) over a 60-min time course .", "target_text": { "AP-1": "protein", "CREB": "protein" } }, { "input_text": "Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50 % decrease in AP-1 , NF kappa B , and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment .", "target_text": { "glucocorticoid response element": "DNA", "cytokine": "protein" } }, { "input_text": "These latter effects were due to increases in the nuclear localization of GR , not to reduced amounts of the other transcription factors .", "target_text": { "GR": "protein", "transcription factors": "protein" } }, { "input_text": "This suggests that in these cells GR within the nucleus interacts with cytokine -stimulated transcription factors by the process of cross coupling .", "target_text": { "GR": "protein", "nucleus": "protein", "cytokine": "protein", "transcription factors": "protein", "cytokine -stimulated transcription factors": "protein" } }, { "input_text": "This may be an important molecular site of steroid action .", "target_text": {} }, { "input_text": "Differential induction of the NF-AT complex during restimulation and the induction of T-cell anergy .", "target_text": { "NF-AT complex": "protein" } }, { "input_text": "Stimulation of human CD4+ T-cell clones through the T-cell receptor ( TcR ) by high doses of specific peptide results in the induction of a long-lived state of nonresponsiveness that has been called anergy .", "target_text": { "human CD4+ T-cell clones": "cell_line", "T-cell receptor": "protein", "TcR": "protein" } }, { "input_text": "During the induction of anergy , T cells are phenotypically similar to cells responding to an immunogenic stimulus .", "target_text": { "T cells": "cell_type" } }, { "input_text": "The amount of TcR at the cell surface is downmodulated , whereas the CD2 and CD25 receptors are increased .", "target_text": { "TcR": "protein" } }, { "input_text": "When restimulated , however , anergic T cells fail to up-regulate transcription of the IL-2 gene and in consequence do not produce IL-2 .", "target_text": { "anergic T cells": "cell_type", "IL-2 gene": "DNA", "IL-2": "protein" } }, { "input_text": "In this study , we have compared the ability of various transcription factors to bind to their appropriate site on DNA .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Factors were isolated from the nuclei of T cells that were in the induction phase of anergy or were undergoing activation .", "target_text": { "T cells": "cell_type" } }, { "input_text": "The pattern of binding activity in restimulated T cells is consistent with the pattern that has previously been shown to regulate T-cell-specific expression of the IL-2 and the beta chain of the TcR genes .", "target_text": { "T cells": "cell_type", "IL-2": "protein", "TcR": "protein", "TcR genes": "DNA" } }, { "input_text": "The measured binding to a TCF-1 site is the same in the nuclei of resting , activated , and anergized cells .", "target_text": { "TCF-1 site": "DNA" } }, { "input_text": "The inducible factors NK-kappa B , beta E2 , CD28RC , and AP-1 are not expressed in resting cells and are twofold lower in anergized as compared with activated cells .", "target_text": { "inducible factors": "protein", "NK-kappa B": "protein", "beta E2": "protein", "CD28RC": "protein", "AP-1": "protein", "resting cells": "cell_type" } }, { "input_text": "In contrast , anergic T cells express approximately eightfold lower amounts of NF-AT , a member of the class of inducible factors that regulates IL-2 gene transcription .", "target_text": { "anergic T cells": "cell_type", "NF-AT": "protein", "inducible factors": "protein", "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "The number of glucocorticoid receptors in peripheral human lymphocytes is elevated by a zinc containing trace element preparation .", "target_text": { "glucocorticoid receptors": "protein", "peripheral human lymphocytes": "cell_type" } }, { "input_text": "A trace element preparation ( Beres Drops Plus , BDP ) elevates the number of glucocorticoid receptors ( gcR ) in peripheral lymphocytes isolated both from healthy blood donors and rheumatoid arthritis patients .", "target_text": { "glucocorticoid receptors": "protein", "gcR": "protein", "peripheral lymphocytes": "cell_type" } }, { "input_text": "This enhancement by BDP was found either for constitutive expression of gcRs or in experiments when the lymphocytes were stimulated by interleukin ( IL ) -6 .", "target_text": { "gcRs": "protein", "lymphocytes": "cell_type", "interleukin ( IL ) -6": "protein" } }, { "input_text": "There was no significant effect of BDP on IL-1 and tumour necrosis factor alpha ( TNF alpha ) -induced changes of gcRs .", "target_text": { "IL-1": "protein", "tumour necrosis factor alpha": "protein", "TNF alpha": "protein", "gcRs": "protein" } }, { "input_text": "The effect of BDP was greatly dependent on the presence of Zn++ ions in the preparation , since the augmenting effect was abolished if BDP did not contain zinc .", "target_text": {} }, { "input_text": "The DNA and steroid binding domains of the glucocorticoid receptor are not altered in mononuclear cells of treated CLL patients .", "target_text": { "steroid binding domains": "protein", "glucocorticoid receptor": "protein", "mononuclear cells": "cell_type" } }, { "input_text": "The aim of this study was to investigate whether mutations in the glucocorticoid receptor could account for the increasing unresponsiveness of patients with chronic lymphatic leukemia ( CLL ) to combination chemotherapy .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "The receptor was tested immunocytochemically , in steroid binding assays , and by a mutation screening ( denaturing gradient gel electrophoresis ) of the receptor-cDNA .", "target_text": { "receptor-cDNA": "protein" } }, { "input_text": "The receptor concentration , as measured by staining and steroid binding test , varied considerably but showed no clear correlation to clinical response .", "target_text": {} }, { "input_text": "Using a highly sensitive mutation screening assay of the DNA- and the steroid -binding region , none of the treated patients revealed any mutation , suggesting that the glucocorticoid receptor in the CLL patients tested is not altered in these domains .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "In one individual who had not been treated before analysis a silent mutation was found in one receptor allele .", "target_text": {} }, { "input_text": "The results suggest that mechanisms other than altered ligand or DNA binding of the receptor may be responsible for the lack of response to chemotherapy .", "target_text": {} }, { "input_text": "This conclusion is discussed in relation to the mechanism of corticoid resistance in mouse and human lymphoma cells in culture .", "target_text": {} }, { "input_text": "An AP1 binding site upstream of the kappa immunoglobulin intron enhancer binds inducible factors and contributes to expression .", "target_text": { "AP1 binding site": "DNA", "kappa immunoglobulin intron enhancer": "DNA", "inducible factors": "protein" } }, { "input_text": "Expression of the kappa immunoglobulin light chain gene requires developmental- and tissue-specific regulation by trans-acting factors which interact with two distinct enhancer elements .", "target_text": { "kappa immunoglobulin light chain gene": "DNA", "trans-acting factors": "protein", "enhancer elements": "DNA" } }, { "input_text": "A new protein-DNA interaction has been identified upstream of the intron enhancer , within the matrix-associated region of the J-C intron .", "target_text": { "intron enhancer": "DNA", "matrix-associated region": "DNA", "J-C intron": "DNA" } }, { "input_text": "The binding activity is greatly inducible in pre-B cells by bacterial lipopolysaccharide and interleukin-1 but specific complexes are found at all stages of B cell development tested .", "target_text": { "pre-B cells": "cell_type", "interleukin-1": "protein" } }, { "input_text": "The footprinted binding site is homologous to the consensus AP1 motif .", "target_text": { "footprinted binding site": "DNA", "consensus AP1 motif": "DNA" } }, { "input_text": "The protein components of this complex are specifically competed by an AP1 consensus motif and were shown by supershift to include c-Jun and c-Fos , suggesting that this binding site is an AP1 motif and that the Jun and Fos families of transcription factors play a role in the regulation of the kappa light chain gene .", "target_text": { "AP1 consensus motif": "DNA", "c-Jun": "protein", "c-Fos": "protein", "binding site": "DNA", "AP1 motif": "DNA", "transcription factors": "protein", "kappa light chain gene": "DNA" } }, { "input_text": "Mutation of the AP1 motif in the context of the intron enhancer was shown to decrease enhancer-mediated activation of the promoter in both pre-B cells induced with LPS and constitutive expression in mature B cells .", "target_text": { "AP1 motif": "DNA", "intron enhancer": "DNA", "pre-B cells": "cell_type", "mature B cells": "cell_type" } }, { "input_text": "Distinct DNase-I hypersensitive sites are associated with TAL-1 transcription in erythroid and T- cell lines .", "target_text": { "DNase-I hypersensitive sites": "DNA", "TAL-1": "protein" } }, { "input_text": "The tal-1 gene , frequently activated in human T-cell acute lymphoblastic leukemia ( T-ALL ) , is expressed in the erythroid , megakaryocytic , and mast cell lineages during normal hematopoiesis .", "target_text": { "tal-1 gene": "DNA" } }, { "input_text": "To gain further insight into the molecular mechanisms that control tal-1 expression , we investigated tal-1 chromatin structure in erythroid/megakaryocytic cell lines and in T-cell lines either with or without tal-1 rearrangements .", "target_text": { "tal-1": "DNA", "tal-1 chromatin structure": "DNA", "erythroid/megakaryocytic cell lines": "cell_line", "T-cell lines": "cell_line", "tal-1 rearrangements": "DNA" } }, { "input_text": "Tal-1 transcription was shown to be monoallelic in Jurkat , a T-cell line that expresses tal-1 in the absence of apparent genomic alteration of the locus .", "target_text": { "Jurkat": "cell_line", "tal-1": "DNA" } }, { "input_text": "Methylation studies indicated that the tal-15 ' GC-rich region behaves like a CpG island , hypomethylated in normal cells , and methylated de novo on transcriptionally inactive alleles in established cell lines .", "target_text": { "tal-15 ' GC-rich region": "DNA", "CpG island": "DNA", "normal cells": "cell_type", "transcriptionally inactive alleles": "DNA", "established cell lines": "cell_line" } }, { "input_text": "Five major DNase-I hypersensitive sites ( HS ) were mapped in the tal-1 locus .", "target_text": { "DNase-I hypersensitive sites": "DNA", "HS": "DNA", "tal-1": "DNA" } }, { "input_text": "HS I , IV , and V were exclusively observed in the erythroid/megakaryocytic cell lines that express tal-1 from the promoters 1a and 1b .", "target_text": { "erythroid/megakaryocytic cell lines": "cell_line", "tal-1": "DNA" } }, { "input_text": "HS II was weak in hematopoietic cell lines , absent in Hela , and greatly enhanced in Jurkat , suggesting that this region might be implicated in the cis-activation of tal-1 promoter 1b in this cell line .", "target_text": { "HS II": "DNA", "hematopoietic cell lines": "cell_line", "Hela": "cell_line", "Jurkat": "cell_line", "tal-1": "DNA", "tal-1 promoter 1b": "DNA" } }, { "input_text": "HS III was weak in HEL and Jurkat , and greatly enhanced in DU528 , a T-cell line that bears a t (1;14) and initiates tal-1 transcription within exon 4 .", "target_text": { "HS III": "DNA", "HEL": "cell_line", "Jurkat": "cell_line", "DU528": "cell_line", "T-cell line": "cell_line", "a t (1;14)": "DNA", "tal-1": "DNA", "exon 4": "DNA" } }, { "input_text": "These results suggest that distinct regulatory elements are associated with the use of the different tal-1 promoters .", "target_text": { "regulatory elements": "DNA", "tal-1": "DNA", "tal-1 promoters": "DNA" } }, { "input_text": "Erythropoietin -dependent induction of hemoglobin synthesis in a cytokine -dependent cell line M-TAT .", "target_text": { "Erythropoietin": "protein", "hemoglobin": "protein", "cytokine": "protein", "cytokine -dependent cell line": "cell_line", "M-TAT": "cell_line" } }, { "input_text": "M-TAT is a cytokine -dependent cell line with the potential to differentiate along the erythroid and megakaryocytic lineages .", "target_text": { "M-TAT": "cell_line", "cytokine": "protein", "cytokine -dependent cell line": "cell_line" } }, { "input_text": "We cultured M-TAT cells long term ( > 1 year ) in the continuous presence of erythropoietin ( EPO ) , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , or stem cell factor ( SCF ) .", "target_text": { "M-TAT cells": "cell_line", "erythropoietin": "protein", "EPO": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "stem cell factor": "protein", "SCF": "protein" } }, { "input_text": "These long term cultures are referred to as M-TAT/EPO , M-TAT/GM-CSF , and M-TAT/SCF cells , respectively .", "target_text": {} }, { "input_text": "Hemoglobin concentration and gamma-globin and erythroid delta-aminolevulinate synthase mRNA levels were significantly higher in M-TAT/EPO cells than in M-TAT/GM-CSF cells .", "target_text": { "Hemoglobin": "protein", "gamma-globin": "protein", "erythroid delta-aminolevulinate synthase": "protein", "erythroid delta-aminolevulinate synthase mRNA": "RNA", "M-TAT/EPO cells": "cell_line", "M-TAT/GM-CSF cells": "cell_line" } }, { "input_text": "When the supplemented cytokine was switched from GM-CSF to EPO , hemoglobin synthesis in M-TAT/GM-CSF cells increased rapidly ( within 5 h ) , and the level of GATA-1 mRNA increased .", "target_text": { "cytokine": "protein", "GM-CSF": "protein", "EPO": "protein", "hemoglobin": "protein", "M-TAT/GM-CSF cells": "cell_line", "GATA-1 mRNA": "RNA" } }, { "input_text": "In contrast , the addition of GM-CSF to the M-TAT/EPO cell culture decreased the amount of hemoglobin , even in the presence of EPO , indicating that the EPO signal for erythroid differentiation is suppressed by GM-CSF .", "target_text": { "GM-CSF": "protein", "M-TAT/EPO cell culture": "cell_line", "EPO": "protein" } }, { "input_text": "Thus , erythroid development of M-TAT cells is promoted by EPO and suppressed by GM-CSF .", "target_text": { "M-TAT cells": "cell_line", "EPO": "protein", "GM-CSF": "protein" } }, { "input_text": "These results support the hypothesis that EPO actively influences the programming of gene expression required for erythroid progenitor cell differentiation .", "target_text": { "EPO": "protein", "erythroid progenitor cell": "cell_type" } }, { "input_text": "The role of cellular transcription factor E2F in the regulation of cdc2 mRNA expression and cell cycle control of human hematopoietic cells .", "target_text": { "transcription factor": "protein", "cellular transcription factor E2F": "protein", "cdc2 mRNA": "RNA", "hematopoietic cells": "cell_type" } }, { "input_text": "cdc2 mRNA transcripts were detected in immature bone marrow cells and became undetectable along with differentiation .", "target_text": { "cdc2 mRNA": "RNA", "cdc2 mRNA transcripts": "RNA", "immature bone marrow cells": "cell_type" } }, { "input_text": "Peripheral blood resting cells did not express cdc2 mRNA , but it was induced in T-lymphocytes when the cells reentered the cell cycle in response to specific mitogens .", "target_text": { "resting cells": "cell_type", "Peripheral blood resting cells": "cell_type", "cdc2 mRNA": "RNA", "T-lymphocytes": "cell_type" } }, { "input_text": "In contrast , cdc2 mRNA could not be induced in granulocytes and monocytes even after the culture with the appropriate stimulants .", "target_text": { "cdc2 mRNA": "RNA", "granulocytes": "cell_type", "monocytes": "cell_type" } }, { "input_text": "In order to investigate the mechanism of the regulation of cdc2 mRNA expression in hematopoietic cells , we isolated the 5'-flanking sequence of the cdc2 gene and found the putative E2F binding site at the position of nucleotides -124 to -117 .", "target_text": { "cdc2 mRNA": "RNA", "hematopoietic cells": "cell_type", "5'-flanking sequence": "DNA", "cdc2 gene": "DNA", "binding site": "DNA", "nucleotides -124 to -117": "DNA" } }, { "input_text": "The binding of E2F at this region was detected by a gel-retardation assay and DNaseI footprinting in phytohemagglutinin -stimulated T-lymphocytes , which was coincident with the expression of cdc2 mRNA .", "target_text": { "E2F": "protein", "DNaseI": "protein", "phytohemagglutinin": "protein", "T-lymphocytes": "cell_type", "phytohemagglutinin -stimulated T-lymphocytes": "cell_line", "cdc2 mRNA": "RNA" } }, { "input_text": "E2F binding was not observed in both granulocytes and monocytes .", "target_text": { "E2F": "protein", "granulocytes": "cell_type", "monocytes": "cell_type" } }, { "input_text": "Transient chloramphenicol acetyltransferase assay revealed that the region containing E2F binding site had a strong promoter activity , and introduction of the mutation at the E2F binding site resulted in a significant loss of the activity .", "target_text": { "chloramphenicol acetyltransferase": "protein", "E2F": "protein", "E2F binding site": "DNA" } }, { "input_text": "E2F-1 and DP-1 mRNAs were not detectable in granulocytes , monocytes and resting T-lymphocytes but were induced after the mitogenic stimulation of T-lymphocytes .", "target_text": { "granulocytes": "cell_type", "monocytes": "cell_type", "resting T-lymphocytes": "cell_type", "T-lymphocytes": "cell_type" } }, { "input_text": "The induction of E2F activity preceded the appearance of cdc2 mRNA , which is consistent with the role of E2F in the regulation of cdc2 mRNA expression .", "target_text": { "E2F": "protein", "cdc2 mRNA": "RNA", "cdc2 mRNA expression": "cell_type" } }, { "input_text": "These results suggest that cdc2 mRNA expression is related to the cell cycling of normal human hematopoietic cells and that E2F plays some roles in the regulation of its expression .", "target_text": { "cdc2 mRNA": "RNA", "hematopoietic cells": "cell_type", "normal human hematopoietic cells": "cell_type", "E2F": "protein" } }, { "input_text": "Association of alterations in NF-kappa B moieties with HIV type 1 proviral latency in certain monocytic cells .", "target_text": { "NF-kappa B moieties": "protein", "monocytic cells": "cell_type" } }, { "input_text": "Human immunodeficiency virus type 1 ( HIV-1 ) replication is controlled by a complex array of virally encoded and cellular proteins .", "target_text": {} }, { "input_text": "A wide spectrum of levels of HIV-1 expression have been demonstrated in various cells , both in cell culture and in vivo .", "target_text": {} }, { "input_text": "Molecular mechanisms leading to restricted HIV-1 replication may differ between certain cell types .", "target_text": {} }, { "input_text": "It is now demonstrated that HIV-1 proviral latency in the monocytic cell line U1 , in which only extremely low levels of HIV-1 expression are detected in the baseline unstimulated state , is associated with alterations in nuclear factor-kappa B ( NF-kappa B ) moieties demonstrated in these cells by electrophoretic mobility shift assays ( EMSAs ) and in situ UV cross-linking studies .", "target_text": { "monocytic cell line U1": "cell_line", "NF-kappa B": "protein", "factor-kappa B ( NF-kappa B ) moieties": "protein" } }, { "input_text": "A predominance of p50 NF-kappa B moieties and possibly p50 homodimers or closely related species , rather than the p50-p56 heterodimer of NF-kappa B that is the predominant NF-kappa B species in most T lymphocytic and monocytic cells , is demonstrated in the nuclei of U1 cells .", "target_text": { "NF-kappa B moieties": "protein", "p50 NF-kappa B moieties": "protein", "p50 homodimers": "protein", "p50-p56 heterodimer": "protein", "NF-kappa B": "protein", "U1 cells": "cell_line" } }, { "input_text": "This pattern of NF-kappa B-related moieties differs from the latently infected T lymphocytic cell line ACH-2 , and from the U937 monocytic line , the parental cell line of the U1 cellular clone .", "target_text": { "NF-kappa B-related moieties": "protein", "latently infected T lymphocytic cell line ACH-2": "cell_line", "U937 monocytic line": "cell_line", "parental cell line": "cell_line", "U1 cellular clone": "cell_line" } }, { "input_text": "As such , these data suggest that different proximal mechanisms may lead to restricted HIV-1 replication in various cell types .", "target_text": {} }, { "input_text": "[ Regulation of transcription of the interleukin-2 gene in B-lymphocytes ]", "target_text": { "interleukin-2": "protein", "interleukin-2 gene": "DNA", "B-lymphocytes": "cell_type" } }, { "input_text": "Since most B cell clones immortalized with EBV virus can be induced to produce interleukin-2 , a typical T cell cytokine , we studied the role of different elements of the IL-2 promoter in such clones by transfection .", "target_text": { "B cell clones": "cell_line", "interleukin-2": "protein", "T cell cytokine": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "It was found , in particular , that the element TCEd , which binds the transcription factor NF-kB , is very active in all three B clones tested .", "target_text": { "TCEd": "DNA", "transcription factor": "protein", "NF-kB": "protein", "B clones": "cell_line" } }, { "input_text": "This element has no activity in T cells of the Jurkat line .", "target_text": { "T cells": "cell_type", "Jurkat line": "cell_line" } }, { "input_text": "The NFATd element , which binds the transcription factor NFAT-1 and is very active in T cells , is only weakly active in one B clone and not at all in another .", "target_text": { "NFATd element": "DNA", "transcription factor": "protein", "NFAT-1": "protein", "T cells": "cell_type", "B clone": "cell_line" } }, { "input_text": "Different elements thus contribute to IL-2 promoter activity in different cells .", "target_text": { "IL-2 promoter": "DNA" } }, { "input_text": "Regulation of I kappa B alpha and p105 in monocytes and macrophages persistently infected with human immunodeficiency virus .", "target_text": { "I kappa B alpha": "protein", "p105": "protein", "monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "The mechanisms regulating human immunodeficiency virus ( HIV ) persistence in human monocytes /macrophages are partially understood .", "target_text": { "monocytes": "cell_type", "/macrophages": "cell_type" } }, { "input_text": "Persistent HIV infection of U937 monocytic cells results in NF-kappa B activation .", "target_text": { "U937 monocytic cells": "cell_line", "NF-kappa B": "protein" } }, { "input_text": "Whether virus-induced NF-kappa B activation is a mechanism that favors continuous viral replication in macrophages remains unknown .", "target_text": { "NF-kappa B": "protein", "macrophages": "cell_type" } }, { "input_text": "To further delineate the molecular mechanisms involved in the activation of NF-kappa B in HIV -infected monocytes and macrophages , we have focused on the regulation of the I kappa B molecules .", "target_text": { "NF-kappa B": "protein", "monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "First , we show that persistent HIV infection results in the activation of NF-kappa B not only in monocytic cells but also in macrophages .", "target_text": { "macrophages": "cell_type" } }, { "input_text": "In HIV -infected cells , I kappa B alpha protein levels are decreased secondary to enhanced protein degradation .", "target_text": { "I kappa B alpha": "protein" } }, { "input_text": "This parallels the increased I kappa B alpha synthesis secondary to increased I kappa B alpha gene transcription , i.e. , increased RNA and transcriptional activity of its promoter-enhancer .", "target_text": { "I kappa B alpha": "protein" } }, { "input_text": "Another protein with I kappa B function , p105 , is also modified in HIV -infected cells : p105 and p50 steady-state protein levels are increased as a result of increased synthesis and proteolytic processing of p105 .", "target_text": { "p105": "protein", "p50": "protein" } }, { "input_text": "Transcriptional activity of p105 is also increased in infected cells and is also mediated by NF-kappa B through a specific kappa B motif .", "target_text": { "p105": "protein", "infected cells": "cell_type", "NF-kappa B": "protein", "kappa B motif": "DNA" } }, { "input_text": "These results demonstrate the existence of a triple autoregulatory loop in monocytes and macrophages involving HIV , p105 and p50 , and MAD3 , with the end result of persistent NF-kappa B activation and viral persistence .", "target_text": { "autoregulatory loop": "DNA", "monocytes": "cell_type", "macrophages": "cell_type", "p105": "protein", "p50": "protein", "MAD3": "protein", "NF-kappa B": "protein" } }, { "input_text": "Furthermore , persistent HIV infection of monocytes and macrophages provides a useful model with which to study concomitant modifications of different I kappa B molecules .", "target_text": { "monocytes": "cell_type", "macrophages": "cell_type", "I kappa B molecules": "protein" } }, { "input_text": "Glucocorticoid -induced apoptosis of human leukemic cells is caused by the repressive function of the glucocorticoid receptor .", "target_text": { "human leukemic cells": "cell_type", "glucocorticoid receptor": "protein" } }, { "input_text": "Induction of apoptosis in lymphocytes , which may account for the therapeutic effects of glucocorticoids in various diseases including leukemia , depends on the glucocorticoid receptor .", "target_text": { "lymphocytes": "cell_type", "glucocorticoid receptor": "protein" } }, { "input_text": "However , the events leading from the activated receptor to cell lysis are not understood .", "target_text": {} }, { "input_text": "A prevailing hypothesis postulates induction of so-called ' lysis genes ' by the activated receptor .", "target_text": { "lysis genes": "DNA", "activated receptor": "protein" } }, { "input_text": "In this study , we show that an activation-deficient glucocorticoid receptor mutant is as effective as the wild-type receptor in repression of AP-1 activity , inhibition of interleukin-2 production , inhibition of c-myc expression and induction of apoptosis .", "target_text": { "glucocorticoid receptor": "protein", "activation-deficient glucocorticoid receptor mutant": "protein", "wild-type receptor": "protein", "AP-1": "protein", "interleukin-2": "protein", "c-myc": "DNA" } }, { "input_text": "Furthermore , we show that retinoic acid can also induce apoptosis in these cells through the retinoic acid receptor , whose repressive functions but not target site specificity , are similar to those of the glucocorticoid receptor .", "target_text": { "retinoic acid receptor": "protein", "glucocorticoid receptor": "protein" } }, { "input_text": "Therefore , the primary effect of the receptor in glucocorticoid -mediated apoptosis correlates with transcriptional repression rather than activation and could be mediated by interference with other transcription factors required for cell survival .", "target_text": { "transcription factors": "protein" } }, { "input_text": "HIV type 1 protease activation of NF-kappa B within T lymphoid cells .", "target_text": { "protease": "protein", "NF-kappa B": "protein", "T lymphoid cells": "cell_type" } }, { "input_text": "NF-kappa B is a nuclear protein of the rel oncogene family capable of enhancing transcription of several cellular genes , including IL-2 and the IL-2 receptor , and viral genes transcribed from the HIV-1 LTR .", "target_text": { "NF-kappa B": "protein", "nuclear protein": "protein", "rel oncogene family": "protein", "several cellular genes": "DNA", "IL-2": "protein", "IL-2 receptor": "protein", "viral genes": "DNA", "HIV-1 LTR": "DNA" } }, { "input_text": "It has been reported that HIV-1 protease may cleave the NF-kappa B precursor to its active form in vitro .", "target_text": { "HIV-1 protease": "protein", "NF-kappa B": "protein" } }, { "input_text": "In this study the effects of HIV protease on NF-kappa B precursor activation were examined in Jurkat T cells by introducing a protease expression vector into the cells .", "target_text": { "NF-kappa B": "protein", "T cells": "cell_type", "protease expression vector": "DNA" } }, { "input_text": "Increased NF-kappa B activity was observed and this increased activity was blocked by a specific inhibitor of the viral protease .", "target_text": { "NF-kappa B": "protein", "viral protease": "protein" } }, { "input_text": "Viral transcription , as measured using LTR -CAT assays , was only slightly enhanced in the HIV-protease expressing cells , while secretion of IL-2 and expression of the IL-2 receptor were not affected .", "target_text": { "LTR": "DNA", "-CAT": "protein", "HIV-protease expressing cells": "cell_type", "IL-2": "protein" } }, { "input_text": "The limited activation of NF-kappa B by HIV protease appears unlikely to have a significant effect on virus expression or T cell function .", "target_text": { "NF-kappa B": "protein", "HIV protease": "protein" } }, { "input_text": "Inhibition of human immunodeficiency virus type 1 replication by a Tat-activated , transduced interferon gene : targeted expression to human immunodeficiency virus type 1 -infected cells .", "target_text": { "Tat-activated , transduced interferon gene": "DNA", "human immunodeficiency virus type 1 -infected cells": "cell_type" } }, { "input_text": "We have examined the feasibility of using interferon ( IFN ) gene transfer as a novel approach to anti- human immunodeficiency virus type 1 ( HIV-1 ) therapy in this study .", "target_text": { "interferon": "protein", "IFN": "protein" } }, { "input_text": "To limit expression of a transduced HIV-1 long terminal repeat ( LTR ) -IFNA2 ( the new approved nomenclature for IFN genes is used throughout this article ) hybrid gene to the HIV-1-infected cells , HIV-1 LTR was modified .", "target_text": { "HIV-1 long terminal repeat ( LTR ) -IFNA2": "DNA", "IFN genes": "DNA", "hybrid gene": "DNA", "HIV-1-infected cells": "cell_line", "HIV-1 LTR": "DNA" } }, { "input_text": "Deletion of the NF-kappa B elements of the HIV-1 LTR significantly inhibited Tat -mediated transactivation in T-cell lines , as well as in a monocyte line , U937 .", "target_text": { "NF-kappa B": "protein", "NF-kappa B elements": "DNA", "HIV-1 LTR": "DNA", "Tat": "protein", "T-cell lines": "cell_line", "monocyte line": "cell_line", "U937": "cell_line" } }, { "input_text": "Replacement of the NF-kappa B elements in the HIV-1 LTR by a DNA fragment derived from the 5'-flanking region of IFN-stimulated gene 15 ( ISG15 ) , containing the IFN-stimulated response element , partially restored Tat -mediated activation of LTR in T cells as well as in monocytes .", "target_text": { "NF-kappa B": "protein", "NF-kappa B elements": "DNA", "HIV-1 LTR": "DNA", "DNA fragment": "DNA", "5'-flanking region": "DNA", "IFN-stimulated gene 15": "DNA", "ISG15": "DNA", "IFN-stimulated response element": "DNA", "Tat": "protein", "LTR": "DNA", "T cells": "cell_type", "monocytes": "cell_type" } }, { "input_text": "Insertion of this chimeric promoter ( ISG15 LTR ) upstream of the human IFNA2 gene directed high levels of IFN synthesis in Tat-expressing cells , while this promoter was not responsive to tumor necrosis factor alpha -mediated activation .", "target_text": { "chimeric promoter": "DNA", "ISG15 LTR": "DNA", "human IFNA2 gene": "DNA", "IFN": "protein", "Tat-expressing cells": "cell_line", "tumor necrosis factor alpha": "protein" } }, { "input_text": "ISG15-LTR-IFN hybrid gene inserted into the retrovirus vector was transduced into Jurkat and U937 cells .", "target_text": { "ISG15-LTR-IFN hybrid gene": "DNA", "retrovirus vector": "DNA", "Jurkat": "cell_line", "U937 cells": "cell_line" } }, { "input_text": "Selected transfected clones produced low levels of IFN A ( IFNA ) constitutively , and their abilities to express interleukin-2 and interleukin-2 receptor upon stimulation with phytohemagglutinin and phorbol myristate acetate were retained .", "target_text": { "transfected clones": "cell_line", "IFN A": "protein", "IFNA": "protein", "interleukin-2": "protein", "interleukin-2 receptor": "protein", "phytohemagglutinin": "protein" } }, { "input_text": "Enhancement of IFNA synthesis observed upon HIV-1 infection resulted in significant inhibition of HIV-1 replication for a period of at least 30 days .", "target_text": { "IFNA": "protein" } }, { "input_text": "Virus isolated from IFNA -producing cells was able to replicate in the U937 cells but did not replicate efficiently in U937 cells transduced with the IFNA gene .", "target_text": { "IFNA": "protein", "IFNA -producing cells": "cell_line", "U937 cells": "cell_line", "IFNA gene": "DNA" } }, { "input_text": "These results suggest that targeting IFN synthesis to HIV-1 -infected cells is an attainable goal and that autocrine IFN synthesis results in a long-lasting and permanent suppression of HIV-1 replication .", "target_text": { "IFN": "protein", "HIV-1 -infected cells": "cell_line" } }, { "input_text": "Chromosomal localization of two KOX zinc finger genes on chromosome bands 7q21-q22 .", "target_text": { "KOX zinc finger genes": "DNA", "chromosome bands": "DNA", "7q21-q22": "DNA" } }, { "input_text": "Human cDNAs encoding Kruppel-type zinc finger domains , designated KOX 1-32 , have been cloned from human T lymphocyte cell line libraries .", "target_text": { "Human cDNAs": "DNA", "Kruppel-type zinc finger domains": "protein", "KOX 1-32": "DNA", "human T lymphocyte cell line": "cell_line", "human T lymphocyte cell line libraries": "DNA" } }, { "input_text": "We report here the regional localizations by in situ hybridization of KOX 18 and KOX 25 on chromosome bands 7q21q22 .", "target_text": { "KOX 18": "DNA", "KOX 25": "DNA", "chromosome bands 7q21q22": "DNA" } }, { "input_text": "Pulse-field gel electrophoresis ( PFGE ) analysis showed that these genes are physically located within a DNA fragment of 250 kb .", "target_text": { "DNA fragment": "DNA", "250 kb": "DNA" } }, { "input_text": "The genes KOX 4 and KOX 9 , mapped on chromosome 8q24 , were found to be located within a DNA fragment of 450 kb .", "target_text": { "KOX 4": "DNA", "KOX 9": "DNA", "chromosome 8q24": "DNA", "DNA fragment": "DNA" } }, { "input_text": "From the present and previous data , eighteen different KOX genes have been located at least two by two within nine DNA fragments of 200 to 580 kb .", "target_text": { "KOX genes": "DNA", "DNA fragments": "DNA" } }, { "input_text": "Influence of age on the production of Fos and Jun by influenza virus-exposed T cells .", "target_text": { "Fos": "protein", "Jun": "protein", "T cells": "cell_type", "influenza virus-exposed T cells": "cell_type" } }, { "input_text": "This study investigated age-related T cell responses after in vitro exposure to influenza A virus .", "target_text": {} }, { "input_text": "Mononuclear leukocytes from young or elderly persons were sham-exposed or exposed to influenza virus for 1 , 24 , and 72 h .", "target_text": { "Mononuclear leukocytes": "cell_type" } }, { "input_text": "Immunofluorescent staining and flow cytometric analysis were then used to detect T cells producing the transcriptional regulating proteins Fos and Jun .", "target_text": { "T cells": "cell_type", "transcriptional regulating proteins": "protein", "Fos": "protein", "Jun": "protein" } }, { "input_text": "Fewer virus-exposed cells from elderly donors stained for Fos and Jun at each data point compared with cells from young donors .", "target_text": { "Fos": "protein", "Jun": "protein" } }, { "input_text": "Flow cytometric analysis also showed that at 72 h of virus exposure fewer T cells from the elderly produced interferon-gamma ( IFN-gamma ) , suggesting a link between the magnitude of the Fos and Jun and IFN-gamma responses .", "target_text": { "T cells": "cell_type", "interferon-gamma": "protein", "IFN-gamma": "protein", "Fos": "protein", "Jun": "protein" } }, { "input_text": "Thus , failure of virus-exposed T cells to produce Fos and Jun could contribute to the increase in illness due to influenza virus in the elderly .", "target_text": { "T cells": "cell_type", "virus-exposed T cells": "cell_type", "Fos": "protein", "Jun": "protein" } }, { "input_text": "The regulation of HIV by retinoic acid correlates with cellular expression of the retinoic acid receptors .", "target_text": { "retinoic acid receptors": "protein" } }, { "input_text": "OBJECTIVES : To analyze the effect of retinoic acids ( RA ) on HIV-1 expression and correlate this effect with expression levels of RA receptors ( RARs ) in T-lymphoid and monocytoid cell lines .", "target_text": { "RA receptors": "protein", "RARs": "protein" } }, { "input_text": "DESIGN AND METHODS : The effect of all-trans and 9-cis RA on HIV-1 production in T-lymphoid ( H9 , CEM ) and monocytoid ( U937 , THP-1 ) cell lines was measured during acute and chronic infection .", "target_text": { "T-lymphoid": "cell_line", "H9 , CEM": "cell_line", "monocytoid ( U937 , THP-1 ) cell lines": "cell_line" } }, { "input_text": "The expression levels of human RAR alpha ( hRAR alpha , receptor for all-trans RA ) and the human retinoid-X receptor alpha ( hRXR alpha receptor for 9-cis RA ) were determined by Northern blot analysis .", "target_text": { "human RAR alpha": "protein", "hRAR alpha , receptor": "protein", "human retinoid-X receptor alpha": "protein", "hRXR alpha receptor": "protein" } }, { "input_text": "RESULTS : Both all-trans and 9-cis RA inhibited virus replication in HIV-1 IIIB-infected monocytoid cells , in the presence and absence of the co-stimulatory agent phorbol myristate acetate ( PMA ) .", "target_text": { "HIV-1 IIIB-infected monocytoid cells": "cell_line" } }, { "input_text": "The retinoids had weak or no stimulatory effects on HIV production by T-cell lines .", "target_text": { "T-cell lines": "cell_line" } }, { "input_text": "HIV production by PMA -stimulated T-cell lines was inhibited by these retinoids .", "target_text": { "T-cell lines": "cell_line", "PMA -stimulated T-cell lines": "cell_line" } }, { "input_text": "The 9-cis RA was generally more effective than all-trans RA in inhibiting HIV production and in combination generally more effective than the single agents alone .", "target_text": {} }, { "input_text": "Human RAR alpha was expressed in H9 , U937 and THP-1 cells , but almost undetectable in CEM cells .", "target_text": { "Human RAR alpha": "protein", "H9": "cell_line", "U937": "cell_line", "THP-1 cells": "cell_line", "CEM cells": "cell_line" } }, { "input_text": "Human RXR alpha was significantly expressed in U937 and THP-1 cells , weakly expressed in H9 cells and not detectable in CEM cells .", "target_text": { "Human RXR alpha": "protein", "H9 cells": "cell_line", "CEM cells": "cell_line" } }, { "input_text": "After stimulation by PMA , RXR alpha expression increased in H9 and U937 cells but not in CEM cells .", "target_text": { "RXR alpha": "protein", "H9": "cell_line", "U937 cells": "cell_line", "CEM cells": "cell_line" } }, { "input_text": "Human RAR alpha expression was unchanged in H9 and CEM cells , and elevated in U937 cells , after PMA stimulation .", "target_text": { "H9": "cell_line", "CEM cells": "cell_line", "U937 cells": "cell_line" } }, { "input_text": "CONCLUSION : The effect of RA on HIV-1 expression was cell-type-dependent and partially correlated with cellular expression of RARs .", "target_text": { "RARs": "protein" } }, { "input_text": "Endogenous or exogenously administered RA may have a significant role in HIV regulation .", "target_text": {} }, { "input_text": "Functions of glutathione and glutathione disulfide in immunology and immunopathology .", "target_text": {} }, { "input_text": "Even a moderate increase in the cellular cysteine supply elevates the intracellular glutathione ( GSH ) and glutathione disulfide ( GSSG ) levels and potentiates immunological functions of lymphocytes in vitro .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "At low GSSG levels , T cells can not optimally activate the immunologically important transcription factor NF kappa B , whereas high GSSG levels inhibit the DNA binding activity of NF kappa B .", "target_text": { "T cells": "cell_type", "transcription factor": "protein", "NF kappa B": "protein" } }, { "input_text": "The effects of GSSG are antagonized by reduced thioredoxin ( TRX ) .", "target_text": { "thioredoxin": "protein", "TRX": "protein" } }, { "input_text": "As the protein tyrosine kinase activities p56lck and p59fyn are activated in intact cells by hydrogen peroxide , they are likely targets for GSSG action .", "target_text": { "protein tyrosine kinase": "protein", "p56lck": "protein", "p59fyn": "protein" } }, { "input_text": "These redox-regulated enzymes trigger signal cascades for NF kappa B activation and transduce signals from the T cell antigen receptor , from CD4 and CD8 molecules , and from the IL-2 receptor beta-chain .", "target_text": { "redox-regulated enzymes": "protein", "NF kappa B": "protein", "T cell antigen receptor": "protein", "CD4": "protein", "CD8 molecules": "protein", "IL-2": "protein", "IL-2 receptor beta-chain": "protein" } }, { "input_text": "The effector phase of cytotoxic T cell responses and IL-2 -dependent functions are inhibited even by a partial depletion of the intracellular GSH pool .", "target_text": { "cytotoxic T cell": "cell_type", "IL-2": "protein" } }, { "input_text": "As signal transduction is facilitated by prooxidant conditions , we propose that the well-known immunological consequences of GSH depletion ultimately may be results of the accompanying GSSG deficiency .", "target_text": {} }, { "input_text": "As HIV -infected patients and SIV-infected rhesus macaques have , on the average , significantly decreased plasma cyst ( e ) ine and intracellular GSH levels , we also hypothesize that AIDS may be the consequence of a GSSG deficiency as well .", "target_text": {} }, { "input_text": "T cells from renal cell carcinoma patients exhibit an abnormal pattern of kappa B-specific DNA-binding activity : a preliminary report .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Recent data suggest that the poor induction of a T-cell response to human renal cell carcinoma ( RCC ) may be related to alterations in signal transduction pathways .", "target_text": {} }, { "input_text": "We report that T cells from RCC patients have two alterations in kappa B motif -specific DNA-binding activity .", "target_text": { "T cells": "cell_type", "kappa B motif": "DNA" } }, { "input_text": "The first alteration involves the constitutive expression of substantial kappa B-binding activity in nuclear extracts , which was observed in the electrophoretic mobility shift assay .", "target_text": {} }, { "input_text": "The magnitude of kappa B activity in unstimulated patient T cells was similar to that observed in T cells from normal individuals that had been activated in vitro .", "target_text": { "T cells": "cell_type", "unstimulated patient T cells": "cell_type" } }, { "input_text": "On the basis of Western blotting experiments using antibodies to kappa B/Rel family proteins , the kappa B-binding activity constitutively expressed in T cells from RCC patients is composed mostly of the NF-kappa B1 ( p50 ) subunit .", "target_text": { "antibodies": "protein", "kappa B/Rel family proteins": "protein", "T cells": "cell_type", "p50": "protein", "NF-kappa B1 ( p50 ) subunit": "protein" } }, { "input_text": "The second abnormality in kappa B-binding activity in T cells from these patients is that RelA , a member of the Rel homology family which is part of the normal NF-kappa B complex , was not induced in the nucleus following activation .", "target_text": { "T cells": "cell_type", "RelA": "protein", "Rel homology family": "protein", "NF-kappa B complex": "protein" } }, { "input_text": "Western blotting analysis did not detect any RelA in nuclear extracts either before or after stimulation of T cells .", "target_text": { "RelA": "protein", "T cells": "cell_type" } }, { "input_text": "The altered kappa B-binding activity in T cells from RCC patients may impair their capacity to respond normally to various stimuli .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Hemoglobin switching in humans is accompanied by changes in the ratio of the transcription factors , GATA-1 and SP1 .", "target_text": { "Hemoglobin": "protein", "transcription factors": "protein", "GATA-1": "protein", "SP1": "protein" } }, { "input_text": "BACKGROUND : Understanding the mechanism of developmental regulation of hemoglobin switching has scientific as well as clinical relevance because of the influence of fetal hemoglobin ( HbF ) production in adulthood on the clinical manifestation of thalassemia and sickle cell anemia .", "target_text": { "hemoglobin": "protein", "HbF": "protein" } }, { "input_text": "We have previously found that the normal developmental patterns of globin gene expression are recapitulated in an experimental system of primary cultures that support differentiation of erythroid progenitors .", "target_text": { "globin gene": "DNA", "primary cultures": "cell_line", "erythroid progenitors": "cell_type" } }, { "input_text": "We further found that high activities of the transcriptional activators , GATA-1 and SP1 , are associated with normal adult erythroid differentiation .", "target_text": { "transcriptional activators": "protein", "GATA-1": "protein", "SP1": "protein" } }, { "input_text": "MATERIALS AND METHODS : In the present work , we have studied , the activities of GATA-1 and SP1 during differentiation of cultured erythroid progenitors derived from cord blood and from fetal livers , as well as from beta zero- thalassemia patients .", "target_text": { "GATA-1": "protein", "SP1": "protein", "erythroid progenitors": "cell_type" } }, { "input_text": "RESULTS : The results showed high GATA-1 binding activity and very low SP1 activity in the fetal liver cultures .", "target_text": { "GATA-1": "protein", "SP1": "protein", "fetal liver cultures": "cell_line" } }, { "input_text": "This pattern was in contrast to cultures derived from normal adult peripheral blood , in which both GATA-1 and SP1 activities were high .", "target_text": { "GATA-1": "protein", "SP1": "protein" } }, { "input_text": "Cord blood cultures showed an additive combination of \" adult \" and \" fetal \" patterns .", "target_text": {} }, { "input_text": "The progenitors derived from a beta zero- thalassemia patient with high HbF production showed \" fetal \" pattern .", "target_text": { "HbF": "protein" } }, { "input_text": "On the other hand , in cultures of 2 beta zero- thalassemia patients without high HbF , \" adult \" pattern was observed .", "target_text": { "HbF": "protein" } }, { "input_text": "CONCLUSIONS : In the present work , we show that human fetal and adult erythroid progenitors are distinct in their transcription factors , and that the commitment to fetal or adult program occurs at a very early differentiation stage .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Our studies also demonstrate that under anemic stress , recruitment of fetal progenitors may occur in adulthood .", "target_text": { "fetal progenitors": "cell_type" } }, { "input_text": "Transcription-independent turnover of I kappa B alpha during monocyte adherence : implications for a translational component regulating I kappa B alpha /MAD-3 mRNA levels .", "target_text": { "I kappa B alpha": "protein", "/MAD-3": "protein", "I kappa B alpha /MAD-3 mRNA": "RNA" } }, { "input_text": "We identified I kappa B alpha /MAD-3 as an immediate-early gene in human monocytes that is expressed in response to a variety of signals , including adhesion , lipopolysaccharide , and phorbol myristate acetate .", "target_text": { "I kappa B alpha": "protein", "I kappa B alpha /MAD-3": "protein", "immediate-early gene": "DNA", "human monocytes": "cell_type" } }, { "input_text": "Within 5 min of monocyte adhesion , the level of the I kappa B alpha protein is markedly diminished but is rapidly replaced in a cycloheximide-sensitive manner within 20 min .", "target_text": { "I kappa B alpha": "protein", "I kappa B alpha protein": "protein" } }, { "input_text": "Accompanying the rapid turnover of the I kappa B alpha protein is simultaneous translocation of NF-kappa B-related transcription factors to nuclei of adhered monocytes .", "target_text": { "I kappa B alpha": "protein", "I kappa B alpha protein": "protein", "transcription factors": "protein", "NF-kappa B-related transcription factors": "protein" } }, { "input_text": "The demonstration that NF-kappa B can regulate I kappa B alpha /MAD-3 gene transcription in other cell types suggested that the rapid increase in steady-state I kappa B alpha /MAD-3 mRNA levels we observed within 30 min of monocyte adherence would result from NF-kappa B -dependent transcriptional stimulation of the I kappa B alpha /MAD-3 gene .", "target_text": { "NF-kappa B": "protein", "I kappa B alpha": "protein", "I kappa B alpha /MAD-3 gene": "DNA", "I kappa B alpha /MAD-3 mRNA": "RNA" } }, { "input_text": "Nuclear run-on analyses indicated that , instead , while several immediate-early cytokine genes , such as the interleukin 1 beta ( IL-1 beta ) gene , were transcriptionally activated during monocyte adhesion , the rate of I kappa B alpha /MAD-3 gene transcription remained constant .", "target_text": { "immediate-early cytokine genes": "DNA", "interleukin 1 beta": "protein", "IL-1 beta": "protein", "interleukin 1 beta ( IL-1 beta ) gene": "DNA", "I kappa B alpha": "protein", "I kappa B alpha /MAD-3 gene": "DNA" } }, { "input_text": "The adherence-dependent increase in I kappa B alpha /MAD-3 mRNA levels was also not a consequence of mRNA stabilization events .", "target_text": { "I kappa B alpha": "protein", "I kappa B alpha /MAD-3 mRNA": "RNA", "mRNA": "RNA" } }, { "input_text": "Interestingly , while increases in both IL-1 beta and I kappa B alpha/MAD-3 mRNA levels were detected in nuclei of adherent monocytes , cytoplasmic levels of IL-1 beta mRNA increased during adherence whereas those of I kappa B alpha /MAD-3 mRNA did not .", "target_text": { "adherent monocytes": "cell_type", "IL-1 beta": "protein", "IL-1 beta mRNA": "RNA", "I kappa B alpha": "protein", "I kappa B alpha /MAD-3 mRNA": "RNA" } }, { "input_text": "Taken together , our data suggest that two interactive mechanisms regulate monocytic I kappa B alpha /MAD-3 mRNA levels .", "target_text": { "I kappa B alpha": "protein", "monocytic I kappa B alpha /MAD-3 mRNA": "RNA" } }, { "input_text": "We propose that adherent monocytes regulate nuclear processing ( or decay ) of I kappa B alpha /MAD-3 mRNA , thereby increasing mRNA levels without stimulating I kappa B alpha /MAD-3 gene transcription .", "target_text": { "adherent monocytes": "cell_type", "I kappa B alpha": "protein", "I kappa B alpha /MAD-3 mRNA": "RNA", "I kappa B alpha /MAD-3 gene": "DNA" } }, { "input_text": "Moreover , since inhibition of protein synthesis leads to accumulation of I kappa B alpha /MAD-3 mRNA without stimulating I kappa B alpha /MAD-3 gene transcription , we suggest that low cytoplasmic levels of I kappa B alpha /MAD-3 mRNA are maintained by a translation-dependent degradation mechanism .", "target_text": { "I kappa B alpha": "protein", "I kappa B alpha /MAD-3 mRNA": "RNA", "I kappa B alpha /MAD-3 gene": "DNA" } }, { "input_text": "Distinct roles of the molecular chaperone hsp90 in modulating dioxin receptor function via the basic helix-loop-helix and PAS domains .", "target_text": { "chaperone hsp90": "protein", "helix-loop-helix": "protein", "PAS domains": "protein" } }, { "input_text": "The intracellular dioxin receptor mediates signal transduction by dioxin and functions as a ligand-activated transcription factor .", "target_text": { "intracellular dioxin receptor": "protein", "ligand-activated transcription factor": "protein" } }, { "input_text": "It contains a basic helix-loop-helix ( bHLH ) motif contiguous with a Per-Arnt-Sim ( PAS ) homology region .", "target_text": { "helix-loop-helix": "protein", "bHLH": "protein", "basic helix-loop-helix ( bHLH ) motif": "protein", "Per-Arnt-Sim ( PAS ) homology region": "protein" } }, { "input_text": "In extracts from nonstimulated cells the receptor is recovered in an inducible cytoplasmic form associated with the 90-kDa heat shock protein ( hsp90 ) , a molecular chaperone .", "target_text": { "90-kDa heat shock protein": "protein", "hsp90": "protein", "molecular chaperone": "protein" } }, { "input_text": "We have reconstituted ligand-dependent activation of the receptor to a DNA-binding form by using the dioxin receptor and its bHLH-PAS partner factor Arnt expressed by in vitro translation in reticulocyte lysate .", "target_text": { "DNA-binding form": "protein", "dioxin receptor": "protein", "bHLH-PAS partner factor": "protein", "Arnt": "protein" } }, { "input_text": "Deletion of the PAS domain of the receptor resulted in constitutive dimerization with Arnt .", "target_text": { "PAS domain": "protein", "Arnt": "protein" } }, { "input_text": "In contrast , this receptor mutant showed low levels of xenobiotic response element-binding activity , indicating that the PAS domain may be important for DNA-binding affinity and/or specificity of the receptor .", "target_text": { "PAS domain": "protein" } }, { "input_text": "It was not possible to reconstitute dioxin receptor function with proteins expressed in wheat germ lysate .", "target_text": { "dioxin receptor": "protein" } }, { "input_text": "In line with these observations , reticulocyte lysate but not wheat germ lysate promoted the association of de novo synthesized dioxin receptor with hsp90 .", "target_text": { "dioxin receptor": "protein", "hsp90": "protein" } }, { "input_text": "At least two distinct domains of the receptor mediated interaction with hsp90 : the ligand-binding domain located within the PAS region and , surprisingly , the bHLH domain .", "target_text": { "hsp90": "protein", "ligand-binding domain": "protein", "PAS region": "protein", "bHLH domain": "protein" } }, { "input_text": "Whereas ligand-binding activity correlated with association with hsp90 , bHLH- hsp90 interaction appeared to be important for DNA-binding activity but not for dimerization of the receptor .", "target_text": { "hsp90": "protein" } }, { "input_text": "Several distinct roles for hsp90 in modulating dioxin receptor function are therefore likely : correct folding of the ligand-binding domain , interference with Arnt heterodimerization , and folding of a DNA-binding conformation of the bHLH domain .", "target_text": { "hsp90": "protein", "dioxin receptor": "protein", "Arnt": "protein", "bHLH domain": "protein" } }, { "input_text": "Thus , the dioxin receptor system provides a complex and interesting model of the regulation of transcription factors by hsp90 .", "target_text": { "dioxin receptor": "protein", "transcription factors": "protein", "hsp90": "protein" } }, { "input_text": "Induction of transcription factors in human T lymphocytes by aspirin -like drugs .", "target_text": { "transcription factors": "protein", "human T lymphocytes": "cell_type" } }, { "input_text": "Aspirin-like drugs ( ALD ) induce calcium mobilization , an essential component of T cell activation , but do not induce the biosynthesis of IL-2 .", "target_text": { "IL-2": "protein" } }, { "input_text": "To understand the extent to which ALD may mimic mitogenic stimulation , we studied cytoplasmic and nuclear signaling steps in ALD -treated T cells .", "target_text": { "ALD -treated T cells": "cell_line" } }, { "input_text": "We found that ALD induce a transient activation of protein kinase ( PKC ) but have no effect ( in comparison to anti-CD3 antibodies ) on protein tyrosine phosphorylation nor on PCL gamma 1 tyrosine phosphorylation .", "target_text": { "protein kinase": "protein", "PKC": "protein", "anti-CD3 antibodies": "protein" } }, { "input_text": "ALD -induced calcium mobilization and PKC activation are independent of tyrosine protein kinase activity as shown by the lack of effect of herbimycin , a tyrosine -protein kinase -specific inhibitor .", "target_text": { "PKC": "protein", "tyrosine protein kinase": "protein", "tyrosine -protein kinase": "protein" } }, { "input_text": "Although we detected no IL-2 mRNA in ALD -treated cells , the nuclei of these cells contain proteins capable of binding to three regulatory sequences in the IL-2 promoter region : NFAT , NF kappa B , and AP-1 .", "target_text": { "IL-2": "protein", "IL-2 mRNA": "RNA", "ALD -treated cells": "cell_line", "regulatory sequences": "DNA", "IL-2 promoter region": "DNA", "NFAT": "protein", "NF kappa B": "protein", "AP-1": "protein" } }, { "input_text": "These binding activities are expressed only in activated T cells .", "target_text": { "activated T cells": "cell_type" } }, { "input_text": "The expression of AP-1 depended on calcium mobilization and PKC activation .", "target_text": { "AP-1": "protein", "PKC": "protein" } }, { "input_text": "These data suggest that ALD cause transient but significant changes in T cell transmembrane signaling , although some events induced by stimulation with anti-CD3 antibodies are not induced by ALD .", "target_text": { "anti-CD3 antibodies": "protein" } }, { "input_text": "The signal is transmitted to the nucleus and induces DNA-binding activity by several transcription factors .", "target_text": { "transcription factors": "protein" } }, { "input_text": "However , the ALD stimulus is not capable of causing complete T cell activation .", "target_text": {} }, { "input_text": "Protein kinase C is not a downstream effector of p21ras in activated T cells .", "target_text": { "Protein kinase C": "protein", "p21ras": "DNA", "activated T cells": "cell_type" } }, { "input_text": "The aim of this present study was to investigate the role of protein kinase C ( PKC ) , downstream of p21ras , in activating interleukin-2 ( IL-2 ) gene expression .", "target_text": { "protein kinase C": "protein", "PKC": "protein", "p21ras": "DNA", "interleukin-2 ( IL-2 ) gene": "DNA" } }, { "input_text": "It has been reported that PKC is an effector of p21ras in T cells .", "target_text": { "PKC": "protein", "effector": "protein", "p21ras": "DNA", "T cells": "cell_type" } }, { "input_text": "Data is presented , using the potent and selective PKC inhibitor Ro 31-8425 and transient expression of a constitutively active ras mutant , which clearly shows that PKC is not downstream of p21ras in the induction of NF-AT and AP-1 transcriptional activity and in the expression of IL-2 in human Jurkat T cells .", "target_text": { "PKC": "protein", "p21ras": "DNA", "NF-AT": "protein", "AP-1": "protein", "IL-2": "protein", "human Jurkat T cells": "cell_line" } }, { "input_text": "Reporter gene experiments demonstrated that NF-kappa B transcriptional activity is not affected by expression of activated p21ras .", "target_text": { "NF-kappa B": "protein", "p21ras": "DNA" } }, { "input_text": "The signaling pathways involving PKC activation , calcium mobilization and ras activation combine to provide the necessary components for production of IL-2 during T cell activation .", "target_text": { "PKC": "protein", "ras": "protein", "IL-2": "protein" } }, { "input_text": "The C-terminus of the B cell activator Oct-2 functions as an activation domain in yeast .", "target_text": { "C-terminus": "protein", "B cell activator": "protein", "Oct-2": "protein", "activation domain": "protein" } }, { "input_text": "Oct-1 and Oct-2 are human transcriptional activators that bind to the same DNA element but activate distinct sets of genes .", "target_text": { "Oct-1": "protein", "Oct-2": "protein", "transcriptional activators": "protein" } }, { "input_text": "We expressed these factors in S. cerevisiae and observed greater than 5-fold stimulation of a lacZ reporter gene only with Oct-2 .", "target_text": { "lacZ reporter gene": "DNA", "Oct-2": "protein" } }, { "input_text": "Transfer of the Oct-2 C-terminal domain onto either Oct-1 ( Oct1.2 ) or a nonactivating DNA-binding domain from GAL4 created activators capable of greater than 15 and 10-fold stimulation of activity , respectively .", "target_text": { "Oct-2": "protein", "Oct-2 C-terminal domain": "protein", "Oct-1": "protein", "Oct1.2": "protein", "nonactivating DNA-binding domain": "protein", "GAL4": "protein" } }, { "input_text": "Thus , the C-terminus of Oct-2 is sufficient to confer activation potential to nonactive DNA-binding fragments in yeast .", "target_text": { "C-terminus": "protein", "Oct-2": "protein", "DNA-binding fragments": "DNA" } }, { "input_text": "Glucocorticoid-induced apoptosis of lymphoid cells .", "target_text": { "lymphoid cells": "cell_type" } }, { "input_text": "The induction of cell death in lymphoid cells by glucocorticoids is one of the earliest and most thoroughly studied models of apoptosis .", "target_text": { "lymphoid cells": "cell_type" } }, { "input_text": "Although the exact mechanism by which apoptosis occurs in lymphocytes is unknown many biochemical and molecular changes have been shown to occur in these cells in response to glucocorticoids .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "The role of chromatin degradation and endonucleases in the apoptotic process has been closely studied , as well as the involvement of several oncogenes in glucocorticoid -induced cell lysis .", "target_text": { "chromatin": "DNA", "endonucleases": "protein", "oncogenes": "DNA" } }, { "input_text": "In addition , the clinical importance of glucocorticoid -induced apoptosis in the treatment of lymphoid neoplasms has recently received increased attention .", "target_text": {} }, { "input_text": "Interleukin-2 induces tyrosine phosphorylation and nuclear translocation of stat3 in human T lymphocytes .", "target_text": { "Interleukin-2": "protein", "stat3": "protein", "lymphocytes": "cell_type", "human T lymphocytes": "cell_type" } }, { "input_text": "An early biochemical event associated with T cell activation through the interleukin-2 receptor ( IL-2R ) is tyrosine phosphorylation of several intracellular substrates .", "target_text": { "interleukin-2 receptor": "protein", "IL-2R": "protein" } }, { "input_text": "The exact mechanism by which IL-2 regulates transcription of different genes is presently unknown .", "target_text": { "IL-2": "protein" } }, { "input_text": "Here , we report that stimulation through the IL-2R induced tyrosine phosphorylation and subsequent nuclear translocation of stat3 , a newly identified member of the signal transducers and activators of transcription ( STAT ) family of proteins .", "target_text": { "IL-2R": "protein", "stat3": "protein", "signal transducers and activators of transcription ( STAT ) family": "protein" } }, { "input_text": "In contrast , stat1 proteins were not tyrosine phosphorylated after IL-2 ligation , whereas tyrosine -phosphorylated stat1 proteins ( 91 and 84 kDa proteins ) were translocated to the nucleus following interferon-gamma treatment of HeLa cells .", "target_text": { "IL-2": "protein", "tyrosine -phosphorylated stat1 proteins": "protein", "interferon-gamma": "protein", "HeLa cells": "cell_line" } }, { "input_text": "Apart from stat3 , another cytoplasmic protein was tyrosine phosphorylated and subsequently translocated to the nucleus in response to IL-2 .", "target_text": { "stat3": "protein", "cytoplasmic protein": "protein", "IL-2": "protein" } }, { "input_text": "This protein had an apparent molecular mass of 84 kDa and was not recognized by stat3 or stat1 mAb or antisera .", "target_text": { "84 kDa": "protein", "stat3": "protein", "stat1 mAb": "protein" } }, { "input_text": "Since IL-2 induced nuclear translocation of the 84 kDa protein and stat3 followed identical kinetics , p84 is a candidate for a new , yet undefined , member of the STAT family .", "target_text": { "IL-2": "protein", "84 kDa protein": "protein", "stat3": "protein", "p84": "protein" } }, { "input_text": "Taken together , we report that IL-2 induces tyrosine phosphorylation and subsequent nuclear translocation of stat3 and an as yet undefined 84-kDa protein in antigen-specific human T cell lines .", "target_text": { "IL-2": "protein", "stat3": "protein", "84-kDa protein": "protein", "antigen-specific human T cell lines": "cell_line" } }, { "input_text": "Human T-cell leukemia virus type I Tax activation of NF-kappa B /Rel involves phosphorylation and degradation of I kappa B alpha and RelA ( p65 ) -mediated induction of the c-rel gene .", "target_text": { "Tax": "protein", "NF-kappa B": "protein", "NF-kappa B /Rel": "protein", "I kappa B alpha": "protein", "RelA": "protein", "p65": "protein", "c-rel gene": "DNA" } }, { "input_text": "The tax gene product of human T-cell leukemia virus type I ( HTLV-I ) is a potent transcriptional activator that both stimulates viral gene expression and activates an array of cellular genes involved in T-cell growth .", "target_text": { "transcriptional activator": "protein", "cellular genes": "DNA", "T-cell": "cell_type" } }, { "input_text": "Tax acts indirectly by inducing or modifying the action of various host transcription factors , including members of the NF-kappa B /Rel family of enhancer-binding proteins .", "target_text": { "transcription factors": "protein", "NF-kappa B": "protein", "NF-kappa B /Rel family": "protein", "enhancer-binding proteins": "protein" } }, { "input_text": "In resting T cells , many of these NF-kappa B /Rel factors are sequestered in the cytoplasm by various ankyrin-rich inhibitory proteins , including I kappa B alpha .", "target_text": { "resting T cells": "cell_type", "NF-kappa B": "protein", "NF-kappa B /Rel factors": "protein", "ankyrin-rich inhibitory proteins": "protein", "I kappa B alpha": "protein" } }, { "input_text": "HTLV-I Tax expression leads to the constitutive nuclear expression of biologically active NF-kappa B and c-Rel complexes ; however , the biochemical mechanism ( s ) underlying this response remains poorly understood .", "target_text": { "Tax": "protein", "HTLV-I Tax": "protein", "NF-kappa B": "protein", "c-Rel complexes": "protein" } }, { "input_text": "In this study , we demonstrate that Tax -stimulated nuclear expression of NF-kappa B in both HTLV-I -infected and Tax -transfected human T cells is associated with the phosphorylation and rapid proteolytic degradation of I kappa B alpha .", "target_text": { "Tax": "protein", "NF-kappa B": "protein", "HTLV-I -infected and Tax -transfected human T cells": "cell_line", "I kappa B alpha": "protein" } }, { "input_text": "In contrast to prior in vitro studies , at least a fraction of the phosphorylated form of I kappa B alpha remains physically associated with the NF-kappa B complex in vivo but is subject to rapid degradation , thereby promoting the nuclear translocation of the active NF-kappa B complex .", "target_text": { "I kappa B alpha": "protein", "NF-kappa B": "protein", "NF-kappa B complex": "protein" } }, { "input_text": "We further demonstrate that Tax induction of nuclear c-Rel expression is activated by the RelA ( p65 ) subunit of NF-kappa B , which activates transcription of the c-rel gene through an intrinsic kappa B enhancer element .", "target_text": { "Tax": "protein", "c-Rel": "protein", "RelA": "protein", "p65": "protein", "NF-kappa B": "protein", "c-rel gene": "DNA", "kappa B enhancer element": "DNA" } }, { "input_text": "In normal cells , the subsequent accumulation of nuclear c-Rel acts to inhibit its own continued production , indicating the presence of an autoregulatory loop .", "target_text": { "c-Rel": "protein", "nuclear c-Rel": "protein" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "Activation of NF-kappa B in vivo is regulated by multiple phosphorylations .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "The activation of nuclear factor kappa B ( NF-kappa B ) in intact cells is mechanistically not well understood .", "target_text": { "nuclear factor kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "Therefore we investigated the modifications imposed on NF-kappa B /I kappa B components following stimulation and show that the final step of NF-kappa B induction in vivo involves phosphorylation of several members of the NF-kappa B /I kappa B protein families .", "target_text": { "NF-kappa B": "protein", "NF-kappa B /I kappa B components": "protein", "NF-kappa B /I kappa B protein families": "protein" } }, { "input_text": "In HeLa cells as well as in B cells , TNF-alpha rapidly induced nuclear translocation primarily of p50-p65 , but not of c-rel .", "target_text": { "HeLa cells": "cell_line", "B cells": "cell_type", "p50-p65": "protein", "c-rel": "protein" } }, { "input_text": "Both NF-kappa B precursors and I kappa B alpha became strongly phosphorylated with the same kinetics .", "target_text": { "NF-kappa B": "protein", "I kappa B alpha": "protein" } }, { "input_text": "In addition to the inducible phosphorylation after stimulation , B lymphocytes containing constitutive nuclear NF-kappa B revealed constitutively phosphorylated p65 and I kappa B alpha .", "target_text": { "lymphocytes": "cell_type", "B lymphocytes": "cell_type", "NF-kappa B": "protein", "p65": "protein", "I kappa B alpha": "protein" } }, { "input_text": "Phosphorylation was accompanied by induced processing of the precursors p100 and p105 and by degradation of I kappa B alpha .", "target_text": { "p100": "protein", "p105": "protein", "I kappa B alpha": "protein" } }, { "input_text": "As an in vitro model we show that phosphorylation of p105 impedes its ability to interact with NF-kappa B , as has been shown before for I kappa B alpha .", "target_text": { "p105": "protein", "NF-kappa B": "protein", "I kappa B alpha": "protein" } }, { "input_text": "Surprisingly , even p65 , but not c-rel , was phosphorylated after induction in vivo , suggesting that TNF-alpha selectively activates only specific NF-kappa B heteromers and that modifications regulate not only I kappa B molecules but also NF-kappa B molecules .", "target_text": { "p65": "protein", "c-rel": "protein", "TNF-alpha": "protein", "NF-kappa B": "protein", "I kappa B": "protein", "I kappa B molecules": "protein" } }, { "input_text": "In fact , cellular NF-kappa B activity was phosphorylation-dependent and the DNA binding activity of p65 -containing NF-kappa B was enhanced by phosphorylation in vitro .", "target_text": { "NF-kappa B": "protein", "p65": "protein", "p65 -containing NF-kappa B": "protein" } }, { "input_text": "Furthermore , we found that the induction by hydrogen peroxide of NF-kappa B translocation to the nucleus , which is assumed to be triggered by reactive oxygen intermediates , also coincided with incorporation of phosphate into the same subunits that were modified after stimulation by TNF-alpha .", "target_text": { "NF-kappa B": "protein", "TNF-alpha": "protein" } }, { "input_text": "Thus , phosphorylation appears to be a general mechanism for activation of NF-kappa B in vivo .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Treatment of HL60 cells with various combinations of retinoids and 1 alpha , 25 dihydroxyvitamin D3 results in differentiation towards neutrophils or monocytes or a failure to differentiate and apoptosis .", "target_text": { "HL60 cells": "cell_line", "neutrophils": "cell_type", "monocytes": "cell_type" } }, { "input_text": "It is well documented that treatment of serum-grown HL60 cells with 10(-7) M all-trans retinoic acid ( all-trans RA ) induces neutrophil differentiation , whereas treatment with 10(-7) M 1 alpha , 25 dihydroxyvitamin D3 ( D3 ) induces differentiation towards monocytes .", "target_text": { "HL60 cells": "cell_line", "serum-grown HL60 cells": "cell_line", "neutrophil": "cell_type", "monocytes": "cell_type" } }, { "input_text": "In recent investigations , using serum-free grown HL60 cells , we observed that all-trans RA , at 10(-7) M , did not induce neutrophil differentiation and that all-trans RA , at 10(-8) M , reduced the D3 concentration required for monocyte differentiation to 5 x 10(-9) M .", "target_text": { "HL60 cells": "cell_line", "serum-free grown HL60 cells": "cell_line", "monocyte": "cell_type" } }, { "input_text": "In this study , co-operative interactions between all-trans and 9-cis RA and D3 which promote neutrophil and monocyte differentiation of HL60 cells have been analysed in detail .", "target_text": { "HL60 cells": "cell_line" } }, { "input_text": "Treatment of serum-free grown HL60 cells with 5 x 10(-7) M all-trans RA or 9-cis RA resulted in sub-optimal neutrophil differentiation ( up to 25 % mature cells ) .", "target_text": { "HL60 cells": "cell_line", "serum-free grown HL60 cells": "cell_line" } }, { "input_text": "As shown for all-trans RA , 9-cis RA cooperated with D3 to promote monocyte differentiation .", "target_text": {} }, { "input_text": "Culture of HL60 cells in 5 x 10(-7) M 9-cis RA together with a wide range of concentrations of D3 resulted in promotion of neutrophil differentiation at 10(-15)-10(-12) D3 , a failure to differentiate and apoptosis at 10(-11)-10(-10) M D3 , followed by co-operativity between 9-cis RA and 5 x 10(-9) M D3 in inducing monocyte differentiation in the absence of neutrophil differentiation .", "target_text": { "HL60 cells": "cell_line" } }, { "input_text": "Similar results were obtained when HL60 cells were treated with 5 x 10(-7) all-trans RA together with a wide range of concentrations of D3 .", "target_text": { "HL60 cells": "cell_line" } }, { "input_text": "Cross titration analyses of the effects of 9-cis RA and D3 on HL60 cell differentiation were undertaken to determine the boundaries of the concentrations of each agent , alone and in combination , that give rise to optimal neutrophil and monocyte differentiation of HL60 cells .", "target_text": { "HL60 cell": "cell_line", "HL60 cells": "cell_line" } }, { "input_text": "The observed cooperativities between either 9-cis RA or all-trans RA and D3 have important implications for the use of combinations of these agents in differentiation therapy .", "target_text": {} }, { "input_text": "Isolation of differentially expressed sequence tags from steroid-responsive cells using mRNA differential display .", "target_text": { "steroid-responsive cells": "cell_type", "mRNA": "RNA" } }, { "input_text": "Transcriptional control of steroid-regulated gene networks by nuclear receptor proteins results in the coordinate expression of a limited number of target genes .", "target_text": { "steroid-regulated gene networks": "DNA", "nuclear receptor proteins": "protein", "target genes": "DNA" } }, { "input_text": "Although much is known about the structure and function of steroid receptors , relatively few cell-specific steroid-regulated genes have been isolated and characterized .", "target_text": {} }, { "input_text": "In this paper we describe results using mRNA differential display reverse transcriptase PCR ( DDPCR ) to identify and isolate short cDNA sequence tags from thymocyte and prostate cells under various hormone conditions .", "target_text": { "mRNA": "RNA", "reverse transcriptase": "protein", "thymocyte": "cell_type", "prostate cells": "cell_type" } }, { "input_text": "Using this technique we have isolated several differentially expressed sequence tags ( DESTs ) from the mouse thymocyte cell line WEHI 7.2 .", "target_text": { "differentially expressed sequence tags": "DNA", "DESTs": "DNA", "mouse thymocyte cell line": "cell_line", "WEHI 7.2": "cell_line" } }, { "input_text": "Two of these DESTs , GIG10 and GIG18 , are rapidly induced by dexamethasone within 2 h of treatment .", "target_text": { "DESTs": "DNA", "GIG10": "DNA", "GIG18": "DNA" } }, { "input_text": "GIG10 is a novel sequence and GIG18 is the mouse homologue of a human expressed sequence tag isolated from activated B lymphocytes .", "target_text": { "GIG10": "DNA", "GIG18": "DNA", "human expressed sequence tag": "DNA", "activated B lymphocytes": "cell_type" } }, { "input_text": "We also used DDPCR to isolate DESTs from androgen-modulated rat ventral prostate tissue , one of which we characterized and found to correspond to the 3' end of prostatic spermine binding protein mRNA , a known androgen-regulated gene .", "target_text": { "DESTs": "DNA", "3' end": "RNA", "prostatic spermine binding protein": "protein", "prostatic spermine binding protein mRNA": "RNA", "androgen-regulated gene": "DNA" } }, { "input_text": "Modifications of the original DDPCR protocol , which we found can potentially decrease the frequency of isolating false-positive DESTs , are described and the merits of DDPCR , relative to other differential cDNA cloning strategies , are discussed .", "target_text": { "DESTs": "DNA" } }, { "input_text": "Activation of human thymocytes after infection by EBV .", "target_text": { "human thymocytes": "cell_type" } }, { "input_text": "The discovery of EBV in certain T cell malignancies and the expression of the EBV receptor , CR2/CD21 , on a population of immature thymocytes , T lymphoblastoid cell lines , and childhood acute T lymphoblastic leukemia cells suggested that EBV -receptor interactions on T cells may be of importance .", "target_text": { "EBV receptor": "protein", "CR2/CD21": "protein", "immature thymocytes": "cell_type", "T lymphoblastoid cell lines": "cell_line", "childhood acute T lymphoblastic leukemia cells": "cell_type", "T cells": "cell_type" } }, { "input_text": "We have shown that , within the thymus , a population of large , immature cells expresses CD21 .", "target_text": { "large , immature cells": "cell_type", "CD21": "protein" } }, { "input_text": "EBV altered the activation responses of immature thymocytes in vitro .", "target_text": { "immature thymocytes": "cell_type" } }, { "input_text": "Triggering through CD2 is mitogenic for mature , but not immature , T cells .", "target_text": { "CD2": "protein", "T cells": "cell_type" } }, { "input_text": "However , during infection by EBV , ligation of CD2 caused thymocytes to proliferate in the absence of exogenous cytokines .", "target_text": { "CD2": "protein", "thymocytes": "cell_type", "exogenous cytokines": "protein" } }, { "input_text": "This function was a result of the interaction of EBV with its receptor , CD21 , but was caused by infection rather than surface signaling , because neither specific mAb nor the P3HR-1 strain of virus mimicked the effect of B95-8 .", "target_text": { "CD21": "protein", "specific mAb": "protein" } }, { "input_text": "Immature thymocytes were infected by EBV , as determined by the internalization of the viral genome and its transcriptional activity .", "target_text": { "thymocytes": "cell_type", "viral genome": "DNA" } }, { "input_text": "Consistent with the activity of B95-8 , EBNA-2 transcripts were identified within infected thymocyte populations .", "target_text": { "B95-8": "protein", "EBNA-2 transcripts": "RNA", "thymocyte": "cell_type", "infected thymocyte populations": "cell_line" } }, { "input_text": "In addition , components of the viral replicative pathway were expressed during infection of thymocytes .", "target_text": { "thymocytes": "cell_type" } }, { "input_text": "These components included transcription of BZLF-1 , an early gene that characterizes EBV -infected B cells after disruption of latency .", "target_text": { "BZLF-1": "DNA", "early gene": "DNA", "EBV -infected B cells": "cell_type" } }, { "input_text": "A second transcript was identified as encoding the recently characterized RAZ , which also is associated with replicative infection .", "target_text": { "RAZ": "protein" } }, { "input_text": "The consequences of EBV infection of T cells at an early stage of differentiation may lead to failure of normal T cell repertoire development , autoimmunity , or malignancy .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Effects of intranasal glucocorticoids on endogenous glucocorticoid peripheral and central function .", "target_text": {} }, { "input_text": "Glucocorticoids are among the most potent antiinflammatory agents that can be used in the treatment of rhinitis .", "target_text": {} }, { "input_text": "Their mechanisms of action are multiple and complex and a number of reports describe significant systemic effects of locally administered glucocorticoids .", "target_text": {} }, { "input_text": "In order to evaluate the short-term systemic effects of intranasally administered glucocorticoids , 14 normal healthy subjects were treated with two doses of either budesonide ( BUD ) or fluticasone propionate ( FP ) for 2 weeks .", "target_text": {} }, { "input_text": "Before treatment , at regular intervals during the treatment , 1 week and finally 6 weeks after termination of treatment , the effects on glucocorticoid receptor ( GR ) and methallothionein ( MTIIa ) mRNA expression levels were examined in peripheral lymphocytes using a solution hybridization assay .", "target_text": { "peripheral lymphocytes": "cell_type" } }, { "input_text": "Serum cortisol , osteocalcin and urinary cortisol levels were also determined .", "target_text": {} }, { "input_text": "An insulin tolerance test ( ITT ) was performed at the end of the second week of treatment and at the end of the 6-week washout period with no statistically significant change in cortisol response .", "target_text": {} }, { "input_text": "In peripheral lymphocytes , GR mRNA levels were significantly down-regulated .", "target_text": { "peripheral lymphocytes": "cell_type", "GR": "protein", "GR mRNA": "RNA" } }, { "input_text": "MTIIa mRNA levels increased significantly .", "target_text": { "MTIIa": "protein", "MTIIa mRNA": "RNA" } }, { "input_text": "Serum osteocalcin decreased significantly during treatment with both BUD and FP .", "target_text": { "osteocalcin": "protein" } }, { "input_text": "Serum cortisol decreased after 1 week of treatment whereas urinary cortisol was not affected until the second week of treatment .", "target_text": {} }, { "input_text": "In conclusion , intranasal glucocorticoids at clinically recommended doses have not only significant systemic effects on adrenal function , but also have an effect on specific gene expression in peripheral lymphocytes .", "target_text": { "peripheral lymphocytes": "cell_type" } }, { "input_text": "These effects are receptor-dependent , reversible , and according to serum and urinary cortisol levels and ITT , leave the hypothalamic-pituitary-adrenal function intact .", "target_text": {} }, { "input_text": "Finally , these short-term systemic effects were not associated with any of the noticeable side-effects usually observed during long-term treatment with glucocorticoids .", "target_text": {} }, { "input_text": "Biphasic control of nuclear factor-kappa B activation by the T cell receptor complex : role of tumor necrosis factor alpha .", "target_text": { "nuclear factor-kappa B": "protein", "T cell receptor complex": "protein", "tumor necrosis factor alpha": "protein" } }, { "input_text": "The regulation of nuclear factor ( NF ) -kappa B activation by the T cell receptor ( TcR ) /CD3 complex in primary human T cells has been studied at various times after activation .", "target_text": { "nuclear factor ( NF ) -kappa B": "protein", "T cell receptor": "protein", "T cell receptor ( TcR ) /CD3 complex": "protein", "T cells": "cell_type" } }, { "input_text": "Only p50 NF-kappa B protein bound the kappa B element of interleukin-2 receptor ( IL-2R ) alpha chain promoter on resting T cells .", "target_text": { "p50 NF-kappa B protein": "protein", "kappa B element": "DNA", "interleukin-2 receptor": "protein", "IL-2R": "protein", "interleukin-2 receptor ( IL-2R ) alpha chain promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "However , immediately after TcR/CD3 cross-linking ( after approximately 1 h ; immediate ) binding of p50.p65 heterodimers was observed .", "target_text": { "TcR/CD3": "protein", "p50.p65 heterodimers": "protein" } }, { "input_text": "p50.c-rel heterodimers were also detected bound to this sequence at early time points ( 7-16 h ; early ) , and both remained active at later time points ( 40 h ; late ) after activation .", "target_text": { "p50.c-rel heterodimers": "protein" } }, { "input_text": "This regulation takes place mainly at the level of nuclear translocation of p65 and c-rel , at immediate and early time points .", "target_text": { "p65": "protein", "c-rel": "protein" } }, { "input_text": "Activation also induced c-rel and p105/p50 mRNA synthesis , but not p65 mRNA whose expression was constitutive .", "target_text": { "p65": "protein", "p65 mRNA": "RNA" } }, { "input_text": "Interestingly , all those early and late events , but not the immediate ones , were inhibited by a neutralizing anti- tumor necrosis factor alpha ( TNF-alpha ) monoclonal antibody .", "target_text": { "tumor necrosis factor alpha": "protein", "anti- tumor necrosis factor alpha ( TNF-alpha ) monoclonal antibody": "protein" } }, { "input_text": "Similarly , cycloheximide prevented the p65 and c-rel translocation and consequent formation of active binding heterodimers , at early and late times .", "target_text": { "p65": "protein", "c-rel": "protein" } }, { "input_text": "Cyclosporin A impaired not only early and late , but also immediate events ; however , addition of TNF-alpha prevented all inhibition .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "These results indicate that the regulation of NF-kappa B activation during T cell activation by TcR/CD3 signals is biphasic : TcR/CD3 triggers its immediate translocation , which is transient if no TNF-alpha is present .", "target_text": { "NF-kappa B": "protein", "TcR/CD3": "protein", "TNF-alpha": "protein" } }, { "input_text": "TNF-alpha , therefore , emerges as the main factor responsible for a second phase of NF-kappa B regulation , controlling both translocation of p65 and c-rel , and new mRNA synthesis for c-rel and p105/p50 .", "target_text": { "TNF-alpha": "protein", "NF-kappa B": "protein", "p65": "protein", "c-rel": "protein", "mRNA": "RNA", "p105/p50": "protein" } }, { "input_text": "The transcription factor Sp1 is required for induction of the murine GM-CSF promoter in T cells .", "target_text": { "Sp1": "protein", "transcription factor Sp1": "protein", "murine GM-CSF promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "The cis-acting region , GM-kappa B/GC-box ( positions -95 and -73 ) , within the murine GM-CSF gene promoter is required for maximal induction by stimulation with phorbol-12-myristate acetate ( PMA ) and calcium ionophore ( A23187 ) in T cells .", "target_text": { "cis-acting region": "DNA", "GM-kappa B/GC-box": "DNA", "positions -95": "DNA", "-73": "DNA", "murine GM-CSF gene promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "GM-kappa B defines a binding site for NF-kappa B , and GC-box defines a binding site for three ( A1 , A2 , B ) constitutive proteins .", "target_text": { "GM-kappa B": "protein", "NF-kappa B": "protein", "GC-box": "DNA", "A1": "protein", "A2": "protein", "B": "protein", "constitutive proteins": "protein" } }, { "input_text": "We report here that three copies of the GC-box can functionally compensate for the GM-kappa B/ GC-box region , suggesting that the GC-motif can function independently of the GM-kappa B motif .", "target_text": { "GC-box": "DNA", "GM-kappa B/ GC-box": "DNA", "GM-kappa B/ GC-box region": "DNA", "GC-motif": "DNA", "GM-kappa B motif": "DNA" } }, { "input_text": "The major GC-box binding activity A1 was purified and identified as the transcription factor Sp1 .", "target_text": { "GC-box": "DNA", "A1": "protein", "Sp1": "protein", "transcription factor Sp1": "protein" } }, { "input_text": "We show that depletion of Sp1 ( A1 ) from nuclear extracts specifically decreases in vitro transcription activity on GM-CSF templates .", "target_text": { "Sp1": "protein", "A1": "protein", "GM-CSF": "protein" } }, { "input_text": "Since the human GM-CSF promoter has a base difference within the GC-box , we speculate that this may explain why the human promoter is weak and that an upstream enhancer is required for the induction of the human GM-CSF gene .", "target_text": { "human GM-CSF promoter": "DNA", "GC-box": "DNA", "upstream enhancer": "DNA", "human GM-CSF gene": "DNA" } }, { "input_text": "A factor that regulates the class II major histocompatibility complex gene DPA is a member of a subfamily of zinc finger proteins that includes a Drosophila developmental control protein .", "target_text": { "class II major histocompatibility complex gene": "DNA", "DPA": "DNA", "zinc finger proteins": "protein", "Drosophila developmental control protein": "protein" } }, { "input_text": "A novel DNA sequence element termed the J element involved in the regulated expression of class II major histocompatibility complex genes was recently described .", "target_text": { "DNA sequence element": "DNA", "J element": "DNA", "class II major histocompatibility complex genes": "DNA" } }, { "input_text": "To study this element and its role in class II gene regulation further , a cDNA library was screened with oligonucleotide probes containing both the S element and the nearby J element of the human DPA gene .", "target_text": { "class II gene": "DNA", "cDNA library": "DNA", "S element": "DNA", "J element": "DNA", "human DPA gene": "DNA" } }, { "input_text": "Several DNA clones were obtained by this procedure , one of which , clone 18 , is reported and characterized here .", "target_text": { "DNA clones": "DNA", "clone 18": "DNA" } }, { "input_text": "It encodes a protein predicted to contain 688 amino acid residues , including 11 zinc finger motifs of the C2H2 type in the C-terminal region , that are Kruppel-like in the conservation of the H/C link sequence connecting them .", "target_text": { "zinc finger motifs": "protein", "C2H2 type": "protein", "C-terminal region": "protein", "H/C link sequence": "protein" } }, { "input_text": "The 160 N-terminal amino acids in the nonfinger region of clone 18 are highly homologous with similar regions of several other human , mouse , and Drosophila sequences , defining a subfamily of Kruppel-like zinc finger proteins termed TAB ( tramtrack [ ttk ] -associated box ) here .", "target_text": { "160 N-terminal amino acids": "protein", "nonfinger region": "protein", "clone 18": "protein", "zinc finger proteins": "protein", "TAB": "protein", "tramtrack [ ttk ] -associated box": "protein" } }, { "input_text": "One of the Drosophila sequences , ttk , is a developmental control gene , while a second does not contain a zinc finger region but encodes a structure important in oocyte development .", "target_text": { "Drosophila sequences": "DNA", "ttk": "DNA", "developmental control gene": "DNA", "zinc finger region": "protein" } }, { "input_text": "An acidic activation domain is located between the N-terminal conserved region of clone 18 and its zinc fingers .", "target_text": { "acidic activation domain": "protein", "N-terminal conserved region": "protein", "clone 18": "protein", "zinc fingers": "protein" } }, { "input_text": "This protein appears to require both the S and J elements , which are separated by 10 bp for optimal binding .", "target_text": {} }, { "input_text": "Antisense cDNA to clone 18 inhibited the expression of a reporter construct containing the DPA promoter , indicating its functional importance in the expression of this class II gene .", "target_text": { "clone 18": "protein", "DPA": "DNA", "DPA promoter": "DNA", "class II gene": "DNA" } }, { "input_text": "Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B signal transduction pathway .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Studies presented here show that overall NF-kappa B signal transduction begins with a parallel series of stimuli-specific pathways through which cytokines ( tumor necrosis factor alpha ) , oxidants ( hydrogen peroxide and mitomycin C ) , and phorbol ester ( phorbol 12-myristate 13-acetate ) individually initiate signaling .", "target_text": { "NF-kappa B": "protein", "cytokines": "protein", "tumor necrosis factor alpha": "protein" } }, { "input_text": "These initial pathways culminate in a common pathway through which all of the stimulating agents ultimately signal NF-kappa B activation .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "We distinguish the stimuli-specific pathways by showing that the oxidative stimuli trigger NF-kappa B activation in only one of two human T-cell lines ( Wurzburg but not Jurkat ) , whereas tumor necrosis factor alpha and phorbol 12-myristate 13-acetate readily stimulate in both lines .", "target_text": { "NF-kappa B": "protein", "human T-cell lines": "cell_line", "Wurzburg": "cell_line", "Jurkat": "cell_line", "tumor necrosis factor alpha": "protein" } }, { "input_text": "We propose the common pathway as the simplest way of accounting for the common requirements and properties of the signaling pathway .", "target_text": {} }, { "input_text": "We include a redox-regulatory mechanism ( s ) in this common pathway to account for the previously demonstrated redox regulation of NF-kappa B activation in Jurkat cells ( in which oxidants do n't activate NF-kappa B ) ; we put tyrosine phosphorylation in the common pathway by showing that kinase activity ( inhibitable by herbimycin A and tyrphostin 47 ) is required for NF-kappa B activation by all stimuli tested in both cell lines .", "target_text": { "NF-kappa B": "protein", "Jurkat cells": "cell_line" } }, { "input_text": "Since internal sites of oxidant production have been shown to play a key role in the cytokine -stimulated activation of NF-kappa B , and since tyrosine kinase and phosphatase activities are known to be altered by oxidants , these findings suggest that intracellular redox status controls NF-kappa B activation by regulating tyrosine phosphorylation event ( s ) within the common step of the NF-kappa B signal transduction pathway .", "target_text": { "cytokine": "protein", "NF-kappa B": "protein" } }, { "input_text": "Deleted chromosome 20 from a patient with Alagille syndrome isolated in a cell hybrid through leucine transport selection : study of three candidate genes .", "target_text": { "chromosome 20": "DNA" } }, { "input_text": "Alagille syndrome ( AGS ) is a well-defined genetic entity assigned to the short arm of Chromosome ( Chr ) 20 by a series of observations of AGS patients associated with microdeletions in this region .", "target_text": { "short arm": "DNA", "Chromosome ( Chr ) 20": "DNA" } }, { "input_text": "By fusing lymphoblastoid cells of an AGS patient that exhibited a microdeletion in the short arm of Chr 20 encompassing bands p11.23 to p12.3 with rodent thermosensitive mutant cells ( CHOtsH1-1 ) deficient in-leucyl-tRNA synthetase , we isolated a somatic cell hybrid segregating the deleted human Chr 20 .", "target_text": { "lymphoblastoid cells": "cell_type", "Chr 20": "DNA", "short arm of Chr 20": "DNA", "p11.23 to p12.3": "DNA", "rodent thermosensitive mutant cells": "cell_line", "CHOtsH1-1": "cell_line", "in-leucyl-tRNA synthetase": "protein", "somatic cell hybrid": "cell_line" } }, { "input_text": "This hybrid clone , designated NR2 , was characterized by several methods , including PCR , with eight pairs of oligonucleotides mapped to Chr 20 : D20S5 , D20S41 , D20S42 , D20S56 , D20S57 , D20S58 , adenosine deaminase ( ADA ) , and Prion protein ( PRIP ) ; Restriction Fragment Length Polymorphism ( RFLP ) analyses with four genomic anonymous probes ( D20S5 , cD3H12 , D20S17 , D20S18 ) ; and fluorescent in situ hybridization ( FISH ) with total human DNA and D20Z1 , a sequence specific to the human Chr 20 centromere , as probes .", "target_text": { "NR2": "cell_line", "Chr 20": "DNA", "D20S5": "DNA", "D20S41": "DNA", "D20S42": "DNA", "D20S56": "DNA", "D20S57": "DNA", "D20S58": "DNA", "adenosine deaminase": "DNA", "ADA": "protein", "Prion protein": "DNA", "PRIP": "protein", "RFLP": "DNA", "genomic anonymous probes": "DNA", "cD3H12": "DNA", "D20S17": "DNA", "D20S18": "DNA", "total human DNA": "DNA", "D20Z1": "DNA", "human Chr 20 centromere": "DNA" } }, { "input_text": "The NR2 hybrid allowed us to exclude three candidate genes for AGS : hepatic nuclear factor 3 beta ( HNF3 beta ) , paired box 1 ( PAX1 ) , and cystatin C ( CST3 ) as shown by their localization outside of the deletion .", "target_text": { "NR2 hybrid": "cell_line", "candidate genes": "DNA", "hepatic nuclear factor 3 beta": "DNA", "HNF3 beta": "DNA", "paired box 1": "DNA", "PAX1": "DNA", "cystatin C": "DNA", "CST3": "DNA" } }, { "input_text": "The NR2 hybrid is a powerful tool for the mapping of new probes of this region , as well as for obtaining new informative probes specific for the deletion by subtractive cloning of the region .", "target_text": { "NR2 hybrid": "cell_line" } }, { "input_text": "Such markers will be useful for linkage analysis and screening of cDNA libraries .", "target_text": { "cDNA libraries": "DNA" } }, { "input_text": "Positive and negative regulation of the composite octamer motif of the interleukin 2 enhancer by AP-1 , Oct-2 , and retinoic acid receptor .", "target_text": { "composite octamer motif": "DNA", "interleukin 2 enhancer": "DNA", "AP-1": "protein", "Oct-2": "protein", "retinoic acid receptor": "protein" } }, { "input_text": "The differentiating agent retinoic acid ( RA ) has been previously reported to interfere with 12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) / Ca(2+) -induced signals for the regulation of the -96 to -66-bp octamer motif found in the enhancer for the interleukin ( IL ) -2 gene , which encodes a major T lymphocyte growth factor .", "target_text": { "-96 to -66-bp octamer motif": "DNA", "interleukin ( IL ) -2 gene": "DNA", "T lymphocyte growth factor": "protein" } }, { "input_text": "The IL-2 octamer motif is a composite cis-element which binds Oct-1 and Oct-2 as well as a TPA / Ca(2+) -inducible nuclear factor , previously termed octamer-associated protein ( OAP40 ) .", "target_text": { "IL-2": "protein", "IL-2 octamer motif": "DNA", "cis-element": "DNA", "Oct-1": "protein", "Oct-2": "protein", "TPA / Ca(2+) -inducible nuclear factor": "protein", "octamer-associated protein": "protein", "OAP40": "protein" } }, { "input_text": "We show here that Oct-2 , despite the presence of an active transcriptional activation domain , requires TPA/Ca(2+)-induced signals to strongly transactivate the IL-2 octamer motif in Jurkat T cells .", "target_text": { "Oct-2": "protein", "IL-2": "protein", "IL-2 octamer motif": "DNA" } }, { "input_text": "This Oct-2 -dependent transactivation is inhibited by RA .", "target_text": { "Oct-2": "protein" } }, { "input_text": "The presence of an intact COOH-terminal domain of Oct-2 contributes to both TPA / Ca(2+) -induced transactivation and the RA -mediated repression .", "target_text": { "intact COOH-terminal domain": "protein", "Oct-2": "protein" } }, { "input_text": "We also show that both Fos and Jun components of the AP-1 factors participate in the OAP40 complex .", "target_text": { "Fos": "protein", "Jun": "protein", "AP-1": "protein", "OAP40 complex": "protein" } }, { "input_text": "Furthermore , transfected c-jun , jun-B , jun-D , c-fos , or Fos-B expression vectors partially substitute for TPA and Ca2+ and cooperate with Oct-2 for the transactivation of the combined OAP/octamer cis-element .", "target_text": { "Oct-2": "protein", "OAP/octamer cis-element": "DNA" } }, { "input_text": "Mutations of the genuine octamer-binding site abrogate both the binding of Oct-1 and Oct-2 and the TPA / Ca(2+) -induced transactivation of the OAP /octamer motif .", "target_text": { "genuine octamer-binding site": "DNA", "Oct-1": "protein", "Oct-2": "protein", "OAP": "protein", "OAP /octamer motif": "DNA" } }, { "input_text": "OAP confers to Oct-2 responsivity to both TPA /Ca2+ and RA , since specific mutations of the AP-1 / OAP -binding site significantly reduce the transactivation by Oct-2 in response to TPA and Ca2+ and abolish the inhibition by RA .", "target_text": { "OAP": "protein", "Oct-2": "protein", "AP-1": "protein", "AP-1 / OAP -binding site": "DNA" } }, { "input_text": "Furthermore , retinoic acid receptor ( RAR ) alpha is able to inhibit in vitro the formation of the complex between the nuclear AP-1 /OAP and its specific binding site , resulting in the interference with Oct-2 -dependent cis-regulatory function of this AP-1 element .", "target_text": { "retinoic acid receptor": "protein", "RAR": "protein", "AP-1": "protein", "/OAP": "protein", "Oct-2": "protein" } }, { "input_text": "Therefore , we propose that the TPA / calcium -activated AP-1 /OAP element is the main target of positive or negative regulatory signals influencing the IL-2 octamer motif , through synergism with Oct-2 and antagonism by RAR .", "target_text": { "AP-1": "protein", "/OAP": "protein", "IL-2": "protein", "IL-2 octamer motif": "DNA", "Oct-2": "protein", "RAR": "protein" } }, { "input_text": "Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency .", "target_text": { "exon 7": "DNA", "common gamma chain gene": "DNA" } }, { "input_text": "Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease ( XCID ) suggested that XCID and X-linked severe combined immunodeficiency ( XSCID ) might arise from different genetic defects .", "target_text": {} }, { "input_text": "The recent discovery of mutations in the common gamma chain ( gamma c ) gene , a constituent of several cytokine receptors , in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID .", "target_text": { "common gamma chain ( gamma c ) gene": "DNA", "cytokine receptors": "protein" } }, { "input_text": "The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic , short tandem repeats ( CAG ) , in the androgen receptor gene , which also contains a methylation-sensitive HpaII site .", "target_text": { "X chromosome": "DNA", "short tandem repeats": "DNA", "androgen receptor gene": "DNA", "methylation-sensitive HpaII site": "DNA" } }, { "input_text": "As in XSCID , X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes .", "target_text": {} }, { "input_text": "In addition , X chromosome inactivation in PMNs was variable .", "target_text": { "X chromosome": "DNA" } }, { "input_text": "Findings from this analysis prompted sequencing of the gamma c gene in this pedigree .", "target_text": { "gamma c gene": "DNA" } }, { "input_text": "A missense mutation in the region coding for the cytoplasmic portion of the gamma c gene was found in three affected males but not in a normal brother .", "target_text": { "gamma c gene": "DNA" } }, { "input_text": "Therefore , this point mutation in the gamma c gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID .", "target_text": { "gamma c gene": "DNA" } }, { "input_text": "Posttranscriptional regulation of macrophage tissue factor expression by antioxidants .", "target_text": { "tissue factor": "protein" } }, { "input_text": "Tissue factor ( TF ) expression by cells of monocyte/macrophage lineage represents an important mechanism underlying the initiation of fibrin deposition at sites of extravascular inflammation .", "target_text": { "Tissue factor": "protein", "TF": "protein", "monocyte/macrophage lineage": "cell_type", "fibrin": "protein" } }, { "input_text": "Recent evidence suggests a role for oxidant stress in the signalling pathway of various cell types by virtue of its ability to induce DNA binding of various transcription factors , including nuclear factor kappa B and AP-1 .", "target_text": { "transcription factors": "protein", "nuclear factor kappa B": "protein", "AP-1": "protein" } }, { "input_text": "The effect of antioxidant treatment on lipopolysaccharide ( LPS ) -induced TF expression was examined in murine peritoneal macrophages and human monocytes .", "target_text": { "TF": "protein", "murine peritoneal macrophages": "cell_type", "human monocytes": "cell_type" } }, { "input_text": "Both pyrrolidine dithiocarbamate , an oxidant scavenger , and N-acetyl-cysteine , a precursor of the endogenous antioxidant glutathione , inhibited stimulation of macrophage procoagulant activity by LPS .", "target_text": {} }, { "input_text": "Northern blot analysis showed that neither of these agents reduced LPS -stimulated TF mRNA accumulation , thereby suggesting a posttranscriptional mechanism for the effect .", "target_text": { "TF": "protein" } }, { "input_text": "Immunofluorescence studies of human monocytes using polyclonal anti- TF antibody showed that N-acetyl-cysteine treatment prevented the characteristic plasmalemmal localization of TF antigen that occurs in response to LPS .", "target_text": { "human monocytes": "cell_type", "TF": "protein", "anti- TF antibody": "protein", "TF antigen": "protein" } }, { "input_text": "Western blot analysis showed that N-acetyl-cysteine reduced the accumulation of the 47-kD mature glycoprotein in LPS -treated cells , a finding consistent with the results of the immunofluorescence studies .", "target_text": { "47-kD mature glycoprotein": "protein", "LPS -treated cells": "cell_line" } }, { "input_text": "Furthermore , these conditions did not result in an accumulation of the less mature forms of TF .", "target_text": { "TF": "protein" } }, { "input_text": "When considered together , these data suggest that antioxidants exert their effects by impairing translation and/or by causing degradation of newly translated protein .", "target_text": { "translated protein": "protein" } }, { "input_text": "The effect of antioxidants on tumor necrosis factor appeared to be species specific , with no effect on LPS -induced tumor necrosis factor in murine cells , but with inhibition in human monocytes .", "target_text": { "tumor necrosis factor": "protein", "human monocytes": "cell_type" } }, { "input_text": "The posttranscriptional effect of antioxidants on TF expression data suggests a novel mechanism whereby these agents might modulate monocyte /macrophage activation .", "target_text": { "TF": "protein", "monocyte": "cell_type", "/macrophage": "cell_type" } }, { "input_text": "Characterization of the CD48 gene demonstrates a positive element that is specific to Epstein-Barr virus -immortalized B-cell lines and contains an essential NF-kappa B site .", "target_text": { "CD48 gene": "DNA", "Epstein-Barr virus -immortalized B-cell lines": "cell_type", "NF-kappa B": "protein", "NF-kappa B site": "DNA" } }, { "input_text": "Epstein-Barr virus ( EBV ) infection of mature , resting B cells drives them to become lymphoblasts expressing high levels of cell surface molecules , such as CD48 , characteristically expressed on normal activated B cells .", "target_text": { "resting B cells": "cell_type", "CD48": "protein", "normal activated B cells": "cell_type" } }, { "input_text": "Here , we report on the identification of an enhancer element in the CD48 gene which reproducibly confers strong transcriptional activity only in EBV -positive B-lymphoblastoid cell lines .", "target_text": { "enhancer element": "DNA", "CD48": "protein", "CD48 gene": "DNA", "EBV -positive B-lymphoblastoid cell lines": "cell_line" } }, { "input_text": "The element is not activated upon infection of established EBV -negative B-cell lines , indicating that EBV fails to drive these cells to a fully lymphoblastoid phenotype .", "target_text": { "EBV -negative B-cell lines": "cell_line", "lymphoblastoid phenotype": "cell_type" } }, { "input_text": "An NF-kappa B binding site is an essential component of the element but alone is not sufficient to account for the activity or the specificity of the element .", "target_text": { "NF-kappa B": "protein", "NF-kappa B binding site": "DNA" } }, { "input_text": "We have detected a specific nuclear protein complex that binds to the element and show that NF-kappa B1 ( p50 ) is a part of this complex .", "target_text": { "nuclear protein complex": "protein", "NF-kappa B1": "protein", "p50": "protein" } }, { "input_text": "The EBV -encoded latent membrane protein 1 is capable of transactivating the isolated CD48 NF-kappa B site but not the intact element , suggesting that the latent membrane protein 1 -driven activation of NF-kappa B/Rel must interact with other regulatory pathways to control expression of cellular genes as EBV drives resting B cells into the cell cycle .", "target_text": { "EBV -encoded latent membrane protein 1": "protein", "CD48": "protein", "NF-kappa B": "protein", "NF-kappa B site": "DNA", "intact element": "DNA", "latent membrane protein 1": "protein", "NF-kappa B/Rel": "protein", "resting B cells": "cell_type" } }, { "input_text": "Thapsigargin induces IL-2 receptor alpha-chain in human peripheral and Jurkat T cells via a protein kinase C -independent mechanism .", "target_text": { "IL-2 receptor alpha-chain": "protein", "human peripheral": "cell_type", "Jurkat T cells": "cell_line", "protein kinase C": "protein" } }, { "input_text": "Thapsigargin ( TG ) , an inhibitor of Ca(2+)-ATPase , depletes intracellular Ca2+ stores and induces a sustained Ca2+ influx without altering phosphatidyl inositol levels .", "target_text": { "Ca(2+)-ATPase": "protein" } }, { "input_text": "TG plus phorbol myristate acetate ( PMA ) but not TG alone induced IL-2 in Jurkat T cells , suggesting that TG had no effect on protein kinase C ( PKC ) .", "target_text": { "IL-2": "protein", "Jurkat T cells": "cell_line", "protein kinase C": "protein", "PKC": "protein" } }, { "input_text": "However , TG induced increases in IL-2R alpha protein as well as IL-2R alpha mRNA in Jurkat T cells in a dose-dependent manner .", "target_text": { "IL-2R alpha protein": "protein", "IL-2R alpha mRNA": "RNA", "Jurkat T cells": "cell_line" } }, { "input_text": "A similar increase in IL-2R alpha by TG was also observed in human peripheral T cells .", "target_text": { "IL-2R alpha": "protein", "human peripheral T cells": "cell_type" } }, { "input_text": "Further , like PMA , TG markedly induced NF kappa B in Jurkat T cells .", "target_text": { "NF kappa B": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "However , TG and PMA exhibited a synergistic action on IL-2R alpha expression , suggesting that TG and PMA induce IL-2R alpha through distinct pathways .", "target_text": { "IL-2R alpha": "protein" } }, { "input_text": "PMA - but not TG -induced IL-2R alpha is inhibited by the PKC inhibitor H7 , whereas TG - but not PMA -induced IL-2R alpha was inhibited by cholera toxin , forskolin and 1 , 9-dideoxy forskolin .", "target_text": { "PKC": "protein" } }, { "input_text": "In toto , these results suggest that TG induces IL-2R alpha in human T cells through a PKC -independent pathway .", "target_text": { "IL-2R alpha": "protein", "human T cells": "cell_type", "PKC": "protein" } }, { "input_text": "Physiological concentration of estradiol inhibits polymorphonuclear leukocyte chemotaxis via a receptor mediated system .", "target_text": { "polymorphonuclear leukocyte": "cell_type" } }, { "input_text": "Estrogen exhibits a variety of actions , including immuno-modulatory effects , in vivo and in vitro .", "target_text": {} }, { "input_text": "The mechanism by which estrogen exerts its anti-inflammatory effect is not yet understood .", "target_text": {} }, { "input_text": "We investigated the possible mechanisms of estradiol acting via the polymorphonuclear leukocytes ( PMNs ) , which are important in the immune response .", "target_text": { "polymorphonuclear leukocytes": "cell_type", "PMNs": "cell_type" } }, { "input_text": "The agent , 17 beta- estradiol , but not 17 alpha- estradiol , significantly reduced PMNs chemotaxis to FMLP in a dose-dependent manner ( control vs estrogen 10(-10)-(-6) M , P < 0.05 ) .", "target_text": { "PMNs": "cell_type" } }, { "input_text": "Physiological concentrations of estradiol significantly reduced the chemotaxis of PMNs ( 10(-10) mol ) .", "target_text": { "PMNs": "cell_type" } }, { "input_text": "Pre-incubation with clomiphene or tamoxifen which are estrogen receptor antagonists , eliminated the inhibitory effect of 17 beta- estradiol on the chemotaxis of PMNs , restoring it to the control level .", "target_text": { "PMNs": "cell_type" } }, { "input_text": "These observations suggest that 17 beta- estradiol suppressed the chemotaxis of PMNs by a receptor-dependent mechanism .", "target_text": { "PMNs": "cell_type" } }, { "input_text": "In addition , the level of estradiol in human plasma , which PMNs were drawn , showed a close , inverse correlation with the PMNs chemotaxis to FMLP ( r = -0.821 p < 0.001 ) .", "target_text": { "human plasma": "cell_type", "PMNs": "cell_type" } }, { "input_text": "Estrogen may modify the activity of neutrophils during the normal menstrual cycle , not only during pregnancy , and influence inflammation .", "target_text": { "neutrophils": "cell_type" } }, { "input_text": "Identification of the TCL1 gene involved in T-cell malignancies .", "target_text": { "TCL1 gene": "DNA", "T-cell": "cell_type" } }, { "input_text": "The TCL1 locus on chromosome 14q32.1 is frequently involved in chromosomal translocations and inversions with one of the T-cell receptor loci in human T-cell leukemias and lymphomas .", "target_text": { "TCL1 locus": "DNA", "chromosome 14q32.1": "DNA", "T-cell receptor loci": "DNA" } }, { "input_text": "The chromosome 14 region translocated or rearranged involves approximately 350 kb of DNA at chromosome band 14q32.1 .", "target_text": { "chromosome 14": "DNA", "chromosome 14 region": "DNA", "chromosome band 14q32.1": "DNA" } }, { "input_text": "Within this region we have identified a gene coding for a 1.3-kb transcript , expressed only in restricted subsets of cells within the lymphoid lineage and expressed at high levels in leukemic cells carrying a t(14;14) (q11;q32) chromosome translocation or a inv(14)(q11;q32) chromosome inversion .", "target_text": { "1.3-kb transcript": "RNA", "lymphoid lineage": "cell_type", "leukemic cells": "cell_type", "t(14;14) (q11;q32) chromosome translocation": "DNA", "inv(14)(q11;q32) chromosome inversion": "DNA" } }, { "input_text": "The cognate cDNA sequence reveals an open reading frame of 342 nt encoding a protein of 14 kDa .", "target_text": { "cognate cDNA sequence": "DNA", "open reading frame": "DNA", "protein of 14 kDa": "protein" } }, { "input_text": "The TCL1 gene sequence , which , to our knowledge , shows no sequence homology with other human genes , is preferentially expressed early in T- and B- lymphocyte differentiation .", "target_text": { "TCL1 gene": "DNA", "human genes": "DNA" } }, { "input_text": "Identification of a region which directs the monocytic activity of the colony-stimulating factor 1 ( macrophage colony-stimulating factor ) receptor promoter and binds PEBP2/CBF ( AML1 ) .", "target_text": { "colony-stimulating factor 1": "protein", "macrophage colony-stimulating factor": "protein", "receptor promoter": "DNA", "colony-stimulating factor 1 ( macrophage colony-stimulating factor ) receptor promoter": "DNA", "PEBP2/CBF": "protein", "AML1": "protein" } }, { "input_text": "The receptor for the macrophage colony-stimulating factor ( or colony-stimulating factor 1 [ CSF-1 ] ) is expressed from different promoters in monocytic cells and placental trophoblasts .", "target_text": { "macrophage colony-stimulating factor": "protein", "colony-stimulating factor 1": "protein", "CSF-1": "protein", "monocytic cells": "cell_type", "placental trophoblasts": "cell_type" } }, { "input_text": "We have demonstrated that the monocyte-specific expression of the CSF-1 receptor is regulated at the level of transcription by a tissue-specific promoter whose activity is stimulated by the monocyte/B-cell-specific transcription factor PU.1 ( D.-E.Zhang , C.J.Hetherington , H.-M.Chen , and D.G.Tenen , Mol .Cell. Biol. 14 : 373-381 , 1994 ) .", "target_text": { "CSF-1": "protein", "CSF-1 receptor": "protein", "tissue-specific promoter": "DNA", "monocyte/B-cell-specific transcription factor": "protein", "PU.1": "protein" } }, { "input_text": "Here we report that the tissue specificity of this promoter is also mediated by sequences in a region II ( bp -88 to - 59 ) , which lies 10 bp upstream from the PU.1 -binding site .", "target_text": { "promoter": "DNA", "region II": "DNA", "10 bp upstream": "DNA", "PU.1": "protein", "PU.1 -binding site": "DNA" } }, { "input_text": "When analyzed by DNase footprinting , region II was protected preferentially in monocytic cells .", "target_text": { "DNase": "protein", "region II": "DNA", "monocytic cells": "cell_type" } }, { "input_text": "Electrophoretic mobility shift assays confirmed that region II interacts specifically with nuclear proteins from monocytic cells .", "target_text": { "region II": "DNA", "nuclear proteins": "protein", "monocytic cells": "cell_type" } }, { "input_text": "Two gel shift complexes ( Mono A and Mono B ) were formed with separate sequence elements within this region .", "target_text": { "gel shift complexes": "protein", "Mono A": "protein", "Mono B": "protein" } }, { "input_text": "Competition and supershift experiments indicate that Mono B contains a member of the polyomavirus enhancer-binding protein 2/core-binding factor ( PEBP2/CBF ) family , which includes the AML1 gene product , while Mono A is a distinct complex preferentially expressed in monocytic cells .", "target_text": { "Mono B": "protein", "PEBP2/CBF": "protein", "polyomavirus enhancer-binding protein 2/core-binding factor ( PEBP2/CBF ) family ,": "protein", "Mono A": "protein", "monocytic cells": "cell_type" } }, { "input_text": "Promoter constructs with mutations in these sequence elements were no longer expressed specifically in monocytes .", "target_text": { "Promoter constructs": "DNA", "monocytes": "cell_type" } }, { "input_text": "Furthermore , multimerized region II sequence elements enhanced the activity of a heterologous thymidine kinase promoter in monocytic cells but not other cell types tested .", "target_text": { "region II": "DNA", "multimerized region II sequence elements": "DNA", "heterologous thymidine kinase promoter": "DNA", "monocytic cells": "cell_type" } }, { "input_text": "These results indicate that the monocyte/B-cell-specific transcription factor PU.1 and the Mono A and Mono B protein complexes act in concert to regulate monocyte-specific transcription of the CSF-1 receptor .", "target_text": { "monocyte/B-cell-specific transcription factor": "protein", "PU.1": "protein", "CSF-1": "protein", "CSF-1 receptor": "protein" } }, { "input_text": "Pyrrolidine dithiocarbamate , a potent inhibitor of nuclear factor kappa B ( NF-kappa B ) activation , prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes .", "target_text": { "nuclear factor kappa B": "protein", "NF-kappa B": "protein", "promyelocytic leukemia HL-60 cells": "cell_line", "thymocytes": "cell_type" } }, { "input_text": "We examined the effect of pyrrolidine dithiocarbamate ( PDTC ) , which potently blocks the activation of nuclear factor kappa B ( NF-kappa B ) , on the induction of apoptosis by a variety of agents .", "target_text": { "nuclear factor kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "Treatment of a human promyelocytic leukemia cell line , HL-60 , with 10 micrograms/mL etoposide or 2 microM 1-beta-D-arabinofuranosylcytosine induced NF-kappa B activation within 1 hr and subsequently caused apoptosis within 3-4 hr .", "target_text": { "human promyelocytic leukemia cell line": "cell_line", "HL-60": "cell_line", "NF-kappa B": "protein" } }, { "input_text": "The simultaneous addition of 50-500 microM PDTC with these agents blocked NF-kappa B activation and completely abrogated both morphologically apoptotic changes and internucleosomal DNA fragmentation for up to 6 hr .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "However , PDTC failed to inhibit the endonuclease activity contained in the whole cell lysates .", "target_text": { "endonuclease": "protein" } }, { "input_text": "The inhibitory effect of PDTC was also observed in etoposide - and dexamethasone-induced apoptosis in human thymocytes at a concentration of 1-10 microM .", "target_text": { "thymocytes": "cell_type", "human thymocytes": "cell_type" } }, { "input_text": "Since PDTC has both antioxidant and metal-ion chelating activities , we tested the effects of N-acetyl-L-cysteine ( NAC ) ( antioxidant ) or o-phenanthroline ( OP ) ( metal-ion chelator ) on the induction of apoptosis .", "target_text": {} }, { "input_text": "Pretreatment of HL-60 cells or thymocytes with 100-500 microM OP for 2 hr , but not 10-60 mM NAC , suppressed subsequent occurrence of apoptosis induced by etoposide .", "target_text": { "thymocytes": "cell_type" } }, { "input_text": "These results suggest that the activation of NF-kappa B plays an important role in the apoptotic process of human hematopoietic cells .", "target_text": { "NF-kappa B": "protein", "human hematopoietic cells": "cell_type" } }, { "input_text": "Overexpression of protein kinase C -zeta stimulates leukemic cell differentiation .", "target_text": { "protein kinase C": "protein", "protein kinase C -zeta": "protein", "leukemic cell": "cell_type" } }, { "input_text": "A function for protein kinase C -zeta ( PKC -zeta ) , a member of the phorbol ester nonresponsive atypical protein kinase C subfamily , in modulating differentiation was examined in the leukemic U937 cell .", "target_text": { "protein kinase C": "protein", "protein kinase C -zeta": "protein", "PKC": "protein", "PKC -zeta": "protein", "protein kinase C subfamily": "protein", "leukemic U937 cell": "cell_line" } }, { "input_text": "Transfected U937 cells stably overexpressing PKC-zeta displayed a longer doubling time , lower saturation density at confluency , and an increase in adherence to plastic as compared to control cells .", "target_text": { "U937 cells": "cell_line", "PKC-zeta": "protein", "control cells": "cell_line" } }, { "input_text": "PKC-zeta cells expressed a more differentiated phenotype as assessed by changes in morphology , surface antigen expression , and lysosomal enzyme activities and were distinct from parental U937 cells stimulated to differentiate by exposure to phorbol esters .", "target_text": { "PKC-zeta": "protein", "PKC-zeta cells": "cell_line", "lysosomal enzyme": "protein", "U937 cells": "cell_line", "parental U937 cells": "cell_line" } }, { "input_text": "In contrast to parental U937 cells , PKC-zeta cells constitutively expressed mRNA transcripts for c-jun and a low mobility AP-1 binding activity .", "target_text": { "U937 cells": "cell_line", "PKC-zeta": "protein", "PKC-zeta cells": "cell_line", "mRNA": "RNA", "mRNA transcripts": "RNA", "c-jun": "DNA", "AP-1": "protein" } }, { "input_text": "Thus , PKC-zeta overexpression stimulates a type of phenotypic differentiation that differs significantly from maturation occurring upon activation of other PKC subfamilies induced by phorbol ester treatment .", "target_text": { "PKC-zeta": "protein", "PKC": "protein", "PKC subfamilies": "protein" } }, { "input_text": "Increased expression of the c-jun protooncogene and an increase in AP-1 binding activity in PKC-zeta cells provides a potential mechanism for explaining the altered differentiation status of this cell .", "target_text": { "c-jun": "DNA", "AP-1": "protein", "PKC-zeta": "protein", "PKC-zeta cells": "cell_line" } }, { "input_text": "A family of serine proteases expressed exclusively in myelo- monocytic cells specifically processes the nuclear factor-kappa B subunit p65 in vitro and may impair human immunodeficiency virus replication in these cells .", "target_text": { "serine proteases": "protein", "monocytic cells": "cell_type", "nuclear factor-kappa B subunit p65": "protein" } }, { "input_text": "Two groups of U937 promonocytic cells were obtained by limiting dilution cloning which differed strikingly in their ability to support human immunodeficiency virus 1 ( HIV-1 ) replication .", "target_text": { "U937 promonocytic cells": "cell_line" } }, { "input_text": "\" Plus \" clones replicated the virus efficiently , whereas \" minus \" clones did not .", "target_text": { "\" Plus \" clones": "cell_line", "\" minus \" clones": "cell_line" } }, { "input_text": "We examined these clones for differences in nuclear factor ( NF ) -kappa B activity which might account for the observed phenomenon .", "target_text": { "nuclear factor ( NF ) -kappa B": "protein" } }, { "input_text": "Stimulation of plus clones liberated the classical p50-p65 complex from cytoplasmic pools , whereas minus clones produced an apparently novel , faster-migrating complex , as judged by electrophoretic mobility shift assays .", "target_text": { "plus clones": "cell_line", "p50-p65 complex": "protein", "minus clones": "cell_line", "faster-migrating complex": "protein" } }, { "input_text": "It is surprising that the faster-migrating complex was composed also of p50 and p65 .", "target_text": { "faster-migrating complex": "protein", "p50": "protein", "p65": "protein" } }, { "input_text": "However , the p65 subunit was COOH-terminally truncated , as shown by immunoprecipitation .", "target_text": { "p65": "protein", "p65 subunit": "protein" } }, { "input_text": "The truncation resulted from limited proteolysis of p65 during cellular extraction which released particular lysosomal serine proteases , such as elastase , cathepsin G , and proteinase 3 .", "target_text": { "p65": "protein", "serine proteases": "protein", "lysosomal serine proteases": "protein", "elastase": "protein", "cathepsin G": "protein", "proteinase 3": "protein" } }, { "input_text": "These specific proteases are coordinately expressed and were present exclusively in the minus U937 clones , but not in the plus clones , as demonstrated in the case of cathepsin G .", "target_text": { "minus U937 clones": "cell_line", "plus clones": "cell_line", "cathepsin G": "protein" } }, { "input_text": "In addition , these proteases were detected in certain subclones of THP-1 and HL-60 cells and in primary monocytes , in each case correlating with the truncated from of p65 .", "target_text": { "THP-1": "cell_line", "HL-60 cells": "cell_line", "monocytes": "cell_type", "p65": "protein" } }, { "input_text": "We demonstrate in vitro cleavage of p65 by purified elastase and cathepsin G .", "target_text": { "p65": "protein", "elastase": "protein", "cathepsin G": "protein" } }, { "input_text": "It is possible that particular serine proteases may have inhibiting effects on the replication of HIV-1 in myelo- monocytic cells .", "target_text": { "serine proteases": "protein", "monocytic cells": "cell_type", "myelo- monocytic cells": "cell_line" } }, { "input_text": "The data also demonstrate that special precautions must be taken when making extracts from myelo- monocytic cells .", "target_text": { "monocytic cells": "cell_type", "myelo- monocytic cells": "cell_line" } }, { "input_text": "A germline TaqI restriction fragment length polymorphism in the progesterone receptor gene in ovarian carcinoma [ see comments ]", "target_text": { "germline TaqI restriction fragment length polymorphism": "DNA", "progesterone receptor gene": "DNA" } }, { "input_text": "Clinical outcome in ovarian carcinoma is predicted by progesterone receptor status , indicating an endocrine aspect to this disease .", "target_text": { "progesterone receptor": "protein" } }, { "input_text": "Peripheral leucocyte genomic DNAs were obtained from 41 patients with primary ovarian carcinoma and 83 controls from Ireland , as well as from 26 primary ovarian carcinoma patients and 101 controls in Germany .", "target_text": { "Peripheral leucocyte genomic DNAs": "DNA" } }, { "input_text": "Southern analysis using a human progesterone receptor ( hPR ) cDNA probe identified a germline TaqI restriction fragment length polymorphism ( RFLP ) defined by two alleles : T1 , represented by a 2.7 kb fragment ; and T2 , represented by a 1.9 kb fragment and characterised by an additional TaqI restriction site with respect to T1 .", "target_text": { "progesterone receptor": "protein", "human progesterone receptor": "protein", "hPR": "protein", "human progesterone receptor ( hPR ) cDNA probe": "DNA", "germline TaqI restriction fragment length polymorphism": "DNA", "RFLP": "DNA", "alleles": "DNA", "T1": "DNA", "2.7 kb fragment": "DNA", "T2": "DNA", "1.9 kb fragment": "DNA", "TaqI restriction site": "DNA" } }, { "input_text": "An over-representation of T2 in ovarian cancer patients compared with controls in the pooled Irish/German population ( P < 0.025 ) was observed .", "target_text": { "T2": "DNA" } }, { "input_text": "A difference ( P < 0.02 ) in the distribution of the RFLP genotypes between Irish and German control populations was also observed .", "target_text": { "RFLP": "DNA" } }, { "input_text": "The allele distributions could not be shown to differ significantly from Hardy-Weinberg distribution in any subgroup .", "target_text": {} }, { "input_text": "Using hPR cDNA region-specific probes , the extra TaqI restriction site was mapped to intron G of the hPR gene .", "target_text": { "hPR": "protein", "hPR cDNA region-specific probes": "DNA", "intron G": "DNA", "hPR gene": "DNA" } }, { "input_text": "OBF-1 , a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins .", "target_text": { "OBF-1": "protein", "novel B cell-specific coactivator": "protein", "immunoglobulin promoter": "DNA", "octamer-binding proteins": "protein" } }, { "input_text": "Recent biochemical and genetic studies indicate that in addition to the octamer-binding proteins Oct-1 and Oct-2 , other B cell components are required for lymphoid-restricted , octamer site-mediated immunoglobulin gene promoter activity .", "target_text": { "octamer-binding proteins": "protein", "Oct-1": "protein", "Oct-2": "protein", "B cell components": "protein", "immunoglobulin gene promoter": "DNA" } }, { "input_text": "Using a genetic screen in yeast , we have isolated B cell-derived cDNAs encoding Oct-binding factor 1 ( OBF-1 ) , a novel protein that specifically associates with Oct-1 and Oct-2 .", "target_text": { "B cell-derived cDNAs": "DNA", "Oct-binding factor 1": "protein", "OBF-1": "protein", "Oct-1": "protein", "Oct-2": "protein" } }, { "input_text": "Biochemical studies demonstrate that OBF-1 has no intrinsic DNA-binding activity and recognizes the POU domains of Oct-1 and Oct-2 , but not those of Oct-4 and Oct-6 .", "target_text": { "OBF-1": "protein", "POU domains": "protein", "Oct-1": "protein", "Oct-2": "protein", "Oct-4": "protein", "Oct-6": "protein" } }, { "input_text": "The OBF-1 mRNA is expressed in a highly cell-specific manner , being most abundant in B cells and essentially absent in most of the other cells or tissues tested .", "target_text": { "OBF-1": "protein", "OBF-1 mRNA": "RNA", "B cells": "cell_type" } }, { "input_text": "Furthermore , expression of OBF-1 in HeLa cells selectively stimulates the activity of a natural immunoglobulin promoter in an octamer site -dependent manner .", "target_text": { "OBF-1": "protein", "HeLa cells": "cell_line", "immunoglobulin promoter": "DNA", "octamer site": "DNA" } }, { "input_text": "Thus , OBF-1 has all the properties expected for a B cell-specific transcriptional coactivator protein .", "target_text": { "OBF-1": "protein", "B cell-specific transcriptional coactivator protein": "protein" } }, { "input_text": "Modulation of transcription factor NF kappa B activity by intracellular glutathione levels and by variations of the extracellular cysteine supply .", "target_text": { "NF kappa B": "protein", "transcription factor NF kappa B": "protein" } }, { "input_text": "HIV -infected individuals and SIV -infected rhesus macaques have , on the average , decreased plasma cysteine and cystine concentrations and decreased intracellular glutathione levels .", "target_text": {} }, { "input_text": "We now show that a depletion of intracellular glutathione in a human T cell line ( Molt-4 ) inhibits the activation and nuclear translocation of the transcription factor NF kappa B , whereas incubation with increasing extracellular concentrations of cysteine inhibits the DNA-binding and transactivating activity of NF kappa B .", "target_text": { "human T cell line": "cell_line", "Molt-4": "cell_line", "NF kappa B": "protein", "transcription factor NF kappa B": "protein" } }, { "input_text": "Because inhibition of DNA-binding activity is associated with increasing intracellular glutathione disulfide levels and GSSG can be shown to inhibit the DNA-binding activity directly in cell-free systems , our studies suggest that GSSG is a physiologically relevant inhibitor in intact cells also .", "target_text": { "GSSG": "protein", "intact cells": "cell_type" } }, { "input_text": "NF kappa B controls many immunologically important genes , so our studies suggest that the immune system may be sensitive not only against a cysteine and glutathione deficiency but also against an excess of cysteine .", "target_text": { "NF kappa B": "protein", "immunologically important genes": "DNA" } }, { "input_text": "Two distinct signalling pathways are involved in the control of the biphasic junB transcription induced by interleukin-6 in the B cell hybridoma 7TD1 .", "target_text": { "junB": "DNA", "interleukin-6": "protein", "B cell hybridoma 7TD1": "cell_line" } }, { "input_text": "We have measured the level of junB mRNA in the B hybridoma cell line 7TD1 , under interleukin-6 ( IL-6 ) stimulation .", "target_text": { "junB mRNA": "RNA", "B hybridoma cell line 7TD1": "cell_line", "interleukin-6": "protein", "IL-6": "protein" } }, { "input_text": "IL-6 increases junB mRNA in a biphasic fashion .", "target_text": { "IL-6": "protein", "junB mRNA": "RNA" } }, { "input_text": "The first early-induced peak was transient and likely corresponds to the well documented typical junB mRNA , stimulated in response to numerous growth factors , including IL-6 .", "target_text": { "junB mRNA": "RNA", "growth factors": "protein", "IL-6": "protein" } }, { "input_text": "At variance , the second peak which has never been reported previously , lasted several hours .", "target_text": {} }, { "input_text": "As a consequence of its effect on junB mRNA , IL-6 stimulated , in a biphasic fashion , the nuclear accumulation of the JunB protein .", "target_text": { "junB mRNA": "RNA", "IL-6": "protein", "JunB protein": "protein" } }, { "input_text": "In this study , we demonstrated that IL-6 regulation occurred exclusively at the transcriptional level and that the bimodal increase of junB mRNA and JunB protein can be accounted for by a biphasic stimulation of junB transcription .", "target_text": { "IL-6": "protein", "junB mRNA": "RNA", "JunB protein": "protein", "junB": "DNA" } }, { "input_text": "Furthermore , our data point to two major differences between the mechanism of control of the early and the late IL-6 -induced junB transcription waves .", "target_text": { "IL-6": "protein", "junB": "DNA" } }, { "input_text": "First , cycloheximide strongly potentiated the transcription of the second wave , whereas it failed to affect the early-induced burst .", "target_text": {} }, { "input_text": "Second , tyrphostin , a tyrosine kinase inhibitor , impaired the expression of the first but not the second junB mRNA peak .", "target_text": { "junB mRNA": "RNA" } }, { "input_text": "Conversely , genistein , another tyrosine kinase inhibitor , totally abolished the expression of the second peak of junB mRNA whereas it did not affect the expression of the first peak .", "target_text": { "junB mRNA": "RNA" } }, { "input_text": "Altogether these data indicate that , in 7TD1 cells , IL-6 controls junB transcription in a biphasic fashion by means of two separate transduction pathways .", "target_text": { "7TD1 cells": "cell_line", "IL-6": "protein", "junB": "DNA" } }, { "input_text": "A newly established megakaryoblastic/erythroid cell line that differentiates to red cells in the presence of erythropoietin and produces platelet-like particles .", "target_text": { "megakaryoblastic/erythroid cell line": "cell_line", "red cells": "cell_type", "erythropoietin": "protein", "platelet-like particles": "cell_type" } }, { "input_text": "In August , 1992 , we established a leukemic cell line ( NS-Meg ) from a patient in megakaryoblastic transformation of Philadelphia chromosome-positive chronic myeloid leukemia .", "target_text": { "leukemic cell line": "cell_line", "NS-Meg": "cell_line" } }, { "input_text": "The NS-Meg cells were positive for alpha-naphthyl acetate esterase and periodic acid-Schiff ( PAS ) staining and for surface CD4 , CD7 , CD13 , CD34 , CD41a , and glycophorin A antigens .", "target_text": { "NS-Meg cells": "cell_line", "alpha-naphthyl acetate esterase": "protein", "CD4": "protein", "CD7": "protein", "CD13": "protein", "CD34": "protein", "CD41a": "protein", "glycophorin A antigens": "protein" } }, { "input_text": "Ultrastructurally , the cells had alpha-granules , demarcation membranes , and platelet peroxidase activity .", "target_text": { "platelet peroxidase": "protein" } }, { "input_text": "The NS-Meg cells spontaneously produced platelet-like particles which contained alpha-granules , mitochondria and dense bodies , strongly suggesting platelet production .", "target_text": { "NS-Meg cells": "cell_line", "platelet-like particles": "cell_type" } }, { "input_text": "Erythropoietin ( Epo ) , granulocyte/macrophage colony stimulating factor ( GM-CSF ) , and interleukin 3 ( IL-3 ) promoted the growth of NS-Meg cells .", "target_text": { "Erythropoietin": "protein", "Epo": "protein", "granulocyte/macrophage colony stimulating factor": "protein", "GM-CSF": "protein", "interleukin 3": "protein", "IL-3": "protein", "NS-Meg cells": "cell_line" } }, { "input_text": "Phorbol-12-myristate-13-acetate increased the expression of both CD41a and CD61 antigens .", "target_text": { "CD41a": "protein" } }, { "input_text": "Ten-day exposure to Epo induced mature erythroblasts and red cells .", "target_text": { "Epo": "protein", "mature erythroblasts": "cell_type", "red cells": "cell_type" } }, { "input_text": "These benzidine-positive cells were positive for hemoglobin F staining .", "target_text": { "benzidine-positive cells": "cell_line", "hemoglobin": "protein" } }, { "input_text": "Untreated NS-Meg cells expressed mRNA for the Epo receptor ( EpoR ) , for GATA-1 , and for alpha 1 , alpha 2 and gamma globin genes .", "target_text": { "NS-Meg cells": "cell_line", "mRNA": "RNA", "Epo receptor": "protein", "EpoR": "protein", "GATA-1": "protein" } }, { "input_text": "These results indicate that NS-Meg cells undergo terminal differentiation of both megakaryocytic and erythroid lineages .", "target_text": { "NS-Meg cells": "cell_line" } }, { "input_text": "This cell line should be a very useful tool for the investigation of both megakaryocytic and erythroid maturation .", "target_text": { "cell line": "cell_line" } }, { "input_text": "Differential regulation of proto-oncogenes c-jun and c-fos in T lymphocytes activated through CD28 .", "target_text": { "proto-oncogenes": "DNA", "c-jun": "DNA", "c-fos": "DNA", "T lymphocytes": "cell_type", "CD28": "protein" } }, { "input_text": "The T cell surface molecule CD28 binds to ligands on accessory cells and APCs , playing an important costimulatory role in the response of T cells to Ags .", "target_text": { "T cell surface molecule": "protein", "CD28": "protein", "accessory cells": "cell_type", "APCs": "cell_type", "T cells": "cell_type", "Ags": "protein" } }, { "input_text": "Our knowledge of the intracellular signaling pathways coupled to this receptor is incomplete .", "target_text": {} }, { "input_text": "In addition to activation of phospholipase C gamma 1 , ligation of this receptor also seems to activate a calcium -independent , CD28 -specific pathway .", "target_text": { "phospholipase C gamma 1": "protein", "CD28": "protein" } }, { "input_text": "In this paper , we report that cross-linking of CD28 ( but not CD2 , CD5 , LFA-1 , or CD7 ) leads to an elevation of c-jun mRNA , with only minimal activation of c-fos expression .", "target_text": { "CD28": "protein", "CD2": "protein", "CD5": "protein", "LFA-1": "protein", "CD7": "protein", "c-jun": "DNA", "c-jun mRNA": "RNA", "c-fos": "DNA" } }, { "input_text": "CD28 -dependent induction of c-jun expression requires protein tyrosine kinase activity , but does not depend on activation of a phorbol ester -responsive protein kinase C or elevation of cytosolic calcium .", "target_text": { "CD28": "protein", "c-jun": "DNA", "protein tyrosine kinase": "protein", "phorbol ester -responsive protein kinase C": "protein" } }, { "input_text": "Furthermore , CD28 -dependent elevation of c-jun mRNA does not appear to be mediated at the level of mRNA stability .", "target_text": { "CD28": "protein", "c-jun": "DNA", "c-jun mRNA": "RNA" } }, { "input_text": "A mechanism is suggested whereby expression of c-jun and junB , in the absence of members of the fos family , can prevent inappropriate activation of T cells caused by ligation of CD28 in the absence of a specific antigenic stimulus .", "target_text": { "c-jun": "DNA", "junB": "DNA", "fos family": "DNA", "T cells": "cell_type", "CD28": "protein" } }, { "input_text": "Enhanced responsiveness to nuclear factor kappa B contributes to the unique phenotype of simian immunodeficiency virus variant SIVsmmPBj14 .", "target_text": { "nuclear factor kappa B": "protein" } }, { "input_text": "Infection with a variant of simian immunodeficiency virus , SIVsmmPBj14 , leads to severe acute disease in macaques .", "target_text": {} }, { "input_text": "This study was designed to investigate the functional significance of previously described mutations in the viral long terminal repeat ( LTR ) and to elucidate their contribution to the unique phenotype of SIVsmmPBj14 .", "target_text": { "viral long terminal repeat": "DNA", "LTR": "DNA" } }, { "input_text": "LTR -directed transcription was measured by using luciferase reporter constructs that were transiently transfected into cultured cells .", "target_text": { "LTR": "DNA", "luciferase reporter constructs": "DNA", "cultured cells": "cell_line" } }, { "input_text": "In a wide range of cell types , the basal transcriptional activity of the LTR from SIVsmmPBj14 was found to be 2- to 4.5-fold higher than that of an LTR from a non-acutely pathogenic strain .", "target_text": { "LTR": "DNA" } }, { "input_text": "These LTRs differ by five point mutations and a 22-bp duplication in SIVsmmPBj14 , which includes a nuclear factor kappa B ( NF kappa B ) site .", "target_text": { "LTRs": "DNA", "22-bp duplication": "DNA", "nuclear factor kappa B": "protein", "NF kappa B": "protein", "nuclear factor kappa B ( NF kappa B ) site": "DNA" } }, { "input_text": "Transcriptional differences between these LTRs were further enhanced by two- to threefold upon treatment of cells with phorbol ester or tumor necrosis factor alpha or by cotransfection with plasmids expressing NF kappa B subunits .", "target_text": { "LTRs": "DNA", "tumor necrosis factor alpha": "protein", "plasmids": "DNA", "NF kappa B": "protein" } }, { "input_text": "Mutagenesis studies , and the use of a reporter construct containing an enhancerless promoter , indicate that these transcriptional effects are due principally to the 22-bp sequence duplication and the NF kappa B site contained within it .", "target_text": { "22-bp sequence duplication": "DNA", "NF kappa B": "protein", "NF kappa B site": "DNA" } }, { "input_text": "Finally , infectious virus stocks that were isogenic except for the LTR were generated .", "target_text": { "LTR": "DNA" } }, { "input_text": "The LTR from SIVsmmPBj14 was found to confer an increase in the kinetics of virus replication in cultured cells .", "target_text": { "LTR": "DNA", "cultured cells": "cell_line" } }, { "input_text": "Inclusion of this LTR in recombinant SIVs also resulted in a two- to threefold rise in the extent of cellular proliferation that was induced in quiescent simian peripheral blood mononuclear cells .", "target_text": { "LTR": "DNA", "quiescent simian peripheral blood mononuclear cells": "cell_line" } }, { "input_text": "These studies are consistent with the hypothesis that LTR mutations assist SIVsmmPBj14 in responding efficiently to cellular stimulation and allow it to replicate to high titers during the acute phase of viral infection .", "target_text": { "LTR": "DNA" } }, { "input_text": "Constitutive nuclear NF-kappa B in cells of the monocyte lineage .", "target_text": { "nuclear NF-kappa B": "protein" } }, { "input_text": "In monocytes , the nuclear factor NF-kappa B has been invoked as an important transcription factor in the expression of cytokine genes , of cell-surface receptors and in the expression of human immunodeficiency virus .", "target_text": { "monocytes": "cell_type", "NF-kappa B": "protein", "nuclear factor NF-kappa B": "protein", "transcription factor": "protein", "cytokine genes": "DNA", "cell-surface receptors": "protein" } }, { "input_text": "In such cells , DNA binding activity of NF-kappa B can be detected without intentional stimulation .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "In our studies , cells of the human monocytic line Mono Mac 6 , cultured in medium containing fetal-calf serum and low levels of lipopolysaccharide ( LPS ) , also exhibit such ' constitutive ' NF-kappa B , as demonstrated by mobility-shift analysis of nuclear extracts .", "target_text": { "human monocytic line": "cell_line", "Mono Mac 6": "cell_line", "NF-kappa B": "protein" } }, { "input_text": "This nuclear NF-kappa B was still present when contaminant LPS was removed by ultrafiltration and when serum was omitted .", "target_text": { "NF-kappa B": "protein", "nuclear NF-kappa B": "protein" } }, { "input_text": "Protein-DNA complexes of constitutive NF-kappa B are similar in mobility to the LPS -induced NF-kappa B and both are recognized by an antibody specific to the p50 subunit of NF-kappa B .", "target_text": { "NF-kappa B": "protein", "LPS -induced NF-kappa B": "protein", "p50 subunit": "protein" } }, { "input_text": "By contrast , treatment of cells with pyrrolidine dithiocarbamate ( PDTC ) will only block LPS -induced NF-kappa B , but not the constitutive binding protein .", "target_text": { "NF-kappa B": "protein", "LPS -induced NF-kappa B": "protein", "constitutive binding protein": "protein" } }, { "input_text": "Using LPS-free and serum-free conditions , constitutive NF-kappa B can be detected in different cell lines of the monocytic lineage ( HL60 , U937 , THP-1 , Mono Mac 1 and Mono Mac 6 ) , but not in Molt 4 T cells or K562 stem cells .", "target_text": { "NF-kappa B": "protein", "cell lines": "cell_line", "monocytic lineage": "cell_type", "HL60": "cell_line", "U937": "cell_line", "THP-1": "cell_line", "Mono Mac 1": "cell_line", "Mono Mac 6": "cell_line", "Molt 4 T cells": "cell_line", "K562 stem cells": "cell_line" } }, { "input_text": "When ordered according to stage of maturation , the amount of constitutive NF-kappa B was not increased in more mature cell lines .", "target_text": { "NF-kappa B": "protein", "mature cell lines": "cell_line" } }, { "input_text": "Furthermore , when inducing differentiation in Mono Mac 6 cells , with vitamin D3 , no change in constitutive or inducible NF-kappa B can be detected .", "target_text": { "Mono Mac 6 cells": "cell_line", "NF-kappa B": "protein" } }, { "input_text": "Analysis of primary cells revealed substantial constitutive NF-kappa B -binding activity in blood monocytes , pleural macrophages and alveolar macrophages .", "target_text": { "NF-kappa B": "protein", "monocytes": "cell_type", "blood monocytes": "cell_type", "pleural macrophages": "cell_type", "alveolar macrophages": "cell_type" } }, { "input_text": "The constitutive NF-kappa B appears to be functionally active , since a low level of tumour necrosis factor ( TNF ) transcript is detectable in monocytes , and this level can be increased by blocking transcript degradation using cycloheximide .", "target_text": { "NF-kappa B": "protein", "tumour necrosis factor ( TNF ) transcript": "RNA", "monocytes": "cell_type" } }, { "input_text": "The level of constitutive NF-kappa B in these cells is variable and is frequently found to be lower in the more mature macrophages .", "target_text": { "NF-kappa B": "protein", "mature macrophages": "cell_type" } }, { "input_text": "Constitutive NF-kappa B was not maintained by autocrine action of cytokines TNF , interleukin 6 , interleukin 10 , granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor , since neutralizing antibodies did not reduce constitutive DNA-binding activity .", "target_text": { "NF-kappa B": "protein", "cytokines": "protein", "TNF": "protein", "interleukin 6": "protein", "interleukin": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "macrophage colony-stimulating factor": "protein" } }, { "input_text": "Furthermore , blockade of prostaglandin or leukotriene biosynthesis did not affect constitutive NF-kappa B .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "( ABSTRACT TRUNCATED AT 400 WORDS )", "target_text": {} }, { "input_text": "Steel factor affects SCL expression during normal erythroid differentiation .", "target_text": { "Steel factor": "protein", "SCL": "protein" } }, { "input_text": "Steel factor is one of the growth factors that controls the proliferation and differentiation of hematopoietic cells and SCL , also known as Tcl-5 or Tal-1 , is a transcription factor involved in erythropoiesis .", "target_text": { "Steel factor": "protein", "growth factors": "protein", "hematopoietic cells": "cell_type", "SCL": "protein", "Tcl-5": "protein", "Tal-1": "protein", "transcription factor": "protein" } }, { "input_text": "In this report , we studied the role of SCL in the proliferation of human peripheral blood burst-forming unit-erythroid ( BFU-E ) and the effects of Steel factor on SCL expression in proliferating erythroid cells .", "target_text": { "human peripheral blood burst-forming unit-erythroid": "cell_type", "BFU-E": "cell_type", "Steel factor": "protein", "SCL": "protein", "proliferating erythroid cells": "cell_type" } }, { "input_text": "BFU-E -derived colonies increase progressively in size , as determined by cell number , from day 7 to day 14 of culture , with the greatest increase in colony size ( 10-fold expansion ) occurring between day 7 and day 10 .", "target_text": { "BFU-E": "cell_type", "BFU-E -derived colonies": "cell_line" } }, { "input_text": "SCL protein levels in BFU-E -derived cells were highest in day 7 cells and decreased progressively from day 7 to day 14 of culture , suggesting an association of SCL with erythroid proliferation .", "target_text": { "SCL protein": "protein", "BFU-E": "cell_type", "BFU-E -derived cells": "cell_line", "SCL": "protein" } }, { "input_text": "In contrast , SCL mRNA levels did not decrease significantly between day 7 and day 14 cells , suggesting that posttranscriptional mechanisms are largely responsible for the decrease in SCL protein observed .", "target_text": { "SCL": "protein", "SCL mRNA": "RNA", "SCL protein": "protein" } }, { "input_text": "The role of SCL in Steel factor -induced erythroid proliferation was then examined .", "target_text": { "SCL": "protein", "Steel factor": "protein" } }, { "input_text": "In BFU-E -derived colonies cultured with Steel factor , colony size was significantly increased compared to control .", "target_text": { "BFU-E": "cell_type", "BFU-E -derived colonies": "cell_line", "Steel factor": "protein" } }, { "input_text": "In day 7 and day 10 erythroid precursors cultured with Steel factor , SCL protein was increased significantly compared to control .", "target_text": { "erythroid precursors": "cell_type", "Steel factor": "protein", "SCL": "protein", "SCL protein": "protein" } }, { "input_text": "The increase in SCL protein levels in early erythroid precursors stimulated with Steel factor suggests one mechanism through which Steel factor may enhance normal erythroid proliferation .", "target_text": { "SCL": "protein", "erythroid precursors": "cell_type", "Steel factor": "protein" } }, { "input_text": "SCL mRNA levels assessed by Northern blot in day 7 cells did not increase significantly in response to Steel factor stimulation , suggesting that posttranscriptional mechanisms may also be important in the increase in SCL protein observed in response to Steel .", "target_text": { "SCL": "protein", "SCL mRNA": "RNA", "Steel factor": "protein", "SCL protein": "protein", "Steel": "protein" } }, { "input_text": "C/EBP beta regulation of the tumor necrosis factor alpha gene .", "target_text": { "C/EBP beta": "protein", "tumor necrosis factor alpha": "protein", "tumor necrosis factor alpha gene": "DNA" } }, { "input_text": "Activated macrophages contribute to chronic inflammation by the secretion of cytokines and proteinases .", "target_text": { "Activated macrophages": "cell_type", "cytokines": "protein", "proteinases": "protein" } }, { "input_text": "Tumor necrosis factor alpha ( TNF alpha ) is particularly important in this process because of its ability to regulate other inflammatory mediators in an autocrine and paracrine fashion .", "target_text": { "Tumor necrosis factor alpha": "protein", "TNF alpha": "protein" } }, { "input_text": "The mechanism ( s ) responsible for the cell type-specific regulation of TNF alpha is not known .", "target_text": { "TNF alpha": "protein" } }, { "input_text": "We present data to show that the expression of TNF alpha is regulated by the transcription factor C/EBP beta ( NF-IL6 ) .", "target_text": { "TNF alpha": "protein", "transcription factor": "protein", "C/EBP beta": "protein", "NF-IL6": "protein" } }, { "input_text": "C/EBP beta activated the TNF alpha gene promoter in cotransfection assays and bound to it at a site which failed to bind the closely related protein C/EBP alpha .", "target_text": { "C/EBP beta": "protein", "TNF alpha": "protein", "TNF alpha gene promoter": "DNA", "C/EBP alpha": "protein" } }, { "input_text": "Finally , a dominant-negative version of C/EBP beta blocked TNF alpha promoter activation in myeloid cells .", "target_text": { "C/EBP beta": "protein", "TNF alpha": "protein", "TNF alpha promoter": "DNA", "myeloid cells": "cell_type" } }, { "input_text": "Our results implicate C/EBP beta as an important regulator of TNF alpha by myelomonocytic cells .", "target_text": { "C/EBP beta": "protein", "TNF alpha": "protein", "myelomonocytic cells": "cell_type" } }, { "input_text": "Calcium/calmodulin-dependent protein kinase II downregulates both calcineurin and protein kinase C -mediated pathways for cytokine gene transcription in human T cells .", "target_text": { "Calcium/calmodulin-dependent protein kinase II": "protein", "cytokine": "protein", "cytokine gene": "DNA", "human T cells": "cell_type" } }, { "input_text": "Engagement of the T cell receptor for antigen activates phospholipase C resulting in an increase in intracellular free calcium concentration ( [ Ca2+ ]i ) and activation of protein kinase C ( PKC ) .", "target_text": { "T cell receptor": "protein", "phospholipase C": "protein", "protein kinase C": "protein", "PKC": "protein" } }, { "input_text": "Increased [ Ca2+ ]i activates Ca2+ /calmodulin-dependent kinases including the multifunctional Ca2+ /calmodulin-dependent protein kinase II ( CaM-K II ) , as well as calcineurin , a type 2B protein phosphatase .", "target_text": { "Ca2+ /calmodulin-dependent kinases": "protein", "Ca2+ /calmodulin-dependent protein kinase II": "protein", "CaM-K II": "protein", "calcineurin": "protein", "type 2B protein phosphatase": "protein" } }, { "input_text": "Recent studies have identified calcineurin as a key enzyme for interleukin ( IL ) -2 and IL-4 promoter activation .", "target_text": { "calcineurin": "protein" } }, { "input_text": "However , the role of CaM-K II remains unknown .", "target_text": { "CaM-K II": "protein" } }, { "input_text": "We have used mutants of these kinases and phosphatases ( gamma B*CaM-K and delta CaM-AI , respectively ) to explore their relative role in cytokine gene transcription and their interactions with PKC -dependent signaling systems .", "target_text": { "kinases": "protein", "phosphatases": "protein", "gamma B*CaM-K": "protein", "delta CaM-AI": "protein", "cytokine": "protein", "cytokine gene": "DNA", "PKC": "protein" } }, { "input_text": "gamma B*CaM-K and delta CaM-AI , known to exhibit constitutive Ca(2+)-independent activity , were cotransfected ( alone or in combination ) in Jurkat T cells with a plasmid containing the intact IL-2 promoter driving the expression of the chloramphenicol acetyltransferase reporter gene .", "target_text": { "gamma B*CaM-K": "protein", "delta CaM-AI": "protein", "Jurkat T cells": "cell_line", "IL-2 promoter": "DNA", "chloramphenicol acetyltransferase reporter gene": "DNA" } }, { "input_text": "Cotransfection of gamma B*CaM-K with the IL-2 promoter construct downregulated its transcription in response to stimulation with ionomycin and phorbol myristate acetate ( PMA ) .", "target_text": { "gamma B*CaM-K": "protein", "IL-2 promoter": "DNA", "IL-2 promoter construct": "DNA" } }, { "input_text": "The inhibitory effect of CaM-K II on IL-2 promoter was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways .", "target_text": { "CaM-K II": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Under the same conditions , delta CaM-AI superinduced IL-2 promoter activity ( approximately twofold increase ) .", "target_text": { "delta CaM-AI": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "When both mutants were used in combination , gamma B*CaM-K inhibited the induction of the IL-2 promoter by delta CaM-AI .", "target_text": { "gamma B*CaM-K": "protein", "IL-2 promoter": "DNA", "delta CaM-AI": "protein" } }, { "input_text": "Similar results were obtained when a construct containing the IL-4 promoter also was used .", "target_text": { "IL-4": "protein", "IL-4 promoter": "DNA" } }, { "input_text": "gamma B*CaM-K also downregulated the activation of AP-1 in response to transfection with a constitutively active mutant of PKC or stimulation with PMA .", "target_text": { "gamma B*CaM-K": "protein", "AP-1": "protein", "PKC": "protein" } }, { "input_text": "These results suggest that CaM-K II may exert negative influences on cytokine gene transcription in human T cells , and provide preliminary evidence for negative cross-talk with the calcineurin- and PKC- dependent signaling systems .", "target_text": { "CaM-K II": "protein", "cytokine": "protein", "cytokine gene": "DNA", "human T cells": "cell_type" } }, { "input_text": "Induction of ICAM-1 and LFA-3 by Tax1 of human T-cell leukemia virus type 1 and mechanism of down-regulation of ICAM-1 or LFA-1 in adult-T-cell-leukemia cell lines .", "target_text": { "ICAM-1": "protein", "LFA-3": "protein", "Tax1": "protein", "LFA-1": "protein", "adult-T-cell-leukemia cell lines": "cell_line" } }, { "input_text": "The present study was undertaken to determine the role of HTLV-I TaxI in the up-regulation of ICAM-I and LFA-3 in human T cells transformed with HTLV-I and the mechanism of down-regulation of ICAM-I and LFA-I in ATL-derived cell lines .", "target_text": { "HTLV-I TaxI": "protein", "ICAM-I": "protein", "LFA-3": "protein", "human T cells": "cell_type", "LFA-I": "protein", "ATL-derived cell lines": "cell_line" } }, { "input_text": "Induction of TaxI in a human T-cell line Jurkat carrying the TaxI gene under the metallothionein promoter led to increases in mRNA and surface expression of ICAM-I .", "target_text": { "TaxI": "protein", "human T-cell line Jurkat": "cell_line", "TaxI gene": "DNA", "metallothionein promoter": "DNA", "mRNA": "RNA", "ICAM-I": "protein" } }, { "input_text": "The response of LFA-3 to TaxI induction was , on the other hand , relatively slow and weak , and might be indirect .", "target_text": { "LFA-3": "protein", "TaxI": "protein" } }, { "input_text": "Transactivation of the ICAM-I promoter by TaxI was further shown by co-transfection of a CAT reporter construct with the ICAM-I promoter and a plasmid expressing TaxI .", "target_text": { "ICAM-I": "protein", "ICAM-I promoter": "DNA", "TaxI": "protein", "CAT reporter construct": "DNA", "plasmid": "DNA" } }, { "input_text": "The mechanism of down-regulation of ICAM-I or LFA-I in 4 ATL cell lines was next examined .", "target_text": { "ICAM-I": "protein", "LFA-I": "protein", "4 ATL cell lines": "cell_line" } }, { "input_text": "ICAM-I mRNA was quite low in MT-I , but no genomic changes were found .", "target_text": { "ICAM-I": "protein", "ICAM-I mRNA": "RNA", "MT-I": "cell_line" } }, { "input_text": "The CAT reporter with the ICAM-I promoter was inactive in MT-I .", "target_text": { "CAT reporter": "DNA", "ICAM-I": "protein", "ICAM-I promoter": "DNA", "MT-I": "cell_line" } }, { "input_text": "Finally , combined treatment of MT-I with 5-azacytidine and IFN-gamma induced re-expression of ICAM-I .", "target_text": { "MT-I": "cell_line", "IFN-gamma": "protein", "ICAM-I": "protein" } }, { "input_text": "Collectively , ( a ) transcriptional factor ( s ) necessary for expression of ICAM-I gene may be repressed in MT-I through DNA methylation .", "target_text": { "transcriptional factor": "protein", "ICAM-I": "protein", "ICAM-I gene": "DNA", "MT-I": "cell_line" } }, { "input_text": "Three other ATL cell lines ( TL-OmI , H582 , HuT102 ) were found to have little mRNA for the LFA-I beta chain ( CD18 ) .", "target_text": { "ATL cell lines": "cell_line", "TL-OmI": "cell_line", "H582": "cell_line", "HuT102": "cell_line", "mRNA": "RNA", "LFA-I beta chain": "protein", "CD18": "protein" } }, { "input_text": "H582 and HuT102 were also negative for the LFA-I alpha chain ( CDIIa ) mRNA .", "target_text": { "H582": "cell_line", "HuT102": "cell_line", "LFA-I": "protein", "LFA-I alpha chain": "protein", "LFA-I alpha chain ( CDIIa ) mRNA": "RNA" } }, { "input_text": "No genomic changes were found , and a CAT reporter gene with the CD18 promoter was inactive in the 3 of them , again suggesting lack of ( a ) transcriptional factor ( s ) necessary for CD18 expression .", "target_text": { "CAT reporter gene": "DNA", "CD18 promoter": "DNA", "transcriptional factor": "protein", "CD18": "protein" } }, { "input_text": "Infection with Theileria annulata induces expression of matrix metalloproteinase 9 and transcription factor AP-1 in bovine leucocytes .", "target_text": { "matrix metalloproteinase 9": "protein", "transcription factor": "protein", "AP-1": "protein", "bovine leucocytes": "cell_type" } }, { "input_text": "Theileria annulata infects bovine leucocytes and results in their reversible transformation such that they become immortalised and metastatic .", "target_text": { "bovine leucocytes": "cell_type" } }, { "input_text": "The present study describes parasite-induced changes in host cell gene expression which have a direct bearing on this transformation process .", "target_text": { "host cell gene": "DNA" } }, { "input_text": "T. annulata -infected leucocytes produce a number of novel metalloproteinase activities .", "target_text": { "T. annulata -infected leucocytes": "cell_type", "metalloproteinase": "protein" } }, { "input_text": "One of these , previously called B1 , is a 97-kDa protein which is secreted in large amounts and has been purified from protein-free , conditioned medium .", "target_text": { "B1": "protein", "97-kDa protein": "protein" } }, { "input_text": "An antiserum to this enzyme was used to isolate a cDNA clone .", "target_text": { "cDNA clone": "DNA" } }, { "input_text": "The predicted protein sequence of B1 is 81 % identical to human matrix metalloproteinase 9 ( MMP9 ) , demonstrating that it is the bovine homologue of this enzyme .", "target_text": { "B1": "protein", "matrix metalloproteinase 9": "protein", "MMP9": "protein" } }, { "input_text": "RNAase protection assays demonstrated that the MMP9 activity , unique to infected cells , is due to increased MMP9 mRNA levels .", "target_text": { "RNAase": "protein", "MMP9": "protein", "infected cells": "cell_type" } }, { "input_text": "We also assayed the levels of transcription factor AP-1 and demonstrated that it was constitutively present in increased amounts in Theileria-infected cells .", "target_text": { "transcription factor": "protein", "AP-1": "protein", "Theileria-infected cells": "cell_type" } }, { "input_text": "In addition we assayed the level of mRNA encoding c-Fos , a common component of AP-1 and observed that it was indeed up-regulated in infected cells .", "target_text": { "mRNA": "RNA", "c-Fos": "protein", "AP-1": "protein", "infected cells": "cell_type" } }, { "input_text": "Since AP-1 is implicated in the control of the cell cycle , and MMP9 can confer metastatic properties , these results are of considerable significance with respect to the transformed phenotype induced by Theileria infection .", "target_text": { "AP-1": "protein", "MMP9": "protein" } }, { "input_text": "B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2 .", "target_text": { "B-cell": "cell_type", "G1-regulating proteins": "protein", "EBNA2": "protein" } }, { "input_text": "Infection of primary B-lymphocytes by Epstein-Barr virus ( EBV ) leads to growth transformation of these B-cells in vitro .", "target_text": { "primary B-lymphocytes": "cell_type", "B-cells": "cell_type" } }, { "input_text": "EBV nuclear antigen 2 ( EBNA2 ) , one of the first genes expressed after EBV infection of B-cells , is a transcriptional activator of viral and cellular genes and is essential for the transforming potential of the virus .", "target_text": { "EBNA2": "protein", "B-cells": "cell_type", "viral": "DNA", "cellular genes": "DNA", "viral and cellular genes": "DNA" } }, { "input_text": "We generated conditional EBV mutants by expressing EBNA2 as chimeric fusion protein with the hormone binding domain of the estrogen receptor on the genetic background of the virus .", "target_text": { "EBNA2": "protein", "chimeric fusion protein": "protein", "estrogen receptor": "protein" } }, { "input_text": "Growth transformation of primary normal B-cells by mutant virus resulted in estrogen -dependent lymphoblastoid cell lines expressing the chimeric EBNA2 protein .", "target_text": { "B-cells": "cell_type", "primary normal B-cells": "cell_type", "estrogen -dependent lymphoblastoid cell lines": "cell_line", "EBNA2": "protein", "EBNA2 protein": "protein" } }, { "input_text": "In the absence of estrogen about half of the cells enter a quiescent non-proliferative state whereas the others die by apoptosis .", "target_text": {} }, { "input_text": "EBNA2 is thus required not only for initiation but also for maintenance of transformation .", "target_text": { "EBNA2": "protein" } }, { "input_text": "Growth arrest occurred at G1 and G2 stages of the cell cycle , indicating that functional EBNA2 is required at different restriction points of the cell cycle .", "target_text": { "EBNA2": "protein" } }, { "input_text": "Growth arrest is reversible for G1/G0 cells as indicated by the sequential accumulation and modification of cell cycle regulating proteins .", "target_text": { "G1/G0 cells": "cell_type", "cell cycle regulating proteins": "protein" } }, { "input_text": "EBV induces the same cell cycle regulating proteins as polyclonal stimuli in primary B-cells .", "target_text": { "B-cells": "cell_type" } }, { "input_text": "These data suggest that EBV is using a common pathway for B-cell activation bypassing the requirement for antigen , T-cell signals and growth factors .", "target_text": { "growth factors": "protein" } }, { "input_text": "IL-1 receptor and TCR signals synergize to activate NF-kappa B -mediated gene transcription .", "target_text": { "IL-1 receptor": "protein", "TCR": "protein", "NF-kappa B": "protein" } }, { "input_text": "Previous studies have demonstrated that IL-1 receptor ( IL-1R ) - and TCR -initiated signals can interact synergistically to increase the rate of transcription of several lymphokine and lymphokine receptor genes during the competence phase of the activation program in T helper lymphocytes .", "target_text": { "IL-1 receptor": "protein", "IL-1R": "protein", "TCR": "protein", "T helper lymphocytes": "cell_type" } }, { "input_text": "In this report we describe how signals initiated through the type I IL-1R interact with signals from the antigen receptor to synergistically augment the transactivating properties of NF-kappa B .", "target_text": { "IL-1R": "protein", "type I IL-1R": "protein", "NF-kappa B": "protein" } }, { "input_text": "The synergistic antigen receptor initiated signals are mediated through protein kinase C because they can be mimicked by the phorbol ester , 12-O-tetradecanoylphorbol-13-acetate , but not with calcium ionophores ; and are staurosporine sensitive but cyclosporine resistant .", "target_text": { "antigen receptor": "protein", "protein kinase C": "protein" } }, { "input_text": "Gel shift analyses demonstrate that NF-kappa B nuclear translocation is stimulated primarily by IL-1 rather than by antigen receptor signals .", "target_text": { "NF-kappa B": "protein", "IL-1": "protein", "antigen receptor": "protein" } }, { "input_text": "Western blot and phosphorylation analyses demonstrate that the synergistic effect on NF-kappa B functional activity is independent of I kappa B alpha ( MAD3 ) - NF-kappa B dissociation in the cytosol and is not associated with I kappa B nuclear translocation .", "target_text": { "NF-kappa B": "protein", "I kappa B alpha": "protein", "MAD3": "protein", "I kappa B": "protein" } }, { "input_text": "The IL-1 -induced NF-kappa B DNA nuclear localization is transient and can be prolonged either by an antigen receptor-initiated signal or by inhibiting protein synthesis .", "target_text": { "IL-1": "protein", "NF-kappa B": "protein" } }, { "input_text": "These results suggest that IL-1 induces both NF-kappa B nuclear translocation and the synthesis of a protein ( s ) responsible for terminating NF-kappa B -DNA interaction in the nucleus .", "target_text": { "IL-1": "protein", "NF-kappa B": "protein" } }, { "input_text": "Antigen receptor signals prolong NF-kappa B -DNA interaction , probably by functionally antagonizing the IL-1 -induced synthesis of a protein ( s ) responsible for the transient NF-kappa B -DNA interaction and consequently synergistically enhance IL-1 -induced NF-kappa B -dependent gene transcription .", "target_text": { "NF-kappa B": "protein", "IL-1": "protein" } }, { "input_text": "Identification of the promoter region of chicken anemia virus ( CAV ) containing a novel enhancer-like element .", "target_text": { "promoter region": "DNA", "enhancer-like element": "DNA" } }, { "input_text": "The single promoter region in the cloned genome [ Noteborn et al. , J. Virol. 65 ( 1991 ) 3131-3139 ] of chicken anemia virus ( CAV ) in chicken T-cells was analysed via CAT assays .", "target_text": { "promoter region": "DNA", "chicken T-cells": "cell_type", "CAT": "protein" } }, { "input_text": "A unique region containing four or five near-perfect direct repeats ( DR ) of 21 bp with one 12-bp insert was proven to be the main transcription-activation element , with enhancer-like characteristics .", "target_text": { "direct repeats": "DNA", "DR": "DNA", "12-bp insert": "DNA", "transcription-activation element": "DNA" } }, { "input_text": "PCR studies revealed that CAV isolates from across the world all contained this promoter sequence .", "target_text": { "promoter sequence": "DNA" } }, { "input_text": "Electrophoretic mobility-shift assays ( EMSA ) showed that individual DR units , as well as the 12-bp insert , can bind to nuclear factors of chicken T-cells .", "target_text": { "individual DR units": "DNA", "12-bp insert": "DNA", "nuclear factors": "protein", "chicken T-cells": "cell_type" } }, { "input_text": "Competition assays revealed that the DR units bound to factors other than the 12-bp insert .", "target_text": { "DR units": "DNA", "12-bp insert": "DNA" } }, { "input_text": "A synthetic oligodeoxyribonucleotide containing an SP1-box ( 5'-GGGCGG ) could compete with factors binding to the 12-bp insert .", "target_text": { "SP1-box": "DNA", "12-bp insert": "DNA" } }, { "input_text": "Purified human SP1 was shown to have very strong affinity for the 12-bp insert .", "target_text": { "human SP1": "protein", "12-bp insert": "DNA" } }, { "input_text": "Functional Myc-Max heterodimer is required for activation-induced apoptosis in T cell hybridomas .", "target_text": { "Myc-Max heterodimer": "protein", "T cell hybridomas": "cell_line" } }, { "input_text": "T cell hybridomas respond to activation signals by undergoing apoptotic cell death , and this is likely to represent comparable events related to tolerance induction in immature and mature T cells in vivo .", "target_text": { "T cell hybridomas": "cell_line" } }, { "input_text": "Previous studies using antisense oligonucleotides implicated the c-Myc protein in the phenomenon of activation-induced apoptosis .", "target_text": { "c-Myc protein": "protein" } }, { "input_text": "This role for c-Myc in apoptosis is now confirmed in studies using a dominant negative form of its heterodimeric binding partner , Max , which we show here inhibits activation-induced apoptosis .", "target_text": { "c-Myc": "protein", "Max": "protein" } }, { "input_text": "Further , coexpression of a reciprocally mutant Myc protein capable of forming functional heterodimers with the mutant Max can compensate for the dominant negative activity and restore activation-induced apoptosis .", "target_text": { "reciprocally mutant Myc protein": "protein", "heterodimers": "protein", "Max": "protein" } }, { "input_text": "These results imply that Myc promotes activation-induced apoptosis by obligatory heterodimerization with Max , and therefore , by regulating gene transcription .", "target_text": { "Myc": "protein", "Max": "protein" } }, { "input_text": "Epstein-Barr virus SM protein .", "target_text": { "Epstein-Barr virus SM protein": "protein" } }, { "input_text": "The protein products of the Epstein-Barr virus ( EBV ) BMLF1 open reading frame have been characterized in the early productive cycle in B95-8 and Akata cells .", "target_text": { "Epstein-Barr virus ( EBV ) BMLF1 open reading frame": "DNA", "B95-8": "cell_line", "Akata cells": "cell_line" } }, { "input_text": "The SM protein derived from the spliced RNA joining BSLF2 to BMLF1 is much the most abundant protein .", "target_text": { "SM protein": "protein", "BSLF2": "protein", "BMLF1": "protein" } }, { "input_text": "SM is a phosphoprotein in EBV -infected cells and can be phosphorylated in vitro with casein kinase II ( CKII ) .", "target_text": { "SM": "protein", "phosphoprotein": "protein", "-infected cells": "cell_type", "casein kinase II": "protein", "CKII": "protein" } }, { "input_text": "Computer analysis of the SM protein sequence showed a C terminal section of SM to be related to genome positional homologues of four other herpesviruses and revealed consensus CKII sites near the N termini of the EBV SM protein , the herpes simplex virus ( HSV ) ICP27 protein and the herpesvirus saimiri ( HVS ) open reading frame 57 protein .", "target_text": { "SM": "protein", "SM protein": "protein", "SM protein sequence": "protein", "C terminal section": "protein", "genome positional homologues": "protein", "CKII": "protein", "consensus CKII sites": "protein", "N termini": "protein", "EBV SM protein": "protein", "herpes simplex virus ( HSV ) ICP27 protein": "protein", "herpesvirus saimiri ( HVS ) open reading frame 57 protein": "protein" } }, { "input_text": "Site-directed mutagenesis of the consensus CKII site in EBV SM greatly reduced the in vitro phosphorylation of SM by CKII .", "target_text": { "CKII": "protein", "consensus CKII site": "DNA", "SM": "protein" } }, { "input_text": "The mechanism of transactivation by BMLF1 proteins has been controversial but SM was shown to transactivate gene expression from a CAT reporter construct by increasing the amount of cytoplasmic CAT mRNA .", "target_text": { "BMLF1": "protein", "BMLF1 proteins": "protein", "SM": "protein", "CAT reporter construct": "DNA", "cytoplasmic CAT mRNA": "RNA" } }, { "input_text": "Mutagenesis of the CKII site in SM made no difference to the transactivation in this transient transfection assay .", "target_text": { "CKII": "protein", "SM": "protein" } }, { "input_text": "Inducible binding to the c-fos serum response element during T cell activation is regulated by a phosphotyrosine-containing protein .", "target_text": { "phosphotyrosine-containing protein": "protein" } }, { "input_text": "The proto-oncogene c-fos is an immediate-early gene , and one of the first genes transcribed after stimulation of most cells with a variety of ligands .", "target_text": { "proto-oncogene c-fos": "DNA", "immediate-early gene": "DNA" } }, { "input_text": "Fos expression may be a pivotal event in converting ligand-receptor interactions at the membrane into functional modulation of cell phenotype .", "target_text": {} }, { "input_text": "The serum response element ( SRE ) in the c-fos regulatory region participates in induction of transcription by various growth factors and by phorbol esters and subsequent squelching of transcription .", "target_text": { "serum response element": "DNA", "SRE": "DNA", "c-fos regulatory region": "DNA", "growth factors": "protein" } }, { "input_text": "We show that an inducible protein complex ( Band A ) binds to SRE DNA within 10 min after mitogenic stimulation of human PBL-T , and becomes nondetectable by 60 min .", "target_text": { "protein complex": "protein", "Band A": "protein", "SRE": "DNA", "SRE DNA": "DNA", "human PBL-T": "cell_line" } }, { "input_text": "Band A contains the serum response factor plus additional factor ( s ) .", "target_text": { "Band A": "protein", "serum response factor": "protein" } }, { "input_text": "A protein that is phosphorylated on a tyrosine residue in resting PBL-T suppresses binding of a component of Band A to the SRE motif .", "target_text": { "resting PBL-T": "cell_line", "Band A": "protein", "SRE": "DNA", "SRE motif": "DNA" } }, { "input_text": "Upon stimulation of the cells , this protein no longer prevents binding of DNA by Band A , and suppression of binding is restored within 30 min .", "target_text": { "Band A": "protein" } }, { "input_text": "The phosphorylated tyrosine residue itself is important for the protein-protein interaction .", "target_text": {} }, { "input_text": "In vivo modification of major histocompatibility complex class II DRA promoter occupancy mediated by the AIR-1 trans-activator .", "target_text": { "major histocompatibility complex class II": "protein", "major histocompatibility complex class II DRA promoter": "DNA", "AIR-1 trans-activator": "protein" } }, { "input_text": "RJ 2.2.5 is a human B cell mutant derived from the Burkitt lymphoma Raji cell which is defective in the AIR-1 locus function .", "target_text": { "RJ 2.2.5": "cell_line", "human B cell mutant": "cell_line", "Burkitt lymphoma Raji cell": "cell_line" } }, { "input_text": "This locus encodes a transcriptional trans-activator required for the constitutive expression of major histocompatibility complex ( MHC ) class II genes .", "target_text": { "major histocompatibility complex ( MHC ) class II genes": "DNA" } }, { "input_text": "Here we show , by in vivo DNase I footprinting , that the AIR-1 locus defect correlates with changes in the DRA promoter occupancy .", "target_text": { "DNase I": "protein", "AIR-1 locus defect": "DNA", "DRA promoter": "DNA" } }, { "input_text": "Interestingly , reexpression of human MHC class II genes in RJ 2.2.5 x mouse spleen cell hybrids is associated with partial reversion of DRA promoter occupancy to the Raji pattern .", "target_text": { "human MHC class II genes": "DNA", "RJ 2.2.5 x mouse spleen cell hybrids": "cell_line", "DRA promoter": "DNA" } }, { "input_text": "DRA promoter occupancy in other class II-negative B cell lines , derived from patients with bare lymphocyte syndrome , is drastically different from the one observed in RJ 2.2.5 and Raji cells .", "target_text": { "DRA promoter": "DNA", "class II-negative B cell lines": "cell_line", "RJ 2.2.5": "cell_line", "Raji cells": "cell_line" } }, { "input_text": "Moreover , the use of the DNase I as an in vivo footprinting agent reveals that the patients ' cell lines do not display a completely \" bare promoter \" as previously reported using dimethyl sulfate as the footprinting agent .", "target_text": { "DNase I": "protein", "patients ' cell lines": "cell_line", "bare promoter": "DNA" } }, { "input_text": "Thus , the use of DNase I allowed us , for the first time , to correlate the AIR-1 locus defect with class II promoter occupancy alterations and distinguish these alterations from the ones observed in phenotypically similar but genetically distinct MHC class II-negative cells .", "target_text": { "DNase I": "protein", "AIR-1 locus defect": "DNA", "class II promoter": "DNA", "MHC class II-negative cells": "cell_line" } }, { "input_text": "Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression : potential role of physical interactions between Elf-1 , HMG-I(Y) , and NF-kappa B family proteins .", "target_text": { "interleukin-2 receptor alpha-chain": "protein", "Elf-1": "protein", "HMG-I(Y)": "protein", "NF-kappa B family proteins": "protein" } }, { "input_text": "The interleukin 2 receptor alpha-chain ( IL-2R alpha ) gene is rapidly and potently induced in T cells in response to mitogenic stimuli .", "target_text": { "interleukin 2 receptor alpha-chain": "protein", "IL-2R alpha": "protein", "interleukin 2 receptor alpha-chain ( IL-2R alpha ) gene": "DNA", "T cells": "cell_type" } }, { "input_text": "Previously , an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified .", "target_text": { "inducible enhancer": "DNA", "nucleotides -299 and -228": "DNA" } }, { "input_text": "We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y) .", "target_text": { "essential positive regulatory element": "DNA", "nucleotides -137 and -64": "DNA", "Elf-1": "protein", "HMG-I(Y)": "protein" } }, { "input_text": "This element had maximal activity in lymphoid cells , paralleling the cell type specificity of Elf-1 expression .", "target_text": { "lymphoid cells": "cell_type", "Elf-1": "protein" } }, { "input_text": "Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I(Y) binding site was mutated .", "target_text": { "IL-2R alpha": "protein", "IL-2R alpha promoter": "DNA", "Elf-1": "protein", "HMG-I(Y)": "protein" } }, { "input_text": "Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells .", "target_text": { "-137 to -64 element": "DNA", "COS-7 cells": "cell_line" } }, { "input_text": "Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro , suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements .", "target_text": { "Elf-1": "protein", "HMG-I": "protein", "NF-kappa B": "protein", "p50": "protein", "c-Rel": "protein" } }, { "input_text": "This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins .", "target_text": { "NF-kappa B": "protein", "NF-kappa B family proteins": "protein" } }, { "input_text": "These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins .", "target_text": { "IL-2R alpha": "protein", "Elf-1": "protein", "NF-kappa B": "protein", "NF-kappa B family proteins": "protein" } }, { "input_text": "Isolation of cDNA clones for 42 different Kruppel-related zinc finger proteins expressed in the human monoblast cell line U-937 .", "target_text": { "cDNA clones": "DNA", "Kruppel-related zinc finger proteins": "protein", "human monoblast cell line U-937": "cell_line" } }, { "input_text": "To study the complexity and structural characteristics of zinc finger proteins expressed during human hematopoiesis and to isolate novel regulators of blood cell development , a degenerate oligonucleotide probe specific for a consensus zinc finger peptide domain was used to isolate 63 cDNA clones for Kruppel-related zinc finger genes from the human monoblast cell line U-937 .", "target_text": { "zinc finger proteins": "protein", "consensus zinc finger peptide domain": "protein", "cDNA clones": "DNA", "Kruppel-related zinc finger genes": "DNA", "human monoblast cell line U-937": "cell_line" } }, { "input_text": "By extensive nucleotide sequence and Northern blot analysis , these cDNA clones were found to originate from approximately 42 different genes ( HZF 1-42 ) of which only 8 have previously been described .", "target_text": { "cDNA clones": "DNA", "HZF 1-42": "DNA" } }, { "input_text": "Northern blot analysis showed that a majority of these genes were expressed at comparable levels in U-937 and HeLa cells .", "target_text": { "U-937": "cell_line", "HeLa cells": "cell_line" } }, { "input_text": "The large number of individual genes represented among the 63 clones and their apparent non-cell-type-specific expression suggest that the majority of the Kruppel-related zinc finger genes are likely to be expressed in most human tissues .", "target_text": { "Kruppel-related zinc finger genes": "DNA" } }, { "input_text": "In contrast , some of the genes displayed a restricted expression pattern , indicating that they represent potential regulators of monocyte differentiation or proliferation .", "target_text": {} }, { "input_text": "Detailed structural analysis of the first 12 cDNAs ( HZF 1-10 ) and a partial characterization of HZF 11-42 revealed that a common feature of human Kruppel-related zinc finger proteins is the presence of tandem arrays of zinc fingers ranging in number from 3 to over 20 that are preferentially located in the carboxy-terminal regions of the proteins .", "target_text": { "cDNAs": "DNA", "HZF 1-10": "DNA", "HZF 11-42": "DNA", "zinc finger proteins": "protein", "Kruppel-related zinc finger proteins": "protein", "human Kruppel-related zinc finger proteins": "protein", "zinc fingers": "protein", "carboxy-terminal regions": "protein" } }, { "input_text": "In addition , several novel KRAB-containing zinc finger genes and a novel conserved sequence element were identified .", "target_text": { "KRAB-containing zinc finger genes": "DNA", "conserved sequence element": "DNA" } }, { "input_text": "CAG repeat length variation in sperm from a patient with Kennedy 's disease .", "target_text": { "CAG repeat length variation": "DNA", "sperm": "cell_type" } }, { "input_text": "Using a modified sperm typing protocol , the mutation frequency of the CAG repeat region at the androgen receptor locus has been measured using a rare semen sample from an individual with spinal and bulbar muscular atrophy ( SBMA ) .", "target_text": { "sperm": "cell_type", "CAG repeat region": "DNA", "androgen receptor locus": "DNA" } }, { "input_text": "Among 258 X chromosome-containing sperm , 19 % had a repeat number equal to the donor 's somatic DNA ( 47 repeats ) , 66 % were expansions and 15 % were contractions .", "target_text": { "sperm": "cell_type", "X chromosome-containing sperm": "cell_type", "donor 's somatic DNA": "DNA" } }, { "input_text": "The average expansion was 2.7 repeats .", "target_text": {} }, { "input_text": "More than half of the expansions involved one or two repeats ; the largest was 11 repeats .", "target_text": {} }, { "input_text": "68 % of the contractions were also one or two repeats but six ( 16 % ) were very large ( 12-25 repeats ) .", "target_text": {} }, { "input_text": "One contraction generated an allele in an intermediate size range ( 33-39 repeats ) .", "target_text": {} }, { "input_text": "Such alleles have not been observed among more than 900 normal and SBMA X-chromosomes that have been examined .", "target_text": { "SBMA X-chromosomes": "DNA" } }, { "input_text": "Comparison of the SBMA sperm typing results with mutation frequency data on normal alleles supports the hypothesis that trinucleotide repeat expansions may have a different molecular origin than contractions .", "target_text": { "sperm": "cell_type", "trinucleotide repeat": "DNA" } }, { "input_text": "Aspirin-like drugs can protect human T lymphocytes against benzoquinone cytotoxicity : evidence for a NAD(P)H:quinone reductase -dependent mechanism .", "target_text": { "human T lymphocytes": "cell_type", "NAD(P)H:quinone reductase": "protein" } }, { "input_text": "Benzene toxicity towards lymphocytes is thought to be mediated by metabolites of benzene including benzoquinone ( BQ ) .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "NAD(P)H:quinone reductase ( QR ) is known to protect against BQ toxicity .", "target_text": { "NAD(P)H:quinone reductase": "protein", "QR": "protein" } }, { "input_text": "The expression of the QR gene is regulated by the transcription factor AP-1 .", "target_text": { "QR": "protein", "QR gene": "DNA", "transcription factor": "protein", "AP-1": "protein" } }, { "input_text": "We had previously found that aspirin-like drugs ( ALD ) induce AP-1 in human T lymphocytes .", "target_text": { "AP-1": "protein", "lymphocytes": "cell_type", "human T lymphocytes": "cell_type" } }, { "input_text": "It was therefore hypothesized that ALD would protect lymphocytes against BQ toxicity by inducing QR .", "target_text": { "lymphocytes": "cell_type", "QR": "protein" } }, { "input_text": "Molt-4 cells ( M4 ) , a human T lymphocyte cell line , were incubated with different concentrations of two ALD , flurbiprofen and sodium diclofenac , and then exposed to BQ .", "target_text": { "Molt-4 cells": "cell_line", "M4": "cell_line", "human T lymphocyte cell line": "cell_line" } }, { "input_text": "Toxicity was measured by viability ( trypan blue exclusion ) .", "target_text": {} }, { "input_text": "Both drugs protected the cells against BQ cytotoxicity in a dose-dependent manner , e.g. , sodium diclofenac at 15 microM reduced the fraction of BQ -treated dead cells by 70 % .", "target_text": {} }, { "input_text": "ALDs induced QR activity in the M4 cells in the same range of concentrations that protected the cells against BQ toxicity .", "target_text": { "QR": "protein" } }, { "input_text": "The protective effect of ALD was significantly reduced by dicoumarol , a QR -specific inhibitor .", "target_text": { "QR": "protein" } }, { "input_text": "Since human T cells and T cell lines do not metabolize arachidonic acid , our data suggest that ALD can protect human T lymphocytes against a metabolite of benzene by induction of QR activity .", "target_text": { "human T cells": "cell_type", "T cell lines": "cell_type", "lymphocytes": "cell_type", "human T lymphocytes": "cell_type", "QR": "protein" } }, { "input_text": "Correlation of differentiation-inducing activity of retinoids on human leukemia cell lines HL-60 and NB4 .", "target_text": { "human leukemia cell lines": "cell_line", "HL-60": "cell_line", "NB4": "cell_line" } }, { "input_text": "Retinoids , including all-trans-retinoic acid , its isomers , and fifty synthetic retinoids ( retinobenzoic acids ) , were tested for differentiation-inducing activity on human leukemia cell lines HL-60 and NB4 .", "target_text": { "human leukemia cell lines": "cell_line", "HL-60": "cell_line", "NB4": "cell_line" } }, { "input_text": "A good linear correlation , with an r value of 0.91 , between the ED50 values for the differentiation-inducing activity towards HL-60 cells and that towards NB4 cells was found .", "target_text": { "HL-60 cells": "cell_line", "NB4 cells": "cell_line" } }, { "input_text": "Platelet-activating factor ( PAF ) positively auto-regulates the expression of human PAF receptor transcript 1 ( leukocyte-type ) through NF-kappa B .", "target_text": { "Platelet-activating factor": "protein", "PAF": "protein", "human PAF receptor transcript 1": "protein", "NF-kappa B": "protein" } }, { "input_text": "The human platelet-activating factor receptor ( PAFR ) gene is transcribed by two distinct promoters ( promoter 1 and promoter 2 ) to generate two transcripts ( designated as PAFR transcript 1 and PAFR transcript 2 ) , though their open reading frames are identical .", "target_text": { "human platelet-activating factor receptor": "protein", "PAFR": "protein", "human platelet-activating factor receptor ( PAFR ) gene": "DNA", "promoters": "DNA", "promoter 1": "DNA", "promoter 2": "DNA", "PAFR transcript 1": "RNA", "PAFR transcript 2": "RNA" } }, { "input_text": "By primer extension analysis to discriminate two transcripts , we found that the levels of PAFR transcript 1 ( leukocyte-type ) , but not PAFR transcript 2 ( tissue-type ) , are upregulated by PAF as well as by 12-O-tetradecanoylphorbol-13-acetate ( TPA ) in the human stomach cancer cell line ( JR-St cells ) which expresses both functional PAFR transcript 1 and PAFR transcript 2 endogenously .", "target_text": { "PAFR": "protein", "PAFR transcript 1": "RNA", "PAFR transcript 2": "RNA", "PAF": "protein", "human stomach cancer cell line": "cell_line", "JR-St cells": "cell_line" } }, { "input_text": "Functional analysis of the promoter 1 with a transient expression assay using chloramphenicol acetyltransferase ( CAT ) gene as a reporter showed that both PAF and TPA activated the promoter 1 but not the deleted promoter lacking the three consensus binding sites for NF-kappa B located from -571 bp to -459 bp .", "target_text": { "promoter 1": "DNA", "chloramphenicol acetyltransferase ( CAT ) gene": "DNA", "PAF": "protein", "deleted promoter": "DNA", "consensus binding sites": "DNA", "NF-kappa B": "protein" } }, { "input_text": "These findings suggest a molecular mechanism of positive regulation of PAFR gene expression by PAF through NF-kappa B , possibly by a phosphorylation reaction involving protein kinase C by PAF .", "target_text": { "PAFR": "protein", "PAF": "protein", "NF-kappa B": "protein", "protein kinase C": "protein" } }, { "input_text": "One gene , two transcripts : isolation of an alternative transcript encoding for the autoantigen La/SS-B from a cDNA library of a patient with primary Sjogrens ' syndrome .", "target_text": { "transcripts": "RNA", "autoantigen La/SS-B": "protein", "cDNA library": "DNA" } }, { "input_text": "A cDNA library was prepared from peripheral blood lymphocytes of an autoimmune patient with primary Sjogrens ' syndrome .", "target_text": { "cDNA library": "DNA", "lymphocytes": "cell_type" } }, { "input_text": "The cDNA library was screened with the patients own autoimmune serum being monospecific for the nuclear autoantigen La/SS-B .", "target_text": { "cDNA library": "DNA", "autoantigen La/SS-B": "protein", "nuclear autoantigen La/SS-B": "protein" } }, { "input_text": "Thereby an alternative type of La mRNA was identified that differed from the known La mRNA due to an exchange of the exon 1 .", "target_text": { "La mRNA": "RNA", "exon 1": "DNA" } }, { "input_text": "Sequencing of the genomic region between the exons 1 and 2 showed that the alternative 5'-end is a part of the intron .", "target_text": { "alternative 5'-end": "DNA", "intron": "DNA" } }, { "input_text": "In addition , the presence of an alternative promoter site , which exists within the intron downstream of the exon 1 , became evident .", "target_text": { "alternative promoter site": "DNA", "intron": "DNA", "exon 1": "DNA" } }, { "input_text": "In consequence , the alternative La mRNA is the result of a promoter switching combined with an alternative splicing mechanism .", "target_text": { "La mRNA": "RNA", "alternative La mRNA": "RNA" } }, { "input_text": "In the intron , further transcription factor binding sites , including a NF-kappa B element , were identified leading to the suggestion that the expression of the gene encoding for the nuclear autoantigen La/SS-B alters in dependence on disease conditions .", "target_text": { "transcription factor": "protein", "NF-kappa B element": "DNA", "autoantigen La/SS-B": "protein", "nuclear autoantigen La/SS-B": "protein" } }, { "input_text": "Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B .", "target_text": { "CD40": "protein", "B cells": "cell_type", "nuclear factor-kappa B": "protein" } }, { "input_text": "The B cell-associated surface molecule CD40 functions to regulate B cell responses .", "target_text": { "CD40": "protein", "B cell-associated surface molecule CD40": "protein" } }, { "input_text": "Cross-linking CD40 on B cells can lead to homotypic cell adhesion , IL-6 production , and , in combination with cytokines , to Ig isotype switching .", "target_text": { "CD40": "protein", "B cells": "cell_type", "IL-6": "protein", "cytokines": "protein" } }, { "input_text": "Tyrosine kinase activity is increased shortly after engagement of this receptor .", "target_text": {} }, { "input_text": "Little is known about how the very early events induced by CD40 cross-linking link to cellular responses .", "target_text": { "CD40": "protein" } }, { "input_text": "In this study , we demonstrate that nuclear factor ( NF ) -kappa B and NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell lines .", "target_text": { "nuclear factor ( NF ) -kappa B": "protein", "transcription factors": "protein", "NF-kappa B-like transcription factors": "protein", "CD40": "protein", "B cells": "cell_type", "human tonsillar B cells": "cell_type", "B cell lines": "cell_line" } }, { "input_text": "The activation is rapid and is mediated through a tyrosine kinase-dependent pathway .", "target_text": {} }, { "input_text": "The complexes detected in electrophoretic mobility shift assays contain p50 , p65 ( RelA ) , c-Rel , and most likely other components .", "target_text": { "p50": "protein", "p65": "protein", "RelA": "protein", "c-Rel": "protein" } }, { "input_text": "By using transient transfection assays , we found that cross-linking CD40 supports NF-kappa B -dependent gene expression .", "target_text": { "CD40": "protein", "NF-kappa B": "protein" } }, { "input_text": "Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites .", "target_text": { "NF-kappa B": "protein", "CD40": "protein", "B cell-associated genes": "DNA", "NF-kappa B consensus sites": "DNA" } }, { "input_text": "Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in human monocytic cells by preventing activation of c-Rel/ p65 heterodimers .", "target_text": { "human monocytic cells": "cell_type", "p65": "protein", "c-Rel/ p65 heterodimers": "protein" } }, { "input_text": "Tissue factor ( TF ) is expressed rapidly by human monocytes exposed to bacterial endotoxin ( lipopolysaccharide , or LPS ) .", "target_text": { "Tissue factor": "protein", "TF": "protein", "human monocytes": "cell_type", "bacterial endotoxin": "protein" } }, { "input_text": "Transcriptional regulation is mediated by binding of c-Rel /p65 heterodimers to a kappa B-like site in the TF promoter .", "target_text": { "c-Rel": "protein", "/p65": "protein", "c-Rel /p65 heterodimers": "protein", "kappa B-like site": "DNA", "TF": "protein", "TF promoter": "DNA" } }, { "input_text": "Nuclear translocation of cytosolic c-Rel/ p65 heterodimers and other members of the NF-kappa B /Rel family requires dissociation and proteolytic degradation of the inhibitor protein , I kappa B alpha .", "target_text": { "p65": "protein", "cytosolic c-Rel/ p65 heterodimers": "protein", "NF-kappa B": "protein", "NF-kappa B /Rel family": "protein", "inhibitor protein": "protein", "I kappa B alpha": "protein" } }, { "input_text": "The protease inhibitors N alpha-tosylphenylalanyl chloromethyl ketone ( TPCK ) and N alpha-tosyl-L-lysine chloromethyl ketone ( TLCK ) block activation of NF-kappa B /Rel proteins by preventing degradation of I kappa B alpha .", "target_text": { "NF-kappa B": "protein", "NF-kappa B /Rel proteins": "protein", "I kappa B alpha": "protein" } }, { "input_text": "To determine if TPCK and TLCK inhibited LPS induction of TF expression , freshly isolated human monocytes and monocytic THP-1 cells were pretreated with these inhibitors for 30 min before LPS stimulation .", "target_text": { "TF": "protein", "human monocytes": "cell_type", "monocytic THP-1 cells": "cell_line" } }, { "input_text": "Both TPCK and TLCK inhibited LPS induction of TF protein , TF mRNA and TF promoter activity in a dose-dependent manner .", "target_text": { "TF protein": "protein", "TF mRNA": "RNA", "TF": "protein" } }, { "input_text": "These inhibitors specifically prevented degradation of I kappa B alpha and nuclear translocation of c-Rel /p65 heterodimers .", "target_text": { "I kappa B alpha": "protein", "c-Rel": "protein", "/p65": "protein", "c-Rel /p65 heterodimers": "protein" } }, { "input_text": "In contrast , TPCK and TLCK did not block induction of an immediate-early gene encoding the transcription factor , Egr-1 .", "target_text": { "immediate-early gene": "DNA", "transcription factor": "protein", "Egr-1": "protein" } }, { "input_text": "Taken together , these data indicated that inhibiting nuclear translocation of c-Rel /p65 heterodimers prevented LPS induction of TF gene transcription in monocytic cells .", "target_text": { "c-Rel": "protein", "/p65": "protein", "c-Rel /p65 heterodimers": "protein", "TF": "protein", "monocytic cells": "cell_type" } }, { "input_text": "1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with primary and secondary hyperparathyroidism .", "target_text": { "1,25-Dihydroxyvitamin D3 receptors": "protein", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "A decreased number of calcitriol ( 1,25(OH)2D3 ) receptors has been observed in parathyroid glands of uremic animals .", "target_text": { "calcitriol ( 1,25(OH)2D3 ) receptors": "protein" } }, { "input_text": "In humans , studies carried out in surgically removed parathyroid glands have shown that calcitriol binding is higher in primary than in secondary hyperparathyroidism .", "target_text": {} }, { "input_text": "Since specific receptors for calcitriol have been described in peripheral blood mononuclear cells ( PBMC ) , we have investigated the specific uptake of 3H-labelled 1,25(OH)2D3 in PBMC of 12 women with primary hyperparathyroidism ( PHP ) , 8 women with hyperparathyroidism secondary to chronic renal failure ( SH ) , 9 women with renal transplant ( RT ) , and 23 healthy women .", "target_text": { "peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "The median dissociation constant ( Kd ) was similar in all three groups of patients and in healthy women ( mean +/- S.D. ( range ) : PHP , 1.2 +/- 1.0 ( 0.2-4 ) x 10(-10) M ; SH , 0.6 +/- 0.4 ( 0.2-1.2 ) x 10(-10) M ; RT , 1.1 +/- 0.5 ( 0.4-1.9 ) x 10(-10) M ; controls , 1.0 +/- 0.6 ( 0.3-2.6 ) x 10(-10) M ) . However , the maximal binding capacity ( Nmax ) was significantly enhanced in PHP ( 3.9 +/- 1.9 ( 1.3-7.6 ) fmol/10(7) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10(7) cells in controls ; P = 0.0006 ) and decreased in SH ( 0.8 +/- 0.5 ( 0.2-1.6 ) fmol/10(7) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10(7) cells in controls ; P = 0.0001 ) , whereas no changes were seen in RT ( 2.3 +/- 0.7 ( 1.2-3.3 ) fmol/10(7) cells vs. 2.3 +/- 0.9 ( 1.1-4.4 ) fmol/10(7) cells in controls ) .", "target_text": {} }, { "input_text": "In three patients with PHP who were subjected to parathyroidectomy , the calcitriol number came down to normal .", "target_text": {} }, { "input_text": "Changes of calcitriol receptors in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia .", "target_text": { "calcitriol receptors": "protein" } }, { "input_text": "The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation .", "target_text": { "X chromosomes": "DNA", "tiny ring X chromosomes": "DNA", "chromosomes": "DNA" } }, { "input_text": "Mental retardation and a constellation of congenital malformations not usually associated with Turner syndrome are seen in some females with a mosaic 45,X/46,X,r(X) karyotype .", "target_text": { "mosaic 45,X/46,X,r(X) karyotype": "DNA" } }, { "input_text": "Studies of these females show that the XIST locus on their tiny ring X chromosomes is either not present or not expressed .", "target_text": { "XIST locus": "DNA", "X chromosomes": "DNA", "tiny ring X chromosomes": "DNA" } }, { "input_text": "As XIST transcription is well correlated with inactivation of the X chromosome in female somatic cells and spermatogonia , nonexpression of the locus even when it is present suggests that these chromosomes are transcriptionally active .", "target_text": { "XIST": "DNA", "X chromosome": "DNA", "female somatic cells": "cell_type", "spermatogonia": "cell_type", "chromosomes": "DNA" } }, { "input_text": "We examined the transcriptional activity of ring X chromosomes lacking XIST expression ( XISTE- ) , from three females with severe phenotypes .", "target_text": { "X chromosomes": "DNA", "XIST": "DNA" } }, { "input_text": "The two tiny ring X chromosomes studied with an antibody specific for the acetylated isoforms of histone H4 marking transcribed chromatin domains were labeled at a level consistent with their being active .", "target_text": { "X chromosomes": "DNA", "antibody": "protein", "histone H4": "protein", "transcribed chromatin domains": "DNA" } }, { "input_text": "We also examined tow of the XISTE- ring chromosomes to determine whether genes that are normally silent on an inactive X are expressed from these chromosomes .", "target_text": { "XISTE- ring chromosomes": "DNA", "genes": "DNA", "inactive X": "DNA", "chromosomes": "DNA" } }, { "input_text": "Analyses of hybrid cells show that TIMP , ZXDA , and ZXDB loci on the proximal short arm , and AR and PHKA1 loci on the long arm , are well expressed from the tiny ring X chromosome lacking XIST DNA .", "target_text": { "hybrid cells": "cell_line", "TIMP": "DNA", "ZXDA": "DNA", "ZXDB loci": "DNA", "proximal short arm": "DNA", "AR": "DNA", "PHKA1 loci": "DNA", "X chromosome": "DNA", "tiny ring X chromosome": "DNA", "XIST DNA": "DNA" } }, { "input_text": "Studies of the ring chromosome that has XIST DNA but does not transcribe it show that its AR allele is transcribed along with the one on the normal X allele .", "target_text": { "ring chromosome": "DNA", "XIST DNA": "DNA" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "Inhibition of activation of transcription factor AP-1 by CD28 signalling in human T-cells .", "target_text": { "AP-1": "protein", "transcription factor AP-1": "protein", "CD28": "protein", "human T-cells": "cell_type" } }, { "input_text": "Co-stimulation of T-lymphocytes by T-cell receptor ( TcR ) occupancy and activation of the CD28 surface molecule results in enhanced proliferation and interleukin 2 ( IL-2 ) production .", "target_text": { "T-lymphocytes": "cell_type", "T-cell receptor": "protein", "TcR": "protein", "CD28": "protein", "CD28 surface molecule": "protein", "interleukin 2": "protein", "IL-2": "protein" } }, { "input_text": "The increase in IL-2 gene expression triggered by CD28 involves a kappa B-like sequence in the 5'-regulatory region of the IL-2 promoter , called CD28 -responsive element .", "target_text": { "IL-2": "protein", "CD28": "protein", "kappa B-like sequence": "DNA", "5'-regulatory region": "DNA", "IL-2 promoter": "DNA", "CD28 -responsive element": "DNA" } }, { "input_text": "Stimulation of T-cells by agonistic anti- CD28 antibodies in conjunction with phorbol 12-myristate 13-acetate ( PMA ) - or TcR -derived signals induces the enhanced activation of the transcription factor NF-kappa B .", "target_text": { "T-cells": "cell_type", "CD28": "protein", "anti- CD28 antibodies": "protein", "TcR": "protein", "transcription factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "Here we report that CD28 engagement , however , exerts opposite effects on the transcription factor AP-1 .", "target_text": { "CD28": "protein", "transcription factor": "protein", "AP-1": "protein", "transcription factor AP-1": "protein" } }, { "input_text": "Whereas anti- CD28 together with PMA increased the DNA binding and trans-activation activity of NF-kappa B , PMA -induced activation of AP-1 was significantly suppressed .", "target_text": { "CD28": "protein", "anti- CD28": "protein", "NF-kappa B": "protein", "AP-1": "protein" } }, { "input_text": "The inhibitory effect exerted by anti- CD28 was observed at the level of DNA binding as well as in functional reporter-gene assays .", "target_text": { "CD28": "protein", "anti- CD28": "protein" } }, { "input_text": "These results suggest that the two transcription factors are independently regulated and may perform different functions during T-cell activation .", "target_text": { "transcription factors": "protein" } }, { "input_text": "HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization .", "target_text": { "HIV-1 Nef": "protein", "T cells": "cell_type" } }, { "input_text": "Nef of primate lentiviruses is required for viremia and progression to AIDS in monkeys .", "target_text": { "Nef": "protein" } }, { "input_text": "Negative , positive , and no effects of Nef have also been reported on viral replication in cells .", "target_text": { "Nef": "protein" } }, { "input_text": "To reconcile these observations , we expressed a hybrid CD8- Nef protein in Jurkat cells .", "target_text": { "Nef": "protein", "hybrid CD8- Nef protein": "protein", "Jurkat cells": "cell_line" } }, { "input_text": "Two opposite phenotypes were found , which depended on the intracellular localization of Nef .", "target_text": { "Nef": "protein" } }, { "input_text": "Expressed in the cytoplasm or on the cell surface , the chimera inhibited or activated early signaling events from the T cell antigen receptor .", "target_text": { "chimera": "protein", "T cell antigen receptor": "protein" } }, { "input_text": "Activated Jurkat cells died by apoptosis , and only cells with mutated nef genes expressing truncated Nefs survived , which rendered Nef nonfunctional .", "target_text": { "Jurkat cells": "cell_line", "nef genes": "DNA", "Nefs": "protein", "Nef": "protein" } }, { "input_text": "These mutations paralleled those in other viral strains passaged in vitro .", "target_text": {} }, { "input_text": "Not only do these positional effects of Nef reconcile diverse phenotypes of Nef and suggest a role for its N-terminal myristylation , but they also explain effects of Nef in HIV infection and progression to AIDS .", "target_text": { "Nef": "protein" } }, { "input_text": "An intricate arrangement of binding sites for the Ets family of transcription factors regulates activity of the alpha 4 integrin gene promoter .", "target_text": { "Ets family": "protein", "transcription factors": "protein", "alpha 4 integrin gene promoter": "DNA" } }, { "input_text": "alpha 4 integrins mediate cell-cell and cell-extracellular matrix interactions that are critical for maturation and function of the immune system as well as differentiation of skeletal muscle .", "target_text": { "alpha 4 integrins": "protein" } }, { "input_text": "Here we examine molecular mechanisms controlling the pattern of alpha 4 expression .", "target_text": { "alpha 4": "protein" } }, { "input_text": "The activity of constructs containing 5' deletion mutants of the alpha 4 gene promoter was compared in transfection assays into cell lines that express alpha 4 and cell lines that do not .", "target_text": { "5' deletion mutants": "DNA", "alpha 4": "protein", "alpha 4 gene promoter": "DNA", "cell lines": "cell_line" } }, { "input_text": "The sequence between position -42 and -76 base pairs ( bp ) was required for efficient transcription in cells that express alpha 4 , but it showed no activity in HeLa cells , which do not express alpha 4 .", "target_text": { "-42 and -76 base pairs": "DNA", "alpha 4": "protein", "HeLa cells": "cell_line" } }, { "input_text": "Three binding sites for the Ets family of transcription factors are found in this region : two adjacent sites at positions -50 and -54 bp and a more 5' site at position -67 bp .", "target_text": { "binding sites": "DNA", "Ets family": "protein", "transcription factors": "protein", "-50 and -54 bp": "DNA", "5' site": "DNA", "-67 bp": "DNA" } }, { "input_text": "Using a series of constructs containing deletions and mutations in this region , we found that the 3'-most site alone was sufficient for binding GA-binding protein alpha ( GABP alpha ) / GABP beta and for a low level of transcriptional activation .", "target_text": { "3'-most site": "DNA", "GA-binding protein alpha": "protein", "GABP alpha": "protein", "GABP beta": "protein", "GABP alpha ) / GABP beta": "protein" } }, { "input_text": "When all three sites were present , a second complex \" a \" was detected , which contains an unknown member of the Ets family .", "target_text": { "Ets family": "protein" } }, { "input_text": "Formation of complex a was cell-type specific and correlated with a high level of transcription .", "target_text": {} }, { "input_text": "Deletion of the 5'-most Ets site had no effect on binding to GABP alpha/GABP beta , but it eliminated a .", "target_text": { "5'-most Ets site": "DNA", "GABP alpha/GABP beta": "protein" } }, { "input_text": "Concomitant with this loss of a , a new Ets-1-containing complex \" c \" appeared .", "target_text": { "new Ets-1-containing complex": "protein", "c": "protein" } }, { "input_text": "Complex c substituted efficiently for complex a in transcriptional activation .", "target_text": {} }, { "input_text": "We conclude that although neither of the two 5'-most Ets sites alone binds nuclear protein , they appear to act as modulators which control the pattern of Ets proteins that bind the alpha 4 gene promoter .", "target_text": { "5'-most Ets sites": "DNA", "nuclear protein": "protein", "Ets proteins": "protein", "alpha 4": "protein", "alpha 4 gene promoter": "DNA" } }, { "input_text": "This arrangement of Ets sites , coupled with the tissue- and developmental- specific expression of Ets members , likely play a key role in defining the pattern of alpha 4 integrin .", "target_text": { "Ets sites": "DNA", "Ets members": "protein", "alpha 4 integrin": "protein" } }, { "input_text": "Mechanism of antiandrogen action : conformational changes of the receptor .", "target_text": {} }, { "input_text": "Androgen receptor mRNA was translated in vitro , and androgen- and antiandrogen- bound receptor complexes were studied using limited proteolytic digestion by trypsin .", "target_text": { "Androgen receptor": "protein", "Androgen receptor mRNA": "RNA", "trypsin": "protein" } }, { "input_text": "Partial proteolysis of androgen -bound receptor protein resulted in a 29-kDa proteolysis-resisting fragment , whereas antiandrogen binding stabilised a 35-kDa fragment .", "target_text": { "androgen -bound receptor protein": "protein", "29-kDa proteolysis-resisting fragment": "protein", "35-kDa fragment": "protein" } }, { "input_text": "Both fragments contain the entire ligand binding domain , and the 35-kDa fragment extended into the hinge region of the receptor .", "target_text": { "ligand binding domain": "protein", "35-kDa fragment": "protein", "hinge region": "protein" } }, { "input_text": "Several antiandrogens show agonistic properties for a mutated androgen receptor ( LNCaP cell variant ) ; trypsin digestion of antiandrogen -bound mutated receptor also resulted in a 29-kDa fragment .", "target_text": { "mutated androgen receptor": "protein", "LNCaP cell variant": "cell_line", "trypsin": "protein", "antiandrogen -bound mutated receptor": "protein", "29-kDa fragment": "protein" } }, { "input_text": "Our results point to an important difference between antiandrogens and antagonists of other steroid hormone receptors .", "target_text": { "steroid hormone receptors": "protein" } }, { "input_text": "Antiandrogens result in protection of both the hinge region and C-terminus of the androgen receptor agonist proteolytic attack , whereas other studies showed that antiestrogens and antiprogestagens expose the C-terminal end of the ligand binding domain of their respective receptors to protease .", "target_text": { "hinge region": "protein", "C-terminus": "protein", "androgen receptor": "protein", "C-terminal end": "protein", "ligand binding domain": "protein", "protease": "protein" } }, { "input_text": "Differences in conformation of the hinge region distinguish androgen -bound from antiandrogen -bound receptor complexes , which represents an important feature of antiandrogen action .", "target_text": { "hinge region": "protein", "androgen -bound": "protein", "antiandrogen -bound receptor complexes": "protein" } }, { "input_text": "Activation of nuclear factor kappa B in human neuroblastoma cell lines .", "target_text": { "nuclear factor kappa B": "protein", "neuroblastoma cell lines": "cell_line", "human neuroblastoma cell lines": "cell_line" } }, { "input_text": "The nuclear factor kappa B ( NF-kappa B ) is a eukaryotic transcription factor .", "target_text": { "nuclear factor kappa B": "protein", "NF-kappa B": "protein", "transcription factor": "protein" } }, { "input_text": "In B cells and macrophages it is constitutively present in cell nuclei , whereas in many other cell types , NF-kappa B translocates from cytosol to nucleus as a result of transduction by tumor necrosis factor alpha ( TNF alpha ) , phorbol ester , and other polyclonal signals .", "target_text": { "B cells": "cell_type", "macrophages": "cell_type", "NF-kappa B": "protein", "tumor necrosis factor alpha": "protein", "TNF alpha": "protein" } }, { "input_text": "Using neuroblastoma cell lines as models , we have shown that in neural cells NF-kappa B was present in the cytosol and translocated into nuclei as a result of TNF alpha treatment .", "target_text": { "neuroblastoma cell lines": "cell_line", "neural cells": "cell_type", "NF-kappa B": "protein", "TNF alpha": "protein" } }, { "input_text": "The TNF alpha -activated NF-kappa B was transcriptionally functional .", "target_text": { "TNF alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "NF-kappa B activation by TNF alpha was not correlated with cell differentiation or proliferation .", "target_text": { "NF-kappa B": "protein", "TNF alpha": "protein" } }, { "input_text": "However , reagents such as nerve growth factor ( NGF ) and the phorbol ester phorbol 12-myristate 13-acetate ( PMA ) , which induce phenotypical differentiation of the SH-SY5Y neuroblastoma cell line , activated NF-kappa B , but only in that particular cell line .", "target_text": { "nerve growth factor": "protein", "NGF": "protein", "SH-SY5Y neuroblastoma cell line": "cell_line", "NF-kappa B": "protein", "cell line": "cell_line" } }, { "input_text": "In a NGF -responsive rat pheochromocytoma cell line , PC12 , PMA activated NF-kappa B , whereas NGF did not .", "target_text": { "NGF": "protein", "NGF -responsive rat pheochromocytoma cell line": "cell_line", "PC12": "cell_line", "NF-kappa B": "protein" } }, { "input_text": "In other neuroblastoma cell lines , such as SK-N-Be(2) , the lack of PMA induction of differentiation was correlated with the lack of NF-kappa B activation .", "target_text": { "neuroblastoma cell lines": "cell_line", "SK-N-Be(2)": "cell_line", "NF-kappa B": "protein" } }, { "input_text": "We found , moreover , that in SK-N-Be(2) cells protein kinase C ( PKC ) enzymatic activity was much lower compared with that in a control cell line and that the low PKC enzymatic activity was due to low PKC protein expression .", "target_text": { "SK-N-Be(2) cells": "cell_line", "protein kinase C": "protein", "PKC": "protein", "control cell line": "cell_line" } }, { "input_text": "NF-kappa B was not activated by retinoic acid , which induced morphological differentiation of all the neuroblastoma cell lines used in the present study .", "target_text": { "NF-kappa B": "protein", "neuroblastoma cell lines": "cell_line" } }, { "input_text": "Thus , NF-kappa B activation was not required for neuroblastoma cell differentiation .", "target_text": { "NF-kappa B": "protein", "neuroblastoma": "cell_type" } }, { "input_text": "Furthermore , the results obtained with TNF alpha proved that NF-kappa B activation was not sufficient for induction of neuroblastoma differentiation .", "target_text": { "TNF alpha": "protein", "NF-kappa B": "protein", "neuroblastoma": "cell_type" } }, { "input_text": "ERP , a new member of the ets transcription factor/oncoprotein family : cloning , characterization , and differential expression during B-lymphocyte development .", "target_text": { "ERP": "protein", "ets transcription factor/oncoprotein family": "protein" } }, { "input_text": "The ets gene family encodes a group of proteins which function as transcription factors under physiological conditions and , if aberrantly expressed , can cause cellular transformation .", "target_text": { "ets gene family": "DNA", "transcription factors": "protein" } }, { "input_text": "We have recently identified two regulatory elements in the murine immunoglobulin heavy-chain ( IgH ) enhancer , pi and microB , which exhibit striking similarity to binding sites for ets-related proteins .", "target_text": { "murine immunoglobulin heavy-chain ( IgH ) enhancer": "DNA", "pi": "DNA", "microB": "DNA", "binding sites": "DNA", "ets-related proteins": "DNA" } }, { "input_text": "To identify ets-related transcriptional regulators expressed in pre-B lymphocytes that may interact with either the pi or the microB site , we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the ets family .", "target_text": { "ets-related transcriptional regulators": "protein", "pre-B lymphocytes": "cell_type", "pi": "DNA", "microB": "DNA", "microB site": "DNA", "ets family": "DNA" } }, { "input_text": "We have cloned the gene for a new ets-related transcription factor , ERP ( ets-related protein ) , from the murine pre-B cell line BASC 6C2 and from mouse lung tissue .", "target_text": { "transcription factor": "protein", "ets-related transcription factor": "protein", "ERP": "protein", "ets-related protein": "protein", "murine pre-B cell line": "cell_line", "BASC 6C2": "cell_line" } }, { "input_text": "The ERP protein contains a region of high homology with the ETS DNA-binding domain common to all members of the ets transcription factor/oncoprotein family .", "target_text": { "ERP": "protein", "ets transcription factor/oncoprotein family": "protein" } }, { "input_text": "Three additional smaller regions show homology to the ELK-1 and SAP-1 genes , a subgroup of the ets gene family that interacts with the serum response factor .", "target_text": { "SAP-1": "protein", "ets gene family": "DNA", "serum response factor": "protein" } }, { "input_text": "Full-length ERP expresses only negligible DNA-binding activity by itself .", "target_text": { "ERP": "protein" } }, { "input_text": "Removal of the carboxy terminus enables ERP to interact with a variety of ets-binding sites including the E74 site , the IgH enhancer pi site , and the lck promoter ets site , suggesting a carboxy-terminal negative regulatory domain .", "target_text": { "carboxy terminus": "protein", "ERP": "protein", "ets-binding sites": "DNA", "E74 site": "DNA", "IgH enhancer pi site": "DNA", "lck promoter ets site": "DNA", "carboxy-terminal negative regulatory domain": "protein" } }, { "input_text": "At least three ERP -related transcripts are expressed in a variety of tissues .", "target_text": { "ERP": "protein", "ERP -related transcripts": "protein" } }, { "input_text": "However , within the B-cell lineage , ERP is highly expressed primarily at early stages of B-lymphocyte development , and expression declines drastically upon B-cell maturation , correlating with the enhancer activity of the IgH pi site .", "target_text": { "B-cell lineage": "cell_type", "ERP": "protein", "B-lymphocyte": "cell_type", "IgH pi site": "DNA" } }, { "input_text": "These data suggest that ERP might play a role in B-cell development and in IgH gene regulation .", "target_text": { "ERP": "protein", "B-cell": "cell_type", "IgH gene": "DNA" } }, { "input_text": "Gene for a tissue-specific transcriptional activator ( EBF or Olf-1 ) , expressed in early B lymphocytes , adipocytes , and olfactory neurons , is located on human chromosome 5 , band q34 , and proximal mouse chromosome 11 .", "target_text": { "tissue-specific transcriptional activator": "protein", "EBF": "protein", "Olf-1": "protein", "early B lymphocytes": "cell_type", "adipocytes": "cell_type", "olfactory neurons": "cell_type", "human chromosome 5": "DNA", "band q34": "DNA", "proximal mouse chromosome 11": "DNA" } }, { "input_text": "Murine B lymphocytes , adipocytes , and olfactory neurons contain a DNA-binding protein that participates in the regulation of genes encoding tissue-specific components of signal transduction .", "target_text": { "Murine B lymphocytes": "cell_type", "adipocytes": "cell_type", "olfactory neurons": "cell_type", "DNA-binding protein": "protein", "genes": "DNA" } }, { "input_text": "Purification and cloning of this protein , termed early B-cell factor ( EBF ) , from murine B lymphocytes and independent cloning of a protein , termed Olf-1 , from olfactory neuronal cells revealed virtual complete amino acid sequence identity between these proteins .", "target_text": { "B-cell factor": "protein", "EBF": "protein", "murine B lymphocytes": "cell_type", "Olf-1": "protein", "olfactory neuronal cells": "cell_type", "amino acid sequence": "protein" } }, { "input_text": "As a first step towards identifying a human genetic disorder or mouse mutation for which EBF could be a candidate gene , we have chromosomally mapped the corresponding locus in both species .", "target_text": { "EBF": "protein" } }, { "input_text": "By Southern hybridization analyses of somatic cell hybrid panels with murine cDNA probe , fluorescence chromosomal in situ hybridization ( FISH ) of human genomic clones , and analysis of recombinant inbred mouse strains , we have found single sites for EBF homologous sequences on human Chromosome ( Chr ) 5 , band q34 , and on proximal mouse Chr 11 , in an evolutionarily conserved region .", "target_text": { "murine cDNA probe": "DNA", "human genomic clones": "DNA", "recombinant inbred mouse strains": "cell_line", "EBF": "protein", "EBF homologous sequences": "DNA", "band q34": "DNA", "proximal mouse Chr 11": "DNA", "evolutionarily conserved region": "DNA" } }, { "input_text": "Calcineurin activates transcription from the GM-CSF promoter in synergy with either protein kinase C or NF-kappa B /AP-1 in T cells .", "target_text": { "Calcineurin": "protein", "GM-CSF promoter": "DNA", "protein kinase C": "protein", "NF-kappa B": "protein", "/AP-1": "protein", "T cells": "cell_type" } }, { "input_text": "Two cis-acting elements GM-kappa B/GC-box and CLE0 , of the granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene are required for maximal induction in Jurkat T cells by costimulation with phorbol-12-myristate acetate ( PMA ) and Ca2+ ionophore ( A23187 ) .", "target_text": { "cis-acting elements": "DNA", "GM-kappa B/GC-box": "DNA", "CLE0": "DNA", "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene": "DNA", "Jurkat T cells": "cell_line" } }, { "input_text": "The GM-kappa B sequence is recognized by NF-kappa B , which is mainly induced by PMA .", "target_text": { "GM-kappa B sequence": "DNA", "NF-kappa B": "protein" } }, { "input_text": "The CLE0 sequence interacts with factors , related to a PMA -induced AP-1 and a PMA / A23187 -induced NF- AT .", "target_text": { "CLE0 sequence": "DNA", "AP-1": "protein", "PMA -induced AP-1": "protein", "PMA / A23187 -induced NF- AT": "protein" } }, { "input_text": "We examined whether signal transducing components in T cells can activate transcription of the GM-CSF gene .", "target_text": { "T cells": "cell_type", "GM-CSF gene": "DNA" } }, { "input_text": "Cotransfection of NF-kappa B ( p50/p65 ) - or AP-1 ( c-Jun/c-Fos ) - expression vectors into Jurkat cells with a luciferase reporter containing the GM-CSF promoter did not stimulate transcription from the GM-CSF promoter .", "target_text": { "Jurkat cells": "cell_line", "luciferase reporter": "DNA", "GM-CSF promoter": "DNA" } }, { "input_text": "In contrast , cotransfection with a combination of NF-kappa B and AP-1 significantly augmented transcription from the GM-CSF promoter containing the GM-kappa B/GC-box and the CLE0 ( AP-1 /NF-AT ) .", "target_text": { "NF-kappa B": "protein", "AP-1": "protein", "GM-CSF promoter": "DNA", "GM-kappa B/GC-box": "DNA", "CLE0": "DNA", "AP-1 /NF-AT": "protein" } }, { "input_text": "Expression of a constitutively active calcineurin ( CN ) , a Ca2+ /calmodulin-dependent protein phosphatase , potentiated by two fold the transcriptional activation by NF-kappa B /AP-1 .", "target_text": { "calcineurin": "protein", "CN": "protein", "Ca2+ /calmodulin-dependent protein phosphatase": "protein", "NF-kappa B": "protein", "/AP-1": "protein" } }, { "input_text": "Both constitutively active forms of CN and protein kinase C ( PKC ) synergistically activated transcription from the GM-CSF promoter .", "target_text": { "CN": "protein", "protein kinase C": "protein", "PKC": "protein", "GM-CSF promoter": "DNA" } }, { "input_text": "These results suggest that cooperation among NF-kappa B- , AP-1- and NF-AT- binding sequences is required for induction of the GM-CSF gene through PKC- and Ca2+- signaling pathways downstream of T cell activation .", "target_text": { "GM-CSF gene": "DNA" } }, { "input_text": "Nonpituitary human prolactin gene transcription is independent of Pit-1 and differentially controlled in lymphocytes and in endometrial stroma .", "target_text": { "Nonpituitary human prolactin gene": "DNA", "Pit-1": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Expression of the human PRL ( hPRL ) gene in extrapituitary sites such as the uterus ( decidualized endometrial stroma and myometrium ) and cells of the hematopoietic lineage is directed by an alternative promoter which is located approximately 6 kilobases ( kb ) upstream of the pituitary-specific start site .", "target_text": { "human PRL ( hPRL ) gene": "DNA", "hematopoietic lineage": "cell_type", "alternative promoter": "DNA", "6 kilobases ( kb ) upstream": "DNA", "pituitary-specific start site": "DNA" } }, { "input_text": "In order to delineate the tissue-specific mechanisms governing the control of nonpituitary PRL gene expression , we have cloned and sequenced 3 kb 5'-flanking DNA of the upstream decidual/lymphoid ( dPRL ) promoter .", "target_text": { "PRL gene": "DNA", "3 kb 5'-flanking DNA": "DNA", "decidual/lymphoid ( dPRL ) promoter": "DNA" } }, { "input_text": "Based on sequence homology we identified two binding motifs for Pit-1 and seven half-sites for glucocorticoid receptor/progesterone receptor ( PR ) binding .", "target_text": { "binding motifs": "DNA", "Pit-1": "protein", "half-sites": "DNA", "glucocorticoid receptor/progesterone receptor": "protein", "PR": "protein" } }, { "input_text": "We focused our studies on the role of Pit-1 and of PR as potential transcriptional regulators , since the POU domain protein Pit-1 is essential in the control of pituitary PRL expression , and progesterone induces decidual transformation of the endometrial stroma , a differentiation process during which the decidual PRL gene is activated .", "target_text": { "Pit-1": "protein", "PR": "protein", "transcriptional regulators": "protein", "POU domain protein": "protein", "PRL": "protein", "PRL gene": "DNA" } }, { "input_text": "We demonstrate in a variety of cell types , including lymphocytes and endometrial stroma , that Pit-1 is not involved in the regulation of dPRL promoter/reporter gene constructs carrying 3 kb 5'-flanking DNA .", "target_text": { "lymphocytes": "cell_type", "Pit-1": "protein", "dPRL promoter/reporter gene constructs": "DNA", "3 kb 5'-flanking DNA": "DNA" } }, { "input_text": "Our experiments also show that activated PR does not confer direct transcriptional control on the dPRL promoter .", "target_text": { "PR": "protein", "dPRL promoter": "DNA" } }, { "input_text": "When we compared the activity of the transfected dPRL promoter in PRL- secreting and nonsecreting lymphoid cells , we found that the 3 kb 5'-flanking region of the dPRL promoter did not contain elements restricting expression to only those lymphocytes that produce PRL but allowed expression of fusion reporter genes irrespective of the status of the endogenous PRL gene .", "target_text": { "dPRL promoter": "DNA", "3 kb 5'-flanking region": "DNA", "lymphocytes": "cell_type", "PRL": "protein", "PRL gene": "DNA" } }, { "input_text": "This was in sharp contrast to endometrial cells where 3 kb 5'-flanking DNA conferred strong transcriptional activation on the dPRL promoter in decidualized endometrial stromal cells actively secreting PRL , but did not allow transcription in undifferentiated non-PRL-secreting endometrial stromal cells .", "target_text": { "dPRL promoter": "DNA", "endometrial stromal cells": "cell_type", "PRL": "protein", "non-PRL-secreting endometrial stromal cells": "cell_type" } }, { "input_text": "Activation of the dPRL promoter construct in these undifferentiated cells could however be induced by the addition of cAMP , in the absence of progesterone , suggesting that a signal transduced through the cAMP signaling pathway is a primary inducer of decidual PRL gene expression .", "target_text": { "dPRL promoter": "DNA", "PRL gene": "DNA" } }, { "input_text": "Signals and nuclear factors that regulate the expression of interleukin-4 and interleukin-5 genes in helper T cells .", "target_text": { "nuclear factors": "protein", "helper T cells": "cell_type" } }, { "input_text": "Mouse thymoma line EL-4 cells produce cytokines such as interleukin ( IL ) -2 , IL-3 , IL-4 , IL-10 , and granulocyte-macrophage colony-stimulating factor in response to phorbol 12-myristate 13-acetate ( PMA ) .", "target_text": { "EL-4 cells": "cell_line", "Mouse thymoma line EL-4 cells": "cell_line", "cytokines": "protein", "interleukin ( IL ) -2": "protein", "IL-3": "protein", "IL-4": "protein", "IL-10": "protein", "granulocyte-macrophage colony-stimulating factor": "protein" } }, { "input_text": "EL-4 cells also produce low levels of IL-5 when stimulated by PMA alone ; however , cAMP greatly augments PMA -dependent IL-5 production .", "target_text": { "EL-4 cells": "cell_line", "IL-5": "protein" } }, { "input_text": "A transient transfection assay revealed that two signals , PMA and cAMP , are required for optimal activation of the IL-5 promoter .", "target_text": { "IL-5": "protein", "IL-5 promoter": "DNA" } }, { "input_text": "In contrast , cAMP almost completely inhibited the PMA -dependent activation of the endogenous IL-2 gene , as well as the transfected IL-2 promoter .", "target_text": { "IL-2": "protein", "IL-2 gene": "DNA", "endogenous IL-2 gene": "DNA", "IL-2 promoter": "DNA" } }, { "input_text": "These results indicate that the IL-5 gene is positively regulated by cAMP in a manner opposite to that for the IL-2 gene .", "target_text": { "IL-5": "protein", "IL-5 gene": "DNA", "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "One of the nuclear factors ( NFs ) that regulates the response of the IL-5 promoter to cAMP and PMA has properties similar to NF for activated t cell .", "target_text": { "nuclear factors": "protein", "NFs": "protein", "IL-5": "protein", "IL-5 promoter": "DNA", "NF": "protein", "activated t cell": "cell_type" } }, { "input_text": "The P sequence of the IL-4 gene , defined as a responsive element for PMA and calcium ionophore ( A23187 ) , shares sequence similarity with the NF kappa B and the NF-activated T cell binding sites .", "target_text": { "P sequence": "DNA", "IL-4": "protein", "IL-4 gene": "DNA", "responsive element": "DNA" } }, { "input_text": "We attempted to determine whether NF(P) , a nuclear factor specific for the P sequence , is related to NF-kappa B and nuclear factor for activated T cell ( NF-AT ) .", "target_text": { "NF(P)": "protein", "P sequence": "DNA", "NF-kappa B": "protein", "nuclear factor for activated T cell": "protein", "NF-AT": "protein" } }, { "input_text": "In electromobility shift assays both NF-kappa B ( P65 or P65/P50 heterodimer ) and NF-AT bound to the P sequence .", "target_text": { "NF-kappa B": "protein", "P65": "protein", "P65/P50 heterodimer": "protein", "NF-AT": "protein", "P sequence": "DNA" } }, { "input_text": "However , sequence specificity of NF-AT was more similar to that of NF(P) , and only a small amount of P65 was detected in NF(P) .", "target_text": { "NF-AT": "protein", "NF(P)": "protein", "P65": "protein" } }, { "input_text": "These results indicate that a component or components of NF-AT have the potential to reconstitute NF(P) , whereas NF-kappa B alone does not account for NF(P) in Jurkat crude extract .", "target_text": { "NF-AT": "protein", "NF(P)": "protein", "NF-kappa B": "protein" } }, { "input_text": "Taken together , these results suggest that NF-AT-like factors are involved in the regulation of IL-4 and IL-5 genes .", "target_text": { "NF-AT-like factors": "protein" } }, { "input_text": "Solution structure of a POU-specific homeodomain : 3D-NMR studies of human B-cell transcription factor Oct-2 .", "target_text": { "POU-specific homeodomain": "protein", "B-cell transcription factor": "protein", "Oct-2": "protein" } }, { "input_text": "The POU DNA-binding motif defines a conserved family of eukaryotic transcription factors involved in regulation of gene expression .", "target_text": { "POU DNA-binding motif": "protein", "eukaryotic transcription factors": "protein" } }, { "input_text": "This bipartite motif consists of an N-terminal POU-specific domain ( POUs ) , a flexible linker , and a C-terminal POU-specific homeodomain ( POUHD ) .", "target_text": { "bipartite motif": "protein", "N-terminal POU-specific domain": "protein", "POUs": "protein", "flexible linker": "protein", "POU-specific homeodomain": "protein", "C-terminal POU-specific homeodomain": "protein", "POUHD": "protein" } }, { "input_text": "Here we describe the solution structure of a POU-specific homeodomain .", "target_text": { "POU-specific homeodomain": "protein" } }, { "input_text": "An NMR model is obtained from Oct-2 , a human B-cell specific transcription factor which participates in the regulation of immunoglobulin genes .", "target_text": { "Oct-2": "protein", "human B-cell specific transcription factor": "protein", "immunoglobulin genes": "DNA" } }, { "input_text": "A fragment of Oct-2 containing POUHD and an adjoining linker was expressed in Escherichia coli and characterized by three-dimensional nuclear magnetic resonance ( 3D-NMR ) spectroscopy .", "target_text": { "Oct-2": "protein", "POUHD": "protein" } }, { "input_text": "Complete 1H and 15N resonance assignment of the POUHD moiety is presented .", "target_text": { "POUHD": "protein", "POUHD moiety": "protein" } }, { "input_text": "The POUHD solution structure , as calculated by distance geometry and simulated annealing ( DG/SA ) , is similar to that of canonical homeodomains .", "target_text": { "POUHD": "protein", "canonical homeodomains": "protein" } }, { "input_text": "A salient difference between solution and crystal structures is observed in the C-terminal segment of alpha-helix 3 ( the HTH recognition helix ) , which is not well ordered in solution .", "target_text": { "C-terminal segment": "protein", "alpha-helix 3": "protein", "HTH recognition helix": "protein" } }, { "input_text": "Because this segment presumably folds upon specific DNA binding , its flexibility in solution may reduce the intrinsic DNA affinity of POUHD in the absence of POUs .", "target_text": { "POUHD": "protein", "POUs": "protein" } }, { "input_text": "NF-kappa B -dependent and -independent pathways of HIV activation in a chronically infected T cell line .", "target_text": { "chronically infected T cell line": "cell_line" } }, { "input_text": "J delta K cells were isolated as a chronically infected survivor cell line , following infection of Jurkat CD4+ T cells with dl-NF , a mutated strain of human immunodeficiency virus type 1 ( HIV-1 ) containing a deletion of the long terminal repeat ( LTR ) NF-kappa B sites .", "target_text": { "J delta K cells": "cell_line", "chronically infected survivor cell line": "cell_line", "Jurkat CD4+ T cells": "cell_line", "long terminal repeat": "DNA", "LTR": "DNA", "NF-kappa B": "protein" } }, { "input_text": "J delta K cells exhibited very low levels of constitutive HIV production .", "target_text": { "J delta K cells": "cell_line" } }, { "input_text": "HIV-1 expression was activated from J delta K cells by treatment with phorbol myristate acetate ( PMA ) , sodium butyrate ( NaB ) , or hexamethylene bisacetamide ( HMBA ) , but not tumor necrosis factor alpha ( TNF-alpha ) , confirming the role of NF-kappa B in mediating TNF-alpha induction of HIV transcription .", "target_text": { "J delta K cells": "cell_line", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "The strong induction of HIV expression by NaB or HMBA in J delta K cells clearly demonstrates the existence of NF-kappa B -independent mechanisms of HIV activation in chronically infected cells .", "target_text": { "J delta K cells": "cell_line", "NF-kappa B": "protein", "chronically infected cells": "cell_type" } }, { "input_text": "J delta K cells may provide a useful model for characterizing NF-kappa B -independent transcriptional activation of the HIV LTR .", "target_text": { "J delta K cells": "cell_line", "NF-kappa B": "protein", "HIV LTR": "DNA" } }, { "input_text": "JNK is involved in signal integration during costimulation of T lymphocytes .", "target_text": { "JNK": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "T lymphocyte activation and interleukin-2 ( IL-2 ) production require at least two signals , generated by phorbol ester ( TPA ) and Ca2+ ionophore or costimulation of the T cell receptor ( TCR ) and the CD28 auxiliary receptor .", "target_text": { "T lymphocyte": "cell_type", "interleukin-2": "protein", "IL-2": "protein", "T cell receptor": "protein", "TCR": "protein", "CD28 auxiliary receptor": "protein" } }, { "input_text": "We investigated how these stimuli affect mitogen activated protein ( MAP ) kinases .", "target_text": { "mitogen activated protein ( MAP ) kinases": "protein" } }, { "input_text": "Full activation of the MAP kinases that phosphorylate the Jun activation domain , JNK1 and JNK2 , required costimulation of T cells with either TPA and Ca2+ ionophore or antibodies to TCR and CD28 .", "target_text": { "MAP kinases": "protein", "Jun activation domain": "protein", "JNK1": "protein", "JNK2": "protein", "T cells": "cell_type", "TCR": "protein", "CD28": "protein" } }, { "input_text": "Alone , each stimulus resulted in little or no activation .", "target_text": {} }, { "input_text": "Similar to its effect on IL-2 induction , cyclosporin A ( CsA ) inhibited the synergistic activation of JNK , and a competitive inhibitor of Jun phosphorylation by JNK inhibited IL-2 promoter activation .", "target_text": { "IL-2": "protein", "JNK": "protein", "Jun": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "By contrast , the MAP kinases ERK1 and ERK2 were fully activated by TPA or TCR stimulation and were not affected by Ca2+ , CD28 , or CsA .", "target_text": { "MAP kinases": "protein", "ERK1": "protein", "ERK2": "protein", "TCR": "protein" } }, { "input_text": "Hence , integration of signals that lead to T cell activation occurs at the level of JNK activation .", "target_text": { "JNK": "protein" } }, { "input_text": "Inhibition of rat splenocyte proliferation with methylprednisolone : in vivo effect of liposomal formulation .", "target_text": { "rat splenocyte": "cell_type" } }, { "input_text": "The effect of a liposomal formulation of methylprednisolone ( MPL ) on the inhibition of lymphocyte proliferation in spleen cells was investigated following IV dosing in rats .", "target_text": { "spleen cells": "cell_type" } }, { "input_text": "Liposomes do not alter the suppressive action of MPL when placed in lymphocyte culture .", "target_text": { "lymphocyte culture": "cell_line" } }, { "input_text": "Rat splenocytes were found to have greater sensitivity to MPL ( EC50 = 7.9 nM ) than do human peripheral blood lymphocytes ( EC50 = 28 nM ) .", "target_text": { "Rat splenocytes": "cell_type", "human peripheral blood lymphocytes": "cell_type" } }, { "input_text": "In vivo studies in rats utilized 2 mg/kg IV bolus doses of liposomal MPL compared to drug in solution .", "target_text": {} }, { "input_text": "Animals were sacrificed at various times post-dosing until 120 h , spleen was excised and , after incubation of lymphocytes with PHA , splenocyte blastogenic responses were assessed by measuring cellular incorporation of 3H-thymidine .", "target_text": { "lymphocytes": "cell_type", "PHA": "protein" } }, { "input_text": "The suppressive effect of liposomal MPL in comparison with free drug was significantly prolonged ( > 120 h vs < 18 h ) .", "target_text": {} }, { "input_text": "Inhibition effects versus time were described by a pharmacodynamic model using MPL concentrations in plasma as an input function .", "target_text": { "plasma": "cell_type" } }, { "input_text": "A nonlinear relationship was found between suppression of splenocyte proliferation and the concentration of bound glucocorticoid receptors in spleen .", "target_text": { "splenocyte": "cell_type", "glucocorticoid receptors": "protein" } }, { "input_text": "Only partial receptor occupancy accompanied complete lymphocyte suppression .", "target_text": {} }, { "input_text": "The suppression of endogenous corticosterone in plasma for both treatments was similar with values from L- MPL rats returning to baseline after 24 h .", "target_text": { "plasma": "cell_type" } }, { "input_text": "These results demonstrate enhanced efficacy of local immunosuppression by targeting spleen with liposomal MPL .", "target_text": {} }, { "input_text": "Function of NF-kappa B /Rel binding sites in the major histocompatibility complex class II invariant chain promoter is dependent on cell-specific binding of different NF-kappa B /Rel subunits .", "target_text": { "NF-kappa B": "protein", "NF-kappa B /Rel binding sites": "DNA", "major histocompatibility complex class II invariant chain promoter": "DNA", "NF-kappa B /Rel subunits": "protein" } }, { "input_text": "The promoter of the human major histocompatibility complex class II-associated invariant-chain gene ( Ii ) contains two NF-kappa B /Rel binding sites located at -109 to -118 ( Ii kappa B-1 ) and -163 to -172 ( Ii kappa B-2 ) from the transcription start site .", "target_text": { "promoter": "DNA", "histocompatibility complex class II-associated invariant-chain gene": "DNA", "Ii": "DNA", "NF-kappa B": "protein", "NF-kappa B /Rel binding sites": "DNA", "-109 to -118": "DNA", "Ii kappa B-1": "DNA", "-163 to -172": "DNA", "Ii kappa B-2": "DNA" } }, { "input_text": "We report here that the differential function of each of these NF-kappa B /Rel sites in several distinct cell types depends on cell-specific binding of NF-kappa B /Rel transcription factors .", "target_text": { "NF-kappa B": "protein", "NF-kappa B /Rel sites": "DNA", "NF-kappa B /Rel transcription factors": "protein" } }, { "input_text": "Ii kappa B-1 is a positive regulatory element in B-cell lines and in the Ii-expressing T-cell line , H9 , but acts as a negative regulatory element in myelomonocytic and glia cell lines .", "target_text": { "Ii kappa B-1": "DNA", "positive regulatory element": "DNA", "B-cell lines": "cell_line", "Ii-expressing T-cell line": "cell_line", "H9": "cell_line", "negative regulatory element": "DNA" } }, { "input_text": "In vivo protein-DNA contacts are detectable at Ii kappa B-1 in cell lines in which this site is functional as either a positive or negative regulator .", "target_text": { "Ii kappa B-1": "DNA", "cell lines": "cell_line" } }, { "input_text": "Electrophoretic mobility supershift assays determine that members of the NF-kappa B /Rel family of transcription factors can bind to this site in vitro and that DNA-binding complexes that contain p50 , p52 , p65 , and cRel correlate with positive regulation whereas the presence of p50 correlates with negative regulation .", "target_text": { "NF-kappa B": "protein", "NF-kappa B /Rel family": "protein", "transcription factors": "protein", "DNA-binding complexes": "protein", "p50": "protein", "p52": "protein", "p65": "protein", "cRel": "protein" } }, { "input_text": "Ii kappa B-2 is a site of positive regulation in B-cell lines and a site of negative regulation in H9 T cells , myelomonocytic , and glial cell lines .", "target_text": { "Ii kappa B-2": "DNA", "B-cell lines": "cell_line", "H9 T cells": "cell_line" } }, { "input_text": "In vivo occupancy of this site is observed only in the H9 T-cell line .", "target_text": { "H9 T-cell line": "cell_line" } }, { "input_text": "Again , in vitro supershift studies indicate that the presence of p50 , p52 , p65 , and cRel correlates with positive function whereas the presence of only p50 and p52 correlates with negative function .", "target_text": { "p50": "protein", "p52": "protein", "p65": "protein", "cRel": "protein" } }, { "input_text": "This differential binding of specific NF-kappa B /Rel subunits is likely to mediate the disparate functions of these two NF-kappa B /Rel binding sites .", "target_text": { "NF-kappa B": "protein", "NF-kappa B /Rel subunits": "protein", "NF-kappa B /Rel binding sites": "DNA" } }, { "input_text": "Epstein-Barr virus ( EBV ) replicative gene expression in tumour cells of AIDS-related non-Hodgkin 's lymphoma in relation to CD4 cell number and antibody titres to EBV .", "target_text": { "tumour cells": "cell_type", "CD4": "protein" } }, { "input_text": "OBJECTIVE : To determine whether activation of Epstein-Barr virus ( EBV ) replication in tumour cells of AIDS-related non-Hodgkin 's lymphoma ( ARNHL ) is correlated with CD4+ cell counts and influences antibody response to EBV [ anti-Z Epstein-Barr replicative activator ( ZEBRA ) , anti-early antigen ( EA ) , anti-viral capsid antigen ( VCA ) ] .", "target_text": { "tumour cells": "cell_type", "CD4+": "protein", "anti-Z Epstein-Barr replicative activator": "protein", "ZEBRA": "protein", "anti-early antigen": "protein", "EA": "protein", "anti-viral capsid antigen": "protein", "VCA": "protein" } }, { "input_text": "DESIGN : Retrospective study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients affected by ARNHL and correlation with CD4+ cell counts and results of EBV serology ( including anti- ZEBRA activity ) in sera from the same patients .", "target_text": { "CD4+": "protein", "ZEBRA": "protein" } }, { "input_text": "METHODS : Seventeen out of 22 cases of ARNHL were selected for the presence of EBV [ Epstein-Barr early region ( EBER ) RNA-positive ] .", "target_text": {} }, { "input_text": "Immunohistochemistry was performed with anti- ZEBRA , anti- EA -restricted , anti- VCA antibodies and in situ hybridization with BHLF1/NotI oligoprobes on tumour samples .", "target_text": { "ZEBRA": "protein", "anti- ZEBRA": "protein", "EA": "protein", "VCA": "protein", "anti- EA -restricted , anti- VCA antibodies": "protein" } }, { "input_text": "Results were statistically correlated with those of CD4+ cell counts ( 17 out of 17 ) and with anti- EBV antibody titres ( 13 out of 17 ) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using recombinant ZEBRA protein and synthetic peptides as antigens .", "target_text": { "CD4+": "protein", "ZEBRA": "protein", "recombinant ZEBRA protein": "protein", "antigens": "protein" } }, { "input_text": "RESULTS : BZLF1 ( ZEBRA ) or early gene products ( EA-R and EA-D/BHLF1/NotI ) were detected in a small proportion ( < 0.01-5 % ) of tumour cells in eight of these 17 cases by immunohistochemistry and in situ hybridization .", "target_text": { "BZLF1": "protein", "ZEBRA": "protein", "early gene products": "protein", "EA-R": "protein", "EA-D/BHLF1/NotI": "protein", "tumour cells": "cell_type" } }, { "input_text": "Demonstration of replicative gene expression did not correlate with either low CD4+ cell counts ( P > 0.05 ) or anti- EBV antibody titres ( P > 0.05 ) .", "target_text": { "CD4+": "protein" } }, { "input_text": "Anti- ZEBRA activity was not significantly increased in patients affected with ARNHL , the cells of which expressed replicative gene products ( P > 0.05 ) .", "target_text": { "ZEBRA": "protein" } }, { "input_text": "CONCLUSION : The degree of immunodeficiency does not clearly enhance replicative gene expression in tumour cells of ARNHL .", "target_text": { "tumour cells": "cell_type" } }, { "input_text": "EBV serology , including anti- ZEBRA activity , is not a reliable tool for predicting the occurrence of such proliferations .", "target_text": { "ZEBRA": "protein" } }, { "input_text": "Effects of prostaglandin E2 on Th0-type human T cell clones : modulation of functions of nuclear proteins involved in cytokine production .", "target_text": { "prostaglandin E2": "protein", "Th0-type human T cell clones": "cell_line", "nuclear proteins": "protein", "cytokine": "protein" } }, { "input_text": "The effects of prostaglandin E2 ( PGE2 ) on cytokine production and proliferation of the CD4+ human helper T cell clone SP-B21 were investigated .", "target_text": { "prostaglandin E2": "protein", "PGE2": "protein", "cytokine": "protein", "CD4+ human helper T cell clone SP-B21": "cell_line" } }, { "input_text": "In cells stimulated with anti-CD3 mAb , PGE2 inhibited cell proliferation and the production of all the cytokines examined .", "target_text": { "anti-CD3 mAb": "protein", "PGE2": "protein", "cytokines": "protein" } }, { "input_text": "Addition of rIL-2 fully restored the proliferative response and partially restored the production of IL-4 and IL-5 , but not that of other cytokines .", "target_text": { "rIL-2": "protein", "IL-4": "protein", "IL-5": "protein", "cytokines": "protein" } }, { "input_text": "In contrast , in cells stimulated with phorbol myristate acetate ( PMA ) / A23187 , PGE2 enhanced the production of IL-4 and IL-5 , and only partially inhibited the production of other cytokines .", "target_text": { "PGE2": "protein", "IL-4": "protein", "IL-5": "protein", "cytokines": "protein" } }, { "input_text": "Therefore , the effects of PGE2 vary depending on the mode of T cell activation , and the IL-4 and IL-5 are regulated differently from other cytokines .", "target_text": { "PGE2": "protein", "IL-4": "protein", "IL-5": "protein", "cytokines": "protein" } }, { "input_text": "In a mobility shift assay , only the NF-kappa B ( p50 /p50 ) homodimer was observed in a complex formed with the kappa B sequence in unstimulated SP-B21 cells .", "target_text": { "NF-kappa B": "protein", "p50": "protein", "/p50": "protein", "NF-kappa B ( p50 /p50 ) homodimer": "protein", "kappa B sequence": "DNA" } }, { "input_text": "When cells were stimulated with anti-CD3 mAb or PMA /A23187 , a complex formation of NF-kappa B ( p50 /p65 ) heterodimer with the kappa B sequence was induced .", "target_text": { "anti-CD3 mAb": "protein", "NF-kappa B": "protein", "p50": "protein", "/p65": "protein", "kappa B sequence": "DNA" } }, { "input_text": "Interestingly , PGE2 or di-butyryl ( Bt2 ) cAMP abolished the binding of NF-kappa B ( p50 /p65 ) heterodimer to the kappa B sequence in cells stimulated with anti-CD3 mAb but not with PMA /A23187 .", "target_text": { "PGE2": "protein", "NF-kappa B": "protein", "p50": "protein", "/p65": "protein", "NF-kappa B ( p50 /p65 ) heterodimer": "protein", "kappa B sequence": "DNA", "anti-CD3 mAb": "protein" } }, { "input_text": "Our results suggest that the target of PGE2 action is a component in the signal transduction pathway leading to the activation of protein kinase C .", "target_text": { "PGE2": "protein", "protein kinase C": "protein" } }, { "input_text": "However , the inhibition of the T cell activation signals by PGE2 is selective .", "target_text": { "PGE2": "protein" } }, { "input_text": "PGE2 enhanced the complex formation with NF-AT , AP-1 and CLE0 sequences when the cells were activated by either anti-CD3 mAb or PMA /A23187 stimulation .", "target_text": { "PGE2": "protein", "anti-CD3 mAb": "protein" } }, { "input_text": "It seems therefore that PGE2 , by elevating cAMP levels , interferes with the activation pathway for NF-kappa B but not for NF-AT , AP-1 or CLE0 binding protein .", "target_text": { "PGE2": "protein", "NF-kappa B": "protein", "NF-AT": "protein", "AP-1": "protein", "CLE0 binding protein": "protein" } }, { "input_text": "Characterization of NF(P) , the nuclear factor that interacts with the regulatory P sequence ( 5'-CGAAAATTTCC-3' ) of the human interleukin-4 gene : relationship to NF-kappa B and NF-AT .", "target_text": { "NF(P)": "protein", "nuclear factor": "protein", "P sequence": "DNA", "human interleukin-4 gene": "DNA", "NF-kappa B": "protein", "NF-AT": "protein" } }, { "input_text": "The P sequence of the human interleukin-4 ( IL-4 ) gene , which was defined as a responsive element for phorbol 12-myristate 13-acetate and calcium ionophore ( A23187 ) in Jurkat T cells , shares sequence similarity with the NF-kappa B and the NF-AT binding sites .", "target_text": { "P sequence": "DNA", "IL-4": "protein", "human interleukin-4 ( IL-4 ) gene": "DNA", "responsive element": "DNA", "Jurkat T cells": "cell_line", "NF-kappa B": "protein", "NF-AT": "protein", "NF-AT binding sites": "DNA", "NF-kappa B and the NF-AT binding sites": "DNA" } }, { "input_text": "We examined whether NF(P) , a nuclear factor specific for the P sequence , is related to NF-kappa B and NF-AT .", "target_text": { "NF(P)": "protein", "nuclear factor": "protein", "P sequence": "DNA", "NF-kappa B": "protein", "NF-AT": "protein" } }, { "input_text": "NF-kappa B ( P65 or P65/P50 heterodimer ) bound to the P sequence in electrophoretic mobility shift assays ( EMSA ) and activated transcription through the P sequence when expression plasmids were cotransfected with P sequence -driven reporter plasmids in Jurkat T cells .", "target_text": { "NF-kappa B": "protein", "P65": "protein", "P65/P50 heterodimer": "protein", "P sequence": "DNA", "expression plasmids": "DNA", "P sequence -driven reporter plasmids": "DNA", "Jurkat T cells": "cell_line" } }, { "input_text": "In EMSAs , NF(P) binding was inhibited by the unlabeled NF-AT binding site but not by the unlabeled AP1 binding site and purified NF-AT contained an activity that bound to the P sequence .", "target_text": { "NF(P)": "protein", "NF-AT": "protein", "unlabeled NF-AT binding site": "DNA", "unlabeled AP1 binding site": "DNA", "purified NF-AT": "protein", "P sequence": "DNA" } }, { "input_text": "Both mobility shift and sequence specificity of NF-AT were similar to those of NF(P) and only a small amount of P65 was detected in NF(P) in crude nuclear extracts .", "target_text": { "NF-AT": "protein", "NF(P)": "protein", "P65": "protein" } }, { "input_text": "These results indicate that the component ( s ) of NF-AT has the potential to reconstitute NF(P) whereas NF-kappa B alone can not account for NF(P) in crude extracts .", "target_text": { "NF-AT": "protein", "NF(P)": "protein", "NF-kappa B": "protein" } }, { "input_text": "Unlike NF-AT , NF(P) does not contain AP1 as its DNA binding component .", "target_text": { "NF-AT": "protein", "NF(P)": "protein", "AP1": "protein", "DNA binding component": "protein" } }, { "input_text": "Activation of early growth response 1 gene transcription and pp90rsk during induction of monocytic differentiation .", "target_text": { "early growth response 1 gene": "DNA", "pp90rsk": "protein" } }, { "input_text": "The present work has studied mechanisms responsible for induction of early growth response 1 ( EGR-1 ) gene expression during monocytic differentiation of U-937 myeloid leukemia cells .", "target_text": { "early growth response 1 ( EGR-1 ) gene": "DNA", "U-937 myeloid leukemia cells": "cell_line" } }, { "input_text": "Differentiation of U-937 cells with 12-O-tetradecanoylphorbol-13-acetate ( TPA ) , an activator of the serine/threonine protein kinase C , was associated with transcriptional activation of EGR-1 promoter-reporter constructs .", "target_text": { "U-937 cells": "cell_line", "protein kinase C": "protein", "serine/threonine protein kinase C": "protein", "EGR-1 promoter-reporter constructs": "DNA" } }, { "input_text": "The EGR-1 promoter contains six CC(A/T)6GG ( CArG ) motifs .", "target_text": { "EGR-1 promoter": "DNA", "CC(A/T)6GG ( CArG ) motifs": "DNA" } }, { "input_text": "The two 5'-most distal CArG sequences conferred TPA inducibility .", "target_text": { "5'-most distal CArG sequences": "DNA" } }, { "input_text": "In contrast , there was little effect of TPA on EGR-1 transcription in a TPA -resistant U-937 cell variant , designated TUR .", "target_text": { "EGR-1": "DNA", "TPA -resistant U-937 cell variant": "cell_line", "TUR": "cell_line" } }, { "input_text": "Treatment of both U-937 and TUR cells with okadaic acid , an inhibitor of serine/threonine protein phosphatases 1 and 2A , was associated with induction of monocytic differentiation and EGR-1 transcription through the 5'-most CArG element .", "target_text": { "U-937": "cell_line", "TUR cells": "cell_line", "EGR-1": "DNA", "5'-most CArG element": "DNA" } }, { "input_text": "Since these findings supported the involvement of serine /threonine protein phosphorylation in the regulation of EGR-1 expression , we studied activation of the 40S ribosomal protein S6 serine /threonine kinases , pp70S6K and pp90rsk .", "target_text": { "EGR-1": "DNA", "40S ribosomal protein S6 serine /threonine kinases": "protein", "pp70S6K": "protein", "pp90rsk": "protein" } }, { "input_text": "Although both kinases participate in regulating cell growth , there was no detectable activation of pp70S6K during TPA- or okadaic acid- induced monocytic differentiation .", "target_text": { "pp70S6K": "protein" } }, { "input_text": "Moreover , rapamycin , an inhibitor of pp70S6K activation , had no effect on induction of EGR-1 expression .", "target_text": { "pp70S6K": "protein", "EGR-1": "DNA" } }, { "input_text": "In contrast , analysis of pp90rsk activity by phosphorylation of a peptide derived from S6 protein demonstrated stimulation of this kinase in TPA-treated U-937 , and not TUR , cells .", "target_text": { "pp90rsk": "protein", "S6 protein": "protein", "kinase": "protein" } }, { "input_text": "Okadaic acid treatment of both cell types was associated with activation of pp90rsk .", "target_text": { "pp90rsk": "protein" } }, { "input_text": "Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals .", "target_text": { "monocyte": "cell_type", "nuclear factor-kappa B": "protein", "vascular cell adhesion molecule-1": "protein", "endothelial cells": "cell_type" } }, { "input_text": "Cell adhesion to endothelial cells stimulated by tumor necrosis factor-alpha ( TNF ) is due to induction of surface receptors , such as vascular cell adhesion molecule-1 ( VCAM-1 ) .", "target_text": { "endothelial cells": "cell_type", "stimulated by tumor necrosis factor-alpha": "protein", "TNF": "protein", "surface receptors": "protein", "vascular cell adhesion molecule-1": "protein", "VCAM-1": "protein" } }, { "input_text": "The antioxidant pyrrolidine dithiocarbamate ( PDTC ) specifically inhibits activation of nuclear factor-kappa B ( NF-kappa B ) .", "target_text": { "nuclear factor-kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "Since kappa B motifs are present in VCAM-1 and intercellular adhesion molecule-1 ( ICAM-1 ) promoters , we used PDTC to study the regulatory mechanisms of VCAM-1 and ICAM-1 induction and subsequent monocyte adhesion in TNF-treated human umbilical vein endothelial cells ( HUVECs ) .", "target_text": { "kappa B motifs": "DNA", "VCAM-1": "protein", "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "intercellular adhesion molecule-1 ( ICAM-1 ) promoters": "DNA", "VCAM-1 and intercellular adhesion molecule-1 ( ICAM-1 ) promoters": "DNA", "monocyte": "cell_type", "endothelial cells": "cell_type", "TNF-treated human umbilical vein endothelial cells": "cell_line", "HUVECs": "cell_line" } }, { "input_text": "PDTC or N-acetylcysteine dose dependently reduced TNF-induced VCAM-1 but not ICAM-1 surface protein ( also in human umbilical arterial endothelial cells ) and mRNA expression ( by 70 % at 100 mumol/L PDTC ) in HUVECs as assessed by flow cytometry and polymerase chain reaction .", "target_text": { "VCAM-1": "protein", "TNF-induced VCAM-1": "protein", "ICAM-1": "protein", "ICAM-1 surface protein": "protein", "endothelial cells": "cell_type", "human umbilical arterial endothelial cells": "cell_type", "HUVECs": "cell_line" } }, { "input_text": "Gel-shift analysis in HUVECs demonstrated that PDTC prevented NF-kappa B mobilization by TNF , suggesting that only VCAM-1 induction was controlled by NF-kappa B .", "target_text": { "HUVECs": "cell_line", "NF-kappa B": "protein", "TNF": "protein", "VCAM-1": "protein" } }, { "input_text": "Since HUVECs released superoxide anions in response to TNF , and H2O2 induces VCAM-1 , PDTC may act as a radical scavenger .", "target_text": { "HUVECs": "cell_line", "VCAM-1": "protein" } }, { "input_text": "Although ICAM-1 induction was unaffected , inhibitors of NADPH oxidase ( apocynin ) or cytochrome P-450 ( SKF525a ) suppressed VCAM-1 induction by TNF , revealing that several radical-generating systems are involved in its regulation .", "target_text": { "ICAM-1": "protein", "NADPH oxidase": "protein", "cytochrome P-450": "protein", "VCAM-1": "protein" } }, { "input_text": "PDTC , apocynin , or SKF525a decreased adhesion of monocytic U937 cells to TNF-treated HUVECs ( by 75 % at 100 mumol/L PDTC ) .", "target_text": { "monocytic U937 cells": "cell_line", "HUVECs": "cell_line", "TNF-treated HUVECs": "cell_line" } }, { "input_text": "Inhibition by anti- VCAM-1 monoclonal antibody 1G11 indicated that U937 adhesion was VCAM-1 dependent and suppression by antioxidants was due to reduced VCAM-1 induction .", "target_text": { "VCAM-1": "protein", "anti- VCAM-1 monoclonal antibody": "protein", "1G11": "protein", "U937": "cell_line" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "Displacement of an E-box-binding repressor by basic helix-loop-helix proteins : implications for B-cell specificity of the immunoglobulin heavy-chain enhancer .", "target_text": { "E-box-binding repressor": "protein", "basic helix-loop-helix proteins": "protein", "immunoglobulin heavy-chain enhancer": "DNA" } }, { "input_text": "The activity of the immunoglobulin heavy-chain ( IgH ) enhancer is restricted to B cells , although it binds both B-cell-restricted and ubiquitous transcription factors .", "target_text": { "immunoglobulin heavy-chain ( IgH ) enhancer": "DNA", "B cells": "cell_type" } }, { "input_text": "Activation of the enhancer in non- B cells upon overexpression of the basic helix-loop-helix ( bHLH ) protein E2A appears to be mediated not only by the binding of E2A to its cognate E box but also by the resulting displacement of a repressor from that same site .", "target_text": { "enhancer": "DNA", "B cells": "cell_type", "non- B cells": "cell_type", "basic helix-loop-helix ( bHLH ) protein": "protein", "E2A": "protein", "E box": "DNA", "repressor": "protein" } }, { "input_text": "We have identified a \" two-handed \" zinc finger protein , denoted ZEB , the DNA-binding specificity of which mimics that of the cellular repressor .", "target_text": { "\" two-handed \" zinc finger protein": "protein", "ZEB": "protein", "cellular repressor": "protein" } }, { "input_text": "By employing a derivative E box that binds ZEB but not E2A , we have shown that the repressor is active in B cells and the IgH enhancer is silenced in the absence of binding competition by bHLH proteins .", "target_text": { "E box": "DNA", "ZEB": "protein", "E2A": "protein", "repressor": "protein", "B cells": "cell_type", "IgH enhancer": "DNA", "bHLH proteins": "protein" } }, { "input_text": "Hence , we propose that a necessary prerequisite of enhancer activity is the B-cell-specific displacement of a ZEB -like repressor by bHLH proteins .", "target_text": { "enhancer": "DNA", "ZEB": "protein", "ZEB -like repressor": "protein", "bHLH proteins": "protein" } }, { "input_text": "Inhibition of NF-kappa B by sodium salicylate and aspirin [ see comments ]", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "The transcription factor nuclear factor-kappa B ( NF-kappa B ) is critical for the inducible expression of multiple cellular and viral genes involved in inflammation and infection including interleukin-1 ( IL-1 ) , IL-6 , and adhesion molecules .", "target_text": { "transcription factor": "protein", "nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "interleukin-1": "protein", "IL-1": "protein", "IL-6": "protein", "adhesion molecules": "protein" } }, { "input_text": "The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of NF-kappa B , which further explains the mechanism of action of these drugs .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "This inhibition prevented the degradation of the NF-kappa B inhibitor , I kappa B , and therefore NF-kappa B was retained in the cytosol .", "target_text": { "NF-kappa B": "protein", "NF-kappa B inhibitor": "protein", "I kappa B": "protein" } }, { "input_text": "Sodium salicylate and aspirin also inhibited NF-kappa B -dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus ( HIV ) long terminal repeat ( LTR ) in transfected T cells .", "target_text": { "NF-kappa B": "protein", "Ig kappa enhancer": "DNA", "human immunodeficiency virus ( HIV ) long terminal repeat": "DNA", "LTR": "DNA", "transfected T cells": "cell_line" } }, { "input_text": "Effects of the antisense myb expression on hemin- and erythropoietin- induced erythroid differentiation of K562 cells .", "target_text": { "K562 cells": "cell_line" } }, { "input_text": "In order to elucidate the role of c-myb gene in erythroid differentiation of K562 cell induced by hemin ( Hm ) and erythropoietin ( Epo ) , we constructed recombinant plasmid that could produce antisense myb RNA after induction with dexamethasone .", "target_text": { "c-myb gene": "DNA", "K562 cell": "cell_line", "hemin": "protein", "Hm": "protein", "erythropoietin": "protein", "Epo": "protein", "recombinant plasmid": "DNA", "antisense myb RNA": "RNA" } }, { "input_text": "During treatment with Hm , K562 cells constitutively expressed c-myb mRNA , and 50 % of them began to synthesize hemoglobin ( Hb ) .", "target_text": { "Hm": "protein", "K562 cells": "cell_line", "c-myb mRNA": "RNA", "hemoglobin": "protein", "Hb": "protein" } }, { "input_text": "Expression of antisense myb RNA reduced the amount of c-myb mRNA , and the percentage of Hb -synthesizing cells was decreased to 20 % .", "target_text": { "antisense myb RNA": "RNA", "c-myb mRNA": "RNA", "Hb": "protein", "Hb -synthesizing cells": "cell_line" } }, { "input_text": "In the presence of Epo , c-myb mRNA declined and 20 % of K562 cells synthesized Hb regardless of antisense myb RNA expression .", "target_text": { "Epo": "protein", "c-myb mRNA": "RNA", "K562 cells": "cell_line", "Hb": "protein", "antisense myb RNA": "RNA" } }, { "input_text": "It is suggested that constitutive expression of c-myb mRNA is necessary for Hm -induced differentiation , and that a decrease in the amount of c-myb mRNA induced by antisense myb RNA expression suppresses Hm -induced differentiation .", "target_text": { "c-myb mRNA": "RNA", "Hm": "protein", "antisense myb RNA": "RNA" } }, { "input_text": "The amount of c-myb mRNA in K562 cells was reduced during the differentiation induced by Epo .", "target_text": { "c-myb mRNA": "RNA", "K562 cells": "cell_line", "Epo": "protein" } }, { "input_text": "Expression of GATA-1 mRNA was almost constant during Hm -induced differentiation , but increased during Epo treatment .", "target_text": { "GATA-1 mRNA": "RNA", "Hm": "protein", "Epo": "protein" } }, { "input_text": "It is supposed that the mechanism of Hm -induced differentiation is distinguished from that of Epo -induced differentiation in K562 cells .", "target_text": { "Hm": "protein", "Epo": "protein", "K562 cells": "cell_line" } }, { "input_text": "Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats .", "target_text": {} }, { "input_text": "We investigated whether non-abortive maternal infections would compromise fetal brain development and alter hypothalamic-pituitary-adrenocortical ( HPA ) axis functioning when adult .", "target_text": {} }, { "input_text": "To study putative teratogenic effects of a T cell-mediated immune response versus an endotoxic challenge , 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10 ( 8 ) human red blood cells ( HRBC ) or gram-negative bacterial endotoxin ( Escherichia coli LPS : 30 micrograms/kg ) .", "target_text": { "human red blood cells": "cell_type", "HRBC": "cell_type" } }, { "input_text": "The adult male progeny ( 3 mo old ) of both experimental groups showed increased basal plasma corticosterone levels .", "target_text": {} }, { "input_text": "In addition , after novelty stress the HRBC group , but not the LPS group , showed increased ACTH and corticosterone levels .", "target_text": { "HRBC": "cell_type", "LPS group": "cell_line" } }, { "input_text": "Both groups showed substantial decreases in mineralocorticoid ( MR ) and glucocorticoid receptor ( GR ) levels in the hippocampus , a limbic brain structure critical for HPA axis regulation , whereas GR concentrations in the hypothalamus were unchanged and in anterior pituitary were slightly increased .", "target_text": { "GR": "protein" } }, { "input_text": "HRBC and LPS indeed stimulated the maternal immune system as revealed by specific anti- HRBC antibody production and enhanced IL-1 beta mRNA expression in splenocytes , respectively .", "target_text": { "HRBC": "cell_type", "anti- HRBC antibody": "protein", "splenocytes": "cell_type" } }, { "input_text": "This study demonstrates that a T cell-mediated immune response as well as an endotoxic challenge during pregnancy can induce anomalies in HPA axis function in adulthood .", "target_text": {} }, { "input_text": "Clinically , it may be postulated that disturbed fetal brain development due to prenatal immune challenge increases the vulnerability to develop mental illness involving inadequate responses to stress .", "target_text": {} }, { "input_text": "A low NM23.H1 gene expression identifying high malignancy human melanomas .", "target_text": { "NM23.H1 gene": "DNA" } }, { "input_text": "The NM23 gene has been proposed as a metastasis-suppressor gene , and its use has been suggested as prognostic factor .", "target_text": { "NM23 gene": "DNA", "metastasis-suppressor gene": "DNA" } }, { "input_text": "NM23 was identified in a system of murine melanoma cell lines , in which an inverse relationship was found between NM23 expression and metastatic ability .", "target_text": { "NM23": "protein", "murine melanoma cell lines": "cell_line" } }, { "input_text": "In a human malignant melanoma study NM23 expression was found to be significantly lower in metastases that developed less than 24 months after diagnosis of the primary tumours .", "target_text": { "NM23": "protein" } }, { "input_text": "The present paper studies the expression of the NM23 .H1 gene in cell lines which derive from primary or metastatic human malignant melanomas in relation to staging , infiltration degree , lymphocytic infiltration , cell morphology , cell pigmentation , karyotype , and disease-free survival .", "target_text": { "NM23": "protein", "NM23 .H1 gene": "DNA", "cell lines": "cell_line" } }, { "input_text": "The level of mRNA expression of the NM23 gene is significantly lower in cell lines that derive from more infiltrating primary melanomas than in cell lines obtained from less infiltrating tumours .", "target_text": { "NM23": "protein", "NM23 gene": "DNA", "cell lines": "cell_line" } }, { "input_text": "Moreover , cell lines derived from tumours of patients with a disease-free survival of more than 24 months ( 24-58 months ) express the NM23 gene at higher levels than cell lines obtained from melanomas of patients with a disease-free survival of less than 24 months ( 6-15 months ) .", "target_text": { "cell lines": "cell_line", "NM23": "protein", "NM23 gene": "DNA" } }, { "input_text": "Activation of a novel serine /threonine kinase that phosphorylates c-Fos upon stimulation of T and B lymphocytes via antigen and cytokine receptors .", "target_text": { "serine /threonine kinase": "protein", "c-Fos": "protein", "cytokine receptors": "protein" } }, { "input_text": "Ligation of Ag receptors in T and B lymphocytes initiates signal transduction cascades which alter the expression of genes that regulate cellular proliferation and differentiation .", "target_text": { "Ag receptors": "protein" } }, { "input_text": "The transmission of signals from the membrane to the nucleus is mediated principally through the action of protein tyrosine and serine/threonine kinases .", "target_text": {} }, { "input_text": "We have identified and characterized a novel serine /threonine kinase that phosphorylated the proto-oncogene product , c-Fos , and is termed Fos kinase .", "target_text": { "serine /threonine kinase": "protein", "proto-oncogene product": "protein", "c-Fos": "protein", "Fos kinase": "protein" } }, { "input_text": "Fos kinase was rapidly activated after ligation of the CD3 and CD2 receptors in Jurkat and normal human T lymphocytes and in response to IL-6 and anti-IgM in the human B cell lines AF10 and Ramos , respectively .", "target_text": { "Fos kinase": "protein", "Jurkat": "cell_line", "normal human T lymphocytes": "cell_type", "IL-6": "protein", "anti-IgM": "protein", "cell lines": "cell_line", "human B cell lines": "cell_line", "AF10": "cell_line", "Ramos": "cell_line" } }, { "input_text": "The phorbol ester , PMA , was also a potent inducer of Fos kinase activity in all of the above populations , suggesting that PKC plays a role in the regulation of this enzyme .", "target_text": { "Fos kinase": "protein", "PKC": "protein", "enzyme": "protein" } }, { "input_text": "Fos kinase phosphorylates c-Fos at a site near the C-terminus , as well as a peptide derived from this region ( residues 359-370 , RKGSSSNEPSSD ) , and Fos peptide competitively inhibited c-Fos phosphorylation .", "target_text": { "Fos kinase": "protein", "c-Fos": "protein", "C-terminus": "protein", "residues 359-370": "protein", "RKGSSSNEPSSD": "protein" } }, { "input_text": "Fos kinase was shown to be distinct from other identified serine /threonine kinases , including protein kinase A , protein kinase C , casein kinase II , MAP kinases , p70S6K and p90RSK .", "target_text": { "Fos kinase": "protein", "serine /threonine kinases": "protein", "protein kinase A": "protein", "protein kinase C": "protein", "casein kinase II": "protein", "MAP kinases": "protein", "p70S6K": "protein", "p90RSK": "protein" } }, { "input_text": "Fos kinase was purified by anion exchange chromatography and exhibited an apparent M(r) = 65,000 and isoelectric point = 6.1 .", "target_text": { "Fos kinase": "protein" } }, { "input_text": "Fos kinase may play a role in transcriptional regulation through its capacity to phosphorylate c-Fos at a site required for expression of the transcriptional transrepressive activity of this molecule .", "target_text": { "Fos kinase": "protein", "c-Fos": "protein" } }, { "input_text": "Moreover , its rapid activation suggests it may have a wider role within signal transduction cascades in lymphocytes .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "Antigenic specificities of human CD4+ T-cell clones recovered from recurrent genital herpes simplex virus type 2 lesions .", "target_text": { "human CD4+ T-cell clones": "cell_line" } }, { "input_text": "Lesions resulting from recurrent genital herpes simplex virus ( HSV ) infection are characterized by infiltration of CD4+ lymphocytes .", "target_text": { "CD4+ lymphocytes": "cell_type" } }, { "input_text": "We have investigated the antigenic specificity of 47 HSV-specific CD4+ T-cell clones recovered from the HSV-2 buttock and thigh lesions of five patients .", "target_text": { "HSV-specific CD4+ T-cell clones": "cell_line" } }, { "input_text": "Clones with proliferative responses to recombinant truncated glycoprotein B ( gB ) or gD of HSV-2 or purified natural gC of HSV-2 comprised a minority of the total number of HSV-specific clones isolated from lesions .", "target_text": { "recombinant truncated glycoprotein B": "protein", "gB": "protein", "gD": "protein", "HSV-specific clones": "cell_line" } }, { "input_text": "The gC2- and gD2- specific CD4+ clones had cytotoxic activity .", "target_text": {} }, { "input_text": "The approximate locations of the HSV-2 genes encoding HSV-2 type-specific CD4+ antigens have been determined by using HSV-1 x HSV-2 intertypic recombinant virus and include the approximate map regions 0.30 to 0.46 , 0.59 to 0.67 , 0.67 to 0.73 , and 0.82 to 1.0 units .", "target_text": { "CD4+ antigens": "protein" } }, { "input_text": "The antigenic specificity of an HLA DQ2-restricted , HSV-2 type-specific T-cell clone was mapped to amino acids 425 to 444 of VP16 of HSV-2 by sequential use of an intertypic recombinant virus containing VP16 of HSV-2 in an HSV-1 background , recombinant VP16 fusion proteins , and synthetic peptides .", "target_text": { "HLA DQ2-restricted , HSV-2 type-specific T-cell clone": "cell_line", "amino acids 425 to 444": "protein", "VP16": "protein", "recombinant VP16 fusion proteins": "protein" } }, { "input_text": "Each of the remaining four patients also yielded at least one type-specific T-cell clone reactive with an HSV-2 epitope mapping to approximately 0.67 to 0.73 map units .", "target_text": { "type-specific T-cell clone": "cell_line" } }, { "input_text": "The antigenic specificities of lesion-derived CD4+ T-cell clones are quite diverse and include at least 10 epitopes .", "target_text": { "lesion-derived CD4+ T-cell clones": "cell_line" } }, { "input_text": "Human T-cell clones reactive with gC and VP16 are reported here for the first time .", "target_text": { "Human T-cell clones": "cell_line", "gC": "protein", "VP16": "protein" } }, { "input_text": "Marked basophilia in acute promyelocytic leukaemia treated with all-trans retinoic acid : molecular analysis of the cell origin of the basophils .", "target_text": { "basophils": "cell_type" } }, { "input_text": "We report a patient with acute promyelocytic leukaemia who developed marked basophilia during all-trans retinoic acid treatment .", "target_text": {} }, { "input_text": "We studied genomic DNA and RNA extracted from the patient 's peripheral leucocytes in order to determine the origin of the basophils .", "target_text": { "genomic DNA": "DNA", "RNA": "RNA", "peripheral leucocytes": "cell_type", "basophils": "cell_type" } }, { "input_text": "The RAR alpha rearranged band in the Southern blot analysis and a chimaeric product of PML-RAR alpha by polymerase chain reaction were strongly visible before ATRA treatment , but at the time of maximal basophilia both of them were markedly diminished .", "target_text": { "RAR alpha": "protein", "chimaeric product": "protein", "PML-RAR alpha": "protein" } }, { "input_text": "These findings suggest that the basophils which appeared during the ATRA treatment are reactive in nature rather than a leukaemic clone .", "target_text": { "basophils": "cell_type", "leukaemic clone": "cell_line" } }, { "input_text": "Activation of the interleukin 6 gene by Mycobacterium tuberculosis or lipopolysaccharide is mediated by nuclear factors NF-IL6 and NF-kappa B [ published erratum appears in Proc Natl Acad Sci U S A 1995 Apr 11 ; 92 ( 8 ) : 3632 ]", "target_text": { "interleukin 6 gene": "DNA", "nuclear factors NF-IL6": "protein", "NF-kappa B": "protein" } }, { "input_text": "The host response to Mycobacterium tuberculosis includes granuloma formation at sites of infection and systemic symptoms .", "target_text": {} }, { "input_text": "Cytokines have been identified by immunohistochemistry in granulomas in animal models of bacillus Calmette-Guerin ( BCG ) infection and are released by mononuclear phagocytes upon stimulation by mycobacterial proteins .", "target_text": { "Cytokines": "protein", "mononuclear phagocytes": "cell_type" } }, { "input_text": "In this regard , the cytokine interleukin 6 ( IL-6 ) may play a role in the clinical manifestations and pathological events of tuberculosis infection .", "target_text": { "cytokine": "protein", "interleukin 6": "protein", "IL-6": "protein", "tuberculosis infection": "protein" } }, { "input_text": "We have demonstrated that lipoarabinomannan ( LAM ) from the mycobacterial cell wall , which was virtually devoid of lipopolysaccharide ( LPS ) , stimulated mononuclear phagocytes to release IL-6 in a dose-response manner .", "target_text": { "lipoarabinomannan": "protein", "LAM": "protein", "mononuclear phagocytes": "cell_type", "IL-6": "protein" } }, { "input_text": "LAM and LPS were potent inducers of IL-6 gene expression in peripheral blood monocytes .", "target_text": { "LAM": "protein", "IL-6 gene": "DNA", "peripheral blood monocytes": "cell_type" } }, { "input_text": "Both LAM - and LPS -inducible IL-6 promoter activity was localized to a DNA fragment , positions -158 to -49 , by deletion analysis and chloramphenicol acetyltransferase assay .", "target_text": { "LAM": "protein", "IL-6": "protein", "LPS -inducible IL-6 promoter": "DNA", "DNA fragment": "DNA", "-158 to -49": "DNA", "chloramphenicol acetyltransferase": "protein" } }, { "input_text": "Two nuclear factor NF-IL6 ( positions -153 to -145 and -83 to -75 ) and one nuclear factor NF-kappa B ( positions -72 to -63 ) motifs are present within this fragment .", "target_text": { "NF-IL6": "DNA", "nuclear factor NF-IL6": "protein", "-153 to -145": "DNA", "NF-kappa B": "protein", "nuclear factor NF-kappa B ( positions -72 to -63 ) motifs": "DNA" } }, { "input_text": "Site-directed mutagenesis of one or more of these motifs within the IL-6 promoter demonstrated that each has positive regulatory activity and that they could act in a function- and orientation-independent manner .", "target_text": { "IL-6": "protein" } }, { "input_text": "Deletion of all three elements abolished inducibility of IL-6 promoter activity by both LAM and LPS .", "target_text": { "IL-6": "protein", "IL-6 promoter": "DNA", "LAM": "protein" } }, { "input_text": "We conclude that the NF-IL6 and NF-kappa B sites mediate IL-6 induction in response to both LPS and LAM , acting as bacterial or mycobacterial response elements .", "target_text": { "IL-6": "protein", "LAM": "protein" } }, { "input_text": "Regulation of CD14 expression during monocytic differentiation induced with 1 alpha,25-dihydroxyvitamin D3 .", "target_text": { "CD14": "protein" } }, { "input_text": "CD14 , a monocyte/macrophage receptor for the complex of LPS and LPS binding protein , is a differentiation marker for the monocyte/macrophage lineage .", "target_text": { "CD14": "protein", "monocyte/macrophage receptor": "protein", "LPS binding protein": "protein", "monocyte/macrophage lineage": "cell_type" } }, { "input_text": "We have analyzed the regulation of CD14 expression during 1 alpha,25-dihydroxyvitamin D3 ( VitD3 ) -induced monocytic differentiation .", "target_text": { "CD14": "protein" } }, { "input_text": "Using FACS , Northern blotting , and nuclear run-on analyses , we demonstrate that the up-regulation of CD14 expression during monocytic cell maturation is regulated mainly at the level of gene transcription , and that new protein synthesis is required for CD14 induction .", "target_text": { "CD14": "protein" } }, { "input_text": "We have recently cloned the CD14 5' upstream sequence and demonstrated its tissue-specific promoter activity .", "target_text": { "CD14": "protein", "CD14 5' upstream sequence": "DNA", "tissue-specific promoter": "DNA" } }, { "input_text": "Using stable transfection of the monocytoid U937 cell line with a series of deletion mutants of the CD14 5' upstream sequence coupled to a reporter gene construct , we show that bp -128 to -70 is the critical region for the induction of CD14 expression .", "target_text": { "monocytoid U937 cell line": "cell_line", "CD14": "protein", "CD14 5' upstream sequence": "DNA", "bp -128 to -70": "DNA" } }, { "input_text": "This region contains two binding sites for the Sp1 transcription factor .", "target_text": { "binding sites": "DNA", "Sp1 transcription factor": "protein" } }, { "input_text": "A 3-bp mutation at the distal Sp1-binding site not only eliminates Sp1 interaction , but also abolishes most of the VitD3 induction of CD14 expression .", "target_text": { "Sp1-binding site": "DNA", "Sp1": "protein", "CD14": "protein" } }, { "input_text": "Electrophoretic mobility shift analysis does not detect a direct interaction of the CD14 distal Sp1-binding site with the vitamin D3 receptor and its partner , the retinoid X receptor .", "target_text": { "CD14": "protein", "Sp1-binding site": "DNA", "vitamin D3 receptor": "protein", "retinoid X receptor": "protein" } }, { "input_text": "These data demonstrate that VitD3 induces CD14 indirectly through some intermediary factor , and suggest a critical role for Sp1 in this process .", "target_text": { "CD14": "protein", "intermediary factor": "protein", "Sp1": "protein" } }, { "input_text": "DNA-binding and transcriptional regulatory properties of hepatic leukemia factor ( HLF ) and the t(17;19) acute lymphoblastic leukemia chimera E2A- HLF .", "target_text": { "hepatic leukemia factor": "protein", "HLF": "protein", "E2A- HLF": "protein", "acute lymphoblastic leukemia chimera E2A- HLF": "protein" } }, { "input_text": "The t(17;19) translocation in acute lymphoblastic leukemias results in creation of E2A- hepatic leukemia factor ( HLF ) chimeric proteins that contain the DNA-binding and protein dimerization domains of the basic leucine zipper ( bZIP ) protein HLF fused to a portion of E2A proteins with transcriptional activation properties .", "target_text": { "t(17;19)": "DNA", "hepatic leukemia factor": "protein", "E2A- hepatic leukemia factor": "protein", "HLF": "protein", "chimeric proteins": "protein", "DNA-binding and protein dimerization domains": "protein", "basic leucine zipper ( bZIP ) protein": "protein", "E2A proteins": "protein" } }, { "input_text": "An in vitro binding site selection procedure was used to determine DNA sequences preferentially bound by wild-type HLF and chimeric E2A- HLF proteins isolated from various t(17;19)-bearing leukemias .", "target_text": { "HLF": "protein", "wild-type HLF": "protein", "E2A- HLF": "protein", "chimeric E2A- HLF": "protein", "t(17;19)-bearing leukemias": "cell_line" } }, { "input_text": "All were found to selectively bind the consensus sequence 5'-GTTACGTAAT-3' with high affinity .", "target_text": { "consensus sequence": "DNA" } }, { "input_text": "Wild-type and chimeric HLF proteins also bound closely related sites identified previously for bZIP proteins of both the proline - and acidic amino acid-rich ( PAR ) and C/EBP subfamilies ; however , E2A- HLF proteins were significantly less tolerant of certain deviations from the HLF consensus binding site .", "target_text": { "HLF": "protein", "chimeric HLF proteins": "protein", "bZIP proteins": "protein", "proline": "protein", "acidic amino acid-rich": "protein", "PAR": "protein", "C/EBP subfamilies": "protein", "E2A- HLF": "protein", "HLF consensus binding site": "DNA" } }, { "input_text": "These differences were directly attributable to loss of an HLF ancillary DNA-binding domain in all E2A- HLF chimeras and were further exacerbated by a zipper mutation in one isolate .", "target_text": { "HLF": "protein", "HLF ancillary DNA-binding domain": "DNA", "E2A- HLF": "protein", "E2A- HLF chimeras": "protein" } }, { "input_text": "Both wild-type and chimeric HLF proteins displayed transcriptional activator properties in lymphoid and nonlymphoid cells on reporter genes containing HLF or C/EBP consensus binding sites .", "target_text": { "wild-type": "protein", "HLF": "protein", "chimeric HLF proteins": "protein", "transcriptional activator": "protein", "reporter genes": "DNA", "C/EBP": "protein" } }, { "input_text": "But on reporter genes with nonoptimal binding sites , their transcriptional properties diverged and E2A- HLF competitively inhibited activation by wild-type PAR proteins .", "target_text": { "reporter genes": "DNA", "nonoptimal binding sites": "DNA", "HLF": "protein", "E2A- HLF": "protein", "wild-type PAR proteins": "protein" } }, { "input_text": "These findings establish a spectrum of binding site-specific transcriptional properties for E2A- HLF which may preferentially activate expression of select subordinate genes as a homodimer and potentially antagonize expression of others through heteromeric interactions .", "target_text": { "HLF": "protein", "E2A- HLF": "protein" } }, { "input_text": "ZAP-70 tyrosine kinase , CD45 , and T cell receptor involvement in UV- and H2O2- induced T cell signal transduction .", "target_text": { "ZAP-70 tyrosine kinase": "protein", "CD45": "protein", "T cell receptor": "protein" } }, { "input_text": "Several mammalian responses to UV irradiation , including the activation of NF-kappa B , are believed to involve tyrosine phosphorylation .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "UV irradiation and H2O2 treatment of T lymphocytes induce protein tyrosine phosphorylation and Ca2+ signals similar to those observed following biological stimulation .", "target_text": { "T lymphocytes": "cell_type" } }, { "input_text": "We have examined the role of cell surface molecules in these responses .", "target_text": {} }, { "input_text": "Normal T lymphocytes whose surface expression of CD3 was depleted showed impaired UV-induced tyrosine phosphorylation and Ca2+ signals .", "target_text": { "T lymphocytes": "cell_type", "CD3": "protein" } }, { "input_text": "Similarly , Jurkat T cell lines deficient in CD3 or CD45 expression also gave impaired UV responses .", "target_text": { "Jurkat T cell lines": "cell_line" } }, { "input_text": "However , all these cell types still gave strong Ca2+ and tyrosine phosphorylation responses to H2O2 .", "target_text": {} }, { "input_text": "The T cell tyrosine kinase ZAP-70 was found to be highly responsive to UV and H2O2 treatment .", "target_text": { "kinase ZAP-70": "protein" } }, { "input_text": "ZAP-70 responsiveness to UV required expression of both CD3 and CD45 , whereas only CD3 was required for the response to H2O2 .", "target_text": { "ZAP-70": "protein", "CD3": "protein", "CD45": "protein" } }, { "input_text": "UV -induced activation of NF-kappa B was blocked by CD3 depletion , indicating the importance of such cell surface molecules in biological responses to UV .", "target_text": { "NF-kappa B": "protein", "CD3": "protein", "cell surface molecules": "protein" } }, { "input_text": "In nonlymphoid cells , the epidermal growth factor receptor displayed increased tyrosine phosphorylation within seconds of UV irradiation .", "target_text": { "nonlymphoid cells": "cell_type", "epidermal growth factor receptor": "protein" } }, { "input_text": "These results suggest that UV -induced signal transduction is mediated via cell surface receptors that normally respond to biological stimulation , whereas H2O2 is able to partially bypass this requirement .", "target_text": { "cell surface receptors": "protein" } }, { "input_text": "Inhibition of the differentiation of human myeloid cell lines by redox changes induced through glutathione depletion .", "target_text": { "human myeloid cell lines": "cell_line" } }, { "input_text": "We have investigated the effect of redox changes in vivo on the differentiation of two human myeloid cell lines , HL-60 and KG-1 .", "target_text": { "human myeloid cell lines": "cell_line", "HL-60": "cell_line", "KG-1": "cell_line" } }, { "input_text": "The glutathione -depleting agent diethyl maleate ( DEM ) prevented the development of differentiated features in response to phorbol esters , including adherence of the cells to plastic surfaces and repression of the myeloperoxidase and CD34 genes .", "target_text": {} }, { "input_text": "Moreover , DEM abolished phorbol 12-myristate 13-acetate -induced activation of the transcription factors AP-1 and Egr-1 , suggesting that inhibition of differentiation may be due , at least in part , to redox modifications of these proteins .", "target_text": { "transcription factors": "protein", "AP-1": "protein", "Egr-1": "protein", "proteins": "protein" } }, { "input_text": "Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site .", "target_text": { "tissue factor gene": "DNA", "monocytic cells": "cell_type", "c-Rel/p65 heterodimers": "protein", "kappa B-like site": "DNA" } }, { "input_text": "Exposure of monocytic cells to bacterial lipopolysaccharide ( LPS ) activates the NF-kappa B /Rel family of proteins and leads to the rapid induction of inflammatory gene products , including tissue factor ( TF ) .", "target_text": { "monocytic cells": "cell_type", "NF-kappa B": "protein", "NF-kappa B /Rel family": "protein", "inflammatory gene products": "protein", "tissue factor": "protein", "TF": "protein" } }, { "input_text": "TF is the primary cellular initiator of the coagulation protease cascades .", "target_text": { "TF": "protein", "coagulation protease": "protein" } }, { "input_text": "Here we report the characterization of a nuclear complex from human monocytic cells that bound to a kappa B-like site , 5'-CGGAGTTTCC-3' , in the 5'-flanking region of the human TF gene .", "target_text": { "nuclear complex": "protein", "monocytic cells": "cell_type", "kappa B-like site": "DNA", "5'-CGGAGTTTCC-3'": "DNA", "5'-flanking region": "DNA", "TF": "protein", "human TF gene": "DNA" } }, { "input_text": "This nuclear complex was activated by LPS with kinetics that preceded induction of the TF gene .", "target_text": { "nuclear complex": "protein", "TF": "protein", "TF gene": "DNA" } }, { "input_text": "In vitro binding studies demonstrated that the TF site bound translated c- Rel and p65 homodimers but not p50/p65 heterodimers or p50 homodimers .", "target_text": { "TF": "protein", "TF site": "DNA", "Rel": "protein", "p50/p65 heterodimers": "protein", "p50 homodimers": "protein" } }, { "input_text": "Base-pair substitutions in the TF site indicated that the presence of a cytosine at position 1 precluded binding of NF-kappa B .", "target_text": { "TF": "protein", "TF site": "DNA", "position 1": "protein", "NF-kappa B": "protein" } }, { "input_text": "In fact , under low-ionic-strength conditions , the TF complex did not migrate with translated p50/p65 dimers but instead comigrated with c-Rel /p65 dimers .", "target_text": { "TF": "protein", "TF complex": "protein", "p50/p65 dimers": "protein", "c-Rel": "protein", "c-Rel /p65 dimers": "protein" } }, { "input_text": "Antibodies against the NF-kappa B and Rel proteins and UV cross-linking studies revealed the presence of c-Rel and p65 and the absence of p50 in the TF complex and further showed that c-Rel/ p65 heterodimers selectively bound to the TF kappa B-like site .", "target_text": { "NF-kappa B": "protein", "c-Rel": "protein", "p65": "protein", "p50": "protein", "TF": "protein", "TF complex": "protein", "c-Rel/ p65 heterodimers": "protein", "TF kappa B-like site": "DNA" } }, { "input_text": "Functional studies indicated that the TF site conferred LPS inducibility on a heterologous promoter and was transactivated by c-Rel or p65 .", "target_text": { "TF": "protein", "TF site": "DNA", "heterologous promoter": "DNA", "c-Rel": "protein", "p65": "protein" } }, { "input_text": "Taken together , our results demonstrated that binding of c-Rel/ p65 heterodimers to a novel kappa B-like site mediated LPS induction of TF gene expression in monocytic cells .", "target_text": { "p65": "protein", "c-Rel/ p65 heterodimers": "protein", "kappa B-like site": "DNA", "TF": "protein", "monocytic cells": "cell_type" } }, { "input_text": "Inhibition of T cell activation by the extracellular matrix protein tenascin .", "target_text": { "extracellular matrix protein": "protein", "tenascin": "protein" } }, { "input_text": "Tenascin ( TN ) is an extracellular matrix protein that is expressed widely in the fetus and sparingly in the adult , but reappears at high levels in certain areas of tissue insult such as tumor matrices and sites of wound healing .", "target_text": { "Tenascin": "protein", "TN": "protein", "extracellular matrix protein": "protein" } }, { "input_text": "We show here that soluble TN inhibits proliferation of human T cells in response to alpha CD3 Ab co- immobilized with the extracellular matrix protein fibronectin ( FN ) .", "target_text": { "TN": "protein", "human T cells": "cell_type", "CD3": "protein", "alpha CD3 Ab": "protein", "extracellular matrix protein": "protein", "fibronectin": "protein", "FN": "protein" } }, { "input_text": "TN also inhibits proliferation driven by alpha CD3 /IL-2 or by phorbol ester/IL-2 , and it prevents high level induction of IL-2R .", "target_text": { "TN": "protein", "CD3": "protein", "alpha CD3 /IL-2": "protein", "phorbol ester/IL-2 ,": "protein", "IL-2R": "protein" } }, { "input_text": "The presence of TN in culture medium does not detectably alter the pattern of tyrosine phosphorylation resulting from T cell triggering with alpha CD3 , but at later time points prevents the appearance of functional NF-AT1 transcription factor complexes in T cell nuclear extracts .", "target_text": { "TN": "protein", "CD3": "protein", "alpha CD3": "protein", "NF-AT1 transcription factor complexes": "protein", "T cell nuclear extracts": "protein" } }, { "input_text": "These findings are consistent with the postulated role for TN as a natural antagonist to FN action , and suggest that T cell responses occurring at tissue sites in which TN is expressed could be influenced by its presence .", "target_text": { "TN": "protein", "FN": "protein" } }, { "input_text": "Human immunodeficiency virus type 1 Nef protein down-regulates transcription factors NF-kappa B and AP-1 in human T cells in vitro after T-cell receptor stimulation .", "target_text": { "Human immunodeficiency virus type 1 Nef protein": "protein", "transcription factors": "protein", "NF-kappa B": "protein", "AP-1": "protein", "human T cells": "cell_type" } }, { "input_text": "Human immunodeficiency virus type 1 ( HIV-1 ) negative factor ( Nef ) has been shown to down-regulate the transcription factors NF-kappa B and AP-1 in vitro .", "target_text": { "negative factor": "protein", "Nef": "protein", "transcription factors": "protein", "NF-kappa B": "protein", "AP-1": "protein" } }, { "input_text": "To define the mechanism of action of the Nef protein , the signal transduction pathways which may be affected in T cells by constitutive expression of the nef gene were examined .", "target_text": { "Nef": "protein", "T cells": "cell_type" } }, { "input_text": "Stimulation of T cells with tumor necrosis factor , interleukin-1 , or lipopolysaccharide resulted in the recruitment of transcriptional factors to a similar level whether or not the cells expressed the nef gene .", "target_text": { "T cells": "cell_type" } }, { "input_text": "On the other hand , stimulation of T cells by mitogens or antibodies to the T-cell receptor ( TCR ) - CD3 complex resulted in the down-regulation of transcriptional factors NF-kappa B and AP-1 in cells expressing the nef gene compared with cells not expressing the nef gene .", "target_text": { "T cells": "cell_type", "CD3": "protein", "NF-kappa B": "protein", "AP-1": "protein" } }, { "input_text": "Because the Nef protein does not affect the surface expression of the CD3 -TCR complex , we conclude that the Nef protein down-regulates the transcriptional factors NF-kappa B and AP-1 in T cells in vitro through an effect on the TCR-dependent signal transduction pathway .", "target_text": { "Nef": "protein", "CD3": "protein", "NF-kappa B": "protein", "AP-1": "protein", "T cells": "cell_type" } }, { "input_text": "Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene c-fos .", "target_text": { "proto-oncogene c-fos": "DNA" } }, { "input_text": "The transcription factor AP-1 is an important human mediator of the cellular response to serum , growth factors , and phorbol esters such as 12-O-tetradecanoyl-phorbol-13 acetate ( TPA ) .", "target_text": { "transcription factor": "protein", "AP-1": "protein", "growth factors": "protein" } }, { "input_text": "The AP-1 complex consists of distinct protein heterodimers encoded by the proto-oncogene c-fos and c-jun mRNA whose gene expression can be induced by TPA , cyclic AMP and growth factors .", "target_text": { "AP-1": "protein", "protein heterodimers": "protein", "proto-oncogene c-fos": "DNA", "c-jun mRNA": "RNA", "growth factors": "protein" } }, { "input_text": "Recent findings suggest an involvement of reactive oxygen species in the pathway of TPA and protein kinase C leading to expression of c-fos and c-jun mRNA .", "target_text": { "protein kinase C": "protein" } }, { "input_text": "To investigate the role of reactive oxygen species we studied the effects of alpha-lipoic acid and dihydrolipoic acid ( natural thiol antioxidants ) on the expression of c-fos mRNA in human Jurkat T cells .", "target_text": { "c-fos mRNA": "RNA", "human Jurkat T cells": "cell_line" } }, { "input_text": "When cells were preincubated with dihydrolipoic acid ( 0.2 mM ) the expression of c-fos mRNA was suppressed at 30 min after stimulation of TPA ( 0.5 microM ) whereas in the case of preincubation of alpha-lipoic acid ( 0.2 microM ) , the expression was enhanced at 30 min .", "target_text": { "c-fos": "DNA", "c-fos mRNA": "RNA" } }, { "input_text": "These studies support the idea that superoxide anion radical plays a role in the expression of c-fos mRNA .", "target_text": { "c-fos": "DNA", "c-fos mRNA": "RNA" } }, { "input_text": "Appraisal of potential therapeutic index of antioxidants on the basis of their in vitro effects on HIV replication in monocytes and interleukin 2 -induced lymphocyte proliferation .", "target_text": { "monocytes": "cell_type", "interleukin 2": "protein" } }, { "input_text": "Antioxidant molecules have been suggested to be of therapeutic value in the treatment of HIV -infected patients .", "target_text": {} }, { "input_text": "To evaluate this possibility , we examined in vitro the effects of two types of antioxidant molecules in terms of inhibition of HIV replication in monocytes , one of the main reservoirs of HIV , and also in terms of modulation of the immune competence as measured by PBMC proliferation .", "target_text": { "monocytes": "cell_type", "PBMC": "cell_type" } }, { "input_text": "We tested the effects of BHA , a phenolic , lipid-soluble , chain-breaking antioxidant , and NAC , a known glutathione precursor with some direct free-radical scavenging properties as well , on the regulation of HIV -1 expression in latently infected U1 cells and in productively and chronically infected U937 cells .", "target_text": { "U1 cells": "cell_line", "U937 cells": "cell_line" } }, { "input_text": "Both antioxidants inhibited TNF - or PMA- induced NF-kappa B activity in U1 cells , as well as the sustained NF-kappa B activity permanently induced by the virus itself in chronically HIV -infected U937 cells .", "target_text": { "TNF": "protein", "NF-kappa B": "protein", "U1 cells": "cell_line", "U937 cells": "cell_line" } }, { "input_text": "This resulted in only a partial inhibition of TNF - or PMA- induced HIV replication in U1 cells , and no detectable effect on HIV replication in chronically infected U937 cells .", "target_text": { "TNF": "protein", "U1 cells": "cell_line", "U937 cells": "cell_line", "chronically infected U937 cells": "cell_line" } }, { "input_text": "This may be the first limitation to potential antiviral effects of antioxidant therapies .", "target_text": {} }, { "input_text": "Another limitation is that antioxidant concentrations high enough to block NK-kappa B activation were shown to have a suppressive effect on immune functions in vitro , because NAC and BHA blocked IL-2 -induced PBMC proliferation .", "target_text": { "NK-kappa B": "protein", "IL-2": "protein", "IL-2 -induced PBMC": "cell_type" } }, { "input_text": "These data warrant prudence in the design of antioxidant-based therapies aimed at suppressing HIV replication .", "target_text": {} }, { "input_text": "Isolation and characterization of gelatinase granules from human neutrophils .", "target_text": { "human neutrophils": "cell_type" } }, { "input_text": "We recently confirmed the existence of gelatinase granules as a subpopulation of peroxidase-negative granules by double-labeling immunogold electron microscopy on intact cells and by subcellular fractionation .", "target_text": {} }, { "input_text": "Further characterization of gelatinase granules has been hampered by poor separation of specific and gelatinase granules on both two-layer Percoll gradients and sucrose gradients .", "target_text": {} }, { "input_text": "We have developed a three-layer Percoll density gradient that allows separation of the different granules and vesicles from human neutrophils ; in particular , it allows separation of specific and gelatinase granules .", "target_text": { "human neutrophils": "cell_type" } }, { "input_text": "This allows us to characterize these two granule populations with regard to their content of membrane proteins , which become incorporated into the plasma membrane during exocytosis .", "target_text": { "membrane proteins": "protein" } }, { "input_text": "We found that gelatinase granules , defined as peroxidase-negative granules containing gelatinase but lacking lactoferrin , contain 50 % of total cell gelatinase , with the remaining residing in specific granules .", "target_text": { "gelatinase": "protein", "lactoferrin": "protein" } }, { "input_text": "Furthermore , we found that 20 % to 25 % of both the adhesion protein Mac-1 and the NADPH-oxidase component cytochrome b558 is localized in gelatinase granules .", "target_text": { "Mac-1": "protein", "adhesion protein Mac-1": "protein", "NADPH-oxidase component cytochrome": "protein", "b558": "protein", "gelatinase": "protein" } }, { "input_text": "Although no qualitative difference was observed between specific granules and gelatinase granules with respect to cytochrome b558 and Mac-1 , stimulation of the neutrophil with FMLP resulted in a selective mobilization of the least dense peroxidase-negative granules , ie , gelatinase granules , which , in concert with secretory vesicles , furnish the plasma membrane with Mac-1 and cytochrome b558 .", "target_text": { "gelatinase": "protein", "cytochrome b558": "protein", "Mac-1": "protein", "neutrophil": "cell_type", "FMLP": "protein" } }, { "input_text": "This shows that gelatinase granules are functionally important relative to specific granules in mediating early inflammatory responses .", "target_text": { "gelatinase": "protein" } }, { "input_text": "Regulation of interleukin-2 receptor alpha chain expression and nuclear factor.kappa B activation by protein kinase C in T lymphocytes .", "target_text": { "interleukin-2 receptor alpha chain": "protein", "nuclear factor.kappa B": "protein", "protein kinase C": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Autocrine role of tumor necrosis factor alpha .", "target_text": { "tumor necrosis factor alpha": "protein" } }, { "input_text": "The regulation of interleukin-2 receptor alpha chain ( IL-2R alpha ) expression and nuclear factor ( NF ) activation by protein kinase C ( PKC ) in resting T cells , has been studied .", "target_text": { "interleukin-2 receptor alpha chain": "protein", "IL-2R alpha": "protein", "nuclear factor": "protein", "protein kinase C": "protein", "PKC": "protein", "resting T cells": "cell_type" } }, { "input_text": "Treatment of human resting T cells with phorbol esters strongly induced the expression of IL-2R alpha and the activation of NF.kappa B .", "target_text": { "resting T cells": "cell_type", "IL-2R alpha": "protein", "NF.kappa B": "protein" } }, { "input_text": "This activation was due to the translocation of p65 and c-Rel NF.kappa B proteins from cytoplasmic stores to the nucleus , where they bound the kappa B sequence of the IL-2R alpha promoter either as p50.p65 or as p50. c-Rel heterodimers .", "target_text": { "p65": "protein", "c-Rel": "protein", "NF.kappa B": "protein", "kappa B sequence": "DNA", "IL-2R alpha promoter": "DNA", "p50.p65": "protein", "p50. c-Rel": "protein" } }, { "input_text": "Interestingly , all of those events were largely indirect and mediated by endogenously secreted tumor necrosis factor alpha ( TNF alpha ) , as they were strongly inhibited by a neutralizing anti- TNF alpha monoclonal antibody .", "target_text": { "tumor necrosis factor alpha": "protein", "TNF alpha": "protein", "neutralizing anti- TNF alpha monoclonal antibody": "protein" } }, { "input_text": "Furthermore , cyclosporin A , which blocked TNF alpha production induced by PKC , strongly inhibited IL-2R alpha and NF.kappa B activation .", "target_text": { "TNF alpha": "protein", "PKC": "protein", "IL-2R": "protein", "IL-2R alpha": "protein", "NF.kappa B": "protein" } }, { "input_text": "The addition of either TNF alpha or IL-2 partially recovered cyclosporin A -induced IL-2R alpha inhibition , but only TNF alpha completely recovered NF.kappa B activation .", "target_text": { "TNF alpha": "protein", "IL-2": "protein", "IL-2R alpha": "protein", "NF.kappa B": "protein" } }, { "input_text": "Those results indicate that , in resting T cells , PKC activation has only a triggering role , whereas the endogenously secreted TNF alpha plays an essential role in the quantitative control of the expression of IL-2R alpha chain or NF.kappa B activation .", "target_text": { "resting T cells": "cell_type", "PKC": "protein", "TNF alpha": "protein", "IL-2R alpha": "protein", "NF.kappa B": "protein" } }, { "input_text": "Superantigens activate HIV-1 gene expression in monocytic cells .", "target_text": { "Superantigens": "protein", "monocytic cells": "cell_type" } }, { "input_text": "Binding of superantigens to MHC class II molecules results in transduction of biochemical signals leading to cellular activation and gene expression .", "target_text": { "MHC class II molecules": "protein" } }, { "input_text": "We demonstrate that the staphylococcal superantigens toxic shock syndrome toxin-1 ( TSST-1 ) and staphylococcal enterotoxin A ( SEA ) activate HIV-1 -LTR -driven transcription of chloramphenicol acetyl transferase in the human monocytic cell line THP-1 .", "target_text": { "staphylococcal superantigens": "protein", "toxic shock syndrome toxin-1": "protein", "TSST-1": "protein", "staphylococcal enterotoxin A": "protein", "SEA": "protein", "HIV-1 -LTR": "DNA", "chloramphenicol acetyl transferase": "protein", "human monocytic cell line": "cell_line", "THP-1": "cell_line" } }, { "input_text": "Induction of HIV-1 - LTR -driven transcription in THP-1 cells by superantigens was associated with the induction of nuclear factor-kappa B DNA-binding activity .", "target_text": { "LTR": "DNA", "THP-1 cells": "cell_line", "superantigens": "protein", "nuclear factor-kappa B": "protein" } }, { "input_text": "Superantigens also increased viral protein secretion from the granulocyte-macrophage colony-stimulating factor -pretreated chronically infected human monocytic cell line U1 .", "target_text": { "Superantigens": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "granulocyte-macrophage colony-stimulating factor -pretreated chronically infected human monocytic cell line U1": "cell_line" } }, { "input_text": "Induction of HIV-1 gene expression in monocytic cells by superantigens occurred via tumor necrosis factor-alpha -dependent and -independent mechanisms .", "target_text": { "monocytic cells": "cell_type", "superantigens": "protein" } }, { "input_text": "Our results suggest that superantigens and other MHC class II ligands may activate HIV-1 gene expression in monocytes/macrophages .", "target_text": { "superantigens": "protein", "MHC class II ligands": "protein", "monocytes/macrophages": "cell_type" } }, { "input_text": "Mitogen activation of human peripheral T lymphocytes induces the formation of new cyclic AMP response element-binding protein nuclear complexes .", "target_text": { "T lymphocytes": "cell_type", "human peripheral T lymphocytes": "cell_type", "cyclic AMP response element-binding protein nuclear complexes": "protein" } }, { "input_text": "A large body of evidence indicates that experimental agents which raise cellular cAMP levels inhibit T cell growth and division .", "target_text": {} }, { "input_text": "By contrast , many studies have reported that mitogen activation of T cells increases cAMP levels , implying a positive physiological role for cAMP in the activation process .", "target_text": { "mitogen": "protein", "T cells": "cell_type" } }, { "input_text": "In the present study we demonstrate that mitogen activation of human peripheral T lymphocytes induces nuclear factors that form complexes with cyclic AMP response element-binding protein ( CREB ) .", "target_text": { "mitogen": "protein", "T lymphocytes": "cell_type", "human peripheral T lymphocytes": "cell_type", "cyclic AMP response element-binding protein": "protein", "CREB": "protein" } }, { "input_text": "Four complexes are identified by the electrophoretic mobility shift assay , two of which are induced by mitogen activation .", "target_text": { "mitogen": "protein" } }, { "input_text": "All four complexes contain CREB and are bound to the cAMP response element ( CRE ) core sequence ( TGACGTCA ) , as indicated by antibody and oligonucleotide competition experiments .", "target_text": { "CREB": "protein", "cAMP response element": "DNA", "CRE": "DNA", "cAMP response element ( CRE ) core sequence": "DNA" } }, { "input_text": "Binding of the four complexes to CRE is prevented by dephosphorylation of nuclear extracts and is restored by rephosphorylation with cAMP -dependent protein kinase or endogenous kinases .", "target_text": { "CRE": "DNA", "cAMP -dependent protein kinase": "protein", "endogenous kinases": "protein" } }, { "input_text": "Similar complexes are detected in nuclear extracts of Jurkat cells .", "target_text": { "Jurkat cells": "cell_line" } }, { "input_text": "Mitogen induction of the electrophoretic mobility shift assay complexes is not accounted for by protein phosphorylation or by induction of CREB .", "target_text": { "electrophoretic mobility shift assay complexes": "protein", "CREB": "protein" } }, { "input_text": "Rather , the data indicate that mitogen increases the levels of a nuclear factor ( s ) that dimerizes with CREB .", "target_text": { "CREB": "protein" } }, { "input_text": "Induction of new CREB complexes implies a physiological role for cAMP in mitogen activation of T lymphocytes .", "target_text": { "CREB": "protein", "CREB complexes": "protein", "mitogen": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells .", "target_text": { "cultured human endothelial cells": "cell_line" } }, { "input_text": "Antioxidants have been proposed to be anti-atherosclerotic agents ; however , the mechanisms underlying their beneficial effects are poorly understood .", "target_text": {} }, { "input_text": "We have examined the effect of alpha-tocopherol ( alpha-tcp ) on one cellular event in atherosclerotic plaque development , monocyte adhesion to stimulated endothelial cells ( ECs ) .", "target_text": { "stimulated endothelial cells": "cell_type", "ECs": "cell_type" } }, { "input_text": "Human umbilical vein ECs were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion : IL-1 ( 10 ng/ml ) , LPS ( 10 ng/ml ) , thrombin ( 30 U/ml ) , or PMA ( 10 nM ) .", "target_text": { "ECs": "cell_type", "IL-1": "protein", "thrombin": "protein" } }, { "input_text": "Agonist-induced monocytic cell adhesion , but not basal adhesion , was inhibited in a time- and concentration-dependent manner by alpha-tcp .", "target_text": {} }, { "input_text": "The IC50 of alpha-tcp on an IL-1 -induced response was 45 microM .", "target_text": { "IL-1": "protein" } }, { "input_text": "The inhibition correlated with a decrease in steady state levels of E-selectin mRNA and cell surface expression of E-selectin which is consistent with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell adhesion in this system .", "target_text": { "E-selectin mRNA": "RNA", "E-selectin": "protein", "monoclonal antibody": "protein" } }, { "input_text": "Probucol ( 50 microM ) and N-acetylcysteine ( 20 mM ) also inhibited agonist-induced monocytic cell adhesion ; whereas , several other antioxidants had no significant effect .", "target_text": {} }, { "input_text": "Protein kinase C ( PKC ) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of PKC substrates was observed .", "target_text": { "Protein kinase C": "protein", "PKC": "protein" } }, { "input_text": "Activation of the transcription factor NF-kappa B is reported to be necessary but not sufficient for E-selectin expression in EC .", "target_text": { "transcription factor": "protein", "NF-kappa B": "protein", "E-selectin": "protein", "EC": "cell_line" } }, { "input_text": "Electrophoretic mobility shift assays failed to show an alpha-tcp -induced decrease in activation of this transcription factor after cytokine stimulation .", "target_text": { "transcription factor": "protein", "cytokine": "protein" } }, { "input_text": "It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule by inhibiting generation of oxidized LDL -- a putative triggering molecule in the atherosclerotic process .", "target_text": {} }, { "input_text": "Our results point to a novel alternative mechanism of action of alpha-tcp .", "target_text": {} }, { "input_text": "Central nervous system -derived cells express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR -independent transactivation by Tat .", "target_text": { "Central nervous system -derived cells": "cell_type", "TAR": "DNA", "Tat": "protein" } }, { "input_text": "The Tat protein of human immunodeficiency virus type 1 ( HIV-1 ) is a potent activator of long terminal repeat -directed transcription .", "target_text": { "Tat protein": "protein", "long terminal repeat": "DNA" } }, { "input_text": "While in most cell types , activation requires interaction of Tat with the unusual transcription element TAR , astrocytic glial cells support TAR -independent transactivation of HIV-1 transcription by Tat .", "target_text": { "transcription element": "DNA", "TAR": "DNA", "astrocytic glial cells": "cell_type" } }, { "input_text": "This alternative pathway of Tat activation is mediated by the viral enhancer , a kappa B domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B ( NF-kappa B ) present in many cell types , including T lymphocytes .", "target_text": { "Tat": "protein", "viral enhancer": "DNA", "transcription factor": "protein", "NF-kappa B": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Tat transactivation mediated by the kappa B domain is sufficient to allow replication of TAR -deleted mutant HIV-1 in astrocytes .", "target_text": { "Tat": "protein", "kappa B domain": "DNA", "TAR": "DNA", "astrocytes": "cell_type" } }, { "input_text": "The present study demonstrates the existence of kappa B-specific binding factors present in human glial astrocytes that differ from prototypical NF-kappa B .", "target_text": { "kappa B-specific binding factors": "protein", "human glial astrocytes": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 Tat affinity column , while prototypical NF-kappa B from Jurkat T cells is not .", "target_text": { "Tat": "protein", "NF-kappa B": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "In vitro transcription studies demonstrate that astrocyte-derived kappa B-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the kappa B domain .", "target_text": { "astrocyte-derived kappa B-binding factors": "protein", "HIV-1 long terminal repeat": "DNA", "kappa B domain": "DNA" } }, { "input_text": "Moreover , TAR -independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity .", "target_text": { "TAR": "DNA" } }, { "input_text": "The importance of the central nervous system -enriched kappa B transcription factor in the regulation of HIV-1 expression is discussed .", "target_text": { "central nervous system -enriched kappa B": "protein", "transcription factor": "protein" } }, { "input_text": "Human interleukin-13 activates the interleukin-4-dependent transcription factor NF-IL4 sharing a DNA binding motif with an interferon-gamma-induced nuclear binding factor .", "target_text": { "Human interleukin-13": "protein", "transcription factor": "protein", "interleukin-4-dependent transcription factor": "protein", "NF-IL4": "protein", "DNA binding motif": "protein", "interferon-gamma-induced nuclear binding factor": "protein" } }, { "input_text": "The effects of interleukin-13 ( IL-13 ) and interleukin-4 ( IL-4 ) on cellular functions were shown to be quite similar .", "target_text": { "interleukin-13": "protein", "IL-13": "protein", "interleukin-4": "protein", "IL-4": "protein" } }, { "input_text": "We provide evidence that in monocytes as well as in T lymphocytes both IL-4 and IL-13 activate the same recently identified transcription factor NF-IL4 which binds to the specific responsive element IL-4RE .", "target_text": { "T lymphocytes": "cell_type", "IL-4": "protein", "IL-13": "protein", "transcription factor": "protein", "NF-IL4": "protein", "specific responsive element IL-4RE": "DNA" } }, { "input_text": "In addition , we show that a nuclear factor activated by interferon-gamma also interacts with the IL-4RE .", "target_text": { "nuclear factor": "protein", "IL-4RE": "DNA" } }, { "input_text": "It differs from NF-IL4 in the electrophoretic mobility of the complex with DNA , in its DNA-binding specificity and in the proteins interacting with the DNA sequence .", "target_text": { "NF-IL4": "protein", "DNA sequence": "DNA" } }, { "input_text": "Sensitivity against various enzyme inhibitors suggests that components of the signal transduction pathway are shared by all three cytokines .", "target_text": { "cytokines": "protein" } }, { "input_text": "Encephalomyocarditis virus internal ribosomal entry site RNA-protein interactions .", "target_text": {} }, { "input_text": "Translational initiation of encephalomyocarditis virus ( EMCV ) mRNA occurs by ribosomal entry into the 5' nontranslated region of the EMCV mRNA , rather than by ribosomal scanning .", "target_text": { "encephalomyocarditis virus ( EMCV ) mRNA": "RNA", "5' nontranslated region": "DNA", "EMCV mRNA": "RNA" } }, { "input_text": "Internal ribosomal binding requires a cis-acting element termed the internal ribosomal entry site ( IRES ) .", "target_text": { "cis-acting element": "DNA", "internal ribosomal entry site": "DNA", "IRES": "DNA" } }, { "input_text": "IRES elements have been proposed to be involved in the translation of picornavirus mRNAs and some cellular mRNAs .", "target_text": { "IRES": "DNA", "IRES elements": "DNA", "picornavirus mRNAs": "RNA", "cellular mRNAs": "RNA" } }, { "input_text": "Internal ribosome binding likely requires the interaction of trans-acting factors that recognize both the mRNA and the ribosomal complex .", "target_text": { "trans-acting factors": "protein", "mRNA": "RNA", "ribosomal complex": "protein" } }, { "input_text": "Five cellular proteins ( p52 , p57 , p70 , p72 , and p100 ) cross-link the EMCV IRES or fragments of the IRES .", "target_text": { "cellular proteins": "protein", "p52": "protein", "p57": "protein", "p70": "protein", "p72": "protein", "p100": "protein", "IRES": "DNA" } }, { "input_text": "For one of these proteins , p57 , binding to the IRES correlates with translation .", "target_text": { "p57": "protein", "IRES": "DNA" } }, { "input_text": "Recently , p57 was identified to be very similar , if not identical , to polypyrimidine tract-binding protein .", "target_text": { "p57": "protein", "polypyrimidine tract-binding protein": "protein" } }, { "input_text": "On the basis of cross-linking results with 21 different EMCV IRES fragments and cytoplasmic HeLa extract or rabbit reticulocyte lysate as the source of polypeptides , consensus binding sites for p52 , p57 , p70 , and p100 are proposed .", "target_text": { "IRES": "DNA", "EMCV IRES fragments": "DNA", "consensus binding sites": "DNA", "p52": "protein", "p57": "protein", "p70": "protein", "p100": "protein" } }, { "input_text": "It is suggested that each of these proteins recognizes primarily a structural feature of the RNA rather than a specific sequence .", "target_text": { "RNA": "RNA" } }, { "input_text": "A novel heterodimerization partner for thyroid hormone receptor .", "target_text": { "heterodimerization partner": "protein", "thyroid hormone receptor": "protein" } }, { "input_text": "Peroxisome proliferator-activated receptor .", "target_text": { "Peroxisome proliferator-activated receptor": "protein" } }, { "input_text": "Retinoid-like receptors play a central role in hormonal responses by forming heterodimers with other nuclear hormone receptors .", "target_text": { "Retinoid-like receptors": "protein", "heterodimers": "protein", "nuclear hormone receptors": "protein" } }, { "input_text": "In this study we have identified the peroxisome proliferator-activated receptor ( PPAR ) as a new thyroid hormone receptor ( THR ) auxiliary nuclear protein , heterodimerizing with THR in solution .", "target_text": { "peroxisome proliferator-activated receptor": "protein", "PPAR": "protein", "thyroid hormone receptor": "protein", "THR": "protein", "thyroid hormone receptor ( THR ) auxiliary nuclear protein": "protein" } }, { "input_text": "Although these heterodimers do not recognize a classical thyroid hormone response element ( TRE ) characterized by direct repeat separated by four nucleotides ( DR+4 ) , PPAR behaves as a dominant negative regulator of thyroid hormone ( TH ) action .", "target_text": { "heterodimers": "protein", "thyroid hormone response element": "DNA", "TRE": "DNA", "direct repeat": "DNA", "DR+4": "DNA", "PPAR": "protein" } }, { "input_text": "However , a TH -dependent positive effect is elicited by selective interaction of the THR beta- PPAR but not the THR alpha- PPAR heterodimer with a novel TRE ( DR+2 ) .", "target_text": { "THR": "protein", "PPAR": "protein", "THR beta- PPAR": "protein", "THR alpha- PPAR heterodimer": "protein", "TRE": "DNA", "DR+2": "DNA" } }, { "input_text": "The critical region of THR beta was mapped to 3 amino acids in the distal box of the DNA binding domain .", "target_text": { "THR": "protein", "distal box": "protein", "DNA binding domain": "protein" } }, { "input_text": "Hence , PPAR can positively or negatively influence TH action depending on TRE structure and THR isotype .", "target_text": { "PPAR": "protein", "TRE": "DNA", "THR": "protein", "THR isotype": "protein" } }, { "input_text": "Comparison of retinoic acid and phorbol myristate acetate as inducers of monocytic differentiation .", "target_text": {} }, { "input_text": "Several human myeloid leukemia cell lines growing in vitro can be induced to differentiate to more mature monocyte/macrophage-like cells by treatment with protein kinase C -activating phorbol esters , such as PMA .", "target_text": { "human myeloid leukemia cell lines": "cell_line", "monocyte/macrophage-like cells": "cell_type", "protein kinase C": "protein" } }, { "input_text": "In addition to PMA , cells of the THP-1 myeloid leukemia cell line acquire macrophage-like characteristics after treatment with all-trans retinoic acid ( RA ) .", "target_text": { "THP-1 myeloid leukemia cell line": "cell_line" } }, { "input_text": "To analyze the signal transduction mechanisms induced by RA , we first compared the effects of PMA and RA on the expression of genes which are known to be regulated during monocytic differentiation .", "target_text": {} }, { "input_text": "Both RA and PMA effectively down-regulated c-myc expression , while c-myb expression decreased only after PMA treatment .", "target_text": { "c-myc": "DNA", "c-myb": "DNA" } }, { "input_text": "Expression of the beta 2-integrin genes , CD11a and CD11b , was clearly increased after both of these treatments .", "target_text": { "beta 2-integrin genes": "DNA", "CD11a": "DNA", "CD11b": "DNA" } }, { "input_text": "Their effects on the src-family tyrosine kinase genes were different : hck expression was similarly induced by these agents but lyn expression was stronger and more rapid after RA treatment .", "target_text": { "src-family tyrosine kinase genes": "DNA", "hck": "DNA" } }, { "input_text": "RA also enhanced lyn mRNA production rapidly in HL-60 , indicating that the activation of lyn gene expression is common in monocytic and granulocytic maturation of myeloid leukemia cells .", "target_text": { "lyn mRNA": "RNA", "HL-60": "cell_line", "lyn gene": "DNA", "myeloid leukemia cells": "cell_type" } }, { "input_text": "To examine whether the AP-1 enhancer activity is involved in RA -induced monocytic differentiation , THP-1 cells were transiently transfected with a chloramphenicol acetyl transferase ( CAT ) -reporter gene containing 5 copies of the AP-1 binding sites .", "target_text": { "AP-1 enhancer": "DNA", "THP-1 cells": "cell_line", "chloramphenicol acetyl transferase": "protein", "CAT": "protein", "chloramphenicol acetyl transferase ( CAT ) -reporter gene": "DNA", "AP-1": "protein", "AP-1 binding sites": "DNA" } }, { "input_text": "In contrast to PMA , RA did not induce any CAT activity in these cells , thus suggesting that the RA -induced changes in the expression of those genes described above were not dependent on the AP-1 enhancer activity .", "target_text": { "CAT": "protein", "AP-1": "protein", "AP-1 enhancer": "DNA" } }, { "input_text": "An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement .", "target_text": { "v-abl protein tyrosine kinase": "protein", "immunoglobulin light-chain gene": "DNA" } }, { "input_text": "Lymphoid cells transformed by Abelson murine leukemia virus have provided one of the classic models for study of early B-cell development and immunoglobulin rearrangement .", "target_text": { "Lymphoid cells": "cell_type", "immunoglobulin": "protein" } }, { "input_text": "Most of these cells have rearranged their heavy-chain locus but not their light chain genes , suggesting that an active v-abl protein interferes with this differentiation step .", "target_text": { "heavy-chain locus": "DNA", "light chain genes": "DNA", "v-abl protein": "protein" } }, { "input_text": "To test this hypothesis , light-chain gene structure was examined in pre-B cells transformed by temperature-sensitive mutants of the Abelson virus and in derivatives that survive at the nonpermissive temperature because they express a human BCL-2 gene .", "target_text": { "light-chain gene structure": "DNA", "pre-B cells": "cell_line", "human BCL-2 gene": "DNA" } }, { "input_text": "Our studies reveal that inactivation of the v-abl protein tyrosine kinase triggers high-frequency rearrangement of kappa and lambda light-chain genes .", "target_text": { "v-abl protein": "protein", "v-abl protein tyrosine kinase": "protein" } }, { "input_text": "These events are accompanied by marked increases in the expression of RAG-1 and RAG-2 RNAs .", "target_text": { "RAG-1": "RNA", "RAG-2 RNAs": "RNA", "RAG-1 and RAG-2 RNAs": "RNA" } }, { "input_text": "These increases occur in the absence of protein synthesis but are dependent on inactivation of the v-abl protein tyrosine kinase .", "target_text": { "v-abl protein": "protein", "v-abl protein tyrosine kinase": "protein" } }, { "input_text": "As documented in the accompanying paper ( Klug et al. , this issue ) , an active v-abl protein also suppresses the activity of NF-kappa B /rel and expression controlled by the kappa intron enhancer .", "target_text": { "v-abl protein": "protein", "NF-kappa B": "protein", "NF-kappa B /rel": "protein", "kappa intron enhancer": "DNA" } }, { "input_text": "Together these data demonstrate that the v-abl protein specifically interferes with light-chain gene rearrangement by suppressing at least two pathways essential for this stage of B-cell differentiation and suggest that tyrosine phosphorylation is important in regulating RAG gene expression .", "target_text": { "v-abl protein": "protein", "light-chain gene": "DNA", "B-cell": "cell_type", "RAG gene": "DNA" } }, { "input_text": "Calcium signalling in T cells stimulated by a cyclophilin B-binding protein .", "target_text": { "T cells": "cell_type", "cyclophilin B-binding protein": "protein" } }, { "input_text": "The immunosuppressant drug cyclosporin A blocks a calcium -dependent signal from the T-cell receptor ( TCR ) that normally leads to T-cell activation .", "target_text": { "T-cell receptor": "protein", "TCR": "protein" } }, { "input_text": "When bound to cyclophilin , cyclosporin A binds and inactivates the key signalling intermediate calcineurin .", "target_text": { "cyclophilin": "protein", "calcineurin": "protein" } }, { "input_text": "To identify potential cellular homologues of cyclosporin A that might regulate calcium signalling , we have cloned human genes encoding cyclophilin B-binding-proteins using the yeast two-hybrid system .", "target_text": { "cyclophilin": "protein", "cyclophilin B-binding-proteins": "protein" } }, { "input_text": "One gene product , when overexpressed in Jurkat T cells , specifically induced transcription from the interleukin-2 enhancer , by activating the T-cell-specific transcription factors NF-AT and NF-IL2A .", "target_text": { "Jurkat T cells": "cell_line", "interleukin-2 enhancer": "DNA", "T-cell-specific transcription factors": "protein", "NF-AT": "protein", "NF-IL2A": "protein" } }, { "input_text": "This protein , termed calcium -signal modulating cyclophilin ligand ( CAML ) , acts downstream of the TCR and upstream of calcineurin by causing an influx of calcium .", "target_text": { "cyclophilin": "protein", "calcium -signal modulating cyclophilin ligand": "protein", "CAML": "protein", "TCR": "protein", "calcineurin": "protein" } }, { "input_text": "CAML appears to be a new participant in the calcium -signal transduction pathway , implicating cyclophilin B in calcium signalling , even in the absence of cyclosporin .", "target_text": { "CAML": "protein", "cyclophilin": "protein", "cyclophilin B": "protein" } }, { "input_text": "Expression and genomic configuration of GM-CSF , IL-3 , M-CSF receptor ( C-FMS ) , early growth response gene-1 ( EGR-1 ) and M-CSF genes in primary myelodysplastic syndromes .", "target_text": { "GM-CSF": "protein", "IL-3": "protein", "M-CSF receptor": "protein", "C-FMS": "protein", "early growth response gene-1": "DNA", "EGR-1": "DNA", "M-CSF genes": "DNA" } }, { "input_text": "Peripheral blood mononuclear cells from seventeen patients with primary myelodysplastic syndromes ( MDS ) in advanced stage were enriched for blasts and tested for ( 1 ) karyotype , ( 2 ) genomic configuration and ( 3 ) expression of IL-3 , GM-CSF , FMS and EGR-1 genes which are all located on the long arm of chromosome 5 .", "target_text": { "blasts": "cell_type", "chromosome 5": "DNA", "long arm of chromosome 5": "DNA" } }, { "input_text": "The expression of the M-CSF gene , that has been recently reassigned to the short arm of chromosome 1 ( lp ) , was also investigated .", "target_text": { "M-CSF gene": "DNA", "chromosome 1": "DNA", "short arm of chromosome 1": "DNA", "lp": "DNA" } }, { "input_text": "Aims of the study were to ( 1 ) assess the potential role of the expression of these genes in the maintenance and expansion of the neoplastic clones and ( 2 ) search for constitutional losses or rearrangements of one allele followed by a deletion of the second allele of the same genes in the leukemic cells .", "target_text": { "neoplastic clones": "cell_line", "allele": "DNA", "leukemic cells": "cell_type" } }, { "input_text": "The latter issue was investigated by comparing , in 8 cases , constitutive DNA from skin fibroblasts with leukemic DNA .", "target_text": { "constitutive DNA": "DNA", "skin fibroblasts": "cell_type", "leukemic DNA": "DNA" } }, { "input_text": "Eleven of the 17 patients had abnormal karyotypes .", "target_text": {} }, { "input_text": "The M-CSF gene was expressed in 6 cases and the FMS and the EGR-1 genes were expressed in 2 of the latter cases .", "target_text": { "M-CSF gene": "DNA", "FMS": "DNA", "EGR-1": "DNA", "EGR-1 genes": "DNA" } }, { "input_text": "An autocrine mechanism of growth could be hypothesized only for the 2 patients whose cells expressed both the M-CSF and FMS genes .", "target_text": {} }, { "input_text": "No germline changes or rearrangements were observed in any of the genes studied .", "target_text": {} }, { "input_text": "Thus , deregulation of genes encoding for certain hemopoietic growth factors or receptors does not seem to represent a major mechanism of MDS progression .", "target_text": { "hemopoietic growth factors": "protein" } }, { "input_text": "A novel human homeobox gene distantly related to proboscipedia is expressed in lymphoid and pancreatic tissues .", "target_text": { "human homeobox gene": "DNA", "proboscipedia": "DNA" } }, { "input_text": "A novel human homeobox gene , HB9 , was isolated from a cDNA library prepared from in vitro stimulated human tonsil B lymphocytes and from a human genomic library .", "target_text": { "human homeobox gene": "DNA", "HB9": "DNA", "cDNA library": "DNA", "vitro stimulated human tonsil B lymphocytes": "cell_type", "human genomic library": "DNA" } }, { "input_text": "The HB9 gene is composed of 3 exons spread over 6 kilobases of DNA .", "target_text": { "HB9": "DNA", "HB9 gene": "DNA", "exons": "DNA" } }, { "input_text": "An open reading frame of 1206 nucleotides is in frame with a diverged homeodomain .", "target_text": { "open reading frame": "DNA", "diverged homeodomain": "DNA" } }, { "input_text": "The predicted HB9 protein has a molecular mass of 41 kilodaltons and is enriched for alanine , glycine , and leucine .", "target_text": { "HB9": "DNA", "HB9 protein": "protein" } }, { "input_text": "The HB9 homeodomain is most similar to that of the Drosophila melanogaster homeobox gene proboscipedia .", "target_text": { "HB9": "DNA", "HB9 homeodomain": "DNA", "Drosophila melanogaster homeobox gene": "DNA", "proboscipedia": "DNA" } }, { "input_text": "Northern blot analysis of poly(A) RNA purified from the human B cell line RPMI 8226 and from activated T cells revealed a major mRNA transcript of 2.2 kilobases .", "target_text": { "poly(A) RNA": "RNA", "human B cell line RPMI 8226": "cell_line", "activated T cells": "cell_type", "major mRNA transcript": "RNA" } }, { "input_text": "Similar analysis of poly(A) RNA from a variety of adult tissues demonstrated HB9 transcripts in pancreas , small intestine , and colon .", "target_text": { "poly(A) RNA": "RNA", "HB9": "DNA" } }, { "input_text": "Reverse transcriptase-polymerase chain reaction was used to examine HB9 RNA transcripts in hematopoietic cell lines .", "target_text": { "HB9": "DNA", "HB9 RNA transcripts": "RNA", "hematopoietic cell lines": "cell_line" } }, { "input_text": "HB9 RNA transcripts were most prevalent in several human B cell lines and K562 cells .", "target_text": { "HB9": "DNA", "HB9 RNA transcripts": "RNA", "human B cell lines": "cell_line", "K562 cells": "cell_line" } }, { "input_text": "In addition , transcripts were detected in RNA prepared from tonsil B cells and in situ hybridization studies localized them in the germinal center region of adult tonsil .", "target_text": { "tonsil B cells": "cell_type" } }, { "input_text": "These findings suggest the involvement of HB9 in regulating gene transcription in lymphoid and pancreatic tissues .", "target_text": { "HB9": "DNA" } }, { "input_text": "Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells .", "target_text": { "Human immunodeficiency virus type 1 Tat": "protein", "interleukin-2": "protein", "activated T cells": "cell_type" } }, { "input_text": "Dysregulation of cytokines secreted by T cells may play an important role in the pathogenesis of AIDS .", "target_text": { "cytokines": "protein", "T cells": "cell_type" } }, { "input_text": "To investigate the effects of human immunodeficiency virus type 1 ( HIV-1 ) Tat on interleukin-2 ( IL-2 ) expression , we used IL-2 promoter -chloramphenicol acetyltransferase constructs and IL-2 -secreting Jurkat T cells as a model system .", "target_text": { "human immunodeficiency virus type 1 ( HIV-1 ) Tat": "protein", "interleukin-2": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "-chloramphenicol acetyltransferase": "protein", "IL-2 promoter -chloramphenicol acetyltransferase constructs": "DNA", "Jurkat T cells": "cell_line", "IL-2 -secreting Jurkat T cells": "cell_line" } }, { "input_text": "Transient expression of HIV-1 Tat induced a five- to eightfold increase in IL-2 promoter activity in Jurkat T cells stimulated with phytohemagglutinin and phorbol myristate acetate .", "target_text": { "HIV-1 Tat": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "Jurkat T cells": "cell_line", "phytohemagglutinin": "protein" } }, { "input_text": "IL-2 secretion was increased more than twofold in both Jurkat T cells and primary T cells stimulated by extracellular HIV-1 Tat protein .", "target_text": { "IL-2": "protein", "Jurkat T cells": "cell_line", "primary T cells": "cell_line", "HIV-1 Tat": "protein", "extracellular HIV-1 Tat protein": "protein" } }, { "input_text": "Analysis of mRNA suggested that Tat exerts its effect on IL-2 primarily at the transcriptional level .", "target_text": { "mRNA": "RNA", "IL-2": "protein" } }, { "input_text": "The NF-kappa B site at positions -206 to -195 of the IL-2 promoter was required but not sufficient for the Tat effect .", "target_text": { "NF-kappa B site": "DNA", "-206 to -195": "DNA", "IL-2": "protein", "IL-2 promoter": "DNA", "Tat": "protein" } }, { "input_text": "The Tat -mediated increase in IL-2 promoter activity could selectively be blocked by antisense tat or - unlike the analogous effect of human T-cell lymphotropic virus type 1 Tax - by cyclosporin A .", "target_text": { "Tat": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "human T-cell lymphotropic virus type 1 Tax": "protein" } }, { "input_text": "The observed increase in IL-2 levels might facilitate virus spread from or to T cells .", "target_text": { "IL-2": "protein", "T cells": "cell_type" } }, { "input_text": "Furthermore , it might contribute to the hypergammaglobulinemia or , together with other cytokines found to be dysregulated , the T-helper cell dysfunctions observed in AIDS patients .", "target_text": { "cytokines": "protein" } }, { "input_text": "Activation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation .", "target_text": { "nuclear factor kappa B": "protein", "human lymphoblastoid cells": "cell_type" } }, { "input_text": "Nuclear factor kappa B ( NF-kappa B ) is a pleiotropic transcription factor which is involved in the transcriptional regulation of several specific genes .", "target_text": { "Nuclear factor kappa B": "protein", "NF-kappa B": "protein", "pleiotropic transcription factor": "protein" } }, { "input_text": "Recent reports demonstrated that ionizing radiation in the dose range of 2-50 Gy results in expression of NF-kappa B in human KG-1 myeloid leukemia cells and human B-lymphocyte precursor cells ; the precise mechanism involved and the significance are not yet known .", "target_text": { "NF-kappa B": "protein", "human KG-1 myeloid leukemia cells": "cell_line", "human B-lymphocyte precursor cells": "cell_type" } }, { "input_text": "The present report demonstrates that even lower doses of ionizing radiation , 0.25-2.0 Gy , are capable of inducing expression of NF-kappa B in EBV-transformed 244B human lymphoblastoid cells .", "target_text": { "NF-kappa B": "protein", "human lymphoblastoid cells": "cell_type", "EBV-transformed 244B human lymphoblastoid cells": "cell_line" } }, { "input_text": "These results are in a dose range where the viability of the cells remains very high .", "target_text": {} }, { "input_text": "After exposure to 137Cs gamma rays at a dose rate of 1.17 Gy/min , a maximum in expression of NF-kappa B was seen at 8 h after a 0.5-Gy exposure .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Time-course studies revealed a biphasic time-dependent expression after 0.5- , 1- and 2-Gy exposures .", "target_text": {} }, { "input_text": "However , for each time examined , the expression of NF-kappa B was maximum after the 0.5-Gy exposure .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "The expression of the p50 and p65 NF-kappa B subunits was also shown to be regulated differentially after exposures to 1.0 and 2.0 Gy .", "target_text": {} }, { "input_text": "Alternative splicing of RNA transcripts encoded by the murine p105 NF-kappa B gene generates I kappa B gamma isoforms with different inhibitory activities .", "target_text": { "RNA transcripts": "RNA", "murine p105 NF-kappa B gene": "DNA", "I kappa B gamma isoforms": "protein" } }, { "input_text": "The gene encoding the 105-kDa protein ( p105 ) precursor of the p50 subunit of transcription factor NF-kappa B also encodes a p70 I kappa B protein , I kappa B gamma , which is identical to the C-terminal 607 amino acids of p105 .", "target_text": { "105-kDa protein": "protein", "p105": "protein", "105-kDa protein ( p105 ) precursor": "protein", "p50": "protein", "NF-kappa B": "protein", "p70 I kappa B protein": "protein", "I kappa B gamma": "protein", "C-terminal 607 amino acids": "protein" } }, { "input_text": "Here we show that alternative RNA splicing generates I kappa B gamma isoforms with properties different from those of p70 .", "target_text": { "I kappa B gamma": "protein", "I kappa B gamma isoforms": "protein", "p70": "protein" } }, { "input_text": "One 63-kDa isoform , termed I kappa B gamma-1 , which lacks 59 amino acids C-terminal to ankyrin repeat 7 , has a novel 35-amino acid C terminus encoded by an alternative reading frame of the p105 gene .", "target_text": { "63-kDa isoform": "protein", "I kappa B gamma-1": "protein", "ankyrin repeat 7": "protein", "35-amino acid C terminus": "protein", "alternative reading frame": "DNA", "p105": "protein", "p105 gene": "DNA" } }, { "input_text": "A 55-kDa isoform , I kappa B gamma-2 , lacks the 190 C-terminal amino acids of p70 I kappa B gamma .", "target_text": { "55-kDa isoform": "protein", "I kappa B gamma-2": "protein", "190 C-terminal amino acids": "protein", "p70": "protein", "I kappa B gamma": "protein" } }, { "input_text": "In contrast to p70 I kappa B gamma , which is a cytoplasmic protein , I kappa B gamma-1 is found in both the cytoplasm and nucleus , whereas I kappa B gamma-2 is predominantly nuclear .", "target_text": { "p70": "protein", "I kappa B gamma": "protein", "cytoplasmic protein": "protein", "I kappa B gamma-1": "protein", "I kappa B gamma-2": "protein" } }, { "input_text": "The I kappa B gamma isoforms also display differences in specificity and affinity for Rel/ NF-kappa B proteins .", "target_text": { "I kappa B gamma": "protein", "I kappa B gamma isoforms": "protein", "NF-kappa B": "protein", "Rel/ NF-kappa B proteins": "protein" } }, { "input_text": "While p70 I kappa B gamma inhibits p50- , p65- , and c-Rel- mediated transactivation and/or DNA binding , both I kappa B gamma-1 and I kappa B gamma-2 are specific for p50 and have different affinities for this subunit .", "target_text": { "p70": "protein", "I kappa B gamma": "protein", "I kappa B gamma-1": "protein", "I kappa B gamma-2": "protein", "p50": "protein" } }, { "input_text": "The absence in I kappa B gamma-1 and I kappa B gamma-2 of a protein kinase A site whose phosphorylation modulates p70 I kappa B gamma inhibitory activity suggests that alternative RNA splicing may be used to generate I kappa B gamma isoforms that respond differently to intracellular signals .", "target_text": { "I kappa B gamma-1": "protein", "I kappa B gamma-2": "protein", "protein kinase A site": "DNA", "p70": "protein", "I kappa B gamma": "protein", "I kappa B gamma isoforms": "protein" } }, { "input_text": "Structure and expression of the human GATA3 gene .", "target_text": { "human GATA3 gene": "DNA" } }, { "input_text": "GATA3 , a member of the GATA family that is abundantly expressed in the T-lymphocyte lineage , is thought to participate in T-cell receptor gene activation through binding to enhancers .", "target_text": { "GATA3": "protein", "GATA family": "protein", "T-lymphocyte lineage": "cell_type", "T-cell receptor": "protein", "enhancers": "DNA" } }, { "input_text": "To understand GATA3 gene regulation , we cloned the human gene and the 5' end of the mouse GATA3 gene .", "target_text": { "GATA3": "protein", "GATA3 gene": "DNA", "human gene": "DNA", "5' end": "DNA", "mouse GATA3 gene": "DNA" } }, { "input_text": "We show that the human GATA3 gene contains six exons distributed over 17 kb of DNA .", "target_text": { "GATA3": "protein", "human GATA3 gene": "DNA", "exons": "DNA" } }, { "input_text": "The two human GATA3 zinc fingers are encoded by two separate exons highly conserved with those of GATA1 , but no other structural homologies between these two genes can be found .", "target_text": { "GATA3": "protein", "human GATA3 zinc fingers": "protein", "exons": "DNA", "GATA1": "protein" } }, { "input_text": "The human and mouse GATA3 transcription units start at a major initiation site .", "target_text": { "major initiation site": "DNA" } }, { "input_text": "The promoter sequence analysis of these two genes revealed that they are embedded within a CpG island and share structural features often found in the promoters of housekeeping genes .", "target_text": { "CpG island": "DNA", "promoters": "DNA", "housekeeping genes": "DNA" } }, { "input_text": "Finally , we show that a DNA fragment containing the human GATA3 transcription unit , 3 kb upstream from the initiation site and 4 kb downstream from the polyadenylation site , displays T-cell specificity .", "target_text": { "DNA fragment": "DNA", "GATA3": "protein", "human GATA3 transcription unit": "DNA", "3 kb upstream": "DNA", "initiation site": "DNA", "4 kb downstream": "DNA", "polyadenylation site": "DNA" } }, { "input_text": "Characterization of the human gene encoding LBR , an integral protein of the nuclear envelope inner membrane .", "target_text": { "human gene": "DNA", "LBR": "protein", "integral protein": "protein" } }, { "input_text": "We have characterized the human gene encoding LBR , an integral protein of the nuclear envelope inner membrane .", "target_text": { "human gene": "DNA", "LBR": "protein", "integral protein": "protein" } }, { "input_text": "Restriction mapping shows that the transcription unit spans approximately 35 kilobases .", "target_text": { "transcription unit": "DNA" } }, { "input_text": "A transcription start site is located approximately 4 kilobases 5' to the translation initiation codon , and an RNA splice of 3863 bases occurs in the 5'-untranslated region to generate mature HeLa cell mRNA .", "target_text": { "translation initiation codon": "DNA", "5'-untranslated region": "DNA", "HeLa cell": "cell_line", "mature HeLa cell mRNA": "RNA" } }, { "input_text": "5' to the identified transcription start site are two CCAAT sequences and potential recognition sites for several transcription factors including Sp1 , AP-1 , AP-2 , and NF-kB .", "target_text": { "transcription start site": "DNA", "CCAAT sequences": "DNA", "potential recognition sites": "DNA", "transcription factors": "protein", "Sp1": "protein", "AP-1": "protein", "AP-2": "protein", "NF-kB": "protein" } }, { "input_text": "There are 13 protein coding exons in the LBR gene .", "target_text": { "exons": "DNA", "LBR": "protein", "LBR gene": "DNA" } }, { "input_text": "LBR 's nucleoplasmic domain is encoded by exons 1-4 , and its hydrophobic domain , with eight putative transmembrane segments , is encoded by exons 5-13 .", "target_text": { "LBR": "protein", "nucleoplasmic domain": "protein", "exons": "DNA", "exons 1-4": "DNA", "hydrophobic domain": "protein", "transmembrane segments": "protein", "exons 5-13": "DNA" } }, { "input_text": "The hydrophobic domain is homologous to three yeast polypeptides , suggesting that this higher eukaryotic gene could have evolved from recombination between a gene that encoded a soluble nuclear protein and a membrane protein gene similar to those in yeast .", "target_text": { "hydrophobic domain": "protein", "higher eukaryotic gene": "DNA", "soluble nuclear protein": "protein", "membrane protein": "protein", "membrane protein gene": "DNA" } }, { "input_text": "These results are the first to demonstrate the structural organization of a vertebrate gene encoding an integral membrane protein of the nuclear envelope that may be a member of a family of polypeptides conserved in evolution .", "target_text": { "vertebrate gene": "DNA", "membrane protein": "protein", "integral membrane protein": "protein" } }, { "input_text": "Retinoic acid-induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid receptor-alpha .", "target_text": { "CD38 antigen": "protein", "myeloid cells": "cell_type", "retinoic acid receptor-alpha": "protein" } }, { "input_text": "CD38 is a leukocyte differentiation antigen that has been thought to be a phenotypic marker of different subpopulations of T- and B- lymphocytes .", "target_text": { "CD38": "protein", "leukocyte differentiation antigen": "protein" } }, { "input_text": "In myeloid cells , CD38 is expressed during early stages of differentiation .", "target_text": { "myeloid cells": "cell_type", "CD38": "protein" } }, { "input_text": "Virtually no information is available on regulation and functions of CD38 .", "target_text": { "CD38": "protein" } }, { "input_text": "Recently we reported that all-trans-retinoic acid ( ATRA ) is a potent and highly specific inducer of CD38 expression in human promyelocytic leukemia cells .", "target_text": { "CD38": "protein", "human promyelocytic leukemia cells": "cell_type" } }, { "input_text": "Here we report that ATRA -induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid-alpha receptor ( RAR alpha ) .", "target_text": { "CD38": "protein", "CD38 antigen": "protein", "myeloid cells": "cell_type", "retinoic acid-alpha receptor": "protein", "RAR alpha": "protein" } }, { "input_text": "ATRA failed to induce CD38 expression in a mutant subclone of the HL-60 myeloid leukemia cell line ( designated HL-60R ) that is relatively resistant to ATRA -induced granulocytic differentiation .", "target_text": { "CD38": "protein", "mutant subclone": "cell_line", "HL-60 myeloid leukemia cell line": "cell_line", "HL-60R": "cell_line" } }, { "input_text": "Retroviral vector-mediated transduction of RA receptor ( RAR alpha ) into this HL-60R subclone completely restored the sensitivity of these cells to ATRA in terms of their ability to express CD38 .", "target_text": { "RA receptor": "protein", "RAR alpha": "protein", "HL-60R subclone": "cell_line", "CD38": "protein" } }, { "input_text": "In contrast , CD38 expression was not inducible by ATRA in HL-60R cells , transfected with a functional RAR beta , RAR gamma , or RXR alpha receptor .", "target_text": { "CD38": "protein", "HL-60R cells": "cell_line", "RAR beta": "protein", "RAR gamma": "protein", "RXR alpha receptor": "protein" } }, { "input_text": "Induction of CD38 in acute promyelocytic and acute myeloblastic leukemia cells was independent of ATRA -induced cytodifferentiation .", "target_text": { "CD38": "protein" } }, { "input_text": "Following culture with ATRA , increased CD38 protein levels were also observed in normal CD34+ bone marrow cells , but not on normal circulating granulocytes .", "target_text": { "CD38": "protein", "normal CD34+ bone marrow cells": "cell_type", "normal circulating granulocytes": "cell_type" } }, { "input_text": "From these results , we conclude that CD38 is ATRA inducible in myeloid leukemia cells and normal CD34+ bone marrow cells .", "target_text": { "CD38": "protein", "myeloid leukemia cells": "cell_type", "normal CD34+ bone marrow cells": "cell_type" } }, { "input_text": "This effect is independent of differentiation and is mediated by RAR alpha in HL-60 cells , suggesting a similar role for RAR alpha in CD38 expression in other hematopoietic cells .", "target_text": { "RAR alpha": "protein", "HL-60 cells": "cell_type", "CD38": "protein", "hematopoietic cells": "cell_type" } }, { "input_text": "Some antioxidants inhibit , in a co-ordinate fashion , the production of tumor necrosis factor-alpha , IL-beta , and IL-6 by human peripheral blood mononuclear cells .", "target_text": { "tumor necrosis factor-alpha": "protein", "IL-beta": "protein", "IL-6": "protein", "human peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Some antioxidants , including butylated hydroxyanisole ( BHA ) , tetrahydropapaveroline ( THP ) , nordihydroguiauretic acid , and 10,11-dihydroxyaporphine ( DHA ) , were found to be potent inhibitors of the production of tumor necrosis factor ( TNF ) -alpha , IL-1 beta , and IL-6 by human peripheral blood mononuclear cells ( PBMC ) stimulated by lipopolysaccharide ( LPS ) ( IC50s in the low micromolar range ) .", "target_text": { "tumor necrosis factor ( TNF ) -alpha": "protein", "IL-1 beta": "protein", "IL-6": "protein", "human peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "Inhibition of cytokine production was gene selective and not due to general effects on protein synthesis .", "target_text": { "cytokine": "protein" } }, { "input_text": "Inhibition of cytokine production by PBMC was observed also when other inducers were used ( staphylococci , silica , zymosan ) .", "target_text": { "cytokine": "protein", "PBMC": "cell_type" } }, { "input_text": "Much higher concentrations of other antioxidants -- including ascorbic acid , trolox , alpha-tocopherol , butylated hydroxytoluene , and the 5-lipoxygenase inhibitor zileuton -- did not affect the production of these cytokines .", "target_text": { "cytokines": "protein" } }, { "input_text": "The active compounds did not inhibit IL-1 -induced production of IL-6 in fibroblasts , showing the cell selectivity of the effect .", "target_text": { "IL-1": "protein", "IL-6": "protein", "fibroblasts": "cell_type" } }, { "input_text": "Antioxidant-mediated inhibition of cytokine production was correlated with low levels of the corresponding messenger RNAs .", "target_text": { "cytokine": "protein", "messenger RNAs": "RNA" } }, { "input_text": "Nuclear run-on experiments showed that THP inhibited transcription of the IL-1 beta gene .", "target_text": { "IL-1": "protein", "IL-1 beta": "protein", "IL-1 beta gene": "DNA" } }, { "input_text": "THP decreased the concentration of the transcription factors NF-kappa B and AP-1 detected in nuclear extracts of PBMC cultured in the presence or absence of LPS .", "target_text": { "transcription factors": "protein", "NF-kappa B": "protein", "AP-1": "protein", "PBMC": "cell_type" } }, { "input_text": "THP and DHA markedly decreased the levels of TNF-alpha and IL-1 beta in the circulation of mice following LPS injection .", "target_text": { "TNF-alpha": "protein", "IL-1": "protein", "IL-1 beta": "protein" } }, { "input_text": "Thus antioxidants vary widely in potency as inhibitors of the activation of transcription factors and of the transcription of genes for pro-inflammatory cytokines .", "target_text": { "transcription factors": "protein", "genes": "DNA", "cytokines": "protein", "pro-inflammatory cytokines": "protein" } }, { "input_text": "Coordinate inhibition of the transcription of genes for inflammatory cytokines could provide a strategy for therapy of diseases with inflammatory pathogenesis and for septic shock .", "target_text": { "cytokines": "protein" } }, { "input_text": "An interleukin-4-induced transcription factor : IL-4 Stat .", "target_text": { "interleukin-4-induced transcription factor": "protein", "IL-4 Stat": "protein" } }, { "input_text": "Interleukin-4 ( IL-4 ) is an immunomodulatory cytokine secreted by activated T lymphocytes , basophils , and mast cells .", "target_text": { "Interleukin-4": "protein", "IL-4": "protein", "T lymphocytes": "cell_type", "basophils": "cell_type", "mast cells": "cell_type" } }, { "input_text": "It plays an important role in modulating the balance of T helper ( Th ) cell subsets , favoring expansion of the Th2 lineage relative to Th1 .", "target_text": { "T helper ( Th ) cell subsets": "cell_type", "Th2 lineage": "cell_type", "Th1": "cell_type" } }, { "input_text": "Imbalance of these T lymphocyte subsets has been implicated in immunological diseases including allergy , inflammation , and autoimmune disease .", "target_text": { "T lymphocyte subsets": "cell_type" } }, { "input_text": "IL-4 may mediate its biological effects , at least in part , by activating a tyrosine-phosphorylated DNA binding protein .", "target_text": { "IL-4": "protein", "tyrosine-phosphorylated DNA binding protein": "protein" } }, { "input_text": "This protein has now been purified and its encoding gene cloned .", "target_text": {} }, { "input_text": "Examination of the primary amino acid sequence of this protein indicates that it is a member of the signal transducers and activators of transcription ( Stat ) family of DNA binding proteins , hereby designated IL-4 Stat .", "target_text": { "primary amino acid sequence": "protein", "signal transducers and activators of transcription ( Stat ) family": "protein", "DNA binding proteins": "protein", "IL-4 Stat": "protein" } }, { "input_text": "Study of the inhibitory activities of phosphotyrosine-containing peptides derived from the intracellular domain of the IL-4 receptor provided evidence for direct coupling of receptor and transcription factor during the IL-4 Stat activation cycle .", "target_text": { "IL-4": "protein", "intracellular domain of the IL-4 receptor": "protein", "receptor": "protein", "transcription factor": "protein", "IL-4 Stat": "protein" } }, { "input_text": "Such observations indicate that IL-4 Stat has the same functional domain for both receptor coupling and dimerization .", "target_text": { "IL-4 Stat": "protein", "functional domain": "protein" } }, { "input_text": "Evaluation of the respiratory epithelium of normals and individuals with cystic fibrosis for the presence of adenovirus E1a sequences relevant to the use of E1a- adenovirus vectors for gene therapy for the respiratory manifestations of cystic fibrosis .", "target_text": { "adenovirus E1a sequences": "DNA" } }, { "input_text": "Lung disease associated with disorders such as cystic fibrosis ( CF ) may be amenable to somatic gene therapy in which there is delivery of the normal gene directly to the respiratory epithelium using E1a- adenovirus ( Ad ) type 2- or 5-based vectors .", "target_text": { "normal gene": "DNA" } }, { "input_text": "For safety reasons , the Ad vectors are rendered replication deficient by deletion of the E1a region .", "target_text": { "E1a region": "DNA" } }, { "input_text": "Because there is the theoretical possibility of an E1a- replication-deficient vector replicating as a result of recombination or complementation with Ad 2/5 E1a sequences present in the target cell , this study is directed toward evaluating respiratory epithelium of normals and individuals with CF for the presence of E1a sequences .", "target_text": { "Ad 2/5 E1a sequences": "DNA" } }, { "input_text": "Using Ad 2/5 E1a-specific primers and the polymerase chain reaction to evaluate DNA recovered from freshly isolated nasal and bronchial epithelium recovered by brushing , E1a sequences were detected in respiratory epithelium of 19 of 91 normals ( 21 % ) .", "target_text": { "Ad 2/5 E1a-specific primers": "DNA", "E1a sequences": "DNA" } }, { "input_text": "In the E1a-positive samples , the average of E1a copy number was 55 +/- 18/10(3) recovered cells .", "target_text": {} }, { "input_text": "In CF individuals , 7 of 52 ( 13 % ) had detectable E1a sequences in the respiratory epithelium , with E1a copy number in the positive samples of 80 +/- 21/10(3) recovered cells .", "target_text": { "E1a sequences": "DNA" } }, { "input_text": "These results demonstrate that there are detectable Ad 2/5 E1a sequences in the respiratory epithelium of a small percentage of normals and individuals with CF .", "target_text": { "E1a sequences": "DNA", "Ad 2/5 E1a sequences": "DNA" } }, { "input_text": "Because of the theoretical potential of such sequences supporting replication of E1a- Ad vectors , human gene therapy protocols for CF utilizing such vectors should consider evaluating study individuals for the presence of Ad 2/5 E1a sequences in the respiratory epithelium .", "target_text": { "E1a sequences": "DNA", "Ad 2/5 E1a sequences": "DNA" } }, { "input_text": "Leiomyosarcoma of the vulva : report of a case .", "target_text": {} }, { "input_text": "A 52-year-old female presented with a progressively enlarging vulvar mass .", "target_text": {} }, { "input_text": "Pathological evaluation revealed a high-grade vulvar leiomyosarcoma .", "target_text": {} }, { "input_text": "Immunohistochemical and ultrastructural studies were performed to support the diagnosis .", "target_text": {} }, { "input_text": "In an effort to better understand the biology of this tumor additional immunohistochemical studies for the protein product of p53 tumor suppressor gene and estrogen receptor expression by tumor cells , as well as the type of immune cells infiltrating the tumor were performed .", "target_text": { "protein product": "protein", "p53 tumor suppressor gene": "DNA", "estrogen receptor": "protein", "tumor cells": "cell_type", "immune cells": "cell_type" } }, { "input_text": "Tumor cells showed an overexpression of p53 protein and were estrogen receptor -positive .", "target_text": { "Tumor cells": "cell_type", "p53 protein": "protein", "estrogen receptor": "protein" } }, { "input_text": "Macrophages and T and B lymphocytes infiltrated the tumor in moderate numbers with occasional lymphoid aggregate formation .", "target_text": { "Macrophages": "cell_type" } }, { "input_text": "This study is the first attempt to better understand the biology of these tumors .", "target_text": {} }, { "input_text": "Stimulation of HIV replication in mononuclear phagocytes by leukemia inhibitory factor .", "target_text": { "mononuclear phagocytes": "cell_type", "leukemia inhibitory factor": "protein" } }, { "input_text": "This study examined the effects of leukemia inhibitory factor ( LIF ) on human immunodeficiency virus ( HIV ) replication in mononuclear phagocytes ( MNP ) .", "target_text": { "leukemia inhibitory factor": "protein", "LIF": "protein", "mononuclear phagocytes": "cell_type", "MNP": "cell_type" } }, { "input_text": "LIF induced a dose-dependent increase in p24 antigen production in the chronically infected promonocytic cell line U1 .", "target_text": { "LIF": "protein", "p24 antigen": "protein", "chronically infected promonocytic cell line U1": "cell_line" } }, { "input_text": "The magnitude and time kinetics of the LIF effects were similar to interleukin 1 ( IL-1 ) , IL-6 , and tumor necrosis factor ( TNF ) , other cytokines known to induce HIV replication in this cell line .", "target_text": { "LIF": "protein", "interleukin 1": "protein", "IL-1": "protein", "IL-6": "protein", "tumor necrosis factor": "protein", "TNF": "protein" } }, { "input_text": "To characterize mechanisms responsible for these LIF effects , levels of HIV mRNA , activation of the DNA binding protein nuclear factor ( NF ) -kB , signal transduction pathways , and potential interactions with other cytokines were analyzed .", "target_text": { "LIF": "protein", "HIV mRNA": "RNA", "DNA binding protein nuclear factor": "protein", "( NF ) -kB": "protein", "cytokines": "protein" } }, { "input_text": "LIF increased steady-state levels of HIV mRNA at 2.0 , 4.3 , and 9.2 kB .", "target_text": { "LIF": "protein", "HIV mRNA": "RNA" } }, { "input_text": "This was detectable by 24 h and persisted until 72 h .", "target_text": {} }, { "input_text": "The DNA binding protein NF-kB is a central mediator in cytokine activation of HIV transcription .", "target_text": { "DNA binding protein NF-kB": "protein", "cytokine": "protein" } }, { "input_text": "NF-kB levels were higher in unstimulated U1 cells as compared to the parent cell line U937 .", "target_text": { "NF-kB": "protein", "unstimulated U1 cells": "cell_line", "parent cell line": "cell_line", "U937": "cell_line" } }, { "input_text": "In both cell lines LIF increased NF-kB activity .", "target_text": { "LIF": "protein", "NF-kB": "protein" } }, { "input_text": "Induction of NF-kB and HIV replication by cytokines are at least in part dependent on reactive oxygen intermediates .", "target_text": { "NF-kB": "protein", "cytokines": "protein" } }, { "input_text": "The oxygen radical scavenger N-acetyl-L-cysteine , but not an inhibitor of nitric oxide synthase , inhibited LIF -induced HIV replication .", "target_text": { "nitric oxide synthase": "protein", "LIF": "protein" } }, { "input_text": "LIF induces the production of other cytokines in monocytes but its effects on HIV replication were not inhibited by antibodies to IL-1 , TNF , or IL-6 .", "target_text": { "LIF": "protein", "cytokines": "protein", "antibodies": "protein", "IL-1": "protein", "TNF": "protein", "IL-6": "protein" } }, { "input_text": "These results identify LIF as a stimulus of HIV replication .", "target_text": { "LIF": "protein" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "Mechanisms involved in the inhibition of growth of a human B lymphoma cell line , B104 , by anti-MHC class II antibodies .", "target_text": { "human B lymphoma cell line": "cell_line", "B104": "cell_line", "anti-MHC class II antibodies": "protein" } }, { "input_text": "The mechanisms involved in the inhibition of growth of a human B lymphoma cell line , B104 , by anti-MHC class II antibodies ( Ab ) were compared with those in anti-IgM Ab -induced B104 growth inhibition .", "target_text": { "human B lymphoma cell line": "cell_line", "B104": "cell_line", "anti-MHC class II antibodies": "protein", "Ab": "protein", "anti-IgM Ab": "protein" } }, { "input_text": "Two anti-MHC class II Ab , L227 and 2.06 , inhibited the growth of B104 cells , although 2.06 , but not L227 , needed to be further cross-linked with a goat anti-mouse IgG Ab ( GAM ) to show the effect .", "target_text": { "anti-MHC class II Ab": "protein", "L227": "protein", "2.06": "protein", "B104 cells": "cell_line", "goat anti-mouse IgG Ab": "protein", "GAM": "protein" } }, { "input_text": "L227 induced an increase in intracellular free Ca2+ concentration ( [ Ca2+ ]i ) from the intracellular pool and little or no protein tyrosine phosphorylation , phosphatidyl inositol turnover , or expression of Egr-1 mRNA , whereas 2.06 plus GAM induced an increase in [ Ca2+ ]i from both the intracellular and , in particular , the extracellular pools .", "target_text": { "L227": "protein", "Egr-1 mRNA": "RNA", "2.06": "protein", "GAM": "protein" } }, { "input_text": "The inhibition of B104 cell growth induced by anti-MHC class II Ab was Ca(2+) -independent and not inhibited by actinomycin D or cyclosporin A , and cell cycle arrest at the G2/M interphase was not observed .", "target_text": { "B104 cell": "cell_line", "anti-MHC class II Ab": "protein" } }, { "input_text": "These features are very different from those observed in B104 cell death induced by anti-IgM Ab .", "target_text": { "B104 cell": "cell_line", "anti-IgM Ab": "protein" } }, { "input_text": "Neither DNA fragmentation nor the morphology of apoptosis was observed .", "target_text": {} }, { "input_text": "These findings demonstrate that cross-linking of MHC class II molecules transduced the negative signals through intracellular mechanisms different from those present in the cross-linking of surface IgM .", "target_text": { "MHC class II molecules": "protein", "IgM": "protein" } }, { "input_text": "Functional block for 1 alpha,25-dihydroxyvitamin D3 -mediated gene regulation in human B lymphocytes .", "target_text": { "human B lymphocytes": "cell_type" } }, { "input_text": "Elements necessary for the steroid hormone 1 alpha,25-dihydroxyvitamin D3 ( 1 alpha,25-(OH)2D3 ) to induce a biological response include the presence of specific intracellular receptors ( vitamin D3 receptors ( VDR ) ) and modulation of gene expression via hormone-activated receptor binding to regulatory regions of target genes .", "target_text": { "intracellular receptors": "protein", "vitamin D3 receptors": "protein", "VDR": "protein", "regulatory regions": "protein", "target genes": "DNA" } }, { "input_text": "These parameters were examined in normal and Epstein-Barr virus-immortalized human B cells and compared with 1 alpha,25-(OH)2D3 -responsive cells of the T and monocytic lineages .", "target_text": { "Epstein-Barr virus-immortalized human B cells": "cell_line", "1 alpha,25-(OH)2D3 -responsive cells": "cell_line" } }, { "input_text": "Although resting tonsillar B cells did not express VDR mRNA , activation of these cells with interleukin-4 induced VDR in the absence of exogenously supplemented 1 alpha,25-(OH)2D3 .", "target_text": { "VDR mRNA": "RNA", "interleukin-4": "protein", "VDR": "protein" } }, { "input_text": "As indicators of hormone-mediated gene regulation we analyzed modulation of CD23 , a common B cell/monocyte surface antigen , and 24-hydroxylase .", "target_text": { "CD23": "protein", "common B cell/monocyte surface antigen": "protein", "24-hydroxylase": "protein" } }, { "input_text": "1 alpha,25-(OH)2D3 inhibited CD23 expression in U937 cells , yet failed to modulate CD23 expression in B cells .", "target_text": { "CD23": "protein", "U937 cells": "cell_line", "B cells": "cell_type" } }, { "input_text": "Furthermore , 1 alpha,25-(OH)2D3 induced 24-hydroxylase mRNA expression and metabolic activity in both U937 cells and lectin-activated T cells , yet failed to induce 24-hydroxylase mRNA or its metabolic activity in B cells .", "target_text": { "24-hydroxylase": "protein", "U937 cells": "cell_line", "lectin-activated T cells": "cell_type", "24-hydroxylase mRNA": "RNA", "B cells": "cell_type" } }, { "input_text": "These findings suggest that although human B lymphocytes can express VDR mRNA and protein , they exhibit a functional block for vitamin D -dependent gene regulation .", "target_text": { "human B lymphocytes": "cell_type", "VDR mRNA": "RNA", "protein": "protein" } }, { "input_text": "Positive and negative regulation of IL-2 gene expression : role of multiple regulatory sites .", "target_text": { "IL-2": "protein" } }, { "input_text": "Interleukin 2 ( IL-2 ) is an important lymphokine required in the process of T cell activation , proliferation , clonal expansion and differentiation .", "target_text": { "Interleukin 2": "protein", "IL-2": "protein", "lymphokine": "protein" } }, { "input_text": "The IL-2 gene displays both T cell specific and inducible expression : it is only expressed in CD4+ T cells after antigenic or mitogenic stimulation .", "target_text": { "IL-2": "protein", "IL-2 gene": "DNA", "CD4+ T cells": "cell_type" } }, { "input_text": "Several cis-acting regulatory sites are required for induction of the IL-2 gene after stimulation .", "target_text": { "cis-acting regulatory sites": "DNA", "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "In this study , we have analysed the function of these cis-acting regulatory sites in the context of the native IL-2 enhancer and promoter sequence .", "target_text": { "cis-acting regulatory sites": "DNA", "IL-2": "protein", "IL-2 enhancer": "DNA", "promoter sequence": "DNA" } }, { "input_text": "The results of this study suggest that the NFAT ( -276 to -261 ) , the distal octamer ( -256 to -248 ) and the proximal octamer ( -75 to -66 ) sites not only act as enhancers of IL-2 gene transcription in the presence of cellular stimulation , but also have a silencing effect on IL-2 gene expression in resting cells .", "target_text": { "NFAT": "protein", "-276 to -261": "DNA", "distal octamer": "DNA", "-256 to -248": "DNA", "proximal octamer": "DNA", "-75 to -66": "DNA", "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "Two other sites display disparate effects on IL-2 gene expression in different T leukemia cell lines : the distal purine box ( -291 to -277 ) and the proximal purine box sites ( -145 to -128 ) .", "target_text": { "IL-2": "protein", "IL-2 gene": "DNA", "T leukemia cell lines": "cell_line", "distal purine box": "DNA", "-291 to -277": "DNA", "proximal purine box sites": "DNA", "-145 to -128": "DNA" } }, { "input_text": "Finally , the AP-1 ( -186 to -176 ) and the kappa B sites ( -206 to -195 ) respond to different cellular activation in EL4 cells .", "target_text": { "-206 to -195": "DNA", "EL4 cells": "cell_line" } }, { "input_text": "The AP-1 site mediated the response to PMA stimulation while the kappa B site responded to IL-1 stimulation .", "target_text": { "AP-1 site": "DNA", "kappa B site": "DNA", "IL-1": "protein" } }, { "input_text": "These data suggest that the regulation of IL-2 gene expression is a complex process and multiple cis-acting regulatory sites interact to exert different effects in T cells representative of alternative stages of differentiation .", "target_text": { "IL-2": "protein", "IL-2 gene": "DNA", "cis-acting regulatory sites": "DNA", "T cells": "cell_type" } }, { "input_text": "Sp1 is a critical factor for the monocytic specific expression of human CD14 .", "target_text": { "Sp1": "protein", "human CD14": "protein" } }, { "input_text": "CD14 is a membrane glycoprotein expressed specifically on monocytes and macrophages , and its expression is markedly increased during the process of monocyte differentiation .", "target_text": { "CD14": "protein", "membrane glycoprotein": "protein", "monocytes": "cell_type", "macrophages": "cell_type", "monocyte": "cell_type" } }, { "input_text": "In order to study CD14 gene regulation , the human CD14 gene was cloned from a partial EcoRI digested chromosome 5 library .", "target_text": { "CD14": "protein", "CD14 gene": "DNA", "human CD14": "protein", "human CD14 gene": "DNA", "EcoRI": "protein", "chromosome 5": "DNA", "EcoRI digested chromosome 5 library": "DNA" } }, { "input_text": "A 5.5-kilobase genomic clone contained the full-length CD14 coding sequence and 4.2 kilobases of 5'-upstream sequence .", "target_text": { "5.5-kilobase genomic clone": "DNA", "CD14": "protein", "CD14 coding sequence": "DNA", "4.2 kilobases of 5'-upstream sequence": "DNA" } }, { "input_text": "One major and one minor transcription start site were identified 101 and 130 base pairs ( bp ) upstream , respectively , from the protein translation start ATG .", "target_text": { "101 and 130 base pairs ( bp ) upstream": "DNA", "protein translation start ATG": "DNA" } }, { "input_text": "A DNA fragment containing 128 bp of upstream sequence had strong , monocyte-specific promoter activity in the CD14 positive monocytic cell line Mono Mac 6 as compared to the nonmonocytic cell lines HeLa and REX .", "target_text": { "DNA fragment": "DNA", "128 bp of upstream sequence": "DNA", "CD14": "protein", "CD14 positive monocytic cell line": "cell_line", "Mono Mac 6": "cell_line", "nonmonocytic cell lines": "cell_line", "HeLa": "cell_line", "REX": "cell_line" } }, { "input_text": "Four regions in this DNA fragment interact with nuclear proteins isolated from monocytic cells .", "target_text": { "DNA fragment": "DNA", "nuclear proteins": "protein", "monocytic cells": "cell_type" } }, { "input_text": "The Sp1 transcription factor bound to three different regions in the CD14 promoter .", "target_text": { "Sp1": "protein", "transcription factor": "protein", "CD14": "protein", "CD14 promoter": "DNA" } }, { "input_text": "Mutation of the major Sp1 binding site ( -110 bp ) decreased tissue-specific promoter activity , and these results , together with transactivation experiments , demonstrate that Sp1 plays a critical role in the tissue-specific expression of CD14 in monocytic cells .", "target_text": { "Sp1": "protein", "major Sp1 binding site": "DNA", "-110 bp": "DNA", "CD14": "protein", "monocytic cells": "cell_type" } }, { "input_text": "CD14 Sp1 site oligonucleotides bound preferentially to a 105-kDa Sp1 species , which is present in higher relative levels in monocytic than non-monocytic cells , suggesting that modification of Sp1 , such as phosphorylation , may explain how the Sp1 site mediates monocytic specific promoter activity .", "target_text": { "CD14": "protein", "Sp1": "protein", "105-kDa Sp1 species": "protein", "monocytic": "cell_type", "non-monocytic cells": "cell_type" } }, { "input_text": "The interleukin-8 AP-1 and kappa B-like sites are genetic end targets of FK506-sensitive pathway accompanied by calcium mobilization .", "target_text": {} }, { "input_text": "FK506 , an immunosuppressant , inhibits the production of several cytokines in T lymphocytes .", "target_text": { "cytokines": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "We observed that FK506 suppressed the transcription of a chemotactic cytokine , interleukin-8 ( IL-8 ) in a human T cell line , Jurkat cells , activated by phorbol 12-myristate 13-acetate ( PMA ) and calcium ( Ca2+ ) ionophore ( ionomycin ) .", "target_text": { "chemotactic cytokine": "protein", "interleukin-8": "protein", "IL-8": "protein", "human T cell line": "cell_line", "Jurkat cells": "cell_line" } }, { "input_text": "By deleted and mutated analysis of the IL-8 promoters , the AP-1 and kappa B-like sites were identified as the responsive elements for PMA and ionomycin .", "target_text": { "IL-8": "protein", "IL-8 promoters": "DNA", "AP-1": "DNA", "kappa B-like sites": "DNA", "AP-1 and kappa B-like sites": "DNA" } }, { "input_text": "FK506 suppressed the transcriptions through the AP-1 or kappa B-like sites induced by PMA plus Ca(2+)-mobilizing agents , but not those induced by Ca(2+)-independent stimuli .", "target_text": { "AP-1": "DNA", "kappa B-like sites": "DNA" } }, { "input_text": "In gel retardation analysis , FK506 had little effect on the binding to the AP-1 site of PMA / ionomycin -induced nuclear factors , which were recognized with anti-JunD or c-Fos antibody .", "target_text": { "AP-1 site": "DNA", "anti-JunD": "protein", "c-Fos antibody": "protein" } }, { "input_text": "In contrast , FK506 or EGTA ( Ca2+ chelator ) similarly affected the formation of kappa B-like site binding complexes , which were not recognized by any antibodies against the human Rel family proteins ( c-Rel , p65 , p50 , and p49 ) .", "target_text": { "kappa B-like site binding complexes": "protein", "antibodies": "protein", "human Rel family proteins": "protein", "c-Rel": "protein", "p65": "protein", "p50": "protein", "p49": "protein" } }, { "input_text": "Furthermore , we confirmed the previous report that FK506 suppressed the PMA / ionomycin -induced activation through authentic kappa B site of immunoglobulin ( Ig ) gene , to which NF-kappa B binding was also decreased by FK506 , indicating that both IL-8 kappa B-like site and Ig kappa B site are FK506 -sensitive in spite of the difference of binding factors .", "target_text": { "kappa B site": "DNA", "immunoglobulin ( Ig ) gene": "DNA", "NF-kappa B": "protein", "IL-8": "protein", "IL-8 kappa B-like site": "DNA", "binding factors": "protein" } }, { "input_text": "Our results indicate that not only the reported IL-2 NF-AT and NFIL-2A sites and Ig kappa B site , but also the IL-8 AP-1 and kappa B-like sites are terminals of FK506 -sensitive pathway involving Ca2+ mobilization .", "target_text": { "kappa B site": "DNA", "IL-8": "protein", "AP-1": "DNA", "kappa B-like sites": "DNA" } }, { "input_text": "Androgen binding sites in peripheral human mononuclear leukocytes of healthy males and females .", "target_text": { "Androgen binding sites": "protein", "peripheral human mononuclear leukocytes": "cell_type" } }, { "input_text": "Androgen binding sites have been identified in circulating human mononuclear leukocytes of healthy donors of both sexes .", "target_text": { "Androgen binding sites": "protein", "circulating human mononuclear leukocytes": "cell_type" } }, { "input_text": "Cells were separated from blood samples on a Ficoll gradient and incubated with different concentrations of [3H]testosterone in the presence or absence of a 400-fold excess of unlabelled testosterone .", "target_text": {} }, { "input_text": "Binding data were derived from Scatchard analysis .", "target_text": {} }, { "input_text": "The binding sites fulfil the required criteria for specific steroid binding sites however differ somewhat from the classic androgen receptors from genital skin fibroblast : in fertile adult males ( n = 20 ) the binding sites showed ( 1 ) a high affinity for testosterone ( 1.32 +/- 0.49 nM ; mean +/- SD ) , ( 2 ) a saturable capacity ( 184 +/- 52 binding sites per cell ; mean +/- SD ) , and ( 3 ) a characteristic competitive binding profile for other steroid hormones ( relative binding affinities : testosterone = dihydrotestosterone > 17 beta-estradiol > progesterone , whereas aldosterone , 17-hydroxy-progesterone and cortisol did not compete appreciably ) .", "target_text": { "binding sites": "protein", "steroid binding sites": "protein", "androgen receptors": "protein", "genital skin fibroblast": "cell_type" } }, { "input_text": "Furthermore the number of binding sites determined using [3H]dihydrotestosterone , [3H]RU-1881 , or [3H] testosterone were comparable .", "target_text": { "binding sites": "protein" } }, { "input_text": "This raises the possibility that androgen receptors in peripheral mononuclear leukocytes differ from those in genital skin fibroblasts .", "target_text": { "androgen receptors": "protein", "peripheral mononuclear leukocytes": "cell_type", "genital skin fibroblasts": "cell_type" } }, { "input_text": "There was no apparent correlation between serum testosterone concentrations and androgen binding sites .", "target_text": { "androgen binding sites": "protein" } }, { "input_text": "In fertile women remarkable changes in androgen binding sites were seen in the course of the menstrual cycle , with a significant increase in the immediate preovulatory period .", "target_text": { "androgen binding sites": "protein" } }, { "input_text": "The presence of androgen receptors in peripheral mononuclear leukocytes provides for the first time the experimental basis for an hypothesis of direct , receptor-mediated effects of androgens on mature immunocompetent cells .", "target_text": { "androgen receptors": "protein", "peripheral mononuclear leukocytes": "cell_type", "mature immunocompetent cells": "cell_type" } }, { "input_text": "The immunological implications of these results are discussed .", "target_text": {} }, { "input_text": "Induction of IL-8 expression in T cells uses the CD28 costimulatory pathway .", "target_text": { "IL-8": "protein", "T cells": "cell_type", "CD28": "protein" } }, { "input_text": "IL-8 , a potent chemotactic factor for neutrophil granulocytes and lymphocytes , is a proinflammatory cytokine secreted by a variety of cell types , including T cells .", "target_text": { "IL-8": "protein", "chemotactic factor": "protein", "neutrophil granulocytes": "cell_type", "lymphocytes": "cell_type", "T cells": "cell_type" } }, { "input_text": "Stimulation of the CD28 cell surface molecule delivers costimulatory signals essential for lymphokine production in activated T cells via a conserved sequence element found in the promoter of several lymphokine genes .", "target_text": { "CD28": "protein", "CD28 cell surface molecule": "protein", "lymphokine": "protein", "activated T cells": "cell_type", "conserved sequence element": "DNA", "promoter": "DNA", "lymphokine genes": "DNA" } }, { "input_text": "Anti- CD28 -stimulated T cells produced significant amounts of IL-8 ; additionally , costimulation with anti-CD3 and anti- CD28 Abs resulted in a synergistic induction of IL-8 secretion .", "target_text": { "CD28": "protein", "Anti- CD28 -stimulated T cells": "cell_line", "IL-8": "protein", "anti-CD3": "protein", "anti- CD28 Abs": "protein" } }, { "input_text": "Sequence homology , single nucleotide mutations , and anti- CD28 Ab stimulation studies established that the NF-kappa B -like sequence in the promoter of the IL-8 gene functioned as a CD28 response element .", "target_text": { "CD28": "protein", "anti- CD28 Ab": "protein", "NF-kappa B": "protein", "NF-kappa B -like sequence": "DNA", "promoter": "DNA", "IL-8": "protein", "IL-8 gene": "DNA", "CD28 response element": "DNA" } }, { "input_text": "Furthermore , cyclosporin A , but not rapamycin , blocked the synergistic induction of IL-8 expression achieved with anti-CD3 and anti- CD28 costimulation .", "target_text": { "IL-8": "protein", "anti-CD3": "protein", "CD28": "protein" } }, { "input_text": "The involvement of a CD28 response element in the induction of IL-8 expression in activated T cells may provide new insights into the pathogenesis and persistence of immune disorders characterized by increased levels of IL-8 , such as psoriasis and rheumatoid arthritis .", "target_text": { "CD28": "protein", "CD28 response element": "DNA", "IL-8": "protein", "activated T cells": "cell_type" } }, { "input_text": "MHC class II signaling in B-cell activation [ see comments ]", "target_text": { "MHC class II": "protein", "B-cell": "cell_type" } }, { "input_text": "The cognate interaction between T cells and antigen-presenting cells ( APCs ) , mediated by major histocompatibility complex ( MHC ) class II molecules , results in the delivery of activation signals to the APC .", "target_text": { "T cells": "cell_type", "antigen-presenting cells": "cell_type", "APCs": "cell_type", "major histocompatibility complex ( MHC ) class II molecules": "protein", "APC": "cell_type" } }, { "input_text": "These signals contribute to the expression of co-stimulatory activity by APCs and have important consequences for cell effector function .", "target_text": { "APCs": "cell_type" } }, { "input_text": "MHC class II molecules also serve as receptors for B-cell stimulation by microbial superantigens .", "target_text": { "MHC class II": "protein", "B-cell": "cell_type", "microbial superantigens": "protein" } }, { "input_text": "In this review , Paul Scholl and Raif Geha discuss recent advances in our understanding of mechanisms of MHC class II signaling and analyse their role in human B-cell activation .", "target_text": { "MHC class II": "protein", "B-cell": "cell_type" } }, { "input_text": "Effects of glucocorticoids in rheumatoid arthritis .", "target_text": {} }, { "input_text": "Diminished glucocorticoid receptors do not result in glucocorticoid resistance .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "OBJECTIVE .", "target_text": {} }, { "input_text": "Lymphocytes of patients with rheumatoid arthritis ( RA ) have diminished receptor density ; thus , patients with RA should show partial resistance to glucocorticoids .", "target_text": {} }, { "input_text": "We investigated the glucocorticoid sensitivity of lymphocytes in RA patients compared with healthy subjects .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "METHODS .", "target_text": {} }, { "input_text": "We determined the effects of glucocorticoids on lymphocyte proliferation and cytokine release .", "target_text": { "lymphocyte": "cell_type", "cytokine": "protein" } }, { "input_text": "RESULTS .", "target_text": {} }, { "input_text": "Proliferation and cytokine release were inhibited in RA patients to the same extent as in healthy controls .", "target_text": { "cytokine": "protein" } }, { "input_text": "CONCLUSION .", "target_text": {} }, { "input_text": "Diminished receptor density in RA patients does not result in glucocorticoid resistance .", "target_text": {} }, { "input_text": "Arrested development : understanding v-abl .", "target_text": { "v-abl": "DNA" } }, { "input_text": "The protein tyrosine kinase activity of the v-abl oncogene has been demonstrated to subvert the normal second messenger systems used by lymphoid cells for growth and differentiation .", "target_text": { "protein tyrosine kinase": "protein", "v-abl": "DNA", "v-abl oncogene": "DNA", "lymphoid cells": "cell_type" } }, { "input_text": "Transformation of bone marrow with the Abelson murine leukemia virus results in the appearance of B cell lineage cells arrested at the pre-B cell stage .", "target_text": { "B cell lineage cells": "cell_type" } }, { "input_text": "Recent reports have characterized these cells expressing high v-abl kinase activity as deficient in detectable NF-kappaB DNA binding activity and low level RAG gene expression .", "target_text": { "v-abl": "DNA", "NF-kappaB": "protein", "RAG gene": "DNA" } }, { "input_text": "These observations suggest that v-abl may be inhibiting the differentiation of B cells by blocking these two crucial elements in the maturation pathway .", "target_text": { "v-abl": "DNA", "B cells": "cell_type" } }, { "input_text": "Corticosteroid receptors in lymphocytes : a possible marker of brain involution ?", "target_text": { "Corticosteroid receptors": "protein", "lymphocytes": "cell_type" } }, { "input_text": "A similarity has recently been found between the regulation of corticosteroid receptors in brain and in lymphoid tissue .", "target_text": { "corticosteroid receptors": "protein" } }, { "input_text": "We have studied the regulation of corticosteroid receptors in human mononuclear leukocytes as a possible marker of brain involution .", "target_text": { "corticosteroid receptors": "protein", "human mononuclear leukocytes": "cell_type" } }, { "input_text": "Type I corticosteroid receptors are down regulated by excess of mineralocorticoids ( primary and secondary hyperaldosteronism , pseudohyperaldosteronism ) and of glucocorticoids ( Cushing 's syndrome ) . Type II corticosteroid receptors are not reduced by excess of endogenous corticosteroids ( Cushing 's syndrome ) .", "target_text": { "corticosteroid receptors": "protein", "Type I corticosteroid receptors": "protein", "Type II corticosteroid receptors": "protein" } }, { "input_text": "In normal adults there is a direct significant correlation between plasma cortisol and Type I and between plasma cortisol and Type II receptors in mononuclear leukocytes , while in Cushing 's syndrome the correlation is inverse between plasma cortisol at 8 a.m. and Type II receptors .", "target_text": { "Type I": "protein", "Type II receptors": "protein", "mononuclear leukocytes": "cell_type" } }, { "input_text": "In an aged population the mean numbers of Type I and of Type II receptors are lower and plasma cortisol is higher than in adult controls , but the increase of plasma cortisol is not followed by a clinical picture of hypercorticism .", "target_text": { "Type I": "protein", "Type II receptors": "protein" } }, { "input_text": "Corticosteroid Type I and Type II receptors are inversely correlated with age .", "target_text": {} }, { "input_text": "After dexamethasone suppression ( 1 mg at 11 p.m. ) Type I receptors always decrease in controls while the response of Type II is not homogeneous .", "target_text": { "Type I receptors": "protein", "Type II": "protein" } }, { "input_text": "In an aged group of patients , both receptors are reduced by dexamethasone .", "target_text": {} }, { "input_text": "We conclude that the decrease with age of corticosteroid receptors is possibly related to a physiological involution of corticosteroid receptors and that this reduction does increase plasma cortisol concentration , without affecting the glucocorticoid effector mechanism .", "target_text": { "corticosteroid receptors": "protein" } }, { "input_text": "All-trans retinoic acid and 1 alpha,25-dihydroxyvitamin D3 co-operate to promote differentiation of the human promyeloid leukemia cell line HL60 to monocytes .", "target_text": { "human promyeloid leukemia cell line": "cell_line", "HL60": "cell_line", "monocytes": "cell_type" } }, { "input_text": "A basis for differentiation therapy of leukemias is provided by knowledge of agents which induce specific lineage maturation .", "target_text": {} }, { "input_text": "All-trans retinoic acid ( RA ) induces differentiation of HL60 cells to neutrophils and is used to treat acute promyelocytic leukemia .", "target_text": { "HL60 cells": "cell_line", "neutrophils": "cell_type" } }, { "input_text": "We observed that RA did not induced neutrophil differentiation in serum-free grown HL60 cells whereas 50 nM 1 alpha,25-dihydroxyvitamin D3 ( D3 ) induced maximal monocyte differentiation .", "target_text": { "HL60 cells": "cell_line", "serum-free grown HL60 cells": "cell_line" } }, { "input_text": "Increasing RA concentrations reduced the D3 concentration required for monocyte differentiation .", "target_text": {} }, { "input_text": "Cells treated with 5 nM D3 showed little response , but differentiated maximally with 5 nM D3 and 10 nM RA .", "target_text": {} }, { "input_text": "The D3 analogs MC903 , EB1089 and KH1060 were more potent inducers of monocyte differentiation .", "target_text": {} }, { "input_text": "The extent to which analog activity was increased after cotreatment with RA was inversely related to potency .", "target_text": {} }, { "input_text": "Twenty-four hour treatment with 10 nM RA primed cells for response to 5 nM D3 ; the reverse sequence being ineffective .", "target_text": { "RA primed cells": "cell_line" } }, { "input_text": "Priming with 10 nM RA , or subsequent treatment with D3 ( 5 nM ) , did not alter expression of mRNAs encoding receptors for D3 ( VDR ) , RA ( RAR alpha ) or 9-CIS RA ( RXR alpha , beta , gamma ) .", "target_text": { "mRNAs": "RNA", "receptors": "protein", "VDR": "protein", "RAR alpha": "protein" } }, { "input_text": "That RA promotes both neutrophil and monocyte differentiation has implications for the use of RA and D3 in treatment of leukemias and provides insight into mechanisms whereby RAR , VDR and RXR facilitate monocyte differentiation .", "target_text": { "VDR": "protein", "RXR": "protein" } }, { "input_text": "[ An overexpression of retinoic acid receptor alpha blocks myeloid cell differentiation at the promyelocyte stage ]", "target_text": { "retinoic acid receptor alpha": "protein", "myeloid cell": "cell_type" } }, { "input_text": "Retinoic acid ( RA ) , a vitamin A derivative , exerts a wide range of biological effects related to cell proliferation and differentiation .", "target_text": {} }, { "input_text": "The pleiotropic effects of RA are thought to be mediated through specific nuclear RA receptors ( RARs ) .", "target_text": { "RA receptors": "protein", "RARs": "protein" } }, { "input_text": "RARs are members of the steroid/thyroid hormone receptor superfamily and exhibit a molecular structure that possess discrete DNA-binding and RA ( ligand ) -binding domains .", "target_text": { "RARs": "protein", "steroid/thyroid hormone receptor superfamily": "protein", "RA ( ligand ) -binding domains": "protein" } }, { "input_text": "In hematopoietic system , RA and RARs , predominantly RAR alpha may play key roles for the proliferation and differentiation of hematopoietic progenitors .", "target_text": { "RARs": "protein", "RAR alpha": "protein", "hematopoietic progenitors": "cell_type" } }, { "input_text": "However , it is currently unknown how RA and RARs are involved in regulating normal hematopoietic differentiation .", "target_text": { "RARs": "protein" } }, { "input_text": "To make clear the roles of RA and RAR alpha in the normal hematopoiesis , I have introduced the construct of human RAR alpha ( hRAR alpha ) into murine bone marrow cells with retroviral vector , and selected infected cells with drug resistant marker ( Neo(r) ) cultured on the stroma cell line ( PA6-neo ) , and analyzed the behavior of infected cells .", "target_text": { "RAR alpha": "protein", "human RAR alpha": "protein", "hRAR alpha": "protein", "murine bone marrow cells": "cell_type", "drug resistant marker": "DNA", "Neo(r)": "DNA", "stroma cell line": "cell_line", "PA6-neo": "cell_line", "infected cells": "cell_type" } }, { "input_text": "All of procedure were done in vitro .", "target_text": {} }, { "input_text": "Most cells infected with hRAR alpha exhibited promyelocytic morphology and were thought to be blocked at the promyelocytic stage in their myeloid differentiation .", "target_text": { "hRAR alpha": "protein", "promyelocytic morphology": "cell_type" } }, { "input_text": "Furthermore , these immature cells differentiated terminally into mature granulocytes by adding with RA ( 10 ( -6 ) M ) .", "target_text": { "immature cells": "cell_type" } }, { "input_text": "RAR alpha infected cells were also able to differentiate into mature macrophages in the both of long term culture and IL3 colony .", "target_text": { "RAR alpha": "protein", "infected cells": "cell_type", "mature macrophages": "cell_type", "IL3 colony": "cell_line" } }, { "input_text": "These observations suggest that an overexpression of RAR alpha alone is effective to suppress myeloid cell differentiation and RAR alpha plays a crucial role in the terminal differentiation of myeloid precursors .", "target_text": { "RAR alpha": "protein", "myeloid cell": "cell_type" } }, { "input_text": "The system described here may serve as a model for studying the the essential genes for differentiation of normal bone marrow cells .", "target_text": { "essential genes": "DNA", "normal bone marrow cells": "cell_type" } }, { "input_text": "Hypoxic induction of interleukin-8 gene expression in human endothelial cells .", "target_text": { "interleukin-8": "protein", "interleukin-8 gene": "DNA", "human endothelial cells": "cell_type" } }, { "input_text": "Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion , we have sought mechanisms by which PMNs are directed into hypoxic tissue .", "target_text": { "PMNs": "cell_type" } }, { "input_text": "Incubation of human endothelial cells ( ECs ) in hypoxia , PO2 approximately 14-18 Torr , led to time-dependent release of IL-8 antigen into the conditioned medium ; this was accompanied by increased chemotactic activity for PMNs , blocked by antibody to IL-8 .", "target_text": { "human endothelial cells": "cell_type", "ECs": "cell_type", "IL-8": "protein", "PMNs": "cell_type" } }, { "input_text": "Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA , based on polymerase chain reaction analysis , and increased IL-8 transcription , based on nuclear run-on assays .", "target_text": { "IL-8": "protein", "ECs": "cell_type", "IL-8 mRNA": "RNA" } }, { "input_text": "Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1 , another member of the chemokine superfamily of proinflammatory cytokines .", "target_text": { "ECs": "cell_type", "mRNA": "RNA", "macrophage chemotactic protein-1": "protein", "chemokine superfamily": "protein", "proinflammatory cytokines": "protein" } }, { "input_text": "IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site .", "target_text": { "IL-8": "protein", "IL-8 gene": "DNA", "ECs": "cell_type", "hypoxic ECs": "cell_type" } }, { "input_text": "Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls .", "target_text": { "IL-8": "protein", "IL-8 antigen": "protein" } }, { "input_text": "In mice exposed to hypoxia ( PO2 approximately 30-40 Torr ) , there was increased pulmonary leukostasis , as evidenced by increased myeloperoxidase activity in tissue homogenates .", "target_text": { "myeloperoxidase": "protein" } }, { "input_text": "In parallel , increased levels of transcripts for IP-10 , a murine homologue in the chemokine family related to IL-8 , were observed in hypoxic lung tissue .", "target_text": { "IP-10": "protein", "chemokine family": "protein", "IL-8": "protein" } }, { "input_text": "Taken together , these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis .", "target_text": {} }, { "input_text": "Thrombin and thrombin receptor agonist peptide induce early events of T cell activation and synergize with TCR cross-linking for CD69 expression and interleukin 2 production .", "target_text": { "Thrombin": "protein", "thrombin receptor": "protein", "TCR": "protein", "CD69": "protein" } }, { "input_text": "Thrombin stimulation of the T leukemic cell line Jurkat induced a transient increase in [ Ca2+ ]i .", "target_text": { "Thrombin": "protein", "T leukemic cell line Jurkat": "cell_line" } }, { "input_text": "Proteolytic activity of the enzyme was required for this effect since diisopropyl fluorophosphate-thrombin failed to increase [ Ca2+ ]i .", "target_text": { "enzyme": "protein", "diisopropyl fluorophosphate-thrombin": "protein" } }, { "input_text": "Furthermore , hirudin and anti-thrombin III inhibited the thrombin-induced [ Ca2+ ]i rise in Jurkat T cells .", "target_text": { "anti-thrombin III": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "A synthetic thrombin receptor agonist peptide ( TRP ) of 7 residues ( SFLLRNP ) was found to be as effective as thrombin for [ Ca2+ ]i mobilization , and both agonists induced Ca2+ release exclusively from internal stores .", "target_text": { "thrombin receptor": "protein", "thrombin": "protein" } }, { "input_text": "Thrombin stimulated tyrosine phosphorylation of several proteins of molecular mass 40 , 42 , 70 , 120 , and 130 kDa .", "target_text": { "Thrombin": "protein" } }, { "input_text": "There was a good correlation between thrombin -induced tyrosine phosphorylation of the latter three proteins and Ca2+ mobilization .", "target_text": { "thrombin": "protein" } }, { "input_text": "Thrombin and TRP also caused translocation of protein kinase C from the cytosol to the plasma membrane .", "target_text": { "Thrombin": "protein", "protein kinase C": "protein" } }, { "input_text": "As a likely consequence of these events , thrombin activated the nuclear factor NF-kB .", "target_text": { "thrombin": "protein", "nuclear factor NF-kB": "protein" } }, { "input_text": "Several cell lines of hematopoietic origin including the leukemic T cell line HPB.ALL and the erythroleukemic cell line K562 were responsive to thrombin , whereas others such as THP1 , a myelomonocytic cell line , and BL2 , a Burkitt lymphoma were refractory to thrombin or TRP stimulation .", "target_text": { "leukemic T cell line HPB.ALL": "cell_line", "erythroleukemic cell line K562": "cell_line", "thrombin": "protein", "THP1": "cell_line", "myelomonocytic cell line": "cell_line", "BL2 ,": "cell_line", "Burkitt lymphoma": "cell_line" } }, { "input_text": "The magnitude of the thrombin response in the different cell types paralleled the expression of the thrombin receptor mRNA .", "target_text": { "thrombin": "protein", "thrombin receptor": "protein", "thrombin receptor mRNA": "RNA" } }, { "input_text": "We found that activation of Jurkat T cells by a combination of phytohemagglutinin and phorbol 12-myristate 13-acetate led to a dramatic inhibition of thrombin receptor mRNA expression and to a concomitant loss of the thrombin response .", "target_text": { "Jurkat T cells": "cell_line", "phytohemagglutinin": "protein", "thrombin": "protein", "thrombin receptor": "protein", "thrombin receptor mRNA": "RNA" } }, { "input_text": "Finally , we demonstrate that thrombin and TRP enhanced CD69 expression and interleukin 2 production induced by T cell receptor cross-linking in both Jurkat T cells and peripheral blood lymphocytes .", "target_text": { "thrombin": "protein", "CD69": "protein", "interleukin 2": "protein", "T cell receptor": "protein", "Jurkat T cells": "cell_line", "lymphocytes": "cell_type" } }, { "input_text": "These findings highlight the role of thrombin as a potential regulator of T lymphocyte activation .", "target_text": { "thrombin": "protein", "T lymphocyte": "cell_type" } }, { "input_text": "Stress response of senescent T lymphocytes : reduced hsp70 is independent of the proliferative block .", "target_text": { "senescent T lymphocytes": "cell_type", "hsp70": "protein" } }, { "input_text": "Senescent human T lymphocyte cultures are unable to undergo proliferation , but show no difference from early passage cells in cytotoxic function or surface antigenic profile .", "target_text": { "Senescent human T lymphocyte cultures": "cell_line", "early passage cells": "cell_line" } }, { "input_text": "A second feature of senescent T cells is the dramatic reduction in hsp70 production in response to heat shock .", "target_text": { "senescent T cells": "cell_line", "hsp70": "protein" } }, { "input_text": "This decline is associated with a decrease in binding of nuclear extracts to the consensus heat shock element .", "target_text": { "consensus heat shock element": "DNA" } }, { "input_text": "Interestingly , the progressive decline in the heat shock response of cultured T cells correlates with the percent proliferative life span completed rather than with the actual proliferative activity at the time of heat shock .", "target_text": { "cultured T cells": "cell_line" } }, { "input_text": "This suggests that for senescent T cells the reduced ability to respond to heat shock by producing hsp70 , although possibly lying at the level of transcriptional control , may nevertheless be unrelated to the reduced DNA synthesis or the diminished proliferative activity also manifested by these cells .", "target_text": { "senescent T cells": "cell_type", "hsp70": "protein", "DNA": "DNA" } }, { "input_text": "Involvement of phospholipase D in the activation of transcription factor AP-1 in human T lymphoid Jurkat cells .", "target_text": { "phospholipase D": "protein", "AP-1": "protein", "transcription factor AP-1": "protein", "Jurkat cells": "cell_line", "human T lymphoid Jurkat cells": "cell_line" } }, { "input_text": "The induction of the AP-1 transcription factor has been ascribed to the early events leading to T lymphocyte activation .", "target_text": { "AP-1": "protein", "transcription factor": "protein" } }, { "input_text": "We have examined the possibility that stimulation of phospholipase D ( PLD ) may regulate activation of transcription factor AP-1 in human T cells by transfecting human T lymphocyte Jurkat cells with a plasmid containing an AP-1 enhancer element and a chloramphenicol acetyltransferase reporter gene .", "target_text": { "phospholipase D": "protein", "PLD": "protein", "AP-1": "protein", "transcription factor AP-1": "protein", "Jurkat cells": "cell_line", "T lymphocyte Jurkat cells": "cell_line", "AP-1 enhancer": "DNA", "AP-1 enhancer element": "DNA", "chloramphenicol acetyltransferase": "protein", "chloramphenicol acetyltransferase reporter gene": "DNA" } }, { "input_text": "We have detected activatable PLD in Jurkat cells , and we have found that addition of phosphatidic acid ( PA ) , the physiologic product of PLD action on phospholipids , is rapidly incorporated into Jurkat cells and leads to activation of transcription factor AP-1 .", "target_text": { "PLD": "protein", "Jurkat cells": "cell_line", "AP-1": "protein", "transcription factor AP-1": "protein" } }, { "input_text": "Treatment of Jurkat cells with anti-CD3 mAb activated both PLD and transcription factor AP-1 .", "target_text": { "Jurkat cells": "cell_line", "anti-CD3 mAb": "protein", "PLD": "protein", "AP-1": "protein", "transcription factor AP-1": "protein" } }, { "input_text": "Wortmannin , an inhibitor of receptor-coupled PLD activation , blocked the anti-CD3 -induced increases in both PLD activity and AP-1 enhancer activity .", "target_text": { "PLD": "protein", "anti-CD3": "protein", "AP-1 enhancer": "DNA" } }, { "input_text": "We found a good correlation in the transfected cells between PLD activation and induction of AP-1 enhancer activity under different experimental conditions .", "target_text": { "transfected cells": "cell_line", "PLD": "protein", "AP-1 enhancer": "DNA" } }, { "input_text": "Furthermore , ethanol , an inhibitor of the PLD pathway , blocked the anti-CD3-stimulated AP-1 enhancer activity .", "target_text": { "PLD": "protein", "AP-1 enhancer": "DNA" } }, { "input_text": "However , this anti-CD3 -mediated response was not inhibited by neomycin , an inhibitor of phosphoinositide hydrolysis .", "target_text": { "anti-CD3": "protein" } }, { "input_text": "The increases in AP-1 enhancer activity induced by PA or anti-CD3 mAb were efficiently abrogated by the presence of propranolol , an inhibitor of PA phosphohydrolase and protein kinase C ( PKC ) .", "target_text": { "AP-1 enhancer": "DNA", "anti-CD3 mAb": "protein", "phosphohydrolase": "protein", "protein kinase C": "protein", "PKC": "protein" } }, { "input_text": "Furthermore , the PA - and the anti-CD3 -induced increases in AP-1 enhancer activity were blocked by the presence of PKC inhibitors or by PKC down-regulation .", "target_text": { "anti-CD3": "protein", "AP-1 enhancer": "DNA", "PKC": "protein" } }, { "input_text": "These data indicate that PLD stimulation can activate the transcription factor AP-1 in T lymphocytes , and suggest that the induction of AP-1 enhancer factor activity by PA is mediated via PKC stimulation , either through a direct activating effect of PA or through PA -derived diacylglycerol formation .", "target_text": { "PLD": "protein", "AP-1": "protein", "transcription factor AP-1": "protein", "T lymphocytes": "cell_type", "AP-1 enhancer": "DNA", "PKC": "protein" } }, { "input_text": "These data also provide evidence for a role of PLD -derived lipids in the induction of AP-1 enhancer activity resulting from stimulation of the TCR/CD3 complex , suggesting that increased PLD activity can play an important role in T lymphocyte activation .", "target_text": { "PLD": "protein", "AP-1 enhancer": "DNA", "TCR/CD3 complex": "protein", "T lymphocyte": "cell_type" } }, { "input_text": "Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1 : a B-cell-specific response that is delayed relative to NF-kappa B activation and to induction of cell surface markers .", "target_text": { "bcl-2": "DNA", "Epstein-Barr virus latent membrane protein": "protein", "LMP1": "protein", "NF-kappa B": "protein", "cell surface markers": "protein" } }, { "input_text": "An ability of the Epstein-Barr virus latent membrane protein LMP1 to enhance the survival of infected B cells through upregulation of the bcl-2 oncogene was first suggested by experiments involving gene transfection and the selection of stable LMP1 + clones ( S.Henderson , M. Rowe , C.Gregory , F.Wang , E.Kieff , and A.Rickinson , Cell 65 : 1107-1115 , 1991 ) .", "target_text": { "Epstein-Barr virus latent membrane protein": "protein", "LMP1": "protein", "infected B cells": "cell_type", "bcl-2": "DNA", "bcl-2 oncogene": "DNA", "LMP1 + clones": "cell_line" } }, { "input_text": "However , it was not possible to ascertain whether Bcl-2 upregulation was a specific consequence of LMP1 expression or an artifact of the selection procedure whereby rare Bcl-2 + cells already present in the starting population might best be able to tolerate the potentially toxic effects of LMP1 .", "target_text": { "Bcl-2": "protein", "LMP1": "protein", "Bcl-2 + cells": "cell_line" } }, { "input_text": "We therefore reexamined this issue by using two different experimental approaches that allowed LMP1 -induced effects to be monitored immediately following expression of the viral protein and in the absence of selective pressures ; activation of the NF-kappa B transcription factor and upregulation of the cell adhesion molecule ICAM-1 were used as early indices of LMP1 function .", "target_text": { "LMP1": "protein", "NF-kappa B": "protein", "transcription factor": "protein", "cell adhesion molecule": "protein", "ICAM-1": "protein" } }, { "input_text": "In the first approach , stable clones of two B-cell lines carrying an LMP1 gene under the control of an inducible metallothionein promoter were induced to express LMP1 in all cells .", "target_text": { "B-cell lines": "cell_line", "LMP1": "protein", "metallothionein promoter": "DNA" } }, { "input_text": "Activation of NK-kappa B and upregulation of ICAM-1 occurred within 24 h and were followed at 48 to 72 h by upregulation of Bcl-2 .", "target_text": { "NK-kappa B": "protein", "ICAM-1": "protein", "Bcl-2": "protein" } }, { "input_text": "In the second approach , we tested the generality of this phenomenon by transiently expressing LMP1 from a strong constitutively active promoter in a range of different cell types .", "target_text": { "LMP1": "protein" } }, { "input_text": "All six B-cell lines tested showed NF-kappa B activation in response to LMP1 expression , and this was followed in five of six lines by expression of ICAM-1 and Bcl-2 .", "target_text": { "B-cell lines": "cell_line", "NF-kappa B": "protein", "LMP1": "protein", "ICAM-1": "protein", "Bcl-2": "protein" } }, { "input_text": "In the same experiments , all three non- B-cell lines showed NF-kappa B activation and ICAM-1 upregulation but never any effect upon Bcl-2 .", "target_text": { "B-cell lines": "cell_line", "NF-kappa B": "protein", "ICAM-1": "protein", "Bcl-2": "protein" } }, { "input_text": "We therefore conclude that Bcl-2 upregulation is part of the panoply of cellular changes induced by LMP1 but that the effect is cell type specific .", "target_text": { "Bcl-2": "protein", "LMP1": "protein" } }, { "input_text": "Our data also suggest that whilst NF-kappa B may be an essential component of LMP1 signal transduction , other cell-specific factors may be required to effect some functions of the viral protein .", "target_text": { "NF-kappa B": "protein", "LMP1": "protein", "cell-specific factors": "protein", "viral protein": "protein" } }, { "input_text": "Long-term inositol phosphate release , but not tyrosine kinase activity , correlates with IL-2 secretion and NF-AT induction in anti-CD3-activated peripheral human T lymphocytes .", "target_text": { "tyrosine kinase": "protein", "IL-2": "protein", "NF-AT": "protein", "anti-CD3-activated peripheral human T lymphocytes": "cell_line" } }, { "input_text": "The cascade of events within the first few minutes of T cell stimulation has been well characterized .", "target_text": { "T cell": "cell_type" } }, { "input_text": "Although many second messengers have been shown to be necessary and sufficient for T cell activation in a number of model systems , the rate-limiting step in peripheral T cells has not been demonstrated .", "target_text": { "T cell": "cell_type", "peripheral T cells": "cell_type" } }, { "input_text": "To model effective versus ineffective CD3 -mediated stimulation in peripheral T cells , we used two anti-CD3 mAbs that differ in their ability to stimulate purified T cells : OKT3 , which causes early second messenger generation but is unable to activate T cells without a second signal , and 64.1 , which stimulates T cell proliferation on its own .", "target_text": { "CD3": "protein", "peripheral T cells": "cell_type", "anti-CD3 mAbs": "protein", "purified T cells": "cell_type", "OKT3": "protein", "T cells": "cell_type", "64.1": "protein", "T cell": "cell_type" } }, { "input_text": "We found that tyrosine kinase activity was similar for both mAbs over a period of hours .", "target_text": { "tyrosine kinase": "protein", "mAbs": "protein" } }, { "input_text": "However , the inositol phosphate response was stronger for 64.1 than for OKT3 .", "target_text": { "64.1": "protein", "OKT3": "protein" } }, { "input_text": "To tie these events to gene activation , we measured NF-kappa B and NF-AT activity in the nucleus after anti-CD3 stimulation .", "target_text": { "NF-kappa B": "protein", "NF-AT": "protein", "anti-CD3": "protein" } }, { "input_text": "Both stimuli induced the appearance of the NF-kappa B components ( c-Rel , p65 ( RelA ) , and p50 ( NF-kappa B1 ) ) and NF-kappa B DNA binding activity in the nucleus .", "target_text": { "NF-kappa B": "protein", "NF-kappa B components": "protein", "c-Rel": "protein", "p65": "protein", "RelA": "protein", "p50": "protein", "NF-kappa B1": "protein" } }, { "input_text": "However , only 64.1 induced NF-AT in the nucleus , correlating with its ability to activate T cells .", "target_text": { "64.1": "protein", "NF-AT": "protein", "T cells": "cell_type" } }, { "input_text": "Thus , NF-AT induction and IL-2 secretion were correlated with the levels of inositol phosphate release but not with gross levels of tyrosine kinase activity induced late following the response .", "target_text": { "NF-AT": "protein", "IL-2": "protein", "tyrosine kinase": "protein" } }, { "input_text": "On the other hand , NF-kappa B induction and IL-2 receptor expression occurred even with the smaller second messenger response generated by OKT3 .", "target_text": { "NF-kappa B": "protein", "IL-2": "protein", "OKT3": "protein" } }, { "input_text": "HLA-DR- , CD33+ , CD56+ , CD16- myeloid/natural killer cell acute leukemia : a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3 [ see comments ]", "target_text": {} }, { "input_text": "We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer ( NK ) cells .", "target_text": {} }, { "input_text": "From a consecutive series of 350 cases of adult de novo acute myeloid leukemia ( AML ) , we identified 20 cases ( 6 % ) with a unique immunophenotype : CD33+ , CD56+ , CD11a+ , CD13lo , CD15lo , CD34+/- , HLA-DR - , CD16 - .", "target_text": { "HLA-DR": "protein", "CD16": "protein" } }, { "input_text": "Multicolor flow cytometric assays confirmed the coexpression of myeloid ( CD33 , CD13 , CD15 ) and NK cell-associated ( CD56 ) antigens in each case , whereas reverse transcription polymerase chain reaction ( RT-PCR ) assays confirmed the identity of CD56 ( neural cell adhesion molecule ) in leukemic blasts .", "target_text": { "CD56": "protein", "neural cell adhesion molecule": "protein", "leukemic blasts": "cell_type" } }, { "input_text": "Although two cases expressed CD4 , no case expressed CD2 , CD3 , or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor ( TCR beta , gamma , delta ) .", "target_text": { "CD4": "protein", "CD2": "protein", "CD3": "protein", "CD8": "protein", "T-cell receptor": "protein" } }, { "input_text": "Leukemic blasts in the majority of cases shared unique morphologic features ( deeply invaginated nuclear membranes , scant cytoplasm with fine azurophilic granularity , and finely granular Sudan black B and myeloperoxidase cytochemical reactivity ) that were remarkably similar to those of acute promyelocytic leukemia ( APL ) ; particularly the microgranular variant ( FAB AML -M3v ) .", "target_text": { "myeloperoxidase": "protein", "microgranular variant": "protein", "FAB AML -M3v": "protein" } }, { "input_text": "However , all 20 cases lacked the t(15;17) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha ( RAR alpha ) fusion transcript in RT-PCR assays ; 12 cases had 46,XX or 46,XY karyotypes , whereas 2 cases had abnormalities of chromosome 17q : 1 with del(17)(q25) and the other with t(11;17)(q23;q21) and the promyelocytic leukemia zinc finger/ RAR alpha fusion transcript .", "target_text": { "promyelocytic/retinoic acid receptor alpha": "protein", "RAR alpha": "protein", "promyelocytic/retinoic acid receptor alpha ( RAR alpha ) fusion transcript": "RNA", "chromosome 17q": "DNA", "del(17)(q25)": "DNA", "t(11;17)(q23;q21)": "DNA", "promyelocytic leukemia zinc finger/ RAR alpha fusion transcript": "RNA" } }, { "input_text": "All cases tested ( 6/20 ) , including the case with t(11;17) , failed to differentiate in vitro in response to all-trans retinoic acid ( ATRA ) , suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA .", "target_text": { "t(11;17)": "DNA" } }, { "input_text": "Four of 6 cases tested showed functional NK cell-mediated cytotoxicity , suggesting a relationship between these unique CD33+ , CD56+ , CD16 - acute leukemias and normal CD56+ , CD16- NK precursor cells .", "target_text": { "CD16": "protein", "normal CD56+ , CD16- NK precursor cells": "cell_type" } }, { "input_text": "Using a combination of panning and multiparameter flow cytometric sorting , we identified a normal CD56+ , CD33+ , CD16- counterpart cell at a frequency of 1 % to 2 % in the peripheral blood of healthy individuals .", "target_text": { "normal CD56+ , CD33+ , CD16- counterpart cell": "cell_type" } }, { "input_text": "Our studies suggest that this form of acute leukemia may arise from transformation of a precursor cell common to both the myeloid and NK cell lineages ; thus we propose the designation myeloid/NK acute leukemia .", "target_text": {} }, { "input_text": "Recognition of this new leukemic entity will be important in distinguishing these ATRA -nonresponsive cases from ATRA -responsive true APL .", "target_text": {} }, { "input_text": "IL-4 down-regulates IL-2 - , IL-3 - , and GM-CSF -induced cytokine gene expression in peripheral blood monocytes .", "target_text": { "IL-4": "protein", "IL-2": "protein", "IL-3": "protein", "GM-CSF": "protein" } }, { "input_text": "IL-4 , a product of the T-helper 0 ( Th0 ) and 2 ( Th2 ) subset , was originally described as a B-cell stimulatory factor and has subsequently been found to suppress IL-1 alpha , IL-1 beta , IL-6 , IL-8 , and TNF-alpha gene expression in monocytes stimulated with LPS , and to upregulate IL-1 receptor antagonist ( IL1-RA ) gene expression .", "target_text": { "IL-4": "protein", "Th0": "cell_type", "Th2": "cell_type", "B-cell stimulatory factor": "protein", "monocytes": "cell_type", "IL-1 receptor antagonist ( IL1-RA ) gene": "DNA" } }, { "input_text": "In this study we investigated the effect of IL-4 on the expression of cytokine genes in monocytes evoked by other T-helper cell cytokines : IL-2 , IL-3 , and GM-CSF .", "target_text": { "IL-4": "protein", "cytokine genes": "DNA", "monocytes": "cell_type", "T-helper cell cytokines": "protein", "IL-2": "protein", "IL-3": "protein", "GM-CSF": "protein" } }, { "input_text": "IL-4 down-regulated mRNA accumulation of the proinflammatory cytokines IL-1 beta , IL-8 , and TNF-alpha in monocytes stimulated with IL-2 , IL-3 , and GM-CSF .", "target_text": { "IL-4": "protein", "proinflammatory cytokines": "protein", "IL-1 beta": "protein", "IL-8": "protein", "TNF-alpha": "protein", "monocytes": "cell_type", "IL-2": "protein", "IL-3": "protein", "GM-CSF": "protein" } }, { "input_text": "IL-4 also suppressed the IL-2 -induced IL-6 mRNA expression .", "target_text": { "IL-4": "protein", "IL-2": "protein", "IL-6": "protein" } }, { "input_text": "Temporal analysis of the IL-4 down-regulatory effect on the IL-2- , IL-3- , or GM-CSF- induced proinflammatory cytokine gene expression in monocytes provided evidence that IL-4 acts predominantly on the post-transcriptional level .", "target_text": { "IL-4": "protein", "monocytes": "cell_type" } }, { "input_text": "This was supported by the observation that the down-regulatory capacity of IL-4 appeared to be dependent on de novo protein synthesis .", "target_text": { "IL-4": "protein" } }, { "input_text": "IL-4 did not exert significant influence on the induction of expression of IL-1-RA or various CSFs by IL-2 , IL-3 , and GM-CSF .", "target_text": { "IL-4": "protein", "IL-1-RA": "protein", "CSFs": "protein", "IL-2": "protein", "IL-3": "protein", "GM-CSF": "protein" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "Induction of proto-oncogene and cytokine expression in human peripheral blood monocytes and the monocytic cell line THP-1 after stimulation with mycoplasma-derived material MDHM .", "target_text": { "proto-oncogene": "DNA", "cytokine": "protein", "monocytes": "cell_type", "monocytic cell line": "cell_line", "THP-1": "cell_line" } }, { "input_text": "Mycoplasma fermentans-derived high-molecular-weight material ( MDHM ) was originally described to induce differentiation of murine thymocytes to cytolytic effector T-cells by stimulating IL-6 release from adherent cells .", "target_text": { "murine thymocytes": "cell_type", "cytolytic effector T-cells": "cell_type", "IL-6": "protein", "adherent cells": "cell_type" } }, { "input_text": "This study shows that human peripheral blood monocytes ( PBMo ) also respond to MDHM with increases in IL-1 beta , IL-6 and TNF alpha expression , both at the mRNA and protein level .", "target_text": { "monocytes": "cell_type", "PBMo": "cell_type", "IL-1 beta": "protein", "IL-6": "protein", "TNF alpha": "protein" } }, { "input_text": "The induced expression of IL-1 beta and TNF alpha mRNA in the monocytic THP-1 cell line increased as quickly as in primary cells .", "target_text": { "THP-1 cell line": "cell_line", "primary cells": "cell_type" } }, { "input_text": "In contrast to PBMo , THP-1 and 14 other monocytic/myeloid leukemia-derived cell lines did not secrete measurable amounts of the cytokines upon treatment with MDHM .", "target_text": { "PBMo": "cell_type", "THP-1": "cell_line", "monocytic/myeloid leukemia-derived cell lines": "cell_line", "cytokines": "protein" } }, { "input_text": "IL-1 beta and IL-6 genes contain AP-1 binding sites as regulatory elements , the AP-1 protein being composed of c-jun and c-fos gene products .", "target_text": { "IL-1 beta": "protein", "IL-6": "protein", "IL-6 genes": "DNA", "IL-1 beta and IL-6 genes": "DNA", "AP-1": "protein", "AP-1 binding sites": "DNA", "regulatory elements": "DNA" } }, { "input_text": "In THP-1 cells c-jun mRNA expression increased after incubation with MDHM while positive c-fos expression remained unaffected .", "target_text": { "THP-1 cells": "cell_line", "c-jun mRNA": "RNA", "c-fos": "DNA" } }, { "input_text": "Although these data suggest AP-1 regulated cytokine mRNA expression , results from PBMo are not in accordance with this notion .", "target_text": { "AP-1": "protein", "cytokine": "protein", "PBMo": "cell_type" } }, { "input_text": "In the primary cells MDHM -induced elevation of cytokine mRNA levels was preceded by a downregulation of c-fos expression while positive c-jun expression was not modulated .", "target_text": { "primary cells": "cell_type", "cytokine mRNA": "RNA", "c-fos": "DNA", "c-jun": "DNA" } }, { "input_text": "c-myc mRNA expression , constitutively high in THP-1 cells , was induced in MDHM -stimulated PBMo .", "target_text": { "c-myc mRNA": "RNA", "THP-1 cells": "cell_line", "PBMo": "cell_type" } }, { "input_text": "In conclusion , MDHM -stimulated induction of cytokine mRNA expression was accompanied by different proto-oncogene responses in PBMo and THP-1 cells .", "target_text": { "cytokine mRNA": "RNA", "proto-oncogene": "DNA", "PBMo": "cell_type", "THP-1 cells": "cell_line" } }, { "input_text": "These differences may represent different regulatory pathways of the two cell systems .", "target_text": {} }, { "input_text": "Alternatively , these data support the notion that neither AP-1 nor the c-myc protein are involved in the MDHM -induced increase in IL-1 beta , IL-6 or TNF alpha mRNA levels .", "target_text": { "AP-1": "protein", "c-myc protein": "protein" } }, { "input_text": "Furthermore , the present results demonstrate clearly that mycoplasma products can have a profound impact on the activation status of eukaryotic cells .", "target_text": { "mycoplasma products": "protein", "eukaryotic cells": "cell_type" } }, { "input_text": "Novel membrane receptors for aldosterone in human lymphocytes : a 50 kDa protein on SDS-PAGE .", "target_text": { "Novel membrane receptors": "protein", "human lymphocytes": "cell_type", "50 kDa protein": "protein" } }, { "input_text": "Fast in vitro effects of aldosterone on the Na+/H(+)-exchanger , inositoltrisphosphate generation and corresponding specific binding to plasma membranes at Kd-values of approximately 0.1 nM have been found in human mononuclear leukocytes and vascular smooth muscle cells .", "target_text": { "Na+/H(+)-exchanger": "protein", "human mononuclear leukocytes": "cell_type", "vascular smooth muscle cells": "cell_type" } }, { "input_text": "The novel aldosterone membrane receptor was analyzed on SDS-PAGE after labeling of microsomal membranes from human mononuclear leukocytes with a [125I]- aldosterone -derivative by use of BASED as a photoactivatable crosslinker .", "target_text": { "human mononuclear leukocytes": "cell_type" } }, { "input_text": "Binding of 1 nM [125I]- aldosterone was found at a molecular weight of approximately 50 kDa which was absent with 1 microM cold aldosterone , but not cortisol in the binding media .", "target_text": {} }, { "input_text": "This aldosterone -selectivity is typical and discriminatory for the new aldosterone membrane receptor .", "target_text": { "aldosterone membrane receptor": "protein" } }, { "input_text": "Solubilization of the receptor protein from membranes by high salt concentrations ( 1 M NaCl , 1 mM EDTA ) was not achieved .", "target_text": { "receptor protein": "protein" } }, { "input_text": "It , thus , appears as an integral membrane protein .", "target_text": { "integral membrane protein": "protein" } }, { "input_text": "Dithiothreitol , a sulfhydryl agent , does not reduce specific aldosterone binding indicating the absence of SH-groups in the binding domain or sensitive structures of the receptors .", "target_text": { "SH-groups": "protein", "binding domain": "protein" } }, { "input_text": "The results are the first to characterize the novel membrane receptor for aldosterone with regard to molecular weight and basic properties .", "target_text": { "novel membrane receptor": "protein" } }, { "input_text": "These findings and other related results are reviewed here .", "target_text": {} }, { "input_text": "A transcriptional regulatory element is associated with a nuclease-hypersensitive site in the pol gene of human immunodeficiency virus type 1 .", "target_text": { "transcriptional regulatory element": "DNA", "nuclease-hypersensitive site": "DNA", "pol gene": "DNA" } }, { "input_text": "Analysis of the chromatin organization of the integrated human immunodeficiency virus type 1 ( HIV-1 ) genome has previously revealed a major constitutive DNase I-hypersensitive site associated with the pol gene ( E . Verdin , J . Virol . 65 : 6790-6799 , 1991 ) .", "target_text": { "human immunodeficiency virus type 1 ( HIV-1 ) genome": "DNA", "major constitutive DNase I-hypersensitive site": "DNA", "pol gene": "DNA" } }, { "input_text": "In the present report , high-resolution mapping of this site with DNase I and micrococcal nuclease identified a nucleosome-free region centered around nucleotides ( nt ) 4490 to 4766 .", "target_text": { "DNase I": "protein", "micrococcal nuclease": "protein", "nucleosome-free region": "DNA", "nucleotides ( nt ) 4490 to 4766": "DNA" } }, { "input_text": "A 500-bp fragment encompassing this hypersensitive site ( nt 4481 to 4982 ) exhibited transcription-enhancing activity ( two- to threefold ) when it was cloned in its natural position with respect to the HIV-1 promoter after transient transfection in U937 and CEM cells .", "target_text": { "500-bp fragment": "DNA", "hypersensitive site": "DNA", "nt 4481 to 4982": "DNA", "HIV-1 promoter": "DNA", "U937": "cell_line", "CEM cells": "cell_line" } }, { "input_text": "Using in vitro footprinting and gel shift assays , we have identified four distinct binding sites for nuclear proteins within this positive regulatory element .", "target_text": { "binding sites": "DNA", "nuclear proteins": "protein", "positive regulatory element": "DNA" } }, { "input_text": "Site B ( nt 4519 to 4545 ) specifically bound four distinct nuclear protein complexes : a ubiquitous factor , a T-cell-specific factor , a B-cell-specific factor , and the monocyte/macrophage- and B-cell-specific transcription factor PU.1/Spi-1 .", "target_text": { "Site B": "DNA", "nt 4519 to 4545": "DNA", "nuclear protein complexes": "protein", "ubiquitous factor": "protein", "T-cell-specific factor": "protein", "B-cell-specific factor": "protein", "transcription factor": "protein", "monocyte/macrophage- and B-cell-specific transcription factor": "protein", "PU.1/Spi-1": "protein" } }, { "input_text": "In most HIV-1 isolates in which this PU box was not conserved , it was replaced by a binding site for the related factor Ets1 .", "target_text": { "PU box": "DNA", "binding site": "DNA", "Ets1": "protein" } }, { "input_text": "Factors binding to site C ( nt 4681 to 4701 ) had a DNA-binding specificity similar to that of factors binding to site B , except for PU.1/Spi-1 .", "target_text": { "site C": "DNA", "nt 4681 to 4701": "DNA", "site B": "DNA", "PU.1/Spi-1": "protein" } }, { "input_text": "A GC box containing a binding site for Sp1 was identified ( nt 4623 to 4631 ) .", "target_text": { "GC box": "DNA", "binding site": "DNA", "Sp1": "protein", "nt 4623 to 4631": "DNA" } }, { "input_text": "Site D ( nt 4816 to 4851 ) specifically bound a ubiquitously expressed factor .", "target_text": { "Site D": "DNA", "nt 4816 to 4851": "DNA", "ubiquitously expressed factor": "protein" } }, { "input_text": "These results identify a transcriptional regulatory element associated with a nuclease- hypersensitive site in the pol gene of HIV-1 and suggest that its activity may be controlled by a complex interplay of cis- regulatory elements .", "target_text": { "transcriptional regulatory element": "DNA", "hypersensitive site": "DNA", "nuclease- hypersensitive site": "DNA", "pol gene": "DNA", "regulatory elements": "DNA" } }, { "input_text": "Expression of v-src in T cells correlates with nuclear expression of NF-kappa B .", "target_text": { "v-src": "DNA", "T cells": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "NF-kappa B is a rapidly inducible transcriptional activator that responds to a variety of signals and influences the expression of many genes involved in the immune response .", "target_text": { "NF-kappa B": "protein", "transcriptional activator": "DNA" } }, { "input_text": "Protein tyrosine kinases transmit signals from cytokine and immune receptors .", "target_text": { "tyrosine kinases": "protein" } }, { "input_text": "Very little information exists linking these two important classes of signaling molecules .", "target_text": { "signaling molecules": "protein" } }, { "input_text": "We now demonstrate that v-src expression correlates with nuclear expression of a kappa B binding complex similar to that induced by phorbol ester and ionomycin , as detected by electrophoretic mobility shift assay using a variety of kappa B sites .", "target_text": { "v-src": "DNA", "kappa B binding complex": "protein", "kappa B sites": "DNA" } }, { "input_text": "This complex was blocked by the tyrosine kinase inhibitor , herbimycin A .", "target_text": { "tyrosine kinase": "protein" } }, { "input_text": "The v-src -induced complex comprised the p50 and p65 components of NF-kappa B , as determined by supershift and immunoblot analysis .", "target_text": { "v-src": "DNA", "v-src -induced complex": "protein", "p50": "protein", "p65": "protein", "NF-kappa B": "protein" } }, { "input_text": "As a functional correlate of this finding , transient co-transfection of HIV-1 LTR reporter constructs in a different T cell line demonstrated that v-src activated this promoter in a kappa B-dependent manner .", "target_text": { "HIV-1 LTR": "DNA", "HIV-1 LTR reporter constructs": "DNA", "T cell line": "cell_line", "v-src": "DNA", "promoter": "protein" } }, { "input_text": "We found that transactivation of the HIV-1 LTR by v-src was more sensitive to mutations of the proximal , rather than the distal , kappa B element .", "target_text": { "HIV-1 LTR": "DNA", "v-src": "DNA", "kappa B element": "DNA" } }, { "input_text": "The implications for T cell receptor signaling and HIV-1 gene expression are considered .", "target_text": { "T cell receptor": "protein", "HIV-1 gene": "DNA" } }, { "input_text": "trans-activation of the HIV promoter by a cDNA and its genomic clones of human herpesvirus-6 .", "target_text": { "HIV promoter": "DNA" } }, { "input_text": "Human herpesvirus 6 ( HHV-6 ) is a lymphotropic herpesvirus , and in vitro , it can productively infect human CD4+ T cells as HIV-1 .", "target_text": { "CD4+ T cells": "cell_line" } }, { "input_text": "Co-infection of T cells by HIV-1 and HHV-6 can lead to both activation of the HIV-1 promoter and acceleration of the cytopathic effects .", "target_text": { "T cells": "cell_type", "HIV-1 promoter": "DNA" } }, { "input_text": "An HHV-6 ( GS ) cDNA clone , pCD41 , encoding for a 41-kDa nuclear protein was identified and characterized previously ( Chang and Balachandran , J. Virol . 65 , 2884-2894 and 7085 , 1991 ) .", "target_text": { "HHV-6 ( GS ) cDNA clone": "DNA", "pCD41": "DNA", "41-kDa nuclear protein": "protein" } }, { "input_text": "Sequence analyses show that this protein has significant homology with the human cytomegalovirus UL44 gene coding for the ICP36 family of early-late-class phosphoprotein .", "target_text": { "human cytomegalovirus UL44 gene": "DNA", "ICP36 family": "protein", "early-late-class phosphoprotein": "protein" } }, { "input_text": "Using this cDNA as the probe , a 3.8-kb EcoRI genomic fragment encoding the HHV-6 ( GS ) P41 was cloned and designated as pGD41 .", "target_text": { "cDNA": "DNA", "3.8-kb EcoRI genomic fragment": "DNA", "HHV-6 ( GS ) P41": "protein", "pGD41": "DNA" } }, { "input_text": "When cotransfected with the HIV LTR CAT into CV-1 cells , both the pCD41 and pGD41 clones trans-activated the HIV LTR .", "target_text": { "HIV LTR CAT": "DNA", "CV-1 cells": "cell_line", "pCD41": "DNA", "pGD41": "DNA", "HIV LTR": "DNA" } }, { "input_text": "Sequence analyses of pCD41 indicate that there are two potential open reading frames ( ORFs ) , A and B , which are homologous to the ORFs found in the genomic clone pGD41 .", "target_text": { "pCD41": "DNA", "open reading frames": "DNA", "ORFs": "DNA", "A": "DNA", "B": "DNA", "pGD41": "DNA" } }, { "input_text": "Deletion constructs of the pCD41 clone demonstrated that ORF-A was critical for the HIV LTR activation .", "target_text": { "pCD41": "DNA", "pCD41 clone": "DNA", "ORF-A": "protein", "HIV LTR": "DNA" } }, { "input_text": "Deletion analyses of the pCD41 ORF-A and the use of promoter constructs further mapped an internal functional promoter within the pCD41 sequence that can direct the synthesis of the trans-activating protein .", "target_text": { "pCD41": "DNA", "ORF-A": "protein", "promoter constructs": "DNA", "trans-activating protein": "protein" } }, { "input_text": "By using HIV LTR deletion mutants , the NF-kappa B binding sites were found to be critical for response to the pCD41 trans-activation .", "target_text": { "HIV LTR": "DNA", "HIV LTR deletion mutants": "DNA", "NF-kappa B": "protein", "binding sites": "DNA", "pCD41": "DNA" } }, { "input_text": "CD14 -mediated translocation of nuclear factor-kappa B induced by lipopolysaccharide does not require tyrosine kinase activity .", "target_text": { "CD14": "protein", "nuclear factor-kappa B": "protein", "tyrosine kinase": "protein" } }, { "input_text": "During the course of serious bacterial infections , lipopolysaccharide ( LPS ) is believed to interact with macrophage receptors , resulting in the generation of inflammatory mediators and systemic symptoms including hemodynamic instability and shock .", "target_text": { "macrophage receptors": "protein" } }, { "input_text": "CD14 , a glycosylphosphatidylinositol-linked antigen , functions as an LPS signaling receptor .", "target_text": { "CD14": "protein", "glycosylphosphatidylinositol-linked antigen": "protein", "LPS signaling receptor": "protein" } }, { "input_text": "A critical issue concerns the mechanism by which CD14 , which has no transmembrane domain , transduces its signal following LPS binding .", "target_text": { "CD14": "protein", "transmembrane domain": "protein" } }, { "input_text": "Recently , investigators have hypothesized that CD14 -mediated signaling is effected through a receptor-associated tyrosine kinase ( TK ) , suggesting a multicomponent receptor model of LPS signaling .", "target_text": { "CD14": "protein", "tyrosine kinase": "protein" } }, { "input_text": "Wild-type Chinese hamster ovary ( CHO ) -K1 cells can be activated by endotoxin to release arachidonate following transfection with human CD14 ( CHO/ CD14 ) .", "target_text": { "Chinese hamster ovary ( CHO ) -K1 cells": "cell_line", "CD14": "protein", "CHO/ CD14": "protein" } }, { "input_text": "Nuclear translocation of cytosolic NF-kappa B is correlated with a number of LPS -inducible responses .", "target_text": {} }, { "input_text": "We sought to determine if this pathway were present in CHO/ CD14 cells and to elucidate the relationship of NF-kappa B activation to the CD14 receptor system .", "target_text": { "CD14": "protein", "CHO/ CD14 cells": "cell_line", "NF-kappa B": "protein" } }, { "input_text": "LPS -stimulated translocation of NF-kappa B in CHO/ CD14 cells resembled the same response in the murine macrophage-like cell line RAW 264.7 .", "target_text": { "NF-kappa B": "protein", "CD14": "protein", "CHO/ CD14 cells": "cell_line", "murine macrophage-like cell line": "cell_line", "RAW 264.7": "cell_line" } }, { "input_text": "Protein synthesis inhibitors and corticosteroids , which suppress arachidonate release and the synthesis of proinflammatory cytokines , had no effect on translocation of NF-kappa B in CHO/ CD14 or RAW 264.7 cells , demonstrating that NF-kappa B translocation is an early event .", "target_text": { "proinflammatory cytokines": "protein", "NF-kappa B": "protein", "CD14": "protein", "RAW 264.7 cells": "cell_line" } }, { "input_text": "Although TK activity was consistently observed by immunoblotting extracts from activated RAW 264.7 cells , LPS-induced phosphotyrosine residues were not observed from similarly treated CHO/CD14 cells .", "target_text": { "RAW 264.7 cells": "cell_line", "CHO/CD14 cells": "cell_line" } }, { "input_text": "Furthermore , the TK inhibitors herbimycin A and genistein failed to inhibit translocation of NF-kappa B in CHO/CD14 or RAW 264.7 cells , although both of these agents inhibited LPS -induced TK activity in RAW 264.7 cells .", "target_text": { "NF-kappa B": "protein", "CHO/CD14": "cell_line", "RAW 264.7 cells": "cell_line" } }, { "input_text": "These results imply that TK activity is not obligatory for CD14 -mediated signal transduction to occur in response to LPS .", "target_text": { "CD14": "protein" } }, { "input_text": "Signals transduced through the CD4 molecule on T lymphocytes activate NF-kappa B .", "target_text": { "CD4 molecule": "protein", "T lymphocytes": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "We have demonstrated that native envelope glycoproteins of HIV-1 , gp160 can induce activation of the transcription factor , NF-kappa B .", "target_text": { "native envelope glycoproteins": "protein", "transcription factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "The stimulatory effects of gp160 are mediated through the CD4 molecule , since pretreatment with soluble CD4 abrogates its activity .", "target_text": { "CD4 molecule": "protein", "CD4": "protein" } }, { "input_text": "The gp160 -induced NF-kappa B complex consists of p65 , p50 and c-rel proteins .", "target_text": { "NF-kappa B": "protein", "gp160 -induced NF-kappa B complex": "protein", "p65": "protein", "p50": "protein", "c-rel proteins": "protein" } }, { "input_text": "The stimulatory effect of gp160 on NF-kappa B activation is protein synthesis independent , is dependent upon protein tyrosine phosphorylation , and abrogated by inhibitors of protein kinase C .", "target_text": { "NF-kappa B": "protein", "protein kinase C": "protein" } }, { "input_text": "The gp160 -mediated activation of NF-kappa B in CD4 positive T cells may be involved in biological effects , e.g. , enhanced HIV replication , hypergammaglobulinemia , increased cytokine secretion , hypercellularity in bone marrow and apoptosis .", "target_text": { "NF-kappa B": "protein", "CD4": "protein", "CD4 positive T cells": "cell_type", "cytokine": "protein" } }, { "input_text": "No evidence for the expression of the progesterone receptor on peripheral blood lymphocytes during pregnancy [ see comments ]", "target_text": { "progesterone receptor": "protein", "peripheral blood lymphocytes": "cell_type" } }, { "input_text": "The expression of the progesterone receptor in human peripheral blood lymphocytes was analysed , using an enzyme linked immunosorbent assay ( Abbott PgR-EIA monoclonal ) , in order to evaluate its prognostic character in the context of spontaneous abortion .", "target_text": { "progesterone receptor": "protein", "peripheral blood lymphocytes": "cell_type", "human peripheral blood lymphocytes": "cell_type" } }, { "input_text": "Cytosols were prepared from lymphocytes of 24 healthy pregnant women ( 11 first , 10 second and three third trimester ) , seven healthy non-pregnant women , nine women with recurrent spontaneous abortion , and six healthy men .", "target_text": {} }, { "input_text": "In addition , a human breast carcinoma cell line ( ZR-75-1 ) , which expresses the progesterone receptor , was analysed throughout .", "target_text": { "human breast carcinoma cell line": "cell_line", "ZR-75-1": "cell_line", "progesterone receptor": "protein" } }, { "input_text": "The ZR-75-1 cell line showed an expression of 642 fmol/mg whereas lymphocytes of pregnant women showed an expression < or = 4 fmol/mg .", "target_text": { "ZR-75-1 cell line": "cell_line" } }, { "input_text": "Lymphocytes of non-pregnant women , women with threatened pre-term delivery , and men showed equivalent levels : 3 +/- 1 , 3 +/- 2 and 5 +/- 4 fmol/mg respectively .", "target_text": { "Lymphocytes": "cell_type" } }, { "input_text": "These results show that there is no evidence of specific expression of the progesterone receptor in pregnancy and exclude any prognostic character in spontaneous abortion .", "target_text": { "progesterone receptor": "protein" } }, { "input_text": "A role for the progesterone receptor in the mechanism of the known effect of progesterone on peripheral blood lymphocytes is also excluded .", "target_text": { "progesterone receptor": "protein", "peripheral blood lymphocytes": "cell_type" } }, { "input_text": "Tolerance to lipopolysaccharide involves mobilization of nuclear factor kappa B with predominance of p50 homodimers .", "target_text": { "nuclear factor kappa B": "protein", "p50": "protein" } }, { "input_text": "Stimulation of the human monocytic cell line Mono Mac 6 with lipopolysaccharide ( LPS ) leads to rapid and transient expression of cytokines like tumor necrosis factor ( TNF ) .", "target_text": { "human monocytic cell line": "cell_line", "Mono Mac 6": "cell_line", "cytokines": "protein", "tumor necrosis factor": "protein", "TNF": "protein" } }, { "input_text": "When such cells are precultured for 2 days with a low dose of LPS ( 20 ng/ml ) followed by stimulation with a high dose of LPS ( 1 microgram/ml ) , expression of the TNF gene is minimal , i.e. the cells are tolerant .", "target_text": { "TNF": "protein", "TNF gene": "DNA" } }, { "input_text": "In nuclear run-on analysis , such tolerant cells show only a low degree of transcription , indicating that tolerance operates at or upstream of the transcription level .", "target_text": { "tolerant cells": "cell_type" } }, { "input_text": "The CD14 LPS receptor is , however , up-regulated ( not down-regulated ) in tolerant cells , and LPS can , in fact , still lead to activation of tolerant cells as evidenced by mobilization of the transcription factor nuclear factor kappa B ( NF-kappa B ) .", "target_text": { "CD14": "protein", "tolerant cells": "cell_line", "transcription factor": "protein", "nuclear factor kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "Resolution of the NF-kappa B complex in gel shift analysis shows that the binding protein , mobilized in naive Mono Mac 6 cells , consists mainly of p50 -p65 heterodimers , while in tolerant cells , the p50 homodimer is predominant .", "target_text": { "NF-kappa B": "protein", "NF-kappa B complex": "protein", "binding protein": "protein", "naive Mono Mac 6 cells": "cell_line", "p50": "protein", "-p65": "protein", "p50 -p65 heterodimers": "protein", "tolerant cells": "cell_line", "p50 homodimer": "protein" } }, { "input_text": "This increase in p50 homodimers coincides with an increase in p105 mRNA , suggestive of a transcriptional up-regulation of p50 .", "target_text": { "p50": "protein", "p50 homodimers": "protein", "p105 mRNA": "RNA" } }, { "input_text": "Reporter gene analysis reveals that the NF-kappa B complex mobilized in tolerant cells is functionally inactive in that NF-kappa B -dependent luciferase constructs containing the human immunodeficiency virus long terminal repeat or the TNF 5'-region show only minimal transactivation after LPS stimulation .", "target_text": { "NF-kappa B": "protein", "NF-kappa B complex": "protein", "tolerant cells": "cell_line", "NF-kappa B -dependent luciferase constructs": "DNA", "human immunodeficiency virus long terminal repeat": "DNA", "TNF": "protein", "TNF 5'-region": "DNA" } }, { "input_text": "Similar to Mono Mac 6 cells , primary blood monocytes , when precultured with a low dose of LPS , also become tolerant and produce little TNF after LPS stimulation .", "target_text": { "Mono Mac 6 cells": "cell_line", "primary blood monocytes": "cell_type", "TNF": "protein" } }, { "input_text": "The tolerant blood monocytes also up-regulate CD14 , and they mobilize NF-kappa B with a predominance of p50 homodimers .", "target_text": { "tolerant blood monocytes": "cell_type", "CD14": "protein", "NF-kappa B": "protein", "p50": "protein", "p50 homodimers": "protein" } }, { "input_text": "Taken together , these results demonstrate that tolerance to LPS is determined by post-receptor mechanisms that involve an altered composition of the NF-kappa B complex .", "target_text": { "NF-kappa B": "protein", "NF-kappa B complex": "protein" } }, { "input_text": "Analysis of Oct2-isoform expression in lipopolysaccharide -stimulated B lymphocytes .", "target_text": { "Oct2-isoform": "protein", "lipopolysaccharide -stimulated B lymphocytes": "cell_line" } }, { "input_text": "Oct2-isoform expression in splenic B cells stimulated with lipopolysaccharide or lipopolysaccharide plus phorbol-di-butyrate was analysed by cDNA cloning .", "target_text": { "Oct2-isoform": "protein", "splenic B cells": "cell_type" } }, { "input_text": "The frequency of Oct2-positive clones was 1/15,000 in both libraries .", "target_text": { "Oct2-positive clones": "cell_line" } }, { "input_text": "Two new isoforms were found that generate novel amino- or carboxy- terminal sequences .", "target_text": {} }, { "input_text": "An isoform lacking exon 11 destroyed the carboxy-terminal leucin-zipper region and introduced a frame shift creating a novel , proline -rich carboxy terminus .", "target_text": { "exon 11": "DNA", "carboxy-terminal leucin-zipper region": "protein", "proline -rich carboxy terminus": "protein" } }, { "input_text": "A new exon containing a highly basic region ( 4c ) was characterized , between exons 4 and 5 .", "target_text": { "exon": "DNA", "between exons 4 and 5": "DNA" } }, { "input_text": "This exon was inserted between glutamine-rich regions 2 and 3 , carboxy terminal of a tentative leucine-zipper structure .", "target_text": { "glutamine-rich regions 2 and 3": "DNA", "between glutamine-rich regions 2 and 3": "DNA", "carboxy terminal": "protein", "leucine-zipper structure": "protein" } }, { "input_text": "In addition , a new combination isoform containing Oct2a 's amino terminal insert ( exon 7a ) and Oct2b 's carboxy terminal insert ( exon 13 ) was found that created a novel large isoform , Oct2ab .", "target_text": { "Oct2a": "protein", "Oct2a 's amino terminal insert": "protein", "exon 7a": "DNA", "Oct2b": "protein", "Oct2b 's carboxy terminal insert": "protein", "exon 13": "DNA", "Oct2ab": "protein" } }, { "input_text": "More frequent use of the classical Oct2a and Oct2b isoforms was observed in the lipopolysaccharide -stimulated B cells , while a preference for the Oct2ab and Oct2ba isoforms was observed in lipopolysaccharide plus phorbol-di-butyrate -treated cells .", "target_text": { "Oct2a": "protein", "Oct2b": "protein", "lipopolysaccharide -stimulated B cells": "cell_line", "Oct2ab": "protein", "Oct2ba": "protein", "lipopolysaccharide plus phorbol-di-butyrate -treated cells": "cell_line" } }, { "input_text": "Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells .", "target_text": { "transcription factor": "protein", "GATA-1": "protein", "differentiating erythroid cells": "cell_type" } }, { "input_text": "The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid , megakaryocyte , and mast cell lineages .", "target_text": { "transcription factor": "protein", "zinc finger transcription factor": "protein", "GATA-1": "protein" } }, { "input_text": "GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes .", "target_text": { "GATA-1": "protein", "WGATAR consensus motifs": "DNA", "regulatory regions": "DNA", "erythroid cell-specific genes": "DNA" } }, { "input_text": "Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation .", "target_text": { "cultured cells": "cell_line", "GATA-1": "protein", "globin gene": "DNA" } }, { "input_text": "Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development .", "target_text": { "GATA-1": "protein", "GATA-1 gene": "DNA", "embryonic stem cells": "cell_type" } }, { "input_text": "Efficient rescue of the defect requires an intact GATA element in the distal promoter , suggesting autoregulatory control of GATA-1 transcription .", "target_text": { "GATA element": "DNA", "distal promoter": "DNA", "GATA-1": "protein" } }, { "input_text": "To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop , we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei .", "target_text": { "GATA-1": "protein", "regulatory factors": "protein", "erythroid factors": "protein", "GATA-1 gene": "DNA" } }, { "input_text": "We show here that proerythroblasts and mature erythroid cells contain a diffusible activity ( TAG ) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells .", "target_text": { "proerythroblasts": "cell_type", "mature erythroid cells": "cell_type", "GATA-1": "protein", "erythroid cells": "cell_type" } }, { "input_text": "Nuclei from GATA-1 -mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons , indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion .", "target_text": { "GATA-1": "protein", "embryonic stem cells": "cell_type", "GATA-1 -mutant embryonic stem cells": "cell_line", "globin genes": "DNA", "erythroid heterokaryons": "cell_type", "globin gene": "DNA" } }, { "input_text": "Role of HIV-1 Nef expression in activation pathways in CD4 + T cells .", "target_text": { "HIV-1 Nef": "protein", "CD4": "protein" } }, { "input_text": "The role of the human immunodeficiency virus ( HIV-1 ) Nef protein in T cell activation pathways was investigated using a Jurkat CD4 + cell line stably transfected with a Nef expression vector .", "target_text": { "Nef protein": "protein", "human immunodeficiency virus ( HIV-1 ) Nef protein": "protein", "CD4": "protein", "Jurkat CD4 + cell line": "cell_line" } }, { "input_text": "Secretion of IL-2 and TNF-alpha , surface expression of IL-2R , and DNA-binding activity of NF-kappa B and AP-1 ( Fos/Jun ) complex in response to phorbol myristate acetate , TNF-alpha , or immobilized antibodies to CD3 were monitored .", "target_text": { "IL-2": "protein", "TNF-alpha": "protein", "IL-2R": "protein", "NF-kappa B": "protein", "AP-1 ( Fos/Jun ) complex": "protein", "CD3": "protein" } }, { "input_text": "These parameters were not modified by Nef expression in Jurkat cells , whereas stimulation with the same stimuli resulted in partial inhibition of LTR activation in Nef + Jurkat cells .", "target_text": { "Nef": "protein", "Jurkat cells": "cell_line", "LTR": "DNA", "Nef + Jurkat cells": "cell_line" } }, { "input_text": "This inhibition was not mediated through Nef phosphorylation on Thr-15 or GTP -binding activity because mutations in critical sites did not alter this inhibition .", "target_text": { "Nef": "protein" } }, { "input_text": "Analysis of truncated LTRs confirmed that inhibition of LTR activation was not mediated through NF-kappa B -binding activity but through the region containing the negative responding elements ( NREs ) .", "target_text": { "LTRs": "DNA", "LTR": "DNA", "NF-kappa B": "protein", "negative responding elements": "DNA", "NREs": "DNA" } }, { "input_text": "These results suggest that Nef downmodulates LTR activation without significantly inhibiting the capacity of T cells to respond to immunological activations .", "target_text": { "Nef": "protein", "LTR": "DNA", "T cells": "cell_type" } }, { "input_text": "Tat-binding protein 7 is a subunit of the 26S protease .", "target_text": { "Tat-binding protein 7": "protein", "26S protease": "protein" } }, { "input_text": "Subunit 6 ( S6 ) , an integral component of the 26S protease from human erythrocytes , has been studied by SDS-PAGE , peptide mapping and sequence analysis .", "target_text": { "Subunit 6": "protein", "S6": "protein", "26S protease": "protein", "human erythrocytes": "cell_type" } }, { "input_text": "S6 was cleaved with CNBr and three internal peptides were sequenced .", "target_text": { "S6": "protein", "CNBr": "protein" } }, { "input_text": "A comparison with known proteins in Genbank revealed that all three S6 peptides match the predicted sequence of TBP7 , Tat-binding protein 7 .", "target_text": { "S6": "protein", "TBP7": "protein", "Tat-binding protein 7": "protein" } }, { "input_text": "Based on peptide matches covering more than 10 % of the TBP7 sequence , and the fact that the migration of S6 on SDS-PAGE is consistent with the estimated molecular mass for TBP7 , we conclude that subunit 6 of the 26S protease is TBP7 .", "target_text": { "TBP7": "protein", "TBP7 sequence": "protein", "S6": "protein", "subunit 6": "protein", "26S protease": "protein" } }, { "input_text": "Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues .", "target_text": { "nuclear factor kappa B": "protein", "I kappa B alpha": "protein" } }, { "input_text": "The response of mammalian cells to stress is controlled by transcriptional regulatory proteins such as nuclear factor kappa B ( NF-kappa B ) to induce a wide variety of early response genes .", "target_text": { "mammalian cells": "cell_type", "transcriptional regulatory proteins": "protein", "nuclear factor kappa B": "protein", "NF-kappa B": "protein", "early response genes": "DNA" } }, { "input_text": "In this report , we show that exposure of cells to hypoxia ( 0.02 % O2 ) results in I kappa B alpha degradation , increased NF-kappa B DNA binding activity , and transactivation of a reporter gene construct containing two NF-kappa B DNA binding sites .", "target_text": { "I kappa B alpha": "protein", "NF-kappa B": "protein", "reporter gene construct": "DNA", "NF-kappa B DNA binding sites": "DNA" } }, { "input_text": "Pretreatment of cells with protein tyrosine kinase inhibitors and the dominant negative allele of c-Raf-1 ( Raf 301 ) inhibited I kappa B alpha degradation , NF-kappa B binding , and transactivation of kappa B reporter constructs by hypoxia .", "target_text": { "tyrosine kinase": "protein", "dominant negative allele": "DNA", "c-Raf-1": "DNA", "Raf 301": "protein", "I kappa B alpha": "protein", "NF-kappa B": "protein", "kappa B reporter constructs": "DNA" } }, { "input_text": "To demonstrate a direct link between changes in the phosphorylation pattern of I kappa B alpha with NF-kappa B activation , we immunoprecipitated I kappa B alpha after varying times of hypoxic exposure and found that its tyrosine phosphorylation status increased during hypoxic exposure .", "target_text": { "I kappa B alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "Inhibition of the transfer of tyrosine phosphoryl groups onto I kappa B alpha prevented I kappa B alpha degradation and NF-kappa B binding .", "target_text": { "I kappa B alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "In comparison to other activators of NF-kappa B such as phorbol myristate acetate or tumor necrosis factor , we did not detect changes in the tyrosine phosphorylation status of I kappa B alpha following treatment with either of these agents .", "target_text": { "NF-kappa B": "protein", "tumor necrosis factor": "protein", "I kappa B alpha": "protein" } }, { "input_text": "These results suggest that tyrosine phosphorylation of I kappa B alpha during hypoxia is an important proximal step which precedes its dissociation and degradation from NF-kappa B .", "target_text": { "I kappa B alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "Overproduction of NFKB2 ( lyt-10 ) and c-Rel : a mechanism for HTLV-I Tax -mediated trans-activation via the NF-kappa B signalling pathway .", "target_text": { "NFKB2": "protein", "lyt-10": "protein", "c-Rel": "protein", "HTLV-I Tax": "protein", "NF-kappa B": "protein" } }, { "input_text": "Molecular , biochemical and epidemiological evidence implicate HTLV-I as an etiologic agent of adult T cell leukemia ( ATL ) .", "target_text": {} }, { "input_text": "The Tax protein of HTLV-I , a positive transcriptional activator of HTLV-I gene expression , is a viral oncogene that also increases transcription of cellular genes including GM-CSF , IL-2R alpha and IL-2 .", "target_text": { "Tax protein": "protein", "positive transcriptional activator": "protein", "cellular genes": "DNA", "GM-CSF": "protein", "IL-2R alpha": "protein", "IL-2": "protein" } }, { "input_text": "One of the cellular targets of the trans-activating effects of Tax is the NF-kappa B /Rel family of transcription factors , pleiotropic regulators of immunoregulatory , cytokine and viral gene expression .", "target_text": { "NF-kappa B": "protein", "NF-kappa B /Rel family": "protein", "transcription factors": "protein", "pleiotropic regulators": "protein" } }, { "input_text": "In this report , we demonstrate that NFKB2 ( lyt-10 ) and c-Rel are overexpressed in HTLV-I infected and Tax-expressing cells and , together , account for the majority of the constitutive NF-kappa B binding activity in these cells before and after PMA stimulation .", "target_text": { "NFKB2": "protein", "lyt-10": "protein", "c-Rel": "protein", "Tax-expressing cells": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "Most importantly , we show a Tax -dependent correlation between expression of NFKB2 ( p100 ) and processing to the DNA binding NFKB2 ( p52 ) form , induction of c-Rel , and trans-activation of NF-kappa B -mediated gene expression .", "target_text": { "Tax": "protein", "NFKB2": "protein", "p100": "protein", "p52": "protein", "c-Rel": "protein", "NF-kappa B": "protein" } }, { "input_text": "Furthermore , the NFKB2 precursor is physically associated with c-Rel and with Tax in HTLV-I infected cells .", "target_text": { "NFKB2": "protein", "c-Rel": "protein", "Tax": "protein", "HTLV-I infected cells": "cell_type" } }, { "input_text": "We propose that NFKB2 synthesis and processing allows continuous nuclear expression of an otherwise cytoplasmic protein and , in conjunction with overexpression of c-Rel , NFKB2 alters the NF-kappa B signalling pathway and contributes to leukemic transformation of T cells by HTLV-I .", "target_text": { "NFKB2": "protein", "cytoplasmic protein": "protein", "c-Rel": "protein", "NF-kappa B": "protein", "T cells": "cell_type" } }, { "input_text": "Retinoic acid downmodulates erythroid differentiation and GATA1 expression in purified adult-progenitor culture .", "target_text": { "GATA1": "protein", "purified adult-progenitor culture": "cell_line" } }, { "input_text": "All-trans retinoic acid ( RA ) is an important morphogen in vertebrate development , a normal constituent in human adult blood and is also involved in the control of cell growth and differentiation in acute promyelocytic leukemia .", "target_text": {} }, { "input_text": "We have examined the effects of RA on normal hematopoiesis by using early hematopoietic progenitor cells ( HPC ) stringently purified from adult peripheral blood .", "target_text": { "hematopoietic progenitor cells": "cell_type", "HPC": "cell_type" } }, { "input_text": "In clonogenetic fetal calf serum -supplemented ( FCS+ ) or -nonsupplemented ( FCS- ) culture treated with saturating levels of interleukin-3 ( IL-3 ) granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and erythropoietin ( Ep ) ( combined with c-kit ligand in FCS(-)-culture conditions ) , RA induces a dramatic dose-dependent shift from erythroid to granulomonocytic colony formation , the latter colonies being essentially represented by granulocytic clones .", "target_text": { "interleukin-3": "protein", "IL-3": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "erythropoietin": "protein", "Ep": "protein", "c-kit": "protein", "granulocytic clones": "cell_line" } }, { "input_text": "This shift is apparently not caused by a recruitment phenomenon , because in FCS+ culture , the total number of colonies is not significantly modified by RA addition .", "target_text": { "FCS+ culture": "cell_line" } }, { "input_text": "In FCS- liquid-suspension culture supplemented with saturating Ep level and low-dose IL-3 /GM-CSF , adult HPC undergo unilineage erythropoietic differentiation : Here again , treatment with high-dose RA induces a shift from the erythroid to granulocytic differentiation pathway .", "target_text": { "FCS- liquid-suspension culture": "cell_line", "Ep": "protein", "IL-3": "protein", "/GM-CSF": "protein", "low-dose IL-3 /GM-CSF": "protein", "HPC": "cell_type" } }, { "input_text": "Studies on RA time-response or pulse treatment in semisolid or liquid culture show that early RA addition is most effective , thus indicating that early but not late HPC are sensitive to its action .", "target_text": { "HPC": "cell_type" } }, { "input_text": "We then analyzed the expression of the master GATA1 gene , which encodes a finger transcription factor required for normal erythroid development ; addition of RA to HPC stimulated into unilineage erythropoietic differentiation in liquid culture caused a virtually complete inhibition of GATA1 mRNA induction .", "target_text": { "master GATA1 gene": "DNA", "finger transcription factor": "protein", "HPC": "cell_type", "GATA1": "protein", "GATA1 mRNA": "RNA" } }, { "input_text": "These results indicate that RA directly inhibits the erythroid differentiation program at the level of early adult HPC , and may lead to a shift from the erythroid to granulocytic differentiation pathway .", "target_text": { "HPC": "cell_type" } }, { "input_text": "This phenomenon is correlated with inhibition of GATA1 induction in the early stages of erythropoietic differentiation .", "target_text": { "GATA1": "protein" } }, { "input_text": "Induction of phosphatidylinositol turnover and EGR-1 mRNA expression by crosslinking of surface IgM and IgD in the human B cell line B104 .", "target_text": { "EGR-1 mRNA": "RNA", "IgM": "protein", "IgD": "protein", "human B cell line B104": "cell_line" } }, { "input_text": "We have previously shown that a human B lymphoma cell line , B104 , expressed surface IgM ( sIgM ) and surface IgD ( sIgD ) , and that crosslinking of sIgM and sIgD by anti- IgM antibody ( Ab ) and anti- IgD Ab , respectively , induced Ca2+ influx to almost the same degree , whereas only sIgM -crosslinking caused B104 cell death .", "target_text": { "human B lymphoma cell line , B104": "cell_line", "IgM": "protein", "surface IgM": "protein", "sIgM": "protein", "IgD": "protein", "surface IgD": "protein", "sIgD": "protein", "anti- IgM antibody ( Ab )": "protein", "anti- IgD Ab": "protein", "B104 cell": "cell_line" } }, { "input_text": "Here , we investigated the accumulation of cyclic AMP ( cAMP ) , the hydrolysis of inositol phosphates , protein kinase C ( PKC ) activity and the induction of Egr-1 and c-fos mRNA expression by sIgM- and sIgD- crosslinking to examine differences in the signals mediated through sIgM and sIgD in B104 cells .", "target_text": { "protein kinase C": "protein", "PKC": "protein", "sIgM": "protein", "sIgD": "protein", "B104 cells": "cell_line" } }, { "input_text": "Both sIgM- and sIgD- crosslinking with antibodies induced elevation of cAMP levels , phosphatidylinositol turnover , PKC activation and expression of Egr-1 and c-fos mRNA , although sIgM -crosslinking was more effective than sIgD -crosslinking , presumably due to the higher expression of sIgM than of sIgD .", "target_text": { "PKC": "protein", "sIgM": "protein", "sIgD": "protein" } }, { "input_text": "Egr-1 mRNA expression induced by sIgM- and sIgD- crosslinking was inhibited by H7 , erbstatin and genistein , but not by HA1004 .", "target_text": { "Egr-1": "DNA", "Egr-1 mRNA": "RNA", "H7": "protein" } }, { "input_text": "Erbstatin and genistein inhibited the sIg-crosslinking-induced Egr-1 mRNA expression in a dose-dependent manner parallel to that observed in the inhibition of sIg-crosslinking-induced protein tyrosine phosphorylation .", "target_text": { "Egr-1": "DNA", "Egr-1 mRNA": "RNA" } }, { "input_text": "Phorbol myristate acetate induced Egr-1 mRNA expression but forskolin and dibutyryl cyclic AMP did not .", "target_text": { "Egr-1": "DNA", "Egr-1 mRNA": "RNA" } }, { "input_text": "These findings suggest that the Egr-1 mRNA activating signals through sIgM and sIgD are protein tyrosine kinase- and PKC- dependent , but protein kinase A -independent .", "target_text": { "Egr-1": "DNA", "Egr-1 mRNA": "RNA", "sIgM": "protein", "sIgD": "protein", "protein kinase A": "protein" } }, { "input_text": "Cyclosporin A ( CsA ) and FK506 rescued B104 cells from death induced by anti-IgM Ab , but did not affect the expression of Egr-1 and c-fos mRNA , showing that CsA and FK506 affect signal transducers differently from or downstream to these molecules .", "target_text": { "B104 cells": "cell_line", "anti-IgM Ab": "protein", "Egr-1": "protein", "c-fos mRNA": "RNA" } }, { "input_text": "The difference in signals transduced through sIgM and sIgD in B104 cells is discussed .", "target_text": { "sIgM": "protein", "sIgD": "protein", "B104 cells": "cell_line" } }, { "input_text": "Direct exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD ) increases infectivity of human erythrocytes to a malarial parasite .", "target_text": { "human erythrocytes": "cell_type" } }, { "input_text": "Direct exposure to 10 nM 2,3,7,8-TCDD caused a 75 % increase and a 2-fold increase in the infectivity of isolated human erythrocytes to P. falciparum after 48 hours when the parasites were in an unsynchronized or synchronized state of growth , respectively .", "target_text": { "human erythrocytes": "cell_type" } }, { "input_text": "Treatment of human erythrocytes with 10 microM sodium orthovanadate ( NaOV ) , an inhibitor of plasma membrane Ca-ATPase and phosphotyrosine phosphatase , decreased parasitemia by 30 % .", "target_text": { "human erythrocytes": "cell_type", "plasma membrane Ca-ATPase": "protein", "phosphotyrosine phosphatase": "protein" } }, { "input_text": "Co-treatment of RBCs with TCDD and NaOV completely blocked the TCDD -induced increase in parasitemia .", "target_text": { "RBCs": "cell_type" } }, { "input_text": "Because erythrocytes are anucleated , these results are discussed as evidence for biochemical changes by TCDD without requiring the activation of gene products .", "target_text": { "erythrocytes": "cell_type", "gene products": "protein" } }, { "input_text": "Evidence for a trans-acting activator function regulating the expression of the human CD5 antigen .", "target_text": { "trans-acting activator": "protein", "CD5": "protein", "human CD5 antigen": "protein" } }, { "input_text": "Interspecies somatic cell hybrids were generated by fusing the mouse T-lymphoma cell line , BW5147 , with normal human T lymphocytes at different stages of differentiation .", "target_text": { "somatic cell hybrids": "cell_line", "mouse T-lymphoma cell line": "cell_line", "BW5147": "cell_line", "normal human T lymphocytes": "cell_type" } }, { "input_text": "Thymocytes , activated peripheral T lymphocytes , or an activated T-cell clone were used as human partners , respectively , in three independent fusions .", "target_text": { "Thymocytes": "cell_type", "activated peripheral T lymphocytes": "cell_type", "activated T-cell clone": "cell_line" } }, { "input_text": "Irrespective of the human cell partner used for fusion , a certain number of hybrids lost CD5 surface expression over a period of time in culture .", "target_text": { "hybrids": "cell_line", "CD5": "protein" } }, { "input_text": "Analysis at the phenotype and genetic level showed that lack of CD5 expression was due neither to segregation of human autosome 11 , on which the CD5 gene has been mapped , nor to deletion of the CD5 structural gene .", "target_text": { "CD5": "protein", "human autosome 11": "DNA", "CD5 gene": "DNA", "CD5 structural gene": "DNA" } }, { "input_text": "Furthermore , loss of CD5 surface expression correlated with the absence of specific mRNA .", "target_text": { "CD5": "protein", "mRNA": "RNA" } }, { "input_text": "Since these hybrids preferentially segregate human chromosomes , these results indicate the existence of a non-syntenic trans-active locus , or loci , positively controlling the expression of the human CD5 gene .", "target_text": { "non-syntenic trans-active locus": "DNA", "CD5": "protein", "human CD5 gene": "DNA" } }, { "input_text": "Induction of the CD11b gene during activation of the monocytic cell line U937 requires a novel nuclear factor MS-2 [ published erratum appears in J Immunol 1999 Jul 15 ; 163 ( 2 ) : 1091 ]", "target_text": { "CD11b gene": "DNA", "monocytic cell line U937": "cell_line", "nuclear factor": "protein", "MS-2": "protein" } }, { "input_text": "The differentiation of myeloid precursors into mature myelomonocytic cells is characterized by the induction of the gene encoding the beta2 integrin CD11b .", "target_text": { "myeloid precursors": "cell_type", "myelomonocytic cells": "cell_type", "beta2 integrin": "protein", "CD11b": "protein" } }, { "input_text": "The transcription factors Sp1 and PU.1 prime the CD11b promoter , but the nature of the factors responsible for its inducible expression are unknown .", "target_text": { "transcription factors": "protein", "Sp1": "protein", "PU.1 prime": "protein", "CD11b": "protein", "CD11b promoter": "DNA" } }, { "input_text": "In addition to the CD11b gene , the homologous genes encoding CD11a and CD11c also exhibit inducible expression during myeloid differentiation .", "target_text": { "CD11b": "protein", "CD11b gene": "DNA", "CD11a": "protein", "CD11c": "protein" } }, { "input_text": "Therefore , we compared the nucleotide sequences of the CD11a , CD11b , and CD11c gene promoters to identify common elements that might contribute to inducible expression .", "target_text": { "nucleotide sequences": "DNA" } }, { "input_text": "This analysis identified one such element repeated four times within the CD11b promoter .", "target_text": { "CD11b": "protein", "CD11b promoter": "DNA" } }, { "input_text": "Mutation of these elements indicated that two , MS-2beta and MS-2gamma , are critical to the induction of the CD11b gene during differentiation of the pro-monocytic cell line U937 .", "target_text": { "MS-2beta": "protein", "MS-2gamma": "protein", "CD11b": "protein", "CD11b gene": "DNA", "pro-monocytic cell line U937": "cell_line" } }, { "input_text": "Electrophoretic mobility shift assays indicate that MS-2beta and MS-2gamma interact with nuclear factors that are induced during U937 differentiation .", "target_text": { "MS-2beta": "protein", "MS-2gamma": "protein", "nuclear factors": "protein", "U937": "cell_line" } }, { "input_text": "These factors are detected at the time the CD11b promoter is activated .", "target_text": { "CD11b": "protein", "CD11b promoter": "DNA" } }, { "input_text": "The molecular mass of these factors is approximately 28 kDa , and their DNA binding characteristics are indistinguishable from those of the novel nuclear factor MS-2 .", "target_text": { "nuclear factor": "protein", "MS-2": "protein" } }, { "input_text": "Taken together , our data indicate that MS-2 mediates induction of the CD11b gene as cells of the monocytic lineage mature .", "target_text": { "MS-2": "protein", "CD11b": "protein", "CD11b gene": "DNA" } }, { "input_text": "The presence of multiple potential binding sites for MS-2 in the promoter regions of a wide range of genes expressed in mature myeloid cells suggests this factor plays a general role in myeloid differentiation .", "target_text": { "MS-2": "protein", "mature myeloid cells": "cell_type" } }, { "input_text": "Acetylsalicylic acid and sodium salicylate inhibit LPS -induced NF-kappa B/c-Rel nuclear translocation , and synthesis of tissue factor ( TF ) and tumor necrosis factor alfa ( TNF-alpha ) in human monocytes .", "target_text": { "NF-kappa B/c-Rel": "protein", "tissue factor": "protein", "TF": "protein", "tumor necrosis factor alfa": "protein", "TNF-alpha": "protein", "human monocytes": "cell_type" } }, { "input_text": "We have investigated the effects of acetylsalicylic acid and sodium salicylate on the LPS -induced synthesis of the pro-coagulant protein tissue factor ( TF ) and the pro-inflammatory protein tumor necrosis factor-alpha ( TNF-alpha ) , as well as the prostaglandin PGE2 in human monocytes .", "target_text": { "TNF-alpha": "protein", "prostaglandin PGE2": "protein", "human monocytes": "cell_type" } }, { "input_text": "Both drugs dose-dependently inhibited LPS -induced TF and TNF-alpha synthesis at the mRNA and the protein level , and reduced PGE2 production .", "target_text": { "LPS -induced TF": "protein", "TNF-alpha": "protein", "mRNA": "RNA", "PGE2": "protein" } }, { "input_text": "As evidenced by electro mobility shift assay ( EMSA ) and the use of a NF-kappa B prototypic probe , these drugs probably exert their inhibitory effects by interference with the nuclear translocation of NF-kappa B/c-Rel proteins .", "target_text": { "NF-kappa B": "protein", "NF-kappa B prototypic probe": "DNA", "NF-kappa B/c-Rel proteins": "protein" } }, { "input_text": "These data may expand the understanding of the anti-thrombotic and anti-inflammatory effects of these drugs when activation of monocytes occurs .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "Interferon augments PML and PML/RAR alpha expression in normal myeloid and acute promyelocytic cells and cooperates with all-trans retinoic acid to induce maturation of a retinoid-resistant promyelocytic cell line .", "target_text": { "PML": "protein", "PML/RAR alpha": "protein", "myeloid": "cell_type", "acute promyelocytic cells": "cell_type", "retinoid-resistant promyelocytic cell line": "cell_line" } }, { "input_text": "The PML gene is fused to the retinoic acid receptor alpha gene ( RAR alpha ) in the acute promyelocytic leukemia ( APL ) 15 ; 17 translocation .", "target_text": { "PML": "protein", "PML gene": "DNA", "retinoic acid receptor alpha gene": "DNA", "RAR alpha": "DNA" } }, { "input_text": "PML is expressed in diverse tissues and cell lines and localized in the nucleus with a typical speckled pattern .", "target_text": { "PML": "protein" } }, { "input_text": "In the bone marrow , it is preferentially expressed in myeloid cells .", "target_text": { "myeloid cells": "cell_type" } }, { "input_text": "PML appears to be transcriptionally regulated by class I and II interferons , which raises the possibility that interferons modulate the function and growth and differentiation potential of normal myeloid cells and precursors by activating PML -dependent pathways .", "target_text": { "PML": "protein", "myeloid cells": "cell_type" } }, { "input_text": "Similarly , interferons could act on APL cells , alone or in combination with all-trans retinoic acid ( RA ) , especially if the PML/RAR alpha fusion transcript that results from the t(15; 17) is induced by interferon .", "target_text": { "APL cells": "cell_type", "PML/RAR alpha": "protein", "PML/RAR alpha fusion transcript": "RNA", "t(15; 17)": "DNA", "interferon": "protein" } }, { "input_text": "We report here that PML is expressed at low levels or not expressed in normal circulating human monocytes , lymphocytes , and polymorphonucleate cells , but is markedly induced by interferon ; that PML and PML/RAR alpha expression is augmented by interferon in the NB4 APL cell line , which carries the t(15; 17) , and in APL blasts from patients ; that interferon inhibits growth and survival of NB4 APL cells in cooperation with RA ; that interferons alone have minimal maturation effect on NB4 cells ; and , finally , that interferon gamma , but not alpha or beta , induces maturation and growth suppression of NB4 cells with de novo retinoid resistance , and partially restores RA response .", "target_text": { "PML": "protein", "monocytes": "cell_type", "human monocytes": "cell_type", "lymphocytes": "cell_type", "polymorphonucleate cells": "cell_type", "interferon": "protein", "PML/RAR alpha": "protein", "NB4 APL cell line": "cell_line", "t(15; 17)": "DNA", "APL blasts": "cell_type", "APL cells": "cell_type", "NB4 cells": "cell_line" } }, { "input_text": "Effects of Ara-C on neutral sphingomyelinase and mitogen- and stress- activated protein kinases in T-lymphocyte cell lines .", "target_text": { "neutral sphingomyelinase": "protein", "T-lymphocyte cell lines": "cell_line" } }, { "input_text": "Neutral sphingomyelinase ( SMase ) can be activated by extracellular signals to produce ceramide , which may affect mitogen-activated protein kinase ( MAPK ) activities .", "target_text": { "Neutral sphingomyelinase": "protein", "SMase": "protein", "mitogen-activated protein kinase": "protein", "MAPK": "protein" } }, { "input_text": "Neutral SMase activity was assessed in membranes from Jurkat , a human T-cell line , and EL4 , a murine T-cell line .", "target_text": { "SMase": "protein", "Jurkat": "cell_line", "human T-cell line": "cell_line", "EL4": "cell_line", "murine T-cell line": "cell_line" } }, { "input_text": "Ara-C activated SMase with 10 minutes in both Jurkat and EL4 cells , while phorbol ester ( PMA ) had no effect .", "target_text": { "SMase": "protein", "EL4 cells": "cell_line" } }, { "input_text": "PMA , but not Ara-C or ceramides , activated ERK MAPKS , in Jurkat and EL4 .", "target_text": { "ERK MAPKS": "protein", "Jurkat": "cell_line", "EL4": "cell_line" } }, { "input_text": "PMA acted synergistically with ionomycin to activate JNK MAPKs in Jurkat and EL4 within 10 minutes .", "target_text": { "JNK MAPKs": "protein", "Jurkat": "cell_line", "EL4": "cell_line" } }, { "input_text": "Ara-C activated JNKs only after prolonged incubation ( 90-120 minutes ) .", "target_text": { "JNKs": "protein" } }, { "input_text": "Thus , ceramide is not a positive signal for ERK activation in T-cell lines .", "target_text": { "ERK": "protein", "T-cell lines": "cell_line" } }, { "input_text": "The effects of Ara-C on JNK activity may be mediated through secondary response pathways .", "target_text": { "JNK": "protein" } }, { "input_text": "Comparative analysis identifies conserved tumor necrosis factor receptor -associated factor 3 binding sites in the human and simian Epstein-Barr virus oncogene LMP1 .", "target_text": { "tumor necrosis factor receptor": "protein", "tumor necrosis factor receptor -associated factor 3": "protein", "tumor necrosis factor receptor -associated factor 3 binding sites": "DNA", "oncogene LMP1": "DNA" } }, { "input_text": "Nonhuman primates are naturally infected with a B-lymphotropic herpesvirus closely related to Epstein-Barr virus ( EBV ) .", "target_text": {} }, { "input_text": "These simian EBV share considerable genetic , biologic , and epidemiologic features with human EBV , including virus-induced tumorigenesis .", "target_text": {} }, { "input_text": "However , latent , transformation-associated viral genes demonstrate marked sequence divergence among species despite the conserved functions .", "target_text": {} }, { "input_text": "We have cloned the latent membrane protein 1 ( LMP1 ) homologs from the simian EBV naturally infecting baboons ( cercopithicine herpesvirus 12 , herpesvirus papio ) and rhesus monkeys ( cercopithicine herpesvirus 15 ) for a comparative study with the human EBV oncogene .", "target_text": { "latent membrane protein 1": "protein", "LMP1": "protein", "latent membrane protein 1 ( LMP1 ) homologs": "protein" } }, { "input_text": "The transmembrane domains are well conserved , but there is striking sequence divergence of the carboxy-terminal cytoplasmic domain essential for B-cell immortalization and interaction with the tumor necrosis factor receptor signaling pathway .", "target_text": { "carboxy-terminal cytoplasmic domain": "protein", "B-cell": "cell_type", "tumor necrosis factor receptor": "protein" } }, { "input_text": "Nevertheless , the simian EBV LMP1s retain most functions in common with EBV LMP1 , including the ability to induce NF-(kappa)B activity in human cells , to bind the tumor necrosis factor-associated factor 3 ( TRAF3 ) in vitro , and to induce expression of tumor necrosis factor-responsive genes , such as ICAM1 , in human B lymphocytes .", "target_text": { "LMP1s": "protein", "simian EBV LMP1s": "protein", "LMP1": "protein", "NF-(kappa)B": "protein", "human cells": "cell_type", "tumor necrosis factor-associated factor 3": "protein", "TRAF3": "protein", "tumor necrosis factor-responsive genes": "DNA", "ICAM1": "DNA", "human B lymphocytes": "cell_type" } }, { "input_text": "Multiple TRAF3 binding sites containing a PXQXT/S core sequence can be identified in the simian EBV LMP1s by an in vitro binding assay .", "target_text": { "TRAF3": "protein", "TRAF3 binding sites": "DNA", "PXQXT/S core sequence": "DNA", "LMP1s": "protein", "simian EBV LMP1s": "protein" } }, { "input_text": "A PXQXT/S-containing sequence is also present in the cytoplasmic domain of the Hodgkin 's disease marker , CD30 , and binds TRAF3 in vitro .", "target_text": { "PXQXT/S-containing sequence": "DNA", "cytoplasmic domain": "protein", "CD30": "protein", "TRAF3": "protein" } }, { "input_text": "The last 13 amino acids containing a PXQXT/S sequence are highly conserved in human and simian EBV LMP1 but do not bind TRAF3 , suggesting a distinct role for this conserved region of LMP1 .", "target_text": { "last 13 amino acids": "protein", "PXQXT/S sequence": "DNA", "LMP1": "protein", "TRAF3": "protein" } }, { "input_text": "The conserved TRAF3 binding sites in LMP1 and the CD30 Hodgkin 's disease marker provides further evidence that a TRAF3 -mediated signal transduction pathway may be important in malignant transformation .", "target_text": { "TRAF3": "protein", "TRAF3 binding sites": "DNA", "LMP1": "protein", "CD30": "protein", "CD30 Hodgkin 's disease marker": "protein" } }, { "input_text": "Chromosome 1 aneusomy with 1p36 under-representation is related to histologic grade , DNA aneuploidy , high c-erb B-2 and loss of bcl-2 expression in ductal breast carcinoma .", "target_text": { "Chromosome 1": "DNA", "1p36": "DNA", "c-erb B-2": "protein", "bcl-2": "DNA" } }, { "input_text": "Chromosome 1 abnormalities with loss of 1p36 have been investigated in 95 breast-cancer samples by means of a dual-target fluorescence in-situ hybridization ( FISH ) technique using the pUC 1.77 and p1-79 probes , specific for the 1q12 and 1p36 regions , respectively .", "target_text": { "Chromosome 1": "DNA", "1p36": "DNA", "pUC 1.77": "DNA", "p1-79 probes": "DNA" } }, { "input_text": "Abnormalities for one or both probes were detected in 83/95 samples .", "target_text": {} }, { "input_text": "Relative 1p36 under-representation was found in 79/95 .", "target_text": { "1p36": "DNA" } }, { "input_text": "The clinical relevance of these alterations was studied by comparing the FISH results with several parameters currently used in breast-cancer pathology .", "target_text": {} }, { "input_text": "Distinct patterns of chromosome 1 abnormalities were found among the histologic types of breast carcinoma .", "target_text": { "chromosome 1": "DNA" } }, { "input_text": "Lobular or mucinous samples showed few or no alterations , whereas most ductal samples had high chromosome 1 polysomy with under-representation of 1p36 .", "target_text": { "chromosome 1": "DNA", "1p36": "DNA" } }, { "input_text": "In ductal carcinomas , chromosome 1 alterations increased with histologic grade , DNA aneuploidy , loss of bcl-2 and high c-erb B-2 expression .", "target_text": { "chromosome 1": "DNA", "c-erb B-2": "protein" } }, { "input_text": "These associations were found to be statistically significant .", "target_text": {} }, { "input_text": "No correlation between chromosome 1 alterations and nuclear grade , age , size , lymph-node involvement , hormonal receptor presence , proliferation activity or p53 protein expression was detected .", "target_text": { "chromosome 1": "DNA", "p53": "protein" } }, { "input_text": "These results indicate the utility of this FISH technique for a better definition of the biological characteristics of ductal carcinomas .", "target_text": {} }, { "input_text": "G(Anh)MTetra , a natural bacterial cell wall breakdown product , induces interleukin-1 beta and interleukin-6 expression in human monocytes .", "target_text": { "interleukin-1 beta": "protein", "interleukin-6": "protein", "human monocytes": "cell_type" } }, { "input_text": "A study of the molecular mechanisms involved in inflammatory cytokine expression [ published erratum appears in J Biol Chem 1994 Jun 17 ; 269 ( 24 ) : 16983 ]", "target_text": { "inflammatory cytokine": "protein" } }, { "input_text": "It is believed that induction of cytokine expression by bacterial cell wall components plays a role in the development and course of sepsis .", "target_text": { "cytokine": "protein" } }, { "input_text": "However , most attention has been focused on lipopolysaccharide ( LPS ) .", "target_text": {} }, { "input_text": "We studied the ability of N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D- isoglutamyl-m-diaminopimelyl-D-alanine ( G(Anh)MTetra ) , a naturally occurring breakdown product of peptidoglycan that is produced by soluble lytic transglycosylase of Escherichia coli , to induce cytokine expression in human monocytes .", "target_text": { "lytic transglycosylase": "protein", "cytokine": "protein", "human monocytes": "cell_type" } }, { "input_text": "G(Anh)MTetra was found to strongly induce interleukin ( IL ) -1 beta and IL-6 mRNA expression after 2 h and IL-1 beta and IL-6 protein secretion after 48 h of activation .", "target_text": { "interleukin ( IL ) -1 beta": "protein", "IL-6": "protein", "IL-6 mRNA": "RNA", "IL-1 beta": "protein", "IL-6 protein": "protein" } }, { "input_text": "The increase in mRNA accumulation was at least partly due to an increase in the transcription rates of the respective genes and was accompanied by a strong induction of nuclear factor-kappa B and activator protein-1 transcription factor expression .", "target_text": { "genes": "DNA" } }, { "input_text": "Experiments using inhibitors of protein kinase C , protein kinase A , and tyrosine kinase-dependent pathways revealed that G(Anh)MTetra -induced IL-1 beta and IL-6 mRNA expression involves activation of an H7-inhibitable pathway .", "target_text": { "protein kinase C": "protein", "protein kinase A": "protein", "IL-1 beta": "protein", "IL-6": "protein", "IL-6 mRNA": "RNA" } }, { "input_text": "By using the protein synthesis inhibitor cycloheximide , it was shown that G(Anh)MTetra -induced IL-6 mRNA expression depends on the synthesis of new protein , whereas G(Anh)MTetra -induced IL-1 beta mRNA accumulation does not .", "target_text": { "IL-6": "protein", "IL-6 mRNA": "RNA", "IL-1 beta": "protein" } }, { "input_text": "When responses to G(Anh)MTetra were compared with those to LPS and muramyldipeptide ( MDP ) , it was found that the optimal response to G(Anh)MTetra induction was similar to that of LPS but significantly higher than the response to MDP .", "target_text": {} }, { "input_text": "Furthermore , maximal G(Anh)MTetra -induced IL-1 beta and IL-6 mRNA expression could be enhanced by co-stimulation with LPS or MDP , suggesting that different receptors and/or transduction pathways were involved .", "target_text": { "IL-1 beta": "protein", "IL-6": "protein", "IL-6 mRNA": "RNA" } }, { "input_text": "These results indicate that G(Anh)MTetra induces IL-1 beta and IL-6 expression in human monocytes suggesting a possible role for G(Anh)MTetra in the release of cytokines during sepsis .", "target_text": { "IL-1 beta": "protein", "IL-6": "protein", "human monocytes": "cell_type", "cytokines": "protein" } }, { "input_text": "Increased proliferation , cytotoxicity , and gene expression after stimulation of human peripheral blood T lymphocytes through a surface ganglioside ( GD3 ) [ published erratum appears in J Immunol 1994 Jul 15 ; 153 ( 2 ) : 910 ]", "target_text": { "human peripheral blood T lymphocytes": "cell_type" } }, { "input_text": "Previous studies have suggested that gangliosides have an important role in cell signaling and recognition .", "target_text": {} }, { "input_text": "However , their specific function in these processes has not been clearly defined .", "target_text": {} }, { "input_text": "A mAb , R24 , that reacts specifically with a cell surface ganglioside ( GD3 ) has been demonstrated to stimulate proliferation of T cells derived from human peripheral blood .", "target_text": { "mAb": "protein", "R24": "protein", "T cells": "cell_type" } }, { "input_text": "In this study , we have investigated the mechanisms by which the R24 mAb affects T cell functions .", "target_text": { "R24": "protein", "R24 mAb": "protein" } }, { "input_text": "We have observed that the R24 mAb stimulates GD3 + T cell proliferation , cytotoxicity , and surface marker expression of IL-2R alpha-chain , IL-2R beta-chain , HLA-DR , CD11a , and CD11c .", "target_text": { "R24": "protein", "R24 mAb": "protein", "IL-2R alpha-chain": "protein", "IL-2R beta-chain": "protein", "HLA-DR": "protein", "CD11a": "protein", "CD11c": "protein" } }, { "input_text": "Additionally , IFN-gamma activity but not IL-1 , IL-2 , or IL-4 activity was present in culture supernatants 72 h after R24 stimulation .", "target_text": { "IFN-gamma": "protein", "R24": "protein" } }, { "input_text": "In some donors , increased IL-6 and TNF-alpha activity also was detected after R24 treatment .", "target_text": { "IL-6": "protein", "TNF-alpha": "protein", "R24": "protein" } }, { "input_text": "Furthermore , R24 treatment resulted in translocation of c-rel , but little or no NF kappa B p50 or p65 , from the cytoplasm to the nucleus and an increase of NF kappa B binding complexes containing c-rel and p50 .", "target_text": { "R24": "protein", "c-rel": "protein", "NF kappa B p50": "protein", "p65": "protein", "NF kappa B": "protein", "NF kappa B binding complexes": "protein", "p50": "protein" } }, { "input_text": "This treatment also caused increased tyrosine phosphorylation of specific protein substrates .", "target_text": {} }, { "input_text": "R24 -stimulated increases in proliferation , cytotoxicity , and cell surface protein expression could be blocked by cyclosporin and staurosporin , indicating that cyclophilin/calcineurin and protein kinase C may be involved in the R24 signaling pathway .", "target_text": { "R24": "protein", "cyclophilin/calcineurin": "protein", "protein kinase C": "protein" } }, { "input_text": "Additionally , herbimycin A , a tyrosine kinase inhibitor , blocked the R24 -stimulated increase in proliferation but not cytotoxicity at concentrations consistent with specificity for tyrosine kinases .", "target_text": { "tyrosine kinase": "protein", "R24": "protein", "tyrosine kinases": "protein" } }, { "input_text": "These results suggest that multiple biochemical pathways are involved in the activation of human T cells by R24 .", "target_text": { "human T cells": "cell_type", "R24": "protein" } }, { "input_text": "Genes encoding general initiation factors for RNA polymerase II transcription are dispersed in the human genome .", "target_text": { "general initiation factors": "protein", "RNA polymerase II": "protein", "human genome": "DNA" } }, { "input_text": "General transcription factors are required for accurate initiation of transcription by RNA polymerase II .", "target_text": { "transcription factors": "protein", "General transcription factors": "protein", "RNA polymerase II": "protein" } }, { "input_text": "Human cDNAs encoding subunits of these factors have been cloned and sequenced .", "target_text": { "Human cDNAs": "DNA" } }, { "input_text": "Using fluorescence in situ hybridization ( FISH ) , we show here that the genes encoding the TATA-box binding protein ( TBP ) , TFIIB , TFIIE alpha , TFIIE beta , RAP30 , RAP74 and the 62 kDa subunit , of TFIIH are located at the human chromosomal bands 6q26-27 , 1p21-22 , 3q21-24 , 8p12 , 13q14 , 19p13.3 and 11p14-15.1 , respectively .", "target_text": { "genes": "DNA", "TATA-box binding protein": "protein", "TBP": "protein", "TFIIB": "protein", "TFIIE alpha": "protein", "TFIIE beta": "protein", "RAP30": "protein", "RAP74": "protein", "62 kDa subunit": "protein", "TFIIH": "protein" } }, { "input_text": "This dispersed localization of a group of functionally related gene provides insights into the molecular mechanism of human genome evolution and their possible involvement in human diseases .", "target_text": { "human genome": "DNA" } }, { "input_text": "BCL-6 and the molecular pathogenesis of B-cell lymphoma .", "target_text": { "BCL-6": "protein" } }, { "input_text": "The results presented identify the first genetic lesion associated with DLCL , the most clinically relevant form of NHL .", "target_text": {} }, { "input_text": "Although no proof yet exists of a role for these lesions in DLCL pathogenesis , the feature of the BCL-6 gene product , its specific pattern of expression in B cells , and the clustering of lesions disrupting its regulatory domain strongly suggest that deregulation of BCL-6 expression may contribute to DLCL development .", "target_text": { "BCL-6": "protein", "BCL-6 gene product": "protein", "B cells": "cell_type" } }, { "input_text": "A more precise definition of the role of BCL-6 in normal and neoplastic B-cell development is the goal of ongoing study of transgenic mice engineered either to express BCL-6 under heterologous promoters or lacking BCL-6 function due to targeted deletions .", "target_text": { "BCL-6": "protein", "heterologous promoters": "DNA" } }, { "input_text": "In addition to contributing to the understanding of DLCL pathogenesis , the identification of BCL-6 lesions may have relevant clinical implications .", "target_text": { "BCL-6": "protein" } }, { "input_text": "DLCL represent a heterogeneous group of neoplasms which are treated homogeneously despite the fact that only 50 % of patients experience long-term disease-free survival ( Schneider et al. 1990 ) .", "target_text": {} }, { "input_text": "The fact that BCL-6 rearrangements identify biologically and clinically distinct subsets of DLCL suggests that these lesions may be useful as markers in selection of differential therapeutic strategies based on different risk groups .", "target_text": { "BCL-6": "protein" } }, { "input_text": "Furthermore , the BCL-6 rearrangements can be used to identify and monitor the malignant clone with sensitive PCR-based techniques .", "target_text": { "BCL-6": "protein", "malignant clone": "cell_type" } }, { "input_text": "Since clinical remission has been observed in a significant fraction of DLCL cases , these markers may serve as critical tools for sensitive monitoring of minimal residual disease and early diagnosis of relapse ( Gribben et al. 1993 ) .", "target_text": {} }, { "input_text": "Pancreatic development and maturation of the islet B cell .", "target_text": { "islet B cell": "cell_type" } }, { "input_text": "Studies of pluripotent islet cultures .", "target_text": { "pluripotent islet cultures": "cell_line" } }, { "input_text": "Pancreas organogenesis is a highly regulated process , in which two anlage evaginate from the primitive gut .", "target_text": {} }, { "input_text": "They later fuse , and , under the influence of the surrounding mesenchyme , the mature organ develops , being mainly composed of ductal , exocrine and endocrine compartments .", "target_text": {} }, { "input_text": "Early buds are characterized by a branching morphogenesis of the ductal epithelium from which endocrine and exocrine precursor cells bud to eventually form the two other compartments .", "target_text": {} }, { "input_text": "The three compartments are thought to be of common endodermal origin ; in contrast to earlier hypotheses , which suggested that the endocrine compartment was of neuroectodermal origin .", "target_text": {} }, { "input_text": "It is thus generally believed that the pancreatic endocrine-lineage possesses the ability to mature along a differentiation pathway that shares many characteristics with those of neuronal differentiation .", "target_text": {} }, { "input_text": "During recent years , studies of insulin-gene regulation and , in particular , the tissue-specific transcriptional control of insulin-gene activity have provided information on pancreas development in general .", "target_text": { "insulin-gene": "DNA" } }, { "input_text": "The present review summarizes these findings , with a special focus on our own studies on pluripotent endocrine cultures of rat pancreas .", "target_text": { "pluripotent endocrine cultures": "cell_line" } }, { "input_text": "Octamer independent activation of transcription from the kappa immunoglobulin germline promoter .", "target_text": { "kappa immunoglobulin germline promoter": "DNA" } }, { "input_text": "Previous analyses of immunoglobulin V region promoters has led to the discovery of a common octamer motif which is functionally important in the tissue-specific and developmentally regulated transcriptional activation of immunoglobulin genes .", "target_text": { "immunoglobulin V region promoters": "DNA", "octamer motif": "DNA", "immunoglobulin genes": "DNA" } }, { "input_text": "The germline promoters ( Ko ) located upstream of the J region gene segments of the kappa locus also contain an octamer motif ( containing a single base pair mutation and referred to as the variant octamer ) which has been shown previously to bind Oct-1 and Oct-2 transcription factors in vitro .", "target_text": { "germline promoters": "DNA", "Ko": "DNA", "J region gene segments": "DNA", "kappa locus": "DNA", "octamer motif": "DNA", "base pair mutation": "DNA", "Oct-1": "protein", "Oct-2": "protein", "transcription factors": "protein" } }, { "input_text": "To further elucidate the role of this variant octamer motif in the regulation of germline transcription from the unrearranged kappa locus , we have quantitated the relative binding affinity of Oct-1 and Oct-2 for the variant octamer motif and determined the functional role of this octamer motif in transcriptional activation .", "target_text": { "octamer motif": "DNA", "germline": "DNA", "kappa locus": "DNA", "Oct-1": "protein", "Oct-2": "protein" } }, { "input_text": "We find that , although the variant octamer motif binds Oct-1 and Oct-2 in vitro with 5-fold lower affinity than the consensus octamer motif , mutation of the variant octamer motif to either a consensus octamer or non- octamer motif has no effect on transcriptional activation from the germline promoter .", "target_text": { "octamer motif": "DNA", "Oct-1": "protein", "Oct-2": "protein", "consensus octamer motif": "DNA", "consensus octamer": "DNA", "non- octamer motif": "DNA", "germline promoter": "DNA" } }, { "input_text": "We also find significant differences in activation of germline and V region promoters by kappa enhancers .", "target_text": { "germline": "DNA", "V region promoters": "DNA", "kappa enhancers": "DNA" } }, { "input_text": "Our results suggest that the germline promoters and V region promoters differ in their dependence on octamer for activation and respond differently to enhancer activation .", "target_text": { "germline promoters": "DNA", "V region promoters": "DNA", "octamer": "DNA" } }, { "input_text": "These findings have important implications in regulation of germline transcription as well as concomitant activation of the V-J recombination of the kappa light chain locus .", "target_text": { "germline": "DNA", "kappa light chain locus": "DNA" } }, { "input_text": "Generation of CD1+RelB+ dendritic cells and tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells from human monocytes .", "target_text": { "CD1+RelB+ dendritic cells": "cell_type", "tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells": "cell_type", "human monocytes": "cell_type" } }, { "input_text": "We previously showed that granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and macrophage colony-stimulating factor ( M-CSF ) stimulate the differentiation of human monocytes into two phenotypically distinct types of macrophages .", "target_text": { "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "macrophage colony-stimulating factor": "protein", "M-CSF": "protein", "human monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "However , in vivo , not only CSF but also many other cytokines are produced under various conditions .", "target_text": { "CSF": "protein", "cytokines": "protein" } }, { "input_text": "Those cytokines may modulate the differentiation of monocytes by CSFs .", "target_text": { "cytokines": "protein", "monocytes": "cell_type", "CSFs": "protein" } }, { "input_text": "In the present study , we showed that CD14+ adherent human monocytes can differentiate into CD1+relB+ dendritic cells ( DC ) by the combination of GM-CSF plus interleukin-4 ( IL-4 ) and that they differentiate into tartrate-resistant acid phosphatase ( TRAP ) -positive osteoclast-like multinucleated giant cells ( MGC ) by the combination of M-CSF plus IL-4 .", "target_text": { "human monocytes": "cell_type", "CD14+ adherent human monocytes": "cell_type", "CD1+relB+ dendritic cells": "cell_type", "DC": "cell_type", "GM-CSF": "protein", "interleukin-4": "protein", "IL-4": "protein", "tartrate-resistant acid phosphatase ( TRAP ) -positive osteoclast-like multinucleated giant cells": "cell_type", "MGC": "cell_type", "M-CSF": "protein" } }, { "input_text": "However , the monocyte-derived DC were not terminally differentiated cells ; they could still convert to macrophages in response to M-CSF .", "target_text": { "DC": "cell_type", "monocyte-derived DC": "cell_line", "terminally differentiated cells": "cell_line", "macrophages": "cell_type", "M-CSF": "protein" } }, { "input_text": "Tumor necrosis factor-alpha ( TNF-alpha ) stimulated the terminal differentiation of the DC by downregulating the expression of the M-CSF receptor , cfms mRNA , and aborting the potential to convert to macrophages .", "target_text": { "Tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "DC": "cell_type", "M-CSF": "protein", "M-CSF receptor": "protein", "cfms mRNA": "RNA", "macrophages": "cell_type" } }, { "input_text": "In contrast to IL-4 , interferon-gamma ( IFN-gamma ) had no demonstrable effect on the differentiation of monocytes .", "target_text": { "IL-4": "protein", "interferon-gamma": "protein", "IFN-gamma": "protein", "monocytes": "cell_type" } }, { "input_text": "Rather , IFN-gamma antagonized the effect of IL-4 and suppressed the DC and MGC formation induced by GM-CSF + IL-4 and M-CSF + IL-4 , respectively .", "target_text": { "IFN-gamma": "protein", "IL-4": "protein", "DC": "cell_type", "MGC": "cell_type", "GM-CSF": "protein", "M-CSF": "protein" } }, { "input_text": "Taken together , these results provide a new aspect to our knowledge of monocyte differentiation and provide evidence that human monocytes are flexible in their differentiation potential and are precursors not only of macrophages but also of CD1+relB+DC and TRAP-positive MGC .", "target_text": { "monocytes": "cell_type", "human monocytes": "cell_type", "macrophages": "cell_type", "CD1+relB+DC": "cell_type", "TRAP-positive MGC": "cell_type" } }, { "input_text": "Such a diverse pathway of monocyte differentiation may constitute one of the basic mechanisms of immune regulation .", "target_text": {} }, { "input_text": "The NF-kappa B inhibitor , tepoxalin , suppresses surface expression of the cell adhesion molecules CD62E , CD11b/CD18 and CD106 .", "target_text": { "NF-kappa B": "protein", "cell adhesion molecules": "protein", "CD62E": "protein", "CD11b/CD18": "protein", "CD106": "protein" } }, { "input_text": "Tepoxalin , a dual enzyme inhibitor of cyclooxygenase and 5-lipoxygenase has been shown to inhibit T-cell activation .", "target_text": { "cyclooxygenase": "protein", "5-lipoxygenase": "protein" } }, { "input_text": "Its immunosuppressive property is distinct from cyclosporin because only tepoxalin , but not cyclosporin , suppresses NF-kappa B activation .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Here we report that tepoxalin selectively inhibits intercellular adhesion molecule-1 ( ICAM-1 , CD54 ) /MAC-1 ( CD11b/CD18 ) dependent adhesion of polymorphonuclear cells to IL-1 activated human umbilical vein endothelial cells .", "target_text": { "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "CD54": "protein", "( ICAM-1 , CD54 ) /MAC-1": "protein", "CD11b/CD18": "protein", "polymorphonuclear cells": "cell_type", "IL-1": "protein", "human umbilical vein endothelial cells": "cell_type" } }, { "input_text": "The mechanism of inhibition is related to the surface expression of several cell adhesion molecules .", "target_text": { "adhesion molecules": "protein" } }, { "input_text": "Flow cytometry analyses on cultured cells that were treated with tepoxalin or antisense oligonucleotides to the P65/p50 subunit of NF-kappa B , and then stimulated with PMA , revealed a reduced expression of CD11b/CD18 on monocytic HL60 cells , and endothelial adhesion molecule-1 ( CD62E ) and vascular adhesion molecule-1 ( CD106 ) on human umbilical vein endothelial cells .", "target_text": { "P65/p50 subunit": "protein", "NF-kappa B": "protein", "CD11b/CD18": "protein", "monocytic HL60 cells": "cell_line", "endothelial adhesion molecule-1": "protein", "CD62E": "protein", "vascular adhesion molecule-1": "protein", "CD106": "protein", "human umbilical vein endothelial cells": "cell_type" } }, { "input_text": "Expression of other adhesion molecules such as lymphocyte function associated-antigen-1 ( CD11a /CD18 ) and CD54 were unaffected .", "target_text": { "adhesion molecules": "protein", "lymphocyte function associated-antigen-1": "protein", "CD11a": "protein", "CD11a /CD18": "protein", "CD54": "protein" } }, { "input_text": "Tepoxalin also inhibited the secretion of a NF-kappa B regulated chemokine , IL-8 , a known inducer of CD11b/CD18 expression .", "target_text": { "NF-kappa B": "protein", "NF-kappa B regulated chemokine": "protein", "IL-8": "protein", "CD11b/CD18": "protein" } }, { "input_text": "Thus the suppression of CD11b/CD18 expression by tepoxalin may involve IL-8 .", "target_text": { "CD11b/CD18": "protein", "IL-8": "protein" } }, { "input_text": "Our results suggest that by inhibiting NF-kappa B activation , surface expression of several adhesion molecules can be modulated and that tepoxalin may be useful in treating selected adhesion mediated events such as leukocyte migration or atherosclerotic plaque formation .", "target_text": { "NF-kappa B": "protein", "adhesion molecules": "protein" } }, { "input_text": "Characterization of a CD43/leukosialin -mediated pathway for inducing apoptosis in human T-lymphoblastoid cells .", "target_text": { "CD43/leukosialin": "protein", "human T-lymphoblastoid cells": "cell_type" } }, { "input_text": "The monoclonal antibody ( mAb ) J393 induces apoptosis in Jurkat T-cells .", "target_text": { "monoclonal antibody": "protein", "mAb": "protein", "J393": "protein", "Jurkat T-cells": "cell_line" } }, { "input_text": "NH2 -terminal amino acid sequence analysis identified the 140-kDa surface antigen for mAb J393 as CD43/leukosialin , the major sialoglycoprotein of leukocytes .", "target_text": { "NH2": "protein", "amino acid sequence": "protein", "140-kDa surface antigen": "protein", "mAb J393": "protein", "CD43/leukosialin": "protein", "sialoglycoprotein": "protein", "leukocytes": "cell_type" } }, { "input_text": "While Jurkat cells co-expressed two discrete cell-surface isoforms of CD43 , recognized by mAb J393 and mAb G10-2 , respectively , only J393/ CD43 signaled apoptosis .", "target_text": { "Jurkat cells": "cell_line", "cell-surface isoforms": "protein", "CD43": "protein", "mAb J393": "protein", "mAb G10-2": "protein", "J393/ CD43": "protein" } }, { "input_text": "J393/ CD43 was found to be hyposialylated , bearing predominantly O-linked monosaccharide glycans , whereas G10-2/ CD43 bore complex sialylated tetra- and hexasaccharide chains .", "target_text": { "CD43": "protein", "J393/ CD43": "protein", "G10-2/ CD43": "protein" } }, { "input_text": "Treatment with soluble , bivalent mAb J393 killed 25-50 % of the cell population , while concomitant engagement of either the CD3.TcR complex or the integrins CD18 and CD29 significantly potentiated this effect .", "target_text": { "mAb J393": "protein", "cell population": "cell_line", "CD3.TcR complex": "protein", "integrins": "protein", "CD18": "protein", "CD29": "protein" } }, { "input_text": "Treatment of Jurkat cells with mAb J393 induced tyrosine phosphorylation of specific protein substrates that underwent hyperphosphorylation upon antigen receptor costimulation .", "target_text": { "Jurkat cells": "cell_line", "mAb J393": "protein", "protein substrates": "protein", "antigen receptor": "protein" } }, { "input_text": "Tyrosine kinase inhibition by herbimycin A diminished J393/ CD43 -mediated apoptosis , whereas inhibition of phosphotyrosine phosphatase activity by bis(maltolato)oxovanadium-IV enhanced cell death .", "target_text": { "Tyrosine kinase": "protein", "CD43": "protein", "J393/ CD43": "protein", "phosphotyrosine phosphatase": "protein" } }, { "input_text": "Signal transduction through tyrosine kinase activation may lead to altered gene expression , as J393/ CD43 ligation prompted decreases in the nuclear localization of the transcriptional regulatory protein NF-kappaB and proteins binding the interferon-inducible regulatory element .", "target_text": { "CD43": "protein", "transcriptional regulatory protein": "protein", "NF-kappaB": "protein", "interferon-inducible regulatory element": "DNA" } }, { "input_text": "Since peripheral blood T-lymphocytes express cryptic epitopes for mAb J393 , these findings demonstrate the existence of a tightly regulated CD43 -mediated pathway for inducing apoptosis in human T-cell lineages .", "target_text": { "peripheral blood T-lymphocytes": "cell_type", "cryptic epitopes": "protein", "mAb J393": "protein", "CD43": "protein", "human T-cell lineages": "cell_type" } }, { "input_text": "Sterol dependent LDL-receptor gene transcription in lymphocytes from normal and CML patients .", "target_text": { "LDL-receptor gene": "DNA", "lymphocytes": "cell_type" } }, { "input_text": "Sterol regulatory element ( SRE ) has been recognized to regulate various key genes coding for especially low density lipoprotein ( LDL ) -receptor , 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase and HMG-CoA synthase known to play a crucial role in the cholesterol feedback mechanism .", "target_text": { "Sterol regulatory element": "DNA", "SRE": "DNA", "genes": "DNA", "low density lipoprotein": "protein", "LDL": "protein", "low density lipoprotein ( LDL ) -receptor": "protein", "3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase": "protein", "HMG-CoA synthase": "protein" } }, { "input_text": "The deranged cholesterol feedback mechanism has been widely recognised in initiation as well as progression of various types of cancers including chronic myeloid leukaemia ( CML ) .", "target_text": {} }, { "input_text": "Consequently , the present study was addressed to understand this phenomenon and revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects as well as its absence in lymphocytes from untreated CML patients .", "target_text": { "unique 47 kDa protein factor": "protein", "SRE sequence": "DNA", "lymphocytes": "cell_type" } }, { "input_text": "However , this factor appeared when the CML patients achieved complete haematological remission ( CHR ) through alpha-interferon therapy .", "target_text": { "alpha-interferon": "protein" } }, { "input_text": "Further , an inverse relationship was also observed between sterol modulated LDL -receptor gene transcription and the binding affinity of this 47 kDa factor to the SRE sequence .", "target_text": { "LDL": "protein", "LDL -receptor gene": "DNA", "47 kDa factor": "protein", "SRE sequence": "DNA" } }, { "input_text": "Based upon these results we propose that alpha-interferon through its receptor initiates phosphatidic acid dependent signalling which in turn regulates the affinity of 47 kDa sterol regulatory element binding factor as well as LDL -receptor gene transcription in lymphocytes from CML patients .", "target_text": { "alpha-interferon": "protein", "47 kDa sterol regulatory element binding factor": "protein", "LDL": "protein", "LDL -receptor gene": "DNA", "lymphocytes": "cell_type" } }, { "input_text": "Multiple prolactin-responsive elements mediate G1 and S phase expression of the interferon regulatory factor-1 gene .", "target_text": { "prolactin-responsive elements": "DNA", "interferon regulatory factor-1 gene": "DNA" } }, { "input_text": "The interferon regulatory factor-1 ( IRF-1 ) gene is both an immediate-early G1 phase gene and an S phase gene inducible by PRL in rat Nb2 T lymphocytes .", "target_text": { "IRF-1": "protein", "interferon regulatory factor-1 ( IRF-1 ) gene": "DNA", "immediate-early G1 phase gene": "DNA", "S phase gene": "DNA", "PRL": "protein", "rat Nb2 T lymphocytes": "cell_line" } }, { "input_text": "To understand the mechanism by which PRL regulates the biphasic expression of IRF-1 , we cloned the rat IRF-1 gene and functionally characterized the IRF-1 promoter .", "target_text": { "PRL": "protein", "IRF-1": "protein", "rat IRF-1 gene": "DNA", "IRF-1 promoter": "DNA" } }, { "input_text": "Upon transfection into Nb2 T cells , 1.7 kilobases ( kb ) of IRF-1 5'-flanking DNA linked to a chloramphenicol acetyl transferase ( CAT ) reporter gene mediated a 30-fold induction of CAT enzyme activity in response to 24 h of PRL stimulation .", "target_text": { "Nb2 T cells": "cell_line", "IRF-1": "protein", "IRF-1 5'-flanking DNA": "DNA", "chloramphenicol acetyl transferase": "protein", "CAT": "protein", "chloramphenicol acetyl transferase ( CAT ) reporter gene": "DNA", "CAT enzyme": "protein", "PRL": "protein" } }, { "input_text": "Deletion mutants containing 1.3 , 0.6 , and 0.2 kb 5'-flanking DNA were incrementally less transcriptionally active , although 0.2 kb still mediated a 12-fold induction by PRL .", "target_text": { "PRL": "protein" } }, { "input_text": "The sequence between -1.7 and -0.2 kb linked to a heterologous thymidine kinase promoter failed to respond to PRL stimulation , suggesting that the activity of upstream PRL response elements may require an interaction with promoter-proximal elements .", "target_text": { "heterologous thymidine kinase promoter": "DNA", "PRL": "protein", "upstream PRL response elements": "DNA", "promoter-proximal elements": "DNA" } }, { "input_text": "By assaying CAT enzyme activity across a 24-h PRL induction time course , we were able to assign G1 vs. S phase PRL responses of the IRF-1 gene to different regions of the IRF-1 5'-flanking and promoter DNA .", "target_text": { "CAT": "protein", "CAT enzyme": "protein", "PRL": "protein", "IRF-1": "protein", "IRF-1 gene": "DNA", "5'-flanking": "DNA", "promoter DNA": "DNA" } }, { "input_text": "The 0.2-kb IRF- CAT construct was induced by PRL stimulation during the G1 phase of the cell cycle .", "target_text": { "CAT": "protein", "IRF- CAT construct": "DNA", "PRL": "protein" } }, { "input_text": "In contrast , the 1.7-kb IRF- CAT construct was inducible by PRL during both G1 and S phase of the cell cycle .", "target_text": { "CAT": "protein", "PRL": "protein" } }, { "input_text": "Hence , the PRL -induced biphasic expression of the IRF-1 gene appears to be controlled by separate PRL -responsive elements : elements in the first 0.2 kb of the IRF-1 promoter region act during early activation , and elements between 0.2 and 1.7 kb act in concert with the proximal 0.2-kb region during S phase progression .", "target_text": { "PRL": "protein", "IRF-1": "protein", "IRF-1 gene": "DNA", "PRL -responsive elements": "DNA", "IRF-1 promoter region": "DNA" } }, { "input_text": "Regulation of the BZLF1 promoter of Epstein-Barr virus by second messengers in anti-immunoglobulin-treated B cells .", "target_text": { "BZLF1 promoter": "DNA", "anti-immunoglobulin-treated B cells": "cell_line" } }, { "input_text": "Initiation of the Epstein-Barr virus ( EBV ) lytic cycle is dependent on the transcription of the BZLF1 gene .", "target_text": { "BZLF1 gene": "DNA" } }, { "input_text": "The BZLF1 gene promoter ( Zp ) was activated by crosslinking of cell surface immunoglobulin ( Ig ) with anti-Ig antibody in B cells , even in the absence of other viral genes .", "target_text": { "BZLF1 gene": "DNA", "BZLF1 gene promoter": "DNA", "Zp": "DNA", "cell surface immunoglobulin": "protein", "Ig": "protein", "anti-Ig antibody": "protein", "B cells": "cell_type" } }, { "input_text": "We identified several anti-Ig response elements within Zp , which were originally defined as 12-O-tetradecanoylphorbol-13-acetate ( TPA ) response elements ( ZI repeats and ZII , an AP-1-like domain ) .", "target_text": { "Zp": "DNA", "12-O-tetradecanoylphorbol-13-acetate ( TPA ) response elements": "DNA", "ZI repeats": "DNA", "ZII": "DNA", "AP-1-like domain": "DNA" } }, { "input_text": "Since anti-Ig crosslinking leads to activation of protein kinase C ( PKC ) and an increase in intracellular calcium level , Zp was tested for the response to these cellular factors .", "target_text": { "protein kinase C": "protein", "PKC": "protein", "Zp": "DNA", "cellular factors": "protein" } }, { "input_text": "Treatment with calcium ionophore A23187 increased Zp activity .", "target_text": { "Zp": "DNA" } }, { "input_text": "When the calcium ionophore was used in conjunction with TPA , a PKC activator , the Zp induction was synergistically enhanced .", "target_text": { "PKC": "protein", "Zp": "DNA" } }, { "input_text": "1-(5-Isoquinolinyl sulfonyl)-2-methylpiperazine , an inhibitor of PKC , inhibited the anti-Ig inducibility of Zp .", "target_text": { "PKC": "protein", "anti-Ig": "protein", "Zp": "DNA" } }, { "input_text": "Calmodulin antagonists , compound R24571 and trifluoperazine , blocked the Zp activation with anti-Ig .", "target_text": { "Zp": "DNA", "anti-Ig": "protein" } }, { "input_text": "These findings suggest that Zp responds directly to changes in the activity of both PKC and calcium /calmodulin-dependent protein kinase .", "target_text": { "Zp": "DNA", "PKC": "protein", "calcium /calmodulin-dependent protein kinase": "protein" } }, { "input_text": "Requirement of tyrosine kinase activation for the anti-Ig -mediated Zp activation was also demonstrated through the use of the tyrosine kinase inhibitor herbimycin .", "target_text": { "tyrosine kinase": "protein", "anti-Ig": "protein", "Zp": "DNA" } }, { "input_text": "These cellular gene regulatory molecules induced with anti-Ig may cooperatively play an important part in achieving efficient EBV activation as seen with anti-Ig treatment in B cells .", "target_text": { "cellular gene regulatory molecules": "protein", "anti-Ig": "protein", "B cells": "cell_type" } }, { "input_text": "The SCL protein displays cell-specific heterogeneity in size .", "target_text": { "SCL protein": "protein" } }, { "input_text": "SCL protein production was examined in a variety of hemopoietic cell lines by immunoblotting using specific polyclonal antisera .", "target_text": { "SCL protein": "protein", "hemopoietic cell lines": "cell_line" } }, { "input_text": "SCL protein was detected in erythroid , megakaryocyte , mast and early myeloid cell lines , as well as in several lymphoid leukemia cell lines which are known to harbor SCL gene rearrangements .", "target_text": { "SCL protein": "protein", "lymphoid leukemia cell lines": "cell_line", "SCL gene rearrangements": "DNA" } }, { "input_text": "In most cell lines , proteins of molecular weight 49 and 44 kDa were found , however two myeloid cell lines expressed only lower molecular weight species of 24 and 22 kDa .", "target_text": { "molecular weight 49 and 44 kDa": "protein", "molecular weight species of 24 and 22 kDa": "protein" } }, { "input_text": "This size discrepancy appeared to be due to cell-specific translational regulation , since overexpression of a retrovirally transfected SCL gene yielded the higher molecular weight forms in most cell lines ( GP+E-86 , AT2.5 , M1 ) but only the 22 kDa form in the myeloid cell line , WEHI-3B/D+ .", "target_text": { "SCL gene": "DNA", "cell lines": "cell_line", "GP+E-86": "cell_line", "AT2.5": "cell_line", "M1": "cell_line", "22 kDa form": "protein", "myeloid cell line": "cell_line", "WEHI-3B/D+": "cell_line" } }, { "input_text": "Overexpression of full-length SCL protein in the lymphoid cell lines , SupT1 and Raji , did not alter cell phenotype and there was no evidence for autoregulation of SCL transcription .", "target_text": { "SCL protein": "protein", "lymphoid cell lines": "cell_line", "SCL": "protein" } }, { "input_text": "The restricted pattern of SCL protein synthesis is consistent with the restricted expression of SCL mRNA documented previously .", "target_text": { "SCL protein": "protein", "SCL mRNA": "RNA" } }, { "input_text": "In addition , the present results indicate that SCL protein size was determined by regulation of translation in a cell-specific manner .", "target_text": { "SCL protein": "protein" } }, { "input_text": "Description and functional implications of a novel mutation in the sex-determining gene SRY .", "target_text": { "sex-determining gene": "DNA", "SRY": "DNA" } }, { "input_text": "The sex-determining gene SRY was screened for molecular alteration in an XY sex-reversed female by single-strand conformation polymorphism ( SSCP ) technique .", "target_text": { "SRY": "DNA" } }, { "input_text": "An A-to-G transition was detected which leads to an exchange of a tyrosine by a cysteine in the SRY protein .", "target_text": { "SRY": "DNA", "SRY protein": "protein" } }, { "input_text": "The affected tyrosine residue located at the C terminus of the DNA binding protein is evolutionarily strongly conserved among the members of the HMG box containing proteins .", "target_text": { "C terminus": "protein", "DNA binding protein": "protein", "HMG box containing proteins": "protein" } }, { "input_text": "Using gel shift assay and peptide synthesis such a mutation is shown to abolish the SRY protein DNA binding ability .", "target_text": { "SRY": "DNA" } }, { "input_text": "The involvement of this particular amino acid in the binding specificity is also discussed .", "target_text": {} }, { "input_text": "Induction of tyrosine phosphorylation and T-cell activation by vanadate peroxide , an inhibitor of protein tyrosine phosphatases .", "target_text": { "T-cell": "cell_type", "protein tyrosine phosphatases": "protein" } }, { "input_text": "Rapid tyrosine phosphorylation of key cellular proteins is a crucial event in the transduction of activation signals to T-lymphocytes .", "target_text": { "T-lymphocytes": "cell_type" } }, { "input_text": "The regulatory role of protein tyrosine phosphatases ( PTPases ) in this process was explored by studying the effects of a powerful PTPase inhibitor , vanadate peroxide ( pervanadate ) , on the activation cascade of Jurkat human leukaemic T-cells .", "target_text": { "protein tyrosine phosphatases": "protein", "PTPases": "protein", "PTPase": "protein", "Jurkat human leukaemic T-cells": "cell_line" } }, { "input_text": "Pervanadate induced activation of the tyrosine kinases lck and fyn ( 4- and 3-fold respectively ) and a dramatic increase in tyrosine phosphorylation of cellular proteins , notably phospholipase C gamma 1 .", "target_text": { "tyrosine kinases": "protein", "lck": "protein", "fyn": "protein", "cellular proteins": "protein", "phospholipase C gamma 1": "protein" } }, { "input_text": "After this event , we observed a rise in intracellular Ca2+ concentration , corresponding to an influx .", "target_text": {} }, { "input_text": "This effect required surface expression of the CD45 PTPase and was not observed in CD45-deficient variants of Jurkat cells .", "target_text": { "CD45 PTPase": "protein", "CD45-deficient variants": "cell_line", "Jurkat cells": "cell_line" } }, { "input_text": "In the CD45-negative variant , the effect of pervanadate on tyrosine phosphorylation was globally decreased and some phosphorylated substrates were specifically missing .", "target_text": { "CD45-negative variant": "cell_line" } }, { "input_text": "Pervanadate also stimulated transcription of the c-fos gene and accumulation of its mRNA as well as several other hallmarks of T-lymphocyte activation such as surface expression of the CD69 antigen and the interleukin 2 receptor alpha-chain ( CD25 ) .", "target_text": { "c-fos gene": "DNA", "mRNA": "RNA", "T-lymphocyte": "cell_type" } }, { "input_text": "Pervanadate synergized with signals delivered by T-cell antigen receptor engagement or by a phorbol ester to induce interleukin 2 production .", "target_text": { "T-cell": "cell_type", "antigen receptor": "protein" } }, { "input_text": "Pervanadate activated NF-kappa B , as shown by an increase in DNA-binding activity of this transcription factor .", "target_text": { "NF-kappa B": "protein", "Pervanadate activated NF-kappa B": "protein", "transcription factor": "protein" } }, { "input_text": "We thus conclude that PTPases play a crucial role in the negative regulation of signal transduction culminating in T-lymphocyte activation .", "target_text": { "PTPases": "protein", "T-lymphocyte": "cell_type" } }, { "input_text": "Moreover , induction of tyrosine phosphorylation appears sufficient per se to initiate a complete activation programme .", "target_text": {} }, { "input_text": "Activation of nuclear factor-kappaB via T cell receptor requires a Raf kinase and Ca2+ influx .", "target_text": { "nuclear factor-kappaB": "protein", "T cell receptor": "protein", "Raf kinase": "protein" } }, { "input_text": "Functional synergy between Raf and calcineurin .", "target_text": { "Raf": "protein", "calcineurin": "protein" } }, { "input_text": "Signals transduced via the TCR activate the transcription factor nuclear factor-kappaB ( NF-kappaB ) , which , in turn , is critical to the transcriptional induction of many genes important for the proliferation and expression of a differentiated phenotype .", "target_text": { "TCR": "protein", "transcription factor": "protein", "nuclear factor-kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "Treatment of T cells with the protein kinase C activator PMA in combination with Ca2+ ionophores mimics this process , and the two agents are often substituted for TCR stimulation , bypassing the TCR .", "target_text": { "T cells": "cell_type", "protein kinase C": "protein", "TCR": "protein" } }, { "input_text": "Here we identify intracellular signaling components involved in activation of NF-kappaB following TCR stimulation .", "target_text": { "NF-kappaB": "protein", "TCR": "protein" } }, { "input_text": "TCR signaling was triggered by treating Jurkat T cells with PHA or anti-CD3 Abs , and NF-kappaB activation was monitored by electrophoretic mobility shift assays and/or by kappaB -dependent reporter assays .", "target_text": { "TCR": "protein", "Jurkat T cells": "cell_line", "PHA": "protein", "anti-CD3 Abs": "protein", "NF-kappaB": "protein", "kappaB": "protein" } }, { "input_text": "Contrary to the idea that protein kinase C is involved in TCR -mediated activation of NF-kappaB , high doses of staurosporine did not interfere with activation of NF-kappaB by PHA , while the same dose of staurosporine completely blocked activation by PMA .", "target_text": { "protein kinase C": "protein", "TCR": "protein", "NF-kappaB": "protein", "PHA": "protein" } }, { "input_text": "PHA -induced kappaB-dependent reporter activity was , however , effectively blocked by a dominant negative form of Raf-1 , suggesting a critical role for a Raf kinase .", "target_text": { "PHA": "protein", "Raf-1": "protein", "Raf kinase": "protein" } }, { "input_text": "The TCR -mediated activation of NF-kappaB was also dependent on a Ca2+ influx , because the Ca2+ channel blocker , SK&F 96365 , as well as other agents that prevented the Ca2+ influx , inhibited NF-kappaB activation .", "target_text": { "TCR": "protein", "NF-kappaB": "protein" } }, { "input_text": "Cotransfection of a constitutively active form of calcineurin largely substituted for the Ca2+ requirement and reversed the blockade by SK&F 96365 .", "target_text": { "calcineurin": "protein" } }, { "input_text": "Consistent with these observations , coexpression of constitutively active forms of Raf-1 and calcineurin synergistically induced kappaB -dependent reporter activity , suggesting a physiologically relevant functional interaction between the kinase and the phosphatase .", "target_text": { "Raf-1": "protein", "calcineurin": "protein", "kappaB": "protein", "kinase": "protein", "phosphatase": "protein" } }, { "input_text": "Synergistic interactions between overlapping binding sites for the serum response factor and ELK-1 proteins mediate both basal enhancement and phorbol ester responsiveness of primate cytomegalovirus major immediate-early promoters in monocyte and T-lymphocyte cell types .", "target_text": { "overlapping binding sites": "DNA", "serum response factor": "protein", "ELK-1 proteins": "protein", "primate cytomegalovirus major immediate-early promoters": "DNA", "T-lymphocyte": "cell_type" } }, { "input_text": "Cytomegalovirus ( CMV ) infection is nonpermissive or persistent in many lymphoid and myeloid cell types but can be activated in differentiated macrophages .", "target_text": { "differentiated macrophages": "cell_type" } }, { "input_text": "We have shown elsewhere that both the major immediate-early gene ( MIE ) and lytic cycle infectious progeny virus expression can be induced in otherwise nonpermissive monocyte-like U-937 cell cultures infected with either human CMV ( HCMV ) or simian CMV ( SCMV ) by treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate ( TPA ) .", "target_text": { "major immediate-early gene": "DNA", "MIE": "DNA", "monocyte-like U-937 cell cultures": "cell_line" } }, { "input_text": "Two multicopy basal enhancer motifs within the SCMV MIE enhancer , namely , 11 copies of the 16-bp cyclic AMP response element ( CRE ) and 3 copies of novel 17-bp serum response factor ( SRF ) binding sites referred to as the SNE ( SRF/NFkappaB-like element ) , as well as four classical NFkappaB sites within the HCMV version , contribute to TPA responsiveness in transient assays in monocyte and T- cell types .", "target_text": { "multicopy basal enhancer motifs": "DNA", "MIE": "DNA", "MIE enhancer": "DNA", "cyclic AMP response element": "DNA", "CRE": "DNA", "serum response factor": "protein", "SRF": "protein", "serum response factor ( SRF ) binding sites": "DNA", "SNE": "DNA", "SRF/NFkappaB-like element": "DNA", "NFkappaB sites": "DNA" } }, { "input_text": "The SCMV SNE sites contain potential overlapping core recognition binding motifs for SRF , Rel/NFkappaB , ETS , and YY1 class transcription factors but fail to respond to either serum or tumor necrosis factor alpha .", "target_text": { "SCMV SNE sites": "DNA", "SRF": "protein", "Rel/NFkappaB": "protein", "ETS": "protein", "YY1 class transcription factors": "protein" } }, { "input_text": "Therefore , to evaluate the mechanism of TPA responsiveness of the SNE motifs and of a related 16-bp SEE ( SRF/ ETS element ) motif found in the HCMV and chimpanzee CMV MIE enhancers , we have examined the functional responses and protein binding properties of multimerized wild-type and mutant elements added upstream to the SCMV MIE or simian virus 40 minimal promoter regions in the U-937 , K-562 , HL-60 , THP-1 , and Jurkat cell lines .", "target_text": { "SNE": "DNA", "SNE motifs": "DNA", "SEE": "DNA", "ETS": "protein", "SRF/ ETS element": "DNA", "MIE": "DNA", "SCMV MIE": "DNA", "simian virus 40 minimal promoter regions": "DNA", "U-937": "cell_line", "K-562": "cell_line", "HL-60": "cell_line", "THP-1": "cell_line", "Jurkat cell lines": "cell_line" } }, { "input_text": "Unlike classical NFkappaB sites , neither the SNE nor the SEE motif responded to phosphatase inhibition by okadaic acid .", "target_text": { "NFkappaB sites": "DNA", "SNE": "DNA", "SEE": "DNA", "SEE motif": "DNA" } }, { "input_text": "However , the TPA responsiveness of both CMV elements proved to involve synergistic interactions between the core SRF binding site ( CCATATATGG ) and the adjacent inverted ETS binding motifs ( TTCC ) , which correlated directly with formation of a bound tripartite complex containing both the cellular SRF and ELK-1 proteins .", "target_text": { "CMV elements": "DNA", "SRF": "protein", "SRF binding site": "DNA", "ETS": "protein", "ETS binding motifs": "DNA", "tripartite complex": "protein", "ELK-1 proteins": "protein" } }, { "input_text": "This protein complex was more abundant in U-937 , K-562 , and HeLa cell extracts than in Raji , HF , BALB/c 3T3 , or HL-60 cells , but the binding activity was altered only twofold after TPA treatment .", "target_text": { "protein complex": "protein", "Raji": "cell_line", "HF": "cell_line", "BALB/c 3T3": "cell_line", "HL-60 cells": "cell_line" } }, { "input_text": "A 40-fold stimulation of chloramphenicol acetyltransferase activity mediated by four tandem repeats of the SNE could be induced within 2 h ( and up to 250-fold within 6 h ) after addition of TPA in DNA-transfected U-937 cells , indicating that the stimulation appeared likely to be a true protein kinase C -mediated signal transduction event rather than a differentiation response .", "target_text": { "chloramphenicol acetyltransferase": "protein", "tandem repeats": "DNA", "SNE": "DNA", "U-937 cells": "cell_line", "DNA-transfected U-937 cells": "cell_line", "protein kinase C": "protein" } }, { "input_text": "Slight differences in the sequence of the core SRF binding site compared with that of the classical c-Fos promoter serum response element , together with differences in the spacing between the SRF and ETS motifs , appear to account for the inability of the SCMV SNEs to respond to serum induction .", "target_text": { "core SRF binding site": "DNA", "c-Fos promoter serum response element": "DNA", "SCMV SNEs": "DNA" } }, { "input_text": "T-cell -directed TAL-1 expression induces T-cell malignancies in transgenic mice .", "target_text": { "T-cell": "cell_type", "TAL-1": "protein" } }, { "input_text": "The TAL-1 gene specifies for a basic domain-helix-loop-helix protein , which is involved in the control of normal hematopoiesis .", "target_text": { "TAL-1 gene": "DNA", "domain-helix-loop-helix protein": "protein" } }, { "input_text": "In human pathology , the TAL-1 gene product is expressed in a high percentage of T-cell acute lymphoblastic leukemias in the pediatric age range ; however , it has not been established whether the expression has a causal role in oncogenesis .", "target_text": { "TAL-1 gene": "DNA", "TAL-1 gene product": "protein", "T-cell": "cell_type" } }, { "input_text": "In this report , we describe the phenotype of mouse transgenic lines obtained by inducing tal-1 protein expression in lymphoid tissues using the LCK promoter .", "target_text": { "mouse transgenic lines": "cell_line", "tal-1 protein": "protein", "LCK promoter": "DNA" } }, { "input_text": "The survival rate of tal-1 transgenic animals was much lower as compared with control mice .", "target_text": { "tal-1": "DNA" } }, { "input_text": "Histopathological analysis revealed lymphomas of T-cell type , often comprising a minor B-cell component .", "target_text": {} }, { "input_text": "Some mice showed marked splenic lymphocyte depletion .", "target_text": {} }, { "input_text": "Primary lymphocyte cultures showed partial independence from exogenous growth stimuli and increased resistance to low-serum apoptosis .", "target_text": { "Primary lymphocyte cultures": "cell_line" } }, { "input_text": "To further unravel the tal-1 oncogenic potential , a strain of tal-1 transgenic mice was crossbred with p53-/- mice ; the survival rate in these animals was reduced by more than one-half when compared with that of tal-1 mice , and histopathological analysis revealed exclusively T-cell lymphomas .", "target_text": { "tal-1": "DNA", "T-cell": "cell_type" } }, { "input_text": "These data indicate that TAL-1 , expressed in T cells , is per se a potent oncogene , which may exert a key leukemogenetic role in the majority of T-cell acute lymphoblastic leukemias .", "target_text": { "TAL-1": "protein", "T cells": "cell_type", "T-cell": "cell_type" } }, { "input_text": "Tissue and cell-type specific expression of the tuberous sclerosis gene , TSC2 , in human tissues .", "target_text": { "tuberous sclerosis gene": "DNA", "TSC2": "DNA" } }, { "input_text": "TSC2 is a gene on chromosome 16p13.3 associated with the autosomal dominant neurocutaneous disorder , tuberous sclerosis complex ( TSC ) .", "target_text": { "TSC2": "DNA", "chromosome 16p13.3": "DNA" } }, { "input_text": "By using a partial nucleotide sequence from the cloned TSC2 and polymerase chain reaction methodology , we constructed a digoxigenin-labeled complementary DNA probe to examine TSC2 gene expression in autopsy- or biopsy-derived human tissues by in situ hybridization .", "target_text": { "partial nucleotide sequence": "DNA", "TSC2": "DNA", "digoxigenin-labeled complementary DNA probe": "DNA" } }, { "input_text": "TSC2 messenger RNA was widely expressed in various cell types throughout the body , including epithelia , lymphocytes , and cells with endocrine functions , e.g. , adrenal cortex and anterior pituitary .", "target_text": { "TSC2": "DNA", "TSC2 messenger RNA": "RNA", "lymphocytes": "cell_type" } }, { "input_text": "It was prominently and selectively ( within the central nervous system ) expressed in pyramidal cells of the cerebral cortex and other motor neurons , e.g. , in spinal cord and brainstem nuclei .", "target_text": { "pyramidal cells": "cell_type", "motor neurons": "cell_type" } }, { "input_text": "Visceral TSC2 expression was comparable in autopsy tissues from patients with and without TSC ; TSC2 messenger RNA expression was most prominent in cells with a rapid mitotic rate and turnover , e.g. , epithelia and lymphocytes , with central nervous system pyramidal cells and other neurons being an obvious exception , and/or in cells with important secretory/transport functions .", "target_text": { "TSC2": "DNA", "lymphocytes": "cell_type", "pyramidal cells": "cell_type" } }, { "input_text": "This widespread expression of the TSC2 gene supports the view that it encodes a protein vital to cell growth and metabolism or one that functions as a tumor/growth suppressor .", "target_text": { "TSC2": "DNA", "TSC2 gene": "DNA" } }, { "input_text": "Apoptosis signaling pathways in normal T cells : differential activity of Bcl-2 and IL-1beta -converting enzyme family protease inhibitors on glucocorticoid- and Fas- mediated cytotoxicity .", "target_text": { "T cells": "cell_type", "Bcl-2": "protein", "IL-1beta": "protein", "IL-1beta -converting enzyme family": "protein" } }, { "input_text": "Fas -mediated apoptosis plays an important role in regulating the immune response in peripheral T cells .", "target_text": { "Fas": "protein", "T cells": "cell_type", "peripheral T cells": "cell_type" } }, { "input_text": "Restimulation of T cell blasts up-regulates Fas and Fas ligand expression , with subsequent interaction leading to cell death .", "target_text": { "T cell blasts": "cell_type", "Fas": "protein" } }, { "input_text": "Overexpression of Bcl-2 in tumor cells blocks apoptosis induced by many stimuli , but inhibition of Fas -mediated killing has not been consistently observed .", "target_text": { "Bcl-2": "protein", "tumor cells": "cell_type", "Fas": "protein" } }, { "input_text": "To examine the behavior of Bcl-2 in normal cells , T cell blasts were transiently transfected with Bcl-2 and related gene products to determine the effect on apoptotic signaling .", "target_text": { "Bcl-2": "protein", "normal cells": "cell_type", "T cell blasts": "cell_type", "gene products": "protein" } }, { "input_text": "Transient overexpression of Bcl-2 in mouse and human T cell blasts did not block Fas -mediated apoptosis , whereas etoposide- and glucocorticoid- induced cytotoxicity was potently inhibited .", "target_text": { "Bcl-2": "protein", "T cell blasts": "cell_type", "Fas": "protein" } }, { "input_text": "Expression of Bcl-xL and adenovirus E1B 19K did not interfere with anti- Fas killing .", "target_text": { "Bcl-xL": "protein", "adenovirus E1B 19K": "protein", "Fas": "protein" } }, { "input_text": "In contrast , interleukin-1beta-converting enzyme family protease inhibitors Ac-DEVD-CHO and CrmA blocked Fas -mediated apoptosis .", "target_text": { "Fas": "protein" } }, { "input_text": "These results suggest that peripheral T cells use distinct apoptosis signaling pathways with differential sensitivity to Bcl-2 and interleukin-1beta-converting enzyme family protease inhibitors .", "target_text": { "T cells": "cell_type", "peripheral T cells": "cell_type", "Bcl-2": "protein" } }, { "input_text": "Since T cells normally express Bcl-2 and Bcl-xL following activation , their inability to block Fas -mediated apoptosis may allow for the elimination of self-reactive cells and the appropriate regulation of immune responses .", "target_text": { "T cells": "cell_type", "Bcl-2": "protein", "Bcl-xL": "protein", "Fas": "protein", "self-reactive cells": "cell_type" } }, { "input_text": "Increased interleukin 2 transcription in murine lymphocytes by ciprofloxacin .", "target_text": { "interleukin 2": "protein", "murine lymphocytes": "cell_type" } }, { "input_text": "The fluoroquinolone antibiotic , ciprofloxacin ( cipro ) , induces hyperproduction of interleukin 2 ( IL-2 ) and interferon-gamma ( IFN-gamma ) in stimulated human peripheral blood lymphocytes .", "target_text": { "interleukin 2": "protein", "IL-2": "protein", "interferon-gamma": "protein", "IFN-gamma": "protein", "human peripheral blood lymphocytes": "cell_type" } }, { "input_text": "In this investigation an enhanced and prolonged IL-2 and IL-2 mRNA response was also detected in both stimulated ( T cell mitogens or alloantigens ) murine splenocytes and in the stimulated murine T cell line EL-4 in the presence of ciprofloxacin ( 5-80 micrograms/ml ) as compared to control cells without antibiotics .", "target_text": { "IL-2": "protein", "IL-2 mRNA": "RNA", "T cell mitogens": "protein", "alloantigens": "protein", "murine splenocytes": "cell_type", "murine T cell line EL-4": "cell_line" } }, { "input_text": "However , in contrast to human lymphocytes , IFN-gamma production was inhibited and IFN-gamma mRNA levels were unaffected at 24 h and only slightly upregulated at 48 and 72 h of culture in murine splenocytes incubated with cipro ( 20 micrograms/ml ) .", "target_text": { "human lymphocytes": "cell_type", "IFN-gamma": "protein", "IFN-gamma mRNA": "RNA", "murine splenocytes": "cell_type" } }, { "input_text": "EL-4 cells were transfected with a plasmid containing the IL-2 promoter and enhancer region linked to the chloramphenicol acetyltransferase ( CAT ) reporter gene .", "target_text": { "EL-4 cells": "cell_type", "IL-2 promoter": "DNA", "enhancer region": "DNA", "chloramphenicol acetyltransferase": "protein", "CAT": "protein", "chloramphenicol acetyltransferase ( CAT ) reporter gene": "DNA" } }, { "input_text": "Analysis of CAT activity revealed that cipro enhanced IL-2 gene induction .", "target_text": { "CAT": "protein" } }, { "input_text": "In addition , EL-4 cells incubated with ciprofloxacin showed an early peak and more activated nuclear factor of activated T cells ( NFAT-1 ) as compared to control cells without antibiotics .", "target_text": { "EL-4 cells": "cell_type", "activated T cells": "cell_type", "NFAT-1": "protein" } }, { "input_text": "Cipro did not affect the nuclear transcription factors AP-1 or NFIL-2A .", "target_text": { "nuclear transcription factors": "protein", "AP-1": "protein", "NFIL-2A": "protein" } }, { "input_text": "Taken together , cipro inhibited IFN-gamma synthesis , but enhanced IL-2 production in murine lymphocytes by means of influencing NFAT-1 and causing an increased IL-2 transcription .", "target_text": { "IFN-gamma": "protein", "IL-2": "protein", "murine lymphocytes": "cell_type", "NFAT-1": "protein" } }, { "input_text": "Human T-cell leukemia virus type I Tax associates with and is negatively regulated by the NF-kappa B2 p100 gene product : implications for viral latency .", "target_text": { "Tax": "protein", "NF-kappa B2 p100 gene": "DNA", "NF-kappa B2 p100 gene product": "protein" } }, { "input_text": "Human T-cell leukemia virus type I ( HTLV-I ) is the etiologic agent of the adult T-cell leukemia , an aggressive and often fatal malignancy of activated human CD4 T cells .", "target_text": { "activated human CD4 T cells": "cell_line" } }, { "input_text": "HTLV-I encodes an essential 40-kDa protein termed Tax that not only transactivates the long terminal repeat of this retrovirus but also induces an array of cellular genes .", "target_text": { "40-kDa protein": "protein", "Tax": "protein", "cellular genes": "DNA" } }, { "input_text": "Tax -mediated transformation of T cells likely involves the deregulated expression of various cellular genes that normally regulate lymphocyte growth produced by altered activity of various endogenous host transcription factors .", "target_text": { "Tax": "protein", "T cells": "cell_type", "cellular genes": "DNA", "lymphocyte": "cell_type", "transcription factors": "protein" } }, { "input_text": "In particular , Tax is capable of modulating the expression or activity of various host transcription factors , including members of the NF-kappa B/Rel and CREB/ATF families , as well as the cellular factors HEB-1 and p67SRF .", "target_text": { "Tax": "protein", "transcription factors": "protein", "NF-kappa B/Rel": "protein", "CREB/ATF families": "protein", "cellular factors": "protein", "HEB-1": "protein", "p67SRF": "protein" } }, { "input_text": "An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating primary leukemic T cells .", "target_text": { "primary leukemic T cells": "cell_type" } }, { "input_text": "In this study , we demonstrate that HTLV-I Tax can physically associate with p100 , the product of the Rel-related NF-kappa B2 gene , both in transfected cells and in HTLV-I -infected leukemic T-cell lines .", "target_text": { "Tax": "protein", "p100": "protein", "Rel-related NF-kappa B2 gene": "DNA", "transfected cells": "cell_line", "HTLV-I -infected leukemic T-cell lines": "cell_line" } }, { "input_text": "Furthermore , the physical interaction of Tax with p100 leads to the inhibition of Tax -induced activation of the HTLV-I and human immunodeficiency virus type 1 long terminal repeats , reflecting p100 -mediated cytoplasmic sequestration of the normally nuclearly expressed Tax protein .", "target_text": { "Tax": "protein", "p100": "protein", "human immunodeficiency virus type 1 long terminal repeats": "DNA", "Tax protein": "protein" } }, { "input_text": "In contrast , a mutant of Tax that selectively fails to activate nuclear NF-kappa B expression does not associate with p100 .", "target_text": { "Tax": "protein", "NF-kappa B": "protein", "p100": "protein" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "Rhabdomyosarcomas do not contain mutations in the DNA binding domains of myogenic transcription factors .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Skeletal myogenesis is regulated by a group of transcription factors ( MyoD , myogenin , myf5 , and myf6 ) that are \" basic helix-loop-helix \" proteins that bind to the promoters of muscle-specific genes and promote their expression .", "target_text": { "transcription factors": "protein", "MyoD": "protein", "myogenin": "protein", "myf5": "protein", "myf6": "protein", "\" basic helix-loop-helix \" proteins": "protein", "promoters": "DNA", "muscle-specific genes": "DNA" } }, { "input_text": "We have previously shown that after a mutation of Leu122 to Arg the DNA binding basic domain of MyoD confers c-myc -like functional characteristics to the protein .", "target_text": { "DNA binding basic domain": "protein", "MyoD": "protein", "c-myc": "DNA" } }, { "input_text": "In this study we used single-strand conformation polymorphism analysis to determine whether such mutations occur naturally in rhabdomyosarcomas .", "target_text": {} }, { "input_text": "We have found that the basic domains of all the myogenic factors remain unaltered in rhabdomyosarcomas .", "target_text": { "basic domains": "protein", "myogenic factors": "protein" } }, { "input_text": "Selection against such mutations may be the result of functional redundancy of these myogenic transcription factors .", "target_text": { "transcription factors": "protein", "myogenic transcription factors": "protein" } }, { "input_text": "Function and activation of NF-kappa B in the immune system .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "NF-kappa B is a ubiquitous transcription factor .", "target_text": { "NF-kappa B": "protein", "ubiquitous transcription factor": "protein" } }, { "input_text": "Nevertheless , its properties seem to be most extensively exploited in cells of the immune system .", "target_text": {} }, { "input_text": "Among these properties are NF-kappa B 's rapid posttranslational activation in response to many pathogenic signals , its direct participation in cytoplasmic/nuclear signaling , and its potency to activate transcription of a great variety of genes encoding immunologically relevant proteins .", "target_text": { "NF-kappa B": "protein", "immunologically relevant proteins": "protein" } }, { "input_text": "In vertebrates , five distinct DNA binding subunits are currently known which might extensively heterodimerize , thereby forming complexes with distinct transcriptional activity , DNA sequence specificity , and cell type- and cell stage-specific distribution .", "target_text": { "DNA binding subunits": "protein" } }, { "input_text": "The activity of DNA binding NF-kappa B dimers is tightly controlled by accessory proteins called I kappa B subunits of which there are also five different species currently known in vertebrates .", "target_text": { "NF-kappa B": "protein", "DNA binding NF-kappa B dimers": "protein", "accessory proteins": "protein", "I kappa B subunits": "protein" } }, { "input_text": "I kappa B proteins inhibit DNA binding and prevent nuclear uptake of NF-kappa B complexes .", "target_text": { "I kappa B proteins": "protein", "NF-kappa B complexes": "protein" } }, { "input_text": "An exception is the Bcl-3 protein which in addition can function as a transcription activating subunit in th nucleus .", "target_text": { "Bcl-3 protein": "protein", "transcription activating subunit": "protein" } }, { "input_text": "Other I kappa B proteins are rather involved in terminating NF-kappa B 's activity in the nucleus .", "target_text": { "I kappa B proteins": "protein", "NF-kappa B": "protein" } }, { "input_text": "The intracellular events that lead to the inactivation of I kappa B , i.e. the activation of NF-kappa B , are complex .", "target_text": { "I kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells ' redox status .", "target_text": {} }, { "input_text": "Interference with the activation or activity of NF-kappa B may be beneficial in suppressing toxic/septic shock , graft-vs-host reactions , acute inflammatory reactions , acute phase response , and radiation damage .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Lack of T-cell-mediated recognition of the fusion region of the pml/RAR-alpha hybrid protein by lymphocytes of acute promyelocytic leukemia patients .", "target_text": { "pml/RAR-alpha hybrid protein": "protein", "lymphocytes": "cell_type" } }, { "input_text": "In previous studies , it was shown that the fusion region of the pml/RAR-alpha protein , expressed by acute promyelocytic leukemia ( APL ) cells , can be specifically recognized in vitro by donor ( D. E. ) CD4 T cells in a HLA class II DR11-restricted fashion .", "target_text": { "pml/RAR-alpha protein": "protein", "acute promyelocytic leukemia ( APL ) cells": "cell_line", "CD4 T cells": "cell_line", "HLA class II": "protein" } }, { "input_text": "We present here the results on the recognition of several pml/RAR-alpha peptides by APL patients expressing HLA DR11 .", "target_text": { "HLA DR11": "protein" } }, { "input_text": "The in vitro immunization of peripheral blood lymphocytes from four patients in remission ( S.R. , F.R. , M.M. , P. G. ) with BCR1/25 , a 25-mer pml/ RAR-alpha , did not elicit either a polyclonal or a clonal immune response specific to the peptide .", "target_text": { "peripheral blood lymphocytes": "cell_type", "RAR-alpha": "protein" } }, { "input_text": "We then generated new donor anti-pml/ RAR-alpha CD4(+) T-cell clones .", "target_text": { "RAR-alpha": "protein", "anti-pml/ RAR-alpha": "protein", "anti-pml/ RAR-alpha CD4(+) T-cell clones": "cell_line" } }, { "input_text": "These clones were tested for their recognition of BCR1/25 .", "target_text": {} }, { "input_text": "One clone ( C3/5 , CD3(+) , CD4(+) , CD8(-) ) was selected for further analysis .", "target_text": { "C3/5 , CD3(+) , CD4(+) , CD8(-)": "cell_line" } }, { "input_text": "Clone C3/5 showed specific proliferation , cytotoxicity , and cytokine ( tumor necrosis factor alpha , granulocyte-macrophage colony-stimulating factor ) production when challenged with autologous lymphoblastic cell lines pulsed with peptide BCR1/25 .", "target_text": { "Clone C3/5": "cell_line", "tumor necrosis factor alpha": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "autologous lymphoblastic cell lines": "cell_line" } }, { "input_text": "C3/5 cells developed specific proliferation and cytotoxicity when challenged with peptide-pulsed lymphoblastic cell lines and peripheral blood lymphocytes from the four DR11(+) APL patients .", "target_text": { "C3/5 cells": "cell_line", "peptide-pulsed lymphoblastic cell lines": "cell_line", "peripheral blood lymphocytes": "cell_type" } }, { "input_text": "APL blasts , available only from patients F.R. and P.G. , were not lysed by C3/5 and were unable to present peptide BCR1/25 .", "target_text": { "APL blasts": "cell_type", "C3/5": "cell_line" } }, { "input_text": "Incubation of APL cells with IFN-gamma failed to induce HLA class II molecules and recognition by the C3/5 clone .", "target_text": { "APL cells": "cell_line", "IFN-gamma": "protein", "HLA class II molecules": "protein", "C3/5 clone": "cell_line" } }, { "input_text": "Since APL cells do not express HLA class II molecules , we tested in two donors ( D.E. and C.H.R. ) and in patients S.R. and P.G. whether the use of 9-mer peptides ( BCR1/9 ) would generate a CD8 /HLA class I -restricted response .", "target_text": { "APL cells": "cell_line", "HLA class II molecules": "protein", "CD8": "protein", "/HLA class I": "protein" } }, { "input_text": "No peptide-specific T-cell line or clone could be generated from both donors and patients .", "target_text": { "peptide-specific T-cell line": "cell_line" } }, { "input_text": "These findings are discussed in relation to possible therapeutic approaches to the immunotherapy of APL .", "target_text": {} }, { "input_text": "The proximal regulatory element of the interferon-gamma promoter mediates selective expression in T cells .", "target_text": { "interferon-gamma": "protein", "interferon-gamma promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "Interferon-gamma ( IFN-gamma ) is produced by natural killer cells and certain subsets of T cells , but the basis for its selective expression is unknown .", "target_text": { "Interferon-gamma": "protein", "IFN-gamma": "protein", "natural killer cells": "cell_type", "T cells": "cell_type" } }, { "input_text": "Within the region between -108 and -40 base pairs of the IFN-gamma promoter are two conserved and essential regulatory elements , which confer activation-specific expression in T cells .", "target_text": { "IFN-gamma": "protein", "regulatory elements": "DNA", "T cells": "cell_type" } }, { "input_text": "This report describes studies indicating that the most proximal of these two regulatory elements is an important determinant of its restricted expression .", "target_text": { "regulatory elements": "DNA" } }, { "input_text": "The proximal element is a composite site that binds members of the CREB/ATF , AP-1 , and octamer families of transcription factors .", "target_text": { "CREB/ATF": "protein", "AP-1": "protein", "octamer families": "protein", "transcription factors": "protein" } }, { "input_text": "Jun is essential for activation-induced transcription and binds preferably as a heterodimer with ATF-2 .", "target_text": { "Jun": "protein", "ATF-2": "protein" } }, { "input_text": "In contrast , CREB appears to dampen transcription from this element .", "target_text": { "CREB": "protein" } }, { "input_text": "The CpG dinucleotide in this element is selectively methylated in Th2 T cells and other cells that do not express IFN-gamma , and methylation markedly reduces transcription factor binding .", "target_text": { "element": "DNA", "Th2 T cells": "cell_type", "IFN-gamma": "protein", "transcription factor": "protein" } }, { "input_text": "As a target for DNA methylation and for binding of transcription factors that mediate or impede transcription , this element appears to play a central role in controlling IFN-gamma expression .", "target_text": { "transcription factors": "protein", "IFN-gamma": "protein" } }, { "input_text": "CD40 , but not lipopolysaccharide and anti-IgM stimulation of primary B lymphocytes , leads to a persistent nuclear accumulation of RelB .", "target_text": { "CD40": "protein", "anti-IgM": "protein", "primary B lymphocytes": "cell_type", "RelB": "protein" } }, { "input_text": "In this study we analyzed the effect of CD40 stimulation on the activity and nuclear appearance of Rel/nuclear factor kappaB ( NF-kappaB ) factors in primary murine B lymphocytes .", "target_text": { "CD40": "protein", "Rel/nuclear factor kappaB": "protein", "NF-kappaB": "protein", "Rel/nuclear factor kappaB ( NF-kappaB ) factors": "protein", "primary murine B lymphocytes": "cell_type" } }, { "input_text": "We show that triggering of CD40 signaling pathway ( s ) by CD40 ligands expressed on L cells led to strong activation of an NF-kappaB-controlled beta-globin reporter gene in primary B lymphocytes from transgenic mice .", "target_text": { "CD40": "protein", "CD40 ligands": "protein", "L cells": "cell_type", "NF-kappaB-controlled beta-globin reporter gene": "DNA", "primary B lymphocytes": "cell_type" } }, { "input_text": "Analyses of nuclear translocation of individual members of Rel proteins after CD40 induction of primary B cells showed a strong and long-lasting accumulation of RelB and , less pronounced , of c-Rel .", "target_text": { "Rel proteins": "protein", "CD40": "protein", "primary B cells": "cell_type", "RelB": "protein", "c-Rel": "protein" } }, { "input_text": "LPS stimulation did not give rise to a persistent nuclear accumulation of RelB and c-Rel , whereas nuclear c-Rel , but not RelB , accumulated after B cell receptor stimulation .", "target_text": { "RelB": "protein", "c-Rel": "protein" } }, { "input_text": "CD40 induced not only nuclear translocation but also de novo synthesis of RelB RNA and protein .", "target_text": { "CD40": "protein", "RelB": "protein", "RelB RNA": "RNA" } }, { "input_text": "S107 plasmacytoma cells , which express CD40 but are defective for the nuclear appearance of p50/p65-NF-kappaB , do not express RelB after CD40 stimulation .", "target_text": { "S107 plasmacytoma cells": "cell_line", "CD40": "protein", "p50/p65-NF-kappaB": "protein", "RelB": "protein" } }, { "input_text": "In S107 cells stably transfected with relB genes , stimulation of nuclear RelB translocation by CD40 was observed .", "target_text": { "S107 cells": "cell_line", "relB genes": "DNA", "RelB": "protein", "CD40": "protein" } }, { "input_text": "These results indicate that stimulation of CD40 signaling pathways exerts a long-lasting stimulatory effect on both the transcription and nuclear translocation of RelB .", "target_text": { "CD40": "protein", "RelB": "protein" } }, { "input_text": "Since LPS and anti-IgM were unable to activate RelB , CD40 appears to trigger a special program of gene expression involved in the proliferation and/or differentiation of B lymphocytes .", "target_text": { "anti-IgM": "protein", "RelB": "protein", "CD40": "protein", "B lymphocytes": "cell_type" } }, { "input_text": "Identification and characterization of a leukocyte-specific component of the nuclear body .", "target_text": {} }, { "input_text": "The nuclear body ( NB ) is a cellular organelle that is involved in the pathogenesis of acute promyelocytic leukemia and viral infection .", "target_text": {} }, { "input_text": "The NB is also a target of antibodies in the serum of patients with the autoimmune disease primary biliary cirrhosis .", "target_text": { "antibodies": "protein" } }, { "input_text": "In this study , serum from a patient with primary biliary cirrhosis was used to identify a cDNA encoding a novel component of the NB , a 140-kDa protein designated Sp140 .", "target_text": { "140-kDa protein": "protein", "Sp140": "protein" } }, { "input_text": "The predicted amino acid sequence of the amino-terminal portion of Sp140 was similar to Sp100 , a previously identified NB protein .", "target_text": { "amino acid sequence": "protein", "amino-terminal portion": "protein", "Sp140": "protein", "Sp100": "protein", "NB protein": "protein" } }, { "input_text": "The carboxyl portion of Sp140 contained a zinc-finger domain and a bromodomain , motifs that are present in proteins regulating gene transcription .", "target_text": { "carboxyl portion": "protein", "Sp140": "protein", "zinc-finger domain": "protein", "bromodomain": "protein" } }, { "input_text": "High levels of Sp140 mRNA were detected in human spleen and peripheral blood leukocytes , but not other human tissues .", "target_text": { "Sp140": "protein", "Sp140 mRNA": "RNA", "peripheral blood leukocytes": "cell_type" } }, { "input_text": "The level of SP140 mRNA in myeloid precursor cell lines HL60 and NB4 markedly increased in response to chemically induced cellular differentiation .", "target_text": { "SP140 mRNA": "RNA", "myeloid precursor cell lines": "cell_line", "HL60": "cell_line", "NB4": "cell_line" } }, { "input_text": "Immunohistochemical techniques were used to demonstrate that SP140 localized to the NB in differentiated HL60 and NB4 cells .", "target_text": { "SP140": "protein", "HL60": "cell_line", "NB4 cells": "cell_line" } }, { "input_text": "The location of Sp140 in the NB , and expression of this gene in cells involved in host defense , suggest that Sp140 may be involved in the pathogenesis of acute promyelocytic leukemia and viral infection .", "target_text": { "Sp140": "protein" } }, { "input_text": "Regulation of cytokine and cytokine receptor expression by glucocorticoids .", "target_text": { "cytokine": "protein", "cytokine receptor": "protein" } }, { "input_text": "Glucocorticoids ( GCS ) profoundly inhibit several aspects of T cell immunity largely through inhibition of cytokine expression at the transcriptional and posttranscriptional levels .", "target_text": { "cytokine": "protein" } }, { "input_text": "GCS were also reported to act indirectly by inducing transforming growth factor-beta expression , which in turn blocks T cell immunity .", "target_text": { "growth factor-beta": "protein" } }, { "input_text": "In exerting their antiproliferative effects , GCS diffuse into target cells where they bind their cytoplasmic receptor , which in turn translocates to the nucleus where it inhibits transcription of cytokine genes through direct binding to the glucocorticoid response elements ( GRE ) , which are located in the promoter region of cytokine genes or , alternatively , through antagonism of the action of transcription factors required for optimal transcriptional activation .", "target_text": { "target cells": "cell_type", "cytoplasmic receptor": "protein", "cytokine": "protein", "cytokine genes": "DNA", "glucocorticoid response elements": "DNA", "GRE": "DNA", "transcription factors": "protein" } }, { "input_text": "In contrast to their inhibitory effects on cytokine expression , GCS up-regulate cytokine receptor expression that correlates with enhanced cytokine effects on target cells .", "target_text": { "cytokine": "protein", "cytokine receptor": "protein", "target cells": "cell_type" } }, { "input_text": "In this review , we summarize the current state of knowledge of the mechanism of action of GCS , including the phenomenon of steroid-induced rebound , which ensues upon GCS withdrawal .", "target_text": {} }, { "input_text": "Isolation and characterization of murine fra-1 : induction mediated by CD40 and surface Ig is protein kinase C dependent .", "target_text": { "murine fra-1": "DNA", "CD40": "protein", "surface Ig": "protein", "protein kinase C": "protein" } }, { "input_text": "The murine fra-1 gene , encoding Fos-related Ag 1 , was isolated from a splenic cDNA library and sequenced .", "target_text": { "murine fra-1 gene": "DNA", "Fos-related Ag 1": "protein", "splenic cDNA library": "DNA" } }, { "input_text": "Murine fra-1 was highly homologous to rat and human fra-1 .", "target_text": { "Murine fra-1": "DNA" } }, { "input_text": "Oligonucleotide primers based on the murine sequence were used to construct a quantitative reverse transcription-PCR assay for gene expression .", "target_text": { "murine sequence": "DNA" } }, { "input_text": "B lymphocyte stimulation via both CD40 and surface Ig ( sIg ) receptors substantially induced fra-1 expression , and for both receptors , induction was protein kinase C ( PKC ) dependent .", "target_text": { "B lymphocyte": "cell_type", "CD40": "protein", "surface Ig": "protein", "sIg": "protein", "surface Ig ( sIg ) receptors": "protein", "fra-1": "DNA", "protein kinase C": "protein", "PKC": "protein" } }, { "input_text": "This contrasts with induction of c-fos by both CD40 and sIg , which is PKC independent and indicates that CD40 is capable of signaling through PKC or a closely related kinase .", "target_text": { "c-fos": "DNA", "CD40": "protein", "sIg": "protein", "PKC": "protein", "kinase": "protein" } }, { "input_text": "Induction of fra-1 following engagement of CD40 did not require protein synthesis , suggesting that the PKC -dependent linkage between CD40 and fra-1 is direct .", "target_text": { "fra-1": "DNA", "CD40": "protein", "PKC": "protein" } }, { "input_text": "CD40 -mediated fra-1 induction did require tyrosine kinase activity .", "target_text": { "CD40": "protein", "fra-1": "DNA", "tyrosine kinase": "protein" } }, { "input_text": "These results demonstrate that CD40 , like sIg , may employ PKC in producing select outcomes , that individual B cell receptors may signal downstream events via both PKC-dependent and PKC-independent pathways , and that multiple signal transduction pathways may be used to activate the expression of closely related genes .", "target_text": { "CD40": "protein", "sIg": "protein", "PKC": "protein", "B cell receptors": "protein", "genes": "DNA" } }, { "input_text": "Pentoxifylline for the treatment of infection with human immunodeficiency virus .", "target_text": {} }, { "input_text": "Cytokine dysregulation in human immunodeficiency virus type 1 ( HIV-1 ) infection has been documented in numerous studies and has been cited as an important component in the pathogenesis of this retroviral infection .", "target_text": {} }, { "input_text": "Pharmacological modification of cytokine dysregulation , therefore , has been suggested as a therapeutic modality for HIV-1 infection .", "target_text": { "cytokine": "protein" } }, { "input_text": "Dr. Dezube of Beth Israel Hospital ( Boston ) concisely reviews the state of our knowledge regarding the effects of pentoxifylline on expression of tumor necrosis factor-alpha , a cytokine known to influence HIV-1 replication and to play a possible role in the clinical manifestations of advanced infection with this virus .", "target_text": { "tumor necrosis factor-alpha": "protein", "cytokine": "protein" } }, { "input_text": "Pentoxifylline , a trisubstituted xanthine derivative , has been used to decrease blood viscosity and is reasonably well tolerated by most recipients of the drug .", "target_text": {} }, { "input_text": "Results of preliminary studies , many of which were conducted by Dr. Dezube , suggest that use of this agent in combination with antiretroviral compounds may prove useful in the treatment of patients with HIV-1 infection .", "target_text": {} }, { "input_text": "Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors .", "target_text": { "granulocyte-macrophage colony-stimulating factor": "protein", "granulocyte-macrophage colony-stimulating factor promoter": "DNA", "T cells": "cell_type", "Elf-1": "protein", "AP-1": "protein", "transcription factors": "protein" } }, { "input_text": "The granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene has been studied extensively as a model system of transcriptional induction during T-lymphocyte activation .", "target_text": { "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene": "DNA" } }, { "input_text": "The GM-CSF gene is not expressed in resting peripheral blood T cells but is rapidly induced at the transcriptional level following activation through the cell surface T-cell receptor .", "target_text": { "GM-CSF": "protein", "GM-CSF gene": "DNA", "peripheral blood T cells": "cell_type", "resting peripheral blood T cells": "cell_type", "cell surface T-cell receptor": "protein" } }, { "input_text": "A highly conserved 19-bp element located immediately 5' of the human GM-CSF TATA box ( bp -34 to -52 ) , herein called purine box 1 ( PB1 ) , has been shown to bind a T-cell nuclear protein complex and to be required for transcriptional induction of the GM-CSF gene following T-cell activation .", "target_text": { "GM-CSF": "protein", "human GM-CSF TATA box": "DNA", "bp -34 to -52": "DNA", "purine box 1": "DNA", "PB1": "DNA", "T-cell nuclear protein complex": "protein", "GM-CSF gene": "DNA" } }, { "input_text": "The PB1 sequence motif is highly conserved in both human and murine GM-CSF genes .", "target_text": { "PB1": "DNA" } }, { "input_text": "In this report , we demonstrate that the PB1 element alone confers inducibility on a heterologous promoter following transfection into human Jurkat T cells .", "target_text": { "PB1": "DNA", "PB1 element": "DNA", "human Jurkat T cells": "cell_line" } }, { "input_text": "In addition , we identify a major PB1 nuclear protein-binding complex that is not present in resting peripheral blood T cells but is rapidly induced following T-cell activation .", "target_text": { "PB1": "DNA", "PB1 nuclear protein-binding complex": "protein", "peripheral blood T cells": "cell_type", "resting peripheral blood T cells": "cell_type" } }, { "input_text": "Sequence analysis revealed that PB1 is composed of adjacent binding sites for Ets and AP-1 transcription factors .", "target_text": { "PB1": "DNA", "adjacent binding sites": "DNA", "Ets": "protein", "AP-1": "protein", "transcription factors": "protein" } }, { "input_text": "In vitro mutagenesis experiments demonstrated that both the Ets and AP-1 sites are required for binding of the inducible PB1 nuclear protein complex and for the transcriptional activity of this element and the GM-CSF promoter in activated T cells .", "target_text": { "PB1": "DNA", "PB1 nuclear protein complex": "protein", "GM-CSF": "protein", "GM-CSF promoter": "DNA", "activated T cells": "cell_type" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "Steroid-resistant asthma .", "target_text": {} }, { "input_text": "Cellular mechanisms contributing to inadequate response to glucocorticoid therapy .", "target_text": {} }, { "input_text": "The current study examined whether alterations in glucocorticoid receptor ( GR ) binding contribute to poor response to glucocorticoid therapy in asthma .", "target_text": { "glucocorticoid receptor": "protein", "GR": "protein" } }, { "input_text": "29 asthma patients with forced expiratory volume in 1 s ( FEV1 ) < 70 % predicted were studied .", "target_text": {} }, { "input_text": "Patients were classified as steroid sensitive ( SS ) if their morning FEV1 increased > 30 % after a 1-wk course of oral prednisone 20 mg twice daily and steroid resistant ( SR ) if they failed to increase > 15 % .", "target_text": {} }, { "input_text": "PBMC obtained from these two groups , 17 SR and 12 SS , as well as 12 normal controls were analyzed . SR patients had two distinguishable GR binding abnormalities : 15 of the 17 SR patients demonstrated a significantly reduced GR binding affinity , as compared with SS patients ( P = 0.0001 ) and normal controls ( P = 0.0001 ) .", "target_text": { "GR": "protein" } }, { "input_text": "This defect was localized to T cells and reverted to normal after 48 h in culture media .", "target_text": { "T cells": "cell_type" } }, { "input_text": "However , incubation with a combination of IL-2 and IL-4 sustained this abnormality .", "target_text": { "IL-2": "protein", "IL-4": "protein" } }, { "input_text": "The other two SR patients had an abnormally low GR number with normal binding affinity that was not limited to T cells .", "target_text": { "GR": "protein", "T cells": "cell_type" } }, { "input_text": "Furthermore , GR number failed to normalize after incubation in media alone or IL-2 and IL-4 .", "target_text": { "GR": "protein", "IL-2": "protein", "IL-4": "protein" } }, { "input_text": "Therefore , SR asthma may be due to more than one abnormality , the majority related to a reversible cytokine -induced reduction in GR binding affinity and the second related to an irreversible reduction in GR number .", "target_text": { "cytokine": "protein", "GR": "protein" } }, { "input_text": "These findings may have important implications for the design of alternative treatment approaches for recalcitrant asthma .", "target_text": {} }, { "input_text": "Prevalence of aneuploidy , overexpressed ER , and overexpressed EGFR in random breast aspirates of women at high and low risk for breast cancer .", "target_text": { "ER": "protein", "EGFR": "protein" } }, { "input_text": "Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available .", "target_text": {} }, { "input_text": "We initiated this study to determine 1 ) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer , and 2 ) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women .", "target_text": {} }, { "input_text": "Eligible high risk women were those with a first degree relative with breast cancer , prior breast cancer , or precancerous mastopathy .", "target_text": {} }, { "input_text": "Low risk women were those without these or other major identifiable risk factors .", "target_text": {} }, { "input_text": "Ductal cells were obtained via random fine needle aspirations and cytologically classified .", "target_text": { "Ductal cells": "cell_type" } }, { "input_text": "Biomarkers included DNA ploidy , estrogen receptor ( ER ) , and epidermal growth factor receptor ( EGFR ) .", "target_text": { "estrogen receptor": "protein", "ER": "protein", "epidermal growth factor receptor": "protein", "EGFR": "protein" } }, { "input_text": "The prevalence of DNA aneuploidy was 30 % , overexpression of ER 10 % , and overexpression of EGFR 35 % , in the 206 high risk women whose median 10 year Gail risk ( projected probability ) of developing breast cancer was 4.5 % .", "target_text": { "ER": "protein", "EGFR": "protein" } }, { "input_text": "The prevalence of aneuploidy and overexpressed EGFR was significantly higher in the high risk women than in the 25 low risk controls ( p < 0.002 ) , whose median 10 year Gail risk was 0.7 % .", "target_text": { "EGFR": "protein" } }, { "input_text": "The difference in the prevalence of ER overexpression between high and low risk groups was not statistically significant ( p = 0.095 ) .", "target_text": { "ER": "protein" } }, { "input_text": "This may be due to the low prevalence of overexpressed ER and the small number of controls .", "target_text": { "ER": "protein" } }, { "input_text": "A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women ( p < 0.001 ) .", "target_text": {} }, { "input_text": "A large prospective trial is needed to determine if one or more of these biomarkers , is predictive of breast cancer development .", "target_text": {} }, { "input_text": "Inhibition of nuclear factor kappa B subunit p65 mRNA accumulation in lipopolysaccharide -stimulated human monocytic cells treated with sodium salicylate .", "target_text": { "nuclear factor kappa B": "protein", "nuclear factor kappa B subunit p65": "protein", "nuclear factor kappa B subunit p65 mRNA": "RNA", "lipopolysaccharide -stimulated human monocytic cells": "cell_line" } }, { "input_text": "Lipopolysaccharide is one of the most potent trigger substances for monocytes and macrophages causing secretion of inflammatory mediators such as tumor necrosis factor and interleukin-1 .", "target_text": { "inflammatory mediators": "protein", "tumor necrosis factor": "protein", "interleukin-1": "protein" } }, { "input_text": "The nature of the nuclear factors involved in regulation of these cytokine genes is still unknown .", "target_text": { "cytokine": "protein", "cytokine genes": "DNA" } }, { "input_text": "Nuclear factor kappa B ( NF-kappa B ; heterodimer of p50 and p65 ) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with lipopolysaccharide .", "target_text": { "Nuclear factor kappa B": "protein", "NF-kappa B": "protein", "p50": "protein", "p65": "protein", "Nuclear factor kappa B ( NF-kappa B ; heterodimer of p50 and p65 ) proteins": "protein", "inflammatory mediators": "protein", "monocytes": "cell_type" } }, { "input_text": "Nonsteroidal anti-inflammatory drugs such as salicylates have been used to treat symptoms of inflammation , and a new mechanism of drug action was suggested recently .", "target_text": {} }, { "input_text": "Salicylates have been shown to inhibit lipopolysaccharide -induced gene transcription via inhibition of NF-kappa B activation by preventing the degradation of NF-kappa B inhibitor \" I kappa B \" , blocking the translocation of NF-kappa B into the nuclear compartment .", "target_text": { "NF-kappa B": "protein", "NF-kappa B inhibitor": "protein", "I kappa B": "protein" } }, { "input_text": "However , the nature of the subunit involved in this mechanism has not been defined .", "target_text": {} }, { "input_text": "To examine the mechanisms by which salicylates affect cytokine gene transcription , the amount of active and inactive NF-kappa B and NF-kappa B mRNA , in Porphyromonas gingivalis lipopolysaccharide -stimulated human monocytic cells was assessed .", "target_text": { "cytokine": "protein", "NF-kappa B": "protein", "NF-kappa B mRNA": "RNA", "lipopolysaccharide -stimulated human monocytic cells": "cell_line" } }, { "input_text": "High doses of sodium salicylate suppressed NF-kappa B p65 mRNA accumulation , resulting in suppression of total NF-kappa B , p50 on tissue oligonucleotide had no effects on lipopolysaccharide -induced NF-kappa B activation .", "target_text": { "NF-kappa B": "protein", "p65": "protein", "p65 mRNA": "RNA", "p50": "protein" } }, { "input_text": "The data demonstrate that the p65 subunit of NF-kappa B is inhibited by salicylate treatment and highlight the role of salicylate in the control of gene expression of inflammatory mediators .", "target_text": { "p65": "protein", "NF-kappa B": "protein", "inflammatory mediators": "protein" } }, { "input_text": "Glucocorticoid -mediated inhibition of RANTES expression in human T lymphocytes .", "target_text": { "RANTES": "protein", "human T lymphocytes": "cell_type" } }, { "input_text": "The chemokine RANTES has been implicated in the pathogenesis of allergic inflammatory diseases including asthma and rhinitis which are frequently treated with glucocorticoids .", "target_text": { "chemokine": "protein", "RANTES": "protein" } }, { "input_text": "We observed that dexamethasone dramatically inhibited RANTES mRNA expression dose dependently in anti-CD3 activated Hut-78 T cells and human PBMCs .", "target_text": { "RANTES": "protein", "RANTES mRNA": "RNA", "anti-CD3 activated Hut-78 T cells": "cell_line", "human PBMCs": "cell_type" } }, { "input_text": "Inhibition of RANTES expression did not appear to be secondary to IL-2 inhibition and required binding to the intracellular glucocorticoid receptor .", "target_text": { "RANTES": "protein", "IL-2": "protein", "glucocorticoid receptor": "protein" } }, { "input_text": "The down-regulation of RANTES expression by glucocorticoids in T cells may directly contribute to the efficacy of these agents in suppressing cellular infiltration and to their anti-inflammatory properties .", "target_text": { "RANTES": "protein", "T cells": "cell_type" } }, { "input_text": "Association of TRAF1 , TRAF2 , and TRAF3 with an Epstein-Barr virus LMP1 domain important for B-lymphocyte transformation : role in NF-kappaB activation .", "target_text": { "TRAF1": "protein", "TRAF2": "protein", "TRAF3": "protein", "Epstein-Barr virus LMP1 domain": "DNA", "B-lymphocyte": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "The Epstein-Barr virus ( EBV ) transforming protein LMP1 appears to be a constitutively activated tumor necrosis factor receptor ( TNFR ) on the basis of an intrinsic ability to aggregate in the plasma membrane and an association of its cytoplasmic carboxyl terminus ( CT ) with TNFR -associated factors ( TRAFs ) .", "target_text": { "transforming protein": "protein", "LMP1": "protein", "Epstein-Barr virus ( EBV ) transforming protein LMP1": "protein", "constitutively activated tumor necrosis factor receptor": "protein", "TNFR": "protein", "cytoplasmic carboxyl terminus": "protein", "CT": "protein", "TNFR -associated factors": "protein", "TRAFs": "protein" } }, { "input_text": "We now show that in EBV-transformed B lymphocytes most of TRAF1 or TRAF3 and 5 % of TRAF2 are associated with LMP1 and that most of LMP1 is associated with TRAF1 or TRAF3 .", "target_text": { "EBV-transformed B lymphocytes": "cell_line", "TRAF1": "protein", "TRAF3": "protein", "TRAF2": "protein", "LMP1": "protein" } }, { "input_text": "TRAF1 , TRAF2 , and TRAF3 bind to a single site in the LMP1 CT corresponding to amino acids ( aa ) 199 to 214 , within a domain which is important for B-lymphocyte growth transformation ( aa 187 to 231 ) .", "target_text": { "TRAF1": "protein", "TRAF2": "protein", "TRAF3": "protein", "LMP1": "protein", "LMP1 CT": "protein" } }, { "input_text": "Further deletional and alanine mutagenesis analyses and comparison with TRAF binding sequences in CD40 , in CD30 , and in the LMP1 of other lymphycryptoviruses provide the first evidence that PXQXT/S is a core TRAF binding motif .", "target_text": { "TRAF": "protein", "TRAF binding sequences": "DNA", "LMP1": "protein", "PXQXT/S": "DNA", "TRAF binding motif": "DNA" } }, { "input_text": "The negative effects of point mutations in the LMP1 (1-231) core TRAF binding motif on TRAF binding and NF-kappaB activation genetically link the TRAFs to LMP1 (1-231)-mediated NF-kappaB activation .", "target_text": { "LMP1": "protein", "LMP1 (1-231) core TRAF binding motif": "DNA", "NF-kappaB": "protein", "TRAFs": "protein" } }, { "input_text": "NF-kappaB activation by LMP1 (1-231) is likely to be mediated by TRAF1 /TRAF2 heteroaggregates since TRAF1 is unique among the TRAFs in coactivating NF-kappaB with LMP1 (1-231) , a TRAF2 dominant-negative mutant can block LMP1 (1-231)-mediated NF-kappaB activation as well as TRAF1 coactivation , and 30 % of TRAF2 is associated with TRAF1 in EBV-transformed B cells .", "target_text": { "NF-kappaB": "protein", "LMP1": "protein", "TRAF1": "protein", "/TRAF2": "protein", "TRAFs": "protein", "TRAF2": "protein" } }, { "input_text": "TRAF3 is a negative modulator of LMP1 (1-231)-mediated NF-kappaB activation .", "target_text": { "TRAF3": "protein", "LMP1": "protein", "NF-kappaB": "protein" } }, { "input_text": "Surprisingly , TRAF 1 , -2 , or -3 does not interact with the terminal LMP1 CT aa 333 to 386 which can independently mediate NF-kappaB activation .", "target_text": { "LMP1": "protein", "terminal LMP1 CT": "protein", "NF-kappaB": "protein" } }, { "input_text": "The constitutive association of TRAFs with LMP1 through the aa 187 to 231 domain which is important in NF-kappaB activation and primary B-lymphocyte growth transformation implicates TRAF aggregation in LMP1 signaling .", "target_text": { "TRAFs": "protein", "LMP1": "protein", "aa 187 to 231 domain": "protein", "NF-kappaB": "protein", "B-lymphocyte": "cell_type", "TRAF": "protein" } }, { "input_text": "Lack of IL-12 signaling in human allergen-specific Th2 cells .", "target_text": { "IL-12": "protein", "human allergen-specific Th2 cells": "cell_line" } }, { "input_text": "IL-12 is a powerful skewer of CD4+ T cell responses toward the Th1 phenotype by inducing IFN-gamma production in naive Th cells .", "target_text": { "IL-12": "protein", "CD4+ T cell": "cell_type", "IFN-gamma": "protein", "naive Th cells": "cell_line" } }, { "input_text": "In the present study we addressed the question of whether IL-12 can reverse established Th2 responses into Th1/Th0 responses by inducing IFN-gamma production in memory Th2 cells .", "target_text": { "IL-12": "protein", "IFN-gamma": "protein", "memory Th2 cells": "cell_line" } }, { "input_text": "To this aim , allergen-specific CD4+ T cell clones ( TCC ) were generated from the peripheral blood of three atopic patients , and their cytokine profiles were analyzed .", "target_text": { "allergen-specific CD4+ T cell clones": "cell_line", "TCC": "cell_line", "cytokine": "protein" } }, { "input_text": "The majority of these TCC exhibited a strongly polarized Th2 cytokine profile , and the production of IFN-gamma could not be induced by exogenous IL-12 .", "target_text": { "TCC": "cell_line", "cytokine": "protein", "IFN-gamma": "protein", "IL-12": "protein" } }, { "input_text": "Only those TCC with low IFN-gamma levels in the absence of IL-12 responded to IL-12 by additional enhancement of IFN-gamma production .", "target_text": { "TCC": "cell_line", "IFN-gamma": "protein", "IL-12": "protein" } }, { "input_text": "The IL-12 nonresponsiveness of the Th2 clones was further evident by the total lack of IL-12 -induced phosphorylation of STAT4 ( signal transducer and activator of transcription-4 ) , a transcription factor that is typically involved in IL-12 signaling .", "target_text": { "IL-12": "protein", "Th2 clones": "cell_line", "STAT4": "protein", "signal transducer and activator of transcription-4": "protein", "transcription factor": "protein" } }, { "input_text": "Consequently , IL-12 also failed to induce the DNA-binding activity of STAT4 -containing complexes in the nuclei of these Th2 clones .", "target_text": { "IL-12": "protein", "STAT4": "protein", "STAT4 -containing complexes": "protein", "Th2 clones": "cell_line" } }, { "input_text": "All TCC expressed equal levels of the low-affinity IL-12R beta1 subunit .", "target_text": { "TCC": "cell_line", "IL-12R": "protein", "low-affinity IL-12R beta1 subunit": "protein" } }, { "input_text": "Our results indicate that human allergen-specific Th cells with strongly polarized Th2 cytokine profiles do not respond to IL-12 and , therefore , can not be induced to produce IFN-gamma .", "target_text": { "cytokine": "protein", "IL-12": "protein", "IFN-gamma": "protein" } }, { "input_text": "The apparent high frequency of IL-12 -nonresponsive Th cells within the allergen-specific populations in atopic patients predicts a limited skewing potential of IL-12 in the case of established Th2 responses , but only affecting newly recruited naive Th cells .", "target_text": { "IL-12": "protein", "IL-12 -nonresponsive Th cells": "cell_line", "Th cells": "cell_line" } }, { "input_text": "Cloning and expression of the Epstein-Barr virus -encoded dUTPase : patients with acute , reactivated or chronic virus infection develop antibodies against the enzyme .", "target_text": { "Epstein-Barr virus -encoded dUTPase": "protein", "antibodies": "protein", "enzyme": "protein" } }, { "input_text": "The gene encoding the Epstein-Barr virus ( EBV ) -specific dUTPase was amplified from virus DNA by PCR .", "target_text": { "Epstein-Barr virus ( EBV ) -specific dUTPase": "protein", "virus DNA": "DNA" } }, { "input_text": "The active enzyme was expressed in Escherichia coli and in insect cells as a non-fusion protein .", "target_text": { "insect cells": "cell_type", "non-fusion protein": "protein" } }, { "input_text": "The protein from E. coli specifically converted dUTP to dUMP and did not react with other dNTPs or NTPs .", "target_text": {} }, { "input_text": "Preliminary experiments yielded a Km value of about 0.8 microM for dUTP .", "target_text": {} }, { "input_text": "MAbs against the dUTPase reacted with a protein of approximately 31 kDa in 12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) -stimulated B cells harbouring either type 1 or type 2 EBV .", "target_text": { "dUTPase": "protein", "12-O-tetradecanoyl-phorbol-13-acetate ( TPA ) -stimulated B cells": "cell_line" } }, { "input_text": "The protein was found in untreated cells at low levels , whereas induction of the lytic replication cycle by TPA treatment or by providing the immediate early transactivator BZLF1 in trans resulted in increased expression .", "target_text": { "untreated cells": "cell_type", "immediate early transactivator": "protein", "BZLF1": "protein" } }, { "input_text": "We demonstrated that the virus dUTPase isolated from EBV -infected cells is a phosphoprotein .", "target_text": { "virus dUTPase": "protein", "EBV -infected cells": "cell_type", "phosphoprotein": "protein" } }, { "input_text": "The protein expressed in insect cells was used to test for the presence of specific antibodies in sera from normal , healthy carriers and from patients with various diseases .", "target_text": { "insect cells": "cell_type", "specific antibodies": "protein" } }, { "input_text": "While the sera of EBV -negative individuals ( 0/3 ) or healthy carriers ( 0/33 ) did not contain detectable levels of antibodies , patients with mononucleosis ( 5/18 ) , chronic EBV infection ( 2/7 ) , EBV reactivation ( 7/20 ) and human immunodeficiency virus infection ( 5/24 ) showed elevated antibody titres against the enzyme .", "target_text": {} }, { "input_text": "This indicated that the dUTPase is expressed during EBV replication and reactivation .", "target_text": {} }, { "input_text": "The enzyme might therefore be a potential target for drug therapy under conditions of active DNA replication .", "target_text": {} }, { "input_text": "The catalytic domain of pp56(lck) , but not its regulatory domain , is sufficient for inducing IL-2 production .", "target_text": { "catalytic domain": "protein", "pp56(lck)": "protein", "regulatory domain": "protein", "IL-2": "protein" } }, { "input_text": "The lymphoid src kinase pp56(lck) has been shown to be essential for the induction of different T lymphocyte responses , including CD4 -mediated enhancement of Ag-induced T cell activation , early T cell differentiation , induction of IL-2 production , and cytotoxicity .", "target_text": { "lymphoid src kinase": "protein", "pp56(lck)": "protein", "T lymphocyte": "cell_type", "CD4": "protein", "IL-2": "protein" } }, { "input_text": "It is assumed that pp56(lck) acts on these processes by phosphorylating substrates .", "target_text": { "pp56(lck)": "protein" } }, { "input_text": "However , it has been recently reported that the NH2 regulatory domain is sufficient to mediate CD4 accessory function .", "target_text": { "NH2": "protein", "regulatory domain": "protein", "CD4": "protein" } }, { "input_text": "In this report we address the contribution of the regulatory and catalytic domains of pp56(lck) to another function of this enzyme independent of CD4 : TCR-induced IL-2 production .", "target_text": { "pp56(lck)": "protein", "CD4": "protein", "IL-2": "protein" } }, { "input_text": "Two pp56(lck) mutants lacking either the entire catalytic domain or the entire NH2 regulatory domain were generated , and their abilities to trigger transactivation of the TCR-regulated nuclear factor of activated T cells ( NF-AT ) region of the IL-2 promoter were compared .", "target_text": { "pp56(lck)": "protein", "pp56(lck) mutants": "protein", "catalytic domain": "protein", "NH2": "protein", "regulatory domain": "protein", "TCR-regulated nuclear factor": "protein", "activated T cells": "cell_type", "NF-AT": "protein", "TCR-regulated nuclear factor of activated T cells ( NF-AT ) region": "DNA", "IL-2 promoter": "DNA" } }, { "input_text": "Only the catalytic , but not the NH2 regulatory , domain of pp56(lck) was able to induce NF-AT region transactivation on its own and to cooperate with other intracellular signals to trigger this response .", "target_text": { "NH2": "protein", "pp56(lck)": "protein", "NF-AT": "protein" } }, { "input_text": "Moreover , the catalytic domain of pp56(lck) was able to induce IL-2 cytokine production to an extent similar to that of wild-type pp56(lck) .", "target_text": { "catalytic domain": "protein", "pp56(lck)": "protein", "IL-2": "protein", "cytokine": "protein" } }, { "input_text": "We conclude that different domains of the pp56(lck) molecule contribute to regulate distinct biologic functions .", "target_text": { "pp56(lck)": "protein" } }, { "input_text": "In fact , while the NH2 regulatory domain is sufficient to mediate CD4 accessory function , we show here that the catalytic domain of pp56(lck) is sufficient for induction of IL-2 production , mimicking TCR ligation .", "target_text": { "NH2": "protein", "regulatory domain": "protein", "CD4": "protein", "catalytic domain": "protein", "pp56(lck)": "protein", "IL-2": "protein", "TCR": "protein" } }, { "input_text": "[ The changes in glucocorticoid receptors in peripheral leukocytes in asthmatic subjects ]", "target_text": { "peripheral leukocytes": "cell_type" } }, { "input_text": "The number of glucocorticoid receptors ( GCR ) in peripheral leukocytes was determined by radioligand-binding assay in extrinsic and intrinsic asthmatics .", "target_text": { "glucocorticoid receptors": "protein", "GCR": "protein", "peripheral leukocytes": "cell_type" } }, { "input_text": "Their corresponding plasma cortisol levels were assessed .", "target_text": {} }, { "input_text": "The results showed that the average number of GCR in asthmatics was significantly lower than that in healthy subjects ( P < 0.01 ) , and there was a linear correlation between the number of GCR and the course of asthma .", "target_text": { "GCR": "protein" } }, { "input_text": "Besides , there was also a linear correlation between the number of GCR and the age of the initial attack of asthma .", "target_text": { "GCR": "protein" } }, { "input_text": "No difference in plasma cortisol level was found between asthmatics and healthy subjects .", "target_text": {} }, { "input_text": "These findings suggest that there is no primary and general impairment of glucocorticoid metabolism in the asthmatics , but the number of GCR in the asthmatics is lower than that in healthy controls .", "target_text": { "GCR": "protein" } }, { "input_text": "The decrease of the number of GCR in asthmatics , we think , is related to heredity and repeated attacks of asthma .", "target_text": { "GCR": "protein" } }, { "input_text": "Novel aldosterone receptors : specificity-conferring mechanism at the level of the cell membrane .", "target_text": { "aldosterone receptors": "protein" } }, { "input_text": "Functional studies in extra-renal , nonepithelial cells such as smooth muscle cells and more recently circulating human lymphocytes have provided increasing evidence that aldosterone produces not only classical genomic effects , but also rapid non-genomic effects on transmembrane electrolyte movements .", "target_text": { "extra-renal , nonepithelial cells": "cell_type", "smooth muscle cells": "cell_type", "human lymphocytes": "cell_type" } }, { "input_text": "These involve activation of the sodium/proton-exchanger of the cell membrane at very low , physiological concentrations of aldosterone with an acute onset within 1-2 minutes .", "target_text": { "sodium/proton-exchanger": "protein" } }, { "input_text": "A second messenger cascade involved is the inositol-1,4,5-trisphosphate /calcium pathway which responds over the same rapid time course .", "target_text": {} }, { "input_text": "Such changes clearly can not be explained by genomic mechanisms , which are responsible for later effects than the membrane-related rapid responses .", "target_text": {} }, { "input_text": "In addition to its rapid time course the unique characteristics of this new pathway for steroid action include a 10000-fold selectivity for aldosterone over cortisol and the ineffectiveness of spironolactones , classical mineralocorticoid antagonists , as antagonists of the response .", "target_text": {} }, { "input_text": "Subsequently binding sites have been demonstrated in the plasma membrane of human lymphocytes which show pharmacological ( aldosterone specificity ) and kinetic ( high turnover ) properties identical with those of the rapid aldosterone effects in the same cells .", "target_text": { "human lymphocytes": "cell_type" } }, { "input_text": "SDS-PAGE analysis of the receptor protein has shown a molecular weight of approximately 50 kD .", "target_text": { "receptor protein": "protein" } }, { "input_text": "The present paper reviews the data supporting a new , two-step model for non-genomic and genomic aldosterone effects .", "target_text": {} }, { "input_text": "It also suggests a novel specificity-conferring mechanism for mineralocorticoid action at the membrane level .", "target_text": {} }, { "input_text": "The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor .", "target_text": { "macrophage transcription factor": "protein", "PU.1": "protein", "macrophage colony-stimulating factor receptor": "protein" } }, { "input_text": "The macrophage colony-stimulating factor ( M-CSF ) receptor is expressed in a tissue-specific fashion from two distinct promoters in monocytes/macrophages and the placenta .", "target_text": { "macrophage colony-stimulating factor": "protein", "M-CSF": "protein", "macrophage colony-stimulating factor ( M-CSF ) receptor": "protein", "promoters": "DNA", "monocytes/macrophages": "cell_type" } }, { "input_text": "In order to further understand the transcription factors which play a role in the commitment of multipotential progenitors to the monocyte/macrophage lineage , we have initiated an investigation of the factors which activate the M-CSF receptor very early during the monocyte differentiation process .", "target_text": { "multipotential progenitors": "cell_type", "M-CSF": "protein", "M-CSF receptor": "protein" } }, { "input_text": "Here we demonstrate that the human monocytic M-CSF receptor promoter directs reporter gene activity in a tissue-specific fashion .", "target_text": { "M-CSF": "protein", "M-CSF receptor": "protein", "human monocytic M-CSF receptor promoter": "DNA" } }, { "input_text": "Since one of the few transcription factors which have been implicated in the regulation of monocyte genes is the macrophage- and B-cell-specific PU.1 transcription factor , we investigated whether PU.1 binds and activates the M-CSF receptor promoter .", "target_text": { "transcription factors": "protein", "monocyte genes": "DNA", "PU.1": "protein", "macrophage- and B-cell-specific PU.1": "protein", "transcription factor": "protein", "M-CSF": "protein", "M-CSF receptor": "protein", "M-CSF receptor promoter": "DNA" } }, { "input_text": "Here we demonstrate that both in vitro-translated PU.1 and PU.1 from nuclear extracts bind to a specific site in the M-CSF receptor promoter just upstream from the major transcription initiation site .", "target_text": { "PU.1": "protein", "vitro-translated PU.1": "protein", "M-CSF": "protein", "M-CSF receptor": "protein", "M-CSF receptor promoter": "DNA", "major transcription initiation site": "DNA" } }, { "input_text": "Mutations in this site which eliminate PU.1 binding decrease M-CSF receptor promoter activity significantly in macrophage cell lines only .", "target_text": { "PU.1": "protein", "M-CSF": "protein", "M-CSF receptor": "protein", "macrophage cell lines": "cell_line" } }, { "input_text": "Furthermore , PU.1 transactivates the M-CSF receptor promoter in nonmacrophage cells .", "target_text": { "PU.1": "protein", "M-CSF": "protein", "M-CSF receptor": "protein", "M-CSF receptor promoter": "DNA", "nonmacrophage cells": "cell_type" } }, { "input_text": "These results suggest that PU.1 plays a major role in macrophage gene regulation and development by directing the expression of a receptor for a key macrophage growth factor .", "target_text": { "PU.1": "protein", "key macrophage growth factor": "protein" } }, { "input_text": "Increased natural killer cell activity correlates with low or negative expression of the HER-2/neu oncogene in patients with breast cancer .", "target_text": { "HER-2/neu oncogene": "DNA" } }, { "input_text": "BACKGROUND .", "target_text": {} }, { "input_text": "Increased expression of the HER-2/neu oncogene in breast cancer correlates with decreased estrogen receptor concentration and seems to be an important prognostic factor .", "target_text": { "HER-2/neu oncogene": "DNA", "estrogen receptor": "protein" } }, { "input_text": "The authors investigated whether there is a correlation between HER-2/neu expression and immunologic parameters representing tumor defense in patients with breast cancer .", "target_text": { "HER-2/neu": "protein" } }, { "input_text": "METHOD .", "target_text": {} }, { "input_text": "A Western blot analysis was used to investigate HER-2/neu expression , whereas a chromium-release assay using the K562 cell line as target was used to measure natural killer ( NK ) cell activity .", "target_text": { "HER-2/neu": "protein", "K562 cell line": "cell_line", "natural killer ( NK ) cell": "cell_type" } }, { "input_text": "RESULTS .", "target_text": {} }, { "input_text": "In patients with breast cancer , NK cell activity was significantly higher compared with patients with benign tumors ( P = 0.006 ) or healthy control subjects ( P = 0.002 ) .", "target_text": { "NK cell": "cell_type", "benign tumors": "cell_type" } }, { "input_text": "Moreover , 23.3 % of patients with breast cancer showed an overexpression of HER-2/neu protein .", "target_text": { "HER-2/neu": "protein", "HER-2/neu protein": "protein" } }, { "input_text": "Within this group of patients , NK cell activity was significantly lower ( 45.6 +/- 16.1 % ) compared with the group with no HER-2/neu overexpression ( 57.3 +/- 11.0 % ) .", "target_text": { "NK cell": "cell_type", "HER-2/neu": "protein" } }, { "input_text": "NK cell activity did not increase in patients with HER-2/neu overexpression .", "target_text": { "NK cell": "cell_type", "HER-2/neu": "protein" } }, { "input_text": "Thus , there was a statistically significant correlation of cytolytic effector cell function with HER-2/neu expression of the tumor ( P = 0.003 ) , and HER-2/neu overexpression correlated with a negative estrogen receptor status ( P = 0.005 ) .", "target_text": { "HER-2/neu": "protein", "estrogen receptor": "protein" } }, { "input_text": "CONCLUSION .", "target_text": {} }, { "input_text": "These data add further evidence to previous observations from the authors ' laboratory that certain tumor characteristics may be associated with reactions of the host with breast cancer .", "target_text": {} }, { "input_text": "[ The value of the clinical test of glucocorticoid receptors of peripheral blood leukocytes in patients with chronic pulmonary heart disease ]", "target_text": { "glucocorticoid receptors": "protein", "peripheral blood leukocytes": "cell_type" } }, { "input_text": "In order to inquire into the functional state of adrenal cortex in patients with pulmonary heart disease , the number of glucocorticoid receptors ( GCR ) of peripheral blood leukocytes in patients with chronic pulmonary heart disease was determined with radioligand-binding assay and the corresponding plasma cortisol levels were assessed with radioimmune assays .", "target_text": { "glucocorticoid receptors": "protein", "GCR": "protein", "peripheral blood leukocytes": "cell_type" } }, { "input_text": "The results showed that the number of GCR in the patients was significantly reduced ( P < 0.01 ) and it was increased when their health state was improved .", "target_text": { "GCR": "protein" } }, { "input_text": "However , it was still lower than that in healthy subjects ( P < 0.01 ) .", "target_text": {} }, { "input_text": "The number of GCR in the patients was greatly increased when these patients were treated with oxygen ( P < 0.01 ) .", "target_text": { "GCR": "protein" } }, { "input_text": "No difference in plasma cortisol was found between the patients and the healthy subjects ( P > 0.05 ) .", "target_text": {} }, { "input_text": "These results indicate that the function of adrenal cortex may be improved by the compensation mechanism of the patients , but the lower GCR number was the result of lacking of oxygen in the patients .", "target_text": { "GCR": "protein" } }, { "input_text": "The number of GCR may be improved by inhalation of oxygen .", "target_text": { "GCR": "protein" } }, { "input_text": "Therefore oxygen therapy is helpful in raising the activity of glucocorticoid receptors and controlling the development of the disease .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "Signaling via IL-2 and IL-4 in JAK3 -deficient severe combined immunodeficiency lymphocytes : JAK3 -dependent and independent pathways .", "target_text": { "IL-2": "protein", "IL-4": "protein", "JAK3": "protein", "JAK3 -deficient severe combined immunodeficiency lymphocytes": "cell_line" } }, { "input_text": "Both IL-2 and IL-4 bind to receptors containing the common gamma chain and JAK3 .", "target_text": { "IL-2": "protein", "IL-4": "protein", "common gamma chain": "protein", "JAK3": "protein" } }, { "input_text": "Although JAK3 is required for proper lymphoid development , the precise roles of this kinase in IL-2 and IL-4 signaling in lymphocytes have not been defined .", "target_text": { "JAK3": "protein", "IL-2": "protein", "IL-4": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Here , we have studied IL-2 and IL-4 signaling in B cell lines lacking JAK3 .", "target_text": { "IL-2": "protein", "IL-4": "protein", "B cell lines": "cell_line", "JAK3": "protein" } }, { "input_text": "Although IL-2 -induced phosphorylation of IL-2R beta , JAK1 , and STAT5 all required the presence of JAK3 , IL-4 -mediated phosphorylation of JAK1 , STAT6 , and insulin receptor substrates 1 and 2 did not .", "target_text": { "IL-2": "protein", "IL-2R beta": "protein", "JAK1": "protein", "STAT5": "protein", "JAK3": "protein", "IL-4": "protein", "STAT6": "protein", "insulin receptor": "protein" } }, { "input_text": "However , IL-4 -induced effects were clearly improved following JAK3 expression .", "target_text": { "IL-4": "protein", "JAK3": "protein" } }, { "input_text": "These data indicate that IL-4 signaling occurs in the absence of of JAK3 , but is comparatively inefficient .", "target_text": { "IL-4": "protein", "JAK3": "protein" } }, { "input_text": "These findings may help in understanding the pathogenesis of the immunodeficiency that occurs with mutations of JAK3 and may suggest a mechanism for the pleiotropic effects of IL-4 .", "target_text": { "JAK3": "protein", "IL-4": "protein" } }, { "input_text": "Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene [ published erratum appears in Mol Cell Biol 1997 Apr ; 17 ( 4 ) : 2351 ]", "target_text": { "Elf-1": "protein", "Stat5": "protein", "human interleukin-2 receptor alpha": "protein", "human interleukin-2 receptor alpha gene": "DNA" } }, { "input_text": "The interleukin 2 receptor alpha-chain ( IL-2R alpha ) gene is a key regulator of lymphocyte proliferation .", "target_text": { "interleukin 2 receptor alpha-chain": "protein", "IL-2R alpha": "protein", "interleukin 2 receptor alpha-chain ( IL-2R alpha ) gene": "DNA" } }, { "input_text": "IL-2R alpha is rapidly and potently induced in T cells in response to mitogenic stimuli .", "target_text": { "IL-2R alpha": "protein", "T cells": "cell_type" } }, { "input_text": "Interleukin 2 ( IL-2 ) stimulates IL-2R alpha .", "target_text": { "Interleukin 2": "protein", "IL-2": "protein", "IL-2R alpha": "protein" } }, { "input_text": "transcription , thereby amplifying expression of its own high-affinity receptor .", "target_text": { "high-affinity receptor": "protein" } }, { "input_text": "IL-2R alpha transcription is at least in part controlled by two positive regulatory regions , PRRI and PRRII .", "target_text": { "IL-2R alpha": "protein", "positive regulatory regions": "protein", "PRRI": "DNA", "PRRII": "DNA" } }, { "input_text": "PRRI is an inducible proximal enhancer , located between nucleotides -276 and -244 , which contains NF-kappaB and SRE/CArG motifs .", "target_text": { "PRRI": "DNA", "inducible proximal enhancer": "DNA", "between nucleotides -276 and -244": "DNA" } }, { "input_text": "PRRII is a T-cell-specific enhancer , located between nucleotides -137 and -64 , which binds the T-cell-specific Ets protein Elf-1 and HMG-I(Y) proteins .", "target_text": { "PRRII": "DNA", "T-cell-specific enhancer": "DNA", "T-cell-specific Ets protein": "protein", "Elf-1": "protein", "HMG-I(Y) proteins": "protein" } }, { "input_text": "However , none of these proximal regions account for the induction of IL-2R alpha transcription by IL-2 .", "target_text": { "IL-2": "protein" } }, { "input_text": "To find new regulatory regions of the IL-2R alpha gene , 8.5 kb of the 5' end noncoding sequence of the IL-2R alpha gene have been sequenced .", "target_text": { "regulatory regions": "DNA", "IL-2R alpha": "protein", "IL-2R alpha gene": "DNA" } }, { "input_text": "We identified an 86-nucleotide fragment that is 90 % identical to the recently characterized murine IL-2 -responsive element ( mIL-2rE ) .", "target_text": { "IL-2": "protein", "murine IL-2 -responsive element": "DNA", "mIL-2rE": "DNA" } }, { "input_text": "This putative human IL-2rE , designated PRRIII , confers IL-2 responsiveness on a heterologous promoter .", "target_text": { "human IL-2rE": "DNA", "PRRIII": "DNA", "IL-2": "protein", "heterologous promoter": "DNA" } }, { "input_text": "PRRIII contains a Stat protein binding site that overlaps with an EBS motif ( GASd/EBSd ) .", "target_text": { "PRRIII": "DNA", "Stat protein binding site": "DNA", "EBS motif": "DNA", "GASd/EBSd": "DNA" } }, { "input_text": "These are essential for IL-2 inducibility of PRRIII /CAT reporter constructs .", "target_text": { "IL-2": "protein", "PRRIII": "DNA", "PRRIII /CAT reporter constructs": "DNA" } }, { "input_text": "IL-2 induced the binding of Stat5 a and b proteins to the human GASd element .", "target_text": { "IL-2": "protein", "human GASd element": "DNA" } }, { "input_text": "To confirm the physiological relevance of these findings , we carried out in vivo footprinting experiments which showed that stimulation of IL-2R alpha expression correlated with occupancy of the GASd element .", "target_text": { "IL-2R alpha": "protein", "GASd element": "DNA" } }, { "input_text": "Our data demonstrate a major role of the GASd/EBSd element in IL-2R alpha regulation and suggest that the T-cell-specific Elf-1 factor can serve as a transcriptional repressor .", "target_text": { "GASd/EBSd": "DNA", "GASd/EBSd element": "DNA", "IL-2R alpha": "protein", "Elf-1": "protein", "T-cell-specific Elf-1 factor": "protein", "transcriptional repressor": "protein" } }, { "input_text": "Signal transduction by DR3 , a death domain -containing receptor related to TNFR-1 and CD95 .", "target_text": { "DR3": "protein", "death domain": "protein", "death domain -containing receptor": "protein", "TNFR-1": "protein", "CD95": "protein" } }, { "input_text": "Tumor necrosis factor receptor-1 ( TNFR-1 ) and CD95 ( also called Fas or APO-1 ) are cytokine receptors that engage the apoptosis pathway through a region of intracellular homology , designated the \" death domain . \" Another death domain -containing member of the TNFR family , death receptor 3 ( DR3 ) , was identified and was shown to induce both apoptosis and activation of nuclear factor kappaB .", "target_text": { "Tumor necrosis factor receptor-1": "protein", "TNFR-1": "protein", "CD95": "protein", "Fas": "protein", "APO-1": "protein", "cytokine receptors": "protein", "death domain": "protein", "death domain -containing member": "protein", "TNFR family": "protein", "death receptor 3": "protein", "DR3": "protein", "nuclear factor kappaB": "protein" } }, { "input_text": "Expression of DR3 appears to be restricted to tissues enriched in lymphocytes .", "target_text": { "DR3": "protein", "lymphocytes": "cell_type" } }, { "input_text": "DR3 signal transduction is mediated by a complex of intracellular signaling molecules including TRADD , TRAF2 , FADD , and FLICE .", "target_text": { "DR3": "protein", "intracellular signaling molecules": "protein", "TRADD": "protein", "TRAF2": "protein", "FADD": "protein", "FLICE": "protein" } }, { "input_text": "Thus , DR3 likely plays a role in regulating lymphocyte homeostasis .", "target_text": { "DR3": "protein" } }, { "input_text": "Differential nuclear localization of p50 , p52 , and RelB proteins in human accessory cells of the immune response in situ .", "target_text": { "p50": "protein", "p52": "protein", "RelB": "protein", "human accessory cells": "cell_type" } }, { "input_text": "The Rel/NF-kappa B proteins , p50 , p52 , p65 , c-Rel , and RelB , constitute a family of transcription factors involved in the positive regulation of a variety of genes during the immune response .", "target_text": { "Rel/NF-kappa B proteins": "protein", "p50": "protein", "p52": "protein", "p65": "protein", "c-Rel": "protein", "RelB": "protein", "transcription factors": "protein" } }, { "input_text": "Recently , it has been shown that RelB knockout mice have no dendritic cells ( DC ) .", "target_text": { "RelB": "protein", "dendritic cells": "cell_type", "DC": "cell_type" } }, { "input_text": "An overexpression of p50 has been described in follicular dendritic cells ( FDC ) .", "target_text": { "p50": "protein", "dendritic cells": "cell_type", "follicular dendritic cells": "cell_type", "FDC": "cell_type" } }, { "input_text": "A constitutive NF-kappa B activity has been reported in mature macrophages .", "target_text": { "NF-kappa B": "protein", "mature macrophages": "cell_type" } }, { "input_text": "This led to the hypothesis that some of the Rel/ NF-kappa B proteins were key nuclear factors in functions of accessory cells of the immune response .", "target_text": { "NF-kappa B": "protein", "Rel/ NF-kappa B proteins": "protein", "nuclear factors": "protein", "accessory cells": "cell_type" } }, { "input_text": "Therefore , we investigated in situ the nuclear localization of Rel/ NF-kappa B proteins in accessory cells of the immune system by immunohistochemistry and double labeling by immunofluorescence from five normal human tonsils and five lymph nodes with follicular hyperplasia .", "target_text": { "NF-kappa B": "protein", "Rel/ NF-kappa B proteins": "protein", "accessory cells": "cell_type" } }, { "input_text": "Nuclear p65 and c-Rel proteins were found in all cell types including lymphocytes .", "target_text": { "p65": "protein", "c-Rel": "protein", "lymphocytes": "cell_type" } }, { "input_text": "In germinal centers GC , p50 , p52 , and RelB were found in the nuclei of FDC only and were not detected in the nuclei of CD68+ cells .", "target_text": { "p50": "protein", "p52": "protein", "RelB": "protein", "FDC": "cell_type", "CD68+ cells": "cell_line" } }, { "input_text": "In T cell areas , p50 , p52 , and RelB were found in the nuclei of HLA-DR+ cells with an antigen-presenting cell ( APC ) morphology .", "target_text": { "p50": "protein", "p52": "protein", "RelB": "protein", "HLA-DR+ cells": "cell_line" } }, { "input_text": "p52 and RelB were detected in the nuclei in both CD1a+ and CD68+ cells from the T cell area , whereas p50 was found only in CD68- and CD1a- cells .", "target_text": { "p52": "protein", "RelB": "protein", "CD1a+": "cell_line", "CD68+ cells": "cell_line", "p50": "protein" } }, { "input_text": "Cells with nuclear p50 were negative for the CD38 , CD20 and CD2 markers .", "target_text": { "p50": "protein", "CD38": "protein", "CD20": "protein", "CD2 markers": "protein" } }, { "input_text": "These results show that , physiologically , high levels of nuclear of p50 , p52 and RelB are restricted to accessory cells of the immune system , which include FDC in GC , and DC and macrophages in the T cell zone , that specialized scavenger macrophages from GC do not have detectable levels of p52 and RelB , whereas macrophages from the T cell area , known to present the antigen to T cells , do have both nuclear p52 and RelB , and that in the T cell zone , p52 and RelB are located in nuclei of both CD1a+ , CD68+ or both , cells APC , whereas p50 is restricted to CD1a- and CD68- APC .", "target_text": { "p50": "protein", "p52": "protein", "RelB": "protein", "accessory cells": "cell_type", "FDC": "cell_type", "DC": "cell_type", "scavenger macrophages": "cell_type", "GC": "cell_type", "macrophages": "cell_type", "T cells": "cell_type", "CD1a+": "cell_line", "CD68+": "cell_line", "APC": "cell_type", "CD1a-": "cell_type", "CD68- APC": "cell_type" } }, { "input_text": "The different patterns of p50 , p52 and RelB protein nuclear localization may provide insight into their different roles during the immune response in vivo .", "target_text": { "p50": "protein", "p52": "protein", "RelB": "protein" } }, { "input_text": "Tyrosines 113 , 128 , and 145 of SLP-76 are required for optimal augmentation of NFAT promoter activity .", "target_text": { "SLP-76": "protein", "NFAT promoter": "DNA" } }, { "input_text": "SLP-76 ( SH2 domain leukocyte protein of 76 kDa ) is a recently identified substrate of the TCR-stimulated protein tyrosine kinases that functions in the signal transduction cascade linking the TCR with IL-2 gene expression .", "target_text": { "SLP-76": "protein", "SH2 domain leukocyte protein": "protein", "TCR-stimulated protein": "protein", "tyrosine kinases": "protein", "TCR": "protein", "IL-2": "protein" } }, { "input_text": "In this report , we demonstrate that engagement of the TCR results in tyrosine phosphorylation of SLP-76 in its amino-terminal acidic region .", "target_text": { "TCR": "protein", "SLP-76": "protein", "amino-terminal acidic region": "protein" } }, { "input_text": "Two tyrosines ( Y113 and Y128 ) fall within an identical five amino-acid motif and are shown to be phosphorylated upon TCR ligation .", "target_text": { "TCR": "protein" } }, { "input_text": "Although mutation of either Y113 and Y128 has a minimal effect on SLP-76 function , mutation of both residues decreases significantly the ability of SLP-76 to promote T cell activation .", "target_text": { "SLP-76": "protein" } }, { "input_text": "A third tyrosine within the amino-terminal region ( Y145 ) appears to be the most important for optimal SLP-76 function , as altering it alone to phenylalanine has a potent impact on SLP-76 augmentation of NFAT promoter activity .", "target_text": { "amino-terminal region": "protein", "SLP-76": "protein", "NFAT promoter": "DNA" } }, { "input_text": "Human interferon regulatory factor 2 gene .", "target_text": { "Human interferon regulatory factor 2 gene": "DNA" } }, { "input_text": "Intron-exon organization and functional analysis of 5'-flanking region .", "target_text": { "5'-flanking region": "DNA" } }, { "input_text": "Interferon regulatory factor 2 ( IRF-2 ) is a transcriptional regulatory protein that terminates interferon beta expression initiated by interferon regulatory factor 1 .", "target_text": { "Interferon regulatory factor 2": "protein", "IRF-2": "protein", "transcriptional regulatory protein": "protein", "interferon beta": "protein", "interferon regulatory factor 1": "protein" } }, { "input_text": "In this study , we isolated the genomic DNA for human IRF-2 gene , determined the intron-exon structure of the human IRF-2 gene , mapped the major transcription initiation site , identified a number of potential regulatory elements in the 5'-flanking region , and localized the IRF-2 gene on human chromosome 4 .", "target_text": { "genomic DNA": "DNA", "IRF-2": "protein", "human IRF-2 gene": "DNA", "intron-exon structure": "DNA", "major transcription initiation site": "DNA", "5'-flanking region": "DNA", "IRF-2 gene": "DNA", "human chromosome 4": "DNA" } }, { "input_text": "The IRF-2 promoter region contains a CpG island , with several GC boxes , a putative NF-kappa B -binding site , and a CAAT box , but no TATA box .", "target_text": { "IRF-2": "protein", "promoter region": "DNA", "CpG island": "DNA", "GC boxes": "DNA", "NF-kappa B": "protein", "NF-kappa B -binding site": "DNA", "CAAT box": "DNA", "TATA box": "DNA" } }, { "input_text": "When the promoter region was linked with a heterologous reporter gene , we found that the promoter region is inducible by both interferons ( interferon -alpha and -gamma ) and interferon regulatory factor 1 .", "target_text": { "promoter region": "DNA", "heterologous reporter gene": "DNA", "interferons": "protein", "interferon regulatory factor 1": "protein" } }, { "input_text": "The region which induced these inductions was identified as being confined to 40 nucleotides 5' to the major transcriptional initiation site by testing a series of clones with truncated promoter of IRF-2 .", "target_text": { "40 nucleotides 5'": "DNA", "major transcriptional initiation site": "DNA", "truncated promoter": "DNA", "IRF-2": "protein" } }, { "input_text": "This region contains elements which are shared with the transcriptional enhancers of other genes including interferon regulatory factor 1 , interferon beta , and interferon-inducible genes .", "target_text": { "transcriptional enhancers": "DNA", "interferon regulatory factor 1": "protein", "interferon beta": "protein", "interferon-inducible genes": "DNA" } }, { "input_text": "These data suggest that interferon regulatory factor 1 not only triggers the activation of the interferon signal transduction pathway , but also may play a role in limiting the duration of this response by activating the transcription of IRF-2 .", "target_text": { "interferon regulatory factor 1": "protein", "interferon": "protein", "IRF-2": "protein" } }, { "input_text": "Interferon alpha selectively affects expression of the human myeloid cell nuclear differentiation antigen in late stage cells in the monocytic but not the granulocytic lineage .", "target_text": { "Interferon alpha": "protein", "human myeloid cell nuclear differentiation antigen": "protein", "late stage cells": "cell_type", "monocytic": "cell_type", "granulocytic lineage": "cell_type" } }, { "input_text": "The human myeloid cell nuclear differentiation antigen ( MNDA ) is expressed constitutively in cells of the myeloid lineage , appearing in myeloblast cells in some cases of acute myeloid leukemia and consistently being detected in promyelocyte stage cells as well as in all later stage cells including peripheral blood monocytes and granulocytes .", "target_text": { "human myeloid cell nuclear differentiation antigen": "protein", "MNDA": "protein", "myeloid lineage": "cell_type", "myeloblast cells": "cell_type", "promyelocyte stage cells": "cell_type", "later stage cells": "cell_type", "peripheral blood monocytes": "cell_type", "granulocytes": "cell_type" } }, { "input_text": "The human myeloid leukemia cell lines , HL-60 , U937 , and THP-1 , express similar levels of immunochemically detectable MNDA .", "target_text": { "human myeloid leukemia cell lines": "cell_line", "HL-60": "cell_line", "U937": "cell_line", "THP-1": "cell_line", "MNDA": "protein" } }, { "input_text": "Although , the level of MNDA mRNA in primary monocytes is very low it was up-regulated at 6 h following the addition of interferon alpha .", "target_text": { "MNDA": "protein", "MNDA mRNA": "RNA", "primary monocytes": "cell_type", "interferon alpha": "protein" } }, { "input_text": "The effect of interferon alpha on the MNDA mRNA is also observed in the cell lines HL-60 , U937 , and THP-1 .", "target_text": { "interferon alpha": "protein", "MNDA": "protein", "MNDA mRNA": "RNA", "cell lines": "cell_line", "HL-60": "cell_line", "U937": "cell_line", "THP-1": "cell_line" } }, { "input_text": "The MNDA mRNA level in primary granulocytes was unaffected by addition of interferon alpha and other agents including interferon gamma , endotoxin , poly (I).poly (C) , and FMLP .", "target_text": { "MNDA": "protein", "MNDA mRNA": "RNA", "primary granulocytes": "cell_type", "interferon alpha": "protein", "interferon gamma": "protein", "endotoxin": "protein", "poly (I).poly (C)": "protein", "FMLP": "protein" } }, { "input_text": "The MNDA mRNA level in the myeloid cell lines was also unaffected by the latter four agents .", "target_text": { "MNDA": "protein", "MNDA mRNA": "RNA", "myeloid cell lines": "cell_line" } }, { "input_text": "Induction of differentiation in the myeloid cell lines with phorbol ester induces monocyte differentiation which was accompanied by a decrease in MNDA mRNA level .", "target_text": { "myeloid cell lines": "cell_line", "MNDA": "protein", "MNDA mRNA": "RNA" } }, { "input_text": "This reduced level of mRNA could then be elevated with subsequent interferon alpha treatment .", "target_text": { "mRNA": "RNA", "interferon alpha": "protein" } }, { "input_text": "The effects of phorbol ester on MNDA mRNA appeared to be associated with induced differentiation since inhibiting cell proliferation did not alter the level of MNDA mRNA and cell cycle variation in MNDA mRNA levels were not observed .", "target_text": { "MNDA": "protein", "MNDA mRNA": "RNA" } }, { "input_text": "The ability of interferon alpha to up-regulate MNDA mRNA in phorbol ester treated myeloid cell lines is consistent with the observations made in primary monocytes .", "target_text": { "interferon alpha": "protein", "MNDA": "protein", "MNDA mRNA": "RNA", "myeloid cell lines": "cell_line", "primary monocytes": "cell_type" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "Involvement of transcription factor YB-1 in human T-cell lymphotropic virus type I basal gene expression .", "target_text": { "transcription factor": "protein", "YB-1": "protein" } }, { "input_text": "Sequences which control basal human T-cell lymphotropic virus type I ( HTLV-I ) transcription likely play an important role in initiation and maintenance of virus replication .", "target_text": {} }, { "input_text": "We previously identified and analyzed a 45-nucleotide sequence ( downstream regulatory element 1 [ DRE 1 ] ) , +195 to +240 , at the boundary of the R/U5 region of the long terminal repeat which is required for HTLV-I basal transcription .", "target_text": { "45-nucleotide sequence": "DNA", "downstream regulatory element 1": "DNA", "DRE 1": "DNA", "+195 to +240": "DNA", "R/U5 region": "DNA", "long terminal repeat": "DNA" } }, { "input_text": "We identified a protein , p37 , which specifically bound to DRE 1 .", "target_text": { "DRE 1": "DNA" } }, { "input_text": "An affinity column fraction , containing p37 , stimulated HTLV-I transcription approximately 12-fold in vitro .", "target_text": { "p37": "protein" } }, { "input_text": "We now report the identification of a cDNA clone ( 15B-7 ) , from a Jurkat expression library , that binds specifically to the DRE 1 regulatory sequence .", "target_text": { "cDNA clone": "DNA", "15B-7": "DNA", "Jurkat expression library": "DNA", "DRE 1": "DNA", "DRE 1 regulatory sequence": "DNA" } }, { "input_text": "Binding of the cDNA fusion protein , similarly to the results obtained with purified Jurkat protein , was decreased by introduction of site-specific mutations in the DRE 1 regulatory sequence .", "target_text": { "cDNA fusion protein": "protein", "DRE 1": "DNA", "DRE 1 regulatory sequence": "DNA" } }, { "input_text": "In vitro transcription and translation of 15B-7 cDNA produced a fusion protein which bound specifically to the HTLV-I +195 to +240 oligonucleotide .", "target_text": { "15B-7 cDNA": "DNA", "fusion protein": "protein" } }, { "input_text": "The partial cDNA encodes a protein which is homologous to the C-terminal 196 amino acids of the 36-kDa transcription factor , YB-1 .", "target_text": { "partial cDNA": "DNA", "C-terminal 196 amino acids": "protein", "transcription factor": "protein", "36-kDa transcription factor": "protein", "YB-1": "protein" } }, { "input_text": "Cotransfection of a YB-1 expression plasmid increases HTLV-I basal transcription approximately 14-fold in Jurkat T lymphocytes .", "target_text": { "YB-1": "protein", "YB-1 expression plasmid": "DNA", "Jurkat T lymphocytes": "cell_line" } }, { "input_text": "On the basis of the molecular weight , DNA-binding characteristics , and in vivo transactivation activity , we suggest that the previously identified DRE 1 -binding protein , p37 , is YB-1 .", "target_text": { "DRE 1": "DNA", "p37": "protein", "YB-1": "protein" } }, { "input_text": "Changes in triiodothyronine ( T3 ) mononuclear leukocyte receptor kinetics after T3 administration and multiple cold-air exposures .", "target_text": {} }, { "input_text": "Repeated cold-air exposures increase human triiodothyronine ( T3 ) plasma clearance rates .", "target_text": {} }, { "input_text": "To study the response of the nuclear T3 receptor ( NT3R ) in this condition , binding characteristics were analyzed in human mononuclear leukocytes ( MNL ) .", "target_text": { "nuclear T3 receptor": "protein", "NT3R": "protein", "human mononuclear leukocytes": "cell_type", "MNL": "cell_type" } }, { "input_text": "In addition , we supplemented one group of individuals with a daily oral replacement dose of T3 to isolate the influence of serum thyroxine ( T4 ) and thyrotropin ( TSH ) levels on receptor kinetics .", "target_text": {} }, { "input_text": "The subjects were exposed to cold air ( 4 degrees C ) twice/d , 30 min/exposure , for a total of 80 exposures .", "target_text": {} }, { "input_text": "The T3 -subjects received placebo [ n = 8 ] and the T3 + subjects received T3 ( 30 micrograms/d ) [ n = 8 ] in a double-blind fashion .", "target_text": {} }, { "input_text": "Mononuclear leukocytes were isolated from peripheral blood before the cold exposure and drug regimen began , and then after every 20 exposures .", "target_text": { "Mononuclear leukocytes": "cell_type" } }, { "input_text": "The dissociation constant ( Kd ) and maximum binding capacity ( MBC ) of the NT3R values were log transformed to minimize between-subject variability .", "target_text": { "NT3R": "protein" } }, { "input_text": "In the T3 + group , serum total thyroxine ( TT4 ) , free T4 ( FT4 ) , and TSH were approx 50 % lower than both basal and T3 -values .", "target_text": {} }, { "input_text": "The log10Kd increased 0.304 +/- 0.139 ( p < 0.04 ) and the log10MBC increased 0.49 +/- 0.10 ( p < 0.001 ) in the T3 + subjects compared to baseline .", "target_text": {} }, { "input_text": "This change in MBC represents a 311 % increase in the MBC over baseline and a fivefold increase over placebo-treated subjects .", "target_text": {} }, { "input_text": "The T3 -group showed no change in MBC over the study .", "target_text": {} }, { "input_text": "These results describe for the first time the rapid modulation of the NT3R in response to the combined influence of cold exposure and reduced circulating T4 and TSH .", "target_text": { "NT3R": "protein" } }, { "input_text": "HIV-1 LTR activity in human CD40-activated B lymphocytes is dependent on NF-kappaB .", "target_text": { "HIV-1 LTR": "DNA", "human CD40-activated B lymphocytes": "cell_line", "NF-kappaB": "protein" } }, { "input_text": "CD40-stimulated human B lymphocytes are highly permissive to a productive infection by the human immunodeficiency virus type 1 .", "target_text": { "CD40-stimulated human B lymphocytes": "cell_line" } }, { "input_text": "In these cells , nuclear factors involved in activation of the HIV-1 LTR , which contains the transcriptional control elements of the virus , are unknown .", "target_text": { "nuclear factors": "protein", "HIV-1 LTR": "DNA", "transcriptional control elements": "DNA" } }, { "input_text": "Transient expression assays with plasmids containing deleted parts of the LTR region linked to a reporter gene showed that the NF-kappaB binding site was essential for HIV-1 LTR activity in CD40-stimulated B lymphocytes .", "target_text": { "LTR region": "DNA", "NF-kappaB": "protein", "NF-kappaB binding site": "DNA", "HIV-1 LTR": "DNA", "CD40-stimulated B lymphocytes": "cell_line" } }, { "input_text": "In addition , electrophoretic mobility shift and supershift assays revealed that important NF-kappaB binding activity composed of at least p50 , p65 , and c-Rel NF-kappaB subunits was present in nuclei of CD40-stimulated B cells .", "target_text": { "NF-kappaB": "protein", "p50": "protein", "p65": "protein", "c-Rel": "protein", "NF-kappaB subunits": "protein", "CD40-stimulated B cells": "cell_line" } }, { "input_text": "These results confirm at a molecular level the ability of HIV-1 to replicate in B cells and that this activity is strongly associated with NF-kappaB .", "target_text": { "B cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "Sequence analysis and expression in cultured lymphocytes of the human FOSB gene ( G0S3 ) .", "target_text": { "cultured lymphocytes": "cell_type", "FOSB gene": "DNA", "G0S3": "DNA" } }, { "input_text": "G0S3 is a member of a set of putative G0/G1 switch regulatory genes ( G0S genes ) selected by screening cDNA libraries prepared from human blood mononuclear cells cultured for 2 hr with lectin and cycloheximide .", "target_text": { "G0S3": "DNA", "putative G0/G1 switch regulatory genes": "DNA", "G0S genes": "DNA", "cDNA libraries": "DNA", "human blood mononuclear cells": "cell_type", "lectin": "protein" } }, { "input_text": "The sequence shows high homology with the murine FOSB gene , which encodes a component of the AP1 transcriptional regulator .", "target_text": { "FOSB gene": "DNA", "murine FOSB gene": "DNA", "AP1 transcriptional regulator": "protein" } }, { "input_text": "Comparison of cDNA and genomic sequences reveals a 4-exon structure characteristic of the FOS family of genes .", "target_text": { "cDNA": "DNA", "genomic sequences": "DNA", "4-exon structure": "DNA", "FOS family of genes": "DNA" } }, { "input_text": "Freshly isolated cells show high levels of FOSB/G0S3 and FOS/G0S7 mRNAs , which decline rapidly during incubation in culture medium .", "target_text": {} }, { "input_text": "The kinetics of expression suggest that the high initial levels are caused by the isolation procedure , and do not reflect constitutive expression .", "target_text": {} }, { "input_text": "In cells preincubated for a day , levels of FOS mRNA reach a maximum 20 min after the addition of lectin and decline to control levels over the next 3 hr .", "target_text": { "FOS mRNA": "RNA", "lectin": "protein" } }, { "input_text": "Levels of FOSB mRNA reach a maximum 40 min after the addition of lectin and decline to control levels over the next 6 hr .", "target_text": { "FOSB mRNA": "RNA", "lectin": "protein" } }, { "input_text": "In freshly isolated cells , both FOS and FOSB mRNAs increase dramatically in response to the protein synthesis inhibitor cycloheximide .", "target_text": {} }, { "input_text": "In preincubated cells , the cycloheximide response is decreased , especially in the case of FOSB .", "target_text": { "FOSB": "DNA" } }, { "input_text": "These differences in expression of FOS and FOSB suggest different roles and regulation .", "target_text": { "FOS": "DNA", "FOSB": "DNA" } }, { "input_text": "Regions of low base order-dependent stem-loop potential in the region of the gene are defined .", "target_text": {} }, { "input_text": "These indicate where base order has been adapted for purposes other than stem-loop stability ( e.g. , encoding proteins or gene regulation ) .", "target_text": {} }, { "input_text": "Regions of low potential in a 68.5-kb genomic segment containing the FOSB gene suggest that the potential may help locate genes in uncharted DNA sequences .", "target_text": { "FOSB": "DNA", "FOSB gene": "DNA", "uncharted DNA sequences": "DNA" } }, { "input_text": "Susceptibility to natural killer cells and down regulation of MHC class I expression in adenovirus 12 transformed cells are regulated by different E1A domains .", "target_text": { "natural killer cells": "cell_type", "MHC": "protein", "adenovirus 12 transformed cells": "cell_line", "E1A domains": "DNA" } }, { "input_text": "All human adenoviruses transform rodent cells in vitro , but only cells transformed by serotypes belonging to subgroups A ( Ad12 ) and B ( Ad3 ) are tumorigenic for immunocompetent animals .", "target_text": { "rodent cells": "cell_type" } }, { "input_text": "In these cells , the expression of MHC-class I antigens is repressed and might allow them to escape from recognition by cytotoxic T lymphocytes ( CTL ) and to develop in tumor .", "target_text": { "MHC-class I antigens": "protein", "cytotoxic T lymphocytes": "cell_type", "CTL": "cell_type" } }, { "input_text": "Furthermore , these cell lines appear resistant to lysis by natural killer ( NK ) cells .", "target_text": { "cell lines": "cell_line", "natural killer ( NK ) cells": "cell_type" } }, { "input_text": "To determine the E1A domain ( s ) responsible for these properties several cell lines were created by transforming baby rat kidney ( BRK ) cells with a set of plasmids expressing different Ad2/Ad12 hybrid E1A gene products .", "target_text": { "E1A domain": "DNA", "cell lines": "cell_line", "baby rat kidney ( BRK ) cells": "cell_line", "plasmids": "DNA", "Ad2/Ad12 hybrid E1A gene products": "protein" } }, { "input_text": "The MHC class 1 gene expression was inhibited in cells expressing the Ad12 13S mRNA product and in cells transformed with Ad2/Ad12 hybrid E1A gene product harboring the C-terminal part of the conserved region ( CR ) 3 of Ad12 .", "target_text": { "MHC class 1 gene": "DNA", "Ad12 13S mRNA": "RNA", "Ad12 13S mRNA product": "protein", "Ad2/Ad12 hybrid E1A gene product": "protein", "C-terminal part": "protein", "conserved region ( CR ) 3": "DNA" } }, { "input_text": "Susceptibility of these transformed cell lines to NK cells was determined by cytolytic assays .", "target_text": { "cell lines": "cell_line", "NK cells": "cell_type" } }, { "input_text": "The results obtained suggest that two Ad12 E1A domains are required to induce resistance of the cell lines to NK cells .", "target_text": { "E1A domains": "DNA", "Ad12 E1A domains": "DNA", "cell lines": "cell_line", "NK cells": "cell_type" } }, { "input_text": "Cell specific expression of human Bruton 's agammaglobulinemia tyrosine kinase gene ( Btk ) is regulated by Sp1- and Spi-1/PU.1-family members .", "target_text": { "human Bruton 's agammaglobulinemia tyrosine kinase gene": "DNA", "Btk": "protein", "Sp1-": "protein", "Spi-1/PU.1-family members": "protein" } }, { "input_text": "Bruton 's agammaglobulinemia tyrosine kinase ( Btk ) is a cytoplasmic tyrosine kinase involved in the human disease X-linked agammaglobulinemia ( XLA ) .", "target_text": { "Bruton 's agammaglobulinemia tyrosine kinase": "protein", "Btk": "protein", "cytoplasmic tyrosine kinase": "protein" } }, { "input_text": "The gene is expressed in all hematopoietic cells with the exception of T-cells and plasma cells .", "target_text": { "hematopoietic cells": "cell_type", "T-cells": "cell_type", "plasma cells": "cell_type" } }, { "input_text": "For this expression pattern the first 280 bp upstream of the major transcriptional start site seems to be sufficient .", "target_text": { "280 bp upstream": "DNA", "major transcriptional start site": "DNA" } }, { "input_text": "In vitro footprinting analysis within this part of the promoter revealed two Sp1 binding sites as well as a PU-box .", "target_text": { "promoter": "DNA", "Sp1 binding sites": "DNA", "PU-box": "DNA" } }, { "input_text": "The transcription factor Spi-1/PU.1 as well as the closely related factor Spi-B bound to the PU-box in B-cells .", "target_text": { "transcription factor": "protein", "Spi-1/PU.1": "protein", "Spi-B": "protein", "PU-box": "DNA" } }, { "input_text": "In the erythroleukemia cell line K562 , due to the absence of Spi-B , only PU.1 bound to the Btk promoter .", "target_text": { "erythroleukemia cell line K562": "cell_line", "Spi-B": "protein", "PU.1": "protein", "Btk": "protein", "Btk promoter": "DNA" } }, { "input_text": "Mutation of either site reduced the expression in transient transfection experiments .", "target_text": {} }, { "input_text": "However , mutation of the PU box had no effect in the T-cell line Jurkat , where none of the Spi-1 family members is expressed .", "target_text": { "PU box": "DNA", "T-cell line Jurkat": "cell_line", "Spi-1 family members": "protein" } }, { "input_text": "In addition Spi-B as well as PU.1 were able to transactivate Btk expression .", "target_text": { "Spi-B": "protein", "PU.1": "protein", "Btk": "protein" } }, { "input_text": "In fetal liver of PU.1-/- mice , which lack lymphoid and myeloid cells , expression of Btk was reduced two- to threefold but not abolished .", "target_text": { "Btk": "protein" } }, { "input_text": "Collectively this study shows that expression of the Btk gene is regulated by the combined action of Sp1- and PU.1- family members .", "target_text": { "Btk": "protein", "Btk gene": "DNA" } }, { "input_text": "T cell response to Epstein-Barr virus transactivators in chronic rheumatoid arthritis .", "target_text": { "Epstein-Barr virus transactivators": "protein" } }, { "input_text": "Rheumatoid arthritis is a multistep disorder associated with autoimmune features of yet unknown etiology .", "target_text": {} }, { "input_text": "Implication of viruses such as Epstein-Barr virus ( EBV ) in rheumatoid arthritis pathogenesis has been suspected on the basis of several indirect observations , but thus far , a direct link between EBV and rheumatoid arthritis has not been provided .", "target_text": {} }, { "input_text": "Here we show that a large fraction of T cells infiltrating affected joints from a patient with chronic rheumatoid arthritis recognizes two EBV transactivators ( BZLF1 and BMLF1 ) in a major histocompatibility complex -restricted fashion .", "target_text": { "T cells": "cell_type", "EBV transactivators": "protein", "BZLF1": "protein", "BMLF1": "protein", "major histocompatibility complex": "protein" } }, { "input_text": "Responses to these EBV antigens by synovial lymphocytes from several other chronic rheumatoid arthritis patients were readily detectable .", "target_text": { "EBV antigens": "protein" } }, { "input_text": "Thus these results suggest a direct contribution of EBV to chronic rheumatoid arthritis pathogenesis .", "target_text": {} }, { "input_text": "They also demonstrate for the first time the occurrence of T cell responses against EBV transactivating factors , which might be central in the control of virus reactivation .", "target_text": { "EBV transactivating factors": "protein" } }, { "input_text": "CD14 -mediated signal pathway of Porphyromonas gingivalis lipopolysaccharide in human gingival fibroblasts .", "target_text": { "CD14": "protein", "human gingival fibroblasts": "cell_type" } }, { "input_text": "Lipopolysaccharide ( LPS ) induces expression of inflammatory cytokines in monocytes/macrophages via CD14 , one of the LPS receptors , which is expressed predominantly in these cells .", "target_text": { "inflammatory cytokines": "protein", "monocytes/macrophages": "cell_type", "CD14": "protein", "LPS receptors": "protein" } }, { "input_text": "It has been demonstrated that Porphyromonas gingivalis LPS ( P- LPS ) also is able to induce inflammatory cytokines in human gingival fibroblasts .", "target_text": { "inflammatory cytokines": "protein", "human gingival fibroblasts": "cell_type" } }, { "input_text": "Therefore , it is important to determine whether CD14 is expressed in gingival fibroblasts and to define the P- LPS -mediated signal-transducing mechanism in the cells .", "target_text": { "CD14": "protein", "gingival fibroblasts": "cell_type", "signal-transducing": "protein" } }, { "input_text": "In this study , we observed unexpectedly by immunohistochemical , Western blotting ( immunoblotting ) , and Northern ( RNA ) blotting assays that CD14 is expressed at high density in human gingival fibroblasts .", "target_text": { "CD14": "protein", "gingival fibroblasts": "cell_type", "human gingival fibroblasts": "cell_type" } }, { "input_text": "P- LPS -induced expression of the monocyte chemoattractant protein 1 ( MCP-1 ) gene in the cells was inhibited markedly by treatment with anti-human CD14 antibody and was completely inhibited by herbimycin A , a potent inhibitor of tyrosine kinase .", "target_text": { "monocyte chemoattractant protein 1": "protein", "MCP-1": "DNA", "monocyte chemoattractant protein 1 ( MCP-1 ) gene": "DNA", "CD14": "protein", "tyrosine kinase": "protein" } }, { "input_text": "The inhibitor also dramatically inhibited monocyte chemotactic activity of and MCP-1 production by the cells .", "target_text": { "MCP-1": "protein" } }, { "input_text": "Furthermore , P- LPS -induced expression of the MCP-1 gene in the cells also was blocked by inhibitors of two transcription factors , i.e. , curcumin , an inhibitor of AP-1 , and pyrolidine dithiocarbamate , an inhibitor of NF-kappaB .", "target_text": { "MCP-1 gene": "DNA", "transcription factors": "protein", "AP-1": "protein", "NF-kappaB": "protein" } }, { "input_text": "Both inhibitors inhibited monocyte chemotactic activity in the culture supernatant of P- LPS -treated cells .", "target_text": {} }, { "input_text": "Gel shift mobility assay showed stimulation of the AP-1 and NF-kappaB contents in P- LPS -treated cells .", "target_text": { "AP-1": "protein", "NF-kappaB": "protein" } }, { "input_text": "This study is the first to demonstrate the expression of CD14 in human gingival fibroblasts and to show that the signal-transducing pathway of P- LPS in the cells is mediated by CD14 .", "target_text": { "CD14": "protein", "gingival fibroblasts": "cell_type", "human gingival fibroblasts": "cell_type" } }, { "input_text": "rel Is rapidly tyrosine-phosphorylated following granulocyte-colony stimulating factor treatment of human neutrophils .", "target_text": { "rel": "protein", "granulocyte-colony stimulating factor": "protein" } }, { "input_text": "Stimulation of neutrophils with granulocyte-colony stimulating factor ( G-CSF ) results in an enhanced respiratory burst , prolonged survival , and increased tumor cell killing .", "target_text": { "neutrophils": "cell_type", "granulocyte-colony stimulating factor": "protein", "G-CSF": "protein" } }, { "input_text": "The effects of G-CSF are mediated by binding to specific , high affinity receptors .", "target_text": { "G-CSF": "protein", "affinity receptors": "protein" } }, { "input_text": "G-CSF receptors lack intrinsic tyrosine kinase activity , but activation of the receptor results in the rapid induction of tyrosine kinase activity .", "target_text": { "G-CSF": "protein", "G-CSF receptors": "protein", "tyrosine kinase": "protein" } }, { "input_text": "Antiphosphotyrosine immunoblots of whole cell lysates prepared from neutrophils show that the G-CSF rapidly induces prominent tyrosine phosphorylation of a protein of a relative molecular mass of 80 kDa .", "target_text": { "neutrophils": "cell_type", "G-CSF": "protein" } }, { "input_text": "Using monospecific antibodies , the 80-kDa tyrosine -phosphorylated protein has been shown to be p80c-rel , a proto-oncogene belonging to a family of transcriptional regulators which include NF-kB .", "target_text": { "monospecific antibodies": "protein", "tyrosine -phosphorylated protein": "protein", "p80c-rel": "protein", "proto-oncogene": "DNA", "transcriptional regulators": "protein", "NF-kB": "protein" } }, { "input_text": "The induction of tyrosine phosphorylation of p80c-rel was unique to G-CSF in that granulocyte-macrophage colony stimulating factor which also stimulates neutrophils and induces tyrosine phosphorylation does not result in tyrosine phosphorylation of p80c-rel .", "target_text": { "p80c-rel": "protein", "G-CSF": "protein", "granulocyte-macrophage colony stimulating factor": "protein", "neutrophils": "cell_type" } }, { "input_text": "The consequences of p80c-rel tyrosine phosphorylation are not yet known ; however , tyrosine -phosphorylated p80c-rel is capable of binding to DNA , and G-CSF stimulation results in an increase in the amount of p80c-rel which binds to DNA .", "target_text": { "p80c-rel": "protein", "G-CSF": "protein" } }, { "input_text": "These results demonstrate that one of the first biochemical events which occurs in neutrophils following G-CSF stimulation , activation of a tyrosine kinase , leads directly to the tyrosine phosphorylation of p80c-rel .", "target_text": { "neutrophils": "cell_type", "G-CSF": "protein", "tyrosine kinase": "protein", "p80c-rel": "protein" } }, { "input_text": "Thus , the tyrosine kinase activated by G-CSF appears to directly transduce a signal to a protein which functions as a transcriptional regulator .", "target_text": { "tyrosine kinase": "protein", "G-CSF": "protein", "transcriptional regulator": "protein" } }, { "input_text": "Patterns of Pan expression and role of Pan proteins in endocrine cell type-specific complex formation .", "target_text": { "Pan": "protein", "Pan proteins": "protein" } }, { "input_text": "The Pan gene encodes at least two distinct transcripts , Pan-1 and Pan-2 ( also known as E47 and E12 , respectively ) , by the mechanism of alternative RNA splicing .", "target_text": { "Pan gene": "DNA", "Pan-1": "protein", "Pan-2": "protein", "E47": "protein", "E12": "protein" } }, { "input_text": "Northern blot analyses performed on rat and mouse tissues have detected ubiquitously expressed Pan transcripts , but the abundance , distribution , and form of Pan proteins have not been clearly defined .", "target_text": { "Pan proteins": "protein" } }, { "input_text": "Studies of cell lines representing endocrine , fibroblast , and lymphoid lineages using polyclonal antisera to detect E2A proteins have suggested that significant E2A protein expression is restricted to B-lymphocytes .", "target_text": { "cell lines": "cell_line", "E2A proteins": "protein", "E2A protein": "protein", "B-lymphocytes": "cell_type" } }, { "input_text": "We have developed a monoclonal antibody , Yae , which is specific for Pan/ E2A proteins , and have used the Yae antibody to examine a variety of endocrine and nonendocrine cell lineages for differences in Pan/ E2A protein expression , subcellular localization , and heteromeric complex formation .", "target_text": { "monoclonal antibody": "protein", "Yae": "protein", "E2A proteins": "protein", "Pan/ E2A proteins": "protein", "Yae antibody": "protein", "E2A protein": "protein" } }, { "input_text": "In contrast to previous results obtained using polyclonal antiseras to detect Pan/ E2A proteins , we report comparable levels of Pan proteins in GH/PRL- and insulin- producing , B- and T- lymphocyte cells .", "target_text": { "E2A proteins": "protein", "Pan proteins": "protein" } }, { "input_text": "IEF-1 , a pancreatic beta-cell type-specific complex believed to regulate insulin expression , is demonstrated to consist of at least two distinct species , one of which does not contain Pan molecules .", "target_text": { "IEF-1": "protein", "Pan molecules": "protein" } }, { "input_text": "Although it has been postulated that pituitary endocrine cells and pancreatic endocrine beta-cells share identical Pan/E2A complexes , native-Western analyses of pituitary and endocrine beta-cells detect Pan proteins in distinct cell type-specific complexes .", "target_text": { "pituitary endocrine cells": "cell_type", "pancreatic endocrine beta-cells": "cell_type", "Pan/E2A complexes": "protein", "endocrine beta-cells": "cell_type", "Pan proteins": "protein", "cell type-specific complexes": "protein" } }, { "input_text": "Visualization of the endogenous NF-kappa B p50 subunit in the nucleus of follicular dendritic cells in germinal centers .", "target_text": { "NF-kappa B": "protein", "endogenous NF-kappa B p50 subunit": "protein", "follicular dendritic cells": "cell_type" } }, { "input_text": "NF-kappa B , a 50 kDa/65 kDa ( p50/p65 ) heterodimer , is a ubiquitous transcription factor involved in the positive regulation of various immune genes .", "target_text": { "NF-kappa B": "protein", "50 kDa/65 kDa ( p50/p65 ) heterodimer": "protein", "ubiquitous transcription factor": "protein", "immune genes": "DNA" } }, { "input_text": "The aim of this study was to determine whether NF-kappa B is related to a particular cell type and/or differentiation step during immunopoiesis .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Using in situ hybridization on sections from non HIV hyperplastic lymph nodes , we found that the gene of the 105 kDa precursor of p50 was overexpressed in the light zone of germinal centers , with a network aspect , which suggested the involvement of follicular dendritic cells ( FDC ) .", "target_text": { "105 kDa precursor": "protein", "p50": "protein", "follicular dendritic cells": "cell_type", "FDC": "cell_type" } }, { "input_text": "By immunohistochemistry , p50 protein was detected in the cytoplasm and nucleus of FDC , confirming the involvement of FDC .", "target_text": { "p50": "protein", "FDC": "cell_type" } }, { "input_text": "Furthermore , p50 protein was detected in the cytoplasm of all lymphocytes .", "target_text": { "p50": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Thus , we focused our study on isolated FDC clusters from normal tonsils .", "target_text": { "FDC": "cell_type" } }, { "input_text": "As showed on tissue sections , we detected the p50 in both cytoplasm and nucleus of FDC .", "target_text": { "p50": "protein", "FDC": "cell_type" } }, { "input_text": "Nuclei of lymphocytes from FDC clusters were negative .", "target_text": { "lymphocytes": "cell_type", "FDC": "cell_type" } }, { "input_text": "We next studied p65 and c-Rel protein expression in FDC clusters .", "target_text": { "FDC": "cell_type" } }, { "input_text": "p65 was detected in the cytoplasm of FDC , whereas nuclei were negative .", "target_text": { "p65": "protein", "FDC": "cell_type" } }, { "input_text": "Furthermore , p65 was detected in the nuclei of some lymphocytes .", "target_text": { "p65": "protein", "lymphocytes": "cell_type" } }, { "input_text": "c-Rel protein was detected only in the cytoplasm of lymphocytes and not in the nucleus and cytoplasm of FDC .", "target_text": { "c-Rel protein": "protein", "lymphocytes": "cell_type", "FDC": "cell_type" } }, { "input_text": "Our results indicated that , in the context of T cell-dependent B cell immunopoiesis occurring in FDC clusters , p50 is mainly related to FDC with a massive overexpression in the nuclei , whereas p65 is expressed in a scattered manner in the nuclei of lymphocytes and c-Rel protein exclusively in the cytoplasm of lymphocytes from FDC clusters .", "target_text": { "FDC": "cell_type", "p50": "protein", "p65": "protein", "lymphocytes": "cell_type" } }, { "input_text": "These results suggested that the two subunits of NF-kappa B and the c-Rel protein have different roles in different cell types during B cell immunopoiesis .", "target_text": { "NF-kappa B": "protein", "c-Rel protein": "protein" } }, { "input_text": "Cloning and characterization of NF-ATc and NF-ATp : the cytoplasmic components of NF-AT .", "target_text": { "NF-ATc": "protein", "NF-ATp": "protein", "NF-AT": "protein" } }, { "input_text": "Present evidence indicates a pathway of signal transmission in T cells that is outlined in figure 1 .", "target_text": { "T cells": "cell_type" } }, { "input_text": "The elevation in intracellular calcium that is induced by interactions at the antigen receptor leads to the activation of the calcium-dependent phosphatase calcineurin .", "target_text": { "antigen receptor": "protein", "calcium-dependent phosphatase": "protein", "calcineurin": "protein" } }, { "input_text": "This in turn leads to the nuclear association of the cytosolic component of NF-ATc .", "target_text": { "cytosolic component": "protein", "NF-ATc": "protein" } }, { "input_text": "The activation of calcineurin and the nuclear import of NF-ATc can both be blocked by cyclosporin A or FK506 in complex with their respective immunophilins .", "target_text": { "calcineurin": "protein", "NF-ATc": "protein", "immunophilins": "protein" } }, { "input_text": "Once in the nucleus , NF-ATc interacts with NF-ATn to form an active transcriptional complex .", "target_text": { "NF-ATc": "protein", "NF-ATn": "protein", "active transcriptional complex": "protein" } }, { "input_text": "NF-ATn is a ubiquitous protein , can be synthesized in response to PMA , and has many similarities to AP-1 .", "target_text": { "NF-ATn": "protein", "AP-1": "protein" } }, { "input_text": "The mechanism by which NF-ATc enters the nucleus is unknown , and although it appears to require calcineurin , NF-ATc has not yet been shown to be an in vivo substrate of calcineurin .", "target_text": { "NF-ATc": "protein", "calcineurin": "protein" } }, { "input_text": "Alternative mechanisms include the possibility that NF-ATc operates on some cytoplasmic anchor or that other proteins that are controlled by calcineurin carry out the nuclear import of NF-ATc .", "target_text": { "NF-ATc": "protein", "cytoplasmic anchor": "protein", "calcineurin": "protein" } }, { "input_text": "Although NF-ATp copurifies with NF-ATc , there is as yet no understanding of how NF-ATp is functioning in vivo .", "target_text": { "NF-ATp": "protein", "NF-ATc": "protein" } }, { "input_text": "Now that these proteins are purified and cloned , the major goals will be to understand their role and the roles of other family members in thymic development .", "target_text": {} }, { "input_text": "Induction of vascular cell adhesion molecule-1 by low-density lipoprotein .", "target_text": { "vascular cell adhesion molecule-1": "protein", "low-density lipoprotein": "protein" } }, { "input_text": "Low-density lipoprotein ( LDL ) is a well-established risk factor for atherosclerosis .", "target_text": { "Low-density lipoprotein": "protein", "LDL": "protein" } }, { "input_text": "When endothelial cells are incubated with this lipoprotein in pathophysiologic amounts , the cells are activated .", "target_text": {} }, { "input_text": "Among the documented cellular responses to LDL is increased recruitment of monocytes , which are believed to play a major role in promoting intimal plaque formation .", "target_text": { "LDL": "protein", "monocytes": "cell_type" } }, { "input_text": "The findings presented here link an atheogenic lipoprotein , LDL , with the induction of an adhesion molecule important in atherogenesis Human LDL induces the vascular cell adhesion molecule-1 ( VCAM-1 ) transcriptionally with an increase in mRNA levels through activation of the VCAM promoter .", "target_text": { "atheogenic lipoprotein": "protein", "LDL": "protein", "vascular cell adhesion molecule-1": "protein", "VCAM-1": "protein", "VCAM promoter": "DNA" } }, { "input_text": "This effect is blocked by anti-VCAM antibodies .", "target_text": { "anti-VCAM antibodies": "protein" } }, { "input_text": "After a 2-day incubation in LDL , the binding of NF-kappa B , which is believed to be a key oxidative-stress sensor for VCAM regulation , remains at basal level .", "target_text": { "LDL": "protein", "NF-kappa B": "protein", "VCAM": "protein" } }, { "input_text": "In contrast , the binding activities of AP-1 and GATA , on the other hand , are increased by LDL .", "target_text": { "AP-1": "protein", "GATA": "protein", "LDL": "protein" } }, { "input_text": "Thus , a component of LDL -enhanced endothelial recruitment of monocytes is attributed to VCAM-1 expression , which appears to be mediated through AP-1 and GATA .", "target_text": { "LDL": "protein", "monocytes": "cell_type", "VCAM-1": "protein", "AP-1": "protein", "GATA": "protein" } }, { "input_text": "These data identify LDL as a VCAM -inducer possibly distinct from cytokines and endotoxin .", "target_text": { "LDL": "protein", "VCAM": "protein", "cytokines": "protein", "endotoxin": "protein" } }, { "input_text": "Involvement of nuclear factor-kappa B activation in IgE synthesis in human B cells .", "target_text": { "nuclear factor-kappa B": "protein", "IgE": "protein", "human B cells": "cell_type" } }, { "input_text": "Nuclear factor-kappa B ( NF-kappa B ) is a transcription factor that binds to the consensus DNA sequence in the cis-acting elements of various genes .", "target_text": { "Nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "consensus DNA sequence": "DNA", "cis-acting elements": "DNA", "various genes": "DNA" } }, { "input_text": "Although NF-kappa B activates the expression of many genes involved in immune and inflammatory responses , little is known about the role of NF-kappa B activation in the induction of IgE synthesis in human B cells .", "target_text": { "NF-kappa B": "protein", "human B cells": "cell_type" } }, { "input_text": "Therefore we first examined the participation of NF-kappa B in germline C epsilon transcription in a human Burkitt lymphoma B cell line , DND39 .", "target_text": { "NF-kappa B": "protein", "germline C epsilon": "cell_line", "human Burkitt lymphoma B cell line": "cell_line", "DND39": "cell_line" } }, { "input_text": "Stimulation of DND39 cells with IL-4 or anti-CD40 monoclonal antibody ( mAb ) activated phosphatidylinositol 3-kinase and subsequently induced nuclear expression of NF-kappa B , which was identified by electrophoretic mobility shift assays .", "target_text": { "DND39 cells": "cell_line", "IL-4": "protein", "anti-CD40 monoclonal antibody": "protein", "mAb": "protein", "phosphatidylinositol 3-kinase": "protein", "NF-kappa B": "protein" } }, { "input_text": "n-Acetyl-L-cysteine ( NAC ) , a potent antioxidant , blocked NF-kappa B activation caused by IL-4 and by anti-CD40 mAb .", "target_text": { "NF-kappa B": "protein", "IL-4": "protein", "anti-CD40 mAb": "protein" } }, { "input_text": "Although inhibition of IL-4 -driven germline C epsilon transcription by NAC was not sufficient , the agent remarkably diminished anti-CD40 mAb -mediated up-regulation of germline C epsilon transcription .", "target_text": { "IL-4": "protein", "IL-4 -driven germline C epsilon": "cell_line", "anti-CD40 mAb": "protein", "germline": "DNA" } }, { "input_text": "Second , we studied the effect of NAC on IgE synthesis in human normal B cells costimulated with IL-4 and anti-CD40 mAb .", "target_text": { "IgE": "protein", "IL-4": "protein", "anti-CD40 mAb": "protein" } }, { "input_text": "NAC was effective in inhibiting mature C epsilon transcription and IgE synthesis in the T cell-independent culture system .", "target_text": { "IgE": "protein" } }, { "input_text": "However , NAC did not significantly affect the spontaneous production of IgE by atopic B cells .", "target_text": { "IgE": "protein", "atopic B cells": "cell_type" } }, { "input_text": "These results indicate that NF-kappa B activity is commonly inducible in DND39 cells by IL-4 and anti-CD40 mAb and suggest that NF-kappa B sensitive to NAC may play a role in regulating IgE synthesis in B cells .", "target_text": { "NF-kappa B": "protein", "DND39 cells": "cell_line", "IL-4": "protein", "anti-CD40 mAb": "protein", "IgE": "protein", "B cells": "cell_type" } }, { "input_text": "Prostaglandin E2 induction of binding activity to CRE and AP-2 elements in human T lymphocytes .", "target_text": { "CRE": "DNA", "AP-2 elements": "DNA", "human T lymphocytes": "cell_type" } }, { "input_text": "Prostaglandins of the E series are immunomodulatory agents which exert inhibitory as well as stimulatory effects on a variety of immune responses .", "target_text": {} }, { "input_text": "Since it is known that PGE2 is able to increase cAMP levels , we investigated whether it can affect gene expression through the activation of the transcription factors which bind enhancer elements in the promoter regions of cAMP -regulated genes .", "target_text": { "transcription factors": "protein", "cAMP -regulated genes": "DNA" } }, { "input_text": "Using electrophoretic mobility shift assay , we demonstrated that a short treatment of human T lymphocytes with PGE2 induces specific binding activity to CRE and AP-2 , but not AP-1 , DNA elements .", "target_text": { "human T lymphocytes": "cell_type", "CRE": "DNA", "AP-2": "DNA", "AP-1": "protein", "AP-1 , DNA elements": "DNA" } }, { "input_text": "Since the okadaic acid , a potent protein phosphatase inhibitor , prolongs the induction of the binding activity , phosphorylation events are likely to occur .", "target_text": {} }, { "input_text": "This activity seems to be due to increased cAMP levels because forskolin and IBMX mimic the effects of PGE2 .", "target_text": {} }, { "input_text": "More interestingly , transfection experiments with CRE -CAT plasmide show that PGE2 activates the transcription of a CRE -containing promoter .", "target_text": { "CRE": "DNA", "CRE -CAT plasmide": "DNA", "CRE -containing promoter": "DNA" } }, { "input_text": "These data support the positive role for PGE2 on some immune functions .", "target_text": {} }, { "input_text": "Nasal NK- and T- cell lymphomas share the same type of Epstein-Barr virus latency as nasopharyngeal carcinoma and Hodgkin 's disease .", "target_text": {} }, { "input_text": "Nasal T/NK-cell lymphomas can be further separated into those of natural killer ( NK ) cell lineage or of T-cell lineage , with differences in cellular phenotype , T-cell receptor ( TcR ) gene rearrangement and TcR transcript expression .", "target_text": { "Nasal T/NK-cell lymphomas": "cell_type", "natural killer ( NK ) cell lineage": "cell_type", "T-cell lineage": "cell_type", "T-cell receptor": "protein", "T-cell receptor ( TcR ) gene": "DNA" } }, { "input_text": "Both NK- and T- cell subtypes are closely associated with Epstein-Barr virus ( EBV ) .", "target_text": {} }, { "input_text": "In this study , EBV gene expression was determined in 23 cases of nasal lymphoma ( NL ) by in situ hybridisation ( ISH ) , reverse transcriptase -polymerase chain reaction ( RT-PCR ) and immunohistochemistry ( IH ) .", "target_text": { "EBV gene": "DNA", "reverse transcriptase": "protein" } }, { "input_text": "Of the 23 cases , 19 were classified as NK-cell and 4 as T-cell tumours .", "target_text": {} }, { "input_text": "ISH for EBV -encoded small non-polyadenylated RNAs showed that all cases , whether NK or T , harboured EBV in virtually all tumour cells .", "target_text": { "EBV -encoded small non-polyadenylated RNAs": "RNA", "tumour cells": "cell_type" } }, { "input_text": "RT-PCR demonstrated that NL of both subtypes expressed EBNAI of the QUK splice pattern , the latent membrane proteins , LMP 1 and 2 and the BamHI A rightward transcripts in the absence of EBNA2 mRNAs , compatible with the latency type II pattern .", "target_text": { "NL": "cell_type", "EBNAI": "protein", "latent membrane proteins": "protein", "BamHI A rightward transcripts": "RNA", "EBNA2 mRNAs": "RNA" } }, { "input_text": "In addition , analysis of EBV protein expression by IH revealed a heterogeneous pattern of EBV gene expression at the single-cell level consisting of both LMP1+ and LMP1- tumour cells , suggesting a mixture of latency I and II .", "target_text": { "EBV gene": "DNA" } }, { "input_text": "Although 2 early lytic transcripts , BZLF1 and BHRF1 , were also detected in 13 and 10 cases , respectively , the lack of ZEBRA staining in any case indicates that these lytic transcripts are most likely expressed by rare cells in the biopsies entering lytic cycle .", "target_text": { "early lytic transcripts": "protein", "BZLF1": "protein", "BHRF1": "protein", "ZEBRA": "protein" } }, { "input_text": "The viral transcriptional pattern similar to that of nasopharyngeal carcinoma and Hodgkin 's disease suggests that EBV can exploit common regulatory mechanisms for gene transcription in diverse host cell types .", "target_text": {} }, { "input_text": "Down-regulation of immunogenic proteins ( EBNA2-EBNA6 ) in nasal lymphoma may enable tumour cells to evade host cytotoxic T-cell surveillance .", "target_text": { "immunogenic proteins": "protein", "EBNA2-EBNA6": "protein", "tumour cells": "cell_type" } }, { "input_text": "Potent gene regulatory and antiproliferative activities of 20-methyl analogues of 1,25 dihydroxyvitamin D3 .", "target_text": {} }, { "input_text": "The biological active form of vitamin D3 , 1,25-dihydroxyvitamin D3 ( VD ) , regulates cellular growth and differentiation .", "target_text": {} }, { "input_text": "This provides the hormone with an interesting therapeutic potential .", "target_text": {} }, { "input_text": "However , hypercalcemia is a side effect , which is caused by VD 's classical action , the regulation of calcium homeostasis .", "target_text": {} }, { "input_text": "This made the need for VD analogues with selectively increased cell regulatory properties .", "target_text": {} }, { "input_text": "Studies with 20-epi analogues pointed out the importance of the carbon-20 position and led to the development of 20-methyl derivatives of VD .", "target_text": {} }, { "input_text": "In this report the biological properties of the compounds ZK161422 and ZK157202 , which are 20-methyl- and 20-methyl-23- eneanalogues , respectively , have been analyzed in comparison with VD .", "target_text": {} }, { "input_text": "Both compounds show about 2-fold lower affinity to the VD receptor ( VDR ) than VD .", "target_text": {} }, { "input_text": "However , compared to VD , their antiproliferative effect is up to 30-fold higher on human peripheral blood mononuclear cells and even up to 300-fold higher on human breast cancer MCF-7 cells .", "target_text": { "human peripheral blood mononuclear cells": "cell_type", "human breast cancer MCF-7 cells": "cell_line" } }, { "input_text": "Whereas the hypercalcemic effect for ZK157202 is also increased 10-fold , ZK161422 has the same calcium -mobilizing potency as VD .", "target_text": {} }, { "input_text": "Moreover , ZK161422 , but not ZK157202 , showed preference for gene activation from a promoter carrying a VD response element with a palindromic arrangement of two hexameric receptor binding sites spaced by 9 nucleotides ( IP9 ) rather than for activation from a response element formed by a direct repeat spaced by 3 nucleotides ( DR3 ) .", "target_text": { "promoter": "DNA", "VD response element": "DNA", "palindromic arrangement": "DNA", "hexameric receptor binding sites": "DNA", "response element": "DNA" } }, { "input_text": "This observation supports a model , in which promoter selectivity reflects the selectively increased antiproliferative effect of VD analogues .", "target_text": {} }, { "input_text": "Calcium -dependent immediate-early gene induction in lymphocytes is negatively regulated by p21Ha-ras .", "target_text": { "immediate-early gene": "DNA", "lymphocytes": "cell_type", "p21Ha-ras": "protein" } }, { "input_text": "The induction of immediate-early ( IE ) response genes , such as egr-1 , c-fos , and c-jun , occurs rapidly after the activation of T lymphocytes .", "target_text": { "immediate-early ( IE ) response genes": "DNA", "egr-1": "DNA", "c-fos": "DNA", "c-jun": "DNA", "T lymphocytes": "cell_type" } }, { "input_text": "The process of activation involves calcium mobilization , activation of protein kinase C ( PKC ) , and phosphorylation of tyrosine kinases .", "target_text": { "protein kinase C": "protein", "PKC": "protein", "tyrosine kinases": "protein" } }, { "input_text": "p21(ras) , a guanine nucleotide binding factor , mediates T-cell signal transduction through PKC -dependent and PKC -independent pathways .", "target_text": { "p21(ras)": "protein", "guanine nucleotide binding factor": "protein", "PKC": "protein" } }, { "input_text": "The involvement of p21(ras) in the regulation of calcium -dependent signals has been suggested through analysis of its role in the activation of NF-AT .", "target_text": { "p21(ras)": "protein", "NF-AT": "protein" } }, { "input_text": "We have investigated the inductions of the IE genes in response to calcium signals in Jurkat cells ( in the presence of activated p21(ras) ) and their correlated consequences .", "target_text": { "IE genes": "DNA", "Jurkat cells": "cell_line", "p21(ras)": "protein" } }, { "input_text": "The expression of activated p21(ras) negatively regulated the induction of IE genes by calcium ionophore .", "target_text": { "p21(ras)": "protein", "IE genes": "DNA" } }, { "input_text": "This inhibition of calcium -activated IE gene induction was reversed by treatment with cyclosporin A , suggesting the involvement of calcineurin in this regulation .", "target_text": { "IE gene": "DNA", "calcineurin": "protein" } }, { "input_text": "A later result of inhibition of this activation pathway by p21(ras) was down-regulation of the activity of the transcription factor AP-1 and subsequent coordinate reductions in IL-2 gene expression and protein production .", "target_text": { "p21(ras)": "protein", "transcription factor": "protein", "AP-1": "protein", "IL-2 gene": "DNA" } }, { "input_text": "These results suggest that p2l(ras) is an essential mediator in generating not only positive but also negative modulatory mechanisms controlling the competence of T cells in response to inductive stimulations .", "target_text": { "p2l(ras)": "protein", "T cells": "cell_type" } }, { "input_text": "Calcineurin acts in synergy with PMA to inactivate I kappa B/MAD3 , an inhibitor of NF-kappa B .", "target_text": { "Calcineurin": "protein", "I kappa B/MAD3": "protein", "NF-kappa B": "protein" } }, { "input_text": "The interleukin-2 ( IL-2 ) promoter consists of several independent T cell receptor ( TcR ) responsive elements .", "target_text": { "interleukin-2": "protein", "IL-2": "protein", "interleukin-2 ( IL-2 ) promoter": "DNA", "T cell receptor": "protein", "TcR": "protein", "T cell receptor ( TcR ) responsive elements": "DNA" } }, { "input_text": "The induction of promoters dependent on these elements is inhibitable by the immunosuppressants cyclosporin A ( CsA ) and tacrolimus ( FK-506 ) .", "target_text": { "promoters": "DNA" } }, { "input_text": "Calcineurin , a Ca2+ /calmodulin-dependent protein phosphatase , is the FK-506 - and CsA -sensitive enzyme required for TcR mediated activation of the IL-2 promoter .", "target_text": { "Calcineurin": "protein", "Ca2+ /calmodulin-dependent protein phosphatase": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "We report that a constitutively active form of calcineurin partially substitutes for the Ca2+ co-stimulus required to activate the IL-2 promoter elements IL-2A ( which binds the factors OAP and Oct-1 ) and IL-2E ( which binds NF-AT ) , and completely substitutes for the Ca2+ co-stimulus required to stimulate an NF-kappa B -dependent element .", "target_text": { "calcineurin": "protein", "IL-2 promoter": "DNA", "IL-2 promoter elements": "DNA", "IL-2A": "DNA", "OAP": "protein", "Oct-1": "protein", "IL-2E": "DNA", "NF-AT": "protein", "NF-kappa B": "protein" } }, { "input_text": "Calcineurin stimulates the NF-kappa B element by enhancing inactivation of I kappa B/MAD3 , an inhibitor of NF-kappa B , thereby increasing the amount of nuclear NF-kappa B DNA binding activity .", "target_text": { "Calcineurin": "protein", "NF-kappa B": "protein", "NF-kappa B element": "DNA", "I kappa B/MAD3": "protein" } }, { "input_text": "These data provide the first demonstration in vivo that activation of a protein phosphatase can inactivate I kappa B , and suggest one possible explanation for mechanism-based toxicities associated with FK-506 and CsA by demonstrating that these drugs can inhibit the calcineurin -dependent activation of a virtually ubiquitous transcription factor .", "target_text": { "protein phosphatase": "protein", "I kappa B": "protein", "calcineurin": "protein", "ubiquitous transcription factor": "protein" } }, { "input_text": "Detection of minimal residual disease in a patient with acute promyelocytic leukemia by RT-PCR : necessity of chemotherapy following ATRA therapy .", "target_text": {} }, { "input_text": "The PML/RAR alpha fusion gene resulting from the t (15;17) translocation is a specific marker for acute promyelocytic leukemia ( APL ) .", "target_text": { "PML/RAR alpha fusion gene": "DNA", "t (15;17) translocation": "DNA" } }, { "input_text": "We examined bone marrow cells by reverse transcriptase-polymerase chain reaction ( RT-PCR ) to detect residual PML/RAR alpha mRNA -containing cells following treatment with all-trans retinoic acid ( ATRA ) and cytotoxic chemotherapy in a patient with APL .", "target_text": { "PML/RAR alpha mRNA": "RNA", "PML/RAR alpha mRNA -containing cells": "cell_type" } }, { "input_text": "This RT-PCR assay can detect one leukemic cell in 10(2) normal cells in vitro .", "target_text": { "leukemic cell": "cell_type", "normal cells": "cell_type" } }, { "input_text": "We show that PML/RAR alpha mRNA was still detectable despite clinical remission following ATRA treatment , but undetectable following consolidation with chemotherapy .", "target_text": { "PML/RAR alpha mRNA": "RNA" } }, { "input_text": "These data show that this technique is useful for the identification of minimal residual disease in patients with APL and that cytotoxic chemotherapy following ATRA therapy is required for the elimination of APL cells .", "target_text": { "APL cells": "cell_type" } }, { "input_text": "Glucocorticoid -mediated inhibition of interleukin-2 receptor alpha and -beta subunit expression by human T cells .", "target_text": {} }, { "input_text": "To determine the mechanism of glucocorticoid ( GC ) -mediated inhibition of T cell functions , the effect of dexamethasone ( DM ) on T cell proliferation and interleukin-2 receptor ( IL-2R ) generation were studied .", "target_text": { "T cell": "cell_type", "interleukin-2 receptor": "protein", "IL-2R": "protein" } }, { "input_text": "Dexamethasone inhibited IL-2 -induced T cell proliferation by 30 % -88 % , relative to its concentration within the cultures .", "target_text": { "IL-2": "protein", "T cell": "cell_type" } }, { "input_text": "The effect of DM on expression of IL-2R alpha ( Tac , p55 , CD25 ) and beta ( p75 ) genes in activated T cells was examined next .", "target_text": { "IL-2R alpha": "protein", "Tac": "protein", "p55": "protein", "CD25": "protein", "beta ( p75 ) genes": "DNA", "activated T cells": "cell_type" } }, { "input_text": "In T cells stimulated with purified phytohemagglutinin ( PHA-p ) and 4 beta-phorbol 12-myristate 13-acetate ( PMA ) addition of DM to the cultures resulted in a 60 % reduction in IL-2R alpha and a 30 % reduction in IL-2R beta membrane expression compared to T cells cultured in the absence of DM ( p < 0.01 ) .", "target_text": { "T cells": "cell_type", "phytohemagglutinin": "protein", "PHA-p": "protein", "IL-2R alpha": "protein", "IL-2R beta": "protein" } }, { "input_text": "Inhibition of membrane IL-2R alpha and IL-2R beta expression by 10(-6) M DM was partially reversible by recombinant human IL-2 ( rhIL-2 ) .", "target_text": { "IL-2R alpha": "protein", "IL-2R beta": "protein", "recombinant human IL-2": "protein", "rhIL-2": "protein" } }, { "input_text": "By Northern blot analysis , DM caused a comparable decrease in IL-2R alpha and in IL-2R beta mRNA levels to membrane receptor expression in mitogen-stimulated T cells .", "target_text": { "IL-2R alpha": "protein", "IL-2R beta": "protein", "T cells": "cell_type", "mitogen-stimulated T cells": "cell_type" } }, { "input_text": "By in vitro transcription assays , DM regulated IL-2R alpha gene expression at a transcriptional level while transcription of IL-2R beta gene was unaffected by DM .", "target_text": { "IL-2R alpha": "protein", "IL-2R beta": "protein", "IL-2R beta gene": "DNA" } }, { "input_text": "The mechanism of action of DM on IL-2R alpha transcription was examined by determining the mRNA levels of the p50 subunit of nuclear factor kappa B ( NF-kappa B ) , a transcription factor that stimulates IL-2R alpha gene expression .", "target_text": { "IL-2R alpha": "protein", "NF-kappa B": "protein", "transcription factor": "protein" } }, { "input_text": "The data indicate that 10(-6) M DM increased T cell p50 NF-kappa B mRNA levels by four-fold compared to the levels obtained in the absence of DM .", "target_text": { "T cell": "cell_type", "NF-kappa B": "protein", "NF-kappa B mRNA": "RNA" } }, { "input_text": "Further , the level of nuclear proteins capable of binding to the NF-kappa B sites in activated T cells increased in response to DM .", "target_text": { "nuclear proteins": "protein", "NF-kappa B sites": "DNA", "T cells": "cell_type", "activated T cells": "cell_type" } }, { "input_text": "In sum , DM regulates T cell membrane expression of IL-2R by more than one molecular mechanism .", "target_text": { "T cell": "cell_type", "IL-2R": "protein" } }, { "input_text": "Alteration of structural order of human erythrocyte ghost membrane by glucocorticoids and the influence of the glucocorticoid receptor antagonist RU 486 .", "target_text": {} }, { "input_text": "High-dose pulse glucocorticoid therapy has been used successfully in the clinic in severe pathological conditions for about 20 years .", "target_text": {} }, { "input_text": "The mode of glucocorticoid action after administration of such megadoses is inexplicable up to now .", "target_text": {} }, { "input_text": "It is supposed that some effects may be due to membrane alterations .", "target_text": {} }, { "input_text": "In the present in-vitro experiments the effect of dexamethasone , of further glucocorticoids , and of the glucocorticoid receptor antagonist RU 486 , on structural order of human erythrocyte ghost membranes was investigated by determining the steady-state fluorescence anisotropy of diphenylhexatriene ( DPH ) .", "target_text": {} }, { "input_text": "Dexamethasone was found to induce a significant decrease in membrane structural order at concentrations of about 10(-6) M in a concentration-dependent manner .", "target_text": {} }, { "input_text": "We found a correlation between the uptake of dexamethasone by the ghost membranes and the decrease in the structural order .", "target_text": {} }, { "input_text": "The other glucocorticoids tested , methylprednisolone and corticosterone , were also effective at concentrations of 10(-5) M or greater .", "target_text": {} }, { "input_text": "We observed no change in membrane structural order with RU 486 up to a concentration of 10(-4) M .", "target_text": {} }, { "input_text": "However , simultaneous incubation of RU 486 with dexamethasone caused a distinct interference of RU 486 with dexamethasone .", "target_text": {} }, { "input_text": "Thus , the glucocorticoid -induced membrane perturbation , the possibility to inhibit it by RU 486 , and the inactivity of the structurally related progesterone , refer to relatively specific binding sites for the glucocorticoids in the membrane of erythrocyte ghosts .", "target_text": { "binding sites": "DNA", "erythrocyte ghosts": "cell_type" } }, { "input_text": "Mutation of tyrosines 492/493 in the kinase domain of ZAP-70 affects multiple T-cell receptor signaling pathways .", "target_text": { "kinase domain": "protein", "ZAP-70": "protein", "T-cell receptor": "protein" } }, { "input_text": "The protein-tyrosine kinase ZAP-70 is implicated , together with the Src kinase p56(lck) , in controlling the early steps of the T-cell antigen receptor ( TCR ) signaling cascade .", "target_text": { "protein-tyrosine kinase": "protein", "ZAP-70": "protein", "Src kinase": "protein", "p56(lck)": "protein", "TCR": "protein" } }, { "input_text": "To help elucidate further the mechanism by which ZAP-70 regulates these initial events , we used a dominant-negative mutant approach .", "target_text": { "ZAP-70": "protein" } }, { "input_text": "We overexpressed in the Jurkat T-cell line ZAP-70 mutated on Tyr-492 and Tyr-493 in the putative regulatory loop of its kinase domain .", "target_text": { "Jurkat T-cell line": "cell_line", "ZAP-70": "protein", "kinase domain": "protein" } }, { "input_text": "This mutant inhibited TCR -induced activation of nuclear factor of activated T cells by interfering with both intracellular calcium increase and Ras -regulated activation of extracellular signal-regulated kinases .", "target_text": { "TCR": "protein", "T cells": "cell_type", "activated T cells": "cell_type", "nuclear factor of activated T cells": "protein", "Ras": "protein", "extracellular signal-regulated kinases": "protein" } }, { "input_text": "Moreover , TCR -induced phosphorylation of pp36-38 , thought to play a role upstream of these pathways , was found to be reduced .", "target_text": { "TCR": "protein", "pp36-38": "protein" } }, { "input_text": "In contrast , overexpression of wild-type ZAP-70 induced constitutive activation of nuclear factor of activated T cells .", "target_text": { "ZAP-70": "protein", "wild-type ZAP-70": "protein", "T cells": "cell_type", "activated T cells": "cell_type", "nuclear factor of activated T cells": "protein" } }, { "input_text": "The ZAP-70 mutant studied here could be phosphorylated on tyrosine when associated to the TCR zeta chain and was able to bind p56(lck) .", "target_text": { "ZAP-70": "protein", "TCR zeta chain": "protein", "p56(lck)": "protein" } }, { "input_text": "This result demonstrates that Tyr-492 and Tyr-493 are not responsible for the Src homology domain 2-mediated association of p56(lck) with ZAP-70 .", "target_text": { "p56(lck)": "protein", "ZAP-70": "protein" } }, { "input_text": "Our data are most consistent with a model in which recruitment to the TCR allows ZAP-70 autophosphorylation and binding to p56(lck) , which in turn phosphorylates Tyr-492 and/or Tyr-493 with consequent up-regulation of the ZAP-70 kinase activity .", "target_text": { "TCR": "protein", "ZAP-70": "protein", "p56(lck)": "protein" } }, { "input_text": "ZAP-70 will then be able to effectively control phosphorylation of its substrates and lead to gene activation .", "target_text": { "ZAP-70": "protein" } }, { "input_text": "Effects of glucocorticoids on lymphocyte activation in patients with steroid-sensitive and steroid-resistant asthma .", "target_text": {} }, { "input_text": "BACKGROUND : Glucocorticoids are important medications used to control the airway inflammation associated with asthma .", "target_text": {} }, { "input_text": "Synthetic glucocorticoids vary in their binding affinity for the glucocorticoid receptor ( GCR ) .", "target_text": {} }, { "input_text": "METHODS : We compared hydrocortisone , beclomethasone dipropionate , triamcinolone acetonide , flunisolide , and budesonide with regard to their capacity to inhibit phytohemagglutinin -induced peripheral blood mononuclear cell proliferation from six patients with steroid-sensitive asthma and seven patients with steroid-resistant asthma .", "target_text": { "phytohemagglutinin": "protein", "peripheral blood mononuclear cell": "cell_type" } }, { "input_text": "Peripheral blood mononuclear cell GCR binding affinities for dexamethasone and budesonide were also determined for both patient groups by using a radioligand binding assay and Scatchard analysis .", "target_text": { "GCR": "protein" } }, { "input_text": "RESULTS : Dose-dependent inhibition was demonstrated for all glucocorticoids in both patient groups , with the steroid-resistant group requiring approximately 2 log-fold more glucocorticoids for an equivalent degree of inhibition .", "target_text": {} }, { "input_text": "The mean concentrations necessary to cause 50 % inhibition of lymphocyte proliferation ( IC50s ) for the steroid-sensitive group ranged from 2 x 10(-10) mol/L for budesonide to 7 x 10(-8) mol/L for hydrocortisone , whereas the mean IC50s for the steroid-resistant group ranged from approximately 2 x 10(-8) mol/L for budesonide to greater than 10(-6) mol/L for hydrocortisone .", "target_text": {} }, { "input_text": "In addition , a significant correlation was noted between the degree of inhibition of lymphocyte proliferation ( IC50 ) and the binding affinity of dexamethasone to the GCR .", "target_text": { "GCR": "protein" } }, { "input_text": "Patients with steroid-resistant asthma have been shown to have a reduced GCR binding affinity .", "target_text": { "GCR": "protein" } }, { "input_text": "The GCR binding affinity for budesonide was significantly higher in both groups ( i.e. , lower dissociation constant ) than that obtained for dexamethasone .", "target_text": { "GCR": "protein" } }, { "input_text": "CONCLUSION : These data suggest that glucocorticoids such as budesonide , by virtue of their high GCR binding affinities and greater ability to suppress lymphocyte proliferation , may therefore be beneficial in the management of difficult-to-control asthma .", "target_text": { "GCR": "protein" } }, { "input_text": "Characterization of the murine cyclin-dependent kinase inhibitor gene p27Kip1 .", "target_text": { "murine cyclin-dependent kinase inhibitor gene": "DNA", "p27Kip1": "DNA" } }, { "input_text": "The cyclin-dependent kinase inhibitor p27Kip1 plays an important role in regulating cell-cycle progression .", "target_text": { "cyclin-dependent kinase inhibitor": "DNA", "p27Kip1": "DNA" } }, { "input_text": "p27Kip1 directly inhibits the catalytic activity of cyclin/cdks ( cyclin-dependent kinase ) complexes and/or interferes physically with cyclin/cdks activation by CAK .", "target_text": { "p27Kip1": "DNA", "cyclin/cdks": "protein", "cyclin-dependent kinase": "protein", "cyclin/cdks ( cyclin-dependent kinase ) complexes": "protein", "CAK": "protein" } }, { "input_text": "Interestingly , the expression level of p27Kip1 mRNA was maximal in resting Go T-cells and rapidly declined following anti-CD3 activation .", "target_text": { "p27Kip1": "DNA", "p27Kip1 mRNA": "RNA", "resting Go T-cells": "cell_type", "anti-CD3": "protein" } }, { "input_text": "We report here the cloning of p27Kip1 gene from murine genomic DNA and the functional analysis of the promoter of the p27Kip1 gene .", "target_text": { "p27Kip1": "DNA", "p27Kip1 gene": "DNA", "murine genomic DNA": "DNA" } }, { "input_text": "The gene consists of at least three exons and spans more than 5.6 kb of DNA .", "target_text": { "5.6 kb of DNA": "DNA" } }, { "input_text": "Primer extension and nuclease S1 protection analysis revealed two major transcription initiation sites .", "target_text": { "transcription initiation sites": "DNA" } }, { "input_text": "The promoter region lacked a TATA box but contained potential binding sites for the transcriptional factors including two Sp1 , CRE , Myb and NFkB located at positions -153 , -178 , -286 , -875 , and -1011 , respectively .", "target_text": { "promoter region": "DNA", "TATA box": "DNA", "transcriptional factors": "protein", "Sp1": "protein", "CRE": "protein", "Myb": "protein", "NFkB": "protein" } }, { "input_text": "To analyze the regulatory mechanisms controlling p27Kip1 gene expression , we characterized the 5'-flanking region from nt -1609 to +178 .", "target_text": { "p27Kip1": "DNA", "5'-flanking region": "DNA", "nt -1609 to +178": "DNA" } }, { "input_text": "The -326 to -615 region contained positive regulatory elements .", "target_text": { "-326 to -615 region": "DNA", "positive regulatory elements": "DNA" } }, { "input_text": "Nuclear NF-ATp is a hallmark of unstimulated B cells from B-CLL patients .", "target_text": { "Nuclear NF-ATp": "protein", "unstimulated B cells": "cell_type" } }, { "input_text": "B lymphocytes from the peripheral blood of patients with chronic lymphocytic leukaemia ( CLL ) were analysed for the nuclear presence and DNA binding of a panel of transcription factors which are involved in the gene control of lymphoid cells .", "target_text": { "B lymphocytes": "cell_type", "transcription factors": "protein", "lymphoid cells": "cell_type" } }, { "input_text": "The following transcription factors were studied : the Octamer factors Oct-1 and Oct-2 , members of the AP-1 factor family , NF-AT factors , in particular NF-ATp , and members of the Rel/NF-kB family .", "target_text": { "transcription factors": "protein", "Octamer factors": "protein", "Oct-1": "protein", "Oct-2": "protein", "AP-1 factor family": "protein", "NF-AT factors": "protein", "NF-ATp": "protein", "Rel/NF-kB family": "protein" } }, { "input_text": "We show that the constitutive nuclear translocation of NF-ATp , a member of the growing family of NF-AT factors , is a hallmark of nonstimulated B cells from CLL patients that distinguishes B-CLL cells from ' normal ' B lymphocytes .", "target_text": { "NF-ATp": "protein", "NF-AT factors": "protein", "nonstimulated B cells": "cell_type", "B-CLL cells": "cell_type", "B lymphocytes": "cell_type", "' normal ' B lymphocytes": "cell_type" } }, { "input_text": "Constitutive nuclear appearance was also observed for NF-kB2/p52 .", "target_text": {} }, { "input_text": "Constitutive binding of further factor proteins to DNA , such as JunD , c-Fos and FosB , was detected in several patients whereas the localisation and DNA binding of other factors such as c-Jun , RelA/p65 and c-Rel was unaltered .", "target_text": { "factor proteins": "protein", "JunD": "protein", "c-Fos": "protein", "FosB": "protein", "c-Jun": "protein", "RelA/p65": "protein", "c-Rel": "protein" } }, { "input_text": "It is remarkable that in B-CLL cells the nuclear appearance and DNA binding of specific transcription factors is dramatically affected whereas other members of the same factor family remained unaltered in these leukemic cells .", "target_text": { "B-CLL cells": "cell_type", "transcription factors": "protein", "factor family": "protein" } }, { "input_text": "It remains to be shown which molecular events lead to the specific ' pre-activation ' , i.e.", "target_text": {} }, { "input_text": "constitutive nuclear translocation and DNA binding , of these members of NF-AT , NF-kB and AP-1 factor families .", "target_text": { "NF-AT": "protein", "NF-kB": "protein", "AP-1 factor families": "protein" } }, { "input_text": "Naive ( CD45RA+ ) T lymphocytes are more sensitive to oxidative stress-induced signals than memory ( CD45RO+ ) cells .", "target_text": { "Naive ( CD45RA+ ) T lymphocytes": "cell_type", "memory ( CD45RO+ ) cells": "cell_type" } }, { "input_text": "Formation of reactive oxygen intermediates ( ROI ) after oxidative stress has been shown to be an activation signal for T lymphocytes , e.g. , expression of IL-2 and its receptor are induced .", "target_text": { "T lymphocytes": "cell_type", "IL-2": "protein", "receptor": "protein" } }, { "input_text": "These ROI -induced effects can , to a large extent , be attributed to the activation of the transcription factor NF-kappaB .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "Now we have examined whether naive and memory T lymphocytes differ in their sensitivity to ROI -mediated signals .", "target_text": {} }, { "input_text": "When CD45RA+ ( naive ) and CD45RO+ ( memory ) T lymphocytes were directly stimulated with H2O2 , NF-kappaB nuclear translocation was stronger in naive cells than in memory cells and it could be induced with lower doses .", "target_text": { "CD45RA+ ( naive )": "cell_type", "CD45RO+ ( memory ) T lymphocytes": "cell_type", "NF-kappaB": "protein", "naive cells": "cell_type", "memory cells": "cell_type" } }, { "input_text": "The composition of the induced nuclear NF-kappaB ( levels of p50 and RelA proteins ) was similar in these cell types .", "target_text": { "NF-kappaB": "protein", "nuclear NF-kappaB": "protein", "p50": "protein", "RelA proteins": "protein" } }, { "input_text": "The magnitude and kinetics of intracellular ROI were similar , suggesting that there were no differences in ROI -forming mechanisms or antioxidative capacities .", "target_text": {} }, { "input_text": "The probable regulatory point was the cytoplasmic IkappaB inhibitor : in CD45RA+ cells , H2O2 caused a more profound depression in the levels of IkappaB alpha .", "target_text": { "IkappaB": "protein", "IkappaB alpha": "protein" } }, { "input_text": "These findings indicate that T cells representing different activation and/or differentiation stages can be differentially responsive to ROI -mediated signals .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Rapid shuttling of NF-AT in discrimination of Ca2+ signals and immunosuppression .", "target_text": { "NF-AT": "protein" } }, { "input_text": "Cells need to distinguish between transient Ca2+ signals that induce events such as muscle contraction , secretion , adhesion and synaptic transmission , and sustained Ca2+ signals that are involved in cell proliferation and differentiation .", "target_text": {} }, { "input_text": "The latter class of events is blocked in lymphocytes by the immunosuppressive drugs cyclosporin A and FK506 , which inhibit calcineurin , a Ca2+ -activated serine/threonine phosphatase necessary for the nuclear import of NF-AT transcription factors .", "target_text": { "lymphocytes": "cell_type", "calcineurin": "protein", "Ca2+ -activated serine/threonine phosphatase": "protein", "NF-AT": "protein", "transcription factors": "protein" } }, { "input_text": "Here we report that sustained high concentrations of Ca2+ , but not transient pulses , are required to maintain NF-AT transcription factors in the nucleus , where they participate in Ca2+ -dependent induction of genes required for lymphocyte activation and proliferation .", "target_text": { "NF-AT": "protein", "transcription factors": "protein", "genes": "DNA", "lymphocyte": "cell_type" } }, { "input_text": "Furthermore , overexpression and constitutive nuclear localization of NF-AT , but not Jun , Fos , NF-kappaB , Oct or Ets family members , renders the interleukin-2 enhancer in Jurkat T lymphocytes resistant to FK506 and cyclosporin A .", "target_text": { "NF-AT": "protein", "interleukin-2 enhancer": "DNA", "Jurkat T lymphocytes": "cell_line" } }, { "input_text": "Thus a primary effect of these immunosuppressive reagents is to control the subcellular localization of the NF-AT family of transcription factors .", "target_text": { "NF-AT": "protein", "transcription factors": "protein" } }, { "input_text": "Autoregulation of the NF-kappa B transactivator RelA ( p65 ) by multiple cytoplasmic inhibitors containing ankyrin motifs .", "target_text": { "NF-kappa B": "protein", "NF-kappa B transactivator": "protein", "RelA": "protein", "p65": "protein", "cytoplasmic inhibitors": "protein", "ankyrin motifs": "protein" } }, { "input_text": "RelA ( p65 ) functions as the critical transactivating component of the heterodimeric p50- p65 NF-kappa B complex and contains a high-affinity binding site for its cytoplasmic inhibitor , I kappa B alpha .", "target_text": { "RelA": "protein", "p65": "protein", "NF-kappa B": "protein", "heterodimeric p50- p65 NF-kappa B complex": "protein", "high-affinity binding site": "protein", "cytoplasmic inhibitor": "protein", "I kappa B alpha": "protein" } }, { "input_text": "After cellular activation , I kappa B alpha is rapidly degraded in concert with the induced nuclear translocation of NF-kappa B .", "target_text": { "I kappa B alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "The present study demonstrates that tumor necrosis factor alpha -induced degradation of I kappa B alpha in human T cells is preceded by its rapid phosphorylation in vivo .", "target_text": { "tumor necrosis factor alpha": "protein", "I kappa B alpha": "protein", "human T cells": "cell_type" } }, { "input_text": "However , these effects on I kappa B alpha result in nuclear mobilization of only a fraction of the entire cytoplasmic pool of RelA .", "target_text": { "I kappa B alpha": "protein", "RelA": "protein" } }, { "input_text": "Subsequent studies have revealed that ( i ) cytoplasmic RelA is stably associated not only with I kappa B alpha but also with other ankyrin motif-rich proteins including the products of the NF-kappa B2 ( p100 ) and NF-kappa B1 ( p105 ) genes ; ( ii ) in contrast to RelA -I kappa B alpha , RelA -p100 cytoplasmic complexes are not dissociated following tumor necrosis factor alpha activation ; ( iii ) p100 functions as a potent inhibitor of RelA -mediated transcription in vivo ; ( iv ) the interaction of RelA and p100 involves the conserved Rel homology domain of both proteins but not the nuclear localization signal of RelA , which is required for I kappa B alpha binding ; ( v ) p100 inhibition of RelA function requires the C-terminal ankyrin motif domain , which mediates cytoplasmic retention of RelA ; and ( vi ) as observed with I kappa B alpha , nuclear RelA stimulates p100 mRNA and protein expression .", "target_text": { "RelA": "protein", "cytoplasmic RelA": "protein", "I kappa B alpha": "protein", "ankyrin motif-rich proteins": "protein", "-I kappa B alpha": "protein", "RelA -p100 cytoplasmic complexes": "protein", "tumor necrosis factor alpha": "protein", "p100": "protein", "conserved Rel homology domain": "protein", "nuclear localization signal": "protein", "C-terminal ankyrin motif domain": "protein", "p100 mRNA": "RNA" } }, { "input_text": "These findings thus reveal the presence of a second inducible autoregulated inhibitory pathway that helps ensure the rapid but transient action of nuclear NF-kappa B .", "target_text": { "NF-kappa B": "protein", "nuclear NF-kappa B": "protein" } }, { "input_text": "Effects of CD45 on NF-kappa B .", "target_text": { "CD45": "protein", "NF-kappa B": "protein" } }, { "input_text": "Implications for replication of HIV-1 .", "target_text": {} }, { "input_text": "Increased levels of replication of the HIV type 1 are observed after the activation of infected T cells through the TCR .", "target_text": { "infected T cells": "cell_type", "TCR": "protein" } }, { "input_text": "However , anti- CD45 antibodies inhibit these effects in cells from infected individuals .", "target_text": { "CD45": "protein" } }, { "input_text": "In this study , we examined interrelationships between CD45 and HIV-1 further .", "target_text": { "CD45": "protein" } }, { "input_text": "We measured effects on the HIV-1 LTR in T cell lines that were stimulated with antibodies against CD45 and in those that lacked the expression of CD45 on their surfaces .", "target_text": { "HIV-1 LTR": "DNA", "T cell lines": "cell_line", "CD45": "protein" } }, { "input_text": "First , anti- CD45 antibodies did not affect basal but decreased activated levels of expression from the HIV-1 LTR .", "target_text": { "CD45": "protein", "anti- CD45 antibodies": "protein", "HIV-1 LTR": "DNA" } }, { "input_text": "Second , T cells , which lack CD45 and can not signal via the TCR , supported higher levels of viral replication and gene expression .", "target_text": { "T cells": "cell_type", "CD45": "protein", "TCR": "protein" } }, { "input_text": "This was due to the presence of active NF-kappa B complexes in the nucleus of CD45 -T cells .", "target_text": { "NF-kappa B": "protein", "NF-kappa B complexes": "protein", "CD45": "protein" } }, { "input_text": "Additionally , infected T cells displayed lower levels of CD45 on their surfaces .", "target_text": { "infected T cells": "cell_type", "CD45": "protein" } }, { "input_text": "Thus , CD45 plays an active role in the physiology of T cells and in the replication of HIV-1 .", "target_text": { "CD45": "protein", "T cells": "cell_type" } }, { "input_text": "Calcineurin potentiates activation of the granulocyte-macrophage colony-stimulating factor gene in T cells : involvement of the conserved lymphokine element 0 .", "target_text": { "Calcineurin": "protein", "granulocyte-macrophage colony-stimulating factor gene": "DNA", "T cells": "cell_type", "conserved lymphokine element 0": "DNA" } }, { "input_text": "Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and interleukin-2 ( IL-2 ) are produced by stimulation with phorbol-12-myristate acetate ( PMA ) and calcium ionophore ( A23187 ) in human T cell leukemia Jurkat cells .", "target_text": { "Granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "interleukin-2": "protein", "IL-2": "protein", "Jurkat cells": "cell_line", "human T cell leukemia Jurkat cells": "cell_line" } }, { "input_text": "The expression of GM-CSF and IL-2 is inhibited by immunosuppressive drugs such as cyclosporin A ( CsA ) and FK506 .", "target_text": { "GM-CSF": "protein", "IL-2": "protein" } }, { "input_text": "Earlier studies on the IL-2 gene expression showed that overexpression of calcineurin ( CN ) , a Ca2+/calmodulin-dependent protein phosphatase , can stimulate transcription from the IL-2 promoter through the NF-AT-binding site .", "target_text": { "IL-2": "protein", "calcineurin": "protein", "CN": "protein", "Ca2+/calmodulin-dependent protein phosphatase": "protein", "IL-2 promoter": "DNA", "NF-AT-binding site": "DNA" } }, { "input_text": "In this study , we obtained evidence that transfection of the cDNAs for CN A ( catalytic ) and CN B ( regulatory ) subunits also augments transcription from the GM-CSF promoter and recovers the transcription inhibited by CsA .", "target_text": { "cDNAs": "DNA", "GM-CSF": "protein", "GM-CSF promoter": "DNA" } }, { "input_text": "The constitutively active type of the CN A subunit , which lacks the auto-inhibitory and calmodulin-binding domains , acts in synergy with PMA to activate transcription from the GM-CSF promoter .", "target_text": { "CN A subunit": "protein", "auto-inhibitory": "protein", "calmodulin-binding domains": "protein", "GM-CSF promoter": "DNA" } }, { "input_text": "We also found that the active CN partially replaces calcium ionophore in synergy with PMA to induce expression of endogenous GM-CSF and IL-2 .", "target_text": { "CN": "protein", "GM-CSF": "protein", "IL-2": "protein" } }, { "input_text": "By multimerizing the regulatory elements of the GM-CSF promoter , we found that one of the target sites for the CN action is the conserved lymphokine element 0 ( CLE0 ) , located at positions between -54 and -40 .", "target_text": { "regulatory elements": "DNA", "GM-CSF": "protein", "GM-CSF promoter": "DNA", "target sites": "DNA", "CN": "protein", "conserved lymphokine element 0": "DNA", "CLE0": "DNA", "-54 and -40": "DNA" } }, { "input_text": "Mobility shift assays showed that the CLE0 sequence has an AP1-binding site and is associated with an NF-AT-like factor , termed NF- CLE0 gamma .", "target_text": { "CLE0": "DNA", "AP1-binding site": "DNA", "NF-AT-like factor": "protein", "NF- CLE0 gamma": "protein" } }, { "input_text": "NF- CLE0 gamma binding is induced by PMA /A23187 and is inhibited by treatment with CsA .", "target_text": { "CLE0": "DNA" } }, { "input_text": "These results suggest that CN is involved in the coordinated induction of the GM-CSF and IL-2 genes and that the CLE0 sequence of the GM-CSF gene is a functional analogue of the NF-AT-binding site in the IL-2 promoter , which mediates signals downstream of T cell activation .", "target_text": { "CN": "protein", "CLE0": "DNA", "CLE0 sequence": "DNA", "GM-CSF": "protein", "GM-CSF gene": "DNA", "NF-AT-binding site": "DNA", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Alternate immune system targets for TCDD : lymphocyte stem cells and extrathymic T-cell development .", "target_text": { "lymphocyte stem cells": "cell_type", "extrathymic T-cell": "cell_type" } }, { "input_text": "We here summarize evidence that thymic atrophy induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD ) can be mediated , at least in part , by damage to extrathymic T-cell precursors in bone marrow and fetal liver .", "target_text": { "extrathymic T-cell precursors": "cell_type" } }, { "input_text": "This atrophy induction does not involve apoptotic mechanisms in thymocytes affected by the bcl-2 proto-oncogene .", "target_text": { "thymocytes": "cell_type", "bcl-2 proto-oncogene": "DNA" } }, { "input_text": "TCDD mediates atrophy induction through its specific receptor ( the AhR ) and not through effects on the estrogen receptor .", "target_text": { "AhR": "protein" } }, { "input_text": "Both TCDD and estradiol induce extrathymic T-cell differentiation in the liver .", "target_text": {} }, { "input_text": "These extrathymic T-cell populations include cells expressing elevated levels of V beta T-cell receptors that are normally deleted in thymic development .", "target_text": { "extrathymic T-cell populations": "cell_type", "V beta T-cell receptors": "protein" } }, { "input_text": "Identification of Bcd , a novel proto-oncogene expressed in B-cells .", "target_text": { "Bcd": "DNA", "proto-oncogene": "DNA", "B-cells": "cell_type" } }, { "input_text": "A novel B-cell derived ( Bcd ) oncogene has been isolated from the peripheral blood lymphocytes of one B-cell chronic lymphocytic leukemia ( B-CLL ) patient using DNA transfer and a mouse tumorigenicity assay .", "target_text": { "novel B-cell": "cell_type", "Bcd": "DNA", "oncogene": "DNA" } }, { "input_text": "The Bcd proto-oncogene was activated by a truncation in the 5' UTR .", "target_text": { "Bcd": "DNA", "proto-oncogene": "DNA", "5' UTR": "DNA" } }, { "input_text": "It predicts for two open reading frames ( ORFs ) .", "target_text": { "open reading frames": "DNA", "ORFs": "DNA" } }, { "input_text": "ORF1 consists of 240 bp that would encode 80 amino acids , while the major ORF2 consists of 648 bp capable of coding for 216 amino acids .", "target_text": { "ORF1": "DNA", "major ORF2": "DNA" } }, { "input_text": "Predicted peptide sequence of ORF2 contained a zinc finger domain which showed significant homology to GC box binding proteins BTEB2 and SP1 .", "target_text": { "Predicted peptide sequence": "protein", "ORF2": "DNA", "zinc finger domain": "protein", "GC box binding proteins": "protein", "BTEB2": "protein", "SP1": "protein" } }, { "input_text": "Transfection of an expression vector containing ORF2 but not full length cDNA was able to transform NIH3T3 cells and induce tumors in nude mice .", "target_text": { "expression vector": "DNA", "ORF2": "DNA", "full length cDNA": "DNA", "NIH3T3 cells": "cell_line" } }, { "input_text": "Bcd mRNA transcripts of < or = 2.6 kb were selectively expressed in PBL and testis of healthy individuals .", "target_text": { "Bcd": "DNA", "Bcd mRNA transcripts": "RNA", "PBL": "cell_line" } }, { "input_text": "Within the PBL , Bcd gene expression was restricted to CD19+ B-cells and absent from CD14+ monocytes and T-cells .", "target_text": { "PBL": "cell_type", "Bcd": "DNA", "B-cells": "cell_type", "CD19+ B-cells": "cell_type", "CD14+ monocytes": "cell_type", "T-cells": "cell_type" } }, { "input_text": "Bcd transcripts were detected in all normal PBL samples tested but not in several malignant human B-cell lines and not in 50 % of B-cells from B-CLL patients .", "target_text": { "Bcd": "DNA", "PBL": "cell_type", "malignant human B-cell lines": "cell_line", "B-cells": "cell_type" } }, { "input_text": "However , stimulation of B-cells from B-CLL patients under conditions which induced differentiation into plasma cells was associated with induction of Bcd gene expression .", "target_text": { "B-cells": "cell_type", "plasma cells": "cell_type", "Bcd": "DNA" } }, { "input_text": "The Bcd gene may therefore play an important role in B-cell growth and development .", "target_text": { "Bcd": "DNA", "Bcd gene": "DNA" } }, { "input_text": "A novel SP-1 site in the human interleukin-1 beta promoter confers preferential transcriptional activity in keratinocytes .", "target_text": { "SP-1 site": "DNA", "novel SP-1 site": "DNA", "human interleukin-1 beta promoter": "DNA", "keratinocytes": "cell_type" } }, { "input_text": "To investigate the mechanisms of transcriptional activation of interleukin-1beta ( IL-1beta ) in non-monocytic cells , we constructed a series of reporter plasmids with the bacterial chloramphenicol acetyltransferase gene linked to various parts of the human IL-1beta promoter and performed transient transfection experiments .", "target_text": { "interleukin-1beta": "protein", "IL-1beta": "protein", "IL-1beta promoter": "DNA", "human IL-1beta promoter": "DNA" } }, { "input_text": "We identified a promoter segment that activates transcription most efficiently in keratinocytes .", "target_text": { "keratinocytes": "cell_type" } }, { "input_text": "Electrophoretic mobility shift assays ( EMSA ) with a 43-mer oligonucleotide derived from the functionally identified cis-acting element revealed specific complexes .", "target_text": { "43-mer oligonucleotide": "DNA", "cis-acting element": "DNA" } }, { "input_text": "By competition analysis with transcription factor consensus sequence oligonucleotides and by immunosupershift , transcription factor SP-1 or a closely related protein was shown to bind to this regulatory element .", "target_text": { "transcription factor consensus sequence oligonucleotides": "DNA", "transcription factor SP-1": "protein", "regulatory element": "DNA" } }, { "input_text": "The closest match to the known SP-1 consensus sequence within the respective region is a TCCCCTCCCCT motif .", "target_text": { "SP-1": "protein", "SP-1 consensus sequence": "DNA", "TCCCCTCCCCT motif": "DNA" } }, { "input_text": "Mutation of this motif almost completely , and specifically , abolished the binding of two low-mobility complexes and led to a 95 % decrease of constitutive transcriptional activation of a reporter construct IL-1beta ( -170/+108 ) .", "target_text": { "low-mobility complexes": "protein", "IL-1beta": "protein" } }, { "input_text": "Likewise , activation of this reporter construct by tumor necrosis factor-alpha depended on the SP-1 site .", "target_text": { "tumor necrosis factor-alpha": "protein", "SP-1": "protein", "SP-1 site": "DNA" } }, { "input_text": "These observations suggest that a so-far-unrecognized SP-1 site in the human IL-1beta promoter may participate in the transcriptional regulation of this gene in keratinocytes .", "target_text": { "SP-1": "protein", "SP-1 site": "DNA", "IL-1beta": "protein", "IL-1beta promoter": "DNA", "human IL-1beta promoter": "DNA", "keratinocytes": "cell_type" } }, { "input_text": "Expression of Egr-1 correlates with the transformed phenotype and the type of viral latency in EBV genome positive lymphoid cell lines .", "target_text": { "Egr-1": "protein", "EBV genome": "DNA", "EBV genome positive lymphoid cell lines": "cell_line" } }, { "input_text": "In this paper we have investigated the role of Egr-1 in B cell growth regulation by examining the gene expression in a panel of B cell lines , including both EBV genome negative and EBV carrying cell lines .", "target_text": { "Egr-1": "protein", "B cell lines": "cell_line", "EBV genome": "DNA", "EBV carrying cell lines": "cell_line" } }, { "input_text": "Egr-1 expression correlates with the cellular phenotype and the specific pattern of viral latency established within the individual cell lines .", "target_text": { "Egr-1": "protein", "individual cell lines": "cell_line" } }, { "input_text": "Thus , constitutive activation of Egr-1 gene is invariably associated with unrestricted expression of viral latent genes in all group III EBV genome carrying cell lines .", "target_text": { "Egr-1": "protein", "EBV genome": "DNA", "group III EBV genome carrying cell lines": "cell_line" } }, { "input_text": "In contrast , Egr-1 expression is abrogated in group I Burkitt tumor cells , irrespective of the EBV genome carrying status .", "target_text": { "Egr-1": "protein", "group I Burkitt tumor cells": "cell_line", "EBV genome": "DNA" } }, { "input_text": "Activated viral gene expression associated with phenotypic conversion of group I cell lines in to group II or III restores the Egr-1 gene expression .", "target_text": { "group I cell lines": "cell_line", "group II": "cell_line", "III": "cell_line", "Egr-1 gene": "DNA" } }, { "input_text": "Several forms of EGR-1 protein are found within the different groups of cell lines , and the binding activity to DNA consensus sequences was investigated .", "target_text": { "EGR-1 protein": "protein", "DNA consensus sequences": "DNA" } }, { "input_text": "Finally , time course analysis of Egr-1 expression during the early steps of EBV infection in vitro demonstrated that Egr-1 is upregulated within minutes from the initial interaction with the B lymphocyte .", "target_text": { "Egr-1": "protein", "B lymphocyte": "cell_type" } }, { "input_text": "Expression of erythroid-specific genes in megakaryoblastic disorders .", "target_text": { "erythroid-specific genes": "DNA" } }, { "input_text": "Currently available data indicate that erythroid and megakaryocytic differentiation pathways are closely related to each other , and there may exist progenitor cells common to those two lineages may exist .", "target_text": { "progenitor cells": "cell_type" } }, { "input_text": "Acute megakaryoblastic leukemia ( AML-M7 ) and transient myeloproliferative disorder in Down 's syndrome ( TMD ) are characterized by rapid growth of abnormal blast cells which express megakaryocytic markers .", "target_text": { "abnormal blast cells": "cell_type", "megakaryocytic markers": "protein" } }, { "input_text": "These blast cells express lineage-specific transcription factors such as GATA-1 common to these lineages and frequently express erythroid-specific mRNAs such as gamma-globin and erythroid delta-aminolevulinate synthase ( ALAS-E ) , indicating that most of the blasts in M7 and TMD cases have erythroid and megakaryocytic phenotypes .", "target_text": { "blast cells": "cell_type", "lineage-specific transcription factors": "protein", "GATA-1": "protein", "erythroid-specific mRNAs": "RNA", "gamma-globin": "protein", "erythroid delta-aminolevulinate synthase": "protein", "ALAS-E": "protein" } }, { "input_text": "These results suggest that blasts in M7 and TMD may correspond to progenitors of both erythroid and megakaryocytic lineages .", "target_text": { "blasts": "cell_type", "progenitors": "cell_type" } }, { "input_text": "Stat3 recruitment by two distinct ligand-induced , tyrosine-phosphorylated docking sites in the interleukin-10 receptor intracellular domain .", "target_text": { "Stat3": "protein", "ligand-induced , tyrosine-phosphorylated docking sites": "protein", "interleukin-10 receptor": "protein", "interleukin-10 receptor intracellular domain": "protein" } }, { "input_text": "Recent work has shown that IL-10 induces activation of the JAK -STAT signaling pathway .", "target_text": { "IL-10": "protein", "JAK": "protein", "-STAT": "protein" } }, { "input_text": "To define the mechanism underlying signal transducer and activator of transcription ( STAT ) protein recruitment to the interleukin 10 ( IL-10 ) receptor , the STAT proteins activated by IL-10 in different cell populations were first defined using electrophoretic mobility shift assays .", "target_text": { "signal transducer and activator of transcription ( STAT ) protein": "protein", "interleukin 10": "protein", "IL-10": "protein", "interleukin 10 ( IL-10 ) receptor": "protein", "STAT proteins": "protein" } }, { "input_text": "In all cells tested , IL-10 activated Stat1 and Stat3 and induced the formation of three distinct DNA binding complexes that contained different combinations of these two transcription factors .", "target_text": { "IL-10": "protein", "Stat1": "protein", "Stat3": "protein", "DNA binding complexes": "protein", "transcription factors": "protein" } }, { "input_text": "IL-10 also activated Stat5 in Ba/F3 cells that stably expressed the murine IL-10 receptor .", "target_text": { "IL-10": "protein", "Stat5": "protein", "Ba/F3 cells": "cell_line", "IL-10 receptor": "protein" } }, { "input_text": "Using a structure-function mutagenesis approach , two tyrosine residues ( Tyr427 and Tyr477 ) in the intracellular domain of the murine IL-10 receptor were found to be redundantly required for receptor function and for activation of Stat3 but not for Stat1 or Stat5 .", "target_text": { "intracellular domain": "protein", "IL-10": "protein", "Stat3": "protein", "Stat1": "protein", "Stat5": "protein" } }, { "input_text": "Twelve amino acid peptides encompassing either of these two tyrosine residues in phosphorylated form coprecipitated Stat3 but not Stat1 and blocked IL-10 -induced Stat3 phosphorylation in a cell-free system .", "target_text": { "phosphorylated form": "protein", "Stat3": "protein", "Stat1": "protein", "IL-10": "protein" } }, { "input_text": "In contrast , tyrosine-phosphorylated peptides containing Tyr374 or Tyr396 did not interact with Stat3 or block Stat3 activation .", "target_text": { "Stat3": "protein" } }, { "input_text": "These data demonstrate that Stat3 but not Stat1 or Stat5 is directly recruited to the ligand-activated IL-10 receptor by binding to specific but redundant receptor intracellular domain sequences containing phosphotyrosine .", "target_text": { "Stat3": "protein", "Stat1": "protein", "Stat5": "protein", "ligand-activated IL-10 receptor": "protein", "intracellular domain": "protein", "receptor intracellular domain sequences": "protein" } }, { "input_text": "This study thus supports the concept that utilization of distinct STAT proteins by different cytokine receptors is dependent on the expression of particular ligand-activatable , tyrosine-containing STAT docking sites in receptor intracellular domains .", "target_text": { "STAT proteins": "protein", "cytokine receptors": "protein", "tyrosine-containing STAT docking sites": "protein", "receptor intracellular domains": "protein" } }, { "input_text": "Silencing of human fetal globin expression is impaired in the absence of the adult beta-globin gene activator protein EKLF .", "target_text": { "globin": "protein", "adult beta-globin gene activator protein": "protein", "EKLF": "protein" } }, { "input_text": "Globin genes are subject to tissue-specific and developmental stage-specific regulation .", "target_text": { "Globin genes": "DNA" } }, { "input_text": "A switch from human fetal ( gamma ) -to adult ( beta ) -globin expression occurs within erythroid precursor cells of the adult lineage .", "target_text": { "human fetal ( gamma )": "protein", "adult ( beta ) -globin": "protein", "erythroid precursor cells": "cell_type", "adult lineage": "cell_type" } }, { "input_text": "Previously we and others showed by targeted gene disruption that the zinc finger gene , erythroid Kruppel-like factor ( EKLF ) , is required for expression of the beta-globin gene in mice , presumably through interaction with a high-affinity binding site in the proximal promoter .", "target_text": { "zinc finger gene": "DNA", "erythroid Kruppel-like factor": "protein", "EKLF": "protein", "beta-globin gene": "DNA", "high-affinity binding site": "DNA", "proximal promoter": "DNA" } }, { "input_text": "To examine the role of EKLF in the developmental regulation of the human gamma-globin gene we interbred EKLF heterozygotes ( +/- ) with mice harboring a human beta-globin yeast artificial chromosome transgene .", "target_text": { "EKLF": "protein", "human gamma-globin gene": "DNA", "EKLF heterozygotes": "protein", "human beta-globin yeast artificial chromosome transgene": "DNA" } }, { "input_text": "We find that in the absence of EKLF , while human beta-globin expression is dramatically reduced , gamma-globin transcripts are elevated approximately 5-fold .", "target_text": { "EKLF": "protein", "human beta-globin": "protein", "gamma-globin transcripts": "RNA" } }, { "input_text": "Impaired silencing of gamma-globin expression identifies EKLF as the first transcription factor participating quantitatively in the gamma-globin to beta-globin switch .", "target_text": { "gamma-globin": "protein", "EKLF": "protein", "transcription factor": "protein", "beta-globin": "protein" } }, { "input_text": "Our findings are compatible with a competitive model of switching in which EKLF mediates an adult stage-specific interaction between the beta-globin gene promoter and the locus control region that excludes the gamma-globin gene .", "target_text": { "EKLF": "protein", "beta-globin gene": "DNA", "beta-globin gene promoter": "DNA", "locus control region": "DNA", "gamma-globin": "protein", "gamma-globin gene": "DNA" } }, { "input_text": "Stimulation of human peripheral blood mononuclear cells by zinc and related cations .", "target_text": { "human peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Zinc is an important trace element for immune function .", "target_text": {} }, { "input_text": "Here , we show that zinc addition in a serum- and lipopolysaccharide-free cell culture system leads to significantly enhanced levels of interleukin 1 beta ( IL-1 beta ) and tumour necrosis factor alpha ( TNF-alpha ) and to expression of the corresponding mRNA in human peripheral blood mononuclear cells ( PBMC ) .", "target_text": { "interleukin 1 beta": "protein", "IL-1 beta": "protein", "tumour necrosis factor alpha": "protein", "TNF-alpha": "protein", "mRNA": "RNA", "human peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "Structurally related divalent cations like cobalt , nickel , and mercury also partially increase monokine secretion but to a much lower and thus insignificant extent .", "target_text": {} }, { "input_text": "They fail to induce mRNA of TNF-alpha after 3 h of culture .", "target_text": { "mRNA": "RNA", "TNF-alpha": "protein" } }, { "input_text": "Therefore , monokine induction is a zinc -specific effect influenced by the physicochemical properties of the ion .", "target_text": {} }, { "input_text": "Confirmation of the unique significance of zinc for immune function provides a better understanding of the mechanisms of specific zinc -mediated immune modulation .", "target_text": {} }, { "input_text": "E3 , a hematopoietic-specific transcript directly regulated by the retinoic acid receptor alpha .", "target_text": { "E3": "protein", "hematopoietic-specific transcript": "protein", "retinoic acid receptor alpha": "protein" } }, { "input_text": "Retinoic acid ( RA ) -induced maturation mediated by the retinoic acid receptor alpha ( RAR alpha ) has been implicated in myeloid development .", "target_text": { "retinoic acid receptor alpha": "protein", "RAR alpha": "protein" } }, { "input_text": "We have used differential hybridization analysis of a cDNA library constructed from the murine RA -inducible MPRO promyelocyte cell line to identify immediate-early genes induced by RA during granulocytic differentiation .", "target_text": { "cDNA library": "DNA", "RA -inducible MPRO promyelocyte cell line": "cell_line", "immediate-early genes": "DNA" } }, { "input_text": "E3 , one of nine sequences identified , was upregulated in an immediate-early manner , with transcript levels peaking after 60 minutes exposure to RA .", "target_text": { "E3": "protein" } }, { "input_text": "E3 transcripts were RA -inducible in HL60 cells , but not in an RA -resistant subclone , HL60R , that harbors a mutated RAR alpha gene .", "target_text": { "E3": "protein", "E3 transcripts": "protein", "HL60 cells": "cell_line", "RA -resistant subclone": "cell_line", "HL60R": "cell_line", "RAR alpha": "protein", "RAR alpha gene": "DNA" } }, { "input_text": "However , when HL60R cells were transduced with a functional copy of the RAR alpha gene , RA induced a 10-fold increase in E3 mRNA levels .", "target_text": { "HL60R cells": "cell_line", "RAR alpha": "protein", "RAR alpha gene": "DNA", "E3": "protein" } }, { "input_text": "E3 transcripts are present in the myeloid , B-lymphoid , and erythroid lineages , absent in nonhematopoietic cells , and encode a highly hydrophobic , potentially phosphorylated polypeptide of unknown function with significant homology to a putative protein expressed in myeloid cells .", "target_text": { "E3": "protein", "E3 transcripts": "protein", "nonhematopoietic cells": "cell_type", "myeloid cells": "cell_type" } }, { "input_text": "The murine E3 promoter harbors a single bipartite retinoic acid response element which in transient transfection assays conferred RA sensitivity .", "target_text": { "E3": "protein", "E3 promoter": "DNA", "bipartite retinoic acid response element": "DNA" } }, { "input_text": "These results indicate that E3 is a hematopoietic-specific gene that is an immediate target for the activated RAR alpha during myelopoiesis .", "target_text": { "E3": "protein", "hematopoietic-specific gene": "DNA", "RAR alpha": "protein" } }, { "input_text": "Multifactor cis-dominant negative regulation of IL-2 gene expression in anergized T cells .", "target_text": { "IL-2": "protein", "IL-2 gene": "DNA", "anergized T cells": "cell_type" } }, { "input_text": "The molecular mechanism underlying IL-2 transcriptional blockade in anergic T cell clones is not fully understood .", "target_text": { "IL-2": "protein", "anergic T cell clones": "cell_line" } }, { "input_text": "To examine whether an active negative regulatory process occurs , we created a reporter construct containing as an enhancer four copies of the NF-AT site and one copy of the octamer site ( 4X NF-AT-Oct ) .", "target_text": { "reporter construct": "DNA", "enhancer": "DNA", "NF-AT site": "DNA", "octamer site": "DNA", "4X NF-AT-Oct": "DNA" } }, { "input_text": "This construct was only slightly reduced ( 1.3-fold ) in its expression when stimulated under anergic conditions , while a whole mouse IL-2 enhancer construct showed a reduction of 4.3-fold .", "target_text": { "IL-2": "protein", "IL-2 enhancer": "DNA", "IL-2 enhancer construct": "DNA" } }, { "input_text": "Addition of the -176 to -96 sequence to the 4X NF-AT-Oct construct did not impart the ability to be affected by anergy , but addition of the -236 to -96 sequence did , demonstrating that anergy is an active inhibitory process and that more than the presence of the -150 AP-1 binding site ( -152 to -147 ) is required to mediate the effect .", "target_text": { "-176 to -96 sequence": "DNA", "4X NF-AT-Oct": "DNA", "4X NF-AT-Oct construct": "DNA", "-236 to -96 sequence": "DNA", "-150 AP-1 binding site": "DNA", "-152 to -147": "DNA" } }, { "input_text": "Mutational studies of the -236 to -96 sequence indicated that the presence of both the -130 AP-1-like site ( -187 to -181 ) and the -150 proximal AP-1 site were necessary to observe anergy .", "target_text": { "-236 to -96 sequence": "DNA", "-130 AP-1-like site": "DNA", "-187 to -181": "DNA", "-150 proximal AP-1 site": "DNA" } }, { "input_text": "Because the -180 site is not required for trans-activation , it was possible to confirm by mutation in the normal mouse IL-2 enhancer that this site is absolutely essential for anergy induction .", "target_text": { "-180 site": "DNA", "IL-2": "protein", "IL-2 enhancer": "DNA", "mouse IL-2 enhancer": "DNA" } }, { "input_text": "The simplest model to explain these results is that anergy is mediated by a complex of multiple transcription factors that exert a cis-acting dominant negative regulatory effect on the trans-activation of the IL-2 gene .", "target_text": { "transcription factors": "protein", "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "Severe combined immunodeficiency due to defective binding of the nuclear factor of activated T cells in T lymphocytes of two male siblings .", "target_text": { "nuclear factor of activated T cells": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Peripheral blood lymphocytes ( PBL ) and alloreactive T cell lines of two male infants born to consanguinous parents and presenting with severe combined immunodeficiency ( SCID ) showed a pronounced deficiency in T cell activation .", "target_text": { "Peripheral blood lymphocytes": "cell_type", "PBL": "cell_type", "alloreactive T cell lines": "cell_line" } }, { "input_text": "Although phenotypically normal , the proliferative response of the childrens ' T cells was strongly reduced but could be improved by the addition of interleukin-2 ( IL-2 ) .", "target_text": { "T cells": "cell_type", "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "Furthermore both childrens ' T cells were unable to produce the cytokines IL-2 , interferon-gamma ( IFN-gamma ) , IL-4 and tumor necrosis factor-alpha ( TNF-alpha ) .", "target_text": { "T cells": "cell_type", "cytokines": "protein", "IL-2": "protein", "interferon-gamma": "protein", "IFN-gamma": "protein", "IL-4": "protein", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "This multiple cytokine production deficiency could not be restored by IL-2 or co-stimulatory signals provided by antigen-presenting cells ( APC ) .", "target_text": { "cytokine": "protein", "IL-2": "protein", "antigen-presenting cells": "cell_type", "APC": "cell_type" } }, { "input_text": "Moreover , mRNA for IL-2 and IFN-gamma could not be detected .", "target_text": { "mRNA": "RNA", "IL-2": "protein", "IFN-gamma": "protein" } }, { "input_text": "In contrast , expression of the activation-dependent cell surface markers CD25 and CD69 was within normal limits .", "target_text": { "cell surface markers": "protein", "activation-dependent cell surface markers": "protein", "CD25": "protein", "CD69": "protein" } }, { "input_text": "To determine whether the functional defect of the patients ' T cells was due to the absence or abnormal binding of transcription factors involved in cytokine gene expression , electrophoretic mobility shift assays were used to examine the DNA binding of AP-1 , Oct , CREB , SP1 , NF-kappa B and the nuclear factor of activated T cells ( NF-AT ) to their respective response elements in the promoter of the IL-2 gene .", "target_text": { "T cells": "cell_type", "transcription factors": "protein", "cytokine gene": "DNA", "AP-1": "protein", "Oct": "protein", "CREB": "protein", "SP1": "protein", "NF-kappa B": "protein", "nuclear factor of activated T cells": "protein", "NF-AT": "protein", "response elements": "DNA", "promoter": "DNA", "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "Whereas AP-1 , NF-kappa B , Oct , CREB and SP1 displayed normal binding activities in nuclear extracts , the binding of NF-AT to its IL-2 promoter response element was barely detectable both before and after T cell stimulation .", "target_text": { "AP-1": "protein", "Oct": "protein", "CREB": "protein", "SP1": "protein", "NF-AT": "protein", "IL-2": "protein" } }, { "input_text": "Our results strongly suggest that this NF-AT /DNA binding defect is responsible for the multiple cytokine deficiency and the SCID phenotype observed in the two infant brothers .", "target_text": { "NF-AT": "protein", "cytokine": "protein" } }, { "input_text": "oriP is essential for EBNA gene promoter activity in Epstein-Barr virus-immortalized lymphoblastoid cell lines .", "target_text": { "oriP": "DNA", "EBNA gene": "DNA", "Epstein-Barr virus-immortalized lymphoblastoid cell lines": "cell_line" } }, { "input_text": "During Epstein-Barr virus latent infection of B lymphocytes in vitro , six viral nuclear antigens ( EBNAs ) are expressed from one of two promoters , Cp or Wp , whose activities are mutually exclusive .", "target_text": { "B lymphocytes": "cell_type", "viral nuclear antigens": "protein", "EBNAs": "protein", "promoters": "DNA", "Cp": "DNA", "Wp": "DNA" } }, { "input_text": "Upon infection , Wp is initially active , followed by a switch to Cp for the duration of latency .", "target_text": { "Wp": "DNA", "Cp": "DNA" } }, { "input_text": "In this study , the region upstream of Cp was analyzed for the presence of cis elements involved in regulating the activities of the EBNA gene promoters in established in vitro immortalized lymphoblastoid cell lines ( LCLs ) .", "target_text": { "Cp": "DNA", "promoters": "DNA", "EBNA gene promoters": "DNA", "in vitro immortalized lymphoblastoid cell lines": "cell_line", "LCLs": "cell_line" } }, { "input_text": "It was determined that oriP , the origin for episomal maintenance during latency , is essential for efficient transcription initiation from either Cp or Wp in LCLs , as well as in some Burkitt 's lymphoma cell lines .", "target_text": { "oriP": "DNA", "Cp": "DNA", "Wp": "DNA", "LCLs": "cell_line", "Burkitt 's lymphoma cell lines": "cell_line" } }, { "input_text": "Deletion of the EBNA2-dependent enhancer located upstream of Cp resulted in a ca. two- to fivefold reduction in Cp activity in the LCLs assayed .", "target_text": { "EBNA2-dependent enhancer": "DNA", "Cp": "DNA", "LCLs": "cell_line" } }, { "input_text": "More extensive deletion of sequences upstream of Cp , including the EBNA2-dependent enhancer , resulted in nearly complete loss of Cp activity .", "target_text": { "Cp": "DNA", "EBNA2-dependent enhancer": "DNA" } }, { "input_text": "This loss of activity was shown to correlate with deletion of two CCAAT boxes , a proximal CCAAT box located at bp -61 to -65 and a distal CCAAT box located at bp -253 to -257 , upstream of Cp .", "target_text": { "CCAAT boxes": "DNA", "proximal CCAAT box": "DNA", "bp -61 to -65": "DNA", "CCAAT box": "DNA", "-253 to -257": "DNA", "Cp": "DNA" } }, { "input_text": "Site-directed mutagenesis of these cis elements demonstrated that Cp activity is highly dependent on the presence of a properly positioned CCAAT box , with the dependence on the distal CCAAT box apparent only when the proximal CCAAT box was deleted or mutated .", "target_text": { "cis elements": "DNA", "Cp": "DNA", "CCAAT box": "DNA", "distal CCAAT box": "DNA", "proximal CCAAT box": "DNA" } }, { "input_text": "Deletion of the glucocorticoid response elements located at ca. bp -850 upstream of Cp did not result in a significant loss in activity .", "target_text": { "ca. bp -850": "DNA", "Cp": "DNA" } }, { "input_text": "In general , deletions which diminished Cp activity resulted in induction of Wp activity , consistent with suppression of Wp activity by transcriptional interference from Cp .", "target_text": { "Cp": "DNA", "Wp": "DNA" } }, { "input_text": "The identification of oriP and the EBNA2-dependent enhancer as the major positive cis elements involved in regulating Cp activity in LCL suggests that EBNA gene transcription is largely autoregulated by EBNA 1 and EBNA 2 .", "target_text": { "oriP": "DNA", "EBNA2-dependent enhancer": "DNA", "cis elements": "DNA", "Cp": "DNA", "LCL": "cell_line", "EBNA gene": "DNA", "EBNA 1": "protein", "EBNA 2": "protein" } }, { "input_text": "Protein-tyrosine kinase activation is required for lipopolysaccharide induction of interleukin 1beta and NFkappaB activation , but not NFkappaB nuclear translocation .", "target_text": { "interleukin 1beta": "protein", "NFkappaB": "protein" } }, { "input_text": "In human monocytes , interleukin 1beta protein production and steady state mRNA levels are increased in response to lipopolysaccharide , predominantly as a result of increased transcription of the interleukin 1beta gene .", "target_text": { "human monocytes": "cell_type", "interleukin 1beta": "protein" } }, { "input_text": "Expression of interleukin 1beta and other cytokines , such as interleukin 6 and tumor necrosis factor alpha , has been shown to be dependent on the activation of the transcription factor , NFkappaB .", "target_text": { "interleukin 1beta": "protein", "cytokines": "protein", "interleukin 6": "protein", "tumor necrosis factor alpha": "protein", "transcription factor": "protein", "NFkappaB": "protein" } }, { "input_text": "Since recent studies have shown that lipopolysaccharide -induced tyrosine kinase activation is not required for NFkappaB nuclear translocation , we sought to determine whether NFkappaB translocated in the absence of tyrosine kinase activity was active in stimulating transcription .", "target_text": { "tyrosine kinase": "protein", "NFkappaB": "protein" } }, { "input_text": "We have found that , in the human pro-monocytic cell line , THP-1 , the lipopolysaccharide -induced expression of interleukin 1beta is dependent on tyrosine kinase activation .", "target_text": { "pro-monocytic cell line": "cell_line", "THP-1": "cell_line", "interleukin 1beta": "protein", "tyrosine kinase": "protein" } }, { "input_text": "Tyrosine kinases are not required for lipopolysaccharide -mediated nuclear translocation of NFkappaB .", "target_text": { "NFkappaB": "protein" } }, { "input_text": "However , in the absence of tyrosine kinase activity , the ability of NFkappaB to stimulate transcription is impaired .", "target_text": { "tyrosine kinase": "protein", "NFkappaB": "protein" } }, { "input_text": "This inhibition of transcription is specific for NFkappaB ; in the absence of tyrosine kinase activity , AP-1 -dependent transcription is enhanced .", "target_text": { "NFkappaB": "protein", "tyrosine kinase": "protein", "AP-1": "protein" } }, { "input_text": "These results suggest that , while lipopolysaccharide -induced expression of inflammatory mediators requires tyrosine kinase activity , tyrosine kinase activity is not obligatory for lipopolysaccharide signal transduction .", "target_text": { "inflammatory mediators": "protein", "tyrosine kinase": "protein" } }, { "input_text": "Chronic human immunodeficiency virus type 1 infection of myeloid cells disrupts the autoregulatory control of the NF-kappaB/Rel pathway via enhanced IkappaBalpha degradation .", "target_text": { "myeloid cells": "cell_type", "NF-kappaB/Rel": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Productive human immunodeficiency virus type 1 ( HIV-1 ) infection causes sustained NF-kappaB DNA-binding activity in chronically infected monocytic cells .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "A direct temporal correlation exists between HIV infection and the appearance of NF-kappaB DNA-binding activity in myelomonoblastic PLB-985 cells .", "target_text": { "NF-kappaB": "protein", "PLB-985 cells": "cell_line", "myelomonoblastic PLB-985 cells": "cell_line" } }, { "input_text": "To examine the molecular basis of constitutive NF-kappaB DNA-binding activity in HIV1 -infected cells , we analyzed the phosphorylation and turnover of IkappaBalpha protein , the activity of the double-stranded RNA-dependent protein kinase ( PKR ) and the intracellular levels of NF-kappaB subunits in the PLB-985 and U937 myeloid cell models .", "target_text": { "NF-kappaB": "protein", "HIV1 -infected cells": "cell_type", "IkappaBalpha": "protein", "double-stranded RNA-dependent protein kinase": "protein", "PKR": "protein", "NF-kappaB subunits": "protein", "PLB-985": "cell_line", "U937 myeloid cell models": "cell_line" } }, { "input_text": "HIV-1 infection resulted in constitutive , low-level expression of type 1 interferon ( IFN ) at the mRNA level .", "target_text": { "type 1 interferon": "protein", "IFN": "protein" } }, { "input_text": "Constitutive PKR activity was also detected in HIV-1 -infected cells as a result of low-level IFN production , since the addition of anti-IFN-alpha/beta antibody to the cells decreased PKR expression .", "target_text": { "PKR": "protein", "HIV-1 -infected cells": "cell_line", "IFN": "protein", "anti-IFN-alpha/beta antibody": "protein" } }, { "input_text": "Furthermore , the analysis of IkappaBalpha turnover demonstrated an increased degradation of IkappaBalpha in HIV-1 -infected cells that may account for the constitutive DNA binding activity .", "target_text": { "IkappaBalpha": "protein", "HIV-1 -infected cells": "cell_line", "constitutive DNA": "DNA" } }, { "input_text": "A dramatic increase in the intracellular levels of NF-kappaB subunits c-Rel and NF-kappaB2 p100 and a moderate increase in NF-kappaB2 p52 and RelA ( p65 ) were detected in HIV-1 -infected cells , whereas NF-kappaB1 p105/p50 levels were not altered relative to the levels in uninfected cells .", "target_text": { "NF-kappaB": "protein", "c-Rel": "protein", "NF-kappaB2": "protein", "NF-kappaB2 p100": "protein", "NF-kappaB2 p52": "protein", "RelA ( p65 )": "protein", "HIV-1 -infected cells": "cell_line", "NF-kappaB1": "protein", "NF-kappaB1 p105/p50": "protein", "uninfected cells": "cell_type" } }, { "input_text": "We suggest that HIV-1 infection of myeloid cells induces IFN production and PKR activity , which in turn contribute to enhanced IkappaBalpha phosphorylation and subsequent degradation .", "target_text": { "myeloid cells": "cell_type", "IFN": "protein", "PKR": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Nuclear translocation of NF-kappaB subunits may ultimately increase the intracellular pool of NF-kappaB /IkappaBalpha by an autoregulatory mechanism .", "target_text": { "NF-kappaB": "protein", "NF-kappaB subunits": "protein", "/IkappaBalpha": "protein", "NF-kappaB /IkappaBalpha": "protein" } }, { "input_text": "Enhanced turnover of IkappaBalpha and the accumulation of NF-kappaB /Rel proteins may contribute to the chronically activated state of HIV-1 -infected cells .", "target_text": { "IkappaBalpha": "protein", "NF-kappaB": "protein", "NF-kappaB /Rel": "protein", "NF-kappaB /Rel proteins": "protein", "HIV-1 -infected cells": "cell_line" } }, { "input_text": "The c-Jun delta-domain inhibits neuroendocrine promoter activity in a DNA sequence- and pituitary- specific manner .", "target_text": { "c-Jun": "protein", "c-Jun delta-domain": "protein", "neuroendocrine promoter": "DNA" } }, { "input_text": "The transcription and transformation activity of c-Jun is governed by a 27-amino acid regulatory motif , labeled the delta-domain , which is deleted in v-Jun .", "target_text": { "c-Jun": "protein", "27-amino acid regulatory motif": "protein", "delta-domain": "protein", "v-Jun": "protein" } }, { "input_text": "We have previously shown that c-Jun is a potent inhibitor of the rat prolactin ( rPRL ) promoter activity induced by either oncogenic Ras or phorbol esters .", "target_text": { "c-Jun": "protein", "rat prolactin ( rPRL ) promoter": "DNA", "oncogenic Ras": "protein" } }, { "input_text": "Here , we have characterized the structural and cell-specific requirements for this c-Jun inhibitory response , and we show that this c-Jun inhibitory response mapped to the rPRL footprint II repressor site , was pituitary-specific and required the c-Jun delta-domain .", "target_text": { "c-Jun": "protein", "rPRL footprint II repressor site": "DNA", "c-Jun delta-domain": "protein" } }, { "input_text": "Moreover , alteration of any one of these features ( e.g. , cis-element , trans-factor , or cell-specific background ) switched c-Jun to a transcriptional activator of the rPRL promoter .", "target_text": { "cis-element": "DNA", "trans-factor": "DNA", "c-Jun": "protein", "transcriptional activator": "protein", "rPRL promoter": "DNA" } }, { "input_text": "In HeLa nonpituitary cells , c-Jun alone activated the rPRL promoter via the most proximal GHF-1/Pit-1 binding site , footprint I , and synergized with GHF-1 .", "target_text": { "HeLa nonpituitary cells": "cell_line", "c-Jun": "protein", "rPRL promoter": "DNA", "GHF-1/Pit-1 binding site": "DNA", "footprint I": "DNA", "GHF-1": "protein" } }, { "input_text": "Finally , recombinant GHF-1 interacted directly with c-Jun but not c-Fos proteins .", "target_text": { "GHF-1": "protein", "c-Jun": "protein", "c-Fos proteins": "protein" } }, { "input_text": "These data provide important fundamental insights into the molecular mechanisms by which the c-Jun delta-domain functions as a modulatory switch and further imply that the functional role of c-Jun is dictated by cell-specific influences and the delta-domain motif .", "target_text": { "c-Jun": "protein", "c-Jun delta-domain": "protein", "delta-domain motif": "protein" } }, { "input_text": "Retinoic acid activates interferon regulatory factor-1 gene expression in myeloid cells .", "target_text": { "interferon regulatory factor-1": "protein", "myeloid cells": "cell_type" } }, { "input_text": "All-trans-retinoic acid ( ATRA ) is the drug of choice in the treatment of acute promyelocytic leukemia ( APL ) .", "target_text": {} }, { "input_text": "ATRA induces both in vitro and in vivo differentiation of APL cells into mature granulocytes .", "target_text": { "APL cells": "cell_line", "mature granulocytes": "cell_type" } }, { "input_text": "However , the molecular mechanisms involved in ATRA -dependent growth inhibition and cellular differentiation are not presently understood .", "target_text": {} }, { "input_text": "The NB4 cell line , which is derived from the bone marrow of a patient with APL during relapse , can be used as a model system to study the growth and differentiation of APL cells .", "target_text": { "NB4 cell line": "cell_line", "APL cells": "cell_line" } }, { "input_text": "Because interferon ( IFN ) regulatory factors ( IRF-1 and IRF-2 ) and other IFN-inducible gene products regulate cell growth , we analyzed the effects of ATRA on the expression of these genes .", "target_text": { "interferon ( IFN ) regulatory factors": "protein", "IRF-1": "protein", "IRF-2": "protein", "IFN-inducible gene products": "protein" } }, { "input_text": "We show that ATRA directly activates IRF-1 gene expression , followed by activation of IRF-2 and 2'-5' oligoadenylate synthetase ( OAS ) gene expression with slower kinetics .", "target_text": { "IRF-1 gene": "DNA", "IRF-2": "protein", "2'-5' oligoadenylate synthetase": "protein" } }, { "input_text": "In addition to NB4 cells , ATRA also activated IRF-1 gene expression in HL-60 , U937 , and THP-1 cells , which all respond to ATRA by growth inhibition .", "target_text": { "IRF-1 gene": "DNA", "HL-60": "cell_line", "U937": "cell_line", "THP-1 cells": "cell_line" } }, { "input_text": "A more than additive increase in IRF-1 gene expression was seen with ATRA and IFN-gamma in NB4 cells .", "target_text": { "IRF-1 gene": "DNA", "IFN-gamma": "protein", "NB4 cells": "cell_line" } }, { "input_text": "ATRA did not activate nuclear factor kappa B or signal transducer and activator of transcription ( STAT ) activation pathways , suggesting that an alternate mechanism is involved in IRF-1 gene activation .", "target_text": { "IRF-1 gene": "DNA" } }, { "input_text": "The ATRA -induced expression of IRF-1 , an activator of transcription and repressor of transformation , may be one of the molecular mechanisms of ATRA -induced growth inhibition , and the basis for the synergistic actions of ATRA and IFNs in myeloid leukemia cells .", "target_text": { "IRF-1": "protein", "IFNs": "protein", "myeloid leukemia cells": "cell_line" } }, { "input_text": "Recombinant NFAT1 ( NFATp ) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes .", "target_text": { "NFAT1": "protein", "T cells": "cell_type", "cytokine genes": "DNA" } }, { "input_text": "Transcription factors of the NFAT family play a key role in the transcription of cytokine genes and other genes during the immune response .", "target_text": { "Transcription factors": "protein", "NFAT family": "protein", "cytokine genes": "DNA" } }, { "input_text": "We have identified two new isoforms of the transcription factor NFAT1 ( previously termed NFATp ) that are the predominant isoforms expressed in murine and human T cells .", "target_text": { "transcription factor": "protein", "NFAT1": "protein", "NFATp": "protein" } }, { "input_text": "When expressed in Jurkat T cells , recombinant NFAT1 is regulated , as expected , by the calmodulin-dependent phosphatase calcineurin , and its function is inhibited by the immunosuppressive agent cyclosporin A ( CsA ) .", "target_text": { "Jurkat T cells": "cell_line", "NFAT1": "protein", "calmodulin-dependent phosphatase": "protein", "calcineurin": "protein" } }, { "input_text": "Transactivation by recombinant NFAT1 in Jurkat T cells requires dual stimulation with ionomycin and phorbol 12-myristate 13-acetate ; this activity is potentiated by coexpression of constitutively active calcineurin and is inhibited by CsA .", "target_text": { "NFAT1": "protein", "Jurkat T cells": "cell_line", "calcineurin": "protein" } }, { "input_text": "Immunocytochemical analysis indicates that recombinant NFAT1 localizes in the cytoplasm of transiently transfected T cells and translocates into the nucleus in a CsA -sensitive manner following ionomycin stimulation .", "target_text": { "NFAT1": "protein", "transiently transfected T cells": "cell_type" } }, { "input_text": "When expressed in COS cells , however , NFAT1 is capable of transactivation , but it is not regulated correctly : its subcellular localization and transcriptional function are not affected by stimulation of the COS cells with ionomycin and phorbol 12-myristate 13-acetate .", "target_text": { "COS cells": "cell_line", "NFAT1": "protein" } }, { "input_text": "Recombinant NFAT1 can mediate transcription of the interleukin-2 , interleukin-4 , tumor necrosis factor alpha , and granulocyte-macrophage colony-stimulating factor promoters in T cells , suggesting that NFAT1 contributes to the CsA -sensitive transcription of these genes during the immune response .", "target_text": { "NFAT1": "protein", "interleukin-2": "protein", "tumor necrosis factor alpha": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "promoters": "DNA", "granulocyte-macrophage colony-stimulating factor promoters": "DNA", "T cells": "cell_type", "genes": "DNA" } }, { "input_text": "Human TAFII 105 is a cell type-specific TFIID subunit related to hTAFII130 .", "target_text": { "Human TAFII 105": "protein", "TFIID": "protein", "cell type-specific TFIID subunit": "protein", "hTAFII130": "protein" } }, { "input_text": "We previously characterized Drosophila and human TAF subunits that make up the core TFIID complex found in all cells .", "target_text": { "TFIID": "protein", "TFIID complex": "protein" } }, { "input_text": "Here , we report that differentiated B cells contain a novel substoichiometric TAF of 105 kDa not found associated with TFIID isolated from other cell types .", "target_text": { "differentiated B cells": "cell_type", "TAF": "protein", "TFIID": "protein" } }, { "input_text": "The cDNA encoding hTAFII105 reveals a highly conserved C-terminal domain shared by hTAFII130 and oTAFII110 , while the N-terminal coactivator domain has diverged significantly .", "target_text": { "cDNA": "DNA", "hTAFII105": "protein", "C-terminal domain": "protein", "hTAFII130": "protein", "oTAFII110": "protein", "N-terminal coactivator domain": "protein" } }, { "input_text": "All cells tested express TAFII105 mRNA , but only B cells contain significant levels of protein associated with TFIID .", "target_text": { "TAFII105 mRNA": "RNA", "B cells": "cell_type", "TFIID": "protein" } }, { "input_text": "Transient overexpression of hTAFII105 selectively squelches the transcription of some genes in B cells .", "target_text": { "hTAFII105": "protein", "B cells": "cell_type" } }, { "input_text": "These properties suggest that TAFII105 is a cell type-specific subunit of TFIID that may be responsible for mediating transcription by a subset of activators in B cells .", "target_text": { "TAFII105": "protein", "TFIID": "protein", "B cells": "cell_type" } }, { "input_text": "Interstitial deletion constitutes the major mechanism for loss of heterozygosity on chromosome 20q in polycythemia vera .", "target_text": { "chromosome 20q": "DNA" } }, { "input_text": "An acquired deletion of the long arm of chromosome 20 is a recurrent abnormality in myeloproliferative disorders , particularly polycythemia vera and myelodysplastic syndromes .", "target_text": { "long arm": "DNA", "chromosome 20": "DNA" } }, { "input_text": "The association of 20q deletions with myeloid \" stem cell \" disorders suggests that the deletions mark the site of one or more genes , loss or inactivation of which plays a role in the regulation of normal hematopoietic progenitors .", "target_text": { "20q deletions": "DNA", "normal hematopoietic progenitors": "cell_type" } }, { "input_text": "We have recently performed a detailed molecular analysis of 20q deletions in peripheral blood ( PB ) granulocytes and defined a commonly deleted region of 16 to 21 centimorgan ( cM ) .", "target_text": { "20q deletions": "DNA", "peripheral blood ( PB ) granulocytes": "cell_type", "commonly deleted region": "DNA", "16 to 21 centimorgan": "DNA", "cM": "DNA" } }, { "input_text": "To further reduce the size of the common deleted region we have searched for small deletions or mitotic recombination events , neither of which would be detected by conventional cytogenetics .", "target_text": {} }, { "input_text": "We have studied 48 patients with polycythemia vera and four patients with idiopathic myelofibrosis .", "target_text": {} }, { "input_text": "In each case , cytogenetic analysis had either failed or had shown no abnormalities of chromosome 20 .", "target_text": { "chromosome 20": "DNA" } }, { "input_text": "Seventeen microsatellite markers that span the common deleted region were used to search for loss of heterozygosity in granulocyte DNA .", "target_text": { "microsatellite markers": "DNA", "granulocyte DNA": "DNA" } }, { "input_text": "No instance of microsatellite instability was observed in a total of 880 comparisons of granulocyte and T-cell DNA .", "target_text": {} }, { "input_text": "Granulocyte DNA from four patients exhibited allele loss on 20q .", "target_text": { "Granulocyte DNA": "DNA", "20q": "DNA" } }, { "input_text": "In each case the allele loss was caused by an interstitial deletion because heterozygosity at distal markers was retained and because quantitative Southern blotting demonstrated hemizygosity .", "target_text": { "distal markers": "DNA" } }, { "input_text": "Loss of heterozygosity in PB granulocytes would be masked by the presence of significant numbers of normal granulocytes not derived from the malignant clone .", "target_text": { "PB granulocytes": "cell_type", "normal granulocytes": "cell_type", "malignant clone": "cell_line" } }, { "input_text": "Therefore , the human androgen receptor assay ( HUMARA ) was used to determine granulocyte clonality .", "target_text": { "human androgen receptor": "protein" } }, { "input_text": "In 21 of 27 informative female patients the majority of the granulocytes were clonally derived .", "target_text": { "granulocytes": "cell_type" } }, { "input_text": "In 5 patients the granulocytes appeared polyclonal and in 1 patient unilateral X inactivation was observed in both granulocytes and T cells .", "target_text": { "granulocytes": "cell_type", "T cells": "cell_type" } }, { "input_text": "These results show that , in the vast majority of patients presented here , the failure to detect loss of heterozygosity can not be attributed to the presence of normal polyclonal granulocytes .", "target_text": { "granulocytes": "cell_type", "normal polyclonal granulocytes": "cell_line" } }, { "input_text": "Our results therefore show that allele loss on chromosome 20q in polycythemia vera does not commonly involve mitotic recombination or chromosome loss and that microsatellite instability is a rare event in this disorder .", "target_text": { "chromosome 20q": "DNA", "chromosome": "DNA" } }, { "input_text": "Interleukin-6 promotes multiple myeloma cell growth via phosphorylation of retinoblastoma protein .", "target_text": { "Interleukin-6": "protein", "retinoblastoma protein": "protein" } }, { "input_text": "Interleukin-6 ( IL-6 ) mediates autocrine and paracrine growth of multiple myeloma ( MM ) cells and inhibits tumor cell apoptosis .", "target_text": { "Interleukin-6": "protein", "IL-6": "protein", "multiple myeloma ( MM ) cells": "cell_line" } }, { "input_text": "Abnormalities of retinoblastoma protein ( pRB ) and mutations of RB gene have been reported in up to 70 % of MM patients and 80 % of MM-derived cell lines .", "target_text": { "retinoblastoma protein": "protein", "pRB": "protein", "MM-derived cell lines": "cell_line" } }, { "input_text": "Because dephosphorylated ( activated ) pRB blocks transition from G1 to S phase of the cell cycle whereas phosphorylated ( inactivated ) pRB releases this growth arrest , we characterized the role of pRB in IL-6 -mediated MM cell growth .", "target_text": { "pRB": "protein", "dephosphorylated ( activated ) pRB": "protein", "phosphorylated ( inactivated ) pRB": "protein", "IL-6": "protein" } }, { "input_text": "Both phosphorylated and dephosphorylated pRB were expressed in all serum-starved MM patient cells and MM-derived cell lines , but pRB was predominantly in its phosphorylated form .", "target_text": { "pRB": "protein", "MM-derived cell lines": "cell_line" } }, { "input_text": "In MM cells that proliferated in response to IL-6 , exogenous IL-6 downregulated dephosphorylated pRB and decreased dephosphorylated pRB -E2F complexes .", "target_text": { "MM cells": "cell_line", "IL-6": "protein", "pRB": "protein", "dephosphorylated pRB": "protein", "pRB -E2F complexes": "protein" } }, { "input_text": "Importantly , culture of MM cells with RB antisense , but not RB sense , oligonucleotide ( ODN ) triggered IL-6 secretion and proliferation in MM cells ; however , proliferation was only partially inhibited by neutralizing anti- IL-6 monoclonal antibody ( MoAb ) .", "target_text": { "MM cells": "cell_line", "IL-6": "protein", "anti- IL-6 monoclonal antibody": "protein", "MoAb": "protein" } }, { "input_text": "In contrast to MM cells , normal splenic B cells express dephosphorylated pRB .", "target_text": { "MM cells": "cell_line", "B cells": "cell_type", "splenic B cells": "cell_type", "pRB": "protein", "dephosphorylated pRB": "protein" } }, { "input_text": "Although CD40 ligand ( CD40L ) triggers a shift from dephosphorylated to phosphorylated pRB and proliferation of B cells , the addition of exogenous IL-6 to CD40L -treated B cells does not alter either pRB or proliferation , as observed in MM cells .", "target_text": { "CD40 ligand": "protein", "CD40L": "protein", "pRB": "protein", "B cells": "cell_type", "IL-6": "protein", "MM cells": "cell_line" } }, { "input_text": "These results suggest that phosphorylated pRB is constitutively expressed in MM cells and that IL-6 further shifts pRB from its dephosphorylated to its phosphorylated form , thereby promoting MM cell growth via two mechanisms ; by decreasing the amount of E2F bound by dephosphorylated pRB due to reduced dephosphorylated pRB , thereby releasing growth arrest ; and by upregulating IL-6 secretion by MM cells and related IL-6 -mediated autocrine tumor cell growth .", "target_text": { "pRB": "protein", "phosphorylated pRB": "protein", "MM cells": "cell_line", "IL-6": "protein", "dephosphorylated pRB": "protein" } }, { "input_text": "Soluble factors secreted by activated T-lymphocytes modulate the transcription of the immunosuppressive cytokine TGF-beta 2 in glial cells .", "target_text": { "Soluble factors": "protein", "activated T-lymphocytes": "cell_type", "immunosuppressive cytokine": "protein", "TGF-beta 2": "protein", "glial cells": "cell_type" } }, { "input_text": "Coordination of the immune response to injury or disease in the brain is postulated to involve bi-directional discourse between the immune system and the central nervous system .", "target_text": {} }, { "input_text": "This cross communication involves soluble mediators , including various growth factors , cytokines , and neuropeptides .", "target_text": { "growth factors": "protein", "cytokines": "protein" } }, { "input_text": "In this report , we demonstrate that the supernatant from activated T-lymphocytes is able to induce the transcription of a potent cytokine , TGF-beta 2 in glial cells .", "target_text": { "activated T-lymphocytes": "cell_type", "cytokine": "protein", "TGF-beta 2": "protein", "glial cells": "cell_type" } }, { "input_text": "The activating stimulus invokes signaling mechanisms distinct from known kinase or protease pathways .", "target_text": {} }, { "input_text": "Activation of TGF-beta 2 transcription correlates with the loss of binding activity for an 80 kDA glial labile repressor protein , GLRP , to a responsive region within the TFG-beta 2 promoter .", "target_text": { "TGF-beta 2": "protein", "80 kDA glial labile repressor protein": "protein", "GLRP": "protein", "TFG-beta 2 promoter": "DNA" } }, { "input_text": "Although GLRP shares some characteristics with the inducible transcription factor AP-1 , it appears to be distinct from known AP-1 family members .", "target_text": { "GLRP": "protein", "transcription factor": "protein", "AP-1": "protein", "AP-1 family members": "protein" } }, { "input_text": "These data along with previous observations demonstrating the potent immunosuppressive activity of TGF-beta 2 , support a model for a feedback mechanism between the activated T-lymphocytes and astrocytes via TGF-beta 2 to regulate the immune response .", "target_text": { "TGF-beta 2": "protein", "T-lymphocytes": "cell_type", "astrocytes": "cell_type" } }, { "input_text": "Various modes of basic helix-loop-helix protein -mediated regulation of murine leukemia virus transcription in lymphoid cell lines .", "target_text": { "basic helix-loop-helix protein": "protein", "lymphoid cell lines": "cell_line" } }, { "input_text": "The transcriptionally regulatory regions of the lymphomagenic Akv and SL3-3 murine leukemia retroviruses ( MLVs ) contain two types of E-box consensus motifs , CAGATG .", "target_text": { "transcriptionally regulatory regions": "DNA", "E-box consensus motifs": "DNA" } }, { "input_text": "One type , EA/S , is located in the upstream promoter region , and the other , E ( gre ) , is located in a tandem repeat with enhancer properties .", "target_text": { "EA/S": "DNA", "upstream promoter region": "DNA", "E ( gre )": "DNA", "tandem repeat": "DNA" } }, { "input_text": "We have examined the requirements of the individual E-boxes in MLV transcriptional regulation .", "target_text": { "E-boxes": "DNA" } }, { "input_text": "In lymphoid cell lines only , the E ( gre ) -binding protein complexes included ALF1 or HEB and E2A basic helix-loop-helix proteins .", "target_text": { "lymphoid cell lines": "cell_line", "E ( gre )": "DNA", "E ( gre ) -binding protein complexes": "protein", "ALF1": "protein", "HEB": "protein", "basic helix-loop-helix proteins": "protein", "E2A basic helix-loop-helix proteins": "protein" } }, { "input_text": "Ectopic ALF1 and E2A proteins required intact E ( gre ) motifs for mediating transcriptional activation .", "target_text": { "ALF1": "protein", "E2A proteins": "protein", "E ( gre )": "DNA", "E ( gre ) motifs": "DNA" } }, { "input_text": "ALF1 transactivated transcription of Akv MLV through the two E ( gre ) motifs equally , whereas E2A protein required the promoter-proximal E ( gre ) motif .", "target_text": { "ALF1": "protein", "E ( gre )": "DNA", "E ( gre ) motifs": "DNA", "E2A protein": "protein" } }, { "input_text": "In T- and B- cell lines , the E ( gre ) motifs were of major importance for Akv MLV transcriptional activity , while the EA/S motif had some effect .", "target_text": { "E ( gre )": "DNA", "E ( gre ) motifs": "DNA", "EA/S": "DNA", "EA/S motif": "DNA" } }, { "input_text": "In contrast , neither E ( gre ) nor EA/S motifs contributed pronouncedly to Akv MLV transcription in NIH 3T3 cells lacking DNA-binding ALF1 or HEB and E2A proteins .", "target_text": { "E ( gre )": "DNA", "EA/S": "DNA", "EA/S motifs": "DNA", "NIH 3T3 cells": "cell_line", "ALF1": "protein", "HEB": "protein", "E2A proteins": "protein" } }, { "input_text": "The Id1 protein was found to repress ALF1 activity in vitro and in vivo .", "target_text": { "ALF1": "protein" } }, { "input_text": "Moreover , ectopic Id1 repressed E ( gre ) -directed but not EA/S -directed MLV transcription in lymphoid cell lines .", "target_text": { "ectopic Id1": "protein", "E ( gre )": "DNA", "EA/S": "DNA", "lymphoid cell lines": "cell_line" } }, { "input_text": "In conclusion , E ( gre ) motifs and interacting basic helix-loop-helix proteins are important determinants for MLV transcriptional activity in lymphocytic cell lines .", "target_text": { "E ( gre )": "DNA", "basic helix-loop-helix proteins": "protein", "lymphocytic cell lines": "cell_line" } }, { "input_text": "Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor .", "target_text": { "transcription factor": "protein", "E2A-HLF chimaeric transcription factor": "protein" } }, { "input_text": "The E2A-HLF ( for hepatic leukaemia factor ) fusion gene , formed by action of the t(17;19) (q22;p13) chromosomal translocation , drives the leukaemic transformation of early B-cell precursors , but the mechanism of this activity remains unknown .", "target_text": { "E2A-HLF": "protein", "E2A-HLF ( for hepatic leukaemia factor ) fusion gene": "DNA", "t(17;19) (q22;p13)": "DNA", "B-cell precursors": "cell_type" } }, { "input_text": "Here we report that human leukaemia cells carrying the translocation t(17;19) rapidly died by apoptosis when programmed to express a dominant-negative suppressor of the fusion protein E2A-HLF , indicating that the chimaeric oncoprotein probably affects cell survival rather than cell growth .", "target_text": { "human leukaemia cells": "cell_type", "t(17;19)": "DNA", "E2A-HLF": "protein", "chimaeric oncoprotein": "protein" } }, { "input_text": "Moreover , when introduced into murine pro-B lymphocytes , the oncogenic E2A-HLF fusion protein reversed both interleukin-3-dependent and p53-mediated apoptosis .", "target_text": { "murine pro-B lymphocytes": "cell_line", "E2A-HLF": "protein", "oncogenic E2A-HLF fusion protein": "protein" } }, { "input_text": "The close homology of the basic region/leucine zipper ( bZIP ) DNA-binding and dimerization domain of HLF to that of the CES-2 cell-death specification protein of Caenorhabditis elegans suggests a model of leukaemogenesis in which E2A-HLF blocks an early step within an evolutionarily conserved cell-death pathway .", "target_text": { "basic region/leucine zipper": "protein", "bZIP": "protein", "dimerization domain": "protein", "HLF": "protein", "CES-2 cell-death specification protein": "protein", "E2A-HLF": "protein" } }, { "input_text": "The role of early growth response gene 1 ( egr-1 ) in regulation of the immune response .", "target_text": { "early growth response gene 1": "DNA", "egr-1": "DNA" } }, { "input_text": "The induction of immediate early genes in cells of the immune system is critical to determining the ultimate outcome of exposure to antigen .", "target_text": { "immediate early genes": "DNA" } }, { "input_text": "The importance of many of these genes relates to the role their transcription factor products play in dictating patterns of expression of downstream , function-related genes .", "target_text": { "transcription factor": "protein", "transcription factor products": "protein", "function-related genes": "DNA" } }, { "input_text": "Evidence from several systems indicates that the immediate early gene , egr-1 may be of particular importance in the immune system .", "target_text": { "immediate early gene": "DNA", "egr-1": "DNA" } }, { "input_text": "Recently , the egr-1 promoter has been shown to be highly responsive to the diverse biochemical signals generated by antigen and cytokines in cells of the immune system .", "target_text": { "egr-1": "DNA", "egr-1 promoter": "DNA", "cytokines": "protein" } }, { "input_text": "Furthermore , an important role for egr-1 in determining the differentiation pathway of myeloid cell precursors has been recently elaborated .", "target_text": { "egr-1": "DNA", "myeloid cell precursors": "cell_type" } }, { "input_text": "Finally , potential targets of regulation by the zinc-finger transcription factor encoded by egr-1 include the interleukin-2 , CD44 , ICAM-1 , and tumor necrosis factor genes .", "target_text": { "transcription factor": "protein", "zinc-finger transcription factor": "protein", "egr-1": "DNA" } }, { "input_text": "The role of egr-1 in regulation of the immune response will be discussed in the context of these recent studies .", "target_text": { "egr-1": "DNA" } }, { "input_text": "Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction .", "target_text": {} }, { "input_text": "Vaccination with synthetic peptides representing cytotoxic T lymphocyte ( CTL ) epitopes can lead to a protective CTL-mediated immunity against tumors or viruses .", "target_text": {} }, { "input_text": "We now report that vaccination with a CTL epitope derived from the human adenovirus type 5 E1A-region ( Ad5E1A234-243 ) , which can serve as a target for tumor-eradicating CTL , enhances rather than inhibits the growth of Ad5E1A-expressing tumors .", "target_text": { "human adenovirus type 5 E1A-region": "DNA", "Ad5E1A234-243": "DNA", "tumor-eradicating CTL": "cell_type" } }, { "input_text": "This adverse effect of peptide vaccination was rapidly evoked , required low doses of peptide ( 10 micrograms ) , and was achieved by a mode of peptide delivery that induces protective T-cell-mediated immunity in other models .", "target_text": {} }, { "input_text": "Ad5E1A -specific CTL activity could no longer be isolated from mice after injection of Ad5E1A-peptide , indicating that tolerization of Ad5E1A -specific CTL activity causes the enhanced tumor outgrowth .", "target_text": { "Ad5E1A": "protein" } }, { "input_text": "In contrast to peptide vaccination , immunization with adenovirus , expressing Ad5E1A , induced Ad5E1A -specific immunity and prevented the outgrowth of Ad5E1A -expressing tumors .", "target_text": { "Ad5E1A": "protein" } }, { "input_text": "These results show that immunization with synthetic peptides can lead to the elimination of anti-tumor CTL responses .", "target_text": {} }, { "input_text": "These findings are important for the design of safe peptide -based vaccines against tumors , allogeneic organ transplants , and T-cell-mediated autoimmune diseases .", "target_text": {} }, { "input_text": "[ NGFI-B/nur77 family involved in T-cell apoptosis ]", "target_text": { "NGFI-B/nur77 family": "protein" } }, { "input_text": "NGFI-B/nur77 is a member of the steroid receptor superfamily .", "target_text": { "NGFI-B/nur77": "protein", "steroid receptor superfamily": "protein" } }, { "input_text": "NGFI-B/nur77 and its related genes constitute a family and the NGFI-B/nur77 family consists of three subtypes , named nur77 alpha , nur77 beta , nur77 gamma .", "target_text": { "NGFI-B/nur77": "protein", "NGFI-B/nur77 family": "protein", "nur77 alpha": "protein", "nur77 beta": "protein", "nur77 gamma": "protein" } }, { "input_text": "We cloned human nur77 beta cDNA , called TINUR .", "target_text": { "nur77 beta": "protein", "nur77 beta cDNA": "DNA", "TINUR": "DNA" } }, { "input_text": "Although NGFI-B/nur77 is essential for TCR-mediated apoptosis in T-cell hybridomas , the reports on nur77 knock-out mice and nur77 dominant negative transgenic mice suggest that there is a functional redundancy among NGFI-B/nur77 family .", "target_text": { "NGFI-B/nur77": "protein", "T-cell hybridomas": "protein", "NGFI-B/nur77 family": "protein" } }, { "input_text": "NGFI-B/nur77 binds to the response element by monomer or heterodimer with retinoid X receptor ( RXR ) .", "target_text": { "NGFI-B/nur77": "protein", "response element": "DNA", "retinoid X receptor": "protein", "RXR": "protein" } }, { "input_text": "Assuming that 9-cis-retinoic acid ( 9-cis-RA ) inhibits TCR-mediated apoptosis , nur77 may cause apoptosis by monomer in the absence of 9-cis-RA and may inhibit apoptosis by heterodimer with RXR in the presence of 9-cis-RA .", "target_text": { "nur77": "protein", "RXR": "protein" } }, { "input_text": "Glucocorticoids and interferon-alpha in the acquired immunodeficiency syndrome .", "target_text": { "interferon-alpha": "protein" } }, { "input_text": "Some patients with acquired immunodeficiency syndrome ( AIDS ) develop glucocorticoid resistance characterized by low receptor affinity ( Kd ) for glucocorticoids in mononuclear , cells and high values of ACTH and cortisol .", "target_text": { "mononuclear": "cell_type" } }, { "input_text": "As glucocorticoids regulate interferon-alpha ( IFN alpha ) production , we hypothesized that IFN alpha , a cytokine produced predominantly by monocytes in AIDS , should be increased in cortisol -resistant AIDS , attributing the lack of cortisol inhibition to IFN alpha production .", "target_text": { "interferon-alpha": "protein", "IFN alpha": "protein", "cytokine": "protein", "monocytes": "cell_type" } }, { "input_text": "Therefore , we examined glucocorticoid receptor characteristics on monocytes by [3H]dexamethasone binding and measured IFN alpha , cortisol , and ACTH in AIDS patients with ( AIDS -GR ) or without glucocorticoid resistance ( AIDS -C ) and controls ( C ) .", "target_text": { "glucocorticoid receptor": "protein", "monocytes": "cell_type", "IFN alpha": "protein" } }, { "input_text": "Monocytes of AIDS -GR patients had a receptor Kd of 10.5 +/- 4.2 nmol/L that was higher than that in the AIDS -C group ( 2.9 +/- 0.8 nmol/L ) and normal subjects ( 2.0 +/- 0.8 nmol/L ; P < 0.01 ) .", "target_text": {} }, { "input_text": "IFN alpha levels were increased in the AIDS -GR group ( 17 +/- 6 vs.", "target_text": { "IFN alpha": "protein" } }, { "input_text": "4 +/- 1 U/mL in the AIDS -C group and 2 +/- 0.5 U/mL in the C group ; P < 0.01 ) .", "target_text": {} }, { "input_text": "Correlations were found between plasma IFN alpha and receptor Kd on monocytes of AIDS -GR ( r = 0.77 ) and between IFN alpha and plasma cortisol in the same group ( r = 0.74 ) .", "target_text": { "IFN alpha": "protein", "plasma IFN alpha": "protein", "monocytes": "cell_type" } }, { "input_text": "The poly(I)-poly(C)-induced IFN alpha production by monocytes was inhibited by glucocorticoids in the C and AIDS -C groups ( approximately 80 % inhibition in both groups ) ; the effect was reversed by the receptor antagonist RU-38486 .", "target_text": { "IFN alpha": "protein", "poly(I)-poly(C)-induced IFN alpha": "protein", "monocytes": "cell_type" } }, { "input_text": "By contrast , glucocorticoids failed to inhibit IFNalpha production from AIDS -GR monocytes ( approximately 20 % inhibition ) .", "target_text": { "IFNalpha": "protein", "monocytes": "cell_type", "AIDS -GR monocytes": "cell_type" } }, { "input_text": "In conclusion , elevated IFN alpha levels in AIDS -GR may be due to the lack of inhibitory effect of cortisol on IFN alpha production due to cortisol resistance in monocytes", "target_text": { "IFN alpha": "protein", "monocytes": "cell_type" } }, { "input_text": "JNK ( c-Jun NH2-terminal kinase ) is a target for antioxidants in T lymphocytes .", "target_text": { "JNK": "protein", "c-Jun NH2-terminal kinase": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "AP-1 has been shown to behave as a redox-sensitive transcription factor that can be activated by both oxidant and antioxidant stimuli .", "target_text": { "AP-1": "protein", "redox-sensitive transcription factor": "protein" } }, { "input_text": "However , the mechanisms involved in the activation of AP-1 by antioxidants are largely unknown .", "target_text": { "AP-1": "protein" } }, { "input_text": "In this study we show that the structurally unrelated antioxidant agents pyrrolidine dithiocarbamate ( PDTC ) , butylated hydroxyanisole , and Nacetylcysteine activated JNK ( c-Jun NH2-terminal kinase ) in Jurkat T cells .", "target_text": { "JNK": "protein", "c-Jun NH2-terminal kinase": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "This activation differed substantially from that mediated by phorbol 12-myristate 13-acetate ( PMA ) and Ca2+ ionophore or produced by costimulation with antibodies against the T cell receptor-CD3 complex and to CD28 .", "target_text": { "antibodies": "protein", "T cell receptor-CD3 complex": "protein", "CD28": "protein" } }, { "input_text": "The activation of JNK by classical T cell stimuli was transient , whereas that mediated by PDTC and butylated hydroxyanisole ( but not N-acetylcysteine ) was sustained .", "target_text": { "JNK": "protein" } }, { "input_text": "The kinetics of JNK activation correlated with the expression of c-jun which was transient after stimulation with PMA plus ionophore and prolonged in response to PDTC , which also transiently induced c-fos .", "target_text": { "JNK": "protein", "c-jun": "DNA", "c-fos": "DNA" } }, { "input_text": "In addition , JNK activation by PMA plus ionophore was sensitive to inhibitors of signaling pathways involving Ca2+ , protein kinase C , and tyrosine phosphorylation , which failed to inhibit the activation mediated by PDTC .", "target_text": { "JNK": "protein", "protein kinase C": "protein" } }, { "input_text": "Transfection of trans-dominant negative expression vectors of ras and raf , together with AP-1 -dependent reporter constructs , as well as Western blot analysis using anti-ERK ( extracellular signal-regulated kinase ) antibodies , indicated that the Ras/Raf/ERK pathway did not appear to mediate the effect of the antioxidant .", "target_text": { "trans-dominant negative expression vectors": "DNA", "ras": "DNA", "raf": "DNA", "AP-1": "protein", "AP-1 -dependent reporter constructs": "DNA", "extracellular signal-regulated kinase": "protein", "anti-ERK ( extracellular signal-regulated kinase ) antibodies": "protein" } }, { "input_text": "However , the combined treatment with PDTC and PMA , two agents that synergize on AP-1 activation , resulted in the persistent phosphorylation of ERK-2 .", "target_text": { "AP-1": "protein", "ERK-2": "protein" } }, { "input_text": "In conclusion , our results identify JNK as a target of antioxidant agents which can be regulated differentially under oxidant and antioxidant conditions .", "target_text": { "JNK": "protein" } }, { "input_text": "[ Molecular mechanisms of age-related lymphocyte dysfunction ]", "target_text": {} }, { "input_text": "Aging is classically accompanied by a dysregulation of the immunologic machinery .", "target_text": {} }, { "input_text": "As a consequence , the immune response developed in senescent organisms is usually inappropriate , often inefficient , sometimes aberrant , and potentially detrimental .", "target_text": {} }, { "input_text": "The age-associated immune dysfunction may be implicated to some degree in the extreme susceptibility of the elderly to infection and neoplasia and may even participate in various aspects of senescence .", "target_text": {} }, { "input_text": "The current understanding of the molecular mechanisms underlying immunosenescence is still fragmentary .", "target_text": {} }, { "input_text": "The most extensively studied phenomenon is the progressive decline in the proliferative capacities of T lymphocytes with aging .", "target_text": { "T lymphocytes": "cell_type" } }, { "input_text": "The loss of proliferative potential in response to antigenic challenge is a characteristic feature of immune senescence .", "target_text": {} }, { "input_text": "It is directly implicated in the emergence of the age-related immune deficiency .", "target_text": {} }, { "input_text": "The purpose of this review is to show how the accumulation of various biochemical lesions with advancing age leads to the failure of a critical cell function , namely the activation-induced lymphocyte proliferation .", "target_text": {} }, { "input_text": "The biochemical modifications responsible for the defect in transduction and execution of the proliferative signal are analyzed as a function of age .", "target_text": {} }, { "input_text": "The multiple alterations observed on the various biochemical pathways may appear as a consequence of a unique deleterious mechanism more fundamentally related to the process of senescence such as the inability to cope with oxidative stress .", "target_text": {} }, { "input_text": "Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis .", "target_text": { "bcl-2": "protein" } }, { "input_text": "Engagement of surface immunoglobulin on mature B cells leads to rescue from apoptosis and to proliferation .", "target_text": {} }, { "input_text": "Levels of bcl-2 mRNA and protein increase with cross-linking of surface immunoglobulin .", "target_text": { "bcl-2 mRNA": "RNA", "surface immunoglobulin": "protein" } }, { "input_text": "We have located the major positive regulatory region for control of bcl-2 expression in B cells in the 5'-flanking region .", "target_text": { "bcl-2": "protein", "B cells": "cell_type", "5'-flanking region": "DNA" } }, { "input_text": "The positive region can be divided into an upstream and a downstream regulatory region .", "target_text": {} }, { "input_text": "The downstream regulatory region contains a cyclic AMP -responsive element ( CRE ) .", "target_text": { "downstream regulatory region": "DNA", "cyclic AMP -responsive element": "DNA", "CRE": "DNA" } }, { "input_text": "We show by antibody supershift experiments and UV cross-linking followed by denaturing polyacrylamide gel electrophoresis that both CREB and ATF family members bind to this region in vitro .", "target_text": {} }, { "input_text": "Mutations of the CRE site that result in loss of CREB binding also lead to loss of functional activity of the bcl-2 promoter in transient-transfection assays .", "target_text": { "CRE site": "DNA", "CREB": "protein" } }, { "input_text": "The presence of an active CRE site in the bcl-2 promoter implies that the regulation of bcl-2 expression is linked to a signal transduction pathway in B cells .", "target_text": { "CRE site": "DNA", "bcl-2 promoter": "DNA", "bcl-2": "protein", "B cells": "cell_type" } }, { "input_text": "Treatment of the mature B-cell line BAL-17 with either anti-immunoglobulin M or phorbol 12-myristate 13-acetate leads to an increase in bcl-2 expression that is mediated by the CRE site .", "target_text": { "mature B-cell line BAL-17": "cell_line", "bcl-2": "protein", "CRE site": "DNA" } }, { "input_text": "Treatment of the more immature B-cell line , Ramos , with phorbol esters rescues the cells from calcium-dependent apoptosis .", "target_text": { "immature B-cell line": "cell_line", "Ramos": "cell_line" } }, { "input_text": "bcl-2 expression is increased following phorbol ester treatment , and the increased expression is dependent on the CRE site .", "target_text": { "bcl-2": "protein", "CRE site": "DNA" } }, { "input_text": "These stimuli result in phosphorylation of CREB at serine 133 .", "target_text": { "CREB": "protein" } }, { "input_text": "The phosphorylation of CREB that results in activation is mediated by protein kinase C rather than by protein kinase A .", "target_text": { "CREB": "protein", "protein kinase C": "protein", "protein kinase A": "protein" } }, { "input_text": "Although the CRE site is necessary , optimal induction of bcl-2 expression requires participation of the upstream regulatory element , suggesting that phosphorylation of CREB alters its interaction with the upstream regulatory element .", "target_text": { "CRE site": "DNA", "bcl-2": "protein", "upstream regulatory element": "DNA", "CREB": "protein" } }, { "input_text": "The CRE site in the bcl-2 promoter appears to play a major role in the induction of bcl-2 expression during the activation of mature B cells and during the rescue of immature B cells from apoptosis .", "target_text": { "CRE site": "DNA", "bcl-2 promoter": "DNA", "bcl-2": "protein", "B cells": "cell_type", "mature B cells": "cell_type", "immature B cells": "cell_type" } }, { "input_text": "It is possible that the CRE site is responsible for induction of bcl-2 expression in other cell types , particularly those in which protein kinase C is involved .", "target_text": { "CRE site": "DNA", "bcl-2": "protein", "protein kinase C": "protein" } }, { "input_text": "Characterization of the human myeloid cell nuclear differentiation antigen gene promoter .", "target_text": { "human myeloid cell nuclear differentiation antigen gene promoter": "DNA" } }, { "input_text": "MNDA ( myeloid cell nuclear differentiation antigen ) is an interferon alpha regulated nuclear protein expressed only in cells of the human myelomonocytic lineage .", "target_text": { "MNDA": "protein", "myeloid cell nuclear differentiation antigen": "protein", "interferon alpha regulated nuclear protein": "protein", "human myelomonocytic lineage": "cell_type" } }, { "input_text": "To identify mechanisms responsible for this lineage-specific and interferon-regulated expression , the 5' flanking sequence of the gene has been characterized .", "target_text": { "5' flanking sequence": "DNA" } }, { "input_text": "Two interferon-stimulated response elements ( ISRE ) flank a multiple transcription start site region identifying MNDA as a TATA-less interferon-regulated gene .", "target_text": { "interferon-stimulated response elements": "DNA", "ISRE": "DNA", "MNDA": "protein", "TATA-less interferon-regulated gene": "DNA" } }, { "input_text": "Other DNA elements present include a cluster of Myb sites , several Ets , an Ets related PU.1 site and an Sp1 site located within 600 bp of the transcription start sites .", "target_text": { "DNA elements": "DNA", "Myb sites": "DNA", "Ets": "DNA", "Ets related PU.1 site": "DNA", "Sp1 site": "DNA", "transcription start sites": "DNA" } }, { "input_text": "In addition , DNA methylation was revealed as one of the possible factors in establishing MNDA expression .", "target_text": { "MNDA": "protein" } }, { "input_text": "The 5' flanking sequence has promoter activity which is elevated by interferon alpha .", "target_text": { "5' flanking sequence": "DNA", "interferon alpha": "protein" } }, { "input_text": "The findings indicate that MNDA expression is regulated by mechanisms similar to other myelomonocytic cell specific genes and genes up-regulated by interferon alpha .", "target_text": { "MNDA": "protein", "myelomonocytic cell specific genes": "DNA", "interferon alpha": "protein" } }, { "input_text": "Abnormality of Oct-1 DNA binding in T cells from Sjogren 's syndrome patients .", "target_text": { "Oct-1": "protein", "T cells": "cell_type" } }, { "input_text": "Primary Sjogren 's syndrome ( SS ) is an autoimmune rheumatic disease characterized by T cell hypoactivity .", "target_text": {} }, { "input_text": "To understand the diminished T cell response to activation signals , we measured nucleoprotein DNA-binding activities regulating gene expression during T cell activation using the electrophoretic mobility shift assay .", "target_text": {} }, { "input_text": "Peripheral blood lymphocytes from 9/19 SS patients were found to be defective in their ability to bind an october sequence ( Oct-1 ) .", "target_text": { "Peripheral blood lymphocytes": "cell_type", "october sequence": "protein", "Oct-1": "protein" } }, { "input_text": "This Oct-1 -binding phenotype remained stable in culture for up to 3 days prior to activation .", "target_text": { "Oct-1": "protein" } }, { "input_text": "This abnormality was not seen in resting T cells nor T cells from patients with systemic lupus erythematosus , rheumatoid arthritis ( RA ) , or SS accompanied by RA .", "target_text": { "resting T cells": "cell_type", "T cells": "cell_type" } }, { "input_text": "The SS Oct-1 DNA-binding abnormality correlated significantly with an inability of cells to exit the Gzero/G1 cell cycle phase when stimulated in vitro .", "target_text": { "Oct-1": "protein" } }, { "input_text": "Importantly , nucleoprotein extracts showing decreased DNA-binding activity had normal amounts of Oct-1 proteins as determined by immunoprecipitation , implying a functional defect in the Oct-1 protein .", "target_text": { "Oct-1": "protein", "Oct-1 protein": "protein" } }, { "input_text": "Moreover , defective DNA binding was corrected by treatment with acid phosphatase .", "target_text": {} }, { "input_text": "Characterization of a new isoform of the NFAT ( nuclear factor of activated T cells ) gene family member NFATc [ published erratum appears in J Biol Chem 1996 Dec 27 ; 271 ( 52 ) : 33705 ]", "target_text": { "NFAT": "protein", "nuclear factor of activated T cells": "protein", "NFATc": "protein" } }, { "input_text": "The cyclosporin A ( CsA ) / FK506 -sensitive nuclear factor of activated T cells ( NFAT ) plays a key role in the inducible expression of cytokine genes in T cells .", "target_text": { "cyclosporin A ( CsA ) / FK506 -sensitive nuclear factor of activated T cells": "protein", "NFAT": "protein", "cytokine genes": "DNA", "T cells": "cell_type" } }, { "input_text": "Although NFAT has been recently shown to be inducible in several non-T immune cells , the NFAT gene family members characterized to date have been isolated only from T cells .", "target_text": { "NFAT": "protein", "non-T immune cells": "cell_type", "NFAT gene": "DNA", "NFAT gene family members": "DNA", "T cells": "cell_type" } }, { "input_text": "To further characterize NFAT function in human B cells and to demonstrate cytokine gene specificity of NFAT proteins , we report here the isolation and characterization of a cDNA clone from the Raji B cell line .", "target_text": { "NFAT": "protein", "human B cells": "cell_type", "NFAT proteins": "protein", "cDNA clone": "DNA", "Raji B cell line": "cell_line" } }, { "input_text": "The cDNA clone encodes a new isoform , NFATc.beta , of the NFAT gene family member NFATc ( designated here NFATc.alpha ) .", "target_text": { "cDNA clone": "DNA", "NFATc.beta": "protein", "NFAT": "protein", "NFAT gene family member": "protein", "NFATc": "protein", "NFATc.alpha": "protein" } }, { "input_text": "The amino acid sequence of NFATc.beta differs from that of NFATc .", "target_text": { "amino acid sequence": "protein", "NFATc.beta": "protein", "NFATc": "protein" } }, { "input_text": "alpha in the first NH2-terminal 29 residues and contains an additional region of 142 residues at the COOH terminus .", "target_text": { "NH2-terminal 29 residues": "protein", "142 residues": "protein", "COOH terminus": "protein" } }, { "input_text": "Northern analysis using a probe encompassing a common region of both isoforms showed two mRNA species of 2.7 and 4.5 kilobase pairs , while an NFATc.beta -specific probe detected only the 4.5-kilobase pair mRNA which was preferentially expressed in the spleen .", "target_text": { "mRNA species": "RNA", "NFATc.beta": "protein", "NFATc.beta -specific probe": "DNA", "4.5-kilobase pair mRNA": "RNA" } }, { "input_text": "Transient expression of NFATc.beta was capable of activating an interleukin-2 NFAT -driven reporter gene in stimulated Jurkat cells in a CsA -sensitive manner .", "target_text": { "NFATc.beta": "protein", "interleukin-2": "protein", "NFAT": "protein", "interleukin-2 NFAT -driven reporter gene": "DNA", "Jurkat cells": "cell_line", "stimulated Jurkat cells": "cell_line" } }, { "input_text": "However , NFATc.beta neither bound to the kappa3 element ( an NFAT -binding site ) in the tumor necrosis factor-alpha promoter nor activated the tumor necrosis factor-alpha promoter in cotransfection assays .", "target_text": { "NFATc.beta": "protein", "kappa3 element": "DNA", "NFAT": "protein", "NFAT -binding site": "DNA", "tumor necrosis factor-alpha promoter": "DNA" } }, { "input_text": "These data suggest that different members or isoforms of NFAT gene family may regulate inducible expression of different cytokine genes .", "target_text": { "NFAT": "protein", "NFAT gene": "DNA", "cytokine genes": "DNA" } }, { "input_text": "Regulation of interferon-gamma gene expression .", "target_text": { "interferon-gamma": "protein" } }, { "input_text": "Interferon-gamma ( IFN-gamma ) , also known as type II interferon , is an important immunoregulatory gene that has multiple effects on the development , maturation , and function of the immune system .", "target_text": { "Interferon-gamma": "protein", "IFN-gamma": "protein", "type II interferon": "protein" } }, { "input_text": "IFN-gamma mRNA and protein are expressed predominantly by T cells and large granular lymphocytes .", "target_text": { "IFN-gamma": "protein", "IFN-gamma mRNA": "RNA", "T cells": "cell_type", "large granular lymphocytes": "cell_type" } }, { "input_text": "The IFN-gamma mRNA is induced/inhibited in these cell types by a wide variety of extracellular signals , thus implicating a number of diverse, yet convergent signal transduction pathways in its transcriptional control .", "target_text": { "IFN-gamma": "protein", "IFN-gamma mRNA": "RNA" } }, { "input_text": "In this review , I describe how DNA methylation and specific DNA binding proteins may regulate transcription of the IFN-gamma gene in response to extracellular signals .", "target_text": { "DNA binding proteins": "protein", "IFN-gamma gene": "DNA" } }, { "input_text": "Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma : unique viral latency in the tumour cells .", "target_text": { "tumour cells": "cell_type" } }, { "input_text": "Although case-oriented evidence for an association of Epstein-Barr virus ( EBV ) with gastric carcinoma has been accumulating recently , the interaction ( s ) between EBV and gastric epithelial cells is/are largely unknown .", "target_text": { "gastric epithelial cells": "cell_type" } }, { "input_text": "In this study , we examined seven EBV -positive gastric carcinoma tissues for viral gene expression at the mRNA level , from which studies on the EBV oncogenicity in human epithelial cells will benefit .", "target_text": { "human epithelial cells": "cell_type" } }, { "input_text": "Reverse transcription-PCR analysis showed that all seven EBV -positive tumour tissues constitutively expressed EBV nuclear antigen ( EBNA ) 1 mRNA , but not EBNA2 mRNA .", "target_text": { "EBV nuclear antigen": "protein", "EBNA": "protein", "EBV nuclear antigen ( EBNA ) 1 mRNA": "RNA", "EBNA2 mRNA": "RNA" } }, { "input_text": "The EBNA transcription was initiated from one of three EBNA promoters , Qp : by contrast , both Cp and Wp were silent , thus resulting in the lack of EBNA2 mRNA .", "target_text": { "EBNA": "protein", "EBNA promoters": "DNA", "Qp": "DNA", "Cp": "DNA", "Wp": "DNA", "EBNA2 mRNA": "RNA" } }, { "input_text": "Latent membrane protein ( LMP ) 2A mRNA was detected in three of seven cases ; however , neither LMP1 nor LMP2B mRNA was detected in any of the tumours tested .", "target_text": { "Latent membrane protein ( LMP ) 2A": "protein", "Latent membrane protein ( LMP ) 2A mRNA": "RNA" } }, { "input_text": "Transcripts from the BamHI-A region of the viral genome were detectable in all cases .", "target_text": { "BamHI-A region": "DNA", "viral genome": "DNA" } }, { "input_text": "BZLF1 mRNA and the product , an immediate-early gene for EBV replication , was not expressed in any of them , thereby suggesting that the tumour cells carried EBV genomes in a tightly latent form .", "target_text": { "BZLF1 mRNA": "RNA", "immediate-early gene": "DNA", "tumour cells": "cell_type", "EBV genomes": "DNA" } }, { "input_text": "These findings further extended our previous data regarding EBV latency in gastric carcinoma cells at the protein level , and have affirmed that the programme of viral gene expression in the tumour more closely resembles ' latency I ' represented by Burkitt 's lymphoma than ' latency II ' represented by the majority of nasopharyngeal carcinomas .", "target_text": { "gastric carcinoma cells": "cell_type" } }, { "input_text": "Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking .", "target_text": { "Grb2-binding proteins": "protein", "human platelets": "cell_type", "Fc gamma RIIA": "protein" } }, { "input_text": "Glutathione-S-transferase ( GST ) -Grb2 fusion proteins have been used to identify the potential role of Grb2-binding proteins in platelet activation by the platelet low-affinity IgG receptor , Fc gamma RIIA .", "target_text": { "Glutathione-S-transferase": "protein", "Glutathione-S-transferase ( GST ) -Grb2 fusion proteins": "protein", "Grb2-binding proteins": "protein", "platelet": "cell_type", "platelet low-affinity IgG receptor": "protein", "Fc gamma RIIA": "protein" } }, { "input_text": "Two tyrosine phosphoproteins of 38 and 63 kD bind to the SH2 domain of Grb2 following Fc gamma RIIA stimulation of platelets .", "target_text": { "tyrosine phosphoproteins": "protein", "SH2 domain": "protein", "Grb2": "protein", "Fc gamma RIIA": "protein", "platelets": "cell_type" } }, { "input_text": "Both are located in the particulate fraction following platelet activation and are also able to bind to a GST-construct containing the SH2 and SH3 domains of phospholipase C gamma 1 .", "target_text": { "platelet": "cell_type", "GST-construct": "protein", "phospholipase C gamma 1": "protein" } }, { "input_text": "p38 also forms a complex with the tyrosine kinase csk in stimulated cells and is a substrate for the kinase .", "target_text": { "tyrosine kinase csk": "protein", "stimulated cells": "cell_type", "kinase": "protein" } }, { "input_text": "The SH3 domains of Grb2 form a stable complex with SOS1 and two proteins of 75 kD and 120 kD , which undergo tyrosine phosphorylation in Fc gamma RIIA stimulated cells .", "target_text": { "SH3 domains": "protein", "Grb2": "protein", "SOS1": "protein", "75 kD": "protein", "120 kD": "protein", "Fc gamma RIIA": "protein", "Fc gamma RIIA stimulated cells": "cell_line" } }, { "input_text": "The 75-kD protein is recognized by antibodies to SLP-76 , which has recently been isolated from T cells and sequenced .", "target_text": { "75-kD protein": "protein", "SLP-76": "protein", "T cells": "cell_type" } }, { "input_text": "Tyrosine phosphorylation of p38 and p63 is also observed in platelets stimulated by the tyrosine kinase -linked receptor agonist collagen and by the G protein -coupled receptor agonist thrombin , although phosphorylation of SLP-76 is only observed in collagen -stimulated platelets .", "target_text": { "p38": "protein", "p63": "protein", "platelets": "cell_type", "tyrosine kinase": "protein", "collagen": "protein", "G protein": "protein", "thrombin": "protein", "SLP-76": "protein" } }, { "input_text": "p38 and p63 may provide a docking site for Grb2 , thereby linking Grb2 SH3-binding proteins SOS1 , SLP-76 , and p120 to downstream signalling events .", "target_text": { "p38": "protein", "p63": "protein", "Grb2": "protein", "Grb2 SH3-binding proteins": "protein", "SOS1": "protein", "SLP-76": "protein", "p120": "protein" } }, { "input_text": "Constitutive expression of specific interferon isotypes in peripheral blood leukocytes from normal individuals and in promonocytic U937 cells .", "target_text": { "interferon isotypes": "protein", "peripheral blood leukocytes": "cell_type", "promonocytic U937 cells": "cell_line" } }, { "input_text": "Constitutive expression of IFN-alpha5 and IFN-beta was detected in different lymphoid cells including peripheral blood mononuclear cells from normal individuals following amplification of IFN mRNA by reverse transcriptase -polymerase chain reaction and direct sequencing of the amplified product .", "target_text": { "IFN-alpha5": "protein", "IFN-beta": "protein", "lymphoid cells": "cell_type", "peripheral blood mononuclear cells": "cell_type", "IFN mRNA": "RNA", "reverse transcriptase": "protein", "amplified product": "DNA" } }, { "input_text": "The activated form of the interferon-induced transcription factor complex ISGF3 was also detected in nuclear extracts from uninduced cells .", "target_text": { "interferon-induced transcription factor complex": "protein", "ISGF3": "protein", "uninduced cells": "cell_line" } }, { "input_text": "Culture supernatants from uninduced U937 cells were also found to activate an ISRE cloned upstream of the luciferase reporter gene , indicating the presence of endogenous IFN activity equivalent to approximately 0.3 to 0.5 IU/mL .", "target_text": { "uninduced U937 cells": "cell_line", "ISRE": "DNA", "luciferase": "protein", "luciferase reporter gene": "DNA", "endogenous IFN": "protein" } }, { "input_text": "This endogenous IFN was also shown to play a role in maintaining the basal level of expression of the major histocompatibility class I genes in lymphoid cells .", "target_text": { "endogenous IFN": "protein", "major histocompatibility class I genes": "DNA", "lymphoid cells": "cell_type" } }, { "input_text": "These results suggest that IFN-alpha5 and IFN-beta are produced at low levels in normal tissues and play an important role in the regulation of cell function and in the maintenance of homeostasis .", "target_text": { "IFN-alpha5": "protein", "IFN-beta": "protein" } }, { "input_text": "An IL-2 response element in the human IL-2 receptor alpha chain promoter is a composite element that binds Stat5 , Elf-1 , HMG-I(Y) and a GATA family protein .", "target_text": { "IL-2 response element": "DNA", "human IL-2 receptor alpha chain promoter": "DNA", "composite element": "DNA", "Stat5": "protein", "Elf-1": "protein", "HMG-I(Y)": "protein", "GATA family protein": "protein" } }, { "input_text": "Expression of the human interleukin-2 ( IL-2 ) receptor alpha chain gene is potently upregulated by its own ligand , IL-2 .", "target_text": { "human interleukin-2 ( IL-2 ) receptor alpha chain gene": "DNA", "IL-2": "protein" } }, { "input_text": "In this study , we characterize an essential upstream IL-2 response element that contains both consensus and non-consensus GAS motifs , two putative Ets binding sites ( EBS ) , one of which overlaps the consensus GAS motif , and a GATA motif , which overlaps the non-consensus GAS motif .", "target_text": { "IL-2": "protein", "IL-2 response element": "DNA", "Ets binding sites": "DNA", "EBS": "DNA", "consensus GAS motif": "DNA", "GATA motif": "DNA", "non-consensus GAS motif": "DNA" } }, { "input_text": "We demonstrate that although the individual components of this element do not respond to IL-2 , together they form a composite element capable of conferring IL-2 responsiveness to a heterologous promoter .", "target_text": { "IL-2": "protein", "heterologous promoter": "DNA" } }, { "input_text": "Multiple factors including Stat5 , Elf-1 , HMG-I(Y) and GATA family proteins bind to the IL-2 response element and mutation of any one of these binding sites diminishes the activity of this element .", "target_text": { "Stat5": "protein", "Elf-1": "protein", "HMG-I(Y)": "protein", "GATA family proteins": "protein", "IL-2": "protein", "IL-2 response element": "DNA" } }, { "input_text": "An unidentified Ets family protein binds to the EBS overlapping the consensus GAS motif and appears to negatively regulate the human IL-2R alpha promoter .", "target_text": { "Ets family protein": "protein", "EBS": "DNA", "consensus GAS motif": "DNA", "human IL-2R alpha promoter": "DNA" } }, { "input_text": "Thus , IL-2 -induced IL-2R alpha promoter activity requires a complex upstream element , which appears to contain binding sites for both positive and negative regulatory factors .", "target_text": { "IL-2": "protein", "IL-2R alpha promoter": "DNA", "complex upstream element": "DNA", "binding sites": "DNA" } }, { "input_text": "Lymphocytes from CML patients lack a 47 kDa factor having affinity for a genomic sterol regulatory sequence .", "target_text": { "Lymphocytes": "cell_type", "47 kDa factor": "protein", "genomic sterol regulatory sequence": "DNA" } }, { "input_text": "Deranged cellular cholesterol homeostasis has been widely recognized in the initiation as well as progression of various types of cancers including chronic myeloid leukaemia ( CML ) .", "target_text": {} }, { "input_text": "Since the human genomic sterol regulatory element ( SRE ) has been shown to regulate various key genes involved in this phenomenon , the present study revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects , as well as its absence in lymphocytes from untreated CML patients .", "target_text": { "human genomic sterol regulatory element": "DNA", "SRE": "DNA", "47 kDa protein factor": "protein", "SRE sequence": "DNA", "lymphocytes": "cell_type" } }, { "input_text": "However , this factor appeared when these CML patients achieved complete haematological remission ( CHR ) through alpha-interferon therapy .", "target_text": { "alpha-interferon": "protein" } }, { "input_text": "Furthermore , an inverse relationship was also observed between the LDL receptor gene expression at the transcriptional level and the binding affinity of this 47 kDa protein factor to the SRE sequence .", "target_text": { "LDL receptor": "protein", "LDL receptor gene": "DNA", "47 kDa protein factor": "protein", "SRE sequence": "DNA" } }, { "input_text": "Based upon these results we propose that this factor may have a role in pathophysiology of chronic myeloid leukaemia .", "target_text": {} }, { "input_text": "Cloning and characterization of the beta subunit of human proximal sequence element -binding transcription factor and its involvement in transcription of small nuclear RNA genes by RNA polymerases II and III .", "target_text": { "beta subunit": "protein", "human proximal sequence element": "DNA", "human proximal sequence element -binding transcription factor": "protein", "small nuclear RNA genes": "DNA" } }, { "input_text": "The proximal sequence element ( PSE ) -binding transcription factor ( PTF ) , which binds the PSE of both RNA polymerase II - and RNA polymerase III -transcribed mammalian small nuclear RNA ( snRNA ) genes , is essential for their transcription .", "target_text": { "proximal sequence element ( PSE ) -binding transcription factor": "protein", "PTF": "protein", "PSE": "DNA", "RNA polymerase II": "protein", "RNA polymerase III": "protein", "mammalian small nuclear RNA ( snRNA ) genes": "DNA", "RNA polymerase II - and RNA polymerase III -transcribed mammalian small nuclear RNA ( snRNA ) genes": "DNA" } }, { "input_text": "We previously reported the purification of human PTF , a complex of four subunits , and the molecular cloning and characterization of PTF gamma and delta subunits .", "target_text": { "human PTF": "protein", "four subunits": "protein" } }, { "input_text": "Here we describe the isolation and expression of a cDNA encoding PTF beta , as well as functional studies using anti- PTF beta antibodies .", "target_text": { "cDNA": "DNA", "PTF beta": "protein", "anti- PTF beta antibodies": "protein" } }, { "input_text": "Native PTF beta , in either protein fractions or a PTF-Oct-1-DNA complex , can be recognized by polyclonal antibodies raised against recombinant PTF beta .", "target_text": { "PTF beta": "protein", "PTF-Oct-1-DNA complex": "protein", "polyclonal antibodies": "protein", "recombinant PTF beta": "protein" } }, { "input_text": "Immunodepletion studies show that PTF beta is required for transcription of both classes of snRNA genes in vitro .", "target_text": { "PTF beta": "protein", "snRNA genes": "DNA" } }, { "input_text": "In addition , immunoprecipitation analyses demonstrate that substantial and similar molar amounts of TATA-binding protein ( TBP ) and TFIIIB90 can weakly associate with PTF at low salt conditions , but this association is dramatically reduced at high salt concentrations .", "target_text": { "TATA-binding protein": "protein", "TBP": "protein", "TFIIIB90": "protein", "PTF": "protein" } }, { "input_text": "Along with our previous demonstration of both physical interactions between PTF gamma / PTF delta and TBP and the involvement of TFIIIB90 in the transcription of class III snRNA genes , these results are consistent with the notion that a TBP -containing complex related to TFIIIB is required for the transcription of class III snRNA genes , and acts through weak interaction with the four-subunit PTF .", "target_text": { "PTF": "protein", "PTF gamma / PTF delta": "protein", "TBP": "protein", "TFIIIB90": "protein", "snRNA genes": "DNA", "class III snRNA genes": "DNA", "TBP -containing complex": "protein", "TFIIIB": "protein", "four-subunit PTF": "protein" } }, { "input_text": "Attenuated function of a variant form of the helix-loop-helix protein , Id-3 , generated by an alternative splicing mechanism .", "target_text": { "helix-loop-helix protein": "protein", "Id-3": "protein" } }, { "input_text": "The Id family of helix-loop-helix proteins function as negative regulators of DNA binding , basic helix-loop-helix proteins in the regulation of cell growth and differentiation .", "target_text": { "helix-loop-helix proteins": "protein" } }, { "input_text": "We report here on the identification of a 17 kDa variant of the 14 kDa Id-3 protein termed Id-3L ( long version ) which possesses a unique 60 amino acid carboxy-terminus generated by read through of a ' coding intron ' and alternative splicing .", "target_text": { "17 kDa variant": "protein", "Id-3": "protein", "14 kDa Id-3": "protein", "Id-3L": "protein", "60 amino acid carboxy-terminus": "protein", "coding intron": "DNA" } }, { "input_text": "Northern analysis revealed expression of a minor 1.1 kb Id-3L transcript together with the predominant 0.95 kb Id-3 transcript in the majority of adult human tissues analysed .", "target_text": { "1.1 kb Id-3L transcript": "RNA", "Id-3": "protein", "0.95 kb Id-3 transcript": "RNA" } }, { "input_text": "The variant Id-3L protein is functionally distinguishable from conventional Id-3 since in in vitro DNA mobility shift assays , it was greatly impaired in its ability to abrogate binding of the basic helix-loop-helix protein , E47 , to an E box recognition sequence .", "target_text": { "Id-3L protein": "protein", "Id-3": "protein", "helix-loop-helix protein": "protein", "E47": "protein", "E box recognition sequence": "DNA" } }, { "input_text": "Tyloxapol inhibits NF-kappa B and cytokine release , scavenges HOCI , and reduces viscosity of cystic fibrosis sputum .", "target_text": { "NF-kappa B": "protein", "cytokine": "protein", "HOCI": "protein" } }, { "input_text": "Cystic fibrosis ( CF ) patients develop progressive cytokine -mediated inflammatory lung disease , with abundant production of thick , tenacious , protease - and oxidant-rich purulent airway secretions that are difficult to clear even with physiotherapy .", "target_text": { "cytokine": "protein", "protease": "protein" } }, { "input_text": "In the search for a potential treatment , we have tested tyloxapol , an alkylaryl polyether alcohol polymer detergent previously used as a mucolytic agent in adult chronic bronchitis .", "target_text": {} }, { "input_text": "Tyloxapol inhibits activation of the transcription factor nuclear factor-kappa B ( NK-kappa B ) , reduces resting secretion of the cytokine interleukin-8 ( IL-8 ) in cultured human monocytes , and inhibits lipopolysaccharide ( LPS ) -stimulated release of tumor necrosis factor-alpha ( TNF-alpha ) , IL-1 beta , IL-6 , IL-8 , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , and the eiconsanoids thromboxane A2 and leukotriene B4 ( LTB4 ) .", "target_text": { "transcription factor nuclear factor-kappa B": "protein", "NK-kappa B": "protein", "cytokine": "protein", "interleukin-8": "protein", "IL-8": "protein", "cultured human monocytes": "cell_line", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "IL-1 beta": "protein", "IL-6": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein" } }, { "input_text": "We have previously shown that tyloxapol is a potent antioxidant for hydroxyl radicals ( OH ) .", "target_text": {} }, { "input_text": "Tyloxapol ( 0.05 to 0.1 % wt/vol ) effectively scavenges the oxidant hypochlorous acid ( HOCl ; 1 to 7.5 mM ) in vitro , and protects from HOCl -mediated lung injury in rats .", "target_text": {} }, { "input_text": "Tyloxapol also reduces the viscosity of CF sputum ( from 463 +/- 133 to 128 +/- 52 centipoise ) .", "target_text": {} }, { "input_text": "We conclude that tyloxapol is potentially useful as a new antiinflammatory therapy for CF lung disease , and could possibly promote clearance of secretions in the CF airway .", "target_text": {} }, { "input_text": "Elevated cyclic AMP inhibits NF-kappaB -mediated transcription in human monocytic cells and endothelial cells .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "The NF-kappaB /Rel family of transcription factors regulates the inducible expression of many genes in activated human monocytes and endothelial cells .", "target_text": { "NF-kappaB": "protein", "NF-kappaB /Rel family": "protein", "transcription factors": "protein", "activated human monocytes": "cell_type", "endothelial cells": "cell_type" } }, { "input_text": "In this study , we examined the molecular mechanism by which agents that elevate intracellular cAMP inhibit the expression of the tumor necrosis factor alpha ( TNFalpha ) , tissue factor , endothelial leukocyte adhesion molecule-1 , and vascular cell adhesion molecule-1 genes .", "target_text": { "tumor necrosis factor alpha": "protein", "TNFalpha": "protein", "tissue factor": "protein", "endothelial leukocyte adhesion molecule-1": "protein", "vascular cell adhesion molecule-1": "protein", "vascular cell adhesion molecule-1 genes": "DNA" } }, { "input_text": "Both forskolin and dibutyryl cAMP , which elevate intracellular cAMP by independent mechanisms , inhibited TNFalpha and tissue factor expression at the level of transcription .", "target_text": { "TNFalpha": "protein", "tissue factor": "protein" } }, { "input_text": "Induction of NF-kappaB -dependent gene expression in transiently transfected human monocytic THP-1 cells and human umbilical vein endothelial cells was inhibited by elevated cAMP and by overexpression of the catalytic subunit of protein kinase A ( PKA ) .", "target_text": { "NF-kappaB": "protein", "human monocytic THP-1 cells": "cell_line", "endothelial cells": "cell_type", "human umbilical vein endothelial cells": "cell_type", "catalytic subunit": "protein", "protein kinase A": "protein", "PKA": "protein" } }, { "input_text": "Elevated cAMP did not prevent nuclear translocation of p50/p65 and c-Rel/p65 heterodimers , decrease nuclear translocation of p65 , or significantly modify TNFalpha -induced phosphorylation of p65 .", "target_text": { "p50/p65": "protein", "c-Rel/p65 heterodimers": "protein", "p65": "protein", "TNFalpha": "protein" } }, { "input_text": "Functional studies demonstrated that transcriptional activation of a plasmid containing multimerized kappaB sites by p65 was inhibited by agents that elevate cAMP and by overexpression of the catalytic subunit of PKA .", "target_text": { "plasmid": "DNA", "multimerized kappaB sites": "DNA", "p65": "protein", "catalytic subunit": "protein", "PKA": "protein" } }, { "input_text": "This study indicates that activation of PKA reduces the induction of a distinct set of genes in monocytes and endothelial cells by inhibiting NF-kappaB -mediated transcription .", "target_text": { "PKA": "protein", "genes": "DNA", "monocytes": "cell_type", "endothelial cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "Molecular mechanisms of steroid action : a novel type of cross-talk between glucocorticoids and NF-kappa B transcription factors .", "target_text": { "NF-kappa B": "protein", "transcription factors": "protein" } }, { "input_text": "Despite the widespread use of glucocorticoids in the treatment of diseases characterized by inflammation , the molecular mechanism ( s ) by which these hormones exert this beneficial effect in patients with asthma remains to be elucidated .", "target_text": {} }, { "input_text": "Therefore , we have studied the transcriptional regulation of intercellular adhesion molecule-1 ( ICAM-1 ) as adhesion molecules are likely to play a causal role in inflammation in promoting cell-cell and cell-matrix interactions .", "target_text": { "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "adhesion molecules": "protein" } }, { "input_text": "We observed that in a monocytic ( U937 ) and a bronchial epithelial ( H292 ) cell-line dexamethasone strongly suppressed basal and induced ICAM-1 expression .", "target_text": { "monocytic ( U937 )": "cell_line", "bronchial epithelial ( H292 ) cell-line": "cell_line", "ICAM-1": "protein" } }, { "input_text": "Subsequent analysis of the human ICAM-1 promoter has revealed that both 12-O-tetradecanoylphorbol 13-acetate ( TPA ) and tumour necrosis factor-alpha ( TNF-alpha ) upregulate ICAM-1 expression through the presence of a nuclear factor ( NF-kappa B ) target sequence ( TGGAAATTCC ) .", "target_text": { "ICAM-1": "protein", "ICAM-1 promoter": "DNA", "human ICAM-1 promoter": "DNA", "tumour necrosis factor-alpha": "protein", "TNF-alpha": "protein", "nuclear factor": "protein", "NF-kappa B": "protein", "nuclear factor ( NF-kappa B ) target sequence": "DNA" } }, { "input_text": "No glucocorticoid recognition sequences are present in this promoter region and dexamethasone is still able to repress transcription when the multimerized NF-kappa B sequence is transactivated by TNF-alpha upon transfection in 293 cells .", "target_text": { "glucocorticoid recognition sequences": "DNA", "promoter region": "DNA", "NF-kappa B": "protein", "multimerized NF-kappa B sequence": "DNA", "TNF-alpha": "protein", "293 cells": "cell_line" } }, { "input_text": "We propose that direct interaction between the glucocorticoid receptor and nuclear factor-kappa B factors is at least a partial explanation for the effects of this hormone in inflammatory diseases .", "target_text": { "glucocorticoid receptor": "protein", "nuclear factor-kappa B factors": "protein", "inflammatory diseases": "protein" } }, { "input_text": "Abnormalities of p16 , p15 and CDK4 genes in recurrent malignant astrocytomas .", "target_text": {} }, { "input_text": "Abnormalities in the p16 , p15 and CDK4 genes that regulate transition through the G1 phase of the cell cycle have been implicated in the malignant progression of astrocytomas .", "target_text": {} }, { "input_text": "The results of the present study demonstrate that dysfunction of these genes also occurs during recurrence of glial tumors that were highly malignant at first presentation .", "target_text": { "genes": "DNA" } }, { "input_text": "Analysis of 10 matched pairs of high grade malignant astrocytomas and their subsequent recurrences identified three distinct groups .", "target_text": {} }, { "input_text": "The primary and recurrent tumors in Group A did not show structural alterations in the p16 , p15 or CDK4 genes , whereas homozygous codeletion of p16 and p15 was observed in both primary and recurrent tumors in Group B .", "target_text": { "p16": "DNA", "p15": "DNA" } }, { "input_text": "The primary tumors in Group C had a normal profile of p16 , p15 and CDK4 at presentation .", "target_text": { "p16": "protein", "p15": "protein", "CDK4": "protein" } }, { "input_text": "Upon recurrence , however , the tumors sustained either deletion of p16 alone or codeletion of both p16 and p15 or amplification of CDK4 .", "target_text": { "p16": "protein", "p15": "protein", "CDK4": "protein" } }, { "input_text": "Analysis of the molecular differences between primary anaplastic astrocytomas /glioblastomas and their subsequent recurrences , which are clinically indistinguishable , may provide better therapeutic options for treatment .", "target_text": {} }, { "input_text": "BCL-6 , a POZ/zinc-finger protein , is a sequence-specific transcriptional repressor .", "target_text": { "BCL-6": "protein", "POZ/zinc-finger protein": "protein", "sequence-specific transcriptional repressor": "protein" } }, { "input_text": "Approximately 40 % of diffuse large cell lymphoma are associated with chromosomal translocations that deregulate the expression of the BCL6 gene by juxtaposing heterologous promoters to the BCL-6 coding domain .", "target_text": { "BCL6 gene": "DNA", "heterologous promoters": "DNA", "BCL-6": "protein", "BCL-6 coding domain": "DNA" } }, { "input_text": "The BCL6 gene encodes a 95-kDa protein containing six C-terminal zinc-finger motifs and an N-terminal POZ domain , suggesting that it may function as a transcription factor .", "target_text": { "BCL6 gene": "DNA", "95-kDa protein": "protein", "C-terminal zinc-finger motifs": "protein", "N-terminal POZ domain": "protein", "transcription factor": "protein" } }, { "input_text": "By using a DNA sequence selected for its ability to bind recombinant BCL-6 in vitro , we show here that BCL-6 is present in DNA-binding complexes in nuclear extracts from various B-cell lines .", "target_text": { "DNA sequence": "DNA", "BCL-6": "protein", "recombinant BCL-6": "protein", "DNA-binding complexes": "protein", "B-cell lines": "cell_line" } }, { "input_text": "In transient transfectin experiments , BCL6 can repress transcription from promoters linked to its DNA target sequence and this activity is dependent upon specific DNA-binding and the presence of an intact N-terminal half of the protein .", "target_text": { "BCL6": "protein", "promoters": "DNA", "DNA target sequence": "DNA", "N-terminal half": "protein" } }, { "input_text": "We demonstrate that this part of the BCL6 molecule contains an autonomous transrepressor domain and that two noncontiguous regions , including the POZ motif , mediate maximum transrepressive activity .", "target_text": { "BCL6": "protein", "BCL6 molecule": "protein", "autonomous transrepressor domain": "protein", "noncontiguous regions": "protein", "POZ motif": "protein" } }, { "input_text": "These results indicate that the BCL-6 protein can function as a sequence-specific transcriptional repressor and have implications for the role of BCL6 in normal lymphoid development and lymphomagenesis .", "target_text": { "BCL-6": "protein", "BCL-6 protein": "protein", "sequence-specific transcriptional repressor": "protein", "BCL6": "protein" } }, { "input_text": "Signals leading to the activation of NF-kappa B transcription factor are stronger in neonatal than adult T lymphocytes .", "target_text": { "NF-kappa B": "protein", "NF-kappa B transcription factor": "protein" } }, { "input_text": "The molecular background of the defects in the immune reactivity of human neonates has not been fully elucidated .", "target_text": {} }, { "input_text": "As the NF-kappa B transcription factor has a central role in the control of transcription of several genes involved in immune and inflammatory responses , the authors have analysed the activation of NF-kappa B in human umbilical cord T lymphocytes .", "target_text": { "NF-kappa B": "protein", "NF-kappa B transcription factor": "protein", "genes": "DNA", "human umbilical cord T lymphocytes": "cell_type" } }, { "input_text": "The activity was tested by quantitating the nuclear proteins binding to an oligonucleotide containing the consensus kappa B binding sequence ( electrophoretic mobility shift assay ) .", "target_text": { "nuclear proteins": "protein", "consensus kappa B binding sequence": "DNA" } }, { "input_text": "The data obtained demonstrate that phorbol dibutyrate/calcium ionophore A23187 ( PDBu/iono ) combination induced a clearly higher nuclear translocation of NF-kappa B in neonatal than adult T cells .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "This higher NF-kappa B activity was restricted to the CD4+ T-cell subset .", "target_text": { "NF-kappa B": "protein", "CD4+ T-cell subset": "cell_type" } }, { "input_text": "Analysis of the nuclear extracts with antibodies directed against the major components of NF-kappa B the p50 and RelA ( p65 ) proteins , indicated that the composition of NF-kappa B was similar in neonatal and adult cells .", "target_text": { "antibodies": "protein", "NF-kappa B": "protein" } }, { "input_text": "These results suggest that neonatal T cells are exposed to oxidative stress-inducing signals during delivery and/or are inherently more sensitive to NF-kappa B activating signals than adult T cells .", "target_text": { "neonatal T cells": "cell_type", "NF-kappa B": "protein", "adult T cells": "cell_type" } }, { "input_text": "Dual action of retinoic acid on human embryonic/fetal hematopoiesis : blockade of primitive progenitor proliferation and shift from multipotent/erythroid/monocytic to granulocytic differentiation program .", "target_text": {} }, { "input_text": "In preliminary studies , we have analyzed the hematopoietic growth factor ( HGF ) requirement of hematopoietic progenitor cells ( HPCs ) purified from embryonic-fetal liver ( FL ) and grown in fetal calf serum-supplemented ( FCS+ ) clonogenic culture .", "target_text": { "hematopoietic growth factor": "protein", "HGF": "protein", "hematopoietic progenitor cells": "cell_type", "HPCs": "cell_type" } }, { "input_text": "The key role of erythropoietin ( Epo ) for colony formation by early erythroid progenitors ( burst-forming units-erythroid [ BFU-E ] ) has been confirmed .", "target_text": { "erythropoietin": "protein", "Epo": "protein", "early erythroid progenitors": "cell_type", "burst-forming units-erythroid": "cell_type", "BFU-E": "cell_type" } }, { "input_text": "Furthermore , in the absence of exogenous HGFs , FL monocytic progenitors ( colony-forming unit monocyte [ CFU-M ] ) generate large colonies exclusively composed of monocytes-macrophages ; these colonies are absent in FCS- clonogenic culture .", "target_text": { "HGFs": "protein", "FL monocytic progenitors": "cell_type", "colony-forming unit monocyte": "cell_type", "CFU-M": "cell_type" } }, { "input_text": "On this basis , we have investigated the role of all-trans retinoic acid ( ATRA ) and its isomer 9-cis RA in FL hematopoiesis .", "target_text": {} }, { "input_text": "Both compounds modulate the growth of purified FL HPCs , which show a dose-dependent shift from mixed / erythroid / monocytic to granulocytic colony formation .", "target_text": { "HPCs": "cell_type", "purified FL HPCs": "cell_line" } }, { "input_text": "Studies on unicellular and paired daughter cell culture unequivocally indicate that the shift is mediated by modulation of the HPC differentiation program to the granulopoietic pathway ( rather than RA-induced down-modulation of multipotent / erythroid /monocytic HPC growth coupled with recruitment of granulocytic HPCs ) .", "target_text": { "HPCs": "cell_type", "granulocytic HPCs": "cell_type" } }, { "input_text": "ATRA and 9-cis RA also exert their effect on the proliferation of primitive HPCs ( high-proliferative potential colony-forming cells [ HPP-CFCs ] ) and putative hematopoietic stem cells ( HSCs ; assayed in Dexter-type long-term culture ) .", "target_text": { "HPCs": "cell_type", "primitive HPCs": "cell_type", "high-proliferative potential colony-forming cells": "cell_line", "HPP-CFCs": "cell_line", "putative hematopoietic stem cells": "cell_type", "HSCs": "cell_type" } }, { "input_text": "High concentrations of either compound ( 1 ) drastically reduced the number of primary HPP-CFC colonies and totally abolished their recloning capacity and ( 2 ) inhibited HSC proliferation .", "target_text": { "HPP-CFC colonies": "cell_line", "HSC": "cell_type" } }, { "input_text": "It is crucial that these results mirror recent observations indicating that murine adult HPCs transduced with dominant negative ATRA receptor ( RAR ) gene are immortalized and show a selective blockade of granulocytic differentiation .", "target_text": { "HPCs": "cell_type", "ATRA receptor ( RAR ) gene": "DNA" } }, { "input_text": "Altogether , these results suggest that ATRA /9-cis RA may play a key role in FL hematopoiesis via a dual effect hypothetically mediated by interaction with the RAR/RXR heterodimer , ie , inhibition of HSC/ primitive HPC proliferation and induction of CFU-GEMM/ BFU-E/CFU-M shift from the multipotent / erythroid / monocytic to the granulocytic-neutrophilic differentiation program .", "target_text": { "RAR/RXR heterodimer": "protein", "HSC/ primitive HPC": "cell_line" } }, { "input_text": "Dexamethasone suppression test : corticosteroid receptors regulation in mononuclear leukocytes of young and aged subjects .", "target_text": { "corticosteroid receptors": "protein", "mononuclear leukocytes": "cell_type" } }, { "input_text": "The dexamethasone suppression test ( DST ) is considered an indicator of the function of the adrenal pituitary axis .", "target_text": {} }, { "input_text": "The effect of the steroid is mediated by its binding to corticosteroid receptors .", "target_text": { "corticosteroid receptors": "protein" } }, { "input_text": "We previously suggested that the measurement of corticosteroid receptors in lymphocytes is an index of an analogous pattern in brain .", "target_text": { "corticosteroid receptors": "protein", "lymphocytes": "cell_type" } }, { "input_text": "In the present study , corticosteroid Type I and Type II receptors in mononuclear leukocytes were measured in 10 elderly subjects and in 9 young adults , before and after overnight DST ( 1 mg ) .", "target_text": { "mononuclear leukocytes": "cell_type" } }, { "input_text": "Receptors were measured by radioreceptor assay .", "target_text": {} }, { "input_text": "In all the subjects , dexamethasone was able to suppress plasma cortisol .", "target_text": {} }, { "input_text": "The number of Type I and Type II receptors before the test was lower in elderly subjects than in adults .", "target_text": {} }, { "input_text": "In the control group , dexamethasone produced a significant depression of Type I receptors ( from 267 +/- 72 to 169 +/- 71 receptors per cell ) , which can be interpreted as a primary involvement of Type I receptors in the response to dexamethasone ; Type II receptors decreased in half the subjects ( from 2849 +/- 703 to 2345 +/- 569 receptors per cell ) .", "target_text": { "Type I receptors": "protein", "Type II receptors": "protein" } }, { "input_text": "In elderly healthy subjects , Type II receptors were also significantly decreased ( from 1796 +/- 671 to 720 +/- 345 ) .", "target_text": { "Type II receptors": "protein" } }, { "input_text": "We suggest that in young subjects Type II receptors are initially up-regulated by dexamethasone , and then down-regulated , while in aged subjects an up-regulation can not be achieved , as suggested by the higher values of plasma cortisol usually found in aging subjects .", "target_text": { "Type II receptors": "protein" } }, { "input_text": "Analysis of the ligand-binding domain of human retinoic acid receptor alpha by site-directed mutagenesis .", "target_text": { "ligand-binding domain": "protein", "human retinoic acid receptor alpha": "protein" } }, { "input_text": "Three subtypes of retinoic acid receptors ( RAR ) , termed RAR alpha , RAR beta , and RAR gamma , have been described .", "target_text": { "retinoic acid receptors": "protein", "RAR": "protein", "RAR alpha": "protein", "RAR beta": "protein", "RAR gamma": "protein" } }, { "input_text": "They are composed of different structural domains , including distinct domains for DNA and ligand binding .", "target_text": { "structural domains": "protein" } }, { "input_text": "RARs specifically bind all-trans-retinoic acid ( RA ) , 9-cis-RA , and retinoid analogs .", "target_text": { "RARs": "protein" } }, { "input_text": "In this study , we examined the functional role of cysteine and arginine residues in the ligand-binding domain of hRAR alpha ( hRAR alpha-LBD , amino acids 154 to 462 ) .", "target_text": { "ligand-binding domain": "protein", "hRAR alpha": "protein", "hRAR alpha-LBD": "protein", "amino acids 154 to 462": "protein" } }, { "input_text": "All conserved cysteine and arginine residues in this domain were mutated by site-directed mutagenesis , and the mutant proteins were characterized by blocking reactions , ligand-binding experiments , transactivation assays , and protease mapping .", "target_text": { "mutant proteins": "protein", "protease": "protein" } }, { "input_text": "Changes of any cysteine residue of the hRAR alpha-LBD had no significant influence on the binding of all-trans RA or 9-cis RA .", "target_text": { "hRAR alpha-LBD": "protein" } }, { "input_text": "Interestingly , residue C-235 is specifically important in antagonist binding .", "target_text": {} }, { "input_text": "With respect to arginine residues , only the two single mutations of R-276 and R-394 to alanine showed a dramatic decrease of agonist and antagonist binding whereas the R272A mutation showed only a slight effect .", "target_text": {} }, { "input_text": "For all other arginine mutations , no differences in affinity were detectable .", "target_text": {} }, { "input_text": "The two mutations R217A and R294A caused an increased binding efficiency for antagonists but no change in agonist binding .", "target_text": {} }, { "input_text": "From these results , we can conclude that electrostatic interactions of retinoids with the RAR alpha -LBD play a significant role in ligand binding .", "target_text": { "RAR alpha": "protein", "RAR alpha -LBD": "protein" } }, { "input_text": "In addition , antagonists show distinctly different requirements for efficient binding , which may contribute to their interference in the ligand-inducible transactivation function of RAR alpha .", "target_text": { "RAR alpha": "protein" } }, { "input_text": "IL4 and IL13 receptors share the gamma c chain and activate STAT6 , STAT3 and STAT5 proteins in normal human B cells .", "target_text": { "gamma c chain": "protein", "normal human B cells": "cell_type" } }, { "input_text": "IL13 induces the same biological effects as IL4 in normal human B cells .", "target_text": { "IL13": "protein", "IL4": "protein", "normal human B cells": "cell_type" } }, { "input_text": "We show that as in the IL4R complex , both IL4R alpha and IL2R gamma c are components of the IL13R and that both cytokines induced STAT6 , STAT3 and STAT5 activation in B cells .", "target_text": { "IL4R complex": "protein", "IL4R alpha": "protein", "IL2R gamma c": "protein", "IL13R": "protein", "cytokines": "protein", "STAT6": "protein", "STAT3": "protein", "STAT5": "protein", "B cells": "cell_type" } }, { "input_text": "In spite of this similar downstream signalling , IL4 and IL13 used a different set of Janus kinases : IL13 is unable to activate JAK1 and JAK3 .", "target_text": { "IL4": "protein", "IL13": "protein", "Janus kinases": "protein", "JAK1": "protein", "JAK3": "protein" } }, { "input_text": "Calcineurin mutants render T lymphocytes resistant to cyclosporin A .", "target_text": { "Calcineurin mutants": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "The immunosuppressants cyclosporin A ( CsA ) and FK506 have been widely used to prevent and treat graft rejection after human organ and tissue transplantations .", "target_text": {} }, { "input_text": "CsA and FK506 associate with intracellular binding proteins ( i.e. , CsA with cyclophilin A and FK506 with FKBP12 ) to form protein/drug complexes that suppress the immune system by preventing activation of T cells in response to antigen presentation .", "target_text": { "intracellular binding proteins": "protein", "cyclophilin A": "protein", "FKBP12": "protein", "T cells": "cell_type" } }, { "input_text": "The common target of CsA and FK506 is calcineurin , a Ca2+/calmodulin-regulated , serine/threonine-specific protein phosphatase that regulates the nuclear import of a transcription factor , NF-AT , required for expression of T cell activation genes .", "target_text": { "calcineurin": "protein", "Ca2+/calmodulin-regulated , serine/threonine-specific protein phosphatase": "protein", "transcription factor": "protein", "NF-AT": "protein", "T cell activation genes": "DNA" } }, { "input_text": "In previous studies , we identified calcineurin mutations that block binding by the cyclophilin A /CsA or FKBP12 /FK506 complexes and thereby render yeast cells resistant to the antifungal effects of CsA or FK506 .", "target_text": { "calcineurin": "protein", "calcineurin mutations": "protein", "cyclophilin A": "protein", "FKBP12": "protein" } }, { "input_text": "In this report , we demonstrate that the corresponding mutations in murine calcineurin render the T cell receptor signal transduction cascade CsA resistant in human Jurkat T cells .", "target_text": { "calcineurin": "protein", "T cell receptor": "protein", "human Jurkat T cells": "cell_line" } }, { "input_text": "Our findings support the recently determined calcineurin X-ray crystal structure , provide evidence that calcineurin is the only CsA -sensitive component limiting signaling from the T cell receptor to the nucleus , and suggest a means to render cells and tissues resistant to the toxic side effects of CsA and FK506 .", "target_text": { "calcineurin": "protein", "CsA -sensitive component": "protein", "T cell receptor": "protein" } }, { "input_text": "Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism .", "target_text": { "immediate-early BRLF1 protein": "protein" } }, { "input_text": "Epstein-Barr virus ( EBV ) , the causative agent of infectious mononucleosis , is a human herpesvirus associated with epithelial cell malignancies ( nasopharyngeal carcinoma ) as well as B-cell malignancies .", "target_text": {} }, { "input_text": "Understanding how viral latency is disrupted is a central issue in herpesvirus biology .", "target_text": {} }, { "input_text": "Epithelial cells are the major site of lytic EBV replication within the human host , and viral reactivation occurs in EBV -associated nasopharyngeal carcinomas .", "target_text": {} }, { "input_text": "It is known that expression of a single viral immediate-early protein , BZLF1 , is sufficient to initiate the switch from latent to lytic infection in B cells .", "target_text": { "viral immediate-early protein": "protein", "BZLF1": "protein", "B cells": "cell_type" } }, { "input_text": "Cellular regulation of BZLF1 transcription is therefore thought to play a key role in regulating the stringency of viral latency .", "target_text": { "BZLF1": "protein" } }, { "input_text": "Here we show that , unexpectedly , expression of another viral immediate-early protein , BRLF1 , can disrupt viral latency in an epithelial cell-specific fashion .", "target_text": { "viral immediate-early protein": "protein", "BRLF1": "protein" } }, { "input_text": "Therefore , the mechanisms leading to disruption of EBV latency appear to be cell-type specific .", "target_text": {} }, { "input_text": "Eosinophil priming by cytokines : from cellular signal to in vivo modulation .", "target_text": { "Eosinophil": "cell_type", "cytokines": "protein" } }, { "input_text": "Eosinophils play an important role in the effector phase of allergic inflammation .", "target_text": { "Eosinophils": "cell_type" } }, { "input_text": "This review will focus on the conversion of the unprimed eosinophil phenotype in the peripheral blood of normal individuals to the primed phenotype found in the peripheral blood and tissues of allergic patients , a phenomenon called priming .", "target_text": {} }, { "input_text": "Recent data on the signals initiated after cytokine receptor activation on eosinophils will be reviewed .", "target_text": { "cytokine receptor": "protein", "eosinophils": "cell_type" } }, { "input_text": "CTL recognition of an altered peptide associated with asparagine bond rearrangement .", "target_text": {} }, { "input_text": "Implications for immunity and vaccine design .", "target_text": {} }, { "input_text": "The extent to which peptides containing chemically and post-translationally modified amino acid side chains are recognized by primed CTL has not been clearly defined .", "target_text": { "amino acid side chains": "protein", "primed CTL": "cell_line" } }, { "input_text": "We report on the CTL recognition of a MHC class I-restricted peptide containing a cyclized asparagine ( succinimide ) residue .", "target_text": {} }, { "input_text": "This modification of the asparagine side chain is a common intermediate structure during deamidation , isomerization , and bond rearrangements of amide-containing amino acids and also occurs as a side reaction in peptide synthesis .", "target_text": {} }, { "input_text": "The CTL specifically recognized the succinimide-containing peptide showing only weak cross-reactivity at high concentrations of the parent peptide containing unmodified asparagine .", "target_text": { "CTL": "cell_type" } }, { "input_text": "Similarly , CTL raised against the parent peptide did not recognize the succinimide derivative of this peptide .", "target_text": { "CTL": "cell_type" } }, { "input_text": "Naturally processed forms of these structures are likely to occur given the importance and frequency of deamidation both in vitro and in vivo .", "target_text": {} }, { "input_text": "Moreover , since succinimide intermediates of deamidated peptides can occasionally be very stable , these peptides have the potential to act as altered self-Ags with significant implications for autoimmunity .", "target_text": {} }, { "input_text": "In addition , unwanted and potentially hazardous specificities may be elicited when using synthetic peptides in subunit vaccines in which succinimide residues may form spontaneously during storage or chemical synthesis .", "target_text": {} }, { "input_text": "A 3' --> 5' XPB helicase defect in repair/transcription factor TFIIH of xeroderma pigmentosum group B affects both DNA repair and transcription .", "target_text": { "XPB helicase": "protein", "repair/transcription factor": "protein", "TFIIH": "protein" } }, { "input_text": "XPB is a subunit of the basal transcription factor TFIIH , which is also involved in nucleotide excision repair ( NER ) and potentially in cell cycle regulation .", "target_text": { "XPB": "protein", "transcription factor": "protein", "TFIIH": "protein" } }, { "input_text": "A frameshift mutation in the 3'-end of the XPB gene is responsible for a concurrence of two disorders : xeroderma pigmentosum ( XP ) and Cockayne 's syndrome ( CS ) .", "target_text": { "XPB": "protein", "XPB gene": "DNA" } }, { "input_text": "We have isolated TFIIH from cells derived from a patient ( XP11BE ) who carries this frameshift mutation ( TFIIHmut ) and from the mother of this patient ( TFIIHwt ) to determine the biochemical consequences of the mutation .", "target_text": { "TFIIH": "protein", "TFIIHmut": "protein", "TFIIHwt": "protein" } }, { "input_text": "Although identical in composition and stoichiometry to TFIIHwt , TFIIHmut shows a reduced 3' --> 5' XPB helicase activity .", "target_text": { "TFIIHwt": "protein", "TFIIHmut": "protein", "XPB": "protein" } }, { "input_text": "A decrease in helicase and DNA-dependent ATPase activities was also observed with the mutated recombinant XPB protein .", "target_text": { "DNA-dependent ATPase": "protein", "XPB": "protein", "XPB protein": "protein" } }, { "input_text": "The XPB mutation causes a severe NER defect .", "target_text": { "XPB": "protein" } }, { "input_text": "In addition , we provide evidence for a decrease in basal transcription activity in vitro .", "target_text": {} }, { "input_text": "The latter defect may provide an explanation for many of the XP and CS symptoms that are difficult to rationalize based solely on an NER defect .", "target_text": {} }, { "input_text": "Thus , this work presents the first detailed analysis of a naturally occurring mutation in a basal transcription factor and supports the concept that the combined XP/ CS clinical entity is actually the result of a combined transcription/repair deficiency .", "target_text": { "transcription factor": "protein", "basal transcription factor": "protein" } }, { "input_text": "The Ets protein Spi-B is expressed exclusively in B cells and T cells during development .", "target_text": { "Spi-B": "protein", "B cells": "cell_type", "T cells": "cell_type" } }, { "input_text": "Spi-B and PU.1 are hematopoietic-specific transcription factors that constitute a subfamily of the Ets family of DNA-binding proteins .", "target_text": { "Spi-B": "protein", "PU.1": "protein", "hematopoietic-specific transcription factors": "protein", "Ets family": "protein", "DNA-binding proteins": "protein" } }, { "input_text": "Here we show that contrary to previous reports , PU.1 and Spi-B have very different expression patterns .", "target_text": { "PU.1": "protein", "Spi-B": "protein" } }, { "input_text": "PU.1 is expressed at high levels in B cells , mast cells , megakaryocytes , macrophages , neutrophils , and immature erythroid cells and at lower levels in mature erythrocytes .", "target_text": { "PU.1": "protein", "B cells": "cell_type", "mast cells": "cell_type", "megakaryocytes": "cell_type", "macrophages": "cell_type", "neutrophils": "cell_type", "immature erythroid cells": "cell_type", "mature erythrocytes": "cell_type" } }, { "input_text": "PU.1 is completely absent from peripheral T cells and most T cell lines based on sensitive RT-PCR assays .", "target_text": { "PU.1": "protein", "peripheral T cells": "cell_type", "T cell lines": "cell_line" } }, { "input_text": "In contrast , Spi-B is expressed exclusively in lymphoid cells and can be detected in early fetal thymus and spleen .", "target_text": { "Spi-B": "protein", "lymphoid cells": "cell_type" } }, { "input_text": "In situ hybridizations of adult murine tissues demonstrate Spi-B mRNA in the medulla of the thymus , the white pulp of the spleen , and the germinal centers of lymph nodes .", "target_text": { "Spi-B": "protein", "Spi-B mRNA": "RNA" } }, { "input_text": "Spi-B expression is very abundant in B cells and both Spi-B mRNA and protein are detected in some T cells .", "target_text": { "Spi-B": "protein", "B cells": "cell_type", "Spi-B mRNA": "RNA", "T cells": "cell_type" } }, { "input_text": "In situ hybridization and Northern blot analysis suggest that Spi-B gene expression increases during B cell maturation and decreases during T cell maturation .", "target_text": { "Spi-B": "protein" } }, { "input_text": "Gel-retardation experiments show that Spi-B can bind to all putative PU.1 binding sites , but do not reveal any preferred Spi-B binding site .", "target_text": { "Spi-B": "protein", "PU.1": "protein", "putative PU.1 binding sites": "DNA", "Spi-B binding site": "DNA" } }, { "input_text": "Finally , both PU.1 and Spi-B function as transcriptional activators of the immunoglobulin light-chain enhancer E lambda 2.4 when coexpressed with Pip ( PU.1 -interaction partner ) in NIH-3T3 cells .", "target_text": { "PU.1": "protein", "Spi-B": "protein", "immunoglobulin light-chain enhancer": "DNA", "E lambda 2.4": "DNA", "immunoglobulin light-chain enhancer E lambda 2.4": "DNA", "Pip": "protein", "PU.1 -interaction partner": "protein", "NIH-3T3 cells": "cell_line" } }, { "input_text": "Taken together , these data suggest that differences in patterns of expression between Spi-B and PU.1 distinguish the function of each protein during development of the immune system .", "target_text": { "Spi-B": "protein", "PU.1": "protein" } }, { "input_text": "A critical role of Sp1- and Ets- related transcription factors in maintaining CTL-specific expression of the mouse perforin gene .", "target_text": { "mouse perforin gene": "DNA" } }, { "input_text": "This study was designed to determine the potential cis-elements involved in transcriptional regulation of the mouse perforin gene .", "target_text": { "cis-elements": "DNA", "mouse perforin gene": "DNA" } }, { "input_text": "DNase I hypersensitive site ( DHS ) mapping revealed that the perforin locus contained six DHS within 7.0 kb of the 5' upstream sequence ( -7.0 kb ) and two DHS in intron 2 .", "target_text": { "DNase I hypersensitive site": "DNA", "DHS": "DNA", "perforin locus": "DNA", "5' upstream sequence": "DNA", "intron 2": "DNA" } }, { "input_text": "The six 5' upstream and one intronic DHS were detected in only perforin-expressing lymphocytes .", "target_text": { "5' upstream": "DNA", "DHS": "DNA", "intronic DHS": "DNA", "perforin-expressing lymphocytes": "cell_type" } }, { "input_text": "Chloramphenicol acetyltransferase ( CAT ) activities directed by 5' upstream promoter were detected preferentially in perforin-expressing cell lines .", "target_text": { "Chloramphenicol acetyltransferase": "protein", "CAT": "protein", "5' upstream promoter": "DNA", "perforin-expressing cell lines": "cell_line" } }, { "input_text": "A construct termed PFP5a containing -795 bp exhibited the highest CAT activity , and PFP9a20 containing only -73 bp also produced significantly high CAT activity in CTLL-R8 cells .", "target_text": { "PFP5a": "DNA", "-795 bp": "DNA", "CAT": "protein", "PFP9a20": "DNA", "-73 bp": "DNA", "CTLL-R8 cells": "cell_line" } }, { "input_text": "The proximal region in PFP9a20 contained two potential Sp1 binding sites ( GC box and GT box ) and one Ets binding site ( EBS ) .", "target_text": { "proximal region": "DNA", "PFP9a20": "DNA", "Sp1 binding sites": "DNA", "GC box": "DNA", "GT box": "DNA", "Ets binding site": "DNA", "EBS": "DNA" } }, { "input_text": "Electrophoretic mobility shift assay showed that each of the cis-elements bound specific protein factors .", "target_text": { "cis-elements": "DNA", "protein factors": "protein" } }, { "input_text": "When single-point mutation was introduced to each GC box , EBS , and GT box in PFP9a20 , at least 3-fold less CAT activity was observed in CTLL-R8 cells .", "target_text": { "GC box": "DNA", "EBS": "DNA", "GT box": "DNA", "PFP9a20": "DNA", "CAT": "protein", "CTLL-R8 cells": "cell_line" } }, { "input_text": "To confirm the importance of the three cis-acting elements in the perforin gene expression , point mutation was introduced again to each proximal GC box , EBS , and GT box of PFP5a .", "target_text": { "cis-acting elements": "DNA", "perforin": "protein", "perforin gene": "DNA", "GC box": "DNA", "proximal GC box": "DNA", "EBS": "DNA", "GT box": "DNA", "PFP5a": "DNA" } }, { "input_text": "The point mutations resulted in a 2.5- to 3-fold reduction of CAT activity .", "target_text": { "CAT": "protein" } }, { "input_text": "The results suggest that a combination of the three proximal cis-acting elements may constitute a minimal region responsible for CTL-specific expression of perforin .", "target_text": { "cis-acting elements": "DNA", "perforin": "protein" } }, { "input_text": "The Oct-2 transcription factor .", "target_text": { "Oct-2 transcription factor": "protein" } }, { "input_text": "The Oct-2 transcription factor is a member of the POU ( Pit-Oct-Unc ) family of transcription factors and is expressed only in B lymphocytes and in neuronal cells but not in other cell types .", "target_text": { "Oct-2 transcription factor": "protein", "POU ( Pit-Oct-Unc ) family": "protein", "transcription factors": "protein", "B lymphocytes": "cell_type", "neuronal cells": "cell_type" } }, { "input_text": "The primary RNA transcript of the gene is subject to alternative splicing to yield different variants which can either activate or repress gene expression .", "target_text": { "primary RNA transcript": "RNA" } }, { "input_text": "The forms produced in B lymphocytes have a predominantly activating effect on gene expression whereas those produced in neuronal cells have a predominantly inhibitory effect and can repress the expression of both the herpes simplex virus immediate-early genes and the cellular tyrosine hydroxylase gene .", "target_text": { "B lymphocytes": "cell_type", "neuronal cells": "cell_type", "herpes simplex virus immediate-early genes": "DNA", "tyrosine hydroxylase": "protein", "cellular tyrosine hydroxylase gene": "DNA" } }, { "input_text": "Thus Oct-2 plays an important role in the regulation of cellular gene expression in both B cells and neuronal cells as well as in the control of viral latency .", "target_text": { "Oct-2": "protein", "B cells": "cell_type", "neuronal cells": "cell_type" } }, { "input_text": "Cell-type-specific regulation of the human tumor necrosis factor alpha gene in B cells and T cells by NFATp and ATF-2/JUN .", "target_text": { "human tumor necrosis factor alpha": "protein", "human tumor necrosis factor alpha gene": "DNA", "B cells": "cell_type", "T cells": "cell_type", "NFATp": "protein", "ATF-2/JUN": "protein" } }, { "input_text": "The human tumor necrosis factor alpha ( TNF-alpha ) gene is one of the earliest genes transcribed after the stimulation of a B cell through its antigen receptor or via the CD-40 pathway .", "target_text": { "human tumor necrosis factor alpha": "protein", "TNF-alpha": "protein", "human tumor necrosis factor alpha ( TNF-alpha ) gene": "DNA", "B cell": "cell_type", "antigen receptor": "protein" } }, { "input_text": "In both cases , induction of TNF-alpha gene transcription can be blocked by the immunosuppressants cyclosporin A and FK506 , which suggested a role for the NFAT family of proteins in the regulation of the gene in B cells .", "target_text": { "TNF-alpha gene": "DNA", "NFAT family": "protein", "B cells": "cell_type" } }, { "input_text": "Furthermore , in T cells , two molecules of NFATp bind to the TNF-alpha promoter element kappa 3 in association with ATF-2 and Jun proteins bound to an immediately adjacent cyclic AMP response element ( CRE ) site .", "target_text": { "T cells": "cell_type", "NFATp": "protein", "TNF-alpha promoter": "DNA", "TNF-alpha promoter element kappa 3": "DNA", "ATF-2": "protein", "Jun proteins": "protein", "cyclic AMP response element": "DNA", "CRE": "DNA", "cyclic AMP response element ( CRE ) site": "DNA" } }, { "input_text": "Here , using the murine B-cell lymphoma cell line A20 , we show that the TNF-alpha gene is regulated in a cell-type-specific manner .", "target_text": { "murine B-cell lymphoma cell line": "cell_line", "A20": "cell_line", "TNF-alpha gene": "DNA" } }, { "input_text": "In A20 B cells , the TNF-alpha gene is not regulated by NFATp bound to the kappa 3 element .", "target_text": { "A20 B cells": "cell_line", "TNF-alpha gene": "DNA", "NFATp": "protein", "kappa 3 element": "DNA" } }, { "input_text": "Instead , ATF-2 and Jun proteins bind to the composite kappa 3/CRE site and NFATp binds to a newly identified second NFAT site centered at -76 nucleotides relative to the TNF-alpha transcription start site .", "target_text": { "ATF-2": "protein", "Jun proteins": "protein", "composite kappa 3/CRE site": "DNA", "NFATp": "protein", "NFAT site": "DNA", "-76 nucleotides": "DNA", "TNF-alpha transcription start site": "DNA" } }, { "input_text": "This new site plays a critical role in the calcium-mediated , cyclosporin A -sensitive induction of TNF-alpha in both A20 B cells and Ar-5 cells .", "target_text": { "TNF-alpha": "protein", "A20 B cells": "cell_line", "Ar-5 cells": "cell_line" } }, { "input_text": "Consistent with these results , quantitative DNase footprinting of the TNF-alpha promoter using increasing amounts of recombinant NFATp demonstrated that the -76 site binds to NFATp with a higher affinity than the kappa 3 site .", "target_text": { "DNase": "protein", "TNF-alpha": "protein", "TNF-alpha promoter": "DNA", "NFATp": "protein", "-76 site": "DNA", "kappa 3 site": "DNA" } }, { "input_text": "Two other previously unrecognized NFATp -binding sites in the proximal TNF-alpha promoter were also identified by this analysis .", "target_text": { "NFATp": "protein", "NFATp -binding sites": "DNA", "TNF-alpha": "protein", "TNF-alpha promoter": "DNA" } }, { "input_text": "Thus , through the differential use of the same promoter element , the composite kappa 3/CRE site , the TNF-alpha gene is regulated in a cell-type-specific manner in response to the same extracellular signal .", "target_text": { "promoter element": "DNA", "composite kappa 3/CRE site": "DNA", "TNF-alpha": "protein", "TNF-alpha gene": "DNA" } }, { "input_text": "Activation of Stat 5b in erythroid progenitors correlates with the ability of ErbB to induce sustained cell proliferation .", "target_text": { "Stat 5b": "protein", "erythroid progenitors": "cell_type", "ErbB": "protein" } }, { "input_text": "Self renewal of normal erythroid progenitors is induced by the receptor tyrosine kinase c-ErbB , whereas other receptors ( c-Kit/Epo-R ) regulate erythroid differentiation .", "target_text": { "erythroid progenitors": "cell_type", "receptor tyrosine kinase": "protein", "c-ErbB": "protein", "receptors": "protein", "c-Kit/Epo-R": "protein" } }, { "input_text": "To address possible mechanisms that could explain this selective activity of c-ErbB , we analyzed the ability of these receptors to activate the different members of the Stat transcription factor family .", "target_text": { "c-ErbB": "protein", "Stat transcription factor family": "protein" } }, { "input_text": "Ligand activation of c-ErbB induced the tyrosine phosphorylation , DNA-binding , and reporter gene transcription of Stat 5b in erythroblasts .", "target_text": { "c-ErbB": "protein", "reporter gene": "DNA", "Stat 5b": "protein", "erythroblasts": "cell_type" } }, { "input_text": "In contrast , ligand activation of c-Kit was unable to induce any of these effects in the same cells .", "target_text": { "c-Kit": "protein" } }, { "input_text": "Activation of the erythropoietin receptor caused specific DNA-binding of Stat 5b , but failed to induce reporter gene transcription .", "target_text": { "erythropoietin receptor": "protein", "Stat 5b": "protein", "reporter gene": "DNA" } }, { "input_text": "These biochemical findings correlate perfectly with the selective ability of c-ErbB to cause sustained self renewal in erythroid progenitors .", "target_text": { "c-ErbB": "protein", "erythroid progenitors": "cell_type" } }, { "input_text": "Defective transcription of the IL-2 gene is associated with impaired expression of c-Fos , FosB , and JunB in anergic T helper 1 cells .", "target_text": { "IL-2 gene": "DNA", "c-Fos": "protein", "FosB": "protein", "JunB": "protein", "anergic T helper 1 cells": "cell_line" } }, { "input_text": "Anergic CD4+ Th cells do not produce IL-2 when challenged with Ag-pulsed accessory cells because of a transcriptional defect .", "target_text": { "Anergic CD4+ Th cells": "cell_line", "IL-2": "protein", "Ag-pulsed accessory cells": "cell_line" } }, { "input_text": "In this work , we report that these anergic T cells are defective in their ability to up-regulate protein binding and transactivation at two critical IL-2 DNA enhancer elements : NF-AT ( nuclear factor of activated T cells ; a sequence that binds a heterotrimeric NFATp , Fos , and Jun protein complex ) and Activator Protein-1 ( AP-1 ) ( that binds Fos and Jun heterodimers ) .", "target_text": { "anergic T cells": "cell_line", "IL-2": "protein", "IL-2 DNA enhancer elements": "DNA", "NF-AT": "protein", "nuclear factor of activated T cells": "protein", "NFATp": "protein", "heterotrimeric NFATp": "protein", "Fos": "protein", "Jun protein complex": "protein", "heterotrimeric NFATp , Fos , and Jun protein complex": "protein", "Activator Protein-1": "protein", "AP-1": "protein", "Fos and Jun heterodimers": "protein" } }, { "input_text": "Western blot analysis of nuclear extracts showed that the impaired DNA-protein interactions in anergic T cells were associated with poor expression of the inducible AP-1 family members c-Fos , FosB , and JunB .", "target_text": { "anergic T cells": "cell_line", "AP-1": "protein", "c-Fos": "protein", "FosB": "protein", "JunB": "protein" } }, { "input_text": "However , the reduced expression of these proteins was not the result of a global TCR/CD3 -signaling defect because CD3 cross-linking induced an equivalent increase in intracellular-free calcium ions , as well as NFATp dephosphorylation , translocation to the nucleus , and DNA binding in both normal and anergic T cells .", "target_text": { "TCR/CD3": "protein", "CD3": "protein", "NFATp": "protein", "normal": "cell_type", "anergic T cells": "cell_line" } }, { "input_text": "Thus , defective IL-2 gene transcription appears to be due , at least in part , to a selective block in the expression of the AP-1 Fos and Jun family members in anergic T cells .", "target_text": { "IL-2": "protein", "IL-2 gene": "DNA", "AP-1 Fos and Jun family members": "protein", "anergic T cells": "cell_line" } }, { "input_text": "Sequence-specific DNA binding of the B-cell-specific coactivator OCA-B .", "target_text": { "B-cell-specific coactivator": "protein", "OCA-B": "protein" } }, { "input_text": "B-cell-specific transcription of immunoglobulin genes is mediated by the interaction of a POU domain containing transcription factor Oct-1 or Oct-2 , with the B-cell-specific coactivator OCA-B ( Bob-1 , OBF-1 ) and a prototype octamer element .", "target_text": { "immunoglobulin genes": "DNA", "POU domain": "DNA", "transcription factor": "protein", "Oct-1": "protein", "Oct-2": "protein", "B-cell-specific coactivator": "protein", "OCA-B": "protein", "Bob-1": "protein", "OBF-1": "protein", "prototype octamer element": "DNA" } }, { "input_text": "We find that OCA-B binds DNA directly in the major groove between the two subdomains of the POU domain , requiring both an A at the fifth position of the octamer element and contact with the POU domain .", "target_text": { "OCA-B": "protein", "major groove": "DNA", "POU domain": "DNA", "fifth position": "DNA", "octamer element": "DNA" } }, { "input_text": "An amino-terminal fragment of OCA-B binds the octamer site in the absence of a POU domain with the same sequence specificity .", "target_text": { "amino-terminal fragment": "protein", "OCA-B": "protein", "octamer site": "DNA", "POU domain": "DNA" } }, { "input_text": "Coactivator OCA-B may undergo a POU-dependent conformational change that exposes its amino terminus , allowing it to recognize specific DNA sequences in the major groove within the binding site for Oct-1 or Oct-2 .", "target_text": { "OCA-B": "protein", "DNA sequences": "DNA", "major groove": "DNA", "Oct-1": "protein", "Oct-2": "protein" } }, { "input_text": "The recognition of both the POU domain and the octamer sequence by OCA-B provides a mechanism for differential regulation of octamer sites containing genes by the ubiquitous factor Oct-1 .", "target_text": { "POU domain": "DNA", "octamer sequence": "DNA", "OCA-B": "protein", "octamer sites": "DNA", "ubiquitous factor": "protein", "Oct-1": "protein" } }, { "input_text": "Uneven X inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the alpha-galactosidase A gene .", "target_text": { "X": "DNA", "alpha-galactosidase A gene": "DNA" } }, { "input_text": "We describe two female monozygotic ( MZ ) twins heterozygous for Fabry disease , an X linked disorder resulting from the deficient activity of alpha-galactosidase A .", "target_text": { "alpha-galactosidase A": "protein" } }, { "input_text": "While one of the twins was clinically affected , the other was asymptomatic .", "target_text": {} }, { "input_text": "Enzymatic assay of alpha-galactosidase in blood leucocytes , skin fibroblasts , Epstein-Barr virus transformed lymphoid cell lines , and hair follicles of the twins and their parents confirmed the heterozygous status of the twins and indicated that Fabry disease had occurred as a result of a de novo mutation .", "target_text": { "alpha-galactosidase": "protein", "blood leucocytes": "cell_type", "skin fibroblasts": "cell_type", "Epstein-Barr virus transformed lymphoid cell lines": "cell_line" } }, { "input_text": "The son of the unaffected twin sister was shown to be hemizygous .", "target_text": {} }, { "input_text": "Molecular analysis of the alpha-galactosidase A gene permitted the identification of an as yet undescribed point mutation at position 10182 of exon 5 which causes an Asp to Asn substitution at codon 231 .", "target_text": { "alpha-galactosidase": "protein", "alpha-galactosidase A": "protein", "alpha-galactosidase A gene": "DNA", "position 10182": "DNA", "exon 5": "DNA", "position 10182 of exon 5": "DNA", "codon 231": "DNA" } }, { "input_text": "Single strand conformation polymorphism ( SSCP ) analysis again showed the heterozygous status of the twins and a normal pattern in their parents .", "target_text": {} }, { "input_text": "The basis for the discordant expression of this d novo mutation in the twins was investigated by studying their X inactivation status .", "target_text": {} }, { "input_text": "Analysis of the inactive X specific methylation at the androgen receptor gene showed unbalanced inactivation in the twins ' fibroblasts and in opposite directions .", "target_text": { "inactive X": "DNA", "androgen receptor gene": "DNA" } }, { "input_text": "While the maternally derived X chromosome was preferentially active in the asymptomatic twin , the paternal X chromosome was active in the other , affected twin and was found in her hemizygotic nephew .", "target_text": { "X chromosome": "DNA", "maternally derived X chromosome": "DNA", "paternal X chromosome": "DNA" } }, { "input_text": "These data suggest that the paternal X chromosome carries the de novo alpha-galactosidase A mutation and that uneven X inactivation is the underlying mechanism for disease expression in this novel female MZ twin pair .", "target_text": { "X chromosome": "DNA", "paternal X chromosome": "DNA", "alpha-galactosidase": "protein", "alpha-galactosidase A": "protein" } }, { "input_text": "This is the first documented case of female twins discordant for Fabry disease .", "target_text": {} }, { "input_text": "Precise alignment of sites required for mu enhancer activation in B cells .", "target_text": { "alignment of sites": "DNA", "mu enhancer": "DNA", "B cells": "cell_type" } }, { "input_text": "The lymphocyte-specific immunoglobulin mu heavy-chain gene intronic enhancer is regulated by multiple nuclear factors .", "target_text": { "immunoglobulin mu heavy-chain": "protein", "lymphocyte-specific immunoglobulin mu heavy-chain gene intronic enhancer": "DNA", "nuclear factors": "protein" } }, { "input_text": "The previously defined minimal enhancer containing the muA , muE3 , and muB sites is transactivated by a combination of the ETS-domain proteins PU.1 and Ets-1 in nonlymphoid cells .", "target_text": { "minimal enhancer": "DNA", "ETS-domain proteins": "protein", "PU.1": "protein", "Ets-1": "protein", "nonlymphoid cells": "cell_type" } }, { "input_text": "The core GGAAs of the muA and muB sites are separated by 30 nucleotides , suggesting that ETS proteins bind to these sites from these same side of the DNA helix .", "target_text": { "ETS proteins": "protein", "DNA helix": "DNA" } }, { "input_text": "We tested the necessity for appropriate spatial alignment of these elements by using mutated enhancers with altered spacings .", "target_text": { "elements": "DNA", "mutated enhancers": "DNA" } }, { "input_text": "A 4- or 10- bp insertion between muE3 and muB inactivated the mu enhancer in S194 plasma cells but did not affect in vitro binding of Ets-1 , PU.1 , or the muE3 -binding protein TFE3 , alone or in pairwise combinations .", "target_text": { "muE3": "DNA", "muB": "DNA", "mu enhancer": "DNA", "S194 plasma cells": "cell_line", "PU.1": "protein", "muE3 -binding protein": "protein", "TFE3": "protein" } }, { "input_text": "Circular permutation and phasing analyses demonstrated that PU.1 binding but not TFE3 or Ets-1 bends mu enhancer DNA toward the major groove .", "target_text": { "PU.1": "protein", "TFE3": "protein", "Ets-1": "protein", "mu enhancer": "DNA", "mu enhancer DNA": "DNA", "major groove": "DNA" } }, { "input_text": "We propose that the requirement for precise spacing of the muA and muB elements is due in part to a directed DNA bend induced by PU.1 .", "target_text": { "DNA bend": "DNA", "PU.1": "protein" } }, { "input_text": "[ Cortisone-resistant bronchial asthma ]", "target_text": {} }, { "input_text": "There is general agreement on the inflammatory pathogenesis of bronchial asthma : an accumulation of activated eosinophils , degranulated mast cells , T lymphocytes and in very severe forms , granulocytes has constantly been found in the bronchial mucosa .", "target_text": { "activated eosinophils": "cell_type", "degranulated mast cells": "cell_type", "T lymphocytes": "cell_type", "granulocytes": "cell_type" } }, { "input_text": "In allergic bronchial asthma , inflammation seems to be orchestrated predominantly by a subset of T lymphocytes , with a phenotype similar to the Th2 subset able to produce IL-4 and IL-5 .", "target_text": { "T lymphocytes": "cell_type", "Th2 subset": "cell_type", "IL-4": "protein", "IL-5": "protein" } }, { "input_text": "Although corticosteroids are the most potent therapeutic agents used for this disease , their anti-inflammatory effect differs from patient to patient .", "target_text": {} }, { "input_text": "Some criteria which can be used to define steroid-resistant bronchial asthma are listed here .", "target_text": {} }, { "input_text": "This review analyzes various molecular alterations responsible for the deficient response to corticosteroid treatment observed in steroid-resistant bronchial asthmatic subjects .", "target_text": {} }, { "input_text": "New knowledge on the mechanism of steroid resistance may have important implications for the treatment of chronic asthma and other diseases .", "target_text": {} }, { "input_text": "Mechanisms of transactivation by nuclear factor of activated T cells -1 .", "target_text": { "nuclear factor of activated T cells": "protein", "nuclear factor of activated T cells -1": "protein" } }, { "input_text": "Nuclear factor of activated T cells-family proteins ( NFAT1/ NFATp , NFATc , NFAT3 , and NFAT4/NFATx/NFATc3 ) play a key role in the transcription of cytokine genes and other genes during the immune response .", "target_text": { "Nuclear factor of activated T cells-family proteins": "protein", "NFATp": "protein", "NFAT1/ NFATp": "protein", "NFATc": "protein", "NFAT3": "protein", "NFAT4/NFATx/NFATc3": "protein", "cytokine genes": "DNA" } }, { "input_text": "We have defined the mechanisms of transactivation by NFAT1 .", "target_text": { "NFAT1": "protein" } }, { "input_text": "NFAT1 possesses two transactivation domains whose sequences are not conserved in the other NFAT-family proteins , and a conserved DNA-binding domain that mediates the recruitment of cooperating nuclear transcription factors even when it is expressed in the absence of other regions of the protein .", "target_text": { "NFAT1": "protein", "transactivation domains": "DNA", "NFAT-family proteins": "protein", "DNA-binding domain": "DNA", "transcription factors": "protein", "nuclear transcription factors": "protein" } }, { "input_text": "The activity of the NH2-terminal transactivation domain is modulated by an adjacent regulatory region that contains several conserved sequence motifs represented only in the NFAT family .", "target_text": { "NH2-terminal transactivation domain": "protein", "regulatory region": "protein", "conserved sequence motifs": "DNA", "NFAT family": "protein" } }, { "input_text": "Our results emphasize the multiple levels at which NFAT-dependent transactivation is regulated , and predict significant differences in the architecture of cooperative transcription complexes containing different NFAT-family proteins .", "target_text": { "transcription complexes": "protein", "NFAT-family proteins": "protein" } }, { "input_text": "Induction of activator protein ( AP ) -1 and nuclear factor-kappaB by CD28 stimulation involves both phosphatidylinositol 3-kinase and acidic sphingomyelinase signals .", "target_text": { "activator protein ( AP ) -1": "protein", "nuclear factor-kappaB": "protein", "CD28": "protein", "phosphatidylinositol 3-kinase": "protein", "acidic sphingomyelinase": "protein" } }, { "input_text": "A major obstacle in understanding the signaling events that follow CD28 receptor ligation arises from the fact that CD28 acts as a costimulus to TCR engagement , making it difficult to assess the relative contribution of CD28 signals as distinct from those of the TCR .", "target_text": { "CD28": "protein", "TCR": "protein" } }, { "input_text": "To overcome this problem , we have exploited the observation that activated human T cell blasts can be stimulated via the CD28 surface molecule in the absence of antigenic challenge ; thus , we have been able to observe the response of normal T cells to CD28 activation in isolation .", "target_text": { "human T cell blasts": "cell_type", "CD28": "protein", "CD28 surface molecule": "protein", "normal T cells": "cell_type" } }, { "input_text": "Using this system , we observed that CD28 stimulation by B7-transfected CHO cells induced a proliferative response in T cells that was not accompanied by measurable IL-2 production .", "target_text": { "CD28": "protein", "B7-transfected CHO cells": "cell_line", "T cells": "cell_type", "IL-2": "protein" } }, { "input_text": "However , subsequent analysis of transcription factor generation revealed that B7 stimulation induced both activator protein-1 ( AP-1 ) and nuclear factor-kappaB ( NF-kappaB ) complexes , but not NF-AT .", "target_text": { "transcription factor": "protein", "activator protein-1": "protein", "AP-1": "protein", "nuclear factor-kappaB": "protein", "NF-kappaB": "protein", "nuclear factor-kappaB ( NF-kappaB ) complexes": "protein", "NF-AT": "protein" } }, { "input_text": "In contrast , engagement of the TCR by class II MHC/superantigen , either with or without CD28 ligation , resulted in the induction of NF-AT , AP-1 , and NF-kappaB as well as IL-2 production .", "target_text": { "TCR": "protein", "class II MHC/superantigen": "protein", "CD28": "protein", "NF-AT": "protein", "AP-1": "protein", "NF-kappaB": "protein", "IL-2": "protein" } }, { "input_text": "Using selective inhibitors , we investigated the signaling pathways involved in the CD28 -mediated induction of AP-1 and NF-kappaB .", "target_text": { "CD28": "protein", "AP-1": "protein", "NF-kappaB": "protein" } }, { "input_text": "This revealed that NF-kappaB generation was sensitive to chloroquine , an inhibitor of acidic sphingomyelinase , but not to the phosphatidylinositol 3-kinase inhibitor , wortmannin .", "target_text": { "NF-kappaB": "protein", "acidic sphingomyelinase": "protein", "phosphatidylinositol 3-kinase": "protein" } }, { "input_text": "In contrast , AP-1 generation was inhibited by wortmannin and was also variably sensitive to chloroquine .", "target_text": { "AP-1": "protein" } }, { "input_text": "These data suggest that in activated normal T cells , CD28 -derived signals can stimulate proliferation at least in part via NF-kappaB and AP-1 generation , and that this response uses both acidic sphingomyelinase and phosphatidylinositol 3-kinase -linked pathways .", "target_text": { "normal T cells": "cell_type", "CD28": "protein", "acidic sphingomyelinase": "protein", "phosphatidylinositol 3-kinase": "protein" } }, { "input_text": "Presence of a variant form of the estrogen receptor in peripheral blood mononuclear cells from normal individuals and lupus patients .", "target_text": { "estrogen receptor": "protein", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Estrogen may participate in the pathogenesis of systemic lupus erythematosus ( SLE ) via its intracellular receptor .", "target_text": { "intracellular receptor": "protein" } }, { "input_text": "To investigate the presence of various isoforms of the estrogen receptor ( ER ) in SLE we isolated RNA from mononuclear cells of lupus patients and normal controls .", "target_text": { "estrogen receptor": "protein", "ER": "protein", "mononuclear cells": "cell_type" } }, { "input_text": "Using RT-PCR we were able to identify both the full length wild-type form and an isoform of the ER which precisely lacks exon V in both patient and normal individuals .", "target_text": { "full length wild-type form": "protein", "ER": "protein", "exon V": "DNA" } }, { "input_text": "Our results , although limited , suggest that normal individuals can express both the wild-type and truncated version at the same time , whereas lupus patients only express either the wild-type or the truncated ER .", "target_text": {} }, { "input_text": "This finding may lead to a better understanding of the reasons for the prevalence of lupus in females and of the estrogenic effects on SLE disease activity .", "target_text": {} }, { "input_text": "Regulation of sialoadhesin expression on rat macrophages .", "target_text": { "sialoadhesin": "protein", "rat macrophages": "cell_type" } }, { "input_text": "Induction by glucocorticoids and enhancement by IFN-beta , IFN-gamma , IL-4 , and lipopolysaccharide .", "target_text": { "IFN-beta": "protein", "IFN-gamma": "protein", "IL-4": "protein" } }, { "input_text": "Sialoadhesin is a macrophage-restricted member of the Ig superfamily that mediates adhesion with lymphoid and myeloid cells .", "target_text": { "Sialoadhesin": "protein", "macrophage-restricted member": "protein", "Ig superfamily": "protein" } }, { "input_text": "It is expressed on a subpopulation of macrophages in lymphoid tissues and in chronic inflammation ( e.g. , during autoimmune diseases ) .", "target_text": { "macrophages": "cell_type" } }, { "input_text": "We have studied the regulation of sialoadhesin expression in vitro and show that glucocorticoids ( GC ) induce sialoadhesin expression on freshly isolated rat macrophages and the rat macrophage cell line R2 .", "target_text": { "sialoadhesin": "protein", "macrophages": "cell_type", "rat macrophages": "cell_type", "rat macrophage cell line R2": "cell_line" } }, { "input_text": "The cytokines IFN-beta , IFN-gamma , IL-4 , and LPS , although unable to induce sialoadhesin expression by themselves , were able to enhance GC -mediated induction of sialoadhesin .", "target_text": { "cytokines": "protein", "IFN-beta": "protein", "IFN-gamma": "protein", "IL-4": "protein", "sialoadhesin": "protein" } }, { "input_text": "Sialoadhesin expression was functional as shown by cell adhesion assays with human RBCs .", "target_text": { "Sialoadhesin": "protein", "human RBCs": "cell_type" } }, { "input_text": "Northern blotting experiments indicated that regulation predominantly occurred at the mRNA level .", "target_text": {} }, { "input_text": "Comparison of the different combinations of GC and cytokines /LPS revealed differences in the level of GC -dependent enhancement of sialoadhesin expression , with IFN-beta and IL-4 being more potent than IFN-gamma and LPS .", "target_text": { "cytokines": "protein", "sialoadhesin": "protein", "IFN-beta": "protein", "IL-4": "protein", "IFN-gamma": "protein" } }, { "input_text": "Moreover , the effects of IFN-gamma and LPS could be reproduced by priming , whereas IFN-beta and IL-4 were required simultaneously with GC .", "target_text": { "IFN-gamma": "protein", "IFN-beta": "protein", "IL-4": "protein" } }, { "input_text": "The regulation of sialoadhesin expression was mediated by the GC receptor , and not by mineralocorticoid receptor , as shown by inhibition experiments with specific antagonists .", "target_text": { "sialoadhesin": "protein", "GC receptor": "protein", "mineralocorticoid receptor": "protein" } }, { "input_text": "Finally , it is demonstrated that macrophages in the adrenal gland , the major site of endogenous GC production , express sialoadhesin .", "target_text": { "macrophages": "cell_type", "sialoadhesin": "protein" } }, { "input_text": "This study demonstrates that GC act as a primary inducer of sialoadhesin expression on rat macrophages , and that the response can be enhanced by IFN-beta , T cell-derived cytokines , or LPS .", "target_text": { "sialoadhesin": "protein", "rat macrophages": "cell_type", "IFN-beta": "protein", "cytokines": "protein", "T cell-derived cytokines": "protein" } }, { "input_text": "Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2 .", "target_text": { "HIV protease": "protein", "Bcl-2": "protein" } }, { "input_text": "Expression of the human immunodeficiency virus type 1 ( HIV ) protease in cultured cells leads to apoptosis , preceded by cleavage of bcl-2 , a key negative regulator of cell death .", "target_text": { "human immunodeficiency virus type 1 ( HIV ) protease": "protein", "cultured cells": "cell_line", "bcl-2": "protein" } }, { "input_text": "In contrast , a high level of bcl-2 protects cells in vitro and in vivo from the viral protease and prevents cell death following HIV infection of human lymphocytes , while reducing the yields of viral structural proteins , infectivity , and tumor necrosis factor alpha .", "target_text": { "bcl-2": "protein", "viral protease": "protein", "human lymphocytes": "cell_type", "viral structural proteins": "protein", "tumor necrosis factor alpha": "protein" } }, { "input_text": "We present a model for HIV replication in which the viral protease depletes the infected cells of bcl-2 , leading to oxidative stress-dependent activation of NF kappa B , a cellular factor required for HIV transcription , and ultimately to cell death .", "target_text": { "viral protease": "protein", "bcl-2": "protein", "NF kappa B": "protein", "cellular factor": "protein" } }, { "input_text": "Purified bcl-2 is cleaved by HIV protease between phenylalanine 112 and alanine 113 .", "target_text": { "bcl-2": "protein", "HIV protease": "protein" } }, { "input_text": "The results suggest a new option for HIV gene therapy ; bcl-2 muteins that have noncleavable alterations surrounding the HIV protease cleavage site .", "target_text": { "bcl-2 muteins": "protein", "noncleavable alterations": "protein", "HIV protease": "protein", "HIV protease cleavage site": "protein" } }, { "input_text": "Alpha 4 beta 1 ( CD49d/CD29 ) integrin costimulation of human T cells enhances transcription factor and cytokine induction in the absence of altered sensitivity to anti-CD3 stimulation .", "target_text": { "CD49d/CD29": "protein", "Alpha 4 beta 1 ( CD49d/CD29 ) integrin": "protein", "human T cells": "cell_type", "transcription factor": "protein", "anti-CD3": "protein" } }, { "input_text": "The integrin alpha 4 beta 1 can provide a costimulus to induce IL-2 secretion and IL-2R expression leading to enhanced proliferation of purified , peripheral blood T cells .", "target_text": { "integrin alpha 4 beta 1": "protein", "IL-2": "protein", "IL-2R": "protein", "peripheral blood T cells": "cell_type" } }, { "input_text": "Similar to expression of IL-2 , we demonstrated that recombinant vascular-cell adhesion molecule-1 , when co-immobilized with anti-CD3 mAb , significantly enhanced the induction of transcription factors NF-AT , AP-1 , and NF-kappa B as determined by electromobility shift assays .", "target_text": { "IL-2": "protein", "recombinant vascular-cell adhesion molecule-1": "protein", "anti-CD3 mAb": "protein", "transcription factors": "protein", "NF-AT": "protein", "AP-1": "protein", "NF-kappa B": "protein" } }, { "input_text": "alpha 4 beta 1 ligation alone had no effect on transcription factor binding .", "target_text": { "alpha 4 beta 1": "protein", "transcription factor": "protein" } }, { "input_text": "The requirements for induction of transcription factors reflected the requirements for the secretion of multiple cytokines , including IL-2 , TNF-alpha , IFN-gamma , and granulocyte macrophage-CSF .", "target_text": { "transcription factors": "protein", "cytokines": "protein", "IL-2": "protein", "TNF-alpha": "protein", "IFN-gamma": "protein", "granulocyte macrophage-CSF": "protein" } }, { "input_text": "In contrast to freshly isolated T cells , in vitro-cultured T cells did not require costimulation for cytokine secretion in response to anti-CD3 alone .", "target_text": { "freshly isolated T cells": "cell_type", "vitro-cultured T cells": "cell_line", "cytokine": "protein", "anti-CD3": "protein" } }, { "input_text": "Comparison of the dose response to anti-CD3 stimulation demonstrated that half-maximal induction of IL-2 was achieved using the same dose of anti-CD3 for both freshly isolated and cultured T cells .", "target_text": { "anti-CD3": "protein", "IL-2": "protein", "freshly isolated": "cell_type", "cultured T cells": "cell_line" } }, { "input_text": "Furthermore , the dose of OKT3 required to achieve half-maximal activation was the same using PMA or different concentrations of alpha 4 beta 1 ligands .", "target_text": { "OKT3": "protein", "alpha 4 beta 1": "protein" } }, { "input_text": "Therefore , costimulation by alpha 4 beta 1 ligands was not due to stabilization of the interaction of the cells with its substrate .", "target_text": { "alpha 4 beta 1": "protein" } }, { "input_text": "We conclude , rather , that alpha 4 beta 1 in freshly isolated T cells delivers a distinct signal that synergizes early with signals initiated by TCR/CD3 ligation to induce DNA binding of multiple transcription factors required for cytokine gene induction .", "target_text": { "alpha 4 beta 1": "protein", "freshly isolated T cells": "cell_type", "TCR/CD3": "protein", "transcription factors": "protein", "cytokine gene": "DNA" } }, { "input_text": "Inhibition of T lymphocyte activation by cAMP is associated with down-regulation of two parallel mitogen-activated protein kinase pathways , the extracellular signal-related kinase and c-Jun N-terminal kinase .", "target_text": { "T lymphocyte": "cell_type", "protein kinase": "protein", "extracellular signal-related kinase": "protein", "c-Jun N-terminal kinase": "protein" } }, { "input_text": "The induction of T cell proliferation requires signals from the TCR and a co-receptor molecule , such as CD28 , that activate parallel and partially cross-reactive signaling pathways .", "target_text": { "TCR": "protein", "co-receptor molecule": "protein", "CD28": "protein" } }, { "input_text": "These pathways are disrupted by agonists that utilize adenylate cyclase and cAMP -dependent protein kinase A ( PKA ) .", "target_text": { "adenylate cyclase": "protein", "cAMP -dependent protein kinase A": "protein", "PKA": "protein" } }, { "input_text": "We found that the adenylate cyclase activator , forskolin , inhibits anti-CD3 -induced shift in Lck electrophoretic mobility , suggesting an intervention at the TCR -coupled phosphoinositide turnover that precedes the activation of PKC .", "target_text": { "adenylate cyclase": "protein", "anti-CD3": "protein", "Lck": "protein", "TCR": "protein", "PKC": "protein" } }, { "input_text": "The shift of Lck following direct PKC activation by 12-O-tetradecanoyl phorbol 13-acetate , which bypasses early receptor-triggered biochemical events , is insensitive to forskolin .", "target_text": { "Lck": "protein", "PKC": "protein" } }, { "input_text": "Nevertheless , forskolin also inhibits PKC downstream events , such as c-jun expression , which is critical for the activation process of T cells .", "target_text": { "PKC": "protein", "c-jun": "DNA", "T cells": "cell_type" } }, { "input_text": "To further analyze potential cross points between positively and negatively regulating signaling pathways in T cells , we tested the effects of activators of the adenylate cyclase or PKA on two parallel mitogen-activated protein kinase signaling pathways mediated by extracellular signal-regulated kinase ( ERK ) and c-Jun N-terminal kinase .", "target_text": { "T cells": "cell_type", "adenylate cyclase": "protein", "PKA": "protein", "extracellular signal-regulated kinase": "protein", "ERK": "protein", "c-Jun N-terminal kinase": "protein" } }, { "input_text": "Using a PKC -specific inhibitor , GF109203X , or PKC -depleted T cells , we found that a large part of the anti-CD3 -induced ERK activation is PKC dependent .", "target_text": { "PKC": "protein", "PKC -depleted T cells": "cell_line", "anti-CD3": "protein", "ERK": "protein" } }, { "input_text": "Both PKC- dependent and -independent activation of ERK were sensitive to inhibition by forskolin or a cell-permeable cAMP analogue , dbcAMP .", "target_text": { "ERK": "protein" } }, { "input_text": "Furthermore , the effect of 12-O-tetradecanoyl phorbol 13-acetate and ionomycin , which synergized to fully activate c-Jun N-terminal kinase , was also sensitive to inhibition by forskolin .", "target_text": { "c-Jun N-terminal kinase": "protein" } }, { "input_text": "Our results suggest that PKA inhibits T cell activation by interfering with multiple events along the two signaling pathways operating downstream of the TCR and the CD28 co-receptor molecules .", "target_text": { "PKA": "protein", "TCR": "protein", "CD28": "protein", "CD28 co-receptor molecules": "protein" } }, { "input_text": "Transcriptional and posttranscriptional regulation of erythroid gene expression in anthracycline -induced differentiation of human erythroleukemic cells .", "target_text": { "erythroid gene": "DNA", "human erythroleukemic cells": "cell_type" } }, { "input_text": "Aclacinomycin ( ACLA ) and doxorubicin ( DOX ) were used at subtoxic concentrations to induce erythroid differentiation in the human leukemic cell line K562 .", "target_text": { "human leukemic cell line K562": "cell_line" } }, { "input_text": "Cell hemoglobinization was accompanied by the increased expression of genes encoding gamma-globin and porphobilinogen deaminase ( PBGD ) , an enzyme of heme synthesis .", "target_text": { "genes": "DNA", "gamma-globin and porphobilinogen deaminase": "protein", "PBGD": "protein" } }, { "input_text": "By using run-on assays , ACLA was shown to induce an enhancement of the transcription of erythroid genes , including gamma-globin , PBGD , erythropoietin receptor , and GATA-1 transcription factor .", "target_text": { "erythroid genes": "DNA", "gamma-globin": "protein", "PBGD": "protein", "erythropoietin receptor": "protein", "GATA-1": "protein", "transcription factor": "protein" } }, { "input_text": "In contrast , in DOX -treated cells , the transcription rate of these genes was unchanged in comparison with control cells .", "target_text": { "DOX -treated cells": "cell_line", "genes": "DNA", "control cells": "cell_type" } }, { "input_text": "In addition , inhibition of mRNA synthesis with actinomycin D indicated that DOX induced an increased stability of PBGD and GATA-1 mRNAs , whereas ACLA did not affect the half-lives of these mRNAs .", "target_text": { "mRNA": "RNA", "mRNAs": "RNA" } }, { "input_text": "Because the increase in erythroid mRNA steady-state level in anthracycline -treated cells was inhibited by cycloheximide , this suggests that transcriptional activation in ACLA -treated cells and mRNA stabilization in DOX -treated cells were dependent on de novo protein synthesis .", "target_text": { "erythroid mRNA": "RNA", "anthracycline -treated cells": "cell_type", "ACLA -treated cells": "cell_line", "DOX -treated cells": "cell_type" } }, { "input_text": "Finally , GATA-1 protein level was shown to be increased in ACLA-treated but not in DOX-treated cells .", "target_text": { "GATA-1": "protein" } }, { "input_text": "These two anthracyclines , although closely related in their structures , appeared to act as differentiation inducers by distinct mechanisms .", "target_text": {} }, { "input_text": "Indeed , erythroid gene expression was demonstrated to be regulated transcriptionally by ACLA and mainly posttranscriptionally by DOX .", "target_text": { "erythroid gene": "DNA" } }, { "input_text": "Interleukin-7 signaling in human B cell precursor acute lymphoblastic leukemia cells and murine BAF3 cells involves activation of STAT1 and STAT5 mediated via the interleukin-7 receptor alpha chain .", "target_text": { "Interleukin-7": "protein", "human B cell precursor acute lymphoblastic leukemia cells": "cell_line", "murine BAF3 cells": "cell_line", "STAT1": "protein", "STAT5": "protein", "interleukin-7 receptor alpha chain": "protein" } }, { "input_text": "Interleukin-7 ( IL-7 ) stimulates the proliferation of normal and leukemic B and T cell precursors and T lymphocytes .", "target_text": { "Interleukin-7": "protein", "IL-7": "protein" } }, { "input_text": "Activation of the JAK /STAT pathway has been implicated in IL-7R signaling .", "target_text": { "JAK": "protein", "/STAT": "protein", "IL-7R": "protein" } }, { "input_text": "We investigated which STAT complexes are formed upon stimulation of B cell precursor acute lymphoblastic leukemia ( BCP-ALL ) cells with IL-7 .", "target_text": { "STAT complexes": "protein", "B cell precursor acute lymphoblastic leukemia ( BCP-ALL ) cells": "cell_line", "IL-7": "protein" } }, { "input_text": "Gel retardation assays with STAT-binding oligonucleotides showed that IL-7 induces the formation of two major STAT complexes in BCP-ALL cells .", "target_text": { "IL-7": "protein", "STAT complexes": "protein", "BCP-ALL cells": "cell_line" } }, { "input_text": "Supershifts with anti-STAT antibodies identified these as STAT1 and STAT5 complexes .", "target_text": { "anti-STAT antibodies": "DNA", "STAT1": "protein", "STAT5": "protein", "STAT5 complexes": "protein" } }, { "input_text": "This pattern of STAT activation was seen in all BCP-ALL cases that respond to IL-7 in proliferation assays .", "target_text": { "STAT": "protein", "IL-7": "protein" } }, { "input_text": "IL-7 also induced STAT /DNA binding in BCP-ALL cases that failed to proliferate in response to IL-7 , suggesting that the ability of IL-7R to activate the JAK /STAT pathway per se is not sufficient for proliferation induction .", "target_text": { "IL-7": "protein", "STAT": "protein", "IL-7R": "protein", "JAK": "protein", "/STAT": "protein" } }, { "input_text": "To determine the contribution of the cytoplasmic domain of the IL-7 receptor alpha chain ( IL-7R alpha ) to activation of STAT proteins , transfectants of the murine pro-B cell line BAF3 were made that express chimeric receptors consisting of the extracellular domain of human granulocyte colony-stimulating factor receptor ( G-CSF-R ) and the transmembrane and intracellular domains of human IL-7R alpha .", "target_text": { "cytoplasmic domain": "protein", "IL-7": "protein", "IL-7 receptor alpha chain": "protein", "IL-7R alpha": "protein", "STAT proteins": "protein", "murine pro-B cell line BAF3": "cell_line", "chimeric receptors": "protein", "extracellular domain": "protein", "human granulocyte colony-stimulating factor receptor": "protein", "G-CSF-R": "protein", "human IL-7R alpha": "protein" } }, { "input_text": "Activation of the chimeric G-CSF-R /IL-7R alpha with G-CSF resulted in a full proliferative response and induced the phosphorylation of JAK1 but not JAK2 .", "target_text": { "G-CSF-R": "protein", "/IL-7R alpha": "protein", "chimeric G-CSF-R /IL-7R alpha": "protein", "G-CSF": "protein", "JAK1": "protein", "JAK2": "protein" } }, { "input_text": "Major STAT complexes activated by G-CSF-R /IL-7R alpha contained STAT1 or STAT5 , while some formation of STAT3-containing complexes was also seen .", "target_text": { "STAT complexes": "protein", "G-CSF-R": "protein", "/IL-7R alpha": "protein", "G-CSF-R /IL-7R alpha": "protein", "STAT1": "protein", "STAT5": "protein", "STAT3-containing complexes": "protein" } }, { "input_text": "These findings establish that STAT1 and STAT5 , and possibly STAT3 , are activated upon stimulation of precursor B cells with IL-7 .", "target_text": { "STAT1": "protein", "STAT5": "protein", "STAT3": "protein", "precursor B cells": "cell_type", "IL-7": "protein" } }, { "input_text": "The data further indicate that the IL-7R alpha chains are directly involved in the activation of JAKs and STATs and have a major role in proliferative signaling in precursor B cells .", "target_text": { "IL-7R alpha chains": "protein", "JAKs": "protein", "STATs": "protein", "precursor B cells": "cell_type" } }, { "input_text": "Stimulation of human lymphocyte proliferation and CD40 antigen expression by phosphorothioate oligonucleotides complementary to hepatitis B virus genome .", "target_text": { "CD40": "protein", "hepatitis B virus genome": "DNA" } }, { "input_text": "We have studied the proliferation and CD40 antigen expression of lymphocytes , and the cytotoxicity to monocytes , of antisense phosphorothioate oligodeoxynucleotides complementary to the SP II promoter of HBV mRNA ( sequence I ) and the X gene ( sequence II ) in patients with chronic hepatitis B .", "target_text": { "CD40": "protein", "lymphocytes": "cell_type", "monocytes": "cell_type", "SP II promoter": "DNA", "HBV mRNA": "RNA", "X gene": "DNA" } }, { "input_text": "The oligo sequence I stimulated proliferation of both T and , to a lesser extent , B cells .", "target_text": {} }, { "input_text": "The percentage of cells expressing CD40 in T and B cell co-cultures increased from 4.2 % to 13.8 % after oligo stimulation in patients , while it increased form 4.7 % to 48.6 % in healthy controls .", "target_text": { "CD40": "protein" } }, { "input_text": "The sense sequence ( sequence III ) of the X gene also enhanced the expression of CD40 antigen in patients with hepatitis B .", "target_text": { "X gene": "DNA", "CD40": "protein", "CD40 antigen": "protein" } }, { "input_text": "The proportion of CD40 cells ( 26 % ) in a resting B-cell preparation from hepatitis B patients decreased to zero after a 5-day culture with sequence I , but IgG levels in the culture supernatant increased .", "target_text": { "CD40 cells": "cell_line", "resting B-cell preparation": "cell_line" } }, { "input_text": "The cytotoxic properties of monocytes were not influenced by the oligos .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "These findings indicate that antisense oligos against hepatitis B virus ( HBV ) have mitogenic effects on the proliferation of human lymphocytes in a non-specific manner and may activate T cells to express CD40 antigen .", "target_text": { "human lymphocytes": "cell_type", "T cells": "cell_type", "CD40": "protein", "CD40 antigen": "protein" } }, { "input_text": "Activation protein 1 -dependent transcriptional activation of interleukin 2 gene by Ca2+ /calmodulin kinase type IV/Gr .", "target_text": { "Activation protein 1": "protein", "interleukin 2 gene": "DNA", "Ca2+ /calmodulin kinase type IV/Gr": "protein" } }, { "input_text": "The Ca2+ /calmodulin-dependent protein kinase ( CaMK ) type IV/Gr is selectively expressed in T lymphocytes and is activated after signaling via the T cell antigen receptor ( TCR ) , indicating that it mediates some of the Ca(2+)-dependent transcriptional events that follow TCR engagement .", "target_text": { "Ca2+ /calmodulin-dependent protein kinase ( CaMK ) type IV/Gr": "protein", "T lymphocytes": "cell_type", "T cell antigen receptor": "protein", "TCR": "protein" } }, { "input_text": "Here we show that CaMKIV/Gr induces the transcription factor activation protein 1 ( AP-1 ) alone or in synergy with T cell mitogens and with the p21ras oncoprotein .", "target_text": { "CaMKIV/Gr": "protein", "transcription factor": "protein", "transcription factor activation protein 1": "protein", "AP-1": "protein", "T cell mitogens": "protein", "p21ras oncoprotein": "protein" } }, { "input_text": "CaMKIV/ Gr signaling is associated with transcriptional activation of c-fos but is independent of p21ras or calcineurin .", "target_text": { "CaMKIV/ Gr": "protein", "c-fos": "DNA", "p21ras": "DNA", "calcineurin": "protein" } }, { "input_text": "AP-1 is an integral component of the nuclear factor of activated T cells ( NFAT ) transcriptional complex , which is required for interleukin 2 gene expression in T cells .", "target_text": { "AP-1": "protein", "T cells": "cell_type", "nuclear factor of activated T cells": "protein", "nuclear factor of activated T cells ( NFAT ) transcriptional complex": "protein", "interleukin 2 gene": "DNA" } }, { "input_text": "We demonstrate that CaMKIV/Gr reconstitutes the capacity of the cytosolic component of NFAT to direct transcription from NFAT sites in non- T cells .", "target_text": { "CaMKIV/Gr": "protein", "NFAT": "protein", "NFAT sites": "DNA", "T cells": "cell_type" } }, { "input_text": "These results reveal a central role for CaMKIV/Gr as a Ca(2+) -regulated activator of gene transcription in T lymphocytes .", "target_text": { "CaMKIV/Gr": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "IL-12 -induced activation of NK and T cells occurs in the absence of immediate-early activation gene expression .", "target_text": { "IL-12": "protein", "immediate-early activation gene": "DNA" } }, { "input_text": "The responses of lymphocytes to IL-2 and IL-12 , involving proliferation , differentiation , and cytokine production , are only partially overlapping , and may depend on induced differential expression of specific sets of genes .", "target_text": { "lymphocytes": "cell_type", "IL-2": "protein", "IL-12": "protein", "cytokine": "protein", "genes": "protein" } }, { "input_text": "Using reverse-transcription PCR differential display , we isolated an mRNA species expressed in IL-2 - but not IL-12 -stimulated NK cells .", "target_text": { "mRNA species": "RNA", "IL-2": "protein", "IL-12": "protein" } }, { "input_text": "This was identified as the mRNA encoding the transcription factor egr-1 , which is expressed with fast kinetics in T and NK cells upon IL-2 , but not IL-12 , stimulation .", "target_text": { "mRNA": "RNA", "transcription factor": "protein", "egr-1": "protein", "IL-2": "protein", "IL-12": "protein" } }, { "input_text": "Analysis of the accumulation of mRNA -encoding members of the AP-1 transcription factor family demonstrated that c-fos and junB are also expressed upon stimulation of NK and T cells with IL-2 , but not IL-12 , whereas expression of c-jun and junD is not modified by either cytokine .", "target_text": { "mRNA": "RNA", "mRNA -encoding members": "protein", "AP-1 transcription factor family": "protein", "c-fos": "DNA", "junB": "DNA", "IL-2": "protein", "IL-12": "protein", "c-jun": "DNA", "junD": "DNA", "cytokine": "protein" } }, { "input_text": "Accordingly , increased AP-1 DNA-binding activity and AP-1 -dependent transcriptional activity were detected exclusively in IL-2 -stimulated cells .", "target_text": { "AP-1": "protein", "IL-2": "protein", "IL-2 -stimulated cells": "cell_line" } }, { "input_text": "Analysis of the expression of genes reported to regulate cytokine -induced proliferation demonstrated that both IL-2 and IL-12 induce c-myc mRNA accumulation in NK and T cells , whereas only IL-2 induces bcl-2 expression .", "target_text": { "genes": "protein", "cytokine": "protein", "IL-2": "protein", "IL-12": "protein", "c-myc mRNA": "RNA", "bcl-2": "DNA" } }, { "input_text": "Our data provide the first demonstration that IL-12 -mediated activation of T and NK cells does not involve expression of members of the immediate-early activation genes family ( egr-1 , c-fos , and junB ) , AP-1 transcriptional activity , or bcl-2 expression .", "target_text": { "IL-12": "protein", "immediate-early activation genes family": "DNA", "egr-1": "DNA", "c-fos": "DNA", "junB": "DNA", "AP-1": "protein", "bcl-2": "DNA" } }, { "input_text": "This indicates that functional differences observed in IL-2- and IL-12- stimulated cells may depend , at least in part , on differential gene regulation .", "target_text": {} }, { "input_text": "Active suppression of the class II transactivator-encoding AIR-1 locus is responsible for the lack of major histocompatibility complex class II gene expression observed during differentiation from B cells to plasma cells .", "target_text": { "class II transactivator-encoding AIR-1 locus": "DNA", "major histocompatibility complex class II gene": "DNA", "B cells": "cell_type", "plasma cells": "cell_type" } }, { "input_text": "In this study the genetic control of major histocompatibility complex ( MHC ) class II gene expression during the transition from B cell to plasma cell has been analyzed .", "target_text": { "major histocompatibility complex ( MHC ) class II gene": "DNA", "B cell": "cell_type", "plasma cell": "cell_type" } }, { "input_text": "Class II molecules are not expressed in plasma cells because of an active suppression resulting in the abrogation of class II gene transcription .", "target_text": { "Class II molecules": "protein", "plasma cells": "cell_type", "class II gene": "DNA" } }, { "input_text": "We show here that the plasma cell-specific repressor function , designated SIR ( suppressor of immune response genes ) , does not act directly on the transcription of class II genes , but instead on the transcription of the AIR-1 gene , whose product , the class II transactivator ( CIITA ) , is fundamental for the regulation of the constitutive and inducible expression of MHC class II genes .", "target_text": { "SIR": "DNA", "suppressor of immune response genes": "DNA", "class II genes": "DNA", "AIR-1 gene": "DNA", "class II transactivator": "protein", "CIITA": "protein", "MHC class II genes": "DNA" } }, { "input_text": "This was unambiguously demonstrated by the fact that plasmacytoma x B cell hybrids carrying an AIR-1 locus derived from CIITA -expressing cells do not express CIITA -specific transcripts .", "target_text": { "plasmacytoma x B cell hybrids": "cell_line", "AIR-1 locus": "DNA", "CIITA": "protein", "CIITA -expressing cells": "cell_line", "CIITA -specific transcripts": "RNA" } }, { "input_text": "Transfection of a cDNA containing the human CIITA coding sequence under the control of an heterologous promoter restores expression of human MHC class II genes in the hybrids and is responsible for de novo expression of mouse MHC class II genes in both the mouse plasmacytoma cell line and the hybrids .", "target_text": { "CIITA": "protein", "human CIITA coding sequence": "DNA", "heterologous promoter": "DNA", "human MHC class II genes": "DNA", "mouse MHC class II genes": "DNA", "mouse plasmacytoma cell line": "cell_line", "hybrids": "cell_line" } }, { "input_text": "These results confirm and extend the notion of the functional conservation of the AIR-1 gene product across species barriers .", "target_text": { "AIR-1 gene": "DNA", "AIR-1 gene product": "protein" } }, { "input_text": "Interestingly , in CIITA -transfected cell hybrids , cell surface expression of the human HLA-DQ heterodimer was not observed .", "target_text": { "CIITA": "protein", "CIITA -transfected cell hybrids": "cell_line", "human HLA-DQ heterodimer": "protein" } }, { "input_text": "This result was not attributable to lack of HLA -DQ alpha or -DQ beta transcription , because both transcripts were present in the CIITA -transfected hybrids , although at reduced levels .", "target_text": { "CIITA": "protein", "CIITA -transfected hybrids": "cell_line" } }, { "input_text": "These findings further support our previous observations on the distinct regulation of expression of the human HLA-DQ class II subset , which may be thus controlled at the posttranscriptional level by a CIITA -independent mechanism .", "target_text": { "human HLA-DQ class II subset": "DNA", "CIITA": "protein" } }, { "input_text": "Requirements for induction of vitamin D-mediated gene regulation in normal human B lymphocytes .", "target_text": { "normal human B lymphocytes": "cell_type" } }, { "input_text": "Mature human lymphocytes are unique targets of 1 alpha,25-dihydroxyvitamin D3 ( 1 alpha,25(OH)2D3 ) in that vitamin D receptors ( VDR ) are not constitutively expressed , and specific cellular activation signals are required for both the up-regulation of VDR and establishment of reactivity to the lipophilic ligand .", "target_text": { "human lymphocytes": "cell_type", "vitamin D receptors": "protein", "VDR": "protein" } }, { "input_text": "Treatment of B lymphocytes with the cytokine IL-4 ( IL-4 ) , in the absence of prior activation , induces a weak up-regulation of VDR expression but fails to generate vitamin D-responsive element ( VDRE ) -reactive nuclear protein complexes or to initiate the genomic transcription of 25-hydroxyvitamin D3 24-hydroxylase .", "target_text": { "B lymphocytes": "cell_type", "cytokine": "protein", "IL-4": "protein", "VDR": "protein", "vitamin D-responsive element": "DNA", "VDRE": "DNA", "vitamin D-responsive element ( VDRE ) -reactive nuclear protein complexes": "protein", "25-hydroxyvitamin D3 24-hydroxylase": "protein" } }, { "input_text": "Stimulation of B lymphocytes by either ligation of CD40 Ag or cross-linking the Ig receptor is also insufficient to render B lymphocytes responsive to 1 alpha,25(OH)2D3 .", "target_text": { "B lymphocytes": "cell_type", "CD40 Ag": "protein", "Ig receptor": "protein" } }, { "input_text": "However , this apparent lack of response to the secosterol can be overcome by stimulation of B lymphocytes with a combination of these cellular activation signals , which are sufficient to lead to G1 cell cycle progression .", "target_text": { "B lymphocytes": "cell_type" } }, { "input_text": "In the presence of 1 alpha,25(OH)2D3 , cellular activation associated with stimulation of such a progression appears to be sufficient for the up-regulation of VDR message and protein and necessary for the establishment of VDRE binding complexes and the induction of 24-hydroxylase message .", "target_text": { "VDR": "protein", "VDRE": "DNA", "VDRE binding complexes": "protein", "24-hydroxylase": "protein" } }, { "input_text": "Furthermore , biologic functions are modulated , in that the hormone inhibits proliferation in a subset of the activated B cells .", "target_text": { "B cells": "cell_type" } }, { "input_text": "These observations suggest that reactivity to 1 alpha,25(OH)2D3 is tightly regulated in B lymphocytes , requiring specific signals for its initiation .", "target_text": { "B lymphocytes": "cell_type" } }, { "input_text": "Cross talk between cell death and cell cycle progression : BCL-2 regulates NFAT -mediated activation .", "target_text": { "BCL-2": "protein", "NFAT": "protein" } }, { "input_text": "BCL-2 -deficient T cells demonstrate accelerated cell cycle progression and increased apoptosis following activation .", "target_text": { "BCL-2": "protein", "BCL-2 -deficient T cells": "cell_line" } }, { "input_text": "Increasing the levels of BCL-2 retarded the G0 --> S transition , sustained the levels of cyclin-dependent kinase inhibitor p27Kip1 , and repressed postactivation death .", "target_text": { "BCL-2": "protein", "cyclin-dependent kinase": "protein" } }, { "input_text": "Proximal signal transduction events and immediate early gene transcription were unaffected .", "target_text": { "immediate early gene": "DNA" } }, { "input_text": "However , the transcription and synthesis of interleukin 2 and other delayed early cytokines were markedly attenuated by BCL-2 .", "target_text": { "interleukin 2": "protein", "cytokines": "protein", "BCL-2": "protein" } }, { "input_text": "In contrast , a cysteine protease inhibitor that also blocks apoptosis had no substantial affect upon cytokine production .", "target_text": { "cytokine": "protein" } }, { "input_text": "InterleUkin 2 expression requires several transcription factors of which nuclear translocation of NFAT ( nuclear factor of activated T cells ) and NFAT -mediated transactivation were impaired by BCL-2 .", "target_text": { "InterleUkin 2": "protein", "transcription factors": "protein", "NFAT": "protein", "nuclear factor of activated T cells": "protein", "BCL-2": "protein" } }, { "input_text": "Thus , select genetic aberrations in the apoptotic pathway reveal a cell autonomous coregulation of activation .", "target_text": {} }, { "input_text": "Interaction of the human T-cell lymphotropic virus type 1 tax transactivator with transcription factor IIA .", "target_text": { "human T-cell lymphotropic virus type 1 tax transactivator": "protein", "transcription factor IIA": "protein" } }, { "input_text": "The Tax protein of human T-cell lymphotropic virus type 1 ( HTLV-1 ) is a 40-kDa transcriptional activator which is critical for HTLV-1 gene regulation and virus-induced cellular transformation .", "target_text": { "Tax protein": "protein", "40-kDa transcriptional activator": "protein" } }, { "input_text": "Tax is localized to the DNA through its interaction with the site-specific activators cyclic AMP-responsive element-binding protein , NF-kappaB , and serum response factor .", "target_text": { "Tax": "protein", "site-specific activators": "protein", "cyclic AMP-responsive element-binding protein": "protein", "NF-kappaB": "protein", "serum response factor": "protein" } }, { "input_text": "It has been suggested that the recruitment of Tax to the DNA positions Tax for interaction with the basal transcriptional machinery .", "target_text": { "Tax": "protein" } }, { "input_text": "On the basis of several independent assays , we now report a physical and functional interaction between Tax and the transcription factor , TFIIA .", "target_text": { "Tax": "protein", "transcription factor": "protein", "TFIIA": "protein" } }, { "input_text": "First , Tax was found to interact with the 35-kDa ( alpha ) subunit of TFIIA in the yeast two-hybrid interaction system .", "target_text": { "Tax": "protein", "35-kDa ( alpha ) subunit": "protein", "TFIIA": "protein" } }, { "input_text": "Importantly , two previously characterized mutants with point mutations in Tax , M32 ( Y196A , K197S ) and M41 ( H287A , P288S ) , which were shown to be defective in Tax -activated transcription were unable to interact with TFIIA in this assay .", "target_text": { "mutants": "protein", "Tax": "protein", "M32": "protein", "M41": "protein", "TFIIA": "protein" } }, { "input_text": "Second , a glutathione -S-transferase ( GST ) affinity-binding assay showed that the interaction of holo- TFIIA with GST- Tax was 20-fold higher than that observed with either the GST- Tax M32 activation mutant or the GST control .", "target_text": { "GST": "protein", "TFIIA": "protein", "Tax": "protein", "GST- Tax": "protein", "M32": "protein", "GST- Tax M32 activation mutant": "protein" } }, { "input_text": "Third , a coimmunoprecipitation assay showed that in HTLV-1 -infected human T lymphocytes , Tax and TFIIA were associated .", "target_text": { "HTLV-1 -infected human T lymphocytes": "cell_line", "Tax": "protein", "TFIIA": "protein" } }, { "input_text": "Finally , TFIIA facilitates Tax transactivation in vitro and in vivo .", "target_text": { "TFIIA": "protein", "Tax": "protein" } }, { "input_text": "In vitro transcription studies showed reduced levels of Tax -activated transcription in cell extracts depleted of TFIIA .", "target_text": { "Tax": "protein", "TFIIA": "protein" } }, { "input_text": "In addition , transfection of human T lymphocytes with TFIIA expression vectors enhanced Tax -activated transcription of an HTLV-1 long terminal repeat-chloramphenicol acetyltransferase reporter construct .", "target_text": { "human T lymphocytes": "cell_type", "TFIIA": "protein", "TFIIA expression vectors": "DNA", "Tax": "protein", "HTLV-1 long terminal repeat-chloramphenicol acetyltransferase reporter construct": "DNA" } }, { "input_text": "Our study suggests that the interaction of Tax with the transcription factor TFIIA may play a role in Tax -mediated transcriptional activation .", "target_text": { "Tax": "protein", "transcription factor": "protein", "TFIIA": "protein" } }, { "input_text": "Inhibition of transcription factor Stat1 activity in mononuclear cell cultures and T cells by the cyclic AMP signaling pathway .", "target_text": { "transcription factor": "protein", "Stat1": "protein", "mononuclear cell cultures": "cell_line", "T cells": "cell_type" } }, { "input_text": "Activation of T cells results in a cascade of gene activation and subsequent proliferation and differentiation into effector phenotypes .", "target_text": { "T cells": "cell_type" } }, { "input_text": "The regulation of transcription factors belonging to the signal transducer and activator of transcription ( STAT ) family was analyzed in PHA-activated mononuclear cells and in purified T cells activated by cross-linking cell surface CD3 .", "target_text": { "transcription factors": "protein", "signal transducer and activator of transcription ( STAT ) family": "protein", "PHA-activated mononuclear cells": "cell_line", "purified T cells": "cell_line", "cell surface CD3": "protein" } }, { "input_text": "Cell activation resulted in a delayed induction of STAT DNA-binding activity , which was sustained for several days , was composed predominantly of Stat1 and Stat3 , and was blocked by cycloheximide and actinomycin D .", "target_text": { "STAT": "protein", "Stat1": "protein", "Stat3": "protein" } }, { "input_text": "Increased Stat1 and Stat3 mRNA and protein levels were detected , respectively 4 and 24 h after activation .", "target_text": {} }, { "input_text": "Stimulation of the cAMP signal transduction pathway , which skews cytokine production toward a Th2 pattern , resulted in the preferential suppression of Stat1 activity .", "target_text": { "cytokine": "protein", "Stat1": "protein" } }, { "input_text": "cAMP inhibited the induction of expression of IL-2 receptor components , but did not inhibit IL-4 receptor alpha-chain and CD69 expression or the induction of activator protein 1 transcription factors .", "target_text": { "IL-2": "protein", "IL-2 receptor components": "protein", "IL-4 receptor alpha-chain": "protein", "CD69": "protein", "activator protein 1": "protein", "transcription factors": "protein", "activator protein 1 transcription factors": "protein" } }, { "input_text": "cAMP signaling inhibited Stat1 at several different levels , including suppression of DNA binding and down-regulation of Stat1 protein and mRNA levels .", "target_text": { "Stat1": "protein" } }, { "input_text": "Our results demonstrate the regulation of STAT activity by a signaling pathway that regulates the T cell functional phenotype and is distinct from the cytokine -activated Janus kinase -STAT signaling pathway .", "target_text": { "STAT": "protein", "cytokine": "protein", "Janus kinase": "protein", "-STAT": "protein" } }, { "input_text": "Suppression of c-jun by antisense oligonucleotides inhibits cell adhesion but not respiratory burst during phorbol ester-induced differentiation of U937 human monoblastic cells .", "target_text": { "c-jun": "DNA", "U937 human monoblastic cells": "cell_line" } }, { "input_text": "We studied the role of the immediate early gene c-jun in cell proliferation and phorbol 12-myristate 13-acetate ( PMA ) -induced differentiation in U937 human monoblastic cells , using c-jun -specific antisense ( AS ) phosphorothioate oligonucleotides .", "target_text": { "immediate early gene": "DNA", "c-jun": "DNA", "U937 human monoblastic cells": "cell_line" } }, { "input_text": "In selecting the most specific and potent oligonucleotide sequence , we performed extensive analyses for the binding specificity between all candidates of c-jun AS oligonucleotides and the whole sequences in GenBank database , using a computer program .", "target_text": { "c-jun": "DNA" } }, { "input_text": "Among the 20 selected oligonucleotides , two potent 15-mer AS oligonucleotides ( C-JUN AS oligonucleotides ) exhibited significant inhibition of cell growth in a dose-dependent manner between 2 and 10 microM .", "target_text": {} }, { "input_text": "Reverse transcription-PCR and Western blot analysis demonstrated that 10 microM of C-JUN AS oligonucleotides reduced c-jun expression at both the mRNA and protein levels .", "target_text": { "c-jun": "DNA", "mRNA": "RNA" } }, { "input_text": "More importantly , C-JUN AS oligonucleotides showed distinct effects on two markers of PMA -induced differentiation ; the C-JUN AS oligonucleotides inhibited cell adhesion , whereas they did not affect another marker of differentiation , respiratory burst ( measured by nitro blue tetrazolium reduction assay ) .", "target_text": {} }, { "input_text": "These results suggest a critical role of c-jun in both cell proliferation and PMA -induced cell adhesion but not in PMA -induced respiratory burst in U937 cells .", "target_text": { "c-jun": "DNA", "U937 cells": "cell_line" } }, { "input_text": "Effects of IL-10 and IL-4 on LPS-induced transcription factors ( AP-1 , NF-IL6 and NF-kappa B ) which are involved in IL-6 regulation .", "target_text": { "IL-10": "protein", "IL-4": "protein", "transcription factors": "protein", "AP-1": "protein", "NF-IL6": "protein", "NF-kappa B": "protein", "IL-6": "protein" } }, { "input_text": "Interleukin-10 ( IL-10 ) , like IL-4 , is known to inhibit cytokine expression in activated human monocytes .", "target_text": { "Interleukin-10": "protein", "IL-10": "protein", "IL-4": "protein", "cytokine": "protein", "activated human monocytes": "cell_type" } }, { "input_text": "We showed that both IL-10 and IL-4 inhibit LPS-induced IL-6 mRNA and protein expression by inhibiting the transcription rate of the IL-6 gene .", "target_text": { "IL-10": "protein", "IL-4": "protein", "IL-6": "protein", "LPS-induced IL-6 mRNA": "RNA", "IL-6 gene": "DNA" } }, { "input_text": "The strong inhibition of the IL-6 transcription rate prompted us to study the effect of IL-10 and IL-4 on the expression of transcription factors .", "target_text": { "IL-6": "protein", "IL-10": "protein", "IL-4": "protein", "transcription factors": "protein" } }, { "input_text": "We questioned whether or not IL-10 and IL-4 affected the expression of transcription factors that are known to be involved in the control of the IL-6 transcription rate , namely activator protein-1 ( AP-1 ) , nuclear factor IL-6 ( NF-IL6 ) , and nuclear factor kappa B ( NF-kappaB ) .", "target_text": { "IL-10": "protein", "IL-4": "protein", "transcription factors": "protein", "IL-6": "protein", "AP-1": "protein", "nuclear factor": "protein", "NF-IL6": "protein", "nuclear factor kappa B": "protein", "NF-kappaB": "protein" } }, { "input_text": "In electrophoretic mobility shift assays ( EMSAs ) we showed that IL-10 and IL-4 inhibited LPS-induced AP-1 binding activity .", "target_text": { "IL-10": "protein", "IL-4": "protein", "AP-1": "protein" } }, { "input_text": "The inhibiting effect of IL-4 was slightly more pronounced than that of IL-10 .", "target_text": { "IL-4": "protein", "IL-10": "protein" } }, { "input_text": "Downregulation of LPS-induced AP-1 was accompanied , and thus possibly explained , by a reduced expression at mRNA level of the two major components of the AP-1 complex , namely c-fos and c-jun as determined by Northern experiments .", "target_text": { "AP-1": "protein", "LPS-induced AP-1": "protein", "mRNA": "RNA", "AP-1 complex": "protein", "c-fos": "DNA", "c-jun": "DNA" } }, { "input_text": "Binding activity of NF-IL6 was also strongly inhibited by IL-4 whereas IL-10 showed no effect .", "target_text": { "NF-IL6": "protein", "IL-4": "protein", "IL-10": "protein" } }, { "input_text": "NF-IL6 mRNA levels were not affected by IL-10 or IL-4 , suggesting that IL-4 affects binding activity of preexisting NF-IL6 .", "target_text": { "NF-IL6": "protein", "NF-IL6 mRNA": "RNA", "IL-10": "protein", "IL-4": "protein" } }, { "input_text": "Neither IL-10 nor IL-4 inhibited LPS-induced NF-kappa B binding activity .", "target_text": { "IL-10": "protein", "IL-4": "protein", "NF-kappa B": "protein" } }, { "input_text": "In agreement with this finding , Northern experiments where p65 and p105 mRNA levels were determined , demonstrated that expression of these components of the NF-kappa B transcription factor were not affected by IL-10 or IL-4 .", "target_text": { "NF-kappa B": "protein", "IL-10": "protein", "IL-4": "protein" } }, { "input_text": "Furthermore , neither IL-10 nor IL-4 showed any effect on I-kappa B mRNA expression as determined by Northern experiments .", "target_text": { "IL-10": "protein", "IL-4": "protein", "I-kappa B mRNA": "RNA" } }, { "input_text": "Thus , IL-10 and IL-4 similarly affect IL-6 expression .", "target_text": { "IL-10": "protein", "IL-4": "protein", "IL-6": "protein" } }, { "input_text": "However , for IL-4 this was accompanied with a reduction of AP-1 and NF-IL6 binding activity whereas IL-10 only inhibited AP-1 binding activity .", "target_text": { "IL-4": "protein", "IL-10": "protein", "AP-1": "protein" } }, { "input_text": "Regulation of GM-CSF gene transcription by core-binding factor .", "target_text": { "GM-CSF gene": "DNA", "core-binding factor": "protein" } }, { "input_text": "GM-CSF gene activation in T cells is known to involve the transcription factors nuclear factor-kappa B , AP-1 , NFAT , and Sp1 .", "target_text": { "GM-CSF gene": "DNA", "T cells": "cell_type", "transcription factors": "protein", "nuclear factor-kappa B": "protein", "AP-1": "protein", "NFAT": "protein" } }, { "input_text": "Here we demonstrate that the human GM-CSF promoter and enhancer also encompass binding sites for core-binding factor ( CBF ) .", "target_text": { "core-binding factor": "protein", "CBF": "protein" } }, { "input_text": "Significantly , the CBF sites are in each case contained within the minimum essential core regions required for inducible activation of transcription .", "target_text": { "CBF": "protein", "CBF sites": "DNA", "essential core regions": "DNA" } }, { "input_text": "Furthermore , these core regions of the enhancer and promoter each encompass closely linked binding sites for CBF , AP-1 , and NFATp .", "target_text": { "closely linked binding sites": "DNA", "CBF": "protein", "AP-1": "protein", "NFATp": "protein" } }, { "input_text": "The GM-CSF promoter CBF site TGTGGTCA is located 51 bp upstream of the transcription start site and also overlaps a YY-1 binding site .", "target_text": { "CBF": "protein", "GM-CSF promoter CBF site": "DNA", "51 bp upstream": "DNA", "transcription start site": "DNA", "YY-1 binding site": "DNA" } }, { "input_text": "A 2-bp mutation within the CBF site resulted in a 2-3-fold decrease in the activities of both a 69-bp proximal promoter fragment and a 627-bp full-length promoter fragment .", "target_text": { "2-bp mutation": "DNA", "CBF": "protein", "69-bp proximal promoter fragment": "DNA", "627-bp full-length promoter fragment": "DNA" } }, { "input_text": "Stepwise deletions into the proximal promoter also revealed that the CBF site , but not the YY-1 site , was required for efficient induction of transcriptional activation .", "target_text": { "proximal promoter": "DNA", "CBF": "protein", "YY-1 site": "DNA" } }, { "input_text": "The AML1 and CBF beta genes that encode CBF each have the ability to influence cell growth and differentiation and have been implicated as proto-oncogenes in acute myeloid leukemia .", "target_text": { "CBF": "protein", "proto-oncogenes": "DNA" } }, { "input_text": "This study adds GM-CSF to a growing list of cytokines and receptors that are regulated by CBF and which control the growth , differentiation , and activation of hemopoietic cells .", "target_text": { "GM-CSF": "protein", "cytokines": "protein", "CBF": "protein", "hemopoietic cells": "cell_type" } }, { "input_text": "The GM-CSF locus may represent one of several target genes that are dysregulated in acute myeloid leukemia .", "target_text": { "GM-CSF locus": "DNA", "genes": "protein" } }, { "input_text": "Sublethal levels of oxidative stress stimulate transcriptional activation of c-jun and suppress IL-2 promoter activation in Jurkat T cells .", "target_text": { "c-jun": "DNA", "IL-2 promoter": "DNA", "Jurkat T cells": "cell_line" } }, { "input_text": "Sublethal levels of oxidative stress are well known to alter T cell functional responses , but the underlying mechanisms are unknown .", "target_text": {} }, { "input_text": "The current study examined the effects of oxidative stress on transcriptional activities mediated by c-Fos/c-Jun AP-1 and the nuclear factor of activated T cells ( NF-AT ) .", "target_text": { "c-Fos/c-Jun": "protein", "AP-1": "protein", "nuclear factor of activated T cells": "protein", "NF-AT": "protein" } }, { "input_text": "The present results show that Jurkat T cells acutely exposed to micromolar concentrations of H2O2 exhibit substantial increases in AP-1 binding activity and the expression of c-jun but not c-fos mRNA .", "target_text": { "Jurkat T cells": "cell_line", "AP-1": "protein", "c-jun": "DNA", "c-fos mRNA": "RNA" } }, { "input_text": "The preferential induction of c-jun by H2O2 did not represent redox stabilization of mRNA transcripts , and oxidative signals closely resembled PHA/ PMA stimulation by effectively transactivating the full length c-jun promoter via the proximal jun1 tumor promoter-responsive element ( TRE ) -like promoter element .", "target_text": { "c-jun": "DNA", "mRNA transcripts": "RNA", "proximal jun1 tumor promoter-responsive element ( TRE ) -like promoter element": "DNA" } }, { "input_text": "Similarly , the complexes binding the consensus AP-1 TRE and jun TRE-like motifs in cells exposed to oxidative signals or PHA/ PMA were indistinguishable , being composed of c-Fos , c-Jun , and JunD .", "target_text": { "AP-1": "protein", "consensus AP-1 TRE": "DNA", "jun TRE-like motifs": "DNA", "c-Fos": "protein", "c-Jun": "protein", "JunD": "protein" } }, { "input_text": "However , PHA/ PMA but not oxidative signals induced the coordinate activation of reporter constructs containing the AP-1 -TRE , NF-AT , and IL-2 promoter regions along with IL-2 mRNA expression .", "target_text": { "reporter constructs": "DNA", "AP-1": "protein", "AP-1 -TRE": "DNA", "NF-AT": "protein", "IL-2": "protein", "IL-2 mRNA": "RNA" } }, { "input_text": "Furthermore , sublethal levels of H2O2 actively suppressed the transcriptional activation of NF-AT and IL-2 reporters as well as the expression of IL-2 mRNA in cells stimulated with PHA/ PMA .", "target_text": { "NF-AT": "protein", "IL-2 reporters": "DNA", "IL-2": "protein", "IL-2 mRNA": "RNA" } }, { "input_text": "Gel shift analysis revealed that oxidative suppression of NF-AT represented inhibition in the early generation of NFAT complexes rather than the binding of preformed NF-AT complexes .", "target_text": { "NF-AT": "protein", "NFAT complexes": "protein", "NF-AT complexes": "protein" } }, { "input_text": "These results suggest that oxidative signals can positively and negatively regulate T cell transcriptional events and that changes in cellular redox can uncouple AP-1 regulation of c-jun from transcriptional up-regulation of IL-2 via NF-AT .", "target_text": { "T cell": "cell_type", "AP-1": "protein", "c-jun": "DNA", "IL-2": "protein", "NF-AT": "protein" } }, { "input_text": "Inorganic lead activates NF-kappa B in primary human CD4+ T lymphocytes .", "target_text": { "NF-kappa B": "protein", "primary human CD4+ T lymphocytes": "cell_type" } }, { "input_text": "Inorganic lead ( Pb ) is a ubiquitous environmental contaminant that produces a variety of effects on humoral and cell mediated immune responses .", "target_text": {} }, { "input_text": "The underlying molecular mechanism for Pb 's complex effects on the immune system remain obscure .", "target_text": {} }, { "input_text": "Many of Pb 's effects on the immune system could be explained through activation of the transcription factor , NF-kappa B .", "target_text": { "transcription factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "NF-kappa B is critical for T lymphocyte function and is a strong inducer of HIV-LTR activation .", "target_text": { "NF-kappa B": "protein", "HIV-LTR": "DNA" } }, { "input_text": "We demonstrate that Pb at physiologically relevant concentrations activates NF-kappa B in primary human CD4+ T lymphocytes .", "target_text": { "NF-kappa B": "protein", "primary human CD4+ T lymphocytes": "cell_type" } }, { "input_text": "Pb -induced activation of NF-kappa B is blocked by antibodies for p65 and p50 subunits but not cRel , indicating that the p65 : p50 heterodimer ( NF-kappa B ) is involved .", "target_text": { "NF-kappa B": "protein", "antibodies": "protein", "p65": "protein", "p50": "protein", "cRel": "protein", "p65 : p50 heterodimer": "protein" } }, { "input_text": "Functional activation of gene expression by Pb was confirmed using primary CD4+ T cells transfected with an NF-kappa B dependent reporter gene construct .", "target_text": { "primary CD4+ T cells": "cell_line", "NF-kappa B": "protein", "NF-kappa B dependent reporter gene construct": "DNA" } }, { "input_text": "Pb did not activate NF-kappa B in 4 different T cell lines , suggesting that lymphoid cell lines may not be reliable surrogates for the study of transcriptional activation in human T cells .", "target_text": { "NF-kappa B": "protein", "T cell lines": "cell_line", "human T cells": "cell_type" } }, { "input_text": "These data suggest that NF-kappa B may be an important molecular mediator of Pb -induced immunotoxicity .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Tyrosine kinase and cAMP -dependent protein kinase activities in CD40-activated human B lymphocytes .", "target_text": { "Tyrosine kinase": "protein", "cAMP -dependent protein kinase": "protein", "CD40-activated human B lymphocytes": "cell_line" } }, { "input_text": "In vitro , human B lymphocytes undergo long-term proliferation when activated through CD40 , a protein expressed on their cell surface .", "target_text": { "human B lymphocytes": "cell_type", "CD40": "protein" } }, { "input_text": "The nature of CD40 -dependent signals in proliferating fresh human Epstein-Barr virus -negative B lymphocytes is currently unknown .", "target_text": { "CD40": "protein", "human Epstein-Barr virus -negative B lymphocytes": "cell_line" } }, { "input_text": "In this study , a CD40 -dependent B cell culture system was used to examine the role of different signal transduction elements .", "target_text": { "CD40": "protein", "signal transduction elements": "DNA" } }, { "input_text": "Protein kinase C ( PKC ) depletion generated by a long-term phorbol 12 myristate 13-acetate treatment had weak effects on proliferation .", "target_text": { "Protein kinase C": "protein", "PKC": "protein" } }, { "input_text": "Rather , tyrosine phosphorylation was shown to be directly involved in mediating CD40 -dependent signals .", "target_text": { "CD40": "protein" } }, { "input_text": "The use of the protein tyrosine kinase ( PTK ) -specific inhibitor herbimycin A dramatically decreased cellular proliferation without altering the activity of the human immunodeficiency virus-1 long terminal repeat ( HIV-1 LTR ) , a promoter largely dependent on the binding of nuclear factor kappa B ( NF- kappa B ) .", "target_text": { "protein tyrosine kinase": "protein", "PTK": "protein", "human immunodeficiency virus-1 long terminal repeat": "DNA", "HIV-1 LTR": "DNA", "promoter": "DNA", "nuclear factor kappa B": "protein", "NF- kappa B": "protein" } }, { "input_text": "In contrast , the cAMP -dependent protein kinase specific inhibitor H-89 totally inhibited HIV-1 LTR activity at a concentration as low as 100 nM without affecting cellular proliferation .", "target_text": { "cAMP -dependent protein kinase": "protein", "HIV-1 LTR": "DNA" } }, { "input_text": "Electrophoretic mobility shift assay ( EMSA ) and supershift assay using an NF-kappa B binding sequence from the kappa light chain as a probe , revealed that both p65 ( RelA ) and c-Rel were present in CD40 -stimulated B cells .", "target_text": { "NF-kappa B": "protein", "NF-kappa B binding sequence": "DNA", "kappa light chain": "protein", "p65": "protein", "RelA": "protein", "c-Rel": "protein", "CD40": "protein", "CD40 -stimulated B cells": "cell_type" } }, { "input_text": "While PKC depletion did not alter the NF-kappa B level , treatment of B lymphocytes with H-89 or herbimycin A provoked a decrease in the NF-kappa B level .", "target_text": { "PKC": "protein", "NF-kappa B": "protein", "B lymphocytes": "cell_type" } }, { "input_text": "These observations establish the importance of different signal transducing pathways leading to CD40 activation of B lymphocytes .", "target_text": { "CD40": "protein", "B lymphocytes": "cell_type" } }, { "input_text": "Interferons induce normal and aberrant retinoic-acid receptors type alpha in acute promyelocytic leukemia cells : potentiation of the induction of retinoid -dependent differentiation markers .", "target_text": { "Interferons": "protein", "retinoic-acid receptors type alpha": "protein", "acute promyelocytic leukemia cells": "cell_type", "differentiation markers": "protein" } }, { "input_text": "Treatment of the acute promyelocytic ( APL ) cell line NB4 with interferon alpha ( IFN ( alpha ) ) , as well as IFN ( beta ) and gamma , results in an increased expression of the transcripts coding for retinoic-acid receptor type alpha ( RAR ( alpha ) ) and the leukemia-specific retinoic acid receptor PML-RAR .", "target_text": { "acute promyelocytic ( APL ) cell line": "cell_line", "NB4": "cell_line", "interferon alpha": "protein", "IFN ( alpha )": "protein", "retinoic-acid receptor type alpha": "protein", "RAR ( alpha )": "protein", "leukemia-specific retinoic acid receptor": "protein", "PML-RAR": "protein" } }, { "input_text": "Transcriptional induction of the RAR ( alpha ) and PML-RAR mRNAs is rapid and it is parallelled by an increase in the corresponding proteins .", "target_text": {} }, { "input_text": "Up-regulation of RAR ( alpha ) and PML-RAR gene expression by IFN ( alpha ) is accompanied by a strong potentiation in the induction of 2 retinoid -dependent granulocytic markers , i.e. , granulocyte-colony-stimulating factor receptor mRNA and leukocyte alkaline phosphatase .", "target_text": { "RAR ( alpha )": "protein", "PML-RAR": "protein", "IFN ( alpha )": "protein", "retinoid -dependent granulocytic markers": "protein", "granulocyte-colony-stimulating factor receptor": "protein", "granulocyte-colony-stimulating factor receptor mRNA": "RNA", "leukocyte alkaline phosphatase": "protein" } }, { "input_text": "However , IFN ( alpha ) does not have any effects on the retinoid -dependent regulation of the myeloid surface markers CD11b and CD33 .", "target_text": { "IFN ( alpha )": "protein", "myeloid surface markers": "protein", "CD11b": "protein", "CD33": "protein" } }, { "input_text": "The IFN -dependent increase in RAR ( alpha ) levels and the enhancing effect of the cytokine on retinoid -dependent granulocytic markers expression may be a characteristic of PML-RAR positive cells , since the phenomena are not observed in HL-60 promyelocytes .", "target_text": { "IFN": "protein", "RAR ( alpha )": "protein", "cytokine": "protein", "retinoid -dependent granulocytic markers": "protein", "PML-RAR": "protein", "PML-RAR positive cells": "cell_line", "HL-60 promyelocytes": "cell_line" } }, { "input_text": "Interferons as well as retinoids inhibit the growth of NB4 cells , although the 2 classes of compounds do not significantly interact in terms of anti-proliferative activity .", "target_text": { "Interferons": "protein", "NB4 cells": "cell_line" } }, { "input_text": "These results suggest the possible use of combinations between IFNs and retinoic acid in the cyto-differentiating treatment of APL patients .", "target_text": { "IFNs": "protein" } }, { "input_text": "Modulatory effects of glucocorticoids and catecholamines on human interleukin -12 and interleukin -10 production : clinical implications .", "target_text": { "interleukin": "protein" } }, { "input_text": "Interleukin-12 ( IL-12 ) is a key inducer of differentiation of uncommitted T helper ( TH ) cells toward the TH1 phenotype , which regulates cellular immunity , whereas IL-10 inhibits TH1 functions and potentiates TH2-regulated responses ( i.e. , humoral immunity ) .", "target_text": { "Interleukin-12": "protein", "IL-12": "protein", "uncommitted T helper ( TH ) cells": "cell_type", "IL-10": "protein" } }, { "input_text": "To examine the potential effects of stress on TH1/TH2 balance , we studied the ability of three prototype stress hormones - dexamethasone ( a synthetic glucocorticoid ) and the catecholamines norepinephrine and epinephrine - to alter the production of IL-12 ( p70 ) and IL-10 induced by bacterial lipopolysaccharide ( LPS ) in human whole blood .", "target_text": { "IL-12": "protein", "p70": "protein", "IL-10": "protein" } }, { "input_text": "Dexamethasone inhibited LPS -induced bioactive IL-12 production in a dose-dependent fashion and at physiologically relevant concentrations ; it had no effect on IL-10 secretion .", "target_text": { "IL-12": "protein", "IL-10": "protein" } }, { "input_text": "The glucocorticoid -induced reduction of IL-12 production was antagonized by RU 486 , a glucocorticoid -receptor antagonist , suggesting that it was mediated by the glucocorticoid receptor .", "target_text": { "IL-12": "protein" } }, { "input_text": "Norepinephrine and epinephrine also suppressed IL-12 production in a dose-dependent fashion and at physiological concentrations ; both catecholamines , however , dose-dependently increased the production of IL-10 .", "target_text": { "IL-12": "protein", "IL-10": "protein" } }, { "input_text": "The effects of either catecholamine on IL-12 or IL-10 secretion were blocked completely by propranolol , a beta-adrenoreceptor antagonist , indicating that they were mediated by the beta-adrenergic receptor .", "target_text": { "IL-12": "protein", "IL-10": "protein", "beta-adrenergic receptor": "protein" } }, { "input_text": "These findings suggest that the central nervous system may regulate IL-12 and IL-10 secretion and , hence , TH1/TH2 balance via the peripheral end-effectors of the stress system .", "target_text": {} }, { "input_text": "Thus , stress may cause a selective suppression of TH1 functions and a shift toward a TH2 cytokine pattern rather than generalized TH suppression .", "target_text": { "TH2 cytokine": "protein" } }, { "input_text": "The TH1-to-TH2 shift may be responsible for the stress-induced susceptibility of the organism to certain infections .", "target_text": {} }, { "input_text": "Through the same or a reciprocal mechanism , states associated with chronic hyperactivity or hypoactivity of the stress system might influence the susceptibility of an individual to certain autoimmune , allergic , infectious , or neoplastic diseases .", "target_text": {} }, { "input_text": "Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kappa B .", "target_text": { "human monocytic cells": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "There is increasing evidence that lipoproteins of Treponema pallidum and Borrelia burgdorferi are key inflammatory mediators during syphilis and Lyme disease .", "target_text": { "lipoproteins": "protein" } }, { "input_text": "A principal objective of the present study was to identify more precisely similarities and divergences among lipopolysaccharide ( LPS ) - and lipoprotein-lipopeptide- induced immune cell signaling events .", "target_text": {} }, { "input_text": "Like LPS , purified native B. burgdorferi OspA and synthetic analogs of OspA , OspB , and two T. pallidum lipoproteins ( Tpp47 and Tpp17 ) all induced NF-kappa B translocation in THP-1 human monocytoid cells .", "target_text": { "purified native B. burgdorferi OspA": "protein", "OspA": "protein", "OspB": "protein", "T. pallidum lipoproteins": "protein", "Tpp47": "protein", "Tpp17": "protein", "NF-kappa B": "protein", "THP-1 human monocytoid cells": "cell_type" } }, { "input_text": "Acylation of OspA and the synthetic peptides was requisite for cell activation .", "target_text": { "OspA": "protein" } }, { "input_text": "Polymyxin B abrogated only the response to LPS .", "target_text": {} }, { "input_text": "By using 70Z/3-derived pre-B-cell lines either lacking or expressing human CD14 ( the LPS receptor ) , it was observed that expression of human CD14 imparted responsiveness to LPS but not to OspA or spirochetal lipopeptides ( assessed by induction of NF-kappa B and expression of surface immunoglobulin M ) .", "target_text": { "70Z/3-derived pre-B-cell lines": "cell_line", "human CD14": "protein", "LPS receptor": "protein", "OspA": "protein", "spirochetal lipopeptides": "protein", "NF-kappa B": "protein", "surface immunoglobulin M": "protein" } }, { "input_text": "Finally , the biological relevance of the observation that T. pallidum lipoproteins -lipopeptides induce both NF-kappa B and cytokine production in monocytes was supported by the ability of the synthetic analogs to promote human immunodeficiency virus replication in chronically infected U1 monocytoid cells ; these observations also suggest a potential mechanism whereby a syphilitic chancre can serve as a cofactor for human immunodeficiency virus transmission .", "target_text": { "T. pallidum lipoproteins": "protein", "NF-kappa B": "protein", "cytokine": "protein", "monocytes": "cell_type" } }, { "input_text": "The combined data lend additional support to the proposal that spirochetal lipoproteins and LPS initiate monocyte activation via different cell surface events but that the signaling pathways ultimately converge to produce qualitatively similar cellular responses .", "target_text": { "spirochetal lipoproteins": "protein" } }, { "input_text": "LYSP100 -associated nuclear domains ( LANDs ) : description of a new class of subnuclear structures and their relationship to PML nuclear bodies .", "target_text": { "LYSP100": "protein" } }, { "input_text": "The PML gene is fused to the retinoic acid receptor alpha ( RAR alpha ) gene in t(15;17) acute promyelocytic leukemia ( APL ) , creating a PML-RAR alpha fusion oncoprotein .", "target_text": { "PML gene": "DNA", "retinoic acid receptor alpha": "protein", "RAR alpha": "protein", "retinoic acid receptor alpha ( RAR alpha ) gene": "DNA", "PML-RAR": "protein", "PML-RAR alpha fusion oncoprotein": "protein" } }, { "input_text": "The PML gene product has been localized to subnuclear dot-like structures variously termed PODs , ND10s , Kr bodies , or PML nuclear bodies ( PML NBs ) .", "target_text": { "PML gene": "DNA", "PML gene product": "protein", "subnuclear dot-like structures": "cell_line" } }, { "input_text": "The present study describes the cloning of a lymphoid-restricted gene , LYSP100 , that is homologous to another protein that localizes to PML NBs , SP100 .", "target_text": { "lymphoid-restricted gene": "DNA", "LYSP100": "DNA", "SP100": "protein" } }, { "input_text": "In addition to SP100 homology regions , one LYSP100 cDNA isoform contains a bromodomain and a PHD/TTC domain , which are present in a variety of transcriptional regulatory proteins .", "target_text": { "SP100": "protein", "SP100 homology regions": "DNA", "LYSP100": "DNA", "LYSP100 cDNA isoform": "DNA", "bromodomain": "protein", "PHD/TTC domain": "protein", "transcriptional regulatory proteins": "protein" } }, { "input_text": "By immunofluorescence , LYSP100 was localized to nuclear dots that were surprisingly largely nonoverlapping with PML NBs .", "target_text": { "LYSP100": "DNA" } }, { "input_text": "However , a minority of LYSP100 nuclear dots exactly colocalized with PML and SP100 .", "target_text": { "LYSP100": "DNA", "PML": "cell_type", "SP100": "protein" } }, { "input_text": "We term the LYSP100 structures \" LANDs , \" for LYSP100 -associated nuclear domains .", "target_text": { "LYSP100": "DNA" } }, { "input_text": "Although LYSP100 is expressed only in lymphoid cells , LANDs could be visualized in HeLa cells by transfection of a LYSP100 cDNA .", "target_text": { "LYSP100": "DNA", "lymphoid cells": "cell_type", "HeLa cells": "cell_line", "LYSP100 cDNA": "DNA" } }, { "input_text": "Immunoelectron microscopy revealed LANDs to be globular , electron-dense structures morphologically distinct from the annular structures characteristic of PML NBs .", "target_text": {} }, { "input_text": "LANDs were most often found in the nucleoplasm , but were also found at the nuclear membrane and in the cytoplasm , suggesting that these structures may traffic between the cytoplasm and the nucleus .", "target_text": {} }, { "input_text": "By double-immunogold labeling of PML and LYSP100 , some LANDs were shown to contain both PML and LYSP100 .", "target_text": { "PML": "cell_type", "LYSP100": "DNA" } }, { "input_text": "Thus , PML is localized to a second subnuclear domain that is morphologically and biochemically distinct from PML NBs .", "target_text": { "PML": "cell_type" } }, { "input_text": "Transcriptional control of steroid-regulated apoptosis in murine thymoma cells .", "target_text": { "murine thymoma cells": "cell_type" } }, { "input_text": "Early studies in murine T cell lines indicated that transcriptional transactivation functions encoded in the glucocorticoid receptor ( GR ) N-terminal domain are required for glucocorticoid -mediated apoptosis .", "target_text": { "T cell lines": "cell_line", "glucocorticoid receptor": "protein", "GR": "protein", "glucocorticoid receptor ( GR ) N-terminal domain": "protein" } }, { "input_text": "However , more recent studies in human T cell lines have suggested that the N-terminal domain is not necessary for steroid-regulated apoptosis and that GR -mediated transrepression may be the more critical mechanism .", "target_text": { "T cell lines": "cell_line", "human T cell lines": "cell_line", "N-terminal domain": "protein", "GR": "protein" } }, { "input_text": "To better understand the contribution of the GR N-terminal transactivation domain in mediating murine thymocyte apoptosis , we stably transfected GR , GR variants , and the androgen receptor ( AR ) into receptor-negative S49 murine thymoma cells .", "target_text": { "GR": "protein", "GR N-terminal transactivation domain": "protein", "GR variants": "protein", "androgen receptor": "protein", "AR": "protein", "murine thymoma cells": "cell_type", "receptor-negative S49 murine thymoma cells": "cell_line" } }, { "input_text": "GR expression levels were shown to be rate-limiting for initiating the apoptotic pathway , and a positive correlation between steroid sensitivity and GR -mediated induction of an integrated mouse mammary tumor virus ( MMTV ) LTR reporter gene was observed .", "target_text": { "GR": "protein", "mouse mammary tumor virus ( MMTV ) LTR reporter gene": "DNA" } }, { "input_text": "Analysis of GR chimeric receptors containing the potent VP16 and E1A viral transactivation domains in place of the GR N terminus revealed that even low level expression of these receptors resulted in both enhanced steroid sensitivity and MMTV induction , thus supporting a role for transactivation in apoptosis .", "target_text": { "GR": "protein", "GR chimeric receptors": "protein", "GR N terminus": "protein" } }, { "input_text": "In contrast , we found that AR can initiate apoptosis in S49 cells after treatment with 5 alpha-dihydrotestosterone , despite its relative inability to induce high level expression of MMTV .", "target_text": { "AR": "protein", "S49 cells": "cell_line" } }, { "input_text": "To investigate this further , we examined the steroid-regulated expression of an endogenous thymocyte-specific gene called GIG18 .", "target_text": { "thymocyte-specific gene": "DNA", "GIG18": "DNA" } }, { "input_text": "We found that GIG18 was rapidly induced to comparable levels by both AR and GR , demonstrating that AR can indeed function as a transcriptional activator in S49 cells and , moreover , that GIG18 induction may be a marker of early apoptotic events in steroid-treated cells .", "target_text": { "GIG18": "DNA", "AR": "protein", "GR": "protein", "S49 cells": "cell_line" } }, { "input_text": "Taken together , these results support our conclusion that transcriptional transactivation is a necessary signaling component of S49 cell apoptosis , although an additional role for GR -mediated transrepression can not be excluded .", "target_text": { "GR": "protein" } }, { "input_text": "Multiple p21ras effector pathways regulate nuclear factor of activated T cells .", "target_text": { "p21ras": "protein", "activated T cells": "cell_type" } }, { "input_text": "The transcription factor , Nuclear Factor of Activated T cells ( NFAT ) is a major target for p21ras and calcium signalling pathways in the IL-2 gene and is induced by p21ras signals acting in synergy with calcium /calcineurin signals .", "target_text": { "transcription factor": "protein", "Nuclear Factor of Activated T cells": "protein", "NFAT": "protein", "p21ras": "protein", "IL-2 gene": "DNA", "/calcineurin": "protein" } }, { "input_text": "One p21ras effector pathway involves the MAP kinase ERK-2 , and we have examined its role in NFAT regulation .", "target_text": { "p21ras": "protein", "MAP kinase": "protein", "ERK-2": "protein", "NFAT": "protein" } }, { "input_text": "Expression of dominant negative MAPKK-1 prevents NFAT induction .", "target_text": { "MAPKK-1": "protein", "dominant negative MAPKK-1": "protein", "NFAT": "protein" } }, { "input_text": "Constitutively active MAPKK-1 fully activates ERK-2 and the transcription factor Elk-1 , but does not substitute for activated p21ras and synergize with calcium /calcineurin signals to induce NFAT .", "target_text": { "MAPKK-1": "protein", "ERK-2": "protein", "transcription factor": "protein", "Elk-1": "protein", "p21ras": "protein", "/calcineurin": "protein", "NFAT": "protein" } }, { "input_text": "Expression of dominant negative N17Rac also prevents TCR and p21ras activation of NFAT , but without interfering with the ERK-2 pathway .", "target_text": { "N17Rac": "protein", "dominant negative N17Rac": "protein", "TCR": "protein", "p21ras": "protein", "NFAT": "protein", "ERK-2": "protein" } }, { "input_text": "The transcriptional activity of the NFAT binding site is mediated by a complex comprising a member of the NFAT group and AP-1 family proteins .", "target_text": { "NFAT": "protein", "NFAT binding site": "DNA", "AP-1 family proteins": "protein" } }, { "input_text": "The induction of AP-1 by p21ras also requires Rac-1 function .", "target_text": { "AP-1": "protein", "p21ras": "protein", "Rac-1": "protein" } }, { "input_text": "Activated Rac-1 could mimic activated p21ras to induce AP-1 but not to induce NFAT .", "target_text": { "Rac-1": "protein", "Activated Rac-1": "protein", "p21ras": "protein", "activated p21ras": "protein", "AP-1": "protein", "NFAT": "protein" } }, { "input_text": "Moreover , the combination of activated MAPKK-1 and Rac-1 could not substitute for activated p21ras and synergize with calcium signals to induce NFAT .", "target_text": { "MAPKK-1": "protein", "Rac-1": "protein", "p21ras": "protein", "NFAT": "protein" } }, { "input_text": "Thus , p21ras regulation of NFAT in T cells requires the activity of multiple effector pathways including those regulated by MAPKK-1 /ERK-2 and Rac-1 .", "target_text": { "p21ras": "protein", "NFAT": "protein", "T cells": "cell_type", "MAPKK-1": "protein", "/ERK-2": "protein", "Rac-1": "protein" } }, { "input_text": "Retinoid differentiation therapy in promyelocytic leukemia .", "target_text": {} }, { "input_text": "Acute promyelocytic leukemia ( APL ) is a specific type of acute myeloid leukemia characterized by the morphology of the blast cells , a specific t(15;17) translocation , and risks of definite coagulopathy .", "target_text": { "blast cells": "cell_type" } }, { "input_text": "Recently this leukemia was further characterized by an exquisite sensitivity to all-trans retinoic acid 's differentiation effect and the production of a fusion gene altering the gene of RARalpha and a novel gene PML .", "target_text": { "fusion gene": "DNA", "RARalpha": "protein", "PML": "DNA", "novel gene PML": "DNA" } }, { "input_text": "In vivo differentiation therapy with retinoids in APL patients follows strict guidelines related both to the APL cell and the biodisposal of all-trans retinoic acid .", "target_text": {} }, { "input_text": "Differential utilization of Janus kinase -signal transducer activator of transcription signaling pathways in the stimulation of human natural killer cells by IL-2 , IL-12 , and IFN-alpha .", "target_text": { "Janus kinase": "protein", "human natural killer cells": "cell_type", "IL-2": "protein", "IL-12": "protein", "IFN-alpha": "protein" } }, { "input_text": "IL-2- , IL-12- , and IFN-alpha- mediated signaling pathways were analyzed in primary NK cells and in the NK3.3 cell line .", "target_text": { "primary NK cells": "cell_type", "NK3.3 cell line": "cell_line" } }, { "input_text": "Gel mobility shift and immunoprecipitation analyses revealed that in addition to activating STAT3 ( signal transducer and activator of transcription-3 ) and STAT5 , IL-2 induced tyrosine and serine phosphorylation of STAT1 alpha , which formed IFN-gamma-activated sequence-binding complexes by itself and with STAT3 .", "target_text": { "STAT3": "protein", "signal transducer and activator of transcription-3": "protein", "STAT5": "protein", "IL-2": "protein", "STAT1 alpha": "protein", "IFN-gamma-activated sequence-binding complexes": "protein" } }, { "input_text": "Although IL-2 and IFN-alpha activated STAT1 alpha and STAT5 , IL-2 predominantly activated STAT5 , while IFN-alpha predominantly activated STAT1 alpha .", "target_text": { "IL-2": "protein", "IFN-alpha": "protein", "STAT1 alpha": "protein", "STAT5": "protein" } }, { "input_text": "IL-2 induced less STAT1 alpha activation and IFN-alpha induced greater STAT5 activation in NK3.3 cells compared with preactivated primary NK cells .", "target_text": { "IL-2": "protein", "STAT1 alpha": "protein", "IFN-alpha": "protein", "STAT5": "protein", "NK3.3 cells": "cell_line", "preactivated primary NK cells": "cell_line" } }, { "input_text": "In NK3.3 cells , IL-2 induced comparable formation of c-fos promoter sis-inducible element IFN-gamma-activated sequence-binding complexes containing STAT3 alone with complexes containing STAT3 and STAT1 alpha , while in preactivated primary NK cells , it preferentially induced complexes containing STAT3 and STAT1 alpha .", "target_text": { "NK3.3 cells": "cell_line", "IL-2": "protein", "c-fos promoter": "DNA", "IFN-gamma-activated sequence-binding complexes": "protein", "c-fos promoter sis-inducible element IFN-gamma-activated sequence-binding complexes": "protein", "STAT3": "protein", "STAT1 alpha": "protein", "preactivated primary NK cells": "cell_line" } }, { "input_text": "Thus , signaling in NK3.3 cells is not always identical with that in primary NK cells .", "target_text": { "NK3.3 cells": "cell_line", "primary NK cells": "cell_type" } }, { "input_text": "In contrast to IL-2 and IFN-alpha , IL-12 induced strong tyrosine phosphorylation of STAT4 and variable weak phosphorylation of STAT3 .", "target_text": { "IL-2": "protein", "IFN-alpha": "protein", "IL-12": "protein", "STAT4": "protein", "STAT3": "protein" } }, { "input_text": "However , supershift analyses using the c-fos promoter sis-inducible element probe showed that IL-12 activated STAT4 , STAT1 alpha , and STAT3 , and induced complexes containing STAT4 only , STAT4 with STAT1 alpha , STAT3 with STAT1 alpha , or STAT1 alpha only in preactivated primary NK cells .", "target_text": { "c-fos promoter sis-inducible element": "DNA", "c-fos promoter sis-inducible element probe": "DNA", "IL-12": "protein", "STAT4": "protein", "STAT1 alpha": "protein", "STAT3": "protein", "preactivated primary NK cells": "cell_line" } }, { "input_text": "STAT1 alpha activation by IL-12 correlated with increased phosphorylation of serine , but not tyrosine .", "target_text": { "STAT1 alpha": "protein", "IL-12": "protein" } }, { "input_text": "Finally , IL-2 induced tyrosine phosphorylation of JAK1 and JAK3 , while IL-12 induced phosphorylation of JAK2 and TYK2 in both preactivated primary NK and NK3.3 cells .", "target_text": { "IL-2": "protein", "JAK1": "protein", "JAK3": "protein", "IL-12": "protein", "JAK2": "protein", "TYK2": "protein" } }, { "input_text": "Differential phosphorylation and consequent differential activation of both separate and overlapping STAT proteins by IL-2 , IL-12 , and IFN-alpha may provide a molecular basis for the similarities and differences in the actions of these cytokines on NK cells .", "target_text": { "STAT proteins": "protein", "IL-2": "protein", "IL-12": "protein", "IFN-alpha": "protein", "cytokines": "protein", "NK cells": "cell_type" } }, { "input_text": "The suppression of T cell function and NF(kappa)B expression by serine protease inhibitors is blocked by N-acetylcysteine .", "target_text": { "T cell": "cell_type", "NF(kappa)B": "protein" } }, { "input_text": "Direct evidence that N-acetylcysteine ( NAC ) enhances the immune response of peripheral blood T cells at the level of NF(kappa)B is presented .", "target_text": { "peripheral blood T cells": "cell_type", "NF(kappa)B": "protein" } }, { "input_text": "In addition , NAC blocks the suppression of T cell mitogenesis and cytokine production by protease inhibitors such as N-tosylphenylalanine chloromethyl ketone ( TPCK ) .", "target_text": { "cytokine": "protein" } }, { "input_text": "The proliferative responses of purified CD4+ or CD8+ T cells are suppressed more strongly by TPCK when anti-CD28 rather than the phorbol ester PMA is used as the mitogenic coactivator .", "target_text": { "anti-CD28": "protein", "coactivator": "protein" } }, { "input_text": "Cytokine ( IL-2 , IL-6 , INF-gamma ) production is inhibited 95-100 % by concentrations of TPCK that totally suppress the mitogenesis of CD4+ or CD8+ cells .", "target_text": { "Cytokine": "protein", "IL-2": "protein", "IL-6": "protein", "INF-gamma": "protein" } }, { "input_text": "Using electrophoretic mobility shift assays , we find that TPCK virtually abolishes ( to less than 1 % ) the levels of NF(kappa)B ( but not Oct-1 ) found in nuclear and whole cell extracts of activated T cells .", "target_text": { "NF(kappa)B": "protein", "Oct-1": "protein", "activated T cells": "cell_type" } }, { "input_text": "Strikingly , the immunosuppressive effects of TPCK are blocked when T cells are pretreated for 15 min with 5 mM NAC .", "target_text": { "T cells": "cell_type" } }, { "input_text": "NAC not only blocks the effect of TPCK but enhances mitogenesis and cytokine production ( > 2.5-fold in some cases ) upon activation of unsuppressed T cells .", "target_text": { "cytokine": "protein", "T cells": "cell_type", "unsuppressed T cells": "cell_type" } }, { "input_text": "Our data support the notion that NF ( kappa ) B and I ( kappa ) B proteases play obligate roles in T cell activation and mitogenesis , roles that are enhanced significantly by NAC .", "target_text": { "NF ( kappa ) B": "protein", "I ( kappa ) B proteases": "protein" } }, { "input_text": "Signaling by IL-2 and related cytokines : JAKs , STATs , and relationship to immunodeficiency .", "target_text": { "IL-2": "protein", "cytokines": "protein", "JAKs": "protein", "STATs": "protein" } }, { "input_text": "Cytokines that bind to the interleukin-2 ( IL-2 ) receptor common gamma chain ( gamma c ) , including IL-2 , IL-4 , IL-7 , IL-9 , and IL-15 , are important for the growth and differentiation of T and B lymphocytes , natural killer cells , macrophages , and monoctyes .", "target_text": { "Cytokines": "protein", "interleukin-2": "protein", "IL-2": "protein", "interleukin-2 ( IL-2 ) receptor common gamma chain": "protein", "gamma c": "protein", "IL-4": "protein", "IL-7": "protein", "IL-9": "protein", "IL-15": "protein", "natural killer cells": "cell_type", "macrophages": "cell_type", "monoctyes": "cell_type" } }, { "input_text": "These cytokines have overlapping biological effects that in part result from the use of the shared receptor subunit gamma c .", "target_text": { "cytokines": "protein", "shared receptor subunit gamma c": "protein" } }, { "input_text": "Recently it has become clear that these cytokines activate a number of important intracellular signaling molecules , including the Janus kinases JAK1 and JAK3 and members of the transcription factor family of signal transducers and activators of transcription ( STATs ) .", "target_text": { "cytokines": "protein", "intracellular signaling molecules": "protein", "Janus kinases": "protein", "JAK1": "protein", "JAK3": "protein", "transcription factor family": "protein", "signal transducers": "protein", "activators of transcription": "protein", "STATs": "protein" } }, { "input_text": "The discovery of these signaling pathways has led to important new insights into their role in lymphocyte maturation , as it has emerged that mutations in the genes encoding both gamma c and JAK3 result in similar forms of severe combined immunodeficiency ( SCID ) .", "target_text": { "gamma c": "protein", "JAK3": "protein" } }, { "input_text": "In this review we examine the structure and function of cytokine receptors and the signaling pathways involved in their regulation of gene expression .", "target_text": { "cytokine receptors": "protein" } }, { "input_text": "Furthermore , we discuss recent advances that have led to a better understanding of how cytokines elicit intracellular responses , as well as their role in normal lymphoid development .", "target_text": { "cytokines": "protein" } }, { "input_text": "Cytomegalovirus modulates interleukin-6 gene expression .", "target_text": { "interleukin-6": "protein", "interleukin-6 gene": "DNA" } }, { "input_text": "Complications after lung transplantation include the development of rejection and an increased incidence of infection , particularly with cytomegalovirus ( CMV ) .", "target_text": {} }, { "input_text": "Several recent studies have suggested that interleukin ( IL ) -6 may be used to detect both infection and rejection after lung transplantation .", "target_text": {} }, { "input_text": "In addition , IL-6 may play a role in the development of bronchiolitis obliterans after transplantation .", "target_text": { "IL-6": "protein" } }, { "input_text": "Because CMV is also associated with the development of bronchiolitis obliterans after transplantation , we determined whether CMV induces IL-6 gene expression .", "target_text": { "IL-6": "protein" } }, { "input_text": "We demonstrated that CMV infection increased both IL-6 protein and mRNA in peripheral blood mononuclear cells .", "target_text": { "IL-6": "protein", "IL-6 protein": "protein", "mRNA": "RNA", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "We also demonstrated that the CMV immediate early 1 gene product increased expression of the IL-6 promoter .", "target_text": { "CMV immediate early 1 gene product": "protein", "IL-6": "protein", "IL-6 promoter": "DNA" } }, { "input_text": "This effect of the CMV immediate early 1 gene product was dependent upon the presence of specific transcription factor binding sites in the IL-6 promoter .", "target_text": { "CMV immediate early 1 gene product": "protein", "transcription factor binding sites": "DNA", "IL-6": "protein", "IL-6 promoter": "DNA" } }, { "input_text": "These studies demonstrate that CMV may be an important cofactor in the development of rejection and infection after transplantation through its effects on IL-6 .", "target_text": { "IL-6": "protein" } }, { "input_text": "Vitamin D3- and retinoic acid- induced monocytic differentiation : interactions between the endogenous vitamin D3 receptor , retinoic acid receptors , and retinoid X receptors in U-937 cells .", "target_text": { "endogenous vitamin D3 receptor": "protein", "retinoic acid receptors": "protein", "retinoid X receptors": "protein", "U-937 cells": "cell_line" } }, { "input_text": "Retinoic acid ( RA ) and 1,25 alpha-dihydroxycholecalciferol ( VitD3 ) are potent regulators of hematopoletic differentiation .", "target_text": {} }, { "input_text": "Yet , little is known as to how the RA and VitD3 receptor network operates in hematopoietic cells , and whether receptor interactions can explain the interplay between the RA - and VitD3 -signaling pathways during differentiation .", "target_text": { "hematopoietic cells": "cell_type" } }, { "input_text": "Therefore , we analyzed the expression , DNA binding , and transcriptional activity of the endogenous RA and VitD3 receptors [ retinoic acid receptors ( RARs ) , retinoid X receptors ( RXRs ) , and VitD3 receptor ( VDR ) ] in the U-937 cell line , in which RA and VitD3 induce distinct monocytic differentiation pathways .", "target_text": { "endogenous RA and VitD3 receptors": "protein", "retinoic acid": "protein", "retinoic acid receptors": "protein", "RARs": "protein", "retinoid X receptors": "protein", "RXRs": "protein", "VitD3 receptor": "protein", "VDR": "protein", "U-937 cell line": "cell_line" } }, { "input_text": "VitD3 induction resulted in the formation of VDR /RXR DNA-binding complexes on both VitD3 response elements and RA response elements ( RAREs ) .", "target_text": { "VDR": "protein", "VDR /RXR DNA-binding complexes": "protein", "VitD3 response elements": "DNA", "RA response elements": "DNA", "RAREs": "DNA" } }, { "input_text": "However , transcriptional activation was only observed from a VitD3 response element-driven reporter construct .", "target_text": { "VitD3 response element-driven reporter construct": "DNA" } }, { "input_text": "Several DNA-binding complexes were detected on RAREs in undifferentiated cells .", "target_text": { "DNA-binding complexes": "protein", "RAREs": "DNA", "undifferentiated cells": "cell_type" } }, { "input_text": "Stimulation by RA resulted in increased RAR beta /RXR DNA binding , activated RARE -dependent transcription , and increased expression of RAR-beta .", "target_text": { "RAR beta": "protein", "/RXR": "protein", "RARE": "DNA", "RAR-beta": "protein" } }, { "input_text": "Concomitant stimulation by VitD3 inhibited the RA -stimulated formation of RAR beta /RXR heterodimers , favoring VDR /RXR binding to the RARE .", "target_text": { "RAR beta": "protein", "RAR beta /RXR heterodimers": "protein", "VDR": "protein", "/RXR": "protein", "RARE": "DNA" } }, { "input_text": "Also , VitD3 inhibited the expression of CD23 and CD49f , characteristic markers of retinoid-induced U-937 cell differentiation .", "target_text": { "CD23": "protein", "CD49f": "protein", "U-937 cell": "cell_line" } }, { "input_text": "In contrast , neither the RA -stimulated , RARE -mediated transcription nor the induced RAR-beta expression was suppressed by VitD3 , suggesting that VitD3 selectively inhibited the retinoid-induced differentiation program but not the RARE -mediated signal .", "target_text": { "RARE": "DNA", "RAR-beta": "protein" } }, { "input_text": "These results demonstrate a complex role for VitD3 in modifying the retinoid differentiation pathway and may have implications for differentiation-inducing therapy of hematopoietic tumors .", "target_text": {} }, { "input_text": "The human T-cell leukemia virus type 1 posttranscriptional trans-activator Rex contains a nuclear export signal .", "target_text": { "human T-cell leukemia virus type 1 posttranscriptional trans-activator": "protein", "Rex": "protein", "nuclear export signal": "protein" } }, { "input_text": "The Rex protein of human T-cell leukemia virus type 1 is required for the nuclear export of unspliced viral mRNA and , therefore , for virus replication .", "target_text": { "Rex": "protein", "Rex protein": "protein", "unspliced viral mRNA": "RNA" } }, { "input_text": "In this manuscript , we demonstrate that Rex shuttles between the nucleus and the cytoplasm and that its activation domain constitutes a nuclear export signal that specifies efficient transport to the cytoplasm .", "target_text": { "Rex": "protein", "activation domain": "protein", "nuclear export signal": "protein" } }, { "input_text": "These findings are consistent with a model for Rex -mediated trans-activation in which Rex -viral mRNA complexes are targeted for nuclear export by the direct action of the activation domain .", "target_text": { "Rex": "protein", "Rex -viral mRNA complexes": "protein", "activation domain": "protein" } }, { "input_text": "Granulocyte-macrophage colony-stimulating factor preferentially activates the 94-kD STAT5A and an 80-kD STAT5A isoform in human peripheral blood monocytes .", "target_text": { "Granulocyte-macrophage colony-stimulating factor": "protein", "94-kD STAT5A": "protein", "80-kD STAT5A isoform": "protein" } }, { "input_text": "Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) induces immediate effects in monocytes by activation of the Janus kinase ( JAK2 ) and STAT transcription factor ( STAT5 ) pathway .", "target_text": { "Granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "Janus kinase": "protein", "JAK2": "protein", "STAT transcription factor": "protein", "STAT5": "protein" } }, { "input_text": "Recent studies have identified homologues of STAT5 , STAT5A , and STAT5B , as well as lower molecular weight variants of STAT5 .", "target_text": { "STAT5": "protein", "STAT5A": "protein", "STAT5B": "protein" } }, { "input_text": "To define the activation of the STAT5 homologues and lower molecular weight variant in human monocytes and monocytes differentiated into macrophages by culture in macrophage-CSF ( M-CSF ) , we measured the GM-CSF induced tyrosine phosphorylation of STAT5A , STAT5B , and any lower molecular weight STAT5 isoforms .", "target_text": { "STAT5": "protein", "STAT5 homologues": "protein", "human monocytes": "cell_type", "monocytes": "cell_type", "macrophages": "cell_type", "macrophage-CSF": "protein", "M-CSF": "protein", "GM-CSF": "protein", "STAT5A": "protein", "STAT5B": "protein", "STAT5 isoforms": "protein" } }, { "input_text": "Freshly isolated monocytes expressed 94-kD STAT5A , 92-kD STAT5B , and an 80-kD STAT5A molecule .", "target_text": { "STAT5A": "protein", "94-kD STAT5A": "protein", "STAT5B": "protein", "80-kD STAT5A molecule": "protein" } }, { "input_text": "Whereas 94-kD STAT5A was clearly tyrosine phosphorylated and bound to the enhancer element , the gamma response region ( GRR ) , of the Fc gamma RI gene , substantially less tyrosine phosphorylated STAT5B bound to the immobilized GRR element .", "target_text": { "STAT5A": "protein", "94-kD STAT5A": "protein", "enhancer element": "DNA", "gamma response region": "DNA", "GRR": "DNA", "Fc gamma RI gene": "DNA", "STAT5B": "protein", "GRR element": "DNA" } }, { "input_text": "Macrophages lost their ability to express the 80-kD STAT5A protein , but retained their ability to activate STAT5A .", "target_text": { "STAT5A": "protein", "80-kD STAT5A protein": "protein" } }, { "input_text": "STAT5A -STAT5A homodimers and STAT5A -STAT5B heterodimers formed in response to GM-CSF .", "target_text": { "STAT5A": "protein", "-STAT5A": "protein", "STAT5A -STAT5A homodimers": "protein", "-STAT5B": "protein", "STAT5A -STAT5B heterodimers": "protein", "GM-CSF": "protein" } }, { "input_text": "Therefore , activation of STAT5A predominates compared to STAT5B when assayed by direct immunoprecipitation and by evaluation of bound STATs to immobilized GRR .", "target_text": { "STAT5A": "protein", "STAT5B": "protein", "STATs": "protein", "GRR": "DNA" } }, { "input_text": "Selective activation of STAT5 homologues in addition to generation of lower molecular isoforms may provide specificity and control to genes expressed in response to cytokines such as GM-CSF .", "target_text": { "STAT5": "protein", "STAT5 homologues": "protein", "cytokines": "protein", "GM-CSF": "protein" } }, { "input_text": "Translocation ( 3 ; 14 ) ( q27 ; q11 ) : a new variant translocation in a patient with non-Hodgkin 's lymphoma of B-cell type with BCL6 rearrangement .", "target_text": { "Translocation ( 3 ; 14 ) ( q27 ; q11 )": "DNA", "BCL6": "DNA" } }, { "input_text": "We report a 65-year-old woman with non-Hodgkin 's lymphoma ( NHL ) carrying a t(3;14)(q27;q11) and BCL6 rearrangement in the affected cells .", "target_text": { "t(3;14)(q27;q11)": "DNA", "BCL6": "DNA", "affected cells": "cell_type" } }, { "input_text": "She had generalized lymphadenopathy and the bone marrow was infiltrated by lymphoma cells at presentation .", "target_text": { "lymphoma cells": "cell_type" } }, { "input_text": "Histological diagnosis was \" malignant lymphoma , diffuse , large cell \" type according to an International Working Formulation .", "target_text": {} }, { "input_text": "Chromosome analysis revealed a t(3;14)(q27;q11) , which is a new variant translocation of t(3;14) (q27;q32) .", "target_text": { "t(3;14)(q27;q11)": "DNA", "t(3;14) (q27;q32)": "DNA" } }, { "input_text": "Southern blot analysis showed rearrangement of BCL6 , JH , and TCR beta but not of TCR delta .", "target_text": { "BCL6": "DNA", "JH": "DNA", "TCR beta": "DNA", "TCR delta": "DNA" } }, { "input_text": "Cosmid probe of BCL6 hybridized to 14q11 and 3q27 by fluorescence in situ hybridization ( FISH ) .", "target_text": { "Cosmid probe": "DNA", "BCL6": "DNA", "14q11": "DNA", "3q27": "DNA" } }, { "input_text": "Although the band 14q11 is a locus of T-cell receptor alpha- and delta- chains ( TCR alpha/delta ) , lymphoma cells expressed B-cell , IgGk phenotype .", "target_text": { "band 14q11": "DNA", "TCR alpha/delta": "protein", "lymphoma cells": "cell_type", "B-cell , IgGk phenotype": "cell_type" } }, { "input_text": "The findings suggest that a novel proto-oncogene in the vicinity of TCR alpha/delta is involved in this translocation .", "target_text": { "novel proto-oncogene": "DNA", "TCR alpha/delta": "DNA" } }, { "input_text": "Transgenic expression of PML/RARalpha impairs myelopoiesis .", "target_text": { "PML/RARalpha": "protein" } }, { "input_text": "The translocation found in acute promyelocytic leukemia rearranges the promyelocytic leukemia gene ( PML ) on chromosome 15 with the retinoic acid receptor alpha ( RARalpha ) on chromosome 17 .", "target_text": { "promyelocytic leukemia gene": "DNA", "PML": "DNA", "chromosome 15": "DNA", "retinoic acid receptor alpha": "DNA", "RARalpha": "protein", "chromosome 17": "DNA" } }, { "input_text": "This yields a fusion transcript , PML/RARalpha , a transcription factor with reported dominant negative functions in the absence of hormone .", "target_text": { "PML/RARalpha": "protein", "transcription factor": "protein" } }, { "input_text": "Clinical remissions induced with all-trans retinoic acid ( RA ) treatment in acute promyelocytic leukemia are linked to PML/RARalpha expression in leukemic cells .", "target_text": { "PML/RARalpha": "protein", "leukemic cells": "cell_type" } }, { "input_text": "To evaluate the PML/RARalpha role in myelopoiesis , transgenic mice expressing PML/RARalpha were engineered .", "target_text": { "PML/RARalpha": "protein" } }, { "input_text": "A full-length PML/RARalpha cDNA driven by the CD11b promoter was expressed in transgenic mice .", "target_text": { "PML/RARalpha": "protein", "PML/RARalpha cDNA": "DNA", "CD11b promoter": "DNA" } }, { "input_text": "Expression was confirmed in the bone marrow with a reverse transcription PCR assay .", "target_text": {} }, { "input_text": "Basal total white blood cell and granulocyte counts did not appreciably differ between PML/RARalpha transgenic and control mice .", "target_text": { "PML/RARalpha": "protein" } }, { "input_text": "Cell sorter analysis of CD11b+ bone marrow cells revealed similar CD11b+ populations in transgenic and control mice .", "target_text": { "CD11b+ bone marrow cells": "cell_type", "CD11b+ populations": "cell_type" } }, { "input_text": "However , in vitro clonal growth assays performed on peripheral blood from transgenic versus control mice revealed a marked reduction of myeloid progenitors , especially in those responding to granulocyte/ macrophage colony-stimulating factor .", "target_text": { "myeloid progenitors": "cell_type", "granulocyte/ macrophage colony-stimulating factor": "protein" } }, { "input_text": "Granulocyte/macrophage colony-stimulating factor and kit ligand cotreatment did not overcome this inhibition .", "target_text": { "Granulocyte/macrophage colony-stimulating factor": "protein" } }, { "input_text": "Impaired myelopoiesis in vivo was shown by stressing these mice with sublethal irradiation .", "target_text": {} }, { "input_text": "Following irradiation , PML/RARalpha transgenic mice , as compared with controls , more rapidly depressed peripheral white blood cell and granulocyte counts .", "target_text": { "PML/RARalpha": "protein" } }, { "input_text": "As expected , nearly all control mice ( 94.4 % ) survived irradiation , yet this irradiation was lethal to 45.8 % of PML/RARalpha transgenic mice .", "target_text": { "PML/RARalpha": "protein" } }, { "input_text": "Lethality was associated with more severe leukopenia in transgenic versus control mice .", "target_text": {} }, { "input_text": "Retinoic acid treatment of irradiated PML/RARalpha mice enhanced granulocyte recovery .", "target_text": { "PML/RARalpha": "protein", "granulocyte": "cell_type" } }, { "input_text": "These data suggest that abnormal myelopoiesis due to PML/RARalpha expression is an early event in oncogenic transformation .", "target_text": { "PML/RARalpha": "protein" } }, { "input_text": "C/EBP activators are required for HIV-1 replication and proviral induction in monocytic cell lines .", "target_text": { "C/EBP activators": "protein", "monocytic cell lines": "cell_line" } }, { "input_text": "Previous work has shown that C/EBP sites and C/EBP transcriptional activators are necessary for HIV-1 LTR activity in monocytes/macrophages .", "target_text": { "C/EBP sites": "DNA", "C/EBP transcriptional activators": "protein", "HIV-1 LTR": "DNA", "monocytes/macrophages": "cell_type" } }, { "input_text": "We have investigated the role that C/EBP proteins play in induction and replication of HIV-1 .", "target_text": { "C/EBP proteins": "protein" } }, { "input_text": "Ectopic expression of the dominant negative C/EBP protein LIP inhibited HIV-1 mRNA and virus production in activated U1 cells , demonstrating that C/EBP proteins are required for provirus induction .", "target_text": { "C/EBP protein LIP": "protein", "activated U1 cells": "cell_line", "C/EBP proteins": "protein" } }, { "input_text": "U1 lines overexpressing C/EBP activator NF-IL-6 produced more viral mRNA and virus particles following cellular activation than control lines , demonstrating that C/EBP proteins are limiting for virus transcription .", "target_text": { "U1 lines": "cell_line", "C/EBP activator": "protein", "NF-IL-6": "protein", "viral mRNA": "RNA", "control lines": "cell_line", "C/EBP proteins": "protein" } }, { "input_text": "HIV-1 harboring mutations within two C/EBP sites were crippled in their ability to replicate in U937 promonocytic cells , indicating that these sites are required for replication .", "target_text": { "C/EBP sites": "DNA", "U937 promonocytic cells": "cell_line" } }, { "input_text": "These data identify C/EBP proteins as regulators of HIV-1 expression in monocytes/macrophages .", "target_text": { "C/EBP proteins": "protein", "monocytes/macrophages": "cell_type" } }, { "input_text": "Epstein-Barr virus nuclear antigen 2 and latent membrane protein independently transactivate p53 through induction of NF-kappaB activity .", "target_text": { "Epstein-Barr virus nuclear antigen 2": "protein", "latent membrane protein": "protein", "p53": "protein", "NF-kappaB": "protein" } }, { "input_text": "B-cell immortalization by Epstein-Barr virus ( EBV ) is dependent on permanent control of the cellular processes which normally regulate cell division and apoptosis , functions possessed by p53 in a number of normal cell types .", "target_text": { "B-cell": "cell_type", "p53": "protein" } }, { "input_text": "In studies initiated to evaluate relationships between EBV latent genes and p53 , p53 levels were found to increase approximately 10-fold 4 to 5 days after EBV infection of purified resting human B cells ; the induced p53 was transcriptionally active .", "target_text": { "EBV latent genes": "DNA", "p53": "protein", "resting human B cells": "cell_type" } }, { "input_text": "Latent membrane protein 1 and , to a lesser extent , EBV nuclear antigen 2 mediated the increase in p53 levels via activation of the NF-kappaB transcription factor .", "target_text": { "Latent membrane protein 1": "protein", "EBV nuclear antigen 2": "protein", "p53": "protein", "NF-kappaB": "protein", "transcription factor": "protein" } }, { "input_text": "Cooperation between core binding factor and adjacent promoter elements contributes to the tissue-specific expression of interleukin-3 .", "target_text": { "core binding factor": "protein", "adjacent promoter elements": "DNA", "interleukin-3": "protein" } }, { "input_text": "Tissue-specific expression of interleukin-3 ( IL-3 ) is mediated via cis-acting elements located within 315 base pairs of the transcription start .", "target_text": { "interleukin-3": "protein", "IL-3": "protein", "cis-acting elements": "DNA", "transcription start": "DNA" } }, { "input_text": "This is achieved in part through the positive activities of the AP-1 and Elf-1 sites in the IL-3 promoter .", "target_text": { "IL-3": "protein", "IL-3 promoter": "DNA" } }, { "input_text": "The contribution to T cell-specific expression by other promoter sites was assessed in a transient expression assay with IL-3 promoter constructs linked to a luciferase gene , focusing initially on the core binding factor ( CBF ) site , which is footprinted in vivo upon T cell activation .", "target_text": { "promoter sites": "DNA", "IL-3": "protein", "IL-3 promoter constructs": "DNA", "luciferase gene": "DNA", "core binding factor": "protein", "core binding factor ( CBF ) site": "DNA" } }, { "input_text": "Activity of the CBF site is shown to be critically dependent on the adjacent activator site Act-1 .", "target_text": { "CBF site": "DNA", "Act-1": "DNA", "adjacent activator site Act-1": "DNA" } }, { "input_text": "Together the Act-1 and CBF sites form a functional unit ( AC unit ) with dual activity .", "target_text": { "Act-1": "DNA", "CBF sites": "DNA", "functional unit": "DNA", "AC unit": "DNA" } }, { "input_text": "The AC unit is demonstrated to enhance basal activity of promoters both in fibroblasts and T cells .", "target_text": { "AC unit": "DNA", "fibroblasts": "cell_type", "T cells": "cell_type" } }, { "input_text": "This activity is further inducible in activated T cells , but not in fibroblasts .", "target_text": { "T cells": "cell_type", "fibroblasts": "cell_type" } }, { "input_text": "In addition to the already identified NIP repressor site , evidence is presented for a second repressor region that restricts promoter activity in fibroblasts .", "target_text": { "NIP repressor site": "DNA", "second repressor region": "DNA", "fibroblasts": "cell_type" } }, { "input_text": "Finally , a novel positive regulatory element has been mapped in the IL-3 promoter between nucleotide -180 and -210 that leads to increased expression in T cells .", "target_text": { "positive regulatory element": "DNA", "IL-3": "protein", "IL-3 promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "Together these results demonstrate that T cell expression of IL-3 is not specified by the activity of a single tissue-specific element , but instead involves multiple interacting elements that provide both specific positive regulation in T cells and specific negative regulation in fibroblasts .", "target_text": { "IL-3": "protein", "tissue-specific element": "DNA", "interacting elements": "DNA", "T cells": "cell_type", "fibroblasts": "cell_type" } }, { "input_text": "Modulation of the expression of the IFN-gamma receptor beta-chain controls responsiveness to IFN-gamma in human peripheral blood T cells .", "target_text": { "IFN-gamma receptor beta-chain": "protein", "IFN-gamma": "protein", "human peripheral blood T cells": "cell_type" } }, { "input_text": "IFN-gamma has potent antiproliferative and apoptotic effects in T cells that are important in determining T cell development and polarized differentiation .", "target_text": { "IFN-gamma": "protein", "T cells": "cell_type" } }, { "input_text": "Therefore , any event that enables T cells to become less responsive to IFN- gamma may potentially alter immune responsiveness to Ag .", "target_text": { "T cells": "cell_type", "IFN- gamma": "protein", "Ag": "protein" } }, { "input_text": "In this work , we show that human peripheral blood T cells that are stimulated through the TCR and expanded with IL-2 are unresponsive to IFN-gamma , as determined by a lack of activation of jak kinases and the transcription factor , STAT1 ( alpha ) , a signal transducer and activator of transcription .", "target_text": { "human peripheral blood T cells": "cell_type", "TCR": "protein", "IL-2": "protein", "IFN-gamma": "protein", "jak kinases": "protein", "transcription factor": "protein", "STAT1 ( alpha )": "protein" } }, { "input_text": "This nonresponsiveness occurs because of a lack of expression of the beta- chain ( accessory factor ) of the IFN-gamma receptor , while at the same time maintaining IFN-gamma receptor alpha-chain expression .", "target_text": { "beta- chain": "protein", "IFN-gamma receptor": "protein", "IFN-gamma receptor alpha-chain": "protein" } }, { "input_text": "Expression of the beta-chain can be restored by secondary TCR ligation or PMA treatment .", "target_text": { "beta-chain": "protein", "TCR": "protein" } }, { "input_text": "T cell blasts treated with PMA are now responsive to IFN-gamma .", "target_text": { "T cell blasts": "cell_type", "IFN-gamma": "protein" } }, { "input_text": "When freshly isolated , highly enriched ( > 98 % ) T cells are examined for IFN-gamma responsiveness ; these cells can respond to IFN-gamma and express beta-chain .", "target_text": { "T cells": "cell_type", "IFN-gamma": "protein", "beta-chain": "protein" } }, { "input_text": "Therefore , as T cells progress from primary TCR activation through IL-2 -dependent proliferation , followed by secondary TCR stimulation , their responsiveness to IFN-gamma varies , and this may affect their ability to participate in an ongoing immune response .", "target_text": { "T cells": "cell_type", "TCR": "protein", "IL-2": "protein", "IFN-gamma": "protein" } }, { "input_text": "Age-related decreases in IL-2 production by human T cells are associated with impaired activation of nuclear transcriptional factors AP-1 and NF-AT .", "target_text": { "IL-2": "protein", "human T cells": "cell_type", "transcriptional factors": "protein", "nuclear transcriptional factors": "protein", "AP-1": "protein", "NF-AT": "protein" } }, { "input_text": "Although transcriptional factors AP-1 and nuclear factor of activated T cells ( NF-AT ) are important for the normal induction of IL-2 , it is unknown if the age-related decline in IL-2 production by activated human T cells may be associated with aberrancies in transcriptional regulatory proteins .", "target_text": { "transcriptional factors": "protein", "AP-1": "protein", "NF-AT": "protein", "IL-2": "protein", "human T cells": "cell_type", "transcriptional regulatory proteins": "protein" } }, { "input_text": "In the current studies , IL-2 production by T cells from elderly ( mean 78 years ) and young ( mean 37 years ) humans was measured in cultures stimulated with PHA , PHA plus PMA , crosslinked anti-CD3 mAB OKT3 plus PMA , or PMA plus ionomycin .", "target_text": { "IL-2": "protein", "T cells": "cell_type", "PHA": "protein" } }, { "input_text": "Substantial decreases of IL-2 production were observed for cell cultures from 7 of 12 elderly individuals in response to the different stimuli , whereas the levels of IL-2 produced by stimulated T cells from other elderly individuals were equivalent to those observed for stimulated T cells of young subjects .", "target_text": { "IL-2": "protein", "T cells": "cell_type" } }, { "input_text": "Analyses of nuclear extracts by electrophoretic DNA mobility shift assays showed that decreased IL-2 production by stimulated T cells of elderly individuals was closely associated with impairments in the activation of both AP-1 and NF-AT .", "target_text": { "IL-2": "protein", "stimulated T cells": "cell_type", "AP-1": "protein", "NF-AT": "protein" } }, { "input_text": "By contrast , T cells from elderly subjects with normal levels of IL-2 production exhibited normal activation of AP-1 and NF-AT .", "target_text": { "T cells": "cell_type", "IL-2": "protein", "AP-1": "protein", "NF-AT": "protein" } }, { "input_text": "In addition , the results of competition experiments analyzing the normal components of NF-AT showed that the age-related reductions in stimulus-dependent NF-AT complexes corresponded to the slow migrating complexes that were composed of c-Fos/c-Jun AP-1 .", "target_text": { "NF-AT": "protein", "NF-AT complexes": "protein", "c-Fos/c-Jun": "protein", "AP-1": "protein" } }, { "input_text": "The resting and stimulated levels of NF kappa B were reduced in T cells from certain elderly individuals ; however , alterations of NF kappa B did not correlate with changes in IL-2 expression .", "target_text": { "NF kappa B": "protein", "T cells": "cell_type", "IL-2": "protein" } }, { "input_text": "Thus , these results show that age-related impairments in the activation of AP-1 and NF-AT are closely associated with decreased expression of IL-2 and further suggest that aberrancies in the signaling pathways important for the induction of transcriptionally active c-Fos/c-Jun AP-1 may contribute to the impaired activation of NF-AT .", "target_text": { "AP-1": "protein", "NF-AT": "protein", "IL-2": "protein", "c-Fos/c-Jun": "protein" } }, { "input_text": "IL-13 induces phosphorylation and activation of JAK2 Janus kinase in human colon carcinoma cell lines : similarities between IL-4 and IL-13 signaling .", "target_text": { "IL-13": "protein", "JAK2 Janus kinase": "protein", "human colon carcinoma cell lines": "cell_line", "IL-4": "protein" } }, { "input_text": "We have recently reported that IL-13R may share a component with IL-4R . Here we report that both IL-4 and IL-13 share signaling events in human colon carcinoma cell lines ( HT-29 and WiDr ) .", "target_text": { "IL-13R": "protein", "IL-4R": "protein", "IL-4": "protein", "IL-13": "protein", "human colon carcinoma cell lines": "cell_line", "HT-29": "cell_line", "WiDr": "cell_line" } }, { "input_text": "IL-13 caused rapid phosphorylation of the three out of four members of the known Janus family of kinases ( JAKs ) .", "target_text": { "IL-13": "protein", "Janus family of kinases": "protein", "JAKs": "protein" } }, { "input_text": "We show that JAK2 kinase is rapidly phosphorylated and activated in response to IL-13 .", "target_text": { "JAK2 kinase": "protein", "IL-13": "protein" } }, { "input_text": "Within 1 min of activation , JAK2 was phosphorylated , and peaked in 10 min .", "target_text": { "JAK2": "protein" } }, { "input_text": "In addition , IL-13 phosphorylated insulin response substrate-1 , IL-4R p140 , JAK1 , and Tyk2 , but not JAK3 kinase .", "target_text": { "IL-13": "protein", "insulin response substrate-1": "protein", "IL-4R": "protein", "IL-4R p140": "protein", "JAK1": "protein", "Tyk2": "protein", "JAK3 kinase": "protein" } }, { "input_text": "IL-4 also stimulated all three kinases and substrates , but unlike in immune cells , IL-4 did not involve JAK3 activation for its signaling in colon cancer cell lines .", "target_text": { "IL-4": "protein", "kinases": "protein", "immune cells": "cell_type", "JAK3": "protein", "colon cancer cell lines": "cell_line" } }, { "input_text": "Furthermore , JAK2 associated with the IL-4R p140 before and after stimulation with IL-13 .", "target_text": { "JAK2": "protein", "IL-4R": "protein", "IL-4R p140": "protein", "IL-13": "protein" } }, { "input_text": "Both IL-13 and IL-4 induced phosphorylation of IL-4 STAT ( STAT6 ) but not STAT1 , STAT3 , or STAT5 .", "target_text": { "IL-13": "protein", "IL-4": "protein", "IL-4 STAT": "protein", "STAT6": "protein", "STAT1": "protein", "STAT3": "protein", "STAT5": "protein" } }, { "input_text": "125I- IL-13 did not bind to colon cancer cell lines , but unlabeled IL-13 competed for the binding of 125I-IL-4 .", "target_text": { "IL-13": "protein", "125I- IL-13": "protein", "colon cancer cell lines": "cell_line", "125I-IL-4": "protein" } }, { "input_text": "Our data suggest that IL-13 utilizes IL-4R and its signaling pathway , and JAK2 may play an important role in the function of IL-4R and IL-13R in colon cancer cells .", "target_text": { "IL-13": "protein", "IL-4R": "protein", "JAK2": "protein", "IL-13R": "protein", "colon cancer cells": "cell_type" } }, { "input_text": "Differential regulation of IL-6 gene transcription and expression by IL-4 and IL-10 in human monocytic cell lines .", "target_text": { "IL-6": "protein", "IL-6 gene": "DNA", "IL-4": "protein", "IL-10": "protein", "human monocytic cell lines": "cell_line" } }, { "input_text": "IL-4 and IL-10 inhibit the cytokine production and mRNA expression by monocytes/macrophages .", "target_text": { "IL-4": "protein", "IL-10": "protein", "cytokine": "protein", "monocytes/macrophages": "cell_type" } }, { "input_text": "To investigate the molecular mechanism of the inhibitory effect on transcriptional or post-transcriptional regulation of IL-6 gene expression by IL-4 and IL-10 , we studied IL-6 production , expression level of IL-6 mRNA , IL-6 promoter activity , transcriptional activity of NF-kappaB and NF- IL-6 , and IL-6 mRNA stability in human monocytic cell lines , THP-1 and U937 , stimulated by PMA and LPS in the absence or the presence of IL-4 or IL-10 .", "target_text": { "IL-6 gene": "DNA", "IL-4": "protein", "IL-10": "protein", "IL-6": "protein", "IL-6 mRNA": "RNA", "NF-kappaB": "protein", "NF- IL-6": "protein", "human monocytic cell lines": "cell_line", "THP-1": "cell_line", "U937": "cell_line" } }, { "input_text": "Both IL-4 and IL-10 were seen to inhibit IL-6 production and the expression of IL-6 mRNA in both monocytic cell lines studied .", "target_text": { "IL-4": "protein", "IL-10": "protein", "IL-6": "protein", "IL-6 mRNA": "RNA", "monocytic cell lines": "cell_line" } }, { "input_text": "In chloramphenicol acetyltransferase assays , utilizing the transient transfection of a chloramphenicol acetyltransferase reporter plasmid containing the IL-6 gene promoter , IL-4 , but not IL-10 , suppressed the transcriptional activity of the IL-6 gene promoter stimulated by PMA and LPS .", "target_text": { "chloramphenicol acetyltransferase": "protein", "chloramphenicol acetyltransferase reporter plasmid": "DNA", "IL-6": "protein", "IL-6 gene": "DNA", "IL-6 gene promoter": "DNA", "IL-4": "protein", "IL-10": "protein" } }, { "input_text": "Electrophoretic mobility shift assays showed that IL-4 , but not IL-10 , inhibited nuclear NF-kappaB activity , and that IL-4 and IL-10 did not affect NF- IL-6 activity .", "target_text": { "IL-4": "protein", "IL-10": "protein", "NF-kappaB": "protein", "IL-6": "protein" } }, { "input_text": "On the other hand , IL-10 enhanced the degradation of IL-6 mRNA in a mRNA stability assay .", "target_text": { "IL-10": "protein", "IL-6": "protein", "IL-6 mRNA": "RNA" } }, { "input_text": "These results suggest that IL-4 may inhibit the transcription of the IL-6 gene by affecting NF-kappaB binding activity , while IL-10 may inhibit the IL-6 mRNA levels post-transcriptionally , without suppressing promoter activity .", "target_text": { "IL-4": "protein", "IL-6": "protein", "IL-6 gene": "DNA", "NF-kappaB": "protein", "IL-10": "protein", "IL-6 mRNA": "RNA" } }, { "input_text": "Therefore , we conclude that IL-4 and IL-10 inhibit IL-6 production by different mechanisms in human monocytic cell lines .", "target_text": { "IL-4": "protein", "IL-10": "protein", "IL-6": "protein", "human monocytic cell lines": "cell_line" } }, { "input_text": "Activation of nuclear factor of activated T cells in a cyclosporin A -resistant pathway .", "target_text": { "T cells": "cell_type", "nuclear factor of activated T cells": "protein" } }, { "input_text": "The mechanism of action of the immunosuppressive drug cyclosporin A ( CsA ) is the inactivation of the Ca2+ /calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex .", "target_text": { "Ca2+ /calmodulin-dependent serine-threonine phosphatase": "protein", "calcineurin": "protein", "drug-immunophilin complex": "protein" } }, { "input_text": "Inactive calcineurin is unable to activate the nuclear factor of activated T cells ( NFAT ) , a transcription factor required for expression of the interleukin 2 ( IL-2 ) gene .", "target_text": { "calcineurin": "protein", "nuclear factor of activated T cells": "protein", "NFAT": "protein", "transcription factor": "protein", "IL-2": "protein", "interleukin 2 ( IL-2 ) gene": "DNA" } }, { "input_text": "IL-2 production by CsA -treated cells is therefore dramatically reduced .", "target_text": { "IL-2": "protein", "CsA -treated cells": "cell_line" } }, { "input_text": "We demonstrate here , however , that NFAT can be activated , and significant levels of IL-2 can be produced by the CsA -resistant CD28 -signaling pathway .", "target_text": { "NFAT": "protein", "IL-2": "protein", "CD28": "protein" } }, { "input_text": "In transient transfection assays , both multicopy NFAT - and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate ( PMA ) /alpha- CD28 stimulation , and this activation was resistant to CsA .", "target_text": { "NFAT": "protein", "IL-2": "protein", "IL-2 promoter-beta-galactosidase reporter gene constructs": "DNA", "CD28": "protein" } }, { "input_text": "Electrophoretic mobility shift assay showed the induction of a CsA -resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alphaCD28 .", "target_text": { "NFAT": "protein", "CsA -resistant NFAT complex": "protein", "peripheral blood T cells": "cell_type", "alphaCD28": "protein" } }, { "input_text": "Peripheral blood T cells stimulated with PMA /alphaCD28 produced IL-2 in the presence of CsA .", "target_text": { "Peripheral blood T cells": "cell_type", "/alphaCD28": "protein", "IL-2": "protein" } }, { "input_text": "Collectively , these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner .", "target_text": { "NFAT": "protein", "IL-2": "protein", "calcineurin": "protein" } }, { "input_text": "Effects of interleukin-10 on human peripheral blood mononuclear cell responses to Cryptococcus neoformans , Candida albicans , and lipopolysaccharide .", "target_text": { "interleukin-10": "protein", "human peripheral blood mononuclear cell": "cell_type" } }, { "input_text": "Deactivation of mononuclear phagocytes is critical to limit the inflammatory response but can be detrimental in the face of progressive infection .", "target_text": { "mononuclear phagocytes": "cell_type" } }, { "input_text": "We compared the effects of the deactivating cytokine interleukin 10 ( IL-10 ) on human peripheral blood mononuclear cell ( PBMC ) responses to lipopolysaccharide ( LPS ) , Cryptococcus neoformans , and Candida albicans .", "target_text": { "deactivating cytokine": "protein", "interleukin 10": "protein", "IL-10": "protein", "human peripheral blood mononuclear cell": "cell_type", "PBMC": "cell_type" } }, { "input_text": "IL-10 effected dose-dependent inhibition of tumor necrosis factor alpha ( TNF-alpha ) release in PBMC stimulated by LPS and C. neoformans , with significant inhibition seen with 0.1 U/ml and greater than 90 % inhibition noted with 10 U/ml .", "target_text": { "IL-10": "protein", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein", "PBMC": "cell_type" } }, { "input_text": "In contrast , even at doses as high as 100 U/ml , IL-10 inhibited TNF-alpha release in response to C. albicans by only 50 % .", "target_text": { "IL-10": "protein", "TNF-alpha": "protein" } }, { "input_text": "IL-10 profoundly inhibited release of IL-1beta from PBMC stimulated by all three stimuli .", "target_text": { "IL-10": "protein", "IL-1beta": "protein", "PBMC": "cell_type" } }, { "input_text": "TNF-alpha mRNA and release was inhibited even if IL-10 was added up to 8 h after cryptococcal stimulation .", "target_text": { "TNF-alpha": "protein", "TNF-alpha mRNA": "RNA", "IL-10": "protein" } }, { "input_text": "In contrast , inhibition of IL-1 beta mRNA was of lesser magnitude and occurred only when IL-10 was added within 2 h of cryptococcal stimulation .", "target_text": { "IL-1 beta mRNA": "RNA", "IL-10": "protein" } }, { "input_text": "IL-10 inhibited translocation of NF-kappaB in response to LPS but not the fungal stimuli .", "target_text": { "IL-10": "protein", "NF-kappaB": "protein" } }, { "input_text": "All three stimuli induced IL-10 production in PBMC , although over 10-fold less IL-10 was released in response to C. neoformans compared with LPS and C. albicans .", "target_text": { "IL-10": "protein", "PBMC": "cell_type" } }, { "input_text": "Thus , while IL-10 has deactivating effects on PBMC responses to all three stimuli , disparate stimulus- and response-specific patterns of deactivation are seen .", "target_text": { "IL-10": "protein", "PBMC": "cell_type" } }, { "input_text": "Inhibition by IL-10 of proinflammatory cytokine release appears to occur at the level of gene transcription for TNF-alpha and both transcriptionally and posttranscriptionally for IL-1beta .", "target_text": { "IL-10": "protein", "proinflammatory cytokine": "protein", "TNF-alpha": "protein", "IL-1beta": "protein" } }, { "input_text": "Characterization and purification of a protein kinase C substrate in human B cells .", "target_text": { "protein kinase C substrate": "protein", "human B cells": "cell_type" } }, { "input_text": "Identification as lymphocyte-specific protein 1 ( LSP1 ) .", "target_text": { "lymphocyte-specific protein 1": "protein", "LSP1": "protein" } }, { "input_text": "Incubation of B-chronic lymphocytic leukemia ( B-CLL ) cells with phorbol esters resulted in the phosphorylation of two major PKC substrates , MARCKS ( myristoylated , alanine-rich C kinase substrate ) and MRP ( MARCKS -related protein ) , and of a third protein , with an apparent m.w. of 60,000 that was the most prominent protein kinase C substrate in these cells .", "target_text": { "B-chronic lymphocytic leukemia ( B-CLL ) cells": "cell_line", "PKC substrates": "protein", "MARCKS": "protein", "myristoylated , alanine-rich C kinase substrate": "protein", "MRP": "protein", "MARCKS -related protein": "protein", "protein kinase C substrate": "protein" } }, { "input_text": "p60 phosphorylation was time and PMA dose dependent , and was induced by cell-permeable diacylglycerol , but not by inactive phorbol esters .", "target_text": { "p60": "protein" } }, { "input_text": "Two-dimensional electrophoretic analysis of the protein phosphorylation pattern from the B cell line CESS demonstrated the identity between the p60 protein expressed in this cell line and that expressed in B-CLL cells .", "target_text": { "B cell line CESS": "cell_line", "p60": "protein", "p60 protein": "protein", "B-CLL cells": "cell_line" } }, { "input_text": "p60 was purified from CESS cells and peptide microsequencing of this protein revealed that it was lymphocyte-specific protein 1 ( LSP1 ) , that is here characterized as the most prominent protein kinase C substrate in B cells .", "target_text": { "p60": "protein", "CESS cells": "cell_line", "lymphocyte-specific protein 1": "protein", "LSP1": "protein", "protein kinase C substrate": "protein", "B cells": "cell_type" } }, { "input_text": "Transcription factors of T and B lymphocytes -- basic research and clinical perspectives for gastroenterology .", "target_text": { "Transcription factors": "protein" } }, { "input_text": "Tissue specific regulation of gene expression by transcription factors is a fascinating new field in molecular immunology .", "target_text": { "transcription factors": "protein" } }, { "input_text": "This review summarizes data on specific regulation of promoters and enhancers by nuclear trans-acting factors in lymphocytes .", "target_text": { "promoters": "DNA", "enhancers": "DNA", "nuclear trans-acting factors": "protein", "lymphocytes": "cell_type" } }, { "input_text": "The structural classes of transcription factors are described and basic methods for detection and analysis of transcription factors are detailed .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Furthermore , the most important trans-acting factors of T and B lymphocytes ( e.g. NF-kB , NF-AT and STAT families ) and their functional importance are described .", "target_text": { "trans-acting factors": "protein", "NF-kB": "protein", "NF-AT": "protein", "STAT families": "protein" } }, { "input_text": "Several methods for specific down-regulation of transcription factors are shown that may be relevant to treatment of human disease .", "target_text": { "transcription factors": "protein" } }, { "input_text": "The data are discussed with regard to their potential clinical relevance for gastroenterology .", "target_text": {} }, { "input_text": "Selective effects of DNA damaging agents on HIV long terminal repeat activation and virus replication in vitro .", "target_text": { "HIV long terminal repeat": "DNA" } }, { "input_text": "Much attention has recently focused on the observation that UV light can activate the long terminal repeat ( LTR ) of the human immunodeficiency virus ( HIV ) .", "target_text": { "long terminal repeat": "DNA", "LTR": "DNA" } }, { "input_text": "Although the mechanism of LTR activation remains obscure , several lines of investigation have suggested that it is a result of activation of the NF-kappa B transcription factor ( s ) following signaling events related to generalized DNA damage .", "target_text": { "LTR": "DNA", "NF-kappa B": "protein", "transcription factor": "protein" } }, { "input_text": "In this report , we present data demonstrating that HIV LTR activation is not a general consequence of cellular DNA damage , but rather a process unique to specific genotoxic stimuli , and that it does not necessarily depend on activation of NF-kappa B .", "target_text": { "LTR": "DNA", "cellular DNA": "DNA", "NF-kappa B": "protein" } }, { "input_text": "Furthermore , we demonstrate that several of these agents can significantly increase HIV replication and accelerate CD4 -positive lymphocyte cytotoxicity in vitro .", "target_text": { "CD4": "protein" } }, { "input_text": "These findings , therefore , could have clinical significance to AIDS patients with malignancies who are undergoing radiotherapy and chemotherapy .", "target_text": {} }, { "input_text": "Receptors for interleukin ( IL ) -10 and IL-6 -type cytokines use similar signaling mechanisms for inducing transcription through IL-6 response elements .", "target_text": { "IL-6 response elements": "DNA" } }, { "input_text": "The cytoplasmic domain of the receptor for interleukin 10 ( IL-10R ) contains two box 3 sequence motifs that have been identified in the signal-transducing receptor subunits for IL-6-type cytokines and noted to be required for activating STAT3 and inducing transcription through IL-6-responsive elements .", "target_text": { "cytoplasmic domain": "protein", "interleukin 10": "protein", "IL-10R": "protein", "box 3 sequence motifs": "protein", "signal-transducing receptor subunits": "protein", "IL-6-type cytokines": "protein", "STAT3": "protein", "IL-6-responsive elements": "DNA" } }, { "input_text": "To determine whether the IL-10R has signaling functions similar to IL-6R in cells normally expressing these receptors , leukocytes of the B- , T- , and NK- cell lineages were treated with either cytokine .", "target_text": { "IL-10R": "protein", "IL-6R": "protein", "leukocytes": "cell_type" } }, { "input_text": "Both cytokines activated factors that bound to the sis-inducible element and included STAT1 and STAT3 .", "target_text": { "cytokines": "protein", "sis-inducible element": "DNA", "STAT1": "protein", "STAT3": "protein" } }, { "input_text": "The cell response to IL-10 characteristically differed from that to IL-2/IL-15 , IL-4 , and interferon gamma .", "target_text": { "IL-10": "protein", "IL-2/IL-15": "protein", "IL-4": "protein", "interferon gamma": "protein" } }, { "input_text": "The signaling capabilities of the IL-10R for activating specific STAT proteins and inducing gene transcription were defined by reconstitution of receptor functions in transfected tissue culture cells .", "target_text": { "IL-10R": "protein", "STAT proteins": "protein", "transfected tissue culture cells": "cell_line" } }, { "input_text": "COS-1 cells , co-expressing the human IL-10R and individual STAT proteins , confirmed a preference of the IL-10R for STAT3 and STAT1 .", "target_text": { "COS-1 cells": "cell_line", "IL-10R": "protein", "STAT proteins": "protein", "STAT3": "protein", "STAT1": "protein" } }, { "input_text": "Unlike many hematopoietin receptors , the IL-10R did not detectably activate STAT5 .", "target_text": { "hematopoietin receptors": "protein", "IL-10R": "protein", "STAT5": "protein" } }, { "input_text": "The IL-10R , together with reporter gene constructs containing different IL-6-responsive gene elements , reconstituted in hepatoma cells an induction of transcription by IL-10 that was comparable to that by IL-6 .", "target_text": { "IL-10R": "protein", "IL-6-responsive gene elements": "DNA", "hepatoma cells": "cell_type", "IL-10": "protein", "IL-6": "protein" } }, { "input_text": "This regulation could not be appreciably modified by enhanced expression of STAT proteins .", "target_text": { "STAT proteins": "protein" } }, { "input_text": "The similar actions of IL-10R and IL-6R on the induction of endogenous IL-6 -responsive genes were demonstrated in hepatoma cells stably expressing the IL-10R .", "target_text": { "IL-10R": "protein", "IL-6R": "protein", "IL-6": "protein", "IL-6 -responsive genes": "DNA", "hepatoma cells": "cell_type" } }, { "input_text": "These receptor functions required the presence of the box 3 motifs , as shown by the analysis of the mouse IL-10R constructs containing progressively truncated cytoplasmic domains .", "target_text": { "box 3 motifs": "protein", "IL-10R": "protein", "progressively truncated cytoplasmic domains": "protein" } }, { "input_text": "The data demonstrate that the IL-10R , unlike other members of the interferon receptor family , is highly effective in recruiting the signaling pathways of IL-6 -type cytokine receptors .", "target_text": { "IL-10R": "protein", "IL-6": "protein", "IL-6 -type cytokine receptors": "protein" } }, { "input_text": "Induction of CIITA and modification of in vivo HLA-DR promoter occupancy in normal thymic epithelial cells treated with IFN-gamma : similarities and distinctions with respect to HLA-DR-constitutive B cells .", "target_text": { "CIITA": "protein", "HLA-DR promoter": "DNA", "normal thymic epithelial cells": "cell_type", "IFN-gamma": "protein", "HLA-DR-constitutive B cells": "cell_type" } }, { "input_text": "In this study , the IFN-gamma induction of MHC class II gene expression in primary cultures of thymic epithelial cells ( TEC ) was analyzed .", "target_text": { "IFN-gamma": "protein", "MHC class II gene": "DNA", "thymic epithelial cells": "cell_line", "TEC": "cell_line" } }, { "input_text": "This cellular system offers the advantage that MHC class II induction is studied in a \" physiologic \" cell lineage that , as a result of this expression within the thymus , is thought to participate to the selection and maturation of the T cells .", "target_text": { "MHC class II": "protein", "\" physiologic \" cell lineage": "cell_type", "T cells": "cell_type" } }, { "input_text": "It was found that the MHC class II gene expression was associated with the de novo transcription of the gene encoding the CIITA trans-activator , a crucial MHC class II gene regulatory factor .", "target_text": { "MHC class II gene": "DNA", "CIITA": "protein", "CIITA trans-activator": "protein", "MHC class II gene regulatory factor": "protein" } }, { "input_text": "Furthermore , the anatomy of interaction between the MHC class II DRA promoter and corresponding binding factors was analyzed by in vivo DNAse I footprint .", "target_text": { "MHC class II DRA promoter": "DNA", "binding factors": "protein", "DNAse I": "protein" } }, { "input_text": "It was found that treatment with IFN-gamma induces changes in the occupancy of the DRA gene regulatory sequences by nuclear factors .", "target_text": { "IFN-gamma": "protein", "DRA gene regulatory sequences": "DNA", "nuclear factors": "protein" } }, { "input_text": "The resulting occupancy displays strong similarities with the one observed in the MHC class II-constitutive B cells , represented by both the Burkitt lymphoma line Raji and normal tonsil- derived B cells .", "target_text": { "MHC class II-constitutive B cells": "cell_type", "Burkitt lymphoma line Raji": "cell_line", "normal tonsil- derived B cells": "cell_type" } }, { "input_text": "However , some peculiar differences were observed between the TEC , either IFN-gamma -induced or not , and the constitutive B cells .", "target_text": { "TEC": "cell_line", "IFN-gamma": "protein", "B cells": "cell_line" } }, { "input_text": "These results suggest that both common mechanisms , such as the one mediated by the CIITA trans-activator , and distinct tissue-specific constraints contribute to the transcriptional control of constitutive and IFN-gamma -induced MHC class II gene expression .", "target_text": { "CIITA": "protein", "CIITA trans-activator": "protein", "IFN-gamma": "protein", "MHC class II gene": "DNA" } }, { "input_text": "Inhibitory effect of E3330 , a novel quinone derivative able to suppress tumor necrosis factor-alpha generation , on activation of nuclear factor-kappa B .", "target_text": { "tumor necrosis factor-alpha": "protein", "nuclear factor-kappa B": "protein" } }, { "input_text": "(2E)-3-[5-(2,3-Dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid ( E3330 ) , is a novel agent with hepatoprotective activity .", "target_text": {} }, { "input_text": "We report the effect of E3330 on transcriptional activation of tumor necrosis factor ( TNF ) -alpha gene and on nuclear factor ( NF ) -kappa B activation .", "target_text": { "tumor necrosis factor ( TNF ) -alpha gene": "DNA", "nuclear factor ( NF ) -kappa B": "protein" } }, { "input_text": "Nuclear run-on experiments showed that E3330 decreases transcriptional activation of TNF-alpha gene induced by lipopolysaccharide ( LPS ) stimulation in human peripheral monocytes .", "target_text": { "TNF-alpha gene": "DNA", "human peripheral monocytes": "cell_type" } }, { "input_text": "To investigate the inhibitory mechanisms , we constructed a secreted-type placental alkaline phosphatase ( PLAP ) reporter gene whose transcription is controlled by a 1.4-kb human TNF-alpha promoter .", "target_text": { "placental alkaline phosphatase": "protein", "PLAP": "protein", "secreted-type placental alkaline phosphatase ( PLAP ) reporter gene": "DNA", "1.4-kb human TNF-alpha promoter": "DNA" } }, { "input_text": "A stable transformant of the PLAP reporter gene derived from human monocytic cell line showed very little activity on the promoter before stimulation , whereas LPS stimulation led to a dramatic increase in PLAP activity .", "target_text": { "PLAP": "protein", "PLAP reporter gene": "DNA", "human monocytic cell line": "cell_line" } }, { "input_text": "E3330 inhibited this induced promoter activity in a dose-dependent manner .", "target_text": {} }, { "input_text": "There are four putative NF-kappa B binding sites ( kappa B-1 , kappa B-2 , kappa B-3 , kappa B-4 ) in human TNF-alpha promoter .", "target_text": { "NF-kappa B": "protein", "NF-kappa B binding sites": "DNA", "kappa B-1": "DNA", "kappa B-2": "DNA", "kappa B-3": "DNA", "kappa B-4": "DNA", "human TNF-alpha": "protein", "human TNF-alpha promoter": "DNA" } }, { "input_text": "By using mutated promoter- PLAP plasmids , we established that these NF-kappa B sites were necessary for induction of TNF-alpha transcription on stimulation with LPS .", "target_text": { "PLAP": "protein", "mutated promoter- PLAP plasmids": "DNA", "NF-kappa B": "protein", "NF-kappa B sites": "DNA", "TNF-alpha": "protein" } }, { "input_text": "A gel retardation experiment with synthetic double-stranded oligonucleotides showed that activated NF-kappa B consisting of p50/p65 heterodimer bound to all four putative NF-kappa B DNA probes , suggesting that all four putative NF-kappa B recognition sites play an important role in inducible TNF-alpha expression .", "target_text": { "NF-kappa B": "protein", "p50/p65 heterodimer": "protein", "NF-kappa B DNA probes": "DNA", "NF-kappa B recognition sites": "DNA", "TNF-alpha": "protein" } }, { "input_text": "E3330 decreased activated NF-kappa B in nuclei , suggesting that E3330 inhibits NF-kappa B activation and/or translocation of the nuclei .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Western blotting analysis with anti-I kappa B-alpha antibody indicated that E3330 inhibited degradation of I kappa B-alpha , which is an inhibitory protein of NF-kappa B , in LPS -stimulated monocytes .", "target_text": { "anti-I kappa B-alpha antibody": "protein", "I kappa B-alpha": "protein", "inhibitory protein": "protein", "NF-kappa B": "protein", "LPS -stimulated monocytes": "cell_line" } }, { "input_text": "E3330 may suppress the production of active oxygen species serving as common messengers to activate NF-kappa B .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "C-terminal activating and inhibitory domains determine the transactivation potential of BSAP ( Pax-5 ) , Pax-2 and Pax-8 .", "target_text": { "BSAP": "protein", "Pax-5": "DNA", "Pax-2": "DNA", "Pax-8": "DNA" } }, { "input_text": "Pax-5 encodes the transcription factor BSAP which plays an essential role in early B cell development and midbrain patterning .", "target_text": { "Pax-5": "DNA", "transcription factor": "protein", "BSAP": "protein" } }, { "input_text": "In this study we have analysed the structural requirements for transcriptional activation by BSAP .", "target_text": { "BSAP": "protein" } }, { "input_text": "In vitro mutagenesis and transient transfection experiments indicate that the C-terminal serine / threonine / proline -rich region of BSAP contains a potent transactivation domain of 55 amino acids which is active from promoter and enhancer positions .", "target_text": { "C-terminal serine / threonine / proline -rich region": "protein", "BSAP": "protein", "transactivation domain": "protein" } }, { "input_text": "This transactivation domain was found to be inactivated by a naturally occurring frameshift mutation in one PAX-5 allele of the acute lymphoblastic leukemia cell line REH .", "target_text": { "transactivation domain": "protein", "PAX-5 allele": "DNA", "acute lymphoblastic leukemia cell line REH": "cell_line" } }, { "input_text": "The function of the transactivation domain is negatively regulated by adjacent sequences from the extreme C-terminus .", "target_text": { "transactivation domain": "protein", "extreme C-terminus": "protein" } }, { "input_text": "The activating and inhibitory domains function together as an independent regulatory module in different cell types as shown by fusion to the GAL4 DNA binding domain .", "target_text": { "GAL4 DNA binding domain": "protein" } }, { "input_text": "The same arrangement of positively and negatively acting sequences has been conserved in the mammalian Pax-2 and Pax-8 , the zebrafish Pax-b as well as the sea urchin Pax-258 proteins .", "target_text": { "Pax-2": "DNA", "mammalian Pax-2": "DNA", "Pax-8": "DNA", "zebrafish Pax-b": "DNA", "sea urchin Pax-258 proteins": "protein" } }, { "input_text": "These data demonstrate that the transcriptional competence of a subfamily of Pax proteins is determined by a C-terminal regulatory module composed of activating and inhibitory sequences .", "target_text": { "Pax proteins": "protein", "C-terminal regulatory module": "protein" } }, { "input_text": "Second messenger up-regulation of androgen receptor gene transcription is absent in androgen insensitive human prostatic carcinoma cell lines , PC-3 and DU-145 .", "target_text": { "androgen receptor gene": "DNA", "androgen insensitive human prostatic carcinoma cell lines": "cell_line", "PC-3": "cell_line", "DU-145": "cell_line" } }, { "input_text": "A theoretical pathway of transcriptional regulation of the androgen receptor ( AR ) gene is via a cAMP response element ( CRE ) present in its promoter region ( -508 to -501 ) .", "target_text": { "androgen receptor ( AR ) gene": "DNA", "cAMP response element": "DNA", "CRE": "DNA", "promoter region": "DNA" } }, { "input_text": "After 20 h of stimulation with 8-bromo-cAMP , AR mRNA was upregulated in LNCaP but not in either PC-3 or DU-145 cell lines .", "target_text": { "AR mRNA": "RNA", "LNCaP": "cell_line", "PC-3": "cell_line", "DU-145 cell lines": "cell_line" } }, { "input_text": "We have demonstrated that the level of CRE binding protein ( CREB ) was the same in all cell lines and that the putative AR-CRE forms specific and compatible protein interactions with CREB .", "target_text": { "CRE binding protein": "protein", "CREB": "protein", "AR-CRE": "protein" } }, { "input_text": "The ability to regulate AR gene transcription via the second messenger pathway is lost in the PC-3 and DU-145 cell lines .", "target_text": { "AR gene": "DNA" } }, { "input_text": "This may be an important primary mechanism of androgen insensitivity in prostate cancer .", "target_text": {} }, { "input_text": "Structural and functional characterization of the human CD36 gene promoter : identification of a proximal PEBP2/CBF site .", "target_text": { "human CD36 gene promoter": "DNA", "PEBP2/CBF site": "DNA" } }, { "input_text": "CD36 is a cell surface glycoprotein composed of a single polypeptide chain , which interacts with thrombospondin , collagens type I and IV , oxidized low density lipoprotein , fatty acids , anionic phospholipids , and erythrocytes parasitized with Plasmodium falciparum .", "target_text": { "CD36": "protein", "glycoprotein": "protein", "thrombospondin": "protein", "low density lipoprotein": "protein", "erythrocytes": "cell_type" } }, { "input_text": "Its expression is restricted to a few cell types , including monocyte/macrophages .", "target_text": { "monocyte/macrophages": "cell_type" } }, { "input_text": "In these cells , CD36 is involved in phagocytosis of apoptotic cells , and foam cell formation by uptake of oxidized low density lipoprotein .", "target_text": { "CD36": "protein", "apoptotic cells": "cell_type", "oxidized low density lipoprotein": "protein" } }, { "input_text": "To study the molecular mechanisms that control the transcription of the CD36 gene in monocytic cells we have isolated and analyzed the CD36 promoter .", "target_text": { "CD36": "protein", "CD36 promoter": "DNA" } }, { "input_text": "Transient expression experiments of 5'-deletion fragments of the CD36 promoter coupled to luciferase demonstrated that as few as 158 base pairs upstream from the transcription initiation site were sufficient to direct the monocyte-specific transcription of the reporter gene .", "target_text": { "5'-deletion fragments": "DNA", "CD36": "protein", "CD36 promoter": "DNA", "luciferase": "protein", "158 base pairs upstream": "DNA", "transcription initiation site": "DNA", "reporter gene": "DNA" } }, { "input_text": "Within the above region , the fragment spanning nucleotides -158 to -90 was required for optimal transcription in monocytic cells .", "target_text": { "nucleotides -158 to -90": "DNA", "monocytic cells": "cell_type" } }, { "input_text": "Biochemical analysis of the region -158/-90 revealed a binding site for transcription factors of the polyomavirus enhancer-binding protein 2/core-binding factor ( PEBP2/CBF ) family at position -103 .", "target_text": { "-158/-90": "DNA", "transcription factors": "protein", "polyomavirus enhancer-binding protein 2/core-binding factor ( PEBP2/CBF ) family": "protein", "position -103": "DNA" } }, { "input_text": "Disruption of the PEBP2/CBF site markedly diminished the role of the PEBP2/CBF factors in the constitutive transcription of the CD36 gene .", "target_text": { "PEBP2/CBF site": "DNA", "PEBP2/CBF factors": "protein", "CD36": "protein", "CD36 gene": "DNA" } }, { "input_text": "The involvement of members of the PEBP2/CBF family in chromosome translocations associated with acute myeloid leukemia , and in the transcriptional regulation of the myeloid-specific genes encoding for myeloperoxidase , elastase , and the colony-stimulating factor receptor , highlights the relevance of the regulation of the CD36 gene promoter in monocytic cells by members of the PEBP2/CBF family .", "target_text": { "PEBP2/CBF family": "protein", "myeloid-specific genes": "DNA", "myeloperoxidase": "protein", "elastase": "protein", "colony-stimulating factor receptor": "protein", "CD36": "protein", "CD36 gene promoter": "DNA", "monocytic cells": "cell_type" } }, { "input_text": "HLA-DQB1 codon 57 is critical for peptide binding and recognition .", "target_text": { "HLA-DQB1 codon 57": "DNA" } }, { "input_text": "The association of specific HLA-DQ alleles with autoimmunity is correlated with discrete polymorphisms in the HLA-DQ sequence that are localized within sites suitable for peptide recognition .", "target_text": { "HLA-DQ alleles": "DNA", "HLA-DQ sequence": "DNA" } }, { "input_text": "The polymorphism at residue 57 of the DQB1 polypeptide is of particular interest since it may play a major structural role in the formation of a salt bridge structure at one end of the peptide-binding cleft of the DQ molecules .", "target_text": { "salt bridge structure": "protein", "peptide-binding cleft": "protein" } }, { "input_text": "This polymorphism at residue 57 is a recurrent feature of HLA-DQ evolution , occurring in multiple distinct allelic families , which implies a functional selection for maintaining variation at this position in the class II molecule .", "target_text": { "class II molecule": "protein" } }, { "input_text": "We directly tested the amino acid polymorphism at this site as a determinant for peptide binding and for antigen-specific T cell stimulation .", "target_text": {} }, { "input_text": "We found that a single Ala --> Asp amino acid 57 substitution in an HLA-DQ3.2 molecule regulated binding of an HSV-2 VP-16-derived peptide .", "target_text": {} }, { "input_text": "A complementary single-residue substitution in the peptide abolished its binding to DQ3.2 and converted it to a peptide that can bind to DQ3.1 and DQ3.3 Asp -57-positive MHC molecules .", "target_text": { "DQ3.3 Asp -57-positive MHC molecules": "protein" } }, { "input_text": "These binding studies were paralleled by specific T cell recognition of the class II-peptide complex , in which the substituted peptide abolished T cell reactivity , which was directed to the DQ3.2 -peptide complex , whereas the same T cell clone recognized the substituted peptide presented by DQ3.3 , a class II restriction element differing from DQ3.2 only at residue 57 .", "target_text": { "class II-peptide complex": "protein", "DQ3.2 -peptide complex": "protein", "T cell clone": "cell_line" } }, { "input_text": "This structural and functional complementarity for residue 57 and a specific peptide residue identifies this interaction as a key controlling determinant of restricted recognition in HLA-DQ -specific immune response .", "target_text": {} }, { "input_text": "Autocrine activation by interferon-gamma of STAT factors following T cell activation .", "target_text": { "interferon-gamma": "protein", "STAT factors": "protein" } }, { "input_text": "The activation of T cells requires engagement of the T cell receptor/CD3 complex and co-stimulatory molecules , and results in the triggering of several signaling pathways which lead rapidly to the nuclear translocation of several transcription factors , such as nuclear factor ( NF ) -kappa B and NF-AT .", "target_text": { "T cells": "cell_type", "T cell receptor/CD3 complex": "protein", "co-stimulatory molecules": "protein", "transcription factors": "protein", "nuclear factor ( NF ) -kappa B": "protein", "NF-AT": "protein" } }, { "input_text": "A result of this activation process is the induction of a number of genes , including those encoding cytokines such as interleukin-2 , tumor necrosis factor-alpha , and interferon ( IFN ) -gamma which have important immunoregulatory effects .", "target_text": { "cytokines": "protein", "interleukin-2": "protein", "tumor necrosis factor-alpha": "protein", "interferon ( IFN ) -gamma": "protein", "immunoregulatory": "protein" } }, { "input_text": "We report here that a DNA-binding factor containing STAT1 also becomes activated in human peripheral blood T lymphocytes or Jurkat cells , although not until 1-2 h after stimulation .", "target_text": { "DNA-binding factor": "protein", "STAT1": "protein", "human peripheral blood T lymphocytes": "cell_type", "Jurkat cells": "cell_line" } }, { "input_text": "Activation is delayed a further 1-2 hr when mononuclear cell cultures are stimulated by an antigen which requires processing .", "target_text": { "mononuclear cell cultures": "cell_line" } }, { "input_text": "Appearance of the STAT1 factor is significantly reduced in the presence of cyclosporin A , and blocked by cycloheximide , indicating that its activation is dependent upon a protein ( s ) synthesized in response to initial signaling events .", "target_text": { "STAT1": "protein" } }, { "input_text": "Neutralizing antiserum against IFN-gamma , but not other cytokines tested , blocked activation of the factor almost completely , and IFN-gamma was found in the culture supernatants of stimulated cells at levels at which recombinant IFN-gamma could activate the factor in naive cells .", "target_text": { "IFN-gamma": "protein", "cytokines": "protein", "stimulated cells": "cell_line", "naive cells": "cell_type" } }, { "input_text": "Therefore , a STAT1 transcription factor is activated by IFN-gamma synthesized and released upon stimulation of T lymphocyte populations .", "target_text": { "STAT1": "protein", "transcription factor": "protein", "IFN-gamma": "protein", "T lymphocyte populations": "cell_type" } }, { "input_text": "While Jurkat cells both secrete and respond to IFN-gamma in an autocrine loop , it seems likely that the responding cells may differ from those synthesizing this cytokine in the mononuclear cell cultures in the light of the recent report that Th1 cells lack the IFN-gamma receptor chain necessary for activation of STAT1 ( Pernis , A. , Gupta , S. , Gollob , K.J. , Garfein , E. , Coffman , R.L. , Schindler , C. , and Rothman , P. , Science 1995 . 269 : 245 ) .", "target_text": { "Jurkat cells": "cell_line", "IFN-gamma": "protein", "cytokine": "protein", "mononuclear cell cultures": "cell_line", "Th1 cells": "cell_line", "STAT1": "protein" } }, { "input_text": "Absence of T-cell- and B-cell- specific transcription factors TCF-1 , GATA-3 , and BSAP in Hodgkin 's Reed-Sternberg cells .", "target_text": { "TCF-1": "protein", "GATA-3": "protein", "BSAP": "protein", "Hodgkin 's Reed-Sternberg cells": "cell_line" } }, { "input_text": "Based on the presence of T cell receptor-beta ( TcR-beta ) gene rearrangements in L428 and HDLM-1 cells , the expression of CD2 in HDLM-1 cells , and the presence of immunoglobulin heavy-chain ( IgH ) gene rearrangement in KM-H2 cells , some researchers have concluded that these long-term cell lines derived from patients with Hodgkin 's disease are lymphoid in nature .", "target_text": { "T cell receptor-beta": "protein", "TcR-beta": "protein", "T cell receptor-beta ( TcR-beta ) gene rearrangements": "DNA", "CD2": "protein", "HDLM-1 cells": "cell_line", "immunoglobulin heavy-chain": "protein", "IgH": "protein", "immunoglobulin heavy-chain ( IgH ) gene rearrangement": "DNA", "KM-H2 cells": "cell_line", "long-term cell lines": "cell_line" } }, { "input_text": "The information obtained from these cell lines has also been used in arguments for a lymphoid origin of H-RS cells in tissue despite the frequent absence of lymphoid markers and Ig/TcR gene rearrangements in these cells .", "target_text": { "cell lines": "cell_line", "H-RS cells": "cell_line", "lymphoid markers": "protein", "Ig/TcR gene rearrangements": "DNA" } }, { "input_text": "We questioned whether one can use the limited expression of lymphoid markers or the limited gene rearrangement to conclude that H-RS cells have a lymphoid origin , because these markers may be aberrant in tumor cells .", "target_text": { "lymphoid markers": "protein", "H-RS cells": "cell_line", "tumor cells": "cell_type" } }, { "input_text": "In this study , we examined the expression of two T-cell-specific transcription factors ( TCF-1 and GATA-3 ) and one B-cell-specific transcription factor ( BSAP ) in cultured H-RS cells by using a gel mobility shift assay .", "target_text": { "transcription factors": "protein", "T-cell-specific transcription factors": "protein", "TCF-1": "protein", "GATA-3": "protein", "transcription factor": "protein", "B-cell-specific transcription factor": "protein", "BSAP": "protein", "H-RS cells": "cell_line", "cultured H-RS cells": "cell_line" } }, { "input_text": "The sensitivity and specificity of this assay for determination of cell lineage have been established in a large number of cultured human and murine cell lines .", "target_text": { "cell lineage": "cell_line" } }, { "input_text": "All three types of H-RS cell lines were consistently negative for BSAP , TCF-1 , and GATA-3 .", "target_text": { "H-RS cell lines": "cell_line", "BSAP": "protein", "TCF-1": "protein", "GATA-3": "protein" } }, { "input_text": "The absence of GATA-3 was confirmed in H-RS cells in tissues by an in situ hybridization technique .", "target_text": { "GATA-3": "protein", "H-RS cells": "cell_line" } }, { "input_text": "Virtually all B-cell lines , with the exception of some myeloma cell lines , are positive for BSAP , which is the transcription factor for promoters for several B-cell markers , including VpreB1 , lambda 5 , CD19 , and CD20 .", "target_text": { "B-cell lines": "cell_line", "myeloma cell lines": "cell_line", "BSAP": "protein", "transcription factor": "protein", "promoters": "DNA", "B-cell markers": "protein", "VpreB1": "protein", "lambda 5": "protein", "CD19": "protein", "CD20": "protein" } }, { "input_text": "All T-cell lines tested were positive for TCF-1 and GATA-3 , which are the transcription factors for promoters for several T-cell-restricted markers , including CD2 , CD3 , TcR , and lck .", "target_text": { "T-cell lines": "cell_line", "TCF-1": "protein", "GATA-3": "protein", "transcription factors": "protein", "T-cell-restricted markers": "protein", "CD2": "protein", "CD3": "protein", "TcR": "protein", "lck": "protein" } }, { "input_text": "The absence of BSAP , TCF-1 , and GATA-3 clearly indicates an underlying difference between H-RS cells and lymphoid cells .", "target_text": { "BSAP": "protein", "TCF-1": "protein", "GATA-3": "protein", "H-RS cells": "cell_line", "lymphoid cells": "cell_type" } }, { "input_text": "MEK1 and the extracellular signal-regulated kinases are required for the stimulation of IL-2 gene transcription in T cells .", "target_text": { "MEK1": "protein", "extracellular signal-regulated kinases": "protein", "IL-2 gene": "DNA", "T cells": "cell_type" } }, { "input_text": "TCR engagement stimulates the activation of the protein kinase Raf-1 .", "target_text": { "TCR": "protein", "protein kinase": "protein", "Raf-1": "protein" } }, { "input_text": "Active Raf-1 phosphorylates and activates the mitogen-activated protein ( MAP ) kinase /extracellular signal-regulated kinase kinase 1 ( MEK1 ) , which in turn phosphorylates and activates the MAP kinases/extracellular signal regulated kinases , ERK1 and ERK2 .", "target_text": { "Raf-1": "protein", "mitogen-activated protein ( MAP ) kinase": "protein", "mitogen-activated protein ( MAP ) kinase /extracellular signal-regulated kinase kinase 1": "protein", "MEK1": "protein", "MAP kinases/extracellular signal regulated kinases": "protein", "ERK1": "protein", "ERK2": "protein" } }, { "input_text": "Raf-1 activity promotes IL-2 production in activated T lymphocytes .", "target_text": { "Raf-1": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Therefore , we sought to determine whether MEK1 and ERK activities also stimulate IL-2 gene transcription .", "target_text": { "MEK1": "protein", "ERK": "protein", "IL-2 gene": "DNA" } }, { "input_text": "Expression of constitutively active Raf-1 or MEK1 in Jurkat T cells enhanced the stimulation of IL-2 promoter -driven transcription stimulated by a calcium ionophore and PMA , and together with a calcium ionophore the expression of each protein was sufficient to stimulate NF-AT activity .", "target_text": { "Raf-1": "protein", "MEK1": "protein", "T cells": "cell_type", "Jurkat T cells": "cell_line", "IL-2": "protein", "IL-2 promoter": "DNA", "NF-AT": "protein" } }, { "input_text": "Expression of MEK1 -interfering mutants inhibited the stimulation of IL-2 promoter -driven transcription and blocked the ability of constitutively active Ras and Raf-1 to costimulate NF-AT activity with a calcium ionophore .", "target_text": { "MEK1": "protein", "MEK1 -interfering mutants": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "Ras": "protein", "Raf-1": "protein", "NF-AT": "protein" } }, { "input_text": "Expression of the MAP kinase-specific phosphatase , MKP-1 , which blocks ERK activation , inhibited IL-2 promoter and NF-AT -driven transcription stimulated by a calcium ionophore and PMA , and in addition , MKP-1 neutralized the transcriptional enhancement caused by active Raf-1 and MEK1 expression .", "target_text": { "MAP kinase-specific phosphatase": "protein", "MKP-1": "protein", "ERK": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "NF-AT": "protein" } }, { "input_text": "We conclude that the MAP kinase signal transduction pathway consisting of Raf-1 , MEK1 , and ERK1 and ERK2 functions in the stimulation IL-2 gene transcription in activated T lymphocytes .", "target_text": { "MAP kinase": "protein", "Raf-1": "protein", "MEK1": "protein", "ERK1": "protein", "ERK2": "protein", "IL-2": "protein", "IL-2 gene": "DNA", "T lymphocytes": "cell_type" } }, { "input_text": "Multiple transcription factors are required for activation of human interleukin 9 gene in T cells .", "target_text": { "transcription factors": "protein", "human interleukin 9 gene": "DNA", "T cells": "cell_type" } }, { "input_text": "The genetic elements and regulatory mechanisms responsible for human interleukin 9 ( IL-9 ) gene expression in a human T cell leukemia virus type I-transformed human T cell line , C5MJ2 , were investigated .", "target_text": { "IL-9": "protein", "human interleukin 9 ( IL-9 ) gene": "DNA", "human T cell leukemia virus type I-transformed human T cell line": "cell_line", "C5MJ2": "cell_line" } }, { "input_text": "We demonstrated that IL-9 gene expression is controlled , at least in part , by transcriptional activation .", "target_text": { "IL-9": "protein", "IL-9 gene": "DNA" } }, { "input_text": "Transient expression of the luciferase reporter gene linked to serially deleted sequences of the 5'-flanking region of the IL-9 gene has revealed several positive and negative regulatory elements involved in the basal and inducible expression of the IL-9 gene in C5MJ2 cells .", "target_text": { "luciferase reporter gene": "DNA", "5'-flanking region": "DNA", "IL-9": "protein", "IL-9 gene": "DNA", "negative regulatory elements": "DNA", "C5MJ2 cells": "cell_line" } }, { "input_text": "An AP-1 site at -146 to -140 was shown to be involved in the expression of the IL-9 gene .", "target_text": { "IL-9": "protein", "IL-9 gene": "DNA" } }, { "input_text": "A proximal region between -46 and -80 was identified as the minimum sequence for the basal and inducible expression of the IL-9 gene in C5MJ2 cells .", "target_text": { "proximal region": "DNA", "-46 and -80": "DNA", "IL-9": "protein", "IL-9 gene": "DNA", "C5MJ2 cells": "cell_line" } }, { "input_text": "Within this region , an NF-kappaB site at -59 to -50 and its adjacent 20-base pair upstream sequence were demonstrated to play a critical role for the IL-9 promoter activity .", "target_text": { "NF-kappaB": "protein", "NF-kappaB site": "DNA", "-59 to -50": "DNA", "20-base pair upstream sequence": "DNA", "IL-9": "protein", "IL-9 promoter": "DNA" } }, { "input_text": "DNA-protein binding studies indicated that NF-kappaB , c-Jun , and potentially novel proteins ( around 35 kDa ) can bind to this important sequence .", "target_text": { "NF-kappaB": "protein", "c-Jun": "protein", "novel proteins": "protein", "35 kDa": "protein" } }, { "input_text": "Mutations at different sites within this proximal promoter region abolished the promoter activity as well as the DNA binding .", "target_text": { "proximal promoter region": "DNA" } }, { "input_text": "Taken together , these results suggest that the cooperation of different transcription factors is essential for IL-9 gene expression in T cells .", "target_text": { "transcription factors": "protein", "IL-9": "protein", "IL-9 gene": "DNA", "T cells": "cell_type" } }, { "input_text": "DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells .", "target_text": { "granulocyte-macrophage colony-stimulating factor": "protein", "granulocyte-macrophage colony-stimulating factor gene": "DNA" } }, { "input_text": "Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) is a hemopoietic growth factor that is expressed in activated T cells , fibroblasts , macrophages , and endothelial cells .", "target_text": { "Granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein" } }, { "input_text": "Although GM-CSF does not appear to be essential for normal hemopoiesis , overexpression of GM-CSF has been implicated in the pathogenesis of some diseases such as myeloid leukemia and chronic inflammation .", "target_text": { "GM-CSF": "protein" } }, { "input_text": "An NF-kappaB /Rel binding site within the GM-CSF promoter , termed the kappaB element appears to be important for controlling expression in reporter gene assays in response to a number of stimuli in T cells .", "target_text": { "NF-kappaB": "protein", "GM-CSF": "protein", "GM-CSF promoter": "DNA", "reporter gene": "DNA", "T cells": "cell_type" } }, { "input_text": "We investigated oligonucleotide -directed triple helix formation across this regulatory sequence as a potential tool to inhibit GM-CSF gene transcription .", "target_text": { "regulatory sequence": "DNA", "GM-CSF": "protein" } }, { "input_text": "A 15-base oligonucleotide , GM3 , was targeted to a purine-rich region in the GM-CSF proximal promoter , which overlaps the kappaB element .", "target_text": { "purine-rich region": "DNA", "GM-CSF": "protein", "GM-CSF proximal promoter": "DNA", "kappaB element": "DNA" } }, { "input_text": "Gel mobility shift assays and DNase I footprinting demonstrated that GM3 formed a sequence-specific collinear triplex with its double-stranded DNA target .", "target_text": { "DNase I": "protein", "sequence-specific collinear triplex": "DNA", "double-stranded DNA target": "DNA" } }, { "input_text": "Triplex formation by GM3 blocked recombinant and nuclear NF-kappaB proteins binding to the GM-CSF element .", "target_text": { "GM-CSF": "protein", "GM-CSF element": "DNA" } }, { "input_text": "GM3 also caused selective inhibition of the human T-cell lymphotrophic virus-1 Tax transactivator-induced luciferase activity from a reporter construct driven by the GM-CSF promoter in Jurkat T cells .", "target_text": { "human T-cell lymphotrophic virus-1 Tax": "protein", "luciferase": "protein", "GM-CSF": "protein", "GM-CSF promoter": "DNA", "Jurkat T cells": "cell_line" } }, { "input_text": "Finally , GM3 greatly reduced the concentration of endogenous GM-CSF mRNA induced by different stimuli in Jurkat T cells but did not affect interleukin 3 mRNA levels in the same cells .", "target_text": { "GM-CSF": "protein", "GM-CSF mRNA": "RNA", "Jurkat T cells": "cell_line", "interleukin 3": "protein", "interleukin 3 mRNA": "RNA" } }, { "input_text": "We conclude that the kappaB element in the GM-CSF promoter plays a central role in the transcriptional activation of the endogenous GM-CSF gene .", "target_text": { "kappaB element": "DNA", "GM-CSF": "protein", "GM-CSF promoter": "DNA", "GM-CSF gene": "DNA" } }, { "input_text": "Colinear triplex formation acts as a selective transcriptional repressor of the GM-CSF gene and may have potential therapeutic application in cases of undesirable overexpression of this protein .", "target_text": { "GM-CSF": "protein", "GM-CSF gene": "DNA" } }, { "input_text": "Reversible differentiation of human monoblastic leukemia U937 cells by ML-9 , an inhibitor of myosin light chain kinase .", "target_text": { "human monoblastic leukemia U937 cells": "cell_line", "myosin light chain kinase": "protein" } }, { "input_text": "Human monoblastic leukemia U937 cells are induced to differentiate into monocytes and macrophages by various agents .", "target_text": { "Human monoblastic leukemia U937 cells": "cell_line", "monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "We have shown that 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride ( ML-9 ) , an inhibitor of myosin light chain kinase , induces differentiation of monocytoid leukemia cell lines U937 and THP-1 but not of myeloblastic leukemic ML-1 cell or erythroleukemia K562 cells .", "target_text": { "myosin light chain kinase": "protein", "monocytoid leukemia cell lines": "cell_line", "U937": "cell_line", "THP-1": "cell_line", "myeloblastic leukemic ML-1 cell": "cell_line", "erythroleukemia K562 cells": "cell_line" } }, { "input_text": "In the present study , we further analyzed the effect of ML-9 in comparison with that of 1 alpha, 25-dihydroxyvitamin D3 ( VD3 ) a typical inducer of monocytic differentiation .", "target_text": {} }, { "input_text": "ML-9 induced nitroblue tetrazolium ( NBT ) -reducing activity of U937 cell more rapidly than VD3 : This differentiation marker was induced significantly after incubation with ML-9 and VD3 for 4 hours and 1 day , respectively .", "target_text": { "U937 cell": "cell_line" } }, { "input_text": "ML-9 also induced alpha-naphthyl acetate esterase ( ANAE ) activity , another monocytic differentiation marker , more rapidly than VD3 .", "target_text": { "alpha-naphthyl acetate esterase": "protein", "ANAE": "protein" } }, { "input_text": "The maximum levels of these markers induced by ML-9 were comparable to those induced by VD3 , but after removal of ML-9 from the medium by washing the cells , the expressions of theses markers decreased within 4 hours and reached basal levels in 1 day , indicating that ML-9 's induction of expression of differentiation-associated phenotypes was reversible .", "target_text": {} }, { "input_text": "The growth inhibition of U937 cells by ML-9 was also reversible .", "target_text": { "U937 cells": "cell_line" } }, { "input_text": "Similar effects were observed in another line of human monoblastic cells , THP-1 .", "target_text": { "human monoblastic cells": "cell_line", "THP-1": "cell_line" } }, { "input_text": "ML-9 had little or no effect on the morphology of U937 cells but increased the expression of monocyte-macrophage lineage-associated surface antigen , CD14 , to some extent .", "target_text": { "U937 cells": "cell_line", "monocyte-macrophage lineage-associated surface antigen": "protein", "CD14": "protein" } }, { "input_text": "Irreversible terminal differentiation induced by VD3 is associated with down regulation of the expression of c-myc and upregulation of the expression of c-fos and c-jun , but ML-9 did not affect the expression of these oncogenes appreciably .", "target_text": {} }, { "input_text": "ML-9 -induced differentiation was also reversible when the cells were cultured with cultured with ML-9 plus an anti-cancer drug such as 1-beta-D-arabino-furanosylcytosine or daunomycin .", "target_text": {} }, { "input_text": "it became irreversible , however , upon simultaneous treatment with dexamethasone and transforming growth factor-beta 1 ( TGF-beta 1 ) , which did not induce differentiation of U937 cells but caused growth arrest of the cells in the G0/G1 phase of the cell cycle .", "target_text": { "transforming growth factor-beta 1": "protein", "TGF-beta 1": "protein", "U937 cells": "cell_line" } }, { "input_text": "These results suggest that ML-9 should be useful for studying the mechanisms of monocytic differentiation .", "target_text": {} }, { "input_text": "Modulation of endogenous IL-1 beta and IL-1 receptor antagonist results in opposing effects on HIV expression in chronically infected monocytic cells .", "target_text": { "IL-1 beta": "protein", "IL-1 receptor": "protein", "chronically infected monocytic cells": "cell_line" } }, { "input_text": "A proportion of HIV -infected individuals experience episodes of localized or systemic bacterial infections caused by Gram-negative bacteria .", "target_text": {} }, { "input_text": "Many of the clinical side effects of these infections are associated with the production of proinflammatory cytokines , which are induced primarily by LPS , a constituent of the bacterial cell wall of Gram-negative bacteria .", "target_text": { "proinflammatory cytokines": "protein" } }, { "input_text": "The present study examines the mechanisms involved in LPS -mediated induction of HIV expression in U1 cells , a promonocytic cell line chronically infected with HIV .", "target_text": { "U1 cells": "cell_line", "promonocytic cell line": "cell_line" } }, { "input_text": "Stimulation of U1 cells by LPS alone induced minimal levels of HIV expression , which was significantly enhanced by granulocyte-macrophage colony-stimulating factor ( GM-CSF ) .", "target_text": { "U1 cells": "cell_line", "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein" } }, { "input_text": "Costimulation of U1 cells with LPS plus GM-CSF resulted in the accumulation of steady-state levels of HIV RNA ; however , only a weak induction of HIV long terminal repeat -driven transcription , which was not associated with the activation of the cellular transcription factor nuclear factor-kappa B , was noted .", "target_text": { "U1 cells": "cell_line", "GM-CSF": "protein", "HIV RNA": "RNA", "HIV long terminal repeat": "DNA", "cellular transcription factor": "protein", "nuclear factor-kappa B": "protein" } }, { "input_text": "Costimulation of cells with LPS plus GM-CSF induced the production of proinflammatory cytokines , IL-8 , IL-1 beta and IL-6 , but not TNF-alpha .", "target_text": { "GM-CSF": "protein", "proinflammatory cytokines": "protein", "IL-8": "protein", "IL-1 beta": "protein", "IL-6": "protein", "TNF-alpha": "protein" } }, { "input_text": "IL-1 receptor antagonist ( ra ) inhibited LPS enhancement of HIV expression in GM-CSF -stimulated cells , suggesting that endogenous IL-1 was involved in LPS -mediated viral production .", "target_text": { "IL-1 receptor": "protein", "GM-CSF": "protein", "GM-CSF -stimulated cells": "cell_line", "endogenous IL-1": "protein" } }, { "input_text": "In this regard , anti-inflammatory cytokines inhibited LPS plus GM-CSF -stimulated HIV expression , and this effect closely correlated with inhibition of IL-1 beta release and , in particular , with up-regulation of endogenous IL-1ra production .", "target_text": { "anti-inflammatory cytokines": "protein", "GM-CSF": "protein", "IL-1 beta": "protein" } }, { "input_text": "Thus , the balance between an endogenously produced viral inducer ( IL-1 beta ) and an inhibitor ( IL-1ra ) may represent an important pathway leading to modulation of HIV expression from monocytic cells .", "target_text": { "endogenously produced viral inducer": "protein", "IL-1 beta": "protein", "IL-1ra": "protein", "monocytic cells": "cell_type" } }, { "input_text": "Herpesvirus saimiri immortalized gamma delta T cell line activated by IL-12 .", "target_text": { "Herpesvirus saimiri immortalized gamma delta T cell line": "cell_line", "IL-12": "protein" } }, { "input_text": "IL-12 is a novel heterodimeric cytokine important for the regulation and differentiation of lymphocytes and NK cells .", "target_text": { "IL-12": "protein", "heterodimeric cytokine": "protein" } }, { "input_text": "Like other cytokines , IL-12 mediates its biologic activity through high-affinity receptors expressed on responsive cells .", "target_text": { "IL-12": "protein", "responsive cells": "cell_type" } }, { "input_text": "To date , a large number of receptors for IL-12 have been found only on PBMC following activation with PHA or IL-2 .", "target_text": { "IL-12": "protein", "PBMC": "cell_type", "PHA": "protein", "IL-2": "protein" } }, { "input_text": "To gain further knowledge of the IL-12R complex and the IL-12 signal transduction pathway in cytotoxic T cells , we studied a number of human T cell lines that had been transformed to permanent growth with Herpesvirus saimiri , an oncogenic virus of nonhuman primates .", "target_text": { "IL-12R complex": "protein", "IL-12": "protein", "cytotoxic T cells": "cell_type", "human T cell lines": "cell_line" } }, { "input_text": "This paper reports the expression of IL-12R on a human gamma delta T cell line that responds to IL-12 with enhanced cytolytic activity and increased expression of cytolytic effector molecules granzyme B and perforin .", "target_text": { "IL-12R": "protein", "human gamma delta T cell line": "cell_line", "IL-12": "protein", "cytolytic effector molecules": "protein", "granzyme B": "protein", "perforin": "protein" } }, { "input_text": "Using these T cells as a model of IL-12 signal transduction , we confirmed that these events involve members of the Janus kinase family of nonreceptor tyrosine kinases JAK2 , TYK2 , and signal transducer and activator of transcription 4 .", "target_text": { "T cells": "cell_type", "IL-12": "protein", "Janus kinase family": "protein", "nonreceptor tyrosine kinases": "protein", "JAK2": "protein", "TYK2": "protein", "signal transducer and activator of transcription 4": "protein" } }, { "input_text": "Regulation of gene expression at early stages of B-cell and T-cell differentiation .", "target_text": {} }, { "input_text": "The expression of distinct sets of genes at different stages of B-lymphocyte and T-lymphocyte differentiation is controlled at the level of transcription .", "target_text": {} }, { "input_text": "A number of recent studies have described interactions between transcription factors in lymphocytes that provide new insights into mechanisms regulating gene expression .", "target_text": { "transcription factors": "protein" } }, { "input_text": "These mechanisms include the assembly of higher order nucleoprotein complexes and other protein-protein interactions that enhance the functional specificity of transcriptional regulators in lymphocytes .", "target_text": { "higher order nucleoprotein complexes": "protein", "transcriptional regulators": "protein" } }, { "input_text": "Identification of a human LIM-Hox gene , hLH-2 , aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1 .", "target_text": { "human LIM-Hox gene": "DNA", "hLH-2": "DNA", "9q33-34.1": "DNA" } }, { "input_text": "We describe the isolation of human LH-2 , a putative transcription factor containing two cysteine -rich regions ( LIM domains ) and a homeobox ( Hox ) DNA-binding domain .", "target_text": { "human LH-2": "protein", "putative transcription factor": "protein", "cysteine -rich regions": "protein", "LIM domains": "protein", "homeobox ( Hox ) DNA-binding domain": "protein" } }, { "input_text": "High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia ( CML ) tested , regardless of disease status .", "target_text": { "hLH-2": "DNA" } }, { "input_text": "hLH-2 was mapped to chromosome 9Q33-34.1 , in the same region as the reciprocal translocation that creates the BCR-ABL chimera of the Philadelphia chromosome ( Ph ' ) , the hallmark of CML ; hLH-2 was retained on the derivative 9 chromosome and is therefore centromeric of c-ABL .", "target_text": { "hLH-2": "DNA", "chromosome 9Q33-34.1": "DNA", "BCR-ABL chimera": "protein", "derivative 9 chromosome": "DNA", "c-ABL": "DNA" } }, { "input_text": "The proximity of hLH-2 to the breakpoint on chromosome 9 raises the possibility of cis-activation by the t(9;22)(q34;q11) translocation .", "target_text": { "hLH-2": "DNA", "chromosome 9": "DNA", "t(9;22)(q34;q11) translocation": "DNA" } }, { "input_text": "In addition to finding hLH-2 expression in all cases of CML , expression was observed in lymphoid malignancies and myeloid cell lines , but not in primary cases of acute myelogenous leukaemia .", "target_text": { "hLH-2": "DNA", "myeloid cell lines": "cell_line" } }, { "input_text": "The role of hLH-2 in the development or progression of leukaemia is not known .", "target_text": { "hLH-2": "DNA" } }, { "input_text": "However , hLH-2 may prove useful as a marker of CML for monitoring residual disease .", "target_text": { "hLH-2": "DNA" } }, { "input_text": "Lymphoid cell resistance to glucocorticoids in HIV infection .", "target_text": {} }, { "input_text": "In humans infected with the HIV-1 virus there may be a disproportionate severity of signs and symptoms of illness compared to the fraction of CD4+ infected T-lymphoid cells .", "target_text": { "CD4+ infected T-lymphoid cells": "cell_line" } }, { "input_text": "In part , this may be due to altered intercellular signalling systems and intracellular signal transduction .", "target_text": {} }, { "input_text": "Glucocorticoids are well known for their effects on the vitality and function of lymphoid cells .", "target_text": { "lymphoid cells": "cell_type" } }, { "input_text": "Patients with HIV infections often show elevated circulating levels of cortisol , suggesting some misfunction in the regulatory systems that maintain the levels of this critical hormone .", "target_text": {} }, { "input_text": "At the cellular level , it is known that both acute HIV infection and glucocorticoids can cause apoptotic cell death in thymic lymphocytes .", "target_text": { "thymic lymphocytes": "cell_type" } }, { "input_text": "However , chronically HIV -infected cells appear to be resistant to glucocorticoid-evoked cell death .", "target_text": { "chronically HIV -infected cells": "cell_type" } }, { "input_text": "Glucocorticoid receptor -ligand binding studies on patients ' cells have shown reduced affinity between the receptor binding sites and test steroids .", "target_text": { "Glucocorticoid receptor": "protein", "receptor binding sites": "protein" } }, { "input_text": "In vitro , chronically HIV -infected cells of the lymphoid CEM line displayed resistance to glucocorticoid-induced apoptosis .", "target_text": { "chronically HIV -infected cells": "cell_line", "lymphoid CEM line": "cell_line" } }, { "input_text": "These cells showed reduced numbers of binding sites with little alteration in apparent affinity between ligand and receptor .", "target_text": { "binding sites": "protein" } }, { "input_text": "Thus it appears that there may often be malfunction of the normal glucocorticoid response in HIV -infected cells probably due to altered interactions between the glucocorticoid receptor and its hormone .", "target_text": { "HIV -infected cells": "cell_type", "glucocorticoid receptor": "protein" } }, { "input_text": "Such alterations may have clinical consequences , including the possibility of a relatively longer life span of infected CD4+ T-lymphocytes , as well as systemic effects of chronically elevated cortisol level .", "target_text": { "infected CD4+ T-lymphocytes": "cell_type" } }, { "input_text": "Abundant expression of erythroid transcription factor P45 NF-E2 mRNA in human peripheral granurocytes .", "target_text": { "erythroid transcription factor": "protein", "P45": "protein", "erythroid transcription factor P45 NF-E2 mRNA": "RNA", "human peripheral granurocytes": "cell_type" } }, { "input_text": "Transcription factor NF-E2 is crucial for regulation of erythroid-specific gene expression .", "target_text": { "Transcription factor NF-E2": "protein" } }, { "input_text": "p45 subunit of NF-E2 contains a basic-leucine zipper domain and dimerizes with the small Maf family protein to form functional NF-E2 complex .", "target_text": { "p45 subunit": "protein", "NF-E2": "protein", "basic-leucine zipper domain": "protein", "small Maf family protein": "protein", "NF-E2 complex": "protein" } }, { "input_text": "While p45 expression was shown to be restricted to erythroid cells , megakaryocytes and mast cells in hematopoietic lineage , we found in this study that p45 mRNA is abundantly transcribed in the granulocyte fraction of human peripheral blood cells .", "target_text": { "p45": "protein", "erythroid cells": "cell_type", "megakaryocytes": "cell_type", "mast cells": "cell_type", "p45 mRNA": "RNA", "granulocyte fraction": "cell_type", "human peripheral blood cells": "cell_type" } }, { "input_text": "As neutrophils occupy approximately 92 % of the cells in granulocyte fraction of human peripheral blood cells .", "target_text": { "neutrophils": "cell_type", "granulocyte fraction": "cell_type", "human peripheral blood cells": "cell_type" } }, { "input_text": "As neutrophils occupy approximately 92 % of the cells in this fraction , the cells expressing p45 is most likely to be neutrophils .", "target_text": { "neutrophils": "cell_type", "p45": "protein" } }, { "input_text": "p45 mRNA is also expressed in HL-60 promyelocytes , albeit the expression level is much lower than that of the granulocyte fraction .", "target_text": { "p45": "protein", "p45 mRNA": "RNA", "HL-60 promyelocytes": "cell_line", "granulocyte fraction": "cell_type" } }, { "input_text": "HL-60 cells were found to express mafK mRNA , indicating the presence of genuine NF-E2 complex in the cells .", "target_text": { "HL-60 cells": "cell_line", "mafK mRNA": "RNA", "NF-E2 complex": "protein" } }, { "input_text": "Although p45 mRNA is transcribed from two different promoters , aNF-E2 promoter and fNF-E2 promoter , in erythroid and megakaryocytic lineage cells , p45 mRNA is transcribed only from aNF-E2 promoter .", "target_text": { "p45": "protein", "p45 mRNA": "RNA", "aNF-E2 promoter": "DNA", "fNF-E2 promoter": "DNA" } }, { "input_text": "The expression of p45 megakaryocytic lineage cells , p45 mRNA is transcribed only from aNF-E2 promoter .", "target_text": { "p45": "protein", "megakaryocytic lineage cells": "cell_type", "p45 mRNA": "RNA", "aNF-E2 promoter": "DNA" } }, { "input_text": "The expression of p45 mRNA in the neutrophils declined rapidly after transfer of the cells to in vitro culture and G-CSF could not sustain the expression from the down-regulation , suggesting the E2 may also participate in the regulation of neutrophil-specific gene expression .", "target_text": { "p45": "protein", "p45 mRNA": "RNA", "neutrophils": "cell_type", "G-CSF": "protein", "E2": "protein" } }, { "input_text": "Expression of c-fos and c-jun proteins and AP-1 binding activity during cell cycle progression of HL60 cells and phytohemagglutinin -stimulated lymphocytes .", "target_text": { "c-fos": "DNA", "c-jun": "DNA", "c-jun proteins": "protein", "c-fos and c-jun proteins": "protein", "AP-1": "protein", "HL60 cells": "cell_line", "phytohemagglutinin": "protein", "phytohemagglutinin -stimulated lymphocytes": "cell_line" } }, { "input_text": "The protein products of the c-fos ( p62c-fos ) and c-jun ( p39c-jun ) genes are members of the AP-1 transcription factor family and are thought to play important roles in the regulation of gene expression during the cell cycle .", "target_text": { "c-fos": "DNA", "p62c-fos": "protein", "c-jun": "DNA", "p39c-jun": "protein", "AP-1": "protein", "AP-1 transcription factor family": "protein" } }, { "input_text": "Most studies on the expression of these proteins in relation to the cell cycle have been performed at the mRNA level , and therefore do not give direct information about the presence of the proteins during the cell cycle .", "target_text": {} }, { "input_text": "We have used Western blotting to investigate the presence of these proteins during the cell cycles of two different cellular systems : a continuously growing myeloid leukemic cell line , HL60 , and normal cells stimulated into cycle , phyto- hemagglutinin ( PHA ) -stimulated normal human peripheral blood lymphocytes ( PBL ) .", "target_text": { "cellular systems": "cell_line", "continuously growing myeloid leukemic cell line": "cell_line", "HL60": "cell_line", "normal cells": "cell_type", "PHA": "protein", "phyto- hemagglutinin ( PHA ) -stimulated normal human peripheral blood lymphocytes": "cell_line", "PBL": "cell_type" } }, { "input_text": "The binding activity of transcription factor AP-1 , which consists of dimers of Fos and Jun family proteins , was also studied using a gel shift assay .", "target_text": { "AP-1": "protein" } }, { "input_text": "We found nuclear p62c-fos , p39c-jun , and AP-1 binding activity throughout the cell cycle both in HL60 cells and in PHA -stimulated PBL , and we postulate that these proteins are required throughout the cell cycle and not transiently in the G0 to G1 transition as previous mRNA studies have indicated .", "target_text": { "p62c-fos": "protein", "p39c-jun": "protein", "AP-1": "protein", "HL60 cells": "cell_line", "PHA": "protein", "PHA -stimulated PBL": "cell_line" } }, { "input_text": "We demonstrated an uncoupling of AP-1 binding activity from p62c-fos , and p39c-jun AP-1 activity was expressed more strongly in the G1- and G2/M- phase enriched samples than in the S-phase enriched samples of HL60 cells , while levels of nuclear p62c-fos and p39c-jun were constant .", "target_text": { "AP-1": "protein", "p62c-fos": "protein", "p39c-jun": "protein", "HL60 cells": "cell_line" } }, { "input_text": "Nuclei of unstimulated PBL from different donors expressed p62c-fos and p39c-jun , but AP-1 was not detected in the majority of samples .", "target_text": { "unstimulated PBL": "cell_type", "p62c-fos": "protein", "p39c-jun": "protein", "AP-1": "protein" } }, { "input_text": "Following PHA stimulation of PBL , the increase in AP-1 activity was delayed with respect to the augmentation of p39c-jun expression .", "target_text": { "PHA": "protein", "PBL": "cell_type", "AP-1": "protein", "p39c-jun": "protein" } }, { "input_text": "We also observed that cytoplasmic p62c-fos and p39c-jun were present in HL60 cells and PHA -stimulated PBL .", "target_text": { "HL60 cells": "cell_line", "PHA": "protein", "PBL": "cell_type", "PHA -stimulated PBL": "cell_line" } }, { "input_text": "However , no cytoplasmic p62c-fos was detected in unstimulated PBL , although in some cases cytoplasmic p39c-jun was detected , suggesting that subcellular compartmentalization of these proteins may occur under certain circumstances .", "target_text": { "p62c-fos": "protein", "cytoplasmic p62c-fos": "protein", "unstimulated PBL": "cell_type", "p39c-jun": "protein", "cytoplasmic p39c-jun": "protein", "proteins": "protein" } }, { "input_text": "Octamer binding factors and their coactivator can activate the murine PU.1 ( spi-1 ) promoter .", "target_text": { "Octamer binding factors": "protein", "coactivator": "protein", "murine PU.1 ( spi-1 ) promoter": "DNA" } }, { "input_text": "PU.1 ( spi-1 ) , a member of the Ets transcription factor family , is predominantly expressed in myeloid and B cells , activates many B cell and myeloid genes , and is critical for development of both of these lineages .", "target_text": { "PU.1": "protein", "spi-1": "protein", "Ets transcription factor family": "protein" } }, { "input_text": "Our previous studies ( Chen , H.M. , Ray-Gallet , D. , Zhang , P. , Hetherington , C.J. , Gonzalez , D.A. , Zhang , D.-E. , Moreau-Gachelin , F. , and Tenen , D.G. ( 1995 ) Oncogene 11 , 1549-1560 ) demonstrate that the PU.1 promoter directs cell type-specific reporter gene expression in myeloid cell lines , and that PU.1 activates its own promoter in an autoregulatory loop .", "target_text": { "PU.1": "protein", "PU.1 promoter": "DNA", "cell type-specific reporter gene": "DNA" } }, { "input_text": "Here we show that the murine PU.1 promoter is also specifically and highly functional in B cell lines as well .", "target_text": { "PU.1": "protein", "PU.1 promoter": "DNA", "murine PU.1 promoter": "DNA", "B cell lines": "cell_line" } }, { "input_text": "Oct-1 and Oct-2 can bind specifically to a site at base pair -55 in vitro , and this site is specifically protected in B cells in vivo .", "target_text": { "Oct-1": "protein", "Oct-2": "protein", "B cells": "cell_type" } }, { "input_text": "We also demonstrate that two other sites contribute to promoter activity in B cells ; an Sp1 binding site adjacent to the octamer site , and the PU.1 autoregulatory site .", "target_text": { "B cells": "cell_type", "Sp1 binding site": "DNA", "octamer site": "DNA", "PU.1": "protein", "PU.1 autoregulatory site": "DNA" } }, { "input_text": "Finally , we show that the B cell coactivator OBF-1/Bob1/OCA-B is only expressed in B cells and not in myeloid cells , and that OBF-1/Bob1/OCA-B can transactivate the PU.1 promoter in HeLa and myeloid cells .", "target_text": { "coactivator": "protein", "OBF-1/Bob1/OCA-B": "protein", "B cells": "cell_type", "myeloid cells": "cell_type", "PU.1": "protein", "PU.1 promoter": "DNA", "HeLa": "cell_line" } }, { "input_text": "This B cell restricted coactivator may be responsible for the B cell specific expression of PU.1 mediated by the octamer site .", "target_text": { "coactivator": "protein", "B cell restricted coactivator": "protein", "PU.1": "protein", "octamer site": "DNA" } }, { "input_text": "Inhibition of p105 processing by NF-kappaB proteins in transiently transfected cells .", "target_text": { "p105": "protein", "NF-kappaB proteins": "protein", "transiently transfected cells": "cell_line" } }, { "input_text": "Regulation of the transcription factor NF-kappaB involves proteasome-mediated processing of the NF-kappaB1 p105 precursor protein , which generates the p50 subunit of NF-kappaB .", "target_text": { "NF-kappaB": "protein", "p105": "protein", "NF-kappaB1 p105 precursor protein": "protein", "p50 subunit": "protein" } }, { "input_text": "The processing of p105 occurs constitutively in vivo but can be markedly enhanced by various cellular activation agents , although the underlying regulatory mechanism is not yet clear .", "target_text": { "p105": "protein" } }, { "input_text": "In the present study , we demonstrate that signal-mediated induction of p105 processing in human T cells is associated with de novo synthesis of this precursor protein .", "target_text": { "p105": "protein", "human T cells": "cell_type", "precursor protein": "protein" } }, { "input_text": "Transient transfection studies performed in COS7 cells revealed that the newly synthesized p105 protein appears to be more rapidly processed compared to its accumulated form that is already associated with the processed product p50 .", "target_text": { "COS7 cells": "cell_line", "p105": "protein", "p50": "protein" } }, { "input_text": "Interestingly , the processing rate of p105 is markedly inhibited in cells co-transfected with p50 or other NF-kappaB subunits , including RelA and c-Rel , that physically interact with p105 .", "target_text": { "p105": "protein", "p50": "protein", "NF-kappaB": "protein", "NF-kappaB subunits": "protein", "RelA": "protein", "c-Rel": "protein" } }, { "input_text": "These findings suggest that the processing of p105 is subject to negative regulation by the various NF-kappaB subunits .", "target_text": { "p105": "protein", "NF-kappaB": "protein", "NF-kappaB subunits": "protein" } }, { "input_text": "We further demonstrate that p105 undergoes degradation in lipopolysaccharide -stimulated human monocytic cells .", "target_text": { "p105": "protein", "lipopolysaccharide -stimulated human monocytic cells": "cell_line" } }, { "input_text": "However , the inducible degradation of p105 is not coupled with the generation of p50 .", "target_text": { "p105": "protein", "p50": "protein" } }, { "input_text": "Together , these studies demonstrate that the processing and inducible degradation of p105 are differentially regulated .", "target_text": { "p105": "protein" } }, { "input_text": "Identification of an inducible regulator of c-myb expression during T-cell activation .", "target_text": { "inducible regulator": "protein", "c-myb": "DNA", "T-cell": "cell_type" } }, { "input_text": "Resting T cells express very low levels of c-Myb protein .", "target_text": { "Resting T cells": "cell_type", "c-Myb protein": "protein" } }, { "input_text": "During T-cell activation , c-myb expression is induced and much of the increase in expression occurs at the transcriptional level .", "target_text": { "c-myb": "DNA" } }, { "input_text": "We identified a region of the c-myb 5' flanking sequence that increased c-myb expression during T-cell activation .", "target_text": { "c-myb 5' flanking sequence": "DNA", "c-myb": "DNA" } }, { "input_text": "In vivo footprinting by ligation-mediated PCR was performed to correlate in vivo protein binding with functional activity .", "target_text": {} }, { "input_text": "A protein footprint was visible over this region of the c-myb 5' flanking sequence in activated T cells but not in unactivated T cells .", "target_text": { "c-myb 5' flanking sequence": "DNA", "activated T cells": "cell_type", "unactivated T cells": "cell_type" } }, { "input_text": "An electrophoretic mobility shift assay ( EMSA ) with nuclear extract from activated T cells and an oligonucleotide of this binding site demonstrated a new protein-DNA complex , referred to as CMAT for c-myb in activated T cells ; this complex was not present in unactivated T cells .", "target_text": { "activated T cells": "cell_type", "protein-DNA complex": "protein", "CMAT": "protein", "c-myb in activated T cells": "protein", "unactivated T cells": "cell_type" } }, { "input_text": "Because the binding site showed some sequence similarity with the nuclear factor of activated T cells ( NFAT ) binding site , we compared the kinetics of induction of the two binding complexes and the molecular masses of the two proteins .", "target_text": { "binding site": "DNA", "activated T cells": "cell_type", "NFAT": "protein", "nuclear factor of activated T cells ( NFAT ) binding site": "DNA" } }, { "input_text": "Studies of the kinetics of induction showed that the NFAT EMSA binding complex appeared earlier than the CMAT complex .", "target_text": { "NFAT": "protein", "NFAT EMSA binding complex": "protein", "CMAT": "protein", "CMAT complex": "protein" } }, { "input_text": "The NFAT protein migrated more slowly in a sodium dodecyl sulfate-polyacrylamide gel than the CMAT protein did .", "target_text": { "NFAT": "protein", "CMAT": "protein", "CMAT protein": "protein" } }, { "input_text": "In addition , an antibody against NFAT did not cross-react with the CMAT protein .", "target_text": { "NFAT": "protein", "CMAT": "protein", "CMAT protein": "protein" } }, { "input_text": "The appearance of the CMAT binding complex was inhibited by both cyclosporin A and rapamycin .", "target_text": { "CMAT": "protein", "CMAT binding complex": "protein" } }, { "input_text": "The CMAT protein appears to be a novel inducible protein involved in the regulation of c-myb expression during T-cell activation .", "target_text": { "CMAT": "protein", "c-myb": "DNA" } }, { "input_text": "CNI-1493 inhibits monocyte/macrophage tumor necrosis factor by suppression of translation efficiency .", "target_text": { "monocyte/macrophage tumor necrosis factor": "protein" } }, { "input_text": "Tumor necrosis factor ( TNF ) mediates a wide variety of disease states including septic shock , acute and chronic inflammation , and cachexia .", "target_text": { "Tumor necrosis factor": "protein", "TNF": "protein" } }, { "input_text": "Recently , a multivalent guanylhydrazone ( CNI-1493 ) developed as an inhibitor of macrophage activation was shown to suppress TNF production and protect against tissue inflammation and endotoxin lethality [ Bianchi , M. , Ulrich , P. , Bloom , O. , Meistrell , M. , Zimmerman , G.A. , Schmidtmayerova , H. , Bukrinsky , M. , Donnelley , T. , Bucala , R. , Sherry , B. , Manogue , K.R. , Tortolani , A.J. , Cerami , A. & Tracey , K.J. ( 1995 ) Mol.Med.1 , 254-266 , and Bianchi , M. , Bloom , O. , Raabe , T. , Cohen , P. S. , Chesney , J. , Sherry , B. , Schmidtmayerova , H. , Zhang , X. , Bukrinsky , M. , Ulrich , P. , Cerami , A. & Tracey , J. ( 1996 ) J.Exp.Med. , in press ] .", "target_text": { "TNF": "protein" } }, { "input_text": "We have now elucidated the mechanism by which CNI-1493 inhibits macrophage TNF synthesis and show here that it acts through suppression of TNF translation efficiency .", "target_text": { "TNF": "protein" } }, { "input_text": "CNI-1493 blocked neither the lipopolysaccharide ( LPS ) -induced increases in the expression of TNF mRNA nor the translocation of nuclear factor NF-kappa B to the nucleus in macrophages activated by 15 min of LPS stimulation , indicating that CNI-1493 does not interfere with early NF-kappa B -mediated transcriptional regulation of TNF .", "target_text": { "TNF": "protein", "TNF mRNA": "RNA", "nuclear factor NF-kappa B": "protein", "macrophages": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "However , synthesis of the 26-kDa membrane form of TNF was effectively blocked by CNI-1493 .", "target_text": { "26-kDa membrane form": "protein", "TNF": "protein" } }, { "input_text": "Further evidence for the translational suppression of TNF is given by experiments using chloram-phenicol acetyltransferase ( CAT ) constructs containing elements of the TNF gene that are involved in TNF translational regulation .", "target_text": { "TNF": "protein", "chloram-phenicol acetyltransferase": "protein", "chloram-phenicol acetyltransferase ( CAT ) constructs": "DNA", "TNF gene": "DNA" } }, { "input_text": "Both the 5' and 3' untranslated regions of the TNF gene were required to elicit maximal translational suppression by CNI-1493 .", "target_text": { "TNF": "protein", "TNF gene": "DNA" } }, { "input_text": "Identification of the molecular target through which CNI- 1493 inhibits TNF translation should provide insight into the regulation of macrophage activation and mechanisms of inflammation .", "target_text": { "TNF": "protein" } }, { "input_text": "Soluble tumor necrosis factor receptors inhibit phorbol myristate acetate and cytokine-induced HIV-1 expression chronically infected U1 cells .", "target_text": { "Soluble tumor necrosis factor receptors": "protein", "infected U1 cells": "cell_type" } }, { "input_text": "Recombinant human tumor necrosis factor ( TNF ) binding protein-1 ( r-h TBP-1 ) and recombinant human soluble dimeric TNF receptor ( rhu TNFR : Fc ) were used to determine the relative contributions of TNF to phorbol myristate acetate ( PMA ) and cytokine-induced human immunodeficiency virus type 1 ( HIV-1 ) replication in chronically infected cell lines .", "target_text": { "TNF": "protein", "Recombinant human tumor necrosis factor ( TNF ) binding protein-1": "protein", "r-h TBP-1": "protein", "recombinant human soluble dimeric TNF receptor": "protein", "rhu TNFR : Fc": "protein" } }, { "input_text": "Treatment of HIV-1 -infected promonocytic U1 cells with r-h-TBP-1 or rhu TNFR : Fc reduced PMA -induced HIV-1 p24 antigen production in a concentration-dependent manner , with a maximal inhibition of approximately 90 % .", "target_text": { "HIV-1 -infected promonocytic U1 cells": "cell_type", "r-h-TBP-1": "protein", "rhu TNFR : Fc": "protein", "HIV-1 p24 antigen": "protein" } }, { "input_text": "Maximal inhibition of p24 antigen production in T-lymphocytic ACH-2 cells was 47 % with r-hTBP-1 and 42 % with rhu TNFR : Fc .", "target_text": { "p24 antigen": "protein", "T-lymphocytic ACH-2 cells": "cell_line", "r-hTBP-1": "protein", "rhu TNFR : Fc": "protein" } }, { "input_text": "r-hTBP-1 and rhu TNFR : Fc also decreased p24 antigen synthesized by U1 cells in response to other stimuli , including phytohemagglutinin ( PHA ) -induced supernatant , granulocyte-macrophage colony-stimulating factor , interleukin-6 , and TNF .", "target_text": { "r-hTBP-1": "protein", "rhu TNFR : Fc": "protein", "p24 antigen": "protein", "U1 cells": "cell_line", "phytohemagglutinin": "protein", "PHA": "protein", "phytohemagglutinin ( PHA ) -induced supernatant": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "interleukin-6": "protein", "TNF": "protein" } }, { "input_text": "Addition of r-hTBP-1 to U1 cells during the last 4 h of a 24 h incubation with PMA still inhibited p24 antigen production by 15 % .", "target_text": { "r-hTBP-1": "protein", "U1 cells": "cell_line", "p24 antigen": "protein" } }, { "input_text": "U1 cells stimulated with 10 ( -7 ) M PMA released approximately 1 ng/ml endogenous TBP-1 with an initial peak observed at 1 h and a second peak at 24 h after PMA stimulation .", "target_text": { "U1 cells": "cell_line", "endogenous TBP-1": "protein" } }, { "input_text": "r-hTBP-1 also partially reversed inhibition of U1 cellular proliferation caused by PMA .", "target_text": { "r-hTBP-1": "protein" } }, { "input_text": "Both r-hTBP-1 and rhu TNFR : Fc blocked PMA induction of nuclear factor ( NK ) - kappa B DNA-binding activity in U1 cells in association with decreases in HIV-1 replication .", "target_text": { "r-hTBP-1": "protein", "rhu TNFR : Fc": "protein", "nuclear factor ( NK ) - kappa B": "protein", "U1 cells": "cell_line" } }, { "input_text": "We conclude that soluble TNF receptors can inhibit stimuli-induced HIV-1 expression and NK- kappa B DNA-binding activity in chronically infected U1 cells .", "target_text": { "NK- kappa B": "protein", "U1 cells": "cell_line", "infected U1 cells": "cell_type" } }, { "input_text": "Transcriptional activation of RNA polymerase III-dependent genes by the human T-cell leukemia virus type 1 tax protein .", "target_text": { "RNA polymerase III-dependent genes": "DNA", "tax protein": "protein", "human T-cell leukemia virus type 1 tax protein": "protein" } }, { "input_text": "The human T-cell leukemia virus -encoded tax protein is a potent activator of many viral and cellular genes transcribed by RNA polymerase II .", "target_text": { "tax protein": "protein", "human T-cell leukemia virus -encoded tax protein": "protein", "RNA polymerase II": "protein" } }, { "input_text": "We find that both chromatin and cell extracts derived from human T-cell leukemia virus type 1 -infected human T lymphocytes support higher levels of 5S rRNA and tRNA gene transcription than chromatin or extracts from uninfected T lymphocytes .", "target_text": { "chromatin": "DNA", "human T-cell leukemia virus type 1 -infected human T lymphocytes": "cell_line", "uninfected T lymphocytes": "cell_type" } }, { "input_text": "The viral protein Tax was likely responsible for this higher level of class II gene transcription , as purified Tax was found to stimulate both genes when added to the uninfected cell extract or in reconstituted systems .", "target_text": { "viral protein Tax": "protein", "class II gene": "DNA", "purified Tax": "protein" } }, { "input_text": "Both limiting-component transcription assays and DNA binding assays identified the class III gene transcription factor TFIIIB as the principle target of Tax activity .", "target_text": { "class III gene transcription factor": "protein", "TFIIIB": "protein", "Tax": "protein" } }, { "input_text": "Surprisingly , we find that Tax increases the effective concentration of active TFIIIB molecules .", "target_text": { "Tax": "protein", "TFIIIB": "protein", "active TFIIIB molecules": "protein" } }, { "input_text": "These data suggest that Tax stimulates RNA polymerase III-dependent gene expression by accelerating the rate and/or extent of transcription initiation complex assembly .", "target_text": { "Tax": "protein", "RNA polymerase III-dependent gene": "DNA", "transcription initiation complex": "protein" } }, { "input_text": "Expression of Retinoid X Receptor alpha is increased upon monocytic cell differentiation .", "target_text": { "Retinoid X Receptor alpha": "protein" } }, { "input_text": "1 alpha, 25-Dihydroxyvitamin D3 ( VD ) is a potent inducer of monocytic differentiation of both normal and leukemic cells .", "target_text": {} }, { "input_text": "Its effects are mediated by its nuclear receptor ( VDR ) .", "target_text": { "nuclear receptor": "protein", "VDR": "protein" } }, { "input_text": "Efficient gene activation requires the heterodimerization of VDR with Retinoid X Receptors ( RXR ) .", "target_text": { "VDR": "protein", "Retinoid X Receptors": "protein", "RXR": "protein" } }, { "input_text": "In the present study using specific antibodies , we analyzed the expression of the RXR alpha protein in blood mononuclear cells from acute myeloid patients ( AML ) ( 10 cases ) and from myelomonocytic cell lines arrested at different stages of differentiation .", "target_text": { "specific antibodies": "protein", "RXR alpha protein": "protein", "blood mononuclear cells": "cell_type", "myelomonocytic cell lines": "cell_line" } }, { "input_text": "We observed that the RXR alpha expression increased during myelomonocytic differentiation , since the highest levels were found in AML samples and in myelomonocytic cell lines having the highest amounts of monocytic precursors .", "target_text": { "RXR alpha": "protein", "myelomonocytic cell lines": "cell_line", "monocytic precursors": "cell_type" } }, { "input_text": "We also demonstrated that fresh leukemic cells , whatever their stage of differentiation , as well as myelomonocytic cell lines , respond to VD by an increase in RXR alpha levels .", "target_text": { "leukemic cells": "cell_type", "myelomonocytic cell lines": "cell_line", "RXR alpha": "protein" } }, { "input_text": "Combinations of all-trans retinoic acid ( RA ) and VD , in some cases , increased this effect .", "target_text": {} }, { "input_text": "This response suggests the involvement of RXR alpha in monocytic differentiation upon VD treatment .", "target_text": { "RXR alpha": "protein" } }, { "input_text": "Expression of p13MTCP1 is restricted to mature T-cell proliferations with t(X;14) translocations .", "target_text": { "p13MTCP1": "protein" } }, { "input_text": "T-cell prolymphocytic leukemia ( T-PLL ) , a rare form of mature T-cell leukemias , and ataxia telangiectasia clonal proliferation , a related condition occurring in patients suffering from ataxia telangiectasia , have been associated to translocations involving the 14q32.1 or Xq28 regions , where are located the TCL1 and MTCP1 putative oncogenes , respectively .", "target_text": { "14q32.1": "DNA", "Xq28 regions": "DNA", "TCL1": "DNA", "MTCP1 putative oncogenes": "DNA", "TCL1 and MTCP1 putative oncogenes": "DNA" } }, { "input_text": "The MTCP1 gene is involved in the t(X;14)(q28;q11) translocation associated with these T-cell proliferations .", "target_text": { "MTCP1 gene": "DNA", "t(X;14)(q28;q11) translocation": "DNA" } }, { "input_text": "Alternative splicing generates type A and B transcripts that potentially encode two entirely distinct proteins ; type A transcripts code for a small mitochondrial protein , p8MTCP1 , and type B transcripts , containing an additional open reading frame , may code for 107 amino-acid protein , p13MTCP1 .", "target_text": { "A transcripts": "RNA", "mitochondrial protein": "protein", "p8MTCP1": "protein", "type B transcripts": "RNA", "open reading frame": "DNA", "107 amino-acid protein": "protein", "p13MTCP1": "protein" } }, { "input_text": "The recently cloned TCL1 gene , also involved in translocations and inversions associated with T-cell proliferations , codes for a 14-kD protein that displays significant homology with p13MTCP1 .", "target_text": { "TCL1 gene": "DNA", "14-kD protein": "protein", "p13MTCP1": "protein" } }, { "input_text": "We have generated rabbit antisera against this putative p13MTCP1 protein and screened for expression of p13MTCP1 normal lymphoid tissues and 33 cases of immature and mature lymphoid T-cell proliferations using a sensitive Western blot assay .", "target_text": { "p13MTCP1": "protein", "p13MTCP1 protein": "protein" } }, { "input_text": "We also investigated the MTCP1 locus configuration by Southern blot analysis .", "target_text": { "MTCP1 locus": "DNA" } }, { "input_text": "The p13MTCP1 protein was detected in the three T-cell proliferations with MTCP1 rearrangements because of t(X;14) translocations , but neither in normal resting and activated lymphocytes nor in the other T-cell leukemias .", "target_text": { "p13MTCP1": "protein", "p13MTCP1 protein": "protein", "MTCP1 rearrangements": "DNA", "activated lymphocytes": "cell_type", "T-cell": "cell_type" } }, { "input_text": "Our data support the hypothesis that p13MTCP1 and p14TCL1 form a new protein family that plays a key role in the pathogenesis of T-PLL and related conditions .", "target_text": { "p13MTCP1": "protein", "p14TCL1": "protein", "protein family": "protein" } }, { "input_text": "Preassociation of STAT1 with STAT2 and STAT3 in separate signalling complexes prior to cytokine stimulation .", "target_text": { "STAT1": "protein", "STAT2": "protein", "STAT3": "protein", "signalling complexes": "protein", "cytokine": "protein" } }, { "input_text": "A variety of cytokines and growth factors act through an induction of gene expression mediated by a family of latent transcription factors called STAT ( signal transducers and activators of transcription ) proteins .", "target_text": { "cytokines": "protein", "growth factors": "protein", "latent transcription factors": "protein", "STAT": "protein", "STAT ( signal transducers and activators of transcription ) proteins": "protein" } }, { "input_text": "Ligand-induced tyrosine phosphorylation of the STATs promotes their homodimer and heterodimer formation and subsequent nuclear translocation .", "target_text": { "STATs": "protein" } }, { "input_text": "We demonstrate here that STAT protein heterocomplexes exist prior to cytokine treatment .", "target_text": { "STAT protein heterocomplexes": "protein", "cytokine": "protein" } }, { "input_text": "When unstimulated HeLa cells are ruptured in hypotonic buffer without salt or detergent , immunoadsorption of either STAT1 or STAT2 from the resulting cytosol yields coimmunoadsorption of the other STAT protein .", "target_text": { "unstimulated HeLa cells": "cell_line", "STAT1": "protein", "STAT2": "protein", "STAT protein": "protein" } }, { "input_text": "Similarly , STAT1 -STAT3 heterocomplexes are coimmunoadsorbed from hypotonic cytosol .", "target_text": { "STAT1": "protein", "-STAT3": "protein" } }, { "input_text": "STAT1 and STAT2 or STAT1 and STAT3 translated in reticulocyte lysate spontaneously form heterocomplexes when the translation lysates are mixed at 0 degrees C .", "target_text": { "STAT1": "protein", "STAT2": "protein", "STAT3": "protein" } }, { "input_text": "Our data suggest that interferon-alpha /beta-induced tyrosine phosphorylation increases the stability of a preexisting , latent , STAT1 - STAT2 signaling complex .", "target_text": { "interferon-alpha": "protein", "STAT1": "protein", "STAT2": "protein", "STAT2 signaling complex": "protein" } }, { "input_text": "Newly translated STAT1 binds in equilibrium fashion to STAT2 and STAT3 , but we show that STAT2 and STAT3 exist in separate heterocomplexes with STAT1 , consistent with a model in which STAT1 contains a common binding site for other STAT proteins .", "target_text": { "STAT1": "protein", "STAT2": "protein", "STAT3": "protein", "heterocomplexes": "protein", "STAT proteins": "protein" } }, { "input_text": "Interferon-gamma modulates the lipopolysaccharide -induced expression of AP-1 and NF-kappa B at the mRNA and protein level in human monocytes .", "target_text": { "Interferon-gamma": "protein", "AP-1": "protein", "NF-kappa B": "protein", "human monocytes": "cell_type" } }, { "input_text": "Interferon-gamma ( IFN-gamma ) modulates the expression of several cytokines by human monocytes at the transcriptional level .", "target_text": { "Interferon-gamma": "protein", "IFN-gamma": "protein", "cytokines": "protein", "human monocytes": "cell_type" } }, { "input_text": "In view of these findings , we analyzed the effects of IFN-gamma on the expression of different transcription factors in activated human monocytes .", "target_text": { "IFN-gamma": "protein", "transcription factors": "protein", "human monocytes": "cell_type" } }, { "input_text": "Priming of human monocytes with IFN-gamma resulted in the down regulation of c-fos and c-jun mRNA in response to stimulation with lipopolysaccharide ( LPS ) compared to the effects of LPS alone .", "target_text": { "human monocytes": "cell_type", "IFN-gamma": "protein" } }, { "input_text": "Not only was this effect observed at the mRNA level , but activator protein-1 ( AP-1 ) DNA binding capacity was affected as well , A strong reduction was observed in the LPS -induced DNA-binding activity of AP-1 in the presence of IFN-gamma .", "target_text": { "activator protein-1": "protein", "AP-1": "protein", "IFN-gamma": "protein" } }, { "input_text": "LPS -stimulated monocytes showed an increased expression of p105 mRNA , the precursor of the p50 subunit of the transcription factor nuclear factor-kappa B ( NF-kappa B ) , while no effect was noticed on the expression of p65 mRNA .", "target_text": { "LPS -stimulated monocytes": "cell_type", "p105": "protein", "p105 mRNA": "RNA", "p50": "protein", "p50 subunit": "protein", "transcription factor nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "p65 mRNA": "RNA" } }, { "input_text": "In contrast , IFN-gamma priming did not affect the expression of p105 transcripts but enhanced the expression of p65 mRNA ( two-fold ) .", "target_text": { "IFN-gamma": "protein", "p105": "protein", "p105 transcripts": "RNA", "p65 mRNA": "RNA" } }, { "input_text": "Priming with IFN-gamma followed by LPS stimulation resulted in a further increase in the expression of p65 mRNA .", "target_text": { "IFN-gamma": "protein", "p65 mRNA": "RNA" } }, { "input_text": "This was due to an increase in the half-life of p65 mRNA ( 75 vs 150 minutes ) .", "target_text": { "p65 mRNA": "RNA" } }, { "input_text": "Electrophoretic mobility shift assays ( EMSAs ) demonstrated that unstimulated monocytes predominantly expressed p50 NF-kappa B .", "target_text": { "p50": "protein", "NF-kappa B": "protein" } }, { "input_text": "Stimulation with LPS or IFN-gamma resulted in the expression of p50 and p65 subunits , while the combination of IFN-gamma plus LPS caused a further increase in the expression of NF-kappa B .", "target_text": { "IFN-gamma": "protein", "p50": "protein", "p65 subunits": "protein", "NF-kappa B": "protein" } }, { "input_text": "With Western blotting , it was shown that nuclear extracts from monocytes contained p50 and p65 protein in response to LPS and IFN-gamma stimulation .", "target_text": { "monocytes": "cell_type", "p50": "protein", "p65 protein": "protein", "IFN-gamma": "protein" } }, { "input_text": "However , the combined stimulation did not result in enhanced p50 and p65 protein expression .", "target_text": { "p50": "protein", "p65 protein": "protein" } }, { "input_text": "The effects of IFN-gamma on the transcription factors were specific , since no change was observed in the expression of NF-IL-6 or I kappa B alpha , the inhibitor of NF-kappa B .", "target_text": { "IFN-gamma": "protein", "transcription factors": "protein", "NF-IL-6": "protein", "I kappa B alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "We conclude that the effects of IFN-gamma on the expression of the transcription factors AP-1 and NF-kappa B may be important for the modulatory effects of IFN-gamma on the cytokine expression in activated human monocytes .", "target_text": { "IFN-gamma": "protein", "transcription factors": "protein", "AP-1": "protein", "NF-kappa B": "protein", "cytokine": "protein", "monocytes": "cell_type", "human monocytes": "cell_type" } }, { "input_text": "HIV-1 tat induces the expression of a new hematopoietic cell-specific transcription factor and downregulates MIP-1 alpha gene expression in activated T-cells .", "target_text": { "HIV-1 tat": "protein", "hematopoietic cell-specific transcription factor": "protein", "MIP-1 alpha": "protein", "MIP-1 alpha gene": "DNA", "activated T-cells": "cell_type" } }, { "input_text": "MIP-1 alpha is a secreted chemokine which can inhibit hematopoietic stem cells and modulate inflammatory responses .", "target_text": { "MIP-1 alpha": "protein", "chemokine": "protein", "hematopoietic stem cells": "cell_type" } }, { "input_text": "It is also an inhibitor of HIV replication in CD8+ T-cells .", "target_text": { "CD8+ T-cells": "cell_type" } }, { "input_text": "The expression of MIP-1 alpha is induced during cellular activation of CD4+ T-cells and monocytes .", "target_text": { "MIP-1 alpha": "protein", "CD4+ T-cells": "cell_type", "monocytes": "cell_type" } }, { "input_text": "It is also expressed in transformed B-cells .", "target_text": { "transformed B-cells": "cell_line" } }, { "input_text": "We have previously identified a new transcription factor family ( the MNP family ) whose expression is crucial for the induction of MIP-1 alpha transcription during cellular activation and in transformed B cells .", "target_text": { "transcription factor family": "protein", "MNP family": "protein", "MIP-1 alpha": "protein", "transformed B cells": "cell_line" } }, { "input_text": "Monocytes and transformed B-cells normally express MNP-1 strongly and MNP-2 weakly , while T-cells strongly express only MNP-2 .", "target_text": { "transformed B-cells": "cell_line", "MNP-1": "protein", "MNP-2": "protein" } }, { "input_text": "Recently , we reported that HIV-1 tat downregulates MIP-1 alpha expression in Jurkat T-cells .", "target_text": { "HIV-1 tat": "protein", "MIP-1 alpha": "protein", "Jurkat T-cells": "cell_line" } }, { "input_text": "In this report we show induction of MNP-1 in Jurkat T-cells expressing HIV-1 tat .", "target_text": { "MNP-1": "protein", "Jurkat T-cells": "cell_line", "HIV-1 tat": "protein" } }, { "input_text": "Expression of neither HTLV-1 tax in Jurkat T-cells nor EBV in B-cells had any effect on MNP-1 or MNP-2 expression , showing that the effect is specific for HIV-1 tat .", "target_text": { "HTLV-1 tax": "protein", "Jurkat T-cells": "cell_line", "B-cells": "cell_type", "MNP-1": "protein", "MNP-2": "protein", "HIV-1 tat": "protein" } }, { "input_text": "We propose that HIV-1 tat may inhibit MIP-1 alpha expression by inducing MNP-1 expression in T-cells , probably by either competing with MNP-2 for binding to the MIP-1 alpha promoter or by sequestering it into inactive forms .", "target_text": { "HIV-1 tat": "protein", "MIP-1 alpha": "protein", "MNP-1": "protein", "T-cells": "cell_type", "MNP-2": "protein", "MIP-1 alpha promoter": "DNA" } }, { "input_text": "Differentiation of T-helper lymphocytes : selective regulation by members of the STAT family of transcription factors .", "target_text": { "T-helper lymphocytes": "cell_type", "STAT family": "protein", "transcription factors": "protein" } }, { "input_text": "Interleukin-4 ( IL-4 ) and interleukin-12 ( IL-12 ) control the differentiation of T-helper cells .", "target_text": { "Interleukin-4": "protein", "IL-4": "protein", "interleukin-12": "protein", "IL-12": "protein", "T-helper cells": "cell_type" } }, { "input_text": "Here we summarize studies which investigate the mechanism by which these cytokines selectively reprogramme gene expression in T-lymphocytes .", "target_text": { "cytokines": "protein", "T-lymphocytes": "cell_type" } }, { "input_text": "Cytokine stimulation leads to the phosphorylation of specific tyrosine residues within the intracellular domain of the corresponding cytokine receptor .", "target_text": { "Cytokine": "protein", "intracellular domain": "protein", "cytokine receptor": "protein" } }, { "input_text": "These phosphotyrosines serve as docking sites for latent , cytoplasmic transcription factors known as signal transducers and activators of transcription ( Stat ) proteins .", "target_text": { "docking sites": "protein", "transcription factors": "protein", "cytoplasmic transcription factors": "protein", "signal transducers and activators of transcription ( Stat ) proteins": "protein" } }, { "input_text": "Receptor/Stat interaction is mediated by the src homology 2 ( SH2 ) domain of the corresponding Stat protein .", "target_text": { "src homology 2 ( SH2 ) domain": "protein", "Stat protein": "protein" } }, { "input_text": "Although Stat binding to the intracellular domain of the cytokine receptor strongly depends on the phosphotyrosine residue , the recruitment of a specific Stat protein is dictated by amino acid residues C-terminal to the phosphotyrosine .", "target_text": { "intracellular domain": "protein", "cytokine receptor": "protein", "Stat protein": "protein" } }, { "input_text": "Specific docking sites within individual cytokine receptors have been identified for almost all Stat proteins .", "target_text": { "docking sites": "protein", "cytokine receptors": "protein", "Stat proteins": "protein" } }, { "input_text": "The direct coupling between cytokine receptor and transcription factor helps to explain how different cytokines elicit distinct patterns of gene expression .", "target_text": { "cytokine receptor": "protein", "transcription factor": "protein", "cytokines": "protein" } }, { "input_text": "Role of EGR1 in regulation of stimulus-dependent CD44 transcription in B lymphocytes .", "target_text": { "EGR1": "protein", "CD44": "protein" } }, { "input_text": "The immediate-early gene egr-1 encodes a transcription factor ( EGR1 ) that links B-cell antigen receptor ( BCR ) signals to downstream activation events through the regulation of previously unidentified target genes .", "target_text": { "immediate-early gene": "DNA", "egr-1": "DNA", "transcription factor": "protein", "EGR1": "protein", "B-cell antigen receptor": "protein", "BCR": "protein", "target genes": "DNA" } }, { "input_text": "Here we identify the gene encoding the lymphocyte homing and migration protein CD44 as a target of EGR1 regulation in B cells .", "target_text": { "lymphocyte homing and migration protein": "protein", "CD44": "protein", "EGR1": "protein", "B cells": "cell_type" } }, { "input_text": "BCR -induced increases in CD44 mRNA expression and transcription levels are shown to occur in EGR1 -expressing but not in nonexpressing subclones of the B-cell line WEHI-231 .", "target_text": { "BCR": "protein", "CD44 mRNA": "RNA", "EGR1": "protein", "B-cell line": "cell_line", "WEHI-231": "cell_line" } }, { "input_text": "Kinetics of egr-1 transcription and the appearance of nuclear EGR1 protein precede CD44 induction and occur within 30 min after stimulation in the EGR1 -expressing subclone .", "target_text": { "egr-1": "DNA", "EGR1": "protein", "EGR1 protein": "protein", "CD44": "protein", "EGR1 -expressing subclone": "cell_line" } }, { "input_text": "A single EGR1 binding motif is demonstrated at bp -301 of the human CD44 promoter .", "target_text": { "EGR1": "protein", "CD44": "protein", "human CD44 promoter": "DNA" } }, { "input_text": "Cotransfection of a CD44 promoter-chloramphenicol acetyltransferase reporter construct with an egr-1 expression vector resulted in a 6.5- to 8.5-fold induction of transcriptional activity relative to an empty expression vector .", "target_text": { "CD44": "protein", "CD44 promoter-chloramphenicol acetyltransferase reporter construct": "DNA", "egr-1": "DNA", "egr-1 expression vector": "DNA", "empty expression vector": "DNA" } }, { "input_text": "The EGR1 binding motif was shown to be necessary for stimulus-induced expression of a CD44 promoter-chloramphenicol acetyltransferase reporter construct in nontransformed B lymphocytes and was required for transactivation by an EGR1 expression vector in a B-cell line .", "target_text": { "EGR1": "protein", "EGR1 binding motif": "DNA", "CD44": "protein", "promoter-chloramphenicol acetyltransferase reporter construct": "DNA", "nontransformed B lymphocytes": "cell_type", "EGR1 expression vector": "DNA", "B-cell line": "cell_line" } }, { "input_text": "These studies identify EGR1 as an intermediary linking BCR -derived signals to the induction of CD44 .", "target_text": { "EGR1": "protein", "BCR": "protein", "CD44": "protein" } }, { "input_text": "The relevance of these molecular events to BCR signal transduction and antigen-stimulated B-cell-mediated immune responses is discussed .", "target_text": { "BCR": "protein" } }, { "input_text": "Involvement of intracellular Ca2+ in oxidant-induced NF-kappa B activation .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "In human Jurkat T cells and its subclone Wurzburg cells oxidant challenge elevated [Ca2+]i by mobilizing Ca2+ from intracellular stores .", "target_text": { "human Jurkat T cells": "cell_line", "Wurzburg cells": "cell_line" } }, { "input_text": "In Jurkat cells this effect was rapid and transient , but in Wurzburg cells the response was slow and sustained .", "target_text": { "Jurkat cells": "cell_line", "Wurzburg cells": "cell_line" } }, { "input_text": "H2O2 -induced NF-kappaB activation in Wurzburg cells was not influenced by the presence of extracellular EGTA but was totally inhibited in cells that were loaded with esterified EGTA .", "target_text": { "NF-kappaB": "protein", "Wurzburg cells": "cell_line" } }, { "input_text": "In Jurkat cells that are not sensitive to H2O2 -induced NF-kappaB activation , H2O2 potentiated NF-kappaB activation in the presence of sustained high [ Ca2+ ]i following thapsigargin treatment .", "target_text": { "Jurkat cells": "cell_line", "NF-kappaB": "protein" } }, { "input_text": "NF-kappaB regulatory effect of alpha-lipoate and N-acetylcysteine appeared to be , at least in part , due to their ability to stabilize elevation of [ Ca2+ ]i following oxidant challenge .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Results of this study indicate that a sustained elevated [Ca2+]i is a significant factor in oxidant-induced NF-kappaB activation .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Transactivation of the interleukin-1alpha promoter by human T-cell leukemia virus type I and type II Tax proteins .", "target_text": { "interleukin-1alpha promoter": "DNA" } }, { "input_text": "Human T-cell leukemia virus type I ( HTLV-I ) -infected T-cell lines constitutively produce high levels of interleukin-1alpha ( IL-1alpha ) .", "target_text": { "Human T-cell leukemia virus type I ( HTLV-I ) -infected T-cell lines": "cell_line", "interleukin-1alpha": "protein", "IL-1alpha": "protein" } }, { "input_text": "To analyze the mechanisms that lead to the expression of IL-1alpha in HTLV-I -infected cell lines , we studied regulatory regions of the human IL-1alpha promoter involved in activation of the IL-1alpha gene .", "target_text": { "IL-1alpha": "protein", "HTLV-I -infected cell lines": "cell_line", "IL-1alpha promoter": "DNA", "IL-1alpha gene": "DNA" } }, { "input_text": "IL-1alpha promoter constructs drive transcription of the chloramphenicol acetyltransferase ( CAT ) reporter gene in HTLV-I -positive MT-2 cells , which constitutively produce IL-1alpha .", "target_text": { "IL-1alpha promoter constructs": "DNA", "chloramphenicol acetyltransferase": "protein", "chloramphenicol acetyltransferase ( CAT ) reporter gene": "DNA", "HTLV-I -positive MT-2 cells": "cell_line", "IL-1alpha": "protein" } }, { "input_text": "In a cotransfection assay , the Tax protein of both HTLV-I and HTLV-II specifically activated transcription from the IL-1alpha promoter in an uninfected Jurkat cell line .", "target_text": { "Tax protein": "protein", "IL-1alpha": "protein", "IL-1alpha promoter": "DNA", "uninfected Jurkat cell line": "cell_line" } }, { "input_text": "A mutant Tax protein deficient in transactivation of genes by the nuclear factor ( NF ) -kappaB pathway was unable to induce transcriptional activity of IL-1alpha promoter -CAT constructs , but was rescued by exogenous provision of p65/p50 NF-kappaB .", "target_text": { "Tax protein": "protein", "nuclear factor ( NF ) -kappaB": "protein", "IL-1alpha": "protein", "IL-1alpha promoter": "DNA", "IL-1alpha promoter -CAT constructs": "DNA", "p65/p50": "protein", "NF-kappaB": "protein" } }, { "input_text": "We found that two IL-1alpha kappaB-like sites ( positions -1,065 to -1,056 and +646 to +655 ) specifically formed a complex with NF-kappaB -containing nuclear extract from MT-2 cells and that NF-kappaB bound with higher affinity to the 3' NF-kappaB binding site than to the 5' NF-kappaB site .", "target_text": { "IL-1alpha": "protein", "IL-1alpha kappaB-like sites": "DNA", "-1,065 to -1,056": "DNA", "+646 to +655": "DNA", "NF-kappaB": "protein", "MT-2 cells": "cell_line", "3' NF-kappaB binding site": "DNA", "5' NF-kappaB site": "DNA" } }, { "input_text": "Moreover , deletion of either 5' or 3' NF-kappaB sites reduced IL-1alpha promoter activity in MT-2 cells and transactivation of the IL-1alpha promoter by exogenous NF-kappaB and Tax in Jurkat cells .", "target_text": { "IL-1alpha": "protein", "IL-1alpha promoter": "DNA", "MT-2 cells": "cell_line", "NF-kappaB": "protein", "Tax": "protein", "Jurkat cells": "cell_line" } }, { "input_text": "These data suggest a general role for Tax induction of IL-1alpha gene transcription by the NF-kappaB pathway .", "target_text": { "Tax": "protein", "IL-1alpha": "protein", "IL-1alpha gene": "DNA", "NF-kappaB": "protein" } }, { "input_text": "Expression of IL-1alpha by HTLV-I productively infected cells may be important in the hypercalcemia , osteolytic bone lesions , neutrophilia , elevation of C-reactive protein , and fever frequently seen in patients with HTLV-I -induced adult T-cell leukemia/lymphoma .", "target_text": { "IL-1alpha": "protein", "infected cells": "cell_type", "C-reactive protein": "protein" } }, { "input_text": "The myeloid-cell-specific c-fes promoter is regulated by Sp1 , PU.1 , and a novel transcription factor .", "target_text": { "myeloid-cell-specific c-fes promoter": "DNA", "Sp1": "protein", "PU.1": "protein", "transcription factor": "protein" } }, { "input_text": "The protein product of the c-fps/fes ( c-fes ) proto-oncogene has been implicated in the normal development of myeloid cells ( macrophages and neutrophils ) .", "target_text": { "c-fps/fes ( c-fes ) proto-oncogene": "DNA", "myeloid cells": "cell_type", "macrophages": "cell_type", "neutrophils": "cell_type" } }, { "input_text": "mRNA for c-fes has been detected exclusively in myeloid cells and vascular endothelial cells in adult mammals .", "target_text": { "myeloid cells": "cell_type", "vascular endothelial cells": "cell_type" } }, { "input_text": "Although a 13-kilobase-pair ( kb ) human c-fes transgene exhibits high levels of expression in mice , the sequences that confer myeloid-cell-specific expression of the human c-fes gene have not been defined .", "target_text": { "13-kilobase-pair ( kb ) human c-fes transgene": "DNA", "human c-fes gene": "DNA" } }, { "input_text": "Transient-transfection experiments demonstrated that plasmids containing 446 bp of c-fes 5'-flanking sequences linked to a luciferase reporter gene were active exclusively in myeloid cells .", "target_text": { "plasmids": "DNA", "c-fes 5'-flanking sequences": "DNA", "myeloid cells": "cell_type" } }, { "input_text": "No other DNA element within the 13-kb human c-fes locus contained positive cis-acting elements , with the exception of a weakly active region within the 3'-flanking sequences .", "target_text": { "13-kb human c-fes locus": "DNA", "positive cis-acting elements": "DNA", "3'-flanking sequences": "DNA" } }, { "input_text": "DNase I footprinting assays revealed four distinct sites that bind myeloid nuclear proteins ( -408 to -386 , -293 to -254 , -76 to -65 , and -34 to +3 ) .", "target_text": { "myeloid nuclear proteins": "protein", "-408 to -386": "DNA", "-293 to -254": "DNA", "-76 to -65": "DNA", "-34 to +3": "DNA" } }, { "input_text": "However , the first two footprints resided in sequences that were largely dispensable for transient activity .", "target_text": {} }, { "input_text": "Plasmids containing 151 bp of 5'-flanking sequences confer myeloid-cell-specific gene expression .", "target_text": { "151 bp": "DNA", "5'-flanking sequences": "DNA" } }, { "input_text": "Electrophoretic mobility shift analyses demonstrated that the 151-bp region contains nuclear protein binding sites for Sp1 , PU.1 , and/or Elf-1 , and a novel factor .", "target_text": { "151-bp region": "DNA", "nuclear protein binding sites": "DNA", "Sp1": "protein", "PU.1": "protein", "Elf-1": "protein", "novel factor": "protein" } }, { "input_text": "This unidentified factor binds immediately 3' of the PU.1 /Elf-1 sites and appears to be myeloid cell specific .", "target_text": { "PU.1": "protein", "/Elf-1": "protein", "PU.1 /Elf-1 sites": "DNA" } }, { "input_text": "Mutation of the PU.1 /Elf-1 site or the 3' site ( FP4-3' ) within the context of the c-fes promoter resulted in substantially reduced activity in transient transfections .", "target_text": { "PU.1": "protein", "/Elf-1": "protein", "3' site": "DNA", "FP4-3'": "DNA", "c-fes promoter": "DNA" } }, { "input_text": "Furthermore , transient-cotransfection assay demonstrated that PU.1 ( and not Elf-1 ) can transactivate the c-fes promoter in nonmyeloid cell lines .", "target_text": { "PU.1": "protein", "Elf-1": "protein", "c-fes promoter": "DNA", "nonmyeloid cell lines": "cell_line" } }, { "input_text": "We conclude that the human c-fes gene contains a strong myeloid-cell-specific promoter that is regulated by Sp1 , PU.1 , and a novel transcription factor .", "target_text": { "human c-fes gene": "DNA", "myeloid-cell-specific promoter": "DNA", "Sp1": "protein", "PU.1": "protein", "transcription factor": "protein" } }, { "input_text": "IL-10 inhibits nuclear factor-kappa B/Rel nuclear activity in CD3-stimulated human peripheral T lymphocytes .", "target_text": { "IL-10": "protein", "nuclear factor-kappa B/Rel": "protein", "CD3-stimulated human peripheral T lymphocytes": "cell_line" } }, { "input_text": "IL-10 markedly reduces nuclear factor ( NF ) -kappa B/Rel nuclear activity induced in PBMC by stimulation with the anti-CD3 mAb OKT3 .", "target_text": { "IL-10": "protein", "( NF ) -kappa B/Rel": "protein", "PBMC": "cell_type", "anti-CD3 mAb": "protein", "OKT3": "protein" } }, { "input_text": "The inhibition is exerted specifically on the NF-kappa B/Rel activation induced by mAb OKT3 , and not that produced by PMA .", "target_text": { "NF-kappa B/Rel": "protein", "OKT3": "protein", "mAb OKT3": "protein" } }, { "input_text": "As judged by supershifting the DNA-protein complexes with Abs recognizing specific components of the NF-kappa B/Rel protein family , the p50/p65 ( Rel A ) heterodimeric form of NF-kappa B is primarily affected .", "target_text": { "DNA-protein complexes": "protein", "Abs": "protein", "NF-kappa B/Rel": "protein", "NF-kappa B/Rel protein family": "protein", "p50/p65": "protein", "Rel A": "protein", "NF-kappa B": "protein" } }, { "input_text": "The maximal effect is observed at the IL-10 concentration of 20 U/ml .", "target_text": { "IL-10": "protein" } }, { "input_text": "IL-10 inhibitory activity is exerted on T lymphocytes and is mediated by monocytes .", "target_text": { "IL-10": "protein", "T lymphocytes": "cell_type", "monocytes": "cell_type" } }, { "input_text": "Indeed , monocytes pretreated with IL-10 are able so inhibit NF-kappa B nuclear activity in purified T lymphocytes stimulated with OKT3 .", "target_text": { "monocytes": "cell_type", "IL-10": "protein", "NF-kappa B": "protein", "T lymphocytes": "cell_type", "OKT3": "protein" } }, { "input_text": "Soluble factors do not appear to be involved in the mechanism of inhibition .", "target_text": {} }, { "input_text": "On the other hand , the up-regulation of CD80 Ag , found on monocytes obtained from PBMC incubated with OKT3 , is not detected after addition of IL-10 , and the anti-CD28 mAb CLB-CD28/1 restores the NF-kappa B/Rel nuclear activity in IL-10 -inhibited lymphocytes .", "target_text": { "CD80 Ag": "protein", "monocytes": "cell_type", "PBMC": "cell_type", "OKT3": "protein", "IL-10": "protein", "anti-CD28 mAb": "protein", "CLB-CD28/1": "protein", "NF-kappa B/Rel": "protein", "IL-10 -inhibited lymphocytes": "cell_line" } }, { "input_text": "Therefore , the NF-kappa B/Rel inhibition might be ascribed to a lack of cooperation between accessory cells and T lymphocytes , resulting from down-regulation of a costimulatory molecule , such as CD80 , produced by IL-10 on activated monocytes .", "target_text": { "NF-kappa B/Rel": "protein", "T lymphocytes": "cell_type", "CD80": "protein", "IL-10": "protein", "monocytes": "cell_type" } }, { "input_text": "Our results demonstrate that IL-10 can inhibit the induction of NF-kappa B/Rel nuclear activity in CD3-stimulated T lymphocytes .", "target_text": { "IL-10": "protein", "NF-kappa B/Rel": "protein", "T lymphocytes": "cell_type", "CD3-stimulated T lymphocytes": "cell_line" } }, { "input_text": "Since inappropriate activation of kappa B-driven genes has a physiopathologic role in a number of diseases , such as HIV infection , our findings support the possibility of using this cytokine to suppress an undesirable activation of these transcription factors .", "target_text": { "kappa B-driven genes": "DNA", "transcription factors": "protein" } }, { "input_text": "Expression of A-myb , but not c-myb and B-myb , is restricted to Burkitt 's lymphoma , sIg+ B-acute lymphoblastic leukemia , and a subset of chronic lymphocytic leukemias .", "target_text": { "A-myb": "DNA", "c-myb": "DNA", "B-myb": "DNA" } }, { "input_text": "The A-myb gene encodes a transcription factor that is related both functionally and structurally to the v-myb oncogene .", "target_text": { "A-myb": "DNA", "A-myb gene": "DNA", "transcription factor": "protein", "v-myb oncogene": "DNA" } }, { "input_text": "Following our observations that A-myb is expressed in a restricted subset of normal mature human B lymphocytes , with the phenotype CD38+ , CD39- , slgM- , we have now investigated the pattern of A-myb expression in neoplastic B cells representating the whole spectrum of B-cell differentiation and compared it to that of c-myb and B-myb .", "target_text": { "A-myb": "DNA", "mature human B lymphocytes": "cell_type", "B cells": "cell_type", "c-myb": "DNA", "B-myb": "DNA" } }, { "input_text": "In a panel of 32 B-cell lines , A-myb was very strongly expressed in most Burkitt 's lymphoma ( BL ) cell lines , but weak or negative in 2 pre-B acute lymphoblastic leukemia ( ALL ) , 4 non-Hodgkin 's lymphoma ( NHL ) , 6 Epstein-Barr virus-immortalized lymphoblastoid cell lines , and 6 myeloma lines .", "target_text": { "B-cell lines": "cell_line", "A-myb": "DNA", "Epstein-Barr virus-immortalized lymphoblastoid cell lines": "cell_line", "myeloma lines": "cell_line" } }, { "input_text": "Protein expression paralleled that of the RNA .", "target_text": {} }, { "input_text": "We have also investigated A-myb expression in 49 fresh cases of B leukemias .", "target_text": { "A-myb": "DNA" } }, { "input_text": "Among 24 ALL , 6 were of the null and 11 of the common type and all these were negative for A-myb expression ; on the other hand , all 7 B- ALL cases ( slg+ ) , as well as one fresh BL case with bone marrow infiltration , expressed A-myb .", "target_text": { "A-myb": "DNA" } }, { "input_text": "A-myb was undetectable in 4 prolymphocytic leukemias ( PLL ) but was strongly expressed in 5/20 ( 25 % ) of chronic lymphocytic leukemia ( CLL ) samples .", "target_text": { "A-myb": "DNA" } }, { "input_text": "In the latter A-myb did not correlate with phenotype or clinical stage .", "target_text": { "A-myb": "DNA" } }, { "input_text": "Finally , we have studied the progression of one case of CLL into Richter 's syndrome and have found that the Richter 's cells expressed about 25-fold less A-myb RNA than the CLL cells from the same patient . The pattern of c-myb and B-myb was clearly distinct from that of A-myb .", "target_text": { "Richter 's cells": "cell_line", "A-myb": "DNA", "A-myb RNA": "RNA", "CLL cells": "cell_line", "c-myb": "DNA", "B-myb": "DNA" } }, { "input_text": "C-myb and B-myb were expressed in all neoplastic groups , except in CLL cells .", "target_text": { "B-myb": "DNA", "CLL cells": "cell_line" } }, { "input_text": "Thus , A-myb expression , unlike that of c-myb and B-myb , is restricted to a subset of B-cell neoplasias ( in particular BL and slg+B- ALL ) representative of a specific stage of B-cell differentiation .", "target_text": { "A-myb": "DNA", "c-myb": "DNA", "B-myb": "DNA" } }, { "input_text": "This expression may in part reflect expression of A-myb by the normal germinal center B cells that are the normal counterpart of these transformed B cells .", "target_text": { "A-myb": "DNA", "B cells": "cell_type", "transformed B cells": "cell_line" } }, { "input_text": "The data presented strongly support a role for this transcription factor in B-cell differentiation and perhaps in B-cell transformation in some neoplasias .", "target_text": { "transcription factor": "protein" } }, { "input_text": "Granulocyte-macrophage colony-stimulating factor stimulates JAK2 signaling pathway and rapidly activates p93fes , STAT1 p91 , and STAT3 p92 in polymorphonuclear leukocytes .", "target_text": { "Granulocyte-macrophage colony-stimulating factor": "protein", "JAK2": "protein", "p93fes": "protein", "STAT1 p91": "protein", "STAT3 p92": "protein", "polymorphonuclear leukocytes": "cell_type" } }, { "input_text": "Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , supports proliferation , differentiation , and functional activation of hemopoietic cells by its interaction with a heterodimeric receptor .", "target_text": { "Granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein" } }, { "input_text": "Although GM-CSF receptor is devoid of tyrosine kinase enzymatic activity , GM-CSF -induced peripheral blood polymorphonuclear leukocytes ( PMN ) functional activation is mediated by the phosphorylation of a large number of intracellular signaling molecules .", "target_text": { "GM-CSF": "protein", "tyrosine kinase": "protein", "polymorphonuclear leukocytes": "cell_type", "GM-CSF -induced peripheral blood polymorphonuclear leukocytes": "cell_line", "PMN": "cell_type", "intracellular signaling molecules": "protein" } }, { "input_text": "We have previously shown that JAK2 becomes tyrosine -phosphorylated in response to GM-CSF in PMN .", "target_text": { "JAK2": "protein", "GM-CSF": "protein", "PMN": "cell_type" } }, { "input_text": "In the present study we demonstrate that also the signal transducers and activators of transcription ( STAT ) family members STAT1 p91 and STAT3 p92 and the product of the c-fps/fes protooncogene become tyrosine -phosphorylated upon GM-CSF stimulation and physically associated with both GM-CSF receptor beta common subunit and JAK2 .", "target_text": { "signal transducers and activators of transcription ( STAT ) family members": "protein", "STAT1 p91": "protein", "STAT3 p92": "protein", "c-fps/fes protooncogene": "DNA", "GM-CSF": "protein", "JAK2": "protein" } }, { "input_text": "Moreover GM-CSF was able to induce JAK2 and p93fes catalytic activity .", "target_text": { "GM-CSF": "protein", "JAK2": "protein", "p93fes": "protein" } }, { "input_text": "We also demonstrate that the association of the GM-CSF receptor beta common subunit with JAK2 is ligand-dependent .", "target_text": { "GM-CSF": "protein", "GM-CSF receptor beta common subunit": "protein", "JAK2": "protein" } }, { "input_text": "Finally we demonstrate that GM-CSF induces a DNA-binding complex that contains both p91 and p92 .", "target_text": { "GM-CSF": "protein", "DNA-binding complex": "protein", "p91": "protein", "p92": "protein" } }, { "input_text": "These results identify a new signal transduction pathway activated by GM-CSF and provide a mechanism for rapid activation of gene expression in GM-CSF -stimulated PMN .", "target_text": { "GM-CSF": "protein", "PMN": "cell_type", "GM-CSF -stimulated PMN": "cell_type" } }, { "input_text": "Epstein-Barr virus nuclear antigen 2 ( EBNA2 ) -oestrogen receptor fusion proteins complement the EBNA2-deficient Epstein-Barr virus strain P3HR1 in transformation of primary B cells but suppress growth of human B cell lymphoma lines .", "target_text": { "Epstein-Barr virus nuclear antigen 2": "protein", "Epstein-Barr virus nuclear antigen 2 ( EBNA2 ) -oestrogen receptor fusion proteins": "protein", "primary B cells": "cell_type", "human B cell lymphoma lines": "cell_line" } }, { "input_text": "To develop a transformation system with a conditional Epstein-Barr virus nuclear antigen 2 ( EBNA2 ) gene , we fused the hormone binding domain of the oestrogen receptor to the N or C terminus of EBNA2 .", "target_text": { "EBNA2": "protein", "Epstein-Barr virus nuclear antigen 2 ( EBNA2 ) gene": "DNA", "hormone binding domain": "protein" } }, { "input_text": "In promoter transactivation as well as primary B cell transformation assays these chimeric EBNA2 proteins are able to substitute for wild-type EBNA2 in the presence of oestrogen .", "target_text": { "EBNA2": "protein", "wild-type EBNA2": "protein" } }, { "input_text": "Here we provide evidence that this transformation is the result of double infection of a cell with two virions , the P3HR1 virus genome and a mini- EBV plasmid carrying the chimeric EBNA2 gene .", "target_text": { "P3HR1 virus genome": "DNA", "mini- EBV plasmid": "DNA", "EBNA2": "protein", "EBNA2 gene": "DNA" } }, { "input_text": "Unexpectedly , expression of the same EBNA2 -oestrogen receptor fusion protein in established human B cell lymphoma lines resulted in growth retardation or growth arrest upon the addition of oestrogen .", "target_text": { "EBNA2": "protein", "established human B cell lymphoma lines": "cell_line" } }, { "input_text": "By titrating the oestrogen concentration in these stably transfected cells , the growth retarding and the transactivating function of the chimeric proteins could not be dissociated .", "target_text": { "stably transfected cells": "cell_line", "chimeric proteins": "protein" } }, { "input_text": "We propose that growth inhibition of established B cell lymphoma lines is a novel function of EBNA2 which has not been detected in the absence of an inducible system .", "target_text": { "B cell lymphoma lines": "cell_line", "EBNA2": "protein" } }, { "input_text": "It remains open whether the growth retarding property of the EBNA2 -oestrogen receptor fusion protein in B cell lymphoma lines is due to unphysiologically high expression of the chimeric protein or to interference with a cellular programme driving proliferation in these cell lines .", "target_text": { "EBNA2": "protein", "EBNA2 -oestrogen receptor fusion protein": "protein", "B cell lymphoma lines": "cell_line", "chimeric protein": "protein", "cell lines": "cell_line" } }, { "input_text": "Tissue-specific activity of the gammac chain gene promoter depends upon an Ets binding site and is regulated by GA-binding protein .", "target_text": { "gammac chain gene": "DNA", "gammac chain gene promoter": "DNA", "Ets binding site": "DNA", "GA-binding protein": "protein" } }, { "input_text": "The gammac chain is a subunit of multiple cytokine receptors ( interleukin ( IL ) -2 , IL-4 , IL-7 , IL-9 , and IL-15 ) , the expression of which is restricted to hematopoietic lineages .", "target_text": { "gammac chain": "protein", "cytokine receptors": "protein", "interleukin ( IL ) -2": "protein", "IL-4": "protein", "IL-7": "protein", "IL-9": "protein", "IL-15": "protein", "hematopoietic lineages": "cell_type" } }, { "input_text": "A defect in gammac leads to the X-linked severe combined immunodeficiency characterized by a block in T cell differentiation .", "target_text": {} }, { "input_text": "In order to better characterize the human gammac promoter and define the minimal tissue-specific promoter region , progressive 5'-deletion constructs of a segment extending 1053 base pairs upstream of the major transcription start site were generated and tested for promoter activity in various hematopoietic and nonhematopoietic cell types .", "target_text": { "human gammac promoter": "DNA", "minimal tissue-specific promoter region": "DNA", "5'-deletion constructs": "DNA", "1053 base pairs upstream": "DNA", "major transcription start site": "DNA" } }, { "input_text": "The -1053/+34 construct allowed promoter activity only in cells of hematopoietic origin , and tissue specificity was conserved in all other constructs tested .", "target_text": { "-1053/+34 construct": "DNA", "hematopoietic origin": "cell_type" } }, { "input_text": "The region downstream of -90 appeared critical for basal promoter activity .", "target_text": {} }, { "input_text": "It contains two potential Ets binding sites conserved in the murine gammac promoter gene , one of which was found essential for functional promoter activity as determined by mutational analysis .", "target_text": { "Ets binding sites": "DNA", "murine gammac promoter gene": "DNA" } }, { "input_text": "The functional Ets binding site was found to bind Ets family proteins , principally GA-binding protein and Elf-1 and could be transactivated by GABPalpha and -beta synergistically .", "target_text": { "Ets binding site": "DNA", "Ets family proteins": "protein", "GA-binding protein": "protein", "Elf-1": "protein", "GABPalpha": "protein", "-beta": "protein" } }, { "input_text": "These results indicate that , as already reported for the IL2Rbeta promoter , GA-binding protein is an essential component of gammac basal promoter activity .", "target_text": { "IL2Rbeta promoter": "DNA", "GA-binding protein": "protein" } }, { "input_text": "Although GABP expression is not restricted to the hematopoietic lineage , its interaction with other specific factors may contribute to the tissue-specific expression of the gammac gene .", "target_text": { "GABP": "protein", "hematopoietic lineage": "cell_type", "specific factors": "protein", "gammac gene": "DNA" } }, { "input_text": "Detection of intracellular signal transduction molecules in PBMC from rhesus macaques and sooty mangabeys .", "target_text": { "intracellular signal transduction molecules": "protein", "PBMC": "cell_type" } }, { "input_text": "One of the manifestations of human HIV-1 and nonhuman primate SIV infection that lead to disease is reasoned to be secondary to generalized T-cell dysfunction .", "target_text": {} }, { "input_text": "The molecular mechanisms associated with the T-cell dysfunction remain to be elucidated .", "target_text": {} }, { "input_text": "To address this issue , we sought to utilize the nonhuman primate model to study intracellular signaling events in cells from disease-susceptible rhesus macaques and disease-resistant sooty mangabeys .", "target_text": {} }, { "input_text": "Because relatively little is known about these events in nonhuman primates , our laboratory defined optimal conditions , reagents , and assays for the study of signal transduction events in cells from nonhuman primates .", "target_text": {} }, { "input_text": "The protein phosphorylation patterns in the two monkeys exhibited quantitative , qualitative , and kinetic differences .", "target_text": {} }, { "input_text": "Antibodies to Stat6 detected a unique band in macaque cell lysates .", "target_text": { "Stat6": "protein" } }, { "input_text": "This band is markedly decreased human cell lysates and never seen in mangabey cell lysates .", "target_text": {} }, { "input_text": "Detection of various other intracellular signaling proteins is also described .", "target_text": { "intracellular signaling proteins": "protein" } }, { "input_text": "Genetic characterization of transactivation of the human T-cell leukemia virus type 1 promoter : Binding of Tax to Tax -responsive element 1 is mediated by the cyclic AMP-responsive members of the CREB/ATF family of transcription factors .", "target_text": { "human T-cell leukemia virus type 1 promoter": "DNA", "Tax": "protein", "Tax -responsive element 1": "DNA", "cyclic AMP-responsive members": "protein", "CREB/ATF family": "protein" } }, { "input_text": "To achieve a better understanding of the mechanism of transactivation by Tax of human T-cell leukemia virus type 1 Tax -responsive element 1 ( TRE-1 ) , we developed a genetic approach with Saccharomyces cerevisiae .", "target_text": { "Tax": "protein", "Tax -responsive element 1": "DNA", "TRE-1": "DNA" } }, { "input_text": "We constructed a yeast reporter strain containing the lacZ gene under the control of the CYC1 promoter associated with three copies of TRE-1 .", "target_text": { "lacZ gene": "DNA", "CYC1 promoter": "DNA", "TRE-1": "DNA" } }, { "input_text": "Expression of either the cyclic AMP response element-binding protein ( CREB ) or CREB fused to the GAL4 activation domain ( GAD ) in this strain did not modify the expression of the reporter gene .", "target_text": { "cyclic AMP response element-binding protein": "protein", "CREB": "protein", "GAL4 activation domain": "protein", "GAD": "protein", "reporter gene": "DNA" } }, { "input_text": "Tax alone was also inactive .", "target_text": { "Tax": "protein" } }, { "input_text": "However , expression of the reporter gene was induced by coexpression of Tax and CREB .", "target_text": { "reporter gene": "DNA", "Tax": "protein", "CREB": "protein" } }, { "input_text": "This effect was stronger with the GAD-CREB fusion protein .", "target_text": { "GAD-CREB fusion protein": "protein" } }, { "input_text": "Analysis of different CREB mutants with this genetic system indicated that the C-terminal 92 amino acid residues , which include the basic domain and the leucine zipper , are necessary and sufficient to mediate transactivation by Tax .", "target_text": { "CREB mutants": "protein", "C-terminal 92 amino acid residues": "protein", "basic domain": "protein", "leucine zipper": "protein", "Tax": "protein" } }, { "input_text": "To identify cellular proteins binding to TRE-1 in a Tax -dependent manner , this strain was also used to screen a library of human cDNAs fused to GAD .", "target_text": { "cellular proteins": "protein", "TRE-1": "DNA", "Tax": "protein", "human cDNAs": "DNA", "GAD": "protein" } }, { "input_text": "Of five positive clones isolated from 0.75 x 10(6) yeast colonies , four were members of the CREB/activating transcription factor ( ATF ) family : CREB , two isoforms of the cyclic AMP-responsive element modulator ( CREM ) , and ATF-1 .", "target_text": { "CREB/activating transcription factor ( ATF ) family": "protein", "CREB": "protein", "two isoforms of the cyclic AMP-responsive element modulator": "protein", "CREM": "protein", "ATF-1": "protein" } }, { "input_text": "Interestingly , these three proteins can be phosphorylated by protein kinase A and thus form a particular subgroup within the CREB/ATF family .", "target_text": { "protein kinase A": "protein", "CREB/ATF family": "protein" } }, { "input_text": "Expression of ATF-2 in S. cerevisiae did not activate TRE-1 in the presence of Tax .", "target_text": { "ATF-2": "protein", "TRE-1": "DNA", "Tax": "protein" } }, { "input_text": "This shows that in a eukaryotic nucleus , Tax specifically interacts with the basic domain -leucine zipper region of ATF-1 , CREB , and CREM .", "target_text": { "Tax": "protein", "basic domain": "protein", "-leucine zipper": "protein", "basic domain -leucine zipper region": "protein", "ATF-1": "protein", "CREB": "protein", "CREM": "protein" } }, { "input_text": "The fifth clone identified in this screening corresponded to the Ku autoantigen p70 subunit .", "target_text": { "Ku autoantigen p70 subunit": "protein" } }, { "input_text": "When fused to GAD , the C-terminal region of Ku was able to activate transcription via TRE-1 but this activation was not dependent on Tax .", "target_text": { "GAD": "protein", "C-terminal region": "protein", "Ku": "protein", "TRE-1": "DNA", "Tax": "protein" } }, { "input_text": "A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p [ see comments ]", "target_text": { "mammalian histone deacetylase": "protein", "yeast transcriptional regulator": "protein", "Rpd3p": "protein" } }, { "input_text": "Trapoxin is a microbially derived cyclotetrapeptide that inhibits histone deacetylation in vivo and causes mammalian cells to arrest in the cell cycle .", "target_text": { "histone": "protein" } }, { "input_text": "A trapoxin affinity matrix was used to isolate two nuclear proteins that copurified with histone deacetylase activity .", "target_text": { "histone": "protein", "histone deacetylase": "protein" } }, { "input_text": "Both proteins were identified by peptide microsequencing , and a complementary DNA encoding the histone deacetylase catalytic subunit ( HD1 ) was cloned from a human Jurkat T cell library .", "target_text": { "complementary DNA": "DNA", "histone": "protein", "histone deacetylase": "protein", "histone deacetylase catalytic subunit": "protein", "HD1": "protein" } }, { "input_text": "As the predicted protein is very similar to the yeast transcriptional regulator Rpd3p , these results support a role for histone deacetylase as a key regulator of eukaryotic transcription .", "target_text": { "yeast transcriptional regulator": "protein", "Rpd3p": "protein", "histone": "protein", "histone deacetylase": "protein" } }, { "input_text": "Coexpression of the interleukin-13 and interleukin-4 genes correlates with their physical linkage in the cytokine gene cluster on human chromosome 5q23-31 .", "target_text": { "cytokine gene cluster": "DNA", "human chromosome 5q23-31": "DNA" } }, { "input_text": "Interleukin-13 ( IL-13 ) and IL-4 are cytokines produced by T cells that are encoded by the q23-31 region of human chromosome 5 .", "target_text": { "Interleukin-13": "protein", "IL-13": "protein", "IL-4": "protein" } }, { "input_text": "To investigate the regulation of IL-13 gene expression by T cells , we isolated and sequenced the human IL-13 gene , analyzed its 5'-flanking region for potential transcriptional activation elements , and examined its expression in nontransformed T-lineage cell populations .", "target_text": { "IL-13": "protein", "IL-13 gene": "DNA", "T cells": "cell_type", "5'-flanking region": "DNA", "transcriptional activation elements": "DNA", "nontransformed T-lineage cell populations": "cell_line" } }, { "input_text": "The human IL-13 gene was located 12.5-kb upstream of the IL-4 gene and 2-kb downstream of a CpG island .", "target_text": { "human IL-13 gene": "DNA", "12.5-kb upstream": "DNA", "IL-4": "protein", "IL-4 gene": "DNA", "2-kb downstream": "DNA", "CpG island": "DNA" } }, { "input_text": "The IL-13 gene 5' flank region included a segment with sequence homology to P elements of the IL-4 promoter involved in transcriptional activation in T cells .", "target_text": { "IL-13": "protein", "IL-13 gene": "DNA", "IL-13 gene 5' flank region": "DNA", "P elements": "DNA", "IL-4": "protein", "IL-4 promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "Mutation of the IL-13 P element site significantly reduced IL-13 promoter activity in response to T-cell activation .", "target_text": { "IL-13 P element site": "DNA", "IL-13": "protein" } }, { "input_text": "Oligonucleotides containing the IL-13 or IL-4 P element sites specifically bound the transcriptional activator protein , nuclear factor-activated T cells , preformed ( NF-ATp ) , when incubated with nuclear protein extracts from activated T cells .", "target_text": { "IL-13": "protein", "IL-4": "protein", "IL-4 P element sites": "DNA", "transcriptional activator protein": "protein", "T cells": "cell_type", "nuclear factor-activated T cells": "protein", "NF-ATp": "protein", "activated T cells": "cell_type" } }, { "input_text": "Similar to IL-4 , IL-13 mRNA expression was highest in T-cell populations enriched for cells that had previously been primed in vivo or in vitro , indicating that priming increases the expression of the IL-13 and IL-4 genes in a coordinate manner .", "target_text": { "IL-4": "protein", "IL-13": "protein", "IL-13 mRNA": "RNA", "T-cell populations": "cell_line" } }, { "input_text": "Because the primed T cells contain higher levels of nuclear NF-ATp , capable of binding to P elements of the IL-4 and IL-13 promoters , than do freshly-isolated T cells , the NF-AT-binding P elements are attractive candidates to mediate the coordinate expression of these two cytokine genes .", "target_text": { "primed T cells": "cell_line", "NF-ATp": "protein", "nuclear NF-ATp": "protein", "P elements": "DNA", "freshly-isolated T cells": "cell_type", "NF-AT-binding P elements": "DNA", "cytokine genes": "DNA" } }, { "input_text": "Inhibition of alpha interferon but not gamma interferon signal transduction by phorbol esters is mediated by a tyrosine phosphatase .", "target_text": { "alpha interferon": "protein", "gamma interferon": "protein", "tyrosine phosphatase": "protein" } }, { "input_text": "Previous studies have indicated that the expression of viral oncoproteins , cell transformation , or phorbol ester treatment of cells can inhibit alpha/beta interferon ( IFN-alpha/beta ) -induced gene expression .", "target_text": {} }, { "input_text": "The mechanisms by which these promoters of cell growth exert their inhibitory effects vary , but in most instances they involve a disruption of the IFN-alpha/beta-induced transcription complex ISGF3 such that the DNA-binding component of this complex ( the 48-kDa ISGF3gamma protein ) does not bind to the interferon-stimulated response element ( ISRE ) .", "target_text": {} }, { "input_text": "In this report , we demonstrated that phorbol ester treatment of human peripheral blood monocytes dramatically inhibits activation of IFN-alpha/B-stimulated early response genes but by a mechanism which does not involve abrogation of the ISRE binding of ISGF3gamma .", "target_text": {} }, { "input_text": "Phorbol ester treatment of monocytes inhibited IFN alpha-stimulated tyrosine phosphorylation of the transcription factors Stat1alpha , Stat2 , and Stat3 and of the tyrosine kinase Tyk2 but had no effect on IFN-gamma activation of Stat1alpha .", "target_text": { "transcription factors": "protein", "Stat1alpha": "protein", "Stat2": "protein", "Stat3": "protein", "tyrosine kinase": "protein", "Tyk2": "protein", "IFN-gamma": "protein" } }, { "input_text": "IFNalpha-stimulated tyrosine phosphorylation of Jak1 and the alpha subunit of the IFN-alpha receptor were unaffected by phorbol 12-myristate 13-acetate ( PMA ) .", "target_text": { "Jak1": "protein", "alpha subunit": "protein", "IFN-alpha receptor": "protein" } }, { "input_text": "Moreover , PMA caused the dephosphorylation of Tyk2 but not of Jak1 , which was activated by IFN .", "target_text": { "Tyk2": "protein", "Jak1": "protein", "IFN": "protein" } }, { "input_text": "Pretreatment of cells with vanadate prevented the effects of PMA with regard to PMA -induced Tyk2 dephosphorylation .", "target_text": { "Tyk2": "protein" } }, { "input_text": "These observations suggest that PMA exerts its inhibitory effects by activation of a tyrosine phosphatase which selectively regulates Tyk2 but not Jak1 activity .", "target_text": { "tyrosine phosphatase": "protein", "Tyk2": "protein", "Jak1": "protein" } }, { "input_text": "Transcriptional regulation of the interleukin-2 gene in normal human peripheral blood T cells .", "target_text": { "interleukin-2": "protein", "interleukin-2 gene": "DNA", "human peripheral blood T cells": "cell_type" } }, { "input_text": "Convergence of costimulatory signals and differences from transformed T cells .", "target_text": { "transformed T cells": "cell_type" } }, { "input_text": "To study transcriptional regulation in normal human T cells , we have optimized conditions for transient transfection .", "target_text": { "normal human T cells": "cell_type" } }, { "input_text": "Interleukin-2 ( IL-2 ) promoter -reporter gene behavior closely parallels the endogenous gene in response to T cell receptor and costimulatory signals .", "target_text": { "IL-2": "protein", "Interleukin-2 ( IL-2 ) promoter": "DNA", "-reporter gene": "DNA", "endogenous gene": "DNA", "T cell receptor": "protein" } }, { "input_text": "As assessed with mutagenized promoters , the most important IL-2 cis-regulatory elements in normal T cells are the proximal AP-1 site and the NF- kappaB site .", "target_text": { "mutagenized promoters": "DNA", "IL-2": "protein", "IL-2 cis-regulatory elements": "DNA", "normal T cells": "cell_type", "AP-1": "protein", "proximal AP-1 site": "DNA", "NF- kappaB": "protein", "NF- kappaB site": "DNA" } }, { "input_text": "Both primary activation , with phytohemagglutinin or antibodies to CD3 , and costimulation , provided by pairs of CD2 antibodies or B7-positive ( B cells ) or B7-negative ( endothelial ) accessory cells , are mediated through the same cis-elements .", "target_text": { "phytohemagglutinin": "protein", "antibodies to CD3": "protein", "CD2 antibodies": "protein", "B7-positive ( B cells )": "cell_type", "B7-negative ( endothelial ) accessory cells ,": "cell_type", "cis-elements": "DNA" } }, { "input_text": "Interestingly , the nuclear factor of activated T cell sites are much less important in normal T cells than in Jurkat T cells .", "target_text": { "nuclear factor of activated T cell sites": "DNA", "normal T cells": "cell_type", "Jurkat T cells": "cell_line" } }, { "input_text": "We conclude that IL-2 transcriptional regulation differs in tumor cell lines compared with normal T cells and that different costimulatory signals converge on the same cis-elements in the IL-2 promoter .", "target_text": { "IL-2": "protein", "tumor cell lines": "cell_line", "normal T cells": "cell_type", "cis-elements": "DNA", "IL-2 promoter": "DNA" } }, { "input_text": "The RAR-RXR as well as the RXR-RXR pathway is involved in signaling growth inhibition of human CD34+ erythroid progenitor cells .", "target_text": { "RAR-RXR": "protein", "RXR-RXR": "protein", "human CD34+ erythroid progenitor cells": "cell_line" } }, { "input_text": "Previous studies have shown that retinoic acid ( RA ) , similar to tumor necrosis factor-alpha ( TNF-alpha ) , can act as a bifunctional regulator of the growth of bone marrow progenitors , in that it can stimulate granulocyte-macrophage colony-stimulating factor ( GM-CSF ) - or interleukin-3 ( IL-3 ) - induced GM colony formation , but potently inhibit G-CSF -induced growth .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "bone marrow progenitors": "cell_type", "G-CSF": "protein" } }, { "input_text": "The present study , using highly enriched human CD34+ as well as Lin- murine bone marrow progenitor cells , demonstrates a potent inhibitory effect of 9-cis-RA on burst-forming unit-erythroid ( BFU-E ) colony formation regardless of the cytokine stimulating growth .", "target_text": { "human CD34+": "protein", "Lin- murine bone marrow progenitor cells": "cell_line", "cytokine": "protein" } }, { "input_text": "Specifically , 9-cis-RA potently inhibited the growth of BFU-E response to erythropoietin ( Epo ) ( 100 % ) , stem cell factor ( SCF ) + Epo ( 92 % ) , IL-3 + Epo ( 97 % ) , IL-4 + Epo ( 88 % ) , and IL-9 + Epo ( 100 % ) .", "target_text": { "erythropoietin": "protein", "Epo": "protein", "stem cell factor": "protein", "SCF": "protein", "IL-3": "protein", "IL-4": "protein", "IL-9": "protein" } }, { "input_text": "Erythroid colony growth was also inhibited when CD34+ progenitors were seeded at one cell per well , suggesting a direct action of RA .", "target_text": { "CD34+ progenitors": "cell_type" } }, { "input_text": "Using synthetic ligands to retinoic acid receptors ( RARs ) and retinoid X receptors ( RXRs ) that selectively bind and activate RAR-RXR or RXR-RXR dimers , respectively , we dissected the involvement of the two retinoid response pathways in the regulation of normal myeloid and erythroid progenitor cell growth .", "target_text": { "retinoic acid receptors": "protein", "RARs": "protein", "retinoid X receptors": "protein", "RXRs": "protein", "RAR-RXR": "protein", "RXR-RXR": "protein" } }, { "input_text": "Transactivation studies showed that both the RAR ( Ro 13-7410 ) and RXR ( Ro 25-6603 and Ro 25-7386 ) ligands were highly selective at 100 nmol/L .", "target_text": { "RAR": "protein", "RXR": "protein" } }, { "input_text": "At this concentration , Ro 13-7410 potently inhibited G-CSF -stimulated myeloid as well as SCF + Epo -induced erythroid colony growth .", "target_text": { "G-CSF": "protein", "SCF": "protein", "Epo": "protein" } }, { "input_text": "At the same concentration , Ro 25-6603 and Ro 25-7386 had little or no effect on G-CSF -induced colony formation , whereas they inhibited 75 % and 53 % , respectively , of SCF + Epo -stimulated BFU-E colony growth .", "target_text": { "G-CSF": "protein", "SCF": "protein", "Epo": "protein" } }, { "input_text": "Thus , the RAR-RXR response pathway can signal growth inhibition of normal bone marrow myeloid and erythroid progenitor cells .", "target_text": { "RAR-RXR": "protein" } }, { "input_text": "In addition , we demonstrate a unique involvement of the RXR-RXR pathway in mediating growth inhibition of erythroid but not myeloid progenitor cells .", "target_text": { "RXR-RXR": "protein", "erythroid": "cell_type", "myeloid progenitor cells": "cell_type" } }, { "input_text": "AM580 , a stable benzoic derivative of retinoic acid , has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells .", "target_text": { "acute promyelocytic leukemia cells": "cell_line" } }, { "input_text": "All-trans retinoic acid ( ATRA ) is successfully used in the cyto-differentiating treatment of acute promyelocytic leukemia ( APL ) .", "target_text": {} }, { "input_text": "Paradoxically , APL cells express PML-RAR , an aberrant form of the retinoic acid receptor type alpha ( RAR alpha ) derived from the leukemia-specific t(15;17) chromosomal translocation .", "target_text": { "APL cells": "cell_line", "PML-RAR": "protein", "retinoic acid receptor type alpha": "protein", "RAR alpha": "protein", "leukemia-specific t(15;17) chromosomal translocation": "DNA" } }, { "input_text": "We show here that AM580 , a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist , is a powerful inducer of granulocytic maturation in NB4 , an APL -derived cell line , and in freshly isolated APL blasts .", "target_text": { "RAR alpha": "protein", "NB4": "cell_line", "APL -derived cell line": "cell_line", "freshly isolated APL blasts": "cell_type" } }, { "input_text": "After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor ( G-CSF ) , the compound induces granulocytic maturation , as assessed by determination of the levels of leukocyte alkaline phosphatase , CD11b , CD33 , and G-CSF receptor mRNA , at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects .", "target_text": { "APL cells": "cell_line", "granulocyte colony-stimulating factor": "protein", "G-CSF": "protein" } }, { "input_text": "By contrast , AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease .", "target_text": { "differentiation markers": "protein", "HL-60 cell line": "cell_line", "freshly isolated granulocytes": "cell_type" } }, { "input_text": "In NB4 cells , two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580 , whereas RAR beta- or RAR gamma-specific ligands are totally ineffective .", "target_text": { "NB4 cells": "cell_line", "LAP": "protein" } }, { "input_text": "These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present .", "target_text": { "PML-RAR": "protein" } }, { "input_text": "Binding experiments , using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha , show that AM580 has a lower affinity than ATRA for both receptors .", "target_text": { "COS-7 cells": "cell_line", "PML-RAR": "protein", "RAR alpha": "protein" } }, { "input_text": "However , in the presence of PML-RAR , the synthetic retinoid is a much better transactivator of retinoic acid -responsive element-containing promoters than the natural retinoid , whereas , in the presence of RAR alpha , AM580 and ATRA have similar activity .", "target_text": { "PML-RAR": "protein", "retinoic acid -responsive element-containing promoters": "DNA", "RAR alpha": "protein" } }, { "input_text": "This may explain the strong cyto-differentiating potential of AM580 in PML-RAR -containing leukemic cells .", "target_text": { "PML-RAR": "protein", "PML-RAR -containing leukemic cells": "cell_type" } }, { "input_text": "Inhibition of vitamin D receptor -retinoid X receptor -vitamin D response element complex formation by nuclear extracts of vitamin D-resistant New World primate cells .", "target_text": { "vitamin D receptor": "protein", "-retinoid X receptor": "protein", "-vitamin D response element": "DNA", "vitamin D receptor -retinoid X receptor -vitamin D response element complex": "protein", "vitamin D-resistant New World primate cells": "cell_type" } }, { "input_text": "Most New World primate ( NWP ) genera evolved to require high circulating levels of steroid hormones and vitamin D .", "target_text": {} }, { "input_text": "We hypothesized that an intracellular vitamin D binding protein ( IDBP ) , present in both nuclear and cytoplasmic fractions of NWP cells , or another protein ( s ) may cause or contribute to the steroid hormone-resistant state in NWP by disruption of the receptor dimerization process and/or by interference of receptor complex binding to the consensus response elements present in the enhancer regions of steroid-responsive genes .", "target_text": { "intracellular vitamin D binding protein": "protein", "IDBP": "protein", "NWP cells": "cell_line", "NWP": "cell_line", "receptor complex": "protein", "consensus response elements": "DNA", "enhancer regions": "DNA", "steroid-responsive genes": "DNA" } }, { "input_text": "We employed electromobility shift assay ( EMSA ) to screen for the presence of proteins capable of binding to the vitamin D response element ( VDRE ) .", "target_text": { "vitamin D response element": "DNA", "VDRE": "DNA" } }, { "input_text": "Nuclear and post- nuclear extracts were prepared from two B-lymphoblastoid cell lines known to be representative of the vitamin D -resistant and wild type phenotypes , respectively .", "target_text": { "B-lymphoblastoid cell lines": "cell_line", "vitamin D -resistant": "cell_line", "wild type phenotypes": "cell_line" } }, { "input_text": "The extracts were compared for their ability to retard the migration of radiolabeled double stranded oligomers representative of the VDREs of the human osteocalcin and the mouse osteopontin gene promoters .", "target_text": { "VDREs": "DNA" } }, { "input_text": "A specific , retarded band containing VDR-RXR was identified when wild type cell but not when vitamin D -resistant cell nuclear extract was used in the binding reaction with either probe .", "target_text": { "VDR-RXR": "protein" } }, { "input_text": "In addition , vitamin D -resistant cell nuclear extract contained a protein ( s ) which was bound specifically to the VDRE and was capable of completely inhibiting VDR-RXR- VDRE complex formation ; these effects were not demonstrated with nuclear extract from the wild type cell line or with the post-nuclear extract of the vitamin D -resistant cell line .", "target_text": { "VDRE": "DNA", "VDR-RXR- VDRE complex": "protein", "wild type cell line": "cell_line", "vitamin D -resistant cell line": "cell_line" } }, { "input_text": "We conclude that a VDRE -binding protein ( s ) , distinct from IDBP and present in nuclear extract of cells from a prototypical vitamin D -resistant NWP , is capable of inhibiting normal VDR-RXR heterodimer binding to the VDRE .", "target_text": { "VDRE": "DNA", "VDRE -binding protein": "protein", "IDBP": "protein", "NWP": "cell_line", "prototypical vitamin D -resistant NWP": "cell_line", "VDR-RXR": "protein" } }, { "input_text": "BCL-6 expression during B-cell activation .", "target_text": { "BCL-6": "protein" } }, { "input_text": "Translocations involving the BCL-6 gene are common in the diffuse large cell subtype of non-Hodgkin 's lymphoma .", "target_text": { "BCL-6": "protein", "BCL-6 gene": "DNA" } }, { "input_text": "Invariably , the BCL-6 coding region is intact , but its 5' untranslated region is replaced with sequences from the translocation partner .", "target_text": { "BCL-6": "protein", "5' untranslated region": "DNA", "translocation partner": "DNA" } }, { "input_text": "The present study shows that BCL-6 expression is regulated in lymphocytes during mitogenic stimulation .", "target_text": { "BCL-6": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Resting B and T lymphocytes contain high levels of BCL-6 mRNA .", "target_text": { "BCL-6": "protein", "BCL-6 mRNA": "RNA" } }, { "input_text": "Stimulation of mouse B cells with anti- IgM or IgD antibodies , bacterial lipopolysaccharide , phorbol 12-myristate 13-acetate plus ionomycin , or CD40 ligand led to a five-fold to 35-fold decrease in BCL-6 mRNA levels .", "target_text": { "mouse B cells": "cell_type", "CD40 ligand": "protein", "BCL-6 mRNA": "RNA" } }, { "input_text": "Similar downregulation of BCL-6 mRNA was seen in human B cells stimulated with Staphylococcus aureus plus interleukin-2 or anti-IgM antibodies and in human T lymphocytes stimulated with phytohemagglutinin .", "target_text": { "BCL-6": "protein", "BCL-6 mRNA": "RNA", "human B cells": "cell_type", "interleukin-2": "protein", "anti-IgM antibodies": "protein", "human T lymphocytes": "cell_type", "phytohemagglutinin": "protein" } }, { "input_text": "BCL-6 mRNA levels began to decrease 8 to 16 hours after stimulation , before cells entered S phase .", "target_text": { "BCL-6": "protein", "BCL-6 mRNA": "RNA" } }, { "input_text": "Although polyclonal activation of B cells in vitro invariably decreased BCL-6 MRNA expression , activated B cells from human germinal centers expressed BCL-6 mRNA at levels comparable to the levels in resting B cells .", "target_text": { "B cells": "cell_type", "BCL-6": "protein", "activated B cells": "cell_type" } }, { "input_text": "Despite these similar mRNA levels , BCL-6 protein expression was threefold to 34-fold higher in germinal center B cells than in resting B cells , suggesting that BCL-6 protein levels are controlled by translational or posttranslational mechanisms .", "target_text": { "BCL-6": "protein", "germinal center B cells": "cell_type", "resting B cells": "cell_type" } }, { "input_text": "These observations suggest that the germinal center reaction provides unique activation signals to B cells that allow for continued , high-level BCL-6 expression .", "target_text": { "B cells": "cell_type", "BCL-6": "protein" } }, { "input_text": "DNA-binding phosphoproteins induced after T cell activation : effects of cyclosporin A .", "target_text": { "DNA-binding phosphoproteins": "protein" } }, { "input_text": "To define novel proteins involved in the early transcriptional response during the activation of human T lymphocytes , we used a high-resolution , two-dimensional gel electrophoresis system to identify nuclear , deoxyribonucleic acid ( DNA ) binding proteins exhibiting rapid changes in phosphorylation following cell stimulation .", "target_text": { "novel proteins": "protein", "human T lymphocytes": "cell_type", "deoxyribonucleic acid": "DNA", "nuclear , deoxyribonucleic acid ( DNA ) binding proteins": "protein" } }, { "input_text": "We identified 18 nuclear proteins whose phosphorylation level changed more than 5-fold upon activation .", "target_text": { "nuclear proteins": "protein" } }, { "input_text": "Of these , 11 were found to possess DNA-binding properties .", "target_text": {} }, { "input_text": "The 11 phosphoproteins with DNA-binding activity , along with 4 others , were analyzed further .", "target_text": { "phosphoproteins": "protein" } }, { "input_text": "Phosphoamino acid analysis revealed several sets of proteins with different phosphorylated residues Kinetic analysis of the phosphorylation of the selected proteins was performed and revealed a complex group of transient and sustained responses to cell activation .", "target_text": {} }, { "input_text": "Finally , the activation-induced changes in one set of phosphoproteins were dramatically inhibited by cyclosporin A .", "target_text": { "phosphoproteins": "protein" } }, { "input_text": "We suggest that these phosphoproteins may be directly involved in regulating the transcriptional response to cellular activation by external stimuli .", "target_text": { "phosphoproteins": "protein" } }, { "input_text": "Inactivation of IkappaBbeta by the tax protein of human T-cell leukemia virus type 1 : a potential mechanism for constitutive induction of NF-kappaB .", "target_text": { "IkappaBbeta": "protein", "tax protein": "protein", "NF-kappaB": "protein" } }, { "input_text": "In resting T lymphocytes , the transcription factor NF-kappaB is sequestered in the cytoplasm via interactions with members of the I kappa B family of inhibitors , including IkappaBalpha and IkappaBbeta .", "target_text": { "resting T lymphocytes": "cell_type", "transcription factor": "protein", "NF-kappaB": "protein", "I kappa B family": "protein", "IkappaBalpha": "protein", "IkappaBbeta": "protein" } }, { "input_text": "During normal T-cell activation , IkappaBalpha is rapidly phosphorylated , ubiquitinated , and degraded by the 26S proteasome , thus permitting the release of functional NF-kappaB .", "target_text": { "IkappaBalpha": "protein", "26S proteasome": "protein", "NF-kappaB": "protein" } }, { "input_text": "In contrast to its transient pattern of nuclear induction during an immune response , NF-kappaB is constitutively activated in cells expressing the Tax transforming protein of human T-cell leukemia virus type I ( HTLV-1 ) .", "target_text": { "NF-kappaB": "protein", "Tax transforming protein": "protein" } }, { "input_text": "Recent studies indicate that HTLV-1 Tax targets IkappaBalpha to the ubiquitin- proteasome pathway .", "target_text": { "Tax": "protein", "IkappaBalpha": "protein" } }, { "input_text": "However , it remains unclear how this viral protein induces a persistent rather than transient NF-kappaB response .", "target_text": { "viral protein": "protein", "NF-kappaB": "protein" } }, { "input_text": "In this report , we provide evidence that in addition to acting on IkappaBalpha , Tax stimulates the turnover Of IkappaBbeta via a related targeting mechanism .", "target_text": { "IkappaBalpha": "protein", "Tax": "protein", "IkappaBbeta": "protein" } }, { "input_text": "Like IkappaBalpha , Tax -mediated breakdown of IkappaBbeta in transfected T lymphocytes is blocked either by cell-permeable proteasome inhibitors or by mutation Of IkappaBbeta at two serine residues present within its N-terminal region .", "target_text": { "IkappaBalpha": "protein", "Tax": "protein", "IkappaBbeta": "protein", "transfected T lymphocytes": "cell_line", "N-terminal region": "protein" } }, { "input_text": "Despite the dual specificity of HTLV-1 Tax for IkappaBalpha and IkappaBbeta at the protein level , Tax selectively stimulates NF-kappaB -directed transcription of the IkappaBalpha gene .", "target_text": { "Tax": "protein", "IkappaBalpha": "protein", "IkappaBbeta": "protein", "NF-kappaB": "protein", "IkappaBalpha gene": "DNA" } }, { "input_text": "Consequently , IkappaBbeta protein expression is chronically downregulated in HTLV-1 -infected T lymphocytes .", "target_text": { "IkappaBbeta": "protein", "HTLV-1 -infected T lymphocytes": "cell_type" } }, { "input_text": "These findings with IkappaBbeta provide a potential mechanism for the constitutive activation of NF-kappaB in Tax -expressing cells .", "target_text": { "IkappaBbeta": "protein", "NF-kappaB": "protein", "Tax": "protein", "Tax -expressing cells": "cell_line" } }, { "input_text": "The role of p16 in the E2F-dependent thymidine kinase regulation .", "target_text": { "p16": "protein", "E2F-dependent thymidine kinase": "protein" } }, { "input_text": "The role of alterations of the MTS1 tumor suppressor gene on chromosome 9p21 , which encodes p16 , the inhibitor of cyclin-dependent-kinase- 4 and 6 , in tumorigenesis is not yet clear .", "target_text": { "MTS1": "DNA", "MTS1 tumor suppressor gene": "DNA", "chromosome 9p21": "DNA", "p16": "protein" } }, { "input_text": "Phosphorylation of the retinoblastoma protein by cyclin-dependent kinases 4 and 6 prevents its interaction with the transcription factor E2F , which subsequently promotes the expression of S phase regulated genes , such as thymidine kinase .", "target_text": { "retinoblastoma protein": "protein", "transcription factor": "protein", "E2F": "protein", "S phase regulated genes": "DNA", "thymidine kinase": "protein" } }, { "input_text": "Although a role of p16 in this regulation has been presumed , there is no proof so far that loss of this tumor suppressor gene really affects E2F -mediated regulations .", "target_text": { "p16": "protein", "tumor suppressor gene": "DNA", "E2F": "protein" } }, { "input_text": "We investigated the regulation of thymidine kinase in phytohemagglutinin -stimulated normal human lymphocytes and in the p16 -negative human acute lymphoblastic leukemia cell lines , MOLT-4 and CEM .", "target_text": { "thymidine kinase": "protein", "phytohemagglutinin": "protein", "phytohemagglutinin -stimulated normal human lymphocytes": "cell_line", "p16": "protein", "p16 -negative human acute lymphoblastic leukemia cell lines": "cell_line", "MOLT-4": "cell_line", "CEM": "cell_line" } }, { "input_text": "Compared to normal lymphocytes , MOLT-4 and CEM cells exhibited an altered cell cycle regulation of thymidine kinase , a much higher intracellular activity of this enzyme , and higher thymidine kinase mRNA expression .", "target_text": { "normal lymphocytes": "cell_type", "thymidine kinase": "protein", "enzyme": "protein", "thymidine kinase mRNA": "RNA" } }, { "input_text": "Transient expression of p16 in normal human lymphocytes caused arrest in G1 , but was without effect on the cell growth of MOLT-4 and CEM cells , although all of them express functional retinoblastoma protein .", "target_text": { "p16": "protein", "retinoblastoma protein": "protein" } }, { "input_text": "Nevertheless , in the two leukemia cell lines transient overexpression of p16 reestablished the normal regulation of thymidine kinase , paralleled by an increase of the underphosphorylated form of retinoblastoma protein and decrease of free E2F bound to its motif in the thymidine kinase promoter .", "target_text": { "leukemia cell lines": "cell_line", "p16": "protein", "thymidine kinase": "protein", "retinoblastoma protein": "protein", "E2F": "protein", "thymidine kinase promoter": "DNA" } }, { "input_text": "We demonstrate that loss of p16 causes upregulation of this DNA precursor pathway enzyme via activation of E2F by a mechanism involving retinoblastoma protein .", "target_text": { "p16": "protein", "enzyme": "protein", "E2F": "protein", "retinoblastoma protein": "protein" } }, { "input_text": "Interactions of a transcriptional activator in the env gene of the mouse mammary tumor virus with activation-dependent , T cell-specific transacting factors .", "target_text": { "transcriptional activator": "DNA", "env gene": "DNA", "activation-dependent , T cell-specific transacting factors": "protein" } }, { "input_text": "The mouse mammary tumor virus env gene contains a transcriptional activator ( META ) that can control transcription of the adjacent long terminal repeat region .", "target_text": { "env gene": "DNA", "transcriptional activator": "DNA", "META": "DNA", "long terminal repeat region": "DNA" } }, { "input_text": "Transcriptional control by META parallels that of several lymphokine genes , being specific to T cells , dependent on their activation , and inhibited by the immunosuppressive drug cyclosporine ( CsA ) .", "target_text": { "META": "DNA", "lymphokine genes": "DNA", "T cells": "cell_type" } }, { "input_text": "DNase I footprinting indicated that nuclear factors from activated T lymphocytes bound a promoter-proximal site , META(P) , and a promoter-distal site , META(D+) , within the 400-base pair META region .", "target_text": { "DNase I": "protein", "nuclear factors": "protein", "activated T lymphocytes": "cell_type", "promoter-proximal site": "DNA", "META(P)": "DNA", "promoter-distal site": "DNA", "META(D+)": "DNA", "400-base pair META region": "DNA" } }, { "input_text": "Nuclear factors from unstimulated , but not from activated cells , bound a site , META(D-) , adjacent to META(D+) .", "target_text": { "Nuclear factors": "protein", "META(D-)": "DNA", "META(D+)": "DNA" } }, { "input_text": "META(D+) directed transcription of a linked luciferase gene , and gel shift analysis revealed binding of inducible , CsA -sensitive T cell factors , in parallel with transfection results .", "target_text": { "META(D+)": "DNA", "luciferase gene": "DNA", "CsA -sensitive T cell factors": "protein" } }, { "input_text": "Authentic NFAT and NF-kappaB targets did not compete for the META(D+) binding factor ( s ) .", "target_text": { "META(D+)": "DNA", "META(D+) binding factor": "protein" } }, { "input_text": "The SV40 core sequence competed for META(D+) binding factors , but META(D+) failed to compete for the complexes obtained with the SV40 probe .", "target_text": { "SV40 core sequence": "DNA", "META(D+)": "DNA", "META(D+) binding factors": "protein" } }, { "input_text": "Our results , taken together , indicate that META(D+) is a novel transcriptional enhancer element that is similar in its cell-type specificity , activation dependence , and CsA sensitivity to the NFAT element .", "target_text": { "META(D+)": "DNA", "transcriptional enhancer element": "DNA", "NFAT element": "DNA" } }, { "input_text": "It may be relevant to the role of MMTV in expression of Mls antigens or the induction of T cell lymphomas .", "target_text": { "Mls antigens": "protein" } }, { "input_text": "A novel interferon regulatory factor family transcription factor , ICSAT/Pip/LSIRF , that negatively regulates the activity of interferon-regulated genes .", "target_text": { "transcription factor": "protein", "interferon regulatory factor family transcription factor": "protein", "ICSAT/Pip/LSIRF": "protein", "interferon-regulated genes": "DNA" } }, { "input_text": "We have isolated a novel cDNA clone encoding interferon ( IFN ) consensus sequence-binding protein in adult T-cell leukemia cell line or activated T cells ( ICSAT ) ; this protein is the human homolog of the recently cloned Pip/LSIRF .", "target_text": { "novel cDNA clone": "DNA", "interferon ( IFN ) consensus sequence-binding protein": "protein", "adult T-cell leukemia cell line": "cell_line", "T cells": "cell_type", "ICSAT": "protein", "Pip/LSIRF": "protein" } }, { "input_text": "ICSAT is structurally most closely related to the previously cloned ICSBP , a member of the IFN regulatory factor ( IRF ) family of proteins that binds to interferon consensus sequences ( ICSs ) found in many promoters of the IFN-regulated genes .", "target_text": { "ICSAT": "protein", "ICSBP": "protein", "IFN regulatory factor ( IRF ) family": "protein", "interferon consensus sequences": "DNA", "ICSs": "DNA", "IFN-regulated genes": "DNA" } }, { "input_text": "Among T-cell lines investigated , ICSAT was abundantly expressed in human T-cell leukemia virus type 1 ( HTLV-1 ) -infected T cells .", "target_text": { "T-cell lines": "cell_line", "ICSAT": "protein", "human T-cell leukemia virus type 1 ( HTLV-1 ) -infected T cells": "cell_line" } }, { "input_text": "When the HTLV-1 tax gene was expressed or phorbol myristake acetate-A23187 stimulation was used , ICSAT expression was induced in Jurkat cells which otherwise do not express ICSAT .", "target_text": { "HTLV-1 tax gene": "DNA", "ICSAT": "protein", "Jurkat cells": "cell_line" } }, { "input_text": "When the binding of ICSAT to four different ICSs was tested , the relative differences in binding affinities for those ICSs were determined .", "target_text": { "ICSAT": "protein", "ICSs": "DNA" } }, { "input_text": "To study the functional role of ICSAT , we performed cotransfection experiments with the human embryonal carcinoma cell line N-Tera2 .", "target_text": { "ICSAT": "protein", "human embryonal carcinoma cell line N-Tera2": "cell_line" } }, { "input_text": "ICSAT was demonstrated to possess repressive function over the gene activation induced by IFN stimulation or by IRF-1 cotransfection .", "target_text": { "ICSAT": "protein", "IFN": "protein", "IRF-1": "protein" } }, { "input_text": "Such repressive function is similar to that seen in IRF-2 or ICSBP .", "target_text": { "IRF-2": "protein", "ICSBP": "protein" } }, { "input_text": "However , we have found that ICSAT has a different repressive effect from that of IRF-2 or ICSBP in some IFN-responsive reporter constructs .", "target_text": { "ICSAT": "protein", "IRF-2": "protein", "ICSBP": "protein", "IFN-responsive reporter constructs": "DNA" } }, { "input_text": "These results suggest that a novel mechanism of gene regulation by \" differential repression \" is used by multiple members of repressor proteins with different repressive effects on the IFN-responsive genes .", "target_text": { "repressor proteins": "protein", "IFN-responsive genes": "DNA" } }, { "input_text": "Regulation of [ Ca2+ ]i rise activated by doxepin-sensitive H1-histamine receptors in Jurkat cells , cloned human T lymphocytes .", "target_text": { "doxepin-sensitive H1-histamine receptors": "protein", "Jurkat cells": "cell_line", "cloned human T lymphocytes": "cell_line" } }, { "input_text": "To clarify the presence of histamine receptor and its transmembrane mechanism in human T lymphocytes , we investigated the effects of agonists or antagonists of histamine receptor subtypes and bacterial toxins on intracellular concentration of Ca2+ [ Ca2+ ]i ) , [3H]pyrilamine binding and c-fos mRNA expression in Jurkat cells , cloned human T lymphocytes .", "target_text": { "histamine receptor": "protein", "human T lymphocytes": "cell_type", "c-fos mRNA": "RNA", "Jurkat cells": "cell_line" } }, { "input_text": "H1-agonists ( histamine and 2-methylhistamine ) caused a transient rise of [ Ca2+ ] , and H1-antagonists ( pyrilamine and doxepin ) inhibited the histamine -induced [ Ca2+ ]i rise more potently than the H2-antagonist ( cimetidine ) on the H3-antagonist ( impromidine ) .", "target_text": {} }, { "input_text": "Binding parameters of [3H] pyrilamine binding were Kd = 5.53 nM and Bmax = 2 , 647 sites/cell .", "target_text": {} }, { "input_text": "Pretreatment with B.pertussis , V.cholera. or C.botulinum toxin did not influence histamine -induced [ Ca2+ ]i rise .", "target_text": {} }, { "input_text": "Western Blot analysis using antibodies against subunits of GTP-binding proteins indicated that Gq/G11 richly existed in Jurkat cells .", "target_text": { "GTP-binding proteins": "protein", "Gq/G11": "protein", "Jurkat cells": "cell_line" } }, { "input_text": "Histamine induced mRNA expression of an immediate early gene c-fos .", "target_text": { "mRNA": "RNA", "immediate early gene": "DNA", "c-fos": "DNA" } }, { "input_text": "Pretreatment with a protein kinase C activator , phorbol 12-myristate 13-acetate , caused almost complete inhibition of histamine -induced [ Ca2+ ]i rise , but did not do so by activators of cAMP- and cGMP- dependent protein kinases .", "target_text": { "protein kinase C": "protein" } }, { "input_text": "STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients .", "target_text": { "transcription factors": "protein", "peripheral blood cells": "cell_type" } }, { "input_text": "A signal transduction pathway activated by many cytokines has recently been elaborated .", "target_text": { "cytokines": "protein" } }, { "input_text": "The JAK kinases and the signal transducers and activators of transcription ( STAT ) factors have been found to be essential components .", "target_text": { "JAK kinases": "protein", "signal transducers and activators of transcription ( STAT ) factors": "protein" } }, { "input_text": "In this report , we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia .", "target_text": { "STAT factors": "protein", "peripheral blood cells": "cell_type" } }, { "input_text": "We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nuclear extracts from acute leukemia cells in bandshift assays .", "target_text": { "STAT proteins": "protein", "acute leukemia cells": "cell_type" } }, { "input_text": "Specific DNA protein complex formation was observed with the probes from the beta-casein and IRF-1 gene promoters , but not with the ISRE oligonucleotide probe , when cell extracts from acute lymphoblastic leukemia ( ALL ) and acute myeloid leukemia ( AML ) were investigated .", "target_text": { "protein complex": "protein", "IRF-1 gene promoters": "DNA" } }, { "input_text": "We used nonradioactive oligonucleotides as competitors to show the specificity of the complex formation .", "target_text": {} }, { "input_text": "Specific antibodies directed against the individual STAT proteins were used in supershift experiments .", "target_text": { "antibodies": "protein", "STAT proteins": "protein" } }, { "input_text": "STAT5- and STAT1- related factors were detected in ALL and STAT1- , STAT3- , and STAT5- related proteins were present in nuclear cell extracts from AML .", "target_text": {} }, { "input_text": "Since the cells were not treated with cytokines before the nuclear proteins were extracted , we conclude that these factors are constitutively activated in vivo .", "target_text": { "cytokines": "protein", "nuclear proteins": "protein" } }, { "input_text": "It is likely that the constitutive activation of STAT proteins is a part of the events of leukemogenesis .", "target_text": { "STAT proteins": "protein" } }, { "input_text": "An element upstream from the human delta-globin-encoding gene specifically enhances beta-globin reporter gene expression in murine erythroleukemia cells .", "target_text": { "element": "DNA", "human delta-globin-encoding gene": "DNA", "beta-globin reporter gene": "DNA", "murine erythroleukemia cells": "cell_type" } }, { "input_text": "We have previously shown that a DNA-binding factor specific to adult hematopoietic cells ( polypryrimidine-binding factor , PYBF ) binds to a pyrimidine-rich region 1 kb upstream from the human delta-globin-encoding gene ( HBD ) .", "target_text": { "DNA-binding factor": "protein", "adult hematopoietic cells": "cell_type", "polypryrimidine-binding factor": "protein", "PYBF": "protein", "pyrimidine-rich region": "DNA", "1 kb upstream": "DNA", "human delta-globin-encoding gene": "DNA", "HBD": "DNA" } }, { "input_text": "The developmental stage-specificity of PYBF and the location of its binding site between the fetal and adult beta-globin ( HBB ) -like genes suggest that PBYF and its binding site may function in fetal-to-adult globin gene switching .", "target_text": { "PYBF": "protein", "fetal and adult beta-globin ( HBB ) -like genes": "DNA", "PBYF": "protein", "globin gene": "DNA" } }, { "input_text": "Here , we describe the effect of 383-bp ( delta383 ) and 99-bp ( delta99 ) sequences containing the PYBF -binding site on transcription from various globin and non-globin promoters , using a transient assay with the cat reporter gene in murine erythroleukemia ( MEL ) cells , a cell line with abundant PYBF activity .", "target_text": { "PYBF": "protein", "PYBF -binding site": "DNA", "cat reporter gene": "DNA", "murine erythroleukemia ( MEL ) cells": "cell_line" } }, { "input_text": "We show that both delta383 and delta99 specifically enhance expression of cat for plasmids containing a human adult globin ( HBB ) promoter , whereas expression of similar constructs using human fetal ( A gamma- ) globin ( HBG1 ) or simian virus 40 ( SV40 ) promoters is not enhanced .", "target_text": { "delta383": "DNA", "delta99": "DNA", "cat": "protein", "plasmids": "DNA", "human adult globin ( HBB ) promoter": "DNA" } }, { "input_text": "The results suggest that PYBF and the pyrimidine-rich region upstream from HBD can specifically enhance HBB transcription in adult erythroid cells .", "target_text": { "PYBF": "protein", "pyrimidine-rich region": "DNA", "HBD": "DNA", "HBB": "DNA", "adult erythroid cells": "cell_type" } }, { "input_text": "Translocation breakpoints in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from SOX9 .", "target_text": { "Translocation breakpoints": "DNA", "SOX9": "DNA" } }, { "input_text": "Campomelic dysplasia ( CMPD1 ) and autosomal XY sex reversal ( SRA1 ) are caused by mutations in the SRY-related gene SOX9 on 17q .", "target_text": { "SRY-related gene": "DNA", "SOX9": "DNA", "17q": "DNA" } }, { "input_text": "Unexpectedly , the 17q breakpoints in four CMPD1 translocation cases previously analyzed by us and others map 50 kb or more from SOX9 .", "target_text": { "17q": "DNA", "17q breakpoints": "DNA", "SOX9": "DNA" } }, { "input_text": "Here , we present clinical , cytogenetic , and molecular data from a new CMPD1 /SRA1 patient with t(6;17)(q14;q24) .", "target_text": { "t(6;17)(q14;q24)": "DNA" } }, { "input_text": "Fluorescence in situ hybridization has shown that the 17q breakpoint in this case maps to the same region as the breakpoints in the other translocation cases , at least 130 kb from SOX9 .", "target_text": { "17q": "DNA", "17q breakpoint": "DNA", "SOX9": "DNA" } }, { "input_text": "Likewise , the breakpoints in two of the previously described cases also map more than 130 kb and , as shown by pulsed field gel electrophoresis analysis , at most 400 kb or 690 kb from SOX9 .", "target_text": { "SOX9": "DNA" } }, { "input_text": "By using a SOX9 coding sequence polymorphism , expression of both SOX9 alleles has been demonstrated by the reverse transcriptase polymerase chain reaction in lymphoblastoid cells from one of the translocation cases .", "target_text": { "SOX9": "DNA", "SOX9 coding sequence polymorphism": "DNA", "reverse transcriptase": "protein", "lymphoblastoid cells": "cell_type" } }, { "input_text": "An alternatively spliced isoform of the Spi-B transcription factor .", "target_text": { "Spi-B": "protein", "transcription factor": "protein" } }, { "input_text": "Spi-B is an Ets transcription factor related to the oncoprotein Spi-1/PU.1 and highly expressed in B lymphoid cells .", "target_text": { "Spi-B": "protein", "transcription factor": "protein", "Ets transcription factor": "protein", "oncoprotein": "protein", "Spi-1/PU.1": "protein", "B lymphoid cells": "cell_type" } }, { "input_text": "The Ets proteins share a conserved Ets domain that mediates specific DNA binding .", "target_text": { "Ets proteins": "protein", "Ets domain": "protein" } }, { "input_text": "Spi-B binds DNA sequences containing a core 5'-GGAA-3' and activates transcription through this motif .", "target_text": { "Spi-B": "protein", "DNA sequences": "DNA" } }, { "input_text": "Up to date , the biological function of Spi-B remains unknown .", "target_text": { "Spi-B": "protein" } }, { "input_text": "Here , we describe the characterization of an alternatively spliced variant of Spi-B , named deltaSpi-B , which has lost the Ets domain .", "target_text": { "Spi-B": "protein", "deltaSpi-B": "protein", "Ets domain": "protein" } }, { "input_text": "In B lymphoid cells , deltaspi-B and spi-B mRNAs were present simultaneously in a ratio of around 10 % .", "target_text": { "B lymphoid cells": "cell_type" } }, { "input_text": "DeltaSpi-B product was not able to bind DNA and was recovered in cytoplasmic cellular extracts .", "target_text": { "DeltaSpi-B": "protein" } }, { "input_text": "We raise the hypothesis that delta Spi-B might affect Spi-B function by recruiting factors involved in Spi-B activity .", "target_text": { "Spi-B": "protein", "delta Spi-B": "protein" } }, { "input_text": "Binding and cooperative interactions between two B cell-specific transcriptional coactivators .", "target_text": { "B cell-specific transcriptional coactivators": "protein" } }, { "input_text": "The class II transactivator ( CIITA ) and B cell octamer-binding protein 1/octamer-binding factor 1/Oct coactivator from B cells ( Bob1/OBF-1/OCA-B ) represent two B cell-specific transcriptional coactivators .", "target_text": { "class II transactivator": "protein", "CIITA": "protein", "B cell octamer-binding protein 1/octamer-binding factor 1/Oct coactivator": "protein", "B cells": "cell_type", "Bob1/OBF-1/OCA-B": "protein", "B cell-specific transcriptional coactivators": "protein" } }, { "input_text": "CIITA and Bob1 interact with proteins that bind to conserved upstream sequences in promoters of class II major histocompatibility genes and octamer-binding transcription factors Oct-1 and Oct-2 , respectively .", "target_text": { "CIITA": "protein", "Bob1": "protein", "conserved upstream sequences": "DNA", "promoters": "DNA", "class II major histocompatibility genes": "DNA", "octamer-binding transcription factors": "protein", "Oct-1": "protein", "Oct-2": "protein" } }, { "input_text": "Both CIITA and Bob1 increase the expression from the DRA promoter , which is a prototypic class II promoter .", "target_text": { "CIITA": "protein", "Bob1": "protein", "DRA promoter": "DNA", "class II promoter": "DNA" } }, { "input_text": "Moreover , in the presence of CIITA , interactions between class II promoters and Bob1 are independent of the octamer-binding site .", "target_text": { "CIITA": "protein", "class II promoters": "DNA", "Bob1": "protein", "octamer-binding site": "RNA" } }, { "input_text": "Using in vivo and in vitro binding assays , we confirm that Bob1 binds to CIITA .", "target_text": { "Bob1": "protein", "CIITA": "protein" } }, { "input_text": "Thus , CIITA not only activates the expression of class II genes but recruits another B cell-specific coactivator to increase transcriptional activity of class II promoters in B cells .", "target_text": { "CIITA": "protein", "class II genes": "DNA", "class II promoters": "DNA", "B cells": "cell_type" } }, { "input_text": "Efficient transcription and replication of simian immunodeficiency virus in the absence of NF-kappaB and Sp1 binding elements .", "target_text": {} }, { "input_text": "Ten mutants of the simian immunodeficiency virus ( SIV ) SIVmac239 bearing deletions ( delta ) or substitutions ( subst ) in the NF-kappaB and/or Sp1 binding elements were created , and the replicative capacities of the mutants were analyzed .", "target_text": { "NF-kappaB": "DNA", "Sp1": "protein", "Sp1 binding elements": "DNA" } }, { "input_text": "All mutants , including one extensively mutagenized strain entirely missing the NF-kappaB and four Spl binding elements , replicated with wild-type kinetics and to a wild-type level in peripheral blood mononuclear cell cultures in 50 to 100 % of the experiments .", "target_text": { "peripheral blood mononuclear cell cultures": "cell_line" } }, { "input_text": "One group of mutants replicated very similarly to SIVmac239 in kinetics and yield in CEMxl74 cells ( 2x NFKappaB > or = SlVmac239 approximately deltaNFkappaB approximately deltaSpl234 approximately substNFkappaB approximately substSpl2 approximately substSp23 ) , while a second group replicated with delayed or slightly delayed kinetics in CEMxl74 cells ( SIVmac239 > substSp34 > deltaNFkappaBdeltaSpl234 approximately deltaNFkappaBdeltaSp1 > substSpl234 ) .", "target_text": { "CEMxl74 cells": "cell_line", "NFKappaB": "protein", "SlVmac239": "protein", "deltaNFkappaB": "protein", "deltaSpl234": "protein", "substNFkappaB": "protein", "substSpl2": "protein", "substSp23": "protein", "substSp34": "protein", "deltaNFkappaBdeltaSpl234": "protein", "deltaNFkappaBdeltaSp1": "protein", "substSpl234": "protein" } }, { "input_text": "Reversions or additional mutations were not detected in the U3 and R regions of proviral DNA from CEMxl74 cells infected with the SIVmac239 mutants .", "target_text": { "proviral DNA": "DNA", "CEMxl74 cells": "cell_line" } }, { "input_text": "Similar results were obtained when mutants of SIVmacMER ( a macrophage-competent derivative of SIVmac239 ) were tested in peripheral blood mononuclear cell and CEMx174 cultures .", "target_text": { "peripheral blood mononuclear cell": "cell_type", "CEMx174 cultures": "cell_line" } }, { "input_text": "However , the growth of most mutated viruses was suppressed in primary rhesus monkey alveolar macrophages ( SIVmacMER approximately 2xNFkappaB approximately substNFkappaB > deltaNFkappaB > deltaNFkappaB deltaSpl234 approximately deltaNFkappaBdeltaSpl > deltaSpl234 approximately substSpl2 > substSp23 approximately substSp34 approximately substSpl234 > or = SIVmac239 ) .", "target_text": { "primary rhesus monkey alveolar macrophages": "cell_type", "2xNFkappaB": "protein", "substNFkappaB": "protein", "deltaNFkappaB": "protein", "deltaSpl234": "protein", "deltaNFkappaBdeltaSpl": "protein", "substSpl2": "protein", "substSp23": "protein", "substSp34": "protein", "substSpl234": "protein" } }, { "input_text": "Thus , changes in the Sp1 binding sites had the most dramatic effects on SIVmac replication in primary macrophage cultures .", "target_text": { "Sp1": "protein", "Sp1 binding sites": "DNA", "primary macrophage cultures": "cell_line" } }, { "input_text": "Analysis of long terminal repeat -driven secreted alkaline phosphatase activity in transient assays showed that , unlike human immunodeficiency virus type 1 , the SIV long terminal repeat possesses an enhancer region just upstream of the NF-kappaB element which maintains significant levels of basal transcription in the absence of NF-kappaB and Sp1 sites .", "target_text": { "long terminal repeat": "DNA", "alkaline phosphatase": "protein", "SIV long terminal repeat": "DNA", "enhancer region": "DNA", "NF-kappaB": "protein", "NF-kappaB element": "DNA" } }, { "input_text": "This region is responsive to transactivation by Tat .", "target_text": { "Tat": "protein" } }, { "input_text": "In addition , the SIV TATA box was shown to be stronger than that of human immunodeficiency virus type 1 .", "target_text": { "SIV TATA box": "DNA" } }, { "input_text": "Therefore , the surprisingly high replicative capacity of NF-kappaB and Sp1 binding site mutants of SIVmac is due to unique features or the enhancer/promoter region .", "target_text": { "enhancer/promoter region": "DNA" } }, { "input_text": "cAMP inducibility of transcriptional repressor ICER in developing and mature human T lymphocytes [ published erratum appears in Proc Natl Acad Sci U S A 1996 Jul 23 ; 93 ( 15 ) : 8154 ]", "target_text": { "transcriptional repressor": "protein", "ICER": "protein", "mature human T lymphocytes": "cell_type" } }, { "input_text": "Stimulation of the cAMP -dependent signaling pathway exerts an inhibitory effect on the proliferation and effector functions of T cells .", "target_text": { "T cells": "cell_type" } }, { "input_text": "The ability of T cells to form high intracellular levels of cAMP is acquired during development in the human thymus and is retained by the majority of mature peripheral T lymphocytes .", "target_text": { "T cells": "cell_type", "peripheral T lymphocytes": "cell_type" } }, { "input_text": "Here we show that elevated cAMP levels in T cells correlate with the expression of the potent transcriptional repressor ICER ( inducible cAMP early repressor ) previously described in the hypothalamic-pituitary-gonadal axis .", "target_text": { "T cells": "cell_type", "potent transcriptional repressor": "protein", "ICER": "protein", "inducible cAMP early repressor": "protein" } }, { "input_text": "Further , in transcriptional assays in vivo , ICER inhibits calcineurin -mediated expression of the interleukin 2 promoter as well as Tax -mediated transactivation of the human T-lymphotropic virus type I ( HTLV-I ) promoter .", "target_text": { "ICER": "protein", "calcineurin": "protein", "interleukin 2": "protein", "interleukin 2 promoter": "DNA", "Tax": "protein", "human T-lymphotropic virus type I ( HTLV-I ) promoter": "DNA" } }, { "input_text": "Thus , the induction of ICER in T cells may play an important role in the cAMP -induced quiescence and the persistent latency of HTLV-I .", "target_text": { "ICER": "protein", "T cells": "cell_type" } }, { "input_text": "A hydrophobic domain of Ca2+ -modulating cyclophilin ligand modulates calcium influx signaling in T lymphocytes .", "target_text": { "Ca2+ -modulating cyclophilin ligand": "protein" } }, { "input_text": "Ca2+ -modulating cyclophilin ligand ( CAML ) was originally described as a cyclophilin B-binding protein whose overexpression in T cells causes a rise in intracellular calcium , thus activating transcription factors responsible for the early immune response .", "target_text": { "Ca2+ -modulating cyclophilin ligand": "protein", "CAML": "protein", "cyclophilin B-binding protein": "protein", "T cells": "cell_type", "transcription factors": "protein" } }, { "input_text": "As reported here , structure-function analysis of the CAML gene in Jurkat T cells indicates that two of CAML 's putative membrane-spanning domains are necessary and sufficient for the modulation of intracellular calcium .", "target_text": { "CAML": "protein", "CAML gene": "DNA", "Jurkat T cells": "cell_line", "putative membrane-spanning domains": "protein" } }, { "input_text": "We propose that the hydrophobic C-terminal tail of CAML forms its effector domain , thus implicating the N-terminal hydrophilic domain in a regulatory role .", "target_text": { "hydrophobic C-terminal tail": "protein", "CAML": "protein", "N-terminal hydrophilic domain": "protein" } }, { "input_text": "These findings define a novel protein motif that functions in intracellular calcium signaling .", "target_text": { "novel protein motif": "protein" } }, { "input_text": "The Epstein-Barr virus -encoded nuclear antigen EBNA-5 accumulates in PML-containing bodies .", "target_text": { "Epstein-Barr virus -encoded nuclear antigen EBNA-5": "protein" } }, { "input_text": "EBNA-5 is one of the Epstein-Barr virus ( EBV ) -encoded nuclear proteins required for immortalization of human B lymphocytes .", "target_text": { "EBNA-5": "protein", "Epstein-Barr virus ( EBV ) -encoded nuclear proteins": "protein", "human B lymphocytes": "cell_type" } }, { "input_text": "In the nuclei of EBV-transformed lymphoblastoid cell lines EBNA-5 is preferentially targetted to distinct nuclear foci .", "target_text": { "EBV-transformed lymphoblastoid cell lines": "cell_line", "EBNA-5": "protein" } }, { "input_text": "Previously we have shown ( W.Q. Jiang , L.Szekely , V.Wendel-Hansen , N.Ringertz , G.Klein , and A. Rosen , Exp.Cell Res .", "target_text": {} }, { "input_text": "A new variant translocation in acute promyelocytic leukaemia : molecular characterization and clinical correlation .", "target_text": {} }, { "input_text": "Translocation t(15;17)(q22;q21 ) is an acquired clonal cytogenetic change present in almost all cases of acute promelocytic leukemia ( APL ) .", "target_text": { "Translocation t(15;17)(q22;q21": "DNA" } }, { "input_text": "The molecular genetic basis of the translocation supports its integral role in pathogenesis .", "target_text": {} }, { "input_text": "We describe a patient with APL in whom the leukaemic clone was characterized by a true variant of the classical t(15;17) .", "target_text": { "classical t(15;17)": "DNA" } }, { "input_text": "The patient whose disease had numerous atypical clinical features , had t(11;17)(q13;121) .", "target_text": { "t(11;17)(q13;121)": "DNA" } }, { "input_text": "The chromosome 17 breakpoint was localized to intron 2 of RARA by Southern blotting , and there was no evidence at the molecular level for rearrangement at PML locus .", "target_text": { "chromosome 17": "DNA", "chromosome 17 breakpoint": "DNA", "intron 2": "DNA", "RARA": "DNA", "PML locus": "DNA" } }, { "input_text": "These data , along with previous reports of rare variant translocations in APL , indicate that while dysregulation of RARA by gene fusion may be essential for the APL phenotype , the particular fusion partner may determine clinicopathological aspects , including presentation , response to treatment with all-trans retinoic acid ( ATRA ) , and prognosis .", "target_text": { "RARA": "DNA" } }, { "input_text": "This heterogeneity suggests that the variant fusion partners of RARA in APL encode factors with properties both common to and distinct from those of PML .", "target_text": { "fusion partners": "protein", "RARA": "DNA", "factors": "protein", "PML": "cell_type" } }, { "input_text": "Investigation of these factors promises to shed light on the complex development pathways involved in the regulation of haematopoiesis .", "target_text": {} }, { "input_text": "A model of latent adenovirus 5 infection in the guinea pig ( Cavia porcellus ) .", "target_text": {} }, { "input_text": "A model of adenovirus 5 ( Ad5 ) infection was developed in guinea pigs to begin to study its role in the pathogenesis of peripheral lung inflammation .", "target_text": {} }, { "input_text": "Forty animals were inoculated intranasally with 10(7.0) pfu of Ad5 /animal , and 15 animals inoculated with sterile culture media served as controls .", "target_text": {} }, { "input_text": "Viral titres were 10(4.4) , 10(6.1) , 10(5.2) , and 10(2.9) pfu/animal , on days 1 , 3 , 4 , and 7 after infection , respectively .", "target_text": {} }, { "input_text": "In situ hybridization to viral DNA and immunocytochemistry for Ad5 E1A protein localized the virus to airway and alveolar epithelial cells .", "target_text": { "viral DNA": "DNA", "E1A protein": "protein", "alveolar epithelial cells": "cell_type" } }, { "input_text": "Histologic examination showed an extensive inflammatory cell infiltration around the airways , with epithelial necrosis and an alveolar exudate that caused localized alveolar collapse in the infected areas .", "target_text": {} }, { "input_text": "Immunocytochemistry identified the cells in the infiltrate as cytotoxic T cells .", "target_text": { "cytotoxic T cells": "cell_type" } }, { "input_text": "Although all animals 20 and 47 days after infection had seroconverted to Ad5 , virus was not detected in these groups either by viral plaque assay or in situ hybridization .", "target_text": {} }, { "input_text": "Ad5 E1A DNA was detected by polymerase chain reaction in five of six animals 20 days after infection and in five of five animals 47 days after infection .", "target_text": { "Ad5 E1A DNA": "DNA" } }, { "input_text": "In these same animals , E1A protein was detected 20 days after infection in two and 47 days after infection in one while persistent bronchiolitis was observed in four and three animals 20 and 47 days after infection , respectively .", "target_text": { "E1A protein": "protein" } }, { "input_text": "These results demonstrate that the guinea pig provides a useful model to study the role of Ad5 infection in chronic airway inflammation .", "target_text": {} }, { "input_text": "Cyclic AMP -responsive element -dependent activation of Epstein-Barr virus zebra promoter by human herpesvirus 6 .", "target_text": { "-responsive element": "DNA", "zebra promoter": "DNA" } }, { "input_text": "We have recently shown that infection of Epstein-Barr virus ( EBV ) genome-positive B cells by human herpesvirus 6 ( HHV-6 ) results in the expression of the immediate-early EBV Zebra gene , followed by virus replication ( L.Flamand , I.Stefanescu , D.V.Ablashi , and J.Menezes , J.Virol.67 : 6768-6777 , 1993 ) .", "target_text": { "B cells": "cell_type", "Epstein-Barr virus ( EBV ) genome-positive B cells": "cell_line", "immediate-early EBV Zebra gene": "DNA" } }, { "input_text": "Here we show that HHV-6 upregulates Zebra gene transcription through a cyclic AMP -responsive element ( CRE ) located within the Zebra promoter ( Zp ) .", "target_text": { "Zebra gene": "DNA", "cyclic AMP -responsive element": "DNA", "CRE": "DNA", "Zebra promoter": "DNA", "Zp": "DNA" } }, { "input_text": "Using human B- or T- cell lines transfected with ZpCat reporter gene constructs , we demonstrate that a region designated the ZII domain of Zp is the target of HHV-6 transactivation .", "target_text": { "ZpCat": "DNA", "ZpCat reporter gene constructs": "DNA", "ZII domain": "DNA", "Zp": "DNA" } }, { "input_text": "Mutation of the consensus AP-1/ CRE site within ZII abolished the inducibility of Zp by HHV-6 , whereas positioning of the ZII domain upstream of the beta-globin minimal promoter conferred responsiveness following HHV-6 infection .", "target_text": { "CRE": "DNA", "consensus AP-1/ CRE site": "DNA", "ZII": "DNA", "Zp": "DNA", "ZII domain": "DNA", "beta-globin minimal promoter": "DNA" } }, { "input_text": "Binding of these factors to ZII was prevented by oligonucleotides containing CRE but not by AP-1 consensus sequences .", "target_text": { "ZII": "DNA", "CRE": "DNA", "AP-1 consensus sequences": "DNA" } }, { "input_text": "Antibodies against CRE -binding ( CREB ) protein but not against c-Fos or c-Jun were able to supershift the DNA-protein complex , identifying the nature of the transcription factor which binds to ZII as a member of the CREB family of proteins .", "target_text": { "CRE": "DNA", "CRE -binding ( CREB ) protein": "protein", "c-Fos": "protein", "c-Jun": "protein", "DNA-protein complex": "protein", "transcription factor": "protein", "ZII": "DNA", "CREB family of proteins": "protein" } }, { "input_text": "Finally , transfection of CREB protein and protein kinase A expression vectors were found to activate Zp in Jurkat cells , suggesting that phosphorylated form of CREB protein can play a determining role in the EBV reactivation process .", "target_text": { "CREB protein": "protein", "protein kinase A expression vectors": "DNA", "Zp": "DNA", "Jurkat cells": "cell_type" } }, { "input_text": "Regulation of the nuclear factor of activated T cells in stably transfected Jurkat cell clones .", "target_text": { "T cells": "cell_type", "nuclear factor of activated T cells": "protein", "Jurkat cell clones": "cell_line" } }, { "input_text": "Two Jurkat cell clones have been stably transfected with a reporter vector for the nuclear factor of activated T cells ( NFAT ) .", "target_text": { "Jurkat cell clones": "cell_line", "reporter vector": "DNA", "nuclear factor of activated T cells": "protein", "NFAT": "protein" } }, { "input_text": "Upon stimulation , they express high levels of secreted heat stable placental alkaline phosphatase .", "target_text": { "placental alkaline phosphatase": "protein" } }, { "input_text": "With these clones , we demonstrated that NFAT activation induced by phorbol 12-myristate 13-acetate and ionomycin was inhibited by both cyclosporin A ( CsA ) ( IC50 = 8 nM ) and FK506 ( IC50 = 160 pM ) , presumably by inhibition of calcineurin activity .", "target_text": { "NFAT": "protein", "calcineurin": "protein" } }, { "input_text": "Selective phosphatase inhibitors for protein phosphatase 1 ( PP1 ) and 2A ( PP2A ) that do not inhibit calcineurin , such as okadaic acid and calyculin A , also inhibited NFAT activation with IC50s of 87 nM and 4 nM , respectively , suggesting that okadaic acid and related inhibitors may block NFAT activation through the inhibition of PP1 , instead of PP2A .", "target_text": { "protein phosphatase 1": "protein", "PP1": "protein", "2A": "protein", "PP2A": "protein", "calcineurin": "protein", "NFAT": "protein" } }, { "input_text": "NFAT activation was also inhibited by agents that increase cAMP concentrations such as dibutyryl cAMP , forskolin and prostaglandin E2 .", "target_text": { "NFAT": "protein" } }, { "input_text": "These stable Jurkat cell clones provide a convenient and sensitive tool to study NFAT regulation .", "target_text": { "Jurkat cell clones": "cell_line", "NFAT": "protein" } }, { "input_text": "Glucocorticoids induced down-regulation of glucocorticoid receptor mRNA expression in asthma .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Although their precise mechanism of action remains to be elucidated , glucocorticoids represent the most effective therapy in the treatment of asthma .", "target_text": {} }, { "input_text": "Interactions between the glucocorticoid receptor and the AP-1 complex have been shown to regulate the transcription of some genes , including glucocorticoid receptor itself .", "target_text": { "glucocorticoid receptor": "protein", "AP-1 complex": "protein" } }, { "input_text": "The aim of the present study was to compare the expression of mRNA for glucocorticoid receptor in human blood monocytes obtained from seven unstable untreated asthmatic patients who were subsequently treated with high doses of parenteral corticosteroid ( methyl prednisolone 120 mg/day ) for 10 days .", "target_text": { "mRNA": "RNA", "glucocorticoid receptor": "protein", "human blood monocytes": "cell_type" } }, { "input_text": "mRNA expression was identified after RNA extraction using RNAzol and analysed after reverse transcriptase , by polymerase chain reaction using a semiquantitative competitive hybridization assay .", "target_text": { "mRNA": "RNA", "reverse transcriptase": "protein" } }, { "input_text": "All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment ( per cent of predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41 , P < 0.02 ) , and a significant decrease for glucocorticoid receptor mRNA expression ( P < 0.02 ) was observed in their monocytes .", "target_text": { "glucocorticoid receptor": "protein", "mRNA": "RNA" } }, { "input_text": "This is the first report of an ex vivo down-regulation for the glucocorticoid receptor mRNA expression , following corticosteroid treatment .", "target_text": { "glucocorticoid receptor": "protein", "mRNA": "RNA" } }, { "input_text": "Mapping of the transcriptional repression domain of the lymphoid-specific transcription factor oct-2A .", "target_text": { "transcriptional repression domain": "protein", "lymphoid-specific transcription factor": "protein", "oct-2A": "protein" } }, { "input_text": "The lymphoid-specific transcription factor Oct-2a is implicated in B cell-specific transcriptional activity via the octamer motif .", "target_text": { "lymphoid-specific transcription factor": "protein", "Oct-2a": "protein" } }, { "input_text": "Structure/function analysis of various Oct-2a effector regions in the context of the GAL4 DNA-binding domain revealed that Oct-2a contains two functionally different activation domains at the N and the C termini .", "target_text": { "Oct-2a": "protein", "Oct-2a effector regions": "protein", "GAL4 DNA-binding domain": "protein", "activation domains": "protein" } }, { "input_text": "The transcriptional activity of both domains is strongly potentiated by interactions with distinct B cell-specific coactivators .", "target_text": { "B cell-specific coactivators": "protein" } }, { "input_text": "Recently , we have identified a repression domain located within the N terminus of Oct-2a ( amino acids 2-99 ) .", "target_text": { "repression domain": "protein", "N terminus": "protein", "Oct-2a": "protein", "amino acids 2-99": "protein" } }, { "input_text": "When this domain was transferred to a potent activator , transcription was strongly inhibited .", "target_text": {} }, { "input_text": "In this study we present a deletion analysis of the N-terminal region of Oct-2a to determine the minimal repression domain .", "target_text": { "N-terminal region": "protein", "Oct-2a": "protein", "minimal repression domain": "protein" } }, { "input_text": "We identified a stretch of 23 amino acids , rich in serine and threonine residues , which was responsible for most of the repression activity .", "target_text": {} }, { "input_text": "We show that repression is strongly dependent on the type of enhancer present in the reporter plasmid as well as on the cell line tested .", "target_text": { "enhancer": "DNA", "reporter plasmid": "DNA", "cell line": "cell_line" } }, { "input_text": "The possibility that Oct-2a can act as an activator and/or a repressor may have important consequences for the function of Oct-2a in B cell differentiation and other developmental processes .", "target_text": { "Oct-2a": "protein" } }, { "input_text": "Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes .", "target_text": {} }, { "input_text": "Eosinophils and neutrophils are closely related , terminally differentiated cells that in vitro undergo constitutive cell death by apoptosis .", "target_text": { "Eosinophils": "cell_type", "neutrophils": "cell_type", "terminally differentiated cells": "cell_type" } }, { "input_text": "The onset of apoptosis in both cell types can be delayed by hemopoietins and inflammatory mediators .", "target_text": { "hemopoietins": "protein", "inflammatory mediators": "protein" } }, { "input_text": "Although there have been a number of reports demonstrating that glucocorticoids ( in particular dexamethasone ) antagonize the eosinophil life-prolonging effects of hemopoietins , direct effects of dexamethasone on eosinophil apoptosis have not been documented .", "target_text": { "hemopoietins": "protein" } }, { "input_text": "In this study we examined the direct effects of glucocorticoids on eosinophil and neutrophil apoptosis in light of their common therapeutic use as anti-inflammatory and anti-allergic /hypereosinophilic agents .", "target_text": { "eosinophil": "cell_type", "neutrophil": "cell_type" } }, { "input_text": "We found that treatment with dexamethasone induced eosinophil apoptosis .", "target_text": { "eosinophil": "cell_type" } }, { "input_text": "In contrast , dexamethasone was a potent inhibitor of neutrophil apoptosis .", "target_text": { "neutrophil": "cell_type" } }, { "input_text": "The effect of dexamethasone on both cell types was mediated through the glucocorticoid receptor , i.e. , it was abolished by the glucocorticoid receptor antagonist RU38486 .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "This is the first description of an agent that promotes eosinophil apoptosis while inhibiting neutrophil apoptosis , and thus presents a novel approach to the study of control of apoptosis in these closely related cell types as well as increases our understanding of the clinical action of glucocorticoids in inflammation .", "target_text": { "eosinophil": "cell_type", "neutrophil": "cell_type" } }, { "input_text": "Permanent occupancy of the human immunodeficiency virus type 1 enhancer by NF-kappa B is needed for persistent viral replication in monocytes .", "target_text": { "human immunodeficiency virus type 1 enhancer": "DNA", "NF-kappa B": "protein", "monocytes": "cell_type" } }, { "input_text": "This work aimed to ascertain the role of kappaB-responsive elements of the human immunodeficiency virus type 1 ( HIV-1 ) enhancer not only in early initiation but also in long-term maintenance of proviral transcription in cells of the monocytic lineage .", "target_text": { "kappaB-responsive elements": "DNA", "human immunodeficiency virus type 1 ( HIV-1 ) enhancer": "DNA", "monocytic lineage": "cell_type" } }, { "input_text": "For this purpose , we used three main approaches .", "target_text": {} }, { "input_text": "The first was to abruptly terminate tumor necrosis factor-induced NF-kappaB binding to the enhancer sequences in U1 monocytic cells , using a short pulse of exogenous tumor necrosis factor .", "target_text": { "NF-kappaB": "protein", "exogenous tumor necrosis factor": "protein" } }, { "input_text": "This resulted in concomitant decrease in nuclear NF-kappaB DNA-binding activity and endogenous long terminal repeat transcriptional activity .", "target_text": { "NF-kappaB": "protein", "endogenous long terminal repeat": "DNA" } }, { "input_text": "The second was to suppress the permanent NF-kappaB translocation induced by HIV-1 replication itself in chronically infected U937 cells , using a specific proteasome inhibitor ( Z-LLL-H ) .", "target_text": { "NF-kappaB": "protein", "chronically infected U937 cells": "cell_line" } }, { "input_text": "As early as 2 h after addition of the inhibitor to the culture medium , there was an inhibition of both constitutive activation of NF-kappaB and HIV-1 genome expression .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "The third approach was to monitor the replication competence in U937 cells of an infectious HIV-1 provirus carrying point mutations in the kappaB-responsive elements of both long terminal repeats .", "target_text": { "U937 cells": "cell_line", "kappaB-responsive elements": "DNA", "long terminal repeats": "DNA" } }, { "input_text": "Compared with its wild-type counterpart , this mutated provirus showed a profoundly decreased , Z-LLL-H -insensitive transcriptional and replicative activity in U937 monocytes .", "target_text": { "monocytes": "cell_type", "U937 monocytes": "cell_line" } }, { "input_text": "Together , our results indicate that occupancy of the viral enhancer by NF-kappaB ( p50/p65 ) heterodimers is required for ongoing transcription of integrated HIV provirus in monocytes , even in cells chronically infected and permanently producing functional HIV Tat protein .", "target_text": { "viral enhancer": "DNA", "NF-kappaB": "protein", "p50/p65": "protein", "NF-kappaB ( p50/p65 ) heterodimers": "protein", "monocytes": "cell_type", "HIV Tat protein": "protein" } }, { "input_text": "Thus , the ability of HIV-1 replication to activate NF-kappaB is crucial to the intense self-perpetuated viral transcription observed in cells of the monocytic lineage .", "target_text": { "NF-kappaB": "protein", "monocytic lineage": "cell_type" } }, { "input_text": "Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor .", "target_text": { "Rel-deficient T cells": "cell_type", "interleukin 3": "protein", "granulocyte-macrophage colony-stimulating factor": "protein" } }, { "input_text": "The c-rel protooncogene encodes a subunit of the NF-kappa B -like family of transcription factors .", "target_text": { "c-rel protooncogene": "DNA", "NF-kappa B": "protein", "transcription factors": "protein", "NF-kappa B -like family of transcription factors": "protein" } }, { "input_text": "Mice lacking Rel are defective in mitogenic activation of B and T lymphocytes and display impaired humoral immunity .", "target_text": { "Rel": "protein" } }, { "input_text": "In an attempt to identify changes in gene expression that accompany the T-cell stimulation defects associated with the loss of Rel , we have examined the expression of cell surface activation markers and cytokine production in mitogen-stimulated Rel -/- T cells .", "target_text": { "Rel": "protein", "cell surface activation markers": "protein", "Rel -/- T cells": "cell_type" } }, { "input_text": "The expression of cell surface markers including the interleukin 2 receptor alpha ( IL-2R alpha ) chain ( CD25 ) , CD69 and L-selectin ( CD62 ) is normal in mitogen-activated Rel -/- T cells , but cytokine production is impaired .", "target_text": { "IL-2R alpha": "protein", "interleukin 2 receptor alpha ( IL-2R alpha ) chain": "protein", "CD25": "protein", "CD69": "protein", "L-selectin": "protein", "CD62": "protein", "Rel": "protein", "mitogen-activated Rel -/- T cells": "cell_line", "cytokine": "protein" } }, { "input_text": "In Rel -/- splenic T cell cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin , the levels of IL-3 , IL-5 , granulocyte- macrophage colony-stimulating factor ( GM-CSF ) , tumor necrosis factor alpha ( TNF-alpha ) , and gamma interferon ( IFN-gamma ) were only 2- to 3-fold lower compared with normal T cells .", "target_text": { "Rel": "protein", "Rel -/- splenic T cell cultures": "cell_line", "granulocyte- macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein", "gamma interferon": "protein", "IFN-gamma": "protein" } }, { "input_text": "In contrast , anti-CD3 and anti-CD28 stimulated Rel -/- T cells , which fail to proliferate , make little or no detectable cytokines .", "target_text": { "anti-CD3": "protein", "anti-CD28": "protein", "Rel": "protein", "Rel -/- T cells": "cell_line", "cytokines": "protein" } }, { "input_text": "Exogenous IL-2 , which restitutes the proliferative response of the anti-CD3- and anti-CD28- treated Rel-/- T cells , restores production of IL-5 , TNF-alpha , and IFN-gamma , but not IL-3 and GM-CSF expression to approximately normal levels .", "target_text": { "IL-2": "protein", "TNF-alpha": "protein", "IFN-gamma": "protein", "IL-3": "protein", "GM-CSF": "protein" } }, { "input_text": "In contrast to mitogen-activated Rel -/- T cells , lipopolysaccharide-stimulated Rel -/- macrophages produce higher than normal levels of GM-CSF .", "target_text": { "Rel": "protein", "mitogen-activated Rel -/- T cells": "cell_line", "Rel -/- macrophages": "cell_line", "GM-CSF": "protein" } }, { "input_text": "These findings establish that Rel can function as an activator or repressor of gene expression and is required by T lymphocytes for production of IL-3 and GM-CSF .", "target_text": { "Rel": "protein", "T lymphocytes": "cell_type", "IL-3": "protein", "GM-CSF": "protein" } }, { "input_text": "Nuclear appearance of a factor that binds the CD28 response element within the interleukin-2 enhancer correlates with interleukin-2 production .", "target_text": { "CD28 response element": "DNA", "interleukin-2 enhancer": "DNA", "interleukin-2": "protein" } }, { "input_text": "Activation of T lymphocytes requires the combined signaling of the T cell receptor and costimulatory molecules such as CD28 .", "target_text": { "T lymphocytes": "cell_type", "T cell receptor": "protein", "costimulatory molecules": "protein", "CD28": "protein" } }, { "input_text": "The ability of T cells to produce interleukin-2 ( IL-2 ) is a critical control point in T lymphocyte activation .", "target_text": { "T cells": "cell_type", "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "The IL-2 enhancer contains a functional motif named CD28 response element ( CD28RE ) that serves a role as a target for mitogenic T cell activation signals .", "target_text": { "IL-2": "protein", "CD28": "protein", "CD28 response element": "DNA", "CD28RE": "DNA" } }, { "input_text": "The CD28RE sequence reveals similarity to the consensus kappaB binding motif .", "target_text": { "CD28RE": "DNA", "consensus kappaB binding motif": "DNA" } }, { "input_text": "Here we demonstrate that CD28RE binds an inducible protein with a molecular mass of approximately 35 kDa called nuclear factor of mitogenic-activated T cells ( NF-MATp35 ) that is clearly different from the known NF- kappaB/ Rel family members .", "target_text": { "CD28RE": "DNA", "T cells": "cell_type", "nuclear factor of mitogenic-activated T cells": "protein", "NF-MATp35": "protein", "Rel": "protein", "NF- kappaB/ Rel family members": "protein" } }, { "input_text": "Induction of NF-MATp35 was shown to depend on de novo protein synthesis and was restricted to T cells that received a mitogenic combination of T cell stimuli , not necessarily including CD28 signaling .", "target_text": { "NF-MATp35": "protein", "T cells": "cell_type", "CD28": "protein" } }, { "input_text": "Nonmitogenic T cell stimulation did not result in appearance of NF-MATp35 .", "target_text": { "NF-MATp35": "protein" } }, { "input_text": "These results indicate that mitogenic combinations of T cell activation signals are integrated at the level of NF-MATp35 induction .", "target_text": { "NF-MATp35": "protein" } }, { "input_text": "Similar to its effect on IL-2 production , cyclosporin A inhibited the induction of NF-MATp35 .", "target_text": { "IL-2": "protein", "NF-MATp35": "protein" } }, { "input_text": "Taken together , these data demonstrate that the nuclear appearance of NF-MATp35 shows excellent correlation with IL-2 production , which is a unique characteristic among nuclear factors implicated in the control of IL-2 gene expression .", "target_text": { "NF-MATp35": "protein", "IL-2": "protein" } }, { "input_text": "Transcriptional basis for hyporesponsiveness of the human inducible nitric oxide synthase gene to lipopolysaccharide/interferon-gamma .", "target_text": { "nitric oxide synthase gene": "DNA", "human inducible nitric oxide synthase gene": "DNA" } }, { "input_text": "The work reported here resolves , at the level of gene regulation , the controversy as to whether or not human monocytes /macrophages can produce nitric oxide ( NO ) when stimulated with lipopolysaccharide ( LPS ) , with or without co-stimulation by interferon-gamma ( IFN-gamma ) .", "target_text": { "monocytes": "cell_type", "human monocytes /macrophages": "cell_type", "IFN-gamma": "protein" } }, { "input_text": "Studies included structural comparison of the promoters for human and mouse inducible NO synthase ( iNOS ) genes , transfection and assay of human and mouse iNOS promoter regions in response to LPS +/- IFN-gamma , and electrophoretic mobility shift assays of kappa B response elements .", "target_text": { "inducible NO synthase": "protein", "iNOS": "protein", "inducible NO synthase ( iNOS ) genes": "DNA", "iNOS promoter regions": "DNA", "IFN-gamma": "protein", "kappa B response elements": "DNA" } }, { "input_text": "Two explanations for hyporesponsiveness of the human iNOS promoter to LPS +/- IFN-gamma were found : ( 1 ) multiple inactivating nucleotide substitutions in the human counterpart of the enhancer element that has been shown to regulate LPS / IFN-gamma induced expression of the mouse iNOS gene ; and ( 2 ) and absence of one or more nuclear factors in human macrophages ( e.g. , an LPS -inducible nuclear factor-kappa B/ Rel complex ) , that is ( are ) required for maximal expression of the gene .", "target_text": { "iNOS": "protein", "human iNOS promoter": "DNA", "IFN-gamma": "protein", "enhancer element": "DNA", "mouse iNOS gene": "DNA", "nuclear factors": "protein", "human macrophages": "cell_type", "Rel": "protein", "LPS -inducible nuclear factor-kappa B/ Rel complex": "protein" } }, { "input_text": "The importance of resolution of this controversy is that future research in this area should be directed toward the understanding of alternative mechanisms that can result in the successful production of NO .", "target_text": {} }, { "input_text": "X inactivation analysis in a female with hypomelanosis of Ito associated with a balanced X ; 17 translocation : evidence for functional disomy of Xp .", "target_text": { "balanced X ; 17 translocation": "DNA" } }, { "input_text": "X inactivation analysis was performed on normal and hypopigmented skin samples obtained from a female with hypomelanosis of Ito associated with a balanced whole arm X ; 17 translocation .", "target_text": { "balanced whole arm X ; 17 translocation": "DNA" } }, { "input_text": "Severe skewing of X inactivation resulting in inactivity of the intact X was found in blood and cultures of both types of skin , but analysis of DNA prepared directly from hypopigmented skin showed significant inactivation of the translocated X , inconsistent with the usual mechanism of phenotypic expression in X ; autosome translocations .", "target_text": { "X": "DNA", "X ; autosome translocations": "DNA" } }, { "input_text": "In addition , dual colour FISH analysis using centromere specific probes for chromosomes X and 17 showed that the breakpoints on both chromosomes lie within the alphoid arrays , making interruption of a locus on either chromosome unlikely .", "target_text": { "X": "DNA", "17": "DNA", "chromosomes": "DNA" } }, { "input_text": "While partial variable monosomy of loci on chromosome 17p can not be excluded as contributing to the phenotype in this patient , it is argued that the major likely factor is partial functional disomy of sequences on Xp in cell lineages that have failed to inactivate the intact X chromosome .", "target_text": { "chromosome 17p": "DNA", "Xp": "DNA", "X": "DNA", "X chromosome": "DNA" } }, { "input_text": "Identification of a herpesvirus Saimiri cis-acting DNA fragment that permits stable replication of episomes in transformed T cells .", "target_text": { "herpesvirus Saimiri cis-acting DNA fragment": "DNA", "T cells": "cell_type" } }, { "input_text": "Herpesvirus saimiri is a lymphotropic herpesvirus capable of immortalizing and transforming T cells both in vitro and in vivo .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Immortalized and transformed T cells harbor several copies of the viral genome as a persisting genome .", "target_text": { "T cells": "cell_type", "viral genome": "DNA", "persisting genome": "DNA" } }, { "input_text": "The mapping of the cis-acting genetic cis-acting segment ( oriP ) required for viral episomal maintenance is reported here .", "target_text": { "cis-acting genetic cis-acting segment": "DNA", "oriP": "DNA" } }, { "input_text": "Viral DNA fragments that potentially contain oriP were cloned into a plasmid that contains the hygromycin resistance gene .", "target_text": { "Viral DNA fragments": "DNA", "oriP": "DNA", "plasmid": "DNA", "hygromycin resistance gene": "DNA" } }, { "input_text": "After several round of subcloning followed by transfection , oriP was mapped to a 1.955-kb viral segment .", "target_text": { "oriP": "DNA", "1.955-kb viral segment": "DNA" } }, { "input_text": "This viral fragment permits stable plasmid replication without deletion or rearrangement as well as episomal maintenance without integration or recombination .", "target_text": { "plasmid": "DNA" } }, { "input_text": "The function of oriP depends on a trans-acting factor ( s ) encoded by the viral genome .", "target_text": { "oriP": "DNA", "trans-acting factor": "protein", "viral genome": "DNA" } }, { "input_text": "The 1.955-kb viral segment includes a dyad symmetry region located between two small nuclear RNA genes and is located upstream of the dihydrofolate reductase gene homolog .", "target_text": { "1.955-kb viral segment": "DNA", "dyad symmetry region": "DNA", "small nuclear RNA genes": "DNA", "dihydrofolate reductase": "protein", "dihydrofolate reductase gene homolog": "DNA" } }, { "input_text": "Therefore , this oriP contains novel elements distinct from those of other DNA viruses .", "target_text": { "oriP": "DNA" } }, { "input_text": "In vivo anergized CD4+ T cells express perturbed AP-1 and NF-kappa B transcription factors .", "target_text": { "T cells": "cell_type", "anergized CD4+ T cells": "cell_line", "NF-kappa B": "protein", "transcription factors": "protein" } }, { "input_text": "Anergy is a major mechanism to ensure antigen-specific tolerance in T lymphocytes in the adult .", "target_text": { "T lymphocytes": "cell_type" } }, { "input_text": "In vivo , anergy has mainly been studied at the cellular level .", "target_text": {} }, { "input_text": "In this study , we used the T-cell-activating superantigen staphylococcal enterotoxin A ( SEA ) to investigate molecular mechanisms of T-lymphocyte anergy in vivo .", "target_text": { "T-cell-activating superantigen": "protein", "staphylococcal enterotoxin A": "protein", "SEA": "protein" } }, { "input_text": "Injection of SEA to adult mice activates CD4+ T cells expressing certain T-cell receptor ( TCR ) variable region beta-chain families and induces strong and rapid production of interleukin 2 ( IL-2 ) .", "target_text": { "SEA": "protein", "T cells": "cell_type", "CD4+ T cells": "cell_type", "T-cell receptor ( TCR ) variable region beta-chain families": "protein", "IL-2": "protein" } }, { "input_text": "In contrast , repeated injections of SEA cause CD4+ T-cell deletion and anergy in the remaining CD4+ T cells , characterized by reduced expression of IL-2 at mRNA and protein levels .", "target_text": { "SEA": "protein", "CD4+ T-cell": "cell_type", "CD4+ T-cell deletion": "protein", "T cells": "cell_type", "IL-2": "protein" } }, { "input_text": "We analyzed expression of AP-1 , NF-kappa B , NF-AT , and octamer binding transcription factors , which are known to be involved in the regulation of IL-2 gene promoter activity .", "target_text": { "AP-1": "protein", "NF-kappa B": "protein", "NF-AT": "protein", "transcription factors": "protein", "octamer binding transcription factors": "protein", "IL-2": "protein" } }, { "input_text": "Large amounts of AP-1 and NF-kappa B and significant quantities of NF-AT were induced in SEA -activated CD4+ spleen T cells , whereas Oct-1 and Oct-2 DNA binding activity was similar in both resting and activated T cells .", "target_text": { "AP-1": "protein", "NF-kappa B": "protein", "NF-AT": "protein", "SEA": "protein", "SEA -activated CD4+ spleen T cells": "cell_line", "activated T cells": "cell_type" } }, { "input_text": "In contrast , anergic CD4+ T cells contained severely reduced levels of AP-1 and Fos/Jun-containing NF-AT complexes but expressed significant amounts of NF-kappa B and Oct binding proteins after SEA stimulation .", "target_text": { "anergic CD4+ T cells": "cell_type", "AP-1": "protein", "NF-AT": "protein", "Fos/Jun-containing NF-AT complexes": "protein", "NF-kappa B": "protein", "Oct binding proteins": "protein", "SEA": "protein" } }, { "input_text": "Resolution of the NF-kappa B complex demonstrated predominant expression of p50-p65 heterodimers in activated CD4+ T cells , while anergic cells mainly expressed the transcriptionally inactive p50 homodimer .", "target_text": { "NF-kappa B": "protein", "NF-kappa B complex": "protein", "p50-p65 heterodimers": "protein", "activated CD4+ T cells": "cell_type", "p50 homodimer": "protein" } }, { "input_text": "These alterations of transcription factors are likely to be responsible for repression of IL-2 in anergic T cells .", "target_text": { "transcription factors": "protein", "IL-2": "protein", "anergic T cells": "cell_type" } }, { "input_text": "Fas ligation induces apoptosis and Jun kinase activation independently of CD45 and Lck in human T cells .", "target_text": { "Fas": "protein", "Jun kinase": "protein", "CD45": "protein", "Lck": "protein", "human T cells": "cell_type" } }, { "input_text": "Stimulation through the Fas/APO-1 receptor results in apoptosis through an incompletely characterized signaling pathway .", "target_text": { "Fas/APO-1 receptor": "protein" } }, { "input_text": "More is known regarding signal transduction events that occur after ligation of the T-cell antigen receptor ( TCR ) .", "target_text": { "T-cell antigen receptor": "protein", "TCR": "protein" } }, { "input_text": "It has been shown that TCR stimulation requires both the membrane tyrosine phosphatase , CD45 , and the Src-family kinase , Lck , to result in cellular activation .", "target_text": { "TCR": "protein", "membrane tyrosine phosphatase": "protein", "CD45": "protein", "Src-family kinase": "protein", "Lck": "protein" } }, { "input_text": "Although prior studies suggest a role for protein tyrosine kinases and phosphatases in Fas signaling , we report here that Fas ligation induces apoptosis in T cells deficient in either CD45 or Lck .", "target_text": { "protein tyrosine kinases": "protein", "Fas": "protein", "T cells": "cell_type", "CD45": "protein", "Lck": "protein" } }, { "input_text": "Further , in normal and CD45- or Lck- deficient cell lines , Fas stimulation results in activation of Jun kinase ( JNK ) , a proposed mediator of stress activation pathways .", "target_text": { "Jun kinase": "protein", "JNK": "protein" } }, { "input_text": "Previous studies have also demonstrated a role for endogenous ceramide release in Fas-mediated apoptosis .", "target_text": {} }, { "input_text": "We show that stimulation with a synthetic ceramide analog results in JNK activation as well as apoptosis , suggesting ceramide release occurs proximal to JNK activation in Fas signaling .", "target_text": { "JNK": "protein", "Fas": "protein" } }, { "input_text": "Our data suggest that although CD45 and Lck are not required for Fas signaling , JNK activation may play an important role transducing distal signals that lead to apoptosis after Fas ligation .", "target_text": { "CD45": "protein", "Lck": "protein", "Fas": "protein", "JNK": "protein" } }, { "input_text": "Globin gene switching .", "target_text": {} }, { "input_text": "In vivo protein-DNA interactions of the human beta-globin locus in erythroid cells expressing the fetal or the adult globin gene program .", "target_text": { "human beta-globin locus": "DNA", "erythroid cells": "cell_type", "globin gene": "DNA" } }, { "input_text": "To characterize the protein-DNA interactions important for the developmental control of the human beta-globin locus , we analyzed by in vivo dimethyl sulfate footprinting erythroid cells expressing either the fetal or the adult globin developmental program .", "target_text": { "human beta-globin locus": "DNA", "erythroid cells": "cell_type" } }, { "input_text": "In the locus control region ( LCR ) of the beta-globin locus , in vivo footprints on NF-E2 ( or AP-1 ) and GATA-1 motifs remained the same regardless of whether the fetal or the adult globin genes are expressed .", "target_text": { "locus control region": "DNA", "LCR": "DNA", "beta-globin locus": "DNA", "NF-E2": "protein", "AP-1": "protein", "GATA-1 motifs": "DNA", "adult globin genes": "DNA" } }, { "input_text": "In contrast , in vivo footprints on GT ( CACCC ) motifs differed between the cells expressing the fetal or the adult globin program .", "target_text": { "GT ( CACCC ) motifs": "DNA" } }, { "input_text": "In promoter regions , the actively transcribed genes demonstrated extensive and consistent footprints over the canonical elements , such as CACCC and CCAAT motifs .", "target_text": { "promoter regions": "DNA", "actively transcribed genes": "DNA" } }, { "input_text": "The adult globin expressing cells displayed more extensive footprints than the fetal globin expressing cells in the 3' regulatory sequences of both the Agamma- and the beta- globin genes , suggesting a role of these 3' elements in beta-globin gene expression .", "target_text": { "adult globin expressing cells": "cell_type", "fetal globin expressing cells": "cell_type", "3' regulatory sequences": "DNA", "3' elements": "DNA", "beta-globin gene": "DNA" } }, { "input_text": "Our results suggest that the bulk of protein-DNA interactions that underlies the developmental control of globin genes takes place in the gamma- and beta- globin gene promoters , and that GT motifs of the beta-globin locus LCR may play a role in the developmental regulation of human beta-globin gene expression , perhaps by increasing the probability of interaction of the LCR holocomplex with the fetal or the adult globin gene .", "target_text": { "globin genes": "DNA", "GT motifs": "DNA", "beta-globin locus": "DNA", "LCR": "DNA", "beta-globin gene": "DNA", "LCR holocomplex": "protein" } }, { "input_text": "Antisense inhibition of vitamin D receptor expression induces apoptosis in monoblastoid U937 cells .", "target_text": { "vitamin D receptor": "protein", "U937 cells": "cell_line", "monoblastoid U937 cells": "cell_line" } }, { "input_text": "The active vitamin D3 metabolite 1,25-dihydroxycholecalciferol ( 1,25(OH)2D3 ) acts as an antiproliferative and differentiating agent for the monoblastoid cell line U937 and as an important immunologic mediator implicated particularly in the function of cells belonging to the monocyte/macrophage lineage .", "target_text": { "monoblastoid cell line U937": "cell_line", "monocyte/macrophage lineage": "cell_type" } }, { "input_text": "These effects are controlled by the vitamin D receptor ( VDR ) , a member of the steroid hormone receptor family .", "target_text": { "vitamin D receptor": "protein", "VDR": "protein", "steroid hormone receptor family": "protein" } }, { "input_text": "The objective of this study was to develop U937 transfectants expressing antisense VDR mRNA , and to use these to examine the role of 1,25(OH)2D3 -VDR interaction in this lineage .", "target_text": { "U937": "cell_line", "VDR mRNA": "RNA", "-VDR": "protein" } }, { "input_text": "A 2-kb VDR cDNA insert ( including the complete VDR coding region ) was cloned in an antisense orientation into the EBV episomal vector pMEP4 under the control of an inducible promoter and transfected into U937 .", "target_text": { "VDR": "protein", "2-kb VDR cDNA insert": "DNA", "VDR coding region": "DNA", "inducible promoter": "DNA", "U937": "cell_line" } }, { "input_text": "The resultant cell line , DH42 , was hygromycin resistant , contained VDR cDNA , expressed fewer VDRs than controls , and showed a substantial decrease in antiproliferative response to 1,25(OH)2D3 .", "target_text": { "resultant cell line": "cell_line", "DH42": "cell_line", "VDR cDNA": "DNA", "VDRs": "protein" } }, { "input_text": "However , 1,25(OH)2D3 increased the number of cells expressing macrophage cell surface Ags , including CD14 and CD11b .", "target_text": { "macrophage cell surface Ags": "protein", "CD14": "protein", "CD11b": "protein" } }, { "input_text": "A subpopulation of smaller cells did not express the differentiation markers after cadmium stimulation .", "target_text": {} }, { "input_text": "Cell cycle analysis showed shifts in the distribution of cells from G1 to S phase , which were more pronounced after cadmium treatment .", "target_text": {} }, { "input_text": "A considerable proportion of cells were outside the cycle and DNA fragmentation confirmed apoptosis .", "target_text": {} }, { "input_text": "Thus , the functional outcome of the VDR antisense transfection suggests that in the myelomonocytic lineage , VDR expression may act as a protective mechanism against programmed cell death .", "target_text": { "VDR": "protein", "myelomonocytic lineage": "cell_type" } }, { "input_text": "Human T lymphotropic virus-I infection of human T lymphocytes induces expression of the beta-galactoside-binding lectin , galectin-3 .", "target_text": { "human T lymphocytes": "cell_type", "beta-galactoside-binding lectin": "protein", "galectin-3": "protein" } }, { "input_text": "Animal lectins play important roles in a variety of biological processes via their recognition of glycoconjugates .", "target_text": { "lectins": "protein" } }, { "input_text": "Galectin-3 is a beta-galactoside-binding lectin previously designated as epsilon BP ( IgE-binding protein ) , CBP35 , Mac-2 , L-29 , and L-34 , and its expression has been associated with various physiological and pathological processes , including cell growth , tumor transformation , and metastasis .", "target_text": { "beta-galactoside-binding lectin": "protein", "epsilon BP": "protein", "IgE-binding protein": "protein", "CBP35": "protein", "Mac-2": "protein", "L-29": "protein", "L-34": "protein" } }, { "input_text": "Galectin-3 is widely distributed in various tissues and cell types and is expressed in many leukocytes , with the notable exception of B and T lymphocytes .", "target_text": { "Galectin-3": "protein", "leukocytes": "cell_type" } }, { "input_text": "We now report that galectin-3 is abundantly expressed in a number of human T lymphotropic virus ( HTLV ) -I -infected human T cell lines , including F6T , HUT 102 , K3T , MT-2 , and SLB-I , but is not expressed in non- HTLV-I -infected T cell lines such as Jurkat , CEM , and MOLT-4 .", "target_text": { "galectin-3": "protein", "human T lymphotropic virus ( HTLV ) -I -infected human T cell lines": "cell_line", "F6T": "cell_line", "HUT 102": "cell_line", "K3T": "cell_line", "MT-2": "cell_line", "SLB-I": "cell_line", "non- HTLV-I -infected T cell lines": "cell_line", "Jurkat": "cell_line", "CEM": "cell_line", "MOLT-4": "cell_line" } }, { "input_text": "In addition , the galectin-3 level was markedly increased in human thymocytes after infection with HTLV-I as compared with uninfected thymocytes .", "target_text": { "galectin-3": "protein", "human thymocytes": "cell_type", "uninfected thymocytes": "cell_type" } }, { "input_text": "The up-regulation of galectin-3 expression appeared to correlate well with HTLV-I gene expression , as undetectable or very low levels of galectin-3 were found in the S1T and ATL-1K cell lines , which are nonproductively infected with HTLV-I .", "target_text": { "galectin-3": "protein" } }, { "input_text": "In co-transfection experiments , the galectin-3 promoter was significantly up-regulated by expression vectors encoding the 40-kd Tax protein , a potent transactivator in HTLV-I .", "target_text": { "galectin-3": "protein", "galectin-3 promoter": "DNA", "expression vectors": "DNA", "40-kd Tax protein": "protein" } }, { "input_text": "Analysis of various Tax mutants suggested that galectin-3 promoter induction is dependent on activation of the cyclic-AMP -responsive element binding protein/activation transcription factor family of transcription factors and , to a lesser extent , nuclear factor-kappa B/Rel induction .", "target_text": { "Tax mutants": "protein", "galectin-3": "protein", "galectin-3 promoter": "DNA", "cyclic-AMP -responsive element binding protein/activation transcription factor family": "protein", "transcription factors": "protein", "nuclear factor-kappa B/Rel": "protein" } }, { "input_text": "Transfection of human promonocytic U-937 cells with an HTLV-I Tax expression vector induced galectin-3 expression in this cell line .", "target_text": { "human promonocytic U-937 cells": "cell_line", "galectin-3": "protein" } }, { "input_text": "Functionally , galectin-3 was shown to activate interleukin-2 production in Jurkat T cells .", "target_text": { "galectin-3": "protein", "interleukin-2": "protein", "Jurkat T cells": "cell_type" } }, { "input_text": "Together , these findings raise the possibility that HTLV-I Tax production induces the transcription and subsequent synthesis and secretion of galectin-3 , which in turn may further activate these T cells and contribute to the altered properties of cell growth found in adult T cell leukemia induced by HTLV-I .", "target_text": { "Tax": "protein", "galectin-3": "protein", "T cells": "cell_type" } }, { "input_text": "Monocytic cell type-specific transcriptional induction of collagenase .", "target_text": { "collagenase": "protein" } }, { "input_text": "Interstitial collagenase ( MMP-1 ) , a metalloproteinase produced by resident and inflammatory cells during connective tissue turnover , cleaves type I collagen fibrils .", "target_text": { "collagenase": "protein", "MMP-1": "protein", "metalloproteinase": "protein", "type I collagen fibrils": "protein" } }, { "input_text": "This catalytic event is rate limiting in remodeling of tissues rich in fibrillar collagen such as the skin and lungs .", "target_text": { "fibrillar collagen": "protein" } }, { "input_text": "The regulation of collagenase expression is cell-type specific ; bacterial LPS and zymosan , a yeast cell wall derivative , are potent inducers of collagenase expression in macrophages , but do not alter fibroblast collagenase expression .", "target_text": { "collagenase": "protein", "macrophages": "cell_type", "fibroblast": "cell_type" } }, { "input_text": "Since promoter elements controlling collagenase transcription in monocytic cells have not been previously defined , we sought to delineate responsive cis-acting elements of the collagenase promoter in transiently transfected human ( U937 ) and murine ( J774 ) monocytic cell lines .", "target_text": { "collagenase": "protein", "cis-acting elements": "DNA", "collagenase promoter": "DNA" } }, { "input_text": "Deletion constructs containing as little as 72 bp of 5' -flanking sequence of the collagenase promoter were sufficient for LPS- or zymosan- mediated transcriptional induction , whereas phorbol inducibility exhibited an absolute requirement for upstream elements including the polyoma enhancer A-binding protein-3 site ( -83 to -91 ) and TTCA sequence ( -102 to -105 ) in both monocytic cells and fibroblasts .", "target_text": { "5' -flanking sequence": "DNA", "collagenase": "protein", "collagenase promoter": "DNA", "polyoma enhancer": "DNA", "polyoma enhancer A-binding protein-3 site": "DNA", "-83 to -91": "DNA", "TTCA sequence": "DNA", "-102 to -105": "DNA", "monocytic cells": "cell_type", "fibroblasts": "cell_type" } }, { "input_text": "Mutagenesis of the activator protein-1 [ AP-1 ] site at -72 abolished basal promoter activity and LPS /zymosan inducibility , while mutagenesis of an NF-kappaB-like site at -20 to -10 had no effect .", "target_text": { "AP-1": "protein", "activator protein-1 [ AP-1 ] site": "DNA", "-72": "DNA", "basal promoter": "DNA", "NF-kappaB-like site": "DNA" } }, { "input_text": "Nuclear extracts from LPS - and zymosan -treated cells showed strong AP-1 activity by gel-shift analysis , and supershift analysis showed the AP-1 complexes contained specific members of both the jun and fos gene families .", "target_text": { "zymosan -treated cells": "cell_type", "AP-1": "protein", "AP-1 complexes": "protein" } }, { "input_text": "These data indicate that , in contrast to most LPS effects , AP-1 , but not nuclear factor-kappaB , mediates LPS induction of collagenase transcription in macrophagelike cells .", "target_text": { "AP-1": "protein", "nuclear factor-kappaB": "protein", "collagenase": "protein", "macrophagelike cells": "cell_type" } }, { "input_text": "Furthermore , as compared to regulation by phorbol ester , collagenase induction in monocytic cells by cell wall derivatives of bacteria or yeast is largely independent of upstream promoter sequences .", "target_text": { "collagenase": "protein", "monocytic cells": "cell_type", "upstream promoter sequences": "DNA" } }, { "input_text": "Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide -stimulated macrophages .", "target_text": { "c-Jun N-terminal kinase": "protein", "macrophages": "cell_type", "bacterial lipopolysaccharide -stimulated macrophages": "cell_type" } }, { "input_text": "Activation of macrophages by bacterial lipopolysaccharide ( LPS ) induces transcription of genes that encode for proinflammatory regulators of the immune response .", "target_text": { "macrophages": "cell_type", "proinflammatory regulators": "protein" } }, { "input_text": "Previous work has suggested that activation of the transcription factor activator protein 1 ( AP-1 ) is one LPS -induced event that mediates this response .", "target_text": { "transcription factor activator protein 1": "protein", "AP-1": "protein" } }, { "input_text": "Consistent with this notion , we found that LPS stimulated AP-1 -mediated transcription of a transfected reporter gene in the murine macrophage cell line RAW 264.7 .", "target_text": { "AP-1": "protein", "transfected reporter gene": "DNA", "murine macrophage cell line RAW 264.7": "cell_line" } }, { "input_text": "As AP-1 activity is regulated in part by activation of the c-Jun N-terminal kinase ( JNK ) , which phosphorylates and subsequently increases the transcriptional activity of c-Jun , we examined whether LPS treatment of macrophages resulted in activation of this kinase .", "target_text": { "AP-1": "protein", "c-Jun N-terminal kinase": "protein", "JNK": "protein", "macrophages": "cell_type", "kinase": "protein" } }, { "input_text": "LPS treatment of RAW 264.7 cells , murine bone marrow-derived macrophages , and the human monocyte cell line THP-1 resulted in rapid activation of the p46 and p54 isoforms of JNK .", "target_text": { "RAW 264.7 cells": "cell_line", "macrophages": "cell_type", "murine bone marrow-derived macrophages": "cell_type", "human monocyte cell line THP-1": "cell_line", "JNK": "protein" } }, { "input_text": "Treatment with wild-type and rough mutant forms of LPS and synthetic lipid A resulted in JNK activation , while pretreatment with the tyrosine kinase inhibitor herbimycin A inhibited this response .", "target_text": { "JNK": "protein", "tyrosine kinase": "protein" } }, { "input_text": "Binding of LPS - LPS binding protein ( LBP ) complexes to CD14 , a surface receptor that mediates many LPS responses , was found to be crucial , as pretreatment of THP-1 cells with the monoclonal antibody 60b , which blocks this binding , inhibited JNK activation .", "target_text": { "LPS binding protein ( LBP ) complexes": "protein", "CD14": "protein", "surface receptor": "protein", "THP-1 cells": "cell_line", "monoclonal antibody 60b": "protein", "JNK": "protein" } }, { "input_text": "These results suggest that LPS activation of JNK in monocyte/macrophage cells is a CD14- and protein tyrosine phosphorylation- dependent event that may mediate the early activation of AP-1 in regulating LPS -triggered gene induction .", "target_text": { "JNK": "protein", "monocyte/macrophage cells": "cell_type", "AP-1": "protein" } }, { "input_text": "Surfactant suppresses NF-kappa B activation in human monocytic cells .", "target_text": { "NF-kappa B": "protein", "monocytic cells": "cell_type" } }, { "input_text": "In addition to biophysical properties , pulmonary surfactant has immunomodulatory activity .", "target_text": {} }, { "input_text": "We previously demonstrated that both synthetic ( Exosurf ) and modified natural surfactant ( Survanta ) downregulated endotoxin-stimulated inflammatory c ytokine mRNA levels and protein products ( tumor necrosis factor-alpha [ TNF ] , interleukin-1-beta [ IL-1 ] , interleukin-6 [ IL-6 ] ) in human alveolar macrophages .", "target_text": { "inflammatory c ytokine mRNA": "RNA", "protein products": "protein", "tumor necrosis factor-alpha": "protein", "interleukin-1-beta": "protein", "IL-1": "protein", "interleukin-6": "protein", "IL-6": "protein", "macrophages": "cell_type", "human alveolar macrophages": "cell_type" } }, { "input_text": "In this study , we report that both Exosurf and Survanta suppress TNF mRNA and secretion ( 85 +/- 4 % mean percent inhibition +/- SEM by Exosurf ; 71 +/- 6 % by Survanta ) by endotoxin-stimulated THP-1 , a human monocytic cell line .", "target_text": { "TNF mRNA": "RNA", "endotoxin-stimulated THP-1": "cell_line", "human monocytic cell line": "cell_line" } }, { "input_text": "Because surfactant downregulated inflammatory cytokine production similarly in both normal human alveolar macrophages and the THP-1 cell line , we used this cell line to investigate whether surfactant affected transcriptional mechanisms .", "target_text": { "inflammatory cytokine": "protein", "macrophages": "cell_type", "normal human alveolar macrophages": "cell_type", "THP-1 cell line": "cell_line", "cell line": "cell_line" } }, { "input_text": "Specifically , we examined nuclear factor-kappa B ( NF-kappa B ) activation because it is crucial in transcriptional regulation of many inflammatory cytokine genes including TNF , IL-1 , and IL-6 .", "target_text": { "nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "inflammatory cytokine": "protein", "inflammatory cytokine genes": "DNA", "TNF": "DNA", "IL-1": "DNA", "IL-6": "DNA" } }, { "input_text": "Electrophoretic mobility shift assays showed that both surfactants decreased activation of NF-kappa B .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "The presence of both p65 and p50 NF-kappa B components in LPS -activated THP-1 cells was confirmed by specific antibody induction of supershifts in mobility assays .", "target_text": { "p65": "protein", "p50": "protein", "NF-kappa B": "protein", "NF-kappa B components": "protein", "THP-1 cells": "cell_line" } }, { "input_text": "These results are the first to suggest that surfactant 's suppressive effects on inflammatory cytokine production may involve transcriptional regulation through inhibition of NF-kappa B activation .", "target_text": { "inflammatory cytokine": "protein", "NF-kappa B": "protein" } }, { "input_text": "A cell type-specific enhancer in the human B7.1 gene regulated by NF-kappaB .", "target_text": { "cell type-specific enhancer": "DNA", "human B7.1 gene": "DNA", "NF-kappaB": "protein" } }, { "input_text": "The costimulatory molecule B7.1 provides a second signal critical for T cell activation .", "target_text": { "costimulatory molecule B7.1": "protein" } }, { "input_text": "The distribution of this integral membrane protein is restricted to certain tissues where its level of expression is modulated by multiple exogenous stimuli .", "target_text": { "integral membrane protein": "protein" } }, { "input_text": "To identify the molecular basis for specificity and inducibility , the chromatin configuration of the human B7.1 gene was examined in intact nuclei from various cell types .", "target_text": { "chromatin": "DNA", "human B7.1 gene": "DNA" } }, { "input_text": "The identification of a tissue-specific deoxyribonuclease I hypersensitive site approximately 3kb upstream of the transcription start site led to the characterization of a cell type-specific enhancer region .", "target_text": { "deoxyribonuclease I": "protein", "deoxyribonuclease I hypersensitive site": "DNA", "3kb upstream": "DNA", "transcription start site": "DNA", "cell type-specific enhancer": "DNA", "cell type-specific enhancer region": "DNA" } }, { "input_text": "This 183-bp region was both cell type specific and responsive to two distinct stimuli , lipopolysaccharide and dibutyryl cAMP , known to regulate B7.1 expression .", "target_text": { "183-bp region": "DNA", "B7.1": "protein" } }, { "input_text": "Deletional and site-directed mutagenesis revealed the presence of multiple functionally critical cis elements within this region , one of which was a nuclear factor ( NF ) -kappaB consensus sequence .", "target_text": { "cis elements": "DNA", "nuclear factor ( NF ) -kappaB consensus sequence": "DNA" } }, { "input_text": "In B7.1 -positive B cells , this element bound several members of the NF-kappaB family , transcription factors already implicated in signal transduction pathways relevant to B7.1 expression .", "target_text": { "B7.1": "protein", "B7.1 -positive B cells": "cell_type", "NF-kappaB family": "protein", "transcription factors": "protein" } }, { "input_text": "This is the first description , to our knowledge , of regulatory elements that control expression of a gene encoding a B7 costimulatory molecule .", "target_text": { "regulatory elements": "DNA", "B7 costimulatory molecule": "protein" } }, { "input_text": "Ubiquitinylation of transcription factors c-Jun and c-Fos using reconstituted ubiquitinylating enzymes .", "target_text": { "transcription factors": "protein", "c-Jun": "protein", "c-Fos": "protein", "reconstituted ubiquitinylating enzymes": "protein" } }, { "input_text": "Recombinant c-Jun and c-Fos were ubiquitinylated by the ubiquitin carrier enzymes E214K , E220K , or E232K in the presence of the ubiquitin-activating enzyme , E1 .", "target_text": { "c-Jun": "protein", "c-Fos": "protein", "ubiquitin carrier enzymes": "protein", "E214K": "protein", "E220K": "protein", "E232K": "protein", "ubiquitin-activating enzyme": "protein", "E1": "protein" } }, { "input_text": "Addition of ubiquitin protein ligase E3 substantially enhanced the E214K -mediated ubiquitinylation of c-Jun and c-Fos .", "target_text": { "ubiquitin protein ligase E3": "protein", "E214K": "protein", "c-Jun": "protein", "c-Fos": "protein" } }, { "input_text": "Truncated c-Jun and c-Fos mutant proteins including wbJun and wbFos were also ubiquitinylated under the same conditions , suggesting the sites of ubiquitinylation are located within the dimerization and DNA binding domains of c-Jun and c-Fos .", "target_text": { "wbJun": "protein", "wbFos": "protein", "c-Jun": "protein", "c-Fos": "protein" } }, { "input_text": "The E3-dependent ubiquitinylation of c-Jun was inhibited upon the heterodimerization of c-Jun with c-Fos .", "target_text": { "c-Jun": "protein", "c-Fos": "protein" } }, { "input_text": "Further addition of E220K significantly enhanced ubiquitinylation of c-Jun in the heterodimer suggesting a regulatory role of E220K .", "target_text": { "E220K": "protein", "c-Jun": "protein" } }, { "input_text": "Polyubiquitinylated c-Jun , wbFos , and wbJun , but not E220K -ubiquitinylated c-Jun , were readily degraded by the ATP-dependent 26 S multicatalytic proteases .", "target_text": { "c-Jun": "protein", "wbFos": "protein", "wbJun": "protein", "E220K": "protein", "E220K -ubiquitinylated c-Jun": "protein", "ATP-dependent 26 S multicatalytic proteases": "protein" } }, { "input_text": "These results suggest that the temporal control of c-Jun and c-Fos may be regulated through the ubiquitinylation pathways , and the ubiquitinylation of c-Jun and c-Fos may in turn be regulated in response to the heterodimerization between them and the cooperation between E220K and E3 mediated polyubiquitinylation .", "target_text": { "c-Jun": "protein", "c-Fos": "protein", "E220K": "protein" } }, { "input_text": "Cloning and characterization of the murine B-cell specific transcriptional coactivator Bob1 .", "target_text": { "murine B-cell specific transcriptional coactivator": "protein", "Bob1": "protein" } }, { "input_text": "From a murine B-cell cDNA-library we have cloned a cDNA encoding the murine B-cell specific coactivator mBob1 .", "target_text": { "murine B-cell cDNA-library": "DNA", "cDNA": "DNA", "murine B-cell specific coactivator": "protein", "mBob1": "protein" } }, { "input_text": "The protein is the murine homologue to the recently described human coactivator Bob1 ( hBob1 ) , also referred to as OBF-1 or OCA-B .", "target_text": { "Bob1": "protein", "human coactivator Bob1": "protein", "hBob1": "protein", "OBF-1": "protein", "OCA-B": "protein" } }, { "input_text": "We have also characterized the genomic mBob1 clone .", "target_text": { "mBob1": "protein", "genomic mBob1 clone": "protein" } }, { "input_text": "Analysis of its intron-exon structure has allowed identification of a C-terminal splice variant .", "target_text": { "C-terminal splice variant": "protein" } }, { "input_text": "mBob1 is B-cell restricted , and is found in all B-cell lines representing different stages of B-cell differentiation .", "target_text": { "mBob1": "protein", "B-cell lines": "cell_line" } }, { "input_text": "mBob1 interacts with the octamer transcription factors Oct-1 and Oct-2 and stimulates transcription mediated by these factors .", "target_text": { "mBob1": "protein", "transcription factors": "protein", "octamer transcription factors": "protein", "Oct-1": "protein", "Oct-2": "protein" } }, { "input_text": "HIV glycoprotein 120 enhances intercellular adhesion molecule-1 gene expression in glial cells .", "target_text": { "HIV glycoprotein 120": "protein", "intercellular adhesion molecule-1": "protein", "glial cells": "cell_type" } }, { "input_text": "Involvement of Janus kinase /signal transducer and activator of transcription and protein kinase C signaling pathways .", "target_text": { "Janus kinase": "protein", "/signal transducer and activator of transcription": "protein", "protein kinase C": "protein" } }, { "input_text": "It is well established that the two major glial cells in the central nervous system ( CNS ) , astrocytes and microglia , are key participants in mediating the neurologic dysfunction associated with HIV infection of the CNS .", "target_text": { "glial cells": "cell_type", "astrocytes": "cell_type", "microglia": "cell_type" } }, { "input_text": "In this study , we investigated the ability of the major envelope glycoprotein of HIV , glycoprotein 120 ( gp120 ) , to regulate intercellular adhesion molecule-1 ( ICAM-1 ) expression in glial cells , because ICAM-1 is important in mediating immune responsiveness in the CNS , facilitating entry of HIV -infected cells into the CNS , and promoting syncytia formation .", "target_text": { "major envelope glycoprotein": "protein", "glycoprotein 120": "protein", "gp120": "protein", "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "glial cells": "cell_type", "HIV -infected cells": "cell_type" } }, { "input_text": "Our results indicate that gp120 enhances ICAM-1 gene expression in primary rat astrocytes , primary human astrocytes , a human astroglioma cell line CRT , and primary rat microglia .", "target_text": { "gp120": "protein", "ICAM-1": "protein", "astrocytes": "cell_type", "primary rat astrocytes": "cell_type", "primary human astrocytes": "cell_type", "human astroglioma cell line CRT": "cell_line", "microglia": "cell_type", "primary rat microglia": "cell_type" } }, { "input_text": "The signal transduction events involved in gp120 -mediated enhancement of ICAM-1 appear to involve activation of both protein kinase C and tyrosine kinase , because inhibitors of protein kinase C and tyrosine kinase abrogate gp120 -mediated ICAM-1 expression in both astrocytes and microglia .", "target_text": { "gp120": "protein", "ICAM-1": "protein", "protein kinase C": "protein", "tyrosine kinase": "protein", "astrocytes": "cell_type", "microglia": "cell_type" } }, { "input_text": "Moreover , gp120 induces tyrosine phosphorylation of signal transducer and activator of transcription ( STAT-1 alpha ) as well as the Janus kinase ( JAK2 ) in glial cells .", "target_text": { "gp120": "protein", "signal transducer and activator of transcription": "protein", "STAT-1 alpha": "protein", "Janus kinase": "protein", "JAK2": "protein", "glial cells": "cell_type" } }, { "input_text": "We also demonstrate that gp120 -mediated ICAM-1 expression has functional significance , as it enhances the ability of monocytic cells to bind to gp120 -stimulated human astrocytes in an ICAM-1 /beta 2 integrin -dependent fashion .", "target_text": { "gp120": "protein", "ICAM-1": "protein", "monocytic cells": "cell_type", "astrocytes": "cell_type", "gp120 -stimulated human astrocytes": "cell_type", "integrin": "protein" } }, { "input_text": "These results provide new insights into how gp120 can influence the involvement of glial cells in the pathogenesis of AIDS dementia complex .", "target_text": { "gp120": "protein", "glial cells": "cell_type" } }, { "input_text": "IL-10 cooperates with TNF-alpha to activate HIV-1 from latently and acutely infected cells of monocyte/macrophage lineage .", "target_text": { "IL-10": "protein", "TNF-alpha": "protein", "monocyte/macrophage lineage": "cell_type" } }, { "input_text": "IL-10 is elevated in HIV-1 -infected individuals and has been implicated in disease progression .", "target_text": { "IL-10": "protein" } }, { "input_text": "In this study , we investigated the effects of IL-10 on the activation of HIV-1 from infected monocytes and macrophages .", "target_text": { "IL-10": "protein", "infected monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "Although IL-10 alone did not induce HIV-1 replication , in the presence of TNF-alpha , IL-10 markedly enhanced virion production from a chronically infected promonocytic cell line ( U1 ) and in acutely infected monocyte-derived macrophages .", "target_text": { "IL-10": "protein", "TNF-alpha": "protein", "promonocytic cell line": "cell_line", "U1": "cell_line", "monocyte-derived macrophages": "cell_type" } }, { "input_text": "Neutralizing mAbs to IL-10 and TNF-alpha indicated that both cytokines were essential for the induction and were required to generate a synergistic increase in virus expression .", "target_text": { "mAbs": "protein", "IL-10": "protein", "TNF-alpha": "protein", "cytokines": "protein" } }, { "input_text": "The effects of the two cytokines were distinguishable functionally since pretreatment with TNF-alpha attenuated the cytokine cooperativity , while pretreatment with IL-10 potentiated their cooperativity , suggesting that IL-10 and TNF-alpha play different roles in the activation of virus .", "target_text": { "cytokines": "protein", "TNF-alpha": "protein", "cytokine": "protein", "IL-10": "protein" } }, { "input_text": "Northern blot analysis as well as Ab blocking and cytokine secretion studies indicated that the induction of either endogenous TNF-alpha or IL-10 was not involved in the cooperativity , nor was an up-regulation of TNF-alpha receptors .", "target_text": { "cytokine": "protein", "TNF-alpha": "protein", "endogenous TNF-alpha": "protein", "IL-10": "protein", "TNF-alpha receptors": "protein" } }, { "input_text": "In combination with TNF-alpha , IL-10 stimulated activating protein-1 ( AP-1 ) and nuclear factor ( NF ) -kappa B binding activities and cooperated to increase HIV-1 steady-state mRNA levels and enhance long terminal repeat -directed transcription through activation of the NF-kappa B binding sites , suggesting the IL-10 effect occurs at least in part at the transcriptional level .", "target_text": { "TNF-alpha": "protein", "IL-10": "protein", "activating protein-1": "protein", "AP-1": "protein", "nuclear factor ( NF ) -kappa B": "protein", "long terminal repeat": "DNA", "NF-kappa B": "protein", "NF-kappa B binding sites": "DNA" } }, { "input_text": "These results indicate that IL-10 , in addition to down-regulating the cellular immune response to HIV-1 , may also play a role in TNF-alpha -mediated activation of HIV-1 replication in the monocyte/macrophage lineage .", "target_text": { "IL-10": "protein", "TNF-alpha": "protein", "monocyte/macrophage lineage": "cell_type" } }, { "input_text": "Interaction of HTLV-I Tax with the human proteasome : implications for NF-kappa B induction .", "target_text": { "HTLV-I Tax": "protein", "proteasome": "protein", "human proteasome": "protein", "NF-kappa B": "protein" } }, { "input_text": "The human T-cell leukemia virus type I ( HTLV-I ) has been etiologically associated with the development of the adult T-cell leukemia ( ATL ) as well as degenerative neurologic syndrome termed tropical spastic paraparesis ( TSP ) .", "target_text": {} }, { "input_text": "HTLV-I encodes a potent transactivator protein termed Tax that appears to play an important role in the process of T-cell immortalization .", "target_text": { "transactivator": "protein", "Tax": "protein" } }, { "input_text": "Even though the mechanisms by which Tax induces transformation are still unknown , it seems likely that the ability of Tax to alter the expression of many cellular genes plays an important part in this process .", "target_text": { "Tax": "protein", "cellular genes": "DNA" } }, { "input_text": "Tax does not bind directly to DNA but rather deregulates the activity of cellular transcription factors .", "target_text": { "Tax": "protein", "cellular transcription factors": "protein" } }, { "input_text": "One family of host transcription factors whose activity is altered by Tax includes NF-kappa B/Rel .", "target_text": { "transcription factors": "protein", "host transcription factors": "protein", "Tax": "protein", "NF-kappa B/Rel": "protein" } }, { "input_text": "These transcription factors are post-transcriptionally regulated by their assembly with a second family of inhibitory proteins termed I kappa B that serve to sequester the NF-kappa B/Rel complexes in the cytoplasm .", "target_text": { "transcription factors": "protein", "inhibitory proteins": "protein", "I kappa B": "protein", "NF-kappa B/Rel": "protein", "NF-kappa B/Rel complexes": "protein" } }, { "input_text": "Upon cellular activation , I kappa B alpha is phosphorylated , polyubiquitinated , and degraded in the proteasome .", "target_text": { "I kappa B alpha": "protein", "proteasome": "protein" } }, { "input_text": "This proteolytic event liberates NF-kappa B , permitting its rapid translocation into the nucleus where it binds to its cognate enhancer elements .", "target_text": { "NF-kappa B": "protein", "cognate enhancer elements": "DNA" } }, { "input_text": "Similarly , the p105 precursor of the NF-kappa B p50 subunit is also post-translationally processed in the proteasome .", "target_text": { "p105 precursor": "protein", "NF-kappa B": "protein", "p50 subunit": "protein", "proteasome": "protein" } }, { "input_text": "The mechanisms by which Tax activates NF-kappa B remain unclear , and findings presented in the literature are often controversial .", "target_text": { "Tax": "protein", "NF-kappa B": "protein" } }, { "input_text": "We identified a physical interaction between Tax and the HsN3 subunit of the human proteasome .", "target_text": { "Tax": "protein", "HsN3 subunit": "protein", "proteasome": "protein", "human proteasome": "protein" } }, { "input_text": "This raises the intriguing possibility that physical association of the HsN3 proteasome subunit with HTLV-I Tax coupled with the independent interaction of Tax with either p100 or p65- I kappa B alpha targets these cytoplasmic NF-kappa B/Rel complexes to the proteasome for processing .", "target_text": { "proteasome": "protein", "HsN3 proteasome subunit": "protein", "Tax": "protein", "HTLV-I Tax": "protein", "I kappa B alpha": "protein", "NF-kappa B/Rel": "protein", "cytoplasmic NF-kappa B/Rel complexes": "protein" } }, { "input_text": "Immunophenotype of intraductal carcinoma .", "target_text": {} }, { "input_text": "OBJECTIVE -- Mammography and breast-conserving therapy have focused attention on the classification of intraductal carcinoma ( IDC ) and emphasized the prognostic importance of comedo versus noncomedo variants .", "target_text": {} }, { "input_text": "We used histochemical markers to define the immunophenotype of 43 IDCs with respect to comedo versus noncomedo status and patterns of angiogenesis .", "target_text": {} }, { "input_text": "RESULTS -- Reactions in comedo carcinomas were significantly negative for estrogen receptor and progesterone receptor , and positive for p53 and HER-2/neu more often than the noncomedo variant .", "target_text": { "estrogen receptor": "protein", "progesterone receptor": "protein", "p53": "protein", "HER-2/neu": "protein" } }, { "input_text": "All seven IDCs associated with Paget 's disease showed positive reactions for HER-2/neu .", "target_text": { "HER-2/neu": "protein" } }, { "input_text": "Basement membrane immunoreactivity for type IV collagen and laminin was discontinuous in most examples of IDC regardless of type , with a trend toward more intense staining in comedo than in noncomedo carcinomas .", "target_text": { "type IV collagen": "protein", "laminin": "protein" } }, { "input_text": "Periductal angiogenesis was not significantly related to the type of IDC but was more pronounced with comedo carcinomas .", "target_text": {} }, { "input_text": "CONCLUSIONS -- These observations indicate that there are immunophenotypic correlates to the current structural classification of IDC .", "target_text": {} }, { "input_text": "The immunophenotype of IDC is helpful in subclassifying an IDC and could prove useful as a prognostic indicator for local control in patients treated by breast-conserving therapy .", "target_text": {} }, { "input_text": "Inhibition of protein phosphatase 2A induces serine /threonine phosphorylation , subcellular redistribution , and functional inhibition of STAT3 .", "target_text": { "protein phosphatase 2A": "protein", "STAT3": "protein" } }, { "input_text": "Signal transducers and activators of transcription ( STATs ) are rapidly phosphorylated on tyrosine residues in response to cytokine and growth factor stimulation of cell surface receptors .", "target_text": { "Signal transducers and activators of transcription": "protein", "STATs": "protein", "cytokine": "protein", "growth factor": "protein", "cell surface receptors": "protein" } }, { "input_text": "STATs hereafter are translocated to the nucleus where they act as transcription factors .", "target_text": { "STATs": "protein", "transcription factors": "protein" } }, { "input_text": "Recent reports suggest that serine phosphorylation of STATs also is involved in the regulation of STAT -mediated gene transcription .", "target_text": { "STATs": "protein", "STAT": "protein" } }, { "input_text": "Here , we studied the role of serine /threonine phosphatases in STAT3 signaling in human antigen-specific CD4(+) T cell lines and cutaneous T cell lymphoma lines , expressing a constitutively activated STAT3 .", "target_text": { "serine /threonine phosphatases": "protein", "STAT3": "protein", "human antigen-specific CD4(+) T cell lines": "cell_line", "cutaneous T cell lymphoma lines": "cell_line" } }, { "input_text": "We show that an inhibitor of protein phosphatases ( PPs ) PP1/PP2A , calyculin A , induces ( i ) phosphorylation of STAT3 on serine and threonine residues , ( ii ) inhibition of STAT3 tyrosine phosphorylation and DNA binding activity , and ( iii ) relocation of STAT3 from the nucleus to the cytoplasm .", "target_text": { "protein phosphatases": "protein", "PPs": "protein", "PP1/PP2A": "protein", "calyculin A": "protein", "STAT3": "protein" } }, { "input_text": "Similar results were obtained with other PP2A inhibitors ( okadaic acid , endothall thioanhydride ) but not with inhibitors of PP1 ( tautomycin ) or PP2B ( cyclosporine A ) .", "target_text": { "PP1": "protein", "PP2B": "protein" } }, { "input_text": "Pretreatment with the broad serine /threonine kinase inhibitor staurosporine partly blocked the calyculin A -induced STAT3 phosphorylation , whereas inhibitors of serine /threonine kinases , such as mitogen-activated protein kinase-1 extracellular-regulated kinase-kinase , mitogen-activated protein p38 kinase , and phosphatidylinositol 3-kinase , did not .", "target_text": { "calyculin A": "protein", "STAT3": "protein", "serine /threonine kinases": "protein", "mitogen-activated protein kinase-1 extracellular-regulated kinase-kinase": "protein", "mitogen-activated protein p38 kinase": "protein", "phosphatidylinositol 3-kinase": "protein" } }, { "input_text": "In conclusion , we provide evidence that PP2A plays a crucial role in the regulation of STAT3 phosphorylation and subcellular distribution in T cells .", "target_text": { "PP2A": "protein", "STAT3": "protein", "T cells": "cell_type" } }, { "input_text": "Moreover , our findings suggest that the level of STAT3 phosphorylation is balanced between a staurosporine -sensitive kinase ( s ) and PP2A .", "target_text": { "STAT3": "protein", "staurosporine -sensitive kinase": "protein", "PP2A": "protein" } }, { "input_text": "Polyamines in human breast cancer and its relations to classical prognostic features : clinical implications .", "target_text": {} }, { "input_text": "Experimental evidence suggest an important role of polyamines in breast cancer development .", "target_text": {} }, { "input_text": "Polyamines have been determined in tissue and erythrocyte samples from 100 patients with primary invasive breast cancer and 30 patients with fibroadenomas .", "target_text": {} }, { "input_text": "Statistical analysis was performed in order to determine the prognostic value of the polyamine patterns of tumor tissues and erythrocytes in comparison with clinical and histological prognostic factors .", "target_text": {} }, { "input_text": "In malignant tissues , polyamine levels were significantly higher than in benign tissues .", "target_text": {} }, { "input_text": "They correlated with markers of tumor aggressivity ( axillary node involvement and especially with markers of high mitotic rate as Ki-67 staining , histological grade ) .", "target_text": {} }, { "input_text": "No correlation was found between estrogen and progesterone status , tumor size and polyamine concentrations .", "target_text": {} }, { "input_text": "Erythrocyte polyamines levels were identical between cancer patients and controls .", "target_text": {} }, { "input_text": "The knowledge of the polyamine pattern in breast cancer could become useful in clinical practice particularly if polyamine metabolism is targeted as a therapeutic approach .", "target_text": {} }, { "input_text": "Signal transduction pathways triggered by the FcepsilonRIIb receptor ( CD23 ) in human monocytes lead to nuclear factor-kappaB activation .", "target_text": { "FcepsilonRIIb receptor": "protein", "CD23": "protein", "human monocytes": "cell_type", "nuclear factor-kappaB": "protein" } }, { "input_text": "BACKGROUND : Alveolar macrophages play a key role in the initiation of the inflammatory reaction of allergic asthma .", "target_text": { "Alveolar macrophages": "cell_type" } }, { "input_text": "Alveolar macrophages and peripheral blood monocytes are activated when IgE/allergen immune complexes bind to the CD23 receptor , which leads to the production of inflammatory cytokines .", "target_text": { "Alveolar macrophages": "cell_type", "peripheral blood monocytes": "cell_type", "IgE/allergen immune complexes": "protein", "CD23": "protein", "CD23 receptor": "protein", "cytokines": "protein", "inflammatory cytokines": "protein" } }, { "input_text": "OBJECTIVE : We sought to investigate the molecular mechanisms regulating this early inflammatory response .", "target_text": {} }, { "input_text": "We have focused on the study of the signal transduction pathways triggered by CD23 in human monocytes and the promonocytic cell line U937 .", "target_text": { "CD23": "protein", "human monocytes": "cell_type", "promonocytic cell line U937": "cell_line" } }, { "input_text": "METHODS : CD23 was cross-linked in human monocytes and U937 cells with IgE immune complexes .", "target_text": { "CD23": "protein", "human monocytes": "cell_type", "U937 cells": "cell_line", "IgE immune complexes": "protein" } }, { "input_text": "Surface expression of CD23 was determined by FACS analysis .", "target_text": { "CD23": "protein" } }, { "input_text": "Transcription factor activation and gene transcription were studied by gel-shift assays and Northern blot analysis , respectively .", "target_text": { "Transcription factor": "protein" } }, { "input_text": "IkappaBalpha phosphorylation and degradation was analyzed by Western blot .", "target_text": { "IkappaBalpha": "protein" } }, { "input_text": "RESULTS : Nuclear factor ( NF ) -kappaB is the main transcription factor involved in the gene activation that follows CD23 cross-linking in monocytes .", "target_text": { "Nuclear factor ( NF ) -kappaB": "protein", "CD23": "protein", "monocytes": "cell_type" } }, { "input_text": "CD23 -induced NF-kappaB is a heterodimer composed of p65/p50 subunits .", "target_text": { "CD23": "protein", "CD23 -induced NF-kappaB": "protein", "p65/p50 subunits": "protein" } }, { "input_text": "NF-kappaB nuclear translocation is secondary to the phosphorylation and subsequent degradation of the NF-kappaB inhibitory molecule IkappaBalpha .", "target_text": { "NF-kappaB inhibitory molecule": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Tyrosine kinase -dependent , and not protein kinase C -dependent , pathways mediate CD23 -triggered NF-kappaB activation but do not participate in the direct phosphorylation of IkappaBalpha .", "target_text": { "Tyrosine kinase": "protein", "protein kinase C": "protein", "CD23": "protein", "NF-kappaB": "protein", "IkappaBalpha": "protein" } }, { "input_text": "IkappaBalpha degradation and NF-kappaB nuclear translocation correlate with transcriptional activation of the inflammatory cytokines TNF-alpha and IL-1beta .", "target_text": { "IkappaBalpha": "protein", "NF-kappaB": "protein", "cytokines": "protein", "inflammatory cytokines": "protein", "TNF-alpha": "protein" } }, { "input_text": "CONCLUSIONS : NF-kappaB is the main transcription factor involved in the signal transduction pathway of CD23 in monocytes .", "target_text": { "NF-kappaB": "protein", "CD23": "protein", "monocytes": "cell_type" } }, { "input_text": "Suppression of TNFalpha -mediated NFkappaB activity by myricetin and other flavonoids through downregulating the activity of IKK in ECV304 cells .", "target_text": { "TNFalpha": "protein", "NFkappaB": "protein", "IKK": "protein", "ECV304 cells": "cell_line" } }, { "input_text": "Flavonoids are a group of naturally-occurring phenolic compounds in the plant kingdom , and many flavonoids are found with vascular protective properties .", "target_text": {} }, { "input_text": "Nevertheless how the protective response is exerted by flavonoids is not well characterized .", "target_text": {} }, { "input_text": "In view of the nuclear factor-kappaB ( NFkappaB ) may play a central role in the initiation of atherosclerosis , prevention of the activation of NFkappaB represents an important role in protecting vascular injury .", "target_text": { "nuclear factor-kappaB": "protein", "NFkappaB": "protein" } }, { "input_text": "In this study , the effects of flavonoids on NFkappaB /inhibitor-kappaB ( IkappaB ) system in ECV304 cells activated with tumor necrosis factor-alpha ( TNFalpha ) were examined .", "target_text": { "NFkappaB": "protein", "IkappaB": "protein", "ECV304 cells": "cell_line", "tumor necrosis factor-alpha": "protein", "TNFalpha": "protein" } }, { "input_text": "We investigated the inhibitory action of six flavonoids on IkappaB kinase ( IKK ) activity , an enzyme recently found to phosphorylate critical serine residues of IkappaB for degradation .", "target_text": { "IkappaB kinase": "protein", "IKK": "protein" } }, { "input_text": "Of six flavonoids tested , myricetin was found to strongly inhibit IKK kinase activity , and prevent the degradation of IkappaBalpha and IkappaBbeta in activated endothelial cells .", "target_text": { "IKK": "protein", "IkappaBalpha": "protein", "IkappaBbeta": "protein" } }, { "input_text": "Furthermore , myricetin was also found to inhibit NFkappaB activity correlated with suppression of monocyte adhesion to ECV304 cells .", "target_text": { "NFkappaB": "protein", "ECV304 cells": "cell_line" } }, { "input_text": "Therefore we conclude that flavonoids may be of therapeutic value for vascular disease through down regulation of NFkappaB /IkappaB system .", "target_text": { "NFkappaB": "protein", "/IkappaB": "protein" } }, { "input_text": "Copyright 1999 Wiley-Liss , Inc .", "target_text": {} }, { "input_text": "Bcl-2 -mediated drug resistance : inhibition of apoptosis by blocking nuclear factor of activated T lymphocytes ( NFAT ) -induced Fas ligand transcription .", "target_text": { "Bcl-2": "protein", "nuclear factor of activated T lymphocytes": "protein", "NFAT": "protein", "Fas": "protein" } }, { "input_text": "Bcl-2 inhibits apoptosis induced by a variety of stimuli , including chemotherapy drugs and glucocorticoids .", "target_text": { "Bcl-2": "protein" } }, { "input_text": "It is generally accepted that Bcl-2 exerts its antiapoptotic effects mainly by dimerizing with proapoptotic members of the Bcl-2 family such as Bax and Bad .", "target_text": { "Bcl-2": "protein", "Bcl-2 family": "protein", "Bax": "protein", "Bad": "protein" } }, { "input_text": "However , the mechanism of the antiapoptotic effects is unclear .", "target_text": {} }, { "input_text": "Paclitaxel and other drugs that disturb microtubule dynamics kill cells in a Fas /Fas ligand ( FasL ) -dependent manner ; antibody to FasL inhibits paclitaxel-induced apoptosis .", "target_text": { "microtubule": "protein", "Fas": "protein", "/Fas ligand": "protein", "FasL": "protein" } }, { "input_text": "We have found that Bcl-2 overexpression leads to the prevention of chemotherapy ( paclitaxel ) -induced expression of FasL and blocks paclitaxel -induced apoptosis .", "target_text": { "Bcl-2": "protein", "FasL": "protein" } }, { "input_text": "The mechanism of this effect is that Bcl-2 prevents the nuclear translocation of NFAT ( nuclear factor of activated T lymphocytes , a transcription factor activated by microtubule damage ) by binding and sequestering calcineurin , a calcium-dependent phosphatase that must dephosphorylate NFAT to move to the nucleus .", "target_text": { "Bcl-2": "protein", "NFAT": "protein", "nuclear factor of activated T lymphocytes": "protein", "transcription factor": "protein", "microtubule": "protein" } }, { "input_text": "Without NFAT nuclear translocation , the FasL gene is not transcribed .", "target_text": { "NFAT": "protein", "FasL": "protein" } }, { "input_text": "Thus , it appears that paclitaxel and other drugs that disturb microtubule function kill cells at least in part through the induction of FasL .", "target_text": { "microtubule": "protein", "FasL": "protein" } }, { "input_text": "Furthermore , Bcl-2 antagonizes drug-induced apoptosis by inhibiting calcineurin activation , blocking NFAT nuclear translocation , and preventing FasL expression .", "target_text": { "Bcl-2": "protein", "calcineurin": "protein", "NFAT": "protein", "FasL": "protein" } }, { "input_text": "The effects of Bcl-2 can be overcome , at least partially , through phosphorylation of Bcl-2 .", "target_text": { "Bcl-2": "protein" } }, { "input_text": "Phosphorylated Bcl-2 can not bind calcineurin , and NFAT activation , FasL expression , and apoptosis can occur after Bcl-2 phosphorylation .", "target_text": { "Bcl-2": "protein", "calcineurin": "protein", "NFAT": "protein", "FasL": "protein" } }, { "input_text": "MHC-peptide ligand interactions establish a functional threshold for antigen-specific T cell recognition .", "target_text": {} }, { "input_text": "Antigen-specific T cell recognition is dependent on the functional density of the TCR -ligand , which consists of specific MHC molecules and a specifically bound peptide .", "target_text": { "TCR": "protein", "MHC molecules": "protein" } }, { "input_text": "We have examined the influence of the affinity and concentration of exogenous peptide and the density of specific MHC molecules on the proliferation of a CD4+ , DQA1*0501/DQB1*0201 ( DQ2.1 ) -restricted , HSV-2 -specific T cell clone .", "target_text": { "MHC molecules": "protein", "CD4+ , DQA1*0501/DQB1*0201 ( DQ2.1 ) -restricted , HSV-2 -specific T cell clone": "cell_line" } }, { "input_text": "Using antigen peptide analogs with different mutations of known DQ2-anchor residues , T cell response was reduced in an peptide-affinity and - concentration specific manner .", "target_text": {} }, { "input_text": "The decrease using weaker binding peptides was gradual as stimulation with a peptide with intermediate affinity yielded intermediate T cell proliferation and the poorest binding peptide induced an even weaker T cell response .", "target_text": { "T cell": "cell_type" } }, { "input_text": "MHC class II density on the APC was modified using DQ2 homo - and hetero zygous B- LCLs as APCs , however this variation of MHC concentration had no effect on T cell proliferation .", "target_text": { "MHC class II": "protein", "APC": "cell_type", "APCs": "cell_type", "T cell": "cell_type" } }, { "input_text": "We interpret this as a reflection of a low threshold for activation of the T cell clone , in which peptide- MHC avidity is the over-riding determinant of the strength of ligand signal .", "target_text": { "T cell": "cell_type", "T cell clone": "cell_line", "MHC": "protein" } }, { "input_text": "Regulatory effects of interleukin-11 during acute lung inflammatory injury .", "target_text": { "interleukin-11": "protein" } }, { "input_text": "The role of interleukin-11 ( IL-11 ) was evaluated in the IgG immune complex model of acute lung injury in rats .", "target_text": { "interleukin-11": "protein", "IL-11": "protein", "IgG immune complex": "protein" } }, { "input_text": "IL-11 mRNA and protein were both up-regulated during the course of this inflammatory response .", "target_text": { "IL-11": "protein", "IL-11 mRNA": "RNA" } }, { "input_text": "Exogenously administered IL-11 substantially reduced , in a dose-dependent manner , the intrapulmonary accumulation of neutrophils and the lung vascular leak of albumin .", "target_text": { "IL-11": "protein", "neutrophils": "cell_type", "albumin": "protein" } }, { "input_text": "These in vivo anti-inflammatory effects of IL-11 were associated with reduced NF-kappaB activation in lung , reduced levels of tumor necrosis factor alpha ( TNF-alpha ) in bronchoalveolar lavage ( BAL ) fluids , and diminished up-regulation of lung vascular ICAM-1 .", "target_text": { "IL-11": "protein", "NF-kappaB": "protein", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein", "lung vascular ICAM-1": "protein" } }, { "input_text": "It is interesting that IL-11 did not affect BAL fluid content of the CXC chemokines , macrophage inflammatory protein-2 ( MIP-2 ) and cytokine -inducible neutrophil chemoattractant ( CINC ) ; the presence of IL-11 did not affect these chemokines .", "target_text": { "IL-11": "protein", "CXC chemokines": "protein", "macrophage inflammatory protein-2": "protein", "MIP-2": "protein", "cytokine": "protein", "cytokine -inducible neutrophil chemoattractant": "protein", "CINC": "protein", "chemokines": "protein" } }, { "input_text": "However , BAL content of C5a was reduced by IL-11 .", "target_text": { "IL-11": "protein" } }, { "input_text": "These data indicate that IL-11 is a regulatory cytokine in the lung and that , like other members of this family , its anti-inflammatory properties appear to be linked to its suppression of NF-kappaB activation , diminished production of TNF-alpha , and reduced up-regulation of lung vascular ICAM-1 .", "target_text": { "IL-11": "protein", "cytokine": "protein", "regulatory cytokine": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein", "lung vascular ICAM-1": "protein" } }, { "input_text": "Thrombopoietin induces tyrosine phosphorylation of Stat3 and Stat5 in human blood platelets .", "target_text": { "Thrombopoietin": "protein", "Stat3": "protein", "Stat5": "protein", "human blood platelets": "cell_type" } }, { "input_text": "Thrombopoietin is known to be essential for megakaryocytopoiesis and thrombopoiesis .", "target_text": { "Thrombopoietin": "protein" } }, { "input_text": "Recently , we and others have shown that thrombopoietin induces rapid tyrosine phosphorylation of Jak2 and other proteins in human platelets and BaF3 cells , genetically engineered to express c-Mpl , a receptor for thrombopoietin .", "target_text": { "thrombopoietin": "protein", "Jak2": "protein", "human platelets": "cell_type", "BaF3 cells": "cell_line", "c-Mpl": "protein" } }, { "input_text": "The Jak family of tyrosine kinases are known to mediate some of the effects of cytokines or hematopoietic growth factors by recruitment and tyrosine phosphorylation of a variety of Stat ( signal transducers and activators of transcription ) proteins .", "target_text": { "tyrosine kinases": "protein", "cytokines": "protein", "hematopoietic growth factors": "protein", "Stat": "protein", "signal transducers and activators of transcription": "protein" } }, { "input_text": "Hence , we have investigated whether Stat proteins are present in platelets and , if so , whether they become tyrosine phosphorylated in response to thrombopoietin .", "target_text": { "Stat proteins": "protein", "platelets": "cell_type", "thrombopoietin": "protein" } }, { "input_text": "We immunologically identified Stat1 , Stat2 , Stat3 , and Stat5 in human platelet lysates .", "target_text": { "Stat1": "protein", "Stat2": "protein", "Stat3": "protein", "Stat5": "protein" } }, { "input_text": "Thrombopoietin induced tyrosine phosphorylation of Stat3 and Stat5 in these cells .", "target_text": { "Thrombopoietin": "protein", "Stat3": "protein", "Stat5": "protein" } }, { "input_text": "Thrombopoietin also induced tyrosine phosphorylation of Stat3 and Stat5 in FDCP-2 cells genetically engineered to constitutively express human c-Mpl .", "target_text": { "Thrombopoietin": "protein", "Stat3": "protein", "Stat5": "protein", "FDCP-2 cells": "cell_line", "human c-Mpl": "protein" } }, { "input_text": "Thus , our data indicate that Stat3 and Stat5 may be involved in signal transduction after ligand binding to c-Mpl and that this event may have a role in megakaryopoiesis/ thrombopoiesis or possibly a mature platelet function such as aggregation .", "target_text": { "Stat3": "protein", "Stat5": "protein", "c-Mpl": "protein" } }, { "input_text": "Mechanisms that contribute to the development of lymphoid malignancies : roles for genetic alterations and cytokine production .", "target_text": { "cytokine": "protein" } }, { "input_text": "Recent studies have defined genetic alterations commonly associated with transformed lymphocytes .", "target_text": { "transformed lymphocytes": "cell_line" } }, { "input_text": "This review suggests roles for these alterations in the development of lymphoid neoplasms .", "target_text": {} }, { "input_text": "Damage to the genes encoding proteins that function in intracellular signaling , transcription , or regulation of the cell cycle has been identified and linked at varying degrees to the progression of certain lymphoid malignancies .", "target_text": {} }, { "input_text": "An understanding of the mechanistic consequences following such genetic alterations is essential to an understanding of the development of these lymphoid neoplasms .", "target_text": {} }, { "input_text": "In contrast , it is also becoming clear that the dysregulated expression of proteins that are not genetically altered can also contribute to the progression of lymphoid malignancies .", "target_text": {} }, { "input_text": "One such example is the excessive expression of \" normal \" lymphokines of cytokines which accompanies many lymphoproliferative diseases .", "target_text": { "\" normal \" lymphokines": "protein", "cytokines": "protein" } }, { "input_text": "The dysregulated expression of cytokines during malignancy can result in the augmentation of growth of transformed lymphocytes , as well as an alteration of the anti-tumor immune response .", "target_text": { "cytokines": "protein", "transformed lymphocytes": "cell_line" } }, { "input_text": "The latter mechanism is especially important because evasion of the impending immune response is a prerequisite for the progression of lymphoproliferative diseases .", "target_text": {} }, { "input_text": "Taken together , this review supports the notion that the development of lymphoid malignancies is multifactorial , involving genetic alterations as well as dysregulated cytokine expression .", "target_text": { "cytokine": "protein" } }, { "input_text": "Dehydroepiandrosterone modulation of lipopolysaccharide -stimulated monocyte cytotoxicity .", "target_text": {} }, { "input_text": "Dehydroepiandrosterone ( DHEA ) , the predominant androgen secreted by the adrenal cortex , can be converted to both potent androgens and estrogens .", "target_text": {} }, { "input_text": "In addition to its role as a precursor for other steroid hormones , DHEA has been proposed to play an important role in immunity .", "target_text": {} }, { "input_text": "This study has investigated DHEA modulation of LPS -induced monocyte cytotoxicity .", "target_text": {} }, { "input_text": "Cytotoxicity markers assessed include tumor cell killing , IL-1 secretion , reactive oxygen intermediate release , nitric oxide synthetase activity as measured by the release of reactive nitrogen intermediates , complement receptor-1 cell surface protein , and TNF-alpha protein presence .", "target_text": { "Cytotoxicity markers": "protein", "IL-1": "protein", "nitric oxide synthetase": "protein", "complement receptor-1 cell surface protein": "protein", "TNF-alpha protein": "protein" } }, { "input_text": "Monocytes stimulated with LPS concentrations of 1.0 micrograms/ml displayed the above cytotoxic markers , whereas monocytes stimulated with DHEA alone or with LPS at a lower concentration of 0.2 ng/ml did not .", "target_text": { "Monocytes": "cell_type", "monocytes": "cell_type" } }, { "input_text": "However , when used simultaneously , DHEA and LPS 0.2 ng/ml displayed a synergistic effect on monocyte cytotoxicity against cancerous cell lines , IL-1 secretion , reactive nitrogen intermediate release , complement receptor-1 cell-surface protein , and TNF-alpha protein to levels comparable with levels obtained using LPS 1.0 microgram/ml .", "target_text": { "cancerous cell lines": "cell_line", "IL-1": "protein", "complement receptor-1 cell-surface protein": "protein", "TNF-alpha protein": "protein" } }, { "input_text": "Finally , Scatchard plot analysis demonstrated the presence of a DHEA receptor in monocytes , suggesting that DHEA effects on LPS -stimulated monocytes are mediated through a receptor-dependent process .", "target_text": { "monocytes": "cell_type", "LPS -stimulated monocytes": "cell_line" } }, { "input_text": "Interferons inhibit activation of STAT6 by interleukin 4 in human monocytes by inducing SOCS-1 gene expression .", "target_text": { "STAT6": "protein", "interleukin 4": "protein", "human monocytes": "cell_type", "SOCS-1 gene": "DNA" } }, { "input_text": "Interferons ( IFNs ) inhibit induction by IL-4 of multiple genes in human monocytes .", "target_text": { "Interferons": "protein", "IFNs": "protein", "IL-4": "protein", "human monocytes": "cell_type" } }, { "input_text": "However , the mechanism by which IFNs mediate this inhibition has not been defined .", "target_text": { "IFNs": "protein" } }, { "input_text": "IL-4 activates gene expression by inducing tyrosine phosphorylation , homodimerization , and nuclear translocation of the latent transcription factor , STAT6 ( signal transducer and activator of transcription-6 ) .", "target_text": { "IL-4": "protein", "latent transcription factor": "protein", "STAT6": "protein", "signal transducer and activator of transcription-6": "protein" } }, { "input_text": "STAT6 -responsive elements are characteristically present in the promoters of IL-4 -inducible genes .", "target_text": { "STAT6": "protein", "promoters": "DNA", "IL-4": "protein", "IL-4 -inducible genes": "DNA" } }, { "input_text": "Because STAT6 activation is essential for IL-4 -induced gene expression , we examined the ability of type I and type II IFNs to regulate activation of STAT6 by IL-4 in primary human monocytes .", "target_text": { "STAT6": "protein", "IL-4": "protein", "IFNs": "protein", "human monocytes": "cell_type", "primary human monocytes": "cell_type" } }, { "input_text": "Pretreatment of monocytes with IFN-beta or IFN-gamma , but not IL-1 , IL-2 , macrophage colony-stimulating factor , granulocyte/macrophage colony-stimulating factor , IL-6 , or transforming growth factor beta suppressed activation of STAT6 by IL-4 .", "target_text": { "monocytes": "cell_type", "IFN-beta": "protein", "IFN-gamma": "protein", "IL-1": "protein", "IL-2": "protein", "macrophage colony-stimulating factor": "protein", "granulocyte/macrophage colony-stimulating factor": "protein", "IL-6": "protein", "STAT6": "protein", "IL-4": "protein" } }, { "input_text": "This inhibition was associated with decreased tyrosine phosphorylation and nuclear translocation of STAT6 and was not evident unless the cells were preincubated with IFN for at least 1 hr before IL-4 stimulation .", "target_text": { "STAT6": "protein", "IFN": "protein", "IL-4": "protein" } }, { "input_text": "Furthermore , inhibition by IFN could be blocked by cotreatment with actinomycin D and correlated temporally with induction of the JAK/STAT inhibitory gene , SOCS-1 .", "target_text": { "IFN": "protein", "JAK/STAT inhibitory gene": "DNA", "SOCS-1": "DNA" } }, { "input_text": "Forced expression of SOCS-1 in a macrophage cell line , RAW264 , markedly suppressed trans-activation of an IL-4 -inducible reporter as well as IL-6- and IFN-gamma- induced reporter gene activity .", "target_text": { "SOCS-1": "DNA", "macrophage cell line": "cell_line", "RAW264": "cell_line", "IL-4": "protein", "IL-4 -inducible reporter": "DNA" } }, { "input_text": "These findings demonstrate that IFNs inhibit IL-4 -induced activation of STAT6 and STAT6 -dependent gene expression , at least in part , by inducing expression of SOCS-1 .", "target_text": { "IFNs": "protein", "IL-4": "protein", "STAT6": "protein", "SOCS-1": "DNA" } }, { "input_text": "An activation-responsive element in single C motif-1/lymphotactin promoter is a site of constitutive and inducible DNA-protein interactions involving nuclear factor of activated T cell .", "target_text": { "C motif-1/lymphotactin promoter": "DNA", "nuclear factor of activated T cell": "protein" } }, { "input_text": "Single C motif-1 ( SCM-1 ) /lymphotactin is a C-type chemokine whose expression is activation dependent , cyclosporin A sensitive and restricted to CD8+ T cells , double-negative thymocytes , gammadelta-type T cells , and NK cells .", "target_text": { "Single C motif-1": "protein", "Single C motif-1 ( SCM-1 ) /lymphotactin": "protein", "C-type chemokine": "protein", "CD8+ T cells": "cell_type", "double-negative thymocytes": "cell_type", "gammadelta-type T cells": "cell_type", "NK cells": "cell_type" } }, { "input_text": "In humans , there are two highly homologous genes encoding SCM-1alpha and SCM-1beta .", "target_text": { "homologous genes": "DNA", "SCM-1alpha": "protein", "SCM-1beta": "protein" } }, { "input_text": "Here we examined the regulatory mechanism of the SCM-1 genes .", "target_text": { "SCM-1 genes": "DNA" } }, { "input_text": "The luciferase reporter gene under the control of the 5' flanking region of 0.7 kb was strongly induced upon activation with anti-CD3 or PHA plus PMA only in SCM-1-producer T cell lines through a cyclosporin A-sensitive mechanism .", "target_text": { "luciferase reporter gene": "DNA", "5' flanking region": "DNA", "anti-CD3": "protein", "PHA": "protein", "SCM-1-producer T cell lines": "cell_line" } }, { "input_text": "An element termed E1 located at -108 to -95 nt relative to the major transcription start site was found to be critical for the promoter activity .", "target_text": { "E1": "DNA", "-108 to -95 nt": "DNA" } }, { "input_text": "In electrophoretic mobility shift assays using the E1 oligonucleotide as probe , nuclear extracts from unstimulated T and B cell lines formed a constitutive complex termed complex I , while nuclear extracts from stimulated SCM-1-producer T cell lines formed a higher mobility complex termed complex II with a concomitant decrease in complex I .", "target_text": { "E1": "DNA", "B cell lines": "cell_line", "constitutive complex": "protein", "complex I": "protein", "SCM-1-producer T cell lines": "cell_line", "higher mobility complex": "protein", "complex II": "protein" } }, { "input_text": "The shift from complex I to complex II seen only in SCM-1-producer T cell lines upon activation was completely suppressed by cyclosporin A .", "target_text": { "complex I": "protein", "complex II": "protein", "SCM-1-producer T cell lines": "cell_line" } }, { "input_text": "Both complexes were critically dependent on the NF-AT core sequence TTTCC in the E1 element and were partially supershifted by anti-NF-ATp .", "target_text": { "NF-AT core sequence": "DNA", "E1": "DNA", "E1 element": "DNA", "anti-NF-ATp": "protein" } }, { "input_text": "One-hybrid assays in yeast isolated NF-ATp as an E1 binding protein , and transfection of NF-ATp into T and B cell lines strongly enhanced the activation-dependent SCM-1 promoter activity .", "target_text": { "yeast isolated NF-ATp": "protein", "E1": "DNA", "E1 binding protein": "protein", "NF-ATp": "protein", "activation-dependent SCM-1": "protein" } }, { "input_text": "Collectively , a unique mechanism involving NF-ATp appears to regulate the cell type-specific and activation-dependent expression of the SCM-1 genes .", "target_text": { "NF-ATp": "protein", "SCM-1 genes": "DNA" } }, { "input_text": "Dopamine stimulates expression of the human immunodeficiency virus type 1 via NF-kappaB in cells of the immune system .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Recent studies have reported that lymphocytes produce , transport and bind dopamine present in plasma .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "However , the action of dopamine on HIV-1 gene expression in cells of the immune system has not yet been examined .", "target_text": {} }, { "input_text": "Here , we have investigated the regulation of HIV-1 expression by dopamine in Jurkat T cells and in primary blood mononuclear cells ( PBMC ) .", "target_text": { "Jurkat T cells": "cell_line", "primary blood mononuclear cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "HIV-1 replication was increased by dopamine , which correlated with the increased levels of HIV-1 transactivation .", "target_text": {} }, { "input_text": "Our transient expression data revealed that dopamine stimulated transcription through the NF-kappaB element present in the long terminal repeat .", "target_text": { "NF-kappaB": "protein", "NF-kappaB element": "DNA", "long terminal repeat": "DNA" } }, { "input_text": "The importance of NF-kappaB sites was confirmed by using vectors containing wild-type or mutant kappaB sites in a heterologous promoter .", "target_text": { "NF-kappaB": "protein", "NF-kappaB sites": "DNA", "heterologous promoter": "DNA" } }, { "input_text": "Consistent with the role of NF-kappaB in mediating dopamine responsiveness , the proteasome inhibitor MG132 abolished dopamine -induced transcriptional activation .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "We further explored the effect of dopamine in the presence of phorbol esters or tumor necrosis factor-alpha ( TNF-alpha ) known to activate NF-kappaB .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "The combination of dopamine and TNF-alpha led to a stimulation of HIV-1 transcription and replication .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "However , in contrast with TNF-alpha , dopamine treatment did not affect NF-kappaB DNA binding activity nor the concentrations of p50 , p65 and IkappaB-alpha proteins , which suggests a distinct NF-kappaB activation mechanism .", "target_text": { "TNF-alpha": "protein", "NF-kappaB": "protein", "p50": "protein", "p65": "protein", "IkappaB-alpha proteins": "protein" } }, { "input_text": "These results reveal a new link between the dopamine system , cytokine signaling pathway and regulation of gene expression via the involvement of NF-kappaB in T cells and PBMC .", "target_text": { "cytokine": "protein", "NF-kappaB": "protein", "T cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "[ Hormonal metabolic status in breast cancer patients after conservative surgery : comparison with known prognostic criteria ]", "target_text": {} }, { "input_text": "Body weight , body mass index , body fat , lean body mass , blood-glucose , cholesterol , HDL-cholesterol , triglyceride , beta-lipoproteins , insulin , gonadotropin , estradiol , testosterone , SHBG , T3 , T4 and TSH levels as well as estradiol and progesterone receptor levels in excised tumor were studied in 40 patients with breast cancer prior to conservative treatment .", "target_text": { "HDL-cholesterol": "protein", "beta-lipoproteins": "protein", "SHBG": "protein", "T3": "protein", "T4": "protein" } }, { "input_text": "Said anthropometric , metabolic and hormonal parameters were compared with the index of lymphocytic infiltration of tumor selected as a prognostic factor .", "target_text": {} }, { "input_text": "A significant correlation between high lymphocytic infiltration ( 2.5 points ) , low body mass and fat was identified .", "target_text": {} }, { "input_text": "Also , smoking contributed to loss of body mass and fat ; however , it caused lymphocytic infiltration to rise .", "target_text": {} }, { "input_text": "Moderate body mass , relatively low fat level and positive receptor status are among factors of good prognosis in breast cancer of early stages .", "target_text": {} }, { "input_text": "Selective DNA-binding activity of interleukin-10 -stimulated STAT molecules in human monocytes .", "target_text": { "interleukin-10": "protein", "interleukin-10 -stimulated STAT molecules": "protein", "human monocytes": "cell_type" } }, { "input_text": "It has been demonstrated that interferon-gamma ( IFN-gamma ) and interleukin-10 ( IL-10 ) have various reverse effects on macrophages ; however , the molecular mechanism of this difference has not been fully understood .", "target_text": { "interferon-gamma": "protein", "IFN-gamma": "protein", "interleukin-10": "protein", "IL-10": "protein", "macrophages": "cell_type" } }, { "input_text": "In this study , we analyzed the binding activity of IL-10- and IFN-gamma- activated STAT molecules to two kinds of GAS -motif sequences .", "target_text": { "GAS": "DNA" } }, { "input_text": "IL-10 -activated STAT1 could bind to the GAS-motif sequence in the promoter region of the Fcgamma receptor , but not to that in the promoter region of the COX-2 gene , whereas IFN-gamma -activated STAT1 and STAT5 could bind to both sequences .", "target_text": { "IL-10": "protein", "STAT1": "protein", "IL-10 -activated STAT1": "protein", "GAS-motif sequence": "DNA", "Fcgamma receptor": "protein", "promoter region": "DNA", "COX-2 gene": "DNA", "IFN-gamma": "protein", "IFN-gamma -activated STAT1": "protein", "STAT5": "protein" } }, { "input_text": "IL-10 inhibited IFN-gamma -induced STAT activation without newly synthesized protein .", "target_text": { "IL-10": "protein", "IFN-gamma": "protein", "STAT": "protein", "newly synthesized protein": "protein" } }, { "input_text": "We further demonstrated that aspirin , but not dexamethasone , suppressed IFN-gamma -induced STAT activation .", "target_text": { "IFN-gamma": "protein", "STAT": "protein" } }, { "input_text": "Taken together , these results suggest that IL-10-activated STAT1 has a specificity in binding to the GAS-motif sequences , whereas IFN-gamma -activated STAT1 and STAT5 have a broader spectrum in binding to the GAS-motif sequences .", "target_text": { "STAT1": "protein", "IL-10-activated STAT1": "protein", "GAS-motif sequences": "DNA", "IFN-gamma": "protein", "IFN-gamma -activated STAT1": "protein", "STAT5": "protein" } }, { "input_text": "This may explain the difference between IL-10 and IFN-gamma in biological activity , and the inhibitory effect of IL-10 on IFN-gamma activities .", "target_text": { "IL-10": "protein", "IFN-gamma": "protein" } }, { "input_text": "Peptide binding affinity and pH variation establish functional thresholds for activation of HLA-DQ -restricted T cell recognition .", "target_text": { "HLA-DQ": "DNA" } }, { "input_text": "Peptides derived from the HSV-2 VP16 protein were utilized for studies of peptide binding to DQ0302 molecules and T cell activation at both neutral and acidic pH .", "target_text": { "HSV-2 VP16 protein": "protein" } }, { "input_text": "The native peptide VP16 430-444 contains an Asp at position 442 , binds to DQ0302 strongly , with a Kd value of 50nM at acidic pH and very weakly , with a Kd value of greater than 10 microM at neutral pH .", "target_text": { "position 442": "protein" } }, { "input_text": "A truncated version of 430-444 , i.e. , VP16 433-442 , binds with an affinity 10-fold lower compared to 430-444 at acidic pH , and binding at neutral pH was barely detectable .", "target_text": {} }, { "input_text": "The homologous peptide 430-444,442A has an Asp to Ala substitution at position 442 and binds to DQ0302 with a Kd similar to 433-442 .", "target_text": {} }, { "input_text": "The short truncated analog 433-442A binds very poorly at both acidic and neutral pH .", "target_text": {} }, { "input_text": "Both the wild type 430-444 and 433-442 peptides stimulated a HSV-specific T cell clone after a brief incubation with antigen presenting cells ( APC ) expressing DQ0302 at acidic pH .", "target_text": { "antigen presenting cells": "cell_type", "APC": "cell_type" } }, { "input_text": "Much higher concentrations of wild type peptides were needed to activate T cells at neutral pH .", "target_text": { "T cells": "cell_type" } }, { "input_text": "In contrast , APC pulsed with Ala -substituted peptides 430-444 , 442A or 433-442A at neutral pH failed to stimulate the T cell clone , while APC pulsed at acidic pH and subsequently washed led to successful T cell activation .", "target_text": { "APC": "cell_type", "T cell clone": "cell_line" } }, { "input_text": "The Ala -substituted peptide was recognized by the T cell clone at neutral pH only when it was present in the APC culture throughout the stimulation process .", "target_text": { "T cell clone": "cell_line", "APC": "cell_type", "APC culture": "cell_line" } }, { "input_text": "While the MHC-peptide complexes formed with the native peptide are stable , complexes formed with the Ala -substituted peptide had a functional t1/2 of less than 4 hr at neutral pH .", "target_text": { "MHC-peptide complexes": "protein" } }, { "input_text": "ETS transcription factors regulate an enhancer activity in the third intron of TNF-alpha .", "target_text": { "ETS transcription factors": "protein", "third intron": "DNA", "TNF-alpha": "protein" } }, { "input_text": "We describe an enhancer site in the third intron of tumor necrosis factor alpha ( TNF-alpha ) .", "target_text": { "third intron": "DNA", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "A reporter construct containing the 5'-flanking region of the mouse TNF-alpha gene displayed weak activity when transfected into RAW264.7 macrophage-like cells .", "target_text": { "reporter construct": "DNA", "5'-flanking region": "DNA", "TNF-alpha": "protein", "TNF-alpha gene": "DNA", "RAW264.7 macrophage-like cells": "cell_line" } }, { "input_text": "The addition of the third intron of TNF-alpha to this construct resulted in an enhancement of CAT protein .", "target_text": { "third intron": "DNA", "TNF-alpha": "protein", "CAT protein": "protein" } }, { "input_text": "This enhancement was eliminated if a conserved 20-bp sequence was removed from the intron or if a dominant-negative ets-binding factor was co-transfected with the reporter gene .", "target_text": { "conserved 20-bp sequence": "DNA", "intron": "DNA", "dominant-negative ets-binding factor": "protein", "reporter gene": "DNA" } }, { "input_text": "Mutations of this site that destroyed potential ets transcription factor binding sites had reduced transcriptional activity .", "target_text": { "ets transcription factor": "protein", "ets transcription factor binding sites": "DNA" } }, { "input_text": "The major transcription factor that bound to the oligonucleotide was confirmed to be GABP by supershift and competition analysis .", "target_text": { "GABP": "protein" } }, { "input_text": "In RAW264.7 cells , the binding was constitutive , however , in bone marrow-derived macrophages binding activity was shown to be interferon-gamma inducible .", "target_text": { "RAW264.7 cells": "cell_line", "macrophages": "cell_type", "bone marrow-derived macrophages": "cell_line", "interferon-gamma": "protein" } }, { "input_text": "This may imply a role for ets transcription factors in the production of TNF-alpha .", "target_text": { "ets transcription factors": "protein", "TNF-alpha": "protein" } }, { "input_text": "E2F-1 blocks terminal differentiation and causes proliferation in transgenic megakaryocytes .", "target_text": { "E2F-1": "protein", "transgenic megakaryocytes": "cell_type" } }, { "input_text": "The transcription factor E2F-1 plays a central role in the cell cycle through its ability to activate genes involved in cell division .", "target_text": { "transcription factor": "protein", "E2F-1": "protein", "activate genes": "DNA" } }, { "input_text": "E2F-1 activity is regulated by a number of proteins , including the retinoblastoma susceptibility gene product , cyclin-dependent kinases , and their inhibitors , proteins that have been implicated in the control of certain developmental processes .", "target_text": { "E2F-1": "protein", "susceptibility gene": "DNA", "cyclin-dependent kinases": "protein" } }, { "input_text": "To investigate a potential role of E2F-1 in differentiation , we assayed the ability of megakaryocytes to form platelets in an in vivo transgenic model .", "target_text": { "E2F-1": "protein", "megakaryocytes": "cell_type", "platelets": "cell_type" } }, { "input_text": "E2F-1 expression in megakaryocytes blocked differentiation during maturation , resulting in severe thrombocytopenia .", "target_text": { "E2F-1": "protein", "megakaryocytes": "cell_type" } }, { "input_text": "Ultrastructural analysis of megakaryocytes revealed abnormal development characterized by hyperdemarcation of cytoplasmic membranes and reduced numbers of alpha granules .", "target_text": { "megakaryocytes": "cell_type" } }, { "input_text": "Administration of megakaryocyte growth and development factor or interleukin 6 could not overcome the differentiation block .", "target_text": { "megakaryocyte": "cell_type", "megakaryocyte growth and development factor": "protein", "interleukin 6": "protein" } }, { "input_text": "Additionally , E2F-1 caused massive megakaryocyte accumulation in both normal and ectopic sites , first evident in E15 embryonic liver .", "target_text": { "E2F-1": "protein", "megakaryocyte": "cell_type" } }, { "input_text": "Furthermore , significant apoptosis was observed in transgenic megakaryocytes .", "target_text": { "megakaryocytes": "cell_type", "transgenic megakaryocytes": "cell_type" } }, { "input_text": "These data indicate that E2F-1 can prevent terminal differentiation , probably through its cell cycle -stimulatory activity .", "target_text": { "E2F-1": "protein" } }, { "input_text": "Polymorphic nucleotides within the human IL-4 promoter that mediate overexpression of the gene .", "target_text": { "IL-4": "protein", "human IL-4 promoter": "DNA" } }, { "input_text": "Atopy , which predisposes individuals to develop asthma , severe systemic anaphylaxis , and atopic dermatitis , is usually associated with dramatically elevated total serum IgE levels and is thought to be controlled by a major susceptibility gene and multiple minor susceptibility genes .", "target_text": { "IgE": "protein", "susceptibility gene": "DNA", "susceptibility genes": "DNA" } }, { "input_text": "A recent sib-pair analysis revealed a tight linkage between markers on 5q31.1 and a major susceptibility gene controlling total serum IgE levels .", "target_text": { "5q31.1": "DNA", "major susceptibility gene": "DNA", "IgE": "protein" } }, { "input_text": "Due to its location within this cluster and its biologic role in Ig class switching and Th2 cell differentiation , the IL-4 gene has emerged as one major candidate for the atopy gene .", "target_text": { "Th2 cell": "cell_line", "IL-4": "protein", "IL-4 gene": "DNA", "atopy gene": "DNA" } }, { "input_text": "In one model , polymorphisms within IL-4 regulatory elements might result in overexpression of the gene , amplifying Th2 cell differentiation and class switching to IgE .", "target_text": { "IL-4": "protein", "IL-4 regulatory elements": "DNA", "Th2 cell": "cell_line", "IgE": "protein" } }, { "input_text": "In support of this model , we report that the human IL-4 promoter exists in multiple allelic forms that exhibit distinct transcriptional activities in IL-4 -positive T cells .", "target_text": { "IL-4": "protein", "human IL-4 promoter": "DNA", "IL-4 -positive T cells": "cell_type" } }, { "input_text": "A particular allele has an unusually high transcriptional activity .", "target_text": {} }, { "input_text": "A nucleotide substitution within a recently described OAP40 element located just upstream of an NF-AT site ( P sequence ) appears to be largely responsible for the increased promotor strength of this particular allelic form of the IL-4 promoter .", "target_text": { "OAP40 element": "DNA", "NF-AT site": "DNA", "P sequence": "DNA", "IL-4": "protein", "IL-4 promoter": "DNA" } }, { "input_text": "In EMSAs , this substitution results in a markedly enhanced affinity for sequence-specific complexes exhibiting an AP-1 specificity .", "target_text": { "AP-1": "protein" } }, { "input_text": "The identification of allelic nucleotides , which results in overexpression of the IL-4 gene , provides specific targets for a comprehensive screening of atopic and nonatopic individuals and may provide a clue for genetic predisposition for atopy .", "target_text": { "IL-4": "protein", "IL-4 gene": "DNA" } }, { "input_text": "Evidence for lowered induction of nuclear factor kappa B in activated human T lymphocytes during aging .", "target_text": { "nuclear factor kappa B": "protein", "activated human T lymphocytes": "cell_type" } }, { "input_text": "Transcription factor NF kappa B ( nuclear factor kappa B ) is induced in T lymphocytes from young individuals following activation with a variety of stimuli including anti-CD3 , phorbol myristate acetate ( PMA ) , and tumor necrosis factor-alpha ( TNF-alpha ) .", "target_text": { "NF kappa B": "protein", "nuclear factor kappa B": "protein", "T lymphocytes": "cell_type", "anti-CD3": "protein", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "In contrast , activated T lymphocytes from older individuals show a significant reduction in the induction of NF kappa B in response to the same stimuli .", "target_text": { "T lymphocytes": "cell_type", "NF kappa B": "protein" } }, { "input_text": "The age-related decline in induction of NF kappa B could not be attributed to alteration in the composition of subunits , p50 and p65 were found to be the predominant subunits of induced NF kappa B in T cells from young as well as elderly donors .", "target_text": { "NF kappa B": "protein", "p50": "protein", "p65": "protein", "T cells": "cell_type" } }, { "input_text": "Furthermore , similar levels of NF kappa B were found in the cytosols of unactivated T cells from both young and elderly donors suggesting that precursor levels of NF kappa B remain unaltered during aging .", "target_text": { "NF kappa B": "protein", "T cells": "cell_type" } }, { "input_text": "These results suggest that an age-associated decline in the induction of NF kappa B in activated T cells from elderly individuals may be attributable to altered regulation of the inhibitor , I kappa B , and may play an important role in immune dysregulation accompanying aging .", "target_text": { "NF kappa B": "protein", "T cells": "cell_type", "I kappa B": "protein" } }, { "input_text": "Inhibition of lipopolysaccharide -induced monocyte interleukin-1 receptor antagonist synthesis by cortisol : involvement of the mineralocorticoid receptor .", "target_text": { "monocyte interleukin-1 receptor": "protein", "mineralocorticoid receptor": "protein" } }, { "input_text": "Glucocorticoids , as a part of their physiological role in the control of inflammatory and immune processes , suppress the expression of interleukin-1 ( IL-1 ) and other cytokines .", "target_text": { "interleukin-1": "protein", "IL-1": "protein", "cytokines": "protein" } }, { "input_text": "Human monocyte IL-1 receptor antagonist ( IL-1ra ) messenger ribonucleic acid ( mRNA ) expression and protein secretion are inhibited by dexamethasone .", "target_text": { "IL-1": "protein", "Human monocyte IL-1 receptor antagonist": "protein", "Human monocyte IL-1 receptor antagonist ( IL-1ra ) messenger ribonucleic acid": "RNA" } }, { "input_text": "We have now further studied the regulation of IL-1ra by the major physiological human glucocorticoid , cortisol .", "target_text": { "IL-1ra": "protein" } }, { "input_text": "We found that cortisol incubation induced a decrease in IL-1ra mRNA expression and a significant inhibition of IL-1ra protein secretion in cell cultures of human peripheral monocytes stimulated with the bacterial endotoxin lipopolysaccharide ( LPS ) .", "target_text": { "IL-1ra": "protein", "IL-1ra mRNA": "RNA", "IL-1ra protein": "protein", "human peripheral monocytes": "cell_type" } }, { "input_text": "Oral administration of 276 mumol cortisol to normal subjects also decreased LPS -induced IL-1ra synthesis in cultured monocytes .", "target_text": { "IL-1ra": "protein", "cultured monocytes": "cell_line" } }, { "input_text": "By coincubating the monocytes with either the mineralocorticoid antagonist spironolactone or the glucocorticoid receptor antagonist RU 38486 , the in vitro cortisol -induced inhibition of LPS -stimulated IL-1ra secretion was partially reversed .", "target_text": { "monocytes": "cell_type", "glucocorticoid receptor": "protein", "IL-1ra": "protein" } }, { "input_text": "The mineralocorticoid aldosterone exerted a significant decrease in LPS -induced monocyte IL-1ra secretion in vitro , which was blocked by coincubation with spironolactone .", "target_text": { "IL-1ra": "protein" } }, { "input_text": "In addition , the expression of mineralocorticoid receptor mRNA in human monocytes was observed by PCR of reversed transcribed RNA .", "target_text": { "mineralocorticoid receptor": "protein", "mineralocorticoid receptor mRNA": "RNA", "monocytes": "cell_type", "reversed transcribed RNA": "RNA" } }, { "input_text": "Our results further indicate that corticosteroids physiologically control the IL-1/ IL-1ra system during inflammatory or immune processes .", "target_text": { "IL-1ra": "protein" } }, { "input_text": "Moreover , we provide evidence that , in addition to a glucocorticoid receptor -mediated effect , the mineralocorticoid receptor is involved in the inhibition of monocyte IL-1ra secretion by cortisol .", "target_text": { "glucocorticoid receptor": "protein", "mineralocorticoid receptor": "protein", "IL-1ra": "protein" } }, { "input_text": "Target structures of the CD8(+)-T-cell response to human cytomegalovirus : the 72-kilodalton major immediate-early protein revisited .", "target_text": { "72-kilodalton major immediate-early protein": "protein" } }, { "input_text": "Cell-mediated immunity plays an essential role in the control of infection with the human cytomegalovirus ( HCMV ) .", "target_text": {} }, { "input_text": "However , only a few CD8(+)-T-cell epitopes are known , with the majority being contained in the pp65 phosphoprotein , which is believed to dominate the CD8(+)-T-cell response to HCMV .", "target_text": { "CD8(+)-T-cell epitopes": "protein", "pp65 phosphoprotein": "protein" } }, { "input_text": "Here , we have readdressed the issue of CD8(+) T cells specific for the 72-kDa major immediate-early protein ( IE-1 ) , which is nonstructural but is found very early and throughout the replicative cycle .", "target_text": { "CD8(+) T cells": "cell_type", "72-kDa major immediate-early protein": "protein", "IE-1": "protein" } }, { "input_text": "Using a novel flow-cytometric assay , we were able to identify CD8(+)-T-cell epitopes ( by IE-1 peptide-specific induction of cytokine synthesis ) and simultaneously measure the frequency of cells directed against them .", "target_text": { "CD8(+)-T-cell epitopes": "protein", "IE-1": "protein", "cytokine": "protein" } }, { "input_text": "For this purpose , 81 pentadecamer peptides covering the complete 491-amino-acid sequence of IE-1 were tested on peripheral blood mononuclear cells of anti- HCMV immunoglobulin G-seropositive donors .", "target_text": { "491-amino-acid sequence": "protein", "IE-1": "protein", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "At least 10 new epitopes were identified , and the fine specificity and presenting HLA molecule of the first of them was determined .", "target_text": { "epitopes": "protein", "HLA molecule": "protein" } }, { "input_text": "The frequencies of CD8(+) T cells directed against IE-1 were similar to those directed against pp65 in donors tested with known pp65 -derived peptides .", "target_text": { "CD8(+) T cells": "cell_type", "IE-1": "protein", "pp65": "protein" } }, { "input_text": "Importantly , additional testing of a corresponding set of peptides covering the complete sequence of pp65 on 10 of these donors identified individuals whose CD8(+) T cells recognized IE-1 but not pp65 and vice versa , clearly illustrating that either protein may be a major target .", "target_text": { "pp65": "protein", "CD8(+) T cells": "cell_type", "IE-1": "protein" } }, { "input_text": "In summary , our results suggest that IE-1 is far more important as a CD8(+)-T-cell target than current opinion suggests .", "target_text": { "IE-1": "protein" } }, { "input_text": "E1A oncogene induction of cellular susceptibility to killing by cytolytic lymphocytes through target cell sensitization to apoptotic injury .", "target_text": { "E1A oncogene": "DNA", "cytolytic lymphocytes": "cell_type" } }, { "input_text": "E1A oncogene expression increases mammalian cell susceptibility to lysis by cytolytic lymphocytes ( CLs ) at a stage in this intercellular interaction that is independent of cell surface recognition events .", "target_text": { "E1A oncogene": "DNA", "cytolytic lymphocytes": "cell_type", "CLs": "cell_type" } }, { "input_text": "Since CLs can induce either apoptotic or necrotic cell death , we asked whether E1A sensitization to injury-induced apoptosis is sufficient to explain E1A -induced cytolytic susceptibility .", "target_text": { "CLs": "cell_type", "E1A": "protein" } }, { "input_text": "Mouse , rat , hamster , and human cells that were rendered cytolytic susceptible by E1A were also sensitized to CL-induced and chemically induced apoptosis .", "target_text": { "E1A": "protein" } }, { "input_text": "In contrast , E1A -positive cells were no more susceptible to injury-induced necrosis than E1A -negative cells .", "target_text": { "E1A": "protein", "E1A -positive cells": "cell_type", "E1A -negative cells": "cell_type" } }, { "input_text": "Similar to induction of cytolytic susceptibility and in contrast to other E1A activities , cellular sensitization to chemically induced apoptosis depended on high-level E1A oncoprotein expression .", "target_text": { "E1A": "protein", "oncoprotein": "protein" } }, { "input_text": "Loss of both cytolytic susceptibility and sensitization to chemically induced apoptosis was coselected during in vivo selection of E1A -positive sarcoma cells for increased tumorigenicity .", "target_text": { "E1A": "protein", "E1A -positive sarcoma cells": "cell_type" } }, { "input_text": "Furthermore , E1A mutant proteins that can not bind the cellular transcriptional coactivator , p300 , and that fail to induce cytolytic susceptibility also failed to sensitize cells to injury-induced apoptosis .", "target_text": { "E1A": "protein", "mutant proteins": "protein", "cellular transcriptional coactivator": "protein", "p300": "protein" } }, { "input_text": "These data indicate that E1A induces susceptibility to killer cell-induced lysis through sensitization of cells to injury-induced apoptosis .", "target_text": { "E1A": "protein" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues .", "target_text": { "TCL1 oncogene": "DNA" } }, { "input_text": "AIDS-related non-Hodgkin 's lymphoma ( AIDS NHL ) comprises a diverse and heterogeneous group of high-grade B cell tumors .", "target_text": {} }, { "input_text": "Certain classes of AIDS NHL are associated with alterations in oncogenes or tumor-suppressor genes or infections by oncogenic herpesviruses .", "target_text": { "oncogenes": "DNA", "tumor-suppressor genes": "DNA" } }, { "input_text": "However , the clinically significant class of AIDS NHL designated immunoblastic lymphoma plasmacytoid ( AIDS IBLP ) lacks any consistent genetic alterations .", "target_text": {} }, { "input_text": "We identified the TCL1 oncogene from a set of AIDS IBLP -associated cDNA fragments generated by subtractive hybridization with non- AIDS IBLP .", "target_text": { "TCL1 oncogene": "DNA", "AIDS IBLP -associated cDNA fragments": "DNA" } }, { "input_text": "Aberrant TCL1 expression has been implicated in T cell leukemia/lymphoma development , and its expression also has been seen in many established B cell tumor lines .", "target_text": { "TCL1": "protein", "B cell tumor lines": "cell_line" } }, { "input_text": "However , TCL1 expression has not been reported in AIDS NHL .", "target_text": { "TCL1": "protein" } }, { "input_text": "We find that TCL1 is expressed in the majority of AIDS IBLP tumors examined .", "target_text": { "TCL1": "protein" } }, { "input_text": "TCL1 protein expression is restricted to tumor cells in AIDS IBLP tissue samples analyzed with immunohistochemical staining .", "target_text": { "TCL1": "protein" } }, { "input_text": "Hyperplastic lymph node and tonsil also exhibit strong TCL1 protein expression in mantle zone B cells and in rare interfollicular zone cells , whereas follicle-center B cells ( centroblasts and centrocytes ) show weaker expression .", "target_text": { "TCL1": "protein", "mantle zone B cells": "cell_type", "interfollicular zone cells": "cell_type", "follicle-center B cells": "cell_type", "centroblasts": "cell_type", "centrocytes": "cell_type" } }, { "input_text": "These results establish TCL1 as the most prevalent of all of the surveyed oncogenes associated with AIDS IBLP .", "target_text": { "TCL1": "protein", "oncogenes": "DNA" } }, { "input_text": "They also indicate that abundant TCL1 expression in quiescent mantle zone B cells is down-regulated in activated germinal center follicular B cells in parallel to the known expression pattern of BCL-2 .", "target_text": { "TCL1": "protein", "mantle zone B cells": "cell_type", "quiescent mantle zone B cells": "cell_type", "germinal center follicular B cells": "cell_type", "BCL-2": "protein" } }, { "input_text": "High-level expression in nonproliferating B cells suggests that TCL1 may function in protecting naive preactivated B cells from apoptosis .", "target_text": { "nonproliferating B cells": "cell_type", "TCL1": "protein", "naive preactivated B cells": "cell_type" } }, { "input_text": "IL-2 -independent activation and proliferation in human T cells induced by CD28 .", "target_text": { "IL-2": "protein", "human T cells": "cell_type", "CD28": "protein" } }, { "input_text": "Although the role of CD28 in T cell costimulation is firmly established , the mechanisms by which it exerts its costimulatory actions are less clear .", "target_text": { "CD28": "protein" } }, { "input_text": "In many circumstances it is difficult to distinguish the effects of CD28 from subsequent actions of cytokines , such as IL-2 , on T cell proliferation .", "target_text": { "CD28": "protein", "cytokines": "protein", "IL-2": "protein" } }, { "input_text": "Here , we report a model of CD28 costimulation using PMA plus the natural ligand CD80 that resulted in very limited stimulation of IL-2 , as evidenced by both cytokine production and IL-2 promoter stimulation .", "target_text": { "CD28": "protein", "natural ligand CD80": "protein", "IL-2": "protein", "cytokine": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Promoter assays revealed CD28 -dependent effects on both NF-kappaB and AP-1 , but not on NF-AT or the intact IL-2 promoter .", "target_text": { "CD28": "protein", "NF-kappaB": "protein", "AP-1": "protein", "NF-AT": "protein", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "In addition , T cell proliferation was completely resistant to the actions of the immunosuppressant cyclosporin A ( CsA ) .", "target_text": {} }, { "input_text": "Moreover T cell proliferation was unaffected by the addition of blocking Abs to both IL-2 and the IL-2 receptor , demonstrating that this form of costimulation by CD28 was independent of IL-2 .", "target_text": { "Abs": "protein", "IL-2": "protein", "IL-2 receptor": "protein", "CD28": "protein" } }, { "input_text": "We also investigated the effects of stimulating T cell blasts with CD80 alone and found that there was a limited requirement for IL-2 in this system .", "target_text": { "T cell blasts": "cell_type", "CD80": "protein", "IL-2": "protein" } }, { "input_text": "We conclude that CD28 costimulation can cause substantial T cell proliferation in the absence of IL-2 , which is driven by a soluble factor independent of NF-AT transactivation .", "target_text": { "CD28": "protein", "IL-2": "protein", "soluble factor": "protein", "NF-AT": "protein" } }, { "input_text": "The Epstein-Barr virus latency BamHI-Q promoter is positively regulated by STATs and Zta interference with JAK /STAT activation leads to loss of BamHI-Q promoter activity .", "target_text": { "Epstein-Barr virus latency BamHI-Q promoter": "DNA", "STATs": "protein", "Zta": "protein", "JAK": "protein", "/STAT": "protein", "BamHI-Q promoter": "DNA" } }, { "input_text": "In Epstein-Barr virus ( EBV ) -associated tumors in nonimmunocompromised patients , EBV gene expression is highly restricted .", "target_text": {} }, { "input_text": "EBV-encoded nuclear antigen ( EBNA ) -1 is expressed , whereas the immunogenic and proliferative EBNAs are not .", "target_text": { "EBNA": "protein", "EBV-encoded nuclear antigen ( EBNA ) -1": "protein", "EBNAs": "protein" } }, { "input_text": "This pattern of EBNA expression is generated by usage of the BamHI-Q promoter ( Qp ) .", "target_text": { "EBNA": "protein", "BamHI-Q promoter": "DNA", "Qp": "DNA" } }, { "input_text": "We have determined that the JAK /STAT pathway positively regulates Qp activity .", "target_text": { "JAK": "protein", "/STAT": "protein", "Qp": "DNA" } }, { "input_text": "In transient-transfection assays , a Qp -CAT reporter was activated by cotransfected JAK-1 and by treatment of cells with the cytokine IL-6 .", "target_text": { "Qp": "DNA", "Qp -CAT reporter": "DNA", "JAK-1": "protein", "cytokine": "protein", "IL-6": "protein" } }, { "input_text": "The ability of Qp to bind signal transducer and activator of transcription ( STAT ) proteins was directly demonstrated by electrophoretic mobility-shift assay , and mutation of potential STAT-binding sites reduced Qp responsiveness to Janus kinase ( JAK ) -1 .", "target_text": { "Qp": "DNA", "signal transducer and activator of transcription ( STAT ) proteins": "protein", "STAT-binding sites": "DNA", "Janus kinase ( JAK ) -1": "protein" } }, { "input_text": "Consistent with a role for STATs in Qp function , Qp using Burkitt 's lymphoma Rael cells and cultured nasopharyngeal carcinoma ( NPC ) cells contained nuclear STAT protein .", "target_text": { "STATs": "protein", "Qp": "DNA", "Burkitt 's lymphoma Rael cells": "cell_line", "cultured nasopharyngeal carcinoma ( NPC ) cells": "cell_type", "STAT protein": "protein" } }, { "input_text": "We investigated whether the inability to maintain EBV-positive NPC cell lines in culture was related to Qp activity .", "target_text": { "EBV-positive NPC cell lines": "cell_line", "Qp": "DNA" } }, { "input_text": "Passaging of the NPC cell line HK666 led to activation of expression of BZLF1 , which encodes Zta and loss of Qp function .", "target_text": { "NPC cell line HK666": "cell_line", "BZLF1": "DNA", "Zta": "protein", "Qp": "DNA" } }, { "input_text": "Transient expression assays linked Zta expression to the down-regulation of Qp .", "target_text": { "Zta": "protein", "Qp": "DNA" } }, { "input_text": "Cotransfection of Zta reduced Qp activity in reporter assays .", "target_text": { "Zta": "protein", "Qp": "DNA" } }, { "input_text": "This negative regulation required Zta DNA-binding activity .", "target_text": { "Zta": "protein" } }, { "input_text": "We provide evidence that Zta up-regulation of p53 leads to p53 -mediated interference with JAK /STAT activation of Qp .", "target_text": { "Zta": "protein", "p53": "protein", "JAK": "protein", "/STAT": "protein", "Qp": "DNA" } }, { "input_text": "The data imply that JAK /STAT signaling has a role in EBV-associated malignancies .", "target_text": { "JAK": "protein", "/STAT": "protein" } }, { "input_text": "Reactive oxygen intermediate -release of fibre -exposed monocytes increases inflammatory cytokine -mRNA level , protein tyrosine kinase and NF-kappaB activity in co-cultured bronchial epithelial cells ( BEAS-2B ) .", "target_text": { "fibre -exposed monocytes": "cell_line", "cytokine": "protein", "cytokine -mRNA": "RNA", "protein tyrosine kinase": "protein", "NF-kappaB": "protein", "co-cultured bronchial epithelial cells": "cell_line", "BEAS-2B": "cell_line" } }, { "input_text": "Some pulmonary diseases like bronchitis or asthma bronchiale are mediated by inflammatory mechanisms in bronchial epithelial cells .", "target_text": { "bronchial epithelial cells": "cell_type" } }, { "input_text": "Alveolar macrophages are located directly in the surrounding of these cells , so that we suppose an interaction between epithelial cells and macrophages regarding to the release of inflammatory mediators .", "target_text": { "Alveolar macrophages": "cell_type", "epithelial cells": "cell_type", "macrophages": "cell_type", "inflammatory mediators": "protein" } }, { "input_text": "For measuring the contribution of macrophages to the release of inflammatory mediators by bronchial epithelial cells , we established an in vitro model of co-cultured blood monocytes ( BM ) and BEAS-2B cells in a transwell system ( Costar ) .", "target_text": { "macrophages": "cell_type", "inflammatory mediators": "protein", "epithelial cells": "cell_type", "bronchial epithelial cells": "cell_type", "co-cultured blood monocytes": "cell_type", "BM": "cell_type", "BEAS-2B cells": "cell_line" } }, { "input_text": "BM were exposed to Chrysotile B and soot particle FR 101 in a concentration of 100 microg/10 ( 6 ) cells .", "target_text": { "BM": "cell_type" } }, { "input_text": "After up to 90 min exposure time ELISA , EMSA ( electromobility shift assay ) and RT- PCR were used to measure protein tyrosine kinase activity , protein activity of NF-kappaB and cytokine ( IL-1beta , IL-6 , TNF-alpha ) specific mRNA levels in BEAS-2B cells .", "target_text": { "protein tyrosine kinase": "protein", "NF-kappaB": "protein", "cytokine": "protein", "IL-1beta": "protein", "IL-6": "protein", "TNF-alpha": "protein", "mRNA": "RNA", "BEAS-2B cells": "cell_type" } }, { "input_text": "We observed an increase in protein tyrosine kinase activity ( up to 1.8 +/- 0.5-fold ) and NF-kappaB protein activity in BEAS-2B cells after particle or fibre exposure of co-cultured BM .", "target_text": { "protein tyrosine kinase": "protein", "NF-kappaB": "protein", "BEAS-2B cells": "cell_type", "BM": "cell_type", "co-cultured BM": "cell_line" } }, { "input_text": "Consecutive IL-1beta- , IL-6- and TNF-alpha- mRNA were elevated ( up to 1.9 +/- 0.58-fold ) .", "target_text": {} }, { "input_text": "Protein tyrosine kinase activity , NF-kappaB activity , and the synthesis of cytokine -specific mRNA were inhibited by antioxidants .", "target_text": { "Protein tyrosine kinase": "protein", "NF-kappaB": "protein", "cytokine": "protein", "cytokine -specific mRNA": "RNA" } }, { "input_text": "These data suggest a ROI-dependent NF-kappaB mediated transcription of inflammatory cytokines in bronchial epithelial cells .", "target_text": { "NF-kappaB": "protein", "cytokines": "protein", "inflammatory cytokines": "protein", "epithelial cells": "cell_type", "bronchial epithelial cells": "cell_type" } }, { "input_text": "Suppression of the human immunodeficiency virus long terminal repeat by CD8+ T cells is dependent on the NFAT-1 element .", "target_text": { "human immunodeficiency virus long terminal repeat": "DNA", "CD8+ T cells": "cell_type", "NFAT-1": "protein", "NFAT-1 element": "DNA" } }, { "input_text": "CD8+ T lymphocytes of HIV-1 infected individuals produce a soluble factor that efficiently suppresses HIV-1 replication at the transcriptional level .", "target_text": { "CD8+ T lymphocytes": "cell_type", "soluble factor": "protein" } }, { "input_text": "We show here that the response of the HIV-1 long terminal repeat ( LTR ) to mitogenic or Tat -mediated activation is sensitive to the suppressive action of a Herpesvirus saimiri ( HVS ) -transformed CD8+ T cell clone from an HIV-infected individual and supernatants from CD8+ T cells of HIV-1 -infected asymptomatic subjects ( CD4+ > 350/microliters ) .", "target_text": { "LTR": "DNA", "Tat": "protein", "Herpesvirus saimiri ( HVS ) -transformed CD8+ T cell clone": "cell_line", "CD8+ T cells": "cell_type", "CD4+": "protein" } }, { "input_text": "Mutagenesis of NF kappa B or Sp-1 elements within the LTR resulted in no change in the ability of CD8+ T cell supernatants to inhibit Tat- or mitogen- mediated LTR transcription .", "target_text": { "LTR": "DNA", "CD8+ T cell": "cell_type" } }, { "input_text": "However , the response to HIV-1 Tat by a LTR in which the interleukin ( IL ) -2 homology NFAT-1 region was mutated resulted in almost complete elimination of suppression by CD8+ T cells .", "target_text": { "Tat": "protein", "HIV-1 Tat": "protein", "LTR": "DNA", "NFAT-1": "protein", "interleukin ( IL ) -2 homology NFAT-1 region": "DNA", "CD8+ T cells": "cell_type" } }, { "input_text": "This was not observed when the NFAT-1 mutant LTR was activated by mitogen .", "target_text": { "NFAT-1": "protein", "LTR": "DNA", "NFAT-1 mutant LTR": "DNA", "mitogen": "protein" } }, { "input_text": "We have previously shown that gene expression directed by the HIV-1 NF kappa B elements is inhibited by CD8 + cell- derived supernatants ( Copeland et al. , AIDS Res Hum Retroviruses , 1995 ; 11 : 1321-1326 ) .", "target_text": { "NF kappa B": "protein", "NF kappa B elements": "DNA", "CD8": "protein" } }, { "input_text": "Taken together , these observations suggest that mitogenic activation , mediated primarily through the NF kappa B enhancer , is susceptible to CD8 -mediated inhibition , however , inhibition of Tat -mediated activation may rely upon a different pathway that is NFAT-1 dependent .", "target_text": { "NF kappa B": "protein", "NF kappa B enhancer": "DNA", "CD8": "protein", "Tat": "protein", "NFAT-1": "protein" } }, { "input_text": "Inhibition of NF-kappa B activation in human T-cell lines by anetholdithiolthione .", "target_text": { "NF-kappa B": "protein", "human T-cell lines": "cell_line" } }, { "input_text": "Nuclear factor ( NF ) -kappa B is a redox sensitive cytosolic transcription factor .", "target_text": { "Nuclear factor ( NF ) -kappa B": "protein", "redox sensitive cytosolic transcription factor": "protein" } }, { "input_text": "Redox regulation of NF-kappa B has been implicated in the activation of the human immuno-deficiency virus ( HIV ) .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Therefore , inhibition of NF-kappa B activation may be an effective strategy for acquired immunodeficiency syndrome therapy .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Anetholdithiolthione ( ADT , 5-[p-methoxyphenyl]-3H-1,2-dithiol-3-thione ) is an antioxidant which has been used to protect against acetaminophen- and CCl4- induced hepatotoxicity , lipid peroxidation , radiation injury , and also has been used clinically as an anti-choleretic agent .", "target_text": {} }, { "input_text": "The present study examined the effect of ADT pretreatment on NF-kappa B activation in response to a variety of stimuli such as H2O2 , phorbol myristate acetate ( PMA ) or tumor necrosis factor alpha ( TNF alpha ) .", "target_text": { "NF-kappa B": "protein", "tumor necrosis factor alpha": "protein", "TNF alpha": "protein" } }, { "input_text": "PMA and TNF alpha induced activation of ( NF ) -kappa B in human Jurkat T-cells was partially inhibited by ADT ( 0.1 mM ) pretreatment .", "target_text": { "TNF alpha": "protein", "( NF ) -kappa B": "protein", "Jurkat T-cells": "cell_line" } }, { "input_text": "ADT ( 0.1 mM ) also inhibited H2O2 induced activation of the transcription factor in the peroxide sensitive human Wurzburg T-cells .", "target_text": { "transcription factor": "protein", "peroxide sensitive human Wurzburg T-cells": "cell_line" } }, { "input_text": "Furthermore , ADT treated Wurzburg cells had significantly higher glutathione levels as compared with untreated cells .", "target_text": { "Wurzburg cells": "cell_line", "untreated cells": "cell_type" } }, { "input_text": "H2O2 induced lipid peroxidation in Wurzburg cells was remarkably inhibited by ADT pretreatment .", "target_text": { "Wurzburg cells": "cell_line" } }, { "input_text": "ADT , a pro- glutathione antioxidant , was observed to be capable of modulating NF-kappa B activation .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Involvement of tyrosine phosphorylation in endothelial adhesion molecule induction .", "target_text": { "endothelial adhesion molecule": "protein" } }, { "input_text": "Induction of endothelial adhesion molecules by the cytokine tumor necrosis factor-alpha ( TNF ) can occur independently of protein kinase C and activation of a protein tyrosine kinase ( PTK ) has recently been implicated in the upregulation of vascular cell adhesion molecule 1 ( VCAM-1 ) by interleukin-4 ( IL-4 ) on endothelial cells .", "target_text": { "endothelial adhesion molecules": "protein", "cytokine": "protein", "tumor necrosis factor-alpha": "protein", "TNF": "protein", "protein kinase C": "protein", "protein tyrosine kinase": "protein", "PTK": "protein", "vascular cell adhesion molecule 1": "protein", "VCAM-1": "protein", "interleukin-4": "protein", "IL-4": "protein", "endothelial cells": "cell_type" } }, { "input_text": "We demonstrate that the PTK inhibitors herbimycin A or genistein suppress induction of endothelial VCAM-1 and E-selectin , as well as subsequent monocytic cell adhesion to endothelial cells stimulated by TNF .", "target_text": { "PTK": "protein", "VCAM-1": "protein", "E-selectin": "protein", "endothelial cells": "cell_type", "TNF": "protein" } }, { "input_text": "Inhibition studies indicate that specific tyrosine phosphorylation following PTK activation is involved in the mobilization of the transcription factor , nuclear factor kappa B , and VCAM-1 mRNA expression .", "target_text": { "PTK": "protein", "transcription factor": "protein", "nuclear factor kappa B": "protein", "VCAM-1": "protein", "VCAM-1 mRNA": "RNA" } }, { "input_text": "This may have implications for pathophysiological conditions that involve the upregulation of these molecules ( e.g. inflammation and atherosclerosis ) .", "target_text": {} }, { "input_text": "Protein kinase C-zeta mediates NF-kappa B activation in human immunodeficiency virus -infected monocytes .", "target_text": { "Protein kinase C-zeta": "protein", "NF-kappa B": "protein", "human immunodeficiency virus -infected monocytes": "cell_type" } }, { "input_text": "The molecular mechanisms regulating human immunodeficiency virus ( HIV ) persistence in a major cell reservoir such as the macrophage remain unknown .", "target_text": { "macrophage": "cell_type" } }, { "input_text": "NF-kappa B is a transcription factor involved in the regulation of the HIV long terminal repeat and is selectively activated following HIV infection of human macrophages .", "target_text": { "NF-kappa B": "protein", "transcription factor": "protein", "HIV long terminal repeat": "DNA", "human macrophages": "cell_type" } }, { "input_text": "Although little information as to what signal transduction pathways mediate NF-kappa B activation in monocytes-macrophages is available , our previous work indicated that classical protein kinase C ( PKC ) isoenzymes were not involved in the HIV -mediated NF-kappa B activation .", "target_text": { "NF-kappa B": "protein", "monocytes-macrophages": "cell_type", "protein kinase C": "protein", "PKC": "protein", "protein kinase C ( PKC ) isoenzymes": "protein" } }, { "input_text": "In this study , we have focused on atypical PKC isoenzymes .", "target_text": { "PKC isoenzymes": "protein" } }, { "input_text": "PKC-zeta belongs to this family and is known to be an important step in NF-kappa B activation in other cell systems .", "target_text": { "PKC-zeta": "protein", "NF-kappa B": "protein" } }, { "input_text": "Immunoblotting experiments with U937 cells demonstrate that PKC-zeta is present in these cells , and its expression can be downmodulated by antisense oligonucleotides ( AO ) .", "target_text": { "U937 cells": "cell_line", "PKC-zeta": "protein" } }, { "input_text": "The HIV -mediated NF-kappa B activation is selectively reduced by AO to PKC-zeta .", "target_text": { "NF-kappa B": "protein", "PKC-zeta": "protein" } }, { "input_text": "In addition , cotransfection of a negative dominant molecule of PKC-zeta ( PKC-zeta mut ) with NF-kappa B -dependent reporter genes selectively inhibits the HIV - but not phorbol myristate acetate- or lipopolysaccharide- mediated activation of NF-kappa B .", "target_text": { "PKC-zeta": "protein", "PKC-zeta mut": "protein", "NF-kappa B": "protein" } }, { "input_text": "That PKC-zeta is specific in regulating NF-kappa B is concluded from the inability of PKC-zeta ( mut ) to interfere with the basal or phorbol myristate acetate -inducible CREB - or AP1 -dependent transcriptional activity .", "target_text": { "PKC-zeta": "protein", "NF-kappa B": "protein", "PKC-zeta ( mut )": "protein", "CREB": "protein", "AP1": "protein" } }, { "input_text": "Lastly , we demonstrate a selective inhibition of p24 production by HIV -infected human macrophages when treated with AO to PKC-zeta .", "target_text": { "p24": "protein", "human macrophages": "cell_type", "HIV -infected human macrophages": "cell_type", "PKC-zeta": "protein" } }, { "input_text": "Altogether , these results suggest that atypical PKC isoenzymes , including PKC-zeta , participate in the signal transduction pathways by which HIV infection results in the activation of NF-kappa B in human monocytic cells and macrophages .", "target_text": { "atypical PKC isoenzymes": "protein", "PKC-zeta": "protein", "NF-kappa B": "protein", "human monocytic cells": "cell_type", "macrophages": "cell_type" } }, { "input_text": "Induction of Bcl-x ( L ) expression by human T-cell leukemia virus type 1 Tax through NF-kappaB in apoptosis-resistant T-cell transfectants with Tax .", "target_text": { "Bcl-x ( L )": "protein", "human T-cell leukemia virus type 1 Tax": "protein", "NF-kappaB": "protein", "apoptosis-resistant T-cell transfectants": "cell_line", "Tax": "protein" } }, { "input_text": "Human T-cell leukemia virus type 1 ( HTLV-1 ) Tax is thought to play a pivotal role in immortalization of T cells .", "target_text": { "Tax": "protein", "T cells": "cell_type" } }, { "input_text": "We have recently shown that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced by interleukin-2 ( IL-2 ) deprivation and converted its growth from being IL-2 dependent to being IL-2 independent .", "target_text": { "Tax": "protein", "mouse T-cell line CTLL-2": "cell_line", "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "In this study , we demonstrate that constitutive expression of bcl-xl but not bcl-2 , bcl-xs , bak , bad , or bax was associated with apoptosis resistance after IL-2 deprivation in CTLL-2 cells that expressed Tax .", "target_text": { "bcl-xl": "protein", "bcl-2": "protein", "bcl-xs": "protein", "bak": "protein", "bad": "protein", "bax": "protein", "IL-2": "protein", "CTLL-2 cells": "cell_line", "Tax": "protein" } }, { "input_text": "Transient-transfection assays showed that bcl-x promoter was transactivated by wild-type Tax .", "target_text": { "bcl-x promoter": "DNA", "Tax": "protein", "wild-type Tax": "protein" } }, { "input_text": "Similar effects were observed in mutant Tax retaining transactivating ability through NF-kappaB .", "target_text": { "Tax": "protein", "NF-kappaB": "protein" } }, { "input_text": "Deletion or substitution of a putative NF-kappaB binding site identified in the bcl-x promoter significantly decreased Tax -induced transactivation .", "target_text": { "NF-kappaB": "protein", "putative NF-kappaB binding site": "protein", "bcl-x promoter": "DNA", "Tax": "protein" } }, { "input_text": "This NF-kappaB -like element was able to form a complex with NF-kappaB family proteins in vitro .", "target_text": { "NF-kappaB": "protein", "NF-kappaB -like element": "DNA", "NF-kappaB family proteins": "protein" } }, { "input_text": "Furthermore , Tax -induced transactivation of the bcl-x promoter was also diminished by the mutant IkappaBalpha , which specifically inhibits NF-kappaB activity .", "target_text": { "Tax": "protein", "bcl-x promoter": "DNA", "mutant IkappaBalpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "Our findings suggest that constitutive expression of Bcl-x ( L ) induced by Tax through the NF-kappaB pathway contributes to the inhibition of apoptosis in CTLL-2 cells after IL-2 deprivation .", "target_text": { "Bcl-x ( L )": "protein", "Tax": "protein", "NF-kappaB": "protein", "CTLL-2 cells": "cell_line", "IL-2": "protein" } }, { "input_text": "The beta-globin promoter is important for recruitment of erythroid Kruppel-like factor to the locus control region in erythroid cells .", "target_text": { "beta-globin promoter": "DNA", "erythroid Kruppel-like factor": "protein", "locus control region": "DNA", "erythroid cells": "cell_type" } }, { "input_text": "Erythroid Kruppel-like factor ( EKLF ) , which binds to the CACCC box in the beta-globin promoter , is required for the expression of the beta-globin gene in adult erythroid cells .", "target_text": { "Erythroid Kruppel-like factor": "protein", "EKLF": "protein", "beta-globin promoter": "DNA", "beta-globin gene": "DNA", "adult erythroid cells": "cell_type" } }, { "input_text": "It was recently demonstrated that EKLF is also required for the activity of the beta-globin locus control region ( LCR ) 5'HS3 .", "target_text": { "EKLF": "protein", "beta-globin locus control region": "DNA", "LCR": "DNA", "5'HS3": "DNA" } }, { "input_text": "Some evidence suggests that the LCR and the beta-globin promoter interact in adult erythroid cells , and the network of protein-protein interactions that exists between these two elements may regulate how EKLF is recruited to the LCR .", "target_text": { "LCR": "DNA", "beta-globin promoter": "DNA", "adult erythroid cells": "cell_type", "EKLF": "protein" } }, { "input_text": "In this report , we use the PIN*POINT assay to study the role of the promoter on the recruitment of EKLF to 5'HS2 and 5'HS3 of the LCR .", "target_text": { "EKLF": "protein", "5'HS2": "DNA", "5'HS3": "DNA", "LCR": "DNA" } }, { "input_text": "We find that recruitment of EKLF to 5'HS2 requires the TATA box , but recruitment to 5'HS3 depends on the CACCC and TATA boxes of the beta-globin promoter .", "target_text": { "EKLF": "protein", "5'HS2": "DNA", "TATA box": "DNA", "5'HS3": "DNA", "TATA boxes": "DNA", "beta-globin promoter": "DNA" } }, { "input_text": "Furthermore , recruitment of EKLF to 5'HS3 only occurred in beta-globin-expressing murine erythroid leukemia cells , whereas recruitment of EKLF to 5'HS2 occurred in both gamma-globin-expressing K562 cells and murine erythroid leukemia cells .", "target_text": { "EKLF": "protein", "5'HS3": "DNA", "beta-globin-expressing murine erythroid leukemia cells": "cell_type", "5'HS2": "DNA", "gamma-globin-expressing K562 cells": "cell_line", "murine erythroid leukemia cells": "cell_type" } }, { "input_text": "Unlike EKLF , Sp1 , which also binds to CACCC boxes , is not recruited to 5'HS3 .", "target_text": { "EKLF": "protein", "Sp1": "protein", "5'HS3": "DNA" } }, { "input_text": "We have also examined how one 5'HS affects the recruitment of EKLF to another 5'HS .", "target_text": { "5'HS": "DNA", "EKLF": "protein" } }, { "input_text": "We have found that the recruitment of EKLF to 5'HS3 depends on the presence of 5'HS2 in cis , but the recruitment to 5'HS2 does not depend on 5'HS3 .", "target_text": { "EKLF": "protein", "5'HS3": "DNA", "5'HS2": "DNA" } }, { "input_text": "Based on these results , we present a model that illustrates how EKLF may be recruited to the beta-globin locus .", "target_text": { "EKLF": "protein", "beta-globin locus": "DNA" } }, { "input_text": "Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD .", "target_text": { "TNF": "protein", "JNK": "protein", "c-Jun": "protein", "JunD": "protein" } }, { "input_text": "Central to the bone-sparing effect of estrogen ( E ( 2 ) ) is its ability to block the monocytic production of the osteoclastogenic cytokine TNF-alpha ( TNF ) .", "target_text": { "osteoclastogenic cytokine TNF-alpha": "protein", "TNF": "protein" } }, { "input_text": "However , the mechanism by which E ( 2 ) downregulates TNF production is presently unknown .", "target_text": { "TNF": "protein" } }, { "input_text": "Transient transfection studies in HeLa cells , an E ( 2 ) receptor-negative line , suggest that E ( 2 ) inhibits TNF gene expression through an effect mediated by estrogen receptor beta ( ERbeta ) .", "target_text": { "HeLa cells": "cell_line", "TNF": "protein", "estrogen receptor beta": "protein", "ERbeta": "protein" } }, { "input_text": "We also report that in RAW 264.7 cells , an E ( 2 ) receptor-positive murine monocytic line , E ( 2 ) downregulates cytokine-induced TNF gene expression by decreasing the activity of the Jun NH(2)-terminal kinase ( JNK ) .", "target_text": { "RAW 264.7 cells": "cell_line", "TNF": "protein", "Jun NH(2)-terminal kinase": "protein", "JNK": "protein" } }, { "input_text": "The resulting diminished phosphorylation of c-Jun and JunD at their NH(2)-termini decreases the ability of these nuclear proteins to autostimulate the expression of the c-Jun and JunD genes , thus leading to lower production of c-Jun and JunD .", "target_text": { "c-Jun": "protein", "JunD": "protein", "NH(2)-termini": "protein" } }, { "input_text": "The consequent decrease in the nuclear levels of c-Jun and JunD leads to diminished binding of c-Jun /c-Fos and JunD /c-Fos heterodimers to the AP-1 consensus sequence in the TNF promoter and , thus , to decreased transactivation of the TNF gene .", "target_text": { "c-Jun": "protein", "JunD": "protein", "c-Jun /c-Fos": "protein", "JunD /c-Fos heterodimers": "protein", "AP-1 consensus sequence": "DNA", "TNF": "protein", "TNF promoter": "DNA", "TNF gene": "DNA" } }, { "input_text": "Cutting edge : TCR stimulation by antibody and bacterial superantigen induces Stat3 activation in human T cells .", "target_text": { "TCR": "protein", "Stat3": "protein", "human T cells": "cell_type" } }, { "input_text": "Recent data show that TCR/CD3 stimulation induces activation of Stat5 in murine T cells .", "target_text": { "TCR/CD3": "protein", "Stat5": "protein", "murine T cells": "cell_type" } }, { "input_text": "Here , we show that CD3 ligation by mAb and Staphylococcal enterotoxin ( SE ) induce a rapid , gradually accumulating , long-lasting tyrosine , and serine phosphorylation of Stat3 ( but not Stat5 ) in allogen-specific human CD4+ T cell lines .", "target_text": { "Stat3": "protein", "Stat5": "protein", "allogen-specific human CD4+ T cell lines": "cell_line" } }, { "input_text": "In contrast , IL-2 induces a rapid and transient tyrosine and serine phosphorylation of Stat3 .", "target_text": { "IL-2": "protein", "Stat3": "protein" } }, { "input_text": "Compared with IL-2 , CD3 ligation induces a delayed Stat3 binding to oligonucleotide probes from the ICAM-1 and IL-2R alpha promoter .", "target_text": { "IL-2": "protein", "CD3": "protein", "Stat3": "protein", "ICAM-1": "protein", "IL-2R alpha": "protein", "IL-2R alpha promoter": "DNA" } }, { "input_text": "CD3 -mediated activation of Stat3 is almost completely inhibited by a Src kinase inhibitor ( PP1 ) , whereas IL-2 -induced Stat3 activation is unaffected .", "target_text": { "CD3": "protein", "Stat3": "protein", "Src kinase inhibitor": "protein", "PP1": "protein", "IL-2": "protein" } }, { "input_text": "In conclusion , we show that CD3 ligation by mAb and SE triggers a rapid , PP1 -sensitive tyrosine and serine phosphorylation of Stat3 in human CD4+ T cells .", "target_text": { "CD3": "protein", "mAb": "protein", "PP1": "protein", "Stat3": "protein", "T cells": "cell_type", "human CD4+ T cells": "cell_type" } }, { "input_text": "Moreover , we provide evidence that TCR/ CD3 and IL-2 induce Stat3 activation via distinct signaling pathways .", "target_text": { "CD3": "protein", "TCR/ CD3": "protein", "IL-2": "protein", "Stat3": "protein" } }, { "input_text": "Distinctive gene expression patterns in human mammary epithelial cells and breast cancers .", "target_text": { "human mammary epithelial cells": "cell_type" } }, { "input_text": "cDNA microarrays and a clustering algorithm were used to identify patterns of gene expression in human mammary epithelial cells growing in culture and in primary human breast tumors .", "target_text": { "cDNA microarrays": "DNA", "human mammary epithelial cells": "cell_type" } }, { "input_text": "Clusters of coexpressed genes identified through manipulations of mammary epithelial cells in vitro also showed consistent patterns of variation in expression among breast tumor samples .", "target_text": { "coexpressed genes": "DNA", "mammary epithelial cells": "cell_type" } }, { "input_text": "By using immunohistochemistry with antibodies against proteins encoded by a particular gene in a cluster , the identity of the cell type within the tumor specimen that contributed the observed gene expression pattern could be determined .", "target_text": {} }, { "input_text": "Clusters of genes with coherent expression patterns in cultured cells and in the breast tumors samples could be related to specific features of biological variation among the samples .", "target_text": { "genes": "DNA", "cultured cells": "cell_type" } }, { "input_text": "Two such clusters were found to have patterns that correlated with variation in cell proliferation rates and with activation of the IFN -regulated signal transduction pathway , respectively .", "target_text": { "IFN": "protein" } }, { "input_text": "Clusters of genes expressed by stromal cells and lymphocytes in the breast tumors also were identified in this analysis .", "target_text": { "genes": "DNA", "stromal cells": "cell_type", "lymphocytes": "cell_type" } }, { "input_text": "These results support the feasibility and usefulness of this systematic approach to studying variation in gene expression patterns in human cancers as a means to dissect and classify solid tumors .", "target_text": {} }, { "input_text": "PPARgamma activation induces the expression of the adipocyte fatty acid binding protein gene in human monocytes .", "target_text": { "PPARgamma": "protein", "adipocyte fatty acid binding protein": "protein", "adipocyte fatty acid binding protein gene": "DNA", "human monocytes": "cell_type" } }, { "input_text": "The peroxisome-proliferator activated receptor gamma ( PPARgamma ) , a member of the nuclear receptor superfamily of ligand activated transcription factors , plays a key role in the anti-diabetic actions of the thiazolidinediones ( TZDs ) .", "target_text": { "peroxisome-proliferator activated receptor gamma": "protein", "PPARgamma": "protein", "nuclear receptor superfamily": "protein", "ligand activated transcription factors": "protein" } }, { "input_text": "PPARgamma induces the expression of many genes involved in lipid anabolism , including the adipocyte fatty acid binding protein ( aP2 ) , and is a key regulator of adipocyte differentiation .", "target_text": { "PPARgamma": "protein", "genes": "DNA", "adipocyte fatty acid binding protein": "protein", "aP2": "protein", "adipocyte": "cell_type" } }, { "input_text": "PPARgamma is also expressed in hematopoietic cells and is up-regulated in activated monocytes/ macrophages .", "target_text": { "PPARgamma": "protein", "hematopoietic cells": "cell_type", "macrophages": "cell_type", "monocytes/ macrophages": "cell_type" } }, { "input_text": "Activation of PPARgamma may play a role in the induction of differentiation of macrophages to foam cells that are associated with atherosclerotic lesions .", "target_text": { "PPARgamma": "protein", "macrophages": "cell_type", "foam cells": "cell_type" } }, { "input_text": "We report that both natural and synthetic PPARgamma agonists induce time- and dose-dependent increases in aP2 mRNA in both primary human monocytes and the monocytic cell line , THP-1 .", "target_text": { "aP2": "protein", "aP2 mRNA": "RNA", "human monocytes": "cell_type", "primary human monocytes": "cell_type", "monocytic cell line": "cell_line", "THP-1": "cell_line" } }, { "input_text": "These data suggest that PPARgamma activation may play a role in monocyte differentiation and function analogous to its well-characterized role in adipocytes .", "target_text": { "PPARgamma": "protein", "monocyte": "cell_type", "adipocytes .": "cell_type" } }, { "input_text": "Identification of a physical interaction between calcineurin and nuclear factor of activated T cells ( NFATp ) .", "target_text": { "calcineurin": "protein", "nuclear factor of activated T cells": "protein", "NFATp": "protein" } }, { "input_text": "In T lymphocytes , the calcium/calmodulin-dependent serine/threonine phosphatase , calcineurin , plays a pivotal role in transducing membrane-associated signals to the nucleus .", "target_text": { "T lymphocytes": "cell_type", "calcium/calmodulin-dependent serine/threonine phosphatase": "protein", "calcineurin": "protein" } }, { "input_text": "One of the putative targets of calcineurin is the pre-existing , cytosolic component of the nuclear factor of activated T cells ( NFATp ; also referred to as NFAT1 ) , which is one of several transcription factors required for the expression of interleukin 2 .", "target_text": { "calcineurin": "protein", "cytosolic component": "protein", "nuclear factor of activated T cells": "protein", "NFATp": "protein", "NFAT1": "protein", "transcription factors": "protein", "interleukin 2": "protein" } }, { "input_text": "Inhibition of calcineurin by the immunosuppressive drugs cyclosporin A and FK506 prevents dephosphorylation of NFATp and its translocation to the nucleus .", "target_text": { "calcineurin": "protein", "NFATp": "protein" } }, { "input_text": "However , a physical interaction between calcineurin and NFATp has not been demonstrated .", "target_text": { "calcineurin": "protein", "NFATp": "protein" } }, { "input_text": "Here we demonstrate the binding of NFATp from lysates of T cells to immobilized calcineurin .", "target_text": { "NFATp": "protein", "T cells": "cell_type", "calcineurin": "protein" } }, { "input_text": "Stimulation of T cells with calcium ionophore induced a shift in the molecular weight of NFATp that is due to its dephosphorylation .", "target_text": { "T cells": "cell_type", "NFATp": "protein" } }, { "input_text": "This dephosphorylation was inhibited by treatment of T cells with cyclosporin A or FK506 prior to stimulation .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Of note , both the phosphorylated and the dephosphorylated form of NFATp bound to calcineurin .", "target_text": { "NFATp": "protein", "calcineurin": "protein" } }, { "input_text": "Furthermore , the binding of both forms of NFATp to calcineurin was inhibited by pretreatment of calcineurin with a complex of FK506 and its ligand FKBP12 .", "target_text": { "NFATp": "protein", "calcineurin": "protein" } }, { "input_text": "Taken together these data strongly suggest a direct interaction of calcineurin with NFATp and that this interaction does not depend upon the phosphorylation sites of NFATp affected by activation .", "target_text": { "calcineurin": "protein", "NFATp": "protein", "phosphorylation sites": "DNA" } }, { "input_text": "Cross-linking CD40 on B cells preferentially induces stress-activated protein kinases rather than mitogen-activated protein kinases .", "target_text": { "CD40": "protein", "B cells": "cell_type", "stress-activated protein kinases": "protein", "mitogen-activated protein kinases": "protein" } }, { "input_text": "The B cell-associated surface molecule CD40 plays a key role in T cell-dependent B cell maturation , as individuals with defects in either CD40 or its ligand are impaired in immunoglobulin isotype class switching and germinal center formation .", "target_text": { "B cell-associated surface molecule": "protein", "CD40": "protein", "immunoglobulin": "protein" } }, { "input_text": "CD40 signaling activates downstream effectors , including the tyrosine protein kinase , Lyn , the phosphatidylinositol-3-kinase ( PI-3 kinase ) , and the transcription factor , NF-kappa B .", "target_text": { "CD40": "protein", "downstream effectors": "protein", "tyrosine protein kinase": "protein", "Lyn": "protein", "phosphatidylinositol-3-kinase": "protein", "PI-3 kinase": "protein", "NF-kappa B": "protein" } }, { "input_text": "In this study , we demonstrate that stress-activated protein kinases ( SAPK ) are activated after CD40 cross-linking on various B cell lines or human tonsillar B cells .", "target_text": { "stress-activated protein kinases": "protein", "SAPK": "protein", "CD40": "protein", "B cell lines": "cell_line", "B cells": "cell_type", "human tonsillar B cells": "cell_type" } }, { "input_text": "The activation is rapid and transient and is mediated through a cyclosporin A -insensitive pathway .", "target_text": {} }, { "input_text": "Furthermore , this signaling pathway appears not to rely on protein kinase C .", "target_text": { "protein kinase C": "protein" } }, { "input_text": "While CD40 ligation strongly activates the SAPKs ( up to 25-fold ) , it does not affect members of the mitogen-activated protein kinase family ( MAPK ; ERK1 and ERK2 ) .", "target_text": { "CD40": "protein", "SAPKs": "protein", "mitogen-activated protein kinase family": "protein", "MAPK": "protein", "ERK1": "protein", "ERK2": "protein" } }, { "input_text": "Consistent with these data , CD40 signals up-regulate c-jun but not c-fos mRNA and alter the transcription factor ATF2 but not the Raf-1 protein .", "target_text": { "CD40": "protein", "transcription factor": "protein", "ATF2": "protein", "Raf-1 protein": "protein" } }, { "input_text": "In summary , CD40 signaling preferentially induces SAPK but not MAPK .", "target_text": { "CD40": "protein", "SAPK": "protein", "MAPK": "protein" } }, { "input_text": "Stimulation of the T-cell antigen receptor-CD3 complex signaling pathway by the tyrosine phosphatase inhibitor pervanadate is mediated by inhibition of CD45 : evidence for two interconnected Lck/Fyn- or zap-70- dependent signaling pathways .", "target_text": { "T-cell antigen receptor-CD3 complex": "protein", "tyrosine phosphatase": "protein", "CD45": "protein" } }, { "input_text": "The tyrosine phosphatase specific inhibitor pervanadate is a potent activator of T lymphocytes through induction of tyrosine phosphorylation and downstream events of the activation cascade .", "target_text": { "tyrosine phosphatase": "protein", "T lymphocytes": "cell_type", "tyrosine phosphorylation": "protein" } }, { "input_text": "Using CD45- or CD3- negative variants of the Jurkat leukemic T-cell line we show that the different biochemical events induced by pervanadate appeared to be dependent on the presence at the cell surface of either CD45 or CD3 .", "target_text": { "Jurkat leukemic T-cell line": "cell_line", "CD45": "protein", "CD3": "protein" } }, { "input_text": "CD45 -dependent events such as tyrosine phosphorylation of Shc , activation of nuclear factor-kappa B ( NF-kappa B ) , activator protein-1 ( AP-1 ) , transcription factors , and stimulation of interleukin-2 ( IL-2 ) promoter and of CD69 and CD25 surface expression paralleled activation of the tyrosine kinases lck and fyn .", "target_text": { "CD45": "protein", "tyrosine phosphorylation": "protein", "Shc": "protein", "nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "activator protein-1": "protein", "AP-1": "protein", "transcription factors": "protein", "interleukin-2": "protein", "IL-2": "protein", "interleukin-2 ( IL-2 ) promoter": "DNA", "CD69": "protein", "CD25": "protein", "tyrosine kinases": "protein", "lck": "protein", "fyn": "protein" } }, { "input_text": "By contrast , stimulation of calcium influx , a CD3 -dependent event , paralleled zap-70 activation .", "target_text": { "CD3": "protein", "zap-70": "protein" } }, { "input_text": "The data demonstrate that the T-cell antigen receptor -CD3 ( TcR- CD3 ) complex is functionally linked to two different protein tyrosine kinase ( PTK ) modules with separate specific functions and that CD45 may be an important regulator of this coupling .", "target_text": { "-CD3": "protein", "CD3": "protein", "-CD3 ( TcR- CD3 ) complex": "protein", "protein tyrosine kinase": "protein", "PTK": "protein", "CD45": "protein" } }, { "input_text": "Vitamin D analogs , 20-Epi-22-oxa-24a,26a,27a,-trihomo-1alpha,25(OH)2- vitamin D3 , 1,24(OH)2-22-ene-24-cyclopropyl-vitamin D3 and 1alpha,25(OH)2-lumisterol3 prime NB4 leukemia cells for monocytic differentiation via nongenomic signaling pathways , involving calcium and calpain .", "target_text": { "NB4 leukemia cells": "cell_line" } }, { "input_text": "Side-chain modified vitamin D analogs including 20-Epi-22-oxa-24a,26a,27a-trihomo-1alpha,2 5-dihydroxyvitamin D3 ( KH1060 ) , and 1,24-dihydroxy-22-ene-24-cyclopropyl-vitamin D3 ( MC903 ) were originally designed to aid in the treatment of hyperproliferative disorders including psoriasis and cancer .", "target_text": {} }, { "input_text": "Here we demonstrate that these analogs , as well as the 6-cis-locked conformer , 1alpha,25-dihydroxy-lumisterol3 ( JN ) prime NB4 cells for monocytic differentiation .", "target_text": { "1alpha,25-dihydroxy-lumisterol3 ( JN ) prime NB4 cells": "cell_line" } }, { "input_text": "Previously , the action of MC903 and KH1060 was presumed to be mediated by the nuclear vitamin D receptor ( VDRnuc ) .", "target_text": { "nuclear vitamin D receptor": "protein", "VDRnuc": "protein" } }, { "input_text": "Differentiation in response to all analogs was shown to be inhibited by 1beta,25-dihydroxyvitamin D3 ( HL ) , the antagonist to the nongenomic activities of 1,25D3 .", "target_text": {} }, { "input_text": "These data suggest that although MC903 and KH1060 may bind the VDRnuc , that the differentiative activities of these agents requires nongenomic signaling pathways .", "target_text": { "VDRnuc": "protein" } }, { "input_text": "Here we show that 1alpha,25(OH)2-d5-previtamin D3 ( HF ) , JN , KH1060 , and MC903 induce expression of PKC alpha and PKC delta and translocation of both isoforms to the particulate fraction , and PKC alpha to the nuclear fraction .", "target_text": { "PKC alpha": "protein", "PKC delta": "protein" } }, { "input_text": "The full differentiation response with combinations of analogs and TPA was inhibited 50 % by the membrane permeable Ca2+ chelator , 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid ( BAPTA-AM ) or calpain inhibitor I .", "target_text": { "calpain": "protein" } }, { "input_text": "These data demonstrate that intracellular free calcium and the calcium -dependent protease , calpain play critical roles in monocytic differentiation .", "target_text": { "calcium -dependent protease": "protein", "calpain": "protein" } }, { "input_text": "Intracellular calcium appears to be most critical in the 1,25D3 -priming stage of differentiation , while calpain is essential in the TPA maturation response .", "target_text": { "calpain": "protein" } }, { "input_text": "Neutrophil maturation and the role of retinoic acid .", "target_text": { "Neutrophil": "cell_type" } }, { "input_text": "Neutrophil maturation occurs in well defined morphological stages that correlate with the acquisition of molecular markers associated with neutrophil function .", "target_text": { "Neutrophil": "cell_type", "molecular markers": "protein" } }, { "input_text": "A variety of factors are known to play a role in terminal neutrophil maturation , including the vitamin A derivative , retinoic acid .", "target_text": { "neutrophil": "cell_type" } }, { "input_text": "Retinoic acid can directly modulate gene expression via binding to its nuclear receptors , which can , in turn , activate transcription of target genes .", "target_text": { "nuclear receptors": "protein", "target genes": "DNA" } }, { "input_text": "A role for retinoic acid during neutrophil maturation has been suggested from a variety of sources . Here we present a review of the mechanism of retinoic acid receptor action and the major evidence showing that normal retinoid signaling is required for neutrophil maturation .", "target_text": { "neutrophil": "cell_type", "retinoic acid receptor": "protein" } }, { "input_text": "Human T-cell lymphotrophic virus type-I tax gene induces secretion of human macrophage inflammatory protein-1alpha .", "target_text": { "Human T-cell lymphotrophic virus type-I tax gene": "DNA", "human macrophage inflammatory protein-1alpha": "protein" } }, { "input_text": "Human T-cell lymphotropic virus I ( HTLV-I ) encodes for a 40-kDa protein , Tax , which is important for the immortalization of T cells .", "target_text": { "40-kDa protein": "protein", "Tax": "protein", "T cells": "cell_type" } }, { "input_text": "Tax has been shown to transactivate several cellular genes .", "target_text": { "Tax": "protein", "cellular genes": "DNA" } }, { "input_text": "In this study , we show that MIP-1alpha is selectively expressed and secreted in the tax transfected Jurkat cell line upon mitogen stimulation .", "target_text": { "MIP-1alpha": "protein", "tax transfected Jurkat cell line": "cell_line", "mitogen": "protein" } }, { "input_text": "Expression of MIP-1alpha-R mRNA in these cells suggests an autocrine role for this chemokine in HTLV-I infected T-cells .", "target_text": { "MIP-1alpha-R": "protein", "MIP-1alpha-R mRNA": "RNA", "chemokine": "protein", "HTLV-I infected T-cells": "cell_type" } }, { "input_text": "Induced MIP-1alpha expression and secretion in PMA/PHA stimulated tax transfected cells correlate with the noninduction of MNP-1 transcription factor , which is intimately involved in downmodulating the MIP-1alpha gene .", "target_text": { "MIP-1alpha": "protein", "PMA/PHA stimulated tax transfected cells": "cell_line", "MNP-1": "protein", "transcription factor": "protein", "MIP-1alpha gene": "DNA" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "Dendritic cells and the pathogenesis of rheumatoid arthritis .", "target_text": { "Dendritic cells": "cell_type" } }, { "input_text": "Rheumatoid arthritis ( RA ) is a chronic autoimmune inflammatory disease in which unknown arthrogenic autoantigen is presented to CD4 + T cells .", "target_text": { "arthrogenic autoantigen": "protein", "CD4": "protein", "CD4 + T cells": "cell_type" } }, { "input_text": "The strong association of the disease with an epitope within the HLA-DR chain shared between various alleles of HLA-DR4 and DR1 emphasizes the importance of antigen presentation .", "target_text": { "epitope": "protein", "HLA-DR chain": "protein", "HLA-DR4": "protein", "DR1": "protein" } }, { "input_text": "This immune response predominantly occurs in the synovial tissue and fluid of the joints and autoreactive T cells are readily demonstrable in both the synovial compartment and blood .", "target_text": { "T cells": "cell_type", "autoreactive T cells": "cell_type" } }, { "input_text": "Circulating dendritic cells ( DC ) are phenotypically and functionally identical with normal peripheral blood ( PB ) DC .", "target_text": { "Circulating dendritic cells": "cell_type", "DC": "cell_type", "normal peripheral blood ( PB ) DC": "cell_type" } }, { "input_text": "In the synovial tissue , fully differentiated perivascular DC are found in close association with T cells and with B cell follicles , sometimes containing follicular DC .", "target_text": { "perivascular DC": "cell_type", "T cells": "cell_type", "B cell follicles": "cell_type", "follicular DC": "cell_type" } }, { "input_text": "These perivascular DC migrate across the activated endothelium from blood and receive differentiative signals within the joint from monocyte-derived cytokines and CD40 -ligand+ T cells .", "target_text": { "perivascular DC": "cell_type", "monocyte-derived cytokines": "protein", "CD40": "protein", "T cells": "cell_type", "CD40 -ligand+ T cells": "cell_type" } }, { "input_text": "In the SF , DC manifest an intermediate phenotype , similar to that of monocyte-derived DC in vitro .", "target_text": { "DC": "cell_type", "monocyte-derived DC": "cell_type" } }, { "input_text": "Like a delayed-type hypersensitivity response , the rheumatoid synovium represents an effector site .", "target_text": {} }, { "input_text": "DC at many effector sites have a characteristic pattern of infiltration and differentiation .", "target_text": {} }, { "input_text": "It is important to note that the effector response is not self-limiting in RA autoimmune inflammation .", "target_text": {} }, { "input_text": "In this article , we argue that the presentation of self-antigen by DC and by autoantibody-producing B cells is critical for the perpetuation of the autoimmune response .", "target_text": { "self-antigen": "protein", "DC": "cell_type", "B cells": "cell_type", "autoantibody-producing B cells": "cell_type" } }, { "input_text": "Permanently arresting this ongoing immune response with either pharmaceutical agents or immunotherapy is a major challenge for immunology .", "target_text": {} }, { "input_text": "Thymocyte-thymic epithelial cell interaction leads to high-level replication of human immunodeficiency virus exclusively in mature CD4 (+) CD8(-) CD3 (+) thymocytes : a critical role for tumor necrosis factor and interleukin-7 .", "target_text": { "epithelial cell": "cell_type", "CD4": "protein", "CD3": "protein", "mature CD4 (+) CD8(-) CD3 (+) thymocytes": "cell_type", "tumor necrosis factor": "protein", "interleukin-7": "protein" } }, { "input_text": "This work aims at identifying the thymocyte subpopulation able to support human immunodeficiency virus ( HIV ) replication under the biological stimuli of the thymic microenvironment .", "target_text": {} }, { "input_text": "In this report we demonstrate that interaction with thymic epithelial cells ( TEC ) induces a high-level replication of the T-tropic primary isolate HIV-1 ( B-LAIp ) exclusively in the mature CD4 (+) CD8(-) CD3 (+) thymocytes .", "target_text": { "thymic epithelial cells": "cell_type", "TEC": "cell_type", "T-tropic primary isolate HIV-1": "protein", "B-LAIp": "protein", "CD4": "protein", "CD3": "protein", "CD4 (+) CD8(-) CD3 (+) thymocytes": "cell_type" } }, { "input_text": "Tumor necrosis factor ( TNF ) and interleukin-7 ( IL-7 ) , secreted during this interaction , are critical cytokines for HIV long terminal repeat transactivation through NF-kappaB -dependent activation .", "target_text": { "Tumor necrosis factor": "protein", "TNF": "protein", "interleukin-7": "protein", "IL-7": "protein", "HIV long terminal repeat": "DNA", "NF-kappaB": "protein" } }, { "input_text": "TNF is the major inducer of NF-kappaB and particularly of the p50-p65 complex , whereas IL-7 acts as a cofactor by sustaining the expression of the p75 TNF receptor .", "target_text": { "TNF": "protein", "NF-kappaB": "protein", "p50-p65 complex": "protein", "IL-7": "protein", "p75 TNF receptor": "protein" } }, { "input_text": "The requirement for TNF is further confirmed by the observation that the inability of the intermediate CD4 (+) CD8(-) CD3 (-) thymocytes to replicate the virus is associated with a defect in TNF production during their interaction with TEC and correlates with the absence of nuclear NF-kappaB activity in these freshly isolated thymocytes .", "target_text": { "TNF": "protein", "CD4": "protein", "CD3": "protein", "intermediate CD4 (+) CD8(-) CD3 (-) thymocytes": "cell_type", "TEC": "cell_type", "NF-kappaB": "protein", "freshly isolated thymocytes": "cell_type" } }, { "input_text": "Addition of exogenous TNF to the intermediate thymocyte cultures induces NF-kappaB activity and is sufficient to promote HIV replication in the cocultures with TEC .", "target_text": { "TNF": "protein", "intermediate thymocyte cultures": "cell_line", "NF-kappaB": "protein", "TEC": "cell_type" } }, { "input_text": "The other major subpopulation expressing the CD4 receptor , namely , the double-positive ( DP ) CD4 (+) CD8(+) CD3 (+/-) thymocytes , despite the entry of the virus , do not produce a significant level of virus , presumably because they are unresponsive to TNF and IL-7 .", "target_text": { "CD4": "protein", "CD4 receptor": "protein", "CD3": "protein", "double-positive ( DP ) CD4 (+) CD8(+) CD3 (+/-) thymocytes": "cell_type", "TNF": "protein", "IL-7": "protein" } }, { "input_text": "Together , these data suggest that in vivo , despite an efficient entry of the virus in all the CD4 (+) subpopulations , a high viral load may be generated exclusively within the mature CD4 (+) CD8(-) CD3 (+) subset of thymocytes .", "target_text": { "CD4": "protein", "CD4 (+) subpopulations": "cell_type", "CD3": "protein", "mature CD4 (+) CD8(-) CD3 (+) subset of thymocytes": "cell_type" } }, { "input_text": "However , under conditions of inflammatory response after infection , TNF might also be present in the intermediate thymocyte compartment , leading to efficient HIV replication in these cells .", "target_text": { "TNF": "protein", "intermediate thymocyte compartment": "cell_type" } }, { "input_text": "NF-kappaB -mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes .", "target_text": { "NF-kappaB": "protein", "NF-kappaB -mediated up-regulation": "cell_type", "Bcl-x": "protein", "Bfl-1/A1": "protein", "CD40": "protein", "B lymphocytes": "cell_type" } }, { "input_text": "Activation of CD40 is essential for thymus-dependent humoral immune responses and rescuing B cells from apoptosis .", "target_text": { "CD40": "protein", "B cells": "cell_type" } }, { "input_text": "Many of the effects of CD40 are believed to be achieved through altered gene expression .", "target_text": { "CD40": "protein" } }, { "input_text": "In addition to Bcl-x , a known CD40 -regulated antiapoptotic molecule , we identified a related antiapoptotic molecule , A1/Bfl-1 , as a CD40 -inducible gene .", "target_text": { "Bcl-x": "protein", "CD40": "protein", "CD40 -regulated antiapoptotic molecule": "protein", "antiapoptotic molecule": "protein", "A1/Bfl-1": "protein", "CD40 -inducible gene": "DNA" } }, { "input_text": "Inhibition of the NF-kappaB pathway by overexpression of a dominant-active inhibitor of NF-kappaB abolished CD40 -induced up-regulation of both the Bfl-1 and Bcl-x genes and also eliminated the ability of CD40 to rescue Fas -induced cell death .", "target_text": { "NF-kappaB": "protein", "CD40": "protein", "Bfl-1": "protein", "Bcl-x": "protein", "Fas": "protein" } }, { "input_text": "Within the upstream promoter region of Bcl-x , a potential NF-kappaB -binding sequence was found to support NF-kappaB -dependent transcriptional activation .", "target_text": { "upstream promoter region": "DNA", "Bcl-x": "protein", "NF-kappaB": "protein", "NF-kappaB -binding sequence": "DNA" } }, { "input_text": "Furthermore , expression of physiological levels of Bcl-x protected B cells from Fas-mediated apoptosis in the absence of NF-kappaB signaling .", "target_text": { "Bcl-x": "protein", "B cells": "cell_type", "Bcl-x protected B cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "Thus , our results suggest that CD40 -mediated cell survival proceeds through NF-kappaB -dependent up-regulation of Bcl-2 family members .", "target_text": { "CD40": "protein", "NF-kappaB": "protein", "Bcl-2 family members": "protein" } }, { "input_text": "Stimulation of neutrophil interleukin-8 production by eosinophil granule major basic protein .", "target_text": { "neutrophil": "cell_type", "interleukin-8": "protein", "eosinophil granule major basic protein": "protein" } }, { "input_text": "We evaluated the ability of eosinophil granule major basic protein ( MBP ) to stimulate interleukin ( IL ) -8 production by neutrophils .", "target_text": { "eosinophil granule major basic protein": "protein", "MBP": "protein", "interleukin ( IL ) -8": "protein", "neutrophils": "cell_type" } }, { "input_text": "MBP over the concentration range of 0.1 to 10 microM stimulated the release of up to approximately 8 ng/ml IL-8 .", "target_text": { "MBP": "protein", "IL-8": "protein" } }, { "input_text": "Incubation with 2 microM MBP showed that , after a 1 h lag , the level of IL-8 release increased with time for approximately 10 h .", "target_text": { "MBP": "protein", "IL-8": "protein" } }, { "input_text": "At the 2 microM concentration , eosinophil cationic protein , eosinophil-derived neurotoxin , and eosinophil peroxidase did not stimulate significant levels of IL-8 production .", "target_text": { "eosinophil cationic protein": "protein", "eosinophil peroxidase": "protein", "IL-8": "protein" } }, { "input_text": "MBP stimulated 2-fold increases in IL-8 messenger RNA ( mRNA ) after 1 and 3 h of incubation , which were blocked by pretreatment with actinomycin D .", "target_text": { "MBP": "protein", "IL-8": "protein", "IL-8 messenger RNA": "RNA", "mRNA": "RNA" } }, { "input_text": "However , stimulation with MBP did not produce an increase in the binding activity of nuclear factor ( NF ) -kappaB or activator protein-1 .", "target_text": { "MBP": "protein", "nuclear factor ( NF ) -kappaB": "protein", "activator protein-1": "protein" } }, { "input_text": "No NF-IL-6 binding activity was detected in the same nuclear extracts .", "target_text": { "NF-IL-6": "protein" } }, { "input_text": "In addition , stimulation with MBP prolonged the stability of IL-8 mRNA .", "target_text": { "MBP": "protein", "IL-8": "protein", "IL-8 mRNA": "RNA" } }, { "input_text": "MBP also induced transient increases in mRNA for macrophage inflammatory protein ( MIP ) -1alpha and MIP-1beta , but did not stimulate the release of either chemokine .", "target_text": { "MBP": "protein", "mRNA": "RNA", "macrophage inflammatory protein ( MIP ) -1alpha": "protein", "MIP-1beta": "protein", "chemokine": "protein" } }, { "input_text": "These findings indicate that MBP is selective among the eosinophil granule proteins as a stimulus for neutrophil IL-8 release and , further , that stimulation of neutrophil IL-8 release by MBP involves both transcriptional and posttranscriptional regulation .", "target_text": { "MBP": "protein", "eosinophil granule proteins": "protein", "neutrophil": "cell_type", "IL-8": "protein" } }, { "input_text": "We postulate that MBP -induced release of IL-8 by neutrophils may contribute to the pathophysiology of acute asthma and other inflammatory lung diseases .", "target_text": { "MBP": "protein", "IL-8": "protein", "neutrophils": "cell_type" } }, { "input_text": "Expression of either the TCL1 oncogene , or transcripts from its homologue MTCP1/c6.1B , in leukaemic and non-leukaemic T cells from ataxia telangiectasia patients .", "target_text": { "TCL1 oncogene": "DNA", "MTCP1/c6.1B": "DNA", "non-leukaemic T cells": "cell_type" } }, { "input_text": "Patients with the recessively inherited disorder ataxia telangiectasia ( A-T ) have a high level of specific chromosome translocations which can be easily observed in peripheral T cells and show a greatly increased predisposition to leukaemia/lymphoma , mainly of T cell origin .", "target_text": { "chromosome translocations": "DNA", "peripheral T cells": "cell_type", "T cell": "cell_type" } }, { "input_text": "Some translocation cells proliferate into a large clone and may develop into T cell prolymphocytic leukaemia ( T-PLL ) .", "target_text": { "translocation cells": "cell_type" } }, { "input_text": "By the time of diagnosis of T-PLL , the clone contains many more genetic changes in the form of additional translocations .", "target_text": {} }, { "input_text": "T-PLL is also seen in non- A-T individuals where expression of either TCL1 ( at 14q32 ) or the c6.1B/MTCP1 A1 transcript ( at-Xq28 ) has been demonstrated in just a few instances .", "target_text": { "TCL1": "protein", "14q32": "DNA", "c6.1B/MTCP1 A1 transcript": "protein", "at-Xq28": "DNA" } }, { "input_text": "We show here , that expression of TCL1 occurs in leukaemic T cells from A-T patients with chromosome 14 rearrangements .", "target_text": { "TCL1": "protein", "leukaemic T cells": "cell_type", "chromosome 14": "DNA" } }, { "input_text": "Expression of TCL1 also occurs in the preleukaemic clone cells of A-T patients containing the primary translocation alone .", "target_text": { "TCL1": "protein", "preleukaemic clone cells": "cell_type" } }, { "input_text": "Some expression of TCL1 could also be detected in randomly selected A-T patients without large cytogenetic clones and without any evidence of leukaemic change .", "target_text": { "TCL1": "protein" } }, { "input_text": "We also show that expression of the B1 transcript from a second gene , MTCP1 , occurred at a relatively high level only in two T-PLL tumours from A-T patients with t(X;14) translocations whereas the MTCP1 /A1 transcript is much more widely expressed in both tumour and non tumour cells of A-T and non- A-T individuals .", "target_text": { "B1 transcript": "RNA", "MTCP1": "DNA", "MTCP1 /A1 transcript": "RNA" } }, { "input_text": "[ Correlation of lymphocytic infiltration of tumor tissue with the hormonal and metabolic state in patients with breast cancer ]", "target_text": {} }, { "input_text": "Lymphocyte infiltration of tumor was studied vis-a-vis hormone metabolic status , tumor tissue hormone sensitivity and tobacco smoking , in 113 breast cancer patients , aged 25-77 .", "target_text": {} }, { "input_text": "On the average , no correlation was established between degree of lymphocyte infiltration in breast tumor and age and menopause onset .", "target_text": {} }, { "input_text": "In smoking menopausal patients , lymphocyte infiltration was found to be higher than in non-smokers ( p < 0.05 ) .", "target_text": {} }, { "input_text": "There was a direct correlation between the rate of lymphocyte infiltration and the level of progesterone receptors in tumor .", "target_text": { "progesterone receptors": "protein" } }, { "input_text": "Some subgroups displayed a direct correlation between infiltration and sex-binding globulin , cholesterol , luteinizing hormone in blood , and lean body mass .", "target_text": { "sex-binding globulin": "protein" } }, { "input_text": "It was matched by an inverse correlation between lymphocyte infiltration and blood-thyroid hormone concentration , urine catecholamines and free cortisol excretion and fat/lean body mass ratio .", "target_text": {} }, { "input_text": "Considering the abovesaid as well as the lymphocyte ability to perform the dual function of immunocytes and hormonocytes , it is suggested that the results may be used in both the study of lymphocyte infiltration and research in means of its control .", "target_text": { "immunocytes": "cell_type", "hormonocytes": "cell_type" } }, { "input_text": "Gene transcription through activation of G-protein-coupled chemoattractant receptors .", "target_text": { "G-protein-coupled chemoattractant receptors": "protein" } }, { "input_text": "Receptors for leukocyte chemoattractants , including chemokines , are traditionally considered to be responsible for the activation of special leukocyte functions such as chemotaxis , degranulation , and the release of superoxide anions .", "target_text": { "leukocyte chemoattractants": "protein", "chemokines": "protein" } }, { "input_text": "Recently , these G-protein-coupled serpentine receptors have been found to transduce signals leading to gene transcription and translation in leukocytes .", "target_text": { "G-protein-coupled serpentine receptors": "protein", "leukocytes": "cell_type" } }, { "input_text": "Transcription factors , such as NF kappa B and AP-1 , are activated upon stimulation of the cells with several chemoattractants at physiologically relevant concentrations .", "target_text": { "Transcription factors": "protein", "NF kappa B": "protein", "AP-1": "protein" } }, { "input_text": "Activation of transcription factors through these receptors involves G-protein coupling and the activation of protein kinases .", "target_text": { "G-protein": "protein", "protein kinases": "protein" } }, { "input_text": "The underlying signaling pathways appear to be different from those utilized by TNF-alpha , a better characterized cytokine that induces the transcription of immediate-early genes .", "target_text": { "TNF-alpha": "protein", "immediate-early genes": "DNA" } }, { "input_text": "Chemoattractants stimulate the expression of several inflammatory cytokines and chemokines , which in turn may activate their respective receptors and initiate an autocrine regulatory mechanism for persistent cytokine and chemokine gene expression .", "target_text": { "inflammatory cytokines": "protein", "chemokines": "protein", "cytokine": "protein", "chemokine": "protein" } }, { "input_text": "Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A [ see comments ]", "target_text": {} }, { "input_text": "The flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells ( NFAT ) -dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT .", "target_text": { "calcium-mobilizing receptors": "protein", "nuclear factor of activated T cells": "protein", "NFAT": "protein", "nuclear factor of activated T cells ( NFAT ) -dependent genes": "DNA", "phosphatase": "protein", "calcineurin": "protein", "transcription factor": "protein" } }, { "input_text": "A high-affinity calcineurin -binding peptide was selected from combinatorial peptide libraries based on the calcineurin docking motif of NFAT .", "target_text": { "calcineurin": "protein", "calcineurin docking motif": "protein", "NFAT": "protein" } }, { "input_text": "This peptide potently inhibited NFAT activation and NFAT -dependent expression of endogenous cytokine genes in T cells , without affecting the expression of other cytokines that require calcineurin but not NFAT .", "target_text": { "NFAT": "protein", "endogenous cytokine genes": "DNA", "T cells": "cell_type", "cytokines": "protein", "calcineurin": "protein" } }, { "input_text": "Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT .", "target_text": { "calcineurin": "protein", "calcineurin docking site": "protein", "NFAT": "protein" } }, { "input_text": "Compounds that interfere selectively with the calcineurin -NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs .", "target_text": { "calcineurin": "protein", "-NFAT": "protein", "phosphatase": "protein" } }, { "input_text": "9-cis retinoic acid induces monocyte chemoattractant protein-1 secretion in human monocytic THP-1 cells .", "target_text": { "monocyte chemoattractant protein-1": "protein", "THP-1 cells": "cell_type", "human monocytic THP-1 cells": "cell_type" } }, { "input_text": "Monocyte migration and activation are regulated by monocyte chemoattractant protein-1 ( MCP-1 ) .", "target_text": { "monocyte chemoattractant protein-1": "protein", "MCP-1": "protein" } }, { "input_text": "Prior studies have shown MCP-1 expression is modulated by a variety of ligands that act through extracellular receptors .", "target_text": { "MCP-1": "protein", "extracellular receptors": "protein" } }, { "input_text": "In the current study , we show 9-cis retinoic acid ( RA ) , a ligand for the nuclear hormone receptor retinoid X receptor ( RXR ) and retinoic acid receptor ( RAR ) , markedly induces the expression of MCP-1 .", "target_text": { "nuclear hormone receptor retinoid X receptor": "protein", "RXR": "protein", "retinoic acid receptor": "protein", "RAR": "protein", "MCP-1": "protein" } }, { "input_text": "In human THP-1 monocytic leukemia cells cultured with RA ( 0.05 to 500 nmol/L ) , MCP-1 expression was induced rapidly , significantly , and dose-dependently by as much as 165-fold .", "target_text": { "human THP-1 monocytic leukemia cells": "cell_line", "MCP-1": "protein" } }, { "input_text": "MCP-1 RNA level was also increased in RA -treated cells .", "target_text": { "MCP-1": "protein", "MCP-1 RNA": "RNA" } }, { "input_text": "Expression of PPARgamma , a heterodimer partner of RXR , is also markedly induced by RA in THP-1 cells .", "target_text": { "PPARgamma": "protein", "RXR": "protein", "THP-1 cells": "cell_type" } }, { "input_text": "However , BRL49653 , a PPARgamma ligand , failed to induce MCP-1 secretion either alone or to modify the expression level induced by RA .", "target_text": { "PPARgamma": "protein", "MCP-1": "protein" } }, { "input_text": "In contrast , BRL49653 significantly increased MCP-1 ( biotinylated MCP-1 ) binding to THP-1 cells , whereas RA had no effect .", "target_text": { "MCP-1": "protein", "biotinylated MCP-1": "protein", "THP-1 cells": "cell_type" } }, { "input_text": "Other peroxisome proliferator activated receptor ( PPAR ) ligands , 15d-PGJ ( 2 ) and troglitazone ( PPARgamma ) , Wy14 , 643 ( PPARalpha ) , and PD195599 ( PPARbeta ) inhibited the induction of MCP-1 by RA .", "target_text": { "peroxisome proliferator activated receptor": "protein", "PPAR": "protein", "PPARgamma": "protein", "PPARalpha": "protein", "PPARbeta": "protein", "MCP-1": "protein" } }, { "input_text": "RA 's effect on MCP-1 expression in human elutriated monocytes were similar to that observed in the THP-1 cells .", "target_text": { "MCP-1": "protein", "THP-1 cells": "cell_line" } }, { "input_text": "These studies identify RA as a nuclear signal for MCP-1 induction in undifferentiated human monocytic cells .", "target_text": { "MCP-1": "protein", "undifferentiated human monocytic cells": "cell_type" } }, { "input_text": "These studies also suggest monocyte MCP-1 expression induced through RA may modulate cell migration .", "target_text": { "MCP-1": "protein" } }, { "input_text": "Classification of IVS1-10T --> C as a polymorphism of BRCA1 .", "target_text": { "BRCA1": "DNA" } }, { "input_text": "Mutations inactivating the tumor suppressor gene BRCA1 may be responsible for disease for up to 80 % of familial ovarian cancer cases .", "target_text": { "tumor suppressor gene": "DNA", "BRCA1": "DNA" } }, { "input_text": "In this syndrome , tumorigenesis classically initiates from an inherited mutation in one allele followed by somatic deletion of the normal allele .", "target_text": { "allele": "DNA", "normal allele": "DNA" } }, { "input_text": "Sequencing of BRCA1 amplified from genomic DNA of lymphocytes and microdissected ovarian tumor cells of a familial ovarian cancer patient revealed three , rare heterozygous DNA variations ( 2418delA , 233G --> A , and IVS1-10T --> C ) in both tumor and constitutional ( lymphocyte ) DNA .", "target_text": { "BRCA1": "DNA", "genomic DNA": "DNA", "lymphocytes": "cell_type", "microdissected ovarian tumor cells": "cell_type" } }, { "input_text": "Thus , both copies of BRCA1 were retained in tumor .", "target_text": { "BRCA1": "DNA" } }, { "input_text": "Haplotype analysis of the patient and four siblings assigned 2418delA to one copy of BRCA1 and 233G --> A and IVS1-10T --> C to the other .", "target_text": { "BRCA1": "DNA" } }, { "input_text": "The DNA change , 2418delA , is considered a mutation that inactivated one BRCA1 allele because it caused a frameshift and generation of a premature stop codon , resulting in synthesis of a truncated peptide as evidenced by an in vitro protein truncation test .", "target_text": { "BRCA1": "DNA", "premature stop codon": "DNA" } }, { "input_text": "The DNA variation , 233G --> A , does not result in an amino acid change , and is considered a benign polymorphism .", "target_text": {} }, { "input_text": "IVS1-10T --> C is a unique BRCA1 change that occurs in the last nucleotide of a consensus sequence for a branch site critical for RNA splicing .", "target_text": { "BRCA1": "DNA", "consensus sequence": "DNA", "branch site": "DNA" } }, { "input_text": "Therefore , we investigated whether IVS1-10T --> C deleteriously affected BRCA1 splicing or expression , and thereby inactivated the other BRCA1 allele .", "target_text": { "BRCA1": "DNA", "BRCA1 allele": "DNA" } }, { "input_text": "Using the technique of reverse transcription-polymerase chain reaction ( PCR ) with RNA isolated from lymphoid cell lines of the patient and of controls , no evidence was found that IVS1-10TC abnormally disrupted mRNA splicing or caused the absence of BRCA1 mRNA .", "target_text": { "lymphoid cell lines": "cell_line", "mRNA": "RNA", "BRCA1": "DNA", "BRCA1 mRNA": "RNA" } }, { "input_text": "Thus , IVS1-10T --> C is not harmful to BRCA1 function , and is classified a benign polymorphism .", "target_text": { "BRCA1": "DNA" } }, { "input_text": "Retention of the normal BRCA1 allele in the tumor with the heterozygous germline BRCA1 mutation , 2418delA , indicated that mutational inactivation of both BRCA1 alleles was not required for tumorigenesis .", "target_text": { "BRCA1": "DNA", "BRCA1 allele": "DNA", "BRCA1 alleles": "DNA" } }, { "input_text": "It is possible that the normal allele may be functionally inactivated by a nonmutational mechanism .", "target_text": { "normal allele": "DNA" } }, { "input_text": "Myb-transformed hematopoietic cells as a model for monocyte differentiation into dendritic cells and macrophages .", "target_text": { "hematopoietic cells": "cell_type", "Myb-transformed hematopoietic cells": "cell_type", "dendritic cells": "cell_type", "macrophages": "cell_type" } }, { "input_text": "Immune induction is effected through the interaction of antigen-presenting cells with specific receptors on the surface of thymus-derived lymphocytes .", "target_text": { "antigen-presenting cells": "cell_type", "receptors": "protein", "lymphocytes": "cell_type", "thymus-derived lymphocytes": "cell_type" } }, { "input_text": "Cells most able to ingest , process , and present antigen appear to be related to the mononuclear phagocyte/neutrophil series .", "target_text": { "mononuclear phagocyte/neutrophil series": "cell_type" } }, { "input_text": "For example dendritic cells ( DC ) can be found in colonies of GM-CSF-responsive bone marrow cells , and under experimental conditions are routinely expanded as a population in vitro from GM-CSF-responsive progenitor cells .", "target_text": { "dendritic cells": "cell_type", "DC": "cell_type", "GM-CSF-responsive bone marrow cells": "cell_type", "GM-CSF-responsive progenitor cells": "cell_type" } }, { "input_text": "To address the question of DC lineage and to determine what genes are involved in lineage commitment , we have generated a series of GM-CSF-responsive cell lines that can be induced to differentiate in a homogeneous manner in vitro .", "target_text": { "DC": "cell_type", "DC lineage": "cell_type", "GM-CSF-responsive cell lines": "cell_line" } }, { "input_text": "The cloned cell lines are derived from 12-day fetal liver and are transformed with a truncated form of c-myb , which lacks the normal autoregulatory sequences .", "target_text": { "cloned cell lines": "cell_line", "c-myb": "DNA", "autoregulatory sequences": "DNA" } }, { "input_text": "As far as we know , these myb-transformed hemopoi-etic cells ( MTHC ) differ from normal only in the unregulated expression of myb , a gene whose expression is obligatory for proliferation of hemopoietic cells .", "target_text": { "myb-transformed hemopoi-etic cells": "cell_line", "MTHC": "cell_line" } }, { "input_text": "MTHC in the presence of TNF-alpha and IL-4 will differentiate into cells that have many of the properties of macrophages .", "target_text": { "MTHC": "cell_line", "TNF-alpha": "protein", "IL-4": "protein", "macrophages": "cell_type" } }, { "input_text": "When the same MTHC lines are exposed to TNF-alpha in combination with IFN-gamma , the cells instead become DC .", "target_text": { "MTHC": "cell_line", "MTHC lines": "cell_line", "TNF-alpha": "protein", "IFN-gamma": "protein", "DC": "cell_type" } }, { "input_text": "The differentiated DC are potent presenters of antigen in mixed lymphocyte reactions and of soluble antigen to specific T cell lines .", "target_text": { "DC": "cell_type", "T cell lines": "cell_line" } }, { "input_text": "Thus , cells with the properties of both macrophages and DC can be derived from a single type of GM-CSF-responsive progenitor cell .", "target_text": { "macrophages": "cell_type", "DC": "cell_type", "GM-CSF-responsive progenitor cell": "cell_type" } }, { "input_text": "We have used this MTHC system to analyze differences in gene expression as the cells mature along the DC and macrophage pathways .", "target_text": { "MTHC": "cell_line", "MTHC system": "cell_line", "DC": "cell_type", "macrophage pathways": "cell_type" } }, { "input_text": "A distinctive pattern of differentially expressed cDNAs is evident where macrophage-specific cDNAs are homologous to genes encoding cytoskeletal and cell-surface proteins , whereas the DC -specific cDNAs are homologous to signaling , chemokine , and IFN-gamma-inducible genes .", "target_text": { "cDNAs": "DNA", "macrophage-specific cDNAs": "DNA", "DC": "cell_type" } }, { "input_text": "We discuss the utility of MTHC in analyzing the relationships between DC and macrophages , and suggest that DC and macrophages represent extreme phenotypes in a spectrum of antigen handling cells that are somewhat interchangeable , depending on their immediate environment .", "target_text": { "MTHC": "cell_line", "DC": "cell_type", "macrophages": "cell_type", "antigen handling cells": "cell_type" } }, { "input_text": "The Legionella pneumophila rpoS gene is required for growth within Acanthamoeba castellanii .", "target_text": { "rpoS gene": "DNA" } }, { "input_text": "To investigate regulatory networks in Legionella pneumophila , the gene encoding the homolog of the Escherichia coli stress and stationary-phase sigma factor RpoS was identified by complementation of an E. coli rpoS mutation .", "target_text": { "Escherichia coli stress and stationary-phase sigma factor": "protein", "RpoS": "protein", "rpoS": "DNA" } }, { "input_text": "An open reading frame that is approximately 60 % identical to the E. coli rpoS gene was identified .", "target_text": { "open reading frame": "DNA", "rpoS gene": "DNA", "E. coli rpoS gene": "DNA" } }, { "input_text": "Western blot analysis showed that the level of L. pneumophila RpoS increased in stationary phase .", "target_text": { "RpoS": "protein" } }, { "input_text": "An insertion mutation was constructed in the rpoS gene on the chromosome of L. pneumophila , and the ability of this mutant strain to survive various stress conditions was assayed and compared with results for the wild-type strain .", "target_text": { "rpoS gene": "DNA" } }, { "input_text": "Both the mutant and wild-type strains were more resistant to stress when in stationary phase than when in the logarithmic phase of growth .", "target_text": {} }, { "input_text": "This finding indicates that L. pneumophila RpoS is not required for a stationary-phase-dependent resistance to stress .", "target_text": { "RpoS": "protein" } }, { "input_text": "Although the mutant strain was able to kill HL-60- and THP-1- derived macrophages , it could not replicate within a protozoan host , Acanthamoeba castellanii .", "target_text": {} }, { "input_text": "These data suggest that L. pneumophila possesses a growth phase-dependent resistance to stress that is independent of RpoS control and that RpoS likely regulates genes that enable it to survive in the environment within protozoa .", "target_text": { "RpoS": "protein" } }, { "input_text": "Our data indicate that the role of rpoS in L. pneumophila is very different from what has previously been reported for E. coli rpoS .", "target_text": { "rpoS": "DNA" } }, { "input_text": "Monoallelic expression of Pax5 : a paradigm for the haploinsufficiency of mammalian Pax genes ?", "target_text": { "Pax5": "protein", "mammalian Pax genes": "DNA" } }, { "input_text": "It is generally assumed that most mammalian genes are transcribed from both alleles .", "target_text": { "mammalian genes": "DNA", "alleles": "DNA" } }, { "input_text": "Hence , the diploid state of the genome offers the advantage that a loss-of-function mutation in one allele can be compensated for by the remaining wild-type allele of the same gene .", "target_text": { "allele": "DNA", "wild-type allele": "DNA" } }, { "input_text": "Indeed , the vast majority of human disease syndromes and engineered mutations in the mouse genome are recessive , indicating that recessiveness is the ' default ' state .", "target_text": { "mouse genome": "DNA" } }, { "input_text": "However , a minority of genes are semi-dominant , as heterozygous loss-of-function mutation in these genes leads to phenotypic abnormalities .", "target_text": {} }, { "input_text": "This condition , known as haploinsufficiency , has been described for five of the nine mammalian Pax genes , which are associated with mouse developmental mutants and human disease syndromes .", "target_text": { "mammalian Pax genes": "DNA" } }, { "input_text": "Recently we have reported that the Pax5 gene is subject to allele -specific regulation during B cell development .", "target_text": { "Pax5": "protein", "Pax5 gene": "DNA", "allele": "DNA" } }, { "input_text": "Pax5 is predominantly transcribed from only one of its two alleles in early B-lymphoid progenitors and mature B cells , while it transiently switches to a biallelic mode of transcription in pre-B and immature B cells .", "target_text": { "Pax5": "protein", "alleles": "DNA", "early B-lymphoid progenitors": "cell_type", "mature B cells": "cell_type" } }, { "input_text": "As a consequence , B-lymphoid tissues are mosaic with regard to the transcribed allele , and heterozygous mutation of Pax5 therefore results in deletion of B lymphocytes expressing only the mutant allele .", "target_text": { "allele": "DNA", "Pax5": "protein", "B lymphocytes": "cell_type", "mutant allele": "DNA" } }, { "input_text": "The allele -specific regulation of Pax5 raises the intriguing possibility that monoallelic expression may also be the mechanism causing the haploinsufficiency of other Pax genes .", "target_text": { "allele": "DNA", "Pax5": "protein", "Pax genes": "DNA" } }, { "input_text": "In this review , we discuss different models accounting for the haploinsufficiency of mammalian Pax genes , provide further evidence in support of the allele -specific regulation of Pax5 and discuss the implication of these findings in the context of the recent literature describing the stochastic and monoallelic activation of other hematopoietic genes .", "target_text": { "Pax genes": "DNA", "mammalian Pax genes": "DNA", "allele": "DNA", "Pax5": "protein", "hematopoietic genes": "DNA" } }, { "input_text": "Activation of STAT5 by IL-4 relies on Janus kinase function but not on receptor tyrosine phosphorylation , and can contribute to both cell proliferation and gene regulation .", "target_text": { "STAT5": "protein", "IL-4": "protein", "Janus kinase": "protein" } }, { "input_text": "We have investigated mechanisms and consequences of STAT5 activation through the human IL-4 receptor ( IL-4R ) .", "target_text": { "STAT5": "protein", "IL-4": "protein", "human IL-4 receptor": "protein", "IL-4R": "protein" } }, { "input_text": "By functionally expressing receptor mutants in the murine pro-B cell line Ba/F3 , we could show that phosphorylated tyrosine residues within the IL-4R alpha chain are dispensable for IL-4 -induced STAT5 activity .", "target_text": { "receptor mutants": "protein", "murine pro-B cell line": "cell_line", "Ba/F3": "cell_line", "IL-4R alpha chain": "protein", "IL-4": "protein", "STAT5": "protein" } }, { "input_text": "However , disruption of a membrane-proximal proline-rich sequence motif ( ' box1 ' ) in either subunit of the bipartite IL-4R abolished not only ligand-induced tyrosine phosphorylation of Janus kinases JAK1 and JAK3 , but also IL-4 -triggered activation of STAT5 and concomitant cell proliferation .", "target_text": { "membrane-proximal proline-rich sequence motif": "protein", "box1": "protein", "bipartite IL-4R": "protein", "Janus kinases": "protein", "JAK1": "protein", "JAK3": "protein", "IL-4": "protein", "STAT5": "protein" } }, { "input_text": "A dominant-negative version of STAT5b , but not of STAT5a , interfered with IL-4 -induced DNA synthesis in Ba/F3 cells , suggesting an involvement of STAT5b in the control of cell proliferation through IL-4R .", "target_text": { "dominant-negative version": "protein", "STAT5b": "protein", "STAT5a": "protein", "IL-4": "protein", "Ba/F3 cells": "cell_line", "IL-4R": "protein" } }, { "input_text": "Reporter gene experiments finally showed that transcription from promoters of STAT5 target genes can be specifically induced by challenging cells with IL-4 , and that both STAT5a and STAT5b can contribute to IL-4 -triggered transcriptional control .", "target_text": { "STAT5": "protein", "IL-4": "protein", "STAT5a": "protein", "STAT5b": "protein" } }, { "input_text": "Inhibition of NF-AT signal transduction events by a dominant-negative form of calcineurin .", "target_text": { "NF-AT": "protein", "calcineurin": "protein" } }, { "input_text": "An inhibitory , \" dominant-negative , \" form of the calcineurin catalytic ( A ) subunit was prepared , which lacks the calmodulin -binding domain , autoinhibitory domain and most of its catalytic core but possesses the regulatory ( B ) subunit binding domain .", "target_text": { "calcineurin": "protein", "calcineurin catalytic ( A ) subunit": "protein", "calmodulin": "protein", "calmodulin -binding domain": "protein", "autoinhibitory domain": "protein", "regulatory ( B ) subunit": "protein" } }, { "input_text": "When tested for its ability to block calcineurin -dependent signaling in Jurkat cells , expression of this \" B-subunit knock-out \" ( BKO ) construct suppressed reporter gene activity driven by NF-AT , the pivotal promoter element for interleukin ( IL ) -2 gene induction .", "target_text": { "calcineurin": "protein", "\" B-subunit knock-out \" ( BKO ) construct": "DNA", "reporter gene": "DNA", "NF-AT": "protein", "promoter element": "DNA", "interleukin ( IL ) -2": "protein", "interleukin ( IL ) -2 gene": "DNA" } }, { "input_text": "Immunoprecipitation of epitope-labeled BKO demonstrated for the formation of a tight complex with endogenous B subunit in Jurkat cells , consistent with an inhibitory mechanism that involves the sequestration of the B subunit .", "target_text": { "epitope-labeled BKO": "protein", "endogenous B subunit": "protein", "Jurkat cells": "cell_line", "B subunit": "protein" } }, { "input_text": "Furthermore , the sharply reduced NF-AT activity produced by co-transfecting BKO could be \" rescued \" by overexpression of transfected B subunit , suggesting that depletion of this subunit was responsible for the inhibition .", "target_text": { "NF-AT": "protein", "co-transfecting BKO": "DNA", "B subunit": "protein" } }, { "input_text": "These data suggest the potential utility of agents that disrupt calcineurin -mediated signal transduction pathways by blocking formation of the catalytically active dimer of calcineurin A and B subunits .", "target_text": { "calcineurin": "protein", "catalytically active dimer": "protein" } }, { "input_text": "Evaluation of monoclonal anti-D reagents using D variant cells .", "target_text": { "D variant cells": "cell_line" } }, { "input_text": "Monoclonal anti-D antibodies submitted to the Third Monoclonal International Workshop were evaluated against a number of D variant cells using standard serological techniques .", "target_text": { "Monoclonal anti-D antibodies": "protein", "D variant cells": "cell_line" } }, { "input_text": "The monoclonal antibodies were able to discriminate between the cells of Categories Va , VI and DFR but not Category III cells .", "target_text": { "monoclonal antibodies": "protein" } }, { "input_text": "Cells within each category did not give any aberrant results .", "target_text": {} }, { "input_text": "The Rh : 33 cells behaved as normal Rh ( D ) positive cells .", "target_text": { "Rh : 33 cells": "cell_line", "normal Rh ( D ) positive cells": "cell_type" } }, { "input_text": "Interleukin 10 induced c-fos expression in human B cells by activation of divergent protein kinases .", "target_text": { "Interleukin 10": "protein", "c-fos": "DNA", "human B cells": "cell_type", "divergent protein kinases": "protein" } }, { "input_text": "IL-10 is a potent mediator of human B cell growth and plasma cell formation .", "target_text": { "IL-10": "protein", "human B cell": "cell_type" } }, { "input_text": "However , signal transduction of IL-10 in B cells is poorly understood .", "target_text": { "IL-10": "protein", "B cells": "cell_type" } }, { "input_text": "In this study the effect of IL-10 on the expression of the protooncogene c-fos was investigated , because Fos plays a potential role in the regulation of B cell proliferation and differentiation .", "target_text": { "IL-10": "protein", "c-fos": "DNA", "protooncogene c-fos": "DNA" } }, { "input_text": "B cells were purified from buffy coat preparations of healthy blood donors by positive selection using an anti CD20 monoclonal antibody and a MiniMACS separation unit .", "target_text": { "B cells": "cell_type", "CD20": "protein", "anti CD20 monoclonal antibody": "protein" } }, { "input_text": "B cells were prestimulated with SAC for 48 hrs .", "target_text": { "B cells": "cell_type" } }, { "input_text": "Then , cells were incubated with medium or IL-10 ( 100 ng/ml ) for 10 to 120 min .", "target_text": { "IL-10": "protein" } }, { "input_text": "RNA was extracted by phenol/chloroform and c-fos expression was analyzed by PCR assisted mRNA assay .", "target_text": { "RNA": "RNA", "c-fos": "DNA" } }, { "input_text": "A significant 2-4 fold increase of c-fos expression was observed within 30 min of stimulation with IL-10 ( p < 0.01 ) .", "target_text": { "c-fos": "DNA", "IL-10": "protein" } }, { "input_text": "After 2 hrs c-fos expression declined to basal levels .", "target_text": { "c-fos": "DNA" } }, { "input_text": "The effect of IL-10 was dose-dependent with a maximum stimulation using 100 ng/ml of IL-10 .", "target_text": { "IL-10": "protein" } }, { "input_text": "The IL-10 effect on c-fos expression was not blocked by polymyxin B .", "target_text": { "IL-10": "protein", "c-fos": "DNA" } }, { "input_text": "Using the tyrosine kinase inhibitor genistein ( 10 microM ) a complete inhibition of IL-10 induced c-fos expression was observed .", "target_text": { "IL-10": "protein", "c-fos": "DNA" } }, { "input_text": "In addition , H-7 ( 10 microM ) , a specific inhibitor of serine /threonine kinases , significantly blocked IL-10 mediated c-fos expression ( p < 0.05 ) .", "target_text": { "serine /threonine kinases": "protein", "IL-10": "protein", "c-fos": "DNA" } }, { "input_text": "In conclusion , these data show that IL-10 induces c-fos expression in human B-cells by activation of tyrosine and serine /threonine kinases .", "target_text": { "IL-10": "protein", "c-fos": "DNA", "human B-cells": "cell_type", "serine /threonine kinases": "protein" } }, { "input_text": "Since this is the first report on IL-10 induced signal transduction , these data may help to identify the intracellular mechanisms by which IL-10 stimulates human B-cells .", "target_text": { "IL-10": "protein", "human B-cells": "cell_type" } }, { "input_text": "Immunocytochemical analysis of MNDA in tissue sections and sorted normal bone marrow cells documents expression only in maturing normal and neoplastic myelomonocytic cells and a subset of normal and neoplastic B lymphocytes .", "target_text": { "MNDA": "protein" } }, { "input_text": "The human myeloid cell nuclear differentiation antigen ( MNDA ) is a nuclear antigen known to be expressed in mature myelomonocytic cell lines .", "target_text": { "MNDA": "protein" } }, { "input_text": "An extensive immunocytochemical evaluation of fixed tissues confirmed MNDA expression in normal maturing granulocytes and monocytes and in acute nonlymphocytic leukemias and chronic myelogenous leukemia .", "target_text": { "MNDA": "protein", "normal maturing granulocytes": "cell_type", "monocytes": "cell_type" } }, { "input_text": "MNDA was not detected in normal tissue histiocytes but was found in activated macrophages and foreign body giant cells associated with inflammation .", "target_text": { "MNDA": "protein", "activated macrophages": "cell_type", "foreign body giant cells": "cell_type" } }, { "input_text": "Flow cytometric cell sorting of normal bone marrow established that MNDA is initially expressed in myeloid blast cells .", "target_text": { "MNDA": "protein", "myeloid blast cells": "cell_type" } }, { "input_text": "Examination of lymphoid tissues showed a low level of expression in a population of normal mande B lymphocytes but not in germinal center cells or plasma cells .", "target_text": { "mande B lymphocytes": "cell_line", "germinal center cells": "cell_type", "plasma cells": "cell_type" } }, { "input_text": "A subset of B cell neoplasms expressing MNDA included hairy cell leukemia , parafollicular ( monocytoid ) B cell lymphoma , mantle cell lymphoma , and small lymphocytic lymphoma .", "target_text": { "B cell neoplasms": "cell_type", "MNDA": "protein" } }, { "input_text": "Cell sorting of normal bone marrow showed MNDA expression in CD20 +/CD10-/CD5- B cells .", "target_text": { "MNDA": "protein", "CD20": "protein", "B cells": "cell_type" } }, { "input_text": "MNDA was not detected in other normal bone marrow or all other nonhematopoietic cells .", "target_text": { "MNDA": "protein", "nonhematopoietic cells": "cell_type" } }, { "input_text": "The hematopoietic cell-specific pattern of MNDA expression was elucidated through a comprehensive analysis of normal and neoplastic tissues , and the results provide further evidence of the coexpression of B- and myeloid cell markers in neoplastic B cells and identify a normal B cell population that might be related to the cell of origin of a subset of B cell neoplasms .", "target_text": { "MNDA": "protein", "neoplastic B cells": "cell_type", "normal B cell population": "cell_type", "B cell neoplasms": "cell_type" } }, { "input_text": "Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte -endothelial cell interaction .", "target_text": { "Peroxisome proliferator-activated receptor activators": "protein", "human endothelial cells": "cell_type", "leukocyte": "cell_type", "-endothelial cell": "cell_type" } }, { "input_text": "An early event in acute and chronic inflammation and associated diseases such as atherosclerosis and rheumatoid arthritis is the induced expression of specific adhesion molecules on the surface of endothelial cells ( ECs ) , which subsequently bind leukocytes .", "target_text": { "adhesion molecules": "protein", "endothelial cells": "cell_type", "ECs": "cell_type", "leukocytes": "cell_type" } }, { "input_text": "Peroxisome proliferator-activated receptors ( PPARs ) , members of the nuclear receptor superfamily of transcription factors , are activated by fatty acid metabolites , peroxisome proliferators , and thiazolidinediones and are now recognized as important mediators in the inflammatory response .", "target_text": { "Peroxisome proliferator-activated receptors": "protein", "PPARs": "protein", "nuclear receptor superfamily": "protein", "transcription factors": "protein" } }, { "input_text": "Whether PPAR activators influence the inflammatory responses of ECs is unknown .", "target_text": { "ECs": "cell_type" } }, { "input_text": "We show that the PPAR activators 15-deoxy-Delta ( 12 , 14 ) -prostaglandin J ( 2 ) ( 15d-PGJ ( 2 ) ) , Wyeth 14643 , ciglitazone , and troglitazone , but not BRL 49653 , partially inhibit the induced expression of vascular cell adhesion molecule-1 ( VCAM-1 ) , as measured by ELISA , and monocyte binding to human aortic endothelial cells ( HAECs ) activated by phorbol 12-myristate 13-acetate ( PMA ) or lipopolysaccharide .", "target_text": { "vascular cell adhesion molecule-1": "protein", "VCAM-1": "protein", "human aortic endothelial cells": "cell_type", "HAECs": "cell_type" } }, { "input_text": "The \" natural \" PPAR activator 15d-PGJ ( 2 ) had the greatest potency and was the only tested molecule capable of partially inhibiting the induced expression of E-selectin and neutrophil-like HL60 cell binding to PMA -activated HAECs .", "target_text": { "E-selectin": "protein", "HL60 cell": "cell_line", "HAECs": "cell_type" } }, { "input_text": "Intracellular adhesion molecule-1 induction by PMA was unaffected by any of the molecules tested .", "target_text": { "Intracellular adhesion molecule-1": "protein" } }, { "input_text": "Both PPAR-alpha and PPAR-gamma mRNAs were detected in HAECs by using reverse transcription-polymerase chain reaction and a ribonuclease protection assay ; however , we have yet to determine which , if any , of the PPARs are mediating this process .", "target_text": { "PPAR-alpha": "RNA", "PPAR-gamma mRNAs": "RNA", "PPAR-alpha and PPAR-gamma mRNAs": "RNA", "HAECs": "cell_type", "ribonuclease": "protein", "PPARs": "protein" } }, { "input_text": "These results suggest that certain PPAR activators may help limit chronic inflammation mediated by VCAM-1 and monocytes without affecting acute inflammation mediated by E-selectin and neutrophil binding .", "target_text": { "VCAM-1": "protein", "monocytes": "cell_type", "E-selectin": "protein", "neutrophil": "cell_type" } }, { "input_text": "Dephosphorylation of ZAP-70 and inhibition of T cell activation by activated SHP1 .", "target_text": { "ZAP-70": "protein", "activated SHP1": "protein" } }, { "input_text": "Studies with motheaten mice , which lack the SHP1 protein tyrosine phosphatase , indicate that this enzyme plays an important negative role in T cell antigen receptor ( TCR ) signaling .", "target_text": { "SHP1": "protein", "SHP1 protein": "protein", "tyrosine phosphatase": "protein", "T cell antigen receptor": "protein", "TCR": "protein" } }, { "input_text": "The physiological substrates for SHP1 in T lymphocytes , however , have remained unclear or controversial .", "target_text": { "SHP1": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "To define these targets for SHP1 we have compared the effects of constitutively active and inactive mutants of SHP1 on TCR signaling .", "target_text": { "SHP1": "protein", "TCR": "protein" } }, { "input_text": "Expression of wild-type SHP1 had a very small effect on the TCR-induced tyrosine phosphorylation of ZAP-70 and Syk , even when SHP1 was overexpressed 20 - 100-fold over endogenous SHP1 .", "target_text": { "SHP1": "protein", "wild-type SHP1": "protein", "ZAP-70": "protein", "Syk": "protein", "endogenous SHP1": "protein" } }, { "input_text": "Inactive SHP1 -D421A and wild-type SHP2 were without effects .", "target_text": { "SHP1": "protein", "Inactive SHP1 -D421A": "protein", "wild-type SHP2": "protein" } }, { "input_text": "Constitutively active SHP1 -DeltaSH2 had a more pronounced effect on ZAP-70 and Syk , even when expressed at near physiological levels .", "target_text": { "SHP1": "protein", "Constitutively active SHP1 -DeltaSH2": "protein", "ZAP-70": "protein", "Syk": "protein" } }, { "input_text": "SHP1 -DeltaSH2 also inhibited events downstream of ZAP-70 and Syk , such as activation of the mitogen-activated protein kinase Erk2 and the transcriptional activation of the interleukin-2 gene .", "target_text": { "SHP1": "protein", "SHP1 -DeltaSH2": "protein", "ZAP-70": "protein", "Syk": "protein", "mitogen-activated protein kinase": "protein", "Erk2": "protein", "interleukin-2": "protein", "interleukin-2 gene": "DNA" } }, { "input_text": "In contrast , a constitutively active SHP2-DeltaSH2 had no statistically significant effect ( although it caused a slight augmentation in some individual experiments ) .", "target_text": { "SHP2-DeltaSH2": "protein" } }, { "input_text": "None of the constructs influenced the anti-CD3-induced tyrosine phosphorylation of the TCR zeta-chain or phospholipase Cgamma1 , indicating that Src family kinase function was intact .", "target_text": { "TCR zeta-chain": "protein", "phospholipase Cgamma1": "protein", "Src family kinase": "protein" } }, { "input_text": "Taken together , our findings support the notion that ZAP-70 and Syk can be direct substrates for SHP1 in intact cells .", "target_text": { "ZAP-70": "protein", "Syk": "protein", "SHP1": "protein" } }, { "input_text": "However , the two SH2 domains of SHP1 did not facilitate its recognition of ZAP-70 and Syk as substrates in intact cells .", "target_text": { "SH2 domains": "protein", "SHP1": "protein", "ZAP-70": "protein", "Syk": "protein" } }, { "input_text": "Therefore , we suggest that SHP1 is not actively recruited to inhibit TCR signaling induced by ligation of this receptor alone .", "target_text": { "SHP1": "protein", "TCR": "protein" } }, { "input_text": "Instead , we propose that ligation of a distinct inhibitory receptor leads to the recruitment of SHP1 via its SH2 domains , activation of SHP1 and subsequently inhibition of TCR signals if the inhibitory receptor is juxtaposed to the TCR .", "target_text": { "inhibitory receptor": "protein", "SHP1": "protein", "SH2 domains": "protein", "TCR": "protein" } }, { "input_text": "Immune responses to adenoviruses : viral evasion mechanisms and their implications for the clinic .", "target_text": {} }, { "input_text": "Adenoviruses encode proteins that block responses to interferons , intrinsic cellular apoptosis , killing by CD8(+) cytotoxic T lymphocytes and killing by the death ligands TNF , Fas ligand and TRAIL .", "target_text": { "interferons": "protein", "CD8(+) cytotoxic T lymphocytes": "cell_type", "death ligands": "protein", "TNF": "protein", "Fas ligand": "protein", "TRAIL": "protein" } }, { "input_text": "The viral proteins are believed to prolong acute and persistent adenovirus infections .", "target_text": { "viral proteins": "protein" } }, { "input_text": "The proteins may prove useful in protecting adenovirus gene therapy vectors and transplanted cells from the immune system .", "target_text": { "adenovirus gene therapy vectors": "DNA", "transplanted cells": "cell_line" } }, { "input_text": "C/EBPbeta and GATA-1 synergistically regulate activity of the eosinophil granule major basic protein promoter : implication for C/EBPbeta activity in eosinophil gene expression .", "target_text": { "C/EBPbeta": "protein", "GATA-1": "protein", "eosinophil granule major basic protein promoter": "DNA" } }, { "input_text": "Eosinophil granule major basic protein ( MBP ) is expressed exclusively in eosinophils and basophils in hematopoietic cells .", "target_text": { "Eosinophil granule major basic protein": "protein", "MBP": "protein", "eosinophils": "cell_type", "basophils": "cell_type", "hematopoietic cells": "cell_type" } }, { "input_text": "In our previous study , we demonstrated a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription .", "target_text": { "GATA-1": "protein", "GATA-2": "protein", "MBP": "protein" } }, { "input_text": "Further analysis of the MBP promoter region identified a C/EBP ( CCAAT/enhancer-binding protein ) consensus binding site 6 bp upstream of the functional GATA-binding site in the MBP gene .", "target_text": { "MBP": "protein", "MBP promoter region": "DNA", "C/EBP": "protein", "CCAAT/enhancer-binding protein": "protein", "C/EBP ( CCAAT/enhancer-binding protein ) consensus binding site": "DNA", "GATA-binding site": "DNA", "MBP gene": "DNA" } }, { "input_text": "In the cell line HT93A , which is capable of differentiating towards both the eosinophil and neutrophil lineages in response to retinoic acid ( RA ) , C/EBPalpha mRNA expression decreased significantly concomitant with eosinophilic and neutrophilic differentiation , whereas C/EBPbeta expression was markedly increased .", "target_text": { "cell line HT93A": "cell_line", "eosinophil": "cell_type", "C/EBPalpha": "protein", "C/EBPalpha mRNA": "RNA", "C/EBPbeta": "protein" } }, { "input_text": "Electrophoretic mobility shift assays ( EMSAs ) showed that recombinant C/EBPbeta protein could bind to the potential C/EBP-binding site ( bp -90 to -82 ) in the MBP promoter .", "target_text": { "C/EBPbeta": "protein", "C/EBP-binding site": "DNA", "bp -90 to -82": "DNA", "MBP": "protein" } }, { "input_text": "Furthermore , we have demonstrated that both C/EBPbeta and GATA-1 can bind simultaneously to the C/EBP- and GATA-binding sites in the MBP promoter .", "target_text": { "C/EBPbeta": "protein", "GATA-1": "protein", "GATA-binding sites": "DNA", "MBP": "protein", "MBP promoter": "DNA" } }, { "input_text": "To determine the functionality of both the C/EBP- and GATA- binding sites , we analyzed whether C/EBPbeta and GATA-1 can stimulate the MBP promoter in the C/EBPbeta and GATA-1 negative Jurkat T-cell line .", "target_text": { "C/EBPbeta": "protein", "GATA-1": "protein", "MBP": "protein", "MBP promoter": "DNA", "Jurkat T-cell line": "cell_line", "C/EBPbeta and GATA-1 negative Jurkat T-cell line": "cell_line" } }, { "input_text": "Cotransfection with C/EBPbeta and GATA-1 expression vectors produced a 5-fold increase compared with cotransfection with the C/EBPbeta or GATA-1 expression vectors individually .", "target_text": { "C/EBPbeta": "protein", "GATA-1": "protein", "GATA-1 expression vectors": "DNA" } }, { "input_text": "In addition , GST pull-down experiments demonstrated a physical interaction between human GATA-1 and C/EBPbeta .", "target_text": { "GST": "protein", "GATA-1": "protein", "C/EBPbeta": "protein" } }, { "input_text": "Expression of FOG ( riend ATA ) , which binds to GATA-1 and acts as a cofactor for GATA-binding proteins , decreased transactivation activity of GATA-1 for the MBP promoter in a dose-dependent manner .", "target_text": { "FOG": "protein", "riend ATA": "protein", "GATA-1": "protein", "GATA-binding proteins": "protein", "MBP": "protein", "MBP promoter": "DNA" } }, { "input_text": "Our results provide the first evidence that both GATA-1 and C/EBPbeta synergistically transactivate the promoter of an eosinophil-specific granule protein gene and that FOG may act as a negative cofactor for the eosinophil lineage , unlike its positively regulatory function for the erythroid and megakaryocyte lineages .", "target_text": { "GATA-1": "protein", "C/EBPbeta": "protein", "promoter": "DNA", "eosinophil-specific granule protein gene": "DNA", "FOG": "protein", "eosinophil lineage": "cell_type" } }, { "input_text": "Tissue-specific regulation of the ecto-5'-nucleotidase promoter .", "target_text": { "ecto-5'-nucleotidase promoter": "DNA" } }, { "input_text": "Role of the camp response element site in mediating repression by the upstream regulatory region .", "target_text": { "camp response element site": "DNA", "upstream regulatory region": "DNA" } }, { "input_text": "We have isolated the 5' region of the ecto-5'-nucleotidase ( low K ( m ) 5'-NT ) gene and established that a 969-base pair ( bp ) fragment confers cell-specific expression of a CAT reporter gene that correlates with the expression of endogenous ecto-5'-NT mRNA and enzymatic activity .", "target_text": { "5' region": "DNA", "ecto-5'-nucleotidase": "protein", "ecto-5'-nucleotidase ( low K ( m ) 5'-NT ) gene": "DNA", "969-base pair ( bp ) fragment": "DNA", "CAT reporter gene": "DNA", "endogenous ecto-5'-NT mRNA": "RNA" } }, { "input_text": "A 768-bp upstream negative regulatory region has been identified that conferred lymphocyte-specific negative regulation in a heterologous system with a 244-bp deoxycytidine kinase core promoter .", "target_text": { "768-bp upstream negative regulatory region": "DNA", "244-bp deoxycytidine kinase core promoter": "DNA" } }, { "input_text": "DNase I footprinting identified several protected areas including Sp1 , Sp1/AP-2 , and cAMP response element ( CRE ) binding sites within the 201-bp core promoter region and Sp1 , NRE-2a , TCF-1/LEF-1 , and Sp1/NF-AT binding sites in the upstream regulatory region .", "target_text": { "DNase I": "protein", "upstream regulatory region": "DNA" } }, { "input_text": "Whereas the CRE site was essential in mediating the negative activity of the upstream regulatory region in Jurkat but not in HeLa cells , mutation of the Sp1/AP-2 site decreased promoter activity in both cell lines .", "target_text": { "CRE site": "DNA", "upstream regulatory region": "DNA", "Jurkat": "cell_line", "HeLa cells": "cell_line", "Sp1/AP-2 site": "DNA" } }, { "input_text": "Electrophoretic mobility shift assay analysis of proteins binding to the CRE site identified both ATF-1 and ATF-2 in Jurkat cells .", "target_text": { "CRE site": "DNA", "ATF-1": "protein", "ATF-2": "protein", "Jurkat cells": "cell_line" } }, { "input_text": "Finally , phorbol 12-myristate 13-acetate increased the activity of both the core and the 969-bp promoter fragments , and this increase was abrogated by mutations at the CRE site .", "target_text": { "969-bp promoter fragments": "DNA", "CRE site": "DNA" } }, { "input_text": "In summary , we have identified a tissue-specific regulatory region 5' of the ecto-5'-NT core promoter that requires the presence of a functional CRE site within the basal promoter for its suppressive activity .", "target_text": { "tissue-specific regulatory region": "DNA", "ecto-5'-NT core promoter": "DNA", "CRE site": "DNA", "basal promoter": "DNA" } }, { "input_text": "Extracellular signal-regulated protein kinase ( ERK ) -dependent and ERK-independent pathways target STAT3 on serine-727 in human neutrophils stimulated by chemotactic factors and cytokines .", "target_text": { "STAT3": "protein", "chemotactic factors": "protein", "cytokines": "protein" } }, { "input_text": "STAT3 ( signal transducer and activator of transcription 3 ) is a latent transcription factor that is activated by tyrosine phosphorylation ( Tyr-705 ) in cells stimulated with cytokines or growth factors .", "target_text": { "STAT3": "protein", "signal transducer and activator of transcription 3": "protein", "cytokines": "protein", "growth factors": "protein" } }, { "input_text": "Recent studies suggest that one or more cytoplasmic serine kinases also phosphorylate STAT3 and are necessary for maximal gene activation .", "target_text": { "cytoplasmic serine kinases": "protein", "STAT3": "protein" } }, { "input_text": "Here we demonstrate , with a site-specific antibody , that STAT3 is phosphorylated on Ser-727 in human neutrophils stimulated with chemotactic factors ( N-formyl-methionyl-leucyl-phenylalanine and complement C5a ) , cytokines [ granulocyte/macrophage colony-stimulating factor ( GM-CSF ) and granulocyte colony-stimulating factor ( G-CSF ) ] , or a protein kinase C activator ( PMA ) .", "target_text": { "STAT3": "protein", "human neutrophils": "cell_type", "chemotactic factors": "protein", "cytokines": "protein", "granulocyte/macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "granulocyte colony-stimulating factor": "protein", "G-CSF": "protein", "protein kinase C": "protein" } }, { "input_text": "(2-Amino-3'-methoxyphenyl)oxanaphthalen-4-one ( PD 98059 ) , an inhibitor of extracellular signal-regulated protein kinase ( ERK ) activation , blocked the serine phosphorylation of STAT3 induced by chemotactic factors or PMA .", "target_text": { "signal-regulated protein kinase": "protein", "ERK": "protein", "STAT3": "protein", "chemotactic factors": "protein" } }, { "input_text": "The drug was less effective on cytokines : it virtually abolished the response to GM-CSF that occurred 5 min after stimulation but only partly decreased those at 15-30 min and did not appreciably alter responses to G-CSF regardless of incubation time .", "target_text": { "cytokines": "protein", "GM-CSF": "protein", "G-CSF": "protein" } }, { "input_text": "1-(5-Isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride ( H7 ) , an inhibitor of a putative STAT3 serine kinase , and 4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl) 1H-imidazole ( SB 203580 ) , an inhibitor of p38 mitogen-activated protein ( MAP ) kinase , did not dampen any of these serine phosphorylation responses .", "target_text": { "STAT3": "protein", "STAT3 serine kinase": "protein", "p38 mitogen-activated protein ( MAP ) kinase": "protein" } }, { "input_text": "We propose that neutrophils use both ERK-dependent and ERK-independent pathways to phosphorylate Ser-727 on STAT3 .", "target_text": { "neutrophils": "cell_type", "STAT3": "protein" } }, { "input_text": "The former pathway is recruited by all ERK -activating stimuli , whereas the latter pathway uses an undefined serine kinase and is recruited selectively by cytokines .", "target_text": { "ERK": "protein", "serine kinase": "protein", "cytokines": "protein" } }, { "input_text": "GATA transcription factors associate with a novel class of nuclear bodies in erythroblasts and megakaryocytes .", "target_text": { "GATA transcription factors": "protein", "erythroblasts": "cell_type", "megakaryocytes": "cell_type" } }, { "input_text": "The nuclear distribution of GATA transcription factors in murine haemopoietic cells was examined by indirect immunofluorescence .", "target_text": { "GATA transcription factors": "protein", "murine haemopoietic cells": "cell_type" } }, { "input_text": "Specific bright foci of GATA-1 fluorescence were observed in erythroleukaemia cells and primary murine erythroblasts and megakaryocytes , in addition to diffuse nucleoplasmic localization .", "target_text": { "GATA-1": "protein", "erythroleukaemia cells": "cell_type", "erythroblasts": "cell_type", "primary murine erythroblasts": "cell_type", "megakaryocytes": "cell_type" } }, { "input_text": "These foci , which were preferentially found adjacent to nucleoli or at the nuclear periphery , did not represent sites of active transcription or binding of GATA-1 to consensus sites in the beta-globin loci .", "target_text": { "GATA-1": "protein", "consensus sites": "DNA", "beta-globin loci": "DNA" } }, { "input_text": "Immunoelectron microscopy demonstrated the presence of intensely labelled structures likely to represent the GATA-1 foci seen by immunofluorescence .", "target_text": { "GATA-1": "protein" } }, { "input_text": "The GATA-1 nuclear bodies differed from previously described nuclear structures and there was no co-localization with nuclear antigens involved in RNA processing or other ubiquitous ( Spl , c-Jun and TBP ) or haemopoietic ( NF-E2 ) transcription factors .", "target_text": { "GATA-1": "protein", "nuclear antigens": "protein", "Spl": "protein", "c-Jun": "protein", "TBP": "protein", "ubiquitous ( Spl , c-Jun and TBP ) or haemopoietic ( NF-E2 ) transcription factors": "protein" } }, { "input_text": "Interestingly , GATA-2 and GATA-3 proteins also localized to the same nuclear bodies in cell lines co-expressing GATA -1 and -2 or GATA -1 and -3 gene products .", "target_text": { "GATA-2": "protein", "GATA-3": "protein", "GATA-3 proteins": "protein" } }, { "input_text": "This pattern of distribution is , thus far , unique to the GATA transcription factors and suggests a protein-protein interaction with other components of the nuclear bodies via the GATA zinc finger domain .", "target_text": { "GATA transcription factors": "protein", "GATA zinc finger domain": "protein" } }, { "input_text": "Energy substrates , hormone responses and glucocorticoid binding in lymphocytes during intense physical exercise in humans following phosphocreatine administration .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "Eight healthy untrained male volunteers pedalled a cycle ergometer according to two exercise protocols : the first involved step-wise increasing physical exercise to maximal ( MPE ) ; the second involved prolonged ( 35 min ) submaximal physical exercise ( PPE ) at 70 % of the individual 's maximal oxygen uptake .", "target_text": {} }, { "input_text": "Each volunteer performed these exercise twice , following either an intravenous injection of phosphocreatine ( PCr ) or a placebo of an isotonic NaCl solution .", "target_text": {} }, { "input_text": "Anaerobic threshold ( AT ) was determined from the point of departure of the ventilatory response from linearity and from the sudden increase in venous blood lactate concentrations during MPE .", "target_text": {} }, { "input_text": "After exercise following placebo administration we observed increases in concentrations of blood substrates , plasma adrenocorticotropin ( ACTH ) , growth hormone and cortisol and in the number of glucocorticoid receptors in lymphocytes without changes in the dissociation constant .", "target_text": { "plasma adrenocorticotropin": "protein", "ACTH": "protein", "glucocorticoid receptors": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Intravenous administration of PCr ( starting 1 day before exercise ) led to an increase in the total workload ( on average by 5.8 % ) and in AT ( on average by 6.8 % ) during MPE and to a better tolerance of exercise during PPE .", "target_text": {} }, { "input_text": "Following PCr administration we observed lower blood lactate concentrations and different patterns of some enzyme activities , less pronounced changes in plasma ACTH and cortisol concentrations and in glucocorticoid binding in lymphocytes , but no changes in plasma growth hormone concentrations compared to the placebo .", "target_text": { "ACTH": "protein", "plasma ACTH": "protein", "lymphocytes": "cell_type" } }, { "input_text": "The results showed that intense physical exercise led not only to increases in blood hormone concentrations but also to an increase in the density of glucocorticoid receptors in lymphocytes .", "target_text": { "glucocorticoid receptors": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Intravenous PCr injection led to smaller changes in ACTH and cortisol concentrations as well as to a lower activation of glucocorticoid binding in lymphocytes .", "target_text": { "ACTH": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Putative steroid binding domain of the human mineralocorticoid receptor , expressed in E. coli in the presence of heat shock proteins shows typical native receptor characteristics .", "target_text": { "Putative steroid binding domain": "protein", "human mineralocorticoid receptor": "protein", "heat shock proteins": "protein" } }, { "input_text": "Domain E , considered as the putative hormone binding domain ( HBD ) of the human mineralocorticoid receptor ( hMR ) was expressed in Escherichia coli as a fusion protein with either maltose binding protein ( MBP ) or glutathione S-transferase ( GST ) .", "target_text": { "Domain E": "protein", "putative hormone binding domain": "protein", "HBD": "protein", "human mineralocorticoid receptor": "protein", "hMR": "protein", "maltose binding protein": "protein", "MBP": "protein", "glutathione S-transferase": "protein", "GST": "protein" } }, { "input_text": "These bacterially-produced MR constructs had no steroid binding activity per se .", "target_text": { "bacterially-produced MR constructs": "DNA" } }, { "input_text": "In fact , heat shock protein association ( hsp ) is required for high affinity ligand-binding of the MR .", "target_text": { "heat shock protein": "protein", "hsp": "protein", "MR": "protein" } }, { "input_text": "After incubation of purified MBP- or GST- HBD with rabbit reticulocyte lysate , known to be rich in heat shock proteins , we obtained saturable binding of [3H]aldosterone .", "target_text": { "heat shock proteins": "protein" } }, { "input_text": "The Kd value for aldosterone was 0.3 nM and the Bmax = 32 pmol/mg .", "target_text": {} }, { "input_text": "Hormone binding specificity was assessed by competition studies with various steroid ligands .", "target_text": {} }, { "input_text": "Sucrose gradient assays performed with [3H]aldosterone -MBP-HBD revealed complex sedimenting at 8.3S and 4.9S with [3H]progesterone-MBP-HBD .", "target_text": { "[3H]aldosterone -MBP-HBD": "protein", "[3H]progesterone-MBP-HBD": "protein" } }, { "input_text": "Western-blot analysis of the sedimentation peak showed the concomitant presence of MBP-HBD by a monoclonal anti-MBP antibody , and hsp90 by a monoclonal anti-hsp antibody .", "target_text": { "MBP-HBD": "protein", "monoclonal anti-MBP antibody": "protein", "hsp90": "protein", "monoclonal anti-hsp antibody": "protein" } }, { "input_text": "Moreover , following incubation with the anti-rabbit hsp90 monoclonal antibody the sedimenting gradient showed a 10.4S sedimenting complex .", "target_text": { "hsp90": "protein", "anti-rabbit hsp90 monoclonal antibody": "protein", "10.4S sedimenting complex": "protein" } }, { "input_text": "These analyses demonstrated that the [3H]aldosterone - MBP-HBD complex is at least associated with hsp90 in reticulocyte lysate and that the HBD of hMR is sufficient to bind hsp90 .", "target_text": { "MBP-HBD": "protein", "MBP-HBD complex": "protein", "hsp90": "protein", "HBD": "protein", "hMR": "protein" } }, { "input_text": "Deletions of a relatively short amino- ( 729-766 ) or carboxy- terminal ( 940-984 ) region of the HBD fragment eliminated all steroid-binding properties .", "target_text": { "HBD": "protein", "HBD fragment": "protein" } }, { "input_text": "Overall , these results indicate that the integrity of domain E is necessary and sufficient to bind steroid ligands , agonists or antagonists , with characteristics similar to the entire native MR .", "target_text": { "domain E": "protein", "MR": "protein" } }, { "input_text": "Renal cell carcinoma-derived gangliosides suppress nuclear factor-kappaB activation in T cells .", "target_text": { "nuclear factor-kappaB": "protein", "T cells": "cell_type" } }, { "input_text": "Activation of the transcription factor nuclear factor-kappaB ( NFkappaB ) is impaired in T cells from patients with renal cell carcinomas ( RCCs ) .", "target_text": { "transcription factor nuclear factor-kappaB": "protein", "NFkappaB": "protein", "T cells": "cell_type" } }, { "input_text": "In circulating T cells from a subset of patients with RCCs , the suppression of NFkappaB binding activity is downstream from the stimulus-induced degradation of the cytoplasmic factor IkappaBalpha .", "target_text": { "T cells": "cell_type", "NFkappaB": "protein", "cytoplasmic factor": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Tumor-derived soluble products from cultured RCC explants inhibit NFkappaB activity in T cells from healthy volunteers , despite a normal level of stimulus-induced IkappaBalpha degradation in these cells .", "target_text": { "Tumor-derived soluble products": "protein", "NFkappaB": "protein", "T cells": "cell_type", "IkappaBalpha": "protein" } }, { "input_text": "The inhibitory agent has several features characteristic of a ganglioside , including sensitivity to neuraminidase but not protease treatment ; hydrophobicity ; and molecular weight less than 3 kDa .", "target_text": { "neuraminidase": "protein", "protease": "protein" } }, { "input_text": "Indeed , we detected gangliosides in supernatants from RCC explants and not from adjacent normal kidney tissue .", "target_text": { "RCC explants": "cell_type" } }, { "input_text": "Gangliosides prepared from RCC supernatants , as well as the purified bovine gangliosides G ( m1 ) and G ( d1a ) , suppressed NFkappaB binding activity in T cells and reduced expression of the cytokines IL-2 and IFN-gamma .", "target_text": { "NFkappaB": "protein", "T cells": "cell_type", "cytokines": "protein", "IL-2": "protein", "IFN-gamma": "protein" } }, { "input_text": "Taken together , our findings suggest that tumor-derived gangliosides may blunt antitumor immune responses in patients with RCCs .", "target_text": {} }, { "input_text": "Nuclear factor-kappaB -dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha : evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation .", "target_text": { "Nuclear factor-kappaB": "protein", "interleukin-8": "protein", "tumor necrosis factor alpha": "protein" } }, { "input_text": "Tumor necrosis factor alpha ( TNFalpha ) is a pluripotent activator of inflammation by inducing a proinflammatory cytokine cascade .", "target_text": { "Tumor necrosis factor alpha": "protein", "TNFalpha": "protein", "proinflammatory cytokine": "protein" } }, { "input_text": "This phenomenon is mediated , in part , through inducible expression of the CXC chemokine , interleukin-8 ( IL-8 ) .", "target_text": { "CXC chemokine": "protein", "interleukin-8": "protein" } }, { "input_text": "In this study , we investigate the role of TNFalpha -inducible reactive oxygen species ( ROS ) in IL-8 expression by \" monocyte-like \" U937 histiocytic lymphoma cells .", "target_text": { "TNFalpha": "protein", "IL-8": "protein", "U937 histiocytic lymphoma cells": "cell_line" } }, { "input_text": "TNFalpha is a rapid activator of IL-8 gene expression by U937 , producing a 50-fold induction of mRNA within 1 hour of treatment .", "target_text": { "TNFalpha": "protein", "IL-8": "protein", "IL-8 gene": "DNA", "U937": "cell_line", "mRNA": "RNA" } }, { "input_text": "In gene transfection assays , the effect of TNFalpha requires the presence of an inducible nuclear factor-kappaB ( NF-kappaB ) ( Rel A ) binding site in the IL-8 promoter .", "target_text": { "TNFalpha": "protein", "NF-kappaB": "protein", "Rel A": "protein", "inducible nuclear factor-kappaB ( NF-kappaB ) ( Rel A ) binding site": "DNA", "IL-8": "protein", "IL-8 promoter": "DNA" } }, { "input_text": "TNFalpha treatment induces a rapid translocation of the 65 kD transcriptional activator NF-kappaB subunit , Rel A , whose binding in the nucleus occurs before changes in intracellular ROS .", "target_text": { "TNFalpha": "protein", "65 kD transcriptional activator": "protein", "NF-kappaB": "protein", "NF-kappaB subunit": "protein", "Rel A": "protein" } }, { "input_text": "Pretreatment ( or up to 15 minutes posttreatment ) relative to TNFalpha with the antioxidant dimethyl sulfoxide ( DMSO ) ( 2 % [ vol/vol ] ) blocks 80 % of NF-kappaB -dependent transcription .", "target_text": { "TNFalpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "Surprisingly , however , DMSO has no effect on inducible Rel A binding .", "target_text": { "Rel A": "protein" } }, { "input_text": "Similar selective effects on NF-kappaB transcription are seen with the unrelated antioxidants , N-acetylcysteine ( NAC ) and vitamin C .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "These data indicate that TNFalpha induces a delayed ROS-dependent signalling pathway that is required for NF-kappaB transcriptional activation and is separable from that required for its nuclear translocation .", "target_text": { "TNFalpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "Further definition of this pathway will yield new insights into inflammation initiated by TNFalpha signalling .", "target_text": { "TNFalpha": "protein" } }, { "input_text": "Gender and vascular reactivity .", "target_text": {} }, { "input_text": "Estrogen receptors are found on vascular endothelial and smooth muscle cells ; their expression is influenced by exposure to the hormone .", "target_text": { "Estrogen receptors": "protein" } }, { "input_text": "Estrogen receptors influence non-genomic events , which are rapid in onset and genomic events , which are longer acting responses .", "target_text": { "Estrogen receptors": "protein" } }, { "input_text": "Estrogens affect vascular tone indirectly by modulating release of endothelium-derived vasoactive factors and directly by modulating intracellular calcium in vascular smooth muscle cells .", "target_text": { "endothelium-derived vasoactive factors": "protein", "vascular smooth muscle cells": "cell_type" } }, { "input_text": "Estrogens indirectly affect thrombotic events and inflammation by altering platelet aggregation and leukocyte adherence and migration , respectively .", "target_text": { "platelet": "cell_type", "leukocyte": "cell_type" } }, { "input_text": "Estrogens also influence production of mitogens which , when released at sites of vascular injury , affect vascular remodeling .", "target_text": {} }, { "input_text": "Although estrogens initiate vascular responses , genomic sex may influence and/or limit expression of estrogen receptors and therefore actions of sex steroid hormones throughout the vasculature .", "target_text": {} }, { "input_text": "Induction of a functional vitamin D receptor in all-trans-retinoic acid -induced monocytic differentiation of M2-type leukemic blast cells .", "target_text": { "vitamin D receptor": "protein", "M2-type leukemic blast cells": "cell_line" } }, { "input_text": "Different types of acute myeloid leukemia blast cells were induced to differentiate in vitro with all-trans-retinoic acid ( ATRA ) and vitamin D3 ( VD ) .", "target_text": { "acute myeloid leukemia blast cells": "cell_type" } }, { "input_text": "M0/M1 leukemic cells are not sensitive to differentiating agents , whereas M3 leukemic cells are induced to undergo granulocytic differentiation after ATRA treatment but are not sensitive to VD .", "target_text": { "M0/M1 leukemic cells": "cell_line", "M3 leukemic cells": "cell_line" } }, { "input_text": "M2 leukemic blast cells behave differently because they undergo monocytic differentiation with both the differentiation inducers .", "target_text": { "M2 leukemic blast cells": "cell_line" } }, { "input_text": "To gain some insight into the maturation of M2-type leukemic cells , we studied the molecular mechanisms underlying monocytic differentiation induced by ATRA and VD in spontaneous M2 blast cells as well as in Kasumi-1 cells ( an acute myeloid leukemia M2-type cell line ) .", "target_text": { "M2-type leukemic cells": "cell_type", "M2 blast cells": "cell_line", "Kasumi-1 cells": "cell_line", "acute myeloid leukemia M2-type cell line": "cell_line" } }, { "input_text": "Our results indicate that ATRA as well as VD efficiently increases the nuclear abundance of VD receptor ( VDR ) and promotes monocytic differentiation .", "target_text": { "VD receptor": "protein", "VDR": "protein" } }, { "input_text": "VDR is functionally active in ATRA -treated Kasumi-1 cells because it efficiently heterodimerizes with retinoid X receptor , binds to a DR3-type vitamin D-responsive element , and activates the transcription of a vitamin D-responsive element-regulated reporter gene .", "target_text": { "VDR": "protein", "Kasumi-1 cells": "cell_line", "retinoid X receptor": "protein", "DR3-type vitamin D-responsive element": "DNA", "vitamin D-responsive element-regulated reporter gene": "DNA" } }, { "input_text": "Consistent with these findings , VD -responsive genes are induced by ATRA treatment of Kasumi-1 cells , suggesting that the genetic program underlying monocytic differentiation is activated .", "target_text": { "VD -responsive genes": "DNA", "Kasumi-1 cells": "cell_line" } }, { "input_text": "The molecular mechanism by which ATRA increases the nuclear abundance of a functional VDR is still unknown , but our data clearly indicate that the M2 leukemic cell context is only permissive of monocytic differentiation .", "target_text": { "VDR": "protein", "M2 leukemic cell": "cell_line" } }, { "input_text": "Protein kinase C and calcineurin synergize to activate IkappaB kinase and NF-kappaB in T lymphocytes .", "target_text": { "Protein kinase C": "protein", "calcineurin": "protein", "IkappaB kinase": "protein", "NF-kappaB": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "The nuclear factor of kappaB ( NF-kappaB ) is a ubiquitous transcription factor that is key in the regulation of the immune response and inflammation .", "target_text": { "NF-kappaB": "protein", "ubiquitous transcription factor": "protein" } }, { "input_text": "T cell receptor ( TCR ) cross-linking is in part required for activation of NF-kappaB , which is dependent on the phosphorylation and degradation of IkappaBalpha .", "target_text": { "T cell receptor": "protein", "TCR": "protein", "NF-kappaB": "protein", "IkappaBalpha": "protein" } }, { "input_text": "By using Jurkat and primary human T lymphocytes , we demonstrate that the simultaneous activation of two second messengers of the TCR -initiated signal transduction , protein kinase C ( PKC ) and calcineurin , results in the synergistic activation of the IkappaBalpha kinase ( IKK ) complex but not of another putative IkappaBalpha kinase , p90 ( rsk ) .", "target_text": { "Jurkat": "cell_line", "T lymphocytes": "cell_type", "primary human T lymphocytes": "cell_type", "TCR": "protein", "protein kinase C": "protein", "PKC": "protein", "calcineurin": "protein", "IkappaBalpha": "protein", "IkappaBalpha kinase ( IKK ) complex": "protein", "putative IkappaBalpha kinase": "protein", "p90 ( rsk )": "protein" } }, { "input_text": "We also demonstrate that the IKK complex , but not p90 ( rsk ) , is responsible for the in vivo phosphorylation of IkappaBalpha mediated by the co-activation of PKC and calcineurin .", "target_text": { "IKK complex": "protein", "p90 ( rsk )": "protein", "IkappaBalpha": "protein", "PKC": "protein", "calcineurin": "protein" } }, { "input_text": "Each second messenger is necessary , as inhibition of either one reverses the activation of the IKK complex and IkappaBalpha phosphorylation in vivo .", "target_text": { "IKK complex": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Overexpression of dominant negative forms of IKK alpha and -beta demonstrates that only IKKbeta is the target for PKC and calcineurin .", "target_text": { "IKKbeta": "protein", "PKC": "protein", "calcineurin": "protein" } }, { "input_text": "These results indicate that within the TCR /CD3 signal transduction pathway both PKC and calcineurin are required for the effective activation of the IKK complex and NF-kappaB in T lymphocytes .", "target_text": { "TCR": "protein", "/CD3": "protein", "PKC": "protein", "calcineurin": "protein", "IKK complex": "protein", "NF-kappaB": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Diminished responses to IL-13 by human monocytes differentiated in vitro : role of the IL-13Ralpha1 chain and STAT6 .", "target_text": { "IL-13": "protein", "IL-13Ralpha1 chain": "protein", "STAT6": "protein" } }, { "input_text": "The primary IL-13 receptor complex on human monocytes is believed to be a heterodimer comprised of the IL-4R alpha chain and the IL-2R gamma chain ( gamma(c) ) -like molecule , IL-13R alpha1 .", "target_text": { "IL-13": "protein", "IL-13 receptor complex": "protein", "human monocytes": "cell_type", "IL-4R alpha chain": "protein", "IL-2R gamma chain": "protein", "( gamma(c) ) -like molecule": "protein", "IL-13R alpha1": "protein" } }, { "input_text": "mRNA levels for IL-13R alpha1 , but not IL-4R alpha , were markedly decreased in in vitro monocyte-derived macrophages ( MDMac ) , and with increasing time of monocytes in culture correlated with the loss of IL-13 regulation of lipopolysaccharide -induced TNF-alpha production .", "target_text": { "mRNA": "RNA", "IL-13R alpha1": "protein", "IL-4R alpha": "protein", "in vitro monocyte-derived macrophages": "cell_line", "MDMac": "cell_line", "monocytes": "cell_type", "IL-13": "protein", "TNF-alpha": "protein" } }, { "input_text": "Analysis of cell lines Daudi and THP-1 that differentially express gamma(c) and IL-13R alpha1 showed that IL-13 can activate STAT6 in IL-13R alpha1 -positive THP-1 cells but not in gamma(c)-positive , IL-13R alpha1 -negative Daudi cells .", "target_text": { "cell lines": "cell_line", "Daudi": "cell_line", "THP-1": "cell_line", "gamma(c)": "protein", "IL-13R alpha1": "protein", "IL-13": "protein", "STAT6": "protein", "IL-13R alpha1 -positive THP-1 cells": "cell_line", "gamma(c)-positive , IL-13R alpha1 -negative Daudi cells": "cell_line" } }, { "input_text": "IL-13 activation of STAT6 was reduced in MDMac which was associated with diminished IL-13 -induced expression of CD23 and MHC class II .", "target_text": { "IL-13": "protein", "STAT6": "protein", "MDMac": "cell_line", "CD23": "protein", "MHC class II": "protein" } }, { "input_text": "However , with reduced IL-13R alpha1 expression and low nuclear STAT6 activity , some IL-13 -induced responses were unaltered in magnitude in MDMac .", "target_text": { "IL-13R alpha1": "protein", "STAT6": "protein", "IL-13": "protein", "MDMac": "cell_line" } }, { "input_text": "In the absence of functional IL-13R alpha1 and gamma(c) , IL-13 must signal through an alternative receptor complex on MDMac .", "target_text": { "IL-13R alpha1": "protein", "gamma(c)": "protein", "IL-13": "protein", "receptor complex": "protein", "MDMac": "cell_line" } }, { "input_text": "Experiments with a blocking antibody to IL-4R alpha showed that this chain remains an essential component of the IL-13 receptor complex on MDMac .", "target_text": { "IL-4R alpha": "protein", "IL-13": "protein", "IL-13 receptor complex": "protein", "MDMac": "cell_line" } }, { "input_text": "The p53 paradox in the pathogenesis of tumor progression .", "target_text": { "p53": "protein" } }, { "input_text": "Recent evidence suggests that the p53 molecule appears in two different forms : the mutant p53 that stimulates tumor progression , and wild type p53 that inhibits tumor progression .", "target_text": { "p53 molecule": "protein", "mutant p53": "protein", "wild type p53": "protein" } }, { "input_text": "In addition , it has been established that tumor necrosis factor-alpha ( TNF-alpha ) can activate the expression of wild type p53 in concert with the nuclear transcription factor , NF-kappa B .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "wild type p53": "protein", "nuclear transcription factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "Both TNF-alpha and NF-kappa B are also involved in the stimulation of the pathway that leads to the expression of major histocompatibility complex ( MHC ) class I molecules and , hence , antigen presentation to the T cells .", "target_text": { "TNF-alpha": "protein", "NF-kappa B": "protein", "major histocompatibility complex ( MHC ) class I molecules": "protein", "T cells": "cell_type" } }, { "input_text": "In this paper we shall advance the hypothesis that : ( i ) TNF-alpha indirectly controls immune surveillance ; and ( ii ) TNF-alpha controls DNA repair and tumor suppression through the regulation of wild type p53 .", "target_text": { "TNF-alpha": "protein", "wild type p53": "protein" } }, { "input_text": "Thus , it is hypothesized that elevated TNF-alpha is primarily responsible for promoting tumor progression .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "The promoter and 5' flanking sequences controlling human B29 gene expression .", "target_text": { "promoter": "DNA", "5' flanking sequences": "DNA", "B29": "protein", "B29 gene": "DNA" } }, { "input_text": "The product of the B-cell-specific B29 gene ( B29 , Ig beta , CD79b ) is essential for Ig-mediated B-cell activation via the B-cell antigen receptor complex ( BCR ) on human and murine B lymphocytes .", "target_text": { "B29": "protein", "B29 gene": "DNA", "B-cell-specific B29 gene": "DNA", "Ig beta": "protein", "CD79b": "protein", "B-cell antigen receptor complex": "protein", "BCR": "protein" } }, { "input_text": "To better understand the regulation of this pivotal gene , we have analyzed the human genomic DNA sequence upstream of the B29 ATG start codon for transcriptional control activity .", "target_text": { "human genomic DNA sequence": "DNA", "B29": "protein", "ATG start codon": "DNA" } }, { "input_text": "The human B29 gene lacks either a TATA or a CAAT box and transcription is initiated at multiple sites .", "target_text": { "B29": "protein", "B29 gene": "DNA", "multiple sites": "DNA" } }, { "input_text": "The minimal promoter of the human B29 gene is contained within a 193-bp region 5' of these multiple start sites .", "target_text": { "B29": "protein", "B29 gene": "DNA", "human B29 gene": "DNA", "193-bp region": "DNA", "multiple start sites": "DNA" } }, { "input_text": "This minimal promoter exhibits B-cell-specific activity and contains SP1 , ETS , OCT , and IKAROS/LYF-1 transcription factor motifs .", "target_text": { "minimal promoter": "DNA" } }, { "input_text": "All these motifs are strikingly conserved in sequence and placement relative to the previously characterized murine B29 promoter .", "target_text": { "B29": "protein", "murine B29 promoter": "DNA" } }, { "input_text": "Additional upstream gene segments dramatically affected B29 minimal promoter activity .", "target_text": { "B29": "protein", "minimal promoter": "DNA" } }, { "input_text": "A newly identified motif called the B29 conserved sequence ( BCS ) , found upstream of both human and murine B29 promoters , appears to stimulate B29 transcription through a novel mechanism .", "target_text": { "B29": "protein", "B29 conserved sequence": "DNA", "BCS": "DNA", "human and murine B29 promoters": "DNA" } }, { "input_text": "A single BCS had little effect either on the minimal B29 promoter or on a heterologous promoter .", "target_text": { "BCS": "DNA", "B29": "protein", "B29 promoter": "DNA" } }, { "input_text": "Instead , the BCS stimulated transcription by counteracting 5' negative regulatory DNA sequences that block the activity of the B29 minimal promoter in its absence .", "target_text": { "BCS": "DNA", "5' negative regulatory DNA sequences": "DNA", "B29": "protein", "minimal promoter": "DNA" } }, { "input_text": "These findings indicate that B29 gene expression is controlled by the complex interplay of positive and negative regulatory elements .", "target_text": { "B29": "protein", "B29 gene": "DNA", "negative regulatory elements": "DNA" } }, { "input_text": "A novel immunosuppressive factor in bovine colostrum blocks activation of the interleukin 2 gene enhancer at the NFAT site .", "target_text": { "immunosuppressive factor": "protein", "interleukin 2 gene enhancer": "DNA", "NFAT site": "DNA" } }, { "input_text": "A factor in bovine colostrum ( colostrum inhibitory factor , CIF ) inhibits interleukin 2 ( IL2 ) production in activated T helper cells by blocking the accumulation of IL2 mRNA .", "target_text": { "colostrum inhibitory factor": "protein", "CIF": "protein", "interleukin 2": "protein", "IL2": "protein", "T helper cells": "cell_type", "IL2 mRNA": "RNA" } }, { "input_text": "To determine whether CIF blocks at the level of IL2 transcription , we introduced reporter plasmids into the human T leukemia cell line Jurkat by transient transfection .", "target_text": { "CIF": "protein", "IL2": "protein", "human T leukemia cell line Jurkat": "cell_line" } }, { "input_text": "These contained the luciferase gene under the control of either the human IL2 upstream enhancer region ( segments -326 to +45 ) or three repeats of the NFAT element contained within it ( segments -255 to -285 ) .", "target_text": { "luciferase": "protein", "luciferase gene": "DNA", "IL2": "protein", "human IL2 upstream enhancer": "DNA", "NFAT element": "DNA" } }, { "input_text": "Expression of luciferase in these cells was induced by phorbol myristate acetate plus a calcium ionophore .", "target_text": { "luciferase": "protein" } }, { "input_text": "CIF inhibited induction of either construct as did cyclosporine , which is known to block activation of the NFAT element .", "target_text": { "CIF": "protein", "NFAT element": "protein" } }, { "input_text": "CIF failed to inhibit several other enhancer elements .", "target_text": { "CIF": "protein", "enhancer elements": "DNA" } }, { "input_text": "The NFAT-controlled luciferase gene system distinguishes CIF from other T cell inhibitory activities present in colostrum , in particular , TGF beta 1 and TGF beta 2 and the glucocorticoids .", "target_text": { "luciferase": "protein", "luciferase gene": "DNA", "NFAT-controlled luciferase gene system": "DNA", "CIF": "protein", "TGF beta 1": "protein", "TGF beta 2": "protein" } }, { "input_text": "Stably transfected Jurkat cells behaved similarly to the transiently transfected ones with respect to inhibition by CIF and cyclosporine .", "target_text": { "CIF": "protein" } }, { "input_text": "The NFAT -luc assay is a useful technique for the rapid , sensitive measurement of CIF or other immunosuppressants with a similar mode of action .", "target_text": { "NFAT": "protein", "CIF": "protein" } }, { "input_text": "Heat shock induces HIV-1 replication in chronically infected promyelocyte cell line OM10.1 .", "target_text": { "promyelocyte cell line OM10.1": "cell_line" } }, { "input_text": "A long period of clinical latency before development of symptoms is characteristic of human immunodeficiency virus type 1 ( HIV-1 ) infection .", "target_text": {} }, { "input_text": "OM10.1 , a promyelocyte cell line latently infected with HIV-1 , has been developed as a model for studying the mechanism of viral latency and the activation of virus expression .", "target_text": { "OM10.1": "cell_line", "promyelocyte cell line": "cell_line" } }, { "input_text": "We found that this latently infected cell line with heat shock at 42 degrees C for 2 h resulted in a high level of HIV-1 production without addition of any cytokines .", "target_text": { "cytokines": "protein" } }, { "input_text": "The mechanism of activation was analyzed by using anti-TNF-alpha antibody and various inhibitors .", "target_text": { "anti-TNF-alpha antibody": "protein" } }, { "input_text": "Although the TNF-alpha level in culture supernatants was below the sensitivity of an ELISA assay system , addition of anti- TNF-alpha antibody in culture medium could partially suppress the heat shock induced HIV-1 production .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "Staurosporine ( PKC inhibitor ) , pentoxifylline ( NF-kappa B inhibitor ) , and Ro5-3335 ( HIV-1 Tat inhibitor ) also inhibited significantly the heat shock induced virus activation .", "target_text": { "Tat": "protein" } }, { "input_text": "In particular , staurosporine achieved approximately 90 % inhibition of the HIV-1 antigen expression in heat shock -treated OM10.1 at a non-toxic concentration .", "target_text": { "heat shock -treated OM10.1": "cell_line" } }, { "input_text": "Although the mechanism of HIV-1 activation with heat shock has not been fully elucidated yet , it is presumed PKC plays an important role in HIV-1 activation .", "target_text": { "PKC": "protein" } }, { "input_text": "Thus , the present observations will provide a further insight into the pathogenesis of HIV-1 infections .", "target_text": {} }, { "input_text": "Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin -based motility .", "target_text": { "CDC42": "protein", "CDC42 effector": "protein", "N-WASP": "protein", "Shigella flexneri IcsA protein": "protein", "actin": "protein", "Arp2/3 complex": "protein" } }, { "input_text": "To propel itself in infected cells , the pathogen Shigella flexneri subverts the Cdc42 -controlled machinery responsible for actin assembly during filopodia formation .", "target_text": { "infected cells": "cell_type", "Cdc42": "protein", "actin": "protein" } }, { "input_text": "Using a combination of bacterial motility assays in platelet extracts with Escherichia coli expressing the Shigella IcsA protein and in vitro analysis of reconstituted systems from purified proteins , we show here that the bacterial protein IcsA binds N-WASP and activates it in a Cdc42 -like fashion .", "target_text": { "Shigella IcsA protein": "protein", "purified proteins": "protein", "bacterial protein IcsA": "protein", "N-WASP": "protein", "Cdc42": "protein" } }, { "input_text": "Dramatic stimulation of actin assembly is linked to the formation of a ternary IcsA- N-WASP - Arp2/3 complex , which nucleates actin polymerization .", "target_text": { "actin": "protein", "N-WASP": "protein", "Arp2/3 complex": "protein", "IcsA- N-WASP - Arp2/3 complex": "protein" } }, { "input_text": "The Arp2/3 complex is essential in initiation of actin assembly and Shigella movement , as previously observed for Listeria monocytogenes .", "target_text": { "Arp2/3 complex": "protein", "actin": "protein" } }, { "input_text": "Activation of N-WASP by IcsA unmasks two domains acting together in insertional actin polymerization .", "target_text": { "N-WASP": "protein", "IcsA": "protein", "actin": "protein" } }, { "input_text": "The isolated COOH-terminal domain of N-WASP containing a verprolin-homology region , a cofilin-homology sequence , and an acidic terminal segment ( VCA ) interacts with G-actin in a unique profilin-like functional fashion .", "target_text": { "COOH-terminal domain": "protein", "N-WASP": "protein", "verprolin-homology region": "protein", "acidic terminal segment": "protein", "VCA": "protein", "G-actin": "protein" } }, { "input_text": "Hence , when N-WASP is activated , its COOH-terminal domain feeds barbed end growth of filaments and lowers the critical concentration at the bacterial surface .", "target_text": { "N-WASP": "protein", "COOH-terminal domain": "protein" } }, { "input_text": "On the other hand , the NH(2)-terminal domain of N-WASP interacts with F-actin , mediating the attachment of the actin tail to the bacterium surface .", "target_text": { "NH(2)-terminal domain": "protein", "N-WASP": "protein", "F-actin": "protein", "actin": "protein", "actin tail": "protein" } }, { "input_text": "VASP is not involved in Shigella movement , and the function of profilin does not require its binding to proline -rich regions .", "target_text": { "profilin": "protein", "proline -rich regions": "protein" } }, { "input_text": "c-Maf induces monocytic differentiation and apoptosis in bipotent myeloid progenitors .", "target_text": { "c-Maf": "protein", "bipotent myeloid progenitors": "cell_type" } }, { "input_text": "The transcriptional mechanisms that drive colony-forming unit granulocyte-macrophage ( CFU-GM ) myeloid progenitors to differentiate into cells of either the granulocytic or monocytic lineage are not fully understood .", "target_text": { "colony-forming unit granulocyte-macrophage ( CFU-GM ) myeloid progenitors": "cell_line" } }, { "input_text": "We have shown that the c-Maf and c-Myb transcription factors physically interact in myeloid cells to form inhibitory complexes that hinder transactivation of c-Myb target genes through direct binding to Myb consensus sites .", "target_text": { "c-Maf": "protein", "c-Myb": "protein", "c-Myb transcription factors": "protein", "c-Myb target genes": "DNA", "Myb consensus sites": "DNA" } }, { "input_text": "These complexes arise in a developmentally regulated pattern , peaking at the promyelocyte stage , or in cell model systems , appearing soon after the induction of monocytic differentiation .", "target_text": { "promyelocyte stage": "cell_type", "cell model systems": "cell_line" } }, { "input_text": "We wished to determine if this developmentally related interaction is a consequence of myeloid differentiation or an intrinsic differentiating stimulus .", "target_text": {} }, { "input_text": "Because the elevated Myb : Maf status seen in differentiating cells can be recapitulated by overexpression of c-Maf in myeloid cell lines , we inducibly expressed the c-Maf cDNA in 2 bipotent human myeloid progenitor cells .", "target_text": { "Myb : Maf": "protein", "differentiating cells": "cell_type", "c-Maf": "protein", "c-Maf cDNA": "DNA", "human myeloid progenitor cells": "cell_type" } }, { "input_text": "Elevated levels of c-Maf protein led to marked increases in Myb : Maf complexes and the accumulation of monocyte/macrophage cells , followed by eventual programmed cell death .", "target_text": { "c-Maf": "protein", "c-Maf protein": "protein", "Myb : Maf complexes": "protein", "monocyte/macrophage cells": "cell_type" } }, { "input_text": "Analysis of targets that could mediate these phenotypic changes indicated that c-Maf likely plays a key role in myeloid cell development through dual mechanisms ; inhibition of a select set of c-Myb regulated targets , such as Bcl-2 and CD13/APN , coupled with the activation of as yet undefined differentiation-promoting genes .", "target_text": { "c-Maf": "protein", "c-Myb": "protein", "Bcl-2": "protein", "CD13/APN": "protein", "differentiation-promoting genes": "DNA" } }, { "input_text": "AML1 ( CBFalpha2 ) cooperates with B cell-specific activating protein ( BSAP/PAX5 ) in activation of the B cell-specific BLK gene promoter .", "target_text": { "AML1": "protein", "CBFalpha2": "protein", "AML1 ( CBFalpha2 )": "protein", "BSAP/PAX5": "protein", "B cell-specific activating protein ( BSAP/PAX5 )": "protein", "B cell-specific BLK gene promoter": "DNA" } }, { "input_text": "AML1 plays a critical role during hematopoiesis and chromosomal translocations involving AML1 are commonly associated with different forms of leukemia , including pre-B acute lymphoblastic leukemia .", "target_text": { "AML1": "protein" } }, { "input_text": "To understand the function of AML1 during B cell differentiation , we analyzed regulatory regions of B cell-specific genes for potential AML1 -binding sites and have identified a putative AML1 -binding site in the promoter of the B cell-specific tyrosine kinase gene , blk .", "target_text": { "AML1": "protein", "B cell": "cell_type", "regulatory regions": "DNA", "B cell-specific genes": "DNA", "AML1 -binding sites": "DNA", "AML1 -binding site": "DNA", "B cell-specific tyrosine kinase gene , blk": "DNA" } }, { "input_text": "Gel mobility shift assays and transient transfection assays demonstrate that AML1 binds specifically to this site in the blk promoter and this binding site is important for blk promoter activity .", "target_text": { "AML1": "protein", "blk": "DNA", "blk promoter": "DNA" } }, { "input_text": "Furthermore , in vitro binding analysis revealed that the AML1 runt DNA-binding domain physically interacts with the paired DNA-binding domain of BSAP , a B cell -specific transcription factor .", "target_text": { "AML1": "protein", "AML1 runt DNA-binding domain": "DNA", "paired DNA-binding domain": "DNA", "BSAP": "protein", "B cell": "cell_type", "B cell -specific transcription factor": "protein" } }, { "input_text": "BSAP has been shown previously to be important for B cell-specific regulation of the blk gene .", "target_text": { "BSAP": "protein", "blk": "DNA" } }, { "input_text": "Physical interaction of AML1 with BSAP correlates with functional cooperativity in transfection studies where AML1 and BSAP synergistically activate blk promoter transcription by more than 50-fold .", "target_text": { "AML1": "protein", "BSAP": "protein", "blk": "DNA" } }, { "input_text": "These results demonstrate physical and functional interactions between AML1 and BSAP and suggest that AML1 is an important factor for regulating a critical B cell-specific gene , blk .", "target_text": { "AML1": "protein", "BSAP": "protein", "B cell-specific gene": "DNA", "blk": "DNA" } }, { "input_text": "Transcriptional inhibition by interleukin-6 of the class A macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line .", "target_text": { "interleukin-6": "protein", "class A macrophage scavenger receptor": "protein", "macrophages": "cell_type", "human peripheral monocytes": "cell_type", "THP-1": "cell_line", "THP-1 monocytic cell line": "cell_line" } }, { "input_text": "Expression of the class A macrophage scavenger receptor ( MSR ) contributes to the uptake of modified low density lipoproteins ( LDL ) by macrophages and transformation of these cells into lipid-laden foam cells , which characterize atherosclerosis .", "target_text": { "MSR": "protein", "class A macrophage scavenger receptor ( MSR )": "protein", "LDL": "protein", "modified low density lipoproteins ( LDL )": "protein", "macrophages": "cell_type", "lipid-laden foam cells": "cell_type" } }, { "input_text": "Many environmental factors , in particular , proinflammatory cytokines and growth factors , can exert regulatory effects on MSR expression , whereas intracellular accumulation of cholesterol itself does not influence MSR levels to any considerable extent .", "target_text": { "proinflammatory cytokines": "protein", "growth factors": "protein", "MSR": "protein" } }, { "input_text": "In the present study , by using an in vitro model , we examined whether stimulation with interleukin-6 ( IL-6 ) , an immunoregulatory , multipotential cytokine , modulates the expression and activities of the MSR in macrophages .", "target_text": { "interleukin-6 ( IL-6 )": "protein", "immunoregulatory": "protein", "multipotential cytokine": "protein", "MSR": "protein", "macrophages": "cell_type" } }, { "input_text": "When treated with IL-6 , macrophages derived from peripheral monocytes and phorbol 12-myristate 13-acetate ( PMA ) -differentiated THP-1 monocytic cells showed significantly reduced uptake and/or binding of the MSR ligand , acetylated LDL .", "target_text": { "IL-6": "protein", "macrophages": "cell_type", "peripheral monocytes": "cell_type", "phorbol 12-myristate 13-acetate ( PMA ) -differentiated THP-1 monocytic cells": "cell_line", "MSR": "protein", "LDL": "protein", "acetylated LDL": "protein" } }, { "input_text": "This effect was paralleled by a reduction in the expression of MSR protein and mRNA .", "target_text": { "MSR": "protein", "mRNA": "RNA" } }, { "input_text": "Analysis of MSR promoter activity in THP-1 cells transfected with an MSR promoter-reporter gene construct demonstrated decreased activity of the MSR promoter in IL-6 -treated THP-1 macrophages .", "target_text": { "MSR": "protein", "MSR promoter": "DNA", "THP-1": "cell_line", "THP-1 cells": "cell_line", "MSR promoter-reporter gene construct": "DNA", "IL-6": "protein", "macrophages": "cell_type" } }, { "input_text": "Electrophoretic mobility gel shift assay also showed a reduction in the binding of a transcription factor to the MSR promoter AP-1/ets elements in IL-6 -treated cells .", "target_text": { "transcription factor": "protein", "MSR": "protein", "MSR promoter": "DNA", "MSR promoter AP-1/ets elements": "DNA", "IL-6": "protein" } }, { "input_text": "Thus , exposure to IL-6 may inhibit expression of the class A MSR in differentiated macrophages at transcriptional levels .", "target_text": { "IL-6": "protein", "MSR": "protein", "class A MSR": "protein", "macrophages": "cell_type" } }, { "input_text": "This result suggests that this cytokine may modulate foam cell formation during atherogenesis .", "target_text": { "cytokine": "protein" } }, { "input_text": "Retinoblastoma protein expression leads to reduced Oct-1 DNA binding activity and enhances interleukin-8 expression .", "target_text": { "Retinoblastoma protein": "protein", "Oct-1": "protein", "interleukin-8": "protein" } }, { "input_text": "Tumor cell lines with a defective retinoblastoma gene are unable to transcribe the HLA class II genes in response to IFN-gamma treatment , and reconstitution of functional Rb rescues IFN-gamma-induced class II gene expression .", "target_text": { "retinoblastoma gene": "DNA", "HLA class II genes": "DNA", "IFN-gamma": "protein", "Rb": "protein", "class II gene": "DNA" } }, { "input_text": "However , the molecular mechanism of Rb rescue of the class II genes is unknown .", "target_text": { "Rb": "protein", "class II genes": "DNA" } }, { "input_text": "We have examined the effect of Rb expression on the activation of the promoter for HLA-DRA , the prototype class II gene .", "target_text": { "Rb": "protein", "HLA-DRA": "DNA", "prototype class II gene": "DNA" } }, { "input_text": "Oct-1 , a POU domain transcription factor , was identified as a repressor of HLA-DRA promoter activity in the Rb-defective cells .", "target_text": { "Oct-1": "protein", "POU domain transcription factor": "protein", "HLA-DRA": "DNA", "Rb-defective cells": "cell_type" } }, { "input_text": "Rb expression led to phosphorylation of Oct-1 , thus relieving its repressive effect .", "target_text": { "Rb": "protein", "Oct-1": "protein" } }, { "input_text": "Oct-1 has also been shown to repress interleukin 8 promoter activity .", "target_text": { "Oct-1": "protein", "interleukin 8": "protein" } }, { "input_text": "Consistent with reduced levels of Oct-1 DNA binding activity in the Rb-transformed cell lines , interleukin 8 expression is higher in these cell lines .", "target_text": { "Oct-1": "protein", "Rb-transformed cell lines": "cell_line", "interleukin 8": "protein" } }, { "input_text": "Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2 .", "target_text": { "bacterial lipoproteins": "protein", "toll-like receptor-2": "protein" } }, { "input_text": "Apoptosis is implicated in the generation and resolution of inflammation in response to bacterial pathogens .", "target_text": {} }, { "input_text": "All bacterial pathogens produce lipoproteins ( BLPs ) , which trigger the innate immune response .", "target_text": { "BLPs": "protein", "lipoproteins ( BLPs )": "protein" } }, { "input_text": "BLPs were found to induce apoptosis in THP-1 monocytic cells through human Toll-like receptor-2 ( hTLR2 ) .", "target_text": { "BLPs": "protein", "THP-1 monocytic cells": "cell_line", "hTLR2": "protein", "human Toll-like receptor-2 ( hTLR2 )": "protein" } }, { "input_text": "BLPs also initiated apoptosis in an epithelial cell line transfected with hTLR2 .", "target_text": { "BLPs": "protein", "epithelial cell line": "cell_line", "hTLR2": "protein" } }, { "input_text": "In addition , BLPs stimulated nuclear factor-kappaB , a transcriptional activator of multiple host defense genes , and activated the respiratory burst through hTLR2 .", "target_text": { "BLPs": "protein", "nuclear factor-kappaB": "protein", "transcriptional activator": "protein", "multiple host defense genes": "DNA", "hTLR2": "protein" } }, { "input_text": "Thus , hTLR2 is a molecular link between microbial products , apoptosis , and host defense mechanisms .", "target_text": { "hTLR2": "protein" } }, { "input_text": "Possible differences in the mechanism ( s ) of action of different glucocorticoid hormone compounds .", "target_text": {} }, { "input_text": "Different glucocorticoid hormones ( GCH ) show differences in the intensity and in the kinetics of their immunomodulating activity .", "target_text": {} }, { "input_text": "The mechanism ( s ) of action of GCH is under investigation , but is has been noted that they exert immune activity via the genomic pathway .", "target_text": {} }, { "input_text": "We have studied the effects of prednisone ( PDN ) , deflazacort ( DFC ) , and dexamethasone ( DXM ) on the production of cytokines ( IL-2 , IL-6 , TNF-alpha , IL-10 ) by peripheral T lymphocytes , and the effects on the inhibition of NF-kB DNA binding activity by activated Jurkat cell line .", "target_text": { "cytokines": "protein", "IL-2": "protein", "IL-6": "protein", "TNF-alpha": "protein", "IL-10": "protein", "peripheral T lymphocytes": "cell_type", "NF-kB": "protein", "activated Jurkat cell line": "cell_line" } }, { "input_text": "The data obtained show that the three GCH molecules exert an immunosuppression on cytokine production by T lymphocytes and a strong decrease in the nuclear translocation of NF-kB in Jurkat cells ; moreover , ( a ) not all the cytokines investigated were affected , and not with the same intensity , by the three GCH and ( b ) DXM inhibited the binding activity of NF-kB less than that of DFC and PDN .", "target_text": { "cytokine": "protein", "T lymphocytes": "cell_type", "NF-kB": "protein", "Jurkat cells": "cell_line", "cytokines": "protein" } }, { "input_text": "These data are in agreement with the concept that different GCH compounds might differ in their binding and affinity properties , tissue-specific metabolism , and interaction with transcription factor .", "target_text": { "transcription factor": "protein" } }, { "input_text": "Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin 's disease .", "target_text": { "BCL-6": "protein", "BCL-6 protein": "protein" } }, { "input_text": "The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger protein is rearranged in about 30 % diffuse large B-cell lymphomas and is expressed predominantly in normal germinal center B cells and related lymphomas .", "target_text": { "BCL-6": "protein", "BCL-6 gene": "RNA", "nuclear-located Kruppel-type zinc finger protein": "protein", "B-cell lymphomas": "cell_type", "germinal center B cells": "cell_type" } }, { "input_text": "These findings suggest that BCL-6 may play a role in regulating differentiation of normal germinal center B cells and that its deregulated expression caused by rearrangements may contribute to lymphomagenesis .", "target_text": { "BCL-6": "protein", "germinal center B cells": "cell_type" } }, { "input_text": "This prompted us to investigate the expression of the BCL-6 protein in Hodgkin 's disease ( HD ) , focusing on the nodular lymphocyte predominance subtype ( NLPHD ) , which differs from classical HD by virtue of the B-cell nature of the malignant cell population ( so-called L & H cells ) and its relationship with germinal centers .", "target_text": { "BCL-6": "protein", "BCL-6 protein": "protein", "malignant cell population": "cell_type", "L & H cells": "cell_type" } }, { "input_text": "Forty-one HD samples ( 19 NLPHD , 12 nodular sclerosis , and 10 mixed cellularity ) were immunostained with the monoclonal antibodies PG-B6 and PG-B6p that react with a fixative-sensitive and a formalin-resistant epitope on the aminoterminal region of the BCL-6 gene product , respectively .", "target_text": { "monoclonal antibodies": "protein", "PG-B6": "protein", "PG-B6p": "protein", "formalin-resistant epitope": "protein", "aminoterminal region": "protein", "BCL-6": "protein", "BCL-6 gene product": "protein" } }, { "input_text": "Strong nuclear positivity for the BCL-6 protein was detected in tumor ( L & H ) cells in all cases of NLPHD .", "target_text": { "BCL-6": "protein", "BCL-6 protein": "protein", "tumor ( L & H ) cells": "cell_type" } }, { "input_text": "In contrast , BCL-6 was expressed only in a small percentage of Hodgkin and Reed-Sternberg cells in about 30 % of classical HD cases .", "target_text": { "BCL-6": "protein", "Hodgkin and Reed-Sternberg cells": "cell_line" } }, { "input_text": "Notably , the nuclei of reactive CD3+/CD4+ T cells nearby to and rosetting around L & H cells in NLPHD were also strongly BCL-6 + , but lacked CD40 ligand ( CD40L ) expression .", "target_text": { "reactive CD3+/CD4+ T cells": "cell_type", "L & H cells": "cell_type", "BCL-6": "protein", "CD40 ligand": "protein", "CD40L": "protein" } }, { "input_text": "This staining pattern clearly differed from that of classical HD , whose cellular background was made up of CD3+/CD4+ T cells showing the BCL-6 -/ CD40L + phenotype .", "target_text": { "CD3+/CD4+ T cells": "cell_type", "BCL-6": "protein", "CD40L": "protein" } }, { "input_text": "These results further support the concept that NLPHD is an histogenetically distinct , B-cell-derived subtype of HD and suggest a role for BCL-6 in its development .", "target_text": { "BCL-6": "protein" } }, { "input_text": "Selenium -mediated inhibition of transcription factor NF-kappa B and HIV-1 LTR promoter activity .", "target_text": { "transcription factor NF-kappa B": "protein", "HIV-1 LTR promoter": "DNA" } }, { "input_text": "The eukaryotic transcription factor NF-kappa B is involved in the inducible expression of various inflammatory genes as well as in HIV-1 replication .", "target_text": { "transcription factor NF-kappa B": "protein", "eukaryotic transcription factor NF-kappa B": "protein", "inflammatory genes": "DNA" } }, { "input_text": "Activation of NF-kappa B is induced by prooxidants and several stimuli eliciting oxidative stress , such as cytokines , lipopolysaccharide , UV irradiation and other mediators .", "target_text": { "NF-kappa B": "protein", "cytokines": "protein" } }, { "input_text": "Various antioxidants inhibit NF-kappa B activation in response to these stimuli .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "In this study , we have investigated the effects of selenium , an integral component of glutathione peroxidase ( GPX ) , on NF-kappa B activation .", "target_text": { "glutathione peroxidase": "protein", "GPX": "protein", "NF-kappa B": "protein" } }, { "input_text": "In selenium -deprived Jurkat and ESb-L T lymphocytes , supplementation of selenium led to a substantial increase of GPX activity .", "target_text": { "selenium -deprived Jurkat": "cell_line", "ESb-L T lymphocytes": "cell_line", "GPX": "protein" } }, { "input_text": "Analysis of DNA binding revealed that NF-kappa B activation in response to TNF was significantly inhibited under these conditions .", "target_text": { "NF-kappa B": "protein", "TNF": "protein" } }, { "input_text": "Likewise , reporter gene assays using luciferase constructs driven by the HIV-1 long terminal repeat showed a dose-dependent inhibition of NF-kappa B controlled gene expression by selenium .", "target_text": { "HIV-1 long terminal repeat": "DNA", "NF-kappa B": "protein" } }, { "input_text": "The effects of selenium were specific for NF-kappa B , since the activity of the transcription factor AP-1 was not suppressed .", "target_text": { "NF-kappa B": "protein", "AP-1": "protein" } }, { "input_text": "These data suggest that selenium supplementation may be used to modulate the expression of NF-kappa B target genes and HIV-1 .", "target_text": { "NF-kappa B": "protein", "NF-kappa B target genes": "DNA" } }, { "input_text": "The involvement of p23 , hsp90 , and immunophilins in the assembly of progesterone receptor complexes .", "target_text": { "p23": "protein", "hsp90": "protein", "immunophilins": "protein", "progesterone receptor complexes": "protein" } }, { "input_text": "To better understand the assembly mechanism for the progesterone receptor ( PR ) , we have developed cell-free systems for studying interactions of PR , hsp90 , and other associated proteins .", "target_text": { "progesterone receptor": "protein", "PR": "protein", "hsp90": "protein", "associated proteins": "protein" } }, { "input_text": "When PR is incubated in rabbit reticulocyte lysate , its association with hsp90 , hsp70 , the three immunophilins FKBP54 , FKBP52 and CyP-40 , and with p23 is observed .", "target_text": { "PR": "protein", "hsp90": "protein", "hsp70": "protein", "immunophilins": "protein", "FKBP54": "protein", "FKBP52": "protein", "CyP-40": "protein", "p23": "protein" } }, { "input_text": "These interactions require ATP/Mg2+ and when ATP is limiting the PR complex is altered to one containing the proteins p60 and p48 , but lacking immunophilins and p23 .", "target_text": { "PR": "protein", "p60": "protein", "p48": "protein", "immunophilins": "protein", "p23": "protein" } }, { "input_text": "We have studied two pre-formed hsp90 complexes that may participate in the assembly of PR complexes .", "target_text": { "hsp90": "protein", "pre-formed hsp90 complexes": "protein", "PR": "protein", "PR complexes": "protein" } }, { "input_text": "One contains hsp90 bound to hsp70 and p60 and this complex forms spontaneously in the absence of ATP .", "target_text": { "hsp90": "protein", "hsp70": "protein", "p60": "protein" } }, { "input_text": "A second complex contains hsp90 bound to p23 plus the three immunophilins and some hsp70 .", "target_text": { "hsp90": "protein", "p23": "protein", "immunophilins": "protein", "hsp70": "protein" } }, { "input_text": "The formation of this complex requires ATP .", "target_text": {} }, { "input_text": "In further studies we have shown that purified hsp90 can bind to purified p23 and this interaction requires both ATP and molybdate .", "target_text": { "hsp90": "protein", "p23": "protein" } }, { "input_text": "This explains , in part , the known effects of ATP and molybdate on assembly of PR complexes .", "target_text": { "PR": "protein", "PR complexes": "protein" } }, { "input_text": "Increased IkappaB expression and diminished nuclear NF-kappaB in human mononuclear cells following hydrocortisone injection .", "target_text": { "IkappaB": "protein", "nuclear NF-kappaB": "protein", "human mononuclear cells": "cell_type" } }, { "input_text": "We have recently demonstrated that hydrocortisone and other glucocorticoids inhibit reactive oxygen species ( ROS ) generation by mononuclear ( MNC ) and polymorphonuclear leucocytes ( PMNL ) .", "target_text": { "PMNL": "cell_type" } }, { "input_text": "Since NF-kappaB/ IkappaB system regulates the transcription of proinflammatory genes , including those responsible for ROS generation , we tested the hypothesis that hydrocortisone may stimulate IkappaB production thus inhibiting NF-kappaB translocation from the cytosol into the nucleus in MNC , in vivo .", "target_text": { "IkappaB": "protein", "proinflammatory genes": "protein", "NF-kappaB": "protein", "MNC": "cell_type" } }, { "input_text": "One hundred milligram of hydrocortisone was injected intravenously into 4 normal subjects .", "target_text": {} }, { "input_text": "Blood samples were obtained prior to the injection and at 1 , 2 , 4 , 8 and 24 hr after the injection .", "target_text": {} }, { "input_text": "Nuclear extracts and total cell lysates were prepared from MNC by standard techniques .", "target_text": { "MNC": "cell_type" } }, { "input_text": "IkappaB levels in MNC homogenates increased at 1 hr , peaked at 2-4 hr , started to decrease at 8 hr , and returned to baseline levels at 24 hr .", "target_text": { "IkappaB": "protein", "MNC": "cell_type" } }, { "input_text": "NF-kappaB in MNC nuclear extracts decreased at 1 hr , reached a nadir at 4 hr , gradually increased at 8 hr and returned back to baseline levels at 24 hr .", "target_text": { "NF-kappaB": "protein", "MNC": "cell_type" } }, { "input_text": "The total protein content of NF-kappaB subunit ( P65 ) in MNC lysates also showed a decrease following hydrocortisone injection .", "target_text": { "NF-kappaB": "protein", "NF-kappaB subunit": "protein", "P65": "protein", "MNC": "cell_type" } }, { "input_text": "This decrease was observed at 2 hr , reached a nadir at 4 hr , and returned to baseline levels at 24 hr .", "target_text": {} }, { "input_text": "ROS generation inhibition paralleled NF-kappaB levels in the nucleus .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "It was inhibited at 1 hr , reached a nadir at 2-4 hr , started to increase at 8 hr , and returned to basal levels at 24 hr .", "target_text": {} }, { "input_text": "Our data demonstrate that hydrocortisone induces IkappaB and suppresses NF-kappaB expression in MNC in parallel .", "target_text": { "IkappaB": "protein", "NF-kappaB": "protein", "MNC": "cell_type" } }, { "input_text": "IkappaB further reduces the translocation of NF-kappaB into the nucleus thus preventing the expression of proinflammatory genes .", "target_text": { "IkappaB": "protein", "NF-kappaB": "protein", "proinflammatory genes": "DNA" } }, { "input_text": "Glucocorticoids induce apoptosis in human monocytes : potential role of IL-1 beta .", "target_text": { "human monocytes": "cell_type", "IL-1 beta": "protein" } }, { "input_text": "Glucocorticoids ( GC ) are potent anti-inflammatory and immunosuppressive agents that act on a variety of immune cells , including monocytes and macrophages .", "target_text": { "immune cells": "cell_type", "monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "However , the exact cellular mechanisms underlying this anti-inflammatory capacity are still unknown .", "target_text": {} }, { "input_text": "In our study , we determined the induction of apoptosis by GC in human monocytes .", "target_text": { "monocytes": "cell_type", "human monocytes": "cell_type" } }, { "input_text": "Peripheral blood monocytes were isolated by density centrifugation methods with a purity of > 90 % and were cultured in RPMI 1640 medium .", "target_text": { "Peripheral blood monocytes": "cell_type" } }, { "input_text": "Monocyte apoptosis was determined by four independent methods , including annexin-V staining , TUNEL , DNA-laddering , and typical morphology by means of transmission electron microscopy .", "target_text": {} }, { "input_text": "TNF-alpha and IL-1beta were measured by ELISA .", "target_text": { "TNF-alpha": "protein", "IL-1beta": "protein" } }, { "input_text": "GC receptor was blocked with mifepristone .", "target_text": { "GC receptor": "protein" } }, { "input_text": "Caspase 3 was inhibited with caspase-3 inhibitor ( DEVD-CHO ) .", "target_text": {} }, { "input_text": "Stimulation with different GC at therapeutic concentrations resulted in monocyte apoptosis in a time- and dose- dependent manner .", "target_text": {} }, { "input_text": "Necrosis was excluded by propidium iodide staining .", "target_text": {} }, { "input_text": "Proinflammatory cytokines such as IL-1beta and TNF-alpha were down-regulated by GC treatment .", "target_text": { "cytokines": "protein", "Proinflammatory cytokines": "protein", "IL-1beta": "protein", "TNF-alpha": "protein" } }, { "input_text": "Continuous treatment of monocytes with IL-1beta , but not with TNF-alpha , could almost completely prevent GC -induced cell death .", "target_text": { "monocytes": "cell_type", "IL-1beta": "protein", "TNF-alpha": "protein" } }, { "input_text": "The addition of mifepristone or caspase-3 inhibitor could partially abrogate GC -induced apoptosis as well as GC -induced inhibition of IL-1beta .", "target_text": { "IL-1beta": "protein" } }, { "input_text": "This is the first study to demonstrate induction of apoptosis by GC in human monocytes .", "target_text": { "human monocytes": "cell_type" } }, { "input_text": "GC -induced monocyte apoptosis may be partially mediated through effects on IL-1beta production .", "target_text": { "IL-1beta": "protein" } }, { "input_text": "It is conceivable that GC exert their anti-inflammatory capacity in various diseases , at least in part , by the induction of apoptosis in monocytes .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "Differential effects of lipopolysaccharide and tumor necrosis factor on monocytic IkappaB kinase signalsome activation and IkappaB proteolysis .", "target_text": { "tumor necrosis factor": "protein", "IkappaB": "protein", "monocytic IkappaB kinase": "protein" } }, { "input_text": "The inflammatory mediators lipopolysaccharide ( LPS ) and tumor necrosis factor ( TNF ) are potent activators of NF-kappaB .", "target_text": { "tumor necrosis factor": "protein", "TNF": "protein", "NF-kappaB": "protein" } }, { "input_text": "This study compared the effect of these stimuli on endogenous IkappaB kinase ( IKK ) signalsome activation and IkappaB phosphorylation/proteolysis in human monocytic cells and investigated the role of the signalsome proteins IKK-alpha , IKK-beta , NF-kappaB -inducing kinase ( NIK ) , IKK-gamma ( NF-kappaB essential modulator ) , and IKK complex -associated protein .", "target_text": { "IkappaB": "protein", "IkappaB kinase": "protein", "IKK": "protein", "human monocytic cells": "cell_type", "signalsome proteins": "protein", "IKK-alpha": "protein", "IKK-beta": "protein", "NF-kappaB": "protein", "NF-kappaB -inducing kinase": "protein", "NIK": "protein", "IKK-gamma": "protein", "IKK complex": "protein", "IKK complex -associated protein": "protein" } }, { "input_text": "Kinase assays showed that TNF elicited a rapid but short-lived induction of IKK activity with a 3-fold greater effect on IKK -alpha than on IKK-beta , peaking at 5 min .", "target_text": { "TNF": "protein", "IKK": "protein", "IKK -alpha": "protein", "IKK-beta": "protein" } }, { "input_text": "In contrast , LPS predominantly stimulated IKK-beta activity , which slowly increased , peaking at 30 min .", "target_text": { "IKK-beta": "protein" } }, { "input_text": "A second peak was observed at a later time point following LPS stimulation , which consisted of both IKK -alpha and -beta activity .", "target_text": {} }, { "input_text": "The endogenous levels of the signalsome components were unaffected by stimulation .", "target_text": {} }, { "input_text": "Furthermore , our studies showed association of the IKK-alpha /beta heterodimer with NIK , IkappaB -alpha and -epsilon in unstimulated cells .", "target_text": { "IKK-alpha": "protein", "IKK-alpha /beta heterodimer": "protein", "NIK": "protein", "IkappaB": "protein", "IkappaB -alpha": "protein", "-epsilon": "protein", "unstimulated cells": "cell_type" } }, { "input_text": "Exposure to LPS or TNF led to differential patterns of IkappaB -alpha and IkappaB -epsilon disappearance from and reassembly with the signalsome , whereas IKK-alpha , IKK-beta , and NIK remained complex-associated .", "target_text": { "TNF": "protein", "IkappaB": "protein", "IkappaB -alpha": "protein", "IkappaB -epsilon": "protein", "IKK-alpha": "protein", "IKK-beta": "protein", "NIK": "protein" } }, { "input_text": "NIK can not phosphorylate IkappaB -alpha directly , but it appears to be a functionally important subunit , because mutated NIK inhibited stimulus-induced kappaB -dependent transcription more effectively than mutated IKK-alpha or -beta .", "target_text": { "NIK": "protein", "IkappaB": "protein", "IkappaB -alpha": "protein", "kappaB": "protein", "IKK-alpha": "protein", "-beta": "protein" } }, { "input_text": "Overexpression of IKK complex -associated protein inhibited stimulus-mediated transcription , whereas NF-kappaB essential modulator enhanced it .", "target_text": { "IKK complex": "protein", "IKK complex -associated protein": "protein", "NF-kappaB": "protein" } }, { "input_text": "The understanding of LPS- and TNF- induced signaling may allow the development of specific strategies to treat sepsis-associated disease .", "target_text": {} }, { "input_text": "Tumor necrosis factor alpha decreases , and interleukin-10 increases , the sensitivity of human monocytes to dexamethasone : potential regulation of the glucocorticoid receptor .", "target_text": { "Tumor necrosis factor alpha": "protein", "interleukin-10": "protein", "human monocytes": "cell_type", "glucocorticoid receptor": "protein" } }, { "input_text": "Resistance to glucocorticoid therapy has been observed in patients with autoimmune/inflammatory diseases and may be related to the inflammatory process itself .", "target_text": {} }, { "input_text": "The aim of this study was to examine the ability of tumor necrosis factor alpha ( TNFalpha , a proinflammatory cytokine ) and interleukin ( IL ) -10 ( an anti-inflammatory cytokine ) to differentially regulate the sensitivity of human monocytes /macrophages to glucocorticoids .", "target_text": { "tumor necrosis factor": "protein", "tumor necrosis factor alpha": "protein", "TNFalpha": "protein", "proinflammatory cytokine": "protein", "interleukin ( IL ) -10": "protein", "anti-inflammatory cytokine": "protein", "human monocytes": "cell_type", "/macrophages": "cell_type" } }, { "input_text": "To accomplish this , we first analyzed the pattern of TNFalpha and IL-10 inhibition by dexamethasone in LPS -stimulated whole-blood cell cultures .", "target_text": { "TNFalpha": "protein", "LPS -stimulated whole-blood cell cultures": "cell_line" } }, { "input_text": "Second , we studied the modulation of the sensitivity of these cells to dexamethasone by preincubation with TNFalpha or IL-10 and measurement of LPS -stimulated IL-6 secretion .", "target_text": { "TNFalpha": "protein", "IL-10": "protein", "IL-6": "protein" } }, { "input_text": "In addition , we evaluated the effect of dexamethasone on phorbolmyristate-acetate -stimulated IL-1 receptor antagonist secretion by the human monocytic cell line U937 .", "target_text": { "IL-1": "protein", "IL-1 receptor": "protein", "human monocytic cell line U937": "cell_line" } }, { "input_text": "Finally , we investigated whether the modulation of corticosensitivity in TNFalpha- and IL-10- pretreated U937 cells was related to a change of the glucocorticoid receptor concentration and affinity .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Dexamethasone had different effects on LPS -induced TNFalpha and IL-10 secretion ; whereas it suppressed TNFalpha in a dose-dependent fashion , its effect on IL-10 secretion was biphasic , producing stimulation at lower , and inhibition at higher doses .", "target_text": { "TNFalpha": "protein", "IL-10": "protein" } }, { "input_text": "The concentration of LPS employed influenced the effect of dexamethasone on IL-10 secretion ( P < 0.001 ) .", "target_text": { "IL-10": "protein" } }, { "input_text": "Pretreatment with TNFalpha diminished , and with IL-10 improved , the ability of dexamethasone to suppress IL-6 secretion in whole-blood cell cultures ( P < 0.01 for both ) and to enhance IL-1 receptor antagonist secretion by U937 cells ( P < 0.05 for both ) .", "target_text": { "TNFalpha": "protein", "IL-10": "protein", "IL-6": "protein", "whole-blood cell cultures": "cell_type", "IL-1": "protein" } }, { "input_text": "TNFalpha decreased ( P < 0.001 ) , while IL-10 increased ( P < 0.001 ) , the concentration of dexamethasone binding sites in these cells , with no discernible effect on their binding affinity .", "target_text": { "TNFalpha": "protein", "IL-10": "protein" } }, { "input_text": "We conclude that glucocorticoids differentially modulate TNFalpha and IL-10 secretion by human monocytes in a LPS dose-dependent fashion and that the sensitivity of these cells to glucocorticoids is altered by TNFalpha or IL-10 pretreatment ; TNFalpha blocks their effects , whereas IL-10 acts synergistically with glucocorticoids .", "target_text": { "TNFalpha": "protein", "IL-10": "protein", "human monocytes": "cell_type" } }, { "input_text": "This is accompanied by opposite glucocorticoid receptor changes , respectively opposing and favoring glucocorticoid actions .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "This study suggests that the pattern of pro-/antiinflammatory cytokine secretion may alter the response of patients to glucocorticoid therapy .", "target_text": { "cytokine": "protein" } }, { "input_text": "Block of granulocytic differentiation of 32Dcl3 cells by AML1/ETO ( MTG8 ) but not by highly expressed Bcl-2 .", "target_text": { "32Dcl3 cells": "cell_line", "AML1/ETO ( MTG8 )": "DNA", "Bcl-2": "protein" } }, { "input_text": "The chimeric gene , AML1/ETO ( MTG8 ) , generated in t(8;21) acute myeloid leukemia enhances the expression of Bcl-2 .", "target_text": { "chimeric gene ,": "DNA", "AML1/ETO ( MTG8 )": "DNA", "t(8;21)": "DNA", "Bcl-2": "protein" } }, { "input_text": "To evaluate whether this enhancement is the primary role of AML1/ETO in leukemogenesis , effects of over-expression of Bcl-2 in the murine myeloid precursor cell line , 32Dcl3 , were examined .", "target_text": { "AML1/ETO": "DNA", "Bcl-2": "protein", "murine myeloid precursor cell line": "cell_line", "32Dcl3": "cell_line" } }, { "input_text": "When 32Dcl3 cells expressing exogenous Bcl-2 were induced to differentiate , the onset of morphological differentiation was delayed .", "target_text": { "32Dcl3 cells": "cell_line", "Bcl-2": "protein" } }, { "input_text": "However , even the cells expressing very high levels of exogenous Bcl-2 eventually underwent differentiation without a significant decrease in the synthesis of Bcl-2 .", "target_text": { "Bcl-2": "protein" } }, { "input_text": "On the contrary , 32Dcl3 cells stably expressing AML1/ETO were completely resistant to differentiation and continued to grow in the presence of G-CSF .", "target_text": { "32Dcl3 cells": "cell_line", "AML1/ETO": "DNA", "G-CSF": "protein" } }, { "input_text": "These results are consistent with the interpretation that stimulation of Bcl-2 expression is not the primary target of AML1/ETO .", "target_text": { "Bcl-2": "protein", "AML1/ETO": "DNA" } }, { "input_text": "Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors .", "target_text": { "microbial lipoproteins": "protein", "toll-like receptors": "protein" } }, { "input_text": "The generation of cell-mediated immunity against many infectious pathogens involves the production of interleukin-12 ( IL-12 ) , a key signal of the innate immune system .", "target_text": { "interleukin-12": "protein", "IL-12": "protein" } }, { "input_text": "Yet , for many pathogens , the molecules that induce IL-12 production by macrophages and the mechanisms by which they do so remain undefined .", "target_text": { "IL-12": "protein", "macrophages": "cell_type" } }, { "input_text": "Here it is shown that microbial lipoproteins are potent stimulators of IL-12 production by human macrophages , and that induction is mediated by Toll-like receptors ( TLRs ) .", "target_text": { "microbial lipoproteins": "protein", "IL-12": "protein", "macrophages": "cell_type", "Toll-like receptors": "protein", "TLRs": "protein" } }, { "input_text": "Several lipoproteins stimulated TLR-dependent transcription of inducible nitric oxide synthase and the production of nitric oxide , a powerful microbicidal pathway .", "target_text": { "nitric oxide synthase": "protein" } }, { "input_text": "Activation of TLRs by microbial lipoproteins may initiate innate defense mechanisms against infectious pathogens .", "target_text": { "TLRs": "protein", "microbial lipoproteins": "protein" } }, { "input_text": "Abnormal NF-kappa B activity in T lymphocytes from patients with systemic lupus erythematosus is associated with decreased p65-RelA protein expression .", "target_text": { "NF-kappa B": "protein", "T lymphocytes": "cell_type", "p65-RelA": "protein" } }, { "input_text": "Numerous cellular and biochemical abnormalities in immune regulation have been described in patients with systemic lupus erythematosus ( SLE ) , including surface Ag receptor -initiated signaling events and lymphokine production .", "target_text": { "Ag receptor": "protein", "lymphokine": "protein" } }, { "input_text": "Because NF-kappa B contributes to the transcription of numerous inflammatory genes and has been shown to be a molecular target of antiinflammatory drugs , we sought to characterize the functional role of the NF-kappa B protein complex in lupus T cells .", "target_text": { "NF-kappa B": "protein", "inflammatory genes": "DNA", "NF-kappa B protein complex": "protein", "lupus T cells": "cell_type" } }, { "input_text": "Freshly isolated T cells from lupus patients , rheumatoid arthritis ( RA ) patients , and normal individuals were activated physiologically via the TCR with anti-CD3 and anti-CD28 Abs to assess proximal membrane signaling , and with PMA and a calcium ionophore ( A23187 ) to bypass membrane-mediated signaling events .", "target_text": { "T cells": "cell_type", "TCR": "protein", "anti-CD3": "protein", "anti-CD28 Abs": "protein" } }, { "input_text": "We measured the NF-kappa B binding activity in nuclear extracts by gel shift analysis .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "When compared with normal cells , the activation of NF-kappa B activity in SLE patients was significantly decreased in SLE , but not in RA , patients .", "target_text": { "normal cells": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "NF-kappa B binding activity was absent in several SLE patients who were not receiving any medication , including corticosteroids .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Also , NF-kappa B activity remained absent in follow-up studies .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "In supershift experiments using specific Abs , we showed that , in the group of SLE patients who displayed undetectable NF-kappa B activity , p65 complexes were not formed .", "target_text": { "Abs": "protein", "NF-kappa B": "protein", "p65 complexes": "protein" } }, { "input_text": "Finally , immunoblot analysis of nuclear extracts showed decreased or absent p65 protein levels .", "target_text": { "p65 protein": "protein" } }, { "input_text": "As p65 complexes are transcriptionally active in comparison to the p50 homodimer , this novel finding may provide insight on the origin of abnormal cytokine or other gene transcription in SLE patients .", "target_text": { "p65 complexes": "protein", "abnormal cytokine": "protein" } }, { "input_text": "Signaling events induced by lipopolysaccharide-activated toll-like receptor 2 .", "target_text": { "lipopolysaccharide-activated toll-like receptor 2": "protein" } }, { "input_text": "Human Toll-like receptor 2 ( TLR2 ) is a signaling receptor that responds to LPS and activates NF-kappaB .", "target_text": { "TLR2": "protein", "Human Toll-like receptor 2 ( TLR2 )": "protein", "signaling receptor": "protein", "NF-kappaB": "protein" } }, { "input_text": "Here , we investigate further the events triggered by TLR2 in response to LPS .", "target_text": { "TLR2": "protein" } }, { "input_text": "We show that TLR2 associates with the high-affinity LPS binding protein membrane CD14 to serve as an LPS receptor complex , and that LPS treatment enhances the oligomerization of TLR2 .", "target_text": { "TLR2": "protein", "high-affinity LPS binding protein": "protein", "CD14": "protein", "LPS receptor complex": "protein" } }, { "input_text": "Concomitant with receptor oligomerization , the IL-1R-associated kinase ( IRAK ) is recruited to the TLR2 complex .", "target_text": { "IRAK": "protein", "IL-1R-associated kinase ( IRAK )": "protein", "TLR2": "protein" } }, { "input_text": "Intracellular deletion variants of TLR2 lacking C-terminal 13 or 141 aa fail to recruit IRAK , which is consistent with the inability of these mutants to transmit LPS cellular signaling .", "target_text": { "TLR2": "protein", "IRAK": "protein" } }, { "input_text": "Moreover , both deletion mutants could still form complexes with wild-type TLR2 and act in a dominant-negative ( DN ) fashion to block TLR2 -mediated signal transduction .", "target_text": { "TLR2": "protein", "wild-type TLR2": "protein" } }, { "input_text": "DN constructs of myeloid differentiation protein , IRAK , TNF receptor-associated factor 6 , and NF-kappaB -inducing kinase , when coexpressed with TLR2 , abrogate TLR2 -mediated NF-kappaB activation .", "target_text": { "myeloid differentiation protein": "protein", "IRAK": "protein", "TNF": "protein", "TNF receptor-associated factor 6": "protein", "NF-kappaB": "protein", "NF-kappaB -inducing kinase": "protein", "TLR2": "protein" } }, { "input_text": "These results reveal a conserved signaling pathway for TLR2 and IL-1Rs and suggest a molecular mechanism for the inhibition of TLR2 by DN variants .", "target_text": { "TLR2": "protein", "IL-1Rs": "protein" } }, { "input_text": "Tyrphostin AG-490 inhibits cytokine-mediated JAK3 /STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells .", "target_text": { "JAK3": "protein", "/STAT5a/b": "protein", "T cells": "cell_type" } }, { "input_text": "Janus kinase 3 ( JAK3 ) is a cytoplasmic tyrosine kinase required for T cell development and activated by cytokines that utilize the interleukin-2 ( IL-2 ) receptor common gamma chain ( gamma(c) ) .", "target_text": { "JAK3": "protein", "Janus kinase 3 ( JAK3 )": "protein", "cytoplasmic tyrosine kinase": "protein", "T cell": "cell_type", "cytokines": "protein", "interleukin-2 ( IL-2 )": "protein", "gamma(c)": "protein", "interleukin-2 ( IL-2 ) receptor common gamma chain ( gamma(c) )": "protein" } }, { "input_text": "Genetic inactivation of JAK3 is manifested as severe combined immunodeficiency disease ( SCID ) in humans and mice .", "target_text": { "JAK3": "protein" } }, { "input_text": "These findings have suggested that JAK3 represents a pharmacological target to control certain lymphoid-derived diseases .", "target_text": { "JAK3": "protein" } }, { "input_text": "Here we provide novel evidence that AG-490 potently inhibits the autokinase activity of JAK3 and tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription 5a and 5b ( STAT5a/b ) .", "target_text": { "JAK3": "protein", "STAT5a/b": "protein", "signal transducer and activator of transcription 5a and 5b ( STAT5a/b )": "protein" } }, { "input_text": "Similar inhibitory effects were observed with other cytokines that use gamma(c) .", "target_text": { "cytokines": "protein", "gamma(c)": "protein" } }, { "input_text": "AG-490 also inhibited IL-2 -mediated proliferative growth in human T cells with an IC50) = 25 microM that was partially recoverable .", "target_text": { "IL-2": "protein", "T cells": "cell_type" } }, { "input_text": "Moreover , we demonstrate that this inhibitor prevented tetanus toxoid antigen-specific T cell proliferation and expansion but failed to block activation of Zap70 or p56Lck after anti-CD3 stimulation of human T cells .", "target_text": { "Zap70": "protein", "p56Lck": "protein", "anti-CD3": "protein", "T cells": "cell_type" } }, { "input_text": "Taken together , these findings suggest that AG-490 inhibits the JAK3 -mediated Type II signaling pathway but not the T cell receptor-derived Type I pathway and possesses therapeutic potential for T cell -derived pathologies such as graft-versus-host disease , allergy , and autoimmune disorders .", "target_text": { "JAK3": "protein", "T cell": "cell_type" } }, { "input_text": "C/EBP beta in rheumatoid arthritis : correlation with inflammation , not disease specificity .", "target_text": { "C/EBP beta": "protein" } }, { "input_text": "Rheumatoid arthritis synovial tissue was examined and compared with osteoarthritis tissue for the presence of the nuclear transcription factor C/EBP beta ( NF-IL-6 ) .", "target_text": { "C/EBP beta": "protein", "NF-IL-6": "protein", "nuclear transcription factor C/EBP beta ( NF-IL-6 )": "protein" } }, { "input_text": "The region ( lining or sublining ) , cell type , and subcellular distribution ( cytoplasmic or nuclear ) of the expression of C/EBP beta was characterized .", "target_text": { "C/EBP beta": "protein" } }, { "input_text": "Rheumatoid arthritis synovial fluid and blood and normal peripheral blood were also examined .", "target_text": {} }, { "input_text": "C/EBP beta was detected in the synovial lining and in sublining cells of synovial tissue from patients with both rheumatoid and osteoarthritis .", "target_text": { "C/EBP beta": "protein", "sublining cells of synovial tissue": "cell_type" } }, { "input_text": "A significant ( P < 0.001 and < 0.05 , respectively ) increase in the percentage of cells with nuclear staining was seen in the lining layer , compared to cells in the sublining region , in rheumatoid and osteoarthritis .", "target_text": {} }, { "input_text": "In both diseases a strong correlation ( r = 0.79 , P < 0.001 ) was observed between the percentage of cells in the synovial lining that were positive for nuclear C/EBP beta and lining cell depth .", "target_text": { "nuclear C/EBP beta": "protein" } }, { "input_text": "Two-color immunohistochemistry demonstrated that both macrophages and fibroblast-like synoviocytes were positive for nuclear C/EBP beta .", "target_text": { "macrophages": "cell_type", "fibroblast-like synoviocytes": "cell_type", "C/EBP beta": "protein" } }, { "input_text": "The presence of C/EBP beta was confirmed by immunohistochemistry and Western blot analysis with isolated synovial fibroblasts .", "target_text": { "C/EBP beta": "protein", "synovial fibroblasts": "cell_type" } }, { "input_text": "Nuclear C/EBP beta was also detected in rheumatoid synovial fluid monocytes /macrophages , but not in lymphocytes or neutrophils .", "target_text": { "C/EBP beta": "protein" } }, { "input_text": "Western blot analysis confirmed the presence of C/EBP beta in these cells .", "target_text": { "C/EBP beta": "protein" } }, { "input_text": "The intensity of C/EBP beta staining was greater ( P < 0.001 ) in synovial fluid monocytes than in those from normal or rheumatoid peripheral blood .", "target_text": { "C/EBP beta": "protein", "synovial fluid monocytes": "cell_type" } }, { "input_text": "In conclusion , the enhanced nuclear staining for C/EBP beta in the synovial lining , compared to the sublining , suggesting activation in the lining , and the positive correlation of lining layer depth with the percentage of cells in the lining positive for nuclear C/EBP beta , suggest a potential role for C/EBP beta in chronic inflammation .", "target_text": { "C/EBP beta": "protein" } }, { "input_text": "The regulation of the production or activity of C/EBP beta , to inhibit inflammatory mediator expression by synovial macrophages and fibroblasts , offers a novel approach to therapeutic intervention .", "target_text": { "C/EBP beta": "protein", "synovial macrophages": "cell_type", "fibroblasts": "cell_type" } }, { "input_text": "Direct interaction of hematopoietic transcription factors PU.1 and GATA-1 : functional antagonism in erythroid cells .", "target_text": { "erythroid cells": "cell_type" } }, { "input_text": "Malignant transformation usually inhibits terminal cell differentiation but the precise mechanisms involved are not understood .", "target_text": {} }, { "input_text": "PU.1 is a hematopoietic-specific Ets family transcription factor that is required for development of some lymphoid and myeloid lineages .", "target_text": { "PU.1": "protein", "hematopoietic-specific Ets family transcription factor": "protein" } }, { "input_text": "PU.1 can also act as an oncoprotein as activation of its expression in erythroid precursors by proviral insertion or transgenesis causes erythroleukemias in mice .", "target_text": { "PU.1": "protein", "oncoprotein": "protein" } }, { "input_text": "Restoration of terminal differentiation in the mouse erythroleukemia ( MEL ) cells requires a decline in the level of PU.1 , indicating that PU.1 can block erythroid differentiation .", "target_text": { "MEL": "cell_line", "mouse erythroleukemia ( MEL ) cells": "cell_line", "PU.1": "protein" } }, { "input_text": "Here we investigate the mechanism by which PU.1 interferes with erythroid differentiation .", "target_text": { "PU.1": "protein" } }, { "input_text": "We find that PU.1 interacts directly with GATA-1 , a zinc finger transcription factor required for erythroid differentiation .", "target_text": { "PU.1": "protein", "GATA-1": "protein", "zinc finger transcription factor": "protein" } }, { "input_text": "Interaction between PU.1 and GATA-1 requires intact DNA-binding domains in both proteins .", "target_text": { "PU.1": "protein", "GATA-1": "protein", "DNA-binding domains": "protein" } }, { "input_text": "PU.1 represses GATA-1 -mediated transcriptional activation .", "target_text": { "PU.1": "protein", "GATA-1": "protein" } }, { "input_text": "Both the DNA binding and transactivation domains of PU.1 are required for repression and both domains are also needed to block terminal differentiation in MEL cells .", "target_text": { "DNA binding": "protein", "transactivation domains": "protein", "PU.1": "protein", "MEL cells": "cell_line" } }, { "input_text": "We also show that ectopic expression of PU.1 in Xenopus embryos is sufficient to block erythropoiesis during normal development .", "target_text": { "PU.1": "protein" } }, { "input_text": "Furthermore , introduction of exogenous GATA-1 in both MEL cells and Xenopus embryos and explants relieves the block to erythroid differentiation imposed by PU.1 .", "target_text": { "GATA-1": "protein", "MEL cells": "cell_line", "PU.1": "protein" } }, { "input_text": "Our results indicate that the stoichiometry of directly interacting but opposing transcription factors may be a crucial determinant governing processes of normal differentiation and malignant transformation .", "target_text": { "transcription factors": "protein" } }, { "input_text": "IL-12 induces IFN regulating factor-1 ( IRF-1 ) gene expression in human NK and T cells .", "target_text": { "IL-12": "protein", "IRF-1": "protein", "IFN regulating factor-1 ( IRF-1 )": "protein", "NK": "cell_type", "T cells": "cell_type" } }, { "input_text": "IL-12 is a critical immunoregulatory cytokine that promotes cell-mediated immune responses and the differentiation of naive CD4+ cells to Th1 cells ; however , relatively few IL-12 target genes have been identified .", "target_text": { "IL-12": "protein", "critical immunoregulatory cytokine": "protein", "CD4+ cells": "cell_type", "Th1 cells": "cell_type" } }, { "input_text": "To better clarify the molecular basis of IL-12 action , we set out to characterize genes up-regulated by IL-12 , first by contrasting IL-12 - and IFN -alpha-inducible genes .", "target_text": { "IL-12": "DNA", "IFN": "protein", "IFN -alpha-inducible genes": "DNA" } }, { "input_text": "We identified several genes up-regulated by IL-12 , namely , MIP-1alpha , MIP-1beta , IL-1RA , and IFN regulatory factor-1 ( IRF-1 ) .", "target_text": { "IL-12": "protein", "MIP-1alpha": "protein", "MIP-1beta": "protein", "IL-1RA": "protein", "IRF-1": "protein", "IFN regulatory factor-1 ( IRF-1 )": "protein" } }, { "input_text": "IRF-1 is a transcription factor regulated by IFNs that is also essential for Th1 responses .", "target_text": { "IRF-1": "protein", "transcription factor": "protein", "IFNs": "protein", "Th1": "cell_type" } }, { "input_text": "We demonstrated that IL-12 directly up-regulates IRF-1 to the same extent as IFN-alpha in normal human T cells and in NK cells .", "target_text": { "IL-12": "protein", "IRF-1": "protein", "IFN-alpha": "protein", "T cells": "cell_type", "NK cells": "cell_type" } }, { "input_text": "We showed that IL-12 had a direct effect on IRF-1 , an effect not mediated indirectly by the induction of IFN-gamma production .", "target_text": { "IL-12": "protein", "IRF-1": "protein", "IFN-gamma": "protein" } }, { "input_text": "Furthermore , IL-2 and IL-12 synergistically induced IRF-1 , whereas IFN-alpha and IL-12 did not .", "target_text": { "IL-2": "protein", "IL-12": "protein", "IRF-1": "protein", "IFN-alpha": "protein" } }, { "input_text": "The participation of STAT4 in the regulation of IRF-1 was demonstrated in two ways .", "target_text": { "STAT4": "protein", "IRF-1": "protein" } }, { "input_text": "First , STAT4 was required for the IL-12 -dependent transactivation of an IRF-1 reporter construct , and second , STAT4 binding to the IRF-1 promoter was shown using EMSA .", "target_text": { "STAT4": "protein", "IL-12": "protein", "IRF-1": "protein", "IRF-1 reporter construct": "DNA", "IRF-1 promoter": "DNA" } }, { "input_text": "In contrast to IL-12 , no up-regulation of IRF-1 was found in IL-4 -stimulated cells , and IL-4 did not block IL-12 -dependent up-regulation of IRF-1 .", "target_text": { "IL-12": "protein", "IRF-1": "protein", "IL-4": "protein", "IL-4 -stimulated cells": "cell_line" } }, { "input_text": "Therefore , IRF-1 may be an important contributor to IL-12 signaling , and we speculate that the defective IL-12 responses seen in IRF -1-/- mice might be attributable , in part , to the absence of this transcription factor .", "target_text": { "IRF-1": "protein", "IL-12": "protein", "IRF": "protein", "transcription factor": "protein" } }, { "input_text": "Targeted remodeling of human beta-globin promoter chromatin structure produces increased expression and decreased silencing .", "target_text": { "human beta-globin promoter chromatin structure": "DNA" } }, { "input_text": "The chromatin structure of the human beta-globin gene locus assumes a transcriptionally-active conformation in erythroid cells .", "target_text": { "chromatin structure": "DNA", "human beta-globin gene locus": "DNA", "erythroid cells": "cell_type" } }, { "input_text": "One feature of this chromatin reorganization is the formation of DNase 1 hypersensitive sites in the regions of active globin gene promoters .", "target_text": { "DNase 1 hypersensitive sites": "DNA", "active globin gene promoters": "DNA" } }, { "input_text": "This reorganization requires the globin locus control region and is associated with normal expression of the beta-like globin genes .", "target_text": { "globin locus control region": "DNA", "beta-like globin genes": "DNA" } }, { "input_text": "To determine whether it is possible to artificially enhance the opening of the chromatin structure of a minimal beta-globin promoter , we placed a 101bp , erythroid-specific DNase 1 hypersensitive site-forming element ( HSFE ) immediately upstream of the beta-globin promoter and gene .", "target_text": { "minimal beta-globin promoter": "DNA", "erythroid-specific DNase 1 hypersensitive site-forming element": "DNA", "HSFE": "DNA" } }, { "input_text": "This element includes binding sites for NF-E2 , AP-1 , GATA-1 and Sp-1 .", "target_text": { "NF-E2": "protein", "AP-1": "protein", "GATA-1": "protein", "Sp-1": "protein" } }, { "input_text": "Constructs were stably transfected into murine erythroleukemia cells and promoter chromatin structure and gene expression were analyzed .", "target_text": { "murine erythroleukemia cells": "cell_type", "promoter chromatin structure": "DNA" } }, { "input_text": "The HSFE induced an area of enhanced DNase 1 hypersensitivity extending from the transcriptional start site to -300bp of the artificial promoter and significantly increased the proportion of beta-globin promoters in an open chromatin configuration .", "target_text": { "HSFE": "DNA", "DNase 1": "protein", "artificial promoter": "DNA", "beta-globin promoters": "DNA", "open chromatin configuration": "DNA" } }, { "input_text": "This remodeling of promoter chromatin structure resulted in 3-fold increases in beta-globin gene transcription and induction , and inhibited long-term beta-globin gene silencing .", "target_text": { "promoter chromatin structure": "DNA", "beta-globin gene": "DNA" } }, { "input_text": "These results indicate that a relatively small cis-acting element is able to enhance remodeling of promoter chromatin structure resulting in increased beta-globin gene expression .", "target_text": { "cis-acting element": "DNA", "promoter chromatin structure": "DNA", "beta-globin gene": "DNA" } }, { "input_text": "Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion .", "target_text": { "HAEC": "cell_line", "VCAM-1": "protein" } }, { "input_text": "We recently reported that prolonged exposure of human aortic endothelial cells ( HAEC ) to low shear stress flow patterns is associated with a sustained increase in the activated form of the transcriptional regulator nuclear factor-kappaB ( NF-kappaB ) .", "target_text": { "human aortic endothelial cells": "cell_type", "HAEC": "cell_line", "nuclear factor-kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "Here we investigate the hypothesis that low shear-induced activation of NF-kappaB is responsible for enhanced expression of vascular cell adhesion molecule ( VCAM-1 ) resulting in augmented endothelial cell-monocyte ( EC-Mn ) adhesion and that this activation is dependent on intracellular oxidant activity .", "target_text": { "NF-kappaB": "protein", "vascular cell adhesion molecule": "protein", "VCAM-1": "protein" } }, { "input_text": "Before exposure to low shear ( 2 dyn/cm2 ) for 6 h , HAEC were preincubated with or without the antioxidants pyrrolidine dithiocarbamate ( PDTC ) or N-acetyl-L-cysteine ( NAC ) .", "target_text": { "HAEC": "cell_line" } }, { "input_text": "PDTC strongly inhibited low shear-induced activation of NF-kappaB , expression of VCAM-1 , and EC-Mn adhesion .", "target_text": { "NF-kappaB": "protein", "VCAM-1": "protein" } }, { "input_text": "Paradoxically , NAC exerted a positive effect on low shear-induced VCAM-1 expression and EC-Mn adhesion and only slightly downregulated NF-kappaB activation .", "target_text": { "VCAM-1": "protein", "NF-kappaB": "protein" } }, { "input_text": "However , cytokine-induced NF-kappaB activation and VCAM-1 expression are blocked by both PDTC and NAC .", "target_text": { "NF-kappaB": "protein", "VCAM-1": "protein" } }, { "input_text": "These data suggest that NF-kappaB plays a key role in low shear-induced VCAM-1 expression and that pathways mediating low shear- and cytokine-induced EC-Mn adhesion may be differentially regulated .", "target_text": { "NF-kappaB": "protein", "VCAM-1": "protein" } }, { "input_text": "Nuclear factor-90 of activated T-cells : A double-stranded RNA -binding protein and substrate for the double-stranded RNA-dependent protein kinase , PKR .", "target_text": { "Nuclear factor-90": "protein", "activated T-cells": "cell_type", "double-stranded RNA": "RNA", "double-stranded RNA-dependent protein kinase": "protein", "PKR": "protein" } }, { "input_text": "NFAT transcription factors play a central role in initiating T-cell activation through the induction of immediate-early T-cell specific genes including interleukin-2 ( IL-2 ) .", "target_text": { "IL-2": "protein" } }, { "input_text": "NFAT transcription factors bind to a sequence in the IL-2 enhancer known as the antigen receptor response element 2 ( ARRE-2 ) .", "target_text": { "IL-2": "protein", "IL-2 enhancer": "DNA", "antigen receptor response element 2": "DNA", "ARRE-2": "DNA" } }, { "input_text": "Multiple proteins exhibiting ARRE-2 binding activity have been isolated , including a heterodimer from stimulated T-cell nuclear extracts consisting of Mr = 90 000 ( NF90 ) and Mr = 45 000 ( NF45 ) subunits .", "target_text": { "ARRE-2": "DNA", "heterodimer": "protein", "NF90": "protein", "NF45": "protein" } }, { "input_text": "The subunits of this heterodimer have been cloned , and NF90 was found to encode a protein containing two domains that are predicted to form motifs capable of binding to double-stranded RNA .", "target_text": { "heterodimer": "protein", "NF90": "protein", "double-stranded RNA": "RNA" } }, { "input_text": "Using in vitro translated polypeptides , we have demonstrated that NF90 specifically binds to double-stranded RNA .", "target_text": { "NF90": "protein", "double-stranded RNA": "RNA" } }, { "input_text": "Furthermore , NF90 was phosphorylated in a double-stranded RNA -dependent manner likely by the interferon-induced , double-stranded RNA -dependent protein kinase , PKR .", "target_text": { "NF90": "protein", "double-stranded RNA": "RNA", "double-stranded RNA -dependent protein kinase": "protein", "PKR": "protein" } }, { "input_text": "The NF90 protein was found to be expressed not only in T-cells , but also in nonimmune HeLa cells .", "target_text": { "NF90": "protein", "T-cells": "cell_type", "nonimmune HeLa cells": "cell_line" } }, { "input_text": "In HeLa cells , the protein was almost exclusively localized to the ribosome salt wash fraction of cell lysates .", "target_text": { "HeLa cells": "cell_line" } }, { "input_text": "NF-kappaB activation is required for C5a -induced interleukin-8 gene expression in mononuclear cells .", "target_text": { "NF-kappaB": "protein", "C5a -induced interleukin-8 gene": "DNA", "mononuclear cells": "cell_type" } }, { "input_text": "C5a , a potent peptide chemoattractant , stimulates interleukin-8 ( IL-8 ) secretion from peripheral blood mononuclear cells ( PBMC ) .", "target_text": { "interleukin-8": "protein", "IL-8": "protein", "mononuclear cells": "cell_type", "peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "Experiments were conducted to understand the mechanisms for C5a -induced IL-8 production , which was 14-fold greater than that in unstimulated cells by 2 hours .", "target_text": { "IL-8": "protein", "unstimulated cells": "cell_type" } }, { "input_text": "IL-8 secretion was accompanied by accumulation of IL-8 mRNA in the cytosol and by nuclear expression of a kappaB DNA binding activity within 30 minutes .", "target_text": { "IL-8": "protein", "IL-8 mRNA": "RNA", "kappaB": "protein" } }, { "input_text": "AP-1 but not NF-IL-6 DNA binding activity was also detected in C5a -stimulated PBMC ; however , its delayed expression ( maximal at 4 hours ) suggested a less important role in the rapid production of IL-8 .", "target_text": { "AP-1": "protein", "NF-IL-6": "protein", "PBMC": "cell_type", "C5a -stimulated PBMC": "cell_line", "IL-8": "protein" } }, { "input_text": "The correlation between C5a -induced kappaB binding activity and IL-8 gene expression was examined in the RAW264.7 macrophage cells using reporter genes directed by the kappaB sequence from IkappaBalpha and IL-8 promoter regions .", "target_text": { "kappaB": "protein", "IL-8": "protein", "RAW264.7 macrophage cells": "cell_line", "kappaB sequence": "DNA", "IkappaBalpha": "protein", "IL-8 promoter regions": "DNA" } }, { "input_text": "C5a -induced reporter gene expression was abolished by introducing mutations into the kappaB sites and by coexpression of a dominant negative IkappaBalpha construct resistant to agonist-induced phosphorylation .", "target_text": { "reporter gene": "DNA", "kappaB sites": "DNA", "IkappaBalpha": "protein", "dominant negative IkappaBalpha construct": "DNA" } }, { "input_text": "Pertussis toxin , which ADP -ribosylates the Gi proteins known to couple to the C5a receptor , produced minimal inhibition of C5a -induced IL-8 expression and had little effect on C5a -induced calcium mobilization in RAW264.7 cells .", "target_text": { "Gi proteins": "protein", "C5a receptor": "protein", "IL-8": "protein", "RAW264.7 cells": "cell_line" } }, { "input_text": "These results suggest that NF-kappaB activation is required for C5a -induced IL-8 gene expression and that this response is mediated primarily through a pertussis toxin -insensitive pathway .", "target_text": { "NF-kappaB": "protein", "IL-8": "protein" } }, { "input_text": "Increased glucocorticoid receptor beta in airway cells of glucocorticoid -insensitive asthma .", "target_text": { "glucocorticoid receptor beta": "protein", "airway cells": "cell_type" } }, { "input_text": "Glucocorticoid ( GC ) -insensitive asthma is a challenging clinical problem that can be associated with life-threatening disease progression .", "target_text": {} }, { "input_text": "The molecular basis of GC insensitivity is unknown .", "target_text": {} }, { "input_text": "Alternative splicing of the GC receptor ( GCR ) pre-mRNA generates a second GCR , termed GCRbeta , which does not bind GC but antagonizes the transactivating activity of the classic GCR .", "target_text": { "GC receptor": "protein", "GCR": "protein", "GC receptor ( GCR ) pre-mRNA": "RNA", "GCRbeta": "protein" } }, { "input_text": "Thus increased expression of GCRbeta could account for glucocorticoid insensitivity .", "target_text": { "GCRbeta": "protein" } }, { "input_text": "Bronchoalveolar lavage ( BAL ) cells and peripheral blood mononuclear cells ( PBMC ) were examined for GCRbeta immunoreactivity using a GCRbeta -specific antibody by immunohistochemical staining .", "target_text": { "Bronchoalveolar lavage ( BAL ) cells": "cell_type", "mononuclear cells": "cell_type", "PBMC": "cell_type", "GCRbeta": "protein", "GCRbeta -specific antibody": "protein" } }, { "input_text": "Cell localization of GCRbeta expression was performed using a double immunostaining technique .", "target_text": { "GCRbeta": "protein" } }, { "input_text": "Patients with GC -insensitive asthma expressed a significantly higher number of GCRbeta -immunoreactive cells in their BAL and peripheral blood than GC -sensitive asthmatics or normal control subjects .", "target_text": { "GCRbeta": "protein", "GCRbeta -immunoreactive cells": "cell_type" } }, { "input_text": "Furthermore , GCRbeta expression in GC-insensitive asthma was particularly high in airway T cells , which are thought to play a major role in the pathogenesis of asthma .", "target_text": { "GCRbeta": "protein", "T cells": "cell_type" } }, { "input_text": "We also examined the expression of GCRbeta in specimens from the airways of patients with chronic bronchitis .", "target_text": { "GCRbeta": "protein" } }, { "input_text": "In chronic bronchitis , few cells were GCRbeta -positive and their numbers did not differ significantly from normal control subjects .", "target_text": { "GCRbeta": "protein", "GCRbeta -positive": "cell_type" } }, { "input_text": "We conclude that GC -insensitive asthma is associated with increased expression of GCRbeta in airway T cells .", "target_text": { "GCRbeta": "protein", "T cells": "cell_type" } }, { "input_text": "Activation of the Janus kinase 3 -STAT5a pathway after CD40 triggering of human monocytes but not of resting B cells .", "target_text": { "Janus kinase 3": "protein", "-STAT5a": "protein", "CD40": "protein", "human monocytes": "cell_type", "resting B cells": "cell_type" } }, { "input_text": "CD40 /CD40 ligand interactions play a key role in the immune responses of B lymphocytes , monocytes , and dendritic cells .", "target_text": { "CD40": "protein", "/CD40": "protein", "B lymphocytes": "cell_type", "monocytes": "cell_type", "dendritic cells": "cell_type" } }, { "input_text": "The signal transduction events triggered by cross-linking of the CD40 receptor have been widely studied in B cell lines , but little is known about signaling following CD40 stimulation of monocytes and resting tonsillar B cells .", "target_text": { "CD40": "protein", "CD40 receptor": "protein", "B cell lines": "cell_line", "monocytes": "cell_type", "resting tonsillar B cells": "cell_line" } }, { "input_text": "Therefore , we studied the CD40 pathway in highly purified human monocytes and resting B cells .", "target_text": { "CD40": "protein", "human monocytes": "cell_type", "resting B cells": "cell_type" } }, { "input_text": "After CD40 triggering , a similar activation of the NF-kappaB ( but not of the AP-1 ) transcription factor complex occurred in both cell preparations .", "target_text": { "CD40": "protein", "NF-kappaB": "protein", "AP-1": "protein", "transcription factor complex": "protein" } }, { "input_text": "However , the components of the NF-kappaB complexes were different in monocytes and B cells , because p50 is part of the NF-kappaB complex induced by CD40 triggering in both monocytes and B cells , whereas p65 was only induced in B cells . In contrast , although the Janus kinase 3 tyrosine kinase was associated with CD40 molecules in both monocytes and resting B cells , Janus kinase 3 phosphorylation induction was observed only in CD40 -activated monocytes , with subsequent induction of STAT5a DNA binding activity in the nucleus .", "target_text": { "NF-kappaB": "protein", "NF-kappaB complexes": "protein", "monocytes": "cell_type", "p50": "protein", "NF-kappaB complex": "protein", "CD40": "protein", "B cells": "cell_type", "p65": "protein", "Janus kinase 3": "protein", "Janus kinase 3 tyrosine kinase": "protein", "resting B cells": "cell_type", "CD40 -activated monocytes": "cell_line", "STAT5a": "protein" } }, { "input_text": "These results suggest that the activation signals in human B cells and monocytes differ following CD40 stimulation .", "target_text": { "human B cells": "cell_type", "monocytes": "cell_type", "CD40": "protein" } }, { "input_text": "This observation is consistent with the detection of normal CD40 -induced monocyte activation in patients with CD40 ligand+ hyper IgM syndrome in whom a defect in CD40 -induced B cell activation has been reported .", "target_text": { "CD40": "protein", "IgM": "protein" } }, { "input_text": "Genetic evidence for an additional factor required for erythropoietin -induced signal transduction .", "target_text": { "erythropoietin": "protein" } }, { "input_text": "Erythropoietin ( EPO ) and its receptor ( EPOR ) are required for the development of mature erythrocytes .", "target_text": { "Erythropoietin": "protein", "EPO": "protein", "EPOR": "protein" } }, { "input_text": "After binding of ligand , the EPOR activates a variety of signaling pathways that ultimately control cellular proliferation , survival , and specific gene expression .", "target_text": { "EPOR": "protein" } }, { "input_text": "Although erythroid progenitors appear to be the principal EPO -responsive cell type in vivo due to the restricted expression of the EPOR , many growth factor-dependent cell lines expressing the EPOR can respond to EPO by activating many or all of these pathways .", "target_text": { "erythroid progenitors": "cell_type", "EPO": "protein", "EPO -responsive cell type": "cell_type", "EPOR": "protein", "growth factor-dependent cell lines": "cell_line" } }, { "input_text": "In the present study , we have identified a cellular context ( the interleukin-2 [ IL-2 ] -dependent HT-2 line ) in which the EPO stimulation of the EPOR fails to support cellular proliferation , STAT-5 induction , or MAPK activation , despite efficient phosphorylation of the EPOR and JAK2 and inhibition of apoptosis after withdrawal of IL-2 .", "target_text": { "interleukin-2 [ IL-2 ] -dependent HT-2 line": "cell_line", "EPO": "protein", "EPOR": "protein", "STAT-5": "protein", "MAPK": "protein", "JAK2": "protein", "IL-2": "protein" } }, { "input_text": "Interestingly , when we fused HT-2 cells expressing the EPOR with Ba/F3 cells in a complementation assay , the resulting hybridomas proliferated and potently activated STAT-5 and MAPK in response to EPO .", "target_text": { "HT-2 cells": "cell_line", "EPOR": "protein", "Ba/F3 cells": "cell_line", "hybridomas": "cell_line", "STAT-5": "protein", "MAPK": "protein", "EPO": "protein" } }, { "input_text": "These data indicate that an unidentified cellular factor is needed to mediate signaling by the EPOR .", "target_text": { "unidentified cellular factor": "protein", "EPOR": "protein" } }, { "input_text": "Moreover , Ba/F3 cells apparently express this factor ( s ) and somatic fusions can , therefore , confer EPO -responsiveness to HT-2 cells that lack this factor .", "target_text": { "Ba/F3 cells": "cell_line", "EPO": "protein", "HT-2 cells": "cell_line" } }, { "input_text": "Novel therapies for inflammatory bowel disease .", "target_text": {} }, { "input_text": "Looking back at successes and failures in newer approaches to treating IBD , it is tempting -- although still difficult -- to draw conclusions about pathogenesis .", "target_text": {} }, { "input_text": "When a therapy proves effective , do clinicians truly know how it works ? Even with a therapy as specific as anti-TNF antibody , it is not clear if the benefit is attributable to simple binding and clearance of TNF-alpha or to binding on the cell surface and subsequent deletion of the activated macrophage .", "target_text": { "anti-TNF antibody": "protein", "TNF-alpha": "protein", "activated macrophage": "cell_type" } }, { "input_text": "When a drug appears to be less effective than preclinical models suggest , can failures in effectiveness from delivery or dosing be differentiated ? The disappointing results of clinical trials with IL-10 -- so at odds with the prediction of benefit from animal models -- bring into question the validity of those models as well as the soundness of design of the clinical trials on which efficacy of IL-10 is judged .", "target_text": { "IL-10": "protein" } }, { "input_text": "The variability of response even to the most narrowly targeted agents suggests that these diseases are far more heterogeneous in humans than in their murine counterparts .", "target_text": {} }, { "input_text": "Clinicians are only just beginning to recognize subclinical markers of response , and it may soon be possible to predict response on the basis of genetic composition .", "target_text": {} }, { "input_text": "For the moment , however , the field of pharmacogenetics is embryonic .", "target_text": {} }, { "input_text": "Challenges in developing new therapeutic strategies include not only identifying novel agents , but also improving the definitions of clinical endpoints and defining efficacy at the biologic level .", "target_text": {} }, { "input_text": "Only through considered evaluation of clinical evidence may clinicians determine which therapies should remain novelties and which should become an accepted part of the armamentarium .", "target_text": {} }, { "input_text": "Potent and stable attenuation of live-HIV-1 by gain of a proteolysis-resistant inhibitor of NF-kappaB ( IkappaB-alphaS32/36A ) and the implications for vaccine development .", "target_text": { "proteolysis-resistant inhibitor": "protein", "NF-kappaB": "protein", "IkappaB-alphaS32/36A": "protein" } }, { "input_text": "Live-attenuated human immunodeficiency viruses ( HIVs ) are candidates for Acquired Immunodeficiency Syndrome ( AIDS ) vaccine .", "target_text": {} }, { "input_text": "Based on the simian immunodeficiency virus ( SIV ) model for AIDS , loss-of-function ( e.g. deletion of accessory genes such as nef ) has been forwarded as a primary approach for creating enfeebled , but replication-competent , HIV-1/SIV .", "target_text": { "nef": "DNA" } }, { "input_text": "Regrettably , recent evidence suggests that loss-of-function alone is not always sufficient to prevent the emergence of virulent mutants .", "target_text": {} }, { "input_text": "New strategies that attenuate via mechanisms distinct from loss-of-function are needed for enhancing the safety phenotype of viral genome .", "target_text": { "viral genome": "DNA" } }, { "input_text": "Here , we propose gain-of-function to be used simultaneously with loss-of-function as a novel approach for attenuating HIV-1 .", "target_text": {} }, { "input_text": "We have constructed an HIV-1 genome carrying the cDNA of a proteolysis-resistant nuclear factor-kappaB inhibitor ( IkappaB-alphaS32/36A ) in the nef region .", "target_text": { "HIV-1 genome": "DNA", "cDNA": "DNA", "proteolysis-resistant nuclear factor-kappaB inhibitor": "protein", "IkappaB-alphaS32/36A": "protein", "nef": "DNA", "nef region": "DNA" } }, { "input_text": "HIV-1 expressing IkappaB-alphaS32/36A down-regulates viral expression and is highly attenuated in both Jurkat and peripheral blood mononuclear cells .", "target_text": { "IkappaB-alphaS32/36A": "protein", "Jurkat": "cell_line", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "We provide formal proof that the phenotypic and attenuating characteristics of IkappaB-alphaS32/36A permit its stable maintenance in a live , replicating HIV-1 despite 180 days of forced ex vivo passaging in tissue culture .", "target_text": { "IkappaB-alphaS32/36A": "protein" } }, { "input_text": "As compared with other open-reading frames embedded into HIV/SIV genome , this degree of stability is unprecedented .", "target_text": { "open-reading frames": "DNA", "HIV/SIV genome": "DNA" } }, { "input_text": "Thus , IkappaB-alphaS32/36A offers proof-of-principle that artifactually gained functions , when used to attenuate the replication of live HIV-1 , can be stable .", "target_text": { "IkappaB-alphaS32/36A": "protein" } }, { "input_text": "These findings illustrate gain-of-function as a feasible strategy for developing safer live-attenuated HIVs to be tested as candidates for AIDS vaccine .", "target_text": {} }, { "input_text": "Multiple NF-ATc isoforms with individual transcriptional properties are synthesized in T lymphocytes .", "target_text": { "NF-ATc isoforms": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "The transcription factor NF-ATc that controls gene expression in T lymphocytes and embryonic cardiac cells is expressed in three prominent isoforms .", "target_text": { "transcription factor": "protein", "NF-ATc": "protein", "T lymphocytes": "cell_type", "embryonic cardiac cells": "cell_type" } }, { "input_text": "This is due to alternative splice/polyadenylation events that lead to the predominant synthesis of two long isoforms in naive T cells and a shorter NF-ATc isoform in effector T cells .", "target_text": { "naive T cells": "cell_type", "NF-ATc": "protein", "NF-ATc isoform": "protein", "effector T cells": "cell_type" } }, { "input_text": "Whereas the previously described isoform NF-ATc /A contains a relatively short C terminus , the longer isoforms , B and C , span extra C-terminal peptides of 128 and 246 aa , respectively .", "target_text": { "NF-ATc": "protein", "isoform NF-ATc /A": "protein", "C terminus": "protein", "B": "protein", "C": "protein" } }, { "input_text": "We show here that in addition to the strong N-terminal trans-activation domain , TAD-A , which is common to all three NF-ATc isoforms , NF-ATc /C contains a second trans-activation domain , TAD-B , in its C-terminal peptide .", "target_text": { "strong N-terminal trans-activation domain": "protein", "TAD-A": "protein", "NF-ATc": "protein", "NF-ATc isoforms": "protein", "NF-ATc /C": "protein", "trans-activation domain": "protein", "TAD-B": "protein" } }, { "input_text": "Various stimuli of T cells that induce the activity of TAD-A also enhance the activity of TAD-B , but , unlike TAD-A , TAD-B remains unphosphorylated by protein from 12-O-tetradecanoyl 12-phorbol 13-acetate -stimulated T cells .", "target_text": { "T cells": "cell_type", "TAD-A": "protein", "TAD-B": "protein", "12-O-tetradecanoyl 12-phorbol 13-acetate -stimulated T cells": "cell_line" } }, { "input_text": "The shorter C-terminal peptide of isoform NF-ATc /B exerts a suppressive transcriptional effect .", "target_text": { "NF-ATc": "protein", "NF-ATc /B": "protein" } }, { "input_text": "These properties of NF-ATc / B and - C might be of importance for gene regulation in naive T lymphocytes in which NF-ATc / B and - C are predominantly synthesized .", "target_text": { "T lymphocytes": "cell_type", "naive T lymphocytes": "cell_type" } }, { "input_text": "Selection and long-term persistence of reactive CTL clones during an EBV chronic response are determined by avidity , CD8 variable contribution compensating for differences in TCR affinities .", "target_text": { "CTL clones": "cell_line", "CD8": "protein", "TCR": "protein" } }, { "input_text": "Recent studies have suggested that the diversity of TCR repertoire after primary immunization is conserved in memory T cells and that a progressive narrowing of this repertoire may take place during recall infections .", "target_text": { "TCR": "protein", "memory T cells": "cell_type" } }, { "input_text": "It now remains to be investigated which parameters determine the repertoire of the memory response and possibly restrict its diversity after subsequent antigenic challenges .", "target_text": {} }, { "input_text": "To address this question , we took advantage of a panel of CD8+ T cell clones from the joint of a rheumatoid arthritis patient and selected for their reactivity against a single MHC/peptide complex .", "target_text": { "CD8+ T cell clones": "cell_line", "single MHC/peptide complex": "protein" } }, { "input_text": "Characterization of both TCR chains documented a great diversity among those clones and the persistence of clonotypes over a 2-yr period .", "target_text": { "TCR": "protein", "TCR chains": "protein" } }, { "input_text": "Strikingly , despite the observed repertoire heterogeneity , all clones displayed a narrow range of MHC /peptide density requirements in cytotoxicity assays ( ED50 between 9 and 36 nM ) .", "target_text": { "MHC": "protein" } }, { "input_text": "TCR affinities were then indirectly estimated by blocking CD8 interaction with an anti-CD8 mAb .", "target_text": { "TCR": "protein", "CD8": "protein", "anti-CD8 mAb": "protein" } }, { "input_text": "We found a wide range of TCR affinities among the different clonotypes that segregated with Vbeta usage .", "target_text": { "TCR": "protein" } }, { "input_text": "We thus propose that during an in vivo chronic response , a narrow range of avidity of the TCR -CD8 complex conditions long-term clonotype persistence , and that the level of CD8 contribution is adjusted to keep clonotypes with variable TCR affinities within this avidity window .", "target_text": { "TCR": "protein", "TCR -CD8 complex": "protein", "CD8": "protein" } }, { "input_text": "Nuclear localization and formation of beta-catenin -lymphoid enhancer factor 1 complexes are not sufficient for activation of gene expression .", "target_text": { "beta-catenin": "protein", "beta-catenin -lymphoid enhancer factor 1 complexes": "protein" } }, { "input_text": "In response to activation of the Wnt signaling pathway , beta-catenin accumulates in the nucleus , where it cooperates with LEF/TCF ( for lymphoid enhancer factor and T-cell factor ) transcription factors to activate gene expression .", "target_text": { "beta-catenin": "protein", "LEF/TCF": "protein", "lymphoid enhancer factor and T-cell factor": "protein", "transcription factors": "protein" } }, { "input_text": "The mechanisms by which beta-catenin undergoes this shift in location and participates in activation of gene transcription are unknown .", "target_text": { "beta-catenin": "protein" } }, { "input_text": "We demonstrate here that beta-catenin can be imported into the nucleus independently of LEF/TCF binding , and it may also be exported from nuclei .", "target_text": { "beta-catenin": "protein", "LEF/TCF": "protein" } }, { "input_text": "We have introduced a small deletion within beta-catenin ( Delta19 ) that disrupts binding to LEF-1 , E-cadherin , and APC but not axin .", "target_text": { "beta-catenin": "protein", "Delta19": "DNA", "LEF-1": "protein", "E-cadherin": "protein", "APC": "protein", "axin": "protein" } }, { "input_text": "This Delta19 beta-catenin mutant localizes to the nucleus because it may not be efficiently sequestered in the cytoplasm .", "target_text": { "Delta19": "DNA", "beta-catenin": "protein", "Delta19 beta-catenin mutant": "protein" } }, { "input_text": "The nuclear localization of Delta19 definitively demonstrates that the mechanisms by which beta-catenin localizes in the nucleus are completely independent of LEF/TCF factors .", "target_text": { "Delta19": "DNA", "beta-catenin": "protein", "LEF/TCF": "protein", "LEF/TCF factors": "protein" } }, { "input_text": "beta-Catenin and LEF-1 complexes can activate reporter gene expression in a transformed T-lymphocyte cell line ( Jurkat ) but not in normal T lymphocytes , even though both factors are nuclear .", "target_text": { "beta-Catenin": "protein", "LEF-1": "protein", "LEF-1 complexes": "protein", "transformed T-lymphocyte cell line": "cell_line", "Jurkat": "cell_line", "T lymphocytes": "cell_type", "normal T lymphocytes": "cell_type" } }, { "input_text": "Thus , localization of both factors to the nucleus is not sufficient for activation of gene expression .", "target_text": {} }, { "input_text": "Excess beta-catenin can squelch reporter gene activation by LEF-1 -beta-catenin complexes but not activation by the transcription factor VP16 .", "target_text": { "beta-catenin": "protein", "LEF-1": "protein", "-beta-catenin": "protein", "LEF-1 -beta-catenin complexes": "protein", "transcription factor": "protein", "VP16": "protein" } }, { "input_text": "Taken together , these data suggest that a third component is necessary for gene activation and that this third component may vary with cell type .", "target_text": {} }, { "input_text": "Control of lymphocyte development by the Ikaros gene family .", "target_text": { "Ikaros gene family": "DNA" } }, { "input_text": "Lymphoid cell differentiation relies on precisely orchestrated gene activation and repression events .", "target_text": {} }, { "input_text": "Gene targeting studies have demonstrated crucial roles for the transcription factors Ikaros and Aiolos in regulating multiple stages of B and T cell development .", "target_text": { "transcription factors": "protein", "Ikaros": "protein", "Aiolos": "protein" } }, { "input_text": "Recent experiments suggest that Ikaros and Aiolos set B cell antigen-receptor ( BCR ) - and TCR- mediated signaling thresholds and that the molecules exist within T cells in nuclear complexes that contain nucleosome remodeling and histone deacetylase activities .", "target_text": { "Ikaros": "protein", "Aiolos": "protein", "T cells": "cell_type", "nuclear complexes": "protein", "histone deacetylase": "protein" } }, { "input_text": "Transcriptional targeting of retroviral vectors to the erythroblastic progeny of transduced hematopoietic stem cells .", "target_text": { "erythroblastic progeny": "cell_type", "transduced hematopoietic stem cells": "cell_line" } }, { "input_text": "Targeted expression to specific tissues or cell lineages is a necessary feature of a gene therapy vector for many clinical applications , such as correction of hemoglobinopathies or thalassemias by transplantation of genetically modified hematopoietic stem cells .", "target_text": { "genetically modified hematopoietic stem cells": "cell_type" } }, { "input_text": "We developed retroviral vectors in which the constitutive viral enhancer in the U3 region of the 3' LTR is replaced by an autoregulatory enhancer of the erythroid-specific GATA-1 transcription factor gene .", "target_text": { "constitutive viral enhancer": "DNA", "U3 region": "DNA", "3' LTR": "DNA", "autoregulatory enhancer": "DNA", "transcription factor": "protein", "erythroid-specific GATA-1 transcription factor gene": "DNA" } }, { "input_text": "The replaced enhancer is propagated to the 5' LTR upon integration into the target cell genome .", "target_text": { "replaced enhancer": "DNA", "5' LTR": "DNA", "target cell genome": "DNA" } }, { "input_text": "The modified vectors were used to transduce human hematopoietic cell lines , cord blood-derived CD34(+) stem/progenitor cells , and murine bone marrow repopulating stem cells .", "target_text": { "human hematopoietic cell lines": "cell_line", "cord blood-derived CD34(+) stem/progenitor cells": "cell_type", "murine bone marrow repopulating stem cells": "cell_line" } }, { "input_text": "The expression of appropriate reporter genes ( triangle upLNGFR , EGFP ) was analyzed in the differentiated progeny of transduced stem cells in vitro , in liquid culture as well as in clonogenic assay , and in vivo , after bone marrow transplantation in lethally irradiated mice .", "target_text": { "reporter genes": "DNA", "triangle upLNGFR": "DNA", "EGFP": "DNA", "transduced stem cells": "cell_line" } }, { "input_text": "The GATA-1 autoregulatory enhancer effectively restricts the expression of the LTR-driven proviral transcription unit to the erythroblastic progeny of both human progenitors and mouse-repopulating stem cells .", "target_text": { "GATA-1 autoregulatory enhancer": "DNA", "LTR-driven proviral transcription unit": "DNA", "erythroblastic progeny": "cell_type", "human progenitors": "cell_type", "mouse-repopulating stem cells": "cell_line" } }, { "input_text": "Packaging of viral particles , integration into the target genome , and stability of the integrated provirus are not affected by the LTR modification .", "target_text": { "LTR": "DNA" } }, { "input_text": "Enhancer replacement is therefore an effective strategy to target expression of a retroviral transgene to a specific progeny of transduced hematopoietic stem cells .", "target_text": { "retroviral transgene": "DNA", "transduced hematopoietic stem cells": "cell_line" } }, { "input_text": "Regulation of Fas ligand expression and cell death by apoptosis-linked gene 4 .", "target_text": { "Fas ligand": "protein", "apoptosis-linked gene 4": "DNA" } }, { "input_text": "Programmed cell death is a process required for the normal development of an organism .", "target_text": {} }, { "input_text": "One of the best understood apoptotic pathways occurs in T lymphocytes and is mediated by Fas /Fas ligand ( FasL ) interaction .", "target_text": { "T lymphocytes": "cell_type", "Fas": "protein", "/Fas ligand": "protein", "FasL": "protein" } }, { "input_text": "During studies of apoptosis induced by T cell-receptor engagement , we identified ALG-4F , a truncated transcript that prevents T cell-receptor-induced FasL upregulation and cell death .", "target_text": { "ALG-4F": "protein", "truncated transcript": "protein", "FasL": "protein" } }, { "input_text": "Overexpression of full-length ALG-4 induced transcription of FasL and , consequently , apoptosis .", "target_text": { "full-length ALG-4": "protein", "FasL": "protein" } }, { "input_text": "These results indicate that ALG-4 is necessary and sufficient for FasL expression .", "target_text": { "ALG-4": "protein", "FasL": "protein" } }, { "input_text": "Fas/ FasL interaction initiates cell death in many other systems , and its dysregulation is a mechanism by which several pathologic conditions arise .", "target_text": { "FasL": "protein" } }, { "input_text": "Understanding the molecular mechanisms of FasL regulation could be very useful in elucidating how these diseases develop and in identifying potential therapeutic targets .", "target_text": { "FasL": "protein" } }, { "input_text": "The Epstein-Barr virus oncoprotein latent membrane protein 1 engages the tumor necrosis factor receptor-associated proteins TRADD and receptor-interacting protein ( RIP ) but does not induce apoptosis or require RIP for NF-kappaB activation .", "target_text": { "Epstein-Barr virus oncoprotein": "protein", "Epstein-Barr virus oncoprotein latent membrane protein 1": "protein", "tumor necrosis factor receptor-associated proteins": "protein", "TRADD": "protein", "receptor-interacting protein": "protein", "RIP": "protein", "NF-kappaB": "protein" } }, { "input_text": "A site in the Epstein-Barr virus ( EBV ) transforming protein LMP1 that constitutively associates with the tumor necrosis factor receptor 1 ( TNFR1 ) -associated death domain protein TRADD to mediate NF-kappaB and c-Jun N-terminal kinase activation is critical for long-term lymphoblastoid cell proliferation .", "target_text": { "Epstein-Barr virus ( EBV ) transforming protein": "protein", "LMP1": "protein", "tumor necrosis factor receptor 1": "protein", "TNFR1": "protein", "tumor necrosis factor receptor 1 ( TNFR1 ) -associated death domain protein": "protein", "TRADD": "protein", "NF-kappaB": "protein", "c-Jun N-terminal kinase": "protein" } }, { "input_text": "We now find that LMP1 signaling through TRADD differs from TNFR1 signaling through TRADD .", "target_text": { "LMP1": "protein", "TRADD": "protein", "TNFR1": "protein" } }, { "input_text": "LMP1 needs only 11 amino acids to activate NF-kappaB or synergize with TRADD in NF-kappaB activation , while TNFR1 requires approximately 70 residues .", "target_text": { "LMP1": "protein", "NF-kappaB": "protein", "TRADD": "protein", "TNFR1": "protein" } }, { "input_text": "Further , LMP1 does not require TRADD residues 294 to 312 for NF-kappaB activation , while TNFR1 requires TRADD residues 296 to 302 .", "target_text": { "LMP1": "protein", "TRADD": "protein", "NF-kappaB": "protein", "TNFR1": "protein" } }, { "input_text": "LMP1 is partially blocked for NF-kappaB activation by a TRADD mutant consisting of residues 122 to 293 .", "target_text": { "LMP1": "protein", "NF-kappaB": "protein", "TRADD": "protein", "residues 122 to 293": "protein" } }, { "input_text": "Unlike TNFR1 , LMP1 can interact directly with receptor-interacting protein ( RIP ) and stably associates with RIP in EBV -transformed lymphoblastoid cell lines .", "target_text": { "TNFR1": "protein", "LMP1": "protein", "receptor-interacting protein": "protein", "RIP": "protein", "EBV -transformed lymphoblastoid cell lines": "cell_line" } }, { "input_text": "Surprisingly , LMP1 does not require RIP for NF-kappaB activation .", "target_text": { "LMP1": "protein", "RIP": "protein", "NF-kappaB": "protein" } }, { "input_text": "Despite constitutive association with TRADD or RIP , LMP1 does not induce apoptosis in EBV-negative Burkitt lymphoma or human embryonic kidney 293 cells .", "target_text": { "TRADD": "protein", "RIP": "protein", "LMP1": "protein" } }, { "input_text": "These results add a different perspective to the molecular interactions through which LMP1 , TRADD , and RIP participate in B-lymphocyte activation and growth .", "target_text": { "LMP1": "protein", "TRADD": "protein", "RIP": "protein" } }, { "input_text": "Inhibition of NF-kappa B activity in human T lymphocytes induces caspase-dependent apoptosis without detectable activation of caspase -1 and -3 .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "NF-kappa B is involved in the transcriptional control of various genes that act as extrinsic and intrinsic survival factors for T cells .", "target_text": { "NF-kappa B": "protein", "various genes": "DNA", "T cells": "cell_type" } }, { "input_text": "Our findings show that suppression of NF-kappa B activity with cell-permeable SN50 peptide , which masks the nuclear localization sequence of NF-kappa B1 dimers and prevents their nuclear localization , induces apoptosis in resting normal human PBL .", "target_text": { "NF-kappa B": "protein", "NF-kappa B1": "protein", "NF-kappa B1 dimers": "protein", "resting normal human PBL": "cell_type" } }, { "input_text": "Inhibition of NF-kappa B resulted in the externalization of phosphatidylserine , induction of DNA breaks , and morphological changes consistent with apoptosis .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "DNA fragmentation was efficiently blocked by the caspase inhibitor Z-VAD-fmk and partially blocked by Ac-DEVD-fmk , suggesting that SN50 -mediated apoptosis is caspase -dependent .", "target_text": { "caspase inhibitor": "protein", "Z-VAD-fmk": "protein", "Ac-DEVD-fmk": "protein", "caspase": "protein" } }, { "input_text": "Interestingly , apoptosis induced by NF-kappa B suppression , in contrast to that induced by TPEN ( N,N,N',N'-tetrakis [2-pyridylmethyl]ethylenediamine ) or soluble Fas ligand ( CD95 ) , was observed in the absence of active death effector proteases caspase-1 -like ( IL-1 converting enzyme ) , caspase-3 -like ( CPP32/Yama/apopain ) , and caspase-6 -like and without cleavage of caspase-3 substrates poly( ADP -ribose) polymerase and DNA fragmentation factor-45 .", "target_text": { "NF-kappa B": "protein", "soluble Fas ligand": "protein", "CD95": "protein", "active death effector proteases": "protein", "caspase-1": "protein", "IL-1 converting enzyme": "protein", "caspase-3": "protein", "CPP32/Yama/apopain": "protein", "caspase-6": "protein", "caspase-3 substrates": "protein", "poly( ADP -ribose) polymerase": "protein", "DNA fragmentation factor-45": "protein" } }, { "input_text": "These findings suggest either low level of activation is required or that different caspases are involved .", "target_text": { "caspases": "protein" } }, { "input_text": "Preactivation of T cells resulting in NF-kappa B nuclear translocation protected cells from SN50 -induced apoptosis .", "target_text": { "T cells": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "Our findings demonstrate an essential role of NF-kappa B in survival of naive PBL .", "target_text": { "NF-kappa B": "protein", "naive PBL": "cell_type" } }, { "input_text": "Signal transduction pathways in normal human monocytes stimulated by cytokines and mediators : comparative study with normal human neutrophils or transformed cells and the putative roles in functionality and cell biology .", "target_text": { "normal human monocytes": "cell_type", "cytokines": "protein", "normal human neutrophils": "cell_type", "transformed cells": "cell_line" } }, { "input_text": "Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and interleukin ( IL ) -3 induced tyrosine phosphorylation of 92-kDa protein in normal human monocytes .", "target_text": { "Granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "interleukin ( IL ) -3": "protein", "92-kDa protein": "protein", "normal human monocytes": "cell_type" } }, { "input_text": "We identified this 92-kDa protein as STAT5 , but not as STATs 1 , 3 , and 6 nor c-fes and vav protooncogene products , and demonstrated its translocation to the nucleus , enhancement of specific DNA binding capacity , and potentiation of trancriptional activity by GM-CSF .", "target_text": { "92-kDa protein": "protein", "STAT5": "protein", "c-fes": "protein", "vav protooncogene products": "protein", "GM-CSF": "protein" } }, { "input_text": "N-formyl-methionyl-leucyl-phenylalanine ( FMLP ) and phorbol myristate acetate ( PMA ) induced tyrosine phosphorylation of 42- and 44- kDa proteins , which were identified as extracellular signal-regulated kinase ( ERK ) , in human monocytes .", "target_text": { "extracellular signal-regulated kinase": "protein", "ERK": "protein", "human monocytes": "cell_type" } }, { "input_text": "In marked contrast to neutrophils and MO7e cells , GM-CSF did not induce tyrosine phosphorylation and activation of ERK in monocytes .", "target_text": { "neutrophils": "cell_type", "MO7e cells": "cell_type", "GM-CSF": "protein", "ERK": "protein", "monocytes": "cell_type" } }, { "input_text": "Among upstream signaling molecules of ERK , Shc was constitutively associated with Grb2 and was not tyrosine -phosphorylated by GM-CSF and FMLP , and Sos1 and c-Raf-1 were not phosphorylated by GM-CSF , IL-3 , TNF , and FMLP in monocytes , whereas all these signaling molecules were affected and/or utilized by GM-CSF in MO7e cells .", "target_text": { "upstream signaling molecules": "protein", "ERK": "protein", "Shc": "protein", "GM-CSF": "protein", "Sos1": "protein", "c-Raf-1": "protein", "monocytes": "cell_type", "MO7e cells": "cell_type" } }, { "input_text": "In contrast to neutrophils , p38 was constitutively phosphorylated and agonist-dependent phosphorylation and activation was not detected in human monocytes .", "target_text": { "neutrophils": "cell_type", "p38": "protein", "monocytes": "cell_type", "human monocytes": "cell_type" } }, { "input_text": "Superoxide release stimulated by FMLP was inhibited partially by PD98059 or SB203580 , a specific inhibitor of ERK or p38 pathway , and was almost completely inhibited by the combination of both inhibitors , whereas PMA -induced superoxide release was resistant to these two inhibitors in monocytes .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "PD98059 inhibited GM-CSF -dependent proliferation of MO7e cells .", "target_text": { "GM-CSF": "protein", "MO7e cells": "cell_type" } }, { "input_text": "Present results indicate trancriptional roles of STAT5 and functional roles of ERK and/or p38 in normal human monocytes stimulated by physiological receptor-mediated agonists GM-CSF and FMLP .", "target_text": { "STAT5": "protein", "ERK": "protein", "p38": "protein", "human monocytes": "cell_type", "normal human monocytes": "cell_type", "GM-CSF": "protein" } }, { "input_text": "Possible roles of ERK in proliferation of transformed cells were also suggested .", "target_text": { "ERK": "protein", "transformed cells": "cell_line" } }, { "input_text": "Aiolos transcription factor controls cell death in T cells by regulating Bcl-2 expression and its cellular localization .", "target_text": { "Aiolos": "protein", "transcription factor": "protein", "T cells": "cell_type", "Bcl-2": "protein" } }, { "input_text": "We searched for proteins that interact with Ras in interleukin ( IL ) -2-stimulated or IL-2-deprived cells , and found that the transcription factor Aiolos interacts with Ras .", "target_text": { "Ras": "protein", "transcription factor": "protein", "Aiolos": "protein" } }, { "input_text": "The Ras -Aiolos interaction was confirmed in vitro and in vivo by co-immunoprecipitation .", "target_text": { "Ras": "protein", "-Aiolos": "protein" } }, { "input_text": "Indirect immunofluorescence shows that IL-2 controls the cellular distribution of Aiolos and induces its tyrosine phosphorylation , required for dissociation from Ras .", "target_text": { "IL-2": "protein", "Aiolos": "protein", "Ras": "protein" } }, { "input_text": "We also identified functional Aiolos -binding sites in the Bcl-2 promoter , which are able to activate the luciferase reporter gene .", "target_text": { "Aiolos": "protein", "Aiolos -binding sites": "DNA", "Bcl-2": "protein", "Bcl-2 promoter": "DNA", "luciferase": "protein", "luciferase reporter gene": "DNA" } }, { "input_text": "Mutation of Aiolos -binding sites within the Bcl-2 promoter inhibits transactivation of the reporter gene luciferase , suggesting direct control of Bcl-2 expression by Aiolos .", "target_text": { "Aiolos": "protein", "Aiolos -binding sites": "DNA", "Bcl-2": "protein", "Bcl-2 promoter": "DNA", "luciferase": "protein", "reporter gene luciferase": "DNA" } }, { "input_text": "Co-transfection experiments confirm that Aiolos induces Bcl-2 expression and prevents apoptosis in IL-2 -deprived cells .", "target_text": { "Aiolos": "protein", "Bcl-2": "protein", "IL-2": "protein", "IL-2 -deprived cells": "cell_line" } }, { "input_text": "We propose a model for the regulation of Bcl-2 expression via Aiolos .", "target_text": { "Bcl-2": "protein", "Aiolos": "protein" } }, { "input_text": "Binding of YY1 and Oct1 to a novel element that downregulates expression of IL-5 in human T cells .", "target_text": { "YY1": "protein", "Oct1": "protein", "IL-5": "protein", "T cells": "cell_type" } }, { "input_text": "BACKGROUND : IL-5 controls development of eosinophilia and has been shown to be involved in the pathogenesis of allergic diseases .", "target_text": { "IL-5": "protein" } }, { "input_text": "In both atopic and nonatopic asthma , elevated IL-5 has been detected in peripheral blood and the airways .", "target_text": { "IL-5": "protein" } }, { "input_text": "IL-5 is produced mainly by activated T cells , and its expression is regulated at the transcriptional level .", "target_text": { "IL-5": "protein", "T cells": "cell_type" } }, { "input_text": "OBJECTIVE : This study focuses on the functional analysis of the human IL-5 ( hIL-5 ) promoter and characterization of cis -regulatory elements and transcription factors involved in the suppression of IL-5 transcription in T cells .", "target_text": { "human IL-5 ( hIL-5 ) promoter": "DNA", "IL-5": "protein", "T cells": "cell_type" } }, { "input_text": "METHODS : Methods used in this study include DNase I footprint assays , electrophoretic mobility shift assays , and functional analysis by mammalian cell transfection involving deletion analysis and site-directed mutagenesis .", "target_text": { "DNase I": "protein" } }, { "input_text": "RESULTS : We identified 5 protein binding regions ( BRs ) located within the proximal hIL-5 promoter .", "target_text": { "protein binding regions": "DNA", "BRs": "DNA", "hIL-5 promoter": "DNA", "proximal hIL-5 promoter": "DNA" } }, { "input_text": "Functional analysis indicates that the BRs are involved in control of hIL-5 promoter activity .", "target_text": { "BRs": "DNA", "hIL-5 promoter": "DNA" } }, { "input_text": "Two of these regions , BR3 and BR4 located at positions -102 to -73 , have not previously been described as regulators of IL-5 expression in T cells .", "target_text": { "BR3": "DNA", "BR4": "DNA", "IL-5": "protein", "T cells": "cell_type" } }, { "input_text": "We show that the BR3 sequence contains a novel negative regulatory element located at positions -90 to -79 of the hIL-5 promoter , which binds Oct1 , octamer-like , and YY1 nuclear factors .", "target_text": { "BR3": "DNA", "negative regulatory element": "DNA", "hIL-5 promoter": "DNA", "Oct1": "protein", "octamer-like": "protein", "YY1": "protein", "YY1 nuclear factors": "protein" } }, { "input_text": "Substitution mutations , which abolished binding of these proteins to the BR3 sequence , significantly increased hIL-5 promoter activity in activated T cells .", "target_text": { "BR3": "DNA", "BR3 sequence": "DNA", "hIL-5 promoter": "DNA", "activated T cells": "cell_type" } }, { "input_text": "CONCLUSION : We suggest that Oct1 , YY1 , and octamer-like factors binding to the -90/-79 sequence within the proximal IL-5 promoter are involved in suppression of IL-5 transcription in T cells .", "target_text": { "Oct1": "protein", "YY1": "protein", "octamer-like factors": "protein", "-90/-79 sequence": "DNA", "IL-5": "protein", "proximal IL-5 promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "New immunosuppressive drug PNU156804 blocks IL-2 -dependent proliferation and NF-kappa B and AP-1 activation .", "target_text": { "IL-2": "protein" } }, { "input_text": "We had previously shown that the drug undecylprodigiosin ( UP ) blocks human lymphocyte proliferation in vitro .", "target_text": { "human lymphocyte": "cell_type" } }, { "input_text": "We have now investigated the mechanism of action of a new analogue of UP , PNU156804 , which shows a more favorable activity profile than UP in mice .", "target_text": {} }, { "input_text": "We demonstrate here that the biological effect of PNU156804 in vitro is indistinguishable from UP : PNU156804 blocks human T cell proliferation in mid-late G1 , as determined by cell cycle analysis , expression of cyclins , and cyclin-dependent kinases and retinoblastoma phosphorylation .", "target_text": { "human T cell": "cell_type", "cyclins": "protein", "cyclin-dependent kinases": "protein" } }, { "input_text": "In addition , we show that PNU156804 does not block significantly the induction of either IL-2 or IL-2R alpha- and gamma- chains but inhibits IL-2 -dependent T cell proliferation .", "target_text": { "IL-2": "protein" } }, { "input_text": "We have investigated several molecular pathways that are known to be activated by IL-2 in T cells .", "target_text": { "IL-2": "protein", "T cells": "cell_type" } }, { "input_text": "We show that PNU156804 does not inhibit c-myc and bcl-2 mRNA induction .", "target_text": {} }, { "input_text": "On the other hand , PNU156804 efficiently inhibits the activation of the NF-kappa B and AP-1 transcription factors .", "target_text": { "NF-kappa B": "protein", "AP-1": "protein" } }, { "input_text": "PNU156804 inhibition of NF-kappa B activation is due to the inhibition of the degradation of I kappa B-alpha and I kappa B-beta .", "target_text": { "NF-kappa B": "protein", "I kappa B-alpha": "protein", "I kappa B-beta": "protein" } }, { "input_text": "PNU156804 action is restricted to some signaling pathways ; it does not affect NF-kappa B activation by PMA in T cells but blocks that induced by CD40 cross-linking in B lymphocytes .", "target_text": { "NF-kappa B": "protein", "T cells": "cell_type", "CD40": "protein", "B lymphocytes": "cell_type" } }, { "input_text": "We conclude that the prodigiosin family of immunosuppressants is a new family of molecules that show a novel target specificity clearly distinct from that of other immunosuppressive drugs such as cyclosporin A , FK506 , and rapamycin .", "target_text": {} }, { "input_text": "Human T-cell leukemia virus type 1 Tax protein induces the expression of STAT1 and STAT5 genes in T-cells .", "target_text": { "Human T-cell leukemia virus type 1 Tax protein": "protein", "T-cells": "cell_type" } }, { "input_text": "Human T-cell leukemia virus type 1 ( HTLV-1 ) Tax transforms normal T-cells in the presence of interleukin ( IL ) -2 in vitro .", "target_text": { "Human T-cell leukemia virus type 1 ( HTLV-1 ) Tax": "protein", "T-cells": "cell_type", "interleukin ( IL ) -2": "protein" } }, { "input_text": "STAT is a family of transcription factors that play a pivotal role in cytokine-induced functions of a various type of cells .", "target_text": { "STAT": "protein", "transcription factors": "protein" } }, { "input_text": "We investigated the involvement of STATs in the transformation of T-cells by HTLV-1 .", "target_text": { "STATs": "protein", "T-cells": "cell_type" } }, { "input_text": "HTLV-1 -transformed T-cell lines expressed higher amounts of STAT1 , STAT3 and STAT5 RNA and proteins than virus-negative T cells .", "target_text": { "HTLV-1 -transformed T-cell lines": "cell_line", "virus-negative T cells": "cell_type" } }, { "input_text": "The expression of STAT1 and STAT5 in a human T-cell line was induced by Tax .", "target_text": { "STAT1": "protein", "STAT5": "protein", "human T-cell line": "cell_line", "Tax": "protein" } }, { "input_text": "IL-2 induced the DNA binding activity of STAT3 and STAT5 of a HTLV-1 -transformed cell line and then stimulated its proliferation .", "target_text": { "IL-2": "protein", "STAT3": "protein", "STAT5": "protein" } }, { "input_text": "In contrast , IL-2 did neither in a cell line lacking STAT3 and STAT5 .", "target_text": { "IL-2": "protein", "STAT3": "protein", "STAT5": "protein" } }, { "input_text": "The expression of STAT1 , STAT3 and STAT5 mRNAs were also induced by a T-cell mitogen in normal human peripheral blood mononuclear cells .", "target_text": { "T-cell mitogen": "protein", "human peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Our results suggest that the induction of STAT1 and STAT5 by Tax enhances cytokine -induced functions of virus-infected T-cells , hence the induction may play a role in IL-2 -dependent transformation steps of T-cells by HTLV-1 .", "target_text": { "STAT1": "protein", "STAT5": "protein", "Tax": "protein", "cytokine": "protein", "T-cells": "cell_type", "IL-2": "protein" } }, { "input_text": "Transcriptional control of the IL-5 gene by human helper T cells : IL-5 synthesis is regulated independently from IL-2 or IL-4 synthesis .", "target_text": { "IL-5": "protein", "human helper T cells": "cell_type", "IL-2": "protein", "IL-4": "protein" } }, { "input_text": "BACKGROUND : IL-5 is fundamentally involved in eosinophilic inflammation .", "target_text": { "IL-5": "protein" } }, { "input_text": "Control of IL-5 production may be effective for the management of allergic diseases .", "target_text": { "IL-5": "protein" } }, { "input_text": "OBJECTIVE : We aimed to find the transcriptional mechanisms that regulate the IL-5 gene to selectively control IL-5 synthesis .", "target_text": { "IL-5": "protein" } }, { "input_text": "METHODS : Allergen-specific T-cell clones and T-cell hybridomas were established from the peripheral blood lymphocytes of patients with asthma , and the transcriptional regulation of the IL-5 gene was investigated with transient transfection and electrophoretic mobility shift analysis .", "target_text": { "Allergen-specific T-cell clones": "cell_line", "T-cell hybridomas": "cell_line", "peripheral blood lymphocytes": "cell_type", "IL-5": "protein", "IL-5 gene": "DNA" } }, { "input_text": "RESULTS : A human IL-5 promoter/enhancer- luciferase gene construct , pIL-5(-511) Luc , was transcribed on activation of IL-5 -producing T-cell clones , but not IL-5 -nonproducing clones .", "target_text": { "IL-5": "protein", "luciferase": "protein", "IL-5 promoter/enhancer- luciferase gene construct": "DNA", "pIL-5(-511) Luc": "DNA", "IL-5 -producing T-cell clones": "cell_line", "IL-5 -nonproducing clones": "cell_line" } }, { "input_text": "pIL-5(-511) Luc was transcribed by T-cell hybridomas derived from fusion between IL-5 -producing T-cell clones and an IL-5 gene-nonexpressing T-cell line , but not by hybridomas derived from IL-5 -nonproducing T-cell clones .", "target_text": { "pIL-5(-511) Luc": "DNA", "T-cell hybridomas": "cell_line", "IL-5": "protein", "IL-5 -producing T-cell clones": "cell_line", "IL-5 gene-nonexpressing T-cell line": "cell_line", "hybridomas": "cell_line", "IL-5 -nonproducing T-cell clones": "cell_line" } }, { "input_text": "IL-5 synthesis was not only induced by T-cell receptor stimulation but also by IL-2 receptor stimulation .", "target_text": { "IL-5": "protein", "IL-2": "protein" } }, { "input_text": "Binding of NF-AT , NF-kappaB , and AP-1 was induced by T-cell receptor ( TcR ) stimulation , although there was no significant upregulation of binding by IL-2 stimulation .", "target_text": { "NF-AT": "protein", "NF-kappaB": "protein", "AP-1": "protein", "T-cell receptor": "protein", "TcR": "protein", "IL-2": "protein" } }, { "input_text": "CONCLUSION : IL-5 synthesis by human helper T cells is regulated at the transcriptional level .", "target_text": { "IL-5": "protein", "human helper T cells": "cell_type" } }, { "input_text": "A unique transcriptional mechanism distinct from those regulating the IL-2 or IL-4 genes seems to control the IL-5 gene .", "target_text": { "IL-5": "protein", "IL-5 gene": "DNA" } }, { "input_text": "Selective regulation of IL-5 gene transcription may be useful for treating eosinophlic inflammation .", "target_text": { "IL-5": "protein" } }, { "input_text": "Defining therapeutic targets by using adenovirus : blocking NF-kappaB inhibits both inflammatory and destructive mechanisms in rheumatoid synovium but spares anti-inflammatory mediators .", "target_text": { "NF-kappaB": "protein", "anti-inflammatory mediators": "protein" } }, { "input_text": "The role of the transcription factor NF-kappaB in the pathogenesis of rheumatoid arthritis has long been a subject of controversy .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "We used an adenoviral technique of blocking NF-kappaB through overexpression of the inhibitory subunit IkappaBalpha , which has the advantage that it can be used in the diseased tissue itself , with > 90 % of the synovial macrophages , fibroblasts , and T cells infected .", "target_text": { "NF-kappaB": "protein", "inhibitory subunit": "protein", "IkappaBalpha": "protein", "synovial macrophages": "cell_type", "fibroblasts": "cell_type", "T cells": "cell_type" } }, { "input_text": "We found that the spontaneous production of tumor necrosis factor alpha and other pro-inflammatory cytokines is NF-kappaB -dependent in rheumatoid synovial tissue , in contrast to the main anti-inflammatory mediators , like IL -10 and -11 , and the IL-1 receptor antagonist .", "target_text": { "tumor necrosis factor alpha": "protein", "cytokines": "protein", "pro-inflammatory cytokines": "protein", "NF-kappaB": "protein", "anti-inflammatory mediators": "protein", "IL-1 receptor antagonist": "protein" } }, { "input_text": "Of even more interest , IkappaBalpha overexpression inhibited the production of matrix metalloproteinases 1 and 3 while not affecting their tissue inhibitor .", "target_text": { "IkappaBalpha": "protein" } }, { "input_text": "Blocking NF-kappaB in the rheumatoid joint thus has a very beneficial profile , reducing both the inflammatory response and the tissue destruction .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "The adenoviral technique described here has widespread applicability , allowing rapid testing of the effects of blocking a potential therapeutic target in either cultures of normal cells or in the diseased tissue itself .", "target_text": { "normal cells": "cell_type" } }, { "input_text": "Resistance to tumor necrosis factor induced apoptosis in vitro correlates with high metastatic capacity of cells in vivo .", "target_text": { "tumor necrosis factor": "protein" } }, { "input_text": "TNF is one of the cytokines secreted by the cells of the immune system .", "target_text": { "TNF": "protein", "cytokines": "protein" } }, { "input_text": "Our data demonstrate that those cell lines lacking capability to form metastatic tumors in vivo are susceptible to TNF induced apoptosis in vitro .", "target_text": { "cell lines": "cell_line", "TNF": "protein" } }, { "input_text": "However , cell lines with high metastatic potential are resistant to TNF in vitro .", "target_text": { "cell lines": "cell_line", "TNF": "protein" } }, { "input_text": "Furthermore , the same cell lines were resistant to cytolytic action of other cytotoxic proteins secreted by LAK cells .", "target_text": { "cell lines": "cell_line", "cytotoxic proteins": "protein", "LAK cells": "cell_line" } }, { "input_text": "Our data showed that TNF resistance in vitro correlates with the increased level of transcription factor NF-kappaB .", "target_text": { "TNF": "protein", "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "This finding may provide a tool to improve current protocols of immunotherapy and insights to how tumor cells are or are not killed by LAK cells .", "target_text": { "tumor cells": "cell_type", "LAK cells": "cell_line" } }, { "input_text": "Clonality analysis of granulocytes and T lymphocytes in healthy females by the PCR-based HUMARA method .", "target_text": { "granulocytes": "cell_type", "T lymphocytes": "cell_type", "HUMARA": "DNA" } }, { "input_text": "Clonality analysis utilizing X-chromosome inactivation has been used in the study of various diseases , including hematological malignancies .", "target_text": { "X-chromosome": "DNA" } }, { "input_text": "The human androgen receptor gene ( HUMARA ) assay is the newest of such methods , and the majority of the female population can be assessed by this relatively simple procedure .", "target_text": { "human androgen receptor": "protein", "human androgen receptor gene": "DNA", "HUMARA": "DNA" } }, { "input_text": "One problem in using these clonality analysis methods , however , is that there may be significant variation in Lyonization in blood cells in normal individuals .", "target_text": { "blood cells": "cell_type" } }, { "input_text": "To determine the diversity in X-chromosome methylation patterns , which reflect Lyonization , assessed by the HUMARA assay in the supposedly normal population , we analyzed granulocytes and T cells from 97 relatively young ( 18- to 35-year-old ) healthy female volunteers .", "target_text": { "X-chromosome": "DNA", "HUMARA": "DNA", "granulocytes": "cell_type", "T cells": "cell_line" } }, { "input_text": "We found that the methylation patterns in the two HUMARA alleles were distributed even more widely , both in granuloctyes and in T cells , than previously reported with other methods .", "target_text": { "HUMARA alleles": "DNA", "granuloctyes": "cell_type", "T cells": "cell_line" } }, { "input_text": "We also found that the deviation of methylation in granulocytes and T cells was well correlated .", "target_text": { "granulocytes": "cell_type", "T cells": "cell_line" } }, { "input_text": "Thus , we conclude that appropriate controls from the same individuals , such as T cells in the case of stem cell disorders , should always be employed to conclusively determine whether certain cells of hematopoietic origin are clonal .", "target_text": { "T cells": "cell_line" } }, { "input_text": "Functional B-cell response in intrahepatic lymphoid follicles in chronic hepatitis C .", "target_text": {} }, { "input_text": "Intrahepatic lymphoid follicle ( ILF ) formation is one of the most characteristic and commonly observed histological features in patients with chronic hepatitis C .", "target_text": {} }, { "input_text": "However , little is known regarding whether follicles in the liver belong to functional lymphoid tissues , where B cells are activated , differentiated , and proliferated , or if the lymphocytes are merely infiltrated after recruitment from the secondary lymphoid organs .", "target_text": {} }, { "input_text": "To ascertain this possibility , we examined the expression of markers for B-cell activation , differentiation , and proliferation in ILFs in patients with chronic hepatitis C using surgically resected specimens , and compared them with specimens of perihepatic lymph nodes by an immunohistochemical technique .", "target_text": {} }, { "input_text": "Germinal center ( GC ) formation in the ILFs was frequently found in HCV-positive cases .", "target_text": {} }, { "input_text": "The distribution of immunoglobulin M ( IgM ) - , IgD- , and IgG-positive cells and the expression patterns of Ki-67 , CD23 , or bcl-2 and bcl-6 gene products in the follicles with GC formation in the liver of patients with chronic hepatitis C were similar to those of lymph nodes , indicating that B cells are activated , proliferated , and differentiated in the ILFs with GC formation in patients with chronic hepatitis C .", "target_text": { "B cells": "cell_type" } }, { "input_text": "Oligoclonal expansion of B cells in the livers with ILFs was confirmed by an analysis of immunoglobulin heavy chain ( IgH ) gene rearrangement determined by polymerase chain reaction ( PCR ) .", "target_text": { "B cells": "cell_type", "immunoglobulin heavy chain": "protein", "IgH": "protein", "immunoglobulin heavy chain ( IgH ) gene": "DNA" } }, { "input_text": "These data strongly suggest that ILFs with GC formation , which are frequently found in patients with chronic hepatitis C , may functionally be the same as those found in lymph nodes with respect to B-cell expansion and maturation .", "target_text": {} }, { "input_text": "Downregulation of Wilms ' tumor gene ( WT1 ) is not a prerequisite for erythroid or megakaryocytic differentiation of the leukemic cell line K562 .", "target_text": { "Wilms ' tumor gene": "DNA", "WT1": "DNA", "leukemic cell line K562": "cell_line" } }, { "input_text": "The Wilms ' tumor gene ( WT1 ) encodes a transcription factor of the zinc finger type .", "target_text": { "Wilms ' tumor gene": "DNA", "WT1": "DNA", "transcription factor": "protein", "zinc finger type": "protein" } }, { "input_text": "A high expression of WT1 has been detected in a range of acute leukemias , and WT1 is downregulated during induced differentiation of some leukemic cell lines .", "target_text": { "WT1": "DNA", "leukemic cell lines": "cell_line" } }, { "input_text": "Overexpression of WT1 in some myeloid cell lines confers resistance to differentiation induction .", "target_text": { "WT1": "DNA", "myeloid cell lines": "cell_line" } }, { "input_text": "These observations suggest that a high WT1 expression in hematopoietic cells is incompatible with differentiation .", "target_text": { "WT1": "DNA", "hematopoietic cells": "cell_type" } }, { "input_text": "In this study , each of the four different isoforms of WT1 was constitutively overexpressed in the leukemic cell line K562 .", "target_text": { "WT1": "DNA", "leukemic cell line K562": "cell_line" } }, { "input_text": "K562 cells express endogenous WT1 , which is downregulated as a response to induced differentiation along the erythroid and megakaryocytic pathways .", "target_text": { "K562 cells": "cell_line", "WT1": "DNA" } }, { "input_text": "We now demonstrate that a forced exogenous expression of the four different isoforms of WT1 in K562 does not affect the differentiation response , as judged by accumulation of hemoglobin in response to hemin or the expression of megakaryocytic cell surface markers in response to 12-O-tetradecanoylphorbol-13-acetate ( TPA ) .", "target_text": { "WT1": "DNA", "K562": "cell_line", "hemoglobin": "protein", "hemin": "protein", "megakaryocytic cell surface markers": "protein" } }, { "input_text": "We conclude that downregulation of WT1 during induced differentiation of K562 cells is not a prerequisite for erythroid or megakaryocytic differentiation of these cells .", "target_text": { "WT1": "DNA", "K562 cells": "cell_line" } }, { "input_text": "Association of the interleukin-4 receptor alpha chain with p47phox , an activator of the phagocyte NADPH oxidase in B cells .", "target_text": { "interleukin-4 receptor alpha chain": "protein", "phagocyte NADPH oxidase": "protein", "B cells": "cell_type" } }, { "input_text": "Interleukin ( IL ) -4 plays an important role in IgE synthesis in B cells and in Th2 differentiation in T cells .", "target_text": { "Interleukin ( IL ) -4": "protein", "IgE": "protein", "B cells": "cell_type", "T cells": "cell_line" } }, { "input_text": "IL-4 conducts its biological activities through binding to the IL-4 receptor ( IL-4R ) on the surface of target cells .", "target_text": { "IL-4": "protein", "IL-4 receptor": "protein", "IL-4R": "protein", "target cells": "cell_type" } }, { "input_text": "IL-4R are thought to be composed of the IL-4R alpha chain ( IL-4R alpha ) and either the IL-2R gamma chain or the IL-13R alpha chain .", "target_text": { "IL-4R": "protein", "IL-4R alpha chain": "protein", "IL-4R alpha": "protein", "IL-2R gamma chain": "protein", "IL-13R alpha chain": "protein" } }, { "input_text": "We have previously shown that the membrane-proximal portion in the cytoplasmic domain of the human IL-4R alpha ( hIL-4R alpha ) is critical for proliferation , generation of germline epsilon transcript , and activation of STAT6 , based on analyses of truncated hIL-4R alphas .", "target_text": { "membrane-proximal portion": "protein", "cytoplasmic domain": "protein", "IL-4R alpha": "protein", "human IL-4R alpha": "protein", "hIL-4R alpha": "protein", "STAT6": "protein", "truncated hIL-4R alphas": "protein" } }, { "input_text": "In this study , we found that p47phox , an activator of the phagocyte NADPH oxidase , binds to this portion by the two-hybrid system .", "target_text": { "phagocyte NADPH oxidase": "protein" } }, { "input_text": "Furthermore , we observed the association of p47phox with the hIL-4R alpha in B cells derived from a normal donor .", "target_text": { "hIL-4R alpha": "protein", "B cells": "cell_type" } }, { "input_text": "These results suggest that p47phox is involved in the signal transduction of IL-4 in B cells .", "target_text": { "IL-4": "protein", "B cells": "cell_type" } }, { "input_text": "However , activation of STAT6 , CD23 expression , and IgE synthesis induced by IL-4 were not affected in p47phox -deficient patients , which raises the possibility that p47phox may be important in other signaling activities as well in B cells .", "target_text": { "STAT6": "protein", "CD23": "protein", "IgE": "protein", "IL-4": "protein", "B cells": "cell_type" } }, { "input_text": "Effects of diesel organic extracts on chemokine production by peripheral blood mononuclear cells .", "target_text": { "chemokine": "protein", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "BACKGROUND : Polyaromatic hydrocarbons ( PAHs ) associated with diesel exhaust particles ( DEPs ) are found in the atmospheric urban pollution .", "target_text": {} }, { "input_text": "Such compounds have been shown to favor IgE production , bronchial hyperresponsiveness , and airway inflammation .", "target_text": { "IgE": "protein" } }, { "input_text": "Chemokines are a group of chemotactic cytokines involved in the recruitment of inflammatory cells .", "target_text": { "chemotactic cytokines": "protein", "inflammatory cells": "cell_type" } }, { "input_text": "OBJECTIVE : We investigated the effect of DEP- PAHs on the release and mRNA expression of IL-8 , MCP-1 , and RANTES by PBMCs obtained from healthy subjects .", "target_text": { "mRNA": "RNA", "IL-8": "protein", "MCP-1": "protein", "RANTES": "protein", "PBMCs": "cell_type" } }, { "input_text": "METHODS : Protein production in supernatants was assessed by ELISA , and mRNA expression was evaluated by semiquantitative RT- PCR .", "target_text": { "mRNA": "RNA" } }, { "input_text": "RESULTS : Secretion of IL-8 and RANTES increased in a dose-dependent manner with increasing concentrations of DEP- PAHs ( range , 0.5 ng to 50 ng/mL ) .", "target_text": { "IL-8": "protein", "RANTES": "protein" } }, { "input_text": "On the contrary , the release of MCP-1 was significantly inhibited , also in a dose-dependent manner .", "target_text": { "MCP-1": "protein" } }, { "input_text": "Messenger RNA production coding for IL-8 , RANTES , and MCP-1 showed parallel variations to the production of the correspondent proteins .", "target_text": { "Messenger RNA": "RNA", "IL-8": "protein", "RANTES": "protein", "MCP-1": "protein", "correspondent proteins": "protein" } }, { "input_text": "Effects of DEP- PAHs became significant at 7 hours and up to 48 hours time culture for MCP-1 , and up to 24 hours time culture for IL-8 and RANTES .", "target_text": { "MCP-1": "protein", "IL-8": "protein", "RANTES": "protein" } }, { "input_text": "Moreover , supernatants from DEP-PAH-activated cells , compared with those of controls , exhibited a significantly enhanced chemotactic activity for neutrophils and eosinophils , which was significantly inhibited by pretreatment with anti- IL-8 and anti- RANTES neutralizing antibodies , respectively .", "target_text": { "DEP-PAH-activated cells": "cell_type", "neutrophils": "cell_type", "eosinophils": "cell_type", "IL-8": "protein", "anti- IL-8": "protein", "RANTES": "protein", "anti- RANTES": "protein" } }, { "input_text": "CONCLUSION : These findings suggest that the chemokine pathways are modulated by DEP- PAHs at the transcriptional level , reinforcing the idea that the development of inflammatory reactions might be affected by diesel exhaust emission .", "target_text": { "chemokine": "protein" } }, { "input_text": "20-Epi analogues of 1,25-dihydroxyvitamin D3 are highly potent inducers of DRIP coactivator complex binding to the vitamin D3 receptor .", "target_text": { "DRIP coactivator complex": "protein", "vitamin D3 receptor": "protein" } }, { "input_text": "1,25-Dihydroxyvitamin D3 ( 1,25(OH)2D3 ) plays a major role in the stimulation of bone growth , mineralization , and intestinal calcium and phosphate absorption ; it also acts as a general inhibitor of cellular proliferation .", "target_text": {} }, { "input_text": "Several new , clinically relevant compounds dissociate antiproliferative and calcemic activities of 1,25(OH)2D3 , but the molecular basis for this has not been clearly elucidated .", "target_text": {} }, { "input_text": "Here , we tested whether the potency of one class of compounds , 20-epi analogues , to induce myeloid cell differentiation , is because of direct molecular effects on vitamin D receptor ( VDR ) .", "target_text": { "vitamin D receptor": "protein", "VDR": "protein" } }, { "input_text": "We report that two 20-epi analogues , MC1627 and MC1288 , induced differentiation and transcription of p21 ( Waf1 , Cip1 ) , a key VDR target gene involved in growth inhibition , at a concentration 100-fold lower than that of 1,25(OH)2D3 .", "target_text": { "p21": "DNA", "Waf1": "DNA", "Cip1": "DNA", "VDR": "protein", "VDR target gene": "DNA" } }, { "input_text": "We compared this sensitivity to analogue effects on VDR interacting proteins : RXR , GRIP-1 , and DRIP205 , a subunit of the DRIP coactivator complex .", "target_text": { "VDR": "protein", "RXR": "protein", "GRIP-1": "protein", "DRIP205": "protein", "DRIP coactivator complex": "protein" } }, { "input_text": "Compared with the interaction of VDR with RXR or GRIP-1 , the differentiation dose-response most closely correlated to the ligand-dependent recruitment of the DRIP coactivator complex to VDR and to the ability of the receptor to activate transcription in a cell-free system .", "target_text": { "VDR": "protein", "RXR": "protein", "GRIP-1": "protein", "DRIP coactivator complex": "protein" } }, { "input_text": "These results provide compelling links between the efficiency of the 20-epi analogue in inducing VDR /DRIP interactions , transactivation in vitro , and its enhanced ability to induce cellular differentiation .", "target_text": { "VDR": "protein" } }, { "input_text": "SLP-76 and Vav function in separate , but overlapping pathways to augment interleukin-2 promoter activity .", "target_text": { "SLP-76": "protein", "Vav": "protein", "interleukin-2": "protein", "interleukin-2 promoter": "DNA" } }, { "input_text": "SLP-76 and Vav , two hematopoietic cell specific molecules , are critical for T cell development and activation .", "target_text": { "SLP-76": "protein", "Vav": "protein", "hematopoietic cell specific molecules": "protein" } }, { "input_text": "Following T cell antigen receptor stimulation , SLP-76 and Vav both undergo tyrosine phosphorylation and associate with each other via the SH2 domain of Vav and phosphorylated tyrosines of SLP-76 .", "target_text": { "T cell antigen receptor": "protein", "SLP-76": "protein", "Vav": "protein" } }, { "input_text": "Furthermore , SLP-76 and Vav have a synergistic effect on interleukin ( IL ) -2 promoter activity in T cells .", "target_text": { "SLP-76": "protein", "Vav": "protein", "interleukin ( IL ) -2 promoter": "DNA", "T cells": "cell_line" } }, { "input_text": "In this report , we show that two tyrosines , Tyr-113 and Tyr-128 , of SLP-76 are required for its binding to Vav , both in vitro and in intact cells .", "target_text": { "SLP-76": "protein", "Vav": "protein", "intact cells": "cell_type" } }, { "input_text": "Surprisingly , we find also that the interaction between SLP-76 and Vav is not required for their cooperation in augmenting IL-2 promoter activity , as the two molecules appear to function in different signaling pathways upstream of IL-2 gene expression .", "target_text": { "SLP-76": "protein", "Vav": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "IL-2 gene": "DNA" } }, { "input_text": "Overexpression of SLP-76 in the Jurkat T cell line potentiates the activities of both nuclear factor of activated T cells and AP-1 transcription factors .", "target_text": { "SLP-76": "protein", "Jurkat T cell line": "cell_line", "nuclear factor of activated T cells": "protein", "AP-1 transcription factors": "protein" } }, { "input_text": "In contrast , overexpression of Vav leads to enhanced nuclear factor of activated T cells activity without affecting AP-1 .", "target_text": { "Vav": "protein", "nuclear factor of activated T cells": "protein", "AP-1": "protein" } }, { "input_text": "Additionally , overexpression of Vav , but not SLP-76 , augments CD28-induced IL-2 promoter activity .", "target_text": { "Vav": "protein", "SLP-76": "protein", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "These findings suggest that the synergy between SLP-76 and Vav in regulating IL-2 gene expression reflects the cooperation between different signaling pathways .", "target_text": { "SLP-76": "protein", "Vav": "protein", "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "Rel/NF-kappaB can trigger the Notch signaling pathway by inducing the expression of Jagged1 , a ligand for Notch receptors .", "target_text": { "Rel/NF-kappaB": "protein", "Jagged1": "protein", "Notch receptors": "protein" } }, { "input_text": "Jagged1 belongs to the DSL family of ligands for Notch receptors that control the proliferation and differentiation of various cell lineages .", "target_text": { "Jagged1": "protein", "DSL family of ligands": "protein", "Notch receptors": "protein", "cell lineages": "cell_type" } }, { "input_text": "However , little is known about the transcription factors that regulate its expression .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Here , we show that Jagged1 is a Rel/NF-kappaB -responsive gene .", "target_text": { "Jagged1": "protein", "Rel/NF-kappaB": "protein", "Rel/NF-kappaB -responsive gene": "DNA" } }, { "input_text": "Both c-Rel and RelA induced jagged1 gene expression , whereas a mutant defective for transactivation did not .", "target_text": { "c-Rel": "protein", "RelA": "protein" } }, { "input_text": "Importantly , jagged1 transcripts were also upregulated by endogenous NF-kappaB activation and this effect was inhibited by a dominant mutant of IkappaBalpha , a physiological inhibitor of NF-kappaB .", "target_text": { "jagged1 transcripts": "protein", "NF-kappaB": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Cell surface expression of Jagged1 in c-Rel -expressing cell monolayers led to a functional interaction with lymphocytes expressing the Notch1/TAN-1 receptor .", "target_text": { "Jagged1": "protein", "c-Rel": "protein", "c-Rel -expressing cell monolayers": "cell_line", "lymphocytes": "cell_type", "Notch1/TAN-1 receptor": "protein" } }, { "input_text": "This correlated with the initiation of signaling downstream of Notch , as evidenced by increased levels of HES-1 transcripts in co-cultivated T cells and of CD23 transcripts in co-cultivated B cells .", "target_text": { "HES-1 transcripts": "RNA", "co-cultivated T cells": "cell_line", "CD23": "protein", "CD23 transcripts": "RNA", "B cells": "cell_type" } }, { "input_text": "Consistent with its Rel/NF-kappaB -dependent induction , Jagged1 was found to be highly expressed in splenic B cells where c-Rel is expressed constitutively .", "target_text": { "Rel/NF-kappaB": "protein", "Jagged1": "protein", "B cells": "cell_type", "splenic B cells": "cell_type", "c-Rel": "protein" } }, { "input_text": "These results demonstrate that c-Rel can trigger the Notch signaling pathway in neighboring cells by inducing jagged1 gene expression , and suggest a role for Jagged1 in B-cell activation , differentiation or function .", "target_text": { "c-Rel": "protein", "Jagged1": "protein" } }, { "input_text": "These findings also highlight the potential for an interplay between the Notch and NF-kappaB signaling pathways in the immune system .", "target_text": {} }, { "input_text": "Bacterial peptidoglycan induces CD14 -dependent activation of transcription factors CREB/ATF and AP-1 .", "target_text": { "CD14": "protein", "transcription factors": "protein", "CREB/ATF": "protein", "AP-1": "protein" } }, { "input_text": "Peptidoglycan ( PGN ) , the major cell wall component of Gram-positive bacteria , induces secretion of cytokines in macrophages through CD14 , the pattern recognition receptor that binds lipopolysaccharide and other microbial products .", "target_text": { "cytokines": "protein", "macrophages": "cell_type", "CD14": "protein" } }, { "input_text": "To begin to elucidate the mechanisms that regulate the transcription of cytokine genes , we wanted to determine which transcription factors are activated by PGN in mouse RAW264.7 and human THP-1 macrophage cells .", "target_text": { "cytokine genes": "DNA", "transcription factors": "protein", "mouse RAW264.7": "cell_line", "human THP-1 macrophage cells": "cell_line" } }, { "input_text": "Our results demonstrated that : ( i ) PGN induced phosphorylation of the transcription factors ATF-1 and CREB ; ( ii ) ATF-1 and CREB bound DNA as a dimer and induced transcriptional activation of a CRE reporter plasmid , which was inhibited by dominant negative CREB and ATF-1 ; ( iii ) PGN induced phosphorylation of c-Jun , protein synthesis of JunB and c-Fos , and transcriptional activation of the AP-1 reporter plasmid , which was inhibited by dominant negative c-Fos ; and ( iv ) PGN -induced activation of CREB /ATF and AP-1 was mediated through CD14 .", "target_text": { "transcription factors": "protein", "ATF-1": "protein", "CREB": "protein", "DNA": "DNA", "CRE reporter plasmid": "DNA", "c-Jun": "protein", "JunB": "protein", "c-Fos": "protein", "AP-1": "protein", "AP-1 reporter plasmid": "DNA", "CREB /ATF": "protein", "CD14": "protein" } }, { "input_text": "This is the first study to demonstrate activation of CREB /ATF and AP-1 transcription factors by PGN or by any other component of Gram-positive bacteria .", "target_text": { "CREB": "protein", "CREB /ATF": "protein", "AP-1": "protein", "transcription factors": "protein", "AP-1 transcription factors": "protein" } }, { "input_text": "Glucocorticoid receptors are down-regulated in inflamed colonic mucosa but not in peripheral blood mononuclear cells from patients with inflammatory bowel disease [ see comments ]", "target_text": { "Glucocorticoid receptors": "protein", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "BACKGROUND : Growing evidence indicates that the immune system and the hypothalamic-pituitary-adrenal system are linked by several mechanisms , for example intracellular glucocorticoid receptors ( hGR ) .", "target_text": { "glucocorticoid receptors": "protein", "hGR": "protein" } }, { "input_text": "Glucocorticoids are the standard treatment of acute attacks of inflammatory bowel disease ( IBD ) .", "target_text": {} }, { "input_text": "Binding of glucocorticoids to hGR down-regulates the transcription of inflammatory genes that can propagate IBD .", "target_text": { "hGR": "protein", "inflammatory genes": "DNA" } }, { "input_text": "PATIENTS AND METHODS : IBD patients were either treated with 5-60 mg of prednisolone for more than 1 week or were without glucocorticoid treatment for more than 4 weeks .", "target_text": {} }, { "input_text": "hGR levels were determined from isolated cytosol of peripheral blood mononuclear cells ( PBMCs ) or mucosal biopsies using a radioassay with [3H]-dexamethasone .", "target_text": { "hGR": "protein", "peripheral blood mononuclear cells": "cell_type", "PBMCs": "cell_type" } }, { "input_text": "Interleukin ( IL ) 6 levels were determined by enzyme-linked immunosorbent assay ( ELISA ) .", "target_text": {} }, { "input_text": "RESULTS : The systemic ( PBMC ) hGR levels of corticosteroid-treated IBD patients were significantly lower than those of control subjects ( 59.6 +/- 57.1 dpm mg-1 cytosol protein vs.", "target_text": { "hGR": "protein", "cytosol protein": "protein" } }, { "input_text": "227.0 +/- 90.8 dpm mg-1 cytosol protein , P = 0.007 ) and IBD patients not receiving glucocorticoid treatment ( 179.7 +/- 171.3 dpm mg-1 cytosol protein , P = 0.002 ) .", "target_text": { "cytosol protein": "protein" } }, { "input_text": "Systemic hGR levels in untreated IBD patients did not differ significantly from those in control subjects .", "target_text": { "hGR": "protein" } }, { "input_text": "In patients with connective tissue diseases , systemic hGR levels were also found to be decreased in the absence of glucocorticoid treatment .", "target_text": { "hGR": "protein" } }, { "input_text": "Systemic hGR levels in patients with Crohn 's disease ( CD ) treated with steroids ( 66.6 +/- 61.0 dpm mg-1 cytosol protein ) were not different from those in patients with ulcerative colitis ( UC ) ( 56.1 +/- 51.6 dpm mg-1 cytosol protein ) .", "target_text": { "hGR": "protein", "cytosol protein": "protein" } }, { "input_text": "In contrast to these findings , mucosal hGR levels were significantly decreased in both steroid-treated ( 18.0 +/- 15.5 ) and not steroid-treated ( 37.8 +/- 30.5 ) patients compared with control subjects ( 125.6 +/- 97.1 ; P = 0.00009 and P = 0.0008 respectively ) .", "target_text": { "hGR": "protein" } }, { "input_text": "IL-6 levels in all IBD groups with and without steroids were significantly different from those in control subjects .", "target_text": {} }, { "input_text": "CONCLUSION : In IBD there is no difference in systemic hGR levels between not steroid-treated patients and control subjects , in spite of inflammatory activity ( IL-6 ) .", "target_text": { "hGR": "protein", "IL-6": "protein" } }, { "input_text": "Mucosal hGR levels were decreased independently of treatment , probably leading to a decreased protection against NF-kappaB action in the intestinal mucosa .", "target_text": { "hGR": "protein", "NF-kappaB": "protein" } }, { "input_text": "ICSAT overexpression is not sufficient to cause adult T-cell leukemia or multiple myeloma .", "target_text": { "ICSAT": "protein" } }, { "input_text": "ICSAT ( Interferon Consensus Sequence binding protein for Activated T cells ) is a lymphocyte-specific member of the interferon regulatory factor ( IRF ) family of transcription factors , originally identified through Southwestern screening of the ATL ( Adult T-cell leukemia ) -16T expression library .", "target_text": { "ICSAT": "protein", "Interferon Consensus Sequence binding protein for Activated T cells": "protein", "interferon regulatory factor ( IRF ) family": "protein", "ATL ( Adult T-cell leukemia ) -16T expression library": "DNA" } }, { "input_text": "In this study , we created transgenic mice overexpressing ICSAT in lymphocytes .", "target_text": { "ICSAT": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Although spontaneous tumorigenesis was not observed , IL-2 production with Concanavalin A stimulation was significantly increased in transgenic mice overexpressing ICSAT .", "target_text": { "IL-2": "protein", "ICSAT": "protein" } }, { "input_text": "ICSAT overexpression in lymphocytes seems insufficient for the leukemogenesis of ATL or multiple myeloma ( MM ) , however , it may regulate T cell activation and its overexpression may lead to leukemogenesis via controlling IL-2 production .", "target_text": { "ICSAT": "protein", "lymphocytes": "cell_type", "IL-2": "protein" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "Altered memory T cell differentiation in patients with early rheumatoid arthritis .", "target_text": { "memory T cell": "cell_type" } }, { "input_text": "The chronic immune response in rheumatoid arthritis ( RA ) might be driven by activated Th1 cells without sufficient Th2 cell differentiation to down-modulate inflammation .", "target_text": {} }, { "input_text": "To test whether disordered memory T cell differentiation contributes to the typical Th1-dominated chronic inflammation in RA we investigated differentiation of resting CD4+ memory T cells in patients with early ( 6 wk to 12 mo ) untreated RA and in age- and sex-matched healthy controls in vitro .", "target_text": { "memory T cell": "cell_type", "resting CD4+ memory T cells": "cell_type" } }, { "input_text": "No difference in cytokine secretion profiles of freshly isolated memory T cells was detected between patients and controls .", "target_text": { "cytokine": "protein", "freshly isolated memory T cells": "cell_type" } }, { "input_text": "A cell culture system was then employed that permitted the differentiation of Th effectors from resting memory T cells by short term priming .", "target_text": { "cell culture system": "cell_line", "Th effectors": "protein", "resting memory T cells": "cell_type" } }, { "input_text": "Marked differences were found in response to priming .", "target_text": {} }, { "input_text": "Th2 cells could be induced in all healthy controls by priming with anti-CD28 in the absence of TCR ligation .", "target_text": { "Th2 cells": "cell_line", "anti-CD28": "protein", "TCR": "protein" } }, { "input_text": "By contrast , priming under those conditions resulted in Th2 differentiation in only 9 of 24 RA patients .", "target_text": {} }, { "input_text": "Exogenous IL-4 could overcome the apparent Th2 differentiation defect in seven patients but was without effect in the remaining eight patients .", "target_text": { "IL-4": "protein" } }, { "input_text": "In all patients a marked decrease in IL-2 -producing cells and a significant increase in well-differentiated Th1 cells that produced IFN-gamma but not IL-2 were evident after priming with anti-CD3 and anti-CD28 .", "target_text": { "IL-2": "protein", "IL-2 -producing cells": "cell_type", "Th1 cells": "cell_type", "IFN-gamma": "protein", "anti-CD3": "protein", "anti-CD28": "protein" } }, { "input_text": "The data suggest that CD4+ memory T cells from patients with early untreated RA manifest an intrinsic abnormality in their ability to differentiate into specific cytokine-producing effector cells that might contribute to the characteristic Th1-dominated chronic ( auto ) immune inflammation in RA .", "target_text": { "CD4+ memory T cells": "cell_type", "cytokine-producing effector cells": "cell_type" } }, { "input_text": "The intracellular parasite Theileria parva protects infected T cells from apoptosis .", "target_text": { "infected T cells": "cell_type" } }, { "input_text": "Parasites have evolved a plethora of strategies to ensure their survival .", "target_text": {} }, { "input_text": "The intracellular parasite Theileria parva secures its propagation and spreads through the infected animal by infecting and transforming T cells , inducing their continuous proliferation and rendering them metastatic .", "target_text": { "T cells": "cell_type" } }, { "input_text": "In previous work , we have shown that the parasite induces constitutive activation of the transcription factor NF-kappaB , by inducing the constitutive degradation of its cytoplasmic inhibitors .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein", "cytoplasmic inhibitors": "protein" } }, { "input_text": "The biological significance of NF-kappaB activation in T. parva-infected cells , however , has not yet been defined .", "target_text": { "NF-kappaB": "protein", "T. parva-infected cells": "cell_type" } }, { "input_text": "Cells that have been transformed by viruses or oncogenes can persist only if they manage to avoid destruction by the apoptotic mechanisms that are activated on transformation and that contribute to maintain cellular homeostasis .", "target_text": { "oncogenes": "DNA" } }, { "input_text": "We now demonstrate that parasite-induced NF-kappaB activation plays a crucial role in the survival of T. parva-transformed T cells by conveying protection against an apoptotic signal that accompanies parasite-mediated transformation .", "target_text": { "NF-kappaB": "protein", "T. parva-transformed T cells": "cell_type" } }, { "input_text": "Consequently , inhibition of NF-kappaB nuclear translocation and the expression of dominant negative mutant forms of components of the NF-kappaB activation pathway , such as IkappaBalpha or p65 , prompt rapid apoptosis of T. parva-transformed T cells .", "target_text": { "NF-kappaB": "protein", "dominant negative mutant": "protein", "IkappaBalpha": "protein", "p65": "protein", "T. parva-transformed T cells": "cell_type" } }, { "input_text": "Our findings offer important insights into parasite survival strategies and demonstrate that parasite-induced constitutive NF-kappaB activation is an essential step in maintaining the transformed phenotype of the infected cells .", "target_text": { "NF-kappaB": "protein", "infected cells": "cell_type" } }, { "input_text": "A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria [ see comments ]", "target_text": { "OCT-1": "protein", "TNF promoter": "DNA", "TNF promoter region": "DNA" } }, { "input_text": "Genetic variation in cytokine promoter regions is postulated to influence susceptibility to infection , but the molecular mechanisms by which such polymorphisms might affect gene regulation are unknown .", "target_text": { "cytokine promoter regions": "DNA" } }, { "input_text": "Through systematic DNA footprinting of the TNF ( encoding tumour necrosis factor , TNF ) promoter region , we have identified a single nucleotide polymorphism ( SNP ) that causes the helix-turn-helix transcription factor OCT-1 to bind to a novel region of complex protein-DNA interactions and alters gene expression in human monocytes .", "target_text": { "transcription factor": "protein", "human monocytes": "cell_type" } }, { "input_text": "The OCT-1-binding genotype , found in approximately 5 % of Africans , is associated with fourfold increased susceptibility to cerebral malaria in large case-control studies of West African and East African populations , after correction for other known TNF polymorphisms and linked HLA alleles .", "target_text": { "HLA alleles": "DNA" } }, { "input_text": "UV-induced CYP1A1 gene expression in human cells is mediated by tryptophan .", "target_text": { "CYP1A1": "protein" } }, { "input_text": "Induction of cytochrome P-4501A1 ( CYP1A1 ) activity by UV has been observed earlier in animal studies via a mechanism that has not yet been resolved .", "target_text": { "cytochrome P-4501A1": "protein", "CYP1A1": "protein" } }, { "input_text": "Our previous data have indicated that formylated indolocarbazoles which are formed by UV irradiation of tryptophan solutions are very potent Ah-receptor agonists .", "target_text": {} }, { "input_text": "To evaluate the effect of UV light on cytochrome P4501A1 gene expression , we studied the induction of CYP1A1 mRNA by UV irradiation of cultured human keratinocytes ( HaCaT cell line ) , primary human blood lymphocytes and mouse Hepa-1 cells .", "target_text": { "cytochrome P4501A1": "protein", "CYP1A1": "protein", "CYP1A1 mRNA": "RNA", "cultured human keratinocytes": "cell_line", "HaCaT cell line": "cell_line", "primary human blood lymphocytes": "cell_type", "mouse Hepa-1 cells": "cell_line" } }, { "input_text": "The cells were exposed to UV light delivered by a bank of 6 Philips TL20/12RS sun lamps emitting primarily in the UVB range in the absence and presence of tryptophan .", "target_text": {} }, { "input_text": "A semiquantitative reverse transcriptase -linked polymerase chain reaction ( RT-PCR ) was used for analysis of gene expression in the treated cells .", "target_text": { "reverse transcriptase": "protein", "treated cells": "cell_type" } }, { "input_text": "The results show that the CYP1A1 mRNA level induced by UV in the presence of tryptophan was higher than that induced by UV alone in both HaCaT cells and lymphocytes after 3 h of incubation post- UV irradiation .", "target_text": { "CYP1A1": "protein", "CYP1A1 mRNA": "RNA", "HaCaT cells": "cell_line", "lymphocytes": "cell_type" } }, { "input_text": "To find out if the induction by UV light is caused by the formation of an Ah receptor ligand , Hepa-1 wild-type and Ah receptor deficient c12 cell lines were applied .", "target_text": {} }, { "input_text": "Wild-type ( wt ) cells were inducible either by the tryptophan photoproduct 6-formylindolo [ 3 , 2-b ] carbazole ( FICZ ) or by UV -irradiation but very low or undetectable levels were observed in the c12 cells .", "target_text": { "Wild-type ( wt ) cells": "cell_line", "c12 cells": "cell_type" } }, { "input_text": "This shows that the induction of gene expression by FICZ and UV is Ah receptor dependent .", "target_text": { "Ah receptor": "protein" } }, { "input_text": "Together , these results indicate that UV -induced CYP1A1 gene expression in mammalian cells is mediated by an Ah receptor ligand formed from tryptophan .", "target_text": { "CYP1A1": "protein", "mammalian cells": "cell_type", "Ah receptor": "protein" } }, { "input_text": "Thus , the photoproducts of tryptophan are suggested to be mediators of light via binding to the Ah receptor and as such also could have a role in light-regulated biological rhythms .", "target_text": { "Ah receptor": "protein" } }, { "input_text": "Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes .", "target_text": { "Ikaros": "protein", "Aiolos": "protein", "histone deacetylase complexes": "protein" } }, { "input_text": "Here we show that the lymphoid lineage-determining factors Ikaros and Aiolos can function as strong transcriptional repressors .", "target_text": { "lymphoid lineage-determining factors": "protein", "Ikaros": "protein", "Aiolos": "protein", "strong transcriptional repressors": "protein" } }, { "input_text": "This function is mediated through two repression domains and is dependent upon the promoter context and cell type .", "target_text": { "repression domains": "protein" } }, { "input_text": "Repression by Ikaros proteins correlates with hypo-acetylation of core histones at promoter sites and is relieved by histone deacetylase inhibitors .", "target_text": { "Ikaros": "protein", "Ikaros proteins": "protein", "core histones": "protein", "promoter sites": "DNA", "histone deacetylase": "protein" } }, { "input_text": "Consistent with these findings , Ikaros and its repression domains can interact in vivo and in vitro with the mSin3 family of co-repressors which bind to histone deacetylases .", "target_text": { "Ikaros": "protein", "repression domains": "protein", "mSin3 family": "protein", "histone deacetylases": "protein" } }, { "input_text": "Based on these and our recent findings of associations between Ikaros and Mi-2-HDAC , we propose that Ikaros family members modulate gene expression during lymphocyte development by recruiting distinct histone deacetylase complexes to specific promoters .", "target_text": { "Ikaros": "protein", "Mi-2-HDAC": "protein", "Ikaros family members": "protein", "histone deacetylase": "protein", "histone deacetylase complexes": "protein", "specific promoters": "DNA" } }, { "input_text": "Protein kinase B ( c-Akt ) , phosphatidylinositol 3-kinase , and STAT5 are activated by erythropoietin ( EPO ) in HCD57 erythroid cells but are constitutively active in an EPO -independent , apoptosis -resistant subclone ( HCD57-SREI cells ) .", "target_text": { "Protein kinase B": "protein", "c-Akt": "protein", "phosphatidylinositol 3-kinase": "protein", "STAT5": "protein", "erythropoietin": "protein", "EPO": "protein", "HCD57 erythroid cells": "cell_line", "EPO -independent , apoptosis -resistant subclone": "cell_line", "HCD57-SREI cells": "cell_line" } }, { "input_text": "We found that erythropoietin ( EPO ) and stem cell factor ( SCF ) activated protein kinase B ( PKB/Akt ) in EPO -dependent HCD57 erythroid cells .", "target_text": { "erythropoietin": "protein", "EPO": "protein", "stem cell factor": "protein", "SCF": "protein", "activated protein kinase B": "protein", "PKB/Akt": "protein", "EPO -dependent HCD57 erythroid cells": "cell_line" } }, { "input_text": "To better understand signals controlling proliferation and viability , erythroid cells that resist apoptosis in the absence of EPO were subcloned and characterized ( HCD57-SREI cells ) .", "target_text": { "EPO": "protein", "HCD57-SREI cells": "cell_line" } }, { "input_text": "Constitutive activations of PKB/Akt , STAT5a , and STAT5b were noted in these EPO -independent cells .", "target_text": { "PKB/Akt": "protein", "STAT5a": "protein", "STAT5b": "protein", "EPO": "protein", "EPO -independent cells": "cell_line" } }, { "input_text": "PI3-kinase activity was an upstream activator of PKB/Akt because the PI3-kinase inhibitor LY294002 blocked both constitutive PKB/Akt and factor-dependent PKB/Akt activity .", "target_text": { "PI3-kinase": "protein", "PKB/Akt": "protein" } }, { "input_text": "The LY294002 study showed that proliferation and viability of both HCD57-SREI and HCD57 cells correlated with the activity of PKB/Akt ; however , PKB/Akt activity alone did not protect these cells from apoptosis .", "target_text": { "HCD57-SREI": "cell_line", "HCD57 cells": "cell_line", "PKB/Akt": "protein" } }, { "input_text": "Treatment of HCD57 cells with SCF also activated PKB/Akt , but did not protect from apoptosis .", "target_text": { "HCD57 cells": "cell_line", "SCF": "protein", "PKB/Akt": "protein" } }, { "input_text": "This result suggested that PKB/PI3-kinase activity is necessary but not sufficient to promote viability and/or proliferation .", "target_text": { "PKB/PI3-kinase": "protein" } }, { "input_text": "Constitutive STAT5 activity , activated through an unknown pathway not including JAK2 or EPOR , may act in concert with the constitutive PI3-kinase /PKB/Akt pathway to protect the EPO -independent HCD57-SREI cells from apoptosis and promote limited proliferation .", "target_text": { "STAT5": "protein", "JAK2": "protein", "EPOR": "protein", "PI3-kinase": "protein", "/PKB/Akt": "protein", "EPO": "protein", "HCD57-SREI cells": "cell_line", "EPO -independent HCD57-SREI cells": "cell_line" } }, { "input_text": "Disruption of alpha beta but not of gamma delta T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors .", "target_text": { "helix-loop-helix protein": "protein", "Id3": "protein", "committed T cell progenitors": "cell_type" } }, { "input_text": "Enforced expression of Id3 , which has the capacity to inhibit many basic helix-loop-helix ( bHLH ) transcription factors , in human CD34(+) hematopoietic progenitor cells that have not undergone T cell receptor ( TCR ) gene rearrangements inhibits development of the transduced cells into TCR alpha beta and gamma delta cells in a fetal thymic organ culture ( FTOC ) .", "target_text": { "Id3": "protein", "basic helix-loop-helix ( bHLH ) transcription factors": "protein", "human CD34(+) hematopoietic progenitor cells": "cell_type", "T cell receptor": "protein", "TCR": "protein", "T cell receptor ( TCR ) gene rearrangements": "DNA", "transduced cells": "cell_type", "fetal thymic organ culture": "cell_line", "FTOC": "cell_line" } }, { "input_text": "Here we document that overexpression of Id3 , in progenitors that have initiated TCR gene rearrangements ( pre-T cells ) , inhibits development into TCRalpha beta but not into TCRgamma delta T cells .", "target_text": { "Id3": "protein", "progenitors": "cell_type", "TCR": "protein", "TCR gene rearrangements": "DNA", "pre-T cells": "cell_type", "TCRalpha beta": "cell_line", "TCRgamma delta T cells": "cell_line" } }, { "input_text": "Furthermore , Id3 impedes expression of recombination activating genes and downregulates pre-Talpha mRNA .", "target_text": { "Id3": "protein", "pre-Talpha mRNA": "RNA" } }, { "input_text": "These observations suggest possible mechanisms by which Id3 overexpression can differentially affect development of pre-T cells into TCR alpha beta and gamma delta cells .", "target_text": { "Id3": "protein", "pre-T cells": "cell_type" } }, { "input_text": "We also observed that cell surface CD4(-)CD8(-)CD3(-) cells with rearranged TCR genes developed from Id3 -transduced but not from control-transduced pre-T cells in an FTOC .", "target_text": { "cell surface CD4(-)CD8(-)CD3(-) cells": "cell_type", "rearranged TCR genes": "DNA", "Id3": "protein", "Id3 -transduced": "cell_line", "pre-T cells": "cell_type", "control-transduced pre-T cells": "cell_line", "FTOC": "cell_line" } }, { "input_text": "These cells had properties of both natural killer ( NK ) and pre-T cells .", "target_text": { "natural killer": "cell_type", "NK": "cell_type", "pre-T cells": "cell_type" } }, { "input_text": "These findings suggest that bHLH factors are required to control T cell development after the T/NK developmental checkpoint .", "target_text": { "bHLH factors": "protein" } }, { "input_text": "HIV-1 reactivation in resting peripheral blood mononuclear cells of infected adults upon in vitro CD4 cross-linking by ligands of the CDR2-loop in extracellular domain 1 .", "target_text": { "resting peripheral blood mononuclear cells": "cell_type", "CD4": "protein", "CDR2-loop": "protein", "extracellular domain 1": "protein" } }, { "input_text": "HIV-1 infects resting peripheral blood mononuclear cells ( PBMCs ) but remains inactive state until subsequent cell activation .", "target_text": { "resting peripheral blood mononuclear cells": "cell_type", "PBMCs": "cell_type" } }, { "input_text": "We have demonstrated that the cross-linking of cell surface CD4 by gp120-anti-gp120 immune complexes or heat-inactivated HIV-1 ( iHIV-1 ) is sufficient to trigger activation signals leading to virus reactivation ( 9 ) .", "target_text": { "CD4": "protein", "cell surface CD4": "protein", "gp120-anti-gp120 immune complexes": "protein" } }, { "input_text": "In this study , we demonstrate that NF-kappaB nuclear translocation and stimulation of virus production by iHIV-1 were strictly linked to the concentrations of viral proteins used as exogenous stimuli .", "target_text": { "NF-kappaB": "protein", "viral proteins": "protein" } }, { "input_text": "Moreover , we further investigated the physiologic relevance of these observations .", "target_text": {} }, { "input_text": "When submitted to an in vitro CD4 cross-linking by iHIV-1 , PBMCs from HIV-1 -infected patients were found to produce virus .", "target_text": { "CD4": "protein", "PBMCs": "cell_type" } }, { "input_text": "This viral reactivation was associated with increased NF-kappaB nuclear translocation in patients ' PBMCs .", "target_text": { "NF-kappaB": "protein", "PBMCs": "cell_type" } }, { "input_text": "Additionally , virus reactivation in resting PBMCs infected in vitro with HIV-1 was found to be specifically induced by ligands of the CDR2-loop in domain 1 ( D1 ) of CD4 ( virus envelope and anti- CD4 monoclonal antibodies ) .", "target_text": { "PBMCs": "cell_type", "resting PBMCs": "cell_type", "CDR2-loop": "protein", "domain 1": "protein", "D1": "protein", "CD4": "protein", "virus envelope and anti- CD4 monoclonal antibodies": "protein" } }, { "input_text": "In contrast , virus reactivation was not observed following CD4 oligomerization by antibodies that bind other epitopes in D1 , including the D1/CDR3-loop .", "target_text": { "CD4": "protein", "antibodies": "protein", "D1": "protein", "D1/CDR3-loop": "protein" } }, { "input_text": "Finally , soluble CD4 ( sCD4 ) prevented virus reactivation by D1/CDR2-loop ligands .", "target_text": { "CD4": "protein", "soluble CD4": "protein", "sCD4": "protein", "D1/CDR2-loop ligands": "protein" } }, { "input_text": "Our results indicate that the signaling events initiated in PBMCs by oligomerization of CD4 at the D1/ CDR2-loop can trigger HIV-1 upregulation in infected individuals .", "target_text": { "PBMCs": "cell_type", "CD4": "protein", "CDR2-loop": "protein", "D1/ CDR2-loop": "protein" } }, { "input_text": "Signaling through the lymphotoxin-beta receptor stimulates HIV-1 replication alone and in cooperation with soluble or membrane-bound TNF-alpha .", "target_text": { "lymphotoxin-beta receptor": "protein", "membrane-bound TNF-alpha": "protein" } }, { "input_text": "The level of ongoing HIV-1 replication within an individual is critical to HIV-1 pathogenesis .", "target_text": {} }, { "input_text": "Among host immune factors , the cytokine TNF-alpha has previously been shown to increase HIV-1 replication in various monocyte and T cell model systems .", "target_text": { "cytokine": "protein", "TNF-alpha": "protein" } }, { "input_text": "Here , we demonstrate that signaling through the TNF receptor family member , the lymphotoxin-beta ( LT-beta ) receptor ( LT-betaR ) , also regulates HIV-1 replication .", "target_text": { "TNF": "protein", "lymphotoxin-beta ( LT-beta ) receptor": "protein", "LT-betaR": "protein" } }, { "input_text": "Furthermore , HIV-1 replication is cooperatively stimulated when the distinct LT-betaR and TNF receptor systems are simultaneously engaged by their specific ligands .", "target_text": { "LT-betaR": "protein", "TNF receptor systems": "protein" } }, { "input_text": "Moreover , in a physiological coculture cellular assay system , we show that membrane-bound TNF-alpha and LT-alpha1beta2 act virtually identically to their soluble forms in the regulation of HIV-1 replication .", "target_text": { "membrane-bound TNF-alpha": "protein", "LT-alpha1beta2": "protein" } }, { "input_text": "Thus , cosignaling via the LT-beta and TNF-alpha receptors is probably involved in the modulation of HIV-1 replication and the subsequent determination of HIV-1 viral burden in monocytes .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "Intriguingly , surface expression of LT-alpha1beta2 is up- regulated on a T cell line acutely infected with HIV-1 , suggesting a positive feedback loop between HIV-1 infection , LT-alpha1beta2 expression , and HIV-1 replication .", "target_text": { "LT-alpha1beta2": "protein", "T cell line": "cell_line" } }, { "input_text": "Given the critical role that LT-alpha1beta2 plays in lymphoid architecture , we speculate that LT-alpha1beta2 may be involved in HIV -associated abnormalities of the lymphoid organs .", "target_text": { "LT-alpha1beta2": "protein" } }, { "input_text": "Monoclonal anti-endothelial cell antibodies from a patient with Takayasu arteritis activate endothelial cells from large vessels .", "target_text": { "Monoclonal anti-endothelial cell antibodies": "protein" } }, { "input_text": "OBJECTIVE : To create monoclonal anti-endothelial cell antibodies ( mAECA ) from a patient with Takayasu arteritis to evaluate their ability to activate human umbilical vein endothelial cells ( HUVEC ) , and to characterize the mechanism of EC activation .", "target_text": { "monoclonal anti-endothelial cell antibodies": "protein", "mAECA": "protein", "human umbilical vein endothelial cells": "cell_line", "HUVEC": "cell_line" } }, { "input_text": "METHODS : A panel of mAECA was generated from peripheral blood lymphocytes of a patient with Takayasu arteritis , using Epstein-Barr virus transformation .", "target_text": { "mAECA": "protein", "peripheral blood lymphocytes": "cell_type" } }, { "input_text": "Activity against macrovascular EC ( HUVEC ) and microvascular EC ( human bone marrow EC immortalized by SV40 ) antigens was detected by enzyme-linked immunosorbent assay .", "target_text": { "macrovascular EC": "cell_line", "HUVEC": "cell_line", "microvascular EC": "cell_line", "human bone marrow EC immortalized by SV40": "cell_line" } }, { "input_text": "Inhibition studies were used to select the monoclonal antibodies ( mAECA ) which share the same EC epitope binding specificity as the total IgG-AECA from the Takayasu arteritis patient .", "target_text": { "monoclonal antibodies": "protein", "mAECA": "protein", "total IgG-AECA": "protein" } }, { "input_text": "The binding of the mAECA to human aortic EC was studied by immunohistochemistry .", "target_text": { "mAECA": "protein", "human aortic EC": "cell_type" } }, { "input_text": "The secretion levels of interleukin-6 ( IL-6 ) and von Willebrand factor ( vWF ) were determined , to serve as markers for EC activation .", "target_text": { "interleukin-6": "protein", "IL-6": "protein" } }, { "input_text": "The activated EC were examined for the adherence of a monocytic cell line ( U937 ) , as well as for expression of vascular cell adhesion molecule 1 , intercellular adhesion molecule 1 , and E-selectin .", "target_text": { "activated EC": "cell_line", "monocytic cell line": "cell_line", "U937": "cell_line", "vascular cell adhesion molecule 1": "protein", "intercellular adhesion molecule 1": "protein", "E-selectin": "protein" } }, { "input_text": "In addition , nuclear extracts of the mAECA -treated EC were analyzed for the induction of translocation of nuclear factor kappaB ( NF-kappaB ) , using a specific NF-kappaB oligoprobe in an electrophoretic mobility shift assay .", "target_text": { "mAECA": "protein", "mAECA -treated EC": "cell_line", "nuclear factor kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "RESULTS : Six mAECA were selected , the mixture of which produced 100 % inhibition of binding of the original IgG ( from the patient with Takayasu arteritis ) to HUVEC .", "target_text": { "mAECA": "protein", "IgG": "protein", "HUVEC": "cell_line" } }, { "input_text": "All mAECA possessed high activity against macrovascular EC , but none had significant antimicrovascular EC activity .", "target_text": { "mAECA": "protein", "macrovascular EC": "cell_line" } }, { "input_text": "The mAECA , but not normal human IgG , had anti-human aortic EC activity .", "target_text": { "mAECA": "protein", "IgG": "protein", "normal human IgG": "protein" } }, { "input_text": "Four of the 6 mAECA activated EC , manifested by increased IL-6 and vWF secretion .", "target_text": { "mAECA": "protein", "activated EC": "cell_line", "IL-6": "protein" } }, { "input_text": "The 4 mAECA induced EC expression of adhesion molecules and increased adhesion of U937 monocytic cells to EC .", "target_text": { "mAECA": "protein", "adhesion molecules": "protein", "U937": "cell_line", "U937 monocytic cells": "cell_type", "EC": "cell_type" } }, { "input_text": "In addition , these mAECA stimulated the nuclear translocation of the NF-kappaB transcription factor .", "target_text": { "mAECA": "protein", "NF-kappaB": "protein", "NF-kappaB transcription factor": "protein" } }, { "input_text": "CONCLUSION : Our findings suggest that AECA may directly stimulate EC in Takayasu arteritis through elevation of adhesion molecule expression associated with NF-kappaB activation and adhesion of monocytes , and may therefore play a pathogenic role in the development of the vasculopathy in Takayasu arteritis .", "target_text": { "AECA": "protein", "EC": "cell_type", "adhesion molecule": "protein", "NF-kappaB": "protein", "monocytes": "cell_type" } }, { "input_text": "Cutting edge : expression of the NF of activated T cells in eosinophils : regulation by IL-4 and IL-5 .", "target_text": { "NF of activated T cells": "protein", "eosinophils": "cell_type", "IL-4": "protein", "IL-5": "protein" } }, { "input_text": "We report that NF-AT1 and NF-AT4 are expressed cytoplasmically in resting eosinophils , whereas NF-AT2 and NF-AT3 have not been seen .", "target_text": { "NF-AT1": "protein", "NF-AT4": "protein", "eosinophils": "cell_type", "resting eosinophils": "cell_type", "NF-AT2": "protein", "NF-AT3": "protein" } }, { "input_text": "Likewise , NF-AT1 mRNA and NF-AT4 mRNA have been detected in resting eosinophils , and their levels can be significantly up-regulated by the Th2-associated cytokines IL-4 and IL-5 .", "target_text": { "NF-AT1": "protein", "NF-AT1 mRNA": "RNA", "NF-AT4": "protein", "NF-AT4 mRNA": "RNA", "eosinophils": "cell_type", "resting eosinophils": "cell_type", "Th2-associated cytokines": "protein", "IL-4": "protein", "IL-5": "protein" } }, { "input_text": "There is no detectable NF-AT protein expression in the nuclei of resting eosinophils .", "target_text": { "NF-AT": "protein", "eosinophils": "cell_type", "resting eosinophils": "cell_type" } }, { "input_text": "However NF-ATs appear in the nuclei of IL-4- , IL-5- , or ionomycin- stimulated eosinophils .", "target_text": { "NF-ATs": "protein" } }, { "input_text": "Only NF-AT1 and NF-AT4 , but not NF-AT2 and NF-AT3 , have translocated into the nuclei in IL-4- or IL-5- stimulated eosinophils .", "target_text": { "NF-AT1": "protein", "NF-AT4": "protein", "NF-AT2": "protein", "NF-AT3": "protein" } }, { "input_text": "These findings delineate a novel pathway in the cytokine network in which Th2 lymphocytes \" control \" eosinophils via the release of IL-4 and IL-5 , and activation of NF-AT in eosinophils .", "target_text": { "Th2 lymphocytes": "cell_line", "eosinophils": "cell_type", "IL-4": "protein", "IL-5": "protein", "NF-AT": "protein" } }, { "input_text": "The findings also suggest that a later feedback \" talking \" may exist between eosinophils and Th2 lymphocytes .", "target_text": { "eosinophils": "cell_type", "Th2 lymphocytes": "cell_line" } }, { "input_text": "PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells .", "target_text": { "vascular cell adhesion molecule-1": "protein", "human endothelial cells": "cell_type" } }, { "input_text": "BACKGROUND : Adhesion molecule expression on the endothelial cell ( EC ) surface is critical for leukocyte recruitment to atherosclerotic lesions .", "target_text": {} }, { "input_text": "Better understanding of transcriptional regulation of adhesion molecules in ECs may provide important insight into plaque formation .", "target_text": { "adhesion molecules": "protein", "ECs": "cell_type" } }, { "input_text": "Peroxisome proliferator-activated receptor-alpha ( PPARalpha ) , a member of the nuclear receptor family , regulates gene expression in response to certain fatty acids and fibric acid derivatives .", "target_text": { "Peroxisome": "cell_type", "Peroxisome proliferator-activated receptor-alpha": "protein", "PPARalpha": "protein", "nuclear receptor family": "protein" } }, { "input_text": "The present study investigated PPARalpha expression in human ECs and their regulation of vascular cell adhesion molecule-1 ( VCAM-1 ) .", "target_text": { "PPARalpha": "protein", "ECs": "cell_type", "human ECs": "cell_type", "vascular cell adhesion molecule-1": "protein", "VCAM-1": "protein" } }, { "input_text": "METHODS AND RESULTS : Immunohistochemistry revealed that human carotid artery ECs express PPARalpha .", "target_text": { "ECs": "cell_type", "human carotid artery ECs": "cell_type", "PPARalpha": "protein" } }, { "input_text": "Pretreatment of cultured human ECs with the PPARalpha activators fenofibrate or WY14643 inhibited TNF-alpha-induced VCAM-1 in a time- and concentration-dependent manner , an effect not seen with PPARgamma activators .", "target_text": { "ECs": "cell_type", "cultured human ECs": "cell_type", "PPARalpha": "protein", "VCAM-1": "protein", "TNF-alpha-induced VCAM-1": "protein", "PPARgamma": "protein" } }, { "input_text": "Both PPARalpha activators decreased cytokine-induced VCAM-1 mRNA expression without altering its mRNA half-life .", "target_text": { "PPARalpha": "protein", "VCAM-1": "protein" } }, { "input_text": "Transient transfection of deletional VCAM-1 promoter constructs and electrophoretic mobility shift assays suggest that fenofibrate inhibits VCAM-1 transcription in part by inhibiting NF-kappaB .", "target_text": { "VCAM-1": "protein", "VCAM-1 promoter constructs": "DNA", "NF-kappaB": "protein" } }, { "input_text": "Finally , PPARalpha activators significantly reduced adhesion of U937 cells to cultured human ECs .", "target_text": { "PPARalpha": "protein", "U937 cells": "cell_line", "cultured human ECs": "cell_type" } }, { "input_text": "CONCLUSIONS : Human ECs express PPARalpha , a potentially important regulator of atherogenesis through its transcriptional control of VCAM-1 gene expression .", "target_text": { "Human ECs": "cell_type", "PPARalpha": "protein", "VCAM-1": "protein" } }, { "input_text": "Such findings also have implications regarding the clinical use of lipid-lowering agents , like fibric acids , which can activate PPARalpha .", "target_text": { "PPARalpha": "protein" } }, { "input_text": "CBP/p300 integrates Raf / Rac -signaling pathways in the transcriptional induction of NF-ATc during T cell activation .", "target_text": { "CBP/p300": "protein", "Raf": "protein", "Rac": "protein", "NF-ATc": "protein" } }, { "input_text": "NF-ATc , an inducibly expressed transcription factor , controls gene expression in T lymphocytes and cardiomyocytes .", "target_text": { "NF-ATc": "protein", "transcription factor": "protein", "T lymphocytes": "cell_type", "cardiomyocytes": "cell_type" } }, { "input_text": "We show here that the transcriptional co-activators CBP/p300 bind to and control the activity of the inducible N-terminal transactivation domain of NF-ATc , TAD-A .", "target_text": { "transcriptional co-activators": "protein", "CBP/p300": "protein", "inducible N-terminal transactivation domain": "protein", "NF-ATc": "protein", "TAD-A": "protein" } }, { "input_text": "Similar to the N terminal transactivation domain of c-Jun , TAD-A is inducibly phosphorylated , but this phosphorylation is dispensable for the interaction with CBP/p300 .", "target_text": { "N terminal transactivation domain": "protein", "c-Jun": "protein", "TAD-A": "protein", "CBP/p300": "protein" } }, { "input_text": "Constitutive active versions of c-Raf and Rac synergistically enhance the CBP/p300 -mediated increase of TAD-A activity , indicating the important role CBP/p300 plays in the integration of T cell activation signals .", "target_text": { "c-Raf": "protein", "Rac": "protein", "CBP/p300": "protein", "TAD-A": "protein" } }, { "input_text": "Since a mutation of CBP abolishing HAT activity is almost as active as wild-type CBP in T cells , functions of CBP/p300 other than histone acetylation appear to control the NF-AT -dependent transcription in T cells .", "target_text": { "CBP": "protein", "wild-type CBP": "protein", "T cells": "cell_type", "CBP/p300": "protein", "NF-AT": "protein" } }, { "input_text": "Immune functions , clinical parameters and hormone receptor status in breast cancer patients .", "target_text": {} }, { "input_text": "We have carried out a detailed analysis of the cellular immune functions of breast cancer patients in comparison with healthy controls .", "target_text": {} }, { "input_text": "A possible correlation between immune and clinical parameters was analysed in 50 breast cancer patients .", "target_text": {} }, { "input_text": "Immune parameters , natural killer cell and T lymphocyte functions and the numbers of circulating T lymphocytes were analysed against the clinical parameters comprising the tumour burden , the stage of the disease and the expression of hormone receptors on the tumour .", "target_text": { "natural killer cell": "cell_type", "circulating T lymphocytes": "cell_type", "hormone receptors": "protein" } }, { "input_text": "In order to analyse the immune function data effectively , low responders were identified with stringent cut-off values .", "target_text": {} }, { "input_text": "Considerably higher proportions of low responders were found among the patient population .", "target_text": {} }, { "input_text": "Elevated numbers of circulating T lymphocytes and CD3 -directed cytolysis correlated with the expression of oestrogen receptors independently of the clinical/histological parameters .", "target_text": { "circulating T lymphocytes": "cell_type", "CD3": "protein", "oestrogen receptors": "protein" } }, { "input_text": "Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and activates STAT proteins .", "target_text": { "Latent membrane protein 1": "protein", "JAK3": "protein", "STAT proteins": "protein" } }, { "input_text": "Latent membrane protein 1 ( LMP1 ) acts like a permanently activated receptor of the tumor necrosis factor ( TNF ) -receptor superfamily and is absolutely required for B cell immortalization by Epstein-Barr virus .", "target_text": { "Latent membrane protein 1": "protein", "LMP1": "protein", "permanently activated receptor": "protein", "tumor necrosis factor ( TNF ) -receptor superfamily": "protein" } }, { "input_text": "Molecular and biochemical approaches demonstrated that LMP1 usurps cellular signaling pathways resulting in the induction of NF-kappaB and AP-1 via two C-terminal activating regions .", "target_text": { "LMP1": "protein", "NF-kappaB": "protein", "AP-1": "protein", "C-terminal activating regions": "protein" } }, { "input_text": "We demonstrate here that a third region encompassing a proline rich sequence within the 33 bp repetitive stretch of LMP1 's C-terminus is required for the activation of Janus kinase 3 ( JAK3 ) .", "target_text": { "proline rich sequence": "protein", "LMP1": "protein", "C-terminus": "protein", "Janus kinase 3": "protein", "JAK3": "protein" } }, { "input_text": "The interaction of LMP1 and JAK3 leads to the enhanced tyrosine auto/transphosphorylation of JAK3 within minutes after crosslinking of a conditional NGF-R : LMP1 chimera and is a prerequisite for the activation of STAT transcription factors .", "target_text": { "LMP1": "protein", "JAK3": "protein", "NGF-R": "protein", "NGF-R : LMP1 chimera": "protein", "STAT transcription factors": "protein" } }, { "input_text": "These results reveal a novel activating region in the LMP1 C-terminus and identify the JAK /STAT pathway as a target of this viral integral membrane protein in B cells .", "target_text": { "LMP1": "protein", "C-terminus": "protein", "JAK": "protein", "/STAT": "protein", "viral integral membrane protein": "protein", "B cells": "cell_type" } }, { "input_text": "Monocyte arrest and transmigration on inflamed endothelium in shear flow is inhibited by adenovirus-mediated gene transfer of IkappaB-alpha .", "target_text": { "IkappaB-alpha": "protein" } }, { "input_text": "Mobilization of nuclear factor-kappaB ( NF-kappaB ) activates transcription of genes encoding endothelial adhesion molecules and chemokines that contribute to monocyte infiltration critical in atherogenesis .", "target_text": { "nuclear factor-kappaB": "protein", "NF-kappaB": "protein", "adhesion molecules": "protein", "endothelial adhesion molecules": "protein" } }, { "input_text": "Inhibition of NF-kappaB has been achieved by pharmacological and genetic approaches ; however , monocyte interactions with activated endothelium in shear flow following gene transfer of the NF-kappaB inhibitor IkappaB-alpha have not been studied .", "target_text": { "NF-kappaB": "protein", "IkappaB-alpha": "protein" } }, { "input_text": "We found that overexpression of IkappaB-alpha in endothelial cells using a recombinant adenovirus prevented tumor necrosis factor-alpha ( TNF-alpha ) -induced degradation of IkappaB-alpha and suppressed the upregulation of vascular cell adhesion molecule-1 ( VCAM-1 ) , intercellular adhesion molecule-1 ( ICAM-1 ) , and E-selectin mRNA and surface protein expression and the upregulation of transcripts for the chemokines monocyte chemoattractant protein 1 ( MCP-1 ) and growth-related activity-alpha ( GRO-alpha ) by TNF-alpha .", "target_text": { "IkappaB-alpha": "protein", "endothelial cells": "cell_type", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "vascular cell adhesion molecule-1": "protein", "VCAM-1": "protein", "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "E-selectin": "protein", "E-selectin mRNA": "RNA", "chemokines": "protein", "monocyte chemoattractant protein 1": "protein", "MCP-1": "protein", "growth-related activity-alpha": "protein", "GRO-alpha": "protein" } }, { "input_text": "This was associated with a reduction in endothelial MCP-1 secretion and GRO-alpha immobilization .", "target_text": { "MCP-1": "protein", "GRO-alpha": "protein" } }, { "input_text": "Adhesion assays under physiological shear flow conditions showed that firm arrest , spreading , and transmigration of monocytes on TNF-alpha -activated endothelium was markedly inhibited by IkappaB-alpha overexpression .", "target_text": { "monocytes": "cell_type", "TNF-alpha": "protein", "IkappaB-alpha": "protein" } }, { "input_text": "Inhibition with monoclonal antibodies and peptide antagonists inferred that this was due to reduced expression of Ig integrin ligand as well as of chemokines specifically involved in these events .", "target_text": { "monoclonal antibodies": "protein", "chemokines": "protein" } }, { "input_text": "In contrast , rolling of monocytes was increased by IkappaB-alpha transfer and was partly mediated by P-selectin ; however , it appeared to be unaffected by the inhibition of E-selectin induction .", "target_text": { "monocytes": "cell_type", "IkappaB-alpha": "protein", "P-selectin": "protein", "E-selectin": "protein" } }, { "input_text": "Thus , our data provide novel evidence that selective modulation of NF-kappaB by adenoviral transfer of IkappaB-alpha impairs the expression of multiple endothelial gene products required for subsequent monocyte arrest and emigration in shear flow and thus for monocyte infiltration in atherosclerotic plaques .", "target_text": { "NF-kappaB": "protein", "IkappaB-alpha": "protein", "endothelial gene products": "protein" } }, { "input_text": "Recognition of NFATp/AP-1 composite elements within genes induced upon the activation of immune cells .", "target_text": { "NFATp/AP-1 composite elements": "DNA", "immune cells": "cell_type" } }, { "input_text": "Composite elements are regulatory modules of promoters or enhancers that consist of binding sites of two different but synergizing transcription factors .", "target_text": { "Composite elements": "DNA", "regulatory modules": "DNA", "promoters": "DNA", "enhancers": "DNA", "transcription factors": "protein" } }, { "input_text": "A well-studied example is nuclear factors of activated T-cell ( NFAT ) sites which are composite elements of a NFATp/c and an activating protein 1 ( AP-1 ) binding site .", "target_text": { "nuclear factors of activated T-cell ( NFAT ) sites": "DNA" } }, { "input_text": "We have developed a computational approach to identify potential NFAT target genes which ( a ) comprises an improved method to scan for individual NFAT composite elements ; ( b ) considers positional effects relative to transcription start sites ; and ( c ) involves cluster analysis of potential NFAT composite elements .", "target_text": { "NFAT target genes": "DNA", "NFAT composite elements": "DNA", "transcription start sites": "DNA" } }, { "input_text": "All three steps progressively helpX?ed to discriminate T-cell-specific promoter sequences against other functional regions ( coding and intronic sequences ) of the same genes , against promoters of muscle-specific genes or against random sequences .", "target_text": { "T-cell-specific promoter sequences": "DNA", "functional regions": "DNA", "promoters": "DNA", "muscle-specific genes": "DNA", "random sequences": "DNA" } }, { "input_text": "Using this approach , we identified potential NFAT composite elements in promoters of cytokine genes and their receptors as well as in promoters of genes for AP-1 family members , Ca2+-binding proteins and some other components of the regulatory network operating in activated T-cells and other immune cells .", "target_text": { "NFAT composite elements": "DNA", "promoters": "DNA", "cytokine genes": "DNA", "AP-1": "protein", "AP-1 family members": "protein", "Ca2+-binding proteins": "protein", "activated T-cells": "cell_type", "immune cells": "cell_type" } }, { "input_text": "The method developed can be adapted to characterize and identify other composite elements as well .", "target_text": { "composite elements": "DNA" } }, { "input_text": "The program for recognition NFAT composite elements is available through the World Wide Web ( http://compel.bionet.nsc.ru/FunSite/CompelScan.html and http://transfac.gbf.de/dbsearch/funsitep/s_comp.html ) .", "target_text": { "composite elements": "DNA", "NFAT composite elements": "DNA" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "The oestrogen receptor codon 10 polymorphism detected in breast cancer is also present in non-malignant cells .", "target_text": { "oestrogen receptor": "protein", "codon 10": "DNA", "non-malignant cells": "cell_type" } }, { "input_text": "The effect of oestrogens on oestrogen -receptive organs and cells is mediated via intracellular receptors ( ERalpha and ERbeta ) .", "target_text": { "intracellular receptors": "protein", "ERalpha": "protein", "ERbeta": "protein" } }, { "input_text": "Oestrogen receptor gene polymorphisms in the region encoding the N-terminal portion of the protein are reportedly associated with pathological conditions including breast cancer , hypertension , spontaneous abortion and coronary heart disease .", "target_text": { "Oestrogen receptor": "protein", "N-terminal portion": "protein" } }, { "input_text": "A silent mutation in codon 10 of exon 1 , detected in ER-negative and ER-positive human breast cancer cell lines , in breast tumors and blood DNA from breast cancer patients , has been recognized as a polymorphic site .", "target_text": { "codon 10": "DNA", "exon 1": "DNA", "blood DNA": "DNA", "polymorphic site": "DNA" } }, { "input_text": "In this study we examined , by denaturing gradient-gel electrophoresis and DNA sequence analysis , the possible presence of a codon 10 polymorphic site in normal oestrogen target organs and cells such as the uterus ( myometrium and endometrium ) , in the placenta and peripheral blood mononuclear cells and in a benign uterus tumour ( leiomyoma ) .", "target_text": { "DNA sequence": "DNA", "codon 10": "DNA", "codon 10 polymorphic site": "DNA", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "We have detected ER codon 10 polymorphism in these samples and have compared them to those observed in breast cancer samples .", "target_text": { "ER codon 10": "DNA" } }, { "input_text": "All tissues and cells studied were homozygous for the wild-type gene , and were heterozygous as well as homozygous for the codon-10-variant type .", "target_text": { "wild-type gene": "DNA", "codon-10-variant type": "DNA" } }, { "input_text": "These results indicate that the presence of the codon-10-variant type is not a characteristic of breast cancer .", "target_text": { "codon-10-variant type": "DNA" } }, { "input_text": "Out current findings suggest that further investigations are warranted to elucidate the possible linkage of ER codon 10 polymorphism to physiological and pathological conditions .", "target_text": { "ER codon 10": "DNA" } }, { "input_text": "USF/c-Myc enhances , while Yin-Yang 1 suppresses , the promoter activity of CXCR4 , a coreceptor for HIV-1 entry .", "target_text": { "USF/c-Myc": "protein", "Yin-Yang 1": "protein", "CXCR4": "protein", "coreceptor": "protein" } }, { "input_text": "Transcription factors USF1 and USF2 up-regulate gene expression ( i.e. , HIV-1 long terminal repeats ) via interaction with an E box on their target promoters , which is also a binding site for c-Myc .", "target_text": { "Transcription factors": "protein", "USF1": "protein", "USF2": "protein", "HIV-1 long terminal repeats": "DNA", "E box": "DNA", "binding site": "DNA", "c-Myc": "protein" } }, { "input_text": "The c-Myc oncoprotein is important in control of cellular proliferation and differentiation , while Yin-Yang 1 ( YY1 ) has been shown to control the expression of a number of cellular and viral genes .", "target_text": { "c-Myc": "protein", "c-Myc oncoprotein": "protein", "Yin-Yang 1": "protein", "YY1": "protein" } }, { "input_text": "These two proteins physically interact with each other and mutually inhibit their respective biological functions .", "target_text": {} }, { "input_text": "In this study , we show that USF/ c-Myc up-regulates , while YY1 down-regulates the promoter activity of CXCR4 , a coreceptor for T cell-tropic HIV-1 entry .", "target_text": { "c-Myc": "protein", "USF/ c-Myc": "protein", "YY1": "protein", "CXCR4": "protein" } }, { "input_text": "We have identified an E box around -260 and a YY1 binding site around -300 relative to the transcription start site .", "target_text": { "E box": "DNA", "-260": "DNA", "YY1": "protein", "YY1 binding site": "DNA", "-300": "DNA", "transcription start site": "DNA" } }, { "input_text": "Mutation of the E box abolished USF/c-Myc - mediated up-regulation of CXCR4 promoter activity , and mutation of the YY1 binding site was associated with unresponsiveness to YY1 -mediated inhibition .", "target_text": { "E box": "DNA", "USF/c-Myc": "protein", "CXCR4": "protein", "YY1": "protein", "YY1 binding site": "DNA" } }, { "input_text": "These data suggest that USF/c-Myc and YY1 may play an important role in the HIV-1 -replicative cycle , by modulating both the viral fusion/entry process and viral expression .", "target_text": { "USF/c-Myc": "protein", "YY1": "protein" } }, { "input_text": "Suppression of NF-kappaB activation in normal T cells by supernatant fluid from human renal cell carcinomas .", "target_text": { "NF-kappaB": "protein", "normal T cells": "cell_type" } }, { "input_text": "T lymphocytes from patients with renal cell carcinoma ( RCC ) show reduced immune function and impaired activation of the transcription factor , NF-kappaB .", "target_text": { "T lymphocytes": "cell_type", "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "We determined the mechanism of NF-kappaB suppression in T cells of RCC patient and determined whether supernatant fluid from RCC explants ( RCC -S ) induced the same phenotype of NF-kappaB suppression in normal T cells that is observed in patient T cells .", "target_text": { "NF-kappaB": "protein", "T cells": "cell_type", "normal T cells": "cell_type" } }, { "input_text": "The pattern of kappaB -binding activity in T cells of RCC patient was altered as compared to that seen in T cells obtained from normal volunteers .", "target_text": { "kappaB": "protein", "T cells": "cell_type" } }, { "input_text": "In some patients , no activation of RelA/NFkappaB1 -binding activity was detectable , while in others kappaB -binding activity was modestly induced but the duration was reduced .", "target_text": { "RelA/NFkappaB1": "protein", "kappaB": "protein" } }, { "input_text": "IkappaBalpha was degraded normally following stimulation in both normal controls and T cells from RCC patients .", "target_text": { "IkappaBalpha": "protein", "T cells": "cell_type" } }, { "input_text": "RCC -S did not alter the cytoplasmic levels of RelA and NF-kappaB1 but did suppress their nuclear localization and inhibited the activation of RelA /NF-kappaB1 binding complexes .", "target_text": { "RelA": "protein", "NF-kappaB1": "protein", "/NF-kappaB1": "protein", "RelA /NF-kappaB1 binding complexes": "protein" } }, { "input_text": "These results show that RCC -S can induce in normal T cells the same phenotype of impaired NF-kappaB activation that is detected in T cells of RCC patient .", "target_text": { "T cells": "cell_type", "normal T cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "It also appears that NF-kappaB suppression by RCC -S may contribute to the immunosuppression of host immunity .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "STAT1 activation during monocyte to macrophage maturation : role of adhesion molecules .", "target_text": { "STAT1": "protein", "adhesion molecules": "protein" } }, { "input_text": "Human monocytes isolated from peripheral blood of healthy donors show a time-dependent differentiation into macrophages upon in vitro cultivation , closely mimicking their in vivo migration and maturation into extravascular tissues .", "target_text": { "Human monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "The mediator ( s ) of this maturation process has not been yet defined .", "target_text": {} }, { "input_text": "We investigated the involvement of signal transducers and activators of transcription ( STAT ) factors in this phenomenon and reported the specific , time-dependent , activation of STAT1 protein starting at day 0/1 of cultivation and maximally expressed at day 5 .", "target_text": { "signal transducers and activators of transcription ( STAT ) factors": "protein", "STAT1": "protein" } }, { "input_text": "STAT1 activity was evident on the STAT binding sequences ( SBE ) present in the promoters of genes which are up-regulated during monocyte to macrophage maturation such as FcgammaRI and ICAM-1 , and in the promoter of the transcription factor IFN regulatory factor-1 .", "target_text": { "STAT1": "protein", "STAT binding sequences": "DNA", "SBE": "DNA", "promoters": "DNA", "FcgammaRI": "DNA", "ICAM-1": "DNA", "transcription factor": "protein", "transcription factor IFN regulatory factor-1": "DNA" } }, { "input_text": "Moreover , the effect of cell adhesion to fibronectin or laminin was studied to investigate mechanisms involved in STAT1 activation .", "target_text": { "STAT1": "protein" } }, { "input_text": "Compared with monocytes adherent on plastic surfaces , freshly isolated cells allowed to adhere either to fibronectin- or laminin- coated flasks exhibited an increased STAT1 binding activity both in control and in IFN-gamma-treated cells .", "target_text": { "monocytes": "cell_type", "STAT1": "protein", "IFN-gamma-treated cells": "cell_line" } }, { "input_text": "The molecular events leading to enhanced STAT1 activation and cytokine responsiveness concerned both Y701 and S727 STAT1 phosphorylation .", "target_text": { "STAT1": "protein", "cytokine": "protein", "Y701": "protein", "S727 STAT1": "protein" } }, { "input_text": "Exogenous addition of transforming growth factor-beta , which exerts an inhibitory effect on some monocytic differentiation markers , inhibited macrophage maturation , integrin expression and STAT1 binding activity .", "target_text": { "transforming growth factor-beta": "protein", "monocytic differentiation markers": "protein", "STAT1": "protein" } }, { "input_text": "Taken together these results indicate that STAT1 plays a pivotal role in the differentiation/maturation process of monocytes as an early transcription factor initially activated by adherence and then able to modulate the expression of functional genes , such as ICAM-1 and FcgammaRI .", "target_text": { "STAT1": "protein", "monocytes": "cell_type", "transcription factor": "protein", "functional genes": "DNA", "ICAM-1": "protein", "FcgammaRI": "protein" } }, { "input_text": "Expression and role of PML gene in normal adult hematopoiesis : functional interaction between PML and Rb proteins in erythropoiesis .", "target_text": { "PML gene": "DNA" } }, { "input_text": "The expression of the PML gene was investigated in purified early hematopoietic progenitor cells ( HPCs ) induced to unilineage erythroid or granulocytic differentiation .", "target_text": { "PML gene": "DNA", "hematopoietic progenitor cells": "cell_type", "HPCs": "cell_type" } }, { "input_text": "PML mRNA and protein , while barely detectable in quiescent HPCs , are consistently induced by growth factor stimulation through the erythroid or granulocytic lineage .", "target_text": { "PML mRNA": "RNA", "protein": "protein", "HPCs": "cell_type", "growth factor": "protein" } }, { "input_text": "Thereafter , PML is downmodulated in late granulocytic maturation , whereas it is sustainably expressed through the erythroid pathway .", "target_text": { "PML": "protein" } }, { "input_text": "In functional studies , PML expression was inhibited by addition of antisense oligomers targeting PML mRNA ( alpha-PML ) .", "target_text": { "PML": "protein", "PML mRNA": "RNA", "alpha-PML": "protein" } }, { "input_text": "Interestingly , early treatment ( day 0 HPCs ) with alpha-PML reduced the number of both erythroid and granulocytic colonies , whereas late treatment ( day 5 culture ) reduced erythroid , but not granulocytic , clonogenesis .", "target_text": { "HPCs": "cell_type", "alpha-PML": "protein" } }, { "input_text": "These findings suggest that PML is required for early hematopoiesis and erythroid , but not granulocytic maturation .", "target_text": { "PML": "protein" } }, { "input_text": "The pattern of PML expression in normal hematopoiesis mimics that of retinoblastoma pRb 105 .", "target_text": { "PML": "protein", "retinoblastoma": "cell_type", "pRb 105": "protein" } }, { "input_text": "Combined treatment of HPCs with alpha-PML and alpha-Rb oligomers inhibited both PML and Rb protein expression and completely blocked erythroid colony development .", "target_text": { "HPCs": "cell_type", "alpha-PML": "protein" } }, { "input_text": "Furthermore , PML and pRb 105 were co-immunoprecipitated in cellular lysates derived from erythroid precursors indicating that this functional interaction may have a biochemical basis .", "target_text": { "PML": "protein", "pRb 105": "protein", "erythroid precursors": "cell_type" } }, { "input_text": "These results suggest a key functional role of PML in early hematopoiesis and late erythropoiesis : the latter phenomenon may be related to the molecular and functional interaction of PML with pRb 105 .", "target_text": { "PML": "protein", "pRb 105": "protein" } }, { "input_text": "Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis .", "target_text": { "glucocorticoid receptor": "protein", "peripheral blood lymphocytes": "cell_type" } }, { "input_text": "Although the exact etiology of multiple sclerosis ( MS ) remains unresolved , immune reactions are believed to be the central pathogenic mechanisms .", "target_text": {} }, { "input_text": "Endogenous and therapeutic steroid hormones affect the immune system , and inflammatory diseases are associated with activation of the hypothalamic-pituitary-adrenal axis , providing evidence of an immune-endocrine interplay .", "target_text": {} }, { "input_text": "Function tests in MS have revealed dysregulation of the hypothalamic-pituitary-adrenal system in a substantial proportion of patients .", "target_text": {} }, { "input_text": "We characterized glucocorticoid receptor ( GR ) binding in peripheral blood lymphocytes from 39 MS patients and 14 age- and sex-matched controls with respect to dissociation constant and binding capacity , using a whole-cell binding assay with [3H]dexamethasone as the ligand .", "target_text": { "glucocorticoid receptor": "protein", "GR": "protein", "peripheral blood lymphocytes": "cell_type" } }, { "input_text": "GR binding parameters did not differ significantly between patients ( Kd 8.98 +/- 1.07 nM , Bmax 183 +/- 29.8 fmol/mg ) and controls ( Kd 9.36 +/- 1.17 nM , Bmax 158 +/- 16 fmol/mg ) .", "target_text": { "GR": "protein" } }, { "input_text": "No effect of age , sex , course , duration or severity of disease , or prior steroid treatments was detected .", "target_text": {} }, { "input_text": "GR binding parameters were analyzed in relation to the results of the combined dexamethasone -CRH test , which reflects corticosteroid receptor function at the hypothalamus , in 30 patients and 9 controls .", "target_text": { "GR": "protein", "-CRH": "protein" } }, { "input_text": "While controls showed a moderate correlation between binding affinity of the GR in lymphocytes and regulatory function at the hypothalamic level , the patients did not .", "target_text": { "GR": "protein" } }, { "input_text": "These data suggest that the physiological relationship between binding and function of the glucocorticoid receptor is disturbed in MS .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Phorbol ester -induced mononuclear cell differentiation is blocked by the mitogen-activated protein kinase kinase ( MEK ) inhibitor PD98059 .", "target_text": { "mitogen-activated protein kinase kinase": "protein", "MEK": "protein" } }, { "input_text": "The purpose of this study was to evaluate whether the mitogen-activated protein kinase ( MAPK ) signaling pathway contributes to 12-O-tetradecanoylphorbol-13-acetate ( TPA ) -induced mononuclear differentiation in the human myeloblastic leukemia ML-1 cells .", "target_text": { "mitogen-activated protein kinase": "protein", "MAPK": "protein", "human myeloblastic leukemia ML-1 cells": "cell_line" } }, { "input_text": "Upon TPA treatment , the activity of ERK1 and ERK2 rapidly increased , with maximal induction between 1 and 3 h , while ERK2 protein levels remained constant .", "target_text": { "ERK1": "protein", "ERK2": "protein" } }, { "input_text": "The activity of JNK1 was also significantly induced , with JNK1 protein levels increasing moderately during exposure to TPA .", "target_text": { "JNK1": "protein" } }, { "input_text": "Treatment of cells with PD98059 , a specific inhibitor of mitogen-activated protein kinase kinase ( MEK ) , inhibited TPA -induced ERK2 activity .", "target_text": { "mitogen-activated protein kinase kinase": "protein", "MEK": "protein", "ERK2": "protein" } }, { "input_text": "Furthermore , PD98059 completely blocked the TPA -induced differentiation of ML-1 cells , as assessed by a number of features associated with mononuclear differentiation including changes in morphology , nonspecific esterase activity , phagocytic ability , NADPH oxidase activity , mitochondrial respiration , and c-jun mRNA inducibility .", "target_text": { "ML-1 cells": "cell_line", "esterase": "protein", "NADPH oxidase": "protein", "c-jun mRNA": "RNA" } }, { "input_text": "We conclude that activation of the MEK /ERK signaling pathway is necessary for TPA -induced mononuclear cell differentiation .", "target_text": { "MEK": "protein" } }, { "input_text": "Glucocorticoid receptors in anorexia nervosa and Cushing 's disease .", "target_text": { "Glucocorticoid receptors": "protein" } }, { "input_text": "BACKGROUND : Patients with anorexia nervosa do not display cushingoid features in spite of elevated cortisol plasma levels .", "target_text": {} }, { "input_text": "Whether a cortisol resistance or a reduced availability of the metabolic substrates necessary to develop the effect of glucocorticoids is responsible for this has not been established .", "target_text": {} }, { "input_text": "METHODS : Twenty-two patients with severe restrictive anorexia nervosa , 10 patients with active Cushing 's disease , and 24 healthy volunteers without psychiatric disorders or mood alterations were investigated .", "target_text": {} }, { "input_text": "Glucocorticoid receptor characteristics were examined on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation , which represents an index of DNA synthesis .", "target_text": { "mononuclear leukocytes": "cell_type" } }, { "input_text": "RESULTS : The number of glucocorticoid receptors on mononuclear leukocytes ( MNL ) was comparable in patients with anorexia nervosa , patients with active Cushing 's disease , and normal subjects ( binding capacity 3.3 +/- 0.23 vs. 3.7 +/- 0.30 and 3.5 +/- 0.20 fmol/10(6) cells ) .", "target_text": { "glucocorticoid receptors": "protein", "mononuclear leukocytes": "cell_type", "MNL": "cell_type" } }, { "input_text": "Conversely , glucocorticoid receptor affinity was significantly decreased in anorexia nervosa as well as in Cushing 's patients compared to control subjects ( dissociation constant 4.0 +/- 0.31 and 4.1 +/- 0.34 vs. 2.9 +/- 0.29 nmol/L , p < .001 ) and inversely correlated with the levels of urinary free cortisol in both groups of patients .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Basal [3H]thymidine incorporation in MNL was significantly reduced in anorexia nervosa as well as in Cushing 's patients compared to control subjects ( p < .001 ) and was diminished by dexamethasone to an extent similar to control subjects in patients with anorexia nervosa , but significantly ( p < .001 ) less in those with Cushing 's disease .", "target_text": { "MNL": "cell_type" } }, { "input_text": "In patients with anorexia nervosa , the incorporation of [3H]thymidine into the MNL was inversely correlated with urinary free cortisol levels .", "target_text": { "MNL": "cell_type" } }, { "input_text": "CONCLUSIONS : These data indicate that the lack of cushingoid features in patients with anorexia nervosa is not ascribable to a reduced sensitivity to glucocorticoids but is more likely due to the paucity of metabolic substrates .", "target_text": {} }, { "input_text": "Different sequence requirements for expression in erythroid and megakaryocytic cells within a regulatory element upstream of the GATA-1 gene .", "target_text": { "regulatory element": "DNA", "GATA-1 gene": "DNA" } }, { "input_text": "The lineage-restricted transcription factor GATA-1 is required for differentiation of erythroid and megakaryocytic cells .", "target_text": { "transcription factor": "protein", "lineage-restricted transcription factor": "protein", "GATA-1": "protein" } }, { "input_text": "We have localized a 317 base pair cis-acting regulatory element , HS I , associated with a hematopoietic-specific DNase I hypersensitive site , which lies approx.", "target_text": { "regulatory element": "DNA", "cis-acting regulatory element": "DNA", "HS I": "DNA", "DNase I": "protein", "hematopoietic-specific DNase I hypersensitive site": "DNA" } }, { "input_text": "3.7 kilobases upstream of the murine hematopoietic-specific GATA-1 IE promoter .", "target_text": { "GATA-1": "protein", "murine hematopoietic-specific GATA-1 IE promoter": "DNA" } }, { "input_text": "HS I directs high-level expression of reporter GATA-1/lacZ genes to primitive and definitive erythroid cells and megakaryocytes in transgenic mice .", "target_text": { "HS I": "DNA", "GATA-1/lacZ genes": "DNA", "megakaryocytes": "cell_type" } }, { "input_text": "Comparative sequence analysis of HS I between human and mouse shows approx.", "target_text": { "HS I": "DNA" } }, { "input_text": "63 % nucleotide identity with a more conserved core of 169 base pairs ( 86 % identity ) .", "target_text": { "169 base pairs": "DNA" } }, { "input_text": "This core contains a GATA site separated by 10 base pairs from an E-box motif .", "target_text": { "GATA site": "DNA", "E-box motif": "DNA" } }, { "input_text": "The composite motif binds a multi-protein hematopoietic-specific transcription factor complex which includes GATA-1 , SCL/tal-1 , E2A , Lmo2 and Ldb-1 .", "target_text": { "composite motif": "DNA", "transcription factor": "protein", "multi-protein hematopoietic-specific transcription factor complex": "protein", "GATA-1": "protein", "SCL/tal-1 ,": "protein", "E2A": "protein", "Lmo2": "protein", "Ldb-1": "protein" } }, { "input_text": "Point mutations of the GATA site abolishes HS I function , whereas mutation of the E-box motif still allows reporter gene expression in both lineages .", "target_text": { "GATA site": "DNA", "HS I": "DNA", "E-box motif": "DNA" } }, { "input_text": "Strict dependence of HS I activity on a GATA site implies that assembly of a protein complex containing a GATA-factor , presumably GATA-1 or GATA-2 , is critical to activating or maintaining its function .", "target_text": { "HS I": "DNA", "GATA site": "DNA", "GATA-factor": "protein", "GATA-1": "protein", "GATA-2": "protein" } }, { "input_text": "Further dissection of the 317 base pair region demonstrates that , whereas all 317 base pairs are required for expression in megakaryocytes , only the 5' 62 base pairs are needed for erythroid-specific reporter expression .", "target_text": { "317 base pair region": "DNA", "317 base pairs": "DNA", "megakaryocytes": "cell_type", "5' 62 base pairs": "DNA" } }, { "input_text": "These findings demonstrate differential lineage requirements for expression within the HS I element .", "target_text": { "HS I": "DNA", "HS I element": "DNA" } }, { "input_text": "Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes .", "target_text": { "cytokines": "protein", "HSP70": "protein", "human monocytes": "cell_type" } }, { "input_text": "Recent studies have shown that the non-steroidal anti-inflammatory drugs ( NSAIDs ) activate heat shock transcription factor ( HSF1 ) from a latent cytoplasmic form to a nuclear , DNA binding state .", "target_text": { "transcription factor": "protein", "heat shock transcription factor": "protein", "HSF1": "protein", "latent cytoplasmic form": "protein", "nuclear , DNA binding state": "protein" } }, { "input_text": "As HSF1 can function as both an activator of heat shock genes and a repressor of non-heat shock genes such as IL1B and c- fos , we have examined the potential role of HSF1 in the effects of NSAIDs on gene expression in a human monocytic cell line THP-1 .", "target_text": { "HSF1": "protein", "heat shock genes": "DNA", "non-heat shock genes": "DNA", "monocytic cell line THP-1": "cell_line" } }, { "input_text": "We found that two members of the NSAIDs , sodium salicylate and sulindac repress the IL1B promoter to similar degree to heat shock or HSF1 overexpression .", "target_text": { "IL1B promoter": "DNA", "HSF1": "protein" } }, { "input_text": "In addition , sodium salicylate and additional NSAIDs used at concentrations that activate HSF1 also inhibited the expression of other monocytic genes ( TNF-alpha , IL-1beta , IL-6 , IL-8 , IL-10 , ICAM-1 ) activated by exposure to a pro-inflammatory stimulus ( lipopolysaccharide , LPS ) .", "target_text": { "HSF1": "protein", "monocytic genes": "DNA", "TNF-alpha": "DNA", "IL-1beta": "DNA", "IL-6": "DNA", "IL-8": "DNA", "IL-10": "DNA", "ICAM-1": "DNA" } }, { "input_text": "At least in the case of the IL1B promoter , repression did not seem to involve another factor whose activity is affected by the NSAIDs , NFkappaB as the IL1B promoter fragment used in our studies is not NFkappaB responsive and binds specifically to HSF1 .", "target_text": { "IL1B promoter": "DNA", "NFkappaB": "protein", "IL1B promoter fragment": "DNA", "HSF1": "protein" } }, { "input_text": "Exposure to NSAIDs had a complex effect on HSP gene expression and while sulindac activated the stress responsive HSP70B promoter , sodium salicylate did not .", "target_text": { "HSP70B": "protein", "HSP70B promoter": "DNA" } }, { "input_text": "In addition , only a subset of the NSAIDs induced HSP70 mRNA species .", "target_text": { "HSP70": "protein", "HSP70 mRNA species": "RNA" } }, { "input_text": "These findings reflect the properties of HSF1 which can be activated to at least two DNA binding forms only one of which activates heat shock promoters and suggest that individual NSAID family members may differentially induce one or other of these forms .", "target_text": { "HSF1": "protein", "DNA binding forms": "protein", "heat shock promoters": "DNA" } }, { "input_text": "Overall therefore , exposure to NSAIDs leads to a profound switch in gene expression in monocytic cells , with suppression of genes involved in macrophage activation and induction of stress genes and HSF1 appears to play a regulatory role in these effects .", "target_text": { "monocytic cells": "cell_type", "stress genes": "DNA", "HSF1": "protein" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "Immortalization of CD4(+) and CD8(+) T lymphocytes by human T-cell leukemia virus type 1 Tax mutants expressed in a functional molecular clone .", "target_text": { "Tax mutants": "protein", "functional molecular clone": "cell_line" } }, { "input_text": "The human T-cell leukemia virus type 1 ( HTLV-1 ) transcriptional trans-activator Tax has been demonstrated to have transforming activity in multiple cell culture and transgenic-mouse models .", "target_text": { "human T-cell leukemia virus type 1 ( HTLV-1 ) transcriptional trans-activator": "protein", "Tax": "protein", "multiple cell culture": "cell_line" } }, { "input_text": "In addition to activating transcription from the viral long terminal repeat ( LTR ) through the cyclic AMP response element binding protein/activating transcription factor ( CREB/ATF ) family of transcription factors , Tax activates the expression of multiple cellular promoters through the NF-kappaB pathway of transcriptional activation .", "target_text": { "viral long terminal repeat": "DNA", "LTR": "DNA", "transcription factor": "protein", "cyclic AMP response element binding protein/activating transcription factor ( CREB/ATF ) family": "protein", "transcription factors": "protein", "Tax": "protein", "multiple cellular promoters": "DNA", "NF-kappaB": "protein" } }, { "input_text": "The Tax mutants M22 and M47 have previously been demonstrated to selectively abrogate the ability of Tax to activate transcription through the NF-kappaB or CREB/ATF pathway , respectively .", "target_text": { "Tax": "protein", "Tax mutants": "protein", "M22": "protein", "M47": "protein" } }, { "input_text": "These mutations were introduced in the tax gene of the ACH functional molecular clone of HTLV-1 , and virus produced from the mutant ACH clones was examined for the ability to replicate and immortalize primary human lymphocytes .", "target_text": { "tax gene": "DNA", "ACH functional molecular clone": "DNA", "mutant ACH clones": "DNA", "primary human lymphocytes": "cell_type" } }, { "input_text": "While virus derived from the clone containing the M47 mutation retained the ability to immortalize T lymphocytes , the M22 mutant lost the ability to immortalize infected cells .", "target_text": { "M47": "protein", "T lymphocytes": "cell_type", "M22": "protein", "infected cells": "cell_type" } }, { "input_text": "These results indicate that activation of the CREB/ATF pathway by Tax is dispensable for the immortalization of T cells by HTLV-1 , whereas activation of the NF-kappaB pathway may be critical .", "target_text": { "CREB/ATF": "protein", "Tax": "protein", "T cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "Fibroblast growth factor-1 ( FGF-1 ) enhances IL-2 production and nuclear translocation of NF-kappaB in FGF receptor -bearing Jurkat T cells .", "target_text": { "Fibroblast growth factor-1": "protein", "FGF-1": "protein", "IL-2": "protein", "NF-kappaB": "protein", "FGF receptor": "protein", "FGF receptor -bearing Jurkat T cells": "cell_line" } }, { "input_text": "Fibroblast growth factors ( FGFs ) are heparin-binding proteins crucial to embryogenesis , angiogenesis , and wound healing .", "target_text": { "Fibroblast growth factors": "protein", "FGFs": "protein", "heparin-binding proteins": "protein" } }, { "input_text": "FGF-1 is abundantly expressed in the synovium in rheumatoid arthritis and in rejecting allografts , sites of chronic immune-mediated inflammation .", "target_text": { "FGF-1": "protein" } }, { "input_text": "The frequency of FGF-1 -responsive T cells is increased in the peripheral blood of these disorders , and a high percentage of infiltrating T cells in rheumatoid arthritis synovium express receptors for FGF-1 .", "target_text": { "FGF-1": "protein", "T cells": "cell_type", "infiltrating T cells": "cell_type" } }, { "input_text": "To understand the action of FGF-1 in T cells , studies were initiated in Jurkat T cells that express the signaling isoform of FGF receptor-1 .", "target_text": { "FGF-1": "protein", "T cells": "cell_type", "Jurkat T cells": "cell_line", "FGF receptor-1": "protein" } }, { "input_text": "These experiments show that FGF-1 stimulation of Jurkat T cells provides a second signal that augments TCR-mediated IL-2 production .", "target_text": { "FGF-1": "protein", "Jurkat T cells": "cell_line", "IL-2": "protein" } }, { "input_text": "Analogous to costimulation via CD28 , this activity is mediated through activation of Rel/kappaB , a family of transcription factors known to regulate IL-2 and other activation-inducible proteins .", "target_text": { "CD28": "protein", "Rel/kappaB": "protein", "transcription factors": "protein", "IL-2": "protein", "activation-inducible proteins": "protein" } }, { "input_text": "FGF-1 alone induces modest nuclear translocation of kappaB-binding proteins , and this translocation is enhanced by the combination of anti-CD3 and FGF-1 .", "target_text": { "FGF-1": "protein", "kappaB-binding proteins": "protein", "anti-CD3": "protein" } }, { "input_text": "This NF-kappaB binding complex is composed of transcriptionally active p65 ( RelA ) /p50 heterodimers and results primarily from the targeted degradation of IkappaB-alpha , an inhibitor that sequesters Rel/kappaB in the cytoplasm .", "target_text": { "NF-kappaB": "protein", "NF-kappaB binding complex": "protein", "RelA": "protein", "transcriptionally active p65 ( RelA ) /p50 heterodimers": "protein", "IkappaB-alpha": "protein", "Rel/kappaB": "protein" } }, { "input_text": "These data are the first to show a connection between FGF-1 signaling and NF-kappaB activation outside of embryonic development .", "target_text": { "FGF-1": "protein", "NF-kappaB": "protein" } }, { "input_text": "The signaling events that link FGF receptor-1 engagement and NF-kappaB activation in Jurkat are probably distinct from the CD28 costimulation pathway , since FGF-1 -induced Rel/kappaB binding proteins do not contain significant levels of c-Rel and are not identical with the CD28 response complex .", "target_text": { "FGF receptor-1": "protein", "NF-kappaB": "protein", "Jurkat": "cell_line", "CD28": "protein", "FGF-1": "protein", "Rel/kappaB": "protein", "Rel/kappaB binding proteins": "protein", "c-Rel": "protein", "CD28 response complex": "protein" } }, { "input_text": "Escape of human cytomegalovirus from HLA-DR -restricted CD4(+) T-cell response is mediated by repression of gamma interferon -induced class II transactivator expression .", "target_text": { "HLA-DR": "protein", "gamma interferon": "protein", "class II transactivator": "protein" } }, { "input_text": "Human cytomegalovirus ( HCMV ) , a betaherpesvirus , is a pathogen which escapes immune recognition through various mechanisms .", "target_text": {} }, { "input_text": "In this paper , we show that HCMV down regulates gamma interferon ( IFN-gamma ) -induced HLA-DR expression in U373 MG astrocytoma cells due to a defect downstream of STAT1 phosphorylation and nuclear translocation .", "target_text": { "IFN-gamma": "protein", "HLA-DR": "protein", "U373 MG astrocytoma cells": "cell_line", "STAT1": "protein" } }, { "input_text": "Repression of class II transactivator ( CIITA ) mRNA expression is detected within the first hours of IFN-gamma -HCMV coincubation and results in the absence of HLA-DR synthesis .", "target_text": { "CIITA": "DNA", "IFN-gamma": "protein", "HLA-DR": "protein" } }, { "input_text": "This defect leads to the absence of presentation of the major immediate-early protein IE1 to specific CD4(+) T-cell clones when U373 MG cells , used as antigen-presenting cells , are treated with IFN-gamma plus HCMV .", "target_text": { "major immediate-early protein": "protein", "IE1": "protein", "CD4(+) T-cell clones": "cell_line", "U373 MG cells": "cell_line", "antigen-presenting cells": "cell_type", "IFN-gamma": "protein" } }, { "input_text": "However , presentation of endogenously synthesized IE1 can be restored when U373 MG cells are transfected with CIITA prior to infection with HCMV .", "target_text": { "IE1": "protein", "U373 MG cells": "cell_line", "CIITA": "DNA" } }, { "input_text": "Altogether , the data indicate that the defect induced by HCMV resides in the activation of the IFN-gamma -responsive promoter of CIITA .", "target_text": { "IFN-gamma": "protein", "IFN-gamma -responsive promoter": "DNA", "CIITA": "DNA" } }, { "input_text": "This is the first demonstration of a viral inhibition of CIITA expression .", "target_text": { "CIITA": "DNA" } }, { "input_text": "3-deazaadenosine , a S-adenosylhomocysteine hydrolase inhibitor , has dual effects on NF-kappaB regulation .", "target_text": { "S-adenosylhomocysteine hydrolase": "protein", "NF-kappaB": "protein" } }, { "input_text": "Inhibition of NF-kappaB transcriptional activity and promotion of IkappaBalpha degradation .", "target_text": { "NF-kappaB": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Previously we reported that 3-deazaadenosine ( DZA ) , a potent inhibitor and substrate for S-adenosylhomocysteine hydrolase inhibits bacterial lipopolysaccharide-induced transcription of tumor necrosis factor-alpha and interleukin-1beta in mouse macrophage RAW 264.7 cells .", "target_text": { "S-adenosylhomocysteine hydrolase": "protein", "tumor necrosis factor-alpha": "protein", "interleukin-1beta": "protein", "mouse macrophage RAW 264.7 cells": "cell_line" } }, { "input_text": "In this study , we demonstrate the effects of DZA on nuclear factor-kappaB ( NF-kappaB ) regulation .", "target_text": { "nuclear factor-kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "DZA inhibits the transcriptional activity of NF-kappaB through the hindrance of p65 ( Rel-A ) phosphorylation without reduction of its nuclear translocation and DNA binding activity .", "target_text": { "NF-kappaB": "protein", "p65": "protein", "Rel-A": "protein" } }, { "input_text": "The inhibitory effect of DZA on NF-kappaB transcriptional activity is potentiated by the addition of homocysteine .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Taken together , DZA promotes the proteolytic degradation of IkappaBalpha , but not IkappaBbeta , resulting in an increase of DNA binding activity of NF-kappaB in the nucleus in the absence of its transcriptional activity in RAW 264.7 cells .", "target_text": { "IkappaBalpha": "protein", "IkappaBbeta": "protein", "NF-kappaB": "protein", "RAW 264.7 cells": "cell_line" } }, { "input_text": "The reduction of IkappaBalpha by DZA is neither involved in IkappaB kinase complex activation nor modulated by the addition of homocysteine .", "target_text": { "IkappaBalpha": "protein", "IkappaB kinase complex": "protein" } }, { "input_text": "This study strongly suggests that DZA may be a potent drug for the treatment of diseases in which NF-kappaB plays a central pathogenic role , as well as a useful tool for studying the regulation and physiological functions of NF-kappaB .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "The role of gamma/delta T cell receptor positive cells in pregnancy .", "target_text": { "gamma/delta T cell receptor": "protein", "gamma/delta T cell receptor positive cells": "cell_type" } }, { "input_text": "PROBLEM : Due to the lack of classical HLA antigens on the trophoblast , fetal antigens are possibly presented in a non major histocompatibility complex ( MHC ) restricted way .", "target_text": { "classical HLA antigens": "protein", "fetal antigens": "protein", "major histocompatibility complex": "protein", "MHC": "protein" } }, { "input_text": "Decidual gammadelta T cells , which significantly increase in number during pregnancy , might play a role in recognition of fetal antigens and also in determining the quality of the response to these antigens .", "target_text": { "Decidual gammadelta T cells": "cell_type", "fetal antigens": "protein", "antigens": "protein" } }, { "input_text": "Our study was aimed at investigating the role of this cell population in progesterone -dependent immunomodulation .", "target_text": {} }, { "input_text": "METHOD OF STUDY : Peripheral lymphocytes from healthy pregnant women and from habitual aborters were tested by immunocytochemistry for the presence of gamma/delta T cell receptor ( TCR ) and progesterone receptor .", "target_text": { "Peripheral lymphocytes": "cell_type" } }, { "input_text": "To investigate the effect of treatment with a pan anti gamma/delta antibody , lymphocytes were incubated for 3 hr with the antibody , and then interleukin ( IL ) -10 , IL-12 and progesterone -induced blocking factor ( PIBF ) expression ( by immuno-cytochemistry ) as well as natural killer ( NK ) cell activity were determined .", "target_text": { "anti gamma/delta antibody": "protein", "lymphocytes": "cell_type", "interleukin ( IL ) -10": "protein", "IL-12": "protein", "progesterone -induced blocking factor": "protein", "PIBF": "protein", "natural killer ( NK ) cell": "cell_type" } }, { "input_text": "RESULTS : In peripheral blood of healthy pregnant women the percentage of gamma/delta TCR+ cells was significantly higher ( P < 0.001 ) than in that of recurrent aborters or of non-pregnant individuals .", "target_text": { "gamma/delta TCR+ cells": "cell_type" } }, { "input_text": "Ninety-seven percent of gamma/delta TCR+ pregnancy lymphocytes expressed progesterone receptor .", "target_text": { "gamma/delta TCR+ pregnancy lymphocytes": "cell_type", "progesterone receptor": "protein" } }, { "input_text": "Binding of a specific antibody to the gamma/delta TCR inhibited PIBF - as well as IL-10 production , whereas it increased NK activity and IL-12 expression .", "target_text": { "IL-12": "protein" } }, { "input_text": "CONCLUSIONS : These data suggest the role of gamma/delta TCR -bearing lymphocytes in progesterone -dependent immunomodulation .", "target_text": { "gamma/delta TCR": "protein", "gamma/delta TCR -bearing lymphocytes": "cell_type" } }, { "input_text": "Monocyte adhesion and spreading on human endothelial cells is dependent on Rho -regulated receptor clustering .", "target_text": { "human endothelial cells": "cell_type", "Rho": "protein" } }, { "input_text": "The GTPase Rho is known to mediate the assembly of integrin-containing focal adhesions and actin stress fibers .", "target_text": { "GTPase": "protein", "Rho": "protein" } }, { "input_text": "Here , we investigate the role of Rho in regulating the distribution of the monocyte-binding receptors E-selectin , ICAM-1 , and VCAM-1 in human endothelial cells .", "target_text": { "Rho": "protein", "monocyte-binding receptors": "protein", "E-selectin": "protein", "ICAM-1": "protein", "VCAM-1": "protein", "human endothelial cells": "cell_type" } }, { "input_text": "Inhibition of Rho activity with C3 transferase or N19RhoA , a dominant negative RhoA mutant , reduced the adhesion of monocytes to activated endothelial cells and inhibited their spreading .", "target_text": { "Rho": "protein", "C3 transferase": "protein", "N19RhoA": "protein", "RhoA mutant": "protein", "monocytes": "cell_type", "endothelial cells": "cell_type" } }, { "input_text": "Similar effects were observed after pretreatment of endothelial cells with cytochalasin D .", "target_text": { "endothelial cells": "cell_type" } }, { "input_text": "In contrast , dominant negative Rac and Cdc42 proteins did not affect monocyte adhesion or spreading .", "target_text": {} }, { "input_text": "C3 transferase and cytochalasin D did not alter the expression levels of monocyte-binding receptors on endothelial cells , but did inhibit clustering of E-selectin , ICAM-1 , and VCAM-1 on the cell surface induced by monocyte adhesion or cross-linking antibodies .", "target_text": { "monocyte-binding receptors": "protein", "endothelial cells": "cell_type", "E-selectin": "protein", "ICAM-1": "protein", "VCAM-1": "protein", "cross-linking antibodies": "protein" } }, { "input_text": "Similarly , N19RhoA inhibited receptor clustering .", "target_text": { "N19RhoA": "protein" } }, { "input_text": "Monocyte adhesion and receptor cross-linking induced stress fiber assembly , and inhibitors of myosin light chain kinase prevented this response but did not affect receptor clustering .", "target_text": { "myosin light chain kinase": "protein" } }, { "input_text": "Finally , receptor clusters colocalized with ezrin / moesin / radixin proteins .", "target_text": {} }, { "input_text": "These results suggest that Rho is required in endothelial cells for the assembly of stable adhesions with monocytes via the clustering of monocyte-binding receptors and their association with the actin cytoskeleton , independent of stress fiber formation .", "target_text": { "Rho": "protein", "endothelial cells": "cell_type", "monocytes": "cell_type", "monocyte-binding receptors": "protein" } }, { "input_text": "Selection of the T cell repertoire .", "target_text": {} }, { "input_text": "Advances in gene technology have allowed the manipulation of molecular interactions that shape the T cell repertoire .", "target_text": {} }, { "input_text": "Although recognized as fundamental aspects of T lymphocyte development , only recently have the mechanisms governing positive and negative selection been examined at a molecular level .", "target_text": { "T lymphocyte": "cell_type" } }, { "input_text": "Positive selection refers to the active process of rescuing MHC -restricted thymocytes from programmed cell death .", "target_text": { "MHC": "protein", "MHC -restricted thymocytes": "cell_type" } }, { "input_text": "Negative selection refers to the deletion or inactivation of potentially autoreactive thymocytes .", "target_text": { "autoreactive thymocytes": "cell_type" } }, { "input_text": "This review focuses on interactions during thymocyte maturation that define the T cell repertoire , with an emphasis placed on current literature within this field .", "target_text": { "thymocyte": "cell_type" } }, { "input_text": "CD28 costimulation augments IL-2 secretion of activated lamina propria T cells by increasing mRNA stability without enhancing IL-2 gene transactivation .", "target_text": { "CD28": "protein", "IL-2": "protein" } }, { "input_text": "The pathways leading to activation in lamina propria ( LP ) T cells are different from peripheral T cells .", "target_text": { "lamina propria ( LP ) T cells": "cell_type", "peripheral T cells": "cell_type" } }, { "input_text": "LP T cells exhibit enhanced IL-2 secretion when activated through the CD2 pathway .", "target_text": { "LP T cells": "cell_type", "IL-2": "protein", "CD2": "protein" } }, { "input_text": "Coligation of CD28 leads to synergistic enhancement of IL-2 secretion .", "target_text": { "CD28": "protein", "IL-2": "protein" } }, { "input_text": "Previous studies have characterized the CD28 augmentation of TCR -mediated signaling in peripheral blood T cells through transcriptional activation of an IL-2 promoter CD28 response element ( CD28RE ) , along with enhanced mRNA stability .", "target_text": { "CD28": "protein", "TCR": "protein", "peripheral blood T cells": "cell_type", "IL-2": "protein", "CD28 response element": "DNA", "CD28RE": "DNA" } }, { "input_text": "This study characterized molecular events involved in CD28 costimulation of IL-2 production in LP mononuclear cells ( LPMC ) .", "target_text": { "CD28": "protein", "IL-2": "protein", "LPMC": "cell_type", "LP mononuclear cells ( LPMC )": "cell_type" } }, { "input_text": "LPMC exhibited increased IL-2 production in response to CD28 costimulation , compared with cells activated through CD2 alone .", "target_text": { "LPMC": "cell_type", "IL-2": "protein", "CD28": "protein", "CD2": "protein" } }, { "input_text": "IL-2 secretion was paralleled by increased expression of IL-2 mRNA , resulting from enhanced IL-2 mRNA stability .", "target_text": { "IL-2": "protein", "IL-2 mRNA": "RNA" } }, { "input_text": "In contrast to transcriptional activation in PBMC , EMSA revealed that CD28 coligation of CD2 -activated LPMC does not result in increased binding of trans-factors to the CD28RE , nor did Western blots detect changes in I-kappaBalpha or I-kappaBbeta levels following CD28 coligation .", "target_text": { "PBMC": "cell_type", "CD28": "protein", "CD2": "protein", "LPMC": "cell_type", "CD2 -activated LPMC": "cell_type", "CD28RE": "DNA", "I-kappaBalpha": "protein", "I-kappaBbeta": "protein" } }, { "input_text": "Furthermore , CD28 coligation fails to enhance IL-2 promoter-reporter or RE/AP construct expression in CD2 -activated LPMC .", "target_text": { "CD28": "protein", "IL-2": "protein", "IL-2 promoter-reporter": "DNA", "RE/AP": "protein", "CD2": "protein", "LPMC": "cell_type", "CD2 -activated LPMC": "cell_type" } }, { "input_text": "The results reported herein indicate that the molecular mechanisms involved in CD28 cosignaling and regulation of IL-2 secretion in LP T cells are unique to that compartment and differ from those seen in peripheral blood T cells .", "target_text": { "CD28": "protein", "IL-2": "protein", "LP T cells": "cell_type", "peripheral blood T cells": "cell_type" } }, { "input_text": "These observations suggest a biological significance for different mechanisms of IL-2 activation in initiation and maintenance of the cytokine repertoire found in the mucosa .", "target_text": { "IL-2": "protein", "cytokine repertoire": "protein" } }, { "input_text": "Expression of Th1 and Th2 type cytokines responding to HBsAg and HBxAg in chronic hepatitis B patients .", "target_text": { "HBsAg": "protein", "HBxAg": "protein" } }, { "input_text": "The cytokine pattern on viral antigen recognition is believed to exert a profound influence on the resolution of viral infections and viral clearance .", "target_text": { "cytokine pattern": "protein" } }, { "input_text": "This study was initiated to investigate whether a cytokine imbalance oriented toward Th2 type response plays a role in chronic hepatitis B .", "target_text": { "cytokine": "protein" } }, { "input_text": "Cytokine profiles of peripheral blood mononuclear cells associated with chronic hepatitis B were analysed by RT-PCR .", "target_text": { "Cytokine profiles": "protein", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Upon HBsAg stimulation , expression of IFN-gamma , IL-2 , IL-4 , and IL-10 was detected in 41 % , 8 % , 41 % , and 50 % of the patients , respectively .", "target_text": { "HBsAg": "protein", "IFN-gamma": "protein", "IL-2": "protein", "IL-4": "protein", "IL-10": "protein" } }, { "input_text": "Among these cytokines , the expression of IFN-gamma was associated with high levels of serum AST/ALT .", "target_text": { "cytokines": "protein", "IFN-gamma": "protein", "serum AST/ALT": "protein" } }, { "input_text": "However , we could not prove that Th2 type cytokines had a protective effect on hepatocytes .", "target_text": { "cytokines": "protein", "Th2 type cytokines": "protein", "hepatocytes": "cell_type" } }, { "input_text": "Upon HBxAg stimulation , there was no recognizable association of cytokine patterns with AST/ALT levels .", "target_text": { "HBxAg": "protein", "cytokine patterns": "protein" } }, { "input_text": "In conclusion , production of a Th1 cytokine , IFN-gamma , by HBsAg -reactive cells was associated with hepatocyte damage in chronic hepatitis B , while no counteracting effect of Th2 cytokines produced by those cells was observed .", "target_text": { "Th1 cytokine": "protein", "IFN-gamma": "protein", "HBsAg": "protein", "cytokines": "protein", "Th2 cytokines": "protein" } }, { "input_text": "Apoptosis and growth inhibition in malignant lymphocytes after treatment with arsenic trioxide at clinically achievable concentrations [ see comments ]", "target_text": { "malignant lymphocytes": "cell_type" } }, { "input_text": "BACKGROUND : Arsenic trioxide ( As2O3 ) can induce clinical remission in patients with acute promyelocytic leukemia via induction of differentiation and programmed cell death ( apoptosis ) .", "target_text": {} }, { "input_text": "We investigated the effects of As2O3 on a panel of malignant lymphocytes to determine whether growth-inhibitory and apoptotic effects of As2O3 can be observed in these cells at clinically achievable concentrations .", "target_text": { "malignant lymphocytes": "cell_type" } }, { "input_text": "METHODS : Eight malignant lymphocytic cell lines and primary cultures of lymphocytic leukemia and lymphoma cells were treated with As2O3 , with or without dithiothreitol ( DTT ) or buthionine sulfoximine ( BSO ) ( an inhibitor of glutathione synthesis ) .", "target_text": { "malignant lymphocytic cell lines": "cell_line", "primary cultures": "cell_line" } }, { "input_text": "Apoptosis was assessed by cell morphology , flow cytometry , annexin V protein level , and terminal deoxynucleotidyl transferase labeling of DNA fragments .", "target_text": { "terminal deoxynucleotidyl transferase": "protein", "DNA fragments": "DNA" } }, { "input_text": "Cellular proliferation was determined by 5-bromo-2'-deoxyuridine incorporation into DNA and flow cytometry and by use of a mitotic arrest assay .", "target_text": {} }, { "input_text": "Mitochondrial transmembrane potential ( delta psi(m) ) was measured by means of rhodamine 123 staining and flow cytometry .", "target_text": {} }, { "input_text": "Protein expression was assessed by western blot analysis or immunofluorescence .", "target_text": {} }, { "input_text": "RESULTS : Therapeutic concentrations of As2O3 ( 1-2 microM ) had dual effects on malignant lymphocytes : 1 ) inhibition of growth through adenosine triphosphate ( ATP ) depletion and prolongation of cell cycle time and 2 ) induction of apoptosis .", "target_text": { "malignant lymphocytes": "cell_type" } }, { "input_text": "As2O3 -induced apoptosis was preceded by delta psi(m) collapse .", "target_text": {} }, { "input_text": "DTT antagonized and BSO enhanced As2O3 -induced ATP depletion , delta psi(m) collapse , and apoptosis .", "target_text": {} }, { "input_text": "Caspase-3 activation , usually resulting from delta psi(m) collapse , was not always associated with As2O3 -induced apoptosis .", "target_text": { "Caspase-3": "protein" } }, { "input_text": "As2O3 induced PML ( promyelocytic leukemia ) protein degradation but did not modulate expression of cell cycle-related proteins , including c-myc , retinoblastoma protein , cyclin-dependent kinase 4 , cyclin D1 , and p53 , or expression of differentiation-related antigens .", "target_text": { "cell cycle-related proteins": "protein", "c-myc": "protein", "retinoblastoma protein": "protein", "cyclin-dependent kinase 4": "protein", "cyclin D1": "protein", "p53": "protein", "differentiation-related antigens": "protein" } }, { "input_text": "CONCLUSIONS : Substantial growth inhibition and apoptosis without evidence of differentiation were induced in most malignant lymphocytic cells treated with 1-2 microM As2O3 .", "target_text": { "malignant lymphocytic cells": "cell_type" } }, { "input_text": "As2O3 may prove useful in the treatment of malignant lymphoproliferative disorders .", "target_text": {} }, { "input_text": "Control of cell cycle entry and apoptosis in B lymphocytes infected by Epstein-Barr virus .", "target_text": { "B lymphocytes": "cell_type" } }, { "input_text": "Infection of human B cells with Epstein-Barr virus ( EBV ) results in activation of the cell cycle and cell growth .", "target_text": { "human B cells": "cell_type" } }, { "input_text": "To interpret the mechanisms by which EBV activates the cell , we have assayed many proteins involved in control of the G0 and G1 phases of the cell cycle and regulation of apoptosis .", "target_text": {} }, { "input_text": "In EBV infection most of the changes , including the early induction of cyclin D2 , are dependent on expression of EBV genes , but an alteration in the E2F-4 profile was partly independent of viral gene expression , presumably occurring in response to signal transduction activated when the virus binds to its receptor , CD21 .", "target_text": { "cyclin D2": "protein", "EBV genes": "DNA", "E2F-4": "protein", "CD21": "protein" } }, { "input_text": "By comparing the expression of genes controlling apoptosis , including those encoding several members of the BCL-2 family of proteins , the known relative resistance of EBV -immortalized B-cell lines to apoptosis induced by low serum was found to correlate with expression of both BCL-2 and A20 .", "target_text": { "BCL-2 family": "protein", "EBV -immortalized B-cell lines": "cell_line", "BCL-2": "protein", "A20": "protein" } }, { "input_text": "A20 can be regulated by the NF-kappaB transcription factor , which is known to be activated by the EBV LMP-1 protein .", "target_text": { "NF-kappaB": "protein", "transcription factor": "protein", "EBV LMP-1 protein": "protein" } }, { "input_text": "Quantitative assays demonstrated a direct temporal relationship between LMP-1 protein levels and active NF-kappaB during the time course of infection .", "target_text": { "LMP-1 protein": "protein", "NF-kappaB": "protein" } }, { "input_text": "CTLA-4 -Mediated inhibition of early events of T cell proliferation .", "target_text": { "CTLA-4": "protein" } }, { "input_text": "CTLA-4 engagement by mAbs inhibits , while CD28 enhances , IL-2 production and proliferation upon T cell activation .", "target_text": { "CTLA-4": "protein", "mAbs": "protein", "CD28": "protein", "IL-2": "protein" } }, { "input_text": "Here , we have analyzed the mechanisms involved in CTLA-4 -mediated inhibition of T cell activation of naive CD4+ T cells using Ab cross-linking .", "target_text": { "CTLA-4": "protein", "CD4+ T cells": "cell_type" } }, { "input_text": "CTLA-4 ligation inhibited CD3/ CD28 -induced IL-2 mRNA accumulation by inhibiting IL-2 transcription , which appears to be mediated in part through decreasing NF-AT accumulation in the nuclei .", "target_text": { "CTLA-4": "protein", "CD28": "protein", "IL-2": "protein", "IL-2 mRNA": "RNA", "NF-AT": "protein" } }, { "input_text": "However , CTLA-4 ligation did not appear to affect the CD28 -mediated stabilization of IL-2 mRNA .", "target_text": { "CTLA-4": "protein", "CD28": "protein", "IL-2": "protein", "IL-2 mRNA": "RNA" } }, { "input_text": "Further , CTLA-4 engagement inhibited progression through the cell cycle by inhibiting the production of cyclin D3 , cyclin-dependent kinase ( cdk ) 4 , and cdk6 when the T cells were stimulated with anti-CD3/ CD28 and with anti-CD3 alone .", "target_text": { "CTLA-4": "protein", "cyclin D3": "protein", "cyclin-dependent kinase": "protein", "( cdk ) 4": "protein", "cdk6": "protein", "T cells": "cell_type", "CD28": "protein", "anti-CD3/ CD28": "protein", "anti-CD3": "protein" } }, { "input_text": "These results indicate that CTLA-4 signaling inhibits events early in T cell activation both at IL-2 transcription and at the level of IL-2 -independent events of the cell cycle , and does not simply oppose CD28 -mediated costimulation .", "target_text": { "CTLA-4": "protein", "IL-2": "protein", "CD28": "protein" } }, { "input_text": "The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro .", "target_text": { "glucocorticoid receptor": "protein", "erythropoietin receptor": "protein", "c-Kit": "protein", "erythroid progenitors": "cell_type" } }, { "input_text": "Although erythropoietin ( Epo ) is essential for the production of mature red blood cells , the cooperation with other factors is required for a proper balance between progenitor proliferation and differentiation .", "target_text": { "erythropoietin": "protein", "Epo": "protein", "mature red blood cells": "cell_type" } }, { "input_text": "In avian erythroid progenitors , steroid hormones cooperate with tyrosine kinase receptors to induce renewal of erythroid progenitors .", "target_text": { "erythroid progenitors": "cell_type", "tyrosine kinase receptors": "protein" } }, { "input_text": "We examined the role of corticosteroids in the in vitro expansion of primary human erythroid cells in liquid cultures and colony assays .", "target_text": { "primary human erythroid cells": "cell_type" } }, { "input_text": "Dexamethasone ( Dex ) , a synthetic glucocorticoid hormone , cooperated with Epo and stem cell factor to induce erythroid progenitors to undergo 15 to 22 cell divisions , corresponding to a 10(5)- to 10(6)-fold amplification of erythroid cells .", "target_text": { "Epo": "protein", "stem cell factor": "protein", "erythroid progenitors": "cell_type", "erythroid cells": "cell_type" } }, { "input_text": "Dex acted directly on erythroid progenitors and maintained the colony-forming capacity of the progenitor cells expanded in liquid cultures .", "target_text": { "erythroid progenitors": "cell_type", "progenitor cells": "cell_type", "liquid cultures": "cell_line" } }, { "input_text": "The hormone delayed terminal differentiation into erythrocytes , which was assayed by morphology , hemoglobin accumulation , and the expression of genes characteristic for immature cells .", "target_text": { "erythrocytes": "cell_type", "hemoglobin": "protein", "immature cells": "cell_type" } }, { "input_text": "Sustained proliferation of erythroid progenitors could be induced equally well from purified erythroid burst-forming units ( BFU-E ) , from CD34(+) blast cells , and from bone marrow depleted from CD34(+) cells .", "target_text": { "erythroid progenitors": "cell_type", "purified erythroid burst-forming units": "cell_line", "BFU-E": "cell_line", "CD34(+) blast cells": "cell_type", "CD34(+) cells": "cell_type" } }, { "input_text": "NF-kappaB functions as both a proapoptotic and antiapoptotic regulatory factor within a single cell type .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Recently NF-kappaB has been shown to have both proapoptotic and antiapoptotic functions .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "In T cell hybridomas , both T cell activators and glucocorticoids induce apoptosis .", "target_text": { "T cell hybridomas": "cell_line" } }, { "input_text": "Here we show that blockade of NF-kappaB activity , using a dominant negative IkappaBalpha , has opposite effects on these two apoptotic signals .", "target_text": { "NF-kappaB": "protein", "dominant negative IkappaBalpha": "protein" } }, { "input_text": "Treatment with PMA plus ionomycin ( P/I ) results in the upregulation of Fas Ligand ( FasL ) and induction of apoptosis .", "target_text": { "Fas Ligand": "protein", "FasL": "protein" } }, { "input_text": "Inhibition of NF-kappaB activity inhibits the P/I mediated induction of FasL mRNA and decreases the level of apoptosis in these cultures , thus establishing NF-kappaB as a proapoptotic factor in this context .", "target_text": { "NF-kappaB": "protein", "FasL": "protein", "FasL mRNA": "RNA", "proapoptotic factor": "protein" } }, { "input_text": "Conversely , inhibition of NF-kappaB confers a tenfold increase in glucocorticoid mediated apoptosis , establishing that NF-kappaB also functions as an antiapoptotic factor .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "We conclude that NF-kappaB is a context-dependent apoptosis regulator .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Our data suggests that NF-kappaB may function as an antiapoptotic factor in thymocytes while functioning as a proapoptotic factor in mature peripheral T cells .", "target_text": { "NF-kappaB": "protein", "thymocytes": "cell_type", "mature peripheral T cells": "cell_type" } }, { "input_text": "SOCS-3 is tyrosine phosphorylated in response to interleukin-2 and suppresses STAT5 phosphorylation and lymphocyte proliferation .", "target_text": { "SOCS-3": "protein", "interleukin-2": "protein", "STAT5": "protein" } }, { "input_text": "Members of the recently discovered SOCS/CIS/SSI family have been proposed as regulators of cytokine signaling , and while targets and mechanisms have been suggested for some family members , the precise role of these proteins remains to be defined .", "target_text": { "SOCS/CIS/SSI family": "protein", "cytokine": "protein" } }, { "input_text": "To date no SOCS proteins have been specifically implicated in interleukin-2 ( IL-2 ) signaling in T cells .", "target_text": { "SOCS proteins": "protein", "interleukin-2": "protein", "IL-2": "protein", "T cells": "cell_type" } }, { "input_text": "Here we report SOCS-3 expression in response to IL-2 in both T-cell lines and human peripheral blood lymphocytes .", "target_text": { "SOCS-3": "protein", "IL-2": "protein", "T-cell lines": "cell_line", "human peripheral blood lymphocytes": "cell_type" } }, { "input_text": "SOCS-3 protein was detectable as early as 30 min following IL-2 stimulation , while CIS was seen only at low levels after 2 h .", "target_text": { "SOCS-3": "protein", "IL-2": "protein", "CIS": "protein" } }, { "input_text": "Unlike CIS , SOCS-3 was rapidly tyrosine phosphorylated in response to IL-2 .", "target_text": { "CIS": "protein", "SOCS-3": "protein", "IL-2": "protein" } }, { "input_text": "Tyrosine phosphorylation of SOCS-3 was observed upon coexpression with Jak1 and Jak2 but only weakly with Jak3 .", "target_text": { "SOCS-3": "protein", "Jak1": "protein", "Jak2": "protein", "Jak3": "protein" } }, { "input_text": "In these experiments , SOCS-3 associated with Jak1 and inhibited Jak1 phosphorylation , and this inhibition was markedly enhanced by the presence of IL-2 receptor beta chain ( IL-2Rbeta ) .", "target_text": { "SOCS-3": "protein", "Jak1": "protein", "IL-2": "protein", "IL-2 receptor beta chain": "protein", "IL-2Rbeta": "protein" } }, { "input_text": "Moreover , following IL-2 stimulation of T cells , SOCS-3 was able to interact with the IL-2 receptor complex , and in particular tyrosine phosphorylated Jak1 and IL-2Rbeta .", "target_text": { "IL-2": "protein", "T cells": "cell_type", "SOCS-3": "protein", "IL-2 receptor complex": "protein", "Jak1": "protein", "tyrosine phosphorylated Jak1": "protein", "IL-2Rbeta": "protein" } }, { "input_text": "Additionally , in lymphocytes expressing SOCS-3 but not CIS , IL-2 -induced tyrosine phosphorylation of STAT5b was markedly reduced , while there was only a weak effect on IL-3-mediated STAT5b tyrosine phosphorylation .", "target_text": { "lymphocytes": "cell_type", "SOCS-3": "protein", "CIS": "protein", "IL-2": "protein", "STAT5b": "protein", "IL-3-mediated STAT5b": "protein" } }, { "input_text": "Finally , proliferation induced by both IL-2 - and IL-3 was significantly inhibited in the presence of SOCS-3 .", "target_text": { "IL-2": "protein", "IL-3": "protein", "SOCS-3": "protein" } }, { "input_text": "The findings suggest that when SOCS-3 is rapidly induced by IL-2 in T cells , it acts to inhibit IL-2 responses in a classical negative feedback loop .", "target_text": { "SOCS-3": "protein", "IL-2": "protein", "T cells": "cell_type" } }, { "input_text": "Human alveolar macrophages are markedly deficient in REF-1 and AP-1 DNA binding activity .", "target_text": { "Human alveolar macrophages": "cell_type", "REF-1": "protein", "AP-1": "protein" } }, { "input_text": "Although many functions of human alveolar macrophages are altered compared with their precursor cell , the blood monocyte ( monocyte ) , the reason ( s ) for these functional changes have not been determined .", "target_text": { "human alveolar macrophages": "cell_type", "precursor cell": "cell_type", "blood monocyte": "cell_type", "monocyte": "cell_type" } }, { "input_text": "We recently reported that human alveolar macrophages do not express AP-1 DNA binding activity ( Monick , M. M. , Carter , A. B. , Gudmundsson , G. , Geist , L. J. , and Hunninghake , G. W. ( 1998 ) Am. J. Physiol. 275 , L389- L397 ) .", "target_text": { "human alveolar macrophages": "cell_type", "AP-1": "protein" } }, { "input_text": "To determine why alveolar macrophages do not express AP-1 DNA binding activity , we first showed that there was not a decrease in expression of the FOS and JUN proteins that make up the AP-1 complex .", "target_text": { "alveolar macrophages": "cell_type", "AP-1": "protein" } }, { "input_text": "There was , however , a significant difference in the amounts of the nuclear protein , REF-1 ( which regulates AP-1 DNA binding by altering the redox status of FOS and JUN proteins ) , in alveolar macrophages compared with monocytes .", "target_text": { "nuclear protein": "protein", "REF-1": "protein", "AP-1": "protein", "FOS": "protein", "JUN proteins": "protein", "alveolar macrophages": "cell_type", "monocytes": "cell_type" } }, { "input_text": "In addition , in vitro differentiation of monocytes to a macrophage-like cell resulted in decreased amounts of REF-1 .", "target_text": { "monocytes": "cell_type", "macrophage-like cell": "cell_type", "REF-1": "protein" } }, { "input_text": "Finally , addition of REF-1 from activated monocytes to alveolar macrophage nuclear proteins resulted in a marked increase in AP-1 DNA binding .", "target_text": { "REF-1": "protein", "activated monocytes": "cell_type", "AP-1": "protein" } }, { "input_text": "These studies strongly suggest that the process of differentiation of monocytes into alveolar macrophages is associated with a loss of REF-1 and AP-1 activity .", "target_text": { "monocytes": "cell_type", "alveolar macrophages": "cell_type", "REF-1": "protein", "AP-1": "protein" } }, { "input_text": "This observation may explain , in part , some of the functional differences observed for alveolar macrophages compared with monocytes .", "target_text": { "alveolar macrophages": "cell_type", "monocytes": "cell_type" } }, { "input_text": "Development and maturation of secondary lymphoid tissues .", "target_text": {} }, { "input_text": "The secondary lymphoid tissues are located at strategic sites where foreign antigens can be efficiently brought together with immune system regulatory and effector cells .", "target_text": { "foreign antigens": "protein" } }, { "input_text": "The organized structure of the secondary lymphoid tissues is thought to enhance the sensitivity of antigen recognition and to support proper regulation of the activation and maturation of the antigen-responsive lymphoid cells .", "target_text": { "antigen-responsive lymphoid cells": "cell_type" } }, { "input_text": "Although a substantial amount is known about the cellular elements that compose the lymphoid and nonlymphoid components of the secondary lymphoid tissues , information concerning the signals that control the development of the tissues and that maintain the organized tissue microenvironment remain undefined .", "target_text": { "cellular elements": "DNA" } }, { "input_text": "Studies over the past few years have identified lymphotoxin as a critical signaling molecule not only for the organogenesis of secondary lymphoid tissues but for the maintenance of aspects of their microarchitecture as well .", "target_text": {} }, { "input_text": "Additional signaling molecules that contribute to the formation of normal lymphoid tissue structure are being identified at an accelerating pace .", "target_text": {} }, { "input_text": "Analyses of mouse strains with congenital defects in different aspects of secondary lymphoid tissue development are beginning to clarify the role of these tissues in immune responses and host defense .", "target_text": {} }, { "input_text": "This review focuses on studies defining recently identified crucial signals for the biogenesis of secondary lymphoid organs and for the maintenance of their proper microarchitecture .", "target_text": {} }, { "input_text": "It also discusses new insights into how the structure of these tissues supports effective immune responses .", "target_text": {} }, { "input_text": "Modulation of CD28 expression : distinct regulatory pathways during activation and replicative senescence .", "target_text": { "CD28": "protein" } }, { "input_text": "The costimulatory molecule CD28 has a restricted tissue distribution and is expressed on T cells and some plasmacytoma cells .", "target_text": { "costimulatory molecule": "protein", "CD28": "protein", "T cells": "cell_type", "plasmacytoma cells": "cell_type" } }, { "input_text": "Although CD28 is constitutively expressed , its expression is transiently down-regulated following T cell activation and declines progressively with in vitro senescence .", "target_text": { "CD28": "protein" } }, { "input_text": "In vivo , CD8+ T cells and , less frequently , CD4+ T cells may completely lose CD28 surface expression during chronic infections and with aging .", "target_text": { "CD8+ T cells": "cell_type", "CD4+ T cells": "cell_type", "CD28": "protein" } }, { "input_text": "This correlates with changes of nuclear protein-binding activities to two motifs , site alpha and beta , within the CD28 minimal promoter .", "target_text": { "CD28": "protein", "CD28 minimal promoter": "DNA" } }, { "input_text": "Both alpha- and beta-bound complexes are found only in lymphoid tissues , in CD28+ T cells , and in some transformed B cells .", "target_text": { "CD28+ T cells": "cell_type", "transformed B cells": "cell_line" } }, { "input_text": "These complexes are coordinately expressed except during replicative senescence , which is characterized by the down-modulation of site beta - but not site alpha -binding activities .", "target_text": { "site beta": "protein", "site alpha": "protein" } }, { "input_text": "In contrast , T cell activation induces a parallel decline in both site alpha- and beta- binding activities .", "target_text": {} }, { "input_text": "CD4+ and CD8+ T cells differ in their beta-binding profiles , which may explain the more pronounced down-regulation of CD28 in senescent CD8+ T cells .", "target_text": { "CD8+ T cells": "cell_type", "CD28": "protein" } }, { "input_text": "In vivo expanded CD4+CD28null and CD8+CD28null T cells uniformly lack alpha- and beta- bound complexes , resembling the pattern seen in chronically activated cells and not of senescent cells .", "target_text": { "chronically activated cells": "cell_type", "senescent cells": "cell_type" } }, { "input_text": "A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export .", "target_text": { "RanBP1": "protein", "CRM1": "protein", "nuclear pore complex": "protein" } }, { "input_text": "We recently developed an assay in which nuclear export of the shuttling transcription factor NFAT ( nuclear factor of activated T cells ) can be reconstituted in permeabilized cells with the GTPase Ran and the nuclear export receptor CRM1 .", "target_text": { "transcription factor NFAT": "protein", "nuclear factor of activated T cells": "protein", "GTPase": "protein", "Ran": "protein", "CRM1": "protein" } }, { "input_text": "We have now used this assay to identify another export factor .", "target_text": {} }, { "input_text": "After preincubation of permeabilized cells with a Ran mutant that can not hydrolyze GTP ( RanQ69L ) , cytosol supports NFAT export , but CRM1 and Ran alone do not .", "target_text": { "permeabilized cells": "cell_line", "Ran": "protein", "Ran mutant": "protein", "RanQ69L": "protein", "NFAT": "protein", "CRM1": "protein" } }, { "input_text": "The RanQ69L preincubation leads to accumulation of CRM1 at the cytoplasmic periphery of the nuclear pore complex ( NPC ) in association with the p62 complex and Can/Nup214 .", "target_text": { "RanQ69L": "protein", "CRM1": "protein", "nuclear pore complex": "protein", "NPC": "protein", "p62 complex": "protein" } }, { "input_text": "Ran GTP -dependent association of CRM1 with these nucleoporins was reconstituted in vitro .", "target_text": { "Ran": "protein", "CRM1": "protein", "nucleoporins": "protein" } }, { "input_text": "By biochemical fractionation and reconstitution , we showed that RanBP1 restores nuclear export after the RanQ69L preincubation .", "target_text": { "RanBP1": "protein", "RanQ69L": "protein" } }, { "input_text": "It also stimulates nuclear export in cells that have not been preincubated with RanQ69L .", "target_text": { "RanQ69L": "protein" } }, { "input_text": "RanBP1 as well as Ran -binding domains of the cytoplasmic nucleoporin RanBP2 promote the release of CRM1 from the NPC .", "target_text": { "RanBP1": "protein", "Ran": "protein", "Ran -binding domains": "protein", "cytoplasmic nucleoporin": "protein", "RanBP2": "protein", "CRM1": "protein", "NPC": "protein" } }, { "input_text": "Taken together , our results indicate that Ran GTP is important for the targeting of export complexes to the cytoplasmic side of the NPC and that RanBP1 and probably RanBP2 are involved in the dissociation of nuclear export complexes from the NPC in a terminal step of transport .", "target_text": { "Ran": "protein", "NPC": "protein", "RanBP1": "protein", "RanBP2": "protein", "nuclear export complexes": "protein" } }, { "input_text": "c-Myc and E1A induced cellular sensitivity to activated NK cells involves cytotoxic granules as death effectors .", "target_text": { "c-Myc": "protein", "E1A": "protein", "activated NK cells": "cell_type" } }, { "input_text": "The contact of natural killer ( NK ) cells with foreign cells and with certain virus-infected or tumor cells triggers the cytolytic machinery of NK cells .", "target_text": { "natural killer ( NK ) cells": "cell_type", "foreign cells": "cell_type", "NK cells": "cell_type" } }, { "input_text": "This triggering leads to exocytosis of the cytotoxic NK cell granules .", "target_text": { "cytotoxic NK cell granules": "cell_type" } }, { "input_text": "The oncoproteins c-Myc and E1A render cells vulnerable to NK cell mediated cytolysis yet the mechanisms of sensitization are not well understood .", "target_text": { "oncoproteins": "protein", "c-Myc": "protein", "E1A": "protein" } }, { "input_text": "In a model where foreign cells ( rat fibroblasts ) were cocultured with human IL-2 activated NK cells , we observed that NK cells were capable of efficiently killing their targets only if the cells overexpressed the oncogene c-Myc or E1A .", "target_text": { "foreign cells": "cell_type", "rat fibroblasts": "cell_type", "IL-2": "protein", "NK cells": "cell_type", "human IL-2 activated NK cells": "cell_type", "c-Myc": "protein", "E1A": "protein" } }, { "input_text": "Both the parental and the oncogene expressing fibroblasts similarly triggered phosphoinositide hydrolysis in the bound NK cells , demonstrating that NK cells were cytolytically activated in contact with both resistant parental and oncogene expressing sensitive target fibroblasts .", "target_text": { "oncogene expressing fibroblasts": "cell_type", "NK cells": "cell_type", "oncogene expressing sensitive target fibroblasts": "cell_type" } }, { "input_text": "The cell death was independent of wild-type p53 and was not inhibited by an anti-apoptotic protein EIB19K .", "target_text": { "wild-type p53": "protein", "anti-apoptotic protein EIB19K": "protein" } }, { "input_text": "These results provided evidence that c-Myc and E1A activated the NK cell induced cytolysis at a post-triggering stage of NK cell-target cell interaction .", "target_text": { "c-Myc": "protein", "E1A": "protein" } }, { "input_text": "In consistence , the c-Myc and E1A overexpressing fibroblasts were more sensitive to the cytolytic effects of isolated NK cell-derived granules than parental cells .", "target_text": { "c-Myc": "protein", "E1A": "protein", "fibroblasts": "cell_type", "parental cells": "cell_type" } }, { "input_text": "The data indicate that oncogenes activate the cytotoxicity of NK cell granules .", "target_text": { "oncogenes": "DNA" } }, { "input_text": "This mechanism can have a role in directing the cytolytic action of NK cells towards the virus-infected and cancer cells .", "target_text": { "NK cells": "cell_type", "virus-infected and cancer cells": "cell_type" } }, { "input_text": "Unicellular-unilineage erythropoietic cultures : molecular analysis of regulatory gene expression at sibling cell level .", "target_text": { "Unicellular-unilineage erythropoietic cultures": "cell_line" } }, { "input_text": "In vitro studies on hematopoietic control mechanisms have been hampered by the heterogeneity of the analyzed cell populations , ie , lack of lineage specificity and developmental stage homogeneity of progenitor/precursor cells growing in culture .", "target_text": { "progenitor/precursor cells": "cell_type" } }, { "input_text": "We developed unicellular culture systems for unilineage differentiation of purified hematopoietic progenitor cells followed by daughter cell analysis at cellular and molecular level .", "target_text": { "progenitor cells": "cell_type", "purified hematopoietic progenitor cells": "cell_type" } }, { "input_text": "In the culture system reported here , ( 1 ) the growth factor ( GF ) stimulus induces cord blood ( CB ) progenitor cells to proliferate and differentiate/mature exclusively along the erythroid lineage ; ( 2 ) this erythropoietic wave is characterized by less than 4 % apoptotic cells ; ( 3 ) asymmetric divisions are virtually absent , ie , nonresponsive hematopoietic progenitors with no erythropoietic potential are forced into apoptosis ; ( 4 ) the system is cell division controlled ( cdc ) , ie , the number of divisions performed by each cell is monitored .", "target_text": { "growth factor": "protein", "GF": "protein", "progenitor cells": "cell_type", "cord blood ( CB ) progenitor cells": "cell_type", "erythroid lineage": "cell_type", "hematopoietic progenitors": "cell_type" } }, { "input_text": "Single-cell reverse transcriptase -polymerase chain reaction ( RT-PCR ) analysis was applied to this culture system to investigate gene expression of diverse receptors , markers of differentiation , and transcription factors ( EKLF , GATA-1 , GATA-2 , p45 NF-E2 , PU.1 , and SCL/Tal1 ) at discrete stages of erythropoietic development .", "target_text": { "reverse transcriptase": "protein", "receptors": "protein", "markers of differentiation": "protein", "transcription factors": "protein", "EKLF": "protein", "GATA-1": "protein", "GATA-2": "protein", "p45 NF-E2": "protein", "PU.1": "protein", "SCL/Tal1": "protein" } }, { "input_text": "Freshly isolated CD34(+) cells expressed CD34 , c-kit , PU.1 , and GATA-2 but did not express CD36 , erythropoietin receptor ( EpoR ) , SCL/Tal1 , EKLF , NF-E2 , GATA-1 , or glyocophorin A ( GPA ) .", "target_text": { "CD34(+) cells": "cell_type", "CD34": "protein", "c-kit": "protein", "PU.1": "protein", "GATA-2": "protein", "CD36": "protein", "erythropoietin": "protein", "erythropoietin receptor": "protein", "EpoR": "protein", "SCL/Tal1": "protein", "EKLF": "protein", "GATA-1": "protein", "glyocophorin A": "protein", "GPA": "protein" } }, { "input_text": "In early to intermediate stages of erythroid differentiation we monitored the induction of CD36 , Tal1 , EKLF , NF-E2 , and GATA-1 that preceeded expression of EpoR .", "target_text": { "CD36": "protein", "Tal1": "protein", "EKLF": "protein", "NF-E2": "protein", "GATA-1": "protein", "EpoR": "protein" } }, { "input_text": "In late stages of erythroid maturation , GPA was upregulated , whereas CD34 , c-kit , PU.1 , and GATA-2 were barely or not detected .", "target_text": { "GPA": "protein", "CD34": "protein", "c-kit": "protein", "PU.1": "protein", "GATA-2": "protein" } }, { "input_text": "In addition , competitive single-cell RT-PCR was used to assay CD34 mRNA transcripts in sibling CD34 (+) CD38(-) cells differentiating in unilineage erythroid cultures : this analysis allowed us to semiquantitate the gradual downmodulation of CD34 mRNA from progenitor cells through their differentiating erythroid progeny .", "target_text": { "CD34": "protein", "CD34 mRNA transcripts": "RNA", "sibling CD34 (+) CD38(-) cells": "cell_line", "unilineage erythroid cultures": "cell_line", "CD34 mRNA": "RNA", "progenitor cells": "cell_type", "differentiating erythroid progeny": "cell_line" } }, { "input_text": "It is concluded that this novel culture system , coupled with single-cell RT-PCR analysis , may eliminate the ambiguities intrinsic to molecular studies on heterogeneous populations of hematopoietic progenitors /precursors growing in culture , particularly in the initial stages of development .", "target_text": { "hematopoietic progenitors": "cell_type", "hematopoietic progenitors /precursors": "cell_type" } }, { "input_text": "Differences in phosphorylation of the IL-2R associated JAK/STAT proteins between HTLV-I(+) , IL-2-independent and IL-2-dependent cell lines and uncultured leukemic cells from patients with adult T-cell lymphoma/leukemia .", "target_text": { "IL-2R associated JAK/STAT proteins": "protein", "uncultured leukemic cells": "cell_type" } }, { "input_text": "To determine activation status of the IL-2R -associated ( Jak/STAT ) pathway in the HTLV-I infected cells , we examined tyrosine phosphorylation of Jak3 , STAT3 , and STAT5 in several HTLV-I(+) T-cell lines and in uncultured leukemic T cells isolated from patients with adult T-cell lymphoma/leukemia ( ATLL ) .", "target_text": { "IL-2R": "protein", "Jak/STAT": "protein", "HTLV-I infected cells": "cell_line", "Jak3": "protein", "STAT3": "protein", "STAT5": "protein", "HTLV-I(+) T-cell lines": "cell_line", "uncultured leukemic T cells": "cell_type" } }, { "input_text": "Constitutive basal phosphorylation of Jak3 and , usually , STAT3 and STAT5 was detected in all four IL-2 -independent cell lines tested , but in none of the three IL-2 -dependent cell lines .", "target_text": { "Jak3": "protein", "STAT3": "protein", "STAT5": "protein", "IL-2": "protein", "IL-2 -independent cell lines": "cell_line", "IL-2 -dependent cell lines": "cell_line" } }, { "input_text": "Similarly , there was no detectable basal phosphorylation of Jak3 and STAT5 in the leukemic cells from ATLL patients ( 0/8 and 0/3 , respectively ) .", "target_text": { "Jak3": "protein", "STAT5": "protein", "leukemic cells": "cell_type" } }, { "input_text": "However , stimulation with IL-2 resulted in Jak3 and STAT5 phosphorylation in both leukemic ATLL cells and IL-2 -dependent lines .", "target_text": { "IL-2": "protein", "Jak3": "protein", "STAT5": "protein", "leukemic ATLL cells": "cell_type", "IL-2 -dependent lines": "cell_line" } }, { "input_text": "Furthermore , expression of SHP-1 phosphatase which is a negative regulator of cytokine receptor signaling , was lost in most IL-2 independent cell lines ( 3/4 ) but not in the leukemic ATLL cells ( 0/3 ) .", "target_text": { "SHP-1 phosphatase": "protein", "cytokine receptor": "protein", "IL-2": "protein", "IL-2 independent cell lines": "cell_line", "ATLL cells": "cell_type" } }, { "input_text": "Finally , the HTLV-I(+) T-cell lines ( 313 ) but not the control , HTLV-I(-) T-cell lines were resistant to rapamycin and its novel analog RAD .", "target_text": { "HTLV-I(+) T-cell lines": "cell_line", "HTLV-I(-) T-cell lines": "cell_line" } }, { "input_text": "We conclude that ( 1 ) HTLV-I infection per se does not result in a constitutive phosphorylation of the Jak3 , STAT3 , and STAT5 proteins ; ( 2 ) malignant transformation in at least some cases of ATLL does not require the constitutive , but may require IL-2 -induced , activation of the IL-2R Jak/STAT pathway ; and ( 3 ) there are major differences in T-cell immortalization mechanism ( s ) which appear to involve SHP-1 and target molecules for rapamycin and RAD .", "target_text": { "Jak3": "protein", "STAT3": "protein", "STAT5": "protein", "IL-2": "protein", "IL-2R": "protein", "Jak/STAT": "protein", "SHP-1": "protein" } }, { "input_text": "Clonality analysis using X-chromosome inactivation at the human androgen receptor gene ( Humara ) .", "target_text": { "X-chromosome": "DNA", "human androgen receptor gene": "DNA", "Humara": "DNA" } }, { "input_text": "Evaluation of large cohorts of patients with chronic myeloproliferative diseases , secondary neutrophilia , and reactive thrombocytosis .", "target_text": {} }, { "input_text": "Chronic myeloproliferative diseases ( MPDs ) are not associated with consistent cytogenetic or molecular abnormalities .", "target_text": {} }, { "input_text": "Demonstration of clonal cell growth by analysis of X-chromosome inactivation ( XCI ) patterns in females provides a promising tool for diagnosis .", "target_text": { "X-chromosome": "DNA" } }, { "input_text": "However , this technique can be complicated by excessive lyonization of normal cells mimicking clonal cell growth : We analyzed XCI patterns at the human androgen receptor ( HUMARA ) locus in 146 healthy females , 65 women with secondary neutrophilia , 31 women with reactive thrombocytosis , and 86 women with chronic MPDs .", "target_text": { "human androgen receptor ( HUMARA ) locus": "DNA" } }, { "input_text": "A skewed XCI pattern with greater than 75 % amplification of 1 allele ( allele ratio > 3 : 1 ) was found in 22 ( 9.1 % ) of 242 control subjects .", "target_text": { "allele": "DNA" } }, { "input_text": "The incidence of skewing was statistically significantly lower in women younger than 30 years ( 2/73 ) compared with women older than 60 years ( 10/53 ) .", "target_text": {} }, { "input_text": "Of 86 patients with a chronic MPD , 71 ( 82 % ) exhibited an allele ratio greater than 3 : 1 , whereas only 10 ( 12 % ) of 86 age-matched control subjects showed a skewed XCI pattern .", "target_text": { "allele": "DNA" } }, { "input_text": "Although statistical evaluation of the data showed a significant difference between patients with a chronic MPD and control subjects , proof of clonality in individual , especially elderly , patients is difficult .", "target_text": {} }, { "input_text": "GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-xL expression .", "target_text": { "GATA-1": "protein", "erythropoietin": "protein", "bcl-xL": "protein" } }, { "input_text": "The transcription factor GATA-1 is essential for normal erythropoiesis .", "target_text": { "transcription factor": "protein", "GATA-1": "protein" } }, { "input_text": "By examining in vitro-differentiated embryonic stem cells , we showed previously that in the absence of GATA-1 , committed erythroid precursors fail to complete maturation and instead undergo apoptosis .", "target_text": { "vitro-differentiated embryonic stem cells": "cell_line", "GATA-1": "protein", "committed erythroid precursors": "cell_line" } }, { "input_text": "The mechanisms by which GATA-1 controls cell survival are unknown .", "target_text": { "GATA-1": "protein" } }, { "input_text": "Here we report that in erythroid cells , GATA-1 strongly induces the expression of the anti-apoptotic protein bcl-xL , but not the related proteins bcl-2 and mcl-1 .", "target_text": { "erythroid cells": "cell_type", "GATA-1": "protein", "anti-apoptotic protein": "protein", "bcl-xL": "protein", "bcl-2": "protein", "mcl-1": "protein" } }, { "input_text": "Consistent with a role for bcl-xL in mediating GATA-1 -induced erythroid cell survival , in vitro-differentiated bcl-xL -/- embryonic stem cells fail to generate viable mature definitive erythroid cells , a phenotype resembling that of GATA-1 gene disruption .", "target_text": { "bcl-xL": "protein", "GATA-1": "protein", "vitro-differentiated bcl-xL -/- embryonic stem cells": "cell_line", "erythroid cells": "cell_type", "GATA-1 gene": "DNA" } }, { "input_text": "In addition , we show that erythropoietin , which is also required for erythroid cell survival , cooperates with GATA-1 to stimulate bcl-xL gene expression and to maintain erythroid cell viability during terminal maturation .", "target_text": { "erythropoietin": "protein", "GATA-1": "protein", "bcl-xL": "protein" } }, { "input_text": "Together , our data show that bcl-xL is essential for normal erythroid development and suggest a regulatory hierarchy in which bcl-xL is a critical downstream effector of GATA-1 and erythropoietin -mediated signals .", "target_text": { "bcl-xL": "protein", "GATA-1": "protein", "erythropoietin": "protein" } }, { "input_text": "p70(s6k) integrates phosphatidylinositol 3-kinase and rapamycin-regulated signals for E2F regulation in T lymphocytes .", "target_text": { "p70(s6k)": "protein", "phosphatidylinositol 3-kinase": "protein", "E2F": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "In T lymphocytes , the hematopoietic cytokine interleukin-2 ( IL-2 ) uses phosphatidylinositol 3-kinase ( PI 3-kinase ) -induced signaling pathways to regulate E2F transcriptional activity , a critical cell cycle checkpoint .", "target_text": { "T lymphocytes": "cell_type", "hematopoietic cytokine": "protein", "interleukin-2": "protein", "IL-2": "protein", "phosphatidylinositol 3-kinase": "protein", "PI 3-kinase": "protein", "E2F": "protein" } }, { "input_text": "PI 3-kinase also regulates the activity of p70(s6k) , the 40S ribosomal protein S6 kinase , a response that is abrogated by the macrolide rapamycin .", "target_text": { "PI 3-kinase": "protein", "p70(s6k)": "protein", "40S ribosomal protein S6 kinase": "protein" } }, { "input_text": "This immunosuppressive drug is known to prevent T-cell proliferation , but the precise point at which rapamycin regulates T-cell cycle progression has yet to be elucidated .", "target_text": {} }, { "input_text": "Moreover , the effects of rapamycin on , and the role of p70(s6k) in , IL-2 and PI 3-kinase activation of E2Fs have not been characterized .", "target_text": { "p70(s6k)": "protein", "IL-2": "protein", "PI 3-kinase": "protein", "E2Fs": "protein" } }, { "input_text": "Our present results show that IL-2 - and PI 3-kinase -induced pathways for the regulation of E2F transcriptional activity include both rapamycin-resistant and rapamycin-sensitive components .", "target_text": { "IL-2": "protein", "PI 3-kinase": "protein", "E2F": "protein" } }, { "input_text": "Expression of a rapamycin -resistant mutant of p70(s6k) in T cells could restore rapamycin -suppressed E2F responses .", "target_text": { "rapamycin -resistant mutant": "protein", "p70(s6k)": "protein", "T cells": "cell_type", "E2F": "protein" } }, { "input_text": "Thus , the rapamycin -controlled processes involved in E2F regulation appear to be mediated by p70(s6k) .", "target_text": { "E2F": "protein", "p70(s6k)": "protein" } }, { "input_text": "However , the rapamycin -resistant p70(s6k) could not rescue rapamycin inhibition of T-cell cycle entry , consistent with the involvement of additional , rapamycin -sensitive pathways in the control of T-cell cycle progression .", "target_text": { "p70(s6k)": "protein", "rapamycin -resistant p70(s6k)": "protein" } }, { "input_text": "The present results thus show that p70(s6k) is able to regulate E2F transcriptional activity and provide direct evidence for the first time for a link between IL-2 receptors , PI 3-kinase , and p70(s6k) that regulates a crucial G1 checkpoint in T lymphocytes .", "target_text": { "p70(s6k)": "protein", "E2F": "protein", "IL-2": "protein", "PI 3-kinase": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Oxidative stress triggers STAT3 tyrosine phosphorylation and nuclear translocation in human lymphocytes .", "target_text": { "STAT3": "protein", "human lymphocytes": "cell_type" } }, { "input_text": "Oxidizing agents are powerful activators of factors responsible for the transcriptional activation of cytokine-encoding genes involved in tissue injury .", "target_text": { "cytokine-encoding genes": "DNA" } }, { "input_text": "In this study we show evidence that STAT3 is a transcription factor whose activity is modulated by H2O2 in human lymphocytes , in which endogenous catalase had previously been inhibited .", "target_text": { "STAT3": "protein", "transcription factor": "protein", "human lymphocytes": "cell_type", "catalase": "protein" } }, { "input_text": "H2O2 -induced nuclear translocation of STAT3 to form sequence-specific DNA-bound complexes was evidenced by immunoblotting of nuclear fractions and electrophoretic mobility shift assays , and vanadate was found to strongly synergize with H2O2 .", "target_text": { "STAT3": "protein", "sequence-specific DNA-bound complexes": "protein" } }, { "input_text": "Moreover , anti- STAT3 antibodies specifically precipitated a protein of 92 kDa that becomes phosphorylated on tyrosine upon lymphocyte treatment with H2O2 .", "target_text": { "STAT3": "protein", "STAT3 antibodies": "protein", "92 kDa": "protein" } }, { "input_text": "Phenylarsine oxide , a tyrosine phosphatase inhibitor , and genistein , a tyrosine kinase inhibitor , cooperated and cancelled , respectively , the H2O2 -promoted STAT3 nuclear translocation .", "target_text": { "STAT3": "protein" } }, { "input_text": "Evidence is also presented , using Fe2+ /Cu2+ ions , that. OH generated from H2O2 through Fenton reactions could be a candidate oxygen reactive species to directly activate STAT3 .", "target_text": { "STAT3": "protein" } }, { "input_text": "Present data suggest that H2O2 and vanadate are likely to inhibit the activity of intracellular tyrosine phosphatase ( s ) , leading to enhanced STAT3 tyrosine phosphorylation and hence its translocation to the nucleus .", "target_text": { "intracellular tyrosine phosphatase": "protein", "STAT3": "protein" } }, { "input_text": "These results demonstrate that the DNA binding activity of STAT3 can be modulated by oxidizing agents and provide a framework to understand the effects of oxidative stress on the JAK -STAT signaling pathway .", "target_text": { "STAT3": "protein", "JAK": "protein", "-STAT": "protein" } }, { "input_text": "Transcriptional regulation of T lymphocyte development and function .", "target_text": {} }, { "input_text": "The development and function of T lymphocytes are regulated tightly by signal transduction pathways that include specific cell-surface receptors , intracellular signaling molecules , and nuclear transcription factors .", "target_text": { "T lymphocytes": "cell_type", "cell-surface receptors": "protein", "intracellular signaling molecules": "protein", "nuclear transcription factors": "protein" } }, { "input_text": "Since 1988 , several families of functionally important T cell transcription factors have been identified .", "target_text": { "T cell transcription factors": "protein" } }, { "input_text": "These include the Ikaros , LKLF , and GATA3 zinc-finger proteins ; the Ets , CREB/ATF , and NF-kappa B/Rel/NFAT transcription factors ; the Stat proteins ; and HMG box transcription factors such as LEF1 , TCF1 , and Sox4 .", "target_text": { "Ikaros": "protein", "LKLF": "protein", "GATA3 zinc-finger proteins": "protein", "Ets": "protein", "CREB/ATF": "protein", "NF-kappa B/Rel/NFAT transcription factors": "protein", "Stat proteins": "protein", "HMG box transcription factors": "protein", "LEF1": "protein", "TCF1": "protein", "Sox4": "protein" } }, { "input_text": "In this review , we summarize our current understanding of the transcriptional regulation of T cell development and function with particular emphasis on the results of recent gene targeting and transgenic experiments .", "target_text": {} }, { "input_text": "In addition to increasing our understanding of the molecular pathways that regulate T cell development and function , these results have suggested novel targets for genetic and pharmacological manipulation of T cell immunity .", "target_text": {} }, { "input_text": "In vivo inhibition of NF-kappa B in T-lineage cells leads to a dramatic decrease in cell proliferation and cytokine production and to increased cell apoptosis in response to mitogenic stimuli , but not to abnormal thymopoiesis .", "target_text": { "NF-kappa B": "protein", "T-lineage cells": "cell_type", "cytokine": "protein" } }, { "input_text": "To understand the role of NF-kappa B complexes in T cell development and activation , we have generated transgenic mice in which RelA and c-Rel complexes were selectively inhibited in the T-lineage cells by specific expression of a trans-dominant form of I kappa B alpha .", "target_text": { "NF-kappa B": "protein", "RelA": "protein", "c-Rel complexes": "protein", "T-lineage cells": "cell_type", "I kappa B alpha": "protein" } }, { "input_text": "Transgene expression did not affect the thymic development , but led to lowered numbers of splenic T cells and to a dramatic decrease in the ex vivo proliferative response of splenic T lymphocytes .", "target_text": { "T cells": "cell_type", "T lymphocytes": "cell_type", "splenic T lymphocytes": "cell_type" } }, { "input_text": "Analysis of IL-2 and IL-2R alpha expression demonstrated that the perturbation of the proliferation response was not attributable to an abnormal expression of these genes .", "target_text": { "IL-2": "protein", "IL-2R alpha": "protein" } }, { "input_text": "In contrast , expression of IL-4 , IL-10 , and IFN-gamma was strongly inhibited in the transgenic T cells .", "target_text": { "IL-4": "protein", "IL-10": "protein", "IFN-gamma": "protein", "T cells": "cell_type", "transgenic T cells": "cell_type" } }, { "input_text": "The proliferative deficiency of the transgenic T cells was associated with an increased apoptosis .", "target_text": { "transgenic T cells": "cell_type" } }, { "input_text": "These results point out the involvement of NF-kappa B /Rel family proteins in growth signaling pathways by either regulating proteins involved in the IL-2 signaling or by functionally interfering with the cell cycle progression .", "target_text": { "NF-kappa B": "protein", "NF-kappa B /Rel family proteins": "protein", "regulating proteins": "protein", "IL-2": "protein" } }, { "input_text": "Paradoxical priming effects of IL-10 on cytokine production .", "target_text": { "IL-10": "protein", "cytokine": "protein" } }, { "input_text": "IL-10 is a well-known immunosuppressive and/or anti-inflammatory cytokine .", "target_text": { "IL-10": "protein" } }, { "input_text": "However , we report in vitro experimental studies in which IL-10 primed leukocytes and led to an enhanced production of tumor necrosis factor ( TNF ) upon further stimulation by lipopolysaccharide ( LPS ) .", "target_text": { "IL-10": "protein", "IL-10 primed leukocytes": "cell_line", "tumor necrosis factor": "protein", "TNF": "protein" } }, { "input_text": "Monocytes and peripheral blood mononuclear cells ( PBMC ) prepared from whole blood maintained for 20 h at 37 degrees C in the presence of recombinant human IL-10 had an enhanced capacity to produce TNF in response to LPS .", "target_text": { "Monocytes": "cell_type", "peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type", "IL-10": "protein", "recombinant human IL-10": "protein", "TNF": "protein" } }, { "input_text": "In addition to TNF , LPS-induced IL-6 and spontaneous IL-1ra production were also enhanced .", "target_text": { "TNF": "protein" } }, { "input_text": "When isolated PBMC were first cultured for 20 h in the presence of IL-10 on Teflon to prevent adherence , washed to remove IL-10 and then further cultured in plastic dishes for an additional 20 h in the presence of LPS or IL-1beta , an enhanced release of TNF was observed .", "target_text": { "PBMC": "cell_type", "IL-10": "protein", "IL-1beta": "protein", "TNF": "protein" } }, { "input_text": "This was not the case when PBMC were pre-cultured in plastic multidishes in the presence of IL-10 .", "target_text": { "PBMC": "cell_type", "IL-10": "protein" } }, { "input_text": "TNF mRNA expression induced by LPS was decreased when the pre-treatment of PBMC with IL-10 was performed on plastic , whereas this was not the case when cells were pre-cultured with IL-10 on Teflon .", "target_text": { "TNF": "protein", "TNF mRNA": "RNA", "PBMC": "cell_type", "IL-10": "protein" } }, { "input_text": "Furthermore , NFkappaB translocation following LPS activation was higher after IL-10 pre-treatment on Teflon than on plastic .", "target_text": { "IL-10": "protein" } }, { "input_text": "Interestingly , an enhanced frequency of CD16 and CD68(+) cells among the CD14(+) cells was observed in the presence of IL-10 , independently of the pre-culture conditions of the PBMC .", "target_text": { "CD16": "protein", "IL-10": "protein", "PBMC": "cell_type" } }, { "input_text": "Altogether , these results indicate that the IL-10 -induced up-regulation of cytokine production depends on the prevention of monocyte adherence by red cells in the whole blood assays or by cultures of PBMC on Teflon .", "target_text": { "IL-10": "protein", "cytokine": "protein", "red cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "In contrast , the adherence parameter has no effect on the IL-10 -induced modulation of some monocyte surface markers .", "target_text": { "IL-10": "protein", "monocyte surface markers": "protein" } }, { "input_text": "Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F .", "target_text": { "transcription factor": "protein", "E2F": "protein" } }, { "input_text": "Initiation of DNA replication requires the function of MCM gene products , which participate in ensuring that DNA replication occurs only once in the cell cycle .", "target_text": { "MCM gene products": "protein" } }, { "input_text": "Expression of all mammalian genes of the MCM family is induced by growth stimulation , unlike yeast , and the mRNA levels peak at G1/S boundary .", "target_text": { "mammalian genes": "DNA", "MCM family": "DNA" } }, { "input_text": "In this study , we examined the transcriptional activities of isolated human MCM gene promoters .", "target_text": { "isolated human MCM gene promoters": "DNA" } }, { "input_text": "Human MCM5 and MCM6 promoters with mutation in the E2F sites failed in promoter regulation following serum stimulation and exogenous E2F expression .", "target_text": { "E2F": "protein", "E2F sites": "DNA" } }, { "input_text": "In addition , we identified a novel E2F -like sequence in human MCM6 promoter which cooperates with the authentic E2F sites in E2F -dependent regulation .", "target_text": { "E2F": "protein", "E2F -like sequence": "DNA", "human MCM6 promoter": "DNA", "E2F sites": "DNA" } }, { "input_text": "Forced expression of E2F1 could induce expression of all members of the endogenous MCM genes in rat embryonal fibroblast REF52 cells .", "target_text": { "E2F1": "protein", "endogenous MCM genes": "DNA", "rat embryonal fibroblast REF52 cells": "cell_line" } }, { "input_text": "Our results demonstrated that the growth-regulated expression of mammalian MCM5 and MCM6 genes , and presumably other MCM members , is primarily regulated by E2F through binding to multiple E2F sites in the promoters .", "target_text": { "E2F": "protein", "E2F sites": "DNA", "multiple E2F sites": "DNA", "promoters": "DNA" } }, { "input_text": "An essential role for NF-kappaB in human CD34(+) bone marrow cell survival .", "target_text": { "NF-kappaB": "protein", "human CD34(+) bone marrow cell": "cell_type" } }, { "input_text": "The transcription factor , NF-kappaB , is important for T-cell activation , B-cell maturation , and human immunodeficiency virus transcription and plays a role in alternatively mediating and protecting against apoptosis in a variety of cell types .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "However , a role for NF-kappaB in human CD34(+) bone marrow cells has not been described .", "target_text": { "NF-kappaB": "protein", "human CD34(+) bone marrow cells": "cell_type" } }, { "input_text": "We provide evidence here that virtually all human CD34(+) bone marrow cells express NF-kappaB that can be activated by exposure to phorbol 12-myristate 13-acetate and a variety of cytokines , eg , tumor necrosis factor alpha , interleukin-3 , and granulocyte-macrophage colony-stimulating factor .", "target_text": { "human CD34(+) bone marrow cells": "cell_type", "NF-kappaB": "protein", "cytokines": "protein", "tumor necrosis factor alpha": "protein", "interleukin-3": "protein", "granulocyte-macrophage colony-stimulating factor": "protein" } }, { "input_text": "In addition , we demonstrate that NF-kappaB may be required for human CD34(+) bone marrow cell clonogenic function and survival .", "target_text": { "NF-kappaB": "protein", "CD34(+) bone marrow cell": "cell_type" } }, { "input_text": "These results offer insight into a new role for NF-kappaB in maintaining survival and function in hematopoietic stem and progenitor cells and suggest that proposed strategies involving inhibition of NF-kappaB activation as an adjunct to cancer chemotherapy should be approached with caution .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "High molecular weight dextran sulfate increases the activity of NF-kappaB -regulated promoter in monocyte-derived macrophages .", "target_text": { "NF-kappaB": "protein", "NF-kappaB -regulated promoter": "DNA", "monocyte-derived macrophages": "cell_type" } }, { "input_text": "It is known that sulfated polysaccharides can mimic the action of common T-cell mitogens .", "target_text": { "common T-cell mitogens": "protein" } }, { "input_text": "To investigate the molecular basis of the mitogenic effect of high molecular weight dextran sulfate ( HMDS ) , monocyte-derived macrophages were transfected with recombinant plasmid containing chloramphenicol acetyl transferase ( CAT ) reporter gene under the control of the HIV-1 long terminal repeat ( LTR ) promoter , which is regulated by transcription factor NF-kappaB .", "target_text": { "monocyte-derived macrophages": "cell_type", "recombinant plasmid": "DNA", "chloramphenicol acetyl transferase": "protein", "chloramphenicol acetyl transferase ( CAT ) reporter gene": "DNA", "HIV-1 long terminal repeat ( LTR ) promoter": "DNA", "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "We observed that HMDS , similar to bacterial lipopolysaccharide ( LPS ) , increases the expression of CAT reporter gene suggesting increased activity of NF-kappaB .", "target_text": { "CAT reporter gene": "DNA", "NF-kappaB": "protein" } }, { "input_text": "The activation of NF-kappaB correlated with the increased expression of B7.1 molecules .", "target_text": { "NF-kappaB": "protein", "B7.1 molecules": "protein" } }, { "input_text": "It was postulated that this NF-kappaB -regulated promoter might play a role in the activation of the accessory cells as well as the rate of replication of HIV-1 in monocyte-derived macrophages .", "target_text": { "NF-kappaB": "protein", "NF-kappaB -regulated promoter": "DNA", "monocyte-derived macrophages": "cell_type" } }, { "input_text": "Transcription factors Sp1 and AP-2 mediate induction of acid sphingomyelinase during monocytic differentiation .", "target_text": { "Transcription factors": "protein", "Sp1": "protein", "AP-2": "protein", "acid sphingomyelinase": "protein" } }, { "input_text": "Cells from the human monocytic leukemia cell line THP-1 differentiate towards a macrophage-like phenotype when stimulated with phorbol 12-myristate -13- acetate ( PMA ) , 1,25-dihydroxy-vitamin D3 , and various other agents .", "target_text": { "human monocytic leukemia cell line": "cell_line", "THP-1": "cell_line" } }, { "input_text": "We demonstrate here that the expression of the lysosomal enzyme acid sphingomyelinase ( ASM ; E.C.3.1.4.12 ) is induced during this process and is strongly elevated in differentiated THP-1 cells , as well as in differentiated human mononuclear phagocytes .", "target_text": { "lysosomal enzyme": "protein", "acid sphingomyelinase": "protein", "THP-1 cells": "cell_line", "human mononuclear phagocytes": "cell_type" } }, { "input_text": "Using Northern blotting , RNase protection assay , and nuclear run-on analyses , we show that the up-regulation of ASM expression is regulated mainly at the level of transcription and that new protein synthesis is required for enhanced ASM activity .", "target_text": { "RNase": "protein" } }, { "input_text": "This cell-type specific induction by PMA treatment was further investigated with respect to transcriptional control .", "target_text": {} }, { "input_text": "A series of 5' deletion derivatives of the upstream regulatory region were used in transient transfection assays to identify promoter elements required for basal and inducible gene expression .", "target_text": { "5' deletion derivatives": "DNA", "upstream regulatory region": "DNA", "promoter elements": "DNA" } }, { "input_text": "A PMA responsive element was localized to a region between -319 and -219 bp upstream of the initiation codon and co-transfections with transcription factor expression plasmids for AP-2 and Sp1 resulted in augmented ASM promoter activity , which was abolished when the binding sites for these two factors were deleted .", "target_text": { "PMA responsive element": "DNA", "-319 and -219 bp upstream": "DNA", "transcription factor expression plasmids": "DNA", "AP-2": "protein", "Sp1": "protein", "binding sites": "DNA" } }, { "input_text": "Using electrophoretic mobility shift assays and supershift assays we demonstrate that this region is specifically bound by Sp1 and AP-2 .", "target_text": { "Sp1": "protein", "AP-2": "protein" } }, { "input_text": "These factors are present in nuclear extracts prepared from both induced and uninduced THP-1 cells .", "target_text": { "THP-1 cells": "cell_line" } }, { "input_text": "However , the intensity of the complex formed appeared to increase when nuclear extracts from PMA -treated cells were used .", "target_text": { "PMA -treated cells": "cell_line" } }, { "input_text": "From these studies , we conclude that a concerted action of the transcription factors AP-2 and Sp1 is essential for the up -regulation of ASM expression during the process of macrophage differentiation .", "target_text": { "transcription factors": "protein", "AP-2": "protein", "Sp1": "protein" } }, { "input_text": "LPS -Induced NF-kappaB activation and TNF-alpha release in human monocytes are protein tyrosine kinase dependent and protein kinase C independent .", "target_text": { "NF-kappaB": "protein", "TNF-alpha": "protein", "human monocytes": "cell_type", "protein tyrosine kinase": "protein", "protein kinase C": "protein" } }, { "input_text": "BACKGROUND : Tumor necrosis factor alpha ( TNF-alpha ) is an important mediator of septic shock .", "target_text": { "Tumor necrosis factor alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "Endotoxin ( LPS ) signal transduction in human monocytes leads to activation of nuclear factor-kappa B ( NF-kappaB ) and TNF-alpha release .", "target_text": { "human monocytes": "cell_type", "nuclear factor-kappa B": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein" } }, { "input_text": "Previous studies have implicated activation of both protein kinase C ( PKC ) and protein tyrosine kinases ( PTK ) in LPS -induced NF-kappaB activation and TNF-alpha production .", "target_text": { "protein kinase C": "protein", "PKC": "protein", "protein tyrosine kinases": "protein", "PTK": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein" } }, { "input_text": "We hypothesized that inhibition of either PKC or PTK would decrease LPS -induced NF-kappaB DNA binding and TNF-alpha release in human monocytes .", "target_text": { "PKC": "protein", "PTK": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein", "human monocytes": "cell_type" } }, { "input_text": "MATERIALS AND METHODS : Human monocytes were stimulated with PMA ( 50 ng/ml ) alone or LPS ( 100 ng/ml ) with and without a nonspecific serine /threonine protein kinase inhibitor staurosporine ( Stauro ) , a specific pan- PKC inhibitor bisindolylmaleimide ( Bis ) , or an inhibitor of PTK genistein ( Gen ) .", "target_text": { "Human monocytes": "cell_type", "serine /threonine protein kinase": "protein", "PKC": "protein", "PTK": "protein" } }, { "input_text": "TNF-alpha release in culture supernatants was measured by an ELISA .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "NF-kappaB DNA binding was evaluated by electrophoretic mobility shift assay .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "RESULTS : LPS increased NF-kappaB DNA binding and TNF-alpha release in human monocytes .", "target_text": { "NF-kappaB": "protein", "TNF-alpha": "protein", "human monocytes": "cell_type" } }, { "input_text": "Nonspecific protein kinase inhibition inhibited NF-kappaB activation and TNF-alpha release , while specific PKC inhibition with Bis had no effect on LPS -induced NF-kappaB DNA binding or TNF-alpha release .", "target_text": { "protein kinase": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein", "PKC": "protein" } }, { "input_text": "PTK inhibition with Gen attenuated both LPS -induced NF-kappaB DNA binding and TNF-alpha production in human monocytes .", "target_text": { "PTK": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein", "human monocytes": "cell_type" } }, { "input_text": "Direct activation of PKC with PMA induced both NF-kappaB activation and TNF-alpha production by human monocytes .", "target_text": { "PKC": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein", "human monocytes": "cell_type" } }, { "input_text": "CONCLUSIONS : These results suggest that LPS -induced NF-kappaB activation and TNF-alpha release in human monocytes are independent of PKC activity .", "target_text": { "NF-kappaB": "protein", "TNF-alpha": "protein", "human monocytes": "cell_type", "PKC": "protein" } }, { "input_text": "Furthermore , our results provide evidence that PTK plays a role in LPS -induced NF-kappaB activation and TNF-alpha release in human monocytes and thus could be a potential therapeutic target in inflammatory states .", "target_text": { "PTK": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein", "human monocytes": "cell_type" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "Amelioration of rat cerulein pancreatitis by guamerin-derived peptide , a novel elastase inhibitor .", "target_text": { "elastase": "protein" } }, { "input_text": "Increased activity of various proteases is observed in both human and experimental pancreatitis ; however , the information on the effects of specific protease inhibitors on the disease is limited .", "target_text": { "proteases": "protein" } }, { "input_text": "In this study we show that a novel elastase inhibitor , guamerin-derived synthetic peptide ( GDSP ) , improves the parameters of cerulein-induced acute pancreatitis in the rat .", "target_text": {} }, { "input_text": "The effects of GDSP on pancreatic weight , serum amylase and lipase , morphologic changes in the pancreas , neutrophil infiltration , and nuclear factor KB ( NF-KB ) activation were measured in rats infused with supramaximal dose of cerulein ( 5 ( g/kg/h ) for 6 h .", "target_text": { "nuclear factor KB": "protein", "NF-KB": "protein" } }, { "input_text": "The effects of GDSP were also measured on superoxide formation by activated human neutrophils .", "target_text": { "activated human neutrophils": "cell_type" } }, { "input_text": "The effects of GDSP were compared with those of another elastase inhibitor , elastatinal .", "target_text": {} }, { "input_text": "GDSP significantly inhibited edema formation , neutrophil infiltration , acinar cell damage , and plasma lipase and amylase increases caused by cerulein .", "target_text": { "plasma lipase": "protein", "amylase": "protein" } }, { "input_text": "GDSP also completely inhibited superoxide formation in the human neutrophils stimulated by N-formyl-methionine-leucine-phenyl-alanine ( fMLP ) or 12-O-tetradecanoylphorbol-13-acetate ( TPA ) .", "target_text": { "human neutrophils": "cell_type" } }, { "input_text": "Elastatinal had some of the same effects as GDSP but was less potent and effective .", "target_text": {} }, { "input_text": "These results demonstrate a beneficial effect of GDSP , a novel specific elastase inhibitor , on the development of rat cerulein pancreatitis .", "target_text": {} }, { "input_text": "A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor alpha gene expression : molecular cloning , sequencing , characterization , and chromosomal assignment .", "target_text": { "lipopolysaccharide-induced transcription factor": "protein", "tumor necrosis factor alpha": "protein" } }, { "input_text": "Lipopolysaccharide ( LPS ) is a potent stimulator of monocytes and macrophages , causing secretion of tumor necrosis factor alpha ( TNF-alpha ) and other inflammatory mediators .", "target_text": { "monocytes": "cell_type", "macrophages": "cell_type", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "Given the deleterious effects to the host of TNF-alpha , it has been postulated that TNF-alpha gene expression must be tightly regulated .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "The nature of the nuclear factor ( s ) that control TNF-alpha gene transcription in humans remains obscure , although NF-kappaB has been suggested .", "target_text": { "nuclear factor": "protein", "TNF-alpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "Our previous studies pertaining to macrophage response to LPS identified a novel DNA-binding domain located from -550 to -487 in the human TNF-alpha promoter that contains transcriptional activity , but lacks any known NF-kappaB -binding sites .", "target_text": { "DNA-binding domain": "protein", "TNF-alpha": "protein", "human TNF-alpha promoter": "DNA", "NF-kappaB": "protein", "-binding sites": "DNA" } }, { "input_text": "We have used this DNA fragment to isolate and purify a 60-kDa protein binding to this fragment and obtained its amino-terminal sequence , which was used to design degenerate probes to screen a cDNA library from THP-1 cells .", "target_text": { "60-kDa protein": "protein", "amino-terminal sequence": "protein", "degenerate probes": "DNA", "THP-1 cells": "cell_line" } }, { "input_text": "A novel cDNA clone ( 1.8 kb ) was isolated and fully sequenced .", "target_text": { "cDNA clone": "DNA" } }, { "input_text": "Characterization of this cDNA clone revealed that its induction was dependent on LPS activation of THP-1 cells ; hence , the name LPS -induced TNF-alpha factor ( LITAF ) .", "target_text": { "cDNA clone": "DNA", "THP-1 cells": "cell_line", "TNF-alpha": "protein", "LPS -induced TNF-alpha factor": "protein", "LITAF": "protein" } }, { "input_text": "Inhibition of LITAF mRNA expression in THP-1 cells resulted in a reduction of TNF-alpha transcripts .", "target_text": { "LITAF": "protein", "LITAF mRNA": "RNA", "THP-1 cells": "cell_line", "TNF-alpha": "protein" } }, { "input_text": "In addition , high level of expression of LITAF mRNA was observed predominantly in the placenta , peripheral blood leukocytes , lymph nodes , and the spleen .", "target_text": { "LITAF": "protein", "LITAF mRNA": "RNA", "peripheral blood leukocytes": "cell_type" } }, { "input_text": "Finally , chromosomal localization using fluorescence in situ hybridization revealed that LITAF mapped to chromosome 16p12-16p13.3 .", "target_text": { "LITAF": "protein", "chromosome 16p12-16p13.3": "DNA" } }, { "input_text": "Together , these findings suggest that LITAF plays an important role in the activation of the human TNF-alpha gene and proposes a new mechanism to control TNF-alpha gene expression .", "target_text": { "LITAF": "protein", "TNF-alpha": "protein", "human TNF-alpha gene": "DNA" } }, { "input_text": "A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection [ see comments ]", "target_text": { "human IFNGR1 small deletion hotspot": "DNA" } }, { "input_text": "The immunogenetic basis of severe infections caused by bacille Calmette-Guerin vaccine and environmental mycobacteria in humans remains largely unknown .", "target_text": {} }, { "input_text": "We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele .", "target_text": { "overlapping IFNGR1 frameshift small deletions": "DNA", "wild-type IFNGR1 allele": "DNA" } }, { "input_text": "There were 12 independent mutation events at a single mutation site , defining a small deletion hotspot .", "target_text": { "single mutation site": "DNA", "small deletion hotspot": "DNA" } }, { "input_text": "Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication .", "target_text": {} }, { "input_text": "The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain , which , through a combination of impaired recycling , abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect .", "target_text": { "cell-surface IFNgamma receptors": "protein", "intra-cytoplasmic domain": "protein", "IFNgamma": "protein" } }, { "input_text": "We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria .", "target_text": { "human IFNGR1 small deletions": "DNA" } }, { "input_text": "Characterization of expression of the gene for human pterin carbinolamine dehydratase/dimerization cofactor of HNF1 .", "target_text": { "human pterin carbinolamine dehydratase/dimerization cofactor": "protein", "HNF1": "protein" } }, { "input_text": "Pterin carbinolamine dehydratase/dimerization cofactor of HNF1 ( PCD/DCoH ) is a dual-function protein .", "target_text": { "Pterin carbinolamine dehydratase/dimerization cofactor": "protein", "HNF1": "protein", "PCD/DCoH": "protein", "dual-function protein": "protein" } }, { "input_text": "In the cytoplasm it acts as a dehydratase in the regeneration of tetrahydrobiopterin , the cofactor for aromatic amino acid hydroxylases .", "target_text": { "dehydratase": "protein", "tetrahydrobiopterin": "protein", "aromatic amino acid hydroxylases": "protein" } }, { "input_text": "In the nucleus , it functions as a dimerization cofactor of HNF1 and increases the transcriptional activity of HNF1 .", "target_text": { "dimerization cofactor": "protein", "HNF1": "protein" } }, { "input_text": "To deepen our understanding of this protein , we characterized its expression in human tissues and cells .", "target_text": {} }, { "input_text": "Human PCD/DCoH was present predominantly in liver and kidney , with significant amounts in testis and ovary , trace amounts in lung , and undetectable levels in whole brain , heart , and spleen .", "target_text": { "PCD/DCoH": "protein" } }, { "input_text": "It was expressed in all of the cells that were examined .", "target_text": {} }, { "input_text": "Importantly , it was also present in the nucleus of HeLa cells , which lack HNF1 , and in the cytoplasm of fibroblasts that have little or no tetrahydrobiopterin .", "target_text": { "HeLa cells": "cell_line", "HNF1": "protein", "fibroblasts": "cell_type", "tetrahydrobiopterin": "protein" } }, { "input_text": "The expression of human PCD/DCoH in the liver and nonhepatic cells was compared at both the mRNA and protein levels .", "target_text": { "PCD/DCoH": "protein", "human PCD/DCoH": "protein", "nonhepatic cells": "cell_type" } }, { "input_text": "Although the mRNA level in liver was only fourfold higher than that in keratinocytes and fibroblasts , the hepatic PCD/DCoH protein level was 20-fold higher than that in normal human epidermal keratinocytes and dermal fibroblasts .", "target_text": { "keratinocytes": "cell_type", "fibroblasts": "cell_type", "PCD/DCoH": "protein", "hepatic PCD/DCoH protein": "protein", "normal human epidermal keratinocytes": "cell_type", "dermal fibroblasts": "cell_type" } }, { "input_text": "Cloning of the 5' and 3' untranslated region ( UTR ) of human keratinocyte PCD/DCoH revealed that it has 53 bp more of GC-rich 5' untranslated sequence than the published liver PCD/DCoH .", "target_text": { "5' and 3' untranslated region": "DNA", "UTR": "DNA", "human keratinocyte": "cell_type", "PCD/DCoH": "protein", "human keratinocyte PCD/DCoH": "protein", "GC-rich 5' untranslated sequence": "DNA", "liver PCD/DCoH": "protein" } }, { "input_text": "In vitro transcription and translation analysis showed that the longer 5' UTR resulted in about a 35 % decrease in translation efficiency .", "target_text": { "UTR": "DNA", "5' UTR": "DNA" } }, { "input_text": "These data show that human PCD/DCoH is not only present in cells where tetrahydrobiopterin is synthesized or HNF1 is present but is a widely distributed protein .", "target_text": { "PCD/DCoH": "protein", "human PCD/DCoH": "protein", "tetrahydrobiopterin": "protein", "HNF1": "protein" } }, { "input_text": "Its differential expression in different tissues and cells is regulated not only at the transcriptional level but also at the translational level .", "target_text": {} }, { "input_text": "NF-kappaB regulates Fas/APO-1/CD95- and TCR- mediated apoptosis of T lymphocytes .", "target_text": { "NF-kappaB": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "The maintenance of lymphocyte homeostasis by apoptosis is a critical regulatory mechanism in the normal immune system .", "target_text": {} }, { "input_text": "The transcription factor NF-kappaB has been shown to play a role in protecting cells against death mediated by TNF We show here that NF-kappaB also has a role in regulating Fas / APO-1 / CD95 -mediated death , a major pathway of peripheral T cell death .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein", "TNF": "protein", "Fas": "protein", "APO-1": "protein", "CD95": "protein", "peripheral T cell": "cell_type" } }, { "input_text": "Transfection of Jurkat cells with the NF-kappaB subunits p50 and p65 confers resistance against Fas-mediated apoptosis .", "target_text": { "Jurkat cells": "cell_line", "NF-kappaB subunits": "protein", "p50": "protein", "p65": "protein" } }, { "input_text": "Reciprocally , inhibition of NF-kappaB activation by a soluble peptide inhibitor or a dominant form of the NF-kappaB inhibitor , IkappaB , makes the cells more susceptible to Fas-mediated apoptosis .", "target_text": { "NF-kappaB": "protein", "IkappaB": "protein" } }, { "input_text": "Furthermore , inhibition of NF-kappaB activation by a soluble peptide inhibitor rendered a T cell hybridoma more susceptible to TCR-mediated apoptosis .", "target_text": { "NF-kappaB": "protein", "T cell hybridoma": "cell_line" } }, { "input_text": "Correspondingly , transfection of p50 and p65 provided considerable protection from TCR-mediated apoptosis .", "target_text": { "p50": "protein", "p65": "protein" } }, { "input_text": "These observations were corroborated by studies on Fas -mediated death in primary T cells .", "target_text": { "Fas": "protein", "primary T cells": "cell_type" } }, { "input_text": "Concanavalin A -activated cycling T cell blasts from mice that are transgenic for the dominant IkappaB molecule have increased sensitivity to Fas-mediated apoptosis , associated with a down-regulation of NF-kappaB complexes in the nucleus .", "target_text": { "cycling T cell blasts": "cell_line", "IkappaB": "protein", "dominant IkappaB molecule": "protein", "NF-kappaB": "protein", "NF-kappaB complexes": "protein" } }, { "input_text": "In addition , blocking TNF , itself a positive regulator of NF-kappaB , with neutralizing antibodies renders the cells more susceptible to anti-Fas-mediated apoptosis .", "target_text": { "TNF": "protein", "NF-kappaB": "protein", "neutralizing antibodies": "protein" } }, { "input_text": "In summary , our results provide compelling evidence that NF-kappaB protects against Fas -mediated death and is likely to be an important regulator of T cell homeostasis and tolerance .", "target_text": { "NF-kappaB": "protein", "Fas": "protein" } }, { "input_text": "T helper differentiation proceeds through Stat1-dependent , Stat4-dependent and Stat4-independent phases .", "target_text": {} }, { "input_text": "Much of our focus in understanding Th1/Th2 development has been on the signals delivered by IL-12 and IL-4 as final determinants of terminal T cell differentiation .", "target_text": { "IL-12": "protein", "IL-4": "protein" } }, { "input_text": "Because extinction of IL-12 signaling in early Th2 development could potentially be important in imprinting a more permanent Th2 phenotype on a population of T cells , we have also examined various parameters regulating the IL-12 signaling pathway .", "target_text": { "IL-12": "protein", "T cells": "cell_type" } }, { "input_text": "Whereas IL-4 appears to repress functional IL-12 signaling through inhibition of IL-12R beta 2 expression , IFN-gamma in the mouse , and IFN-alpha in the human appear to induce IL-12R beta 2 expression and promote IL-12 responsiveness .", "target_text": { "IL-4": "protein", "IL-12": "protein", "IL-12R beta 2": "protein", "IFN-gamma": "protein", "IFN-alpha": "protein" } }, { "input_text": "We propose that Th1 development can be considered in two stages , capacitance and development .", "target_text": {} }, { "input_text": "Capacitance would simply involve expression of IL-12R beta 1 and beta 2 subunits , regulated by TCR , IL-4 and IFNs .", "target_text": { "IL-4": "protein", "IFNs": "protein" } }, { "input_text": "The second stage , development , we propose is the true IL-12 induced developmental stage , involving expression of Stat4 inducible proteins .", "target_text": { "IL-12": "protein", "Stat4": "protein", "Stat4 inducible proteins": "protein" } }, { "input_text": "In the human , this may also occur via IFN-alpha , which is able to activate Stat4 .", "target_text": { "IFN-alpha": "protein", "Stat4": "protein" } }, { "input_text": "It is perhaps possible that all of Stat4 actions on Th1 development may be exert directly by Stat4 at the IFN-gamma gene , however we suggest that , more likely , Stat4 may act to induce Th1 development through the induction of other non-cytokine genes , whose stable expression maintains the transcriptional state of a Th1 cell .", "target_text": { "Stat4": "protein", "IFN-gamma": "protein", "IFN-gamma gene": "DNA", "non-cytokine genes": "DNA", "Th1 cell": "cell_type" } }, { "input_text": "Lineage-specific activation of STAT3 by interferon-gamma in human neutrophils .", "target_text": { "STAT3": "protein", "interferon-gamma": "protein", "human neutrophils": "cell_type" } }, { "input_text": "Binding of interferon-gamma ( IFN-gamma ) to its heterodimeric receptor induces activation of the tyrosine kinases JAK1 and JAK2 followed by tyrosine phosphorylation of STAT1alpha .", "target_text": { "interferon-gamma": "protein", "IFN-gamma": "protein", "tyrosine kinases": "protein", "JAK1": "protein", "JAK2": "protein", "STAT1alpha": "protein" } }, { "input_text": "Selective activation of STAT1alpha at the IFN-gamma receptor is achieved by specific interaction between a cytosolic tyrosine motif including Y440 in the IFN-gamma receptor alpha-chain and the SH2 domain of STAT1alpha .", "target_text": { "STAT1alpha": "protein", "IFN-gamma": "protein", "IFN-gamma receptor": "protein", "cytosolic tyrosine motif": "protein", "Y440": "protein", "IFN-gamma receptor alpha-chain": "protein", "SH2 domain": "protein" } }, { "input_text": "We demonstrate that , in addition to STAT1alpha , STAT3 is also activated by IFN-gamma in human neutrophils .", "target_text": { "STAT1alpha": "protein", "STAT3": "protein", "IFN-gamma": "protein", "human neutrophils": "cell_type" } }, { "input_text": "The activation of STAT3 was not found in human eosinophils , monocytes , and HL-60 cells , although the STAT3 protein was expressed in these cells .", "target_text": { "STAT3": "protein", "human eosinophils": "cell_type", "monocytes": "cell_type", "HL-60 cells": "cell_line", "STAT3 protein": "protein" } }, { "input_text": "The cell type-specific activation of STAT3 by IFN-gamma was also observed in neutrophils that are differentiated in vitro from human CD34+ hematopoietic stem cells .", "target_text": { "STAT3": "protein", "IFN-gamma": "protein", "neutrophils": "cell_type", "human CD34+ hematopoietic stem cells": "cell_type" } }, { "input_text": "These results indicate that a single cytokine receptor can activate different STAT family members in a cell-specific manner , which might result in cell-specific gene transcription .", "target_text": { "cytokine receptor": "protein", "STAT family members": "protein" } }, { "input_text": "Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells .", "target_text": { "NF-ATc": "protein", "effector T cells": "cell_type" } }, { "input_text": "The transcription factor NF-ATc is synthesized in three prominent isoforms .", "target_text": { "transcription factor": "protein", "NF-ATc": "protein", "isoforms": "protein" } }, { "input_text": "These differ in the length of their C terminal peptides and mode of synthesis .", "target_text": {} }, { "input_text": "Due to a switch from the use of a 3' polyA site to a more proximal polyA site , NF-ATc expression switches from the synthesis of the two longer isoforms in naive T cells to that of short isoform A in T effector cells .", "target_text": { "3' polyA site": "DNA", "proximal polyA site": "DNA", "NF-ATc": "protein", "naive T cells": "cell_type", "isoform A": "protein", "T effector cells": "cell_type" } }, { "input_text": "The relative low binding affinity of cleavage stimulation factor CstF-64 to the proximal polyA site seems to contribute to its neglect in naive T cells .", "target_text": { "cleavage stimulation factor": "protein", "CstF-64": "protein", "proximal polyA site": "DNA", "naive T cells": "cell_type" } }, { "input_text": "These alternative polyadenylation events ensure the rapid accumulation of high concentrations of NF-ATc necessary to exceed critical threshold levels of NF-ATc for gene induction in effector T cells .", "target_text": { "NF-ATc": "protein", "effector T cells": "cell_type" } }, { "input_text": "Estrogen and progesterone induction of survival of monoblastoid cells undergoing TNF-alpha -induced apoptosis .", "target_text": { "monoblastoid cells": "cell_type", "TNF-alpha": "protein" } }, { "input_text": "Induction of apoptosis of mononucleated cells is a physiological process for regulating the intensity of the immune response .", "target_text": { "mononucleated cells": "cell_type" } }, { "input_text": "The female steroid hormones estrogen ( E2 ) and progesterone ( Prog ) are known to modulate the reactivity of the immune system ; recently it has been demonstrated that they can regulate induction of apoptosis of endothelial cells and osteoblasts .", "target_text": { "endothelial cells": "cell_type", "osteoblasts": "cell_type" } }, { "input_text": "TNF-alpha -mediated induction of apoptosis has been well characterized in myeloid cells .", "target_text": { "TNF-alpha": "protein", "myeloid cells": "cell_type" } }, { "input_text": "We investigated whether E2 and Prog could interfere with TNF-alpha -induced apoptosis of the monoblastoid U937 cell line .", "target_text": { "TNF-alpha": "protein", "monoblastoid U937 cell line": "cell_line" } }, { "input_text": "Treatment with E2 or Prog increased survival and prevented apoptosis induced by TNF-alpha in both undifferentiated and macrophage-like PMA-differentiated U937 cells , as assessed by trypan blue exclusion cell counting , thymidine incorporation , AnnexinV labeling , followed by flow cytometry and DNA fragmentation studies .", "target_text": { "TNF-alpha": "protein", "PMA-differentiated U937 cells": "cell_line" } }, { "input_text": "This effect can be associated with the activation of specific hormone receptors , since we observed the expression of the estrogen receptor alpha ( ER-alpha ) , ER-beta , and progesterone receptor ( PR ) mRNAs ; the ER-alpha protein expression was confirmed by immunocytochemical analysis .", "target_text": { "ER-alpha": "protein" } }, { "input_text": "In addition , hormone-mediated survival against apoptosis was concentration dependent , reaching the half-maximal effect at 10 nM and blocked by the ER antagonist ICI 182 , 780 in undifferentiated cells , further supporting a receptor-mediated mechanism of cell survival .", "target_text": { "undifferentiated cells": "cell_type" } }, { "input_text": "Other steroid receptor drugs such as Raloxifene , RU486 , or the ICI 182 , 780 in PMA-differentiated cells displayed agonist activity by preventing TNF-alpha -induced apoptosis as efficiently as the hormones alone , providing further evidence to the notion that steroid receptor drugs may manifest agonist or antagonist activities depending on the cellular context in which they are studied .", "target_text": { "PMA-differentiated cells": "cell_line", "TNF-alpha": "protein" } }, { "input_text": "Treatment with E2 was also associated with a time-dependent decrease in the mRNA level of the proapoptotic Nip-2 protein , supporting the hypothesis that hormone responsiveness of U937 cells is mediated by target gene transcription .", "target_text": { "proapoptotic Nip-2 protein": "protein", "U937 cells": "cell_line" } }, { "input_text": "Together , these results demonstrate that ER and PR can be activated by endogenous or exogenous ligands to induce a genetic response that impairs TNF-alpha -induced apoptosis in U937 cells .", "target_text": { "ER": "protein", "PR": "protein", "TNF-alpha": "protein", "U937 cells": "cell_line" } }, { "input_text": "The data presented here suggest that the female steroid receptors play a role in regulation of the immune response by preventing apoptosis of monoblastoid cells ; this effect might have important consequences in the clinical use of steroid receptor drugs .", "target_text": { "female steroid receptors": "protein", "monoblastoid cells": "cell_type" } }, { "input_text": "-- Vegeto , E. , Pollio , G. , Pellicciari , C. , Maggi , A .", "target_text": {} }, { "input_text": "Estrogen and progesterone induction of survival of monoblastoid cells undergoing TNF-alpha -inuced apoptosis .", "target_text": { "monoblastoid cells": "cell_type", "TNF-alpha": "protein" } }, { "input_text": "Dicarba-closo-dodecaboranes as a pharmacophore .", "target_text": {} }, { "input_text": "Retinoidal antagonists and potential agonists .", "target_text": {} }, { "input_text": "Synthesis and biological evaluation of the first dicarba-closo-dodecaborane ( carborane ) derivatives of retinoids are described .", "target_text": {} }, { "input_text": "Their retinoidal activity were examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells .", "target_text": { "human promyelocytic leukemia HL-60 cells": "cell_line" } }, { "input_text": "High retinoidal activity ( agonist or antagonist for retinoic acid receptor ( RAR ) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule .", "target_text": { "retinoic acid receptor": "protein", "RAR": "protein" } }, { "input_text": "The 4-carboranyl-substituted compounds ( 7 , 11 ) showed antagonistic activity but no agonistic activity even in the presence of the potent synergist HX630 .", "target_text": {} }, { "input_text": "On the other hand , the 3-carboranyl-substituted compounds ( 8 , 12 ) showed potential agonistic activity , but no antagonistic activity .", "target_text": {} }, { "input_text": "The results indicates that carboranes are applicable as the hydrophobic moiety of biologically active molecules .", "target_text": {} }, { "input_text": "Inhibition of T cell signaling by mitogen-activated protein kinase -targeted hematopoietic tyrosine phosphatase ( HePTP ) .", "target_text": { "mitogen-activated protein kinase": "protein", "hematopoietic tyrosine phosphatase": "protein", "mitogen-activated protein kinase -targeted hematopoietic tyrosine phosphatase": "protein", "HePTP": "protein" } }, { "input_text": "Activation of T lymphocytes to produce cytokines is regulated by the counterbalance of protein- tyrosine kinases and protein- tyrosine phosphatases , many of which have a high degree of substrate specificity because of physical association with their targets .", "target_text": { "T lymphocytes": "cell_type", "cytokines": "protein", "protein- tyrosine kinases": "protein" } }, { "input_text": "Overexpression of hematopoietic protein- tyrosine phosphatase ( HePTP ) results in suppression of T lymphocyte activation as measured by T cell antigen receptor -induced activation of transcription factors binding to the 5' promoter of the interleukin-2 gene .", "target_text": { "hematopoietic protein- tyrosine phosphatase": "protein", "HePTP": "protein", "T cell antigen receptor": "protein", "transcription factors": "protein", "5' promoter": "DNA", "interleukin-2 gene": "DNA" } }, { "input_text": "Efforts to pinpoint the exact site of action and specificity of HePTP in the signaling cascade revealed that HePTP acts directly on the mitogen-activated protein ( MAP ) kinases Erk 1 and 2 and consequently reduces the magnitude and duration of their catalytic activation in intact T cells .", "target_text": { "HePTP": "protein", "mitogen-activated protein ( MAP ) kinases": "protein", "intact T cells": "cell_type" } }, { "input_text": "In contrast , HePTP had no effects on N-terminal c-Jun kinase or on events upstream of the MAP kinases .", "target_text": { "HePTP": "protein", "N-terminal c-Jun kinase": "protein" } }, { "input_text": "The specificity of HePTP correlated with its physical association through its noncatalytic N terminus with Erk and another MAP kinase , p38 , but not Jnk or other proteins .", "target_text": { "HePTP": "protein", "N terminus": "protein", "Erk": "protein", "MAP kinase": "protein", "p38": "protein", "Jnk": "protein" } }, { "input_text": "We propose that HePTP plays a negative role in antigen receptor signaling by specifically regulating MAP kinases in the cytosol and at early time points of T cell activation before the activation-induced expression of nuclear dual-specific MAP kinase phosphatases .", "target_text": { "HePTP": "protein", "MAP kinases": "protein", "nuclear dual-specific MAP kinase phosphatases": "protein" } }, { "input_text": "p38 mitogen-activated protein kinase mediates signal integration of TCR /CD28 costimulation in primary murine T cells .", "target_text": { "p38": "protein", "p38 mitogen-activated protein kinase": "protein", "TCR": "protein", "/CD28": "protein", "primary murine T cells": "cell_type" } }, { "input_text": "Optimal T cell activation requires two signals , one generated by TCR and another by the CD28 costimulatory receptor .", "target_text": { "TCR": "protein", "CD28 costimulatory receptor": "protein" } }, { "input_text": "In this study , we investigated the regulation of costimulation-induced mitogen-activated protein kinase ( MAPK ) activation in primary mouse T cells .", "target_text": { "mitogen-activated protein kinase": "protein", "MAPK": "protein", "primary mouse T cells": "cell_type" } }, { "input_text": "In contrast to that reported for human Jurkat T cells , we found that p38 MAPK , but not Jun NH2-terminal kinase ( JNK ) , is weakly activated upon stimulation with either anti-CD3 or anti-CD28 in murine thymocytes and splenic T cells .", "target_text": { "human Jurkat T cells": "cell_type", "p38 MAPK": "protein", "Jun NH2-terminal kinase": "protein", "JNK": "protein", "anti-CD3": "protein", "anti-CD28": "protein", "murine thymocytes": "cell_type", "splenic T cells": "cell_type" } }, { "input_text": "However , p38 MAPK is activated strongly and synergistically by either CD3/CD28 coligation or PMA/Ca2+ ionophore stimulation , which mimics TCR - CD3/CD28 -mediated signaling .", "target_text": { "p38 MAPK": "protein", "CD3/CD28": "protein", "TCR": "protein" } }, { "input_text": "Activation of p38 MAPK correlates closely with the stimulation of T cell proliferation .", "target_text": { "p38 MAPK": "protein" } }, { "input_text": "In contrast , PMA-induced JNK activation is inhibited by Ca2+ ionophore .", "target_text": { "JNK": "protein" } }, { "input_text": "T cell proliferation and production of IL-2 , IL-4 , and IFN-gamma induced by both CD3 and CD3 /CD28 ligation and the nuclear expression of the c-Jun and ATF-2 proteins are each blocked by the p38 MAPK inhibitor SB203580 .", "target_text": { "IL-2": "protein", "IL-4": "protein", "IFN-gamma": "protein", "CD3": "protein", "/CD28": "protein", "p38 MAPK": "protein" } }, { "input_text": "Our findings demonstrate that p38 MAPK 1 ) plays an important role in signal integration during costimulation of primary mouse T cells , 2 ) may be involved in the induction of c-Jun activation and augmentation of AP-1 transcriptional activity , and 3 ) regulates whether T cells enter a state of functional unresponsiveness .", "target_text": { "p38 MAPK": "protein", "primary mouse T cells": "cell_type", "c-Jun": "protein", "AP-1": "protein", "T cells": "cell_type" } }, { "input_text": "Erythroid gene expression is differentially regulated by erythropoietin , haemin and delta-aminolaevulinic acid in UT-7 cells .", "target_text": { "erythropoietin": "protein", "UT-7 cells": "cell_line" } }, { "input_text": "Erythropoietin ( Epo ) is essential for the later stages of erythropoiesis , acting to promote cell survival and proliferation , but its role in differentiation remains to be defined .", "target_text": {} }, { "input_text": "The UT-7 cell line exhibits both erythroid and megakaryocytic characteristics and can be induced to differentiate along the erythroid pathway by Epo or the megakaryocytic pathway by phorbol myristic acetate .", "target_text": { "UT-7 cell line": "cell_line", "Epo": "protein" } }, { "input_text": "We have compared the effects of Epo and the chemical inducers , delta-aminolaevulinic acid ( delta-ALA ) and haemin on the differentiation capacity of UT-7 cells .", "target_text": { "Epo": "protein", "UT-7 cells": "cell_line" } }, { "input_text": "Epo alone promoted relatively early events in erythroid maturation , without significant changes in haemoglobin production or morphology .", "target_text": { "Epo": "protein" } }, { "input_text": "GATA-2 and c-myb were down-regulated by Epo , and GATA-2 was further down-modulated by the inducers .", "target_text": { "GATA-2": "protein", "c-myb": "protein", "Epo": "protein" } }, { "input_text": "Conversely , SCL expression was up-regulated by Epo and further increased by haemin and delta-ALA .", "target_text": { "SCL": "protein", "Epo": "protein" } }, { "input_text": "Epo caused an increase in the proportion of cells expressing cell surface glycophorin A ( GPA ) and up-regulated beta- and gamma- globin by several fold .", "target_text": { "Epo": "protein", "glycophorin A": "protein", "GPA": "protein" } }, { "input_text": "Both haemin and delta-ALA caused a de novo increase in alpha-globin expression as well as enhancing Epo -induced beta-globin expression , leading to a marked increase in haemoglobin production .", "target_text": { "alpha-globin": "protein", "Epo": "protein", "beta-globin": "protein" } }, { "input_text": "These results suggest that haemoglobin production in UT-7 cells is limited by a deficiency of erythroid-specific aminolaevulinic acid synthase ( ALAS-E ) activity or globin synthesis as a consequence of their immaturity as a multipotential cell line .", "target_text": { "UT-7 cells": "cell_line", "erythroid-specific aminolaevulinic acid synthase": "protein", "ALAS-E": "protein", "erythroid-specific aminolaevulinic acid synthase ( ALAS-E ) activity": "protein", "multipotential cell line": "cell_line" } }, { "input_text": "Essential role of alveolar macrophages in intrapulmonary activation of NF-kappaB .", "target_text": { "alveolar macrophages": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "Acute inflammatory injury in rat lung induced by deposition of immunoglobulin G immune complexes requires expression of cytokines and chemokines as well as activation of the transcription factor nuclear factor ( NF ) -kappaB .", "target_text": { "immunoglobulin G immune complexes": "protein", "cytokines": "protein", "chemokines": "protein", "transcription factor": "protein", "nuclear factor ( NF ) -kappaB": "protein" } }, { "input_text": "There is little direct evidence regarding the role of alveolar macrophages in these activation events .", "target_text": { "alveolar macrophages": "cell_type" } }, { "input_text": "In the present studies , rat lungs were depleted of alveolar macrophages by airway instillation of liposome-encapsulated dichloromethylene diphosphonate .", "target_text": { "alveolar macrophages": "cell_type" } }, { "input_text": "These procedures , which greatly reduced the number of retrievable alveolar macrophages , suppressed activation of lung NF-kappaB in the inflammatory model .", "target_text": { "alveolar macrophages": "cell_type", "NF-kappaB": "protein", "lung NF-kappaB": "protein" } }, { "input_text": "In addition , bronchoalveolar lavage levels of tumor necrosis factor-alpha ( TNF-alpha ) and the CXC chemokine , macrophage inflammatory protein-2 , were substantially reduced .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "CXC chemokine": "protein", "macrophage inflammatory protein-2": "protein" } }, { "input_text": "In parallel , upregulation of the lung vascular adhesion molecule , intercellular adhesion molecule-1 , was greatly reduced by intrapulmonary instillation of phosphonate-containing liposomes .", "target_text": { "lung vascular adhesion molecule": "protein", "intercellular adhesion molecule-1": "protein" } }, { "input_text": "Neutrophil accumulation and development of lung injury were also substantially diminished .", "target_text": {} }, { "input_text": "Lung instillation of TNF-alpha in alveolar macrophage-depleted rats restored the NF-kappaB activation response in whole lung .", "target_text": { "TNF-alpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "These data suggest that , in this inflammatory model , initial activation of NF-kappaB occurs in alveolar macrophages and the ensuing production of TNF-alpha may propagate NF-kappaB activation to other cell types in the lung .", "target_text": { "NF-kappaB": "protein", "alveolar macrophages": "cell_type", "TNF-alpha": "protein" } }, { "input_text": "Interferon-beta mediates stromal cell rescue of T cells from apoptosis .", "target_text": { "Interferon-beta": "protein", "T cells": "cell_type" } }, { "input_text": "The resolution of immune responses is characterized by extensive apoptosis of activated T cells .", "target_text": { "T cells": "cell_type" } }, { "input_text": "However , to generate and maintain immunological memory , some antigen-specific T cells must survive and revert to a resting G0/G1 state .", "target_text": { "antigen-specific T cells": "cell_type" } }, { "input_text": "Cytokines that bind to the common gamma chain of the IL-2 receptor promote the survival of T cell blasts , but also induce proliferation .", "target_text": { "Cytokines": "protein", "gamma chain": "protein", "IL-2": "protein", "T cell blasts": "cell_type" } }, { "input_text": "In contrast , soluble factors secreted by stromal cells induce Tcell survival in a resting G0/G1 state .", "target_text": { "soluble factors": "protein", "stromal cells": "cell_type" } }, { "input_text": "We now report that interferon-beta is the principal mediator of stromal cell-mediated Tcell rescue from apoptosis .", "target_text": {} }, { "input_text": "Interferon -alpha and -beta promote the reversion of blast Tcells to a resting G0/G1 configuration with all the characteristic features of stromal cell rescue ; such as high Bcl-XL expression and low Bcl-2 .", "target_text": { "blast Tcells": "cell_type", "Bcl-XL": "protein", "Bcl-2": "protein" } }, { "input_text": "Type I interferons and stromal cells stimulate apparently identical signaling pathways , leading to STAT-1 activation .", "target_text": { "Type I interferons": "protein", "stromal cells": "cell_type", "STAT-1": "protein" } }, { "input_text": "We also show that this mechanism may play a fundamental role in the persistence of T cells at sites of chronic inflammation ; suggesting that chronic inflammation is an aberrant consequence of immunological memory .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Reduction of tumour necrosis factor alpha expression and signalling in peripheral blood mononuclear cells from patients with thalassaemia or sickle cell anaemia upon treatment with desferrioxamine .", "target_text": { "tumour necrosis factor alpha": "protein", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Recent evidence indicates that the rate of progression of the HIV-1 disease is significantly reduced in thalassaemia major patients upon treatment with high doses of desferrioxamine ( DFX ) .", "target_text": {} }, { "input_text": "The authors have previously demonstrated that in vitro exposure of mononuclear cells to DFX decreases the bioavailability of tumour necrosis factor alpha ( TNF-alpha ) which has a stimulatory effect on HIV-1 replication .", "target_text": { "mononuclear cells": "cell_type", "tumour necrosis factor alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "In this study , therefore , TNF-alpha bioavailability from mononuclear cells isolated from 10 patients with thalassaemia or sickle cell anaemia given DFX as compared to 10 untreated subjects has been evaluated .", "target_text": { "TNF-alpha": "protein", "mononuclear cells": "cell_type" } }, { "input_text": "Evidence is presented showing that DFX treatment reduces TNF-alpha bioavailability ( P < 0.05 ) by inhibiting its steady state ( P < 0.05 ) and by enhancing its inactivation through binding to soluble TNF-alpha receptor type II ( P < 0.05 ) .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "We also show that DFX treatment limits the in vivo activation of NF-kappaB , a transcription factor involved in both TNF-alpha gene transcription and TNF-alpha signalling ( P < 0.005 ) .", "target_text": { "NF-kappaB": "protein", "transcription factor": "protein", "TNF-alpha": "protein" } }, { "input_text": "We conclude that TNF-alpha bioavailability and signalling are impaired in patients upon DFX treatment .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "This mechanism may contribute to delayed progression of the HIV-1 infection in vivo .", "target_text": {} }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "Involvement of NF-kappaB p50/p65 heterodimer in activation of the human pro-interleukin-1beta gene at two subregions of the upstream enhancer element .", "target_text": { "NF-kappaB": "protein", "NF-kappaB p50/p65 heterodimer": "protein", "human pro-interleukin-1beta gene": "DNA", "upstream enhancer element": "DNA" } }, { "input_text": "A region between -3134 and -2729 bp upstream from the transcription site of the human pro-interleukin 1beta ( proIL-1beta ) gene was identified as an LPS-responsive enhancer element .", "target_text": { "transcription site": "DNA", "human pro-interleukin 1beta": "protein", "proIL-1beta": "protein", "human pro-interleukin 1beta ( proIL-1beta ) gene": "DNA", "LPS-responsive enhancer element": "DNA" } }, { "input_text": "In this study , the influence of the sequences located between -3134 and -2987 on the transcriptional activity of the proIL-1beta gene in LPS-stimulated Raw 264.7 cells was examined in detail .", "target_text": { "between -3134 and -2987": "DNA", "proIL-1beta gene": "DNA", "LPS-stimulated Raw 264.7 cells": "cell_line" } }, { "input_text": "The results obtained by transient transfection of fos -CAT constructs that contained serial 5'-deletion mutations showed that the region between -3134 and -3059 appears to be required for the induction of transcription by LPS .", "target_text": { "-CAT constructs": "DNA", "serial 5'-deletion mutations": "DNA" } }, { "input_text": "Gel shift assay studies with synthetic oligonucleotides corresponding to partial sequences of the latter region and nuclear extracts from stimulated cells revealed specific protein binding sites between -3110 and -3090 and between -3079 and -3059 .", "target_text": { "synthetic oligonucleotides": "DNA", "protein binding sites": "DNA" } }, { "input_text": "These specific bindings were time and LPS dose dependent .", "target_text": {} }, { "input_text": "The results of supershift analysis using specific antibodies against transcription factors suggested that both binding complexes contained the NF-kappaB components p50 and p65 , and did not contain other NF-kappaB proteins ( p52 , c-Rel , Rel B ) , AP-1 proteins ( c-Fos , C-Jun ) , CREB or C/EBPbeta ( NF-IL6 ) .", "target_text": { "transcription factors": "protein", "NF-kappaB": "protein", "NF-kappaB components": "protein", "p50": "protein", "p65": "protein", "NF-kappaB proteins": "protein", "p52": "protein", "c-Rel": "protein", "Rel B": "protein", "AP-1 proteins": "protein", "c-Fos": "protein", "C-Jun": "protein", "CREB": "protein", "C/EBPbeta": "protein", "NF-IL6": "protein" } }, { "input_text": "Mutation of either of the putative NF-kappaB-binding sites in the enhancer element decreased the LPS -stimulated transcriptional activity .", "target_text": { "NF-kappaB-binding sites": "DNA" } }, { "input_text": "These data indicated that two NF-kappaB-binding sites , which are located between -3134 and -3059 , are critical for the activation of proIL-1beta gene transcription .", "target_text": { "NF-kappaB-binding sites": "DNA", "-3134 and -3059": "DNA", "proIL-1beta gene": "DNA" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "N-acetyl-L-cysteine inhibits primary human T cell responses at the dendritic cell level : association with NF-kappaB inhibition .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "N-acetyl-L-cysteine ( NAC ) is an antioxidant molecule endowed with immunomodulatory properties .", "target_text": {} }, { "input_text": "To investigate the effect of NAC on the induction phase of T cell responses , we analyzed its action on human dendritic cells ( DC ) derived from adherent PBMC cultured with IL-4 and granulocyte-macrophage CSF .", "target_text": { "IL-4": "protein", "granulocyte-macrophage CSF": "protein" } }, { "input_text": "We first found that NAC inhibited the constitutive as well as the LPS -induced activity of the transcription factor NF-kappaB .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "In parallel , NAC was shown to down-regulate the production of cytokines by DC as well as their surface expression of HLA-DR , CD86 ( B7-2 ) , and CD40 molecules both at the basal state and upon LPS activation .", "target_text": { "cytokines": "protein", "DC": "cell_type", "HLA-DR": "protein", "CD86": "protein", "B7-2": "protein", "CD40 molecules": "protein" } }, { "input_text": "NAC also inhibited DC responses induced by CD40 engagement .", "target_text": { "CD40": "protein" } }, { "input_text": "The inhibitory effects of NAC were not due to nonspecific toxicity as neither the viability of DC nor their mannose receptor-mediated endocytosis were modified by NAC .", "target_text": { "DC": "cell_type" } }, { "input_text": "Finally , we found that the addition of NAC to MLR between naive T cells and allogeneic DC resulted in a profound inhibition of alloreactive responses , which could be attributed to a defect of DC as APC-independent T cell responses were not inhibited by NAC .", "target_text": { "naive T cells": "cell_type", "DC": "cell_type" } }, { "input_text": "Altogether , our results suggest that NAC might impair the generation of primary immune responses in humans through its inhibitory action on DC .", "target_text": { "DC": "cell_type" } }, { "input_text": "Thrombin -induced p65 homodimer binding to downstream NF-kappa B site of the promoter mediates endothelial ICAM-1 expression and neutrophil adhesion .", "target_text": { "Thrombin": "protein", "p65": "protein", "Thrombin -induced p65 homodimer": "protein", "NF-kappa B": "protein", "NF-kappa B site": "DNA", "ICAM-1": "protein", "neutrophil": "cell_type" } }, { "input_text": "We investigated the mechanisms by which proinflammatory mediator , thrombin , released during intravascular coagulation and tissue injury , induces ICAM-1 ( CD54 ) expression in endothelial cells .", "target_text": { "proinflammatory mediator": "protein", "thrombin": "protein", "ICAM-1": "protein", "CD54": "protein", "endothelial cells": "cell_type" } }, { "input_text": "Stimulation of HUVEC with thrombin resulted in dose- and time-dependent increases in ICAM-1 mRNA and cell surface expression and in ICAM-1 -dependent endothelial adhesivity toward polymorphonuclear leukocytes .", "target_text": { "HUVEC": "cell_line", "thrombin": "protein", "ICAM-1 mRNA": "RNA", "ICAM-1": "protein", "polymorphonuclear leukocytes": "cell_type" } }, { "input_text": "Transient transfection of endothelial cells with ICAM-1 promoter luciferase reporter gene ( ICAM-1LUC ) constructs indicated that deletion of upstream NF-kappa B site ( -533 bases from translation start site ) had no effect on thrombin responsiveness , whereas mutation/deletion of downstream NF-kappa B site ( -223 bases from the translation start site ) prevented the activation of ICAM-1 promoter , indicating that the downstream NF-kappa B site is critical for thrombin inducibility .", "target_text": { "endothelial cells": "cell_type", "ICAM-1": "protein", "ICAM-1 promoter": "DNA", "ICAM-1 promoter luciferase reporter gene ( ICAM-1LUC ) constructs": "DNA", "NF-kappa B": "protein", "NF-kappa B site": "DNA", "-533 bases": "DNA", "translation start site": "DNA", "thrombin": "protein", "-223 bases": "DNA" } }, { "input_text": "NF-kappa B -directed luciferase activity increased approximately 3-fold when cells transfected with the plasmid pNF-kappa BLUC containing five copies of consensus NF-kappa B site linked to a minimal adenovirus E1B promoter-luciferase gene were exposed to thrombin , indicating that activation of NF-kappa B was essential for thrombin response .", "target_text": { "NF-kappa B": "protein", "luciferase": "protein", "plasmid pNF-kappa BLUC": "DNA", "NF-kappa B site": "DNA", "consensus NF-kappa B site": "DNA", "adenovirus E1B promoter-luciferase gene": "DNA", "thrombin": "protein" } }, { "input_text": "Gel supershift assays demonstrated that thrombin induced binding of NF-kappa Bp65 ( Rel A ) to downstream NF-kappa B site of the ICAM-1 promoter .", "target_text": { "thrombin": "protein", "NF-kappa Bp65": "protein", "Rel A": "protein", "NF-kappa B": "protein", "NF-kappa B site": "DNA", "ICAM-1": "protein", "ICAM-1 promoter": "DNA" } }, { "input_text": "Thrombin receptor activation peptide , a 14-amino-acid peptide representing the new NH2 terminus of proteolytically activated receptor-1 , mimicked thrombin 's action in inducing ICAM-1 expression .", "target_text": { "Thrombin": "protein", "NH2 terminus": "protein", "receptor-1": "protein", "thrombin": "protein", "ICAM-1": "protein" } }, { "input_text": "These data indicate that thrombin activates endothelial ICAM-1 expression and polymorphonuclear leukocyte adhesion by NF-kappa Bp65 binding to the downstream NF-kappa B site of ICAM-1 promoter after proteolytically activated receptor-1 activation .", "target_text": { "thrombin": "protein", "ICAM-1": "protein", "polymorphonuclear leukocyte": "cell_type", "NF-kappa Bp65": "protein", "NF-kappa B": "protein", "NF-kappa B site": "DNA", "ICAM-1 promoter": "DNA" } }, { "input_text": "Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin- mediated growth arrest and apoptosis in B cells .", "target_text": { "Smad6": "protein", "Smad7": "protein", "B cells": "cell_type" } }, { "input_text": "Smad6 and Smad7 prevent ligand-induced activation of signal-transducing Smad proteins in the transforming growth factor-beta family .", "target_text": { "Smad6": "protein", "Smad7": "protein", "signal-transducing Smad proteins": "protein", "transforming growth factor-beta family": "protein" } }, { "input_text": "Here we demonstrate that both Smad6 and Smad7 are human bone morphogenetic protein-2 ( hBMP-2 ) -inducible antagonists of hBMP-2 -induced growth arrest and apoptosis in mouse B cell hybridoma HS-72 cells .", "target_text": { "Smad6": "protein", "Smad7": "protein", "human bone morphogenetic protein-2": "protein", "hBMP-2": "protein", "mouse B cell hybridoma": "cell_line", "HS-72 cells": "cell_line" } }, { "input_text": "Moreover , we confirmed that the ectopic expressions of Smad6 and Smad7 inhibited the hBMP-2 -induced Smad1/Smad5 phosphorylation .", "target_text": { "Smad6": "protein", "Smad7": "protein", "hBMP-2": "protein", "Smad1/Smad5": "protein" } }, { "input_text": "We previously reported that Smad7 is an activin A-inducible antagonist of activin A-induced growth arrest and apoptosis in HS-72 cells .", "target_text": { "Smad7": "protein", "HS-72 cells": "cell_line" } }, { "input_text": "Interestingly , although mRNA expression of Smad6 was induced by activin A in HS-72 cells , Smad6 showed no antagonistic effect on activin A -induced growth arrest and apoptosis .", "target_text": { "Smad6": "protein", "HS-72 cells": "cell_line" } }, { "input_text": "Moreover , we found that the ectopic expression of Smad7 , but not Smad6 , inhibited the activin A -induced Smad2 phosphorylation in HS-72 cells .", "target_text": { "Smad7": "protein", "Smad6": "protein", "HS-72 cells": "cell_line" } }, { "input_text": "Thus , Smad6 and Smad7 exhibit differential inhibitory effects in bone morphogenetic protein-2- and activin A- mediated signaling in B lineage cells .", "target_text": { "Smad6": "protein", "Smad7": "protein", "B lineage cells": "cell_type" } }, { "input_text": "Retinoic acid induces apoptosis of human CD34+ hematopoietic progenitor cells : involvement of retinoic acid receptors and retinoid X receptors depends on lineage commitment of the hematopoietic progenitor cells .", "target_text": { "human CD34+ hematopoietic progenitor cells": "cell_type", "retinoic acid receptors": "protein", "retinoid X receptors": "protein", "hematopoietic progenitor cells": "cell_type" } }, { "input_text": "Retinoids are bifunctional regulators of growth and differentiation of hematopoietic cells .", "target_text": { "hematopoietic cells": "cell_type" } }, { "input_text": "In this study we explored the effects of retinoic acid ( RA ) on apoptosis of human CD34+ hematopoietic progenitor cells isolated from normal bone marrow .", "target_text": { "hematopoietic progenitor cells": "cell_type", "human CD34+ hematopoietic progenitor cells": "cell_type" } }, { "input_text": "RA ( 100 nM ) induced an increase in the percentage of dead cells from 24 % to 44 % at day 6 ( p < 0.05 , n = 6 ) as compared to control cells cultured in medium alone .", "target_text": { "dead cells": "cell_type", "control cells": "cell_type" } }, { "input_text": "The effect was dose dependent and appeared relatively late .", "target_text": {} }, { "input_text": "Significant differences were observed from day 4 onward .", "target_text": {} }, { "input_text": "Apoptosis , or programmed cell death , was demonstrated as the mode of cell death by using the TUNEL assay , which detects single strand nicks in DNA , or by the Nicoletti technique demonstrating a subdiploid population by DNA staining .", "target_text": {} }, { "input_text": "RA previously was found to inhibit granulocyte colony-stimulating factor -- and not granulocyte-macrophage colony-stimulating factor -- stimulated proliferation of CD34+ cells .", "target_text": { "granulocyte colony-stimulating factor": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "CD34+ cells": "cell_type" } }, { "input_text": "However , we found that RA opposed anti-apoptotic effects of G-CSF and GM-CSF on CD34+ cells ( G-CSF : 8 % dead cells at day 6 ; G-CSF + RA : 20 % ; GM-CSF : 12 % ; GM-CSF + RA : 27 % ) .", "target_text": { "G-CSF": "protein", "GM-CSF": "protein", "CD34+ cells": "cell_type", "dead cells": "cell_type" } }, { "input_text": "Moreover , RA induced apoptosis of CD34+ cells and CD34+CD71+ cells stimulated with erythropoietin .", "target_text": { "CD34+ cells": "cell_type", "CD34+CD71+ cells": "cell_type", "erythropoietin": "protein" } }, { "input_text": "To explore the receptor signaling pathways involved in RA -induced apoptosis , we used selective ligands for retinoic acid receptors ( RARs ; RO13-7410 ) and retinoid X receptors ( RXRs ; RO 25-6603 ) .", "target_text": { "retinoic acid receptors": "protein", "retinoid X receptors": "protein", "RXRs": "protein" } }, { "input_text": "We found that RARs were involved in RA -mediated apoptosis of myeloid progenitor cells , whereas RARs as well as RXRs were involved in RA -mediated apoptosis of erythroid progenitor cells .", "target_text": { "RARs": "protein", "RXRs": "protein", "erythroid progenitor cells": "cell_type" } }, { "input_text": "Suppressive effects of anti-inflammatory agents on human endothelial cell activation and induction of heat shock proteins .", "target_text": { "human endothelial cell": "cell_type", "heat shock proteins": "protein" } }, { "input_text": "BACKGROUND : Studies from our laboratory have shown that the earliest stages of atherosclerosis may be mediated by an autoimmune reaction against heat shock protein 60 ( Hsp60 ) .", "target_text": { "heat shock protein 60": "protein", "Hsp60": "protein" } }, { "input_text": "The interactions of Hsp60 -specific T cells with arterial endothelial cells ( EC ) require expression of both Hsp60 and certain adhesion molecules shown to be induced simultaneously in EC by mechanical and other types of stress .", "target_text": { "Hsp60": "protein", "Hsp60 -specific T cells": "cell_line", "endothelial cells": "cell_type", "EC": "cell_type", "adhesion molecules": "protein" } }, { "input_text": "Recently , it was shown that suppression of T cell-mediated immune responses by cyclosporin A ( CyA ) enhanced atherosclerotic lesion formation in mice .", "target_text": {} }, { "input_text": "In contrast , aspirin was found to lower the risk of myocardial infarction in men .", "target_text": {} }, { "input_text": "These conflicting observations may be due to different effects of anti-inflammatory agents on adhesion molecule and Hsp expression in EC , respectively .", "target_text": { "EC": "cell_type" } }, { "input_text": "MATERIAL AND METHODS : In the present study , we analyzed the effects of CyA , aspirin , and indomethacin on T cell proliferation using a proliferation assay .", "target_text": {} }, { "input_text": "To explore the expression of adhesion molecules , monocyte chemoattractant protein-1 ( MCP-1 ) , and Hsp60 in human umbilical vein endothelial cells ( HUVECs ) , Northern blot analyses were used .", "target_text": { "adhesion molecules": "protein", "monocyte chemoattractant protein-1": "protein", "MCP-1": "protein", "Hsp60": "protein", "endothelial cells": "cell_type", "human umbilical vein endothelial cells": "cell_type", "HUVECs": "cell_type" } }, { "input_text": "To examine the activation status of the transcription factors nuclear factor kappaB ( NF-kappaB ) and heat shock factor-1 ( HSF-1 ) , electrophoretic mobility shift assays were performed .", "target_text": { "transcription factors": "protein", "nuclear factor kappaB": "protein", "NF-kappaB": "protein", "heat shock factor-1": "protein", "HSF-1": "protein" } }, { "input_text": "RESULTS : With the exception of indomethacin , the used immunosuppressive and anti-inflammatory agents significantly inhibited T cell proliferation in response to influenza virus antigen in a dose-dependent manner .", "target_text": { "influenza virus antigen": "protein" } }, { "input_text": "Interestingly , CyA and indomethacin did not suppress tumor necrosis factor-alpha ( TNF-alpha ) -induced adhesion molecule expression on HUVECs , whereas aspirin had an inhibitory effect .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "HUVECs": "cell_type" } }, { "input_text": "These observations correlated with the modulation of NF-kappaB activity in EC .", "target_text": { "NF-kappaB": "protein", "EC": "cell_type" } }, { "input_text": "All agents tested induced expression of Hsp60 6 hr after application .", "target_text": { "Hsp60": "protein" } }, { "input_text": "In addition , aspirin and indomethacin , but not CyA , induced Hsp70 expression in HUVECs that correlated with induction of HSF-1 activity .", "target_text": { "Hsp70": "protein", "HUVECs": "cell_type", "HSF-1": "protein" } }, { "input_text": "CONCLUSION : Our results show that the tested agents ( except indomethacin ) are inhibitors of the T cell-mediated immune response , as expected , that aspirin is an effective suppressor of adhesion molecule expression , and that all three agents can induce Hsp60 in HUVECs .", "target_text": { "adhesion molecule": "protein", "Hsp60": "protein", "HUVECs": "cell_type" } }, { "input_text": "These data provide the molecular basis for the notion that ( 1 ) part of the anti-atherogenic effect of aspirin may be due to the prevention of the adhesion of sensitized T cells to stressed EC ; ( 2 ) that part of the atherosclerosis-promoting effect of CyA may be due to its potential as an inducer of Hsp60 expression and its inability to down-regulate adhesion molecule expression on EC ; and ( 3 ) that down-regulation of MCP-1 expression by aspirin may result in decreased recruitment of monocytes into the arterial intima beneath stressed EC .", "target_text": { "sensitized T cells": "cell_type", "EC": "cell_type", "Hsp60": "protein", "adhesion molecule": "protein", "MCP-1": "protein", "monocytes": "cell_type" } }, { "input_text": "In vivo modulation of glucocorticoid receptor mRNA by inhaled fluticasone propionate in bronchial mucosa and blood lymphocytes in subjects with mild asthma .", "target_text": { "glucocorticoid receptor": "protein", "glucocorticoid receptor mRNA": "RNA", "blood lymphocytes": "cell_type" } }, { "input_text": "BACKGROUND : In vivo regulation of the glucocorticoid receptor ( GR ) by glucocorticoids provides a means of modulating sensitivity of targeted cells .", "target_text": { "glucocorticoid receptor": "protein", "GR": "protein" } }, { "input_text": "OBJECTIVE : We sought to determine the in vivo modulation of GR mRNA expression by fluticasone propionate ( FP ) in subjects with mild asthma .", "target_text": { "GR mRNA": "RNA" } }, { "input_text": "METHODS : Ten atopic asthmatic subjects were treated with FP 250 microg twice daily for 4 weeks .", "target_text": {} }, { "input_text": "Before and after treatment , the patients underwent fiberoptic bronchoscopy with endobronchial biopsy and sampling of venous blood for measurements of GR mRNA levels .", "target_text": { "GR mRNA": "RNA" } }, { "input_text": "A solution hybridization assay was used for quantitative analysis of GR mRNA .", "target_text": { "GR mRNA": "RNA" } }, { "input_text": "In addition , a 24-hour urinary cortisol excretion and an adrenocorticotropic hormone test before and after treatment with FP were performed .", "target_text": {} }, { "input_text": "RESULTS : A high interindividual variation in GR mRNA expression was seen .", "target_text": { "GR": "protein", "GR mRNA": "RNA" } }, { "input_text": "However , we detected a significant reduction of the GR mRNA levels in the endobronchial biopsy specimens after FP treatment ( 36.6 +/- 23.1 and 25.0 +/- 10.9 amol GR mRNA /microg RNA , respectively ; P < .01 ) .", "target_text": { "GR mRNA": "RNA" } }, { "input_text": "In the peripheral blood lymphocytes an even more striking downregulation of the GR by its cognate ligand was documented ( 30.3 +/- 26.5 and 8.8 +/- 5 amol GR mRNA /microg RNA , respectively ; P < .001 ) , possibly reflecting differences in glucocorticoid sensitivity between tissues .", "target_text": { "blood lymphocytes": "cell_type", "GR mRNA": "RNA" } }, { "input_text": "A small but significant reduction of the 24-hour urinary cortisol excretion was observed ( 233 +/- 109 and 157 +/- 66 nmol/L , respectively ; P < .01 ) , whereas the feedback regulation of glucocorticoid synthesis by means of the hypothalamic-pituitary-adrenal axis as assessed by the adrenocorticotropic hormone test remained normal after treatment with FP .", "target_text": {} }, { "input_text": "CONCLUSION : The results in this study confirm the potency of the inhaled corticosteroid FP and provide evidence for a considerable tissue-specific interindividual variation in the expression of the GR .", "target_text": { "GR": "protein" } }, { "input_text": "[ Corticoids and allergy ]", "target_text": {} }, { "input_text": "Inflammation is constantly observed in allergic reactions .", "target_text": {} }, { "input_text": "Corticosteroids are most effective in preventing the late phase of allergic reaction .", "target_text": {} }, { "input_text": "The action of glucocorticosteroids is mediated through glucocorticoid receptors present in the cellular cytoplasm .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "When activated , glucocorticoid receptors form a dimer and bind to DNA after migration into the nucleus .", "target_text": { "glucocorticoid receptors": "protein", "dimer": "protein" } }, { "input_text": "Interaction to DNA induces changes in the transcription rate , leading to either gene induction or gene repression .", "target_text": {} }, { "input_text": "Glucocorticoid receptors are also able to interact with transcriptional factors such as AP-1 ( activator protein-1 ) of NF-kappa B ( nuclear factor-kappa B ) .", "target_text": { "AP-1": "protein", "activator protein-1": "protein", "NF-kappa B": "protein", "nuclear factor-kappa B": "protein" } }, { "input_text": "Through these actions glucocorticosteroids are susceptible to modify functions of cells involved in the allergic inflammatory response .", "target_text": {} }, { "input_text": "They are in particular able to inhibit most of the pro-inflammatory functions of the eosinophils .", "target_text": { "eosinophils": "cell_type" } }, { "input_text": "Jeg-3 human choriocarcinoma-induced immunosuppression : downregulation of interleukin-2 , interleukin-2 receptor alpha-chain , and its Jak/Stat signaling pathway .", "target_text": { "interleukin-2": "protein", "interleukin-2 receptor alpha-chain": "protein", "Jak/Stat": "protein" } }, { "input_text": "PROBLEM : The mechanisms of the immunosuppressive and immunosuppression-inducing capacities of Jeg-3 human choriocarcinoma cell line supernatants ( HCSs ) are not yet completely understood .", "target_text": { "Jeg-3 human choriocarcinoma cell line": "cell_line" } }, { "input_text": "The influence on interleukin ( IL ) -2 , IL-4 and interferon ( IFN ) -gamma production ; IL-2 receptor ( IL-2R ) alpha - , beta - , and gamma-chain ; and the signaling pathway molecules Janus kinase ( Jak ) 1 , Jak3 , signal transducers and activators of transcription ( Stat ) 1 , Stat3 , and Stat5 should be investigated .", "target_text": { "interleukin ( IL ) -2": "protein", "IL-4": "protein", "interferon ( IFN ) -gamma": "protein", "IL-2 receptor ( IL-2R ) alpha": "protein", "beta": "protein", "gamma-chain": "protein", "signaling pathway molecules": "protein", "Janus kinase": "protein", "( Jak ) 1": "protein", "Jak3": "protein", "activators of transcription": "protein", "( Stat ) 1": "protein", "Stat3": "protein", "Stat5": "protein" } }, { "input_text": "METHOD OF STUDY : For assessment of IL production , whole peripheral venous blood from healthy donors was stimulated with phorbol-myristate-acetate and ionomycine .", "target_text": {} }, { "input_text": "Secretion of ILs was blocked with monensine .", "target_text": { "ILs": "protein" } }, { "input_text": "Intracellular ILs were analyzed by flow cytometry .", "target_text": { "ILs": "protein" } }, { "input_text": "For IL-2R and signaling pathway molecule analysis , peripheral blood lymphocytes were stimulated with phytohemagglutinin ( PHA ) .", "target_text": { "IL-2R": "protein", "blood lymphocytes": "cell_type", "phytohemagglutinin": "protein", "PHA": "protein" } }, { "input_text": "IL-2R chains were measured by flow cytometry , and Jaks/Stats by sodium dodecyl sulfate polyacrylamide gel electrophoresis ( SDS-PAGE ) and Western blot .", "target_text": { "Jaks/Stats": "protein" } }, { "input_text": "RESULTS : Phorbol-myristate-acetate and ionomycine strongly increase the percent-age of IL-2+ cells ; an additional 50 % HCSs significantly suppresses the percentage to , or below the level of unstimulated cells .", "target_text": { "IL-2+ cells": "cell_line", "unstimulated cells": "cell_type" } }, { "input_text": "IFN-gamma production is strongly decreased by HCSs in some cases , but not in others .", "target_text": {} }, { "input_text": "PHA stimulates IL-2R alpha- , beta- , and gamma- chain expression and their signaling pathway molecules Jak1 , Jak3 , Stat1 , Stat3 , and Stat5 .", "target_text": { "PHA": "protein", "signaling pathway molecules": "protein", "Jak1": "protein", "Jak3": "protein", "Stat3": "protein", "Stat5": "protein" } }, { "input_text": "50 % HCS downregulates the alpha-chain and slightly upregulates the beta-chain .", "target_text": { "alpha-chain": "protein", "beta-chain": "protein" } }, { "input_text": "Jak1 , Jak3 , Stat1 , Stat3 , and Stat5 expression is suppressed approximately to , or below the level of unstimulated cells .", "target_text": { "unstimulated cells": "cell_type" } }, { "input_text": "CONCLUSIONS : HCS forcefully blocks the production of IL-2 ; the IL-2R alpha-chain ; and Jak1 , Jak3 , Stat1 , Stat3 , and Stat5 expression .", "target_text": { "IL-2": "protein", "IL-2R alpha-chain": "protein" } }, { "input_text": "The observed phenomena might be caused by downregulation of an IL-2R regulation gene , and might play a key role in the expansion of choriocarcinoma , and possibly in the survival of the fetal allograft .", "target_text": { "IL-2R": "protein", "IL-2R regulation gene": "DNA" } }, { "input_text": "Apoptosis -resistant T cells have a deficiency in NF-kappaB -mediated induction of Fas ligand transcription .", "target_text": { "Apoptosis -resistant T cells": "cell_line", "NF-kappaB": "protein", "Fas ligand": "protein" } }, { "input_text": "Apoptosis induced through the TCR in CD4+ T cells is mostly mediated by the inducible expression of Fas ligand ( FasL ) as a primary event leading to the commitment to death .", "target_text": { "TCR": "protein", "CD4+ T cells": "cell_type", "Fas ligand": "protein", "FasL": "protein" } }, { "input_text": "To gain a better understanding of the transcriptional events that regulate this expression , we took advantage of our previously described mutant Jurkat cells .", "target_text": { "mutant Jurkat cells": "cell_line" } }, { "input_text": "These cells are deficient in FasL expression and apoptosis induced upon TCR triggering , although their cytokine ( IL-2 and IFN-gamma ) production is normal .", "target_text": { "FasL": "protein", "TCR": "protein", "IL-2": "protein", "IFN-gamma": "protein" } }, { "input_text": "Here we show that both a FasL- and a consensus NF-kappaB- reporter construct are inefficiently induced in these cells compared to wild-type cells .", "target_text": { "wild-type cells": "cell_type" } }, { "input_text": "In addition , we demonstrate that the inducible transcriptional activity of the FasL reporter is abolished by specific inhibitors of NF-kappaB activation .", "target_text": { "FasL": "protein", "FasL reporter": "DNA", "NF-kappaB": "protein" } }, { "input_text": "Thus , we could trace the deficit of the mutant cells to an inefficient NF-kappaB activation , evidencing a relevant role for NF-kappaB in the regulation of FasL expression in activated T cells .", "target_text": { "mutant cells": "cell_type", "NF-kappaB": "protein", "FasL": "protein", "activated T cells": "cell_type" } }, { "input_text": "Furthermore , our results suggest that the induction of FasL versus cytokine gene expression is differentially sensitive to NF-kappaB deprivation .", "target_text": { "FasL": "protein", "cytokine gene": "DNA", "NF-kappaB": "protein" } }, { "input_text": "Decreased proteasome -mediated degradation in T cells from the elderly : A role in immune senescence .", "target_text": { "proteasome": "protein", "T cells": "cell_type" } }, { "input_text": "Induction of NFkappaB is a highly regulated process requiring phosphorylation , ubiquitination , and proteasome -mediated degradation of the cytosolic inhibitor IkappaBalpha .", "target_text": { "NFkappaB": "protein", "proteasome": "protein", "cytosolic inhibitor": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Analyses of the regulation of IkappaBalpha in TNF-alpha -treated T lymphocytes from young and elderly donors revealed severely compromised degradation of IkappaBalpha in T cells from the elderly .", "target_text": { "IkappaBalpha": "protein", "TNF-alpha": "protein", "TNF-alpha -treated T lymphocytes": "cell_type", "T cells": "cell_type" } }, { "input_text": "Examination of activation-induced phosphorylation and ubiquitination of IkappaBalpha did not demonstrate any significant age-related alterations .", "target_text": { "IkappaBalpha": "protein" } }, { "input_text": "However , examination of proteasome activity in these T cells using fluorogenic peptide assays revealed a significant age-related decline in chymotryptic activity .", "target_text": { "proteasome": "protein", "T cells": "cell_type" } }, { "input_text": "These results suggest that a decline in proteasome activity results in a failure to fully degrade IkappaBalpha in the elderly .", "target_text": { "proteasome": "protein", "IkappaBalpha": "protein" } }, { "input_text": "This failure to degrade IkappaBalpha may underlie both the observed decrease in NFkappaB induction and the IL-2 receptor expression in TNF-treated T cells during aging .", "target_text": { "IkappaBalpha": "protein", "NFkappaB": "protein", "IL-2": "protein", "T cells": "cell_type", "TNF-treated T cells": "cell_line" } }, { "input_text": "Thus , decreased proteasome -mediated degradation may be central to immune dysfunction that accompanies aging .", "target_text": { "proteasome": "protein" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "Inhibition of IL-4 -inducible gene expression in human monocytes by type I and type II interferons .", "target_text": { "IL-4": "protein", "human monocytes": "cell_type" } }, { "input_text": "The Th2-type cytokines , interleukin-4 ( IL-4 ) and interleukin-13 ( IL-13 ) , induce expression of a distinct subset of genes in human monocytes , including FcepsilonRIIb ( CD23 ) , 15-lipoxygenase , IL-1 receptor antagonist ( IL-1ra ) , and type I and type II IL-1 receptors ( IL-1R ) .", "target_text": { "Th2-type cytokines": "protein", "interleukin-4": "protein", "IL-4": "protein", "interleukin-13": "protein", "IL-13": "protein", "human monocytes": "cell_type", "FcepsilonRIIb": "protein", "CD23": "protein", "15-lipoxygenase": "protein", "IL-1 receptor antagonist": "protein", "IL-1ra": "protein", "IL-1R": "protein" } }, { "input_text": "Type I interferons ( IFN-alpha and IFN-beta ) and type II interferon ( IFN-gamma ) inhibit induction of these genes by IL-4 and IL-13 .", "target_text": { "Type I interferons": "protein", "IFN-alpha": "protein", "IFN-beta": "protein", "type II interferon": "protein", "IFN-gamma": "protein", "IL-4": "protein", "IL-13": "protein" } }, { "input_text": "However , the mechanism by which IFNs mediate this inhibition has not been defined .", "target_text": { "IFNs": "protein" } }, { "input_text": "In this overview , we discuss the role of the transcription factor , STAT6 ( signal transducer and activator of transcription-6 ) in mediating IL-4- and IL-13- induced gene expression in monocytes .", "target_text": { "transcription factor": "protein", "STAT6": "protein", "signal transducer and activator of transcription-6": "protein", "monocytes": "cell_type" } }, { "input_text": "We also discuss our recent findings that type I and type II IFNs suppress IL-4 / IL-13 -inducible gene expression by inhibiting tyrosine phosphorylation and nuclear translocation of STAT6 .", "target_text": { "IL-4": "protein", "IL-13": "protein", "STAT6": "protein" } }, { "input_text": "The ability of type I and type II IFNs to inhibit IL-4 / IL-13 -induced STAT6 activity is dose- and time-dependent , and is not unique to monocytes because IFNs induce the same effects in fibroblasts .", "target_text": { "IL-4": "protein", "IL-13": "protein", "STAT6": "protein", "monocytes": "cell_type", "IFNs": "protein", "fibroblasts": "cell_type" } }, { "input_text": "Inhibition of STAT6 activity is not evident unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation .", "target_text": { "STAT6": "protein", "IFN": "protein", "IL-4": "protein" } }, { "input_text": "Furthermore , inhibition can be blocked by actinomycin D , indicating a requirement for de novo transcription .", "target_text": {} }, { "input_text": "We propose a model in which stimulation of monocytes by IFN activates de novo synthesis of an inhibitory factor , possibly one or more members of the SOCS/ SSI/CIS gene family , capable of suppressing activation of STAT6 by IL-4 and IL-13 .", "target_text": { "monocytes": "cell_type", "IFN": "protein", "inhibitory factor": "protein", "SOCS/ SSI/CIS gene family": "protein", "STAT6": "protein", "IL-4": "protein", "IL-13": "protein" } }, { "input_text": "Because STAT6 activation plays an essential role in IL-4 / IL-13 -induced gene expression , the ability of IFN-beta and IFN-gamma to inhibit STAT6 activity provides an explanation for how IFNs can suppress IL-4 / IL-13 -inducible gene expression .", "target_text": { "STAT6": "protein", "IL-4": "protein", "IL-13": "protein", "IFN-beta": "protein", "IFN-gamma": "protein", "IFNs": "protein" } }, { "input_text": "HLA class I -mediated induction of cell proliferation involves cyclin E -mediated inactivation of Rb function and induction of E2F activity .", "target_text": { "HLA class I": "protein", "cyclin E": "DNA", "E2F": "protein" } }, { "input_text": "Chronic rejection of transplanted organs is manifested as atherosclerosis of the blood vessels of the allograft .", "target_text": {} }, { "input_text": "HLA class I Ags have been implicated to play a major role in this process , since signaling via HLA class I molecules can induce the proliferation of aortic endothelial as well as smooth muscle cells .", "target_text": { "HLA class I Ags": "protein", "HLA class I molecules": "protein", "aortic endothelial": "cell_type", "smooth muscle cells": "cell_type" } }, { "input_text": "In this study , we show that HLA class I -mediated induction of cell proliferation correlates with inactivation of the Rb protein in the T cell line Jurkat as well as human aortic endothelial cells .", "target_text": { "HLA class I": "protein", "Rb protein": "protein", "T cell line Jurkat": "cell_line", "human aortic endothelial cells": "cell_type" } }, { "input_text": "HLA class I -mediated inactivation of Rb can be inhibited specifically by neutralizing Abs to basic fibroblast growth factor ( bFGF ) , suggesting a role for FGF receptors in the signaling process .", "target_text": { "HLA class I": "protein", "Rb": "protein", "neutralizing Abs": "protein", "basic fibroblast growth factor": "protein", "bFGF": "protein", "FGF receptors": "protein" } }, { "input_text": "Signaling through HLA class I molecules induced cyclin E -associated kinase activity within 4 h in quiescent endothelial cells , and appeared to mediate the inactivation of Rb .", "target_text": { "HLA class I molecules": "protein", "cyclin E": "DNA", "quiescent endothelial cells": "cell_type", "Rb": "protein" } }, { "input_text": "A cdk2 inhibitor , Olomoucine , as well as a dominant-negative cdk2 construct prevented HLA class I -mediated inactivation of Rb ; in contrast , dominant-negative cdk4 and cdk6 constructs had no effect .", "target_text": { "dominant-negative cdk2 construct": "DNA", "HLA class I": "protein", "Rb": "protein" } }, { "input_text": "Furthermore , there was no increase in cyclin D-associated kinase activity upon HLA class I ligation , suggesting that cyclin E-dependent kinase activity mediates Rb inactivation , leading to E2F activation and cell proliferation .", "target_text": { "cyclin D-associated kinase": "protein", "HLA class I": "protein", "cyclin E-dependent kinase": "protein", "Rb": "protein", "E2F": "protein" } }, { "input_text": "Immunosuppressant PG490 ( triptolide ) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation .", "target_text": { "T-cell interleukin-2": "protein", "purine-box/nuclear factor": "protein", "activated T-cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "PG490 ( triptolide ) is a diterpene triepoxide with potent immunosuppressive and antiinflammatory properties .", "target_text": {} }, { "input_text": "PG490 inhibits interleukin ( IL ) -2 expression by normal human peripheral blood lymphocytes stimulated with phorbol 12-myristate 13-acetate ( PMA ) and antibody to CD3 ( IC50 of 10 ng/ml ) , and with PMA and ionomycin ( Iono , IC50 of 40 ng/ml ) .", "target_text": { "interleukin ( IL ) -2": "protein", "normal human peripheral blood lymphocytes": "cell_type", "CD3": "protein" } }, { "input_text": "In Jurkat T-cells , PG490 inhibits PMA /Iono-stimulated IL-2 transcription .", "target_text": { "Jurkat T-cells": "cell_line", "IL-2": "protein" } }, { "input_text": "PG490 inhibits the induction of DNA binding activity at the purine-box/antigen receptor response element ( ARRE ) /nuclear factor of activated T-cells ( NF-AT ) target sequence but not at the NF-kappaB site .", "target_text": { "purine-box/antigen receptor response element ( ARRE ) /nuclear factor of activated T-cells ( NF-AT ) target sequence": "DNA", "NF-kappaB site": "DNA" } }, { "input_text": "PG490 can completely inhibit transcriptional activation at the purine-box/ARRE/NF-AT and NF-kappaB target DNA sequences triggered by all stimuli examined ( PMA , PMA /Iono , tumor necrosis factor-alpha ) .", "target_text": { "tumor necrosis factor-alpha": "protein" } }, { "input_text": "PG490 also inhibits PMA -stimulated activation of a chimeric transcription factor in which the C-terminal TA1 transactivation domain of NF-kappaB p65 is fused to the DNA binding domain of GAL4 .", "target_text": { "chimeric transcription factor": "protein", "C-terminal TA1 transactivation domain": "protein", "NF-kappaB p65": "protein", "DNA binding domain": "protein", "GAL4": "protein" } }, { "input_text": "In 16HBE human bronchial epithelial cells , IL-8 expression is regulated predominantly by NF-kappaB , and PG490 but not cyclosporin A can completely inhibit expression of IL-8 .", "target_text": { "16HBE human bronchial epithelial cells": "cell_type", "IL-8": "protein", "NF-kappaB": "protein" } }, { "input_text": "The mechanism of PG490 inhibition of cytokine gene expression differs from cyclosporin A and involves nuclear inhibition of transcriptional activation of NF-kappaB and the purine-box regulator operating at the ARRE/NF-AT site at a step after specific DNA binding .", "target_text": { "cytokine gene": "DNA", "NF-kappaB": "protein", "purine-box regulator": "DNA", "ARRE/NF-AT site": "DNA" } }, { "input_text": "Unexpected and coordinated expression of Spi-1 , Fli-1 , and megakaryocytic genes in four Epo-dependent cell lines established from transgenic mice displaying erythroid-specific expression of a thermosensitive SV40 T antigen .", "target_text": { "Spi-1": "protein", "Fli-1": "protein", "megakaryocytic genes": "DNA", "Epo-dependent cell lines": "cell_line", "thermosensitive SV40 T antigen": "protein" } }, { "input_text": "Most erythroleukemic cell lines established in vitro coexpress erythrocytic and megakaryocytic markers that often are associated with expression of Spi-1 and/or Fli-1 transcription factors known as transactivators of megakaryocyte-specific promoters .", "target_text": { "erythroleukemic cell lines": "cell_line", "Spi-1": "protein", "Fli-1": "protein", "Fli-1 transcription factors": "protein", "megakaryocyte-specific promoters": "DNA", "transactivators of megakaryocyte-specific promoters": "protein" } }, { "input_text": "In the present study , we examined the possibility of establishing new cell lines keeping strictly erythroid-specific properties in vitro through the targeted and conditional immortalization of erythrocytic progenitors .", "target_text": { "new cell lines": "cell_line", "erythrocytic progenitors": "cell_type" } }, { "input_text": "For that purpose , we established several lines of transgenic mice displaying erythroid-specific expression of a thermosensitive SV40 T antigen .", "target_text": { "thermosensitive SV40 T antigen": "protein" } }, { "input_text": "As expected , these transgenic mice developed splenomegaly due to the massive amplification of Ter 119 positive erythroid nucleated cells expressing T antigen .", "target_text": { "Ter 119 positive erythroid nucleated cells": "cell_line", "T antigen": "protein" } }, { "input_text": "Despite this drastic effect in vivo , the in vitro immortalization of erythropoietin-dependent erythroid progenitors unexpectedly occurred at low frequency , and all four cell lines established expressed both erythrocytic ( globins ) and megakaryocytic markers ( glycoprotein IIb , platelet factor 4 ) as well as Spi-1 and Fli-1 transcripts at permissive temperature .", "target_text": { "erythropoietin-dependent erythroid progenitors": "cell_type", "cell lines": "cell_line", "glycoprotein IIb": "protein", "platelet factor 4": "protein", "Spi-1": "protein", "Fli-1 transcripts": "protein" } }, { "input_text": "Switching the cells to the nonpermissive temperature led to a marked increase in globin gene expression and concomitant decrease in expression of Spi-1 , Fli-1 , and megakaryocytic genes in an erythropoietin -dependent manner .", "target_text": { "globin gene": "DNA", "Spi-1": "protein", "Fli-1": "protein", "megakaryocytic genes": "DNA", "erythropoietin": "protein" } }, { "input_text": "Interestingly , enhanced expression of Spi-1 and Fli-1 genes already was detected in the Ter 119 positive cell population of transgenic mice spleen in vivo .", "target_text": { "Ter 119 positive cell population": "cell_line" } }, { "input_text": "However , like normal Ter 119 erythroid cells , these Ter 119 positive cells from transgenic mice still expressed high levels of beta-globin and very low or undetectable glycoprotein IIb and platelet factor 4 megakaryocytic transcripts .", "target_text": { "normal Ter 119 erythroid cells": "cell_line", "Ter 119 positive cells": "cell_line", "beta-globin": "protein", "glycoprotein IIb": "protein", "platelet factor 4": "protein", "platelet factor 4 megakaryocytic transcripts": "protein" } }, { "input_text": "Taken together , these data indicate that the unexpected expression of megakaryocytic genes is a specific property of immortalized cells that can not be explained only by enhanced expression of Spi-1 and/or Fli-1 genes .", "target_text": { "megakaryocytic genes": "DNA", "immortalized cells": "cell_line" } }, { "input_text": "Fludarabine -induced immunosuppression is associated with inhibition of STAT1 signaling .", "target_text": { "STAT1": "protein" } }, { "input_text": "Fludarabine is a nucleoside analog used in the treatment of hematologic malignancies that can induce severe and prolonged immunosuppression .", "target_text": {} }, { "input_text": "Although it can be incorporated into the DNA of dividing cells , fludarabine is also a potent inhibitor of cells with a low growth fraction , thus it must have other mechanisms of action .", "target_text": {} }, { "input_text": "STAT1 , which is activated in response to many lymphocyte-activating cytokines including the interferons , is essential for cell-mediated immunity , as the absence of this protein is associated with prominent defects in the ability to control viral infections .", "target_text": { "STAT1": "protein", "lymphocyte-activating cytokines": "protein", "interferons": "protein" } }, { "input_text": "Here we show that fludarabine , but not the immunosuppressant cyclosporine A , inhibits the cytokine -induced activation of STAT1 and STAT1 -dependent gene transcription in normal resting or activated lymphocytes .", "target_text": { "cytokine": "protein", "STAT1": "protein" } }, { "input_text": "Fludarabine caused a specific depletion of STAT1 protein ( and mRNA ) but not of other STATs .", "target_text": { "STAT1": "protein", "STAT1 protein": "protein", "STATs": "protein" } }, { "input_text": "This loss of STAT1 was also seen in cells from patients treated with fludarabine in vivo .", "target_text": { "STAT1": "protein" } }, { "input_text": "Brief exposure to fludarabine led to a sustained loss of STAT1 , analogous to the prolonged period of immunosuppression induced by exposure to the drug in vivo .", "target_text": { "STAT1": "protein" } }, { "input_text": "Thus , STAT1 may be a useful target in the development of new immunosuppressive and antineoplastic agents .", "target_text": { "STAT1": "protein" } }, { "input_text": "Studies into the effect of tyrosine phosphatase inhibitor phenylarsine oxide on NFkappaB activation in T lymphocytes during aging : evidence for altered IkappaB-alpha phosphorylation and degradation .", "target_text": { "tyrosine phosphatase": "protein", "NFkappaB": "protein", "T lymphocytes": "cell_type", "IkappaB-alpha": "protein" } }, { "input_text": "Nuclear Factor kappa B ( NFkappaB ) is a critical regulator of several genes involved in immune and inflammatory responses .", "target_text": { "Nuclear Factor kappa B": "protein", "NFkappaB": "protein" } }, { "input_text": "Treatment of T cells with a variety of stimuli , including TNF-alpha , leads to the translocation of the active p65-50 heterodimer to the nucleus , albeit at a lower level in T cells from the elderly .", "target_text": { "T cells": "cell_type", "TNF-alpha": "protein", "p65-50 heterodimer": "protein" } }, { "input_text": "We demonstrate here that pretreatment with PAO results in the inhibition of NFkappaB induction in TNF-alpha treated T cells , suggesting a role for PAO -sensitive phosphatase in the activation of the NFkappaB via this pathway in human T cells .", "target_text": { "NFkappaB": "protein", "TNF-alpha": "protein", "T cells": "cell_type", "PAO -sensitive phosphatase": "protein", "human T cells": "cell_type" } }, { "input_text": "Furthermore , it demonstrates that aging does not influence the sensitivity of this phosphatase .", "target_text": { "phosphatase": "protein" } }, { "input_text": "Treatment with DMP prior to treatment with PAO and TNF abolishes the inhibition induced by PAO , in T cells from both young and old donors , alike .", "target_text": { "TNF": "protein", "T cells": "cell_type" } }, { "input_text": "Finally , we demonstrate that a failure to degrade IkappaB-alpha in cytosols of TNF -treated T cells pretreated with PAO is due to its interference with the phosphorylation of IkappaB-alpha and not due to its inhibitory effect on proteasomal degradation .", "target_text": { "IkappaB-alpha": "protein", "TNF": "protein", "T cells": "cell_type", "TNF -treated T cells": "cell_type" } }, { "input_text": "These data collectively suggest that PAO interferes with the phosphorylation and the regulated degradation of IkappaB-alpha , induced by TNF , without affecting the chymotryptic activity of the proteasome , independent of age .", "target_text": { "IkappaB-alpha": "protein", "TNF": "protein", "proteasome": "protein" } }, { "input_text": "Spi-C , a novel Ets protein that is temporally regulated during B lymphocyte development .", "target_text": { "Spi-C": "protein", "Ets protein": "protein" } }, { "input_text": "A novel Ets protein was isolated by yeast one-hybrid screening of a cDNA library made from lipopolysaccharide-stimulated mouse splenic B cells , using the SP6 kappa promoter kappaY element as a bait .", "target_text": { "Ets protein": "protein", "cDNA library": "DNA", "lipopolysaccharide-stimulated mouse splenic B cells": "cell_line", "SP6 kappa promoter kappaY element": "DNA" } }, { "input_text": "The novel Ets protein was most closely related to PU.1 and Spi-B within the DNA binding Ets domain and was therefore named Spi-C .", "target_text": { "Ets protein": "protein", "PU.1": "protein", "Spi-B": "protein", "DNA binding Ets domain": "DNA", "Spi-C": "protein" } }, { "input_text": "However , Spi-C may represent a novel subgroup within the Ets protein family , as it differed significantly from Spi-B and PU.1 within helix 1 of the Ets domain .", "target_text": { "Spi-C": "protein", "Ets protein": "protein", "Ets protein family": "protein", "Spi-B": "protein", "PU.1": "protein", "helix 1": "protein", "Ets domain": "protein" } }, { "input_text": "Spi-C was encoded by a single-copy gene that was mapped to chromosome 10 , region C .", "target_text": { "Spi-C": "protein", "single-copy gene": "DNA", "chromosome 10": "DNA", "region C": "DNA" } }, { "input_text": "Spi-C interacted with DNA similarly to PU.1 as judged by methylation interference , band-shift and site selection analysis , and activated transcription of a kappaY element reporter gene upon co-transfection of HeLa cells .", "target_text": { "Spi-C": "protein", "PU.1": "protein", "kappaY element reporter gene": "DNA", "HeLa cells": "cell_line" } }, { "input_text": "Spi-C RNA was expressed in mature B lymphocytes and at lower levels in macrophages .", "target_text": { "Spi-C": "protein", "Spi-C RNA": "RNA", "mature B lymphocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "Furthermore , pre-B cell and plasma cell lines were Spi-C -negative , suggesting that Spi-C might be a regulatory molecule during a specific phase of B lymphoid development .", "target_text": { "Spi-C": "protein", "regulatory molecule": "protein" } }, { "input_text": "Glucocorticoid -induced cell death requires autoinduction of glucocorticoid receptor expression in human leukemic T cells .", "target_text": { "glucocorticoid receptor": "protein", "human leukemic T cells": "cell_type" } }, { "input_text": "In contrast to the negative autoregulation of glucocorticoid receptor ( GR ) expression seen in most cells and tissues , GR expression is positively autoregulated in human leukemic T cells and in other cells sensitive to glucocorticoid-induced cell death .", "target_text": { "glucocorticoid receptor": "protein", "GR": "protein", "human leukemic T cells": "cell_type" } }, { "input_text": "To determine whether positive autoregulation is a necessary component of glucocorticoid-induced cell death , a wild-type GR gene under the control of a tetracycline -regulated promoter was stably transfected into glucocorticoid-resistant cells lacking endogenous functional receptor .", "target_text": { "GR": "protein", "wild-type GR gene": "DNA", "tetracycline -regulated promoter": "DNA", "glucocorticoid-resistant cells": "cell_line" } }, { "input_text": "Transfectants grown in the presence of tetracycline contained about 15,000 receptors/cell , a value approximately equal to basal level GR expression in glucocorticoid-sensitive 6TG1.1 cells before steroid treatment .", "target_text": { "Transfectants": "cell_line", "GR": "protein", "glucocorticoid-sensitive 6TG1.1 cells": "cell_line" } }, { "input_text": "Under these conditions , dexamethasone had a minimal effect on cell growth , elicited little internucleosomal DNA fragmentation , and induced no cell cycle perturbation .", "target_text": {} }, { "input_text": "In the absence of tetracycline , GR mRNA and protein expression increased 2-3-fold , and cells expressed 48,000 receptors , a level nearly equivalent to that present in 6TG1.1 cells after 18 h of autoinduction .", "target_text": { "GR mRNA": "RNA", "6TG1.1 cells": "cell_line" } }, { "input_text": "Under these conditions , dexamethasone markedly inhibited cell growth , caused G1 arrest , and induced significant internucleosomal DNA fragmentation .", "target_text": {} }, { "input_text": "These studies therefore suggest that basal level GR expression is inadequate to mediate glucocorticoid-induced apoptosis in glucocorticoid-sensitive T cells and that positive autoregulation is a necessary component of this process .", "target_text": { "GR": "protein", "glucocorticoid-sensitive T cells": "cell_line" } }, { "input_text": "Constitutive activation of NF-kappaB in primary adult T-cell leukemia cells .", "target_text": { "NF-kappaB": "protein", "primary adult T-cell leukemia cells": "cell_type" } }, { "input_text": "Human T-cell leukemia virus type I ( HTLV-I ) is an etiologic agent of adult T-cell leukemia ( ATL ) .", "target_text": {} }, { "input_text": "The viral protein Tax induces the activation and nuclear translocalization of transcription factor NF-kappaB , which is proposed to play a crucial role in the transformation of T cells by HTLV-I .", "target_text": { "viral protein": "protein", "Tax": "protein", "transcription factor": "protein", "NF-kappaB": "protein", "T cells": "cell_type" } }, { "input_text": "However , the HTLV-I genes including Tax are not expressed significantly in primary leukemic cells from ATL patients .", "target_text": { "HTLV-I genes": "DNA", "Tax": "protein", "primary leukemic cells": "cell_type" } }, { "input_text": "In this study , we examined the basis for NF-kappaB activation in freshly isolated leukemic cells from ATL patients .", "target_text": { "NF-kappaB": "protein", "freshly isolated leukemic cells": "cell_type" } }, { "input_text": "We found that leukemic cells from ATL patients , like HTLV-I -infected T-cell lines , display constitutive NF-kappaB DNA binding activity and increased degradation of IkappaBalpha ( an inhibitor of NF-kappaB ) .", "target_text": { "leukemic cells": "cell_type", "HTLV-I -infected T-cell lines": "cell_line", "NF-kappaB": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Whereas the NF-kappaB binding activity in Tax -expressing T-cell lines consisted mostly of p50/c-Rel , fresh ATL samples contained p50/p50 and p50/p65 heterodimers .", "target_text": { "NF-kappaB": "protein", "Tax": "protein", "Tax -expressing T-cell lines": "cell_line", "p50/c-Rel": "protein" } }, { "input_text": "One T-cell line derived from ATL leukemic cells , TL-Om1 , displayed constitutive NF-kappaB activity , as well as enhanced degradation of IkappaBalpha , despite the lack of detectable Tax expression .", "target_text": { "T-cell line": "cell_line", "leukemic cells": "cell_type", "NF-kappaB": "protein", "IkappaBalpha": "protein", "Tax": "protein" } }, { "input_text": "Interestingly , the NF-kappaB in TL-Om1 consists of p50/p50 and p50/p65 like that in fresh primary leukemic cells .", "target_text": { "NF-kappaB": "protein", "p50/p50": "protein", "p50/p65": "protein", "leukemic cells": "cell_type", "primary leukemic cells": "cell_type" } }, { "input_text": "Our results suggest that activation of NF-kappaB occurs through a Tax -independent mechanism in leukemic cells of ATL patients , possibly due to differential NF-kappaB subunit activation .", "target_text": { "NF-kappaB": "protein", "Tax": "protein", "leukemic cells": "cell_type" } }, { "input_text": "Interferon-alpha induction of STATs 1 , -3 DNA binding and growth arrest is independent of Lck and active mitogen-activated kinase in T cells .", "target_text": { "Interferon-alpha": "protein", "Lck": "protein", "mitogen-activated kinase": "protein", "T cells": "cell_type" } }, { "input_text": "Type I interferons ( IFNs ) are a family of cytokines that have antiviral and antiproliferative effects .", "target_text": { "interferons": "protein", "IFNs": "protein", "cytokines": "protein" } }, { "input_text": "Data regarding the processes by which these cytokines transduce signals from the cell membrane to the nucleus are becoming increasingly complex .", "target_text": { "cytokines": "protein" } }, { "input_text": "The most characterized pathway is via JAK -STAT signaling .", "target_text": { "JAK": "protein", "-STAT": "protein" } }, { "input_text": "Previous studies established a potential role for the Src-family kinase Lck in JAK -STAT signaling .", "target_text": { "Src-family kinase": "protein", "Lck": "protein", "JAK": "protein", "-STAT": "protein" } }, { "input_text": "Therefore , this study was designed to analyze the role of Lck in IFN-alpha signaling by using the Jurkat , JCam ( an Lck -defective cell line derived from Jurkat ) , and JCam/ Lck ( JCam cells with Lck restored ) .", "target_text": { "Lck": "protein", "IFN-alpha": "protein", "Lck -defective cell line": "cell_line", "Jurkat": "cell_line", "JCam/ Lck": "cell_line", "JCam cells": "cell_line" } }, { "input_text": "The results show that IFN-alpha can induce MAPK activity , but only in cells containing Lck .", "target_text": { "IFN-alpha": "protein", "MAPK": "protein", "Lck": "protein" } }, { "input_text": "Furthermore , STATs 1 and -3 are effectively phosphorylated and activated to bind DNA in the absence of Lck expression in IFN-alpha -treated cells .", "target_text": { "Lck": "protein", "IFN-alpha": "protein", "IFN-alpha -treated cells": "cell_line" } }, { "input_text": "Finally , the results demonstrate that IFN-alpha exerts an antiproliferative effect in all three cell lines .", "target_text": { "IFN-alpha": "protein" } }, { "input_text": "These data indicate that Lck and active MAPK do not affect IFN-alpha -induced growth arrest or induction of STAT1s1 and -3 DNA binding ability .", "target_text": { "Lck": "protein", "MAPK": "protein", "IFN-alpha": "protein" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "Selective activation and functional significance of p38alpha mitogen-activated protein kinase in lipopolysaccharide -stimulated neutrophils .", "target_text": { "p38alpha mitogen-activated protein kinase": "protein", "lipopolysaccharide -stimulated neutrophils": "cell_line" } }, { "input_text": "Activation of leukocytes by proinflammatory stimuli selectively initiates intracellular signal transduction via sequential phosphorylation of kinases .", "target_text": { "leukocytes": "cell_type", "kinases": "protein" } }, { "input_text": "Lipopolysaccharide ( LPS ) stimulation of human neutrophils is known to result in activation of p38 mitogen-activated protein kinase ( MAPk ) ; however , the upstream activator ( s ) of p38 MAPk is unknown , and consequences of p38 MAPk activation remain largely undefined .", "target_text": { "human neutrophils": "cell_type", "p38 mitogen-activated protein kinase": "protein", "MAPk": "protein", "upstream activator": "protein", "p38 MAPk": "protein" } }, { "input_text": "We investigated the MAPk kinase ( MKK ) that activates p38 MAPk in response to LPS , the p38 MAPk isoforms that are activated as part of this pathway , and the functional responses affected by p38 MAPk activation .", "target_text": { "MAPk kinase": "protein", "MKK": "protein", "p38 MAPk": "protein", "p38 MAPk isoforms": "protein" } }, { "input_text": "Although MKK3 , MKK4 , and MKK6 all activated p38 MAPk in experimental models , only MKK3 was found to activate recombinant p38 MAPk in LPS -treated neutrophils .", "target_text": { "MKK3": "protein", "MKK4": "protein", "MKK6": "protein", "p38 MAPk": "protein" } }, { "input_text": "Of p38 MAPk isoforms studied , only p38alpha and p38delta were detected in neutrophils .", "target_text": { "p38 MAPk": "protein", "p38 MAPk isoforms": "protein", "p38alpha": "protein", "p38delta": "protein", "neutrophils": "cell_type" } }, { "input_text": "LPS stimulation selectively activated p38alpha .", "target_text": { "p38alpha": "protein" } }, { "input_text": "Specific inhibitors of p38alpha MAPk blocked LPS -induced adhesion , nuclear factor-kappa B ( NF-kappaB ) activation , and synthesis of tumor necrosis factor-alpha ( TNF-alpha ) .", "target_text": { "p38alpha": "protein", "p38alpha MAPk": "protein", "NF-kappaB": "protein", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "Inhibition of p38alpha MAPk resulted in a transient decrease in TNF-alpha mRNA accumulation but persistent loss of TNF-alpha synthesis .", "target_text": { "p38alpha": "protein", "p38alpha MAPk": "protein", "TNF-alpha mRNA": "RNA", "TNF-alpha": "protein" } }, { "input_text": "These findings support a pathway by which LPS stimulation of neutrophils results in activation of MKK3 , which in turn activates p38alpha MAPk , ultimately regulating adhesion , NF-kappaB activation , enhanced gene expression of TNF-alpha , and regulation of TNF-alpha synthesis .", "target_text": { "neutrophils": "cell_type", "MKK3": "protein", "p38alpha": "protein", "p38alpha MAPk": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein" } }, { "input_text": "The evolutionarily conserved sequence upstream of the human Ig heavy chain S gamma 3 region is an inducible promoter : synergistic activation by CD40 ligand and IL-4 via cooperative NF-kappa B and STAT-6 binding sites .", "target_text": { "evolutionarily conserved sequence": "DNA", "human Ig heavy chain S gamma 3 region": "protein", "inducible promoter": "DNA", "CD40 ligand": "protein", "IL-4": "protein" } }, { "input_text": "Germline C gamma gene transcription is a crucial event in the process that leads to switch DNA recombination to IgG , but its regulation in the human is poorly understood .", "target_text": { "IgG": "protein" } }, { "input_text": "We took advantage of our monoclonal model of germinal center B cell differentiation , IgM+ IgD+ CL-01 cells , to define the role of the I gamma 3 evolutionarily conserved sequence ( ECS ) in the germline transcriptional activation of the human C gamma 3 gene .", "target_text": { "germinal center B cell": "cell_type", "IgM+ IgD+ CL-01 cells": "cell_line", "I gamma 3": "protein", "evolutionarily conserved sequence": "DNA", "ECS": "DNA", "germline": "DNA", "human C gamma 3 gene": "DNA" } }, { "input_text": "The I gamma 3 ECS lies upstream of the major I gamma 3 transcription initiation site and displays more than 90 % identity with the corresponding human I gamma 1 , I gamma 2 , and I gamma 4 regions .", "target_text": { "I gamma 3": "protein", "ECS": "DNA", "major I gamma 3 transcription initiation site": "DNA", "human I gamma 1": "DNA", "I gamma 2": "DNA", "I gamma 4": "DNA" } }, { "input_text": "Reporter luciferase gene vectors containing the human gamma 3 ECS were used to transfect CL-01 cells , which have been shown to undergo Smu --> S gamma 3 DNA recombination , upon engagement of CD40 by CD40 ligand ( CD40L ) and exposure to IL-4 .", "target_text": { "Reporter luciferase gene vectors": "DNA", "ECS": "DNA", "human gamma 3 ECS": "DNA", "CL-01 cells": "cell_line", "CD40": "protein", "CD40 ligand": "protein", "CD40L": "protein", "IL-4": "protein" } }, { "input_text": "In these transfected CL-01 cells , CD40: CD40L engagement and exposure to IL-4 synergistically induced gamma 3 ECS-dependent luciferase reporter gene activation .", "target_text": { "CL-01 cells": "cell_line", "CD40L": "protein", "IL-4": "protein", "luciferase reporter gene": "DNA" } }, { "input_text": "Targeted mutational analysis demonstrated that a tandem NF-kappa B /Rel binding motif is critical for the gamma 3 ECS responsiveness to both CD40L and IL-4 , while a STAT-6-binding site is additionally required for IL-4 inducibility .", "target_text": { "NF-kappa B": "protein", "NF-kappa B /Rel binding motif": "DNA", "gamma 3 ECS": "DNA", "CD40L": "protein", "IL-4": "protein", "STAT-6-binding site": "DNA" } }, { "input_text": "Electrophoretic mobility shift assays showed that p50/p65/c-Rel and STAT-6 are effectively induced by CD40L and IL-4 , respectively , and bind to specific DNA motifs within the ECS .", "target_text": { "p50/p65/c-Rel": "protein", "STAT-6": "protein", "CD40L": "protein", "IL-4": "protein", "DNA motifs": "DNA", "ECS": "DNA" } }, { "input_text": "These partially overlapping CD40L and IL-4 responsive elements are functionally cooperative as the disruption of one of them prevents synergistic promoter activation .", "target_text": {} }, { "input_text": "Thus , the gamma 3 ECS is an inducible promoter containing cis elements that critically mediate CD40L and IL-4 -triggered transcriptional activation of the human C gamma 3 gene .", "target_text": { "gamma 3 ECS": "DNA", "cis elements": "DNA", "CD40L": "protein", "IL-4": "protein", "human C gamma 3 gene": "DNA" } }, { "input_text": "CIITA -induced occupation of MHC class II promoters is independent of the cooperative stabilization of the promoter-bound multi-protein complexes .", "target_text": { "CIITA": "protein", "MHC class II": "cell_type", "MHC class II promoters": "DNA", "promoter-bound multi-protein complexes": "protein" } }, { "input_text": "Precise regulation of MHC class II expression plays a crucial role in the control of the immune response .", "target_text": { "MHC class II": "cell_type" } }, { "input_text": "The transactivator CIITA behaves as a master controller of constitutive and inducible MHC class II gene activation , but its exact mechanism of action is not known .", "target_text": { "transactivator": "protein", "CIITA": "protein", "MHC class II": "cell_type", "MHC class II gene": "DNA" } }, { "input_text": "Activation of MHC class II promoters requires binding of at least three distinct multi-protein complexes ( RFX , X2BP and NF-Y ) .", "target_text": { "MHC class II": "cell_type", "MHC class II promoters": "DNA", "multi-protein complexes": "protein", "RFX": "protein", "X2BP": "protein", "NF-Y": "protein" } }, { "input_text": "It is known that the stability of this binding results from cooperative interactions between these proteins .", "target_text": {} }, { "input_text": "We show here that expression of CIITA in MHC class II -cells triggers occupation of the promoters by these complexes .", "target_text": { "CIITA": "protein", "MHC class II": "cell_type", "MHC class II -cells": "cell_line" } }, { "input_text": "This observation raised the possibility that the effect of CIITA on promoter occupation is mediated by an effect on the cooperative stabilization of the DNA-bound multi-protein complexes .", "target_text": { "CIITA": "protein", "DNA-bound multi-protein complexes": "protein" } }, { "input_text": "We show , however , that the presence of CIITA does not affect the stability of the higher-order protein complex formed on DNA by RFX , X2BP and NF-Y .", "target_text": { "CIITA": "protein", "RFX": "protein", "X2BP": "protein", "NF-Y": "protein" } }, { "input_text": "This suggests other mechanisms for CIITA -induced promoter occupancy , such as an effect on chromatin structure leading to increased accessibility of MHC class II promoters .", "target_text": { "CIITA": "protein", "chromatin": "DNA", "MHC class II": "cell_type", "MHC class II promoters": "DNA" } }, { "input_text": "This ability of CIITA to facilitate promoter occupation is undissociable from its transactivation potential .", "target_text": { "CIITA": "protein" } }, { "input_text": "Finally , we conclude that this effect of CIITA is cell-type specific , since expression of CIITA is not required for normal occupation of MHC class II promoters in B lymphocytes .", "target_text": { "CIITA": "protein", "MHC class II": "cell_type", "MHC class II promoters": "DNA", "B lymphocytes": "cell_type" } }, { "input_text": "GrpL , a Grb2 -related adaptor protein , interacts with SLP-76 to regulate nuclear factor of activated T cell activation .", "target_text": { "GrpL": "protein", "Grb2": "protein", "adaptor protein": "protein", "SLP-76": "protein", "activated T cell": "cell_type", "nuclear factor of activated T cell": "protein" } }, { "input_text": "Propagation of signals from the T cell antigen receptor ( TCR ) involves a number of adaptor molecules .", "target_text": { "T cell": "cell_type", "T cell antigen receptor": "protein", "TCR": "protein" } }, { "input_text": "SH2 domain-containing protein 76 ( SLP-76 ) interacts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells ( NF-AT ) , and its expression is required for normal T cell development .", "target_text": { "SH2 domain-containing protein 76": "protein", "SLP-76": "protein", "guanine nucleotide exchange factor": "protein", "Vav": "protein", "nuclear factor of activated cells": "protein", "NF-AT": "protein", "T cell": "cell_type" } }, { "input_text": "We report the cloning and characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system ( GrpL ) .", "target_text": { "Grb2-like adaptor molecule": "protein", "Grb2-related protein of the lymphoid system": "protein", "GrpL": "protein" } }, { "input_text": "Expression of GrpL is restricted to hematopoietic tissues , and it is distinguished from Grb2 by having a proline -rich region .", "target_text": { "GrpL": "protein", "Grb2": "protein", "proline -rich region": "protein" } }, { "input_text": "GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell lysates .", "target_text": { "GrpL": "protein", "SLP-76": "protein", "Sos1": "protein", "Sos2": "protein", "Jurkat cell": "cell_line" } }, { "input_text": "In contrast , Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not with SLP-76 .", "target_text": { "Grb2": "protein", "Sos1": "protein", "Sos2": "protein", "SLP-76": "protein" } }, { "input_text": "Moreover , tyrosine -phosphorylated LAT / pp36 / 38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL .", "target_text": { "LAT": "protein", "pp36": "protein", "38": "protein", "tyrosine -phosphorylated LAT / pp36 / 38": "protein", "anti-CD3 stimulated T cells": "cell_type", "Grb2": "protein", "GrpL": "protein" } }, { "input_text": "These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells .", "target_text": { "GrpL": "protein", "Grb2": "protein", "T cells": "cell_type" } }, { "input_text": "A functional role of the GrpL -SLP-76 complex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells .", "target_text": { "GrpL": "protein", "-SLP-76": "protein", "GrpL -SLP-76 complex": "protein", "SLP-76": "protein", "NF-AT": "protein", "Jurkat": "cell_line", "T cells": "cell_type" } }, { "input_text": "Differential induction of interferon ( IFN ) -inducible protein 10 following differentiation of a monocyte , macrophage cell lineage is related to the changes of nuclear proteins bound to IFN stimulus response element and kappaB sites .", "target_text": { "interferon ( IFN ) -inducible protein 10": "protein", "monocyte": "cell_type", "macrophage cell": "cell_type", "nuclear proteins": "protein", "IFN stimulus response element": "DNA", "kappaB": "DNA", "kappaB sites": "DNA" } }, { "input_text": "We examined chemokine gene expression following the differentiation of a monocyte , macrophage cell lineage .", "target_text": { "chemokine": "protein", "monocyte": "cell_type", "macrophage": "cell_type", "macrophage cell lineage": "cell_line" } }, { "input_text": "The human monoblastic cell line , U937 was differentiated to macrophages by the treatment with either phorbol 12-myristate 13-acetate ( PMA ) , retinoic acid ( RA ) , or vitamin D3 ( VitD3 ) .", "target_text": { "human monoblastic cell line": "cell_line", "U937": "cell_line", "macrophages": "cell_type" } }, { "input_text": "The gene expression of interferon ( IFN ) -inducible protein 10 ( IP-10 ) ( a CXC chemokine ) was markedly augmented by the IFNgamma treatment in PMA - or RA -differentiated U937 cells , but only marginally in undifferentiated or VitD3 -treated cells .", "target_text": { "interferon ( IFN ) -inducible protein 10": "protein", "IP-10": "protein", "CXC chemokine": "protein", "IFNgamma": "protein", "U937 cells": "cell_line", "VitD3 -treated cells": "cell_line" } }, { "input_text": "In contrast , another inducible gene expression of monocyte chemotactic protein-1 ( a CC chemokine ) and the activation of the transcriptional factor ( FcRFgamma ) bound to the gamma response region were similarly or less abundantly induced by IFNgamma treatment in PMA - or RA -differentiated U937 cells , indicating that increased IP-10 mRNA induction was not due to the augmented ability of the cells to respond to the presence of IFNgamma .", "target_text": { "monocyte chemotactic protein-1": "protein", "CC chemokine": "protein", "transcriptional factor": "protein", "FcRFgamma": "protein", "gamma response region": "DNA", "IFNgamma": "protein", "U937 cells": "cell_line", "IP-10": "protein", "IP-10 mRNA": "RNA" } }, { "input_text": "Increased expression of IFNgamma -induced IP-10 mRNA following the differentiation of U937 cells was mediated largely by augmented transcriptional activity of the gene and was related to differentiation-dependent changes of the proteins bound to IFN stimulus response element ( ISRE ) and kB sites , suggesting that these nuclear proteins may determine the IP-10 mRNA inducibility by IFNgamma .", "target_text": { "IFNgamma": "protein", "IP-10": "protein", "IP-10 mRNA": "RNA", "U937 cells": "cell_line", "ISRE": "DNA", "IFN stimulus response element ( ISRE )": "DNA", "kB sites": "DNA", "nuclear proteins": "protein" } }, { "input_text": "Role of cellular tumor necrosis factor receptor-associated factors in NF-kappaB activation and lymphocyte transformation by herpesvirus Saimiri STP .", "target_text": { "cellular tumor necrosis factor receptor-associated factors": "protein", "NF-kappaB": "protein", "lymphocyte": "cell_type", "STP": "protein" } }, { "input_text": "The STP oncoproteins of the herpesvirus saimiri ( HVS ) subgroup A strain 11 and subgroup C strain 488 are now found to be stably associated with tumor necrosis factor receptor-associated factor ( TRAF ) 1 , 2 , or 3 .", "target_text": { "STP oncoproteins": "protein", "tumor necrosis factor receptor-associated factor": "protein", "TRAF": "protein" } }, { "input_text": "Mutational analyses identified residues of PXQXT/S in STP-A11 as critical for TRAF association .", "target_text": { "PXQXT/S": "protein", "STP-A11": "protein", "TRAF": "protein" } }, { "input_text": "In addition , a somewhat divergent region of STP-C488 is critical for TRAF association .", "target_text": { "STP-C488": "protein", "TRAF": "protein" } }, { "input_text": "Mutational analysis also revealed that STP-C488 induced NF-kappaB activation that was correlated with its ability to associate with TRAFs .", "target_text": { "STP-C488": "protein", "NF-kappaB": "protein", "TRAFs": "protein" } }, { "input_text": "The HVS STP-C488 P10 --> R mutant was deficient in human T-lymphocyte transformation to interleukin-2-independent growth but showed wild-type phenotype for marmoset T-lymphocyte transformation in vitro and in vivo .", "target_text": { "STP-C488": "protein" } }, { "input_text": "The STP-C488 P10 --> R mutant was also defective in Rat-1 fibroblast transformation , and fibroblast cell transformation was blocked by a TRAF2 dominant-negative mutant .", "target_text": { "STP-C488 P10 --> R mutant": "protein", "TRAF2": "protein" } }, { "input_text": "These data implicate TRAFs in STP-C488 -mediated transformation of human lymphocytes and rodent fibroblasts .", "target_text": { "TRAFs": "protein", "STP-C488": "protein", "human lymphocytes": "cell_type", "fibroblasts": "cell_type" } }, { "input_text": "Other factors are implicated in immortalization of common marmoset T lymphocytes and may also be critical in the transformation of human lymphocytes and rodent fibroblasts .", "target_text": { "common marmoset T lymphocytes": "cell_type", "human lymphocytes": "cell_type", "fibroblasts": "cell_type", "rodent fibroblasts": "cell_type" } }, { "input_text": "Cleavage of transcription factor SP1 by caspases during anti-IgM-induced B-cell apoptosis .", "target_text": { "transcription factor": "protein", "SP1": "protein", "caspases": "protein", "B-cell": "cell_type" } }, { "input_text": "Apoptosis is instrumental in the processes generating the diversity of the B-cell repertoire .", "target_text": {} }, { "input_text": "Autoreactive B-cells are eliminated by anti-IgM crosslinking after encountering self-antigens , but precise mechanisms leading to B-cell apoptosis are still not well understood .", "target_text": { "Autoreactive B-cells": "cell_type", "anti-IgM": "protein", "self-antigens": "protein", "B-cell": "cell_type" } }, { "input_text": "We report here the cleavage of the transcription factor SP1 in the human Burkitt lymphoma cell line BL60 during anti-IgM -induced apoptosis .", "target_text": { "transcription factor": "protein", "SP1": "protein", "human Burkitt lymphoma cell line BL60": "cell_line", "anti-IgM": "protein" } }, { "input_text": "Western blot analysis revealed two cleavage products of approximately 68 kDa and 45 kDa after induction of apoptosis .", "target_text": { "68 kDa": "protein", "45 kDa": "protein" } }, { "input_text": "Cleavage could be completely inhibited by zDEVD-fmk , an inhibitor specific for caspase 3-like proteases .", "target_text": { "caspase 3-like proteases": "protein" } }, { "input_text": "In-vitro cleavage of recombinant SP1 by recombinant caspase 3 ( CPP32 ) or caspase 7 ( Mch 3 ) results in similar cleavage products as those observed in vivo .", "target_text": { "SP1": "protein", "recombinant SP1": "protein", "recombinant caspase 3": "protein", "CPP32": "protein", "caspase 7": "protein", "Mch 3": "protein" } }, { "input_text": "Recombinant caspase 6 ( Mch 2 ) primarily generates a 68-kDa cleavage product , as observed after calcium ionophore ( CaI ) induced B-cell apoptosis .", "target_text": { "Recombinant caspase 6": "protein", "Mch 2": "protein", "B-cell": "cell_type" } }, { "input_text": "In contrast , caspase 1 ( ICE ) did not cleave SP1 in vitro .", "target_text": { "SP1": "protein" } }, { "input_text": "The time course of SP1 cleavage during anti-IgM-induced apoptosis is paralleled by an increase of caspase activity measured by DEVD-p-nitroanilide ( DEVD-pNA ) cleavage .", "target_text": { "SP1": "protein" } }, { "input_text": "DNA band-shift assays revealed a decrease in the intensity of the full length SP1 /DNA complex and an increase in the intensity of a smaller complex due to the binding of one SP1 cleavage product .", "target_text": { "SP1": "protein" } }, { "input_text": "By Edman sequencing we could identify a caspase 3 cleavage site after Asp584 ( D584AQPQAGR ) , generating a 22-kDa C-terminal SP1 protein fragment which still contains the DNA binding site .", "target_text": { "SP1": "protein" } }, { "input_text": "Our results show the cleavage of the human transcription factor SP1 in vivo and in vitro , underlining the central role of caspase 3-like proteases during the process of anti-IgM-induced apoptosis .", "target_text": { "transcription factor": "protein", "SP1": "protein", "caspase 3-like proteases": "protein" } }, { "input_text": "Stimulation of CD40 on immunogenic human malignant melanomas augments their cytotoxic T lymphocyte -mediated lysis and induces apoptosis .", "target_text": { "CD40": "protein", "cytotoxic T lymphocyte": "cell_type" } }, { "input_text": "Here , we report the functional expression of CD40 on human malignant melanomas ( MMs ) .", "target_text": { "CD40": "protein" } }, { "input_text": "Comparison of tumor specimen from MM precursor lesions , primary tumors , and metastases revealed that CD40 surface expression is down-regulated during tumor progression .", "target_text": { "CD40": "protein" } }, { "input_text": "CD40 expression was confirmed in 7 human MM cell lines established from immunogenic primary tumors or metastases , whereas 11 cell lines established from advanced stages were CD40 negative .", "target_text": { "CD40": "protein", "human MM cell lines": "cell_line", "cell lines": "cell_line" } }, { "input_text": "CD40 expression could be enhanced in CD40 -positive MM by stimulation with IFN-gamma and tumor necrosis factor-alpha but not by interleukin ( IL ) -1beta or CD40 triggering .", "target_text": { "CD40": "protein", "IFN-gamma": "protein", "tumor necrosis factor-alpha": "protein", "interleukin ( IL ) -1beta": "protein" } }, { "input_text": "CD40 ligation on MM by CD40L -transfected murine L-cells or by a soluble CD40L fusion protein up-regulated their expression of intercellular adhesion molecule-1 and MHC class I and class II molecules and their secretion of IL-6 , IL-8 , tumor necrosis factor-a , and granulocyte macrophage colony-stimulating factor and also induced a rapid activation of the transcription factor nuclear factor kappaB .", "target_text": { "CD40": "protein", "CD40L": "protein", "CD40L -transfected murine L-cells": "cell_line", "CD40L fusion protein": "protein", "intercellular adhesion molecule-1": "protein", "IL-6": "protein", "IL-8": "protein", "tumor necrosis factor-a": "protein", "granulocyte macrophage colony-stimulating factor": "protein", "transcription factor": "protein", "nuclear factor kappaB": "protein" } }, { "input_text": "Furthermore , CD40 ligation of a HLA-A2+ , MelanA/MART1+ MM cell line enhanced its susceptibility to specific lysis by a HLA-A2-restricted , MelanA/MART-1-specific CTL clone .", "target_text": { "CD40": "protein", "HLA-A2+ , MelanA/MART1+ MM cell line": "cell_line", "HLA-A2-restricted , MelanA/MART-1-specific CTL clone": "cell_line" } }, { "input_text": "Finally , CD40 ligation induced growth inhibition and apoptosis in MM .", "target_text": { "CD40": "protein" } }, { "input_text": "These results indicate that CD40 -CD40L interactions may play an important role in augmenting antitumor immunity and inducing apoptosis in some CD40 -positive immunogenic human MMs .", "target_text": { "CD40": "protein", "-CD40L": "protein" } }, { "input_text": "Human immunodeficiency virus -associated Hodgkin 's disease derives from post-germinal center B cells .", "target_text": { "post-germinal center B cells": "cell_type" } }, { "input_text": "Human immunodeficiency virus -associated Hodgkin 's disease ( HIV-HD ) displays several peculiarities when compared with HD of the general population .", "target_text": {} }, { "input_text": "These include overrepresentation of clinically aggressive histologic types and frequent infection of Reed-Sternberg ( RS ) cells by Epstein-Barr virus ( EBV ) .", "target_text": { "Reed-Sternberg ( RS ) cells": "cell_line" } }, { "input_text": "Recently , we have reported that the histogenesis of HD of the general population may be assessed by monitoring the expression pattern of BCL-6 , a transcription factor expressed in germinal center ( GC ) B cells , and of CD138/syndecan-1 ( syn-1 ) , a proteoglycan associated with post-GC , terminal B-cell differentiation .", "target_text": { "BCL-6": "protein", "transcription factor": "protein", "germinal center ( GC ) B cells": "cell_line", "CD138/syndecan-1": "protein", "syn-1": "protein", "B-cell": "cell_type" } }, { "input_text": "In this study , we have applied these two markers to the study of HIV- HD histogenesis and correlated their expression status to the virologic features of this disease .", "target_text": {} }, { "input_text": "We have found that RS cells of all histologic categories of HIV- HD consistently display the BCL-6 (-)/syn-1(+) phenotype and thus reflect post-GC B cells .", "target_text": { "RS cells": "cell_line", "BCL-6": "protein", "post-GC B cells": "cell_line" } }, { "input_text": "Although BCL-6 (-)/syn-1(+) RS cells of HIV-HD express CD40 , they are not surrounded by CD40 ligand -positive ( CD40L + ) reactive T lymphocytes , which , in HD of the general population , are thought to regulate the disease phenotype through CD40 /CD40L interactions .", "target_text": { "BCL-6": "protein", "RS cells": "cell_line", "CD40": "protein", "CD40 ligand": "protein", "CD40L": "protein", "CD40 ligand -positive ( CD40L + ) reactive T lymphocytes": "cell_type", "/CD40L": "protein" } }, { "input_text": "Conversely , RS cells of virtually all HIV- HD express the EBV -encoded latent membrane protein 1 ( LMP1 ) , which , being functionally homologous to CD40 , may contribute , at least in part , to the modulation of the HIV- HD phenotype .", "target_text": { "RS cells": "cell_line", "EBV -encoded latent membrane protein 1": "protein", "LMP1": "protein", "CD40": "protein" } }, { "input_text": "MDS1/EVI1 enhances TGF-beta1 signaling and strengthens its growth-inhibitory effect but the leukemia-associated fusion protein AML1/MDS1/EVI1 , product of the t(3;21) , abrogates growth-inhibition in response to TGF-beta1 .", "target_text": { "MDS1/EVI1": "DNA", "TGF-beta1": "protein", "leukemia-associated fusion protein": "protein", "AML1/MDS1/EVI1": "protein" } }, { "input_text": "MDS1/EVI1 , located on chromosome 3 band q26 , encodes a zinc-finger DNA-binding transcription activator not detected in normal hematopoietic cells but expressed in several normal tissues .", "target_text": { "MDS1/EVI1": "DNA", "chromosome 3": "DNA", "chromosome 3 band q26": "DNA", "zinc-finger DNA-binding transcription activator": "protein", "normal hematopoietic cells": "cell_type" } }, { "input_text": "MDS1/EVI1 is inappropriately activated in myeloid leukemias following chromosomal rearrangements involving band 3q26 .", "target_text": { "MDS1/EVI1": "DNA", "myeloid leukemias": "cell_type", "band 3q26": "protein" } }, { "input_text": "The rearrangements lead either to gene truncation , and to expression of the transcription repressor EVI1 , as seen in the t(3;3)(q21;q26) and inv(3)(q21q26) , or to gene fusion , as seen in the t(3;21)(q26;q22) which results in the fusion protein AML1/MDS1/EVI1 .", "target_text": { "transcription repressor EVI1": "protein", "t(3;3)(q21;q26)": "DNA", "inv(3)(q21q26)": "DNA", "t(3;21)(q26;q22)": "DNA", "AML1/MDS1/EVI1": "protein" } }, { "input_text": "This fusion protein contains the DNA-binding domain of the transcription factor AML1 fused in-frame to the entire MDS1/EVI1 with the exclusion of its first 12 amino acids .", "target_text": { "DNA-binding domain": "protein", "transcription factor": "protein", "AML1": "protein", "MDS1/EVI1": "DNA" } }, { "input_text": "In this report , we have analyzed the response of the hematopoietic precursor cell line 32Dcl3 , expressing either the normal protein MDS1/EVI1 or the fusion protein AML1/MDS1/EVI1 , to factors that control cell differentiation or cell replication .", "target_text": { "hematopoietic precursor cell line 32Dcl3": "cell_line", "MDS1/EVI1": "DNA", "normal protein MDS1/EVI1": "protein", "AML1/MDS1/EVI1": "protein", "fusion protein AML1/MDS1/EVI1": "protein" } }, { "input_text": "The 32Dcl3 cells are IL-3 -dependent for growth and they differentiate into granulocytes when exposed to G-CSF .", "target_text": { "32Dcl3 cells": "cell_line", "IL-3": "protein", "G-CSF": "protein" } }, { "input_text": "They are growth-inhibited by TGF-beta1 .", "target_text": { "TGF-beta1": "protein" } }, { "input_text": "We show that whereas the expression of MDS1/EVI1 has no effect on granulocytic differentiation induced by G-CSF , expression of AML1/MDS1/EVI1 blocks differentiation resulting in cell death .", "target_text": { "MDS1/EVI1": "DNA", "G-CSF": "protein", "AML1/MDS1/EVI1": "protein" } }, { "input_text": "This effect is similar to that previously described by others for 32Dcl3 cells that express transgenic Evil .", "target_text": { "32Dcl3 cells": "cell_line", "transgenic Evil": "protein" } }, { "input_text": "Furthermore , we show that whereas the expression of the fusion protein AML1/MDS1/EVI1 completely abrogates the growth-inhibitory effect of TGF-beta1 and allows 32Dcl3 cells to proliferate , expression of the normal protein MDS1/EVI1 has the opposite effect , and it strengthens the response of cells to the growth-inhibitory effect of TGF-beta1 .", "target_text": { "AML1/MDS1/EVI1": "protein", "TGF-beta1": "protein", "32Dcl3 cells": "cell_line", "MDS1/EVI1": "DNA" } }, { "input_text": "By using the yeast two-hybrid system , we also show that EVI1 ( contained in its entirety in MDS1/EVI1 and AML1/MDS1/EVI1 ) physically interacts with SMAD3 , which is an intracellular mediator of TGF-beta1 signaling .", "target_text": { "EVI1": "protein", "MDS1/EVI1": "DNA", "AML1/MDS1/EVI1": "protein", "SMAD3": "protein", "TGF-beta1": "protein" } }, { "input_text": "Finally , we have correlated the response of the cells to G-CSF or TGF-beta1 with the ability of the normal and fusion proteins to activate or repress promoters which they can directly regulate by binding to the promoter site .", "target_text": { "G-CSF": "protein", "TGF-beta1": "protein", "fusion proteins": "protein", "promoter site": "DNA" } }, { "input_text": "We propose that mutations of MDS1/EVI1 either by gene truncation resulting in the transcription repressor EVI1 or by gene fusion to AML1 lead to an altered cellular response to growth and differentiation factors that could result in leukemic transformation .", "target_text": { "MDS1/EVI1": "DNA", "EVI1": "protein", "transcription repressor EVI1": "protein", "AML1": "protein", "differentiation factors": "protein" } }, { "input_text": "The different response of myeloid cells ectopically expressing the normal or the fusion protein to G-CSF and TGF-beta1 could depend on the different transactivation properties of these proteins resulting in divergent expression of downstream genes regulated by the two proteins .", "target_text": { "fusion protein": "protein", "G-CSF": "protein", "TGF-beta1": "protein", "downstream genes": "DNA" } }, { "input_text": "Abnormalities of cyclic adenosine monophosphate signaling in platelets from untreated patients with bipolar disorder .", "target_text": { "platelets": "cell_type" } }, { "input_text": "BACKGROUND : Abnormalities in the cyclic adenosine monophosphate ( cAMP ) -dependent phosphorylation system have been recently reported in patients with bipolar disorder .", "target_text": {} }, { "input_text": "We evaluated the immunoreactivity of the regulatory and catalytic subunits of cAMP-dependent protein kinase ( protein kinase A ) and 1 of its substrates , Rap1 , in platelets from untreated euthymic , manic , and depressed patients with bipolar disorder and healthy subjects .", "target_text": { "cAMP-dependent protein kinase": "protein", "protein kinase A": "protein", "Rap1": "protein", "platelets": "cell_type" } }, { "input_text": "METHODS : Platelets were collected from 112 drug-free patients with bipolar disorder ( 52 euthymic , 29 depressed , and 31 manic ) and 62 healthy subjects .", "target_text": { "Platelets": "cell_type" } }, { "input_text": "The levels of cAMP-dependent protein kinase and Rap1 were assessed by Western blot analysis , immunostaining , and computer-assisted imaging .", "target_text": { "cAMP-dependent protein kinase": "protein", "Rap1": "protein" } }, { "input_text": "RESULTS : The immunolabeling of the catalytic subunit of cAMP-dependent protein kinase was significantly different among groups ( P < .001 ) , with higher values in untreated depressed and manic patients with bipolar disorder compared with untreated euthymic patients with bipolar disorder and healthy subjects .", "target_text": { "catalytic subunit": "protein", "cAMP-dependent protein kinase": "protein" } }, { "input_text": "No significant differences were found in the immunolabeling of the regulatory subunits ( type I and type II ) of cAMP-dependent protein kinase .", "target_text": { "regulatory subunits": "protein", "cAMP-dependent protein kinase": "protein" } }, { "input_text": "The immunolabeling of Rap1 was significantly higher ( P < .001 ) in untreated euthymic , depressed , and manic patients than in healthy persons .", "target_text": { "Rap1": "protein" } }, { "input_text": "CONCLUSIONS : Levels of Rap1 and the catalytic subunit of cAMP-dependent protein kinase are altered in the platelets of bipolar patients .", "target_text": { "Rap1": "protein", "catalytic subunit": "protein", "cAMP-dependent protein kinase": "protein", "platelets": "cell_type" } }, { "input_text": "These findings may provide clues toward understanding the involvement of cAMP signaling in the pathogenesis of bipolar disorder .", "target_text": {} }, { "input_text": "Molecular regulation of cytokine gene expression during the immune response .", "target_text": { "cytokine": "protein", "cytokine gene": "DNA" } }, { "input_text": "Cytokine expression by immune system cells plays an important role in the regulation of the immune response .", "target_text": { "Cytokine": "protein" } }, { "input_text": "On first encounter with antigen , naive CD4+ T helper ( Th ) cells differentiate into cytokine -producing effector cells .", "target_text": { "naive CD4+ T helper ( Th ) cells": "cell_type", "cytokine": "protein", "cytokine -producing effector cells": "cell_line" } }, { "input_text": "Two types of effector cells characterized by their distinct expression of cytokine profiles have been described .", "target_text": { "cytokine": "protein" } }, { "input_text": "Th1 cells produce IL-2 and IFN-gamma , whereas Th2 cells produce IL-4 , IL-5 , IL-6 , IL-10 , and IL-13 .", "target_text": { "IL-2": "protein", "IFN-gamma": "protein", "Th2 cells": "cell_line", "IL-4": "protein", "IL-5": "protein", "IL-6": "protein", "IL-10": "protein", "IL-13": "protein" } }, { "input_text": "In many pathological situations , the balance between Th1 and Th2 immune responses determines the outcome of diverse immunologically mediated clinical syndromes including infectious , autoimmune , and allergic diseases .", "target_text": {} }, { "input_text": "However , the molecular basis for the tissue-specific expression of Th1/Th2-like cytokines has remained elusive .", "target_text": { "Th1/Th2-like cytokines": "protein" } }, { "input_text": "In this review we evaluate the possible in vivo role of different transcription factors and transcriptional mechanisms in T cell differentiation and the immune response .", "target_text": {} }, { "input_text": "Tcf-1 -mediated transcription in T lymphocytes : differential role for glycogen synthase kinase-3 in fibroblasts and T cells .", "target_text": { "Tcf-1": "protein", "T lymphocytes": "cell_type", "glycogen synthase kinase-3": "protein", "fibroblasts": "cell_type", "T cells": "cell_type" } }, { "input_text": "Beta-catenin is the vertebrate homolog of the Drosophila segment polarity gene Armadillo and plays roles in both cell-cell adhesion and transduction of the Wnt signaling cascade .", "target_text": { "Drosophila segment polarity gene": "DNA", "Armadillo": "DNA" } }, { "input_text": "Recently , members of the Lef/Tcf transcription factor family have been identified as protein partners of beta-catenin , explaining how beta-catenin alters gene expression .", "target_text": { "Lef/Tcf transcription factor family": "protein", "beta-catenin": "protein" } }, { "input_text": "Here we report that in T cells , Tcf-1 also becomes transcriptionally active through interaction with beta-catenin , suggesting that the Wnt signal transduction pathway is operational in T lymphocytes as well .", "target_text": { "T cells": "cell_type", "Tcf-1": "protein", "beta-catenin": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "However , although Wnt signals are known to inhibit the activity of the negative regulatory protein kinase glycogen synthase kinase-3beta ( GSK-3beta ) , resulting in increased levels of beta-catenin , we find no evidence for involvement of GSK-3beta in Tcf-mediated transcription in T cells .", "target_text": { "negative regulatory protein kinase": "protein", "glycogen synthase kinase-3beta": "protein", "GSK-3beta": "protein", "beta-catenin": "protein", "T cells": "cell_type" } }, { "input_text": "That is , a dominant negative GSK-3beta does not specifically activate Tcf transcription and stimuli ( lithium or phytohemagglutinin ) that inhibit GSK-3beta activity also do not activate Tcf reporter genes .", "target_text": { "dominant negative GSK-3beta": "protein", "phytohemagglutinin": "protein", "GSK-3beta": "protein", "Tcf reporter genes": "DNA" } }, { "input_text": "Thus , inhibition of GSK-3beta is insufficient to activate Tcf-dependent transcription in T lymphocytes .", "target_text": { "GSK-3beta": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "In contrast , in C57MG fibroblast cells , lithium inactivates GSK-3beta and induces Tcf-controlled transcription .", "target_text": { "C57MG fibroblast cells": "cell_line", "GSK-3beta": "protein" } }, { "input_text": "This is the first demonstration that lithium can alter gene expression of Tcf-responsive genes , and points to a difference in regulation of Wnt signaling between fibroblasts and lymphocytes .", "target_text": { "Tcf-responsive genes": "DNA", "fibroblasts": "cell_type", "lymphocytes": "cell_type" } }, { "input_text": "SHP2-interacting transmembrane adaptor protein ( SIT ) , a novel disulfide-linked dimer regulating human T cell activation .", "target_text": { "SHP2-interacting transmembrane adaptor protein": "protein", "SIT": "protein", "disulfide-linked dimer": "protein" } }, { "input_text": "T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology ( SH ) 2 domain -containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs .", "target_text": { "T lymphocytes": "cell_type", "low molecular weight transmembrane adaptor proteins": "protein", "src homology ( SH ) 2 domain": "protein", "src homology ( SH ) 2 domain -containing intracellular molecules": "protein" } }, { "input_text": "We describe here a novel molecule of this group termed SIT ( SHP2 interacting transmembrane adaptor protein ) .", "target_text": { "SIT": "protein", "SHP2 interacting transmembrane adaptor protein": "protein" } }, { "input_text": "SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes .", "target_text": { "SIT": "protein", "disulfide-linked homodimeric glycoprotein": "protein", "lymphocytes": "cell_type" } }, { "input_text": "After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain -containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif .", "target_text": { "src": "protein", "syk": "protein", "protein tyrosine kinases": "protein", "SIT": "protein", "SH2 domain": "protein", "SH2 domain -containing tyrosine phosphatase": "protein", "SHP2": "protein" } }, { "input_text": "Overexpression of SIT in Jurkat cells downmodulates T cell receptor- and phytohemagglutinin- mediated activation of the nuclear factor of activated T cells ( NF-AT ) by interfering with signaling processes that are probably located upstream of activation of phospholipase C .", "target_text": { "SIT": "protein", "Jurkat cells": "cell_line", "T cells": "cell_type", "nuclear factor of activated T cells": "protein", "NF-AT": "protein", "phospholipase C": "protein" } }, { "input_text": "However , binding of SHP2 to SIT is not required for inhibition of NF-AT induction , suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2 .", "target_text": { "SHP2": "protein", "SIT": "protein", "NF-AT": "protein" } }, { "input_text": "Extracellular-regulated kinase 1/2 , Jun N-terminal kinase , and c-Jun are involved in NF-kappa B -dependent IL-6 expression in human monocytes .", "target_text": { "Extracellular-regulated kinase 1/2": "protein", "Jun N-terminal kinase": "protein", "c-Jun": "protein", "NF-kappa B": "protein", "IL-6": "protein" } }, { "input_text": "In the present study we investigated the possible involvement of the mitogen-activated protein kinase family members extracellular-regulated kinase 1/2 ( ERK1/2 ) and c- Jun N-terminal kinase ( JNK ) in mediating IL-6 gene expression in human monocytes , in particular their role in enhancing NF-kappa B activity .", "target_text": { "mitogen-activated protein kinase family": "protein", "extracellular-regulated kinase 1/2": "protein", "ERK1/2": "protein", "Jun N-terminal kinase": "protein", "JNK": "protein", "IL-6": "protein", "human monocytes": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "Freshly isolated monocytes treated with the protein phosphatase inhibitor okadaic acid secreted high levels of IL-6 protein , which coincided with enhanced binding activity of NF-kappa B as well as with phosphorylation and activation of the ERK1/2 and JNK proteins .", "target_text": { "IL-6": "protein", "IL-6 protein": "protein", "NF-kappa B": "protein" } }, { "input_text": "The ERK pathway-specific inhibitor PD98059 inhibited IL-6 secretion from monocytes .", "target_text": { "IL-6": "protein", "monocytes": "cell_type" } }, { "input_text": "Transient overexpression of inactive mutants of either Raf-1 or JNK1 showed that both pathways were involved in kappa B-dependent IL-6 promoter activity .", "target_text": { "Raf-1": "protein", "JNK1": "protein", "IL-6": "protein" } }, { "input_text": "By using PD98059 , we demonstrated that the Raf1/MEK1/ ERK1/2 pathway did not affect the DNA binding of NF-kappa B but , rather , acted at the level of transcriptional activity of NF-kappa B .", "target_text": { "ERK1/2": "protein", "NF-kappa B": "protein" } }, { "input_text": "Interestingly , it was shown that NF-kappa B -mediated gene transcription , both in the context of the IL-6 promoter as well as on its own , was dependent on both serine kinase activity and interaction with c-Jun protein .", "target_text": { "NF-kappa B": "protein", "IL-6": "protein", "IL-6 promoter": "DNA", "c-Jun": "protein", "c-Jun protein": "protein" } }, { "input_text": "We conclude that okadaic acid -induced IL-6 gene expression is at least partly mediated through the ERK1/2 and JNK pathway-dependent activation of NF-kappa B transcriptional capacity .", "target_text": { "IL-6": "protein", "ERK1/2": "protein", "JNK": "protein", "NF-kappa B": "protein" } }, { "input_text": "Our results suggest that the JNK pathway may regulate NF-kappa B -mediated gene transcription through its phosphorylation and activation of c-Jun .", "target_text": { "JNK": "protein", "NF-kappa B": "protein", "c-Jun": "protein" } }, { "input_text": "The Epstein-Barr virus nuclear antigen 2 ( EBNA2 ) , a protein required for B lymphocyte immortalization , induces the synthesis of type I interferon in Burkitt 's lymphoma cell lines .", "target_text": { "Epstein-Barr virus nuclear antigen 2": "protein", "EBNA2": "protein", "B lymphocyte": "cell_type", "type I interferon": "protein", "Burkitt 's lymphoma cell lines": "cell_line" } }, { "input_text": "Epstein-Barr virus nuclear antigen 2 ( EBNA2 ) , a protein involved in cell transformation , interferes with the cellular response to type I interferons ( IFN-alpha/beta ) .", "target_text": { "Epstein-Barr virus nuclear antigen 2": "protein", "EBNA2": "protein", "type I interferons": "protein", "IFN-alpha/beta": "protein" } }, { "input_text": "We investigated the function of conditionally expressed EBNA2 in the context of the IFN response in Burkitt 's lymphoma cell lines .", "target_text": { "EBNA2": "protein", "IFN": "protein", "Burkitt 's lymphoma cell lines": "cell_line" } }, { "input_text": "Expression of EBNA2 led to the transcriptional activation of both endogenous or transfected IFN-stimulated genes ( ISGs ) , genes which contain within their promoters either the interferon-stimulated response element ( ISRE ) or the gamma interferon activation site ( GAS ) .", "target_text": { "EBNA2": "protein", "IFN-stimulated genes": "DNA", "ISGs": "DNA", "promoters": "DNA", "interferon-stimulated response element": "DNA", "ISRE": "DNA", "gamma interferon activation site": "DNA", "GAS": "DNA" } }, { "input_text": "In search of a molecular mechanism for the transcriptional induction of ISGs , we observed an EBNA2 -dependent synthesis of IFN-beta mRNA at low levels and the secretion of low amounts of IFN .", "target_text": { "ISGs": "DNA", "EBNA2": "protein" } }, { "input_text": "A transfected IFN-beta promoter responded to EBNA2 activation , and a sequence closely resembling a RBP-Jkappa binding site was pinpointed as a potential target of EBNA2 activity .", "target_text": { "EBNA2": "protein", "RBP-Jkappa binding site": "DNA" } }, { "input_text": "EBNA2 -dependent transcriptional induction of the IFN-beta promoter occurred in EBV-negative Burkitt 's lymphoma cells , indicating that other EBV genes were not required for the induction of IFN-beta synthesis .", "target_text": { "EBNA2": "protein", "IFN-beta promoter": "DNA", "EBV-negative Burkitt 's lymphoma cells": "cell_line", "EBV genes": "DNA", "IFN-beta": "protein" } }, { "input_text": "PGG-glucan , a soluble beta-(1,3)-glucan , enhances the oxidative burst response , microbicidal activity , and activates an NF-kappa B -like factor in human PMN : evidence for a glycosphingolipid beta-(1,3)-glucan receptor .", "target_text": { "NF-kappa B": "protein", "NF-kappa B -like factor": "protein", "human PMN": "cell_type", "glycosphingolipid beta-(1,3)-glucan receptor": "protein" } }, { "input_text": "PGG-Glucan , a soluble beta-(1,6)-branched beta-(1,3)-linked glucose homopolymer derived from the cell wall of the yeast Saccharomyces cerevisiae , is an immunomodulator which enhances leukocyte anti-infective activity and enhances myeloid and megakaryocyte progenitor proliferation .", "target_text": {} }, { "input_text": "Incubation of human whole blood with PGG-Glucan significantly enhanced the oxidative burst response of subsequently isolated blood leukocytes to both soluble and particulate activators in a dose-dependent manner , and increased leukocyte microbicidal activity .", "target_text": { "subsequently isolated blood leukocytes": "cell_type" } }, { "input_text": "No evidence for inflammatory cytokine production was obtained under these conditions .", "target_text": { "cytokine": "protein" } }, { "input_text": "Electrophoretic mobility shift assays demonstrated that PGG-Glucan induced the activation of an NF-kappaB -like nuclear transcription factor in purified human neutrophils .", "target_text": { "NF-kappaB": "protein", "NF-kappaB -like nuclear transcription factor": "protein", "purified human neutrophils": "cell_type" } }, { "input_text": "The binding of 3 H- PGG-Glucan to human leukocyte membranes was specific , concentration-dependent , saturable , and high affinity ( Kd approximately 6 nM ) .", "target_text": {} }, { "input_text": "A monoclonal antibody specific to the glycosphingolipid lactosylceramide was able to inhibit activation of the NF-kappaB -like factor by PGG-Glucan , and ligand binding data , including polysaccharide specificity , suggested that the PGG-Glucan binding moiety was lactosylceramide .", "target_text": { "monoclonal antibody": "protein", "NF-kappaB": "protein", "NF-kappaB -like factor": "protein" } }, { "input_text": "These results indicate that PGG-Glucan enhances neutrophil anti-microbial functions and that interaction between this beta-glucan and human neutrophils is mediated by the glycosphingolipid lactosylceramide present at the cell surface .", "target_text": { "human neutrophils": "cell_type" } }, { "input_text": "Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes .", "target_text": { "apoptotic leukocytes": "cell_type" } }, { "input_text": "Phagocyte recognition , uptake , and nonphlogistic degradation of neutrophils and other leukocytes undergoing apoptosis promote the resolution of inflammation .", "target_text": { "neutrophils": "cell_type", "leukocytes": "cell_type" } }, { "input_text": "This study assessed the effects of anti-inflammatory glucocorticoids on this leukocyte clearance mechanism .", "target_text": {} }, { "input_text": "Pretreatment of \" semimature \" 5-day human monocyte-derived macrophages ( M phi ) for 24 h with methylprednisolone , dexamethasone , and hydrocortisone , but not the nonglucocorticoid steroids aldosterone , estradiol , and progesterone , potentiated phagocytosis of apoptotic neutrophils .", "target_text": { "human monocyte-derived macrophages": "cell_type", "apoptotic neutrophils": "cell_type" } }, { "input_text": "These effects were specific in that the potentiated phagocytosis of apoptotic neutrophils was completely blocked by the glucocorticoid receptor antagonist RU38486 , and glucocorticoids did not promote 5-day M phi ingestion of opsonized erythrocytes .", "target_text": { "apoptotic neutrophils": "cell_type", "glucocorticoid receptor": "protein", "opsonized erythrocytes": "cell_type" } }, { "input_text": "Similar glucocorticoid-mediated potentiation was observed with 5-day M phi uptake of alternative apoptotic \" targets \" ( eosinophils and Jurkat T cells ) and in uptake of apoptotic neutrophils by alternative phagocytes ( human glomerular mesangial cells and murine M phi elicited into the peritoneum or derived from bone marrow ) .", "target_text": { "eosinophils": "cell_type", "Jurkat T cells": "cell_line", "apoptotic neutrophils": "cell_type", "phagocytes": "cell_type", "human glomerular mesangial cells": "cell_type", "murine M phi": "cell_line" } }, { "input_text": "Importantly , methylprednisolone -mediated enhancement of the uptake of apoptotic neutrophils did not trigger the release of the chemokines IL-8 and monocyte chemoattractant protein-1 .", "target_text": { "apoptotic neutrophils": "cell_type", "chemokines": "protein", "IL-8": "protein", "monocyte chemoattractant protein-1": "protein" } }, { "input_text": "Furthermore , longer-term potentiation by methylprednisolone was observed in maturing human monocyte-derived M phi , with greater increases in 5-day M phi uptake of apoptotic cells being observed the earlier glucocorticoids were added during monocyte maturation into M phi .", "target_text": { "maturing human monocyte-derived M phi": "cell_line", "M phi": "cell_line", "apoptotic cells": "cell_type" } }, { "input_text": "We conclude that potentiation of nonphlogistic clearance of apoptotic leukocytes by phagocytes is a hitherto unrecognized property of glucocorticoids that has potential implications for therapies aimed at promoting the resolution of inflammatory diseases .", "target_text": { "apoptotic leukocytes": "cell_type", "phagocytes": "cell_type" } }, { "input_text": "1,25-Dihydroxyvitamin D3 induces differentiation of a retinoic acid -resistant acute promyelocytic leukemia cell line ( UF-1 ) associated with expression of p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) .", "target_text": { "retinoic acid -resistant acute promyelocytic leukemia cell line": "cell_line", "UF-1": "cell_line", "p21 ( WAF1/CIP1 )": "protein", "p27 ( KIP1 )": "protein" } }, { "input_text": "Retinoic acid ( RA ) resistance is a serious problem for patients with acute promyelocytic leukemia ( APL ) who are receiving all-trans RA .", "target_text": {} }, { "input_text": "However , the mechanisms and strategies to overcome RA resistance by APL cells are still unclear .", "target_text": { "APL cells": "cell_type" } }, { "input_text": "The biologic effects of RA are mediated by two distinct families of transcriptional factors : RA receptors ( RARs ) and retinoid X receptors ( RXRs ) .", "target_text": { "transcriptional factors": "protein", "RA receptors": "protein", "RARs": "protein", "retinoid X receptors": "protein", "RXRs": "protein" } }, { "input_text": "RXRs heterodimerize with 1, 25-dihydroxyvitamin D3 [ 1,25(OH)2D3 ] receptor ( VDR ) , enabling their efficient transcriptional activation .", "target_text": { "RXRs": "protein", "1, 25-dihydroxyvitamin D3 [ 1,25(OH)2D3 ] receptor": "protein", "VDR": "protein" } }, { "input_text": "The cyclin-dependent kinase ( cdk ) inhibitor p21 ( WAF1/CIP1 ) has a vitamin D3-responsive element ( VDRE ) in its promoter , and 1,25(OH)2D3 enhances the expression of p21 ( WAF1/CIP1 ) and induces differentiation of selected myeloid leukemic cell lines .", "target_text": { "cyclin-dependent kinase": "protein", "cdk": "protein", "cyclin-dependent kinase ( cdk ) inhibitor": "protein", "p21 ( WAF1/CIP1 )": "protein", "vitamin D3-responsive element": "DNA", "VDRE": "DNA", "promoter": "DNA", "myeloid leukemic cell lines": "cell_line" } }, { "input_text": "We have recently established a novel APL cell line ( UF-1 ) with features of RA resistance .", "target_text": { "APL cell line": "cell_line", "UF-1": "cell_line" } }, { "input_text": "1,25(OH)2D3 can induce growth inhibition and G1 arrest of UF-1 cells , resulting in differentiation of these cells toward granulocytes .", "target_text": { "UF-1 cells": "cell_line", "granulocytes": "cell_type" } }, { "input_text": "This 1, 25(OH)2D3 -induced G1 arrest is enhanced by all-trans RA .", "target_text": {} }, { "input_text": "Also , 1, 25(OH)2D3 ( 10(-10) to 10(-7) mol/L ) in combination with RA markedly inhibits cellular proliferation in a dose- and time-dependent manner .", "target_text": {} }, { "input_text": "Associated with these findings , the levels of p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) mRNA and protein increased in these cells .", "target_text": { "p21 ( WAF1/CIP1 )": "protein", "p27 ( KIP1 )": "protein", "p27 ( KIP1 ) mRNA": "RNA" } }, { "input_text": "Northern blot analysis showed that p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) mRNA and protein increased in these cells .", "target_text": {} }, { "input_text": "Northern blot analysis showed that p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) transcripts were induced after 6 hours ' exposure to 1,25(OH)2D3 and then decreased to basal levels over 48 hours .", "target_text": { "p21 ( WAF1/CIP1 )": "protein", "p27 ( KIP1 )": "protein" } }, { "input_text": "Western blot experiments showed that p21 ( WAF1/CIP1 ) protein levels increased and became detectable after 12 hours of 1,25(OH)2D3 treatment and induction of p27 ( KIP1 ) protein was much more gradual and sustained in UF-1 cells .", "target_text": { "p21 ( WAF1/CIP1 )": "protein", "p27 ( KIP1 )": "protein", "UF-1 cells": "cell_line" } }, { "input_text": "Interestingly , the combination of 1, 25(OH)2D3 and RA markedly enhanced the levels of p27 ( KIP1 ) transcript and protein as compared with levels induced by 1, 25(OH)2D3 alone .", "target_text": { "p27 ( KIP1 )": "protein" } }, { "input_text": "In addition , exogenous p27 ( KIP1 ) expression can enhance the level of CD11b antigen in myeloid leukemic cells .", "target_text": { "p27 ( KIP1 )": "protein", "CD11b antigen": "protein", "myeloid leukemic cells": "cell_type" } }, { "input_text": "In contrast , RA alone can induce G1 arrest of UF-1 cells ; however , it did not result in an increase of p21 ( WAF1/CIP1 ) and p27 ( KIP1 ) transcript and protein expression in RA -resistant cells .", "target_text": { "UF-1 cells": "cell_line", "p21 ( WAF1/CIP1 )": "protein", "p27 ( KIP1 )": "protein" } }, { "input_text": "Taken together , we conclude that 1,25(OH)2D3 induces increased expression of cdk inhibitors , which mediates a G1 arrest , and this may be associated with differentiation of RA -resistant UF-1 cells toward mature granulocytes .", "target_text": { "cdk": "protein", "cdk inhibitors": "protein", "UF-1 cells": "cell_line", "granulocytes": "cell_type" } }, { "input_text": "Molecular mechanisms of neutrophil-endothelial cell adhesion induced by redox imbalance .", "target_text": {} }, { "input_text": "Previous studies have implicated a role for intracellular thiols in the activation of nuclear factor-kappaB and transcriptional regulation of endothelial cell adhesion molecules .", "target_text": { "nuclear factor-kappaB": "protein", "endothelial cell adhesion molecules": "protein" } }, { "input_text": "This study was designed to determine whether changes in endothelial cell glutathione ( GSH ) or oxidized glutathione ( GSSG ) can alter neutrophil adhesivity and to define the molecular mechanism that underlies this GSSG / GSH -induced adhesion response .", "target_text": {} }, { "input_text": "Treatment of human umbilical vein endothelial cell ( HUVEC ) monolayers for 6 hours with 0.2 mmol/L diamide and 1 mmol/L buthionine sulfoximine ( BSO ) decreased GSH levels and increased the ratio of GSSG to GSH without cell toxicity .", "target_text": { "human umbilical vein endothelial cell": "cell_line", "HUVEC": "cell_line", "human umbilical vein endothelial cell ( HUVEC ) monolayers": "cell_line" } }, { "input_text": "These redox changes are similar to those observed with anoxia/reoxygenation .", "target_text": {} }, { "input_text": "Diamide plus BSO -induced thiol/disulfide imbalance was associated with a biphasic increase in neutrophil adhesion to HUVECs with peak responses observed at 15 minutes ( phase 1 ) and 240 minutes ( phase 2 ) .", "target_text": { "neutrophil": "cell_type", "HUVECs": "cell_line" } }, { "input_text": "N-Acetylcysteine treatment attenuated neutrophil adhesion in both phases , which indicated a role for GSH in the adhesion responses .", "target_text": { "neutrophil": "cell_type" } }, { "input_text": "Interestingly , phase 1 adhesion was inversely correlated with GSH levels but not with the GSSG / GSH ratio , whereas phase 2 neutrophil adhesion was positively correlated with GSSG /GSH ratio but not with GSH levels .", "target_text": { "neutrophil": "cell_type" } }, { "input_text": "Intercellular adhesion molecule-1 and P-selectin-specific monoclonal antibodies attenuated the increased neutrophil adhesion during both phases , whereas an anti-E-selectin monoclonal antibody also attenuated the phase 2 response .", "target_text": { "Intercellular adhesion molecule-1": "protein", "P-selectin-specific monoclonal antibodies": "protein", "neutrophil": "cell_type", "monoclonal antibody": "protein", "anti-E-selectin monoclonal antibody": "protein" } }, { "input_text": "Pretreatment with actinomycin D and cycloheximide or with competing ds-oligonucleotides that contained nuclear factor-kappaB or activator protein-1 cognate DNA sequences significantly attenuated the phase 2 response , which implicated a role for de novo protein synthesis .", "target_text": { "nuclear factor-kappaB": "protein", "activator protein-1": "protein" } }, { "input_text": "Surface expression of intercellular adhesion molecule-1 , P- selectin , and E-selectin on HUVECs correlated with the phase 1 and 2 neutrophil adhesion responses .", "target_text": { "intercellular adhesion molecule-1": "protein", "P- selectin": "protein", "E-selectin": "protein", "HUVECs": "cell_line", "neutrophil": "cell_type" } }, { "input_text": "This study demonstrates that changes in endothelial cell GSSG /GSH cause transcription-independent and transcription-dependent surface expression of different endothelial cell adhesion molecules , which leads to a 2-phase neutrophil -endothelial adhesion response .", "target_text": { "endothelial cell adhesion molecules": "protein", "neutrophil": "cell_type" } }, { "input_text": "Glucocorticoid hormone suppression of human neutrophil -mediated tumor cell cytostasis .", "target_text": { "neutrophil": "cell_type" } }, { "input_text": "In the present study , we have investigated the effect of glucocorticoid hormones on neutrophil -mediated tumor cell cytostasis and found that hydrocortisone and a synthetic hormone , dexamethasone ( Dex ) , inhibited cytostasis in the presence or absence of tumor necrosis factor-alpha .", "target_text": { "neutrophil": "cell_type", "tumor necrosis factor-alpha": "protein" } }, { "input_text": "The effect of Dex was completely reversed by a glucocorticoid receptor antagonist , RU38486 .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "To clarify the underlying mechanisms , we examined effects of Dex on the binding avidity of beta2 integrin on the neutrophil surface and how these might in turn affect neutrophil -to-tumor cell binding .", "target_text": { "beta2 integrin": "protein", "neutrophil": "cell_type" } }, { "input_text": "Dex was found to inhibit these neutrophil properties , and RU38486 completely suppressed both forms of Dex inhibition .", "target_text": { "neutrophil": "cell_type" } }, { "input_text": "Taken together , our findings suggest that glucocorticoid hormone inhibition of neutrophil -mediated tumor cell cytostasis is at least partially due to a lowering of the ligand binding avidity of beta2 integrin on the neutrophil surface .", "target_text": { "neutrophil": "cell_type", "beta2 integrin": "protein" } }, { "input_text": "Constitutive activation of an epithelial signal transducer and activator of transcription ( STAT ) pathway in asthma .", "target_text": { "STAT": "protein" } }, { "input_text": "Cytokine effects on immunity and inflammation often depend on the transcription factors termed signal transducers and activators of transcription ( STATs ) , so STAT signaling pathways are candidates for influencing inflammatory disease .", "target_text": { "Cytokine": "protein", "transcription factors": "protein", "signal transducers and activators of transcription": "protein", "STATs": "protein", "STAT": "protein" } }, { "input_text": "We reasoned that selective IFN responsiveness of the first STAT family member ( Stat1 ) and Stat1 -dependent immune-response genes such as intercellular adhesion molecule-1 ( ICAM-1 ) , IFN regulatory factor-1 ( IRF-1 ) , and Stat1 itself in airway epithelial cells provides a basis for detecting cytokine signaling abnormalities in inflammatory airway disease .", "target_text": { "IFN": "protein", "STAT family member": "protein", "Stat1": "protein", "Stat1 -dependent immune-response genes": "DNA", "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "IFN regulatory factor-1": "protein", "IRF-1": "protein", "airway epithelial cells": "cell_type", "cytokine": "protein" } }, { "input_text": "On the basis of nuclear localization and phosphorylation , we found that epithelial Stat1 ( but not other control transcription factors ) was invariably activated in asthmatic compared with normal control or chronic bronchitis subjects .", "target_text": { "Stat1": "protein", "epithelial Stat1": "protein", "transcription factors": "protein" } }, { "input_text": "Furthermore , epithelial levels of activated Stat1 correlated with levels of expression for epithelial ICAM-1 , IRF-1 , and Stat1 , and in turn , ICAM-1 levels correlated with T-cell accumulation in tissue .", "target_text": { "Stat1": "protein", "ICAM-1": "protein", "epithelial ICAM-1": "protein", "IRF-1": "protein" } }, { "input_text": "However , only low levels of IFN-gamma or IFN-gamma -producing cells were detected in airway tissue in all subjects .", "target_text": { "IFN-gamma": "protein", "IFN-gamma -producing cells": "cell_type" } }, { "input_text": "The results therefore provide initial evidence linking abnormal behavior of STAT pathways for cytokine signaling to the development of an inflammatory disease .", "target_text": { "STAT": "protein", "cytokine": "protein" } }, { "input_text": "In that context , the results also change the current scheme for asthma pathogenesis to one that must include a localized gain in transcriptional signal ordinarily used for a T helper 1-type cytokine ( IFN-gamma ) in combination with allergy-driven overproduction of T helper 2-type cytokines .", "target_text": { "T helper 1-type cytokine": "protein", "IFN-gamma": "protein", "T helper 2-type cytokines": "protein" } }, { "input_text": "Leukocyte populations , hormone receptors and apoptosis in eutopic and ectopic first trimester human pregnancies .", "target_text": { "Leukocyte populations": "cell_type", "hormone receptors": "protein" } }, { "input_text": "The implantation of trophoblast cells at extrauterine sites still results in decidualization .", "target_text": { "trophoblast cells": "cell_type" } }, { "input_text": "The objective of the present study was to compare decidualization at eutopic and ectopic implantation sites .", "target_text": {} }, { "input_text": "Tissues from women undergoing elective termination of uterine pregnancy and from women with ectopic pregnancy were used to detect the presence of cells important for the maintenance of pregnancy , such as BCL-2+ , CD56+ , CD3+ , CD8+ and CD68+ cells , and the presence of oestrogen ( ER ) and progesterone receptors ( PR ) by immunohistochemistry .", "target_text": { "oestrogen": "protein", "ER": "protein", "progesterone receptors": "protein", "oestrogen ( ER ) and progesterone receptors": "protein", "PR": "protein" } }, { "input_text": "In-situ detection of fragmented DNA was performed to identify apoptotic cells .", "target_text": { "apoptotic cells": "cell_type" } }, { "input_text": "The percentage of CD3+ cells among all immunocompetent cells in the tubal epithelium was 46.6 % ( 39.9 % of CD3+ were also CD8+ ) ; the other 53.4 % were CD68+ cells .", "target_text": { "CD3+ cells": "cell_type", "immunocompetent cells": "cell_type", "CD3+": "cell_type", "CD8+": "cell_type", "CD68+ cells": "cell_type" } }, { "input_text": "CD56+ cells were undetectable in ectopic decidua at the feto-maternal interface in ectopic tissue .", "target_text": { "CD56+ cells": "cell_type" } }, { "input_text": "In uterine decidua , we found 29.9 % CD3+ cells ( 2.2 % of CD3+ were CD8+ ) , 51.6 % CD56+ cells and 18.5 % CD68+ cells .", "target_text": { "CD3+ cells": "cell_type", "CD56+ cells": "cell_type", "CD68+ cells": "cell_type" } }, { "input_text": "The ratio of BCL2+ to CD3+ cells in ectopic pregnancy was 0.41 .", "target_text": { "BCL2+": "cell_type", "CD3+ cells": "cell_type" } }, { "input_text": "In uterine pregnancy , the ratio of BCL-2 to CD3 was 0.44 and 0.39 for CD56 .", "target_text": { "BCL-2": "protein" } }, { "input_text": "Tissues from both ectopic and uterine pregnancies were positive for PR .", "target_text": { "PR": "protein" } }, { "input_text": "Fewer apoptotic cell bodies were present in ectopic pregnancy .", "target_text": { "apoptotic cell bodies": "cell_type" } }, { "input_text": "The use of tissue obtained from ectopic pregnancy may become an excellent model to identify the mechanism of trophoblast invasion in eutopic pregnancies .", "target_text": {} }, { "input_text": "Angiotensin II activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes .", "target_text": { "Angiotensin II": "protein", "proinflammatory transcription factor": "protein", "nuclear factor-kappaB": "protein", "human monocytes": "cell_type" } }, { "input_text": "The renin -angiotensin system may contribute to the pathogenesis of atherosclerosis .", "target_text": { "renin": "protein" } }, { "input_text": "A common feature of all stages of atherosclerosis is inflammation of the vessel wall .", "target_text": {} }, { "input_text": "The transcription factor nuclear factor-kappaB ( NF-kappaB ) participates in most signaling pathways involved in inflammation .", "target_text": { "nuclear factor-kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "This study therefore examined the effect of angiotensin ( ANG ) II on NF-kappaB activation in monocytic cells , a major cellular component of human atheroma , by electrophoretic mobility shift assay .", "target_text": { "angiotensin ( ANG ) II": "protein", "NF-kappaB": "protein", "monocytic cells": "cell_type" } }, { "input_text": "ANG II , like TNFalpha , caused rapid activation of NF-kappaB in human mononuclear cells isolated from peripheral blood by Ficoll density gradient .", "target_text": { "ANG II": "protein", "TNFalpha": "protein", "NF-kappaB": "protein", "human mononuclear cells": "cell_type" } }, { "input_text": "This ANG II effect was blocked by the angiotensin AT1 receptor antagonist losartan .", "target_text": { "ANG II": "protein" } }, { "input_text": "Specificity of ANG II -induced NF-kappaB activation was ascertained by supershift and competition experiments .", "target_text": { "ANG II": "protein", "NF-kappaB": "protein" } }, { "input_text": "Moreover , ANG II stimulated NF-kappaB activation in human monocytes , but not in lymphocytes from the same preparation .", "target_text": { "ANG II": "protein", "NF-kappaB": "protein", "human monocytes": "cell_type", "lymphocytes": "cell_type" } }, { "input_text": "Together , the data demonstrate the ability of the vasoactive peptide ANG II to activate inflammatory pathways in human monocytes .", "target_text": { "ANG II": "protein", "human monocytes": "cell_type" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "Signal transduction pathways activated in endothelial cells following infection with Chlamydia pneumoniae .", "target_text": { "endothelial cells": "cell_type" } }, { "input_text": "Chlamydia pneumoniae is an important respiratory pathogen .", "target_text": {} }, { "input_text": "Recently , its presence has been demonstrated in atherosclerotic lesions .", "target_text": {} }, { "input_text": "In this study , we characterized C. pneumoniae-mediated activation of endothelial cells and demonstrated an enhanced expression of endothelial adhesion molecules followed by subsequent rolling , adhesion , and transmigration of leukocytes ( monocytes , granulocytes ) .", "target_text": { "endothelial cells": "cell_type", "endothelial adhesion molecules": "protein", "leukocytes": "cell_type", "monocytes": "cell_type", "granulocytes": "cell_type" } }, { "input_text": "These effects were blocked by mAbs against endothelial and/or leukocyte adhesion molecules ( beta1 and beta2 integrins ) .", "target_text": { "mAbs": "protein" } }, { "input_text": "Additionally , activation of different signal transduction pathways in C. pneumoniae -infected endothelial cells was shown : protein tyrosine phosphorylation , up-regulation of phosphorylated p42/p44 mitogen-activated protein kinase , and NF-kappaB activation/translocation occurred within 10-15 min .", "target_text": { "endothelial cells": "cell_type", "C. pneumoniae -infected endothelial cells": "cell_type", "p42/p44 mitogen-activated protein kinase": "protein", "NF-kappaB": "protein" } }, { "input_text": "Increased mRNA and surface expression of E-selectin , ICAM-1 , and VCAM-1 were noted within hours .", "target_text": { "mRNA": "RNA", "E-selectin": "protein", "ICAM-1": "protein", "VCAM-1": "protein" } }, { "input_text": "Thus , C. pneumoniae triggers a cascade of events that could lead to endothelial activation , inflammation , and thrombosis , which in turn may result in or may promote atherosclerosis .", "target_text": {} }, { "input_text": "Transient pseudo-hypoaldosteronism following resection of the ileum : normal level of lymphocytic aldosterone receptors outside the acute phase .", "target_text": { "lymphocytic aldosterone receptors": "protein" } }, { "input_text": "Pseudo-hypoaldosteronism ( PHA ) is due to mineralocorticoid resistance and manifests as hyponatremia and hyperkalemia with increased plasma aldosterone levels .", "target_text": {} }, { "input_text": "It may be familial or secondary to abnormal renal sodium handling .", "target_text": {} }, { "input_text": "We report the case of a 54-year-old woman with multifocal cancer of the colon , who developed PHA after subtotal colectomy , ileal resection and jejunostomy .", "target_text": {} }, { "input_text": "She was treated with 6 g of salt daily to prevent dehydration , which she stopped herself because of reduced fecal losses .", "target_text": {} }, { "input_text": "One month later she was admitted with signs of acute adrenal failure , i.e. fatigue , severe nausea , blood pressure of 80/60 mmHg , extracellular dehydration , hyponatremia ( 118 mmol/l ) ; hyperkalemia ( 7.6 mmol/l ) , increased blood urea nitrogen ( BUN ) ( 200 mg/dl ) and creatininemia ( 2.5 mg/dl ) , and decreased plasma bicarbonates level ( HCO3- : 16 mmol/l ; N : 27-30 ) .", "target_text": {} }, { "input_text": "However , the plasma cortisol was high ( 66 microg/100 ml at 10:00 h ; N : 8-15 ) and the ACTH was normal ( 13 pg/ml , N : 10-60 ) ; there was a marked increase in plasma renin activity ( > 37 ng/ml/h ; N supine < 3 ) , active renin ( 869 pg/ml ; N supine : 1.120 ) , aldosterone ( > 2000 pg/ml ; N supine < 150 ) and plasma AVP ( 20 pmol/l ; N : 0.5-2.5 ) .", "target_text": {} }, { "input_text": "The plasma ANH level was 38 pmol/l ( N supine : 5-25 ) .", "target_text": {} }, { "input_text": "A urinary steroidogram resulted in highly elevated tetrahydrocortisol ( THF : 13.3 mg/24h ; N : 1.4+/-0.8 ) with no increase in tetrahydrocortisone ( THE : 3.16 mg/24h ; N : 2.7+/-2.0 ) excretion , and with low THE/THF ( 0.24 ; N : 1.87+/-0.36 ) and alpha THF/THF ( 0.35 ; N : 0.92+/-0.42 ) ratios .", "target_text": {} }, { "input_text": "The number of mineralocorticoid receptors in mononuclear leukocytes was in the lower normal range for age , while the number of glucocorticoid receptors was reduced .", "target_text": { "mineralocorticoid receptors": "protein", "leukocytes": "cell_type", "mononuclear leukocytes": "cell_type", "glucocorticoid receptors": "protein" } }, { "input_text": "Small-bowel resection in ileostomized patients causes excessive fecal sodium losses and results in chronic sodium depletion with contraction of the plasma volume and severe secondary hyperaldosteronism .", "target_text": {} }, { "input_text": "Nevertheless , this hyperaldosteronism may be associated with hyponatremia and hyperkalemia suggesting PHA related to the major importance of the colon for the absorption of sodium .", "target_text": {} }, { "input_text": "In conclusion , this case report emphasizes 1 ) the possibility of a syndrome of acquired PHA with severe hyperkalemia after resection of the ileum and colon responding to oral salt supplementation ; 2 ) the major increase in AVP and the small increase in ANH ; 3 ) the strong increase in urinary THF with low THE/THF and alpha THF/THF ratios ; 4 ) the normal number of lymphocytic mineralocorticoid receptors outside the acute episode .", "target_text": { "mineralocorticoid receptors": "protein", "lymphocytic mineralocorticoid receptors": "protein" } }, { "input_text": "Modulation of the immune response by progesterone-induced lymphocyte factors .", "target_text": { "progesterone-induced lymphocyte factors": "protein" } }, { "input_text": "Rat spleen and peripheral blood lymphocytes express progesterone receptors whose concentration is increased greatly during the early phase of pregnancy .", "target_text": { "peripheral blood lymphocytes": "cell_type", "progesterone receptors": "protein" } }, { "input_text": "After stimulation of progesterone the expression of receptors was augmented 2-3 times .", "target_text": {} }, { "input_text": "When cells were cultured in the presence of progesterone they released a soluble factor that inhibited cellular immunoreactions ( MLR , CRC ) and cellular proliferation as measured by thymidine incorporation by spleen-cell culture .", "target_text": { "soluble factor": "protein", "spleen-cell culture": "cell_line" } }, { "input_text": "This factor also inhibited the synthesis of anti-DNP antibodies by a mouse hybridoma and diminished the proportion of cells in phase S .", "target_text": { "anti-DNP antibodies": "protein", "mouse hybridoma": "cell_line" } }, { "input_text": "However , the percentage of asymmetric molecules produced by the hybridoma remained unaltered .", "target_text": { "asymmetric molecules": "protein", "hybridoma": "cell_line" } }, { "input_text": "These results support the hypothesis that soluble factors released by rat lymphocytes modulate the immune response of the mother and participate in the mechanism that protects the fetus against antipaternal antibodies .", "target_text": { "soluble factors": "protein", "rat lymphocytes": "cell_type", "antipaternal antibodies": "protein" } }, { "input_text": "Differential regulation of 4E-BP1 and 4E-BP2 , two repressors of translation initiation , during human myeloid cell differentiation .", "target_text": { "4E-BP1": "protein", "4E-BP2": "protein", "human myeloid cell": "cell_type" } }, { "input_text": "Human myeloid differentiation is accompanied by a decrease in cell proliferation .", "target_text": {} }, { "input_text": "Because the translation rate is an important determinant of cell proliferation , we have investigated translation initiation during human myeloid cell differentiation using the HL-60 promyelocytic leukemia cell line and the U-937 monoblastic cell line .", "target_text": { "human myeloid cell": "cell_type", "HL-60 promyelocytic leukemia cell line": "cell_line", "U-937 monoblastic cell line": "cell_line" } }, { "input_text": "A decrease in the translation rate is observed when the cells are induced to differentiate along the monocytic/macrophage pathway or along the granulocytic pathway .", "target_text": {} }, { "input_text": "The inhibition in protein synthesis correlates with specific regulation of two repressors of translation initiation , 4E-BP1 and 4E-BP2 .", "target_text": { "4E-BP1": "protein", "4E-BP2": "protein" } }, { "input_text": "Induction of HL-60 and U-937 cell differentiation into monocytes /macrophages by IFN-gamma or PMA results in a dephosphorylation and consequent activation of 4E-BP1 .", "target_text": { "HL-60": "cell_line", "U-937": "cell_line", "monocytes": "cell_type", "monocytes /macrophages": "cell_type", "IFN-gamma": "protein", "4E-BP1": "protein" } }, { "input_text": "Dephosphorylation of 4E-BP1 was also observed when U-937 cells were induced to differentiate into monocytes /macrophages following treatment with retinoic acid or DMSO .", "target_text": { "4E-BP1": "protein", "U-937 cells": "cell_line", "monocytes": "cell_type", "monocytes /macrophages": "cell_type" } }, { "input_text": "In contrast , treatment of HL-60 cells with retinoic acid or DMSO , which results in a granulocytic differentiation of these cells , decreases 4E-BP1 amount without affecting its phosphorylation and strongly increases 4E-BP2 amount .", "target_text": { "HL-60 cells": "cell_line", "4E-BP1": "protein", "4E-BP2": "protein" } }, { "input_text": "Taken together , these data provide evidence for differential regulation of the translational machinery during human myeloid differentiation , specific to the monocytic/macrophage pathway or to the granulocytic pathway .", "target_text": {} }, { "input_text": "Nonimmunoglobulin gene hypermutation in germinal center B cells .", "target_text": { "germinal center B cells": "cell_type" } }, { "input_text": "Somatic hypermutation is the most critical mechanism underlying the diversification of Ig genes .", "target_text": { "Ig genes": "DNA" } }, { "input_text": "Although mutation occurs specifically in B cells during the germinal center reaction , it remains a matter of debate whether the mutation machinery also targets non- Ig genes .", "target_text": { "B cells": "cell_type", "Ig genes": "DNA", "non- Ig genes": "DNA" } }, { "input_text": "We have studied mutations in the 5' noncoding region of the Bcl6 gene in different subtypes of lymphomas .", "target_text": { "5' noncoding region": "DNA", "Bcl6 gene": "DNA" } }, { "input_text": "We found frequent hypermutation in follicular lymphoma ( 25 of 59 = 42 % ) ( germinal center cell origin ) and mucosa-associated lymphoid tissue ( MALT ) lymphoma ( 19 of 45 = 42 % ) ( postgerminal center ) , but only occasionally in mantle cell lymphoma ( 1 of 21 = 4.8 % ) ( pregerminal center ) .", "target_text": {} }, { "input_text": "Most mutations were outside the motifs potentially important for transcription , suggesting they were not important in lymphomagenesis but may , like Ig mutation , represent an inherent feature of the lymphoma precursor cells .", "target_text": { "lymphoma precursor cells": "cell_type" } }, { "input_text": "Therefore , we investigated their normal cell counterparts microdissected from a reactive tonsil .", "target_text": {} }, { "input_text": "Bcl6 mutation was found in 13 of 24 ( 54 % ) clones from the germinal centre but only in 1 of 24 ( 4 % ) clones from the naive B cells of the mantle zone .", "target_text": { "B cells": "cell_type", "naive B cells": "cell_type" } }, { "input_text": "The frequency , distribution , and nature of these mutations were similar to those resulting from the Ig hypermutation process .", "target_text": {} }, { "input_text": "The results show unequivocal evidence of non- Ig gene hypermutation in germinal center B cells and provide fresh insights into the process of hypermutation and lymphomagenesis .", "target_text": { "Ig gene": "DNA", "B cells": "cell_type", "germinal center B cells": "cell_type" } }, { "input_text": "Impaired binding of a DQ2 and DQ8 -binding HSV VP16 peptide to a DQA1*0501/DQB1*0302 trans class II heterodimer .", "target_text": { "DQ2": "protein", "DQ8": "protein", "DQA1*0501/DQB1*0302 trans class II heterodimer": "protein" } }, { "input_text": "DQalpha and DQbeta trans heterodimeric HLA-DQ molecules form in individuals heterozygous for the DQ2 and DQ8 specificities .", "target_text": { "HLA-DQ molecules": "protein", "DQalpha and DQbeta trans heterodimeric HLA-DQ molecules": "protein", "DQ2": "protein", "DQ8": "protein" } }, { "input_text": "Unique functions and disease associations have been postulated for such trans-dimers , which may be different from cis-encoded DQ molecules encoded by the corresponding haplotypes .", "target_text": { "trans-dimers": "protein", "cis-encoded DQ molecules": "protein" } }, { "input_text": "We analyzed the ability of the trans-dimer encoded by HLA-DQA1*0501/DQB1*0302 to bind a peptide antigen which interacts with DQ molecules encoded by both parental haplotypes .", "target_text": { "HLA-DQA1*0501/DQB1*0302": "protein", "DQ molecules": "protein" } }, { "input_text": "Markedly impaired binding was observed , consistent with both the use of different anchor residues and with changes in levels of DQ cis- dimer availability for peptide binding interactions .", "target_text": { "dimer": "protein" } }, { "input_text": "Detection of intracellular phosphorylated STAT-1 by flow cytometry .", "target_text": { "intracellular phosphorylated STAT-1": "protein" } }, { "input_text": "We have applied flow cytometry to the investigation of interferon-gamma activation of human monocytes .", "target_text": { "interferon-gamma": "protein", "human monocytes": "cell_type" } }, { "input_text": "This approach uses monoclonal antibodies that distinguish between the native and phosphorylated forms of STAT-1 .", "target_text": { "monoclonal antibodies": "protein", "STAT-1": "protein" } }, { "input_text": "It enables rapid and quantitative assessment of STAT-1 phosphorylation on a discrete cell basis and is both more sensitive and less time consuming than immunoblotting .", "target_text": { "STAT-1": "protein" } }, { "input_text": "Furthermore , it allows for discrimination between a mixture of cells that differ in their response to interferon-gamma .", "target_text": { "interferon-gamma": "protein" } }, { "input_text": "This approach should allow for the evaluation of different intracellular signaling pathways using a combination of monoclonal reagents that are specific for native and activation modified proteins .", "target_text": { "activation modified proteins": "protein" } }, { "input_text": "Application of this form of testing should prove valuable in screening for signaling defects in selected patients with recurrent infections .", "target_text": {} }, { "input_text": "In addition , this technique should permit dissection of a full range of cellular signaling pathways at the protein level .", "target_text": {} }, { "input_text": "Activation of nuclear factor-kappaB by lipopolysaccharide in mononuclear leukocytes is prevented by inhibitors of cytosolic phospholipase A2 .", "target_text": { "nuclear factor-kappaB": "protein", "mononuclear leukocytes": "cell_type", "cytosolic phospholipase A2": "protein" } }, { "input_text": "In monocytes , lipopolysaccharide induces synthesis and activity of the 85-kDa cytosolic phospholipase A2 .", "target_text": { "monocytes": "cell_type", "cytosolic phospholipase A2": "protein" } }, { "input_text": "This enzyme releases arachidonic acid and lyso-phospholipids from membranes which are metabolized to eicosanoids and platelet-activating-factor .", "target_text": {} }, { "input_text": "These lipid mediators increase activity of transcription factors and expression of cytokine genes indicating a function for cytosolic phospholipase A2 in signal transduction and inflammation .", "target_text": { "transcription factors": "protein", "cytokine genes": "DNA", "cytosolic phospholipase A2": "protein" } }, { "input_text": "We have shown previously that trifluoromethylketone inhibitors of cytosolic phospholipase A2 suppressed interleukin-1beta protein and steady-state mRNA levels in human lipopolysaccharide -stimulated peripheral blood mononuclear leukocytes .", "target_text": { "cytosolic phospholipase A2": "protein", "interleukin-1beta protein": "protein", "mononuclear leukocytes": "cell_type", "lipopolysaccharide -stimulated peripheral blood mononuclear leukocytes": "cell_type" } }, { "input_text": "In this study , the subcellular mechanisms were analyzed by which trifluoromethylketones interfere with gene expression .", "target_text": {} }, { "input_text": "We found that they reduced the initial interleukin-1beta mRNA transcription rate through prevention of degradation of inhibitor-kappaB alpha .", "target_text": { "interleukin-1beta mRNA": "RNA", "inhibitor-kappaB alpha": "protein" } }, { "input_text": "Consequently , cytosolic activation , nuclear translocation and DNA-binding of nuclear factor-kappaB were decreased .", "target_text": { "nuclear factor-kappaB": "protein" } }, { "input_text": "Trifluoromethylketones ameliorate chronic inflammation in vivo .", "target_text": {} }, { "input_text": "Thus , this therapeutic potency may reside in retention of inactive nuclear factor-kappaB in the cytosol thereby abrogating interleukin-1beta gene transcription .", "target_text": { "nuclear factor-kappaB": "protein", "cytosol": "cell_type", "interleukin-1beta": "protein" } }, { "input_text": "Cellular disposition of sulphamethoxazole and its metabolites : implications for hypersensitivity .", "target_text": {} }, { "input_text": "1. Bioactivation of sulphamethoxazole ( SMX ) to chemically-reactive metabolites and subsequent protein conjugation is thought to be involved in SMX hypersensitivity .", "target_text": {} }, { "input_text": "We have therefore examined the cellular metabolism , disposition and conjugation of SMX and its metabolites in vitro .", "target_text": {} }, { "input_text": "2. Flow cytometry revealed binding of N-hydroxy ( SMX-NHOH ) and nitroso ( SMX-NO ) metabolites of SMX , but not of SMX itself , to the surface of viable white blood cells .", "target_text": { "white blood cells": "cell_type" } }, { "input_text": "Cellular haptenation by SMX -NO was reduced by exogenous glutathione ( GSH ) .", "target_text": {} }, { "input_text": "3. SMX -NHOH and SMX -NO were rapidly reduced back to the parent compound by cysteine ( CYS ) , GSH , human peripheral blood cells and plasma , suggesting that this is an important and ubiquitous bioinactivation mechanism .", "target_text": { "human peripheral blood cells": "cell_type", "ubiquitous": "protein" } }, { "input_text": "4. Fluorescence HPLC showed that SMX -NHOH and SMX -NO depleted CYS and GSH in buffer , and to a lesser extent , in cells and plasma .", "target_text": {} }, { "input_text": "5. Neutrophil apoptosis and inhibition of neutrophil function were induced at lower concentrations of SMX -NHOH and SMX -NO than those inducing loss of membrane viability , with SMX having no effect .", "target_text": {} }, { "input_text": "Lymphocytes were significantly ( P < 0.05 ) more sensitive to the direct cytotoxic effects of SMX -NO than neutrophils .", "target_text": { "Lymphocytes": "cell_type", "neutrophils": "cell_type" } }, { "input_text": "6. Partitioning of SMX -NHOH into red blood cells was significantly ( P < 0.05 ) lower than with the hydroxylamine of dapsone .", "target_text": { "red blood cells": "cell_type" } }, { "input_text": "7. Our results suggest that the balance between oxidation of SMX to its toxic metabolites and their reduction is an important protective cellular mechanism .", "target_text": {} }, { "input_text": "If an imbalance exists , haptenation of the toxic metabolites to bodily proteins including the surface of viable cells can occur , and may result in drug hypersensitivity .", "target_text": {} }, { "input_text": "Bcl-6 expression in reactive follicular hyperplasia , follicular lymphoma , and angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers : heterogeneity of intrafollicular T-cells and their altered distribution in the pathogenesis of angioimmunoblastic T-cell lymphoma .", "target_text": { "Bcl-6": "protein", "intrafollicular T-cells": "cell_type" } }, { "input_text": "BACKGROUND : The Bcl-6 gene product , a nuclear phosphoprotein , is expressed independently of Bcl-6 gene rearrangement .", "target_text": { "Bcl-6": "protein", "Bcl-6 gene product": "protein", "nuclear phosphoprotein": "protein" } }, { "input_text": "In lymph nodes , expression of Bcl-6 protein is restricted to germinal center ( GC ) B-cells and 10 % to 15 % of CD3/CD4+ intrafollicular T cells .", "target_text": { "Bcl-6": "protein", "germinal center ( GC ) B-cells": "cell_type", "CD3/CD4+ intrafollicular T cells": "cell_type" } }, { "input_text": "Interfollicular cells are negative for Bcl-6 protein , except for rare CD3+/CD4+ T cells .", "target_text": { "Bcl-6": "protein", "Bcl-6 protein": "protein", "CD3+/CD4+ T cells": "cell_type" } }, { "input_text": "Recently , we reported cases of angioimmunoblastic T-cell lymphoma ( AITL ) with hyperplastic GCs ( AITL/GC ) , and observed that borders of enlarged GCs were ill defined , with features suggestive of an outward migration of GC cells to surrounding interfollicular zones .", "target_text": { "GC cells": "cell_type" } }, { "input_text": "This prompted a study of follicular borders with Bcl-6 staining in reactive follicular hyperplasias and follicular lymphomas to compare with AITL /GC .", "target_text": { "Bcl-6": "protein" } }, { "input_text": "MATERIALS AND METHODS : Formalin-fixed paraffin sections were used for immunostaining of Bcl-6 .", "target_text": { "Bcl-6": "protein" } }, { "input_text": "Six cases of AITL/GC , 12 nonspecific reactive follicular hyperplasia ( FH ) , 7 HIV adenopathy , 10 follicular lymphoma ( FL ) , and 8 typical AITL ( ie , AITL without GC ) were studied .", "target_text": {} }, { "input_text": "Double staining for Bcl-6 /CD20 , Bcl-6 /CD3 , and Bcl-6 /CD57 was performed in selected cases .", "target_text": { "Bcl-6": "protein", "Bcl-6 /CD20": "protein", "Bcl-6 /CD3": "protein", "Bcl-6 /CD57": "protein" } }, { "input_text": "RESULTS : In FH and HIV adenopathy , staining for Bcl-6 revealed densely populated GCs with well-defined and regular GC borders , whereas Bcl-6 + cells were rare in the interfollicular areas .", "target_text": { "Bcl-6": "protein", "Bcl-6 + cells": "cell_type" } }, { "input_text": "An occasional GC with an ill-defined border was invariably surrounded by a broad mantle zone ; those with indistinct mantle zones had well-defined , regular borders .", "target_text": {} }, { "input_text": "In FL , follicles were densely populated , and their borders were irregular , with some Bcl-6 + cells in the interfollicular zones .", "target_text": { "Bcl-6": "protein", "Bcl-6 + cells": "cell_type" } }, { "input_text": "In AITL /GC , GCs were less dense , GC borders were ill defined and irregular , and the number of interfollicular Bcl-6 + cells was markedly increased .", "target_text": { "Bcl-6": "protein", "interfollicular Bcl-6 + cells": "cell_type" } }, { "input_text": "Double staining revealed that these interfollicular Bcl-6 + cells in AITL /GC were Bcl6+/CD3+/CD20-/CD57- T cells .", "target_text": { "Bcl-6": "protein", "interfollicular Bcl-6 + cells": "cell_type", "Bcl6+/CD3+/CD20-/CD57- T cells": "cell_type" } }, { "input_text": "Moreover , CD3+ intrafollicular T cells were depleted in AITL /GC , whereas they were abundant in FH .", "target_text": { "CD3+ intrafollicular T cells": "cell_type" } }, { "input_text": "Intrafollicular CD57+ cells did not stain for Bcl-6 , and were also depleted in AITL /GC .", "target_text": { "CD57+ cells": "cell_type", "Bcl-6": "protein" } }, { "input_text": "In typical AITL , some neoplastic cells were positive for Bcl-6 , showing variable degrees of staining .", "target_text": { "Bcl-6": "protein" } }, { "input_text": "CONCLUSIONS : ( 1 ) GCs of AITL/GC differed from those of other reactive follicular hyperplasias and follicular lymphomas , and staining for Bcl-6 was useful to discern them .", "target_text": { "Bcl-6": "protein" } }, { "input_text": "( 2 ) Intrafollicular CD3+ T cells , many of which were also positive for Bcl-6 , were markedly depleted in AITL /GC , with increased interfollicular Bcl-6 +/CD3+ cells , suggesting an outward migration of intrafollicular T cells in this condition .", "target_text": { "Intrafollicular CD3+ T cells": "cell_type", "Bcl-6": "protein", "Bcl-6 +/CD3+ cells": "cell_type", "intrafollicular T cells": "cell_type" } }, { "input_text": "( 3 ) Interfollicular Bcl-6 +/CD3+ cells in AITL/GC were too numerous to be accounted for by migration alone , suggesting local proliferation .", "target_text": { "Bcl-6": "protein", "Interfollicular Bcl-6 +/CD3+ cells": "cell_type" } }, { "input_text": "( 4 ) Intrafollicular CD57+ cells were negative for Bcl-6 , indicating heterogeneity of the intrafollicular T-cell population .", "target_text": { "Intrafollicular CD57+ cells": "cell_type", "Bcl-6": "protein", "intrafollicular T-cell population": "cell_type" } }, { "input_text": "( 5 ) Some neoplastic cells in AITL stained for Bcl-6 , suggesting up-regulation of Bcl-6 expression in this tumor .", "target_text": { "Bcl-6": "protein" } }, { "input_text": "Human cytomegalovirus binding to human monocytes induces immunoregulatory gene expression .", "target_text": { "monocytes": "cell_type", "human monocytes": "cell_type" } }, { "input_text": "To continue our investigation of the cellular events that occur following human CMV ( HCMV ) infection , we focused on the regulation of cellular activation following viral binding to human monocytes .", "target_text": { "monocytes": "cell_type", "human monocytes": "cell_type" } }, { "input_text": "First , we showed that viral binding induced a number of immunoregulatory genes ( IL-1beta , A20 , NF-kappaB-p105/p50 , and IkappaBalpha ) in unactivated monocytes and that neutralizing Abs to the major HCMV glycoproteins , gB ( UL55 ) and gH ( UL75 ) , inhibited the induction of these genes .", "target_text": { "immunoregulatory genes": "cell_type", "IL-1beta": "protein", "A20": "protein", "NF-kappaB-p105/p50": "protein", "IkappaBalpha": "protein", "monocytes": "cell_type", "neutralizing Abs": "protein", "HCMV glycoproteins": "protein", "gB": "protein", "UL55": "protein", "gH": "protein", "UL75": "protein" } }, { "input_text": "Next , we demonstrated that these viral ligands directly up-regulated monocyte gene expression upon their binding to their appropriate cellular receptors .", "target_text": {} }, { "input_text": "We then investigated if HCMV binding also resulted in the translation and secretion of cytokines .", "target_text": { "cytokines": "protein" } }, { "input_text": "Our results showed that HCMV binding to monocytes resulted in the production and release of IL-1beta protein .", "target_text": { "monocytes": "cell_type", "IL-1beta": "protein", "IL-1beta protein": "protein" } }, { "input_text": "Because these induced gene products have NF-kappaB sites in their promoter regions , we next examined whether there was an up-regulation of nuclear NF-kappaB levels .", "target_text": { "NF-kappaB": "protein", "NF-kappaB sites": "DNA", "promoter regions": "DNA" } }, { "input_text": "These experiments showed that , in fact , NF-kappaB was translocated to the nucleus following viral binding or purified viral ligand binding .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Changes in IkappaBalpha levels correlated with the changes in NF-kappaB translocation .", "target_text": { "IkappaBalpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "Lastly , we demonstrated that p38 kinase activity played a central role in IL-1beta production and that it was rapidly up-regulated following infection .", "target_text": { "p38": "protein", "IL-1beta": "protein" } }, { "input_text": "These results support our hypothesis that HCMV initiates a signal transduction pathway that leads to monocyte activation and pinpoints a potential mechanism whereby HCMV infection of monocytes can result in profound pathogenesis , especially in chronic inflammatory-type conditions .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "Regulation of the megakaryocytic glycoprotein IX promoter by the oncogenic Ets transcription factor Fli-1 .", "target_text": { "megakaryocytic glycoprotein IX promoter": "DNA", "oncogenic Ets transcription factor": "protein", "Fli-1": "protein" } }, { "input_text": "Glycoprotein ( GP ) IX is a subunit of the von Willebrand receptor , GPIb- V-IX , which mediates adhesion of platelets to the subendothelium of damaged blood vessels .", "target_text": { "Glycoprotein ( GP ) IX": "protein", "von Willebrand receptor": "protein", "GPIb- V-IX": "protein", "platelets": "cell_type" } }, { "input_text": "Previous characterization of the GPIX promoter identified a functional Ets site that , when disrupted , reduced promoter activity .", "target_text": { "GPIX promoter": "DNA" } }, { "input_text": "However , the Ets protein ( s ) that regulated GPIX promoter expression was unknown .", "target_text": { "Ets protein": "protein", "GPIX promoter": "DNA" } }, { "input_text": "In this study , transient cotransfection of several GPIX promoter /reporter constructs into 293T kidney fibroblasts with a Fli-1 expression vector shows that the oncogenic protein Fli-1 can transactivate the GPIX promoter when an intact GPIX Ets site is present .", "target_text": { "GPIX promoter": "DNA", "GPIX promoter /reporter constructs": "DNA", "293T kidney fibroblasts": "cell_line", "Fli-1": "protein", "Fli-1 expression vector": "DNA", "GPIX Ets site": "DNA" } }, { "input_text": "In addition , Fli-1 binding of the GPIX Ets site was identified in antibody supershift experiments in nuclear extracts derived from hematopoietic human erythroleukemia cells .", "target_text": { "Fli-1": "protein", "GPIX Ets site": "DNA", "hematopoietic human erythroleukemia cells": "cell_type" } }, { "input_text": "Comparative studies showed that Fli-1 was also able to transactivate the GPIbalpha and , to a lesser extent , the GPIIb promoter .", "target_text": { "Fli-1": "protein", "GPIbalpha": "DNA", "GPIIb promoter": "DNA" } }, { "input_text": "Immunoblot analysis identified Fli-1 protein in lysates derived from platelets .", "target_text": { "Fli-1": "protein", "Fli-1 protein": "protein", "platelets": "cell_type" } }, { "input_text": "In addition , expression of Fli-1 was identified immunohistochemically in megakaryocytes derived from CD34(+) cells treated with the megakaryocyte differentiation and proliferation factor , thrombopoietin .", "target_text": { "Fli-1": "protein", "megakaryocytes": "cell_type", "CD34(+) cells": "cell_type", "megakaryocyte differentiation and proliferation factor": "protein", "thrombopoietin": "protein" } }, { "input_text": "These results suggest that Fli-1 is likely to regulate lineage-specific genes during megakaryocytopoiesis .", "target_text": { "Fli-1": "protein", "lineage-specific genes": "DNA" } }, { "input_text": "Expression of IkappaBalpha in the nucleus of human peripheral blood T lymphocytes .", "target_text": { "IkappaBalpha": "protein", "human peripheral blood T lymphocytes": "cell_type" } }, { "input_text": "According to current models the inhibitory capacity of I ( kappa ) B ( alpha ) would be mediated through the retention of Rel/NF-kappaB proteins in the cytosol .", "target_text": { "I ( kappa ) B ( alpha )": "protein", "Rel/NF-kappaB proteins": "protein", "cytosol": "cell_type" } }, { "input_text": "However , I ( kappa ) B ( alpha ) has also been detected in the nucleus of cell lines and when overexpressed by transient transfection .", "target_text": { "I ( kappa ) B ( alpha )": "protein" } }, { "input_text": "To gain better insight into the potential role of nuclear I ( kappa ) B ( alpha ) in a physiological context we have analysed its presence in the nucleus of human peripheral blood T lymphocytes ( PBL ) .", "target_text": { "I ( kappa ) B ( alpha )": "protein", "nuclear I ( kappa ) B ( alpha )": "protein", "human peripheral blood T lymphocytes": "cell_type", "PBL": "cell_type" } }, { "input_text": "We demonstrate the nuclear localization of I ( kappa ) B ( alpha ) in PBL by different techniques : Western blot , indirect immunofluorescence and electron microscopy .", "target_text": { "I ( kappa ) B ( alpha )": "protein", "PBL": "cell_type" } }, { "input_text": "Low levels of nuclear I ( kappa ) B ( alpha ) were detected in resting cells whereas a superinduction was obtained after PMA activation .", "target_text": { "I ( kappa ) B ( alpha )": "protein" } }, { "input_text": "The nuclear pool of I ( kappa ) B ( alpha ) showed a higher stability than cytosolic I ( kappa ) B ( alpha ) and was partially independent of the resynthesis of the protein .", "target_text": { "I ( kappa ) B ( alpha )": "protein" } }, { "input_text": "Unexpectedly , the presence of nuclear I ( kappa ) B ( alpha ) did not inhibit NF-kappaB binding to DNA and this phenomenon was not due to the presence of IkappaBbeta at the nuclear level .", "target_text": { "I ( kappa ) B ( alpha )": "protein", "nuclear I ( kappa ) B ( alpha )": "protein", "NF-kappaB": "protein", "IkappaBbeta": "protein" } }, { "input_text": "Immunoprecipitation experiments failed to demonstrate an association between nuclear I ( kappa ) B ( alpha ) and NF-kappaB proteins .", "target_text": { "I ( kappa ) B ( alpha )": "protein", "NF-kappaB": "protein" } }, { "input_text": "Our results demonstrate that in resting and PMA-activated human PBL , I ( kappa ) B ( alpha ) is present in the nucleus in an apparently inactive form unable to disrupt NF-kappaB binding from DNA .", "target_text": { "PBL": "cell_type", "PMA-activated human PBL": "cell_type", "I ( kappa ) B ( alpha )": "protein", "NF-kappaB": "protein", "DNA": "DNA" } }, { "input_text": "Impaired fetal thymocyte development after efficient adenovirus -mediated inhibition of NF-kappa B activation .", "target_text": { "fetal thymocyte": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "We introduce a new experimental system combining adenovirus -mediated gene transfer and fetal thymic organ culture ( FTOC ) .", "target_text": {} }, { "input_text": "This system allowed us to efficiently express in developing thymocytes a mutant form of the NF-kappa B inhibitor I kappa B alpha ( mut-I kappa B ) and to study the maturation defects occurring when NF-kappa B activation is inhibited during fetal development .", "target_text": { "NF-kappa B": "protein", "I kappa B alpha": "protein", "mut-I kappa B": "protein" } }, { "input_text": "Fetal thymocytes infected with adenovirus containing mut-I kappa B were found to develop normally until the CD44 -CD25+ , CD4 - CD8 - double-negative stage , while production of more mature double-positive and single-positive populations was strongly decreased .", "target_text": { "Fetal thymocytes": "cell_type", "mut-I kappa B": "protein", "CD44": "protein", "CD4": "protein", "CD8": "protein" } }, { "input_text": "Proliferation , as measured by the percentage of cells in cycle appeared normal , as did rearrangement and expression of the TCR beta-chain .", "target_text": { "TCR beta-chain": "protein" } }, { "input_text": "However , apoptosis was much higher in FTOC infected with adenovirus containing mut-I kappa B than in FTOC infected with a control virus .", "target_text": { "mut-I kappa B": "protein" } }, { "input_text": "Taken together , these results suggest that NF-kappa B plays a crucial role in ensuring the differentiation and survival of thymocytes in the early stages of their development .", "target_text": { "NF-kappa B": "protein", "thymocytes": "cell_type" } }, { "input_text": "The relationship between Ca2+-ATPase and freely exchangeable Ca2+ in the dense tubules : a study in platelets from women .", "target_text": { "Ca2+-ATPase": "protein", "platelets": "cell_type" } }, { "input_text": "The main aims of this work were to examine in women : the relationship between the freely exchangeable Ca2+ ( FECa2+ ) in the dense tubules and the activity of the sarco ( endo ) plasmic reticulum ( SER ) Ca2+-ATPase ( SERCA ) in platelets , and the relationship of these parameters with blood pressure and serum lipoproteins .", "target_text": { "Ca2+-ATPase": "protein", "SERCA": "protein", "sarco ( endo ) plasmic reticulum ( SER ) Ca2+-ATPase ( SERCA )": "protein", "platelets": "cell_type", "serum lipoproteins": "protein" } }, { "input_text": "Platelets from 14 white and 13 black women in good health were studied .", "target_text": {} }, { "input_text": "The FECa2+ was measured as the ionomycin-evoked Ca2+ release ( in the presence of thapsigargin ) in Ca2+ - free medium .", "target_text": {} }, { "input_text": "SERCA activity was measured as the thapsigargin sensitive , Ca2+ dependent and ouabain resistant , ATP hydrolyses in platelet membranes .", "target_text": { "SERCA": "protein" } }, { "input_text": "Relative expressions of SERCA 2 and 3 isoforms and Ras-related protein ( Rap ) 1 in platelet membranes were determined by Western immunoblots .", "target_text": { "SERCA": "protein", "Ras-related protein ( Rap ) 1": "protein" } }, { "input_text": "Highly significant correlations were observed for FECa2+ in the dense tubules with : 1 ) the maximal reaction velocity ( Vmax ) of the SERCA ( r = 0.592 , P = .0014 ) , and 2 ) Rapl ( r = 0.551 , P = .0035 ) .", "target_text": { "SERCA": "protein", "Rapl": "protein" } }, { "input_text": "In addition , negative correlations were observed between FECa2+ in the dense tubules and age .", "target_text": {} }, { "input_text": "No correlations were observed for these variables with blood pressure or serum lipoproteins .", "target_text": { "serum lipoproteins": "protein" } }, { "input_text": "We conclude the FECa2+ and the Vmax of the SERCA are reliable indicators of Ca2+ load in platelets from women .", "target_text": { "SERCA": "protein", "platelets": "cell_type" } }, { "input_text": "However , in women , unlike previous observations in men , these platelet parameters are not correlated with blood pressure and serum lipoproteins .", "target_text": { "serum lipoproteins": "protein" } }, { "input_text": "Cobalt chloride -induced signaling in endothelium leading to the augmented adherence of sickle red blood cells and transendothelial migration of monocyte-like HL-60 cells is blocked by PAF-receptor antagonist .", "target_text": { "red blood cells": "cell_type", "sickle red blood cells": "cell_type", "monocyte-like HL-60 cells": "cell_line" } }, { "input_text": "In response to hypoxia , sickle red blood cells ( SS RBC ) and leukocytes exhibit increased adherence to the vascular endothelium , while diapedesis of leukocytes through the blood vessel increases .", "target_text": { "sickle red blood cells": "cell_type", "SS RBC": "cell_type", "leukocytes": "cell_type" } }, { "input_text": "However , the cellular signaling pathway ( s ) caused by hypoxia is poorly understood .", "target_text": {} }, { "input_text": "We utilized CoCl2 as a mimetic molecule for hypoxia to study cellular signaling pathways .", "target_text": {} }, { "input_text": "We found that in human umbilical vein endothelial cells ( HUVEC ) , CoCl2 at 2 mM concentration induced the surface expression of a subset of CAMs ( VCAM-1 ) and activation of transcription factor NF-kappaB in the nuclear extracts of HUVEC .", "target_text": { "human umbilical vein endothelial cells": "cell_type", "HUVEC": "cell_type", "CAMs": "protein", "VCAM-1": "protein", "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "Furthermore , CoCl2 also caused time-dependent tyrosine phosphorylation of mitogen-activated protein ( MAP ) kinase isoform ERK2 without significantly affecting ERK1 , indicating ERK2 is the preferred substrate for upstream kinase of the MAPK pathway .", "target_text": { "mitogen-activated protein ( MAP ) kinase": "protein", "ERK2": "protein", "ERK1": "protein", "upstream kinase": "protein", "MAPK": "protein" } }, { "input_text": "Inhibitors of MAP kinase ( PD98059 ) or platelet-activating factor ( PAF ) - receptor antagonist ( CV3988 ) inhibited the CoCl2 -induced NF-kappaB activation and VCAM-1 expression .", "target_text": { "MAP kinase": "protein", "NF-kappaB": "protein", "VCAM-1": "protein" } }, { "input_text": "Augmented expression of VCAM-1 led to increased SS RBC adhesion , inhibitable by a VCAM-1 antibody .", "target_text": { "VCAM-1": "protein", "SS RBC": "cell_type", "VCAM-1 antibody": "protein" } }, { "input_text": "Additionally , CoCl2 caused a two- to threefold increase in the rate of transendothelial migration of monocyte-like HL-60 cells and a twentyfold increase in phosphorylation of platelet endothelial cell adhesion molecules ( PECAM-1 ) .", "target_text": { "monocyte-like HL-60 cells": "cell_line", "endothelial cell adhesion molecules": "protein", "platelet endothelial cell adhesion molecules": "protein", "PECAM-1": "protein" } }, { "input_text": "The transendothelial migration of monocytes was inhibited by an antibody to PECAM-1 .", "target_text": { "monocytes": "cell_type", "PECAM-1": "protein" } }, { "input_text": "Both phosphorylation of PECAM-1 and transendothelial migration of monocytes in response to CoCl2 were inhibited by protein kinase inhibitor ( GF109203X ) and augmented by protein phosphatase inhibitor ( Calyculin A ) .", "target_text": { "PECAM-1": "protein", "monocytes": "cell_type" } }, { "input_text": "Our data suggests that CoCl2 -induced cellular signals directing increased expression of VCAM-1 in HUVEC involve downstream activation of MAP kinase and NF-kappaB , while the phosphorylation of PECAM-1 occurs as a result of activation of PKC .", "target_text": { "VCAM-1": "protein", "HUVEC": "cell_type", "MAP kinase": "protein", "NF-kappaB": "protein", "PECAM-1": "protein", "PKC": "protein" } }, { "input_text": "We conclude that PAF-receptor antagonist inhibits the CoCl2 - or hypoxia -induced increase in the adhesion of SS RBC , PECAM-1 phosphorylation , and the concomitant transendothelial migration of monocytes .", "target_text": { "SS RBC": "cell_type", "PECAM-1": "protein", "monocytes": "cell_type" } }, { "input_text": "Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes .", "target_text": { "nuclear factor-kappaB": "protein", "interleukin-1 signaling mediators": "protein", "cultured human dermal endothelial cells": "cell_line", "mononuclear phagocytes": "cell_type" } }, { "input_text": "Bacterial lipopolysaccharide ( LPS ) -mediated immune responses , including activation of monocytes , macrophages , and endothelial cells , play an important role in the pathogenesis of Gram-negative bacteria -induced sepsis syndrome .", "target_text": { "monocytes": "cell_type", "macrophages": "cell_type", "endothelial cells": "cell_type" } }, { "input_text": "Activation of NF-kappaB is thought to be required for cytokine release from LPS-responsive cells , a critical step for endotoxic effects .", "target_text": { "NF-kappaB": "protein", "LPS-responsive cells": "cell_type" } }, { "input_text": "Here we investigated the role and involvement of interleukin-1 ( IL-1 ) and tumor necrosis factor ( TNF-alpha ) signal transducer molecules in LPS signaling in human dermal microvessel endothelial cells ( HDMEC ) and THP-1 monocytic cells .", "target_text": { "interleukin-1": "protein", "IL-1": "protein", "tumor necrosis factor": "protein", "TNF-alpha": "protein", "signal transducer molecules": "protein", "endothelial cells": "cell_type", "human dermal microvessel endothelial cells": "cell_type", "HDMEC": "cell_type", "THP-1 monocytic cells": "cell_line" } }, { "input_text": "LPS stimulation of HDMEC and THP-1 cells initiated an IL-1 receptor -like NF-kappaB signaling cascade .", "target_text": { "HDMEC": "cell_type", "THP-1 cells": "cell_line", "IL-1": "protein", "IL-1 receptor": "protein", "NF-kappaB": "protein" } }, { "input_text": "In transient cotransfection experiments , dominant negative mutants of the IL-1 signaling pathway , including MyD88 , IRAK , IRAK2 , and TRAF6 inhibited both IL-1 - and LPS -induced NF-kappaB -luciferase activity .", "target_text": { "IL-1": "protein", "MyD88": "protein", "IRAK": "protein", "IRAK2": "protein", "TRAF6": "protein", "NF-kappaB": "protein", "-luciferase": "protein" } }, { "input_text": "LPS -induced NF-kappaB activation was not inhibited by a dominant negative mutant of TRAF2 that is involved in TNF signaling .", "target_text": { "NF-kappaB": "protein", "TRAF2": "protein", "TNF": "protein" } }, { "input_text": "LPS -induced activation of NF-kappaB -responsive reporter gene was not inhibited by IL-1 receptor antagonist .", "target_text": { "NF-kappaB": "protein", "NF-kappaB -responsive reporter gene": "DNA", "IL-1": "protein" } }, { "input_text": "TLR2 and TLR4 were expressed on the cell surface of HDMEC and THP-1 cells .", "target_text": { "TLR2": "protein", "TLR4": "protein", "HDMEC": "cell_type", "THP-1 cells": "cell_line" } }, { "input_text": "These findings suggest that a signal transduction molecule in the LPS receptor complex may belong to the IL-1 receptor/toll-like receptor ( TLR ) super family , and the LPS signaling cascade uses an analogous molecular framework for signaling as IL-1 in mononuclear phagocytes and endothelial cells .", "target_text": { "signal transduction molecule": "protein", "IL-1": "protein", "mononuclear phagocytes": "cell_type", "endothelial cells": "cell_type" } }, { "input_text": "Signal transduction through interferon-gamma receptor on human eosinophils .", "target_text": { "interferon-gamma receptor": "protein", "human eosinophils": "cell_type" } }, { "input_text": "BACKGROUND : We reported on the constitutive interferon-gamma receptor ( IFN-gammaR ) expression on eosinophils .", "target_text": { "interferon-gamma receptor": "protein", "IFN-gammaR": "protein", "eosinophils": "cell_type" } }, { "input_text": "But signal transduction through IFN-gammaR on eosinophils remains to be elucidated .", "target_text": { "IFN-gammaR": "protein", "eosinophils": "cell_type" } }, { "input_text": "In this study , we examined the involvement of the Jak/Stat pathway in the signaling of eosinophils after IFN-gammaR conjugation by the ligand binding .", "target_text": { "Jak/Stat": "protein", "eosinophils": "cell_type", "IFN-gammaR": "protein" } }, { "input_text": "METHODS : Purified peripheral eosinophils were stimulated with IFN-gamma at 37 degrees C for 1-60 min .", "target_text": { "eosinophils": "cell_type", "Purified peripheral eosinophils": "cell_type", "IFN-gamma": "protein" } }, { "input_text": "Tyrosine phosphorylation of IFN-gammaR , Jak1 , Jak2 , and Stat1alpha was examined by immunoblotting .", "target_text": { "IFN-gammaR": "protein", "Jak1": "protein", "Jak2": "protein", "Stat1alpha": "protein" } }, { "input_text": "Gel-shift assay was also examined to show the formation of Stat1alpha -DNA complexes .", "target_text": { "Stat1alpha": "protein", "Stat1alpha -DNA complexes": "protein" } }, { "input_text": "RESULTS : We show that binding of IFN-gamma to human eosinophils initiated a series of events that resulted in the rapid tyrosine phosphorylation of not only the IFN-gammaRalpha chain but also Jak1 , Jak2 , and Stat1alpha .", "target_text": { "IFN-gamma": "protein", "eosinophils": "cell_type", "human eosinophils": "cell_type", "IFN-gammaRalpha chain": "protein", "Jak1": "protein", "Jak2": "protein", "Stat1alpha": "protein" } }, { "input_text": "In addition , IFN-gamma enhanced the DNA-binding activity of Stat1alpha .", "target_text": { "IFN-gamma": "protein", "Stat1alpha": "protein" } }, { "input_text": "CONCLUSION : These data indicate that IFN-gamma affects eosinophils through its specific receptor and utilizes the Jak/Stat pathway as its mode of signaling .", "target_text": { "IFN-gamma": "protein", "eosinophils": "cell_type", "Jak/Stat": "protein" } }, { "input_text": "Expression of E2A-HLF chimeric protein induced T-cell apoptosis , B-cell maturation arrest , and development of acute lymphoblastic leukemia .", "target_text": { "E2A-HLF chimeric protein": "protein" } }, { "input_text": "The E2A-HLF fusion gene , generated by t(17;19)(q22;p13) in acute lymphoblastic leukemia ( ALL ) , encodes a chimeric transcription factor in which the trans-activating domains of E2A are fused to the DNA- binding and dimerization domains of hepatic leukemic factor ( HLF ) .", "target_text": { "E2A-HLF fusion gene": "DNA", "t(17;19)(q22;p13)": "DNA", "chimeric transcription factor": "protein", "trans-activating domains": "protein", "E2A": "protein", "hepatic leukemic factor": "protein", "HLF": "protein" } }, { "input_text": "To investigate its biological role , we generated transgenic mice expressing E2A-HLF using Ig enhancer and promoter , which direct transgene expression in cells committed to the lymphoid lineage .", "target_text": { "E2A-HLF": "protein" } }, { "input_text": "The transgenic mice exhibited abnormal development in the thymus and spleen and were susceptible to infection .", "target_text": {} }, { "input_text": "The thymus contained small numbers of thymocytes , and TUNEL staining showed that higher population of thymocytes were undergoing apoptosis .", "target_text": { "thymocytes": "cell_type" } }, { "input_text": "The spleen exhibited a marked reduction in splenic lymphocytes and the flow cytometric analyses and the in vitro colony formation assays showed that the B-cell maturation was blocked at a very early developmental stage .", "target_text": { "splenic lymphocytes": "cell_type" } }, { "input_text": "These findings indicated that the expression of E2A-HLF induced T-cell apoptosis and B-cell maturation arrest in vivo and that the susceptibility of the transgenic mice to infection was due to immunodeficiency .", "target_text": { "E2A-HLF": "protein" } }, { "input_text": "Moreover , several transgenic mice developed acute leukemia , classified as T- ALL based on the surface marker analysis and DNA rearrangements , suggesting that an additional event is required for malignant transformation of lymphoid cells expressing E2A-HLF .", "target_text": { "lymphoid cells": "cell_type", "E2A-HLF": "protein" } }, { "input_text": "Our findings provide insight into the biological function of E2A-HLF in lymphoid development and also its role in leukemogenesis .", "target_text": { "E2A-HLF": "protein" } }, { "input_text": "Retinoid X receptor ( RXR ) agonist-induced activation of dominant-negative RXR -retinoic acid receptor alpha403 heterodimers is developmentally regulated during myeloid differentiation .", "target_text": { "Retinoid X receptor": "protein", "RXR": "protein" } }, { "input_text": "The multiple biologic activities of retinoic acid ( RA ) are mediated through RAR and retinoid X receptor ( RXR ) nuclear receptors that interact with specific DNA target sequences as heterodimers ( RXR-RAR ) or homodimers ( RXR-RXR ) .", "target_text": { "RAR": "protein", "RXR": "protein", "retinoid X receptor ( RXR ) nuclear receptors": "protein", "DNA target sequences": "DNA", "heterodimers": "protein", "RXR-RAR": "protein", "homodimers": "protein", "RXR-RXR": "protein" } }, { "input_text": "RA receptor activation appears critical to regulating important aspects of hematopoiesis , since transducing a COOH-terminally truncated RARalpha exhibiting dominant-negative activity ( RARalpha403 ) into normal mouse bone marrow generates hematopoietic growth factor-dependent cell lines frozen at the multipotent progenitor ( EML ) or committed promyelocyte ( MPRO ) stages .", "target_text": { "COOH-terminally truncated RARalpha": "protein", "RARalpha403": "protein", "hematopoietic growth factor-dependent cell lines": "cell_line" } }, { "input_text": "Nevertheless , relatively high , pharmacological concentrations of RA ( 1 to 10 & mgr ; M ) overcome these differentiation blocks and induce terminal granulocytic differentiation of the MPRO promyelocytes while potentiating interleukin-3 ( IL-3 ) -induced commitment of EML cells to the granulocyte/monocyte lineage .", "target_text": { "MPRO promyelocytes": "cell_type", "interleukin-3": "protein", "IL-3": "protein", "EML cells": "cell_type" } }, { "input_text": "In the present study , we utilized RXR - and RAR -specific agonists and antagonists to determine how RA overcomes the dominant-negative activity of the truncated RARalpha in these different myeloid developmental stages .", "target_text": { "RXR": "protein", "RAR": "protein", "truncated RARalpha": "protein" } }, { "input_text": "Unexpectedly , we observed that an RXR -specific , rather than an RAR -specific , agonist induces terminal granulocytic differentiation of MPRO promyelocytes , and this differentiation is associated with activation of DNA response elements corresponding to RAR-RXR heterodimers rather than RXR-RXR homodimers .", "target_text": { "RXR": "protein", "RAR": "protein", "MPRO promyelocytes": "cell_type", "DNA response elements": "DNA", "RAR-RXR heterodimers": "protein", "RXR-RXR": "protein", "RXR-RXR homodimers": "protein" } }, { "input_text": "This RXR agonist activity is blocked by RAR -specific antagonists , suggesting extensive cross-talk between the partners of the RXR -RARalpha403 heterodimer .", "target_text": { "RXR": "protein", "RAR": "protein", "-RARalpha403": "protein", "RXR -RARalpha403 heterodimer": "protein" } }, { "input_text": "In contrast , in the more immature , multipotent EML cells we observed that this RXR -specific agonist is inactive either in potentiating IL-3 -mediated commitment of EML cells to the granulocyte lineage or in transactivating RAR-RXR response elements .", "target_text": { "EML cells": "cell_type", "RXR": "protein", "IL-3": "protein", "granulocyte lineage": "cell_type", "RAR-RXR response elements": "DNA" } }, { "input_text": "RA -triggered GALdbd- RARalpha hybrid activity in these cells indicates that the multipotent EML cells harbor substantial nuclear hormone receptor coactivator activity .", "target_text": { "RARalpha": "protein", "EML cells": "cell_type", "coactivator": "protein" } }, { "input_text": "However , the histone deacetylase ( HDAC ) inhibitor trichostatin A readily activates an RXR-RAR reporter construct in the multipotent EML cells but not in the committed MPRO promyelocytes , indicating that differences in HDAC-containing repressor complexes in these two closely related but distinct hematopoietic lineages might account for the differential activation of the RXR-RARalpha403 heterodimers that we observed at these different stages of myeloid development .", "target_text": { "histone deacetylase ( HDAC ) inhibitor": "protein", "RXR-RAR": "protein", "RXR-RAR reporter construct": "DNA", "EML cells": "cell_type", "MPRO promyelocytes": "cell_type", "HDAC-containing repressor complexes": "protein", "hematopoietic lineages": "cell_type", "RXR-RARalpha403 heterodimers": "protein" } }, { "input_text": "The functional synergy between IL-12 and IL-2 involves p38 mitogen-activated protein kinase and is associated with the augmentation of STAT serine phosphorylation .", "target_text": { "IL-12": "protein", "IL-2": "protein", "p38 mitogen-activated protein kinase": "protein" } }, { "input_text": "IL-12 and IL-2 can stimulate mitogen- or CD3- activated T cells to proliferate , produce IFN-gamma , and kill tumor cells .", "target_text": { "IL-12": "protein", "IL-2": "protein", "IFN-gamma": "protein", "tumor cells": "cell_type" } }, { "input_text": "The magnitude of these functional responses is greatly augmented when T cells are activated by the combination of IL-12 and IL-2 .", "target_text": { "T cells": "cell_type", "IL-12": "protein", "IL-2": "protein" } }, { "input_text": "Although peripheral blood T cells are largely unresponsive to these cytokines without prior activation , a small subset of CD8+ T cells ( CD8+CD18bright ) is strongly activated by the combination of IL-12 and IL-2 .", "target_text": { "T cells": "cell_type", "cytokines": "protein", "CD8+ T cells": "cell_type", "CD8+CD18bright": "cell_type", "IL-12": "protein", "IL-2": "protein" } }, { "input_text": "In this report we show that the functional synergy between IL-12 and IL-2 in CD8+CD18bright T cells correlates with the activation of the stress kinases , p38 mitogen-activated protein ( MAP ) kinase and stress-activated protein kinase ( SAPK ) /Jun N-terminal kinase , but not with the activation of the extracellular signal-regulated kinases .", "target_text": { "IL-12": "protein", "IL-2": "protein", "CD8+CD18bright T cells": "cell_type", "stress kinases": "protein", "p38 mitogen-activated protein ( MAP ) kinase": "protein", "stress-activated protein kinase ( SAPK ) /Jun N-terminal kinase": "protein", "extracellular signal-regulated kinases": "protein" } }, { "input_text": "The functional synergy between IL-2 and IL-12 is also associated with a prominent increase in STAT1 and STAT3 serine phosphorylation over that observed with IL-12 or IL-2 alone .", "target_text": { "IL-2": "protein", "IL-12": "protein", "STAT1": "protein", "STAT3": "protein" } }, { "input_text": "By contrast , STAT tyrosine phosphorylation is not augmented over that seen with either cytokine alone .", "target_text": { "STAT": "protein" } }, { "input_text": "A specific inhibitor of p38 MAP kinase completely inhibits the serine phosphorylation of STAT1 and STAT3 induced by IL-12 and IL-2 and abrogates the functional synergy between IL-12 and IL-2 without affecting STAT tyrosine phosphorylation .", "target_text": { "STAT1": "protein", "STAT3": "protein", "IL-12": "protein", "IL-2": "protein" } }, { "input_text": "This suggests that p38 MAP kinase may play an important role in regulating STAT serine phosphorylation in response to the combination of IL-12 and IL-2 .", "target_text": { "IL-12": "protein", "IL-2": "protein" } }, { "input_text": "Furthermore , these findings indicate that the optimal activation of T cells by IL-12 and IL-2 may depend on an interaction between the p38 MAP kinase and Janus kinase/STAT signaling pathways .", "target_text": { "T cells": "cell_type", "IL-12": "protein", "IL-2": "protein", "p38 MAP kinase": "protein", "Janus kinase/STAT": "protein" } }, { "input_text": "Activation of NF-kappaB in Mycobacterium tuberculosis -induced interleukin-2 receptor expression in mononuclear phagocytes .", "target_text": { "NF-kappaB": "protein", "interleukin-2 receptor": "protein", "mononuclear phagocytes": "cell_type" } }, { "input_text": "Soluble interleukin-2 receptor -alpha ( IL-2Ralpha ) has been reported to be increased in the sera of patients with advanced tuberculosis , and levels decline after therapy in accordance with improvement of radiologic findings .", "target_text": { "interleukin-2 receptor": "protein", "interleukin-2 receptor -alpha": "protein", "IL-2Ralpha": "protein" } }, { "input_text": "We investigated expression of the IL-2Ralpha in bronchoalveolar lavage ( BAL ) cells in active pulmonary tuberculosis , and evaluated the mechanism Mycobacterium tuberculosis induces in the IL-2Ralpha using the THP-1 mononuclear phagocyte cell line .", "target_text": { "IL-2Ralpha": "protein", "bronchoalveolar lavage ( BAL ) cells": "cell_type", "THP-1": "cell_line", "THP-1 mononuclear phagocyte cell line": "cell_line" } }, { "input_text": "We found IL-2Ralpha expression to be increased in BAL cells from involved sites of active pulmonary tuberculosis .", "target_text": { "IL-2Ralpha": "protein" } }, { "input_text": "Expression of the alpha-chain of IL-2Ralpha on peripheral blood monocytes ( PBM ) was induced by M. tuberculosis by flow cytometry evaluation .", "target_text": { "alpha-chain": "protein", "IL-2Ralpha": "protein", "peripheral blood monocytes": "cell_type", "PBM": "cell_type" } }, { "input_text": "Northern analysis demonstrated increased IL-2Ralpha gene expression after stimulation with M. tuberculosis which was further induced by interferon-gamma ( IFN-gamma ) .", "target_text": { "IL-2Ralpha": "protein", "interferon-gamma": "protein", "IFN-gamma": "protein" } }, { "input_text": "The IL-2Ralpha promoter containing the nuclear factor kappa B ( NF-kappaB ) site was transcriptionally induced by M. tuberculosis and this NF-kappaB site could confer inducibility to a heterologous herpes thymidine kinase ( TK ) promoter by M. tuberculosis .", "target_text": { "IL-2Ralpha": "protein", "IL-2Ralpha promoter": "DNA", "nuclear factor kappa B": "protein", "NF-kappaB": "protein", "nuclear factor kappa B ( NF-kappaB ) site": "DNA", "thymidine kinase": "protein", "heterologous herpes thymidine kinase ( TK ) promoter": "DNA" } }, { "input_text": "Electrophoretic mobility shift assays ( EMSAs ) revealed specific binding of nuclear protein to the NF-kappaB site upon induction with M. tuberculosis .", "target_text": { "NF-kappaB": "protein", "NF-kappaB site": "DNA" } }, { "input_text": "Using antibodies against the p50 and p65 subunits of NF-kappaB in EMSAs , the involvement of both p50 and p65 proteins was further demonstrated .", "target_text": { "p50": "protein", "p65 subunits": "protein", "NF-kappaB": "protein", "p65 proteins": "protein" } }, { "input_text": "Functional expression of the IL-2Ralpha on mononuclear phagocytes in M. tuberculosis infection may play an important immunomodulatory role in the host response .", "target_text": { "IL-2Ralpha": "protein", "mononuclear phagocytes": "cell_type" } }, { "input_text": "Vitamin D receptor 3'-untranslated region polymorphisms : lack of effect on mRNA stability .", "target_text": { "Vitamin D receptor": "protein", "3'-untranslated region": "DNA" } }, { "input_text": "Allelic variation at the 3'-end of the vitamin D receptor ( VDR ) gene has been associated with a 3-5-fold increased risk of developing prostate cancer and with differences in bone mineralization .", "target_text": { "vitamin D receptor ( VDR ) gene": "DNA" } }, { "input_text": "This genetic diversity does not alter the VDR protein structurally , but instead may be a marker ( s ) of other , nearby polymorphisms that influence message stability or translation .", "target_text": { "VDR protein": "protein" } }, { "input_text": "The work reported here was instigated to identify additional VDR 3'-UTR polymorphisms that may have functional significance and to then test whether these genetic variants alter message stability .", "target_text": { "VDR": "protein", "3'-UTR": "DNA" } }, { "input_text": "Initially , four novel , frequently occurring sequence variants were identified that associated with two common haplotypes that were described previously .", "target_text": { "sequence variants": "DNA" } }, { "input_text": "These common sequence variants were not found within three message-destabilizing elements that we mapped within the 3'-UTR of the vitamin D receptor mRNA .", "target_text": { "message-destabilizing elements": "DNA", "3'-UTR": "DNA", "vitamin D receptor mRNA": "RNA" } }, { "input_text": "Furthermore , the two VDR 3'-UTR haplotypes conferred an identical half-life on a heterologous beta-globin reporter gene , in an in vitro assay .", "target_text": { "VDR 3'-UTR": "DNA", "heterologous beta-globin reporter gene": "DNA" } }, { "input_text": "We therefore conclude that common polymorphisms within the VDR 3'-UTR do not influence message stability .", "target_text": { "VDR 3'-UTR": "DNA" } }, { "input_text": "IL-2 -mediated cell cycle progression and inhibition of apoptosis does not require NF-kappa B or activating protein-1 activation in primary human T cells .", "target_text": { "IL-2": "protein", "NF-kappa B": "protein" } }, { "input_text": "The IL-2 growth hormone is the major growth factor of activated T lymphocytes during a developing immune response .", "target_text": { "IL-2": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "IL-2 is required not only for cell cycle progression but also to protect Ag-activated T cells from programmed cell death .", "target_text": { "IL-2": "protein", "Ag-activated T cells": "cell_type" } }, { "input_text": "In several cell types , activation of NF-kappa B and/or activating protein-1 ( AP-1 ) has been demonstrated to be extremely important in blocking apoptosis .", "target_text": { "NF-kappa B": "protein", "activating protein-1": "protein", "AP-1": "protein" } }, { "input_text": "To determine whether either or both of these transcription factors are involved in cell survival or cell cycle progression in response to IL-2 , primary human T cells responsive to the growth factor were analyzed for NF-kappa B and AP-1 activation .", "target_text": { "transcription factors": "protein", "IL-2": "protein", "primary human T cells": "cell_type" } }, { "input_text": "The current study clearly demonstrates that IL-2 does not induce I kappa B alpha degradation or NF-kappa B activation in primary human T cells that respond to IL-2 by entering the cell cycle and avoiding apoptosis .", "target_text": { "IL-2": "protein", "I kappa B": "protein", "NF-kappa B": "protein", "primary human T cells": "cell_type" } }, { "input_text": "Similarly , IL-2 neither activates JNK nor increases AP-1 binding activity to a consensus o-tetradecanoylphorbol 13-acetate ( TPA ) response element .", "target_text": { "IL-2": "protein", "JNK": "protein", "AP-1": "protein", "o-tetradecanoylphorbol 13-acetate ( TPA ) response element": "DNA" } }, { "input_text": "On the other hand , the growth factor does induce the activation of STAT3 and STAT5 in these cells , as has been previously demonstrated .", "target_text": { "growth factor": "protein", "STAT3": "protein", "STAT5": "protein" } }, { "input_text": "These data show that neither NF-kappa B nor AP-1 activation is required for IL-2 -mediated survival or cell cycle progression in activated primary human T cells .", "target_text": { "NF-kappa B": "protein", "AP-1": "protein", "IL-2": "protein", "primary human T cells": "cell_type" } }, { "input_text": "Estrone potentiates myeloid cell differentiation : a role for 17 beta-hydroxysteroid dehydrogenase in modulating hemopoiesis .", "target_text": { "17 beta-hydroxysteroid dehydrogenase": "protein" } }, { "input_text": "Hormones such as 1 alpha, 25-dihydroxy vitamin D3 ( D3 ) , all-trans retinoic acid , and 9-cis retinoic acid stimulate differentiation of myeloid progenitor cells via their interaction with specific hormone receptors .", "target_text": { "myeloid progenitor cells": "cell_type", "hormone receptors": "protein" } }, { "input_text": "However , the sensitivity of cells to these agents is not merely governed by the expression of their receptors and the availability of ligand to bind them .", "target_text": {} }, { "input_text": "Recent studies from our group suggested that the actions of D3 and retinoids on myelopoiesis also are influenced by endogenous mechanisms involving other steroid hormones .", "target_text": {} }, { "input_text": "In this study we examined the influence of local estrogen metabolism on the differentiation of HL60 cells and normal primitive myeloid progenitor cells .", "target_text": { "HL60 cells": "cell_line", "myeloid progenitor cells": "cell_type" } }, { "input_text": "Quantitative thin-layer chromatography ( TLC ) analyses showed that HL60 and normal cells are able to generate estrone ( E1 ) from estradiol ( E2 ) .", "target_text": { "HL60": "cell_line", "normal cells": "cell_type" } }, { "input_text": "Neither cell population generated significant amounts of E2 from E1 .", "target_text": {} }, { "input_text": "Reverse transcriptase polymerase chain reaction and Northern analyses confirmed that normal and leukemic myeloid progenitor cells expressed mRNA for the type I and IV isoforms of 17 beta-hydroxysteroid dehydrogenase .", "target_text": { "myeloid progenitor cells": "cell_type", "mRNA": "RNA", "17 beta-hydroxysteroid dehydrogenase": "protein" } }, { "input_text": "Conversion of E2 to E1 was upregulated within 24 hours when HL60 cells were treated with either all-trans retinoic acid or D3 at doses that induce their differentiation toward neutrophils or monocytes , respectively .", "target_text": { "HL60 cells": "cell_line", "neutrophils": "cell_type", "monocytes": "cell_type" } }, { "input_text": "Similarly , D3 -induced monocyte differentiation of normal myeloid progenitor cells was associated with increased capacity to generate E1 from E2 .", "target_text": { "myeloid progenitor cells": "cell_type" } }, { "input_text": "When HL60 cells or normal myeloid progenitor cells were exposed to exogenous E1 they became more sensitive to the differentiation-inducing effects of D3 .", "target_text": { "HL60 cells": "cell_line", "myeloid progenitor cells": "cell_type" } }, { "input_text": "Data presented provide further evidence for the local modulation of myelopoiesis by intracrine mechanisms .", "target_text": {} }, { "input_text": "In particular , our findings suggest that local metabolism of steroids by normal as well as leukemic myeloid cells influences their responsiveness to D3 and retinoids .", "target_text": { "leukemic myeloid cells": "cell_type" } }, { "input_text": "Phosphorylation of TRAF2 inhibits binding to the CD40 cytoplasmic domain .", "target_text": { "TRAF2": "protein", "CD40 cytoplasmic domain": "protein" } }, { "input_text": "TRAF2 is a signal transducing adaptor molecule which binds to the CD40 cytoplasmic domain .", "target_text": { "TRAF2": "protein", "signal transducing adaptor molecule": "protein", "CD40 cytoplasmic domain": "protein" } }, { "input_text": "We have found that it is phosphorylated , predominantly on serine residues , when transiently overexpressed in 293 cells .", "target_text": { "293 cells": "cell_line" } }, { "input_text": "The phosphorylation appears to be related to the signaling events that are activated by TRAF2 under these circumstances , since two nonfunctional mutants were found to be phosphorylated significantly less than the wild-type protein .", "target_text": { "TRAF2": "protein", "wild-type protein": "protein" } }, { "input_text": "Furthermore , the phosphorylation status of TRAF2 had significant effects on the ability of the protein to bind to CD40 , as evidenced by our observations that the CD40 cytoplasmic domain interacted preferentially with underphosphorylated TRAF2 and that phosphatase treatment significantly enhanced the binding of TRAF2 to CD40 .", "target_text": { "TRAF2": "protein", "CD40": "protein", "CD40 cytoplasmic domain": "protein", "phosphatase": "protein" } }, { "input_text": "We conclude from these studies that the phosphorylation of TRAF2 is likely to play an important role in regulating signaling by virtue of its ability to influence the CD40 -TRAF2 interaction .", "target_text": { "TRAF2": "protein", "CD40": "protein", "-TRAF2": "protein" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "A direct interaction between the adaptor protein Cbl-b and the kinase zap-70 induces a positive signal in T cells .", "target_text": { "adaptor protein": "protein", "Cbl-b": "protein", "kinase": "protein", "zap-70": "protein", "T cells": "cell_type" } }, { "input_text": "Engagement of the T-cell receptor ( TCR ) -CD3 complex induces a rapid increase in the activities of Src-family and Syk/Zap-70-family kinases [ 1 ] [ 2 ] .", "target_text": { "T-cell receptor": "protein", "TCR": "protein", "T-cell receptor ( TCR ) -CD3 complex": "protein", "Src-family": "protein", "Syk/Zap-70-family kinases": "protein" } }, { "input_text": "These activated kinases then induce the tyrosine phosphorylation of multiple intracellular proteins , eventually leading to T-cell activation .", "target_text": { "activated kinases": "protein", "multiple intracellular proteins": "protein" } }, { "input_text": "One of the prominent substrates for these kinases is the adaptor protein Cbl [ 3 ] and recent studies suggest that Cbl negatively regulates upstream kinases such as Syk and Zap-70 [ 4 ] [ 5 ] .", "target_text": { "kinases": "protein", "adaptor protein": "protein", "Cbl": "protein", "upstream kinases": "protein", "Syk": "protein", "Zap-70": "protein" } }, { "input_text": "Cbl-b , a homologue of Cbl , is widely expressed in many tissues and cells including hematopoietic cells [ 6 ] [ 7 ] .", "target_text": { "Cbl-b": "protein", "Cbl": "protein", "hematopoietic cells": "cell_type" } }, { "input_text": "Cbl-b undergoes rapid tyrosine phosphorylation upon stimulation of the TCR and cytokine receptors [ 8 ] [ 9 ] .", "target_text": { "Cbl-b": "protein", "TCR": "protein" } }, { "input_text": "The role of Cbl-b is unclear , however .", "target_text": { "Cbl-b": "protein" } }, { "input_text": "Here , we show that overexpression of Cbl-b in T cells induced the constitutive activation of the transcription factor nuclear factor of activated T cells ( NFAT ) .", "target_text": { "Cbl-b": "protein", "T cells": "cell_type", "transcription factor nuclear factor of activated T cells": "protein", "NFAT": "protein" } }, { "input_text": "A loss-of-function mutation in Cbl-b disrupted the interaction between Cbl-b and Zap-70 and nearly completely abrogated the Cbl-b -mediated activation of NFAT .", "target_text": { "Cbl-b": "protein", "Zap-70": "protein", "NFAT": "protein" } }, { "input_text": "Unlike the proposed role of Cbl as a negative regulator , our results suggest that the Cbl homologue Cbl -b has a positive role in T-cell signaling , most likely via a direct interaction with the upstream kinase Zap-70 .", "target_text": { "Cbl": "protein", "Cbl -b": "protein", "upstream kinase": "protein", "Zap-70": "protein" } }, { "input_text": "Grf40 , A novel Grb2 family member , is involved in T cell signaling through interaction with SLP-76 and LAT .", "target_text": { "Grf40": "protein", "Grb2 family member": "protein", "SLP-76": "protein", "LAT": "protein" } }, { "input_text": "We molecularly cloned a new Grb2 family member , named Grf40 , containing the common SH3-SH2-SH3 motif .", "target_text": { "Grb2 family member": "protein", "Grf40": "protein", "SH3-SH2-SH3 motif": "protein" } }, { "input_text": "Expression of Grf40 is predominant in hematopoietic cells , particularly T cells .", "target_text": { "Grf40": "protein", "hematopoietic cells": "cell_type", "T cells": "cell_type" } }, { "input_text": "Grf40 binds to the SH2 domain -containing leukocyte protein of 76 kD ( SLP-76 ) via its SH3 domain more tightly than Grb2 .", "target_text": { "Grf40": "protein", "SH2 domain": "protein", "SH2 domain -containing leukocyte protein": "protein", "SLP-76": "protein", "Grb2": "protein" } }, { "input_text": "Incidentally , Grf40 binds to linker for activation of T cells ( LAT ) possibly via its SH2 domain .", "target_text": { "Grf40": "protein", "T cells": "cell_type", "linker for activation of T cells": "protein", "LAT": "protein", "SH2 domain": "protein" } }, { "input_text": "Overexpression of wild-type Grf40 in Jurkat cells induced a significant increase of SLP-76 -dependent interleukin ( IL ) -2 promoter and nuclear factor of activated T cell ( NF-AT ) activation upon T cell receptor ( TCR ) stimulation , whereas the COOH-terminal SH3-deleted Grf40 mutant lacked any recognizable increase in IL-2 promoter activity .", "target_text": { "Grf40": "protein", "wild-type Grf40": "protein", "Jurkat cells": "cell_line", "SLP-76": "protein", "SLP-76 -dependent interleukin ( IL ) -2 promoter": "DNA", "nuclear factor of activated T cell": "protein", "NF-AT": "protein", "T cell receptor": "protein", "TCR": "protein", "COOH-terminal SH3-deleted Grf40 mutant": "protein", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Furthermore , the SH2-deleted Grf40 mutant led to a marked inhibition of these regulatory activities , the effect of which is apparently stronger than that of the SH2-deleted Grb2 mutant .", "target_text": { "Grf40": "protein", "SH2-deleted Grf40 mutant": "protein", "Grb2": "protein", "SH2-deleted Grb2 mutant": "protein" } }, { "input_text": "Our data suggest that Grf40 is an adaptor molecule involved in TCR -mediated signaling through a more efficient interaction than Grb2 with SLP-76 and LAT .", "target_text": { "Grf40": "protein", "adaptor molecule": "protein", "TCR": "protein", "Grb2": "protein", "SLP-76": "protein", "LAT": "protein" } }, { "input_text": "Modulation of the immune response and tumor growth by activated Ras .", "target_text": { "Ras": "protein" } }, { "input_text": "As a result of its transforming abilities , activated Ras is expressed in a great number of cancers .", "target_text": { "activated Ras": "protein" } }, { "input_text": "The ras mutation frequency varies between 95 % in pancreatic cancer and 5 % in breast cancer .", "target_text": {} }, { "input_text": "In leukemia , the highest frequency ( 30 % ) is found in acute myeloid leukemia .", "target_text": {} }, { "input_text": "The presence of ras mutations has been correlated with a poor prognosis and negative clinical outcome .", "target_text": {} }, { "input_text": "This suggests that mutated Ras activates mechanisms , which favor tumor growth , enhance the metastatic capacity of tumors or modulate tumor-specific immune responses .", "target_text": { "mutated Ras": "protein" } }, { "input_text": "Several new functions of Ras , such as downregulation of major histocompatibility complex molecules , upregulation of certain cytokines , growth factors and degradative enzymes have been uncovered in the last decade .", "target_text": { "Ras": "protein", "major histocompatibility complex molecules": "protein", "cytokines": "protein", "growth factors": "protein", "degradative enzymes": "protein" } }, { "input_text": "Additionally , mutated Ras can also serve as a primary target for the development of immunotherapy or drug therapy .", "target_text": { "mutated Ras": "protein" } }, { "input_text": "This review will discuss the mechanisms by which Ras expressing tumors are able to evade destruction by the immune system and enhance their growth and metastatic potential .", "target_text": { "Ras": "protein" } }, { "input_text": "It will further elaborate on the attempts to develop successful immunotherapy and drug therapy targeting Ras expressing tumors .", "target_text": { "Ras": "protein" } }, { "input_text": "Modulation of E2F complexes during G0 to S phase transition in human primary B-lymphocytes .", "target_text": { "E2F complexes": "protein", "human primary B-lymphocytes": "cell_type" } }, { "input_text": "The pocket protein- E2F complexes are convergence points for cell cycle signaling .", "target_text": { "E2F complexes": "protein", "pocket protein- E2F complexes": "protein" } }, { "input_text": "In the present report , we identified and monitored the pocket protein- E2F complexes in human primary B-lymphocytes after activation by phorbol 12-myristate 13-acetate .", "target_text": { "E2F complexes": "protein", "pocket protein- E2F complexes": "protein", "human primary B-lymphocytes": "cell_type" } }, { "input_text": "Consistent with previous data from human and mouse fibroblasts and T-lymphocytes , E2F4 and DP1 form the predominant E2F heterodimers both in G0 and G1 phases of the human B-lymphocyte cell cycle , whereas E2F 1 and -3 are first detected in late G1 , and their expression levels increase towards S phase .", "target_text": { "T-lymphocytes": "cell_type", "E2F4": "protein", "DP1": "protein", "E2F heterodimers": "protein" } }, { "input_text": "Intriguingly , the major E2F complex that we detected in quiescent human B-lymphocytes is consisted of pRB , E2F4 , and DP1 .", "target_text": { "major E2F complex": "protein", "quiescent human B-lymphocytes": "cell_type", "pRB": "protein", "E2F4": "protein", "DP1": "protein" } }, { "input_text": "Though the levels of DP 1 and -2 increase when cells progress from G0 to S , the proportion of DP1 to DP2 remains relatively constant during the cell cycle .", "target_text": { "DP1": "protein", "DP2": "protein" } }, { "input_text": "We also observed an increase in electrophoretic mobility of the predominant E2F components , DP1 and E2F4 , as B-lymphocytes progressed from G0 into early G1 .", "target_text": { "E2F components": "protein", "DP1": "protein", "E2F4": "protein", "B-lymphocytes": "cell_type" } }, { "input_text": "This increase in mobility was attributable to dephosphorylation , as lambda phosphatase treatment could convert the slower migrating forms into the corresponding faster mobility forms .", "target_text": { "slower migrating forms": "protein", "corresponding faster mobility forms": "protein" } }, { "input_text": "We further demonstrated that this change in phosphorylation status correlates with a decrease in DNA binding activity .", "target_text": {} }, { "input_text": "This modulation of DNA binding activity mediated through the dephosphorylation of DP1 and E2F4 could help to explain the lack of in vivo DNA footprinting in late G1 and S phases of gene promoters negatively regulated through E2F sites and suggests a novel mechanism for controlling E2F transcriptional activity during the transition from quiescence to proliferation .", "target_text": { "DP1": "protein", "E2F4": "protein", "gene promoters": "DNA", "E2F sites": "DNA", "E2F": "protein" } }, { "input_text": "Engagement of natural cytotoxicity programs regulates AP-1 expression in the NKL human NK cell line .", "target_text": { "AP-1": "protein", "NKL human NK cell line": "cell_line" } }, { "input_text": "NK cell cytotoxicity is a fast and efficient mechanism of target cell lysis .", "target_text": {} }, { "input_text": "Using transcription analysis , such as multiplex messenger assays , we show here that natural cytotoxicity exerted by the human NKL cell line correlates with mRNA accumulation of very early activator protein ( AP ) -1 transcription factor genes such as JunB , FosB and c-Fos .", "target_text": { "human NKL cell line": "cell_line", "very early activator protein ( AP ) -1": "protein", "transcription factor genes": "DNA", "JunB": "DNA", "FosB": "DNA", "c-Fos": "DNA" } }, { "input_text": "In addition , DNA-binding activities of Jun-Fos heterodimers were observed by electrophoretic mobility shift assays during the course of natural cytotoxicity .", "target_text": { "Jun-Fos heterodimers": "protein" } }, { "input_text": "Interaction between immunoglobulin-like transcript-2/leukocyte Ig-like receptor 1 on NKL cells and HLA-B27 on target cells leads to an impairment of NKL natural cytotoxicity , which correlates with an absence of JunB , FosB , and c-Fos transcription , as well as an absence of their DNA-binding activity .", "target_text": { "immunoglobulin-like transcript-2/leukocyte Ig-like receptor 1": "protein", "NKL cells": "cell_type", "HLA-B27": "protein", "target cells": "cell_type", "DNA-binding activity": "protein" } }, { "input_text": "Our studies thus indicate that , despite the rapidity of NK cell-mediated lysis , AP-1 transcription factor is activated during the early stage of NK cell cytolytic programs and that engagement of NK cell inhibitory receptors for MHC class I molecules impairs the very early activation of AP-1 .", "target_text": { "AP-1 transcription factor": "protein", "NK cell inhibitory receptors": "protein", "MHC class I molecules": "protein", "AP-1": "protein" } }, { "input_text": "Evidence for a polyclonal etiology of palmar fibromatosis .", "target_text": {} }, { "input_text": "X chromosome inactivation patterns at the androgen receptor locus were evaluated to determine clonality in microdissected lesional tissue and in leukocytes from 2 women with Dupuytren 's disease .", "target_text": { "X chromosome": "DNA", "leukocytes": "cell_type" } }, { "input_text": "The tissue from both patients generated a polyclonal pattern of X chromosome inactivation of the human androgen receptor gene .", "target_text": { "X chromosome": "DNA", "human androgen receptor gene": "DNA" } }, { "input_text": "This finding supports a polyclonal reactive process as the underlying etiology for palmar fibromatosis .", "target_text": {} }, { "input_text": "Inhibition of cyclooxygenase-2 expression by 4-trifluoromethyl derivatives of salicylate , triflusal , and its deacetylated metabolite , 2-hydroxy-4-trifluoromethylbenzoic acid .", "target_text": { "cyclooxygenase-2": "protein" } }, { "input_text": "The therapeutic potential of drugs that block the induction of cyclooxygenase-2 has been emphasized .", "target_text": { "cyclooxygenase-2": "protein" } }, { "input_text": "When two 4-trifluoromethyl salicylate derivatives [ 2-acetoxy-4-trifluoromethyl-benzoic acid ( triflusal ) and its deacetylated metabolite 2-hydroxy-4-trifluoromethylbenzoic acid ( HTB ) ] were compared with aspirin and sodium salicylate as cyclooxygenase-2 ( COX-2 ) inhibitors , we observed that in bacterial lipopolysaccharide-activated human blood , triflusal , aspirin , and HTB , but not sodium salicylate , inhibited COX-2-mediated prostaglandin E2 ( PGE2 ) production ( IC50 = 0.16 , 0.18 , 0.39 , and > 10 mM , respectively ) .", "target_text": { "cyclooxygenase-2": "protein" } }, { "input_text": "However , only triflusal and aspirin inhibited purified COX-2 enzyme .", "target_text": { "purified COX-2 enzyme": "protein" } }, { "input_text": "To test this apparent discrepancy , we realized that HTB and triflusal ( but neither aspirin nor salicylate ) produced a concentration-dependent inhibition of COX-2 protein expression in peripheral human mononuclear cells .", "target_text": { "COX-2": "protein", "peripheral human mononuclear cells": "cell_type" } }, { "input_text": "This observation was further confirmed in a rat air pouch model in vivo , in which both aspirin and triflusal inhibited PGE2 production ( ID50 = 18.9 and 11.4 mg/kg p.o. , respectively ) but only triflusal -treated animals showed a decrease in COX-2 expression .", "target_text": { "COX-2": "protein" } }, { "input_text": "This different behavior may be , at least in part , due to the ability of HTB and triflusal to block the activation of the transcription factor nuclear factor-kappaB to a higher extent than aspirin and sodium salicylate .", "target_text": { "nuclear factor-kappaB": "protein" } }, { "input_text": "Thus , in addition to inhibiting the COX-2 activity at therapeutic concentrations , triflusal is able to block through its metabolite HTB the expression of new enzyme , and hence the resumption of PGE2 synthesis .", "target_text": {} }, { "input_text": "Triflusal and HTB may exert beneficial effects in processes in which de novo COX-2 expression is involved and , in a broader sense , in pathological situations in which genes under nuclear factor-kappaB control are up-regulated .", "target_text": { "COX-2": "protein", "nuclear factor-kappaB": "protein" } }, { "input_text": "Evidence for distinct intracellular signaling pathways in CD34+ progenitor to dendritic cell differentiation from a human cell line model .", "target_text": { "CD34+ progenitor": "cell_type" } }, { "input_text": "Intracellular signals that mediate differentiation of pluripotent hemopoietic progenitors to dendritic cells ( DC ) are largely undefined .", "target_text": { "pluripotent hemopoietic progenitors": "cell_type", "dendritic cells": "cell_type", "DC": "cell_type" } }, { "input_text": "We have previously shown that protein kinase C ( PKC ) activation ( with phorbol ester ( PMA ) alone ) specifically induces differentiation of primary human CD34+ hemopoietic progenitor cells ( HPC ) to mature DC .", "target_text": { "protein kinase C": "protein", "PKC": "protein", "primary human CD34+ hemopoietic progenitor cells": "cell_line", "HPC": "cell_line", "mature DC": "cell_type" } }, { "input_text": "We now find that cytokine-driven ( granulocyte-macrophage CSF and TNF-alpha ) CD34+ HPC --> DC differentiation is preferentially blocked by inhibitors of PKC activation .", "target_text": { "HPC": "cell_line", "PKC": "protein" } }, { "input_text": "To further identify intracellular signals and downstream events important in CD34+ HPC --> DC differentiation we have characterized a human leukemic cell line model of this process .", "target_text": { "CD34+ HPC": "cell_line", "DC": "cell_type" } }, { "input_text": "The CD34+ myelomonocytic cell line KG1 differentiates into dendritic-like cells in response to granulocyte-macrophage CSF plus TNF-alpha , or PMA ( with or without the calcium ionophore ionomycin , or TNF-alpha ) , with different stimuli mediating different aspects of the process .", "target_text": { "CD34+ myelomonocytic cell line": "cell_line", "KG1": "cell_line", "granulocyte-macrophage CSF": "protein", "TNF-alpha": "protein" } }, { "input_text": "Phenotypic DC characteristics of KG1 dendritic-like cells include morphology ( loosely adherent cells with long neurite processes ) , MHC I+/ MHC IIbright/CD83+/CD86+/ CD14 - surface Ag expression , and RelB and DC -CK1 gene expression .", "target_text": { "DC": "cell_type", "KG1 dendritic-like cells": "cell_line", "loosely adherent cells": "cell_type", "MHC": "protein", "CD14": "protein", "RelB": "protein" } }, { "input_text": "Functional DC characteristics include fluid phase macromolecule uptake ( FITC-dextran ) and activation of resting T cells .", "target_text": { "DC": "cell_type", "resting T cells": "cell_type" } }, { "input_text": "Comparison of KG1 to the PMA -unresponsive subline KG1a reveals differences in expression of TNF receptors 1 and 2 ; PKC isoforms alpha , beta I , beta II , and mu ; and RelB , suggesting that these components/pathways are important for DC differentiation .", "target_text": { "KG1": "cell_line", "PMA -unresponsive subline KG1a": "cell_line", "RelB": "protein", "DC": "cell_type" } }, { "input_text": "Together , these findings demonstrate that cytokine or phorbol ester stimulation of KG1 is a model of human CD34+ HPC to DC differentiation and suggest that specific intracellular signaling pathways mediate specific events in DC lineage commitment .", "target_text": { "KG1": "cell_line", "CD34+ HPC": "cell_line", "human CD34+ HPC": "cell_line", "DC": "cell_type" } }, { "input_text": "Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 envelope protein of human immunodeficiency virus type 1 .", "target_text": { "adenylate cyclase": "protein", "p70(S6)-kinase": "protein", "IL-10": "protein", "human monocytes": "cell_type", "gp41 envelope protein": "protein" } }, { "input_text": "Our previous results show that recombinant gp41 ( aa565-647 ) , the extracellular domain of HIV-1 transmembrane glycoprotein , stimulates interleukin-10 ( IL-10 ) production in human monocytes .", "target_text": { "recombinant gp41": "protein", "aa565-647": "protein", "extracellular domain": "protein", "HIV-1 transmembrane glycoprotein": "protein", "interleukin-10": "protein", "IL-10": "protein", "human monocytes": "cell_type" } }, { "input_text": "The signal cascade transducing this effect is not yet clear .", "target_text": {} }, { "input_text": "In this study , we examined whether gp41 -induced IL-10 up-regulation is mediated by the previously described synergistic activation of cAMP and NF-kappaB pathways .", "target_text": { "gp41": "protein", "IL-10": "protein", "NF-kappaB": "protein" } }, { "input_text": "gp41 induced cAMP accumulation in monocytes in a time- and concentration-dependent manner and the adenylate cyclase inhibitor SQ 22536 suppressed gp41 -induced IL-10 production in monocytes .", "target_text": { "gp41": "protein", "monocytes": "cell_type", "adenylate cyclase": "protein", "IL-10": "protein" } }, { "input_text": "In contrast , gp41 failed to stimulate NF-kappaB binding activity in as much as no NF-kappaB bound to the main NF-kappaB -binding site 2 of the IL-10 promoter after addition of gp41 .", "target_text": { "gp41": "protein", "NF-kappaB": "protein", "main NF-kappaB -binding site": "DNA", "IL-10": "protein", "IL-10 promoter": "DNA" } }, { "input_text": "We also examined the involvement of other signal transduction pathways .", "target_text": {} }, { "input_text": "Specific inhibitors of p70(S6)-kinase ( rapamycin ) , and Gi protein ( pertussis toxin ) , prevented induction of IL-10 production by gp41 in monocytes , while inhibitors of the phosphatidylinositol 3-kinase ( PI 3-kinase ) ( wortmannin ) and mitogen-activated protein kinase ( MAPK ) pathway ( PD 98059 ) did not .", "target_text": { "p70(S6)-kinase": "protein", "Gi protein": "protein", "pertussis toxin": "protein", "IL-10": "protein", "gp41": "protein", "monocytes": "cell_type", "phosphatidylinositol 3-kinase": "protein", "PI 3-kinase": "protein", "MAPK": "protein" } }, { "input_text": "Thus HIV-1 gp41 -induced IL-10 up-regulation in monocytes may not involve NF-kappaB , MAPK , or PI 3-kinase activation , but rather may operate through activation of adenylate cyclase and pertussis-toxin-sensitive Gi/Go protein to effect p70(S6)-kinase activation .", "target_text": { "gp41": "protein", "IL-10": "protein", "monocytes": "cell_type", "NF-kappaB": "protein", "MAPK": "protein", "PI 3-kinase": "protein", "adenylate cyclase": "protein", "pertussis-toxin-sensitive Gi/Go protein": "protein", "p70(S6)-kinase": "protein" } }, { "input_text": "Analysis of the modulation of transcriptional activity in myelopoiesis and leukemogenesis .", "target_text": {} }, { "input_text": "Acute myeloid leukemia ( AML ) is still associated with a mortality of 60 to 80 % .", "target_text": {} }, { "input_text": "AML is characterized by a block in myeloid differentiation .", "target_text": {} }, { "input_text": "The transcription factors PU.1 and C/EBPalpha are responsible for normal myeloid differentiation from stem cells to monocytes or granulocytes .", "target_text": { "transcription factors": "protein", "PU.1": "protein", "C/EBPalpha": "protein", "stem cells": "cell_type", "monocytes": "cell_type" } }, { "input_text": "In particular , PU.1 induces expression of the macrophage colony-stimulating factor ( M-CSF ) receptor and the development of monocytes , whereas C/EBPalpha increases the expression of the granulocyte colony-stimulating factor ( G-CSF ) receptor and leads to mature granulocytes .", "target_text": { "PU.1": "protein", "macrophage colony-stimulating factor ( M-CSF ) receptor": "protein", "monocytes": "cell_type", "C/EBPalpha": "protein", "granulocyte colony-stimulating factor ( G-CSF ) receptor": "protein", "granulocytes": "cell_type" } }, { "input_text": "In AML , chromosomal aberrations result in oncoproteins such as AML1/ETO , PML/RARalpha , or activated Ras , which can deregulate genes important for normal myelopoiesis .", "target_text": { "oncoproteins": "protein", "AML1/ETO": "protein", "PML/RARalpha": "protein", "activated Ras": "protein" } }, { "input_text": "Thus , AML1/ETO can bind to the transcription factor C/EBPalpha , inhibit C/EBPalpha -dependent transcription , and block granulocytic differentiation .", "target_text": { "AML1/ETO": "protein", "transcription factor": "protein", "C/EBPalpha": "protein" } }, { "input_text": "However , AML1/ETO can also synergize with the transcription factor AML1 to enhance the activity of the M-CSF receptor promoter .", "target_text": { "AML1/ETO": "protein", "transcription factor": "protein", "AML1": "protein", "M-CSF receptor promoter": "DNA" } }, { "input_text": "On the other hand , the PML/RARalpha fusion protein causes transcriptional repression by recruiting the nuclear corepressor ( N-CoR ) histone deacetylase complex to the DNA , which results in decreased histone acetylation and a repressive chromatin organization .", "target_text": { "PML/RARalpha": "protein", "PML/RARalpha fusion protein": "protein", "nuclear corepressor ( N-CoR ) histone deacetylase complex": "protein", "histone": "protein", "chromatin": "DNA" } }, { "input_text": "Here we describe methods to investigate whether and how signaling agonists induce myeloid differentiation and how oncoproteins might cause AML by modulating the activity of transcription factors that are pivotal for normal myeloid development .", "target_text": { "oncoproteins": "protein", "transcription factors": "protein" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "NF-ATc isoforms are differentially expressed and regulated in murine T and mast cells .", "target_text": { "NF-ATc isoforms": "protein" } }, { "input_text": "NF of activated T cells ( NF-AT ) denotes a family of transcription factors that regulate the activation-dependent expression of many immunologically important proteins .", "target_text": { "NF of activated T cells": "protein", "NF-AT": "protein", "transcription factors": "protein", "immunologically important proteins": "protein" } }, { "input_text": "At least four distinct genes encode the various family members , and several isoforms of these have been identified as well .", "target_text": {} }, { "input_text": "The overlapping expression patterns and similar in vitro binding and trans-activation activities on various promoter elements of NF-AT -regulated genes suggest some redundancy in the function of these proteins .", "target_text": { "promoter elements": "DNA", "NF-AT": "protein", "NF-AT -regulated genes": "DNA" } }, { "input_text": "However , the phenotypic analysis of NF-AT -deficient mice supports the idea that there are tissue- and gene- specific functions as well .", "target_text": { "NF-AT": "protein" } }, { "input_text": "In this study we have characterized the expression of NF-AT cDNAs in murine mast cells .", "target_text": { "NF-AT": "protein", "NF-AT cDNAs": "DNA", "mast cells": "cell_type" } }, { "input_text": "The majority of clones identified correspond to two NF-ATc isoforms that differ only in their amino-terminal sequence .", "target_text": { "NF-ATc isoforms": "protein", "amino-terminal sequence": "protein" } }, { "input_text": "Despite minimal discrepancies in the coding region , there are striking tissue- and cell type-specific differences in isoform expression patterns .", "target_text": { "coding region": "DNA" } }, { "input_text": "Detection of NF-ATc.alpha mRNA is strictly dependent on cell activation signals in both T and mast cell lines .", "target_text": { "NF-ATc.alpha mRNA": "RNA" } }, { "input_text": "In contrast , the beta isoform is expressed at very low constitutive levels in both cell types but is only up-regulated in response to mast cell activation signals delivered through the FcepsilonRI or via calcium ionophores .", "target_text": { "beta isoform": "protein", "FcepsilonRI": "protein" } }, { "input_text": "These results demonstrate another level of regulation within the NF-AT family that can contribute to cell type-specific gene expression .", "target_text": { "NF-AT family": "protein" } }, { "input_text": "Crossreactive recognition of viral , self , and bacterial peptide ligands by human class I-restricted cytotoxic T lymphocyte clonotypes : implications for molecular mimicry in autoimmune disease .", "target_text": { "human class I-restricted cytotoxic T lymphocyte clonotypes :": "cell_type" } }, { "input_text": "The immunodominant , CD8(+) cytotoxic T lymphocyte ( CTL ) response to the HLA-B8-restricted peptide , RAKFKQLL , located in the Epstein-Barr virus immediate-early antigen , BZLF1 , is characterized by a diverse T cell receptor ( TCR ) repertoire .", "target_text": { "CD8(+) cytotoxic T lymphocyte": "cell_type", "Epstein-Barr virus immediate-early antigen": "protein", "BZLF1": "protein", "T cell receptor ( TCR ) repertoire": "protein" } }, { "input_text": "Here , we show that this diversity can be partitioned on the basis of crossreactive cytotoxicity patterns involving the recognition of a self peptide - RSKFRQIV - located in a serine /threonine kinase and a bacterial peptide - RRKYKQII - located in Staphylococcus aureus replication initiation protein .", "target_text": { "serine /threonine kinase": "protein", "Staphylococcus aureus replication initiation protein": "protein" } }, { "input_text": "Thus CTL clones that recognized the viral , self , and bacterial peptides expressed a highly restricted alphabeta TCR phenotype .", "target_text": { "CTL clones": "cell_line", "TCR": "protein" } }, { "input_text": "The CTL clones that recognized viral and self peptides were more oligoclonal , whereas clones that strictly recognized the viral peptide displayed a diverse TCR profile .", "target_text": { "CTL clones": "cell_line", "TCR": "protein" } }, { "input_text": "Interestingly , the self and bacterial peptides equally were substantially less effective than the cognate viral peptide in sensitizing target cell lysis , and also resulted only in a weak reactivation of memory CTLs in limiting dilution assays , whereas the cognate peptide was highly immunogenic .", "target_text": { "memory CTLs": "cell_type" } }, { "input_text": "The described crossreactions show that human antiviral , CD8(+) CTL responses can be shaped by peptide ligands derived from autoantigens and environmental bacterial antigens , thereby providing a firm structural basis for molecular mimicry involving class I-restricted CTLs in the pathogenesis of autoimmune disease .", "target_text": { "I-restricted CTLs": "cell_line" } }, { "input_text": "RFLAT-1 : a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes .", "target_text": { "RFLAT-1": "protein", "zinc finger transcription factor": "protein", "RANTES": "protein", "RANTES gene": "DNA", "T lymphocytes": "cell_type" } }, { "input_text": "RANTES ( Regulated upon Activation , Normal T cell Expressed and Secreted ) is a chemoattractant cytokine ( chemokine ) important in the generation of inflammatory infiltrate and human immunodeficiency virus entry into immune cells .", "target_text": { "RANTES": "protein", "Regulated upon Activation , Normal T cell Expressed and Secreted": "protein", "chemoattractant cytokine": "protein", "chemokine": "protein", "immune cells": "cell_type" } }, { "input_text": "RANTES is expressed late ( 3-5 days ) after activation in T lymphocytes .", "target_text": { "RANTES": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Using expression cloning , we identified the first \" late \" T lymphocyte associated transcription factor and named it \" RANTES Factor of Late Activated T Lymphocytes-1 \" ( RFLAT-1 ) .", "target_text": { "T lymphocyte associated transcription factor": "protein", "RANTES": "protein", "RANTES Factor of Late Activated T Lymphocytes-1": "protein", "RFLAT-1": "protein" } }, { "input_text": "RFLAT-1 is a novel , phosphorylated , zinc finger transcription factor that is expressed in T cells 3 days after activation , coincident with RANTES expression .", "target_text": { "RFLAT-1": "protein", "zinc finger transcription factor": "protein", "T cells": "cell_type", "RANTES": "protein" } }, { "input_text": "While Rel proteins play the dominant role in RANTES gene expression in fibroblasts , RFLAT-1 is a strong transactivator for RANTES in T cells .", "target_text": { "Rel proteins": "protein", "RANTES": "protein", "RANTES gene": "DNA", "RFLAT-1": "protein", "T cells": "cell_type" } }, { "input_text": "Fas ligand induction in human NK cells is regulated by redox through a calcineurin-nuclear factors of activated T cell-dependent pathway .", "target_text": { "Fas ligand": "protein", "human NK cells": "cell_type", "calcineurin-nuclear factors": "protein" } }, { "input_text": "Fas ligand ( FasL ) on cytotoxic lymphocytes is important for mediating apoptosis of activated lymphocytes and other target cells .", "target_text": { "Fas ligand": "protein", "FasL": "protein" } }, { "input_text": "We have reported that NK cell functions , such as proliferation , cell death , and killing activity , are subject to regulation by cellular redox status .", "target_text": {} }, { "input_text": "Here , we report that expression of FasL protein and mRNA in activated NK cells is also regulated by redox .", "target_text": { "FasL protein": "protein", "mRNA": "RNA", "activated NK cells": "cell_type" } }, { "input_text": "Ligation of CD16 on IL-2- preactivated NK cells resulted in reduction of intracellular peroxide level as well as induction of FasL expression .", "target_text": { "CD16": "protein", "preactivated NK cells": "cell_type", "IL-2- preactivated NK cells": "cell_type", "FasL": "protein" } }, { "input_text": "This CD16 -induced FasL expression was suppressed by oxidative stress , including thiol deprivation or treatment with hydrogen peroxide ( H2O2 ) .", "target_text": { "CD16": "protein", "FasL": "protein" } }, { "input_text": "Addition of thiol-reducing compounds , such as L-cystine , 2-ME , or N-acetyl cysteine , restored FasL expression .", "target_text": { "FasL": "protein" } }, { "input_text": "These data suggest that CD16 stimulation requires cellular reducing status for FasL induction in NK cells .", "target_text": { "CD16": "protein", "FasL": "protein", "NK cells": "cell_type" } }, { "input_text": "Because FasL gene activation following CD16 cross-linking is regulated by the NF of activated T cells ( NFAT ) , we examined the effect of oxidative stresses on NFAT activation .", "target_text": { "CD16": "protein", "T cells": "cell_type", "NF of activated T cells": "protein", "NFAT": "protein" } }, { "input_text": "Electrophoretic mobility shift assays revealed that both thiol insufficiency and H2O2 treatment suppressed DNA-binding activity of NFAT and that addition of thiol-reducing compounds reversed or even enhanced it .", "target_text": { "NFAT": "protein" } }, { "input_text": "Furthermore , these oxidative stresses inhibited activity of calcineurin , a serine / threonine phosphatase that regulates NFAT activation .", "target_text": { "threonine phosphatase": "protein", "NFAT": "protein" } }, { "input_text": "These results suggest that suppression of calcineurin and NFAT activation is a mechanism by which oxidative stress inhibits FasL induction in activated NK cells and further support the hypothesis that thiol-reducing compounds might be required for maintenance of optimal NK functions under physiologic oxidative conditions .", "target_text": { "calcineurin": "protein", "NFAT": "protein", "FasL": "protein", "NK cells": "cell_type", "activated NK cells": "cell_type" } }, { "input_text": "Heterogeneity of clonal development in chronic myeloproliferative disorders .", "target_text": { "chronic myeloproliferative disorders": "DNA" } }, { "input_text": "Recent reports have suggested a previously unexpected variability in the expression of the dominant neoplastic clone in myeloproliferative disorders ( MPD ) .", "target_text": { "dominant neoplastic clone": "cell_line" } }, { "input_text": "We evaluated 49 female patients with MPD and informative at the X-linked androgen receptor ( AR ) locus to establish the X chromosome inactivation pattern of hemopoietic cells .", "target_text": { "X-linked androgen receptor ( AR ) locus": "DNA", "X chromosome": "DNA", "hemopoietic cells": "cell_type" } }, { "input_text": "Whereas in chronic myelogenous leukemia ( CML ) the granulocytes ( PMN ) were uniformly of monoclonal origin , a striking heterogeneity of clonal development was found in PMN from patients with other MPD , with up to 50 % of them expressing a polyclonal pattern of X inactivation .", "target_text": { "granulocytes": "cell_type", "PMN": "cell_type" } }, { "input_text": "CD80 and CD86 are not equivalent in their ability to induce the tyrosine phosphorylation of CD28 .", "target_text": { "CD80": "protein", "CD86": "protein", "CD28": "protein" } }, { "input_text": "Ligation of either CD80 ( B7-1 ) or CD86 ( B7-2 ) , two principal ligands for CD28 , is thought to skew the immune response toward Th1 or Th2 differentiation .", "target_text": { "CD80": "protein", "B7-1": "protein", "CD86": "protein", "B7-2": "protein", "CD28": "protein" } }, { "input_text": "We have examined early signal transduction pathways recruited following T cell stimulation with either CD80 or CD86 .", "target_text": { "CD80": "protein", "CD86": "protein" } }, { "input_text": "Purified human peripheral T cells or Jurkat T cells were stimulated with Chinese hamster ovary ( CHO ) cells expressing either human CD80 ( CHO-CD80 ) or human CD86 ( CHO-CD86 ) or with anti- CD28 monoclonal antibody ( mAb ) .", "target_text": { "Purified human peripheral T cells": "cell_line", "Jurkat T cells": "cell_line", "CD80": "protein", "human CD80": "protein", "CHO-CD80": "protein", "human CD86": "protein", "CHO-CD86": "protein", "CD28": "protein", "anti- CD28 monoclonal antibody": "protein" } }, { "input_text": "In the presence of phorbol 12-myristate 13-acetate , both CHO-CD80 and CHO-CD86 , like anti-CD28 mAb , were capable of stimulating cytokine production from both human peripheral T cells and Jurkat T cells .", "target_text": { "CHO-CD80": "protein", "CHO-CD86": "protein", "anti-CD28 mAb": "protein", "cytokine": "protein", "human peripheral T cells": "cell_type", "Jurkat T cells": "cell_line" } }, { "input_text": "Both CHO-CD80 and CHO-CD86 , in the presence of anti-CD3 mAb , costimulated NFAT -dependent transcriptional activation .", "target_text": { "CHO-CD80": "protein", "CHO-CD86": "protein", "anti-CD3 mAb": "protein", "NFAT": "protein" } }, { "input_text": "Several intracellular signaling proteins , such as CBL and VAV , were phosphorylated on tyrosine in response to CD80 , CD86 , and anti-CD28 mAb .", "target_text": { "signaling proteins": "protein", "CBL": "protein", "VAV": "protein", "CD80": "protein", "CD86": "protein", "anti-CD28 mAb": "protein" } }, { "input_text": "Surprisingly , although stimulation of Jurkat T cells with either CHO-CD80 or anti-CD28 mAb resulted in robust tyrosine phosphorylation of CD28 itself , ligation with CHO-CD86 was unable to induce detectable CD28 tyrosyl phosphorylation over a range of stimulation conditions .", "target_text": { "Jurkat T cells": "cell_line", "CHO-CD80": "protein", "anti-CD28 mAb": "protein", "CD28": "protein", "CHO-CD86": "protein" } }, { "input_text": "In addition , the association of phosphoinositide 3-kinase with CD28 and enhanced tyrosine phosphorylation of phospholipase Cgamma were seen after anti-CD28 mAb and CHO-CD80 stimulation but to a much lesser extent after CHO-CD86 stimulation .", "target_text": { "phosphoinositide 3-kinase": "protein", "CD28": "protein", "CHO-CD86": "protein" } }, { "input_text": "Thus , ligation of CD28 with either CD80 or CD86 leads to shared early signal transduction events such as the tyrosine phosphorylation of CBL and VAV , to NFAT -mediated transcriptional activation , and to the costimulation of interleukin-2 and granulocyte-macrophage colony-stimulating factor production .", "target_text": { "CD28": "protein", "CD80": "protein", "CD86": "protein", "CBL": "protein", "VAV": "protein", "NFAT": "protein", "interleukin-2": "protein", "granulocyte-macrophage colony-stimulating factor": "protein" } }, { "input_text": "However , CD80 and CD86 also induce distinct signal transduction pathways including the tyrosine phosphorylation of CD28 and phospholipase Cgamma1 and the SH2 -dependent association of phosphoinositide 3-kinase with CD28 .", "target_text": { "CD80": "protein", "CD86": "protein", "CD28": "protein", "phospholipase Cgamma1": "protein", "SH2": "protein", "phosphoinositide 3-kinase": "protein" } }, { "input_text": "These quantitative , if not qualitative , differences between signaling initiated by these two ligands for CD28 may contribute to functional differences ( e.g. Th1 or Th2 differentiation ) in T cell responses .", "target_text": { "CD28": "protein" } }, { "input_text": "Binding of HMG-I ( Y ) elicits structural changes in a silencer of the human beta-globin gene .", "target_text": { "HMG-I ( Y )": "protein", "human beta-globin gene": "DNA" } }, { "input_text": "Proteins involved in repression of the human beta-globin gene may be useful in the treatment of sickle cell anemia , in conjunction with therapy to reactivate fetal globin genes .", "target_text": { "human beta-globin gene": "DNA", "fetal globin genes": "DNA" } }, { "input_text": "If there is a reciprocal elevation of gamma-globin expression upon repression , this approach could be useful in additional hemoglobinopathies .", "target_text": { "gamma-globin": "protein" } }, { "input_text": "We previously showed that repression of the beta-globin gene appears to be mediated through two DNA sequences , silencers I and II , and identified a protein termed BP1 which binds to both silencer sequences .", "target_text": { "DNA sequences": "DNA", "BP1": "protein" } }, { "input_text": "In this study , we cloned two cDNAs encoding proteins which bind to an oligonucleotide in silencer I containing a BP1 binding site .", "target_text": { "cDNAs": "DNA", "silencer I": "DNA", "BP1": "protein" } }, { "input_text": "These cDNAs correspond to HMG-I and HMG-Y , isoforms regarded as architectural proteins .", "target_text": { "cDNAs": "DNA", "HMG-I": "protein", "HMG-Y": "protein", "architectural proteins": "protein" } }, { "input_text": "We demonstrate that binding of HMG-I(Y) to this oligonucleotide causes bending/flexure of the DNA .", "target_text": { "HMG-I(Y)": "protein" } }, { "input_text": "HMG-I(Y) also binds to a second oligonucleotide containing a BP1 binding site located in a negative control region upstream of the delta-globin gene , suggesting a role for HMG-I(Y) in repression of adult globin genes .", "target_text": { "HMG-I(Y)": "protein", "BP1": "protein", "BP1 binding site": "DNA", "negative control region": "DNA", "delta-globin gene": "DNA" } }, { "input_text": "Expression studies revealed that HMG-I(Y) is ubiquitously expressed in human tissues that do not express beta-globin , being present in 48 of 50 tissues and six hematopoietic cell lines examined .", "target_text": { "HMG-I(Y)": "protein", "beta-globin": "protein", "hematopoietic cell lines": "cell_line" } }, { "input_text": "Furthermore , HMG-I(Y) expression is down-regulated during differentiation of primary erythroid cells .", "target_text": { "HMG-I(Y)": "protein", "primary erythroid cells": "cell_type" } }, { "input_text": "We present a model in which HMG-I(Y) alters DNA conformation to allow binding of repressor proteins , and in which the relative amount of HMG-I(Y) helps to determine the repressive state of the beta-globin gene .", "target_text": { "HMG-I(Y)": "protein", "repressor proteins": "protein", "beta-globin gene": "DNA" } }, { "input_text": "Interactions between the class II transactivator and CREB binding protein increase transcription of major histocompatibility complex class II genes .", "target_text": { "class II transactivator": "protein", "CREB binding protein": "protein", "major histocompatibility complex class II genes": "DNA" } }, { "input_text": "Class II major histocompatibility ( class II ) genes are regulated in a B-cell-specific and gamma interferon-inducible fashion .", "target_text": { "Class II major histocompatibility ( class II ) genes": "DNA" } }, { "input_text": "The master switch for the expression of these genes is the class II transactivator ( CIITA ) .", "target_text": { "class II transactivator": "protein", "CIITA": "protein" } }, { "input_text": "In this report , we demonstrate that one of the functions of CIITA is to recruit the CREB binding protein ( CBP ) to class II promoters .", "target_text": { "CIITA": "protein", "CREB binding protein": "protein", "CBP": "protein", "class II promoters": "DNA" } }, { "input_text": "Not only functional but also specific binding interactions between CIITA and CBP were demonstrated .", "target_text": { "CIITA": "protein", "CBP": "protein" } }, { "input_text": "Moreover , a dominant negative form of CBP decreased the activity of class II promoters and levels of class II determinants on the surface of cells .", "target_text": { "CBP": "protein", "class II promoters": "DNA", "class II determinants": "protein" } }, { "input_text": "Finally , the inhibition of class II gene expression by the glucocorticoid hormone could be attributed to the squelching of CBP by the glucocorticoid receptor .", "target_text": { "class II gene": "DNA", "CBP": "protein", "glucocorticoid receptor": "protein" } }, { "input_text": "We conclude that CBP , a histone acetyltransferase , plays an important role in the transcription of class II genes .", "target_text": { "CBP": "protein", "histone acetyltransferase": "protein", "class II genes": "DNA" } }, { "input_text": "Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of NF-kappaB -mediated transcription .", "target_text": { "cyclic AMP response element-binding protein": "protein", "NF-kappaB": "protein" } }, { "input_text": "The NF-kappaB family of transcription factors regulates the inducible expression of a variety of genes .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Recently , we showed that elevation of intracellular cyclic AMP inhibits NF-kappaB -mediated transcription in human monocytes and endothelial cells without preventing nuclear translocation of NF-kappaB complexes .", "target_text": { "NF-kappaB": "protein", "human monocytes": "cell_type", "endothelial cells": "cell_type", "NF-kappaB complexes": "protein" } }, { "input_text": "The present study examined the molecular mechanism of this inhibition .", "target_text": {} }, { "input_text": "We hypothesized that activation of the protein kinase A signaling pathway may inhibit NF-kappaB -mediated transcription by phosphorylating proteins , such as cAMP response element-binding protein ( CREB ) , which compete for limiting amounts of the coactivator CBP .", "target_text": { "protein kinase A": "protein", "NF-kappaB": "protein", "cAMP response element-binding protein": "protein", "CREB": "protein", "CBP": "protein" } }, { "input_text": "Here , we show that the amino-terminal region ( amino acids 1-450 ) of CBP specifically interacts with the carboxyl-terminal region ( amino acids 286-551 ) of NF-kappaB p65 ( RelA ) both in vitro and in vivo .", "target_text": { "amino-terminal region": "protein", "amino acids 1-450": "protein", "CBP": "protein", "carboxyl-terminal region": "protein", "amino acids 286-551": "protein", "NF-kappaB": "protein", "p65": "protein", "RelA": "protein" } }, { "input_text": "Functional studies using human endothelial cells demonstrated that overexpression of CBP rescued cAMP inhibition of NF-kappaB -mediated transcription and transcription mediated by a chimeric protein , GAL4-p65 ( 286-551 ) , which contained the GAL4 DNA binding domain fused to the carboxyl-terminal region of p65 ( amino acids 286-551 ) .", "target_text": { "endothelial cells": "cell_type", "CBP": "protein", "NF-kappaB": "protein", "chimeric protein": "protein", "GAL4-p65 ( 286-551 )": "protein", "GAL4 DNA binding domain": "protein", "carboxyl-terminal region": "protein", "p65": "protein", "amino acids 286-551": "protein" } }, { "input_text": "In contrast , overexpression of CREB inhibited GAL4 -p65(286-551)-mediated transcription .", "target_text": { "CREB": "protein", "GAL4": "protein" } }, { "input_text": "These results suggest that activation of the protein kinase A pathway inhibits NF-kappaB transcription by phosphorylating CREB , which competes with p65 for limiting amounts of CBP .", "target_text": { "protein kinase A": "protein", "NF-kappaB": "protein", "CREB": "protein", "p65": "protein", "CBP": "protein" } }, { "input_text": "Glucocorticoid receptors in cord blood lymphocytes of healthy neonates and of preterms suffering from respiratory distress syndrome .", "target_text": { "Glucocorticoid receptors": "protein", "cord blood lymphocytes": "cell_type" } }, { "input_text": "We measured the number of glucocorticoid receptors ( GR ) in cord blood lymphocytes and the binding affinity ( Kd ) in 15 term and in 20 preterm babies .", "target_text": { "glucocorticoid receptors": "protein", "GR": "protein", "cord blood lymphocytes": "cell_type" } }, { "input_text": "Thirteen preterms of the latter group received prenatal steroid treatment .", "target_text": {} }, { "input_text": "Seven preterms developed neonatal respiratory distress syndrome ( NRDS ) .", "target_text": {} }, { "input_text": "The number of GR and the Kd were similar in the term and preterm ( with and without NRDS ) babies .", "target_text": { "GR": "protein" } }, { "input_text": "The maximum (3H)-thymidine incorporation into DNA of cord blood lymphocytes from all preterms , with or without NRDS was suppressed when compared to that from term babies or adults .", "target_text": { "cord blood lymphocytes": "cell_type" } }, { "input_text": "This could partly be explained by the antenatal steroid treatment .", "target_text": {} }, { "input_text": "Sensitivity ( ID50 ) of the lymphocytes for the inhibitory effect of dexamethasone was the same in all groups .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "In this study on the number and function of GR in lymphocytes , we were unable to find a relation between the functionality of the GR and the development of NRDS .", "target_text": { "GR": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Inefficient termination of antigen responses in NF-ATp -deficient mice .", "target_text": { "NF-ATp": "protein" } }, { "input_text": "In order to elucidate the role of NF-ATp , one of the most prominent members of family of NF-AT transcription factors in peripheral T lymphocytes , in T cell activation and differentiation we created NF-ATp -deficient mice by gene targeting .", "target_text": { "NF-ATp": "protein", "NF-AT transcription factors": "protein", "T lymphocytes": "cell_type", "peripheral T lymphocytes": "cell_type" } }, { "input_text": "Such NF-ATp -/- mice are born and appear to develop a normal immune system .", "target_text": { "NF-ATp": "protein" } }, { "input_text": "Apart from clear-cut defects in the synthesis of mRNAs for Th2-type lymphokines , such as IL-4 , IL-5 , IL-10 and IL-13 , in primary and secondary stimulations of spleen cells in vitro , of a distinct impaired deletion of V beta 11+/CD4+ T lymphocytes from these mice was detected after superantigen injection .", "target_text": { "mRNAs": "RNA", "Th2-type lymphokines": "protein", "IL-4": "protein", "IL-5": "protein", "IL-10": "protein", "IL-13": "protein", "spleen cells": "cell_type", "T lymphocytes": "cell_type", "V beta 11+/CD4+ T lymphocytes": "cell_line" } }, { "input_text": "Moreover , NF-ATp -/- mice older than 6 weeks show an 2-5 fold increase in number of lymphocytes .", "target_text": { "NF-ATp": "protein", "lymphocytes": "cell_type" } }, { "input_text": "This is correlated with an increased expression of activation markers CD44 and CD69 and decreased expression of CD62 .", "target_text": { "activation markers": "protein", "CD44": "protein", "CD69": "protein", "CD62": "protein" } }, { "input_text": "AML and Ets proteins regulate the I alpha1 germ-line promoter .", "target_text": { "I alpha1 germ-line promoter": "DNA" } }, { "input_text": "The immunoglobulin heavy chain ( IgH ) class switch recombination of B lymphocytes preferentially targets unrearranged IgH genes that have already been rendered transcriptionally active .", "target_text": { "immunoglobulin heavy chain": "protein", "IgH": "protein", "B lymphocytes": "cell_type", "IgH genes": "DNA" } }, { "input_text": "Transcription of the germ-line IgH genes is controlled by intervening ( I ) regions upstream of their switch regions .", "target_text": { "IgH genes": "DNA", "germ-line IgH genes": "DNA", "intervening ( I ) regions": "DNA" } }, { "input_text": "The I alpha1 promoter activates transcription of the human germ-line C alpha1 gene for IgA1 and mediates the transforming growth factor ( TGF ) -beta1 responsiveness of this locus .", "target_text": { "human germ-line C alpha1 gene": "DNA", "IgA1": "protein", "transforming growth factor ( TGF ) -beta1": "protein" } }, { "input_text": "Here we show that the I alpha1 promoter contains several binding sites for the AML /PEBP2/CBF family of transcription factors and that AML and Ets proteins are major regulators of the basal and TGF-beta-inducible promoter activity .", "target_text": { "AML": "protein", "transcription factors": "protein", "AML /PEBP2/CBF family of transcription factors": "protein" } }, { "input_text": "Our data constitute a starting point for studies to elucidate the molecular mechanism by which TGF-beta regulates IgA production .", "target_text": { "TGF-beta": "protein", "IgA": "protein" } }, { "input_text": "Daidzein and genistein glucuronides in vitro are weakly estrogenic and activate human natural killer cells at nutritionally relevant concentrations .", "target_text": { "human natural killer cells": "cell_type" } }, { "input_text": "Daidzein and genistein glucuronides ( DG and GG ) , major isoflavone metabolites , may be partly responsible for biological effects of isoflavones , such as estrogen receptor binding and natural killer cell ( NK ) activation or inhibition .", "target_text": { "natural killer cell": "cell_type" } }, { "input_text": "DG and GG were synthesized using 3-methylcholanthrene -induced rat liver microsomes .", "target_text": {} }, { "input_text": "The Km and Vmax for daidzein and genistein were 9.0 and 7.7 micromol/L , and 0.7 and 1.6 micromol/ ( mg protein. min ) , respectively .", "target_text": {} }, { "input_text": "The absence of ultraviolet absorbance maxima shifts in the presence of sodium acetate confirmed that the synthesized products were 7-O- glucuronides .", "target_text": {} }, { "input_text": "DG and GG were further purified by a Sephadex LH-20 column .", "target_text": {} }, { "input_text": "DG and GG competed with the binding of 17beta-(3H) estradiol to estrogen receptors of B6D2F1 mouse uterine cytosol .", "target_text": { "estrogen receptors": "protein" } }, { "input_text": "The concentrations required for 50 % displacement of 17beta-(3H) estradiol ( CB50 ) were : 17beta-estradiol , 1.34 nmol/L ; diethylstilbestrol , 1.46 nmol/L ; daidzein , 1.6 micromol/L ; DG , 14.7 micromol/L ; genistein , 0.154 micromol/L ; GG , 7.27 micromol/L .", "target_text": {} }, { "input_text": "In human peripheral blood NK cells , genistein at < 0.5 micromol/L and DG and GG at 0.1-10 micromol/L enhanced NK cell-mediated K562 cancer cell killing significantly ( P < 0.05 ) .", "target_text": { "human peripheral blood NK cells": "cell_type", "K562 cancer cell": "cell_line" } }, { "input_text": "At > 0.5 micromol/L , genistein inhibited NK cytotoxicity significantly ( P < 0.05 ) .", "target_text": {} }, { "input_text": "The glucuronides only inhibited NK cytotoxicity at 50 micromol/L .", "target_text": {} }, { "input_text": "Isoflavones , and especially the isoflavone glucuronides , enhanced activation of NK cells by interleukin-2 ( IL-2 ) , additively .", "target_text": { "NK cells": "cell_type", "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "At physiological concentrations , DG and GG were weakly estrogenic , and they activated human NK cells in nutritionally relevant concentrations in vitro , probably at a site different from IL-2 action .", "target_text": { "NK cells": "cell_type", "human NK cells": "cell_type", "IL-2": "protein" } }, { "input_text": "Cross-linking of CD44 on rheumatoid synovial cells up-regulates VCAM-1 .", "target_text": { "CD44": "protein", "rheumatoid synovial cells": "cell_type", "VCAM-1": "protein" } }, { "input_text": "CD44 is a ubiquitous molecule also known as hyaluronic acid or homing receptor .", "target_text": {} }, { "input_text": "However , the cellular functions and its role in inflammation , for example , rheumatoid synovitis , are currently unknown .", "target_text": {} }, { "input_text": "In this study , we propose a novel function for CD44 .", "target_text": {} }, { "input_text": "Using synovial cells from rheumatoid arthritis ( RA ) patients , we demonstrated that CD44 cross-linking and binding to hyaluronan augmented VCAM-1 expression and subsequently VCAM-1 -mediated cell adhesion .", "target_text": { "VCAM-1": "protein" } }, { "input_text": "Briefly , we found that 1 ) rheumatoid synovial cells highly expressed CD44 ; 2 ) cross-linking of CD44 markedly but transiently augmented VCAM-1 expression and its mRNA transcription much more than did IL-1beta and TNF-alpha ; 3 ) hyaluronan , especially when fragmented , also up-regulated VCAM-1 ; 4 ) CD44 activated the transcription factor AP-1 ; and 5 ) the integrin -dependent adhesive function of RA synovial cells to T cells was also amplified by CD44 cross-linking .", "target_text": { "rheumatoid synovial cells": "cell_type", "CD44": "protein", "VCAM-1": "protein", "IL-1beta": "protein", "integrin": "protein", "RA synovial cells": "cell_type", "T cells": "cell_type" } }, { "input_text": "These results indicate that the adhesion of RA synovial cells to matrices such as hyaluronic acid through CD44 could up-regulate VCAM-1 expression and VCAM-1 -mediated adhesion to T cells , which might in turn cause activation of T cells and synovial cells in RA synovitis .", "target_text": { "RA synovial cells": "cell_type", "CD44": "protein", "VCAM-1": "protein", "T cells": "cell_type", "synovial cells": "cell_type" } }, { "input_text": "We therefore propose that such cross-talking among distinct adhesion molecules may be involved in the pathogenesis of inflammation , including RA synovitis .", "target_text": {} }, { "input_text": "NF-kappaB activation is a critical regulator of human granulocyte apoptosis in vitro .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "During beneficial inflammation , potentially tissue-damaging granulocytes undergo apoptosis before being cleared by phagocytes in a non-phlogistic manner .", "target_text": { "tissue-damaging granulocytes": "cell_type" } }, { "input_text": "Here we show that the rate of constitutive apoptosis in human neutrophils and eosinophils is greatly accelerated in both a rapid and concentration-dependent manner by the fungal metabolite gliotoxin , but not by its inactive analog methylthiogliotoxin .", "target_text": { "human neutrophils": "cell_type", "eosinophils": "cell_type" } }, { "input_text": "This induction of apoptosis was abolished by the caspase inhibitor zVAD-fmk , correlated with the inhibition of nuclear factor-kappa B ( NF-kappaB ) , and was mimicked by a cell permeable inhibitory peptide of NF-kappaB , SN-50 ; other NF-kappaB inhibitors , curcumin and pyrrolidine dithiocarbamate ; and the proteasome inhibitor , MG-132 .", "target_text": { "nuclear factor-kappa B": "protein", "NF-kappaB": "protein" } }, { "input_text": "Gliotoxin also augmented dramatically the early ( 2-6 h ) pro-apoptotic effects of tumor necrosis factor-alpha ( TNF-alpha ) in neutrophils and unmasked the ability of TNF-alpha to induce eosinophil apoptosis .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "neutrophils": "cell_type", "eosinophil": "cell_type" } }, { "input_text": "In neutrophils , TNF-alpha caused a gliotoxin -inhibitable activation of an inducible form of NF-kappaB , a response that may underlie the ability of TNF-alpha to delay apoptosis at later times ( 12-24 h ) and limit its early killing effect .", "target_text": { "neutrophils": "cell_type", "TNF-alpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "Furthermore , cycloheximide displayed a similar capacity to enhance TNF-alpha induced neutrophil apoptosis even at time points when cycloheximide alone had no pro-apoptotic effect , suggesting that NF-kappaB may regulate the production of protein ( s ) which protect neutrophils from the cytotoxic effects of TNF-alpha .", "target_text": { "TNF-alpha": "protein", "NF-kappaB": "protein", "neutrophils": "cell_type" } }, { "input_text": "These data shed light on the biochemical and molecular mechanisms regulating human granulocyte apoptosis and , in particular , indicate that the transcription factor NF-kappaB plays a crucial role in regulating the physiological cell death pathway in granulocytes .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein", "granulocytes": "cell_type" } }, { "input_text": "Role of Egr-2 in up-regulation of Fas ligand in normal T cells and aberrant double-negative lpr and gld T cells .", "target_text": { "Egr-2": "protein", "Fas ligand": "protein", "T cells": "cell_type" } }, { "input_text": "We previously identified a Fas ligand regulatory element ( FLRE ) in the Fas ligand ( fasL ) promoter that binds Egr family proteins and demonstrated that Egr-3 ( PILOT ) but not Egr-1 ( NGFI-A , Krox-24 , Tis-8 , and Zif-268 ) induces transcription of fasL .", "target_text": { "Fas ligand regulatory element": "DNA", "FLRE": "DNA", "Fas ligand ( fasL ) promoter": "DNA", "Egr family proteins": "protein", "Egr-3": "protein", "PILOT": "protein", "Egr-1": "protein", "NGFI-A": "protein", "Krox-24": "protein", "Tis-8": "protein", "Zif-268": "protein", "fasL": "protein" } }, { "input_text": "The aberrant CD4(-) CD8(-) T cells from lpr/lpr and gld/gld mice , which have mutations in the genes encoding Fas and FasL , respectively , have an activated phenotype and constitutively express high levels of fasL mRNA , prompting us to ask what role if any the FLRE and Egr family proteins have in this aberrant expression of fasL .", "target_text": { "aberrant CD4(-) CD8(-) T cells": "cell_type", "Fas": "protein", "FasL": "protein", "fasL mRNA": "RNA", "FLRE": "DNA", "Egr family proteins": "protein", "fasL": "protein" } }, { "input_text": "Unstimulated MRL-lpr/lpr and C3H-gld/gld CD4(-) CD8(-) T cells constitutively contained high levels of two proteins that bound to the FLRE .", "target_text": { "FLRE": "DNA" } }, { "input_text": "Supershift analysis revealed these proteins to be Egr-1 and Egr-2 ( Krox-20 ) ; Egr-3 was not detected .", "target_text": { "Egr-1": "protein", "Egr-2": "protein", "Egr-3": "protein" } }, { "input_text": "Activation of normal lymph node cells resulted in increased expression of Egr -1 , -2 , and -3 .", "target_text": { "normal lymph node cells": "cell_type" } }, { "input_text": "As with egr-3 , expression of egr-2 was blocked by cyclosporin A .", "target_text": { "egr-3": "DNA", "egr-2": "DNA" } }, { "input_text": "Although overexpressed Egr-1 was ineffective , overexpressed Egr-2 was as potent as Egr-3 in inducing fasL promoter-dependent reporter constructs in T cell hybridomas and HeLa cells , and both up-regulated endogenous fasL mRNA in HeLa cells .", "target_text": { "Egr-1": "protein", "Egr-2": "protein", "Egr-3": "protein", "fasL": "protein", "fasL promoter-dependent reporter constructs": "DNA", "fasL mRNA": "RNA", "HeLa cells": "cell_line" } }, { "input_text": "FasL -dependent reporter constructs in MRL-lpr/lpr and C3H-gld/gld CD4(-) CD8(-) T cells were constitutively active , and this activity was largely prevented by mutation of the critical Egr family binding element .", "target_text": { "FasL": "protein", "FasL -dependent reporter constructs": "DNA", "Egr family binding element": "DNA" } }, { "input_text": "Thus , Egr-2 , in addition to Egr-3 , regulates FasL expression in activated normal T cells , and Egr-2 is likely to play a direct role in aberrant fasL up-regulation in lpr/lpr and gld/gld CD4(-) CD8(-) T cells .", "target_text": { "Egr-2": "protein", "Egr-3": "protein", "FasL": "protein", "T cells": "cell_type", "fasL": "protein" } }, { "input_text": "The activity of the CCAAT-box binding factor NF-Y is modulated through the regulated expression of its A subunit during monocyte to macrophage differentiation : regulation of tissue-specific genes through a ubiquitous transcription factor .", "target_text": { "CCAAT-box": "DNA", "NF-Y": "protein", "CCAAT-box binding factor NF-Y": "protein", "A subunit": "protein", "tissue-specific genes": "DNA", "transcription factor": "protein" } }, { "input_text": "In this study , we analyzed the regulation of NF-Y expression during human monocyte to macrophage maturation .", "target_text": { "NF-Y": "protein" } }, { "input_text": "NF-Y is a ubiquitous and evolutionarily conserved transcription factor that binds specifically to the CCAAT motif present in the 5' promoter region of a wide variety of genes .", "target_text": { "NF-Y": "protein", "transcription factor": "protein", "CCAAT motif": "DNA", "5' promoter region": "DNA" } }, { "input_text": "We show here that in circulating monocytes , NF-Y binding activity is not detected on the CCAAT motif present in the promoters of genes such as major histocompatibility complex ( MHC ) class II , gp91-phox , mig , and fibronectin , whereas during macrophage differentiation , a progressive increase in NF-Y binding activity is observed on these promoters .", "target_text": { "circulating monocytes": "cell_type", "NF-Y": "protein", "CCAAT motif": "DNA", "promoters of genes": "DNA", "major histocompatibility complex ( MHC ) class II": "DNA", "gp91-phox": "DNA", "mig": "DNA" } }, { "input_text": "Analysis of NF-Y subunit expression indicates that the absence of NF-Y activity in circulating monocytes is caused by a lack of the A subunit .", "target_text": { "NF-Y": "protein", "circulating monocytes": "cell_type", "A subunit": "protein" } }, { "input_text": "Furthermore , addition of the recombinant NF-Y A subunit restores NF-Y binding .", "target_text": { "NF-Y": "protein", "A subunit": "protein" } }, { "input_text": "We show that the lack of NF-YA protein is due to posttranscriptional regulation and not to a specific proteolytic activity .", "target_text": { "NF-YA protein": "protein" } }, { "input_text": "In fact , NF-YA mRNA is present at the same level at all days of monocyte cultivation , whereas the protein is absent in freshly isolated monocytes but is progressively synthesized during the maturation process .", "target_text": { "NF-YA": "protein", "NF-YA mRNA": "RNA", "freshly isolated monocytes": "cell_type" } }, { "input_text": "We thus conclude that the NF-Y A subunit plays a relevant role in activating transcription of genes highly expressed in mature monocytes .", "target_text": { "NF-Y": "protein", "A subunit": "protein", "mature monocytes": "cell_type" } }, { "input_text": "In line with this conclusion , we show that the cut/CDP protein , a transcriptional repressor that inhibits gpc91-phox gene expression by preventing NF-Y binding to the CAAT box , is absent in monocytes .", "target_text": { "cut/CDP protein": "protein", "gpc91-phox gene": "DNA", "NF-Y": "protein", "CAAT box": "DNA", "monocytes": "cell_type" } }, { "input_text": "Interdomain B in ZAP-70 regulates but is not required for ZAP-70 signaling function in lymphocytes .", "target_text": { "Interdomain B": "protein", "ZAP-70": "protein", "lymphocytes": "cell_type" } }, { "input_text": "The protein tyrosine kinase ZAP-70 plays an important role in T-cell activation and development .", "target_text": { "ZAP-70": "protein" } }, { "input_text": "After T-cell receptor stimulation , ZAP-70 associates with the receptor and is phosphorylated on many tyrosines , including Y292 , Y315 , and Y319 within interdomain B .", "target_text": { "T-cell receptor": "protein", "ZAP-70": "protein" } }, { "input_text": "Previously , we demonstrated that Y292 negatively regulates ZAP-70 function and that Y315 positively regulates ZAP-70 function by interacting with Vav .", "target_text": { "ZAP-70": "protein", "Vav": "protein" } }, { "input_text": "Recent studies have suggested that Y319 also positively regulate ZAP-70 function .", "target_text": { "ZAP-70": "protein" } }, { "input_text": "Paradoxically , removal of interdomain B ( to create the construct designated Delta ) , containing the Y292 , Y315 , and Y319 sites , did not eliminate the ability of ZAP-70 to induce multiple gene reporters in Syk-deficient DT-40 B cells and ZAP-70 /Syk-deficient Jurkat cells .", "target_text": { "interdomain B": "protein", "Delta": "protein", "ZAP-70": "protein", "multiple gene reporters": "DNA", "Syk-deficient DT-40 B cells": "cell_line", "ZAP-70 /Syk-deficient Jurkat cells": "cell_line" } }, { "input_text": "Here we show that Delta still utilizes the same pathways as wild-type ZAP-70 to mediate NF-AT induction .", "target_text": { "Delta": "protein", "ZAP-70": "protein", "NF-AT": "protein" } }, { "input_text": "This is manifested by the ability of Delta to restore induction of calcium fluxes and mitogen-activated protein kinase activation and by the ability of dominant negative Ras and FK506 to block the induction of NF-AT activity mediated by Delta .", "target_text": { "Delta": "protein", "mitogen-activated protein kinase": "protein", "Ras": "protein", "FK506": "protein", "NF-AT": "protein" } }, { "input_text": "Biochemically we show that the stimulated tyrosine phosphorylation of Vav , Shc , and ZAP-70 itself is diminished , whereas that of Slp-76 is increased in cells reconstituted with Delta .", "target_text": { "Vav": "protein", "Shc": "protein", "ZAP-70": "protein", "Slp-76": "protein", "Delta": "protein" } }, { "input_text": "Deletion of interdomain B did not affect the ability of ZAP-70 to bind to the receptor .", "target_text": { "interdomain B": "protein", "ZAP-70": "protein" } }, { "input_text": "The in vitro kinase activity of ZAP-70 lacking interdomain B was markedly reduced , but the kinase activity was still required for the protein 's in vivo activity .", "target_text": { "ZAP-70": "protein", "interdomain B": "protein" } }, { "input_text": "Based on these data , we concluded that interdomain B regulates but is not required for ZAP-70 signaling function leading to cellular responses .", "target_text": { "interdomain B": "protein", "ZAP-70": "protein" } }, { "input_text": "Differential induction of DNA-binding activities following CD19 cross-linking in human B lineage cells .", "target_text": { "DNA-binding activities": "protein", "CD19": "protein", "human B lineage cells": "cell_type" } }, { "input_text": "The B cell-specific cell surface molecule CD19 is expressed at all stages of B cell development , including normal plasma cells , and mediates signal transduction via interaction with cytoplasmic effector proteins .", "target_text": { "B cell-specific cell surface molecule": "protein", "CD19": "protein", "cytoplasmic effector proteins": "protein" } }, { "input_text": "Cross-linking CD19 on early human B lineage cells induces the formation of a CD19 /Vav/phosphatidylinositol-3 kinase complex , tyrosine phosphorylation of CD19 and Vav , and activation of the Ras pathway .", "target_text": { "CD19": "protein", "human B lineage cells": "cell_type", "CD19 /Vav/phosphatidylinositol-3 kinase complex": "protein", "Vav": "protein", "Ras": "protein" } }, { "input_text": "To further explore the ramifications of CD19 signaling , the current study examined whether phosphorylation of Elk-1 , activation of activator protein-1 ( AP-1 ) , or activation of nuclear factor-kappaB ( NF-kappaB ) transcription factors occurred following CD19 cross-linking .", "target_text": { "CD19": "protein", "Elk-1": "protein", "activator protein-1": "protein", "AP-1": "protein", "NF-kappaB": "protein", "transcription factors": "protein" } }, { "input_text": "The cells used were the BLIN-1 pre-B cell line expressing low levels of cell surface mu heavy chain associated with surrogate light chain and the 1E8 immature B cell line expressing cell surface mu/kappa .", "target_text": { "BLIN-1 pre-B cell line": "cell_line", "cell surface mu heavy chain": "protein", "surrogate light chain": "protein", "cell surface mu/kappa": "protein" } }, { "input_text": "Lysates from CD19 cross-linked 1E8 cells induced robust phosphorylation of an Elk-1 fusion protein in vitro , whereas no phosphorylation of Elk-1 fusion protein occurred using lysates from CD19 cross-linked BLIN-1 cells .", "target_text": { "CD19": "protein", "1E8 cells": "cell_line", "Elk-1": "protein", "Elk-1 fusion protein": "protein", "CD19 cross-linked BLIN-1 cells": "cell_line" } }, { "input_text": "An electrophoretic mobility shift assay employing AP-1 and NF-kappaB consensus oligonucleotides was used to demonstrate that AP-1 -binding activity increased , while constitutive NF-kappaB -binding activity was not enhanced , following 2 h of CD19 cross-linking in 1E8 cells . Supershift experiments revealed that JunD and c-Fos proteins mediated anti- CD19 induced AP-1 -binding activity in 1E8 cells .", "target_text": { "AP-1": "protein", "NF-kappaB": "protein", "CD19": "protein", "1E8 cells": "cell_line", "JunD": "protein", "c-Fos proteins": "protein" } }, { "input_text": "In contrast , CD19 cross-linking in BLIN-1 cells resulted in the induction of NF-kappaB , but had no apparent effect on AP-1 -binding activity .", "target_text": { "CD19": "protein", "BLIN-1 cells": "cell_line", "NF-kappaB": "protein", "AP-1": "protein" } }, { "input_text": "These data suggest that CD19 -mediated signal transduction activates different transcription factors at juxtaposed stages of B cell development that may culminate in the activation or suppression of distinct sets of genes .", "target_text": { "CD19": "protein", "transcription factors": "protein", "genes": "DNA" } }, { "input_text": "Oxidants , transcription factors , and intestinal inflammation .", "target_text": { "transcription factors": "protein" } }, { "input_text": "It is now well appreciated that chronic gut inflammation is characterized by enhanced production of reactive metabolites of oxygen and nitrogen .", "target_text": {} }, { "input_text": "Some of these oxidants are known to modulate the expression of a variety of genes that are involved in the immune and inflammatory responses .", "target_text": {} }, { "input_text": "For example , certain oxidants are known to activate the nuclear transcription factor kappa B , which regulates the expression of a variety of different adhesion molecules , cytokines , and enzymes .", "target_text": { "transcription factor": "protein", "nuclear transcription factor kappa B": "protein", "adhesion molecules": "protein", "cytokines": "protein", "enzymes": "protein" } }, { "input_text": "Oxidants are also known to activate another transcription factor , activator protein-1 .", "target_text": { "transcription factor": "protein", "activator protein-1": "protein" } }, { "input_text": "This transcription factor is composed of products from the fos and jun proto-oncogene family and is believed to be important in regulating cell growth and proliferation .", "target_text": { "transcription factor": "protein", "fos and jun proto-oncogene family": "protein" } }, { "input_text": "Finally , oxidants are believed to promote intestinal epithelial cell apoptosis , and the B-cell lymphoma/leukemia-2 gene product is believed to inhibit this phenomenon in an antioxidant-dependent manner .", "target_text": { "intestinal epithelial cell": "cell_type", "B-cell lymphoma/leukemia-2 gene product": "protein" } }, { "input_text": "Taken together , these observations suggest that nontoxic concentrations of reactive metabolites of oxygen and nitrogen play an important role in regulating the expression of genes involved in the inflammatory response and in modulating apoptosis .", "target_text": {} }, { "input_text": "Identification of target genes of the lymphoid-specific transcription factor Oct2 .", "target_text": { "target genes": "DNA", "transcription factor": "protein", "lymphoid-specific transcription factor Oct2": "protein" } }, { "input_text": "The Oct2 transcription factor is expressed predominantly in B lymphocytes and plays an essential role during the terminal phase of B cell differentiation .", "target_text": { "Oct2": "protein", "transcription factor": "protein", "lymphocytes": "cell_type", "B lymphocytes": "cell_type" } }, { "input_text": "The regulatory regions of several genes specifically expressed in B cells contain functional binding sites for Oct2 .", "target_text": { "regulatory regions": "DNA", "B cells": "cell_type", "functional binding sites": "DNA", "Oct2": "protein" } }, { "input_text": "Nevertheless , none of the genes originally thought to be regulated by Oct2 were affected in their expression in Oct2 -deficient B cells .", "target_text": { "Oct2": "protein", "B cells": "cell_type", "Oct2 -deficient B cells": "cell_line" } }, { "input_text": "In an attempt to find such elusive Oct2 target genes and to understand the molecular function of Oct2 in B cell development , we isolated cDNAs for Oct2 target genes .", "target_text": { "Oct2": "protein", "target genes": "DNA", "cDNAs": "DNA" } }, { "input_text": "So far , we have identified five potential targets for Oct2 : the membrane glycoprotein CD36 , the cysteine-rich secreted protein 3 ( CRISP-3 ) , a mouse homolog of the human monocyte/neutrophil elastase inhibitor ( mEI ) and two unknown cDNA sequences Nov1 and Nov2 .", "target_text": { "Oct2": "protein", "membrane glycoprotein": "protein", "CD36": "protein", "cysteine-rich secreted protein 3": "protein", "CRISP-3": "protein", "human monocyte/neutrophil elastase inhibitor": "protein", "mEI": "protein", "cDNA sequences": "DNA", "Nov1": "DNA", "Nov2": "DNA" } }, { "input_text": "These target genes show quite distinct expression patterns demonstrating that transcription factors in addition to Oct2 are involved in their regulation .", "target_text": { "target genes": "DNA", "transcription factors": "protein", "Oct2": "protein" } }, { "input_text": "Whereas CD36 and mEI were expressed in all hematopoetic cell lines containing Oct2 , .", "target_text": { "CD36": "protein", "mEI": "protein", "hematopoetic cell lines": "cell_line", "Oct2": "protein" } }, { "input_text": "CRISP-3 is pre-B cell-specific , Nov1 is plasma B cell-specific and Nov2 is B cell-specifically expressed .", "target_text": { "CRISP-3": "protein", "Nov1": "DNA", "Nov2": "DNA" } }, { "input_text": "RFX-B is the gene responsible for the most common cause of the bare lymphocyte syndrome , an MHC class II immunodeficiency [ published erratum appears in Immunity 1999 Mar ; 10 ( 3 ) : 399 ]", "target_text": { "RFX-B": "DNA", "MHC class II": "protein" } }, { "input_text": "The bare lymphocyte syndrome ( BLS ) is characterized by the absence of MHC class II transcription and humoral- and cellular- mediated immune responses to foreign antigens .", "target_text": { "MHC class II": "protein" } }, { "input_text": "Three of the four BLS genetic complementation groups have defects in the activity of the MHC class II transcription factor RFX .", "target_text": { "MHC class II transcription factor": "protein", "RFX": "protein" } }, { "input_text": "We have purified the RFX complex and sequenced its three subunits .", "target_text": { "RFX": "protein", "RFX complex": "protein" } }, { "input_text": "The sequence of the smallest subunit describes a novel gene , termed RFX-B .", "target_text": { "RFX-B": "DNA" } }, { "input_text": "RFX-B complements the predominant BLS complementation group ( group B ) and was found to be mutant in cell lines from this BLS group .", "target_text": { "RFX-B": "DNA", "BLS complementation group": "protein", "group B": "protein", "cell lines": "cell_line" } }, { "input_text": "The protein has no known DNA-binding domain but does contain three ankyrin repeats that are likely to be important in protein-protein interactions .", "target_text": { "DNA-binding domain": "protein" } }, { "input_text": "Binding of c-Rel to STAT5 target sequences in HTLV-I-transformed T cells .", "target_text": { "c-Rel": "protein", "STAT5 target sequences": "DNA", "HTLV-I-transformed T cells": "cell_type" } }, { "input_text": "The type I human T-cell leukemia virus ( HTLV-I ) induces abnormal growth and subsequent transformation of T cells , which is associated with the development of an acute T-cell malignancy termed adult T-cell leukemia .", "target_text": { "T cells": "cell_type" } }, { "input_text": "A characteristic of HTLV-I -transformed T cells is the constitutive nuclear expression of NF-kappaB/Rel family of transcription factors , which appears to be essential for the growth of these transformed cells .", "target_text": { "HTLV-I -transformed T cells": "cell_type", "NF-kappaB/Rel family": "protein", "transformed cells": "cell_type" } }, { "input_text": "Although NF-kappaB/Rel factors are known to induce the expression of T-cell growth factor interleukin ( IL ) -2 , it is unclear how they participate in the IL-2 -independent growth of HTLV-I -transformed cells .", "target_text": { "NF-kappaB/Rel factors": "protein", "T-cell growth factor interleukin ( IL ) -2": "protein", "IL-2": "protein", "-transformed cells": "cell_type", "HTLV-I -transformed cells": "cell_line" } }, { "input_text": "In this study , we show that certain NF-kappaB/Rel members , predominantly c-Rel , interact with enhancer sequences for STAT5 , a key transcription factor mediating IL-2 -induced T-cell proliferation .", "target_text": { "NF-kappaB/Rel members": "protein", "c-Rel": "protein", "STAT5": "protein", "IL-2": "protein" } }, { "input_text": "Reporter gene assays reveal that the binding of c-Rel to the STAT5 site present in the Fc gammaR1 gene leads to potent transactivation of this enhancer .", "target_text": { "c-Rel": "protein", "STAT5": "protein", "Fc gammaR1 gene": "DNA" } }, { "input_text": "Binding of c-Rel to the Fc gammaR1 STAT site also occurs in human peripheral blood T cells immortalized with HTLV-I in vitro and is correlated with enhanced levels of proliferation of these cells .", "target_text": { "c-Rel": "protein", "Fc gammaR1 STAT site": "DNA", "peripheral blood T cells": "cell_type" } }, { "input_text": "These results raise the possibility that NF-kappaB/Rel may participate in the growth control of HTLV-I -transformed T cells by regulating genes driven by both kappaB and certain STAT enhancers .", "target_text": { "NF-kappaB/Rel": "protein", "HTLV-I -transformed T cells": "cell_line", "kappaB": "DNA", "STAT enhancers": "DNA" } }, { "input_text": "Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment .", "target_text": { "human Fas promoter": "DNA", "NF-kappaB p50-p65": "protein" } }, { "input_text": "Fas ( CD95 ) and Fas ligand ( CD95L ) are an interacting receptor-ligand pair required for immune homeostasis .", "target_text": { "Fas": "protein", "CD95": "protein", "Fas ligand": "protein", "CD95L": "protein", "receptor-ligand pair": "protein" } }, { "input_text": "Lymphocyte activation results in the upregulation of Fas expression and the acquisition of sensitivity to FasL -mediated apoptosis .", "target_text": { "Fas": "protein", "FasL": "protein" } }, { "input_text": "Although Fas upregulation is central to the preservation of immunologic tolerance , little is known about the molecular machinery underlying this process .", "target_text": {} }, { "input_text": "To investigate the events involved in activation-induced Fas upregulation , we have examined mRNA accumulation , fas promoter activity , and protein expression in the Jurkat T-cell line treated with phorbol myristate acetate and ionomycin ( P/I ) , pharmacological mimics of T-cell receptor activation .", "target_text": { "Fas": "protein", "Jurkat T-cell line": "cell_line", "T-cell receptor": "protein" } }, { "input_text": "Although resting Jurkat cells express Fas , Fas mRNA was induced approximately 10-fold in 2 h upon P/I stimulation .", "target_text": { "resting Jurkat cells": "cell_line", "Fas": "protein", "Fas mRNA": "RNA" } }, { "input_text": "Using sequential deletion mutants of the human fas promoter in transient transfection assays , we identified a 47-bp sequence ( positions -306 to -260 relative to the ATG ) required for activation-driven fas upregulation .", "target_text": { "sequential deletion mutants": "DNA", "human fas promoter": "DNA", "47-bp sequence": "DNA", "positions -306 to -260": "DNA" } }, { "input_text": "Sequence analysis revealed the presence of a previously unrecognized composite binding site for both the Sp1 and NF-kappaB transcription factors at positions -295 to -286 .", "target_text": { "unrecognized composite binding site": "DNA", "Sp1": "protein", "NF-kappaB": "protein", "transcription factors": "protein", "positions -295 to -286": "DNA" } }, { "input_text": "Electrophoretic mobility shift assay ( EMSA ) and supershift analyses of this region documented constitutive binding of Sp1 in unactivated nuclear extracts and inducible binding of p50-p65 NF-kappaB heterodimers after P/I activation .", "target_text": { "Sp1": "protein", "NF-kappaB": "protein", "p50-p65 NF-kappaB heterodimers": "protein" } }, { "input_text": "Sp1 and NF-kappaB transcription factor binding was shown to be mutually exclusive by EMSA displacement studies with purified recombinant Sp1 and recombinant p50 .", "target_text": { "Sp1": "protein", "NF-kappaB": "protein", "p50": "protein" } }, { "input_text": "The functional contribution of the kappaB- Sp1 composite site in P/I -inducible fas promoter activation was verified by using kappaB- Sp1 concatamers ( -295 to -286 ) in a thymidine kinase promoter-driven reporter construct and native promoter constructs in Jurkat cells overexpressing IkappaB-alpha .", "target_text": { "Sp1": "protein", "kappaB- Sp1 composite site": "DNA", "P/I -inducible fas promoter": "DNA", "-295 to -286": "DNA", "thymidine kinase promoter-driven reporter construct": "DNA", "native promoter constructs": "DNA", "Jurkat cells": "cell_line", "IkappaB-alpha": "protein" } }, { "input_text": "Site-directed mutagenesis of the critical guanine nucleotides in the kappaB- Sp1 element documented the essential role of this site in activation-dependent fas promoter induction .", "target_text": { "Sp1": "protein", "kappaB- Sp1 element": "DNA" } }, { "input_text": "Evidence for repression of IL-2 gene activation in anergic T cells .", "target_text": { "IL-2 gene": "DNA", "anergic T cells": "cell_type" } }, { "input_text": "The induction of clonal anergy in a T cell inhibits IL-2 secretion because of the development of a proximal signal transduction defect .", "target_text": { "IL-2": "protein" } }, { "input_text": "Fusion of anergic murine T cells to human Jurkat T leukemia cells and formation of heterokaryons failed to result in a complementation of this signaling defect and restoration of murine IL-2 mRNA inducibility .", "target_text": { "anergic murine T cells": "cell_type", "human Jurkat T leukemia cells": "cell_type", "heterokaryons": "cell_line", "murine IL-2 mRNA": "RNA" } }, { "input_text": "Instead , signal transduction to the human IL-2 gene became disrupted .", "target_text": { "IL-2 gene": "DNA" } }, { "input_text": "Heterokaryons formed by the fusion of anergic murine T cells to normal murine T cells also failed to accumulate intracellular IL-2 protein in response to stimulation either with the combination of CD3 and CD28 mAbs or with ionomycin plus a protein kinase C -activating phorbol ester .", "target_text": { "Heterokaryons": "cell_line", "anergic murine T cells": "cell_type", "normal murine T cells": "cell_type", "intracellular IL-2 protein": "protein", "CD3": "protein", "CD28 mAbs": "protein", "protein kinase C": "protein" } }, { "input_text": "The results argue against a loss-of-function signaling defect as the sole basis for clonal anergy induction and document the presence of a dominant-acting repressor molecule that inhibits signal transduction to the IL-2 gene within viable anergic T cells .", "target_text": { "dominant-acting repressor molecule": "protein", "IL-2 gene": "DNA", "anergic T cells": "cell_type" } }, { "input_text": "Comparison of HTLV-I basal transcription and expression of CREB/ATF-1/CREM family members in peripheral blood mononuclear cells and Jurkat T cells .", "target_text": { "CREB/ATF-1/CREM family members": "protein", "peripheral blood mononuclear cells": "cell_type", "Jurkat T cells": "cell_line" } }, { "input_text": "HTLV-I is the etiologic agent of adult T-cell leukemia /lymphoma and is associated with tropical spastic paraparesis/ HTLV-I -associated myelopathy .", "target_text": {} }, { "input_text": "Following integration into the host cell genome , HTLV-I replication is regulated by both host and viral mechanisms that control transcription .", "target_text": {} }, { "input_text": "Low levels of viral transcription ( basal transcription ) occur before expression of the virally encoded Tax protein ( Tax -mediated transcription ) .", "target_text": { "virally encoded Tax protein": "protein", "Tax": "protein" } }, { "input_text": "Members of the cyclic adenosine monophosphate ( cAMP ) response element binding ( CREB ) /activating transcription factor 1 ( ATF-1 ) family of transcription factors bind three 21-bp repeats ( Tax-responsive element-1 , or TRE-1 ) within the viral promoter and are important for basal and Tax-mediated transcription .", "target_text": { "cyclic adenosine monophosphate ( cAMP ) response element": "DNA", "ATF-1": "protein", "cyclic adenosine monophosphate ( cAMP ) response element binding ( CREB ) /activating transcription factor 1 ( ATF-1 ) family": "protein", "transcription factors": "protein", "21-bp repeats": "DNA", "Tax-responsive element-1": "DNA", "TRE-1": "DNA", "viral promoter": "DNA" } }, { "input_text": "Using mitogen stimulated and quiescent peripheral blood mononuclear cells ( PBMC ) and Jurkat cells , we compared differences in basal transcription and amounts and binding of transcription factors with TRE-1 .", "target_text": { "peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type", "Jurkat cells": "cell_line", "transcription factors": "protein", "TRE-1": "DNA" } }, { "input_text": "We demonstrate that amounts of transcriptionally active phosphorylated CREB protein ( P-CREB ) differ between activated PBMC and Jurkat cells .", "target_text": { "phosphorylated CREB protein": "protein", "P-CREB": "protein", "PBMC": "cell_type", "Jurkat cells": "cell_line" } }, { "input_text": "Following stimulation , P-CREB levels remain elevated in PBMC for up to 24 hours whereas CREB is dephosphorylated in Jurkat cells within 4 hours following stimulation .", "target_text": { "P-CREB": "protein", "PBMC": "cell_type", "Jurkat cells": "cell_line" } }, { "input_text": "The differences in P-CREB levels between PBMC and Jurkat cells were directly correlated with basal transcription of HTLV-I in the two cell types .", "target_text": { "P-CREB": "protein", "PBMC": "cell_type", "Jurkat cells": "cell_line" } }, { "input_text": "Using electrophoretic mobility shift assays , we determined that the pattern of band migration differed between the two cell types .", "target_text": {} }, { "input_text": "These data demonstrate that PBMC differentially regulate basal HTLV-I transcription compared with Jurkat T cells , and this differential regulation is due , in part to differential phosphorylation and binding of CREB/ATF-1 to TRE-1 in the HTLV-I promoter .", "target_text": { "PBMC": "cell_type", "Jurkat T cells": "cell_line", "CREB/ATF-1": "protein", "TRE-1": "DNA" } }, { "input_text": "We demonstrate the utility of using primary lymphocyte models to study HTLV-I transcription in the context of cell signaling and suggest that activated PBMC maintain elevated levels of P-CREB , which promote basal HTLV-I transcription and enhance viral persistence in vivo .", "target_text": { "PBMC": "cell_type", "P-CREB": "protein" } }, { "input_text": "Anoxia/reoxygenation-induced tolerance with respect to polymorphonuclear leukocyte adhesion to cultured endothelial cells .", "target_text": { "cultured endothelial cells": "cell_line" } }, { "input_text": "A nuclear factor-kappaB -mediated phenomenon .", "target_text": { "nuclear factor-kappaB": "protein" } }, { "input_text": "Exposing human umbilical vein endothelial cells ( HUVECs ) to anoxia/reoxygenation ( A/R ) results in an increase in polymorphonuclear leukocyte ( PMN ) adhesion to HUVECs .", "target_text": { "human umbilical vein endothelial cells": "cell_line", "HUVECs": "cell_line", "PMN": "cell_type" } }, { "input_text": "This A/R -induced hyperadhesion is completely prevented by a previous ( 24 hours earlier ) exposure of HUVECs to A/R .", "target_text": { "HUVECs": "cell_line" } }, { "input_text": "This phenomenon has been termed \" A/R tolerance . \"", "target_text": {} }, { "input_text": "Exposing HUVECs to A/R induces an increase in nuclear factor kappaB ( NF-kappaB ) in HUVEC nuclei within 4 hours .", "target_text": { "HUVECs": "cell_line", "nuclear factor kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "Interfering with either NF-kappaB activation ( proteasome inhibitor ) or translocation ( double-stranded oligonucleotides containing NF-kappaB binding sequence ) prevents the development of A/R tolerance ( ie , the increase in A/R -induced PMN adhesion to HUVECs is the same after the first and second A/R challenges ) .", "target_text": { "NF-kappaB": "protein", "proteasome": "protein", "NF-kappaB binding sequence": "DNA", "HUVECs": "cell_line" } }, { "input_text": "NO production by HUVECs is increased after the second A/R challenge , but not after the first A/R challenge .", "target_text": { "HUVECs": "cell_line" } }, { "input_text": "Inhibition of NO synthase ( NOS ) during the second A/R challenge prevents the development of A/R tolerance with respect to PMN adhesion .", "target_text": { "NO synthase": "protein", "NOS": "protein" } }, { "input_text": "However , while HUVECs contained endothelial NOS protein , no inducible NOS was detected in either tolerant or nontolerant cells .", "target_text": { "HUVECs": "cell_line", "NOS protein": "protein", "NOS": "protein", "nontolerant cells": "cell_type" } }, { "input_text": "Further studies indicated that inhibition of GTP-cyclohydrolase I ( an enzyme involved in de novo synthesis of an important cofactor for NOS activity , tetrahydrobiopterin ) prevented the generation of NO in A/R -tolerant cells .", "target_text": { "GTP-cyclohydrolase I": "protein", "NOS": "protein", "A/R -tolerant cells": "cell_line" } }, { "input_text": "Extracellular generation of NO ( NO donor ) did not effect the hyperadhesion response induced by the initial A/R challenge .", "target_text": {} }, { "input_text": "A/R also induced an oxidant stress in naive HUVECs , but not in A/R -tolerant HUVECs .", "target_text": { "HUVECs": "cell_line", "A/R -tolerant HUVECs": "cell_line" } }, { "input_text": "Inhibition of NOS during the second A/R insult results in the generation of an oxidant stress similar to that observed after the first A/R challenge .", "target_text": { "NOS": "protein" } }, { "input_text": "Taken together , the findings of the present study are consistent with a role for NF-kappaB in the development of A/R tolerance ( with respect to PMN adhesion ) , perhaps by transcriptional regulation of GTP -cyclohydrolase .", "target_text": { "NF-kappaB": "protein", "PMN": "cell_type", "GTP -cyclohydrolase": "protein" } }, { "input_text": "The increased NO production during the second A/R insult reduces PMN adhesion most likely by reducing the intracellular oxidant stress induced by A/R .", "target_text": {} }, { "input_text": "Mildly oxidized low-density lipoproteins decrease early production of interleukin 2 and nuclear factor kappaB binding to DNA in activated T- lymphocytes .", "target_text": { "low-density lipoproteins": "protein", "interleukin 2": "protein", "nuclear factor kappaB": "protein", "activated T- lymphocytes": "cell_type" } }, { "input_text": "Activated T-lymphocytes are found early in atherosclerosis lesions , but little is known about their role .", "target_text": {} }, { "input_text": "Oxidized low-density lipoproteins ( oxLDLs ) are considered to be involved in the pathogenesis of the lesions , and we have previously demonstrated that oxLDLs inhibit not only interleukin ( IL ) -2-receptor expression on the surface of in vitro-activated T-lymphocytes but also their proliferation .", "target_text": { "low-density lipoproteins": "protein", "oxLDLs": "protein", "interleukin ( IL ) -2-receptor": "protein" } }, { "input_text": "We have now investigated the effect of oxLDLs on blast differentiation , on IL-2 synthesis and on the activation of the nuclear factor kappaB ( NF-kappaB ) system in activated lymphocytes .", "target_text": { "oxLDLs": "protein", "IL-2": "protein", "nuclear factor kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "Mildly oxLDLs ( 50 and 100 microgram/ml ) decreased the number of lymphoblasts and the level of IL-2 concentration in the culture supernatants after activation of lymphocytes by phytohaemagglutinin and PMA+ ionomycin .", "target_text": { "oxLDLs": "protein", "lymphoblasts": "cell_type", "lymphocytes": "cell_type", "phytohaemagglutinin": "protein" } }, { "input_text": "The inhibition of IL-2 production was observed in the CD3 (+) T-lymphocyte cytoplasm as early as 4 h after activation by PMA+ ionomycin .", "target_text": { "IL-2": "protein", "CD3": "protein" } }, { "input_text": "The study of NF-kappaB showed that oxLDLs led to a decrease of activation-induced p65/ p50 NF-kappaB heterodimer binding to DNA , whereas the presence of the constitutive nuclear form of p50 dimer was unchanged .", "target_text": { "NF-kappaB": "protein", "oxLDLs": "protein", "p50": "protein", "activation-induced p65/ p50": "protein", "p50 dimer": "protein" } }, { "input_text": "This was correlated with an unchanged level of the active form of the cytosolic inhibitor protein IkappaB-alpha .", "target_text": { "cytosolic inhibitor protein": "protein", "IkappaB-alpha": "protein" } }, { "input_text": "Taken together , these observations suggest that the immunosuppressive effect of oxLDLs might operate via a dysregulation of the T-lymphocyte activation mechanisms .", "target_text": { "oxLDLs": "protein", "T-lymphocyte": "cell_type" } }, { "input_text": "The B29 ( immunoglobulin beta-chain ) gene is a genetic target for early B-cell factor .", "target_text": { "immunoglobulin beta-chain": "protein", "B29 ( immunoglobulin beta-chain ) gene": "DNA", "early B-cell factor": "protein" } }, { "input_text": "Early B-cell factor ( EBF ) is a transcription factor suggested as essential for early B-lymphocyte development by findings in mice where the coding gene has been inactivated by homologous disruption .", "target_text": { "Early B-cell factor": "protein", "EBF": "protein", "transcription factor": "protein", "B-lymphocyte": "cell_type" } }, { "input_text": "This makes the identification of genetic targets for this transcription factor pertinent for the understanding of early B-cell development .", "target_text": { "transcription factor": "protein" } }, { "input_text": "The lack of B29 transcripts , coding for the beta subunit of the B-cell receptor complex , in pro-B cells from EBF -deficient mice suggested that B29 might be a genetic target for EBF .", "target_text": { "B29 transcripts": "RNA", "beta subunit": "protein", "pro-B cells": "cell_type", "EBF": "protein" } }, { "input_text": "We here present data suggesting that EBF interacts with three independent sites within the mouse B29 promoter .", "target_text": { "EBF": "protein", "B29 promoter": "DNA", "mouse B29 promoter": "DNA" } }, { "input_text": "Furthermore , ectopic expression of EBF in HeLa cells activated a B29 promoter -controlled reporter construct 13-fold and induced a low level of expression from the endogenous B29 gene .", "target_text": { "EBF": "protein", "HeLa cells": "cell_line", "B29": "DNA", "B29 promoter": "DNA", "B29 promoter -controlled reporter construct": "DNA", "endogenous B29 gene": "DNA" } }, { "input_text": "Finally , mutations in the EBF binding sites diminished B29 promoter activity in pre-B cells while the same mutations did not have as striking an effect on the promoter function in B-cell lines of later differentiation stages .", "target_text": { "EBF": "protein", "B29": "DNA", "B29 promoter": "DNA", "pre-B cells": "cell_type", "B-cell lines": "cell_line" } }, { "input_text": "These data suggest that the B29 gene is a genetic target for EBF in early B-cell development .", "target_text": { "B29": "DNA", "B29 gene": "DNA", "EBF": "protein" } }, { "input_text": "Delta-opioid receptors expressed by Jurkat T cells enhance IL-2 secretion by increasing AP-1 complexes and activity of the NF-AT/AP-1-binding promoter element .", "target_text": { "Jurkat T cells": "cell_line", "IL-2": "protein", "AP-1 complexes": "protein", "NF-AT/AP-1-binding promoter element": "DNA" } }, { "input_text": "Recent molecular evidence points to transient and/or stage-specific expression of delta- and kappa- opioid receptors by thymic and peripheral T lymphocytes .", "target_text": {} }, { "input_text": "Since medical treatments or stress commonly increase opioid levels , it is important to understand the mechanisms by which opioids affect T lymphocyte functions .", "target_text": {} }, { "input_text": "We therefore created and studied a T cell line expressing the cloned delta-opioid receptor ( DOR1 ) .", "target_text": { "T cell line": "cell_line", "cloned delta-opioid receptor": "protein", "DOR1": "protein" } }, { "input_text": "DOR1 ligation by a specific DOR1 agonist , deltorphin , augmented IL-2 secretion by synergizing with signals from TCR- CD3 and CD28 .", "target_text": { "DOR1": "protein", "IL-2": "protein", "CD3": "protein", "TCR- CD3": "protein", "CD28": "protein" } }, { "input_text": "Reporter gene constructs were used to map this effect of deltorphin to the AP-1- and NF-AT/AP-1- binding sites of the IL-2 promoter .", "target_text": { "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Although DOR1 signaling increased [ Ca2+ ]i , deltorphin enhanced transcriptional activity of the NF-AT/AP-1-binding site via a mechanism independent of calcineurin and distinct from the effects of elevated [ Ca2+ ]i .", "target_text": { "DOR1": "protein", "NF-AT/AP-1-binding site": "DNA", "calcineurin": "protein" } }, { "input_text": "Deltorphin also increased accumulation of AP-1 transcription factor complexes , suggesting that DOR1 augments IL-2 secretion by increasing the AP-1 component of the NF-AT/AP-1 transcription factor .", "target_text": { "transcription factor": "protein", "AP-1 transcription factor complexes": "protein", "DOR1": "protein", "IL-2": "protein", "AP-1 component": "protein", "NF-AT/AP-1 transcription factor": "protein" } }, { "input_text": "These results advance the molecular understanding of opioid effects on lymphocytes , and in addition , demonstrate regulation of IL-2 synthesis and secretion by the novel mechanism of receptor-mediated AP-1 induction .", "target_text": { "lymphocytes": "cell_type", "IL-2": "protein", "AP-1": "protein" } }, { "input_text": "Induction of interleukin-12 p40 transcript by CD40 ligation via activation of nuclear factor-kappaB .", "target_text": { "interleukin-12": "protein", "p40": "protein", "p40 transcript": "RNA", "CD40": "protein", "nuclear factor-kappaB": "protein" } }, { "input_text": "Interleukin-12 is produced in response to infection with bacteria or parasites or to bacterial constituents such as LPS in monocytes/macrophages and dendritic cells , and also generated by the interaction between activated T cells and antigen-presenting cells via CD40 -CD40 ligand ( CD40L ) .", "target_text": { "Interleukin-12": "protein", "monocytes/macrophages": "cell_type", "dendritic cells": "cell_type", "activated T cells": "cell_type", "antigen-presenting cells": "cell_type", "CD40": "protein", "-CD40": "protein", "CD40 -CD40 ligand": "protein", "CD40L": "protein" } }, { "input_text": "So far , transcriptional analyses of p40 have been carried out only using bacterial constituents such as LPS as stimuli .", "target_text": { "p40": "protein" } }, { "input_text": "In the present study , we have characterized the transcriptional induction of p40 by CD40 ligation in a human B lymphoblastoid cell line , Daudi , and a human acute monocytic leukemia cell line , THP-1 .", "target_text": { "p40": "protein", "CD40": "protein", "human B lymphoblastoid cell line": "cell_line", "Daudi": "cell_line", "human acute monocytic leukemia cell line": "cell_line", "THP-1": "cell_line" } }, { "input_text": "These cells , stimulated by an agonistic monoclonal antibody against CD40 or by transfection with a CD40L expression vector , secreted p40 and showed enhanced p40 mRNA expression .", "target_text": { "CD40": "protein", "CD40L": "protein", "CD40L expression vector": "DNA", "p40": "protein", "p40 mRNA": "RNA" } }, { "input_text": "Sequence analysis of the p40 promoter region identified two potential nuclear factor ( NF ) -kappaB binding sites conserved between mouse and human .", "target_text": { "p40": "protein", "p40 promoter region": "DNA", "potential nuclear factor ( NF ) -kappaB binding sites": "DNA" } }, { "input_text": "Electrophoretic mobility shift assay revealed that the potential NF-kappaB binding sequence which is located around 120 bp upstream of the transcription initiation site in murine and human p40 genes formed an NF-kappaB complex with nuclear extract from Daudi cells stimulated by CD40 ligation .", "target_text": { "NF-kappaB": "protein", "NF-kappaB binding sequence": "DNA", "120 bp upstream": "DNA", "transcription initiation site": "DNA", "NF-kappaB complex": "protein", "Daudi cells": "cell_line", "CD40": "protein" } }, { "input_text": "Moreover , transfection of Daudi cells with the polymerized NF-kappaB binding sequence ligated to a thymidine kinase /chloramphenicol acetyltransferase ( CAT ) reporter plasmid greatly induced CAT activity , but transfection with the polymerized mutated NF-kappaB binding sequence did not .", "target_text": { "Daudi cells": "cell_line", "NF-kappaB": "protein", "NF-kappaB binding sequence": "DNA", "thymidine kinase": "protein", "/chloramphenicol acetyltransferase": "protein", "CAT": "protein", "thymidine kinase /chloramphenicol acetyltransferase ( CAT ) reporter plasmid": "DNA", "polymerized mutated NF-kappaB binding sequence": "DNA" } }, { "input_text": "These results suggest that the NF-kappaB binding site located around 120 bp upstream of the transcription initiation site in murine and human p40 promoter regions could be important for the p40 induction by CD40 ligation via activation of NF-kappaB .", "target_text": { "NF-kappaB": "protein", "NF-kappaB binding site": "DNA", "transcription initiation site": "DNA", "p40": "protein", "CD40": "protein" } }, { "input_text": "High frequency of germ-line BRCA2 mutations among Hungarian male breast cancer patients without family history .", "target_text": { "BRCA2": "DNA" } }, { "input_text": "To determine the contribution of BRCA1 and BRCA2 mutations to the pathogenesis of male breast cancer in Hungary , the country with the highest male breast cancer mortality rates in continental Europe , a series of 18 male breast cancer patients and three patients with gynecomastia was analyzed for germ-line mutations in both BRCA1 and BRCA2 .", "target_text": { "BRCA1": "DNA", "BRCA2": "DNA" } }, { "input_text": "Although no germ-line BRCA1 mutation was observed , 6 of the 18 male breast cancer cases ( 33 % ) carried truncating mutations in the BRCA2 gene .", "target_text": { "BRCA1": "DNA", "BRCA2": "DNA" } }, { "input_text": "Unexpectedly , none of them reported a family history for breast/ovarian cancer .", "target_text": {} }, { "input_text": "Four of six truncating mutations were novel , and two mutations were recurrent .", "target_text": {} }, { "input_text": "Four patients ( 22 % ) had a family history of breast/ovarian cancer in at least one first- or second-degree relative ; however , no BRCA2 mutation was identified among them .", "target_text": { "BRCA2": "DNA" } }, { "input_text": "No mutation was identified in either of the genes in the gynecomastias .", "target_text": {} }, { "input_text": "These results provide evidence for a strong genetic component of male breast cancer in Hungary .", "target_text": {} }, { "input_text": "T-cell expression of the human GATA-3 gene is regulated by a non-lineage-specific silencer .", "target_text": { "human GATA-3 gene": "DNA", "non-lineage-specific silencer": "DNA" } }, { "input_text": "The GATA-3 transcription factor is required for development of the T-cell lineage and Th2 cytokine gene expression in CD4 T-cells .", "target_text": { "GATA-3 transcription factor": "protein", "T-cell lineage": "cell_line", "Th2 cytokine gene": "DNA", "CD4 T-cells": "cell_type" } }, { "input_text": "We have mapped the DNase-I-hypersensitive ( HS ) regions of the human GATA-3 gene in T-cells and non-T-cells and studied their transcriptional activities .", "target_text": { "DNase-I-hypersensitive ( HS ) regions": "DNA", "human GATA-3 gene": "DNA", "T-cells": "cell_type", "non-T-cells": "cell_type" } }, { "input_text": "HS I-III , located 5' from the transcriptional initiation site , were found in hematopoietic and non-hematopoietic cells , whereas HS IV-VII , located 3' from the transcriptional start site , were exclusively observed in T-cells .", "target_text": { "HS I-III": "DNA", "transcriptional initiation site": "DNA", "HS IV-VII": "DNA", "transcriptional start site": "DNA", "T-cells": "cell_type" } }, { "input_text": "Among these hypersensitive sites , two transcriptional control elements were found , one in the first intron of the GATA-3 gene and the other between 8.3 and 5.9 kilobases 5' from the GATA-3 transcriptional initiation site .", "target_text": { "hypersensitive sites": "DNA", "transcriptional control elements": "DNA", "first intron": "DNA", "GATA-3 gene": "DNA", "between 8.3 and 5.9 kilobases": "DNA", "transcriptional initiation site": "DNA", "GATA-3 transcriptional initiation site": "DNA" } }, { "input_text": "The first intron acted as a strong transcriptional activator in a position-dependent manner and with no cell-type specificity .", "target_text": { "first intron": "DNA" } }, { "input_text": "The upstream regulatory element could confer T-cell specificity to the GATA-3 promoter activity , and analysis of this region revealed a 707-base pair silencer that drastically inhibited GATA-3 promoter activity in non- T-cells .", "target_text": { "upstream regulatory element": "DNA", "GATA-3 promoter": "DNA", "707-base pair silencer": "DNA", "T-cells": "cell_type", "non- T-cells": "cell_type" } }, { "input_text": "Two CAGGTG E-boxes , located at the 5'- and 3'- ends of the silencer , were necessary for this silencer activity .", "target_text": { "CAGGTG E-boxes": "DNA" } }, { "input_text": "The 3'-CAGGTG E-box could bind USF proteins , the ubiquitous repressor ZEB , or the basic helix-loop-helix proteins E2A and HEB , and we showed that a competition between ZEB and E2A /HEB proteins is involved in the silencer activity .", "target_text": { "3'-CAGGTG E-box": "DNA", "USF proteins": "protein", "ubiquitous repressor": "protein", "ZEB": "protein", "basic helix-loop-helix proteins": "protein", "E2A": "protein", "HEB": "protein", "E2A /HEB proteins": "protein" } }, { "input_text": "Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity .", "target_text": { "NF-kappaB": "protein", "interleukin-1beta": "protein", "5-lipoxygenase": "protein" } }, { "input_text": "We previously reported that the role of reactive oxygen intermediates ( ROIs ) in NF-kappaB activation by proinflammatory cytokines was cell specific .", "target_text": { "NF-kappaB": "protein", "proinflammatory cytokines": "protein" } }, { "input_text": "However , the sources for ROIs in various cell types are yet to be determined and might include 5-lipoxygenase ( 5-LOX ) and NADPH oxidase .", "target_text": { "5-lipoxygenase": "protein", "5-LOX": "protein" } }, { "input_text": "5-LOX and 5-LOX activating protein ( FLAP ) are coexpressed in lymphoid cells but not in monocytic or epithelial cells .", "target_text": { "5-LOX": "protein", "5-LOX activating protein": "protein", "FLAP": "protein", "lymphoid cells": "cell_type" } }, { "input_text": "Stimulation of lymphoid cells with interleukin-1beta ( IL-1beta ) led to ROI production and NF-kappaB activation , which could both be blocked by antioxidants or FLAP inhibitors , confirming that 5-LOX was the source of ROIs and was required for NF-kappaB activation in these cells .", "target_text": { "lymphoid cells": "cell_type", "interleukin-1beta": "protein", "IL-1beta": "protein", "NF-kappaB": "protein", "FLAP": "protein", "5-LOX": "protein" } }, { "input_text": "IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappaB induction was not influenced by 5-LOX inhibitors .", "target_text": { "IL-1beta": "protein", "epithelial cells": "cell_type", "NF-kappaB": "protein", "5-LOX": "protein" } }, { "input_text": "However , reintroduction of a functional 5-LOX system in these cells allowed ROI production and 5-LOX -dependent NF-kappaB activation .", "target_text": { "5-LOX": "protein", "NF-kappaB": "protein" } }, { "input_text": "In monocytic cells , IL-1beta treatment led to a production of ROIs which is independent of the 5-LOX enzyme but requires the NADPH oxidase activity .", "target_text": { "monocytic cells": "cell_type", "IL-1beta": "protein", "5-LOX": "protein", "5-LOX enzyme": "protein" } }, { "input_text": "This pathway involves the Rac1 and Cdc42 GTPases , two enzymes which are not required for NF-kappaB activation by IL-1beta in epithelial cells .", "target_text": { "Rac1": "protein", "Cdc42": "protein", "GTPases": "protein", "NF-kappaB": "protein", "IL-1beta": "protein", "epithelial cells": "cell_type" } }, { "input_text": "In conclusion , three different cell-specific pathways lead to NF-kappaB activation by IL-1beta : a pathway dependent on ROI production by 5-LOX in lymphoid cells , an ROI- and 5-LOX -independent pathway in epithelial cells , and a pathway requiring ROI production by NADPH oxidase in monocytic cells .", "target_text": { "NF-kappaB": "protein", "IL-1beta": "protein", "5-LOX": "protein", "lymphoid cells": "cell_type", "epithelial cells": "cell_type", "NADPH oxidase": "protein", "monocytic cells": "cell_type" } }, { "input_text": "Cutting edge : dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis .", "target_text": { "Ile50Val variant": "protein", "human IL-4 receptor alpha-chain": "protein", "IgE": "protein" } }, { "input_text": "Two variants of the IL-4R alpha-chain ( IL-4Ralpha ) gene have been recently identified in association with different atopic disorders .", "target_text": { "IL-4R alpha-chain": "protein", "IL-4Ralpha": "protein", "IL-4R alpha-chain ( IL-4Ralpha ) gene": "DNA" } }, { "input_text": "To clarify the etiological relationship between the two variants , we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551 .", "target_text": { "IL-4": "protein", "IL-4Ralpha": "protein", "50": "protein", "551": "protein" } }, { "input_text": "The substitution of Ile for Val augmented STAT6 activation , proliferation , and transcription activity of the Iepsilon promoter by IL-4 , whereas that of Arg for Gln did not change these IL-4 signals .", "target_text": { "STAT6": "protein", "Iepsilon promoter": "DNA", "IL-4": "protein" } }, { "input_text": "Arg551 was not associated with atopic asthma in the Japanese population .", "target_text": {} }, { "input_text": "CD23 expression and IgE synthesis by IL-4 were augmented in Ile50 -bearing PBMC , compared with those bearing Val50 .", "target_text": { "CD23": "protein", "IgE": "protein", "IL-4": "protein", "Ile50 -bearing PBMC": "cell_line" } }, { "input_text": "Taken together , substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript , whereas the substitution of Ile50 contributes to enhancement of IgE synthesis .", "target_text": { "IL-4": "protein", "IgE": "protein" } }, { "input_text": "A novel growth-factor-dependent myeloid cell line derived from mouse bone marrow cells contains progenitors endowed with high proliferative potential .", "target_text": { "growth-factor-dependent myeloid cell line": "cell_line", "mouse bone marrow cells": "cell_type" } }, { "input_text": "Constitutive expression of human colony-stimulating factor-1 receptor ( CSF-1R ) confers long-lasting CSF-1 -dependent proliferation to mouse myeloid cell lines .", "target_text": { "human colony-stimulating factor-1 receptor": "protein", "CSF-1R": "protein", "CSF-1": "protein", "mouse myeloid cell lines": "cell_line" } }, { "input_text": "We developed mice transgenic for human CSF-1R because mouse CSF-1 can not activate human CSF-1R .", "target_text": { "CSF-1R": "protein", "CSF-1": "protein" } }, { "input_text": "Then bone marrow cells from transgenic mice were plated onto MS-5 stromal cells expressing the membrane form of human CSF-1 ( 2M-1 cells ) in order to combine the hematopoietic supporting properties of stromal cells and the proliferative effects of CSF-1 .", "target_text": { "bone marrow cells": "cell_type", "membrane form": "protein", "CSF-1": "protein", "human CSF-1": "protein", "2M-1 cells": "cell_line", "stromal cells": "cell_type" } }, { "input_text": "Thus , we were able to derive a hematopoietic cell line , called 47.10 , that grew indefinitely under these conditions , whereas no cell line could be developed from nontransgenic mice .", "target_text": { "hematopoietic cell line": "cell_line", "47.10": "cell_line" } }, { "input_text": "Proliferation of 47.10 cells is severely affected by neutralizing anti- CSF-1R monoclonal antibodies .", "target_text": { "47.10 cells": "cell_line", "CSF-1R": "protein", "anti- CSF-1R monoclonal antibodies": "protein" } }, { "input_text": "Morphologic and cytofluorometry analysis established that most 47.10 cells are immature myelomonocytic cells .", "target_text": { "47.10 cells": "cell_line", "immature myelomonocytic cells": "cell_type" } }, { "input_text": "Consistent with this phenotype , the myeloid transcription factor PU.1 , but not the erythroid transcription factor GATA-1 , is expressed in 47.10 cells .", "target_text": { "PU.1": "protein", "myeloid transcription factor PU.1": "protein", "GATA-1": "protein", "erythroid transcription factor GATA-1": "protein", "47.10 cells": "cell_line" } }, { "input_text": "A few 47.10 cells ( 3-5 % ) do not express lineage specific markers ; they differentiate spontaneously to lineage-positive cells after replating on 2M-1 cells .", "target_text": { "47.10 cells": "cell_line", "lineage-positive cells": "cell_line", "2M-1 cells": "cell_line" } }, { "input_text": "In agar cultures , 47.10 cells form 7- and 14-day colonies in response to a cocktail of granulocyte/macrophage colony-stimulating factor ( 2.5 ng/mL ) , interleukin-3 ( 1 ng/mL ) , and mouse CSF-1 ( 10 ng/mL ) .", "target_text": { "47.10 cells": "cell_line", "granulocyte/macrophage colony-stimulating factor": "protein", "interleukin-3": "protein", "CSF-1": "protein" } }, { "input_text": "Under these conditions , about 0.5 % of 47.10 cells formed large 14-day colonies ( > 1 mm ) composed of mature monocytes and granulocytes , reflecting the presence of progenitors endowed with high proliferative potential ( HPP- 47.10 cells ) .", "target_text": { "47.10 cells": "cell_line", "mature monocytes": "cell_type", "granulocytes": "cell_type", "HPP- 47.10 cells": "cell_line" } }, { "input_text": "In conclusion , we have characterized a novel continuous myeloid cell line presenting a hierarchical structure similar to that of the bone marrow progenitor cell compartment .", "target_text": { "continuous myeloid cell line": "cell_line", "bone marrow progenitor cell compartment": "cell_line" } }, { "input_text": "Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation .", "target_text": { "IL-4": "protein", "transcription factor": "protein", "JunB": "protein" } }, { "input_text": "The molecular basis for restricted cytokine expression by T helper 1 ( Th1 ) and T helper 2 ( Th2 ) cells is unclear .", "target_text": { "cytokine": "protein" } }, { "input_text": "Previous studies found that P1 , an element of the interleukin 4 ( IL-4 ) promoter that binds AP-1 , is important for Th2-restricted IL-4 expression .", "target_text": { "P1": "DNA", "IL-4": "protein", "interleukin 4 ( IL-4 ) promoter": "DNA" } }, { "input_text": "Here we show that JunB , but not the other Jun family members , was selectively induced in Th2 cells and not in Th1 cells during differentiation .", "target_text": { "JunB": "protein", "Jun family members": "protein", "Th2 cells": "cell_type", "Th1 cells": "cell_type" } }, { "input_text": "JunB has previously been considered to be a negative regulator of transcription .", "target_text": { "JunB": "protein" } }, { "input_text": "However , we show that JunB binds directly to the P1 site and synergizes with c-Maf to activate an IL-4 luciferase reporter gene .", "target_text": { "JunB": "protein", "P1 site": "DNA", "c-Maf": "protein", "IL-4": "protein", "IL-4 luciferase reporter gene": "DNA" } }, { "input_text": "JunB -control of IL-4 expression is mediated by the phosphorylation of JunB at Thr 102 and - 104 by JNK MAP kinase .", "target_text": { "JunB": "protein", "IL-4": "protein", "JNK MAP kinase": "protein" } }, { "input_text": "The synergy between c-Maf and JunB can be attributed to cooperative DNA binding , which is facilitated by JunB phosphorylation .", "target_text": { "c-Maf": "protein", "JunB": "protein" } }, { "input_text": "In transgenic mice , elevated JunB levels caused increased expression of several Th2 cytokines in developing Th1 cells .", "target_text": { "JunB": "protein", "Th2 cytokines": "protein", "Th1 cells": "cell_type" } }, { "input_text": "JunB also upregulated IL-4 expression in response to immunization .", "target_text": { "JunB": "protein", "IL-4": "protein" } }, { "input_text": "Thus , the early increase of JunB protein in Th2 cells can provide the specificity for c-Maf in IL-4 expression during T cell development and directs thereby Th2 differentiation .", "target_text": { "JunB": "protein", "Th2 cells": "cell_type", "c-Maf": "protein", "IL-4": "protein" } }, { "input_text": "Human T-cell leukemia virus type 1 tax protein abrogates interleukin-2 dependence in a mouse T-cell line .", "target_text": { "Human T-cell leukemia virus type 1 tax protein": "protein", "interleukin-2": "protein", "mouse T-cell line": "cell_line" } }, { "input_text": "Human T-cell leukemia virus type 1 ( HTLV-1 ) is the etiologic agent of adult T-cell leukemia .", "target_text": {} }, { "input_text": "Tax , the viral protein , is thought to be crucial in the development of the disease , since it transforms healthy T cells in vitro and induces tumors in transgenic animals .", "target_text": { "Tax": "protein", "viral protein": "protein", "healthy T cells": "cell_type" } }, { "input_text": "We examined the effect of Tax activity on the growth of the interleukin-2 ( IL-2 ) -dependent T-cell line CTLL-2 .", "target_text": { "Tax": "protein", "interleukin-2 ( IL-2 ) -dependent T-cell line": "cell_line", "CTLL-2": "cell_line" } }, { "input_text": "Stable expression of Tax in CTLL-2 transformed cell growth from being IL-2 dependent to IL-2 independent .", "target_text": { "Tax": "protein", "CTLL-2": "cell_line", "IL-2": "protein" } }, { "input_text": "Tax stimulated transcription through NF-kappaB and the cyclic AMP -responsive element-like sequence in the HTLV-1 promoter .", "target_text": { "Tax": "protein", "NF-kappaB": "protein", "cyclic AMP -responsive element-like sequence": "DNA" } }, { "input_text": "The finding of Tax mutants segregating these two pathways suggested that the NF-kappaB pathway was essential for IL-2 -independent growth of CTLL-2 cells while the CRE pathway was unnecessary .", "target_text": { "Tax": "protein", "NF-kappaB": "protein", "IL-2": "protein", "CTLL-2 cells": "cell_type", "CRE": "DNA" } }, { "input_text": "However , both pathways were necessary for another transformation-related activity ( colony formation in soft agar ) of CTLL-2/ Tax .", "target_text": { "Tax": "protein", "CTLL-2/ Tax": "protein" } }, { "input_text": "Our results show that Tax has at least two distinct activities on T cells , and suggest that Tax plays a crucial role in IL-2 -independent T-cell transformation induced by HTLV-1 , in addition to its well-known IL-2 -dependent cell transformation .", "target_text": { "Tax": "protein", "T cells": "cell_type", "IL-2": "protein" } }, { "input_text": "Accessing Epstein-Barr virus -specific T-cell memory with peptide-loaded dendritic cells .", "target_text": { "peptide-loaded dendritic cells": "cell_line" } }, { "input_text": "The conventional means of studying Epstein-Barr virus ( EBV ) -induced cytotoxic T-lymphocyte ( CTL ) memory , by in vitro stimulation with the latently infected autologous lymphoblastoid cell line ( LCL ) , has important limitations .", "target_text": { "cytotoxic T-lymphocyte": "cell_type", "lymphoblastoid cell line": "cell_line", "LCL": "cell_line" } }, { "input_text": "First , it gives no information on memory to lytic cycle antigens ; second , it preferentially amplifies the dominant components of latent antigen-specific memory at the expense of key subdominant reactivities .", "target_text": { "lytic cycle antigens": "protein" } }, { "input_text": "Here we describe an alternative approach , based on in vitro stimulation with epitope peptide-loaded dendritic cells ( DCs ) , which allows one to probe the CTL repertoire for any individual reactivity of choice ; this method proved significantly more efficient than stimulation with peptide alone .", "target_text": { "peptide-loaded dendritic cells": "cell_line", "epitope peptide-loaded dendritic cells": "cell_line", "DCs": "cell_line" } }, { "input_text": "Using this approach we first show that reactivities to the immunodominant and subdominant lytic cycle epitopes identified by T cells during primary EBV infection are regularly detectable in the CTL memory of virus carriers ; this implies that in such carriers chronic virus replication remains under direct T-cell control .", "target_text": { "lytic cycle epitopes": "protein", "T cells": "cell_type" } }, { "input_text": "We further show that subdominant latent cycle reactivities to epitopes in the latent membrane protein LMP2 , though rarely undetectable in LCL -stimulated populations , can be reactivated by DC stimulation and selectively expanded as polyclonal CTL lines ; the adoptive transfer of such preparations may be of value in targeting certain EBV-positive malignancies .", "target_text": { "latent membrane protein LMP2": "protein", "LCL": "cell_line", "CTL lines": "cell_line" } }, { "input_text": "Regulation of the human interleukin-2 gene by the alpha and beta isoforms of the glucocorticoid receptor .", "target_text": { "human interleukin-2 gene": "DNA", "alpha": "protein", "beta isoforms": "protein", "alpha and beta isoforms": "protein", "glucocorticoid receptor": "protein" } }, { "input_text": "The immunosuppressive effects of glucocorticoids are largely due to transcriptional inhibition of immunologically relevant genes , such as the interleukin-2 ( IL-2 ) gene .", "target_text": { "immunologically relevant genes": "DNA", "IL-2": "protein", "interleukin-2 ( IL-2 ) gene": "DNA" } }, { "input_text": "These effects are mediated by the intracellular glucocorticoid receptor ( GR ) .", "target_text": { "glucocorticoid receptor": "protein", "GR": "protein" } }, { "input_text": "In humans , alternative splicing of the GR precursor mRNA gives rise to two receptor isoforms , termed GRalpha and GRbeta .", "target_text": { "GR precursor mRNA": "RNA", "GRalpha": "protein", "GRbeta": "protein" } }, { "input_text": "We previously demonstrated that GRbeta could antagonize GRalpha -mediated transactivation of a glucocorticoid- responsive element ( GRE ) -driven reporter gene in COS-7 cells .", "target_text": { "GRbeta": "protein", "GRalpha": "protein", "glucocorticoid- responsive element": "DNA", "glucocorticoid- responsive element ( GRE ) -driven reporter gene": "DNA", "COS-7 cells": "cell_line" } }, { "input_text": "The present study was designed to analyze the roles of the two GR isoforms on glucocorticoid-mediated transrepression of the IL-2 gene .", "target_text": { "GR isoforms": "protein", "IL-2 gene": "DNA" } }, { "input_text": "Using a recently developed transfection technique , we demonstrate that in primary human lymphocytes , stimulation of a 548 bp IL-2 promoter -luciferase reporter construct by phorbol ester and calcium ionophore is reversed by dexamethasone to a similar extent as in Jurkat T lymphoma cells transfected with a GRalpha expression vector .", "target_text": { "primary human lymphocytes": "cell_type", "IL-2 promoter": "DNA", "-luciferase": "protein", "548 bp IL-2 promoter -luciferase reporter construct": "DNA", "GRalpha": "protein" } }, { "input_text": "Transfection of a GRbeta expression vector alone did not result in IL-2 promoter repression in response to glucocorticoids .", "target_text": { "GRbeta": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Furthermore , GRbeta did not antagonize the repressive effects of GRalpha on IL-2 promoter activity .", "target_text": { "GRbeta": "protein", "GRalpha": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Surprisingly , overexpression of GRbeta in Jurkat cells did not cause significant inhibition of GRalpha -induced transactivation of a GRE-dependent luciferase reporter gene either .", "target_text": { "GRbeta": "protein", "Jurkat cells": "cell_line", "GRalpha": "protein", "luciferase": "protein", "GRE-dependent luciferase reporter gene": "DNA" } }, { "input_text": "We conclude that the transrepressive effect of glucocorticoids on IL-2 gene transcription is exclusively mediated by GRalpha .", "target_text": { "IL-2 gene": "DNA", "GRalpha": "protein" } }, { "input_text": "GRbeta can neither antagonize GRalpha -mediated transactivation nor transrepression in Jurkat cells , indicating a cell type-specific pattern of GRbeta -mediated antiglucocorticoid activity .", "target_text": { "GRbeta": "protein", "GRalpha": "protein", "Jurkat cells": "cell_line" } }, { "input_text": "Extinction of immunoglobulin gene expression in B cells upon fusion with HeLa cells is preceded by rapid nuclear depletion of essential transcription factors and is accompanied by widespread inactivation of genes expressed in a B cell-specific manner .", "target_text": { "immunoglobulin gene": "DNA", "B cells": "cell_type", "HeLa cells": "cell_line", "essential transcription factors": "protein" } }, { "input_text": "When immunoglobulin ( Ig ) expressing B cells are fused with non-B cells , Ig expression is rapidly suppressed at the level of transcription , a phenomenon termed extinction .", "target_text": { "immunoglobulin": "protein", "Ig": "protein", "B cells": "cell_type", "immunoglobulin ( Ig ) expressing B cells": "cell_type", "non-B cells": "cell_type" } }, { "input_text": "Here we demonstrate that fusion of HeLa cells with either diploid or tetraploid B cells ( Daudi ) results in widespread extinction of several other B cell-encoded genes that are expressed in a B cell-specific manner .", "target_text": { "HeLa cells": "cell_line", "Daudi": "cell_line", "B cell-encoded genes": "DNA" } }, { "input_text": "In contrast , expression of B cell-expressed genes that are not dependent on cell-specific controls is unaffected .", "target_text": { "B cell-expressed genes": "DNA" } }, { "input_text": "We show that the molecular mechanism ( s ) underlying Ig gene extinction can be explained , at least in part , by a lack of transcription factors that are essential for Ig gene transcription .", "target_text": { "Ig gene": "DNA", "transcription factors": "protein" } }, { "input_text": "These transcription factors are either not produced due to block of transcription of their respective genes ( Oct-2 , OBF-1 , PU.1 ) , or are rendered inactive posttranslationally ( NF-kappa B , E47 ) .", "target_text": { "transcription factors": "protein", "Oct-2": "DNA", "OBF-1": "DNA", "PU.1": "protein", "NF-kappa B": "protein", "E47": "DNA" } }, { "input_text": "By isolating Daudi x HeLa heterokaryons a few hours after fusion , we have studied the initial fate of two B cell-specific transcription factors involved in Ig gene transcription , Oct-2 and NF-kappa B .", "target_text": { "Daudi x HeLa heterokaryons": "cell_line", "transcription factors": "protein", "B cell-specific transcription factors": "protein", "Ig gene": "DNA", "Oct-2": "DNA", "NF-kappa B": "protein" } }, { "input_text": "This report provides the first demonstration that upon fusion with HeLa cells , the nuclear contents of B cell-expressed transcription factors are depleted within a few hours with kinetics that are as fast or faster than that of Ig gene extinction .", "target_text": { "HeLa cells": "cell_line", "transcription factors": "protein", "B cell-expressed transcription factors": "protein", "Ig gene": "DNA" } }, { "input_text": "Thus , the extinguishing mechanism is effective very early after fusion .", "target_text": {} }, { "input_text": "We suggest that extinction of Ig genes is part of a global mechanism that suppresses the differentiation program foreign to the HeLa phenotype .", "target_text": { "Ig genes": "DNA", "HeLa phenotype": "cell_line" } }, { "input_text": "Evidence for suppressed activity of the transcription factor NFAT1 at its proximal binding element P0 in the IL-4 promoter associated with enhanced IL-4 gene transcription in T cells of atopic patients .", "target_text": { "transcription factor": "protein", "NFAT1": "protein", "proximal binding element": "DNA", "P0": "DNA", "IL-4 promoter": "DNA", "IL-4 gene": "DNA", "T cells": "cell_type" } }, { "input_text": "Allergen-specific T cells in atopic patients are polarized IL-4-producing Th2 cells , promoting IgE synthesis by B cells .", "target_text": { "T cells": "cell_type", "IL-4-producing Th2 cells": "cell_line", "IgE": "protein", "B cells": "cell_type" } }, { "input_text": "The molecular basis for increased IL-4 gene expression in atopy is not fully understood .", "target_text": { "IL-4 gene": "DNA" } }, { "input_text": "IL-4 gene regulation in general involves the nuclear factor of activated T cells ( NFAT ) family of transcription factors , of which NFAT1 and NFAT2 are most prominent in peripheral T cells .", "target_text": { "IL-4 gene": "DNA", "T cells": "cell_type", "nuclear factor of activated T cells": "protein", "NFAT": "protein", "nuclear factor of activated T cells ( NFAT ) family": "protein", "transcription factors": "protein", "NFAT1": "protein", "NFAT2": "protein", "peripheral T cells": "cell_type" } }, { "input_text": "Recently , a unique inhibitory role of NFAT1 in IL-4 gene control was shown in the mouse .", "target_text": { "NFAT1": "protein", "IL-4 gene": "DNA" } }, { "input_text": "In a series of electrophoretic mobility shift assays with protein extracts of highly polarized Th2 clones from atopics and Th1 clones from controls we compared DNA-binding activities at the two NFAT-binding elements P0 and P1 of the crucial proximal human IL-4 promoter .", "target_text": { "highly polarized Th2 clones": "cell_line", "Th1 clones": "cell_line", "NFAT-binding elements": "DNA", "P0": "DNA", "P1": "DNA", "IL-4 promoter": "DNA" } }, { "input_text": "At the most proximal P0 site , NFAT-containing complexes devoid of NFAT2 were readily inducible in the Th1 clones , but hardly or not in the Th2 clones .", "target_text": { "P0": "DNA", "NFAT2": "protein", "Th1 clones": "cell_line", "Th2 clones": "cell_line" } }, { "input_text": "In contrast , both in Th1 and Th2 clones NFAT-containing complexes were strongly inducible at the P1 site , consisting of NFAT2 and a P0 -compatible NFAT activity , without apparent differences between Th1 and Th2 clones .", "target_text": { "P1 site": "DNA", "NFAT2": "protein", "P0": "DNA", "NFAT": "protein" } }, { "input_text": "Like in Th2 clones , suppressed NFAT- P0 complex formation was observed also at the polyclonal level in peripheral blood mononuclear cells ( PBMC ) of three of five severe atopic dermatitis patients with strongly elevated serum IgE levels , but not in control PBMC .", "target_text": { "Th2 clones": "cell_line", "P0": "DNA", "peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type", "IgE": "protein" } }, { "input_text": "These findings suggest that high-level IL-4 production in atopic Th2 cells is associated with selective reduction of suppressive NFAT1 activity at the IL-4 P0 element and that some patients with this multifactorial disease may have a putative systemic disorder at this level .", "target_text": { "IL-4": "protein", "atopic Th2 cells": "cell_type", "NFAT1": "protein", "IL-4 P0 element": "DNA" } }, { "input_text": "Differential expression and phosphorylation of CTCF , a c-myc transcriptional regulator , during differentiation of human myeloid cells .", "target_text": { "CTCF": "protein" } }, { "input_text": "CTCF is a transcriptional repressor of the c-myc gene .", "target_text": { "CTCF": "protein" } }, { "input_text": "Although CTCF has been characterized in some detail , there is very little information about the regulation of CTCF activity .", "target_text": { "CTCF": "protein" } }, { "input_text": "Therefore we investigated CTCF expression and phosphorylation during induced differentiation of human myeloid leukemia cells .", "target_text": { "CTCF": "protein", "human myeloid leukemia cells": "cell_type" } }, { "input_text": "We found that : ( i ) both CTCF mRNA and protein are down-regulated during terminal differentiation in most cell lines tested ; ( ii ) CTCF down-regulation is retarded and less pronounced than that of c-myc ; ( iii ) CTCF protein is differentially phosphorylated and the phosphorylation profiles depend on the differentiation pathway .", "target_text": { "CTCF": "protein", "CTCF mRNA": "RNA", "c-myc": "DNA", "CTCF protein": "protein" } }, { "input_text": "We concluded that CTCF expression and activity is controlled at transcriptional and post-transcriptional levels .", "target_text": { "CTCF": "protein" } }, { "input_text": "Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the immunophilin FKBP51 .", "target_text": { "immunophilin FKBP51": "protein" } }, { "input_text": "Squirrel monkeys are neotropical primates that have high circulating cortisol to compensate for expression of glucocorticoid receptors ( GRs ) with reduced affinity .", "target_text": { "glucocorticoid receptors": "protein", "GRs": "protein" } }, { "input_text": "The low binding affinity of squirrel monkey GR does not result from substitutions in the receptor , because squirrel monkey GR expressed in vitro exhibits high affinity .", "target_text": { "GR": "protein", "squirrel monkey GR": "protein" } }, { "input_text": "Rather , squirrel monkeys express a soluble factor that , in mixing studies of cytosol from squirrel monkey lymphocytes ( SML ) and mouse L929 cells , reduced GR binding affinity by 11-fold .", "target_text": { "squirrel monkey lymphocytes": "cell_type", "SML": "cell_type" } }, { "input_text": "In an effort to identify this factor , the cellular levels of components of the GR heterocomplex in SML and human lymphocytes ( HL ) were compared .", "target_text": { "GR heterocomplex": "protein", "SML": "cell_type", "human lymphocytes": "cell_type", "HL": "cell_type" } }, { "input_text": "The immunophilin FKBP51 was 13-fold higher in SML than in HL cytosol ; FKBP52 in SML was 42 % of that in HL cytosol .", "target_text": { "immunophilin FKBP51": "protein", "SML": "cell_type", "FKBP52": "protein" } }, { "input_text": "A role for changes in immunophilins , causing glucocorticoid resistance in neotropical primates , is supported by the following : the changes in FKBP51 and FKBP52 were observed in cells from other neotropical primates with glucocorticoid resistance ; the elevated level of FKBP51 was reflected in an abundance of FKBP51 in heat shock protein 90 complexes in SML ; when cytosols of SML and L929 cells were mixed , the decrease in GR binding was associated with incorporation of FKBP51 into GR heterocomplexes ; the effect of SML cytosol on GR binding was reproduced with cytosol from COS cells expressing squirrel monkey FKBP51 ; and both the effect of SML cytosol on GR binding and the incorporation of FKBP51 into GR heterocomplexes were blocked by FK506 .", "target_text": { "immunophilins": "protein", "FKBP51": "protein", "FKBP52": "protein", "heat shock protein 90 complexes": "protein", "SML": "cell_type", "L929 cells": "cell_line", "GR heterocomplexes": "protein", "COS cells": "cell_line" } }, { "input_text": "Regulation of GR binding by FKBP51 represents a previously unrecognized mechanism for regulating glucocorticoid sensitivity .", "target_text": { "FKBP51": "protein" } }, { "input_text": "High-level replication of human immunodeficiency virus in thymocytes requires NF-kappaB activation through interaction with thymic epithelial cells .", "target_text": { "thymocytes": "cell_type", "NF-kappaB": "protein", "thymic epithelial cells": "cell_type" } }, { "input_text": "We have previously demonstrated that interaction of infected thymocytes with autologous thymic epithelial cells ( TEC ) is a prerequisite for a high level of human immunodeficiency virus type 1 ( HIV-1 ) replication in thymocytes ( M.Rothe , L.Chene , M.Nugeyre , F.Barre-Sinoussi , and N.Israel , J.Virol.72 : 5852-5861 , 1998 ) .", "target_text": { "thymocytes": "cell_type", "thymic epithelial cells": "cell_type", "TEC": "cell_type" } }, { "input_text": "We report here that this activation of HIV replication takes place at the transcriptional level through activation of the Rel/ NF-kappaB transcription factors .", "target_text": { "NF-kappaB": "protein", "Rel/ NF-kappaB": "protein", "transcription factors": "protein" } }, { "input_text": "We first demonstrate that an HIV-1 provirus ( SF-2 strain ) very effectively replicates in thymocytes cocultured with TEC whereas this provirus , with kappaB sites deleted , fails to replicate .", "target_text": { "thymocytes": "cell_type", "TEC": "cell_type", "kappaB sites": "DNA" } }, { "input_text": "We provide evidence that several NF-kappaB complexes are constitutively found in the nuclei of thymocytes either freshly isolated from the thymus or maintained in coculture with autologous or heterologous TEC .", "target_text": { "NF-kappaB": "protein", "NF-kappaB complexes": "protein", "thymocytes": "cell_type", "TEC": "cell_type" } }, { "input_text": "The prevalent complex is the heterodimer p50-p65 .", "target_text": { "heterodimer p50-p65": "protein" } }, { "input_text": "NF-kappaB activity is tightly correlated with the transcriptional activity of a long terminal repeat ( LTR ) of HIV-1 transfected in thymocytes .", "target_text": { "NF-kappaB": "protein", "long terminal repeat": "DNA", "LTR": "DNA", "thymocytes": "cell_type" } }, { "input_text": "The cotransfection of this LTR with a mutated IkappaBalpha molecule formally demonstrates that LTR transactivation is regulated by members of the Rel/ NF-kappaB family in thymocytes .", "target_text": { "LTR": "DNA", "IkappaBalpha molecule": "protein", "NF-kappaB": "protein", "Rel/ NF-kappaB family": "protein", "thymocytes": "cell_type" } }, { "input_text": "We also showed that tumor necrosis factor ( TNF ) and to a lesser extent interleukin-1 ( IL-1 ) , secreted within the coculture , induce NF-kappaB activity and a correlative LTR transactivation .", "target_text": { "tumor necrosis factor": "protein", "TNF": "protein", "interleukin-1": "protein", "IL-1": "protein", "NF-kappaB": "protein", "LTR": "DNA" } }, { "input_text": "However IL-7 , a crucial factor for thymopoiesis that is secreted mainly by TEC , is a necessary cofactor for NF-kappaB activation elicited by TNF or IL-1 .", "target_text": { "IL-7": "protein", "TEC": "cell_type", "NF-kappaB": "protein", "TNF": "protein", "IL-1": "protein" } }, { "input_text": "Together , these data indicate that NF-kappaB activation , required for a high level of HIV replication in thymocytes , is regulated in a specific manner in the thymic microenvironment which provides the necessary cytokines : TNF , IL-1 , and IL-7 .", "target_text": { "NF-kappaB": "protein", "thymocytes": "cell_type", "TNF": "protein", "IL-1": "protein", "IL-7": "protein" } }, { "input_text": "Imbalanced expression of the glucocorticoid receptor isoforms in cultured lymphocytes from a patient with systemic glucocorticoid resistance and chronic lymphocytic leukemia .", "target_text": { "glucocorticoid receptor isoforms": "protein", "cultured lymphocytes": "cell_type" } }, { "input_text": "The human glucocorticoid receptor ( GR ) is expressed as two alternatively spliced isoforms , GRalpha and GRbeta .", "target_text": { "human glucocorticoid receptor": "protein", "GR": "protein", "GRalpha": "protein", "GRbeta": "protein" } }, { "input_text": "Whereas GRalpha is a hormone-activated transcription factor , GRbeta does not bind glucocorticoids ( GCs ) , is transcriptionally inactive , and is a potential inhibitor of activated GRalpha .", "target_text": { "GRalpha": "protein", "transcription factor": "protein", "GRbeta": "protein" } }, { "input_text": "Differential expression of GR isoforms may play a role in generalized or tissue-specific GC resistance .", "target_text": { "GR isoforms": "protein" } }, { "input_text": "GCs induce apoptosis in neoplastic lymphoid cells ; and , defective apoptosis is implicated in the genesis of chronic lymphocytic leukemia ( CLL ) .", "target_text": { "neoplastic lymphoid cells": "cell_type" } }, { "input_text": "We studied a patient with generalized GC resistance and CLL .", "target_text": {} }, { "input_text": "GR number in the patient 's transformed lymphocytes was approximately one half that of control cells with a approximately 10-fold reduction in binding affinity for dexamethasone .", "target_text": { "transformed lymphocytes": "cell_line" } }, { "input_text": "In vitro apoptosis induction in CLL cells was delayed in response to GCs , but not to other apoptosis inducers .", "target_text": { "CLL cells": "cell_line" } }, { "input_text": "Sequencing of the GR cDNA and gene including the 2.3-kb coding region , the intron/exon junctions , the known 5'-regulatory region , and approximately 300 bp of the 3'-region revealed no alterations .", "target_text": { "GR cDNA": "DNA", "5'-regulatory region": "DNA", "3'-region": "DNA" } }, { "input_text": "Western blot with an N-terminal antibody showed normal levels of immunoreactive GR , but quantitative analysis with isoform-specific C-terminal antibodies revealed a markedly reduced GRalpha expression , and high GRbeta expression .", "target_text": { "immunoreactive GR": "protein", "C-terminal antibodies": "protein", "GRalpha": "protein", "GRbeta": "protein" } }, { "input_text": "These findings indicate that imbalanced expression of the GR isoforms may be a mechanism of GC resistance , and may have implications for tumorigenesis by enhancing cell survival .", "target_text": { "GR isoforms": "protein" } }, { "input_text": "Copyright 1999 Academic Press .", "target_text": {} }, { "input_text": "Intranuclear targeted delivery of functional NF-kappaB by 70 kDa heat shock protein .", "target_text": { "NF-kappaB": "protein", "70 kDa heat shock protein": "protein" } }, { "input_text": "The 70 kDa heat shock protein ( Hsp70 ) is a highly conserved , ubiquitous protein involved in chaperoning proteins to various cellular organelles .", "target_text": { "70 kDa heat shock protein": "protein", "Hsp70": "protein", "ubiquitous protein": "protein", "chaperoning proteins": "protein" } }, { "input_text": "Here we show that when added exogenously to cells , Hsp70 is readily imported into both cytoplasmic and nuclear compartments in a cell-type-specific fashion .", "target_text": { "Hsp70": "protein" } }, { "input_text": "We exploited this ability of Hsp70 to deliver NF-kappaB , a key transcriptional regulator of inflammatory responses .", "target_text": { "Hsp70": "protein", "NF-kappaB": "protein" } }, { "input_text": "We demonstrate that a fusion protein composed of a C-terminal Hsp70 peptide and the p50 subunit of NF-kappaB was directed into the nucleus of cells , could bind DNA specifically , and activated Igkappa expression and TNFalpha production .", "target_text": { "Hsp70": "protein", "p50 subunit": "protein", "NF-kappaB": "protein", "Igkappa": "protein", "TNFalpha": "protein" } }, { "input_text": "We therefore propose that Hsp70 can be used as a vehicle for intracytoplasmic and intranuclear delivery of proteins or DNA to modulate gene expression and thereby control immune responses .", "target_text": { "Hsp70": "protein" } }, { "input_text": "Characterization of the human elk-1 promoter .", "target_text": { "elk-1": "DNA", "human elk-1 promoter": "DNA" } }, { "input_text": "Potential role of a downstream intronic sequence for elk-1 gene expression in monocytes .", "target_text": { "downstream intronic sequence": "DNA", "elk-1": "DNA", "elk-1 gene": "DNA", "monocytes": "cell_type" } }, { "input_text": "To characterize the human elk-1 promoter , we mapped the transcriptional start site and isolated elk-1 -specific genomic phage clones that contained extensive upstream and downstream sequences .", "target_text": { "elk-1": "DNA", "human elk-1 promoter": "DNA", "transcriptional start site": "DNA", "elk-1 -specific genomic phage clones": "cell_line" } }, { "input_text": "A TATA-like motif was identified immediately upstream of the transcriptional start site .", "target_text": { "TATA-like motif": "DNA", "transcriptional start site": "DNA" } }, { "input_text": "Functional analyses of DNA fragments containing the TATA element and the identification of a DNase I-hypersensitive chromatin site ( HS 1 ) in close proximity to the TATA box suggest that the identified TATA motif is important for elk-1 transcription in vivo .", "target_text": { "DNA fragments": "DNA", "TATA element": "DNA", "DNase I-hypersensitive chromatin site": "DNA", "HS 1": "DNA", "TATA box": "DNA", "TATA motif": "DNA", "elk-1": "DNA" } }, { "input_text": "Sequences upstream and downstream from the TATA box were found to contribute to elk-1 promoter activity .", "target_text": { "TATA box": "DNA", "elk-1": "DNA" } }, { "input_text": "A second hypersensitive site ( HS 2 ) was identified within the first intron in pre-monocytic cells , which express Elk-1 only when differentiating to monocytes .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "In a variety of other cell types , which display a constitutive Elk-1 expression , HS 2 did not exist , suggesting that inducibility of elk-1 expression is associated with the presence of HS 2 .", "target_text": { "Elk-1": "protein", "elk-1": "DNA" } }, { "input_text": "Egr-1 and the serum response factor were found to interact specifically with the intronic sequence at +265 and +448 , respectively .", "target_text": { "intronic sequence": "DNA" } }, { "input_text": "Because Egr-1 mRNA and protein levels were observed to increase significantly before induction of elk-1 expression , we propose that Egr-1 is important for the regulation of elk-1 transcription in differentiating monocytes .", "target_text": { "Egr-1 mRNA": "RNA", "elk-1": "DNA", "Egr-1": "protein", "monocytes": "cell_type" } }, { "input_text": "Immunohistochemical study of c-fos-positive lymphocytes infiltrated into human squamous cell carcinomas of the head and neck during radiation therapy and its clinical significance .", "target_text": { "c-fos-positive lymphocytes": "protein" } }, { "input_text": "C-fos has been reported to be one of the immediate early genes in signal transduction systems after many kinds of stresses , including ionizing radiation .", "target_text": { "C-fos": "DNA", "immediate early genes": "DNA" } }, { "input_text": "Changes in c-fos expression induced by radiation therapy in tumor tissues have not yet been reported .", "target_text": { "c-fos": "DNA" } }, { "input_text": "In this study , we have attempted to determine whether c-fos expression is induced by radiotherapy in human squamous cell carcinomas of the head and neck and to establish a possible correlation between c-fos expression and the therapeutic effects of radiation therapy .", "target_text": { "c-fos": "DNA" } }, { "input_text": "Twenty-seven patients with tumors of the oral cavity , oropharynx , and maxillary sinus were examined , all of which were confirmed as squamous cell carcinomas .", "target_text": {} }, { "input_text": "After obtaining the patients ' informed consent , biopsies were performed before treatment and at doses of 4 , 10 , and 20 Gy of radiotherapy , and the specimens were preserved in liquid nitrogen for further examination .", "target_text": {} }, { "input_text": "Serial sectioning of 6 micrometer was performed using a cryostat , and samples were immunohistochemically stained using the streptoavidin -biotin peroxidase method and a monoclonal antibody against c-fos .", "target_text": { "streptoavidin": "protein", "-biotin peroxidase": "protein" } }, { "input_text": "Three of the 27 patients with squamous cell carcinoma showed slight expression of c-fos in their tumor cells before and/or at 4 or 10 Gy of radiotherapy .", "target_text": {} }, { "input_text": "The tumors showed high radiosensitivity .", "target_text": {} }, { "input_text": "Concerning tumor-infiltrating lymphocytes , the rate of moderate or remarkable grades of c-fos-positive lymphocytes before radiotherapy and at radiation doses of 4 , 10 , and 20 Gy was 8.0 , 29.2 , 4.8 , and 0 % , respectively .", "target_text": { "tumor-infiltrating lymphocytes": "cell_type", "c-fos-positive lymphocytes": "protein" } }, { "input_text": "The relationship between the immunohistochemical findings and the antitumor effect at a radiation dose of 20 Gy was examined on the corresponding H & E-stained sections .", "target_text": {} }, { "input_text": "In patients whose infiltration of c-fos-positive lymphocytes into tumor tissues were moderate or remarkable at 4 Gy of radiotherapy , the tumors responded significantly well to radiation therapy ( P < 0.025 , chi2 test ) , and the patients took a significantly favorable clinical course ( P < 0.05 , chi2 test ) .", "target_text": { "c-fos-positive lymphocytes": "protein" } }, { "input_text": "In a sample from one of the patients , c-fos-positive lymphocytes were identified as CD4 positive and CD8 negative .", "target_text": { "c-fos-positive lymphocytes": "protein" } }, { "input_text": "Therefore , the high radiosensitivity of squamous cell carcinomas in our samples could be explained by an overexpression of c-fos in the tumor-infiltrating lymphocytes induced by small doses of radiation therapy , and these activated lymphocytes exerted a cytotoxic effect against the cancer cells .", "target_text": { "c-fos": "protein", "tumor-infiltrating lymphocytes": "cell_type", "activated lymphocytes": "cell_type", "cancer cells": "cell_type" } }, { "input_text": "Paternal expression of WT1 in human fibroblasts and lymphocytes .", "target_text": { "WT1": "protein", "human fibroblasts": "cell_type", "lymphocytes": "cell_type" } }, { "input_text": "The Wilms ' tumor suppressor gene ( WT1 ) was previously identified as being imprinted , with frequent maternal expression in human placentae and fetal brains .", "target_text": { "Wilms ' tumor suppressor gene": "DNA", "WT1": "protein" } }, { "input_text": "We examined the allele-specific expression of WT1 in cultured human fibroblasts from 15 individuals .", "target_text": { "WT1": "protein", "human fibroblasts": "cell_type" } }, { "input_text": "Seven of 15 fibroblast lines were heterozygous for polymorphic alleles , and the expression patterns were variable , i.e. , equal , unequal or monoallelic paternal expression in three , two and two cases , respectively .", "target_text": { "fibroblast lines": "cell_line", "polymorphic alleles": "DNA" } }, { "input_text": "Exclusive paternal expression of WT1 was also shown in non-cultured peripheral lymphocytes from the latter two individuals .", "target_text": { "WT1": "protein", "non-cultured peripheral lymphocytes": "cell_type" } }, { "input_text": "The allele-specific expression profiles of other imprinted genes , IGF2 and H19 , on human chromosome 11 were constant and consistent with those in other tissues .", "target_text": { "imprinted genes": "DNA", "IGF2": "DNA", "H19": "DNA", "human chromosome 11": "DNA" } }, { "input_text": "Our unexpected observations of paternal or biallelic expression of WT1 in fibroblasts and lymphocytes , together with the previous findings of maternal or biallelic expression in placentae and brains , suggest that the allele-specific regulatory system of WT1 is unique and may be controlled by a putative tissue- and individual-specific modifier .", "target_text": { "WT1": "protein", "fibroblasts": "cell_type", "lymphocytes": "cell_type" } }, { "input_text": "T cell reactivity to Sjogren 's syndrome related antigen La ( SSB ) .", "target_text": { "La ( SSB )": "protein" } }, { "input_text": "OBJECTIVE .", "target_text": {} }, { "input_text": "Many patients with primary Sjogren 's syndrome ( SS ) make high titer IgG autoantibodies to the La ( SSB ) antigen , suggesting antigen specific T cell-B cell interactions .", "target_text": { "IgG autoantibodies": "protein", "La ( SSB )": "protein" } }, { "input_text": "T cell responses to some nuclear antigens , particularly U1RNP , have been detected in patients with systemic lupus erythematosus ( SLE ) and in healthy subjects .", "target_text": { "U1RNP": "protein" } }, { "input_text": "We investigated T cell reactivity to the autoantigen SSB in patients with SS and healthy controls .", "target_text": { "autoantigen SSB": "protein" } }, { "input_text": "METHODS .", "target_text": {} }, { "input_text": "Using the [3H]thymidine proliferation assay , we determined reactivity to purified recombinant SSB ( rSSB ) in 20 patients with SS and 19 controls .", "target_text": { "purified recombinant SSB": "protein", "rSSB": "protein" } }, { "input_text": "Specificity was determined using tetanus toxoid , endotoxin , and 3 other autoantigens ( PBC.M2 , Sc170 , and GAD ) .", "target_text": { "autoantigens": "protein", "PBC.M2": "protein", "Sc170": "protein", "GAD": "protein" } }, { "input_text": "Precursor frequency was calculated by limiting dilution analysis .", "target_text": {} }, { "input_text": "HLA Class II dependency was investigated using anti-Class II monoclonal antibodies .", "target_text": { "anti-Class II monoclonal antibodies": "protein" } }, { "input_text": "HLA-DR typing was by polymerase chain reaction and sequence specific oligonucleotide typing .", "target_text": {} }, { "input_text": "RESULTS .", "target_text": {} }, { "input_text": "Six of 20 patients with SS and 10/19 controls proliferated to La ( rSSB ) .", "target_text": { "rSSB": "protein" } }, { "input_text": "Precursor frequency of anti-SSB T cells was 1:77,040 and 1:115,000 in 2 healthy subjects and 1:230,250 and 1:103,034 in two patients with SS .", "target_text": { "anti-SSB T cells": "cell_line" } }, { "input_text": "Anti- HLA-DR abrogated proliferation to SSB and tetanus toxoid .", "target_text": { "HLA-DR": "protein", "SSB": "protein" } }, { "input_text": "Thirteen of 15 patients with SS and 4/17 controls were HLA-DR3 positive , with no apparent association of HLA-DR3 with SSB reactivity in controls .", "target_text": { "HLA-DR3": "protein", "SSB": "protein" } }, { "input_text": "CONCLUSION .", "target_text": {} }, { "input_text": "Anti- La(SSB) specific T cells occur in a significant proportion of controls and in some patients with SS .", "target_text": { "La(SSB)": "protein", "Anti- La(SSB) specific T cells": "cell_line" } }, { "input_text": "The function of SSB T cells in controls remains to be defined .", "target_text": { "SSB T cells": "cell_line" } }, { "input_text": "They may represent immunoregulatory cells , and further analysis of these cells , and a comparison to those found in patients with SS , may elucidate normal immunoregulation and the derangements that lead to Sjogren 's syndrome .", "target_text": { "immunoregulatory cells": "cell_type" } }, { "input_text": "Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-alpha -induced HIV-1 replication in latently infected OM10.1 and Ach2 cells .", "target_text": { "tumor necrosis factor-alpha": "protein" } }, { "input_text": "NF-kappaB is a potent cellular activator of HIV-1 gene expression .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Down-regulation of NF-kappaB activation is known to inhibit HIV replication from the latently infected cells .", "target_text": { "NF-kappaB": "protein", "latently infected cells": "cell_type" } }, { "input_text": "Gold compounds have been effectively used for many decades in the treatment of rheumatoid arthritis .", "target_text": {} }, { "input_text": "We previously reported that gold compounds , especially aurothioglucose ( AuTG ) containing monovalent gold ion , inhibited the DNA-binding of NF-kappaB in vitro .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "In this report we have examined the efficacy of the gold compound AuTG as an inhibitor of HIV replication in latently infected OM10.1 and Ach2 cells .", "target_text": {} }, { "input_text": "Tumor necrosis factor ( TNF ) -alpha -induced HIV-1 replication in OM10.1 or Ach2 cells was significantly inhibited by non-cytotoxic doses of AuTG ( > 10 microM in OM10.1 cells and > 25 F.M in Ach2 cells ) , while 25 microM of the counter-anion thioglucose ( TG ) or gold compound containing divalent gold ion , HAuCl3 , had no effect .", "target_text": { "Tumor necrosis factor ( TNF ) -alpha": "protein", "OM10.1": "cell_line", "Ach2 cells": "cell_line", "counter-anion thioglucose": "protein", "TG": "protein" } }, { "input_text": "The effect of AuTG on NF-kappaB -dependent gene expression was confirmed by a transient CAT assay .", "target_text": { "NF-kappaB": "protein", "CAT": "protein" } }, { "input_text": "Specific staining as well as electron microscopic examinations revealed the accumulation of metal gold in the cells , supporting our previous hypothesis that gold ions could block NF-kappaB -DNA binding by a redox mechanism .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "These observations indicate that the monovalent gold compound AuTG is a potentially useful drug for the treatment of patients infected with HIV .", "target_text": {} }, { "input_text": "Clonality of isolated eosinophils in the hypereosinophilic syndrome .", "target_text": { "isolated eosinophils": "cell_type" } }, { "input_text": "The idiopathic hypereosinophilic syndrome ( IHES ) is a rare disorder characterized by unexplained , persistent eosinophilia associated with multiple organ dysfunction due to eosinophilic tissue infiltration .", "target_text": {} }, { "input_text": "In the absence of karyotypic abnormalities , there is no specific test to detect clonal eosinophilia in IHES .", "target_text": {} }, { "input_text": "Analysis of X-chromosome inactivation patterns can be used to determine whether proliferative disorders are clonal in origin .", "target_text": { "X-chromosome": "DNA" } }, { "input_text": "Methylation of HpaII and Hha I sites near the polymorphic trinucleotide repeat of the human androgen receptor gene ( HUMARA ) has been shown to correlate with X-inactivation .", "target_text": { "polymorphic trinucleotide repeat": "DNA", "human androgen receptor gene": "DNA", "HUMARA": "DNA" } }, { "input_text": "In this study , we have used the polymerase chain reaction ( PCR ) with nested primers to analyze X-inactivation patterns of the HUMARA loci in purified eosinophils from female patients with eosinophilia .", "target_text": { "HUMARA": "DNA", "HUMARA loci": "DNA", "purified eosinophils": "cell_type" } }, { "input_text": "Peripheral blood eosinophils were isolated by their autofluoresence using flow cytometric sorting .", "target_text": { "Peripheral blood eosinophils": "cell_type" } }, { "input_text": "Eosinophils purified from a female patient presenting with IHES were found to show a clonal pattern of X-inactivation .", "target_text": { "Eosinophils": "cell_type" } }, { "input_text": "Eosinophil-depleted leukocytes from this patient were polyclonal by HUMARA analysis , thus excluding skewedness of random X- inactivation .", "target_text": { "Eosinophil-depleted leukocytes": "cell_type", "HUMARA": "DNA" } }, { "input_text": "After corticosteroid suppression of her blood eosinophilia , a clonal population of eosinophils could no longer be detected in purified eosinophils .", "target_text": { "eosinophils": "cell_type", "purified eosinophils": "cell_type" } }, { "input_text": "In contrast , eosinophils purified from a patient with Churg-Strauss syndrome and from six patients with reactive eosinophilias attributed to allergy , parasitic infection , or drug reaction showed a polyclonal pattern of X-inactivation by HUMARA analysis .", "target_text": { "eosinophils": "cell_type", "HUMARA": "DNA" } }, { "input_text": "The finding of clonal eosinophilia in a patient presenting with IHES indicates that such patients may have , in reality , a low-grade clonal disorder that can be distinguished from reactive eosinophilias by HUMARA analysis .", "target_text": { "HUMARA": "DNA" } }, { "input_text": "Further , the method described can be used to monitor disease progression .", "target_text": {} }, { "input_text": "GA-binding protein factors , in concert with the coactivator CREB binding protein/p300 , control the induction of the interleukin 16 promoter in T lymphocytes .", "target_text": { "GA-binding protein factors": "protein", "coactivator CREB binding protein/p300": "protein", "interleukin 16 promoter": "DNA", "T lymphocytes": "cell_type" } }, { "input_text": "Interleukin 16 ( IL-16 ) is a chemotactic cytokine that binds to the CD4 receptor and affects the activation of T cells and replication of HIV .", "target_text": { "Interleukin 16": "protein", "IL-16": "protein", "chemotactic cytokine": "protein", "CD4 receptor": "protein", "T cells": "cell_type" } }, { "input_text": "It is expressed as a large 67-kDa precursor protein ( pro-IL-16 ) in lymphocytes , macrophages , and mast cells , as well as in airway epithelial cells from asthmatics after challenge with allergen .", "target_text": { "67-kDa precursor protein": "protein", "pro-IL-16": "protein", "lymphocytes": "cell_type", "macrophages": "cell_type", "mast cells": "cell_type", "airway epithelial cells": "cell_type" } }, { "input_text": "This pro-IL-16 is subsequently processed to the mature cytokine of 13 kDa .", "target_text": { "pro-IL-16": "protein", "13 kDa": "protein" } }, { "input_text": "To study the expression of IL-16 at the transcriptional level , we cloned the human chromosomal IL-16 gene and analyzed its promoter .", "target_text": { "IL-16": "protein", "human chromosomal IL-16 gene": "DNA" } }, { "input_text": "The human IL-16 gene consists of seven exons and six introns .", "target_text": { "IL-16": "protein", "human IL-16 gene": "DNA", "exons": "DNA", "introns": "DNA" } }, { "input_text": "The 5' sequences up to nucleotide -120 of the human and murine IL-16 genes share > 84 % sequence homology and harbor promoter elements for constitutive and inducible transcription in T cells .", "target_text": { "5' sequences": "DNA", "IL-16": "protein", "harbor promoter elements": "DNA", "T cells": "cell_type" } }, { "input_text": "Although both promoters lack any TATA box , they contain two CAAT box-like motifs and three binding sites of GA-binding protein ( GABP ) transcription factors .", "target_text": { "TATA box": "DNA", "CAAT box-like motifs": "DNA", "binding sites": "DNA", "GA-binding protein ( GABP ) transcription factors": "protein" } }, { "input_text": "Two of these motifs are part of a highly conserved and inducible dyad symmetry element shown previously to control a remote IL-2 enhancer and the CD18 promoter .", "target_text": { "dyad symmetry element": "DNA", "IL-2 enhancer": "DNA", "CD18 promoter": "DNA" } }, { "input_text": "In concert with the coactivator CREB binding protein/p300 , which interacts with GABPalpha , the binding of GABPalpha and -beta to the dyad symmetry element controls the induction of IL-16 promoter in T cells .", "target_text": { "coactivator CREB binding protein/p300": "protein", "GABPalpha": "protein", "-beta": "protein", "dyad symmetry element": "DNA", "IL-16": "protein", "IL-16 promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "Supplementing the data on the processing of pro-IL-16 , our results indicate the complexity of IL-16 expression , which is tightly controlled at the transcriptional and posttranslational levels in T lymphocytes .", "target_text": { "pro-IL-16": "protein", "IL-16": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene .", "target_text": { "vitamin D receptor gene": "DNA" } }, { "input_text": "The active metabolite of vitamin D , 1,25 dihydroxyvitamin D3 , is an important immunoregulatory hormone [ 1 ] .", "target_text": {} }, { "input_text": "Its effects are exerted by interaction with the vitamin D receptor , which is present on human monocytes and activated T and B lymphocytes .", "target_text": { "vitamin D receptor": "protein", "human monocytes": "cell_type" } }, { "input_text": "Variation in the vitamin D receptor gene was typed in 2015 subjects from large case-control studies of three major infectious diseases : tuberculosis , malaria , and hepatitis B virus .", "target_text": { "vitamin D receptor": "protein", "vitamin D receptor gene": "DNA" } }, { "input_text": "Homozygotes for a polymorphism at codon 352 ( genotype tt ) were significantly underrepresented among those with tuberculosis ( chi2 = 6.22 , 1 df , P = .01 ) and persistent hepatitis B infection ( chi2 = 6.25 , 1 df , P = .01 ) but not in subjects with clinical malaria compared with the other genotypes .", "target_text": { "codon 352": "DNA" } }, { "input_text": "Therefore , this genetic variant , which predisposes to low bone mineral density in many populations , may confer resistance to certain infectious diseases .", "target_text": {} }, { "input_text": "Inhibition of NF-kappa B activation in vitro and in vivo : role of 26S proteasome .", "target_text": { "NF-kappa B": "protein", "26S proteasome": "protein" } }, { "input_text": "It is becoming increasingly apparent that NF-kappa B plays a critical role in regulating the inflammatory response .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Data obtained from studies in our laboratories demonstrate that the proteasome plays an important role in the inflammatory cascade by regulating the activation of NF-kappa B .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Indeed , the availability of selective and orally active proteasome inhibitors should prove useful in delineating the roles of the proteasome and NF-kappa B in other pathophysiological conditions such as cancer and heart disease .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Tissue factor expression of human monocytes is suppressed by lysophosphatidylcholine .", "target_text": { "human monocytes": "cell_type" } }, { "input_text": "The expression of tissue factor ( TF ) , the principal initiator of coagulation , is increased during inflammation and atherosclerosis .", "target_text": { "tissue factor": "protein", "TF": "protein" } }, { "input_text": "Both conditions are promoted by lysophosphatidylcholine ( lysoPC ) .", "target_text": {} }, { "input_text": "We observed in the present study that lysoPC ( 1 to 10 micromol/L ) dose-dependently reduced TF activity in human monocytes , as elicited by lipopolysaccharide ( LPS ) .", "target_text": { "TF": "protein", "human monocytes": "cell_type" } }, { "input_text": "Lysophosphatidylethanolamine ( lysoPE ) and other lysophospholipids did not affect LPS -induced TF activity of human monocytes .", "target_text": { "human monocytes": "cell_type" } }, { "input_text": "TF antigen expression as elicited by LPS was also lowered by lysoPC .", "target_text": {} }, { "input_text": "Phospholipid analyses indicated a selective increase in the lysoPC content of the monocytes after preincubation with the lysophospholipid .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "LysoPC inhibited the TF activity of Mono Mac-6 cells to a similar extent as in the monocytes .", "target_text": { "Mono Mac-6 cells": "cell_line", "monocytes": "cell_type" } }, { "input_text": "LPS binding to plasma membrane receptors and internalization of LPS into monocytes were not affected by lysoPC .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "In contrast , LPS -mediated nuclear binding of nuclear factor-kappaB/Rel to a TF-specific kappaB site was inhibited by lysoPC .", "target_text": { "nuclear factor-kappaB/Rel": "protein", "TF-specific kappaB site": "DNA" } }, { "input_text": "Induction of TF mRNA expression by LPS tended to be partially reduced by the lysophospholipid .", "target_text": { "TF mRNA": "RNA" } }, { "input_text": "Preincubation with lysoPC increased monocytic cAMP levels .", "target_text": {} }, { "input_text": "Inhibition of adenylyl cyclase by pretreatment with 2'-deoxy-3'-adenosine monophosphate partially reversed the inhibition of TF activity promoted by lysoPC .", "target_text": { "adenylyl cyclase": "protein", "2'-deoxy-3'-adenosine monophosphate": "protein" } }, { "input_text": "In conclusion , lysoPC markedly decreases LPS -mediated TF expression of human monocytes , the effect probably being mediated by both transcriptional and posttranscriptional mechanisms .", "target_text": { "human monocytes": "cell_type" } }, { "input_text": "LysoPC may thus attenuate activation of coagulation during inflammation and atherosclerosis .", "target_text": {} }, { "input_text": "Regulation of fas-ligand expression during activation-induced cell death in T lymphocytes via nuclear factor kappaB .", "target_text": { "T lymphocytes": "cell_type", "nuclear factor kappaB": "protein" } }, { "input_text": "T cell receptor engagement activates transcription factors important for cytokine gene regulation .", "target_text": { "transcription factors": "protein", "cytokine gene": "DNA" } }, { "input_text": "Additionally , this signaling pathway also leads to activation-induced apoptosis in T lymphocytes that is dependent on FasL transcription and expression .", "target_text": { "T lymphocytes": "cell_type" } }, { "input_text": "Here we demonstrate that nuclear factor kappaB ( NF-kappaB ) , which is involved in the transcriptional regulation of many cytokine genes expressed in activated lymphocytes , also plays a role in T cell activation-induced FasL expression .", "target_text": { "nuclear factor kappaB": "protein", "NF-kappaB": "protein", "cytokine genes": "DNA", "activated lymphocytes": "cell_type", "FasL": "protein" } }, { "input_text": "Inhibition of NF-kappaB activity in a T cell hybridoma leads to decreased FasL expression and apoptosis upon T cell receptor stimulation .", "target_text": { "NF-kappaB": "protein", "T cell hybridoma": "cell_line", "FasL": "protein", "T cell receptor": "protein" } }, { "input_text": "We identified the NF-kappaB site in the FasL promoter that contributes to such regulation .", "target_text": { "NF-kappaB": "protein", "NF-kappaB site": "DNA", "FasL": "protein", "FasL promoter": "DNA" } }, { "input_text": "Co-expression of p65 ( Rel A ) with the FasL promoter enhanced its activity , and co-expression of IkappaB dramatically inhibited the inducible promoter activity .", "target_text": { "p65 ( Rel A )": "protein", "FasL": "protein", "FasL promoter": "DNA", "IkappaB": "protein", "inducible promoter": "DNA" } }, { "input_text": "In contrast , the transcription factor AP-1 is not required for activation-induced FasL promoter activity .", "target_text": { "transcription factor AP-1": "protein", "FasL": "protein" } }, { "input_text": "These results define a role for NF-kappaB in mediating FasL expression during T cell activation .", "target_text": { "NF-kappaB": "protein", "FasL": "protein" } }, { "input_text": "Promoter sequence , exon : intron structure , and synteny of genetic location show that a chicken cytokine with T-cell proliferative activity is IL2 and not IL15 .", "target_text": { "Promoter sequence": "DNA", "exon : intron structure": "DNA", "chicken cytokine": "protein", "IL2": "protein", "IL15": "protein" } }, { "input_text": "The gene encoding a chicken cytokine with T-cell proliferative activity was cloned , sequenced , and mapped .", "target_text": { "chicken cytokine": "protein" } }, { "input_text": "The results show that this cytokine is chicken IL2 and not IL15 .", "target_text": { "cytokine": "protein", "IL2": "protein", "IL15": "protein" } }, { "input_text": "The exon:intron structure of chicken IL2 corresponds almost exactly to those of mammalian IL2s with the exceptions of exon 2 and introns 2 and 3 which are shorter .", "target_text": { "exon:intron structure": "DNA", "IL2": "protein", "chicken IL2": "protein", "IL2s": "protein", "exon 2": "DNA", "introns": "DNA" } }, { "input_text": "Chicken IL2 contains five repeats of the \" instability \" motif ATTTA in the 3'untranslated region in exon 4 .", "target_text": { "IL2": "protein", "3'untranslated region": "DNA", "exon 4": "DNA" } }, { "input_text": "It is a single-copy gene , with neither structural ( amino acid ) nor promoter sequence polymorphisms identified .", "target_text": { "single-copy gene": "DNA" } }, { "input_text": "Analysis of the predicted amino acid sequence suggests that overall protein structure is conserved , but the receptor binding sites are not .", "target_text": { "predicted amino acid sequence": "protein", "protein structure": "protein" } }, { "input_text": "A number of potential regulatory sequences similar to those found in mammals have been identified in the promoter .", "target_text": { "potential regulatory sequences": "DNA", "promoter": "DNA" } }, { "input_text": "These include ( 5'-3' ) a composite NF-AT/ \" AP-1 \" element , a CD28 response element , an AP-1 element , an NF-AT element , and the AP-1 part of an AP-1/octamer composite element .", "target_text": { "NF-AT/ \" AP-1 \" element": "DNA", "CD28 response element": "DNA", "AP-1 element": "DNA", "NF-AT element": "DNA", "AP-1 part of an AP-1/octamer composite element": "DNA" } }, { "input_text": "The mammalian NF-kappaB and octamer binding sites seem to be absent , although there are alternative potential NF-kappaB and octamer-binding elements in the chicken IL2 promoter , in close proximity to their mammalian homologues .", "target_text": { "NF-kappaB": "protein", "mammalian NF-kappaB": "protein", "octamer binding sites": "DNA", "octamer-binding elements": "DNA", "IL2": "protein", "chicken IL2 promoter": "DNA", "mammalian homologues": "DNA" } }, { "input_text": "Sequence comparisons also predict other potential transcription factor binding sites as yet undescribed in mammalian IL2 promoters .", "target_text": { "IL2": "protein", "mammalian IL2 promoters": "DNA" } }, { "input_text": "A Taq I polymorphism was identified which enabled chicken IL2 to be mapped to chromosome 4 , linked to ANX5 , with synteny with mouse chromosome 3 and human chromosome 4 .", "target_text": { "Taq I polymorphism": "DNA", "IL2": "protein", "chromosome 4": "DNA", "ANX5": "DNA", "mouse chromosome 3": "DNA", "human chromosome 4": "DNA" } }, { "input_text": "This is the first non-mammalian cytokine gene to be mapped .", "target_text": { "non-mammalian cytokine gene": "DNA" } }, { "input_text": "Endothelial production of MCP-1 : modulation by heparin and consequences for mononuclear cell activation .", "target_text": { "MCP-1": "protein" } }, { "input_text": "Heparin is a polyanionic glycosaminoglycan ( GAG ) that can bind with high affinity to a range of cytokines including interferon-gamma ( IFN-gamma ) and members of the chemokine superfamily .", "target_text": { "cytokines": "protein", "interferon-gamma": "protein", "IFN-gamma": "protein", "chemokine superfamily": "protein" } }, { "input_text": "This GAG also possesses immunomodulatory activity in vivo and can antagonize the capacity of IFN-gamma to induce class II MHC antigen expression , and to up-regulate intercellular adhesion molecule-1 , by cultured endothelial cells .", "target_text": { "IFN-gamma": "protein", "class II MHC antigen": "protein", "intercellular adhesion molecule-1": "protein", "cultured endothelial cells": "cell_line" } }, { "input_text": "Previous studies have shown that binding to cell-surface heparan sulphate is essential for optimal activity of IFN-gamma and that free heparin competitively inhibits this sequestration process .", "target_text": { "IFN-gamma": "protein" } }, { "input_text": "The present study was performed to increase our understanding of the immunosuppressive activity of heparin by investigation of potential antagonism of the production and function of monocyte chemotactic peptide-1 ( MCP-1 ) , a chemokine important for mononuclear leucocyte recruitment across vascular endothelium .", "target_text": { "monocyte chemotactic peptide-1": "protein", "MCP-1": "protein", "chemokine": "protein" } }, { "input_text": "It was found that mixture of heparin with IFN-gamma inhibited up-regulation of the signal transducer and activator of transcription protein , STAT-1 produced normally by treatment of endothelial cells with IFN-gamma .", "target_text": { "IFN-gamma": "protein", "STAT-1": "protein", "endothelial cells": "cell_type" } }, { "input_text": "An inhibition of MCP-1 production was observed that was specifically caused by mixture of IFN-gamma with heparin-like , and therefore cytokine-binding , GAGs .", "target_text": { "MCP-1": "protein", "IFN-gamma": "protein" } }, { "input_text": "It was also shown that mixture of heparin -like GAGs with MCP-1 inhibited the rapid tyrosine phosphorylation of phosphatidylinositol 3-kinase which is normally produced by treatment of mononuclear leucocytes with this chemokine .", "target_text": { "MCP-1": "protein", "phosphatidylinositol 3-kinase": "protein", "mononuclear leucocytes": "cell_type", "chemokine": "protein" } }, { "input_text": "Blockade of this intracellular signalling event was associated with a reduction in the normal transendothelial migration response towards MCP-1 .", "target_text": { "MCP-1": "protein" } }, { "input_text": "Results from this study indicate that soluble , heparin -like GAGs can block IFN-gamma -dependent up-regulation of MCP-1 production by cultured endothelial cells , and can also antagonize the leucocyte-activating and migration-promoting properties of pre-existing MCP-1 .", "target_text": { "IFN-gamma": "protein", "MCP-1": "protein", "endothelial cells": "cell_type", "cultured endothelial cells": "cell_line" } }, { "input_text": "These activities may contribute to the immunomodulatory properties of heparin .", "target_text": {} }, { "input_text": "[ Molecular-biologic aspects of interaction between nervous and immune systems ]", "target_text": {} }, { "input_text": "The problem of the neuro-immuno interactions on the level of the protein trans-factors , stimulating interleukin-2 ( IL-2 ) gene expression was discussed .", "target_text": { "protein trans-factors": "protein", "interleukin-2": "protein", "IL-2": "protein", "interleukin-2 ( IL-2 ) gene": "DNA" } }, { "input_text": "The physico-chemical and functional parameters of the low molecular nuclear proteins ( SP and BP- 14 , 18 , 19 kDs ) isolated from splenic and brain cells of immunized rats were studied .", "target_text": { "low molecular nuclear proteins": "protein", "SP": "protein" } }, { "input_text": "The binding of these proteins to the regulatory region of IL-2 gene in vitro and stimulation of the IL-2mRNA synthesis in splenic T- lymphocytes culture in normal conditions were shown .", "target_text": { "IL-2 gene": "DNA", "IL-2mRNA": "RNA", "splenic T- lymphocytes culture": "cell_line" } }, { "input_text": "The protective effect of SP and BP on the IL-2mRNA synthesis in stressful conditions and by the T-cells treatment with the CsA was demonstrated .", "target_text": { "SP": "protein", "BP": "protein", "IL-2mRNA": "RNA", "T-cells": "cell_type" } }, { "input_text": "Interferon-alpha activates multiple STAT proteins and upregulates proliferation-associated IL-2Ralpha , c-myc , and pim-1 genes in human T cells .", "target_text": { "Interferon-alpha": "protein", "STAT proteins": "protein", "IL-2Ralpha": "protein", "c-myc": "DNA", "pim-1 genes": "DNA", "c-myc , and pim-1 genes": "DNA", "human T cells": "cell_type" } }, { "input_text": "Interferon-alpha ( IFN-alpha ) is a pleiotropic cytokine that has antiviral , antiproliferative , and immunoregulatory functions .", "target_text": { "Interferon-alpha": "protein", "IFN-alpha": "protein", "pleiotropic cytokine": "protein", "immunoregulatory": "protein" } }, { "input_text": "There is increasing evidence that IFN-alpha has an important role in T-cell biology .", "target_text": { "IFN-alpha": "protein" } }, { "input_text": "We have analyzed the expression of IL-2Ralpha , c-myc , and pim-1 genes in anti-CD3-activated human T lymphocytes .", "target_text": { "IL-2Ralpha": "protein", "c-myc": "DNA", "pim-1 genes": "DNA", "anti-CD3-activated human T lymphocytes": "cell_type" } }, { "input_text": "The induction of these genes is associated with interleukin-2 ( IL-2 ) -induced T-cell proliferation .", "target_text": { "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "Treatment of T lymphocytes with IFN-alpha , IL-2 , IL-12 , and IL-15 upregulated IL-2Ralpha , c-myc , and pim-1 gene expression .", "target_text": { "T lymphocytes": "cell_type", "IFN-alpha": "protein", "IL-2": "protein", "IL-12": "protein", "IL-15": "protein", "IL-2Ralpha": "protein", "c-myc": "DNA", "pim-1 gene": "DNA" } }, { "input_text": "IFN-alpha also sensitized T cells to IL-2 -induced proliferation , further suggesting that IFN-alpha may be involved in the regulation of T-cell mitogenesis .", "target_text": { "IFN-alpha": "protein", "sensitized T cells": "cell_line", "IL-2": "protein" } }, { "input_text": "When we analyzed the nature of STAT proteins capable of binding to IL-2Ralpha , pim-1 , and IRF-1 GAS elements after cytokine stimulation , we observed IFN-alpha -induced binding of STAT1 , STAT3 , and STAT4 , but not STAT5 to all of these elements .", "target_text": { "STAT proteins": "protein", "IL-2Ralpha": "protein", "cytokine": "protein", "IFN-alpha": "protein", "STAT1": "protein", "STAT3": "protein", "STAT4": "protein", "STAT5": "protein" } }, { "input_text": "Yet , IFN-alpha was able to activate binding of STAT5 to the high-affinity IFP53 GAS site .", "target_text": { "IFN-alpha": "protein", "STAT5": "protein" } }, { "input_text": "IFN-alpha enhanced tyrosine phosphorylation of STAT1 , STAT3 , STAT4 , STAT5a , and STAT5b .", "target_text": { "IFN-alpha": "protein", "STAT3": "protein", "STAT4": "protein", "STAT5a": "protein", "STAT5b": "protein" } }, { "input_text": "IL-12 induced STAT4 and IL-2 and IL-15 induced STAT5 binding to the GAS elements .", "target_text": { "IL-12": "protein", "STAT4": "protein", "IL-2": "protein", "IL-15": "protein", "STAT5": "protein", "GAS elements": "DNA" } }, { "input_text": "Taken together , our results suggest that IFN-alpha , IL-2 , IL-12 , and IL-15 have overlapping activities on human T cells .", "target_text": { "IFN-alpha": "protein", "IL-2": "protein", "IL-12": "protein", "IL-15": "protein", "human T cells": "cell_type" } }, { "input_text": "These findings thus emphasize the importance of IFN-alpha as a T-cell regulatory cytokine .", "target_text": { "IFN-alpha": "protein", "T-cell regulatory cytokine": "protein" } }, { "input_text": "The Megakaryocyte/Platelet-specific enhancer of the alpha2beta1 integrin gene : two tandem AP1 sites and the mitogen-activated protein kinase signaling cascade .", "target_text": { "Megakaryocyte/Platelet-specific enhancer": "DNA", "alpha2beta1 integrin gene": "DNA", "AP1 sites": "DNA", "mitogen-activated protein kinase": "protein" } }, { "input_text": "The alpha2beta1 integrin , a collagen receptor on platelets and megakaryocytes , is required for normal platelet function .", "target_text": { "alpha2beta1 integrin": "protein", "platelets": "cell_type", "megakaryocytes": "cell_type" } }, { "input_text": "Transcriptional regulation of the alpha2 integrin gene in cells undergoing megakaryocytic differentiation requires a core promoter between bp -30 and -92 , a silencer between bp -92 and -351 , and megakaryocytic enhancers in the distal 5' flank .", "target_text": { "alpha2 integrin gene": "DNA", "core promoter": "DNA", "silencer": "DNA", "megakaryocytic enhancers": "DNA", "distal 5' flank": "DNA" } }, { "input_text": "We have now identified a 229-bp region of the distal 5 ' flank of the alpha2 integrin gene required for high-level enhancer activity in cells with megakaryocytic features .", "target_text": { "229-bp region": "DNA", "distal 5 ' flank": "DNA", "alpha2 integrin gene": "DNA", "high-level enhancer activity in cells": "cell_type" } }, { "input_text": "Two tandem AP1 binding sites with dyad symmetry are required for enhancer activity and for DNA-protein complex formation with members of the c-fos/c-jun family .", "target_text": { "AP1 binding sites": "DNA", "DNA-protein complex": "protein", "c-fos/c-jun family": "protein" } }, { "input_text": "The requirement for AP1 activation suggested a role for the mitogen-activated protein kinase ( MAPK ) signaling pathway in regulating alpha2 integrin gene expression .", "target_text": { "AP1": "protein", "mitogen-activated protein kinase": "protein", "MAPK": "protein", "alpha2 integrin gene": "DNA" } }, { "input_text": "Inhibition of the MAP kinase cascade with PD98059 , a specific inhibitor of MAPK kinase 1 , prevented the expression of the alpha2 integrin subunit in cells induced to become megakaryocytic .", "target_text": { "MAP kinase": "protein", "MAPK kinase 1": "protein", "alpha2 integrin subunit": "protein" } }, { "input_text": "We provide a model of megakaryocytic differentiation in which expression of the alpha2 integrin gene requires signaling via the MAP kinase pathway to activate two tandem AP1 binding sites in the alpha2 integrin enhancer .", "target_text": { "alpha2 integrin gene": "DNA", "MAP kinase": "protein", "AP1 binding sites": "DNA", "alpha2 integrin enhancer": "DNA" } }, { "input_text": "Functional association of Nmi with Stat5 and Stat1 in IL-2 - and IFNgamma -mediated signaling .", "target_text": { "Nmi": "protein", "Stat5": "protein", "Stat1": "protein", "IL-2": "protein", "IFNgamma": "protein" } }, { "input_text": "Using the coiled-coil region of Stat5b as the bait in a yeast two-hybrid screen , we identified the association of Nmi , a protein of unknown function previously reported as an N-Myc interactor .", "target_text": { "Stat5b": "protein", "Nmi": "protein", "N-Myc": "protein" } }, { "input_text": "We further show that Nmi interacts with all STATs except Stat2 .", "target_text": { "Nmi": "protein", "STATs": "protein", "Stat2": "protein" } }, { "input_text": "We evaluated two cytokine systems , IL-2 and IFNgamma , and demonstrate that Nmi augments STAT -mediated transcription in response to these cytokines .", "target_text": { "IL-2": "protein", "IFNgamma": "protein", "Nmi": "protein", "STAT": "protein", "cytokines": "protein" } }, { "input_text": "Interestingly , Nmi lacks an intrinsic transcriptional activation domain ; instead , Nmi enhances the association of CBP/p300 coactivator proteins with Stat1 and Stat5 , and together with CBP/p300 can augment IL-2- and IFNgamma- dependent transcription .", "target_text": { "Nmi": "protein", "transcriptional activation domain": "protein", "CBP/p300 coactivator proteins": "protein", "Stat1": "protein", "Stat5": "protein", "CBP/p300": "protein" } }, { "input_text": "Therefore , our data not only reveal that Nmi can potentiate STAT -dependent transcription , but also suggest that it can augment coactivator protein recruitment to at least some members of a group of sequence-specific transcription factors .", "target_text": { "Nmi": "protein", "STAT": "protein", "sequence-specific transcription factors": "protein" } }, { "input_text": "Lactobacilli and vaginal host defense : activation of the human immunodeficiency virus type 1 long terminal repeat , cytokine production , and NF-kappaB .", "target_text": { "human immunodeficiency virus type 1 long terminal repeat": "DNA", "cytokine": "protein", "NF-kappaB": "protein" } }, { "input_text": "Lactobacilli , a component of the normal vaginal flora , can activate the human immunodeficiency virus ( HIV ) -1 long terminal repeat ( LTR ) in the Jurkat T lymphocyte and THP-1 macrophage cell lines .", "target_text": { "human immunodeficiency virus ( HIV ) -1 long terminal repeat": "DNA", "LTR": "DNA", "Jurkat T lymphocyte": "cell_line", "THP-1 macrophage cell lines": "cell_line" } }, { "input_text": "Activation of the LTR in Jurkat cells was strongly enhanced by vanadate and inhibited by catalase , implicating H2O2 .", "target_text": { "LTR": "DNA", "Jurkat cells": "cell_line", "catalase": "protein" } }, { "input_text": "In contrast , activation in THP-1 cells occurred in the absence of vanadate and was unaffected by catalase .", "target_text": { "THP-1 cells": "protein", "catalase": "protein" } }, { "input_text": "The active material partitioned into the phenol layer on hot aqueous phenol extraction .", "target_text": {} }, { "input_text": "Lactobacilli also increased tumor necrosis factor -alpha and interleukin -1beta production and activated NF-kappaB in THP-1 cells and increased tumor necrosis factor -alpha production by human monocytes .", "target_text": { "tumor necrosis factor": "protein", "interleukin": "protein", "NF-kappaB": "protein", "THP-1 cells": "protein", "human monocytes": "cell_type" } }, { "input_text": "Human vaginal fluid specimens had comparable properties , which correlated with their bacterial content .", "target_text": {} }, { "input_text": "These findings suggest the presence in vaginal fluid of agent ( s ) derived from indigenous bacteria that can activate the HIV-1 LTR , cytokine production , and NF-kappaB in cells of macrophage lineage , with possible influence on vaginal physiology and host defense .", "target_text": { "LTR": "DNA", "HIV-1 LTR": "DNA", "cytokine": "protein", "NF-kappaB": "protein", "macrophage lineage": "cell_type" } }, { "input_text": "T cell priming enhances IL-4 gene expression by increasing nuclear factor of activated T cells .", "target_text": { "IL-4 gene": "DNA", "nuclear factor of activated T cells": "protein" } }, { "input_text": "The repetitive activation of T cells ( priming ) enhances the expression of many cytokines , such as IL-4 , but not others , such as IL-2 .", "target_text": { "T cells": "cell_type", "cytokines": "protein", "IL-2": "protein" } }, { "input_text": "Molecular mechanisms underlying selective expression of cytokines by T cells remain poorly understood .", "target_text": { "cytokines": "protein", "T cells": "cell_type" } }, { "input_text": "Here we show that priming of CD4 T cells selectively enhances IL-4 expression relative to IL-2 expression by a transcriptional mechanism involving nuclear factor of activated T cells ( NFAT ) proteins .", "target_text": { "CD4 T cells": "cell_type", "IL-4": "protein", "IL-2": "protein", "nuclear factor of activated T cells": "protein", "nuclear factor of activated T cells ( NFAT ) proteins": "protein" } }, { "input_text": "As detected by in vivo footprinting , priming markedly increases the activation-dependent engagement of the P0 and P1 NFAT-binding elements of the IL-4 promoter .", "target_text": { "P0": "DNA", "P1": "DNA", "NFAT-binding elements": "DNA", "IL-4": "protein", "IL-4 promoter": "DNA" } }, { "input_text": "Moreover , each proximal P element is essential for optimal IL-4 promoter activity .", "target_text": { "proximal P element": "DNA", "IL-4": "protein", "IL-4 promoter": "DNA" } }, { "input_text": "Activated primed CD4 T cells contain more NFAT1 and support greater NFAT -directed transcription than unprimed CD4 T cells , while activator protein 1 binding and activator protein 1 -mediated transcription by both cell types is similar .", "target_text": { "CD4 T cells": "cell_type", "NFAT1": "protein", "NFAT": "protein", "activator protein 1": "protein" } }, { "input_text": "Increased expression of wild-type NFAT1 substantially increases IL-4 promoter activity in unprimed CD4 T cells , suggesting NFAT1 may be limiting for IL-4 gene expression in this cell type .", "target_text": { "NFAT1": "protein", "IL-4": "protein", "IL-4 promoter": "DNA", "CD4 T cells": "cell_type" } }, { "input_text": "Furthermore , a truncated form of NFAT1 acts as a dominant-negative , reducing IL-4 promoter activity in primed CD4 T cells and confirming the importance of endogenous NFAT to increased IL-4 gene expression by effector T cells .", "target_text": { "NFAT1": "protein", "IL-4": "protein", "IL-4 promoter": "DNA", "CD4 T cells": "cell_type", "endogenous NFAT": "protein" } }, { "input_text": "NFAT1 appears to be the major NFAT family member responsible for the initial increased expression of IL-4 by primed CD4 T cells .", "target_text": { "NFAT1": "protein", "NFAT family member": "protein", "IL-4": "protein", "CD4 T cells": "cell_type" } }, { "input_text": "Differential monocyte adhesion and adhesion molecule expression in venous and arterial endothelial cells .", "target_text": { "adhesion molecule": "protein" } }, { "input_text": "We compared U-937 cell adhesion and adhesion molecule expression in human umbilical venous ( HUVECs ) and arterial ( HUAECs ) endothelial cells exposed to tumor necrosis factor ( TNF ) , interleukin-1 , and lipopolysaccharide ( LPS ) .", "target_text": { "U-937 cell": "cell_line", "adhesion molecule": "protein", "human umbilical venous": "cell_type", "HUVECs": "cell_type", "arterial ( HUAECs ) endothelial cells": "cell_type", "tumor necrosis factor": "protein", "TNF": "protein", "interleukin-1": "protein" } }, { "input_text": "TNF and LPS stimulated vascular cell adhesion molecule ( VCAM ) -1 surface expression and adhesion of U-937 monocyte-like cells to HUVECs but not to HUAECs .", "target_text": { "TNF": "protein", "adhesion molecule": "protein", "vascular cell adhesion molecule": "protein", "VCAM": "protein", "U-937 monocyte-like cells": "cell_line", "HUVECs": "cell_type", "HUAECs": "cell_type" } }, { "input_text": "Antibody studies demonstrated that in HUVECs at least 75 % of the adhesion response is VCAM-1 mediated .", "target_text": { "HUVECs": "cell_type", "VCAM-1": "protein" } }, { "input_text": "Interleukin-1 stimulated U-937 cell adhesion to and VCAM-1 surface expression in both HUVECs and HUAECs .", "target_text": { "Interleukin-1": "protein", "U-937 cell": "cell_line", "VCAM-1": "protein", "HUVECs": "cell_type", "HUAECs": "cell_type" } }, { "input_text": "Pyrrolidinedithiocarbamate and the proteasome inhibitor MG-132 blocked TNF - and LPS -stimulated U-937 cell adhesion to HUVECs .", "target_text": { "TNF": "protein", "U-937 cell": "cell_line", "HUVECs": "cell_type" } }, { "input_text": "These agents also significantly decreased TNF - and LPS -stimulated increases in HUVEC surface VCAM-1 .", "target_text": { "TNF": "protein", "VCAM-1": "protein", "HUVEC surface VCAM-1": "protein" } }, { "input_text": "TNF increased VCAM-1 protein and mRNA in HUVECs that was blocked by pyrrolidinedithiocarbamate .", "target_text": { "TNF": "protein", "VCAM-1": "protein", "mRNA": "RNA", "HUVECs": "cell_type" } }, { "input_text": "However , neither TNF or LPS stimulated VCAM-1 expression in HUAECs .", "target_text": { "TNF": "protein", "VCAM-1": "protein", "HUAECs": "cell_type" } }, { "input_text": "TNF stimulated expression of both intercellular adhesion molecule-1 and E-selectin in HUVECs , but in HUAECs , only intercellular adhesion molecule-1 was increased .", "target_text": { "TNF": "protein", "intercellular adhesion molecule-1": "protein", "E-selectin": "protein", "HUVECs": "cell_type", "HUAECs": "cell_type" } }, { "input_text": "Electrophoretic mobility shift assays demonstrated no difference in the pattern of TNF -stimulated nuclear factor-kappaB activation between HUVECs and HUAECs .", "target_text": { "TNF": "protein", "nuclear factor-kappaB": "protein", "HUVECs": "cell_type", "HUAECs": "cell_type" } }, { "input_text": "These studies demonstrate a novel and striking insensitivity of arterial endothelium to the effects of TNF and LPS and indicate a dissociation between the ability of HUAECs to upregulate nuclear factor-kappaB and VCAM-1 .", "target_text": { "TNF": "protein", "HUAECs": "cell_type", "nuclear factor-kappaB": "protein", "VCAM-1": "protein" } }, { "input_text": "Functional testosterone receptors in plasma membranes of T cells .", "target_text": { "testosterone receptors": "protein", "T cells": "cell_type" } }, { "input_text": "T cells are considered to be unresponsive to testosterone due to the absence of androgen receptors ( AR ) .", "target_text": { "T cells": "cell_type", "androgen receptors": "protein", "AR": "protein" } }, { "input_text": "Here , we demonstrate the testosterone responsiveness of murine splenic T cells in vitro as well as the presence of unconventional cell surface receptors for testosterone and classical intracellular AR .", "target_text": { "T cells": "cell_type", "murine splenic T cells": "cell_type", "unconventional cell surface receptors": "protein", "classical intracellular AR": "protein" } }, { "input_text": "Binding sites for testosterone on the surface of both CD4(+) and CD8(+) subsets of T cells are directly revealed with the impeded ligand testosterone -BSA-FITC by confocal laser scanning microscopy ( CLSM ) and flow cytometry , respectively .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Binding of the plasma membrane impermeable testosterone -BSA conjugate induces a rapid rise ( < 5 s ) in [Ca2+]i of Fura-2-loaded T cells .", "target_text": { "testosterone -BSA conjugate": "protein", "Fura-2-loaded T cells": "cell_type" } }, { "input_text": "This rise reflects influx of extracellular Ca2+ through non-voltage-gated and Ni2+-blockable Ca2+ channels of the plasma membrane .", "target_text": { "Ni2+-blockable Ca2+ channels": "protein" } }, { "input_text": "The testosterone -BSA-induced Ca2+ import is not affected by cyproterone , a blocker of the AR .", "target_text": { "AR": "protein" } }, { "input_text": "In addition , AR are not detectable on the surface of intact T cells when using anti- AR antibodies directed against the amino and carboxy terminus of the AR , although T cells contain AR , as revealed by reverse transcription-polymerase chain reactions and Western blotting .", "target_text": { "AR": "protein", "intact T cells": "cell_type", "anti- AR antibodies": "protein", "amino": "protein", "carboxy terminus": "protein", "amino and carboxy terminus": "protein", "T cells": "cell_type" } }, { "input_text": "AR can be visualized with the anti- AR antibodies in the cytoplasm of permeabilized T cells by using CLSM , though AR are not detectable in cytosol fractions when using the charcoal binding assay with 3H-R1881 as ligand .", "target_text": { "AR": "protein", "anti- AR antibodies": "protein", "permeabilized T cells": "cell_type" } }, { "input_text": "Cytoplasmic AR do not translocate to the nucleus of T cells in the presence of testosterone , in contrast to cytoplasmic AR in human cancer LNCaP cells .", "target_text": { "AR": "protein", "Cytoplasmic AR": "protein", "T cells": "cell_type", "cytoplasmic AR": "protein", "human cancer LNCaP cells": "cell_line" } }, { "input_text": "These findings suggest that the classical AR present in splenic T cells are not active in the genomic pathway .", "target_text": { "AR": "protein", "classical AR": "protein", "splenic T cells": "cell_type" } }, { "input_text": "By contrast , the cell surface receptors for testosterone are in a functionally active state , enabling T cells a nongenomic response to testosterone .", "target_text": { "cell surface receptors": "protein", "T cells": "cell_type" } }, { "input_text": "Limited proteolysis for assaying ligand binding affinities of nuclear receptors .", "target_text": { "nuclear receptors": "protein" } }, { "input_text": "The binding of natural or synthetic ligands to nuclear receptors is the triggering event leading to gene transcription activation or repression .", "target_text": { "nuclear receptors": "protein" } }, { "input_text": "Ligand binding to the ligand binding domain of these receptors induces conformational changes that are evidenced by an increased resistance of this domain to proteases .", "target_text": { "ligand binding domain": "protein", "receptors": "protein", "proteases": "protein" } }, { "input_text": "In vitro labeled receptors were incubated with various synthetic or natural agonists or antagonists and submitted to trypsin digestion .", "target_text": { "In vitro labeled receptors": "protein", "trypsin": "protein" } }, { "input_text": "Proteolysis products were separated by SDS-PAGE and quantified .", "target_text": {} }, { "input_text": "The amount of trypsin -resistant fragments was proportional to receptor occupancy by the ligand , and allowed the determination of dissociation constants ( kDa ) .", "target_text": { "trypsin": "protein" } }, { "input_text": "Using the wild-type or mutated human retinoic acid receptor alpha as a model , kDa values determined by classical competition binding assays using tritiated ligands are in agreement with those measured by the proteolytic assay .", "target_text": {} }, { "input_text": "This method was successfully extended to human retinoic X receptor alpha , glucocorticoid receptor , and progesterone receptor , thus providing a basis for a new , faster assay to determine simultaneously the affinity and conformation of receptors when bound to a given ligand .", "target_text": { "human retinoic X receptor alpha": "protein", "glucocorticoid receptor": "protein", "progesterone receptor": "protein" } }, { "input_text": "Genes that regulate interleukin-4 expression in T cells .", "target_text": { "interleukin-4": "protein", "T cells": "cell_type" } }, { "input_text": "Interleukin-4 is an immunomodulatory cytokine which plays a central role in the regulation of allergic and atopic immune responses .", "target_text": { "Interleukin-4": "protein", "cytokine": "protein", "immunomodulatory cytokine": "protein" } }, { "input_text": "Significant progress has been made in gaining a detailed understanding of the transcriptional regulation of the interleukin-4 gene .", "target_text": { "interleukin-4": "protein", "interleukin-4 gene": "DNA" } }, { "input_text": "The recent identification and characterization of several key transcription factors has helped to elucidate the molecular mechanisms of T helper cell cytokine gene expression .", "target_text": { "transcription factors": "protein", "T helper cell cytokine gene": "DNA" } }, { "input_text": "B lymphocytes from patients with chronic lymphocytic leukemia contain signal transducer and activator of transcription ( STAT ) 1 and STAT3 constitutively phosphorylated on serine residues .", "target_text": { "B lymphocytes": "cell_type", "signal transducer and activator of transcription ( STAT ) 1": "protein", "STAT3": "protein" } }, { "input_text": "To explore the pathogenesis of chronic lymphocytic leukemia ( CLL ) , we examined whether phosphorylation of one or more signal transducer and activator of transcription ( STAT ) factors was abnormal in cells from CLL patients .", "target_text": { "signal transducer and activator of transcription ( STAT ) factors": "protein" } }, { "input_text": "No constitutive tyrosine phosphorylation was detected on any STAT in CLL cells .", "target_text": { "STAT": "protein", "CLL cells": "cell_line" } }, { "input_text": "To assess the phosphorylation of serine residues of STAT1 and STAT3 in CLL cells , we raised antibodies that specifically recognize the form of STAT1 phosphorylated on ser-727 and the form of STAT3 phosphorylated on ser-727 .", "target_text": { "STAT1": "protein", "STAT3": "protein", "CLL cells": "cell_line" } }, { "input_text": "We found that in 100 % of patients with CLL ( n = 32 ) , STAT1 and STAT3 were constitutively phosphorylated on serine .", "target_text": { "STAT1": "protein", "STAT3": "protein" } }, { "input_text": "This was in contrast to normal peripheral blood B lymphocytes or CD5+) B cells isolated from tonsils , in which this phosphorylation was absent .", "target_text": { "B lymphocytes": "cell_type", "CD5+) B cells": "cell_type" } }, { "input_text": "Serine phosphorylation of STAT1 and STAT3 was seen occasionally in other leukemias , but it was a universal finding only in CLL .", "target_text": { "STAT1": "protein", "STAT3": "protein" } }, { "input_text": "The serine phosphorylation of these STATs was a continuous process , as incubation of CLL cells with the kinase inhibitor H7 led to the dephosphorylation of these serine residues .", "target_text": { "STATs": "protein", "CLL cells": "cell_line", "kinase inhibitor H7": "protein" } }, { "input_text": "The STAT serine kinase in CLL cells has not been identified , and appears to be neither mitogen-activated protein kinase nor pp70(s6k) .", "target_text": { "mitogen-activated protein kinase": "protein", "pp70(s6k)": "protein" } }, { "input_text": "In summary , the constitutive serine phosphorylation of STAT1 and STAT3 is present in all CLL samples tested to date , although the physiologic significance of this modification remains to be determined .", "target_text": { "STAT1": "protein", "STAT3": "protein" } }, { "input_text": "Activation of human immunodeficiency virus type 1 expression by Gardnerella vaginalis .", "target_text": {} }, { "input_text": "Bacterial vaginosis ( BV ) is associated with an increased rate of sexual transmission of human immunodeficiency virus ( HIV ) type 1 , and Gardnerella vaginalis is frequently isolated from the genital tracts of women with BV .", "target_text": {} }, { "input_text": "G. vaginalis lysates were found to significantly stimulate HIV expression in monocytoid cells .", "target_text": { "monocytoid cells": "cell_type" } }, { "input_text": "Stimulation was significantly higher when lysates were heated at 100 degrees C for 5 min but was reduced by treatment with lysozyme or protease .", "target_text": { "lysozyme": "protein", "protease": "protein" } }, { "input_text": "G. vaginalis lysates also activated HIV expression in certain T cell lines .", "target_text": { "T cell lines": "cell_line" } }, { "input_text": "G. vaginalis lysates activated HIV long-terminal repeat transcription in HIV -infected cells and increased NF-kappaB binding activity , indicating an effect by G. vaginalis on HIV transcription .", "target_text": { "HIV -infected cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "The activation of HIV production by G. vaginalis suggests that genital tract infection with G. vaginalis increases the risk of HIV transmission by increasing HIV expression in the genital tract .", "target_text": {} }, { "input_text": "This may explain , at least in part , the increased rate of HIV transmission in women with BV .", "target_text": {} }, { "input_text": "Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1 .", "target_text": { "Interleukin-10": "protein", "STAT1": "protein" } }, { "input_text": "Interleukin-10 ( IL-10 ) helps maintain polarized T-helper cells in a T-helper lymphocyte 2 ( Th2 ) phenotype .", "target_text": { "Interleukin-10": "protein", "IL-10": "protein", "polarized T-helper cells": "cell_type", "T-helper lymphocyte 2 ( Th2 ) phenotype": "cell_type" } }, { "input_text": "Part of this process involves the prevention of the development of Th1 cells , which are a primary source of interferon gamma ( IFNgamma ) , a potent activator of monocytes and an inhibitor of Th2 proliferation .", "target_text": { "Th1 cells": "cell_type", "interferon gamma": "protein", "IFNgamma": "protein", "monocytes": "cell_type" } }, { "input_text": "Because monocytes and macrophages are important mediators of Th1-type responses , such as delayed-type hypersensitivity , we sought to determine if IL-10 could directly mediate inhibition of IFNgamma- and IFNalpha- induced gene expression in these cells .", "target_text": { "monocytes": "cell_type", "IL-10": "protein" } }, { "input_text": "Highly purified monocytes were incubated with IL-10 for 60 to 90 minutes before the addition of IFNgamma or IFNalpha .", "target_text": { "monocytes": "cell_type", "IL-10": "protein", "IFNgamma": "protein", "IFNalpha": "protein" } }, { "input_text": "IL-10 preincubation resulted in the inhibition of gene expression for several IFN-induced genes , such as IP-10 , ISG54 , and intercellular adhesion molecule-1 .", "target_text": { "IL-10": "protein", "IFN-induced genes": "DNA", "IP-10": "protein", "ISG54": "protein", "intercellular adhesion molecule-1": "protein" } }, { "input_text": "The reduction in gene expression resulted from the ability of IL-10 to suppress IFN -induced assembly of signal transducer and activator of transcription ( STAT ) factors to specific promoter motifs on IFNalpha- and IFNgamma- inducible genes .", "target_text": { "IL-10": "protein", "IFN": "protein", "signal transducer and activator of transcription ( STAT ) factors": "protein", "specific promoter motifs": "DNA" } }, { "input_text": "This was accomplished by preventing the IFN-induced tyrosine phosphorylation of STAT1 , a component of both IFNalpha- and IFNgamma- induced DNA binding complexes .", "target_text": { "STAT1": "protein" } }, { "input_text": "Therefore , IL-10 can directly inhibit STAT-dependent early response gene expression induced by both IFNalpha and IFNgamma in monocytes by suppressing the tyrosine phosphorylation of STAT1 .", "target_text": { "IL-10": "protein", "STAT-dependent early response gene": "DNA", "IFNalpha": "protein", "IFNgamma": "protein", "monocytes": "cell_type", "STAT1": "protein" } }, { "input_text": "This may occur through the ability of IL-10 to induce expression of the gene , suppressor of cytokine signaling 3 ( SOCS3 ) .", "target_text": { "IL-10": "protein", "cytokine signaling 3": "protein", "SOCS3": "protein" } }, { "input_text": "Clonality analysis of refractory anemia with ring sideroblasts : simultaneous study of clonality and cytochemistry of bone marrow progenitors .", "target_text": { "ring sideroblasts": "cell_type", "bone marrow progenitors": "cell_type" } }, { "input_text": "X chromosome inactivation and polymorphism of the human androgen receptor ( HUMARA ) gene has been applied for analyzing the clonality of blood cells .", "target_text": { "HUMARA": "protein", "human androgen receptor ( HUMARA ) gene": "DNA", "blood cells": "cell_type" } }, { "input_text": "In the present study , the clonal relationship was investigated between peripheral blood polymorphonuclear cells ( PMNCs ) and marrow progenitor cells and the origin of ringed sideroblasts in patients with refractory anemia with ring sideroblasts ( RARS ) by polymerase chain reaction ( PCR ) of HUMARA gene .", "target_text": { "peripheral blood polymorphonuclear cells": "cell_type", "PMNCs": "cell_type", "marrow progenitor cells": "cell_type", "ringed sideroblasts": "cell_type", "ring sideroblasts": "cell_type", "RARS": "cell_type", "HUMARA gene": "DNA" } }, { "input_text": "The X-inactivation patterns of circulating PMNCs and T lymphocytes as well as individual granulocyte colonies grown in vitro from bone marrow cells were analyzed .", "target_text": { "PMNCs": "cell_type", "T lymphocytes": "cell_type", "granulocyte colonies": "cell_line" } }, { "input_text": "The development of ringed sideroblasts in erythroid colonies by iron staining and their X-inactivation pattern were also examined .", "target_text": { "ringed sideroblasts": "cell_type", "erythroid colonies": "cell_line" } }, { "input_text": "All three RARS patients showed monoclonal PMNCs .", "target_text": { "RARS": "cell_type", "PMNCs": "cell_type" } }, { "input_text": "In granulocyte colonies , however , two different X-inactivation patterns were observed in all patients , indicating that non-clonal progenitor cells remained in the bone marrow .", "target_text": { "granulocyte colonies": "cell_line", "non-clonal progenitor cells": "cell_type" } }, { "input_text": "All erythroid colonies consisted of ringed sideroblasts exclusively showed one pattern dominant in those of PMNCs .", "target_text": { "erythroid colonies": "cell_line", "ringed sideroblasts": "cell_type", "PMNCs": "cell_type" } }, { "input_text": "Our findings suggest that non-clonal progenitor cells persist in some RARS cases , that erythroid progenitors show mosaicism , and that ringed sideroblasts may be derived from an abnormal clone involved in the pathogenesis of this disease .", "target_text": { "non-clonal progenitor cells": "cell_type", "RARS": "cell_type", "erythroid progenitors": "cell_type", "ringed sideroblasts": "cell_type" } }, { "input_text": "Granulosa cell tumor of the ovary .", "target_text": {} }, { "input_text": "Immunohistochemical evidence of low proliferative activity and virtual absence of mutation of the p53 tumor-suppressor gene .", "target_text": { "p53 tumor-suppressor gene": "DNA" } }, { "input_text": "BACKGROUND AND METHODS : Because the use of immunohistochemistry in the diagnosis of granulosa cell tumor ( GCT ) has not been fully explored , routinely processed ( formalin-fixed , paraffin-embedded ) tissue from 11 GCT , adult type , was investigated immunohistochemically ( ABC method ) with a broad spectrum of antibodies against various markers , including p53 and Ki-67 .", "target_text": { "p53": "protein", "Ki-67": "protein" } }, { "input_text": "All of the tumors exhibited typical morphology , were limited to the ovary ( stage I ) , and 7 cases followed a benign clinical course .", "target_text": {} }, { "input_text": "RESULTS : All the tumors exhibited strong expression of vimentin , but most other antigens ( including smooth muscle actin ) were expressed infrequently by a minority of tumor cells or not at all .", "target_text": { "vimentin": "protein", "smooth muscle actin": "protein", "tumor cells": "cell_type" } }, { "input_text": "Tumor cells in 9 GCT expressed inhibin A .", "target_text": {} }, { "input_text": "All the tumors exhibited very low proliferative activity , fewer than 10 % of the tumor cell nuclei being stained by the antibody MIB-1 ( Ki-67 antigen ) .", "target_text": { "antibody MIB-1": "protein", "Ki-67": "protein", "Ki-67 antigen": "protein" } }, { "input_text": "The antibody D07 revealed marked overexpression of p53 protein in only one tumor .", "target_text": { "antibody D07": "protein", "p53 protein": "protein" } }, { "input_text": "Clinical outcome was not found to be related to immunophenotypic differences .", "target_text": {} }, { "input_text": "CONCLUSIONS : The diagnosis of GCT should be based primarily on the typical morphology revealed by conventional stains , but additional immunohistochemical staining with a small panel of selected antibodies ( for example , against keratin , vimentin , and inhibin A ) may be helpful in a few cases .", "target_text": { "keratin": "protein", "vimentin": "protein", "inhibin A": "protein" } }, { "input_text": "The very low proliferative activity and the lack of overexpression of p53 protein are consistent with the benign clinical behavior of the majority of GCT .", "target_text": { "p53 protein": "protein" } }, { "input_text": "Protective effects of notch-1 on TCR -induced apoptosis .", "target_text": { "notch-1": "protein", "TCR": "protein" } }, { "input_text": "The Notch receptor protein was originally identified in Drosophila and is known to mediate cell to cell communication and influence cell fate decisions .", "target_text": { "Notch receptor protein": "protein" } }, { "input_text": "Members of this family have been isolated from invertebrates as well as vertebrates .", "target_text": {} }, { "input_text": "We isolated mouse Notch-1 in a yeast two-hybrid screen with Nur77 , which is a protein that has been shown previously to be required for apoptosis in T cell lines .", "target_text": { "mouse Notch-1": "protein", "Nur77": "protein", "T cell lines": "cell_line" } }, { "input_text": "The data presented below indicate that Notch-1 expression provides significant protection to T cell lines from TCR -mediated apoptosis .", "target_text": { "Notch-1": "protein", "T cell lines": "cell_line", "TCR": "protein" } }, { "input_text": "These data demonstrate a new antiapoptotic role for Notch-1 , providing evidence that , in addition to regulating cell fate decisions , Notch-1 can play a critical role in controlling levels of cell death in T cells .", "target_text": { "Notch-1": "protein", "T cells": "cell_type" } }, { "input_text": "Comparison of primary sensitization of naive human T cells to varicella-zoster virus peptides by dendritic cells in vitro with responses elicited in vivo by varicella vaccination .", "target_text": { "naive human T cells": "cell_type", "dendritic cells": "cell_type" } }, { "input_text": "Dendritic cells ( DC ) are potent APC during primary and secondary immune responses .", "target_text": { "Dendritic cells": "cell_type", "DC": "cell_type", "APC": "cell_type" } }, { "input_text": "The first objective of this study was to determine whether human DC mediate in vitro sensitization of naive CD4+ T cells to epitopes of the immediate early 62 ( IE62 ) protein of varicella zoster virus ( VZV ) .", "target_text": { "DC": "cell_type", "human DC": "cell_type", "naive CD4+ T cells": "cell_type", "epitopes": "protein", "immediate early 62 ( IE62 ) protein": "protein" } }, { "input_text": "The induction of CD4+ T cell proliferative responses to eight synthetic peptides representing amino acid sequences of the VZV IE62 protein was assessed using T cells and DC from VZV -susceptible donors .", "target_text": { "CD4+": "protein", "amino acid sequences": "protein", "VZV IE62 protein": "protein", "T cells": "cell_type", "DC": "cell_type" } }, { "input_text": "The second objective was to compare in vitro responses of naive T cells with responses to VZV peptides induced in vivo after immunization with varicella vaccine .", "target_text": { "naive T cells": "cell_type" } }, { "input_text": "T cell proliferation was induced by three peptides , P1 , P4 , and P7 , in 71-100 % of the donors tested before and after vaccination using DC as APC .", "target_text": { "DC": "cell_type", "APC": "cell_type" } }, { "input_text": "Monocytes were effective APC for VZV peptides only after immunization .", "target_text": { "Monocytes": "cell_type", "APC": "cell_type" } }, { "input_text": "Two peptides , P2 and P8 , induced naive T cell proliferation less effectively and were also less immunogenic for T cells from vaccinated or naturally immune donors .", "target_text": { "T cells": "cell_type" } }, { "input_text": "T cell recognition of specific peptides was concordant between naive , DC -mediated responses , and postvaccine responses using monocytes as APC in 69 % of comparisons ( p = 0.05 ; chi2 ) ; the predictive value of a positive response to an IE62 peptide before immunization for T cell sensitization in vivo was 82 % .", "target_text": { "DC": "cell_type", "monocytes": "cell_type", "APC": "cell_type" } }, { "input_text": "These observations indicate that primary T cell responses detected in vitro using DC as APC may be useful to characterize the potential immunogenicity of viral protein epitopes in vivo .", "target_text": { "DC": "cell_type", "APC": "cell_type" } }, { "input_text": "Mechanism of interleukin-10 inhibition of T-helper cell activation by superantigen at the level of the cell cycle .", "target_text": { "interleukin-10": "protein", "superantigen": "protein" } }, { "input_text": "We have analyzed the effects of interleukin-10 ( IL-10 ) on the entry of quiescent CD4(+) T cells into the cell cycle upon stimulation with the superantigen staphylococcal enterotoxin B ( SEB ) .", "target_text": { "interleukin-10": "protein", "IL-10": "protein", "CD4(+) T cells": "cell_type", "superantigen": "protein", "staphylococcal enterotoxin B": "protein", "SEB": "protein" } }, { "input_text": "IL-10 arrested cells at G0/G1 .", "target_text": { "IL-10": "protein" } }, { "input_text": "IL-10 treatment prevented the downregulation of p27 ( Kip1 ) , an inhibitory protein that controls progression out of the G0 phase of the cell cycle .", "target_text": { "IL-10": "protein", "p27 ( Kip1": "protein", "inhibitory protein": "protein" } }, { "input_text": "IL-10 also prevented the upregulation of the G1 cyclins D2 and D3 , proteins necessary for entry and progression through the G1 phase of the cell cycle .", "target_text": { "IL-10": "protein", "G1 cyclins": "protein", "D2": "protein", "D3": "protein" } }, { "input_text": "Associated with the inhibition of the cell cycle , IL-10 suppressed SEB induction of interleukin-2 ( IL-2 ) .", "target_text": { "IL-10": "protein", "SEB": "protein", "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "Addition of exogenous IL-2 to IL-10 -treated cells significantly reversed the antiproliferative effects of IL-10 .", "target_text": { "IL-2": "protein", "IL-10": "protein", "IL-10 -treated cells": "cell_line" } }, { "input_text": "Moreover , IL-10 effects on the early G1 proteins p27 ( Kip1 ) and cyclin D2 were similarly reversed by exogenous IL-2 .", "target_text": { "IL-10": "protein", "early G1 proteins": "protein", "p27 ( Kip1 )": "protein", "D2": "protein", "cyclin D2": "protein", "IL-2": "protein" } }, { "input_text": "Although this reversal by IL-2 was pronounced , it was not complete , suggesting that IL-10 may have some effects not directly related to the suppression of IL-2 production .", "target_text": { "IL-2": "protein", "IL-10": "protein" } }, { "input_text": "Cell separation experiments suggest that IL-10 can effect purified CD4(+) T cells directly , providing functional evidence for the presence of IL-10 receptors on CD4(+) T cells .", "target_text": { "IL-10": "protein", "CD4(+) T cells": "cell_type" } }, { "input_text": "IL-10 also inhibited expression of IL-2 transcriptional regulators c-fos and c-jun , which also inhibit other cell functions .", "target_text": { "IL-10": "protein", "IL-2": "protein", "IL-2 transcriptional regulators": "protein", "c-fos": "protein", "c-jun": "protein" } }, { "input_text": "Our studies show that the mechanism of IL-10 regulation of quiescent CD4(+) T-cell activation is mainly by blocking induction of IL-2 that is critical to downregulation of p27 ( Kip1 ) and upregulation of D cyclins in T-cell activation and entry into the cell cycle .", "target_text": { "IL-10": "protein", "IL-2": "protein", "p27 ( Kip1 )": "protein", "D cyclins": "protein" } }, { "input_text": "IFN-gamma and IL-10 inhibit induction of IL-1 receptor type I and type II gene expression by IL-4 and IL-13 in human monocytes .", "target_text": { "IFN-gamma": "protein", "IL-10": "protein", "IL-4": "protein", "IL-13": "protein", "monocytes": "cell_type" } }, { "input_text": "The Th2-type cytokines IL-4 and IL-13 induce expression of a distinct subset of genes in human monocytes .", "target_text": { "Th2-type cytokines": "protein", "IL-4": "protein", "IL-13": "protein", "monocytes": "cell_type", "human monocytes": "cell_type" } }, { "input_text": "These include Fc epsilonRII ( CD23 ) , 15-lipoxygenase , IL-1 receptor antagonist ( IL-1ra ) , and type I and type II IL-1 receptors ( IL-1R ) .", "target_text": { "Fc epsilonRII": "protein", "CD23": "protein", "15-lipoxygenase": "protein", "IL-1 receptor antagonist": "protein", "IL-1ra": "protein", "IL-1R": "protein" } }, { "input_text": "IFN-gamma has been shown to inhibit induction of CD23 and 15-lipoxygenase in monocytes ; however , the effects of IFN-gamma on type I and type II IL-1R gene expression have not been defined .", "target_text": { "IFN-gamma": "protein", "CD23": "protein", "15-lipoxygenase": "protein", "monocytes": "cell_type" } }, { "input_text": "We examined the effects of IFN-gamma on both basal and IL-4 / IL-13 -induced IL-1R gene expression in primary monocytes .", "target_text": { "IFN-gamma": "protein", "IL-4": "protein", "IL-13": "protein", "IL-1R": "protein", "IL-1R gene": "DNA", "monocytes": "cell_type", "primary monocytes": "cell_type" } }, { "input_text": "IL-4 and IL-13 induced dose- and time-dependent increases in IL-1RI and IL-1RII mRNA levels .", "target_text": { "IL-4": "protein", "IL-13": "protein" } }, { "input_text": "IFN-gamma decreased basal expression as well as the induction of these genes by IL-4 and IL-13 .", "target_text": { "IFN-gamma": "protein", "IL-4": "protein", "IL-13": "protein" } }, { "input_text": "Inhibition of IL-1RI and IL-1RII mRNA levels by IFN-gamma was transcriptionally mediated , and correlated directly with decreased production of soluble IL-1RII .", "target_text": { "IL-1RI": "protein", "IFN-gamma": "protein", "IL-1RII": "protein" } }, { "input_text": "Furthermore , the ability to suppress IL-1RI and IL-1RII mRNA levels was not unique to IFN-gamma because IL-10 also inhibited expression of these genes in IL-4 / IL-13 -stimulated monocytes .", "target_text": { "IL-1RII": "protein", "IFN-gamma": "protein", "IL-10": "protein", "IL-4": "protein", "IL-13": "protein", "monocytes": "cell_type", "IL-4 / IL-13 -stimulated monocytes": "cell_line" } }, { "input_text": "Inhibition of IL-1R gene expression by IFN-gamma and IL-10 was not due to down-regulation of surface IL-4R because pretreatment with these cytokines did not decrease the number of IL-4 binding sites per cell .", "target_text": { "IL-1R": "protein", "IL-1R gene": "DNA", "IFN-gamma": "protein", "IL-10": "protein", "IL-4R": "protein", "surface IL-4R": "protein", "IL-4": "protein" } }, { "input_text": "However , suppression of IL-1R gene expression by IFN-gamma and IL-10 was associated with decreased tyrosine phosphorylation and nuclear translocation of the IL-4 / IL-13 -inducible transcription factor , Stat6 , suggesting a potential mechanism by which IFN-gamma and IL-10 may mediate their suppressive effects .", "target_text": { "IL-1R": "protein", "IL-1R gene": "DNA", "IFN-gamma": "protein", "IL-10": "protein", "IL-4": "protein", "IL-13": "protein", "IL-4 / IL-13 -inducible transcription factor": "protein", "Stat6": "protein" } }, { "input_text": "These findings demonstrate that certain cytokines , including IFN-gamma and IL-10 , antagonize the ability of IL-4 and IL-13 to induce increased expression of the IL-1RI and IL-1RII genes in monocytes .", "target_text": { "IFN-gamma": "protein", "IL-10": "protein", "IL-4": "protein", "IL-13": "protein", "IL-1RII": "protein", "IL-1RII genes": "DNA", "monocytes": "cell_type" } }, { "input_text": "Cytokine rescue from glucocorticoid induced apoptosis in T cells is mediated through inhibition of IkappaBalpha .", "target_text": { "Cytokine": "protein", "T cells": "cell_type", "IkappaBalpha": "protein" } }, { "input_text": "We previously reported that dexamethasone ( DEX ) , a synthetic glucocorticoid , causes apoptosis in mature Th cell lines , and that this induction of cell death is prevented by specific cytokines , namely , by IL-2 in Th1 cells and by IL-4 in Th2 cells .", "target_text": { "mature Th cell lines": "cell_line", "cytokines": "protein", "IL-2": "protein", "Th1 cells": "cell_type", "IL-4": "protein", "Th2 cells": "cell_type" } }, { "input_text": "We now show that this differential rescue by specific cytokines in Th cells correlates with the level of IkappaBalpha that is regulated by DEX and cytokines .", "target_text": { "cytokines": "protein", "Th cells": "cell_type", "IkappaBalpha": "protein" } }, { "input_text": "In both cell types the cellular levels of IkappaBalpha mRNA and protein were evaluated by DEX treatment .", "target_text": { "IkappaBalpha": "protein", "IkappaBalpha mRNA": "RNA" } }, { "input_text": "Interestingly , the DEX -mediated IkappaBalpha induction was completely inhibited by IL-2 , but not IL-4 , in Th1 cells , while the reverse profile was seen in Th2 cells .", "target_text": { "IkappaBalpha": "protein", "IL-2": "protein", "IL-4": "protein", "Th1 cells": "cell_type", "Th2 cells": "cell_type" } }, { "input_text": "In both cell types , the cytokine that inhibits the induction of IkappaBalpha by DEX , also rescues these cells from DEX -induced apoptosis , although the rescue cytokine is different in Th1 and Th2 cells .", "target_text": { "cytokine": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Our results imply that T cells need to maintain a certain level of NF-kappaB transcriptional activity in order to survive ; up- or down-regulation of nuclear NF kappaB through modulation of IkappaBalpha expression by cytokines or DEX may lead to cell survival or cell death , respectively .", "target_text": { "T cells": "cell_type", "NF-kappaB": "protein", "nuclear NF kappaB": "protein", "IkappaBalpha": "protein", "cytokines": "protein" } }, { "input_text": "Expression of transcription factor genes after influenza A virus infection .", "target_text": { "transcription factor genes": "DNA" } }, { "input_text": "Infection of human monocytes with influenza A virus induces a broad range of proinflammatory cytokines and mononuclear cell attracting chemokines before the infected cells undergo apoptosis .", "target_text": { "monocytes": "cell_type", "cytokines": "protein", "proinflammatory cytokines": "protein", "chemokines": "protein", "infected cells": "cell_type" } }, { "input_text": "The underlying mechanisms by which the corresponding genes are transcriptionally initiated after virus infection are still poorly understood .", "target_text": {} }, { "input_text": "Activation of NF-kappa B seems to play an important role in the regulation of many proinflammatory cytokine genes , but can not be the only mechanism , since several cytokine genes lack respective binding sites in their promoter regions .", "target_text": { "NF-kappa B": "protein", "proinflammatory cytokine genes": "DNA", "cytokine genes": "DNA", "binding sites": "DNA", "promoter regions": "DNA" } }, { "input_text": "Therefore , we additionally investigated other transcription factors of possible importance such as CREB , CTF , OTF-1 , and OTF-2 .", "target_text": { "transcription factors": "protein", "CREB": "protein", "CTF": "protein", "OTF-1": "protein", "OTF-2": "protein" } }, { "input_text": "To explore long-term regulatory mechanisms , we investigated the induction of transcription factors on the gene expression level which may be important to substitute for metabolized transcription factor proteins after their activation .", "target_text": { "transcription factors": "protein", "metabolized transcription factor proteins": "protein" } }, { "input_text": "We identified a cell-type-specific differential response : CREB , CTF , OTF-1 , OFT-2 , and NF-kappa B genes were strongly induced 1 to 4 hours after influenza A virus infection in the monocytic cell line Mono Mac 6 , while in freshly prepared human monocytes no significant changes were detected .", "target_text": { "monocytic cell line": "cell_line", "Mono Mac 6": "cell_line", "monocytes": "cell_type" } }, { "input_text": "In infected monocytes , which die by apoptosis , the expression of CREB , CTF , and OTF-2 was rather suppressed 8 hours after infection .", "target_text": { "monocytes": "cell_type", "CREB": "protein", "CTF": "protein", "OTF-2": "protein" } }, { "input_text": "In conclusion , the long-term regulation of transcription factor gene expression in non-proliferating cells seems to be of minor importance after influenza infection since in apoptosisprone cells an immediate availability of transcription factor proteins is required .", "target_text": { "transcription factor": "protein", "non-proliferating cells": "cell_type", "apoptosisprone cells": "cell_type", "transcription factor proteins": "protein" } }, { "input_text": "Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kappaB .", "target_text": { "Peripheral blood mononuclear cells": "cell_type", "oxidative-stress sensitive transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "Increased oxidative stress and subsequent activation of the transcription factor NF-kappaB has been linked to the development of late diabetic complications .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "To determine whether oxidative stress dependent NF-kappaB activation is evident in patients with diabetic nephropathy we used an Electrophoretic Mobility Shift Assay based semiquantitative detection system which enabled us to determine NF-kappaB activation in ex vivo isolated peripheral blood mononuclear cells .", "target_text": { "NF-kappaB": "protein", "isolated peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "We examined 33 patients with diabetes mellitus ( Type I and Type II ) .", "target_text": {} }, { "input_text": "Patients with diabetic nephropathy showed higher NF-kappaB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kappaBp65 than patients without renal complications .", "target_text": { "NF-kappaB": "protein", "NF-kappaBp65": "protein" } }, { "input_text": "NF-kappaB binding activity correlated with the degree of albuminuria ( r = 0.316 ) and with thrombomodulin plasma concentrations ( r = 0.33 ) , indicative for albuminuria associated endothelial dysfunction .", "target_text": { "NF-kappaB": "protein", "thrombomodulin": "protein" } }, { "input_text": "In a 3 day intervention study in which 600 mg of the antioxidant thioctic acid ( alpha-lipoic acid ) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48 % and NF-kappaB binding activity in ex vivo isolated peripheral blood mononuclear cells by 38 % .", "target_text": { "NF-kappaB": "protein", "isolated peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "In conclusion , activation of the transcription factor NF-kappaB in ex vivo isolated peripheral blood mononuclear cells of patients with diabetes mellitus correlates with the degree of diabetic nephropathy .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein", "isolated peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "NF-kappaB activation is at least in part dependent on oxidative stress since thioctic acid ( alpha-lipoic acid ) reduced NF-kappaB binding activity .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Osteoclast markers accumulate on cells developing from human peripheral blood mononuclear precursors .", "target_text": { "Osteoclast": "cell_type", "Osteoclast markers": "protein", "human peripheral blood mononuclear precursors": "cell_type" } }, { "input_text": "Recent studies show that human osteoclasts develop in vitro from hematopoietic cells ; however , special cultures conditions and/or cytokine mobilized peripheral blood are apparently required .", "target_text": { "human osteoclasts": "cell_type", "hematopoietic cells": "cell_type" } }, { "input_text": "Here , we report that cells expressing osteoclast markers differentiate from precursors present in nonmobilized peripheral blood mononuclear cells ( PBMC ) , without the addition of stromal cells , growth factors , cytokines or steroids ; and characterize their phenotype .", "target_text": { "osteoclast": "cell_type", "osteoclast markers": "protein", "nonmobilized peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type", "stromal cells": "cell_type", "growth factors": "protein" } }, { "input_text": "Three days after establishing high-density PBMC cultures ( 1.5 x 10(6) cells/cm2 ) , in serum-containing medium , small adherent colonies of tartrate resistant acid phosphatase positive ( TRAP+ ) cells emerge , amidst massive monocyte cell death .", "target_text": { "PBMC": "cell_type", "adherent colonies": "cell_line", "tartrate resistant acid phosphatase positive ( TRAP+ ) cells": "cell_line" } }, { "input_text": "These adherent cells have an eccentrically placed , round nucleus , and express low levels of TRAP and sodium fluoride-resistant- alpha-naphthyl-acetate-esterase ( NaF-R-NSE ) .", "target_text": { "adherent cells": "cell_type", "TRAP": "protein", "sodium fluoride-resistant- alpha-naphthyl-acetate-esterase": "protein", "NaF-R-NSE": "protein" } }, { "input_text": "Over the next week , this cell population accumulates phenotypic markers of osteoclasts ( vitronectin receptor [ VR ] , calcitonin receptor , TRAP , cathepsin K protein , and mRNA ) with increased nuclearity , covering the entire surface by 15 days .", "target_text": { "osteoclasts": "cell_type", "vitronectin receptor": "protein", "VR": "protein", "calcitonin receptor": "protein", "TRAP": "protein", "cathepsin K protein": "protein", "mRNA": "RNA" } }, { "input_text": "When cultured on bone , VR + , TRAP + cells of low multinuclearity appear and cover up to 50 % of the surface .", "target_text": { "VR": "protein", "TRAP": "protein", "VR + , TRAP + cells": "cell_line" } }, { "input_text": "Resorption lacunae can be observed by day 22 .", "target_text": {} }, { "input_text": "Although these pits are not nearly as numerous as the cells of preosteoclast phenotype , they do represent the activity of a subset of osteoclast -like cells that has achieved osteoclastic maturity under these culture conditions .", "target_text": { "preosteoclast phenotype": "cell_type", "osteoclast": "cell_type", "osteoclast -like cells": "cell_type" } }, { "input_text": "Transcripts for osteoprotegerin ligand ( OPGL ) , an osteoclast differentiation factor ( also known as RANKL and TRANCE ) are expressed , likely by adherent cells .", "target_text": { "osteoprotegerin ligand": "protein", "OPGL": "protein", "osteoclast": "cell_type", "osteoclast differentiation factor": "protein", "RANKL": "protein", "TRANCE": "protein", "adherent cells": "cell_type" } }, { "input_text": "Thus , an adherent population of cells , with preosteoclast/ osteoclast phenotypic properties , arises selectively under simple culture conditions from normal PBMC .", "target_text": { "osteoclast": "cell_type", "PBMC": "cell_type" } }, { "input_text": "Further characterization of these cells should identify factors involved in the growth , terminal differentiation and activation of osteoclasts .", "target_text": { "osteoclasts": "cell_type" } }, { "input_text": "Oleic acid inhibits endothelial activation : A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet .", "target_text": {} }, { "input_text": "Because oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet , we investigated whether this fatty acid can modulate endothelial activation , ie , the concerted expression of gene products involved in leukocyte recruitment and early atherogenesis .", "target_text": { "gene products": "protein" } }, { "input_text": "We incubated sodium oleate with human umbilical vein endothelial cells for 0 to 72 hours , followed by coincubation of oleate with human recombinant tumor necrosis factor , interleukin ( IL ) -1alpha , IL-1beta , IL-4 , Escherichia coli lipopolysaccharide ( LPS ) , or phorbol 12-myristate 13-acetate for a further 6 to 24 hours .", "target_text": { "human umbilical vein endothelial cells": "cell_type", "human recombinant tumor necrosis factor": "protein", "interleukin ( IL ) -1alpha": "protein", "IL-1beta": "protein", "IL-4": "protein" } }, { "input_text": "The endothelial expression of vascular cell adhesion molecule-1 ( VCAM-1 ) , E-selectin , and intercellular adhesion molecule-1 was monitored by cell surface enzyme immunoassays or flow cytometry , and steady-state levels of VCAM-1 mRNA were assessed by Northern blot analysis .", "target_text": { "vascular cell adhesion molecule-1": "protein", "VCAM-1": "protein", "E-selectin": "protein", "intercellular adhesion molecule-1": "protein", "VCAM-1 mRNA": "RNA" } }, { "input_text": "At 10 to 100 micromol/L for > 24 hours , oleate inhibited the expression of all adhesion molecules tested .", "target_text": { "adhesion molecules": "protein" } }, { "input_text": "After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 microg/mL LPS , VCAM-1 expression was reduced by > 40 % compared with control .", "target_text": { "VCAM-1": "protein" } }, { "input_text": "Adhesion of monocytoid U937 cells to LPS -treated endothelial cells was reduced concomitantly .", "target_text": { "monocytoid U937 cells": "cell_line" } }, { "input_text": "Oleate also produced a quantitatively similar reduction of VCAM-1 mRNA levels on Northern blot analysis and inhibited nuclear factor-kappaB activation on electrophoretic mobility shift assays .", "target_text": { "VCAM-1": "protein", "VCAM-1 mRNA": "RNA", "nuclear factor-kappaB": "protein" } }, { "input_text": "Incubation of endothelial cells with oleate for 72 hours decreased the relative proportions of saturated ( palmitic and stearic ) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids .", "target_text": { "endothelial cells": "cell_type" } }, { "input_text": "Although less potent than polyunsaturated fatty acids in inhibiting endothelial activation , oleic acid may contribute to the prevention of atherogenesis through selective displacement of saturated fatty acids in cell membrane phospholipids and a consequent modulation of gene expression for molecules involved in monocyte recruitment .", "target_text": {} }, { "input_text": "Both Stat3 -activation and Stat3 -independent BCL2 downregulation are important for interleukin-6 -induced apoptosis of 1A9-M cells .", "target_text": { "Stat3": "protein", "BCL2": "protein", "interleukin-6": "protein", "1A9-M cells": "cell_line" } }, { "input_text": "A unique subclone of a bone marrow-derived stromal cell line , BMS2.4 , produces soluble factors that inhibit proliferation of several types of hematopoietic cell lines .", "target_text": { "bone marrow-derived stromal cell line": "cell_line", "BMS2.4": "cell_line", "soluble factors": "protein", "hematopoietic cell lines": "cell_line" } }, { "input_text": "An understanding of these molecules may be informative about negative regulatory circuits that can potentially limit blood cell formation .", "target_text": {} }, { "input_text": "We used expression cloning to identify interleukin-6 ( IL-6 ) as one factor that suppressed growth of a pre-B-cell variant line , 1A9-M .", "target_text": { "interleukin-6": "protein", "IL-6": "protein", "pre-B-cell variant line": "cell_line", "1A9-M": "cell_line" } }, { "input_text": "Moreover , IL-6 induced macrophage-differentiation and apoptosis of 1A9-M cells .", "target_text": { "IL-6": "protein", "1A9-M cells": "cell_line" } }, { "input_text": "During this process , IL-6 downregulated expression of BCL2 in 1A9-M cells and stimulated BCL-XL expression , but had no effect on p53 , Bax , or Bak gene expression .", "target_text": { "IL-6": "protein", "BCL2": "protein", "1A9-M cells": "cell_line" } }, { "input_text": "Mechanisms for transduction of IL-6 -induced signals were then evaluated in IL-6 -stimulated 1A9-M cells .", "target_text": { "IL-6": "protein", "1A9-M cells": "cell_line", "IL-6 -stimulated 1A9-M cells": "cell_line" } }, { "input_text": "Whereas the signal transducer and activator of transcription 3 ( Stat3 ) was phosphorylated and activated , there was no effect on either Stat1 or Stat5 .", "target_text": { "signal transducer and activator of transcription 3": "protein", "Stat3": "protein", "Stat1": "protein", "Stat5": "protein" } }, { "input_text": "The importance of BCL2 and Stat3 on IL-6 -induced macrophage-differentiation and apoptosis was studied with 1A9-M cells expressing human BCL2 or a dominant-negative form of Stat3 , respectively .", "target_text": { "BCL2": "protein", "Stat3": "protein", "IL-6": "protein", "1A9-M cells": "cell_line", "human BCL2": "protein" } }, { "input_text": "IL-6 -induced apoptosis , but not macrophage-differentiation , was blocked by continuously expressed BCL2 .", "target_text": { "IL-6": "protein", "BCL2": "protein" } }, { "input_text": "A dominant-negative form of Stat3 inhibited both macrophage-differentiation and apoptosis induced by IL-6 .", "target_text": { "Stat3": "protein", "dominant-negative form of Stat3": "protein", "IL-6": "protein" } }, { "input_text": "However , diminished Stat3 activity did not prevent IL-6 -induced downregulation of the BCL2 gene .", "target_text": { "Stat3": "protein", "IL-6": "protein", "BCL2": "protein", "BCL2 gene": "DNA" } }, { "input_text": "Therefore , activation of Stat3 is essential for IL-6 -induced macrophage-differentiation and programmed cell death in this model .", "target_text": { "Stat3": "protein", "IL-6": "protein" } }, { "input_text": "Whereas overexpression of BCL2 abrogates the apoptotic response , Stat3 -independent signals appear to downregulate expression of the BCL2 gene .", "target_text": { "BCL2": "protein", "Stat3": "protein", "BCL2 gene": "DNA" } }, { "input_text": "Involvement of mitogen-activated protein kinase pathways in interleukin-8 production by human monocytes and polymorphonuclear cells stimulated with lipopolysaccharide or Mycoplasma fermentans membrane lipoproteins .", "target_text": { "mitogen-activated protein kinase": "protein", "interleukin-8": "protein", "human monocytes": "cell_type", "polymorphonuclear cells": "cell_type", "Mycoplasma fermentans membrane lipoproteins": "protein" } }, { "input_text": "Interleukin-8 ( IL-8 ) is a chemokine that belongs to the alpha-chemokine or CXC subfamily and is produced by a wide variety of human cells , including monocytes and polymorphonuclear cells ( PMN ) .", "target_text": { "Interleukin-8": "protein", "IL-8": "protein", "chemokine": "protein", "alpha-chemokine": "protein", "CXC subfamily": "protein", "monocytes": "cell_type", "polymorphonuclear cells": "cell_type", "PMN": "cell_type" } }, { "input_text": "IL-8 is secreted in response to inflammatory stimuli , notably bacterial products such as lipopolysaccharide ( LPS ) , but little is known about the mechanisms by which these agents mediate IL-8 induction .", "target_text": { "IL-8": "protein" } }, { "input_text": "In this report , we show that Mycoplasma fermentans lipid-associated membrane proteins ( LAMPf ) induce the production of high levels of IL-8 by THP-1 ( human monocyte ) cells and PMN at the same extent as LPS .", "target_text": { "Mycoplasma fermentans lipid-associated membrane proteins": "protein", "LAMPf": "protein", "IL-8": "protein", "THP-1 ( human monocyte ) cells": "cell_line", "PMN": "cell_type" } }, { "input_text": "It was previously demonstrated that stimulation of monocytic cells with either LPS or LAMPf led to a series of common downstream signaling events , including the activation of protein tyrosine kinase and of mitogen-activated protein kinase cascades .", "target_text": { "LAMPf": "protein", "protein tyrosine kinase": "protein", "mitogen-activated protein kinase": "protein" } }, { "input_text": "By using PD-98059 and SB203580 , two potent and selective inhibitors of MEK1 ( a kinase upstream of ERK1/2 ) and p38 , respectively , we have demonstrated that both ERK1/2 and p38 cascades play a key role in the production of IL-8 by monocytes and PMN stimulated with bacterial fractions .", "target_text": { "MEK1": "protein", "kinase": "protein", "ERK1/2": "protein", "p38": "protein", "IL-8": "protein", "monocytes": "cell_type", "PMN": "cell_type" } }, { "input_text": "Regulation of IL-6 synthesis in human peripheral blood mononuclear cells by C3a and C3a ( desArg ) .", "target_text": { "IL-6": "protein", "human peripheral blood mononuclear cells": "cell_type", "C3a": "protein", "C3a ( desArg )": "protein" } }, { "input_text": "The anaphylatoxin C3a has been reported to have immunomodulatory effects on a number of different cell types .", "target_text": { "anaphylatoxin": "protein", "C3a": "protein" } }, { "input_text": "In this study we investigated the effects of C3a and C3a ( desArg ) on gene expression and protein secretion of IL-6 in human PBMCs , either alone or in combination with LPS or IL-1beta .", "target_text": { "C3a": "protein", "C3a ( desArg )": "protein", "IL-6": "protein", "PBMCs": "cell_type", "IL-1beta": "protein" } }, { "input_text": "C3a or C3a ( desArg ) alone exhibited no effect on the expression or secretion of IL-6 .", "target_text": { "C3a": "protein", "C3a ( desArg )": "protein", "IL-6": "protein" } }, { "input_text": "However , when PBMC were stimulated with LPS or IL-1beta , both C3a and C3a ( desArg ) were found to enhance IL-6 release by PBMC in a dose-dependent manner .", "target_text": { "PBMC": "cell_type", "IL-1beta": "protein", "C3a": "protein", "C3a ( desArg )": "protein", "IL-6": "protein" } }, { "input_text": "Since C3a has been shown to induce PGE2 production by monocytes , and PGE2 has been shown to influence cytokine production , we investigated the potential role of PGE2 in C3a -mediated enhancement of LPS- and IL-1beta- induced IL-6 production .", "target_text": { "C3a": "protein", "monocytes": "cell_type" } }, { "input_text": "Indomethacin blocked PGE2 release , but had no influence on the observed effects of C3a , suggesting that the effects of C3a on IL-6 production are independent of PGE2 formation by monocytes .", "target_text": { "C3a": "protein", "IL-6": "protein", "monocytes": "cell_type" } }, { "input_text": "Northern blot analysis showed that C3a as well as C3a ( desArg ) enhanced LPS -induced mRNA levels for IL-6 .", "target_text": { "C3a": "protein", "C3a ( desArg )": "protein", "-induced mRNA": "RNA", "IL-6": "protein" } }, { "input_text": "Pretreatment of PBMCs with pertussis toxin blocked the functions of C3a and C3a ( desArg ) , indicating that the actions of these two molecules are mediated by a G protein -coupled pathway .", "target_text": { "PBMCs": "cell_type", "pertussis toxin": "protein", "C3a": "protein", "C3a ( desArg )": "protein", "G protein": "protein" } }, { "input_text": "Furthermore , we investigated the effects of C3a and C3a ( desArg ) on induction of NF-kappaB and activating protein-1 binding .", "target_text": { "C3a": "protein", "C3a ( desArg )": "protein", "NF-kappaB": "protein", "activating protein-1": "protein" } }, { "input_text": "Both molecules enhanced LPS -induced NF-kappaB and activating protein-1 binding activity .", "target_text": { "NF-kappaB": "protein", "activating protein-1": "protein" } }, { "input_text": "These results demonstrate the capacity of intact C3a and its circulating des-Arg form to exert immunmodulatory effects in vitro .", "target_text": { "C3a": "protein", "des-Arg form": "protein" } }, { "input_text": "Phenylarsine oxide inhibits ex vivo HIV-1 expression .", "target_text": {} }, { "input_text": "Phenylarsine oxide ( PAO ) , which is described as an inhibitor of tyrosine phosphatase activity , inhibits H2O2 release from human peripheral blood mononuclear cells ( PBMCs ) as measured by electrochemistry .", "target_text": { "tyrosine phosphatase": "protein", "human peripheral blood mononuclear cells": "cell_type", "PBMCs": "cell_type" } }, { "input_text": "Since human immunodeficiency virus type 1 ( HIV-1 ) replication is known to be favored under oxidative stress conditions , ex vivo experiments using uninfected PBMCs , primary monocytes or a latently infected promonocytic U1 cell line show that HIV-1 replication and reactivation , monitored by p24 antigen measurement , are inhibited by PAO in a time- and concentration-dependent manner .", "target_text": { "PBMCs": "cell_type", "primary monocytes": "cell_type", "promonocytic U1 cell line": "cell_line", "p24 antigen": "protein" } }, { "input_text": "These observations can be linked with the inhibition of NF-kappa B activation when uninfected monocytes are induced by either tumor necrosis factor alpha ( TNF-alpha ) phorbol 12-myristate 13-acetate ( PMA ) or lipopolysaccharide ( LPS ) .", "target_text": { "NF-kappa B": "protein", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "Pharmacological control of antigen responsiveness in genetically modified T lymphocytes .", "target_text": { "genetically modified T lymphocytes": "cell_line" } }, { "input_text": "A chimeric TCR gene , comprising an anti-hapten single-chain Ab variable fragment fused to the transmembrane and cytoplasmic regions of the human TCR zeta-chain , was used to determine whether the tetracycline-regulatable system could be used to regulate gene expression in T cells .", "target_text": { "chimeric TCR gene": "DNA", "anti-hapten single-chain Ab variable fragment": "protein", "transmembrane and cytoplasmic regions": "protein", "human TCR zeta-chain": "protein", "T cells": "cell_type" } }, { "input_text": "Jurkat T cells were stably transfected with a single vector encoding the tetracycline trans-activator protein , controlled by a constitutive promoter , and the chimeric TCR , under the control of a trans-activator protein-responsive promoter .", "target_text": { "Jurkat T cells": "cell_line", "tetracycline trans-activator protein": "protein", "constitutive promoter": "DNA", "chimeric TCR": "protein", "trans-activator protein-responsive promoter": "DNA" } }, { "input_text": "In the absence of tetracyclines , the transfected T cells were shown to express the chimeric receptor on the cell surface and could be activated by its cognate Ag , leading to the secretion of IL-2 .", "target_text": { "T cells": "cell_type", "chimeric receptor": "protein", "cognate Ag": "protein", "IL-2": "protein" } }, { "input_text": "When the cells were exposed to increasing concentrations of tetracyclines , surface expression of the chimeric receptor was suppressed in a dose-dependent manner , and this suppression was sufficient to result in complete loss of responsiveness to the targeted Ag .", "target_text": { "chimeric receptor": "protein", "targeted Ag": "protein" } }, { "input_text": "Prolonged suppression of trans- gene expression for up to 7 days was observed after doxycycline was removed from the cultures , but eventual recovery of surface expression was complete , and the absolute time to recovery was directly proportional to the initial concentration of the drug .", "target_text": {} }, { "input_text": "Pharmacologic control of trans-gene expression in gene-modified T cells will not only facilitate new approaches to the study of different aspects of T cell biology , but will also provide the basis for new gene therapy strategies .", "target_text": { "gene-modified T cells": "cell_line" } }, { "input_text": "Glucocorticoid receptors , fibromyalgia and low back pain .", "target_text": { "Glucocorticoid receptors": "protein" } }, { "input_text": "Recently , fibromyalgia ( FMS ) was shown to be a disorder associated with an altered functioning of the stress response system .", "target_text": {} }, { "input_text": "FMS patients display a hyperreactive pituitary adrenocorticotropic hormone ( ACTH ) release in response to corticotropin-releasing hormone ( CRH ) and to insulin-induced hypoglycemia .", "target_text": {} }, { "input_text": "We suggested that negative feedback of cortisol could be deranged .", "target_text": {} }, { "input_text": "Therefore we investigated the properties and function of the glucocorticoid receptors ( GR ) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain ( LBP a localized pain condition ) .", "target_text": { "glucocorticoid receptors": "protein", "GR": "protein" } }, { "input_text": "Forty primary FMS patients ( F : M = 36 : 4 ) , 28 LBP patients ( 25 : 3 ) and 14 ( 12 : 2 ) healthy , sedentary control persons were recruited for the study .", "target_text": {} }, { "input_text": "Urinary free cortisol excretion in FMS and LBP patients was lower compared to controls .", "target_text": {} }, { "input_text": "Only FMS patients displayed lower CBG and basal serum cortisol concentrations when compared to controls .", "target_text": {} }, { "input_text": "However , plasma free cortisol concentrations were similar in the three groups .", "target_text": {} }, { "input_text": "There was no difference in the number of GR per cell among the three groups ( FMS : 6498 +/- 252 , LBP : 6625 +/- 284 , controls : 6576 +/- 304 ) , but the dissociation constant ( Kd ) of the FMS ( 14.5 +/- 0.9 nmol/l ) and LBP ( 14.7 +/- 1.3 nmol/l ) subjects was significantly higher than that of the controls ( 10.9 +/- 0.8 nmol/l ) ( p < .05 ) .", "target_text": { "GR": "protein" } }, { "input_text": "The maximal stimulation of the lymphocytes , as measured by the maximal thymidine incorporation ( in the absence of cortisol ) in the FMS group was approximately 1.5 times higher ( p < .05 ) than in the control or LBP group .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "The ED50 ( the cortisol concentration giving 50 % inhibition of the thymidine incorporation ) , however , was identical in all three groups .", "target_text": {} }, { "input_text": "We conclude that FMS patients have a mild hypocortisolemia , increased cortisol feedback resistance in combination probably with a reduced CRH synthesis or release in the hypothalamus .", "target_text": {} }, { "input_text": "The role of the GR and mineralocorticoid receptor ( MR ) in the CRH regulation in the FMS patients remains to be solved .", "target_text": { "GR": "protein", "mineralocorticoid receptor": "protein", "MR": "protein" } }, { "input_text": "Temporal control of IgH gene expression in developing B cells by the 3' locus control region .", "target_text": { "IgH gene": "DNA", "developing B cells": "cell_type", "3' locus control region": "DNA" } }, { "input_text": "The suggested roles of the downstream 3' regions acting as a Locus Control Region ( LCR ) , have allowed comparisons to be made between the regulation of the IgH locus with other model systems whose gene expression is governed by LCR activity .", "target_text": { "downstream 3' regions": "DNA", "Locus Control Region": "DNA", "LCR": "DNA", "IgH locus": "DNA" } }, { "input_text": "Here we summarize the importance of the IgH 3' LCR and its putative functional role in IgH gene expression and compare it with the 5' LCR regulatory region of the human beta-globin locus .", "target_text": { "LCR": "DNA", "IgH 3' LCR": "DNA", "IgH gene": "DNA", "5' LCR regulatory region": "DNA", "human beta-globin locus": "DNA" } }, { "input_text": "HLA binding characteristics and generation of cytotoxic lymphocytes against peptides derived from oncogenic proteins .", "target_text": { "cytotoxic lymphocytes": "cell_type", "oncogenic proteins": "protein" } }, { "input_text": "AIMS AND BACKGROUND : Structurally altered proteins ( derived from chromosomal translocations or gene mutations ) can be considered tumor specific antigens and represent an attractive target for a T-cell mediated response .", "target_text": {} }, { "input_text": "T lymphocytes recognize antigens in the form of peptides bound to HLA-molecules .", "target_text": { "HLA-molecules": "protein" } }, { "input_text": "MATERIALS AND METHODS : Peptides derived from oncogenic proteins were screened for the presence of HLA binding motifs ; actual binding were evaluated by HLA stabilization experiments using transfectants and specific anti-HLA antibodies .", "target_text": { "oncogenic proteins": "protein", "HLA binding motifs": "protein", "anti-HLA antibodies": "protein" } }, { "input_text": "Specific lymphocytes were induced by in vitro peptide sensitization and screened by thymidine uptake or cellular cytotoxic assays .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "RESULTS : We identified peptides derived from EWS/FLI-1 fusion protein and from mutated K-RAS protein ( encompassing respectively the fusion point and the mutation at position 12 ) that showed binding motif for HLA-Cw*0702 and HLA-A3 respectively .", "target_text": { "EWS/FLI-1 fusion protein": "protein", "mutated K-RAS protein": "protein", "fusion point": "protein", "position 12": "protein", "binding motif": "protein", "HLA-Cw*0702": "protein", "HLA-A3": "protein" } }, { "input_text": "The actual binding of these peptides was analysed in a stabilization assay .", "target_text": {} }, { "input_text": "We detected binding for the EWS/FLI-1 peptide and for 5 RAS peptides ( 1 wild type and 4 mutated ) .", "target_text": {} }, { "input_text": "The effect of temperature , beta 2-microglobulin ( beta 2-m ) and fetal calf serum ( FCS ) on the binding and the stability of the HLA/peptide complex was studied .", "target_text": { "beta 2-microglobulin": "protein", "beta 2-m": "protein", "HLA/peptide complex": "protein" } }, { "input_text": "A low temperature ( 26 degrees C ) increased the binding both in HLA-A3 and HLA-Cw*0702 , while FCS reduced it .", "target_text": { "HLA-A3": "protein", "HLA-Cw*0702": "protein" } }, { "input_text": "beta 2-m increased the binding to the HLA-A3 molecule but did not influence the binding to the HLA-Cw*0702 .", "target_text": { "beta 2-m": "protein", "HLA-A3": "protein", "HLA-A3 molecule": "protein", "HLA-Cw*0702": "protein" } }, { "input_text": "The stability of already formed complexed was somewhat different in the HLA-A3 and HLA-Cw*0702 system : both were more stable at 26 degrees C than at 37 degrees C but while the beta 2-m and FCS did not influence the stability of the HLA-A3 /peptide complex , they seemed to cause opposite effects in the HLA-Cw*0702 system ( beta 2-m stabilized and FCS destabilized the complex ) .", "target_text": { "HLA-A3": "protein", "HLA-Cw*0702": "protein", "beta 2-m": "protein", "HLA-A3 /peptide complex": "protein" } }, { "input_text": "Finally , we were able to generate a specific CD8+ CTL line against a K-RAS mutated peptide .", "target_text": { "CD8+ CTL line": "cell_line" } }, { "input_text": "CONCLUSIONS : Although binding motifs and actual HLA binding can be detected in several cases , the generation of a cellular response is infrequent , confirming that HLA binding is necessary but not sufficient to obtain an in vitro response .", "target_text": { "binding motifs": "protein" } }, { "input_text": "Further optimization of culture conditions , type of Antigen Presenting Cells ( APC ) , peptides , use of stabilizers like beta 2-m are still needed .", "target_text": { "Antigen Presenting Cells": "cell_type", "APC": "cell_type", "beta 2-m": "protein" } }, { "input_text": "OCA-B is a functional analog of VP16 but targets a separate surface of the Oct-1 POU domain [ published erratum appears in Mol Cell Biol 1998 Apr ; 18 ( 4 ) : 2430 ]", "target_text": { "OCA-B": "protein", "VP16": "protein", "Oct-1 POU domain": "protein" } }, { "input_text": "OCA-B is a B-cell-specific coregulator of the broadly expressed POU domain transcription factor Oct-1 .", "target_text": { "OCA-B": "protein", "B-cell-specific coregulator": "protein", "POU domain transcription factor": "protein", "Oct-1": "protein" } }, { "input_text": "OCA-B associates with the Oct-1 POU domain , a bipartite DNA-binding structure containing a POU-specific ( POU[S] ) domain joined by a flexible linker to a POU homeodomain ( POU[H] ) .", "target_text": { "OCA-B": "protein", "Oct-1": "protein", "Oct-1 POU domain": "protein", "POU-specific ( POU[S] ) domain": "protein", "POU homeodomain": "protein", "POU[H]": "protein" } }, { "input_text": "Here , we show that OCA-B alters the activity of Oct-1 in two ways .", "target_text": { "OCA-B": "protein", "Oct-1": "protein" } }, { "input_text": "It provides a transcriptional activation domain which , unlike Oct-1 , activates an mRNA-type promoter effectively , and it stabilizes Oct-1 on the Oct-1 -responsive octamer sequence ATGCAAAT .", "target_text": { "Oct-1": "protein", "mRNA-type promoter": "DNA", "Oct-1 -responsive octamer sequence": "DNA" } }, { "input_text": "These properties of OCA-B parallel those displayed by the herpes simplex virus Oct-1 coregulator VP16 .", "target_text": { "OCA-B": "protein", "Oct-1": "protein", "herpes simplex virus Oct-1 coregulator": "protein", "VP16": "protein" } }, { "input_text": "OCA-B , however , interacts with a different surface of the DNA-bound Oct-1 POU domain , interacting with both the POU(S) and POU(H) domains and the center of the ATGCAAAT octamer sequence .", "target_text": { "OCA-B": "protein", "Oct-1": "protein", "Oct-1 POU domain": "protein", "POU(S)": "protein", "POU(H) domains": "protein", "POU(S) and POU(H) domains": "protein", "ATGCAAAT octamer sequence": "DNA" } }, { "input_text": "The OCA-B and VP16 interactions with the Oct-1 POU domain are sufficiently different to permit OCA-B and VP16 to bind the Oct-1 POU domain simultaneously .", "target_text": { "VP16": "protein", "Oct-1": "protein", "Oct-1 POU domain": "protein", "OCA-B": "protein" } }, { "input_text": "These results emphasize the structural versatility of the Oct-1 POU domain in its interaction with coregulators .", "target_text": { "Oct-1": "protein", "Oct-1 POU domain": "protein" } }, { "input_text": "Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F .", "target_text": { "Phosphatidylinositol 3-kinase": "protein", "interleukin-2 receptor": "protein", "cell cycle regulator": "protein", "E2F": "protein" } }, { "input_text": "Cell cycle progression initiated by interleukin-2 ( IL-2 ) in T cells is critical for lymphoproliferation and an immune response .", "target_text": { "interleukin-2": "protein", "IL-2": "protein", "T cells": "cell_type" } }, { "input_text": "Phosphatidyl inositol 3-kinase ( PI3K ) is activated by IL-2 .", "target_text": { "Phosphatidyl inositol 3-kinase": "protein", "PI3K": "protein", "IL-2": "protein" } }, { "input_text": "However , nuclear targets for PI3K are not known .", "target_text": { "PI3K": "protein" } }, { "input_text": "Here we identify the cell cycle regulator E2F as an IL-2 target in T lymphocytes and PI3K as the critical signaling pathway .", "target_text": { "cell cycle regulator": "protein", "E2F": "protein", "IL-2": "protein", "lymphocytes": "cell_type", "PI3K": "protein" } }, { "input_text": "We eliminate both Stat5 and Raf /MEK pathways from E2F regulation .", "target_text": { "Stat5": "protein", "Raf": "protein", "/MEK": "protein", "E2F": "protein" } }, { "input_text": "Protein kinase B ( PKB ) is activated by IL-2 via PI3K .", "target_text": { "Protein kinase B": "protein", "PKB": "protein", "IL-2": "protein", "PI3K": "protein" } }, { "input_text": "The expression of an active PKB is sufficient to induce E2F activity .", "target_text": { "PKB": "protein", "E2F": "protein" } }, { "input_text": "Inhibition of PI3K inhibits phosphorylation of Rb , induction of cyclin D3 , and degradation of p27kip1 .", "target_text": { "PI3K": "protein", "Rb": "protein", "cyclin D3": "protein", "p27kip1": "protein" } }, { "input_text": "These results establish a crucial PI3K / PKB -mediated link between the IL-2 teceptor and the cell cycle machinery .", "target_text": { "PI3K": "protein", "PKB": "protein", "IL-2": "protein", "IL-2 teceptor": "protein" } }, { "input_text": "The Epstein-Barr virus oncogene product latent membrane protein 1 engages the tumor necrosis factor receptor-associated death domain protein to mediate B lymphocyte growth transformation and activate NF-kappaB .", "target_text": { "Epstein-Barr virus oncogene product": "protein", "latent membrane protein 1": "protein" } }, { "input_text": "The Epstein-Barr virus latent membrane protein 1 ( LMP1 ) is essential for the transformation of B lymphocytes into lymphoblastoid cell lines .", "target_text": { "latent membrane protein 1": "protein", "LMP1": "protein", "lymphocytes": "cell_type", "B lymphocytes": "cell_type", "lymphoblastoid cell lines": "cell_line" } }, { "input_text": "Previous data are consistent with a model that LMP1 is a constitutively activated receptor that transduces signals for transformation through its carboxyl-terminal cytoplasmic tail .", "target_text": { "LMP1": "protein", "constitutively activated receptor": "protein", "carboxyl-terminal cytoplasmic tail": "protein" } }, { "input_text": "One transformation effector site ( TES1 ) , located within the membrane proximal 45 residues of the cytoplasmic tail , constitutively engages tumor necrosis factor receptor-associated factors .", "target_text": { "transformation effector site": "protein", "TES1": "protein", "membrane proximal 45 residues": "protein", "tumor necrosis factor receptor-associated factors": "protein" } }, { "input_text": "Signals from TES1 are sufficient to drive initial proliferation of infected resting B lymphocytes , but most lymphoblastoid cells infected with a virus that does not express the 155 residues beyond TES1 fail to grow as long-term cell lines .", "target_text": { "TES1": "protein", "lymphocytes": "cell_type", "lymphoblastoid cells": "cell_type", "155 residues": "protein", "long-term cell lines": "cell_line" } }, { "input_text": "We now find that mutating two tyrosines to an isoleucine at the carboxyl end of the cytoplasmic tail cripples the ability of EBV to cause lymphoblastoid cell outgrowth , thereby marking a second transformation effector site , TES2 .", "target_text": { "carboxyl end": "protein", "cytoplasmic tail": "protein", "transformation effector site": "protein", "TES2": "protein" } }, { "input_text": "A yeast two-hybrid screen identified TES2 interacting proteins , including the tumor necrosis factor receptor-associated death domain protein ( TRADD ) .", "target_text": { "TES2": "protein", "TES2 interacting proteins": "protein", "tumor necrosis factor receptor-associated death domain protein": "protein", "TRADD": "protein" } }, { "input_text": "TRADD was the only protein that interacted with wild-type TES2 and not with isoleucine -mutated TES2 .", "target_text": { "TRADD": "protein", "TES2": "protein", "wild-type TES2": "protein", "isoleucine -mutated TES2": "protein" } }, { "input_text": "TRADD associated with wild-type LMP1 but not with isoleucine -mutated LMP1 in mammalian cells , and TRADD constitutively associated with LMP1 in EBV -transformed cells .", "target_text": { "TRADD": "protein", "LMP1": "protein", "wild-type LMP1": "protein", "EBV -transformed cells": "cell_line" } }, { "input_text": "In transfection assays , TRADD and TES2 synergistically mediated high-level NF-kappaB activation .", "target_text": { "TRADD": "protein", "TES2": "protein", "NF-kappaB": "protein" } }, { "input_text": "These results indicate that LMP1 appropriates TRADD to enable efficient long-term lymphoblastoid cell outgrowth .", "target_text": { "LMP1": "protein", "TRADD": "protein" } }, { "input_text": "High-level NF-kappaB activation also appears to be a critical component of long-term outgrowth .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Inhibition of T cell and promotion of natural killer cell development by the dominant negative helix loop helix factor Id3 .", "target_text": { "T cell": "cell_type", "dominant negative helix loop helix factor": "protein", "Id3": "protein" } }, { "input_text": "Bipotential T/natural killer ( NK ) progenitor cells are present in the human thymus .", "target_text": { "Bipotential T/natural killer ( NK ) progenitor cells": "cell_type" } }, { "input_text": "Despite their bipotential capacity , these progenitors develop predominantly to T cells in the thymus .", "target_text": { "T cells": "cell_type" } }, { "input_text": "The mechanisms controlling this developmental choice are unknown .", "target_text": {} }, { "input_text": "Here we present evidence that a member ( s ) of the family of basic helix loop helix ( bHLH ) transcription factors determines lineage specification of NK/T cell progenitors .", "target_text": { "basic helix loop helix ( bHLH ) transcription factors": "protein", "NK/T cell progenitors": "cell_type" } }, { "input_text": "The natural dominant negative HLH factor Id3 , which blocks transcriptional activity of a number of known bHLH factors , was expressed in CD34+ progenitor cells by retrovirus-mediated gene transfer .", "target_text": { "dominant negative HLH factor": "protein", "Id3": "protein", "bHLH factors": "protein", "CD34+ progenitor cells": "cell_type" } }, { "input_text": "Constitutive expression of Id3 completely blocks development of CD34+ cells into T cells in a fetal thymic organ culture ( FTOC ) .", "target_text": { "Id3": "protein", "CD34+ cells": "cell_type", "T cells": "cell_type" } }, { "input_text": "In contrast , development into NK cells in an FTOC is enhanced .", "target_text": { "NK cells": "cell_type" } }, { "input_text": "Thus , the activity of a bHLH transcription factor is necessary for T lineage differentiation of bipotential precursors , in the absence of which a default pathway leading to NK cell development is chosen .", "target_text": { "bHLH transcription factor": "protein", "bipotential precursors": "cell_type" } }, { "input_text": "Our results identify a molecular switch for lineage specification in early lymphoid precursors of humans .", "target_text": { "early lymphoid precursors": "cell_type" } }, { "input_text": "Late gene expression from the Epstein-Barr virus BcLF1 and BFRF3 promoters does not require DNA replication in cis .", "target_text": {} }, { "input_text": "Late gene expression follows and is dependent upon lytic replication of the viral genome .", "target_text": { "viral genome": "DNA" } }, { "input_text": "Although experimental evidence is lacking , lytic viral DNA replication is believed to remove modifications or binding factors from the genome which serve to repress late gene expression during latency or the early lytic cycle .", "target_text": { "binding factors": "protein" } }, { "input_text": "We have developed a reporter assay to begin characterizing the mechanisms that regulate late gene expression in Epstein-Barr virus ( EBV ) .", "target_text": {} }, { "input_text": "In this model system , the activities of late promoter-reporter fusions are measured following transient transfection into tissue culture cells expressing EBV during different stages of the lytic cycle .", "target_text": { "late promoter-reporter fusions": "DNA", "tissue culture cells": "cell_line" } }, { "input_text": "This system faithfully recapitulates late expression patterns from the endogenous virus , implicating specific cis-active sequences in the control of late gene expression .", "target_text": { "cis-active sequences": "DNA" } }, { "input_text": "In addition , these promoters respond only indirectly to the viral immediate-early transactivator , ZEBRA .", "target_text": { "viral immediate-early transactivator": "DNA", "ZEBRA": "DNA" } }, { "input_text": "This indirect response is mediated by other viral or virally induced activities downstream of ZEBRA in the lytic cascade .", "target_text": { "ZEBRA": "DNA" } }, { "input_text": "In this system , late gene expression is sensitive to inhibitors of the viral DNA polymerase such as phosphonoacetic acid , although the reporters lack a eukaryotic origin of replication and are not replicated under the assay conditions .", "target_text": { "viral DNA polymerase": "protein" } }, { "input_text": "Thus , replication of the transcriptional template is not a prerequisite for expression with late kinetics , a finding inconsistent with the current models which posit a cis-active relationship between lytic EBV DNA replication and late gene expression .", "target_text": { "transcriptional template": "DNA" } }, { "input_text": "Rather , analysis of this system has revealed a trans relationship between late gene expression and viral DNA replication and highlights the indirect and complex link between these two events .", "target_text": {} }, { "input_text": "Modulation of mRNA expression of a novel human myeloid-selective CCAAT/enhancer binding protein gene ( C/EBP epsilon ) .", "target_text": { "novel human myeloid-selective CCAAT/enhancer binding protein gene": "DNA", "C/EBP epsilon": "DNA" } }, { "input_text": "Human C/EBP epsilon is a newly cloned gene coding for a CCAAT/enhancer binding protein that may be involved in the regulation of myeloid differentiation .", "target_text": { "C/EBP epsilon": "DNA", "CCAAT/enhancer binding protein": "protein" } }, { "input_text": "Our studies showed that levels of C/EBP epsilon mRNA were markedly increased in NB4 cells ( promyelocytic leukemia line ) , because they were induced by 9-cis retinoic acid ( 9-cis RA ) to differentiate towards granulocytes .", "target_text": { "C/EBP epsilon mRNA": "RNA", "NB4 cells": "cell_line", "promyelocytic leukemia line": "cell_line", "granulocytes": "cell_type" } }, { "input_text": "Accumulation of C/EBP epsilon mRNA occurred as early as 1 hour after exposure of NB4 cells to 9-cis RA ( 5 x 10(-7) mol/L ) ; and at 48 hours , levels were increased by 5.1-fold .", "target_text": { "C/EBP epsilon mRNA": "RNA", "NB4 cells": "cell_line" } }, { "input_text": "Dose-response studies showed that 10(-7) to 10(-6) mol/L 9-cis RA ( 12 hours ) resulted in peak levels of C/EBP epsilon mRNA ; but even 10(-10) mol/L 9-cis RA increased levels of these transcripts .", "target_text": { "C/EBP epsilon mRNA": "RNA" } }, { "input_text": "NB4 cells pulse-exposed ( 30 minutes ) to all-trans retinoic acid ( ATRA ) , washed , and cultured ( 3 days ) with either dimethylsulfoxide ( DMSO ) or hexamethylene bisacetamide ( HMBA ) had a prominent increase in levels of C/EBP epsilon mRNA and an increase in granulocytic differentiation , but exposure to either DMSO or HMBA alone had no effect on base levels of C/EBP epsilon and did not induce differentiation .", "target_text": { "NB4 cells": "cell_line", "C/EBP epsilon mRNA": "RNA" } }, { "input_text": "Macrophage-differentiation of NB4 reduced levels of C/EBP epsilon mRNA .", "target_text": { "NB4": "cell_line", "C/EBP epsilon mRNA": "RNA" } }, { "input_text": "Nuclear run-off assays and half-life studies showed that accumulation of C/EBP epsilon mRNA by 9-cis RA was due to enhanced transcription .", "target_text": { "C/EBP epsilon mRNA": "RNA" } }, { "input_text": "Furthermore , this C/EBP epsilon mRNA accumulation did not require synthesis of new protein factors because 9-cis RA induced C/EBP epsilon mRNA accumulation in the absence of new protein synthesis .", "target_text": { "C/EBP epsilon mRNA": "RNA", "protein factors": "protein" } }, { "input_text": "ATRA also induced expression of C/EBP epsilon protein in NB4 cells , as shown by Western blotting .", "target_text": { "C/EBP epsilon protein": "protein", "NB4 cells": "cell_line" } }, { "input_text": "In contrast to the increase of C/EBP epsilon in 9-cis RA -mediated granulocytic differentiation , the DMSO -induced differentiation of HL-60 cells down the granulocytic pathway was associated with an initial reduction of C/EBP epsilon mRNA levels .", "target_text": { "HL-60 cells": "cell_line", "C/EBP epsilon mRNA": "RNA" } }, { "input_text": "In summary , we have discovered that expression of C/EBP epsilon mRNA is markedly enhanced as the NB4 promyelocytes are induced by retinoids to differentiate towards granulocytes .", "target_text": { "C/EBP epsilon mRNA": "RNA", "NB4 promyelocytes": "cell_line", "granulocytes": "cell_type" } }, { "input_text": "This induction of C/EBP epsilon mRNA expression is transcriptionally mediated and occurs in the absence of synthesis of additional protein factors .", "target_text": { "C/EBP epsilon mRNA": "RNA", "protein factors": "protein" } }, { "input_text": "We suspect that the C/EBP epsilon promoter/enhancer contains a retinoic acid-response element that is directly stimulated by retinoids .", "target_text": { "C/EBP epsilon promoter/enhancer": "DNA", "retinoic acid-response element": "DNA" } }, { "input_text": "Dual effects of LPS antibodies on cellular uptake of LPS and LPS -induced proinflammatory functions .", "target_text": { "LPS antibodies": "protein" } }, { "input_text": "Human phagocytes recognize bacterial LPS ( endotoxin ) through membrane CD14 ( mCD14 ) , a proinflammatory LPS receptor .", "target_text": { "Human phagocytes": "cell_type", "membrane CD14": "protein", "mCD14": "protein", "proinflammatory LPS receptor": "protein" } }, { "input_text": "This study tested the hypothesis that anti- LPS Abs neutralize endotoxin by blocking cellular uptake through mCD14 .", "target_text": { "anti- LPS Abs": "protein", "mCD14": "protein" } }, { "input_text": "Ab-associated changes in the uptake and cellular distribution of FITC- LPS were assessed by flow cytometry and laser scanning confocal microscopy in human CD14-transfected Chinese hamster ovary fibroblasts ( CHO-CD14 cells ) and human peripheral blood monocytes .", "target_text": { "human CD14-transfected Chinese hamster ovary fibroblasts": "cell_line", "CHO-CD14 cells": "cell_line", "human peripheral blood monocytes": "cell_type" } }, { "input_text": "LPS core- and O-side chain- specific mAbs inhibited mCD14 -mediated LPS uptake by both cell types in the presence of serum .", "target_text": { "mCD14": "protein" } }, { "input_text": "O-side chain-specific mAb concurrently enhanced complement-dependent LPS uptake by monocytes through complement receptor-1 ( CR1 ) and uptake by CHO-CD14 cells involving another heat-labile serum factor ( s ) and cell-associated recognition molecule ( s ) .", "target_text": { "O-side chain-specific mAb": "protein", "complement receptor-1": "protein", "CR1": "protein", "CHO-CD14 cells": "cell_line", "heat-labile serum factor": "protein", "cell-associated recognition molecule": "protein" } }, { "input_text": "Core-specific mAb inhibited mCD14 -mediated uptake of homologous and heterologous LPS , while producing less concurrent enhancement of non- mCD14 -mediated LPS uptake .", "target_text": { "Core-specific mAb": "protein", "mCD14": "protein" } }, { "input_text": "The modulation by anti- LPS mAbs of mCD14 -mediated LPS uptake was associated with inhibition of LPS -induced nuclear factor-kappaB ( NF-kappaB ) translocation and TNF-alpha secretion in CHO-CD14 cells and monocytes , respectively , while mAb enhancement of non- mCD14 -mediated LPS uptake stimulated these activities .", "target_text": { "anti- LPS mAbs": "protein", "mCD14": "protein", "LPS -induced nuclear factor-kappaB": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein", "CHO-CD14 cells": "cell_line" } }, { "input_text": "LPS -specific Abs thus mediate anti-inflammatory and proinflammatory functions , respectively , by preventing target cell uptake of LPS through mCD14 and augmenting uptake through CR1 or other cell receptors .", "target_text": { "LPS -specific Abs": "protein", "mCD14": "protein", "CR1": "protein", "cell receptors": "protein" } }, { "input_text": "Four P-like elements are required for optimal transcription of the mouse IL-4 gene : involvement of a distinct set of nuclear factor of activated T cells and activator protein-1 family proteins .", "target_text": { "P-like elements": "DNA", "mouse IL-4 gene": "DNA", "T cells": "cell_type", "nuclear factor of activated T cells": "protein", "activator protein-1 family proteins": "protein" } }, { "input_text": "We previously identified the P sequence as a critical regulatory element of the human IL-4 promoter .", "target_text": { "P sequence": "DNA", "regulatory element": "DNA", "human IL-4 promoter": "DNA" } }, { "input_text": "In the mouse IL-4 promoter , there are five elements homologous to the human P sequence designated conserved lymphokine element 0 ( CLE0 ) , P , P2 , P3 and P4 .", "target_text": { "mouse IL-4 promoter": "DNA", "P sequence": "DNA", "conserved lymphokine element 0": "DNA", "CLE0": "DNA", "P": "DNA", "P2": "DNA", "P3": "DNA", "P4": "DNA" } }, { "input_text": "To characterize the role of these P -like elements and their binding factors in the native promoter , we did transient transfection and electrophoretic mobility shift assays ( EMSA ) .", "target_text": { "P": "DNA", "P -like elements": "DNA", "binding factors": "protein", "native promoter": "DNA" } }, { "input_text": "Transfection of EL-4 cells with the IL-4 promoter-reporter constructs carrying mutated P -like elements showed that four P-like elements , CLE0 , P , P2 and P4 , but not P3 , were required for optimal activation of the IL-4 promoter .", "target_text": { "EL-4 cells": "cell_line", "IL-4 promoter-reporter constructs": "DNA", "P": "DNA", "mutated P -like elements": "DNA", "P-like elements": "DNA", "CLE0": "DNA", "P2": "DNA", "P4": "DNA", "P3": "DNA", "IL-4 promoter": "DNA" } }, { "input_text": "EMSA showed that both constitutive and inducible complexes bound to CLE0 , P , P2 and P4 , whereas only a constitutive complex bound to P3 .", "target_text": { "CLE0": "DNA", "P": "DNA", "P2": "DNA", "P4": "DNA", "P3": "DNA" } }, { "input_text": "In competition and antibody supershift assays in EMSA , complexes formed with P or P2 proved to contain nuclear factor of activated T cells ( NFAT ) family proteins as major components .", "target_text": { "P": "DNA", "P2": "DNA", "nuclear factor of activated T cells ( NFAT ) family proteins": "protein" } }, { "input_text": "Activator protein ( AP ) -1 family proteins interacted with CLE0 , P , P2 and P4 .", "target_text": { "Activator protein ( AP ) -1 family proteins": "protein", "CLE0": "DNA", "P2": "DNA", "P4": "DNA" } }, { "input_text": "NFAT/AP-1 complex formed only with P and P2 .", "target_text": { "NFAT/AP-1 complex": "protein", "P": "DNA", "P2": "DNA" } }, { "input_text": "Cross-competition assays among the P-like elements revealed element-specific and common complexes .", "target_text": { "P-like elements": "DNA" } }, { "input_text": "Six tandem repeats of the P element linked to the SV40 promoter responded to phorbol 12-myristate 13-acetate , while that of other elements did not . It would thus appear that components of each P-like element-binding complexes are not identical and may coordinately contribute to transcriptional activity .", "target_text": { "P element": "DNA", "SV40 promoter": "DNA", "P-like element-binding complexes": "protein" } }, { "input_text": "Constitutive expression c-fos , c-jun , and NF kappa B mRNA is in nucleated fetal blood cells and up-regulation of c-fos and c-jun with anti-CD3 stimulation .", "target_text": { "nucleated fetal blood cells": "cell_type", "c-fos": "protein", "c-jun": "protein", "anti-CD3": "protein" } }, { "input_text": "Fetal and neonatal lymphocytes are relatively resistant to activation and cytokine production when stimulated either via their T-cell antigen receptors or lectins .", "target_text": { "cytokine": "protein", "T-cell antigen receptors": "protein", "lectins": "protein" } }, { "input_text": "The molecular mechanism ( s ) responsible for this phenomenon have not been clearly elucidated .", "target_text": { "molecular mechanism": "protein" } }, { "input_text": "We have hypothesized that such defects in fetal/neonatal T-cell activation may be due to lack of expression of the transcriptional regulatory elements required for T-cell activation .", "target_text": { "transcriptional regulatory elements": "protein" } }, { "input_text": "We used reverse transcriptase -polymerase chain reaction to examine both fetal and term neonatal cord bloods for mRNA expression of three transcription factors implicated in T-cell activation : c-jun , c-fos , and NF kappa B ( p50 subunit ) .", "target_text": { "reverse transcriptase": "protein", "transcription factors": "protein", "c-jun": "protein", "c-fos": "protein", "NF kappa B": "protein", "p50 subunit": "protein" } }, { "input_text": "We demonstrate that mRNAs for all three of these regulatory factors are expressed in fetal blood cells by the 27th week of gestation and in term cord bloods .", "target_text": { "mRNAs": "RNA", "fetal blood cells": "cell_type" } }, { "input_text": "Activation of term infant cord blood mononuclear cells with anti-CD3 monoclonal antibodies resulted in up-regulation of both c-jun and c-fos mRNAs within 15 min of stimulation .", "target_text": { "term infant cord blood mononuclear cells": "cell_type", "anti-CD3 monoclonal antibodies": "protein", "c-jun": "protein", "mRNAs": "RNA" } }, { "input_text": "However , secretion of IL-2 by anti-CD3-stimulated cord blood mononuclear cells was still blunted compared with control cells from adults .", "target_text": { "IL-2": "protein", "anti-CD3-stimulated cord blood mononuclear cells": "cell_line", "control cells": "cell_type" } }, { "input_text": "We conclude that fetal nucleated blood cells constitutively express important genes for cytokine regulation and are able to increase intracellular accumulation of the mRNAs for these factors in response to anti-CD3 stimulation .", "target_text": { "fetal nucleated blood cells": "cell_type", "cytokine": "protein", "mRNAs": "RNA", "anti-CD3": "protein" } }, { "input_text": "Thus , qualitative differences in the capacity to regulate these factors could not be shown in fetal blood cells .", "target_text": { "fetal blood cells": "cell_type" } }, { "input_text": "Quantitative experiments comparing binding of these transcription factors to the IL-2 promoter are currently under investigation .", "target_text": { "transcription factors": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway .", "target_text": { "NFAT4": "protein", "JNK": "protein" } }, { "input_text": "The nuclear factor of activated T cells ( NFAT ) group of transcription factors is retained in the cytoplasm of quiescent cells .", "target_text": { "nuclear factor of activated T cells ( NFAT ) group": "protein", "transcription factors": "protein", "quiescent cells": "cell_type" } }, { "input_text": "NFAT activation is mediated in part by induced nuclear import .", "target_text": { "NFAT": "protein" } }, { "input_text": "This process requires calcium -dependent dephosphorylation of NFAT caused by the phosphatase calcineurin .", "target_text": { "NFAT": "protein", "phosphatase": "protein", "calcineurin": "protein" } }, { "input_text": "The c-Jun amino-terminal kinase ( JNK ) phosphorylates NFAT4 on two sites .", "target_text": { "c-Jun amino-terminal kinase": "protein", "JNK": "protein", "NFAT4": "protein" } }, { "input_text": "Mutational removal of the JNK phosphorylation sites caused constitutive nuclear localization of NFAT4 .", "target_text": { "JNK phosphorylation sites": "protein", "NFAT4": "protein" } }, { "input_text": "In contrast , JNK activation in calcineurin -stimulated cells caused nuclear exclusion of NFAT4 .", "target_text": { "JNK": "protein", "calcineurin": "protein", "calcineurin -stimulated cells": "cell_line", "NFAT4": "protein" } }, { "input_text": "These findings show that the nuclear accumulation of NFAT4 promoted by calcineurin is opposed by the JNK signal transduction pathway .", "target_text": { "NFAT4": "protein", "calcineurin": "protein", "JNK": "protein" } }, { "input_text": "Thiol modulation inhibits the interleukin ( IL ) -1 -mediated activation of an IL-1 receptor-associated protein kinase and NF-kappa B .", "target_text": { "interleukin ( IL ) -1": "protein", "IL-1 receptor-associated protein kinase": "protein", "NF-kappa B": "protein" } }, { "input_text": "The interleukin-1 receptor type I ( IL-1RI ) is associated with other proteins thus forming a complex system by which IL-1 exerts its various signals .", "target_text": { "interleukin-1 receptor type I": "protein", "IL-1RI": "protein", "complex system": "protein", "IL-1": "protein" } }, { "input_text": "The initiating event is still uncertain , but activation of a recently described receptor-associated protein kinase is one of the earliest events detectable ( Martin et al. , Eur.J.Immunol.1994.24 : 1566 ) .", "target_text": { "receptor-associated protein kinase": "protein" } }, { "input_text": "IL-1 signaling is commonly accompanied by oxidative processes and is thought to be subject to redox regulation .", "target_text": { "IL-1": "protein" } }, { "input_text": "We therefore investigated whether the activation of the IL-1RI -associated protein kinase could be a target for redox regulation and whether an altered activity of the kinase could influence IL-1 -mediated NF-kappa B activation .", "target_text": { "IL-1RI": "protein", "IL-1RI -associated protein kinase": "protein", "IL-1": "protein", "NF-kappa B": "protein" } }, { "input_text": "A murine T cell line , EL4 , was stimulated with IL-1 with and without pretreatment with different compounds known to influence the cellular redox status .", "target_text": { "murine T cell line": "cell_line", "EL4": "cell_line", "IL-1": "protein" } }, { "input_text": "Thiol modifying agents like diamide , menadione , pyrrolidine dithiocarbamate ( PDTC ) , diethyl dithiocarbamate or phenylarsine oxide inhibited the IL-1 -induced activation of the IL-1RI-associated protein kinase .", "target_text": { "IL-1": "protein", "IL-1RI-associated protein kinase": "protein" } }, { "input_text": "N-Acetylcysteine , alpha,alpha'-dipyridyl , aminotriazole or nitrofurantoin did not show any effect .", "target_text": {} }, { "input_text": "The inhibition by PDTC was reversible unless glutathione synthesis was blocked by buthionine sulfoximine .", "target_text": {} }, { "input_text": "The described conditions which inhibited or prevented the activation of the IL-1RI -associated kinase similarly impaired the activation of NF-kappa B in EL4 cells .", "target_text": { "IL-1RI": "protein", "IL-1RI -associated kinase": "protein", "NF-kappa B": "protein", "EL4 cells": "cell_line" } }, { "input_text": "From these observations we conclude that free thiols in the IL-1RI complex are essential for the activation of the IL-1RI -associated protein kinase and that this process is mandatory for IL-1 signaling leading to NF-kappa B activation .", "target_text": { "IL-1RI": "protein", "IL-1RI complex": "protein", "IL-1RI -associated protein kinase": "protein", "IL-1": "protein", "NF-kappa B": "protein" } }, { "input_text": "Switching gears during T-cell maturation : RANTES and late transcription .", "target_text": { "RANTES": "protein" } }, { "input_text": "Although much is understood about the induction of genes expressed early ( within 24 h ) after T-cell activation , little is known about the regulation of expression of genes expressed ' late ' ( three or more days ) post-stimulation .", "target_text": { "genes": "DNA" } }, { "input_text": "A better understanding of transcriptional regulation at this important stage of T-cell maturation may yield new insights into T-cell development and new immunotherapeutic targets .", "target_text": {} }, { "input_text": "Involvement of different transduction pathways in NF-kappa B activation by several inducers .", "target_text": { "NF-kappa B": "protein", "inducers": "DNA" } }, { "input_text": "Double-stimulation was used to demonstrate that , in a T lymphocytic cell line ( CEM ) , phorbol myristate acetate ( PMA ) rapidly induced NF-kappa B through a signaling pathway which did not involve reactive oxygen species ( ROS ) and was different from the activation triggered by either H2O2 or tumor necrosis factor-alpha ( TNF-alpha ) .", "target_text": { "T lymphocytic cell line": "cell_line", "CEM": "cell_line", "NF-kappa B": "protein", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "Since these latter compounds were known to activate NF-kappa B translocation in a redox-sensitive way , we have demonstrated that NF-kappa B activation by PMA was resistant to antioxidant N-acetyl-L-cysteine ( NAC ) and sensitive to kinase inhibitors staurosporine and H7 while activation by H2O2 or TNF-alpha were not .", "target_text": { "NF-kappa B": "protein", "TNF-alpha": "protein" } }, { "input_text": "Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells .", "target_text": { "nuclear factor of activated T cells": "protein" } }, { "input_text": "Dithiocarbamates ( DTCs ) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Given the role of this transcription factor in the regulation of gene expression in the inflammatory response , NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "We show here that DTCs inhibited both interleukin 2 ( IL-2 ) synthesis and membrane expression of antigens which are induced during T-cell activation .", "target_text": { "interleukin 2": "protein", "IL-2": "protein", "antigens": "protein" } }, { "input_text": "This inhibition , which occurred with a parallel activation of c-Jun transactivating functions and expression , was reflected by transfection experiments at the IL-2 promoter level , and involved not only the inhibition of NF-kappaB -driven reporter activation but also that of nuclear factor of activated T cells ( NFAT ) .", "target_text": { "c-Jun": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "NF-kappaB": "protein", "nuclear factor of activated T cells": "protein", "NFAT": "protein" } }, { "input_text": "Accordingly , electrophoretic mobility shift assays ( EMSAs ) indicated that pyrrolidine DTC ( PDTC ) prevented NF-kappaB , and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1 .", "target_text": { "NF-kappaB": "protein", "NFAT": "protein", "T cells": "cell_type", "CD3-T-cell receptor complex": "protein", "AP-1": "protein" } }, { "input_text": "Furthermore , PDTC differentially targeted both NFATp and NFATc family members , inhibiting the transactivation functions of NFATp and mRNA induction of NFATc .", "target_text": { "NFATp": "protein", "NFATc": "protein" } }, { "input_text": "Strikingly , Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc , leading to their accelerated export from the nucleus of activated T cells .", "target_text": { "NFATp": "protein", "NFATc": "protein", "T cells": "cell_type", "activated T cells": "cell_type" } }, { "input_text": "We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT , therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation , and show that c-Jun NH2-terminal kinase ( JNK ) can act by directly phosphorylating NFATp .", "target_text": { "NFAT": "protein", "transcription factor": "protein", "c-Jun NH2-terminal kinase": "protein", "JNK": "protein", "NFATp": "protein" } }, { "input_text": "In addition , the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants .", "target_text": { "NFAT": "protein", "NF-KB": "protein" } }, { "input_text": "Activation of a novel gene in 3q21 and identification of intergenic fusion transcripts with ecotropic viral insertion site I in leukemia .", "target_text": { "novel gene": "DNA", "3q21": "DNA", "ecotropic viral insertion site I": "DNA" } }, { "input_text": "We have identified a novel gene , GR6 , located within the leukemia breakpoint region of 3q21 , that is normally expressed in early fetal development but not in adult peripheral blood .", "target_text": { "novel gene": "DNA", "GR6": "DNA", "3q21": "DNA" } }, { "input_text": "GR6 is activated in the UCSD-AML1 cell line and in a leukemic sample , both of which carry a t(3;3)(q21;q26) .", "target_text": { "GR6": "DNA", "UCSD-AML1 cell line": "cell_line", "leukemic sample": "cell_line", "t(3;3)(q21;q26)": "DNA" } }, { "input_text": "In UCSD-AML1 , we have also identified fusion transcripts between the ecotropic viral insertion site I ( EVI1 ) gene in 3q26 and GR6 and between EVI1 and Ribophorin I that maps 30 kb telomeric to GR6 in 3q21 .", "target_text": { "UCSD-AML1": "cell_line", "fusion transcripts": "RNA", "ecotropic viral insertion site I ( EVI1 ) gene": "DNA", "3q26": "DNA", "GR6": "DNA", "EVI1": "DNA", "Ribophorin I": "DNA", "3q21": "DNA" } }, { "input_text": "All fusions splice the 5' ends of the 3q21 genes into exon 2 of the EVI1 gene , an event that is similar to the normal intergenic splicing of MDS1- EVI1 and to those previously documented in leukemias with t(3;21) and t(3;12) , in which acute myelogenous leukemia 1- EVI1 fusions and ETV6- EVI1 fusions , respectively , occur .", "target_text": { "5' ends": "DNA", "3q21": "DNA", "3q21 genes": "DNA", "exon 2": "DNA", "EVI1": "DNA", "MDS1- EVI1": "DNA", "t(3;21)": "DNA", "t(3;12)": "DNA", "myelogenous leukemia 1- EVI1 fusions": "DNA", "ETV6- EVI1 fusions": "DNA" } }, { "input_text": "The Ribophorin I -EVI1 fusion in particular may be a common occurrence in t(3;3) .", "target_text": { "Ribophorin I": "DNA", "-EVI1": "DNA", "Ribophorin I -EVI1 fusion": "DNA", "t(3;3)": "DNA" } }, { "input_text": "The A-myb transcription factor in neoplastic and normal B cells .", "target_text": { "A-myb": "protein", "A-myb transcription factor": "protein" } }, { "input_text": "The myb family of transcription factors has been strongly implicated in the regulation of cell growth and differentiation in the haematopoietic system .", "target_text": { "myb family": "protein", "transcription factors": "protein" } }, { "input_text": "The v-myb oncogene , carried by avian defective retroviruses , causes leukaemias in the chicken and transforms haematopoietic cells in vitro .", "target_text": { "v-myb oncogene": "DNA", "haematopoietic cells": "cell_type" } }, { "input_text": "Its normal cellular equivalent c-myb , has been shown to promote the proliferation and block the differentiation of haematopoietic cells in several experimental models and is required for fetal haematopoiesis .", "target_text": { "c-myb": "DNA", "haematopoietic cells": "cell_type" } }, { "input_text": "Two other members of the family have been cloned more recently , A-myb and B-myb , which show sequence homology with c-myb in several domains , of which the DNA binding domain as well as other regulatory domains .", "target_text": { "A-myb": "protein", "B-myb": "protein", "c-myb": "DNA", "DNA binding domain": "protein", "regulatory domains": "protein" } }, { "input_text": "Both have been shown to be transcription factors .", "target_text": { "transcription factors": "protein" } }, { "input_text": "B-myb is also involved in the control of proliferation and differentiation , but , unlike c-myb , it is expressed in many cell types .", "target_text": { "B-myb": "protein", "c-myb": "DNA" } }, { "input_text": "The third member of the family , A-myb , shows the most restricted pattern of expression , suggesting a very specific role for this transcription factor .", "target_text": { "family": "protein", "A-myb": "protein", "transcription factor": "protein" } }, { "input_text": "A-myb is expressed in a subpopulation of normal B lymphocytes activated in vivo and localised in the germinal center of peripheral lymphoid organs and is not detected at significant levels in all other mature or immature haematopoietic populations studied , including bone marrow cells , T lymphocytes , granulocytes , monocytes , either at rest or after in vitro activation .", "target_text": { "A-myb": "protein", "normal B lymphocytes": "cell_type", "immature haematopoietic populations": "cell_type", "bone marrow cells": "cell_type", "T lymphocytes": "cell_type", "granulocytes": "cell_type", "monocytes": "cell_type" } }, { "input_text": "These studies indicate that A-myb plays a role during a narrow window of normal B cell differentiation .", "target_text": { "A-myb": "protein", "normal B cell": "cell_type" } }, { "input_text": "A-myb expression has also been studied in a wide range of neoplastic B cells , representing the whole spectrum of B cell differentiation .", "target_text": { "A-myb": "protein", "neoplastic B cells": "cell_type" } }, { "input_text": "A-myb is strongly expressed in Burkitt 's lymphomas ( BL ) and slg+ B-acute lymphoblastic leukaemias ( B-ALL ) and not in all other leukaemias /lymphomas tested , with the exception of a subset of CLL ( about 25 % of cases ) .", "target_text": { "A-myb": "protein" } }, { "input_text": "It is intriguing that the A-myb genome has been localised relatively close to the c-myc gene on chromosome 8 , suggesting that the c-myc translocation in BL and B-ALL may affect A-myb transcription .", "target_text": { "A-myb": "protein", "A-myb genome": "DNA", "c-myc gene": "DNA", "chromosome 8": "DNA" } }, { "input_text": "Studies are in progress to investigate the functional relationship between A-myb and c-myc , particularly in the context of BL cells and to determine whether A-myb is deregulated in these cells .", "target_text": { "A-myb": "protein", "c-myc": "DNA", "BL cells": "cell_type" } }, { "input_text": "Expression of bcl-6 protein in normal skin and epidermal neoplasms .", "target_text": { "bcl-6 protein": "protein" } }, { "input_text": "Bcl-6 protein is a recently identified novel transcription factor whose deregulated expression is associated with diffuse large B cell lymphomas .", "target_text": { "Bcl-6 protein": "protein", "transcription factor": "protein" } }, { "input_text": "It was recently shown by us that the protein is located in germinal center B cells and their neoplastic counterparts .", "target_text": { "germinal center B cells": "cell_type", "neoplastic counterparts": "cell_type" } }, { "input_text": "In the present study , the expression of bcl-6 protein on normal epidermis , benign , and malignant tumors originating from epidermal cells , and squamous cell carcinoma ( SCC ) cell lines are investigated .", "target_text": { "bcl-6 protein": "protein", "epidermal cells": "cell_type", "squamous cell carcinoma ( SCC ) cell lines": "cell_line" } }, { "input_text": "With the use of immunohistochemistry , bcl-6 protein was shown to stain intensely on normal prickle cells , but none to only slightly on epidermal basal cells .", "target_text": { "bcl-6 protein": "protein", "normal prickle cells": "cell_line", "epidermal basal cells": "cell_type" } }, { "input_text": "Papillomas and keratoacanthomas copied their normal counterparts in the mode of expression .", "target_text": {} }, { "input_text": "Various levels of expression were found on seborrheic keratoses , while the expression level on basal cell epitheliomas was low .", "target_text": {} }, { "input_text": "Peculiarly , eccrine poromas and undifferentiated spindle-shaped basal cell epitheliomas were totally unstained .", "target_text": {} }, { "input_text": "Squamous cell carcinomas showed a variety of expression levels , while two undifferentiated spindle-shaped carcinomas and one undifferentiated SCC cell line remained unstained .", "target_text": { "SCC cell line": "cell_line" } }, { "input_text": "These results suggest that the expression of bcl-6 protein may be associated with morphological differentiation in normal and neoplastic epidermal cells .", "target_text": { "bcl-6 protein": "protein", "epidermal cells": "cell_type", "neoplastic epidermal cells": "cell_type" } }, { "input_text": "Sp3 mediates transcriptional activation of the leukocyte integrin genes CD11C and CD11B and cooperates with c-Jun to activate CD11C .", "target_text": { "Sp3": "protein", "leukocyte integrin genes": "DNA", "CD11C": "DNA", "CD11B": "DNA" } }, { "input_text": "The leukocyte integrin genes CD11c and CD11b are expressed predominately in myelomonocytic cells .", "target_text": { "leukocyte integrin genes": "DNA", "CD11c": "DNA", "CD11b": "DNA" } }, { "input_text": "In previous experiments , the -70 to -65 and -121 to -103 regions of the CD11c promoter and the -66 to -59 region of the CD11b promoter were shown to be essential for Sp1- mediated activation of these genes .", "target_text": { "CD11c": "DNA", "CD11c promoter": "DNA", "-66 to -59 region": "DNA", "CD11b": "DNA", "CD11b promoter": "DNA", "Sp1-": "protein" } }, { "input_text": "In vivo genomic footprinting had also revealed cell-specific binding of protein , presumably Sp1 , to these regions .", "target_text": { "Sp1": "protein" } }, { "input_text": "In this study , electrophoretic mobility shift analysis showed that the Sp1 -related factor , Sp3 , also binds at or near these same regions .", "target_text": { "Sp1": "protein", "Sp1 -related factor": "protein", "Sp3": "protein" } }, { "input_text": "Cotransfection of Sp3 along with CD11c promoter -luciferase constructs into Sp-deficient Drosophila Schneider 2 cells showed that Sp3 could activate the CD11c promoter .", "target_text": { "Sp3": "protein", "CD11c": "DNA", "CD11c promoter": "DNA", "-luciferase": "protein", "CD11c promoter -luciferase constructs": "DNA", "Sp-deficient Drosophila Schneider 2 cells": "cell_line" } }, { "input_text": "Deletion of both the -70 to -65 and -121 to -103 regions of the CD11c promoter resulted in the loss of activation by Sp3 .", "target_text": { "CD11c": "DNA", "CD11c promoter": "DNA", "Sp3": "protein" } }, { "input_text": "Both sites showed activation by Sp3 ; however , the -70 to -65 region was more responsive to Sp3 than to Sp1 .", "target_text": { "Sp3": "protein", "-70 to -65 region": "DNA", "Sp1": "protein" } }, { "input_text": "Similar transfection analysis of the -66 to -59 region of the CD11b promoter showed Sp3 -dependent expression .", "target_text": { "-66 to -59 region": "DNA", "CD11b": "DNA", "CD11b promoter": "DNA", "Sp3": "protein" } }, { "input_text": "Further , cotransfection analysis in Drosophila cells showed that Sp3 , as was previously shown for Sp1 , also synergizes with c-Jun to activate CD11c .", "target_text": { "Drosophila cells": "cell_line", "Sp3": "protein", "Sp1": "protein", "c-Jun": "protein", "CD11c": "DNA" } }, { "input_text": "Antisense experiments that knocked out endogenous Sp3 expression in the myelomocytic cell line , HL60 , revealed that Sp3 participates in activation of the CD11c and CD11b promoters in vivo .", "target_text": { "Sp3": "protein", "myelomocytic cell line": "cell_line", "HL60": "cell_line" } }, { "input_text": "The winged-helix transcription factor Trident is expressed in actively dividing lymphocytes .", "target_text": { "winged-helix transcription factor": "protein", "Trident": "protein", "dividing lymphocytes": "cell_type" } }, { "input_text": "We recently identified the winged-helix transcription factor Trident and described its expression pattern in synchronized fibroblasts .", "target_text": { "winged-helix transcription factor": "protein", "Trident": "protein", "synchronized fibroblasts": "cell_type" } }, { "input_text": "We have now studied Trident expression in cell lines , differentiating thymocytes and in lymphocytes derived from peripheral blood .", "target_text": { "Trident": "protein", "cell lines": "cell_line", "differentiating thymocytes": "cell_type" } }, { "input_text": "During T cell differentiation , expression peaked in the actively dividing immature single positive cells .", "target_text": { "actively dividing immature single positive cells": "cell_type" } }, { "input_text": "In peripheral blood lymphocytes , expression of Trident mRNA was absent , but could be induced upon stimulation with mitogens in vitro .", "target_text": { "Trident": "protein", "Trident mRNA": "RNA" } }, { "input_text": "These observations imply a function for Trident in dividing lymphocytes .", "target_text": { "Trident": "protein", "dividing lymphocytes": "cell_type" } }, { "input_text": "Estrogen receptor diminishes DNA-binding activities of chicken GATA-1 and CACCC-binding proteins .", "target_text": { "Estrogen receptor": "protein", "chicken GATA-1": "protein", "CACCC-binding proteins": "protein" } }, { "input_text": "The estrogen receptor ( ER ) repressed erythroid differentiation and erythroid-specific gene expression .", "target_text": { "estrogen receptor": "protein", "ER": "protein", "erythroid-specific gene": "DNA" } }, { "input_text": "In this study , we investigated the effect of ER alpha ( referred to throughout as ER ) on DNA-binding activities of transcription factors involved in regulating the expression of erythroid-specific genes , and , in particular , the histone H5 gene .", "target_text": { "ER alpha": "protein", "ER": "protein", "transcription factors": "protein", "erythroid-specific genes": "DNA", "histone H5 gene": "DNA" } }, { "input_text": "Using electrophoretic mobility shift assays , we found that in the presence of rabbit reticulocyte lysate , human ER reduced the binding activities of chicken immature erythrocyte nuclear extracted proteins to GATA and CACCC sites in the H5 promoter and enhancer .", "target_text": { "human ER": "protein", "chicken immature erythrocyte nuclear extracted proteins": "protein" } }, { "input_text": "In contrast , the binding activities of NF1 and Sp1 were not affected by ER .", "target_text": { "NF1": "protein", "Sp1": "protein", "ER": "protein" } }, { "input_text": "Binding of ER to an estrogen response element was enhanced by addition of rabbit reticulocyte lysate .", "target_text": { "ER": "protein", "estrogen response element": "DNA" } }, { "input_text": "This lysate was also necessary for ER to diminish the DNA-binding activity of GATA-1 .", "target_text": { "ER": "protein", "GATA-1": "protein" } }, { "input_text": "These results suggest that additional factor ( s ) are necessary for full ER function .", "target_text": { "ER": "protein" } }, { "input_text": "Both GATA-1 and CACCC-binding proteins are critical for the developmentally regulated expression of erythroid-specific genes .", "target_text": { "GATA-1": "protein", "CACCC-binding proteins": "protein", "erythroid-specific genes": "DNA" } }, { "input_text": "We hypothesize that interference in DNA-binding activities of GATA-1 and CACCC-binding proteins is the mechanism by which the ER inhibits regulation of these genes .", "target_text": { "GATA-1": "protein", "CACCC-binding proteins": "protein", "ER": "protein" } }, { "input_text": "Regulation of Id3 cell cycle function by Cdk-2-dependent phosphorylation .", "target_text": { "Id3": "protein" } }, { "input_text": "The functions of basic helix-loop-helix ( bHLH ) transcription factors in activating differentiation-linked gene expression and in inducing G1 cell cycle arrest are negatively regulated by members of the Id family of HLH proteins .", "target_text": { "transcription factors": "protein", "basic helix-loop-helix ( bHLH ) transcription factors": "protein", "Id family of HLH proteins": "protein" } }, { "input_text": "These bHLH antagonists are induced during a mitogenic signalling response , and they function by sequestering their bHLH targets in inactive heterodimers that are unable to bind to specific gene regulatory ( E box ) sequences .", "target_text": { "bHLH antagonists": "protein", "bHLH targets": "protein", "inactive heterodimers": "protein", "gene regulatory ( E box ) sequences": "DNA" } }, { "input_text": "Recently , cyclin E-Cdk2- and cyclin A-Cdk2- dependent phosphorylation of a single conserved serine residue ( Ser5 ) in Id2 has been shown to occur during late G1-to-S phase transition of the cell cycle , and this neutralizes the function of Id2 in abrogating E-box-dependent bHLH homo - or hetero dimer complex formation in vitro ( E.Hara , M.Hall , and G.Peters , EMBO J.16 : 332-342 , 1997 ) .", "target_text": { "Id2": "protein", "E-box-dependent bHLH": "protein" } }, { "input_text": "We now show that an analogous cell-cycle-regulated phosphorylation of Id3 alters the specificity of Id3 for abrogating both E-box-dependent bHLH homo- or heterodimer complex formation in vitro and E-box-dependent reporter gene function in vivo .", "target_text": { "Id3": "protein", "E-box-dependent bHLH": "protein", "reporter gene": "DNA" } }, { "input_text": "Furthermore , compared with wild-type Id3 , an Id3 Asp5 mutant ( mimicking phosphorylation ) is unable to promote cell cycle S phase entry in transfected fibroblasts , whereas an Id3 Ala5 mutant ( ablating phosphorylation ) displays an activity significantly greater than that of wild-type Id3 protein .", "target_text": { "Id3": "protein", "wild-type Id3": "protein", "Id3 Asp5 mutant": "protein", "transfected fibroblasts": "cell_line", "Id3 Ala5 mutant": "protein", "wild-type Id3 protein": "protein" } }, { "input_text": "Cdk2-dependent phosphorylation therefore provides a switch during late G1-to-S phase that both nullifies an early G1 cell cycle regulatory function of Id3 and modulates its target bHLH specificity .", "target_text": { "Id3": "protein", "bHLH": "protein" } }, { "input_text": "These data also demonstrate that the ability of Id3 to promote cell cycle S phase entry is not simply a function of its ability to modulate bHLH heterodimer-dependent gene expression and establish a biologically important mechanism through which Cdk2 and Id-bHLH functions are integrated in the coordination of cell proliferation and differentiation .", "target_text": { "Id3": "protein", "bHLH": "protein" } }, { "input_text": "Molecular cloning and functional characterization of murine cDNA encoding transcription factor NFATc .", "target_text": { "murine cDNA encoding transcription factor": "protein", "NFATc": "protein" } }, { "input_text": "Transcription factors of the NFAT ( nuclear factor of activated T cells ) family play important roles in immune and inflammatory responses by regulating the expression of genes encoding cytokines and immunoregulatory proteins .", "target_text": { "Transcription factors": "protein", "nuclear factor of activated T cells": "protein", "NFAT ( nuclear factor of activated T cells ) family": "protein", "cytokines": "protein", "immunoregulatory proteins": "protein" } }, { "input_text": "Here we describe cloning and characterization of full-length cDNA encoding murine ( m ) NFATc which predicts that the protein has all the conserved structural motifs of NFAT family members , including the rel homology domain , the NFAT homology domain and the nuclear translocation signals .", "target_text": { "NFATc": "protein", "cDNA encoding murine ( m ) NFATc": "protein", "conserved structural motifs": "protein", "NFAT family members": "protein", "NFAT homology domain": "protein" } }, { "input_text": "mNFATc complexed with AP-1 bound specifically to the murine IL-2 NFAT recognition sequence and activated transcription from the co-transfected IL-2 promoter in COS-7 cells .", "target_text": { "mNFATc": "protein", "AP-1": "protein", "murine IL-2 NFAT recognition sequence": "protein", "co-transfected IL-2 promoter": "DNA", "COS-7 cells": "cell_line" } }, { "input_text": "Northern blot analysis showed that the cDNA probe hybridized with a 4.5 kb transcript which is highly inducible in murine T cells .", "target_text": { "cDNA probe": "DNA", "murine T cells": "cell_type" } }, { "input_text": "By Northern and in situ hybridization , mNFATc transcript was detected from the early stage of development .", "target_text": { "mNFATc": "protein", "mNFATc transcript": "RNA" } }, { "input_text": "In the mouse embryo , mNFATc transcript was strongly expressed in thymus , lung and submandibular gland and weakly in skeletal muscle and heart suggesting that mNFATc may have a role both in embryogenesis and in mature T cells .", "target_text": { "mNFATc": "protein", "mNFATc transcript": "RNA", "mature T cells": "cell_type" } }, { "input_text": "TNFalpha cooperates with the protein kinase A pathway to synergistically increase HIV-1 LTR transcription via downstream TRE-like cAMP response elements .", "target_text": { "TNFalpha": "protein", "protein kinase A": "protein", "HIV-1 LTR": "DNA", "TRE-like cAMP response elements": "DNA" } }, { "input_text": "Activating protein-1 ( AP-1 ) binding TPA responsive elements ( TRE ) are located downstream of the transcription initiation site in the U5 region of the HIV-1 long terminal repeat ( LTR ) .", "target_text": { "Activating protein-1": "protein", "AP-1": "protein", "TPA responsive elements": "DNA", "TRE": "DNA", "transcription initiation site": "DNA", "U5 region": "DNA", "HIV-1 long terminal repeat": "DNA", "LTR": "DNA" } }, { "input_text": "These downstream sequence elements , termed DSE , can bind both AP-1 and CREB/ATF transcription factors .", "target_text": { "downstream sequence elements": "DNA", "DSE": "DNA", "AP-1": "protein", "CREB/ATF": "protein", "transcription factors": "protein" } }, { "input_text": "Recently , we demonstrated that the DSE are also cAMP-responsive elements ( CRE ) , since they mediated activation signals elicited by cholera toxin ( Ctx ) , a potent activator of the cAMP-dependent protein kinase A ( PKA ) signal transduction pathway .", "target_text": { "DSE": "DNA", "cAMP-responsive elements": "DNA", "CRE": "DNA", "cholera toxin": "protein", "Ctx": "protein", "protein kinase A": "protein", "PKA": "protein" } }, { "input_text": "In the present study , we demonstrate that the HIV-1 DSE can mediate the transcriptional synergy elicited by the combination of Ctx and TNFalpha .", "target_text": { "DSE": "DNA", "HIV-1 DSE": "DNA", "Ctx": "protein", "TNFalpha": "protein" } }, { "input_text": "Ctx combined with TNFalpha or IL-1beta to produce a synergistic increase in p24 antigen production in U1 promonocytic cells .", "target_text": { "Ctx": "protein", "TNFalpha": "protein", "IL-1beta": "protein", "p24 antigen": "protein", "U1 promonocytic cells": "cell_line" } }, { "input_text": "Transfection studies of LTR reporter constructs indicated that mutation of the DSE sites abrogated the LTR -mediated synergy induced by Ctx and TNFalpha , whereas the synergy induced by Ctx and IL-1beta was unaffected , suggesting TNFalpha and IL-1beta cooperate differently with the cAMP /PKA activation pathway to induce HIV-1 expression in U1 cells .", "target_text": { "LTR reporter constructs": "DNA", "DSE": "DNA", "DSE sites": "DNA", "LTR": "DNA", "Ctx": "protein", "TNFalpha": "protein", "IL-1beta": "protein", "/PKA": "protein", "U1 cells": "cell_line" } }, { "input_text": "Because the DSE are also TRE sites , we assessed the effect of the agonist combinations on AP-1 -dependent transcription .", "target_text": { "DSE": "DNA", "TRE": "DNA", "AP-1": "protein" } }, { "input_text": "TNFalpha as well as IL-1beta cooperated with Ctx to produce a synergistic activation of AP-1 -mediated transcription .", "target_text": { "TNFalpha": "protein", "IL-1beta": "protein", "Ctx": "protein", "AP-1": "protein" } }, { "input_text": "These data indicate that the TRE -like cAMP-responsive DSE sites within the 5'-untranslated leader can mediate the transcriptional cooperativity between TNFalpha and the cAMP /PKA pathway .", "target_text": { "TRE": "DNA", "DSE": "DNA", "TRE -like cAMP-responsive DSE sites": "DNA", "5'-untranslated leader": "DNA", "TNFalpha": "protein", "/PKA": "protein" } }, { "input_text": "Since the DSE and TRE sites can not bind CREB/ATF homodimers , we propose a mechanism in which the HIV-1 DSE bind heterodimers composed of both AP-1 and CREB/ATF proteins .", "target_text": { "DSE": "DNA", "TRE": "DNA", "CREB/ATF": "protein", "CREB/ATF homodimers": "protein", "heterodimers": "protein" } }, { "input_text": "Copyright 1997 Academic Press .", "target_text": {} }, { "input_text": "Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor beta .", "target_text": { "glucocorticoid receptor beta": "protein" } }, { "input_text": "In many chronic inflammatory disorders , glucocorticoid ( GC ) insensitivity is a challenging clinical problem associated with life-threatening disease progression .", "target_text": {} }, { "input_text": "The molecular basis of GC insensitivity , however , is unknown .", "target_text": {} }, { "input_text": "Alternative splicing of the GC receptor ( R ) pre-messenger RNA generates a second GCR , termed GCR-beta , which does not bind GCs but antagonizes the transactivating activity of the classic GCR , termed GCR-alpha .", "target_text": { "GC receptor": "protein", "GC receptor ( R ) pre-messenger RNA": "RNA", "GCR": "protein", "GCR-beta": "protein", "GCR-alpha": "protein" } }, { "input_text": "In the current study , we demonstrate that GC-insensitive asthma is associated with a significantly higher number of GCR-beta -immunoreactive cells in peripheral blood than GC-sensitive asthmatics or normal controls .", "target_text": { "GCR-beta": "protein", "GCR-beta -immunoreactive cells": "cell_type" } }, { "input_text": "Furthermore , we show that patients with GC-insensitive asthma have cytokine-induced abnormalities in the DNA binding capability of the GCR .", "target_text": { "GCR": "protein" } }, { "input_text": "These abnormalities can be reproduced by transfection of cell lines with the GCR-beta gene resulting in significant reduction of their GCR-alpha DNA binding capacity .", "target_text": { "cell lines": "cell_line", "GCR-beta": "protein", "GCR-alpha": "protein" } }, { "input_text": "We conclude that increased expression of GCR-beta is cytokine inducible and may account for GC insensitivity in this common inflammatory condition .", "target_text": { "GCR-beta": "protein", "cytokine": "protein" } }, { "input_text": "Epstein-Barr virus EBNA3C represses Cp , the major promoter for EBNA expression , but has no effect on the promoter of the cell gene CD21 .", "target_text": { "EBNA3C": "protein", "Cp": "DNA", "EBNA": "protein", "cell gene CD21": "DNA" } }, { "input_text": "EBNA3C is a potent repressor of transcription when bound to DNA as a fusion with the DNA binding domain ( DBD ) of GALA .", "target_text": { "EBNA3C": "protein", "DNA binding domain": "protein", "DBD": "protein" } }, { "input_text": "A survey of promoters has revealed that the wild-type , unfused EBNA3C can specifically repress expression from reporter plasmids containing the Epstein-Barr virus Cp latency-associated promoter .", "target_text": { "EBNA3C": "protein", "wild-type , unfused EBNA3C": "protein", "reporter plasmids": "DNA", "Cp": "DNA", "Cp latency-associated promoter": "DNA" } }, { "input_text": "Repression of Cp activity required amino acids 207 to 368 , which encompasses a region resembling a basic DBD adjacent to a leucine zipper DNA binding motif and a site which binds to the cellular factor CBF1/RBP-Jkappa .", "target_text": { "Cp": "DNA", "amino acids 207 to 368": "protein", "DBD": "protein", "basic DBD": "protein", "leucine zipper DNA binding motif": "protein", "CBF1/RBP-Jkappa": "protein", "cellular factor CBF1/RBP-Jkappa": "protein" } }, { "input_text": "However , amino acids 207 to 368 are dispensable when the protein is bound to DNA as a fusion with the GAL4 DBD , thus implicating this region in DNA binding .", "target_text": { "DBD": "protein" } }, { "input_text": "Mutation of the CBF1/RBP-Jkappa binding site in EBNA3C abrogated repression , strongly suggesting that CBF1/RBP-Jkappa is necessary for targeting the viral protein to Cp .", "target_text": { "CBF1/RBP-Jkappa": "protein", "CBF1/RBP-Jkappa binding site": "protein", "EBNA3C": "protein", "Cp": "DNA" } }, { "input_text": "Consistent with this result , mutation of the EBNA2 response element ( a CBF1/RBP-Jkappa binding site ) in Cp also prevented significant repression .", "target_text": { "EBNA2 response element": "DNA", "CBF1/RBP-Jkappa": "protein", "CBF1/RBP-Jkappa binding site": "DNA", "Cp": "DNA" } }, { "input_text": "In addition , amino acids 346 to 543 , which were previously defined as important for the repressor activity of the GAL4-EBNA3C fusion proteins , also appear to be necessary for the repression of Cp .", "target_text": { "amino acids 346 to 543": "protein", "GAL4-EBNA3C fusion proteins": "protein", "Cp": "DNA" } }, { "input_text": "Since repression by these fusions was not observed in all cell types , it seems likely that EBNA3C either depends on a corepressor which may interact with amino acids 346 to 543 or is modified in a cell-specific manner in order to repress .", "target_text": { "EBNA3C": "protein", "corepressor": "protein", "amino acids 346 to 543": "protein" } }, { "input_text": "These data are consistent with EBNA3C contributing to the regulation of EBNA expression in latently infected B cells through CBF1/RBP-Jkappa and another factor , but this need not directly involve EBNA2 .", "target_text": { "EBNA3C": "protein", "EBNA": "protein", "B cells": "cell_type", "latently infected B cells": "cell_type", "CBF1/RBP-Jkappa": "protein", "EBNA2": "protein" } }, { "input_text": "Finally , although it has been reported that EBNA3C can upregulate CD21 in some B cells , we were unable to demonstrate any effect of EBNA3C on reporter plasmids which contain the CD21 promoter .", "target_text": { "EBNA3C": "protein", "CD21": "protein", "B cells": "cell_type", "reporter plasmids": "DNA", "CD21 promoter": "DNA" } }, { "input_text": "Relationship between glucocorticoid receptor and response to glucocorticoid therapy in ulcerative colitis .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "PURPOSE : To clarify the relationship between the glucocorticoid receptor and the effectiveness of glucocorticoid therapy in patients with ulcerative colitis , we investigated the number and apparent dissociation constant of glucocorticoid receptor in peripheral blood mononuclear leukocytes of patients with ulcerative colitis .", "target_text": { "glucocorticoid receptor": "protein", "peripheral blood mononuclear leukocytes": "cell_type" } }, { "input_text": "MATERIALS AND METHODS : Eleven patients with ulcerative colitis ( 5 who responded to intravenous glucocorticoids and 6 who did not ) and ten control subjects were studied .", "target_text": {} }, { "input_text": "The number and apparent dissociation constant of glucocorticoid receptor were measured using a whole-cell binding assay .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Results were expressed as a median ( interquartile range ) .", "target_text": {} }, { "input_text": "RESULTS : The number of glucocorticoid receptors from the six nonresponders , five responders , and ten healthy controls were 4922 ( range , 4484-5643 ) , 3413 ( range , 3183-4450 ) , and 3610 ( range , 2594-3979 ) binding sites/cell , respectively .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "The apparent dissociation constant of the glucocorticoid receptors from the nonresponders , responders , and healthy controls were 7.03 ( range , 5.66-10 ) , 4.27 ( range , 4-5.13 ) , and 6.18 ( range , 5.86-6.74 ) nM , respectively .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "Nonresponders had a significant increase both in the number of binding sites and in the apparent dissociation constant compared with responders ( P = 0.045 ; P = 0.029 ) .", "target_text": { "binding sites": "protein" } }, { "input_text": "CONCLUSIONS : The increased number and apparent dissociation constant of glucocorticoid receptor are closely associated with the effectiveness of glucocorticoid therapy .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "The measurement of the number and apparent dissociation constant of glucocorticoid receptor may be useful in predicting response to glucocorticoids .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Cooperation of binding sites for STAT6 and NF kappa B/rel in the IL-4 -induced up-regulation of the human IgE germline promoter .", "target_text": { "binding sites": "protein", "STAT6": "protein", "NF kappa B/rel": "protein", "IL-4": "protein", "human IgE germline promoter": "DNA" } }, { "input_text": "Ig heavy chain class switching is directed by cytokines inducing transcription from unrearranged CH genes .", "target_text": { "Ig heavy chain": "protein", "cytokines": "protein", "CH genes": "DNA" } }, { "input_text": "Subsequently , such primed cells can undergo switch recombination to express the selected new isotype .", "target_text": { "primed cells": "cell_type" } }, { "input_text": "In the case of IgE class switching , IL-4 activates the IgE germline promoter by inducing the interaction of the transcription factor STAT6 ( IL-4STAT ) with a responsive DNA element in the proximal region of the promoter .", "target_text": { "IgE": "protein", "IL-4": "protein", "IgE germline promoter": "DNA", "transcription factor": "protein", "STAT6": "protein", "IL-4STAT": "protein", "responsive DNA element": "DNA", "proximal region": "DNA", "promoter": "DNA" } }, { "input_text": "This study describes the characterization of two additional cis-acting elements that interact with members of the NF kappa B/rel transcription factor family in an IL-4 -independent fashion .", "target_text": { "cis-acting elements": "DNA", "NF kappa B/rel": "protein", "NF kappa B/rel transcription factor family": "protein", "IL-4": "protein" } }, { "input_text": "Electrophoretic mobility shift assays show that the nucleoprotein complex formed on the upstream site ( NF kappa B1 ) contains the classical p50/p65 heterodimer .", "target_text": { "nucleoprotein complex": "protein", "upstream site": "DNA", "NF kappa B1": "protein", "classical p50/p65 heterodimer": "protein" } }, { "input_text": "The complex on the proximal site ( NF kappa B2 ) appears to be composed of p50 and relB .", "target_text": { "proximal site": "DNA", "NF kappa B2": "protein", "p50": "protein", "relB": "protein" } }, { "input_text": "IgE germline promoter reporter gene constructs carrying point mutations in the NF kappa B2 site were largely unresponsive to IL-4 stimulation in transient transfection experiments , while plasmids with similar mutations in the NF kappa B1 site responded to cytokine stimulation better than the wild-type promoter .", "target_text": { "IgE": "protein", "IgE germline promoter": "DNA", "IgE germline promoter reporter gene constructs": "DNA", "NF kappa B2": "protein", "IL-4": "protein", "NF kappa B1": "protein", "cytokine": "protein", "wild-type promoter": "DNA" } }, { "input_text": "The NF kappa B2 effect was dependent on the presence of the STAT6 binding site , demonstrating that the NF kappa B2 motif is necessary but not sufficient for mediating cytokine up-regulation .", "target_text": { "NF kappa B2": "protein", "STAT6": "protein", "STAT6 binding site": "DNA", "NF kappa B2 motif": "protein", "cytokine": "protein" } }, { "input_text": "In addition , the combination of a NF kappa B/rel binding site and the STAT6 response element conferred IL-4 inducibility to a heterologous minimal promoter , while the individual sites had no effect .", "target_text": { "NF kappa B/rel": "protein", "NF kappa B/rel binding site": "DNA", "STAT6": "protein", "STAT6 response element": "DNA", "IL-4": "protein", "heterologous minimal promoter": "DNA" } }, { "input_text": "The available data suggest that the NF kappa B2 nucleoprotein complex may cooperate with DNA-bound STAT6 to achieve IL-4 -dependent activation of the human IgE germline gene .", "target_text": { "NF kappa B2": "protein", "nucleoprotein complex": "protein", "NF kappa B2 nucleoprotein complex": "protein", "STAT6": "protein", "DNA-bound STAT6": "protein", "IL-4": "protein", "IgE": "protein", "human IgE germline gene": "DNA" } }, { "input_text": "Alcohol-induced regulation of nuclear regulatory factor-kappa beta in human monocytes .", "target_text": { "nuclear regulatory factor-kappa beta": "protein", "human monocytes": "cell_type" } }, { "input_text": "Acute ethanol exposure has the capacity to modulate immune functions , particularly , to down regulate monocyte production of inflammatory cytokines .", "target_text": { "cytokines": "protein", "inflammatory cytokines": "protein" } }, { "input_text": "However , the intracellular mechanisms for these effects of ethanol are yet to be understood .", "target_text": {} }, { "input_text": "Considering that nuclear regulatory factor-kappa beta ( NF-kappa B ) /Rel is a common regulatory element of the promoter region of the inflammatory cytokine genes , herein , we tested the hypothesis that acute ethanol affects NF-kappa B activation in human monocytes .", "target_text": { "nuclear regulatory factor-kappa beta": "protein", "( NF-kappa B ) /Rel": "protein", "regulatory element": "protein", "promoter region": "DNA", "inflammatory cytokine genes": "DNA", "NF-kappa B": "protein", "human monocytes": "cell_type" } }, { "input_text": "Adherence-isolated monocytes showed constitutive DNA binding activity of NF-kappa B .", "target_text": { "Adherence-isolated monocytes": "cell_line", "NF-kappa B": "protein" } }, { "input_text": "A clinically relevant dose ( 25 mM ) of acute ethanol treatment in vitro increased NF-kappa B binding activity in monocytes with a preferential induction of the inhibitory , p50 /p50 , NF-kappa B /Rel homodimer , and resulted in no induction of the p65 /p50 heterodimer .", "target_text": { "NF-kappa B": "protein", "monocytes": "cell_type", "p50": "protein", "/p50": "protein", "p50 /p50": "protein", "NF-kappa B /Rel homodimer": "protein", "p65": "protein", "p65 /p50 heterodimer": "protein" } }, { "input_text": "In contrast , lipopolysaccharide stimulation primarily induced the p65 /p50 heterodimer that has been shown to result in gene activation .", "target_text": { "p65": "protein", "/p50": "protein", "p65 /p50 heterodimer": "protein" } }, { "input_text": "Thus , such unique activation of the inhibitory p50 /p50 homodimer by acute ethanol treatment may result in inhibition rather than activation of NF-kappa B -regulated inflammatory cytokine genes .", "target_text": { "p50": "protein", "/p50": "protein", "inhibitory p50 /p50 homodimer": "protein", "NF-kappa B": "protein", "inflammatory cytokine genes": "DNA", "NF-kappa B -regulated inflammatory cytokine genes": "DNA" } }, { "input_text": "Consequently , these results suggest that physiologically relevant concentrations of ethanol may affect production of inflammatory cytokines , such as tumor necrosis factor-alpha , interleukin-1 beta , and interleukin-6 by disrupting NF-kappa B signaling in monocytes .", "target_text": { "cytokines": "protein", "inflammatory cytokines": "protein", "tumor necrosis factor-alpha": "protein", "interleukin-1 beta": "protein", "interleukin-6": "protein", "NF-kappa B": "protein", "monocytes": "cell_type" } }, { "input_text": "LPS tolerance in monocytes/macrophages : three 3' cytosins are required in the DNA binding motif for detection of upregulated NF-kappa B p50 homodimers .", "target_text": { "monocytes/macrophages": "cell_type", "DNA binding motif": "DNA", "NF-kappa B p50 homodimers": "protein" } }, { "input_text": "When monocytes are stimulated with LPS ( lipopolysaccharide ) repeatedly then the initially high expression of the TNF ( tumor necrosis factor ) gene is only very low , i.e. the cells are tolerant to LPS .", "target_text": { "monocytes": "cell_type", "TNF": "protein", "tumor necrosis factor": "protein", "TNF ( tumor necrosis factor ) gene": "DNA" } }, { "input_text": "Tolerant cells still express the CD14 receptor and they can still be activated to mobilize NF-kappa B into nucleus .", "target_text": { "CD14 receptor": "protein", "NF-kappa B": "protein" } }, { "input_text": "Analysis of the binding proteins employing the -605 motif of the human TNF promoter ( GGGGCTGTCCC ) revealed that in tolerant cells of the human monocytic cell line Mono Mac 6 there is a predominance of p50p50 of NF-kappa B .", "target_text": { "human TNF promoter": "DNA", "human monocytic cell line": "cell_line", "Mono Mac 6": "cell_line", "p50p50": "protein", "NF-kappa B": "protein" } }, { "input_text": "We now show that a mutant motif that exchanges the terminal 3' C for a G fails to bind the p50 homodimer that is upregulated in LPS toler ant human Mono Mac 6 cells .", "target_text": { "mutant motif": "DNA", "p50 homodimer": "protein", "human Mono Mac 6 cells": "cell_line" } }, { "input_text": "The same is true for nuclear extracts taken from the murine P388D1 macrophage cell line when tested with the -516 motif of the murine TNF promoter ( GGGGGCTTTCCC ) .", "target_text": { "murine P388D1 macrophage cell line": "cell_line", "-516 motif": "DNA", "murine TNF promoter": "DNA" } }, { "input_text": "Here the wild type motif gives efficient binding of p50p50 that again is upregulated in tolerant cells whereas a mutant with a 3' G shows hardly any binding of p50p50 .", "target_text": { "wild type motif": "DNA", "p50p50": "protein", "tolerant cells": "cell_type" } }, { "input_text": "Conversely , the murine kappa light chain enhancer motif ( GGGGACTTTCCG ) does not efficiently bind the nuclear p50p50 from tolerant murine P388 macrophages .", "target_text": { "murine kappa light chain enhancer motif": "DNA", "p50p50": "protein", "tolerant murine P388 macrophages": "cell_line" } }, { "input_text": "Binding is , however , readily detected when the 3' G is replaced by a C .", "target_text": {} }, { "input_text": "These data show that the detection of upregulated p50 homodimers in LPS tolerant cells is dependent on subtle differences in the sequence of the DNA binding motif .", "target_text": { "p50 homodimers": "protein", "tolerant cells": "cell_type", "DNA binding motif": "DNA" } }, { "input_text": "Cyclosporin A inhibits early mRNA expression of G0/G1 switch gene 2 ( G0S2 ) in cultured human blood mononuclear cells .", "target_text": { "G0/G1 switch gene 2": "DNA", "G0S2": "DNA", "cultured human blood mononuclear cells": "cell_line" } }, { "input_text": "Cyclosporin A ( CsA ) may achieve its immunosuppressive effects by inhibiting the calcium- and calmodulin-dependent phosphatase calcineurin which is required for activation of target genes by members of the NFAT ( nuclear factor of activated T cells ) transcription factor family .", "target_text": { "calcium- and calmodulin-dependent phosphatase": "protein", "calcineurin": "protein", "target genes": "DNA", "nuclear factor of activated T cells": "protein", "NFAT ( nuclear factor of activated T cells ) transcription factor family": "protein" } }, { "input_text": "Among these target genes is the gene encoding interleukin-2 ( IL2 ) , a cytokine facilitating progression through the G1 phase of the cell cycle .", "target_text": { "target genes": "DNA", "interleukin-2": "protein", "IL2": "protein", "cytokine": "protein" } }, { "input_text": "However , IL2 does not reverse CsA inhibition , suggesting that at least one other NFAT-sensitive gene may be involved .", "target_text": { "IL2": "protein", "NFAT-sensitive gene": "DNA" } }, { "input_text": "The human G0/G1 switch gene , G0S2 , has potential NFAT-binding sites in the 5' flank and encodes a small basic potential phosphoprotein of unknown function .", "target_text": { "human G0/G1 switch gene": "DNA", "G0S2": "DNA", "NFAT-binding sites": "DNA", "5' flank": "DNA", "small basic potential phosphoprotein": "protein" } }, { "input_text": "Using a sensitive , reverse transcription-polymerase chain reaction ( RT-PCR ) assay , G0S2 mRNA levels were assayed in cultured blood mononuclear cells .", "target_text": { "G0S2": "DNA", "cultured blood mononuclear cells": "cell_line" } }, { "input_text": "Freshly isolated cells contain high levels of G0S2 mRNA which rapidly decline .", "target_text": { "G0S2": "DNA", "G0S2 mRNA": "RNA" } }, { "input_text": "This \" spontaneous stimulation \" is also noted with some other G0S genes and has been attributed to some aspect of the isolation procedure .", "target_text": { "G0S genes": "DNA" } }, { "input_text": "In cells that have been preincubated to lower mRNA levels , there is a transient increase in G0S2 mRNA , peaking between 1-2 h , in response to Concanavalin-A ( ConA ) , or to the combination of phorbol ester ( TPA ) , and the calcium ionophore , ionomycin .", "target_text": { "G0S2": "DNA", "G0S2 mRNA": "RNA" } }, { "input_text": "Both these responses are inhibited by CsA .", "target_text": {} }, { "input_text": "Our results suggest that G0S2 expression is required to commit cells to enter the G1 phase of the cell cycle , and that , while not excluding other possible targets , early inhibition of G0S2 expression by CsA may be important in achieving immunosuppression .", "target_text": { "G0S2": "DNA" } }, { "input_text": "G0S2 may be of value as a reporter gene for analyzing the mechanism of action of CsA and its influence on the positive and negative selection of lymphocytes in response to self and not-self antigens .", "target_text": { "G0S2": "DNA", "lymphocytes": "cell_type" } }, { "input_text": "c-Rel and p65 subunits bind to an upstream NF-kappaB site in human granulocyte macrophage-colony stimulating factor promoter involved in phorbol ester response in 5637 cells .", "target_text": { "upstream NF-kappaB site": "DNA", "human granulocyte macrophage-colony stimulating factor": "protein", "human granulocyte macrophage-colony stimulating factor promoter": "DNA", "5637 cells": "cell_line" } }, { "input_text": "To further clarify the complex transcriptional regulation of the human GM-CSF gene , which was extensively investigated in activated T cells , we have studied the role of an upstream NF-kappaB like site in the 5637 non-lymphoid cell line , which derives from a bladder carcinoma and constitutively produces GM-CSF .", "target_text": { "human GM-CSF gene": "DNA", "activated T cells": "cell_type", "NF-kappaB": "protein", "NF-kappaB like site": "DNA", "5637 non-lymphoid cell line": "cell_line", "GM-CSF": "protein" } }, { "input_text": "This sequence , named the A element , has an active role on GM-CSF transcription and is responsive to the tumor promoter PMA in transient transfection experiments .", "target_text": { "GM-CSF": "protein", "tumor promoter PMA": "DNA" } }, { "input_text": "We describe here a heterodimeric binding complex of NF-kappaB subunits ( c-Rel and p65 ) which is identical to the one obtained using the HIV-LTR-kappaB site as recognition sequence and different from the one ( c-Rel and p50 ) observed with nuclear extracts from Mo T-lymphoid HTLV-II infected cells .", "target_text": { "heterodimeric binding complex": "protein", "NF-kappaB": "protein", "NF-kappaB subunits": "protein", "c-Rel": "protein", "p65": "protein", "HIV-LTR-kappaB site": "DNA", "p50": "protein", "Mo T-lymphoid HTLV-II infected cells": "cell_line" } }, { "input_text": "Repression of human immunodeficiency virus type 1 through the novel cooperation of human factors YY1 and LSF [ published erratum appears in J Virol 1998 Feb ; 72 ( 2 ) : 1709 ]", "target_text": { "human factors": "protein", "YY1": "protein", "LSF": "protein" } }, { "input_text": "A subpopulation of stably infected CD4+ cells capable of producing virus upon stimulation has been identified in human immunodeficiency virus ( HIV ) -positive individuals ( T.-W.Chun , D.Finzi , J.Margolick , K.Chadwick , D.Schwartz , and R.F.Siliciano , Nat.Med.1 : 1284-1290 , 1995 ) .", "target_text": { "stably infected CD4+ cells": "cell_type" } }, { "input_text": "Few host factors that directly limit HIV-1 transcription and could support this state of nonproductive HIV-1 infection have been described .", "target_text": {} }, { "input_text": "YY1 , a widely distributed human transcription factor , is known to inhibit HIV-1 long terminal repeat ( LTR ) transcription and virus production .", "target_text": { "YY1": "protein", "human transcription factor": "protein", "HIV-1 long terminal repeat": "DNA", "LTR": "DNA" } }, { "input_text": "LSF ( also known as LBP-1 , UBP , and CP-2 ) has been shown to repress LTR transcription in vitro , but transient expression of LSF has no effect on LTR activity in vivo .", "target_text": { "LSF": "protein", "LBP-1": "protein", "UBP": "protein", "CP-2": "protein", "LTR": "DNA" } }, { "input_text": "We report that both YY1 and LSF participate in the formation of a complex that recognizes the initiation region of the HIV-1 LTR .", "target_text": { "YY1": "protein", "LSF": "protein", "HIV-1 LTR": "DNA" } }, { "input_text": "Further , we have found that these factors cooperate in the repression of LTR expression and viral replication .", "target_text": { "LTR": "DNA" } }, { "input_text": "This cooperative function may account for the divergent effects of LSF previously observed in vitro and in vivo .", "target_text": { "LSF": "protein" } }, { "input_text": "Thus , the cooperation of two general cellular transcription factors may allow for the selective downregulation of HIV transcription .", "target_text": {} }, { "input_text": "Through this mechanism of gene regulation , YY1 and LSF could contribute to the establishment and maintenance of a population of cells stably but nonproductively infected with HIV-1 .", "target_text": { "YY1": "protein", "LSF": "protein" } }, { "input_text": "Analysis of interactions between huGATA-3 transcription factor and three GATA regulatory elements of HIV-1 long terminal repeat , by surface plasmon resonance .", "target_text": { "huGATA-3": "protein", "GATA regulatory elements": "DNA", "HIV-1 long terminal repeat": "DNA" } }, { "input_text": "Relative affinities of transcriptional regulatory elements for their respective factor have been essentially studied by bandshift analysis .", "target_text": { "transcriptional regulatory elements": "DNA" } }, { "input_text": "Here we report a real-time study of factor/DNA interactions using a surface plasmon resonance approach and further characterization of recovered proteins involved in this interaction .", "target_text": { "recovered proteins": "protein" } }, { "input_text": "For this purpose , human GATA-3 , either recombinant or in nuclear extracts , and three natural GATA elements of the HIV-1 long terminal repeat ( sites 1 , 2 , and 3 ) were chosen , in which only site 2 is a noncanonical GATA site .", "target_text": { "human GATA-3": "protein", "natural GATA elements": "DNA", "HIV-1 long terminal repeat": "DNA", "site 2": "DNA", "GATA site": "DNA" } }, { "input_text": "Direct analysis of sensorgrams , with recombinant huGATA-3 , allowed the comparison of association and dissociation profiles of the three DNA regions and their ranking according to their relative affinities .", "target_text": { "huGATA-3": "protein", "recombinant huGATA-3": "protein", "DNA regions": "DNA" } }, { "input_text": "This result , confirmed by competitions with each GATA site , demonstrated the higher relative affinity ( at least sevenfold ) of site 3 .", "target_text": { "GATA site": "DNA" } }, { "input_text": "Interactions between the canonical and unique GATA site 3 and nuclear extracts were also studied in real time and provided information on its association and dissociation rates for native huGATA-3 .", "target_text": { "GATA site": "DNA", "GATA site 3": "DNA", "huGATA-3": "protein" } }, { "input_text": "Finally , recovered protein was identified as genuine huGATA-3 by SDS-PAGE , Western blotting , and bandshift assays .", "target_text": { "huGATA-3": "protein" } }, { "input_text": "Copyright 1997 Academic Press .", "target_text": {} }, { "input_text": "Stable transfection of U937 cells with sense or antisense RXR-alpha cDNA suggests a role for RXR-alpha in the control of monoblastic differentiation induced by retinoic acid and vitamin D .", "target_text": { "U937 cells": "cell_line", "antisense RXR-alpha cDNA": "DNA", "RXR-alpha": "protein" } }, { "input_text": "Although retinoic acid ( RA ) has been known for many years to be a modulating agent that plays a role in generating both granulocytes and monocytes , the molecular mechanism underlying this role has not been defined in the monoblast lineage .", "target_text": { "granulocytes": "cell_type", "monocytes": "cell_type", "monoblast lineage": "cell_type" } }, { "input_text": "In particular , the part played by the retinoid X receptors ( RXRs ) , which are members of the steroid/thyroid hormone nuclear receptor family , has not been explored .", "target_text": { "retinoid X receptors": "protein", "RXRs": "protein", "steroid/thyroid hormone nuclear receptor family": "protein" } }, { "input_text": "In this study , therefore , the human monoblastic leukemia cell line U937 has been used as a model system to investigate the role of one of the RXRs , RXR-alpha , in monoblast differentiation .", "target_text": { "human monoblastic leukemia cell line U937": "cell_line", "RXRs": "protein", "RXR-alpha": "protein" } }, { "input_text": "RXR-alpha mRNA was present in untreated U937 cells , and levels increased after induction of differentiation with phorbol ester .", "target_text": { "RXR-alpha": "protein", "RXR-alpha mRNA": "RNA", "U937 cells": "cell_line" } }, { "input_text": "The same was found for RXR-beta mRNA .", "target_text": { "RXR-beta": "protein", "RXR-beta mRNA": "RNA" } }, { "input_text": "Using plasmids containing sense or antisense RXR-alpha sequences under the control of an inducible promoter , we generated stably transfected cell lines which expressed either increased or decreased levels of RXR-alpha , respectively .", "target_text": { "RXR-alpha": "protein", "antisense RXR-alpha sequences": "DNA" } }, { "input_text": "The sense cell lines ( U alpha S and its clonal derivative alpha G2S ) showed increased sensitivity to RA , while the antisense cell lines ( U alpha A and its clonal derivative alpha B5A ) showed decreased sensitivity to RA , as demonstrated by growth inhibition and by regulation of an RA -responsive reporter gene .", "target_text": { "sense cell lines": "cell_line", "U alpha S": "cell_line", "G2S": "cell_line", "antisense cell lines": "cell_line", "U alpha A": "cell_line", "B5A": "cell_line", "RA -responsive reporter gene": "DNA" } }, { "input_text": "Both U alpha A and alpha B5A also failed to respond to another modulating agent , 1 alpha,25-dihydroxycholecalciferol ( DHCC ) , but only U alpha S and not alpha G2S showed an enhanced response to DHCC .", "target_text": { "U alpha A": "cell_line", "B5A": "cell_line", "U alpha S": "cell_line", "G2S": "cell_line", "alpha G2S": "protein" } }, { "input_text": "The combination of RA and DHCC together inhibited growth of both sense and antisense cell lines .", "target_text": { "antisense cell lines": "cell_line" } }, { "input_text": "In addition , alpha G2S exhibited increased expression of CD11b and CD54 , while alpha B5A cells showed increased expression of CD102 , suggesting that RXR-alpha has a role in regulating expression of cell adhesion molecules in U937 cells .", "target_text": { "G2S": "cell_line", "alpha G2S": "protein", "CD11b": "protein", "CD54": "protein", "B5A": "cell_line", "alpha B5A cells": "cell_line", "CD102": "protein", "RXR-alpha": "protein", "cell adhesion molecules": "protein", "U937 cells": "cell_line" } }, { "input_text": "These results demonstrate that RXR-alpha has a role in mediating growth inhibition and cell adhesion during myelomonocytic differentiation , and suggest that different species of heterodimers involving RXR-alpha may control the acquisition of different features of mature monocyte/macrophage function .", "target_text": { "RXR-alpha": "protein", "heterodimers": "protein" } }, { "input_text": "Transcriptional activation of the vascular cell adhesion molecule-1 gene in T lymphocytes expressing human T-cell leukemia virus type 1 Tax protein .", "target_text": { "vascular cell adhesion molecule-1 gene": "DNA", "T lymphocytes": "cell_type", "human T-cell leukemia virus type 1 Tax protein": "protein" } }, { "input_text": "Recruitment and extravasation of T cells through the blood-brain barrier are favored by adhesion molecule -mediated interactions of circulating T cells with endothelial cells .", "target_text": { "T cells": "cell_type", "adhesion molecule": "protein", "circulating T cells": "cell_type", "endothelial cells": "cell_type" } }, { "input_text": "Since a common pathological finding in human T-cell leukemia virus type 1 ( HTLV-1 ) -associated diseases is the infiltration of HTLV-1-infected T lymphocytes into various organs , we have looked for the profile of adhesion molecules expressed by HTLV-1-transformed T cells .", "target_text": { "T lymphocytes": "cell_type", "HTLV-1-infected T lymphocytes": "cell_type", "adhesion molecules": "protein", "HTLV-1-transformed T cells": "cell_type" } }, { "input_text": "Flow cytometry analysis indicated that these cells were expressing high levels of vascular cell adhesion molecule 1 ( VCAM-1 [ CD106 ] ) , a 110-kDa member of the immunoglobulin gene superfamily , first identified on endothelial cells stimulated with inflammatory cytokines .", "target_text": { "vascular cell adhesion molecule 1": "protein", "VCAM-1": "protein", "CD106": "protein", "immunoglobulin gene superfamily": "protein", "endothelial cells": "cell_type", "inflammatory cytokines": "protein" } }, { "input_text": "This adhesion molecule was also expressed by T cells obtained from one patient with HTLV-1 -associated myelopathy/tropical spastic paraparesis but not by activated T cells isolated from one normal blood donor .", "target_text": { "T cells": "cell_type", "activated T cells": "cell_type" } }, { "input_text": "The role of the viral trans-activator Tax protein in the induction of VCAM-1 was first indicated by the detection of this adhesion molecule on Jurkat T-cell clones stably expressing the tax gene .", "target_text": { "viral trans-activator Tax protein": "protein", "VCAM-1": "protein", "adhesion molecule": "protein", "Jurkat T-cell clones": "cell_line" } }, { "input_text": "The effect of Tax on VCAM-1 gene transcription was next confirmed in JPX-9 cells , a subclone of Jurkat cells , carrying the tax sequences under the control of an inducible promoter .", "target_text": { "Tax": "protein", "VCAM-1": "protein", "JPX-9 cells": "cell_line", "Jurkat cells": "cell_line", "tax sequences": "DNA", "inducible promoter": "DNA" } }, { "input_text": "Furthermore , deletion and mutation analyses of the VCAM-1 promoter performed with chloramphenicol acetyltransferase constructs revealed that Tax was trans activating the VCAM-1 promoter via two NF-kappaB sites present at bp -72 and -57 in the VCAM-1 gene promoter , with both of them being required for the Tax -induced expression of this adhesion molecule .", "target_text": { "VCAM-1": "protein", "VCAM-1 promoter": "DNA", "chloramphenicol acetyltransferase constructs": "DNA", "Tax": "protein", "NF-kappaB": "protein", "NF-kappaB sites": "DNA", "VCAM-1 gene promoter": "DNA", "adhesion molecule": "protein" } }, { "input_text": "Finally , gel mobility shift assays demonstrated the nuclear translocation of proteins specifically bound to these two NF-kappaB motifs , confirming that VCAM-1 was induced on Tax -expressing cells in a kappaB -dependent manner .", "target_text": { "NF-kappaB": "protein", "NF-kappaB motifs": "DNA", "VCAM-1": "protein", "Tax": "protein", "Tax -expressing cells": "cell_line", "kappaB": "protein" } }, { "input_text": "Collectively , these results therefore suggest that the exclusive Tax -induced expression of VCAM-1 on T cells may represent a pivotal event in the progression of HTLV-1 -associated diseases .", "target_text": { "Tax": "protein", "VCAM-1": "protein", "T cells": "cell_type" } }, { "input_text": "HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B [ see comments ]", "target_text": { "HIV-1 Vpr": "protein", "nuclear factor kappa B": "protein" } }, { "input_text": "The HIV-1 accessory gene product Vpr can influence viral pathogenesis by affecting viral replication as well as host cell transcription and proliferation .", "target_text": { "HIV-1 accessory gene product": "protein", "Vpr": "protein" } }, { "input_text": "We have investigated the effects of Vpr on host cell activation and confirm that it influences cellular proliferation .", "target_text": { "Vpr": "protein" } }, { "input_text": "However , we have also found that Vpr modulates T-cell receptor ( TCR ) -triggered apoptosis in a manner similar to that of glucocorticoids .", "target_text": { "Vpr": "protein", "TCR": "protein" } }, { "input_text": "In the absence of TCR -mediated activation , Vpr induces apoptosis whereas in its presence , Vpr interrupts the expected induction of apoptosis .", "target_text": { "TCR": "protein", "Vpr": "protein" } }, { "input_text": "This regulation of apoptosis is linked to Vpr suppression of NF-kappa B activity via the induction of I kappa B , an inhibitor of NF-kappa B .", "target_text": { "Vpr": "protein", "NF-kappa B": "protein", "I kappa B": "protein" } }, { "input_text": "Further , Vpr suppresses expression of IL-2 , IL-10 , IL-12 , TNF alpha and IL-4 , all of which are NF-kappa B -dependent .", "target_text": { "Vpr": "protein", "IL-2": "protein", "IL-10": "protein", "IL-12": "protein", "TNF alpha": "protein", "IL-4": "protein", "NF-kappa B": "protein" } }, { "input_text": "The effects of Vpr could be reversed by RU486 .", "target_text": { "Vpr": "protein" } }, { "input_text": "Our finding that Vpr can regulate NF-kappa B supports the hypothesis that some aspects of viral pathogenesis are the consequence of cell dysregulation by Vpr .", "target_text": { "Vpr": "protein", "NF-kappa B": "protein" } }, { "input_text": "Tissue transglutaminase-dependent posttranslational modification of the retinoblastoma gene product in promonocytic cells undergoing apoptosis .", "target_text": { "retinoblastoma gene product": "protein", "promonocytic cells": "cell_line" } }, { "input_text": "The retinoblastoma gene product ( pRB ) plays an important role in controlling both cell release from the G1 phase and apoptosis .", "target_text": { "retinoblastoma gene product": "protein", "pRB": "protein" } }, { "input_text": "We show here that in the early phases of apoptosis , pRB is posttranslationally modified by a tissue transglutaminase ( tTG ) -catalyzed reaction .", "target_text": { "pRB": "protein", "tTG": "protein" } }, { "input_text": "In fact , by employing a novel haptenized lysis synthetic substrate which allows the isolation of glutaminyl-tTG substrates in vivo , we identified pRB as a potential tTG substrate in U937 cells undergoing apoptosis .", "target_text": { "pRB": "protein", "U937 cells": "cell_line" } }, { "input_text": "In keeping with this finding , we showed that apoptosis of U937 cells is characterized by the rapid disappearance of the 105,000- to 110,000-molecular-weight pRB forms concomitantly with the appearance of a smear of immunoreactive products with a molecular weight of greater than 250,000 .", "target_text": { "U937 cells": "cell_line", "pRB": "protein" } }, { "input_text": "The shift in pRB molecular weight was reproduced by adding exogenous purified tTG to extracts obtained from viable U937 cells and was prevented by dansylcadaverine , a potent enzyme inhibitor .", "target_text": { "pRB": "protein", "U937 cells": "cell_line" } }, { "input_text": "The effect of the pRB posttranslational modification during apoptosis was investigated by determining the E2F-1 levels and by isolating and characterizing pRB -null clones from U937 cells .", "target_text": { "pRB": "protein", "E2F-1": "protein", "pRB -null clones": "cell_line", "U937 cells": "cell_line" } }, { "input_text": "Notably , the lack of pRB in these U937-derived clones renders these p53-null cells highly resistant to apoptosis induced by serum withdrawal , calphostin C , and ceramide .", "target_text": { "pRB": "protein", "U937-derived clones": "cell_line", "p53-null cells": "cell_line" } }, { "input_text": "Taken together , these data suggest that tTG , acting on the pRB protein , might play an important role in the cell progression through the death program .", "target_text": { "tTG": "protein", "pRB": "protein", "pRB protein": "protein" } }, { "input_text": "STAT3 is a serine kinase target in T lymphocytes .", "target_text": { "STAT3": "protein", "serine kinase target": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Interleukin 2 and T cell antigen receptor signals converge upon serine 727 .", "target_text": { "Interleukin 2": "protein", "T cell antigen receptor": "protein" } }, { "input_text": "Interleukin 2 ( IL-2 ) induces tyrosine phosphorylation of STATs 3 and 5 ( signal transducer and activator of transcription ) .", "target_text": { "Interleukin 2": "protein", "IL-2": "protein" } }, { "input_text": "We now show that IL-2 regulation of STAT3 proteins in T cells is a complex response involving activation of two forms of STAT3 : 90-kDa STAT3alpha and an 83-kDa carboxyl-terminal truncated STAT3beta .", "target_text": { "IL-2": "protein", "STAT3": "protein", "STAT3 proteins": "protein", "T cells": "cell_type", "STAT3alpha": "protein", "STAT3beta": "protein", "83-kDa carboxyl-terminal truncated STAT3beta": "protein" } }, { "input_text": "The phosphorylation of STAT proteins on serine residues is also required for competent STAT transcription .", "target_text": { "STAT proteins": "protein", "STAT": "protein" } }, { "input_text": "A critical serine phosphorylation site in STAT3alpha is at position 727 .", "target_text": { "serine phosphorylation site": "protein", "STAT3alpha": "protein" } }, { "input_text": "In this study we have produced an antisera specific for STAT3alpha proteins phosphorylated on serine 727 and used this to monitor the phosphorylation of this residue during T lymphocyte activation .", "target_text": { "STAT3alpha proteins": "protein" } }, { "input_text": "Our results show that phosphorylation of STAT3alpha on serine 727 is not constitutive in quiescent T cells but can be induced by the cytokine IL-2 .", "target_text": { "STAT3alpha": "protein", "quiescent T cells": "cell_type", "IL-2": "protein", "cytokine IL-2": "protein" } }, { "input_text": "Interestingly , triggering of the T cell antigen receptor complex or activation of protein kinase C with phorbol esters also induces phosphorylation of serine 727 but without simultaneously inducing STAT3 tyrosine phosphorylation or DNA binding .", "target_text": { "T cell antigen receptor complex": "protein", "protein kinase C": "protein", "STAT3": "protein" } }, { "input_text": "Hence , the present results show that STAT3 serine phosphorylation can be regulated independently of the tyrosine phosphorylation of this molecule .", "target_text": { "STAT3": "protein" } }, { "input_text": "IL-2 and T cell antigen receptor complex induction of STAT3alpha serine 727 phosphorylation is dependent on the activity of the MEK /ERK pathway .", "target_text": { "IL-2": "protein", "T cell antigen receptor complex": "protein", "STAT3alpha": "protein", "MEK": "protein", "/ERK": "protein" } }, { "input_text": "Previous studies have identified H-7-sensitive kinase pathways that regulate STAT3 DNA binding .", "target_text": { "STAT3": "protein" } }, { "input_text": "We show that H-7-sensitive pathways regulate STAT3 DNA binding in T cells .", "target_text": { "STAT3": "protein", "T cells": "cell_type" } }, { "input_text": "Nevertheless , we show that H-7-sensitive kinases do not regulate STAT3 tyrosine phosphorylation or phosphorylation of serine 727 .", "target_text": { "H-7-sensitive kinases": "protein", "STAT3": "protein" } }, { "input_text": "These results thus show that STAT3 proteins are targets for multiple kinase pathways in T cells and can integrate signals from both cytokine receptors and antigen receptors .", "target_text": { "STAT3": "protein", "STAT3 proteins": "protein", "T cells": "cell_type", "cytokine receptors": "protein", "antigen receptors": "protein" } }, { "input_text": "NF-kappa B/Rel family members regulating the ICAM-1 promoter in monocytic THP-1 cells .", "target_text": { "NF-kappa B/Rel family members": "protein", "ICAM-1 promoter": "DNA", "monocytic THP-1 cells": "cell_line" } }, { "input_text": "A kappa B-site was identified in the promoter of the intercellular adhesion molecule-1 ( ICAM-1 ) gene , which is involved in regulation of ICAM-1 expression by tumor necrosis factor alpha ( TNF-alpha ) and glucocorticoids .", "target_text": { "kappa B-site": "DNA", "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "intercellular adhesion molecule-1 ( ICAM-1 ) gene": "DNA", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "We now report on the transcription factors which bind and transactivate this enhancer sequence .", "target_text": { "transcription factors": "protein", "enhancer sequence": "DNA" } }, { "input_text": "In vitro , the ICAM-1 kappa B site appeared to bind RelA and c-Rel homodimers as well as heterodimers with NF-kappa B1 , but weakly NF-kappa B1 homodimers .", "target_text": { "ICAM-1 kappa B site": "DNA", "RelA": "protein", "c-Rel homodimers": "protein", "NF-kappa B1": "protein", "NF-kappa B1 homodimers": "protein" } }, { "input_text": "In addition , both RelA and c-Rel , but not NF-kappa B1 , were shown to transactivate an ICAM-1 kappa B-reporter construct .", "target_text": { "RelA": "protein", "c-Rel": "protein", "NF-kappa B1": "protein", "ICAM-1": "protein", "ICAM-1 kappa B-reporter construct": "DNA" } }, { "input_text": "In monocytic THP-1 cells TNF-alpha induced two nuclear complexes which in vitro bound to the ICAM-1 kappa B site .", "target_text": { "monocytic THP-1 cells": "cell_line", "TNF-alpha": "protein", "nuclear complexes": "protein", "ICAM-1 kappa B site": "DNA" } }, { "input_text": "Using antibodies in an electrophoretic mobility supershift assay , one of these complexes was shown to contain NF-kappa B1 and RelA , and to bind with higher affinity to the consensus kappa B site in the HIV long terminal repeat .", "target_text": { "NF-kappa B1": "protein", "RelA": "protein", "consensus kappa B site": "DNA", "HIV long terminal repeat": "DNA" } }, { "input_text": "The second complex contained RelA , and exhibited higher affinity towards the ICAM-1 kappa B than to the HIV kappa B site .", "target_text": { "RelA": "protein", "ICAM-1 kappa B": "DNA", "HIV kappa B site": "DNA" } }, { "input_text": "The glucocorticoid receptor was shown to repress activity of both the RelA homodimer and the NF-kappa B1 /RelA heterodimer .", "target_text": { "glucocorticoid receptor": "protein", "RelA": "protein", "RelA homodimer": "protein", "NF-kappa B1": "protein", "/RelA": "protein", "NF-kappa B1 /RelA heterodimer": "protein" } }, { "input_text": "We argue that in vivo RelA homodimers are likely to play a dominant role in TNF-alpha -induced ICAM-1 transcription in monocytic cells .", "target_text": { "RelA": "protein", "RelA homodimers": "protein", "TNF-alpha": "protein", "ICAM-1": "protein", "monocytic cells": "cell_type" } }, { "input_text": "Competent transcription initiation by RNA polymerase II in cell-free extracts from xeroderma pigmentosum groups B and D in an optimized RNA transcription assay .", "target_text": { "RNA polymerase II": "protein", "cell-free extracts": "cell_type" } }, { "input_text": "The human autosomal recessive disease , xeroderma pigmentosum ( XP ) , can result from mutations in any one of seven genes , designated XPA through XPG .", "target_text": { "XPA": "DNA", "XPG": "DNA" } }, { "input_text": "Of these , the XPB and XPD genes encode proteins that are subunits of a general transcription factor , TFIIH , involved in both nucleotide excision repair ( NER ) and initiation of mRNA transcription by RNA polymerase II .", "target_text": { "general transcription factor": "protein", "TFIIH": "protein", "RNA polymerase II": "protein" } }, { "input_text": "In humans , mutation of the XPB or XPD gene impairs NER , resulting in hyper-sensitivity to sunlight and greatly increased skin tumor formation .", "target_text": {} }, { "input_text": "However , no transcription deficiency has been demonstrated in either XP-B or XP-D .", "target_text": {} }, { "input_text": "We have employed an optimized cell-free RNA transcription assay to analyze transcription activity of XP-B and XP-D .", "target_text": {} }, { "input_text": "Although the growth rate was normal , the XP-B and XP-D cells contained reduced amounts of TFIIH .", "target_text": { "TFIIH": "protein" } }, { "input_text": "Extracts prepared from XP-B and XP-D lymphoblastoid cells exhibited similar transcription activity from the adenovirus major late promoter when compared to that in extracts from normal cells .", "target_text": { "adenovirus major late promoter": "DNA" } }, { "input_text": "Thus , we conclude that the XP-B and XP-D lymphoblastoid cells do not have impaired RNA transcription activity .", "target_text": {} }, { "input_text": "We consider the possible consequences of the reduced cellular content of TFIIH for the clinical symptoms in XP-B or XP-D patients , and discuss a ' conditional phenotype ' that may involve an impairment of cellular function only under certain growth conditions .", "target_text": { "TFIIH": "protein" } }, { "input_text": "A novel form of the myeloid-specific zinc finger protein ( MZF-2 ) .", "target_text": { "myeloid-specific zinc finger protein": "protein", "MZF-2": "protein" } }, { "input_text": "BACKGROUND : Myeloid cell development is controlled by tissue-specific transcription factors .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Human myeloid zinc finger protein ( MZF-1 ) is a putative transcription factor containing 13 zinc fingers , and has been suggested that it regulates the development of neutrophilic granulocytes .", "target_text": { "Human myeloid zinc finger protein": "protein", "MZF-1": "protein", "13 zinc fingers": "protein", "neutrophilic granulocytes": "cell_type" } }, { "input_text": "RESULTS : Here , we have isolated the murine and human cDNAs which encode a novel form of MZF protein ( MZF-2 ) .", "target_text": { "MZF protein": "protein", "MZF-2": "protein" } }, { "input_text": "Murine and human MZF-2 proteins consisted of 814 and 775 amino acids , respectively , and have identity of 75.3 % between them .", "target_text": {} }, { "input_text": "The C-terminal half of human MZF-2 , carrying the zinc finger domains , was completely identical with that of human MZF-1 , whereas the N-terminal half of MZF-2 was different from the corresponding region of human MZF-1 , and was coded by distinct exons .", "target_text": { "C-terminal half": "protein", "human MZF-2": "protein", "zinc finger domains": "protein", "human MZF-1": "protein", "N-terminal half": "protein", "MZF-2": "protein", "MZF-1": "protein", "exons": "DNA" } }, { "input_text": "MZF-2 mRNA was expressed in myeloid cells , particularly in the cells committed to the neutrophilic lineage , and down-regulated by G-CSF .", "target_text": { "MZF-2": "protein", "MZF-2 mRNA": "RNA", "neutrophilic lineage": "cell_type", "G-CSF": "protein" } }, { "input_text": "CONCLUSIONS : MZF-1 and MZF-2 mRNAs seem to be produced by the alternative use of two different transcription initiation sites .", "target_text": { "transcription initiation sites": "DNA" } }, { "input_text": "The distinct N-terminal half of MZF-2 carries two characteristic domains , a leucine-rich domain called LeR and an acidic domain , which suggests a unique function of MZF-2 in neutrophil development .", "target_text": { "N-terminal half": "protein", "MZF-2": "protein", "leucine-rich domain": "protein", "LeR": "protein", "acidic domain": "protein" } }, { "input_text": "Impaired cortisol binding to glucocorticoid receptors in hypertensive patients .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "We compared glucocorticoid receptor binding characteristics and glucocorticoid responsiveness of human mononuclear leukocytes ( HML ) from hypertensive patients and matched normotensive volunteers .", "target_text": { "human mononuclear leukocytes": "cell_type", "HML": "cell_type" } }, { "input_text": "We also considered associations of these variables with plasma renin activity , aldosterone , cortisol , corticotropin , and electrolyte concentrations .", "target_text": { "renin": "protein" } }, { "input_text": "We calculated binding affinity ( Kd ; nmol/L ) and capacity ( Bmax ; sites/cell ) for dexamethasone and cortisol from homologous and heterologous competition curves for specific [3H]dexamethasone binding sites on HML isolated from the blood of normotensive volunteers and subjects with essential hypertension .", "target_text": { "HML": "cell_type" } }, { "input_text": "Glucocorticoid responsiveness of HML was evaluated as IC50 values ( nmol/L ) for dexamethasone and cortisol for the inhibition of lysozyme release .", "target_text": { "HML": "cell_type", "lysozyme": "protein" } }, { "input_text": "We measured plasma hormones by radioimmunoassay .", "target_text": {} }, { "input_text": "Kd values ( mean+/-SE ) for cortisol in HML of hypertensive patients were higher than in control subjects ( 24.6+/-2.4 versus 17.5+/-1.7 nmol/L , P < .04 ) .", "target_text": { "HML": "cell_type" } }, { "input_text": "Binding capacity ( 4978+/-391 versus 4131+/-321 sites/cell ) , Kd values for dexamethasone ( 6.7+/-0.5 versus 5.7+/-0.3 nmol/L ) , and IC50 values for dexamethasone ( 3.4+/-0.3 versus 3.1+/-0.2 nmol/L ) and cortisol ( 12.2+/-1.6 versus 9.5+/-0.3 nmol/L ) were not significantly different .", "target_text": {} }, { "input_text": "Patients with renin values less than 0.13 ng angiotensin I/L per second were markedly less sensitive to cortisol than those with higher values .", "target_text": { "renin": "protein" } }, { "input_text": "Both Kd ( 30.3+/-2.5 versus 19.2+/-2.4 nmol/L ) and IC50 values ( 15.5+/-1.8 versus 8.9+/-1.2 nmol/L ) for cortisol were significantly higher in patients with lower renin values ( P < .03 ) .", "target_text": { "renin": "protein" } }, { "input_text": "Other variables , including plasma hormone and electrolyte values and binding characteristics for dexamethasone , were not different .", "target_text": {} }, { "input_text": "These data suggest that cortisol binding to glucocorticoid receptor is slightly impaired in patients with essential hypertension .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "In vivo , this could lead to inappropriate binding of cortisol to mineralocorticoid receptors .", "target_text": {} }, { "input_text": "Hence , decreased sensitivity to cortisol is associated with renin suppression .", "target_text": { "renin": "protein" } }, { "input_text": "This hypothesis is supported by evidence of hypertension and low renin activity , which others have described in patients with primary glucocorticoid resistance due to mutations of the glucocorticoid receptor .", "target_text": { "renin": "protein", "glucocorticoid receptor": "protein" } }, { "input_text": "PU.1/Pip and basic helix loop helix zipper transcription factors interact with binding sites in the CD20 promoter to help confer lineage- and stage-specific expression of CD20 in B lymphocytes .", "target_text": { "PU.1/Pip": "protein", "transcription factors": "protein", "basic helix loop helix zipper transcription factors": "protein", "binding sites": "DNA", "CD20 promoter": "DNA", "CD20": "protein", "B lymphocytes": "cell_type" } }, { "input_text": "CD20 is a B-lineage-specific gene expressed at the pre-B-cell stage of B-cell development that disappears on differentiation to plasma cells .", "target_text": { "CD20": "protein", "B-lineage-specific gene": "DNA", "plasma cells": "cell_type" } }, { "input_text": "As such , it serves as an excellent paradigm for the study of lineage and developmental stage-specific gene expression .", "target_text": {} }, { "input_text": "Using in vivo footprinting we identified two sites in the promoter at -45 and -160 that were occupied only in CD20 + B cells .", "target_text": { "-45 and -160": "DNA", "CD20": "protein" } }, { "input_text": "The -45 site is an E box that binds basic helix-loop-helix-zipper proteins whereas the -160 site is a composite PU.1 and Pip binding site .", "target_text": { "-45 site": "DNA", "E box": "DNA", "basic helix-loop-helix-zipper proteins": "protein", "-160 site": "DNA", "composite PU.1 and Pip binding site": "DNA" } }, { "input_text": "Transfection studies with reporter constructs and various expression vectors verified the importance of these sites .", "target_text": { "reporter constructs": "DNA" } }, { "input_text": "The composite PU.1 and Pip site likely accounts for both lineage and stage -specific expression of CD20 whereas the CD20 E box binding proteins enhance overall promoter activity and may link the promoter to a distant enhancer .", "target_text": { "composite PU.1 and Pip site": "DNA", "CD20": "protein", "E box": "DNA", "CD20 E box binding proteins": "protein", "distant enhancer": "DNA" } }, { "input_text": "Glucocorticoids and the immune function in the human immunodeficiency virus infection : a study in hypercortisolemic and cortisol-resistant patients .", "target_text": {} }, { "input_text": "Immunological studies in human immunodeficiency virus ( HIV ) -positive patients suggest that the disease progression is accompanied by a defective production of type 1 cytokines ( interleukin-2 ( IL-2 ) and IL-12 ] , an increased production of type 2 cytokines ( IL-4 , IL-6 , and IL-10 ) , and an increased production of IgE .", "target_text": { "1 cytokines": "protein", "interleukin-2": "protein", "IL-2": "protein", "IL-12": "protein", "type 2 cytokines": "protein", "IL-4": "protein", "IL-6": "protein", "IL-10": "protein", "IgE": "protein" } }, { "input_text": "HIV infection is also associated with activation of the hypothalamo-pituitary-adrenal axis function and increased plasma and urinary cortisol concentrations .", "target_text": {} }, { "input_text": "As cortisol is involved in the physiological regulation of cytokines , a study was conducted to examine cytokine patterns in two groups of hypercortisolemic patients , one with normal sensitivity to glucocorticoids and the other with glucocorticoid resistance .", "target_text": { "cytokines": "protein", "cytokine": "protein" } }, { "input_text": "Ten HIV-infected patients with normal receptor affinity to glucocorticoids ( AIDS-C ) , 10 HIV-infected patients with low receptor affinity to glucocorticoids ( AIDS-GR ) , and 20 healthy subjects were studied .", "target_text": {} }, { "input_text": "Receptor characteristics of peripheral blood mononuclear cells were evaluated by [3H]dexamethasone binding .", "target_text": { "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Serum cortisol and urinary free cortisol were measured by RIA .", "target_text": {} }, { "input_text": "Serum ACTH and IgE were measured by immunoradiometric assay , and IL-2 , IL-4 , and IL-10 cytokines and interferon-gamma were measured by enzyme-linked immunosorbent assay .", "target_text": { "IgE": "protein", "IL-2": "protein", "IL-4": "protein", "IL-10": "protein", "cytokines": "protein", "interferon-gamma": "protein" } }, { "input_text": "AIDS-C patients showed low IL-2 and high IL-4 , IL-10 , and IgE concentratios ; conversely , AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations .", "target_text": { "IL-2": "protein", "IL-4": "protein", "IL-10": "protein", "IgE": "protein" } }, { "input_text": "Thus , in HIV infection , elevated cortisol levels suppress cell-mediated immunity and stimulate humoral immunity , whereas this response is not detected in cortisol -resistant patients .", "target_text": {} }, { "input_text": "These findings indicate that cortisol and its receptors are critically involved in the regulation of immune function in HIV infection .", "target_text": {} }, { "input_text": "Monocytic differentiation of HL-60 promyelocytic leukemia cells correlates with the induction of Bcl-xL .", "target_text": { "HL-60 promyelocytic leukemia cells": "cell_line", "Bcl-xL": "protein" } }, { "input_text": "Treatment of human promyelocytic leukemia HL-60 cells with phorbol esters ultimately induces the differentiation of these cells along the monocyte/macrophage lineage , whereas treatment with retinoic acid or DMSO induces granulocytic/neutrophillic differentiation .", "target_text": { "human promyelocytic leukemia HL-60 cells": "cell_line", "monocyte/macrophage lineage": "cell_type" } }, { "input_text": "In this study , we demonstrate the disparate fates of HL-60 cells treated with the phorbol ester 12,13-phorbol dibutyric acid ( PDBu ) or DMSO .", "target_text": { "HL-60 cells": "cell_line" } }, { "input_text": "After DMSO treatment , HL-60 cells eventually died via apoptosis , whereas the viability of PDBu -treated cells was not affected during the same interval .", "target_text": { "HL-60 cells": "cell_line", "PDBu -treated cells": "cell_line" } }, { "input_text": "The levels of the apoptosis effector proteins Bak and Bad were enhanced , whereas there was a slight down-regulation of the apoptosis suppressor protein Bcl-2 after treatment of the cells with PDBu and DMSO .", "target_text": { "Bak": "protein", "Bad": "protein", "apoptosis suppressor protein": "protein", "Bcl-2": "protein" } }, { "input_text": "Treatment with DMSO resulted in the elevation of the apoptosis effector Bax , whereas treatment with PDBu did not significantly alter the levels of this protein .", "target_text": { "apoptosis effector": "protein", "Bax": "protein" } }, { "input_text": "However , treatment of HL-60 cells with PDBu induced the rapid expression of the apoptosis suppressor protein Bcl-xL , whereas the expression of this protein remained unaltered in DMSO -treated cells .", "target_text": { "HL-60 cells": "cell_line", "apoptosis suppressor protein": "protein", "Bcl-xL": "protein" } }, { "input_text": "The generality of this finding was confirmed by the induction of Bcl-xL in human myeloid U-937 cells , human peripheral blood monocytes exposed to phorbol ester , and mouse thioglycollate-activated and resident peritoneal macrophages .", "target_text": { "Bcl-xL": "protein", "human myeloid U-937 cells": "cell_line", "human peripheral blood monocytes": "cell_type", "mouse thioglycollate-activated and resident peritoneal macrophages": "cell_line" } }, { "input_text": "PDBu -treated HL-60 cells remained viable for 7 days and thereafter began to die via apoptosis , with a concomitant down-regulation of Bcl-xL .", "target_text": { "HL-60 cells": "cell_line", "PDBu -treated HL-60 cells": "cell_line", "Bcl-xL": "protein" } }, { "input_text": "In conclusion , we propose that Bcl-xL expression is associated with differentiation and survival of hematopoietic cells along the monocyte/macrophage lineage .", "target_text": { "Bcl-xL": "protein", "hematopoietic cells": "cell_type", "monocyte/macrophage lineage": "cell_type" } }, { "input_text": "Monochloramine inhibits phorbol ester -inducible neutrophil respiratory burst activation and T cell interleukin-2 receptor expression by inhibiting inducible protein kinase C activity .", "target_text": { "interleukin-2": "protein", "protein kinase C": "protein" } }, { "input_text": "Monochloramine derivatives are long lived physiological oxidants produced by neutrophils during the respiratory burst .", "target_text": { "neutrophils": "cell_type" } }, { "input_text": "The effects of chemically prepared monochloramine ( NH2Cl ) on protein kinase C ( PKC ) and PKC -mediated cellular responses were studied in elicited rat peritoneal neutrophils and human Jurkat T cells .", "target_text": { "protein kinase C": "protein", "PKC": "protein", "neutrophils": "cell_type", "elicited rat peritoneal neutrophils": "cell_type", "human Jurkat T cells": "cell_line" } }, { "input_text": "Neutrophils pretreated with NH2Cl ( 30-50 microM ) showed a marked decrease in the respiratory burst activity induced by phorbol 12-myristate 13-acetate ( PMA ) , which is a potent PKC activator .", "target_text": { "PKC": "protein" } }, { "input_text": "These cells , however , were viable and showed a complete respiratory burst upon arachidonic acid stimulation , which induces the respiratory burst by a PKC -independent mechanism .", "target_text": { "PKC": "protein" } }, { "input_text": "The NH2Cl -treated neutrophils showed a decrease in both PKC activity and PMA -induced phosphorylation of a 47-kDa protein , which corresponds to the cytosolic factor of NADPH oxidase , p47 ( phox ) .", "target_text": { "NH2Cl -treated neutrophils": "cell_line", "PKC": "protein", "47-kDa protein": "protein", "cytosolic factor": "protein", "NADPH oxidase": "protein", "p47 ( phox )": "protein" } }, { "input_text": "Jurkat T cells pretreated with NH2Cl ( 20-70 microM ) showed a decrease in the expression of the interleukin-2 receptor alpha chain following PMA stimulation .", "target_text": { "Jurkat T cells": "cell_line", "interleukin-2": "protein", "receptor alpha chain": "protein" } }, { "input_text": "This was also accompanied by a decrease in both PKC activity and nuclear transcription factor- kappaB activation , also without loss of cell viability .", "target_text": { "PKC": "protein", "kappaB": "protein" } }, { "input_text": "These results show that NH2Cl inhibits PKC -mediated cellular responses through inhibition of the inducible PKC activity .", "target_text": { "PKC": "protein" } }, { "input_text": "Evidence that calcineurin is rate-limiting for primary human lymphocyte activation .", "target_text": {} }, { "input_text": "Cyclosporine ( CsA ) is both a clinical immunosuppressive drug and a probe to dissect intracellular signaling pathways .", "target_text": {} }, { "input_text": "In vitro , CsA inhibits lymphocyte gene activation by inhibiting the phosphatase activity of calcineurin ( CN ) .", "target_text": { "lymphocyte gene": "DNA", "phosphatase": "protein", "calcineurin": "protein", "CN": "protein" } }, { "input_text": "In clinical use , CsA treatment inhibits 50-75 % of CN activity in circulating leukocytes .", "target_text": { "CN": "protein", "circulating leukocytes": "cell_type" } }, { "input_text": "We modeled this degree of CN inhibition in primary human leukocytes in vitro in order to study the effect of partial CN inhibition on the downstream signaling events that lead to gene activation .", "target_text": { "CN": "protein", "primary human leukocytes": "cell_type" } }, { "input_text": "In CsA -treated leukocytes stimulated by calcium ionophore , the degree of reduction in CN activity was accompanied by a similar degree of inhibition of each event tested : dephosphorylation of nuclear factor of activated T cell proteins , nuclear DNA binding , activation of a transfected reporter gene construct , IFN-gamma and IL-2 mRNA accumulation , and IFN-gamma production .", "target_text": { "CsA -treated leukocytes": "cell_line", "CN": "protein", "nuclear factor of activated T cell proteins": "protein", "transfected reporter gene construct": "DNA", "IFN-gamma": "protein" } }, { "input_text": "Furthermore , the degree of CN inhibition was reflected by a similar degree of reduction in lymphocyte proliferation and IFN-gamma production in the allogeneic mixed lymphocyte cultures .", "target_text": { "CN": "protein", "IFN-gamma": "protein", "allogeneic mixed lymphocyte cultures": "cell_line" } }, { "input_text": "These data support the conclusion that CN activity is rate-limiting for the activation of primary human T lymphocytes .", "target_text": { "CN": "protein", "primary human T lymphocytes": "cell_type" } }, { "input_text": "Thus , the reduction of CN activity observed in CsA -treated patients is accompanied by a similar degree of reduction in lymphocyte gene activation , and accounts for the immunosuppression observed .", "target_text": { "CN": "protein", "lymphocyte gene": "DNA" } }, { "input_text": "Selection of down-regulated sequences along the monocytic differentiation of leukemic HL60 cells .", "target_text": { "down-regulated sequences": "DNA", "leukemic HL60 cells": "cell_line" } }, { "input_text": "In order to dissect the molecular mechanisms of monocytic differentiation we have developed a subtractive hybridisation method based on a simplified ' representational difference analysis ' .", "target_text": {} }, { "input_text": "We have selected 16 sequences and confirmed their down-regulation along the TPA -induced monocytic differentiation of HL60 cells .", "target_text": { "16 sequences": "DNA", "HL60 cells": "cell_line" } }, { "input_text": "Among these sequences we have identified the alpha-tubulin , the TaxREB protein and two ribosomal protein sequences which had not been previously described as differentially expressed .", "target_text": { "alpha-tubulin": "protein", "TaxREB protein": "protein", "ribosomal protein sequences": "DNA" } }, { "input_text": "These results add to our knowledge about the molecules implicated along the monocytic differentiation and growth arrest of leukemic cells and provide a first step in the study of their respective roles .", "target_text": { "leukemic cells": "cell_type" } }, { "input_text": "Control of NF-kappa B activity by the I kappa B beta inhibitor .", "target_text": { "NF-kappa B": "protein", "I kappa B beta inhibitor": "protein" } }, { "input_text": "The transcription factor NF-kappa B is maintained in an inactive cytoplasmic state by I kappa B inhibitors .", "target_text": { "transcription factor": "protein", "NF-kappa B": "protein", "I kappa B inhibitors": "protein" } }, { "input_text": "In mammalian cells , I kappa B alpha and I kappa B beta proteins have been purified and shown to be the inhibitors of NF-kappa B through their association with the p65 or c-Rel subunits .", "target_text": { "mammalian cells": "cell_type", "I kappa B alpha": "protein", "I kappa B beta": "protein", "I kappa B beta proteins": "protein", "NF-kappa B": "protein" } }, { "input_text": "In addition , we have isolated a third NF-kappa B inhibitor , I kappa B epsilon ( 1 ) .", "target_text": { "NF-kappa B": "protein", "NF-kappa B inhibitor": "protein", "I kappa B epsilon": "protein" } }, { "input_text": "Upon treatment with a large variety of inducers , I kappa B alpha , I kappa B beta are proteolytically degraded , resulting in NF-kappa B translocation into the nucleus .", "target_text": { "I kappa B alpha": "protein", "I kappa B beta": "protein", "NF-kappa B": "protein" } }, { "input_text": "Here we show that in E29.1 T cell hybridoma I kappa B alpha and I kappa B beta are equally associated with p65 and that I kappa B beta is degraded in response to TNF alpha in contrast to what has been originally published .", "target_text": { "E29.1 T cell hybridoma": "cell_line", "I kappa B alpha": "protein", "I kappa B beta": "protein", "p65": "protein", "TNF alpha": "protein" } }, { "input_text": "Our data also suggest that , unlike I kappa B alpha , I kappa B beta is constitutively phosphorylated and resynthesized as a hypophosphorylated form .", "target_text": { "I kappa B alpha": "protein", "I kappa B beta": "protein", "hypophosphorylated form": "protein" } }, { "input_text": "The absence of slow migrating forms of I kappa B beta following stimulation suggests that the phosphorylation does not necessarily constitute the signal-induced event which targets the molecule for proteolysis .", "target_text": { "I kappa B beta": "protein" } }, { "input_text": "Agonistic activity of a CD40-specific single-chain Fv constructed from the variable regions of mAb G28-5 .", "target_text": { "CD40-specific single-chain Fv": "protein", "variable regions": "protein", "mAb G28-5": "protein" } }, { "input_text": "A single-chain Fv ( sFv ) was expressed from the variable regions of the CD40-specific mAb G28-5 .", "target_text": { "single-chain Fv": "protein", "sFv": "protein", "variable regions": "protein", "mAb G28-5": "protein" } }, { "input_text": "The molecule bound CD40 with a high affinity ( 2.2 nM ) and was a monomer in solution .", "target_text": { "CD40": "protein" } }, { "input_text": "Surprisingly , G28-5 sFv was a potent CD40 agonist that rapidly crosslinked CD40 on the cell surface but did not crosslink CD40 -Ig in solution .", "target_text": { "G28-5 sFv": "protein", "CD40": "protein", "CD40 agonist": "protein", "CD40 -Ig": "protein" } }, { "input_text": "G28-5 sFv was a more potent agonist than G28-5 IgG and was able to stimulate CD40 responses by B cells and monocytes .", "target_text": { "G28-5 sFv": "protein", "G28-5 IgG": "protein", "CD40": "protein", "B cells": "cell_type" } }, { "input_text": "G28-5 IgG partially blocked , whereas G28-5 sFv augmented CD40 responses during stimulation with natural ligand ( gp39-CD8 fusion protein ) .", "target_text": { "G28-5 IgG": "protein", "G28-5 sFv": "protein", "CD40": "protein", "natural ligand": "protein", "gp39-CD8 fusion protein": "protein" } }, { "input_text": "These results indicate that the functional activity of ligands built from the binding site of G28-5 is highly dependent upon the size and physical properties of the molecule both in solution and on the cell surfaces .", "target_text": { "binding site": "protein", "G28-5": "protein" } }, { "input_text": "C/EBP activates the human corticotropin-releasing hormone gene promoter .", "target_text": { "C/EBP": "protein", "human corticotropin-releasing hormone gene promoter": "DNA" } }, { "input_text": "The purpose of these studies was to identify whether transcription factors , associated with cytokine signalling , affected promoter activity of the corticotropin releasing hormone ( CRH ) gene .", "target_text": { "CRH": "protein", "corticotropin releasing hormone ( CRH ) gene": "DNA" } }, { "input_text": "Fragments of a 3.6 kb sequence of the human CRH gene promoter were amplified by PCR and ligated upstream of a CAT reporter .", "target_text": { "CRH": "protein", "human CRH gene promoter": "DNA", "CAT reporter": "DNA" } }, { "input_text": "These constructs were transfected into a variety of cell lines , either alone or together , with transcription factor expression vectors .", "target_text": { "transcription factor": "protein" } }, { "input_text": "Basal activity of a 3070 bp CRH promoter fragment was only seen in neuronal and lymphoblastoid cell lines .", "target_text": { "CRH": "protein", "3070 bp CRH promoter fragment": "DNA", "lymphoblastoid cell lines": "cell_line" } }, { "input_text": "Promoter activity was increased by the transcription factors C/EBPbeta ( NF-IL6 ) and more strongly , by C/EBPdelta ( NF-IL6beta ) .", "target_text": { "transcription factors": "protein", "C/EBPbeta": "protein", "NF-IL6": "protein", "C/EBPdelta": "protein", "NF-IL6beta": "protein" } }, { "input_text": "Increased CRH promoter activity following phorbol ester treatment was inhibited by a dominant negative NF-IL6 mutant , showing that the effects of phorbol ester were principally mediated by C/EBP .", "target_text": { "CRH": "protein", "NF-IL6 mutant": "protein", "C/EBP": "protein" } }, { "input_text": "Moreover , the inverse changes in the expression of CRH in the hypothalamus and spleens of arthritic rats were paralleled by similar inverse changes in NF-IL6beta expression in these organs .", "target_text": { "CRH": "protein", "NF-IL6beta": "protein" } }, { "input_text": "These data show that some transcription factors associated with cytokine signalling can also activate the CRH promoter .", "target_text": { "transcription factors": "protein", "cytokine": "protein", "CRH": "protein", "CRH promoter": "DNA" } }, { "input_text": "Aberrant splicing of the TSG101 and FHIT genes occurs frequently in multiple malignancies and in normal tissues and mimics alterations previously described in tumours .", "target_text": {} }, { "input_text": "Intragenic deletions of TSG101 , the human homolog of a mouse gene ( tsg101 ) that acts to suppress malignant cell growth , were reported in human breast tumours .", "target_text": { "TSG101": "DNA", "mouse gene": "DNA", "tsg101": "DNA", "human breast tumours": "cell_type" } }, { "input_text": "We screened TSG101 for somatic mutations in DNA and RNA samples isolated from a variety of common human malignancies , EBV-immortalised B-cells , and normal lung parenchyma .", "target_text": { "TSG101": "DNA", "EBV-immortalised B-cells": "cell_type" } }, { "input_text": "Intragenic TSG101 deletions in RNA transcripts were frequently found in all types of samples .", "target_text": { "TSG101": "DNA", "RNA transcripts": "RNA" } }, { "input_text": "Analysis of DNA failed to show genomic rearrangements corresponding to transcripts containing deletions in the same samples .", "target_text": {} }, { "input_text": "The breakpoints of most transcript deletions coincide with genuine or cryptic splice site sequences , suggesting that they result from alternative or aberrant splicing .", "target_text": { "splice site sequences": "DNA" } }, { "input_text": "A similar spectrum of transcript deletions has previously been described in the putative tumour suppressor gene FHIT .", "target_text": { "putative tumour suppressor gene": "DNA", "FHIT": "DNA" } }, { "input_text": "We analysed FHIT in the same series of RNA samples and detected truncated FHIT transcripts frequently in both tumour and normal tissues .", "target_text": { "FHIT": "DNA", "RNA samples": "RNA", "FHIT transcripts": "RNA" } }, { "input_text": "In addition , transcripts from TSG101 , FHIT and seven other genes were analysed in RNA isolated from normal peripheral blood lymphocytes .", "target_text": { "TSG101": "DNA", "FHIT": "DNA", "normal peripheral blood lymphocytes": "cell_type" } }, { "input_text": "Large TSG101 and FHIT intragenic transcript deletions were detected and these appeared to be the predominant transcript in ' aged ' lymphocytes .", "target_text": { "TSG101": "DNA", "FHIT": "DNA", "' aged ' lymphocytes": "cell_type" } }, { "input_text": "Similar alterations were not detected in transcripts of the other genes which were analysed .", "target_text": {} }, { "input_text": "Our findings demonstrate that truncated TSG101 and FHIT transcripts are commonly detected in both normal and malignant tissues and that a significant fraction of these are likely to be the result of aberrant splicing .", "target_text": {} }, { "input_text": "While we can not exclude that alterations in TSG101 and FHIT occur during cancer development , our data indicate that in this context the commonly observed transcript abnormalities are misleading .", "target_text": { "TSG101": "DNA", "FHIT": "DNA" } }, { "input_text": "Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin , a curry pigment .", "target_text": {} }, { "input_text": "Curcumin ( diferuoylmethane ) , the yellow pigment in the rhizome of tumeric ( Curcuma longa ) , an ingredient of curry spice , is known to exhibit a variety of pharmacological effects including antitumor , antiinflammatory , and antiinfectious activities .", "target_text": {} }, { "input_text": "Although its precise mode of action remains elusive , curcumin has been shown to suppress the activity of the AP-1 transcription factor in cells stimulated to proliferate .", "target_text": { "AP-1": "protein", "transcription factor": "protein" } }, { "input_text": "In this study , we observed that curcumin ( 50 microM ) inhibited proliferation of rat thymocytes stimulated with concanavalin A ( Con A ) as well as that of human Jurkat lymphoblastoid cells in the logarithmic growth phase .", "target_text": { "rat thymocytes": "cell_type", "human Jurkat lymphoblastoid cells": "cell_type" } }, { "input_text": "The pigment also inhibited apoptosis in dexamethasone-treated rat thymocytes and in UV-irradiated Jurkat cells as judged by DNA ladder formation , cellular morphological changes , and flow cytometry analysis .", "target_text": { "rat thymocytes": "cell_type", "dexamethasone-treated rat thymocytes": "cell_line", "UV-irradiated Jurkat cells": "cell_line" } }, { "input_text": "The inhibition of apoptosis by curcumin in rat thymocytes was accompanied by partial suppression of AP-1 activity .", "target_text": { "rat thymocytes": "cell_type", "AP-1": "protein" } }, { "input_text": "Complete suppression of AP-1 activity was observed in Con A -treated , proliferating thymocytes .", "target_text": { "AP-1": "protein", "Con A -treated , proliferating thymocytes": "cell_line" } }, { "input_text": "The capacity of curcumin to inhibit both cell growth and death strongly implies that these two biological processes share a common pathway at some point and that curcumin affects a common step , presumably involving a modulation of the AP-1 transcription factor .", "target_text": { "AP-1": "protein", "transcription factor": "protein" } }, { "input_text": "Interleukin-7 upregulates the interleukin-2-gene expression in activated human T lymphocytes at the transcriptional level by enhancing the DNA binding activities of both nuclear factor of activated T cells and activator protein-1 .", "target_text": { "Interleukin-7": "protein", "interleukin-2-gene": "DNA", "activated human T lymphocytes": "cell_type", "activated T cells": "cell_type", "activator protein-1": "protein" } }, { "input_text": "In the present report , we studied the role of the stromal-derived cytokine interleukin-7 ( IL-7 ) in the IL-2-gene regulation in activated T lymphocytes .", "target_text": { "stromal-derived cytokine": "protein", "interleukin-7": "protein", "stromal-derived cytokine interleukin-7": "protein", "IL-7": "protein", "IL-2-gene": "DNA", "activated T lymphocytes": "cell_type" } }, { "input_text": "Production of IL-2 requires the formation of transcription factors involved in the IL-2 -gene regulation .", "target_text": { "IL-2": "protein", "transcription factors": "protein", "IL-2 -gene": "DNA" } }, { "input_text": "T-cell receptor ( TCR ) /CD3 engagement results in the activation of nuclear factor of activated T cells ( NFAT ) , activator protein-1 ( AP-1 ) , and nuclear factor kappaB ( NFkappaB ) , whereas the CD28 responsive complex ( CD28RC ) is activated in response to the CD28 signal .", "target_text": { "T-cell receptor": "protein", "( TCR ) /CD3": "protein", "activated T cells": "cell_type", "NFAT": "protein", "activator protein-1": "protein", "AP-1": "protein", "nuclear factor kappaB": "protein", "NFkappaB": "protein", "CD28 responsive complex": "protein", "CD28RC": "protein", "CD28": "protein" } }, { "input_text": "Costimulation of phytohemagglutinin /anti-CD28 activated T lymphocytes with IL-7 induces a fivefold enhanced IL-2 -mRNA accumulation and a 2.5-fold enhanced protein secretion .", "target_text": { "phytohemagglutinin": "protein", "activated T lymphocytes": "cell_type", "phytohemagglutinin /anti-CD28 activated T lymphocytes": "cell_line", "IL-7": "protein", "IL-2": "protein" } }, { "input_text": "The IL-2 -gene transcription rate is increased 3.4-fold , indicating that the effect of IL-7 is in part mediated at the transcriptional level .", "target_text": { "IL-2": "protein", "IL-2 -gene": "DNA", "IL-7": "protein" } }, { "input_text": "The molecular mechanisms underlying the IL-7 effect involve the upregulation of the DNA binding activity of NFAT ( 60 % ) and AP-1 ( 120 % ) , without affecting the activities of NFkappaB and CD28RC , which was confirmed by transfection assays .", "target_text": { "IL-7": "protein", "NFAT": "protein", "AP-1": "protein", "NFkappaB": "protein", "CD28RC": "protein" } }, { "input_text": "We also show that the IL-7 -induced enhancement of the AP-1 -DNA binding activity is not cyclosporin A-sensitive .", "target_text": { "IL-7": "protein", "AP-1": "protein" } }, { "input_text": "Since AP-1 is part of the NFAT complex , we conclude that the IL-7 -signaling pathway is involved in the activation of the fos and jun proteins of which AP-1 consists .", "target_text": { "AP-1": "protein", "NFAT complex": "protein", "IL-7": "protein" } }, { "input_text": "The spatial distribution of human immunoglobulin genes within the nucleus : evidence for gene topography independent of cell type and transcriptional activity .", "target_text": { "human immunoglobulin genes": "DNA" } }, { "input_text": "The three-dimensional positioning of immunoglobulin ( Ig ) genes within the nucleus of human cells was investigated using in situ hybridization and confocal microscopy .", "target_text": { "immunoglobulin ( Ig ) genes": "DNA", "human cells": "cell_type" } }, { "input_text": "The visualization of heavy and light chain genes in B-lymphoid cells showed that the three Ig genes are differentially and nonrandomly distributed in different nuclear subvolumes : the kappa genes were found to be preferentially confined to an outer nuclear volume , whereas the gamma and lambda genes consistently occupied more central positions within the nucleus , the lambda genes being more interior when compared with the gamma genes .", "target_text": { "B-lymphoid cells": "cell_type", "Ig genes": "DNA", "kappa genes": "DNA", "lambda genes": "DNA", "gamma genes": "DNA" } }, { "input_text": "The data further show that these overall topographical distributions are independent of gene transcriptional activity and are conserved in different cell types .", "target_text": { "different cell types": "cell_type" } }, { "input_text": "Although subtle gene movements within those defined topographical regions can not be excluded by this study , the results indicate that tissue specificity of gene expression is not accompanied by drastic changes in gene nuclear topography , rather suggesting that gene organization within the nucleus may be primarily dependent on structural constraints imposed on the respective chromosomes .", "target_text": { "chromosomes": "DNA" } }, { "input_text": "Dominant cytotoxic T lymphocyte response to the immediate-early trans-activator protein , BZLF1 , in persistent type A or B Epstein-Barr virus infection .", "target_text": { "cytotoxic T lymphocyte": "cell_type", "immediate-early trans-activator protein": "protein", "BZLF1": "protein" } }, { "input_text": "Five healthy human leukocyte antigen-B8 ( HLA-B8 ) -positive virus carriers were studied to investigate the CD8+ cytotoxic T lymphocyte ( CTL ) response to an HLA-B8-restricted peptide , RAKFKQLLQ , located in the Epstein-Barr virus ( EBV ) immediate-early trans-activator protein , BZLF1 .", "target_text": { "CD8+ cytotoxic T lymphocyte": "cell_type", "Epstein-Barr virus ( EBV ) immediate-early trans-activator protein": "protein", "BZLF1": "protein" } }, { "input_text": "Of the 5 virus carriers , 4 were infected with type A and 1 with type B EBV .", "target_text": {} }, { "input_text": "Using limiting-dilution analysis of peripheral blood mononuclear cells , a high RAKFKQLLQ -specific CTL precursor frequency was demonstrated after specific peptide or autologous lymphoblastoid cell line stimulation in both type A and type B EBV carriers .", "target_text": { "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "The RAKFKQLLQ -specific CTL precursor frequencies in all 5 persons were at least as dominant as those observed with two other EBV-associated , HLA-B8-restricted latent epitopes , FLRGRAYGL and QAKWRLQTL .", "target_text": { "EBV-associated , HLA-B8-restricted latent epitopes": "protein" } }, { "input_text": "These findings show that healthy virus carriers maintain a high frequency of BZLF1 -specific memory T cells , potentially to control virus spread from lytically infected cells .", "target_text": { "BZLF1": "protein", "BZLF1 -specific memory T cells": "cell_type", "lytically infected cells": "cell_type" } }, { "input_text": "The DNA binding domain of the A-MYB transcription factor is responsible for its B cell-specific activity and binds to a B cell 110-kDa nuclear protein .", "target_text": { "DNA binding domain": "protein", "A-MYB": "protein", "transcription factor": "protein", "B cell 110-kDa nuclear protein": "protein" } }, { "input_text": "Expression studies as well as the use of transgenic animals have demonstrated that the A-MYB transcription factor plays central and specific role in the regulation of mature B cell proliferation and/or differentiation .", "target_text": { "A-MYB": "protein", "transcription factor": "protein", "mature B cell": "cell_type" } }, { "input_text": "Furthermore , it is highly expressed in Burkitt 's lymphoma cells and may participate in the pathogenesis of this disease .", "target_text": { "Burkitt 's lymphoma cells": "cell_line" } }, { "input_text": "We have therefore investigated the transcriptional activity of A-MYB and its regulation in several human lymphoid cell lines using co-transfection assays and show that A-MYB is transcriptionally active in all the B cell lines studied , but not in T cells .", "target_text": { "A-MYB": "protein", "human lymphoid cell lines": "cell_line", "B cell lines": "cell_line", "T cells": "cell_type" } }, { "input_text": "In particular the best responder cell line was the Burkitt 's cell line Namalwa .", "target_text": { "responder cell line": "cell_line", "Burkitt 's cell line Namalwa": "cell_line" } }, { "input_text": "The activity of A-MYB in B and not T cells was observed when either an artificial construct or the c-MYC promoter was used as a reporter .", "target_text": { "A-MYB": "protein", "c-MYC promoter": "DNA" } }, { "input_text": "Furthermore , the functional domains responsible for DNA binding , transactivation , and negative regulation , previously characterized in a fibroblast context , were found to have similar activity in B cells .", "target_text": { "functional domains": "protein", "B cells": "cell_type" } }, { "input_text": "The region of A-MYB responsible for the B cell specific activity was defined to be the N-terminal 218 amino acids containing the DNA binding domain .", "target_text": { "A-MYB": "protein", "N-terminal 218 amino acids": "protein", "DNA binding domain": "protein" } }, { "input_text": "Finally , a 110-kDa protein has been identified in the nuclei of all the B , but not T , cell lines that specifically binds to this A-MYB N-terminal domain .", "target_text": { "110-kDa protein": "protein", "A-MYB": "protein", "A-MYB N-terminal domain": "protein" } }, { "input_text": "We hypothesize that this 110-kDa protein may be a functionally important B cell-specific co-activator of A-MYB .", "target_text": { "110-kDa protein": "protein", "B cell-specific co-activator": "protein", "A-MYB": "protein" } }, { "input_text": "Transcription factor Egr-1 activity down-regulates Fas and CD23 expression in B cells .", "target_text": { "Egr-1": "protein", "B cells": "cell_type" } }, { "input_text": "Activation of mature B cells via Ag receptor cross-linking induces transient expression of the transcription factor Egr-1 .", "target_text": { "B cells": "cell_type", "Ag receptor": "protein", "transcription factor": "protein", "Egr-1": "protein" } }, { "input_text": "Although the activating signals leading to Egr-1 induction have been studied extensively , little is known about the genes that are placed further downstream within this activation cascade and that are transcriptionally regulated by Egr-1 .", "target_text": { "Egr-1": "protein" } }, { "input_text": "To identify such target genes , we established Egr-1 -overexpressing transfectants from the murine B cell line K46 and from human Ramos B cells .", "target_text": { "target genes": "DNA", "Egr-1": "protein", "Egr-1 -overexpressing transfectants": "cell_line", "murine B cell line K46": "cell_line", "human Ramos B cells": "cell_line" } }, { "input_text": "All clones derived from K46 B cells showed increased expression of CD44 .", "target_text": { "K46 B cells": "cell_line", "CD44": "protein" } }, { "input_text": "Most interestingly , expression of CD95 ( Fas /Apo-1 ) and of CD23 was down-regulated in all K46 transfectants .", "target_text": { "CD95": "protein", "Fas": "protein", "Fas /Apo-1": "protein", "CD23": "protein", "K46 transfectants": "cell_line" } }, { "input_text": "As a consequence , they became resistant to apoptosis induced by anti-CD95 Ab treatment .", "target_text": { "anti-CD95 Ab": "protein" } }, { "input_text": "Similarly , the Egr-1 -expressing Ramos cells showed reduced levels of CD95 expression .", "target_text": { "Egr-1": "protein", "Egr-1 -expressing Ramos cells": "cell_line", "CD95": "protein" } }, { "input_text": "Thus , Egr-1 seems to control the expression of downstream target genes not only as a transcriptional activator , but also as a repressor molecule .", "target_text": { "Egr-1": "protein", "downstream target genes": "DNA", "repressor molecule": "protein" } }, { "input_text": "In B cells , Egr-1 therefore plays a critical role in integrating the short-lived signal delivered by triggering of the Ag receptor into phenotypic changes , including repression of CD95 and CD23 transcription .", "target_text": { "B cells": "cell_type", "Egr-1": "protein", "Ag receptor": "protein", "CD95": "protein", "CD23": "protein" } }, { "input_text": "Regulation of NF-kappa B activity by I kappa B alpha and I kappa B beta stability .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Transcription factor NF-kappa B must be released from cytoplasmic inhibitory molecules ( I kappa Bs ) in order to move to the nucleus and to activate its target genes .", "target_text": { "Transcription factor": "protein", "NF-kappa B": "protein", "cytoplasmic inhibitory molecules": "protein", "I kappa Bs": "protein", "target genes": "DNA" } }, { "input_text": "Little is known about the mechanisms regulating the maintenance of constitutive nuclear NF-kappa B in some cell-types and of sustained nuclear NF-kappa B activity after stimulation .", "target_text": { "NF-kappa B": "protein", "constitutive nuclear NF-kappa B": "protein" } }, { "input_text": "Increased turnover has been implicated in the regulation of constitutive NF-kappa B activity in mature B cells .", "target_text": { "NF-kappa B": "protein", "mature B cells": "cell_type" } }, { "input_text": "We therefore compared the turnover of I kappa B alpha and I kappa B beta in mature B cells and HeLa cells .", "target_text": { "I kappa B alpha": "protein", "I kappa B beta": "protein", "mature B cells": "cell_type", "HeLa cells": "cell_line" } }, { "input_text": "Both proteins display a high turnover in B cells although I kappa B beta is considerably more stable than I kappa B alpha .", "target_text": { "B cells": "cell_type", "I kappa B beta": "protein", "I kappa B alpha": "protein" } }, { "input_text": "The half-life of both inhibitors is increased in HeLa cells .", "target_text": { "HeLa cells": "cell_line" } }, { "input_text": "In contrast , all other NF-kappa B /I kappa B molecules tested are relatively stable in both cell-types .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "The elevated turnover of endogenous I kappa B alpha in Namalwa cells is inhibited by a proteasome inhibitor and thus seems to be driven by the same degradation machinery as the slower turnover in non-B cells .", "target_text": { "I kappa B alpha": "protein", "Namalwa cells": "cell_type", "non-B cells": "cell_type" } }, { "input_text": "Furthermore , we investigated the processes involved in persistent activation of NF-kappa B .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "TNF-alpha signaling leads to a rapid depletion of cellular I kappa B beta pools .", "target_text": { "I kappa B beta": "protein" } }, { "input_text": "I kappa B alpha is efficiently resynthesized whereas I kappa B beta levels stay low for a prolonged time .", "target_text": { "I kappa B alpha": "protein", "I kappa B beta": "protein" } }, { "input_text": "NF-kappa B binding activity can be detected for several hours after stimulation .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "We found that removal of the TNF-alpha containing medium causes a rapid decrease in nuclear NF-kappa B .", "target_text": { "TNF-alpha": "protein", "NF-kappa B": "protein", "nuclear NF-kappa B": "protein" } }, { "input_text": "A phosphoform of newly synthesized I kappa B alpha is visible when degradation by the proteasome is inhibited and new I kappa B alpha displays the same properties regarding phosphorylation and degradation in response to a second inducer .", "target_text": { "I kappa B alpha": "protein", "proteasome": "protein" } }, { "input_text": "There is no significant difference in the turnover of pre- and post-inductive I kappa B alpha .", "target_text": { "I kappa B alpha": "protein" } }, { "input_text": "These observations suggest that resynthesis of I kappa B alpha and removal of the stimulus are obligatory steps for the inactivation of nuclear NF kappa B .", "target_text": { "I kappa B alpha": "protein", "nuclear NF kappa B": "protein" } }, { "input_text": "Selection of a diverse TCR repertoire in response to an Epstein-Barr virus -encoded transactivator protein BZLF1 by CD8+ cytotoxic T lymphocytes during primary and persistent infection .", "target_text": { "TCR": "protein", "TCR repertoire": "protein", "Epstein-Barr virus -encoded transactivator protein": "protein", "BZLF1": "protein", "CD8+ cytotoxic T lymphocytes": "cell_type" } }, { "input_text": "We investigated the CD8+ cytotoxic T lymphocyte ( CTL ) repertoire to an HLA B8-restricted peptide , RAKFKQLLQ , located in the Epstein-Barr virus ( EBV ) immediate-early protein , BZLF1 .", "target_text": { "CD8+ cytotoxic T lymphocyte": "cell_type", "CD8+ cytotoxic T lymphocyte ( CTL ) repertoire": "protein", "Epstein-Barr virus ( EBV ) immediate-early protein": "protein", "BZLF1": "protein" } }, { "input_text": "Repertoire selection was monitored by determining the TCR beta chain sequences of RAKFKQLLQ -specific CTL established from primary infected and healthy virus carriers .", "target_text": { "TCR beta chain sequences": "protein", "RAKFKQLLQ -specific CTL": "cell_line" } }, { "input_text": "PCR analysis of spontaneous EBV -transformed lymphoblastoid cell lines ( LCL ) from three individuals with primary infection showed that two were infected with type A and one with type B EBV .", "target_text": { "spontaneous EBV -transformed lymphoblastoid cell lines": "cell_line", "LCL": "cell_line" } }, { "input_text": "Polyclonal and clonal CTL that were generated by stimulating peripheral blood mononuclear cells with an HLA B8+ homozygous LCL lysed T cell blasts pulsed with the peptide , RAKFKQLLQ ; lysis of certain HLA B8+ LCL targets was associated with the abundance of BZLF1 transcripts .", "target_text": { "peripheral blood mononuclear cells": "cell_type", "HLA B8+ homozygous LCL lysed T cell blasts": "cell_line", "BZLF1": "protein", "BZLF1 transcripts": "RNA" } }, { "input_text": "TCR beta analysis showed that while there was loop length restriction in the putative peptide contact site of all responding beta chains , diverse and unique ( non-recurrent ) TCR beta clonotypes were selected in individuals during primary infection and continued to emerge after long-term virus exposure .", "target_text": { "TCR beta": "DNA", "beta chains": "protein", "TCR beta clonotypes": "cell_line", "unique ( non-recurrent ) TCR beta clonotypes": "cell_line" } }, { "input_text": "TCR -contact site heterogeneity was excluded as the selective force in diversity generation since the epitope-encoded sequences were found to be identical within endogenous virus isolates .", "target_text": { "TCR": "protein" } }, { "input_text": "In this first study of TCR repertoire selection for an EBV lytic antigen , a BZLF1 -reactive component of diverse clonotypes was identified in primary type A or type B EBV infection which was sustained in the EBV -specific memory response throughout life-long infection .", "target_text": { "TCR": "protein", "TCR repertoire": "protein", "EBV lytic antigen": "protein", "BZLF1": "protein" } }, { "input_text": "This diversity selection is likely to play a critical role in maintaining a balanced viral load throughout EBV persistence .", "target_text": {} }, { "input_text": "Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells .", "target_text": { "cultured endothelial cells": "cell_line" } }, { "input_text": "The objectives of this study were to ( 1 ) determine the time course of neutrophil adhesion to monolayers of human umbilical vein endothelial cells ( HUVECs ) that were exposed to 60 minutes of anoxia followed by 30 to 600 minutes of reoxygenation and ( 2 ) define the mechanisms responsible for both the early ( minutes ) and late ( hours ) hyperadhesivity of postanoxic HUVECs to human neutrophils .", "target_text": { "human umbilical vein endothelial cells": "cell_line", "HUVECs": "cell_line", "postanoxic HUVECs": "cell_line", "human neutrophils": "cell_type" } }, { "input_text": "The results clearly demonstrate that anoxia /reoxygenation ( A/R ) leads to a biphasic increase in neutrophil adhesion to HUVECs , with peak responses occurring at 30 minutes ( phase 1 ) and 240 minutes ( phase 2 ) after reoxygenation .", "target_text": { "HUVECs": "cell_line" } }, { "input_text": "Oxypurinol and catalase inhibited phase-1 adhesion , suggesting a role for xanthine oxidase and H2O2 .", "target_text": { "catalase": "protein", "xanthine oxidase": "protein" } }, { "input_text": "In comparison , platelet activating factor ( PAF ) contributed to both phases of neutrophil adhesion .", "target_text": { "platelet activating factor": "protein", "PAF": "protein" } }, { "input_text": "Anti-intercellular adhesion molecule-1 ( ICAM-1 ) and anti-P-selectin antibodies ( monoclonal antibodies [ mAbs ] ) attenuated phase-1 neutrophil adhesion , consistent with roles for constitutively expressed ICAM-1 and enhanced surface expression of preformed P-selectin .", "target_text": { "Anti-intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "anti-P-selectin antibodies": "protein", "monoclonal antibodies": "protein", "mAbs": "protein", "P-selectin": "protein" } }, { "input_text": "Phase-2 neutrophil adhesion was attenuated by an anti-E-selectin mAb , indicating a dominant role of this adhesion molecule in the late phase response .", "target_text": { "anti-E-selectin mAb": "protein" } }, { "input_text": "Pretreatment with actinomycin D and cycloheximide or with competing ds-oligonucleotides containing the nuclear factor-kappa B or activator protein-1 cognate DNA sequences significantly attenuated phase-2 response , suggesting a role for de novo macromolecule synthesis .", "target_text": { "nuclear factor-kappa B": "protein", "activator protein-1": "protein", "cognate DNA sequences": "DNA" } }, { "input_text": "Surface expression of ICAM-1 , P-selectin , and E-selectin on HUVECs correlated with the phase -1 and -2 neutrophil adhesion responses .", "target_text": { "ICAM-1": "protein", "P-selectin": "protein", "E-selectin": "protein", "HUVECs": "cell_line" } }, { "input_text": "Collectively , these findings indicate that A/R elicits a two-phase neutrophil-endothelial cell adhesion response that involves transcription-independent and transcription-dependent surface expression of different endothelial cell adhesion molecules .", "target_text": { "endothelial cell adhesion molecules": "protein" } }, { "input_text": "Characterization of CD40 signaling determinants regulating nuclear factor-kappa B activation in B lymphocytes .", "target_text": { "CD40": "protein", "nuclear factor-kappa B": "protein", "B lymphocytes": "cell_type" } }, { "input_text": "CD40 signaling to B cells is important for generating an effective humoral immune response .", "target_text": { "CD40": "protein", "B cells": "cell_type" } }, { "input_text": "CD40 ligation leads to B cell activation events such as proliferation , Ig secretion , isotype switching , and up-regulation of cell surface molecules , as well as the generation of memory B cells .", "target_text": { "CD40": "protein", "cell surface molecules": "protein", "memory B cells": "cell_type" } }, { "input_text": "Many of these events are dependent upon the ability of CD40 to activate the transcription factor NF-kappa B ( NF-kappa B ) .", "target_text": { "CD40": "protein", "NF-kappa B": "protein" } }, { "input_text": "To define the CD40 signaling components upstream of NF-kappa B activation and the functional consequences downstream of NF-kappa B activation , we examined mouse B cell transfectants expressing wild-type or mutant human CD40 .", "target_text": { "CD40": "protein", "NF-kappa B": "protein", "mouse B cell transfectants": "cell_line" } }, { "input_text": "Analysis of CD40 cytoplasmic domain truncation and point mutants defined a 10-amino acid CD40 cytoplasmic signaling determinant required for NF-kappa B activation .", "target_text": { "CD40": "protein", "CD40 cytoplasmic domain": "protein", "10-amino acid CD40 cytoplasmic signaling determinant": "protein", "NF-kappa B": "protein" } }, { "input_text": "A threonine residue at position 234 , previously shown to be important for CD40 association with TNF receptor-associated factor 2 ( TRAF2 ) , TRAF3 , and TRAF5 , was not required for NF-kappa B activation .", "target_text": { "position 234": "protein", "CD40": "protein", "TNF receptor-associated factor 2": "protein", "TRAF2": "protein", "TRAF3": "protein", "TRAF5": "protein", "NF-kappa B": "protein" } }, { "input_text": "This suggests that in B cells , CD40 -induced NF-kappa B activation can occur independently of TRAF2 and TRAF5 association .", "target_text": { "B cells": "cell_type", "CD40": "protein", "NF-kappa B": "protein", "TRAF2": "protein", "TRAF5": "protein" } }, { "input_text": "NF-kappa B activation was independent of the transmembrane domain of CD40 , suggesting that it is independent of p23 , a molecule that associates with CD40 in a region other than the cytoplasmic domain .", "target_text": { "NF-kappa B": "protein", "transmembrane domain": "protein", "CD40": "protein", "p23": "protein", "cytoplasmic domain": "protein" } }, { "input_text": "Proteasome-dependent inhibitory kappa B alpha ( I kappa B alpha ) and I kappa B beta degradation occurred downstream of CD40 ligation and preceded CD40 -mediated NF-kappa B nuclear translocation .", "target_text": { "I kappa B alpha": "protein", "I kappa B beta": "protein", "CD40": "protein", "NF-kappa B": "protein" } }, { "input_text": "CD40- or pervanadate- mediated I kappa B tyrosine phosphorylation was not detected .", "target_text": {} }, { "input_text": "NF-kappa B activation correlated with the ability of CD40 to induce Ab secretion and the up-regulation of ICAM-1 and LFA-1 .", "target_text": { "NF-kappa B": "protein", "CD40": "protein", "ICAM-1": "protein", "LFA-1": "protein" } }, { "input_text": "However , NF-kappa B activation was insufficient for CD40 -mediated up-regulation of B7-1 , Fas , and CD23 .", "target_text": { "NF-kappa B": "protein", "CD40": "protein", "B7-1": "protein", "Fas": "protein", "CD23": "protein" } }, { "input_text": "CD30 -dependent degradation of TRAF2 : implications for negative regulation of TRAF signaling and the control of cell survival .", "target_text": { "CD30": "protein", "TRAF2": "protein", "TRAF": "protein" } }, { "input_text": "CD30 is a cell-surface receptor that can augment lymphocyte activation and survival through its ability to induce the transcription factor NF-kappaB .", "target_text": { "CD30": "protein", "cell-surface receptor": "protein", "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "CD30 , however , has also been implicated in the induction of apoptotic cell death of lymphocytes .", "target_text": { "CD30": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Here we show that one of the effects of CD30 signal transduction is to render cells sensitive to apoptosis induced by the type 1 tumor necrosis factor receptor ( TNFR1 ) .", "target_text": { "CD30": "protein", "type 1 tumor necrosis factor receptor": "protein", "TNFR1": "protein" } }, { "input_text": "This sensitization is dependent on the TRAF-binding sites within the CD30 cytoplasmic domain .", "target_text": { "TRAF-binding sites": "protein", "CD30": "protein", "cytoplasmic domain": "protein" } }, { "input_text": "One of the proteins that binds to these sites is TRAF2 , a signal transduction molecule that is also utilized by TNFR1 to mediate the activation of several downstream kinases and transcription factors .", "target_text": { "TRAF2": "protein", "signal transduction molecule": "protein", "TNFR1": "protein", "kinases": "protein", "transcription factors": "protein" } }, { "input_text": "During CD30 signal transduction , we found that binding of TRAF2 to the cytoplasmic domain of CD30 results in the rapid depletion of TRAF2 and the associated protein TRAF1 by proteolysis .", "target_text": { "CD30": "protein", "TRAF2": "protein", "cytoplasmic domain": "protein", "TRAF1": "protein" } }, { "input_text": "These data suggest a model in which CD30 limits its own ability to transduce cell survival signals through signal-coupled depletion of TRAF2 .", "target_text": { "CD30": "protein", "TRAF2": "protein" } }, { "input_text": "Depletion of intracellular TRAF2 and its coassociated proteins also increased the sensitivity of the cell to undergoing apoptosis during activation of death-inducing receptors such as TNFR1 .", "target_text": { "TRAF2": "protein", "coassociated proteins": "protein", "death-inducing receptors": "protein", "TNFR1": "protein" } }, { "input_text": "Consistent with this hypothesis , expression of a dominant-negative form of TRAF2 was found to potentiate TNFR1 -mediated death .", "target_text": { "dominant-negative form": "protein", "TRAF2": "protein", "TNFR1": "protein" } }, { "input_text": "These studies provide a potential mechanism through which CD30 , as well as other TRAF-binding members of the TNFR superfamily , can negatively regulate cell survival .", "target_text": { "CD30": "protein", "TRAF-binding members": "protein", "TNFR superfamily": "protein" } }, { "input_text": "Analysis of myeloid-associated genes in human hematopoietic progenitor cells .", "target_text": { "myeloid-associated genes": "DNA", "human hematopoietic progenitor cells": "cell_type" } }, { "input_text": "The distribution of myeloid lineage-associated cytokine receptors and lysosomal proteins was analyzed in human CD34+ cord blood cell ( CB ) subsets at different stages of myeloid commitment by reverse-transcriptase polymerase chain reaction ( RT-PCR ) .", "target_text": { "myeloid lineage-associated cytokine receptors": "protein", "lysosomal proteins": "protein", "human CD34+ cord blood cell ( CB ) subsets": "cell_line" } }, { "input_text": "The highly specific granulomonocyte-associated lysosomal proteins myeloperoxidase ( MPO ) and lysozyme ( LZ ) , as well as the transcription factor PU.1 , were already detectable in the most immature CD34+Thy-1+ subset .", "target_text": { "lysosomal proteins": "protein", "granulomonocyte-associated lysosomal proteins": "protein", "myeloperoxidase": "protein", "MPO": "protein", "lysozyme": "protein", "LZ": "protein", "transcription factor": "protein", "PU.1": "protein", "CD34+Thy-1+ subset": "cell_line" } }, { "input_text": "Messenger RNA ( mRNA ) levels for the granulocyte-colony stimulating factor ( G-CSF ) receptor , granulocyte-macrophage ( GM ) -CSF receptor alpha subunit and tumor necrosis factor ( TNF ) receptors I ( p55 ) and II ( p75 ) were also detected in this subset in addition to c-kit and flt-3 , receptors known to be expressed on progenitor cells .", "target_text": { "Messenger RNA": "RNA", "mRNA": "RNA", "granulocyte-colony stimulating factor": "protein", "G-CSF": "protein", "granulocyte-colony stimulating factor ( G-CSF ) receptor": "protein", "granulocyte-macrophage ( GM ) -CSF receptor alpha subunit": "protein", "c-kit": "protein", "flt-3": "protein", "progenitor cells": "cell_type" } }, { "input_text": "By contrast , the monocyte-macrophage colony stimulating factor ( M-CSF ) receptor was largely absent at this stage and in the CD34+Thy-1-CD45RA- subsets .", "target_text": { "monocyte-macrophage colony stimulating factor ( M-CSF ) receptor": "protein", "CD34+Thy-1-CD45RA- subsets": "cell_line" } }, { "input_text": "The M-CSF receptor was first detectable in the myeloid-committed CD34+Thy-l-CD45RA+ subset .", "target_text": { "M-CSF receptor": "protein", "myeloid-committed CD34+Thy-l-CD45RA+ subset": "cell_line" } }, { "input_text": "All other molecules studied were found to be expressed at this stage of differentiation .", "target_text": {} }, { "input_text": "Different cocktails of the identified ligands were added to sorted CD34+Thy-1+ single cells .", "target_text": { "sorted CD34+Thy-1+ single cells": "cell_line" } }, { "input_text": "Low proliferative capacity was observed after 1 week in culture in the presence of stem cell factor ( SCF ) + Flt-3 ligand ( FL ) + G-CSF .", "target_text": { "stem cell factor": "protein", "SCF": "protein", "Flt-3 ligand": "protein", "FL": "protein", "G-CSF": "protein" } }, { "input_text": "Addition of GM-CSF to this basic cocktail consistently increased the clonogenic capacity of single CD34+Thy-1+ cells , and this effect was further enhanced ( up to 72.3 +/- 4.3 % on day 7 ) by the inclusion of TNF-alpha .", "target_text": { "GM-CSF": "protein", "single CD34+Thy-1+ cells": "cell_line", "TNF-alpha": "protein" } }, { "input_text": "In conclusion , the presence of myeloid-associated growth factor receptor transcripts in CD34+ CB subsets does not discriminate the various stages of differentiation , with the exception of the M-CSF receptor .", "target_text": { "myeloid-associated growth factor receptor": "protein", "myeloid-associated growth factor receptor transcripts": "RNA", "CD34+ CB subsets": "cell_line", "M-CSF receptor": "protein" } }, { "input_text": "In addition , we show that TNF-alpha is a potent costimulatory factor of the very immature CD34+Thy-1+ CB subset .", "target_text": { "TNF-alpha": "protein", "immature CD34+Thy-1+ CB subset": "cell_line" } }, { "input_text": "Induction of endothelial cell surface adhesion molecules by tumor necrosis factor is blocked by protein tyrosine phosphatase inhibitors : role of the nuclear transcription factor NF-kappa B .", "target_text": { "endothelial cell surface adhesion molecules": "protein", "tumor necrosis factor": "protein", "transcription factor": "protein", "NF-kappa B": "protein", "nuclear transcription factor NF-kappa B": "protein" } }, { "input_text": "Recent studies from our laboratory have indicated that protein tyrosine phosphatase ( PTPase ) inhibitors can down-modulate the tumor necrosis factor ( TNF ) -mediated activation of the nuclear transcription factor NF-kappa B in ML-1a , a monocytic cell line ( Singh and Aggarwal , J. Biol. Chem. 1995 : 270 : 10631 ) .", "target_text": { "protein tyrosine phosphatase": "protein", "PTPase": "protein", "tumor necrosis factor": "protein", "TNF": "protein", "nuclear transcription factor NF-kappa B": "protein", "ML-1a": "cell_line", "monocytic cell line": "cell_line" } }, { "input_text": "Since TNF is one of the major inducers of various adhesion molecules in human endothelial cells and their expression is known to require the activation of NF-kappa B , we examined the effect of PTPase inhibitors on the TNF -mediated induction of intracellular adhesion molecule ( ICAM ) -1 , vascular cell adhesion molecule ( VCAM ) -1 and endothelial leukocyte adhesion molecule ( ELAM ) -1 .", "target_text": { "TNF": "protein", "adhesion molecules": "protein", "NF-kappa B": "protein", "PTPase": "protein", "intracellular adhesion molecule ( ICAM ) -1": "protein", "vascular cell adhesion molecule ( VCAM ) -1": "protein", "endothelial leukocyte adhesion molecule ( ELAM ) -1": "protein" } }, { "input_text": "Like ML-1a , human dermal microvessel endothelial cells ( MVEC ) treated with TNF rapidly activated ( within 30 min ) NF-kappa B ; this effect was completely abolished by co-treatment with phenylarsine oxide ( PAO ) , a specific inhibitor of PTPase .", "target_text": { "ML-1a": "cell_line", "human dermal microvessel endothelial cells": "cell_line", "MVEC": "cell_line", "TNF": "protein", "NF-kappa B": "protein", "PTPase": "protein" } }, { "input_text": "The induction of ICAM-1 , VCAM-1 , and ELAM-1 by TNF in MVEC occurred within 6 h and was also completely down-regulated by PAO in a dose-dependent manner .", "target_text": { "ICAM-1": "protein", "VCAM-1": "protein", "ELAM-1": "protein", "TNF": "protein", "MVEC": "cell_line" } }, { "input_text": "PAO was found to be effective even when added 3 h after TNF , suggesting a rapid mode of action of this inhibitor .", "target_text": { "TNF": "protein" } }, { "input_text": "Besides PAO , other inhibitors of PTPase , including pervanadate and diamide , also blocked TNF -dependent NF-kappa B activation and induction of all the three adhesion proteins .", "target_text": { "PTPase": "protein", "TNF": "protein", "NF-kappa B": "protein", "adhesion proteins": "protein" } }, { "input_text": "Consistent with these results , the attachment of monocytes to MVEC was also blocked by the PTPase inhibitors .", "target_text": { "MVEC": "cell_line", "PTPase": "protein" } }, { "input_text": "Thus , overall , our results demonstrate that a PTPase is involved either directly or indirectly in the pathway leading to the induction of endothelial cell adhesion molecules by TNF .", "target_text": { "PTPase": "protein", "adhesion molecules": "protein", "endothelial cell adhesion molecules": "protein", "TNF": "protein" } }, { "input_text": "Because of their role in cell adhesion , PTPase may provide a novel target of drug development for treatment of inflammation , atherogenesis , and tumor metastasis .", "target_text": { "PTPase": "protein" } }, { "input_text": "Regulation of nuclear factor-kappa B and its inhibitor I kappa B-alpha/MAD-3 in monocytes by Mycobacterium tuberculosis and during human tuberculosis .", "target_text": { "nuclear factor-kappa B": "protein", "I kappa B-alpha/MAD-3": "protein", "monocytes": "cell_type" } }, { "input_text": "Blood monocytes from patients with active tuberculosis are activated in vivo , as evidenced by an increase in the stimulated release of proinflammatory cytokines , such as TNF -alpha , and the spontaneous expression of IL-2R .", "target_text": { "Blood monocytes": "cell_type", "proinflammatory cytokines": "protein", "TNF": "protein", "TNF -alpha": "protein", "IL-2R": "protein" } }, { "input_text": "Further , monocytes from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "Mycobacterium tuberculosis and its components are strong signals to activate monocytes to production of cytokines .", "target_text": { "monocytes": "cell_type", "cytokines": "protein" } }, { "input_text": "In this study we examined the basis of activation of monocytes during active tuberculosis and by M. tuberculosis .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "We found a constitutive degradation of I kappa B-alpha , the major cytoplasmic inhibitor of nuclear factor kappa B ( NF-kappa B ) , in freshly isolated PBMC and monocytes from patients with tuberculosis .", "target_text": { "I kappa B-alpha": "protein", "cytoplasmic inhibitor": "protein", "nuclear factor kappa B": "protein", "NF-kappa B": "protein", "PBMC": "cell_type", "monocytes": "cell_type" } }, { "input_text": "In contrast , I kappa B-alpha levels in PBMC and monocytes from healthy subjects or from patients with nontuberculous pulmonary conditions were intact .", "target_text": { "I kappa B-alpha": "protein", "PBMC": "cell_type", "monocytes": "cell_type" } }, { "input_text": "Further , by electrophoretic mobility shift assay , NF-kappa B was activated in monocytes from tuberculous patients .", "target_text": { "NF-kappa B": "protein", "monocytes": "cell_type" } }, { "input_text": "The expression of I kappa B-alpha gene , which is responsive to activation by NF-kappa B , was up-regulated in PBMC and monocytes from patients , but not in mononuclear cells from healthy subjects or those with nontuberculous lung diseases .", "target_text": { "I kappa B-alpha": "protein", "NF-kappa B": "protein", "PBMC": "cell_type", "monocytes": "cell_type", "mononuclear cells": "cell_type" } }, { "input_text": "By contrast , the expression of other adherence-associated early genes , such as IL-8 and IL-1 beta , was not up-regulated in PBMC of tuberculous patients .", "target_text": { "adherence-associated early genes": "DNA", "IL-8": "protein", "IL-1 beta": "protein", "PBMC": "cell_type" } }, { "input_text": "Further , M. tuberculosis and its tuberculin , purified protein derivative , induced the degradation of I kappa B-alpha and the expression of I kappa B-alpha mRNA , and purified protein derivative induced the activation of NF-kappa B in monocytes .", "target_text": { "tuberculin": "protein", "purified protein derivative": "protein", "I kappa B-alpha": "protein", "I kappa B-alpha mRNA": "RNA", "NF-kappa B": "protein", "monocytes": "cell_type" } }, { "input_text": "Cooperation of Spi-1/ PU.1 with an activated erythropoietin receptor inhibits apoptosis and Epo -dependent differentiation in primary erythroblasts and induces their Kit ligand-dependent proliferation .", "target_text": { "PU.1": "protein", "Spi-1/ PU.1": "protein", "activated erythropoietin receptor": "protein", "Epo": "protein", "primary erythroblasts": "cell_type" } }, { "input_text": "Spi-1/ PU.1 is a myeloid- and B-cell specific transcription factor which is also involved in Friend virus -induced murine erythroleukemia .", "target_text": { "PU.1": "protein", "Spi-1/ PU.1": "protein", "transcription factor": "protein", "myeloid- and B-cell specific transcription factor": "protein" } }, { "input_text": "The pre-leukemic phase of Friend erythroleukemia results from activation of the erythropoietin receptor ( EpoR ) by the spleen focus forming virus ( SFFV ) envelope glycoprotein , followed by the emergence of leukemic clones characterized by overexpression of Spi-1 and mutation of the p53 tumor suppressor gene .", "target_text": { "erythropoietin receptor": "protein", "EpoR": "protein", "spleen focus forming virus ( SFFV ) envelope glycoprotein": "protein", "Spi-1": "protein", "p53 tumor suppressor gene": "DNA" } }, { "input_text": "We developed a heterologous system to analyze the contribution of these alterations to the induction of primary erythroblast transformation .", "target_text": {} }, { "input_text": "Avian erythroblasts expressing the activated mouse EpoR ( R129C ) differentiated into erythrocytes in response to hEpo .", "target_text": { "Avian erythroblasts": "cell_type", "EpoR": "protein", "activated mouse EpoR ( R129C )": "protein", "erythrocytes": "cell_type", "hEpo": "protein" } }, { "input_text": "Expression of Spi-1 in these cells inhibited this ability to differentiate and rescued the cells from the apoptotic cell death program normally induced upon hEpo withdrawal .", "target_text": { "Spi-1": "protein", "hEpo": "protein" } }, { "input_text": "Although devoid of any effect by itself , a mutant p53 cooperated with Spi-1 and EpoR ( R129C ) to reinforce both phenotypes .", "target_text": { "mutant p53": "protein", "Spi-1": "protein", "EpoR": "protein", "EpoR ( R129C )": "protein" } }, { "input_text": "Analysis of erythroblasts co-expressing Spi-1 and the wild-type mouse EpoR showed that differentiation arrest and inhibition of apoptosis depended on specific cooperation between Spi-1 and EpoR ( R129C ) .", "target_text": { "Spi-1": "protein", "EpoR": "protein", "wild-type mouse EpoR": "protein", "EpoR ( R129C )": "protein" } }, { "input_text": "This cooperation was also required to induce the sustained proliferation of differentiation-blocked erythroblasts in response to ligand activation of the endogenous tyrosine kinase receptor c-Kit .", "target_text": { "differentiation-blocked erythroblasts": "cell_line", "endogenous tyrosine kinase receptor": "protein", "c-Kit": "protein" } }, { "input_text": "These results show that Spi-1/ PU.1 requires signals emanating from specific cytokine and growth factor receptors to affect the survival , proliferation and differentiation control of primary erythroblasts .", "target_text": { "PU.1": "protein", "primary erythroblasts": "cell_type" } }, { "input_text": "They also suggest that the function of Spi-1 /PU.1 in the late phase of Friend leukemia requires specific signaling from the gp55 -modified EpoR generated during the early phase of the disease .", "target_text": { "Spi-1": "protein", "/PU.1": "protein", "Spi-1 /PU.1": "protein", "gp55": "protein", "EpoR": "protein", "gp55 -modified EpoR": "protein" } }, { "input_text": "The role of Rel/ NF-kappa B proteins in viral oncogenesis and the regulation of viral transcription .", "target_text": { "NF-kappa B": "protein", "Rel/ NF-kappa B proteins": "protein" } }, { "input_text": "Rel /NF-kappa B is a ubiquitous transcription factor that consists of multiple polypeptide subunits , and is subject to complex regulatory mechanisms that involve protein-protein interactions , phosphorylation , ubiquitination , proteolytic degradation , and nucleocytoplasmic translocation .", "target_text": { "Rel": "protein", "/NF-kappa B": "protein", "Rel /NF-kappa B": "protein", "transcription factor": "protein", "ubiquitous transcription factor": "protein", "multiple polypeptide subunits": "protein" } }, { "input_text": "The sophisticated control of Rel /NF-kappa B activity is not surprising since this transcription factor is involved in a wide array of cellular responses to extracellular cues , associated with growth , development , apoptosis , and pathogen invasion .", "target_text": { "Rel": "protein", "/NF-kappa B": "protein", "Rel /NF-kappa B": "protein", "transcription factor": "protein" } }, { "input_text": "Thus , it is not unexpected that this versatile cellular homeostatic switch would be affected by a variety of viral pathogens , which have evolved mechanisms to utilize various aspects of Rel /NF-kappa B activity to facilitate their replication , cell survival and possibly evasion of immune responses .", "target_text": { "Rel": "protein", "/NF-kappa B": "protein", "Rel /NF-kappa B": "protein" } }, { "input_text": "This review will cover the molecular mechanisms that are utilized by mammalian oncogenic viruses to affect the activity of Rel/ NF-kappa B transcription factors and the role of Rel /NF-kappa B in the regulation of viral gene expression and replication .", "target_text": { "NF-kappa B": "protein", "Rel/ NF-kappa B": "protein", "transcription factors": "protein", "Rel": "protein", "/NF-kappa B": "protein", "Rel /NF-kappa B": "protein" } }, { "input_text": "Cellular and molecular mechanisms of IL-5 synthesis in atopic diseases : a study with allergen-specific human helper T cells .", "target_text": { "IL-5": "protein", "allergen-specific human helper T cells": "cell_line" } }, { "input_text": "BACKGROUND : Cytokines produced by helper T cells are intimately involved in chronic allergic diseases associated with eosinophilic inflammation .", "target_text": { "Cytokines": "protein", "helper T cells": "cell_type" } }, { "input_text": "OBJECTIVE : We investigated the production of IL-5 , a potent growth factor and chemotactic factor for eosinophils , by CD4+ T lymphocytes in patients with asthma .", "target_text": { "IL-5": "protein", "eosinophils": "cell_type", "CD4+ T lymphocytes": "cell_type" } }, { "input_text": "METHODS : Allergen-specific T cell clones and T cell hybridomas were established from the peripheral blood lymphocytes of patients with asthma , and the responses to various stimuli were determined .", "target_text": { "Allergen-specific T cell clones": "cell_line", "T cell hybridomas": "cell_line", "peripheral blood lymphocytes": "cell_type" } }, { "input_text": "RESULTS : After nonspecific stimulation , IL-5 production by CD4+ T cells from both atopic and nonatopic subjects with asthma was significantly enhanced compared with that by cells from healthy controls .", "target_text": { "IL-5": "protein", "CD4+ T cells": "cell_type" } }, { "input_text": "Peripheral blood mononuclear cells from atopic asthma patients both proliferated and produced IL-5 after incubation with mite allergen , suggesting that mite-specific helper T cells were involved in the eosinophilic inflammation of atopic asthma .", "target_text": { "Peripheral blood mononuclear cells": "cell_type", "IL-5": "protein", "helper T cells": "cell_type", "mite-specific helper T cells": "cell_type" } }, { "input_text": "A human IL-5 promoter/enhancer luciferase gene construct transfected into IL-5 -producing T cell clones was clearly transcribed after stimulation , indicating that the 515 base pair IL-5 gene segment upstream of the coding region was sufficient to respond to activating signals in human helper T cells .", "target_text": { "IL-5": "protein", "IL-5 promoter/enhancer luciferase gene construct": "DNA", "IL-5 -producing T cell clones": "cell_line", "IL-5 gene segment": "DNA", "helper T cells": "cell_type" } }, { "input_text": "The same gene segment was not transcribed in IL-5 -nonproducing T cell clones , suggesting that human T cell IL-5 synthesis is regulated at the transcriptional level .", "target_text": { "IL-5": "protein", "IL-5 -nonproducing T cell clones": "cell_line" } }, { "input_text": "Experiments with T cell hybridomas confirmed these findings and suggested that a unique transcription factor may be essential for human IL-5 gene transcription .", "target_text": { "T cell hybridomas": "cell_line", "unique transcription factor": "protein", "IL-5": "protein" } }, { "input_text": "CONCLUSION : Enhanced IL-5 production by helper T cells seems to cause the eosinophilic inflammation of both atopic and nonatopic asthma .", "target_text": { "IL-5": "protein", "helper T cells": "cell_type" } }, { "input_text": "Elucidation of IL-5 -specific regulatory mechanisms may facilitate the development of novel treatments for allergic diseases associated with eosinophilic inflammation .", "target_text": { "IL-5": "protein" } }, { "input_text": "Cyclosporin A inhibits monocyte tissue factor activation in cardiac transplant recipients .", "target_text": { "tissue factor": "protein" } }, { "input_text": "BACKGROUND : Fibrin deposition and thrombosis have been implicated in both allograft rejection and vasculopathy after cardiac transplantation .", "target_text": {} }, { "input_text": "Because monocytes play a pivotal role in the pathophysiology of intravascular coagulation activation through their ability to synthesize tissue factor ( TF ) , we asked ( 1 ) whether monocyte TF activation occurs in cardiac transplant recipients and ( 2 ) whether monocyte TF expression is affected by treatment with cyclosporin A ( CsA ) .", "target_text": { "monocytes": "cell_type", "tissue factor": "protein", "TF": "protein" } }, { "input_text": "METHODS AND RESULTS : We measured levels of TF activity in peripheral blood mononuclear cells and highly purified monocytes /macrophages from 10 consecutive cardiac transplant recipients and 10 healthy control subjects .", "target_text": { "TF": "protein", "peripheral blood mononuclear cells": "cell_type", "monocytes": "cell_type", "highly purified monocytes /macrophages": "cell_type" } }, { "input_text": "TF activity generated by both unstimulated and endotoxin-stimulated cells was significantly higher in transplant recipients than in control subjects ( P < .05 ) .", "target_text": { "TF": "protein", "unstimulated": "cell_line", "endotoxin-stimulated cells": "cell_line" } }, { "input_text": "Increased monocyte TF expression in transplant recipients was shown to be adversely affected by treatment with CsA : TF induction was markedly reduced by CsA serum concentrations reaching peak CsA drug levels .", "target_text": { "TF": "protein" } }, { "input_text": "Inhibition of TF induction in the presence of high CsA blood concentrations was also observed when stimulation of cells was performed with interferon-gamma or interleukin-1beta .", "target_text": { "TF": "protein", "interferon-gamma": "protein", "interleukin-1beta": "protein" } }, { "input_text": "As shown by reverse transcription-polymerase chain reaction and electrophoretic mobility shift assay , respectively , treatment with CsA leads to decreased TF mRNA expression and reduced activation of the NF-kappaB transcription factor , which is known to contribute to the induction of the TF promotor in human monocytes .", "target_text": { "TF": "protein", "TF mRNA": "RNA", "NF-kappaB": "protein", "NF-kappaB transcription factor": "protein", "TF promotor": "DNA", "monocytes": "cell_type", "human monocytes": "cell_type" } }, { "input_text": "CONCLUSIONS : This study demonstrates that TF activation , occurring in mononuclear cells of cardiac transplant recipients , is inhibited by treatment with CsA .", "target_text": { "TF": "protein", "mononuclear cells": "cell_type" } }, { "input_text": "Inhibition of monocyte TF induction by CsA may contribute to its successful use in cardiac transplant medicine and might be useful in managing further settings of vascular pathology also known to involve TF expression and NF-kappaB activation .", "target_text": { "TF": "protein", "NF-kappaB": "protein" } }, { "input_text": "IL-2 and IL-7 induce heterodimerization of STAT5 isoforms in human peripheral blood T lymphoblasts .", "target_text": { "IL-2": "protein", "IL-7": "protein", "STAT5 isoforms": "protein", "human peripheral blood T lymphoblasts": "cell_type" } }, { "input_text": "Despite differences in T cell responses induced by interleukin ( IL ) -2 and IL-7 , both cytokines modulate T cell functions by activation of signal transducers and activators of transcription ( STAT ) proteins .", "target_text": { "interleukin ( IL ) -2": "protein", "IL-7": "protein", "cytokines": "protein", "signal transducers and activators of transcription ( STAT ) proteins": "protein" } }, { "input_text": "We examined the contribution of the two isoforms of STAT5 , STAT5A and STAT5B , to IL-2- and IL-7- induced activation of human peripheral blood T lymphoblasts .", "target_text": { "STAT5": "protein", "STAT5A": "protein", "STAT5B": "protein", "human peripheral blood T lymphoblasts": "cell_type" } }, { "input_text": "Both cytokines induced assembly of STAT5A and STAT5B containing complexes capable of binding to the interferon-gamma activation sequence ( GAS ) , and these complexes rapidly translocated ( within 1 min ) into the nucleus of IL-2- or IL-7- treated cells .", "target_text": { "cytokines": "protein", "STAT5A": "protein", "STAT5B": "protein", "interferon-gamma": "protein", "interferon-gamma activation sequence": "DNA", "GAS": "DNA" } }, { "input_text": "The kinetics of this translocation were delayed in IL-7 -treated as compared to IL-2 -treated cells .", "target_text": { "IL-7": "protein", "IL-7 -treated": "cell_line", "IL-2": "protein", "IL-2 -treated cells": "cell_line" } }, { "input_text": "IL-2 and IL-7 were equivalent in their ability to induce tyrosine phosphorylation of STAT5A and STAT5B and to facilitate binding of these STATs to an immobilized GAS element .", "target_text": { "IL-2": "protein", "IL-7": "protein", "STAT5A": "protein", "STAT5B": "protein", "STATs": "protein", "immobilized GAS element": "DNA" } }, { "input_text": "Both IL-2 and IL-7 induced substantial amounts of STAT5A /STAT5B heterodimerization .", "target_text": { "IL-2": "protein", "IL-7": "protein", "STAT5A": "protein", "/STAT5B": "protein" } }, { "input_text": "Moreover , we observed constitutive association of STAT3 with each STAT5 isomer .", "target_text": { "STAT3": "protein", "STAT5 isomer": "protein" } }, { "input_text": "These data suggest that IL-2 and IL-7 induce assembly of STAT heterodimers in a similar manner and that subsequent cellular responses may be driven by induction of similar sets of genes .", "target_text": { "IL-2": "protein", "IL-7": "protein", "STAT heterodimers": "protein", "genes": "DNA" } }, { "input_text": "Transcription factor NF-kappaB regulates inducible Oct-2 gene expression in precursor B lymphocytes .", "target_text": { "Transcription factor": "protein", "NF-kappaB": "protein", "Oct-2": "protein", "Oct-2 gene": "DNA", "precursor B lymphocytes": "cell_type" } }, { "input_text": "The POU transcription factors Oct-1 and Oct-2 regulate the activity of octamer-dependent promoters , including those that direct transcription from rearranged immunoglobulin genes .", "target_text": { "POU transcription factors": "protein", "Oct-1": "protein", "Oct-2": "protein", "octamer-dependent promoters": "DNA", "immunoglobulin genes": "protein" } }, { "input_text": "Unlike Oct-1 , which is constitutively expressed in many cell types , Oct-2 expression is restricted primarily to B lymphocytes and can be induced in precursor B cells by stimulation with bacterial lipopolysaccharide ( LPS ) .", "target_text": { "Oct-1": "protein", "Oct-2": "protein", "B lymphocytes": "cell_type", "precursor B cells": "cell_type" } }, { "input_text": "However , the precise factors that mediate this induction mechanism remain unknown .", "target_text": {} }, { "input_text": "In the present study , we monitored Oct-2 expression in cells arrested for the activation of NF-kappaB , an LPS -responsive member of the Rel transcription factor family .", "target_text": { "Oct-2": "protein", "NF-kappaB": "protein", "LPS -responsive member": "protein", "Rel transcription factor family": "protein" } }, { "input_text": "Despite stimulation with LPS , disruption of the NF-kappaB signaling pathway in precursor B cells led to the loss of inducible Oct-2 DNA binding activity in vitro and the suppression of Oct-2 -directed transcription in vivo .", "target_text": { "NF-kappaB": "protein", "precursor B cells": "cell_type", "Oct-2": "protein" } }, { "input_text": "This biochemical defect correlated with a specific block to Oct-2 gene expression at the level of transcription , whereas the expression of Oct-1 was unaffected .", "target_text": { "Oct-2": "protein", "Oct-2 gene": "DNA", "Oct-1": "protein" } }, { "input_text": "The finding that Oct-2 is under NF-kappaB control highlights an important cross-talk mechanism involving two distinct transcription factor families that regulate B lymphocyte function .", "target_text": { "Oct-2": "protein", "NF-kappaB": "protein", "transcription factor families": "protein", "B lymphocyte": "cell_type" } }, { "input_text": "Suppression of MHC class II expression by human class II trans-activator constructs lacking the N-terminal domain .", "target_text": { "MHC class II": "protein", "human class II trans-activator constructs": "DNA", "N-terminal domain": "protein" } }, { "input_text": "The class II trans-activator ( CIITA ) is a bi- or multi-functional domain protein which plays a critical role in the expression of MHC class II genes .", "target_text": { "class II trans-activator": "protein", "CIITA": "protein", "bi- or multi-functional domain protein": "protein", "MHC class II genes": "DNA" } }, { "input_text": "We report that removal of the N-terminal 151 amino acids , encompassing all of the acidic domain but leaving intact the proline / serine / threonine -rich domain , results in a mutant protein with potent suppressive properties for MHC class II expression .", "target_text": { "N-terminal 151 amino acids": "protein", "acidic domain": "protein", "proline / serine / threonine -rich domain": "protein", "MHC class II": "protein" } }, { "input_text": "HeLa cells stably or transiently transfected with mutant CIITA constructs showed up to 99 % suppression of MHC class II antigen induction by IFN-gamma and marked suppression of HLA-DRA mRNA expression .", "target_text": { "HeLa cells": "cell_line", "CIITA": "protein", "mutant CIITA constructs": "DNA", "MHC class II": "protein", "IFN-gamma": "protein", "HLA-DRA mRNA": "RNA" } }, { "input_text": "Transient transfection of a B lymphoma line resulted in up to 89 % reduction of constitutive MHC class II expression within 5 days and suppression of HLA-DRA mRNA synthesis .", "target_text": { "MHC class II": "protein", "HLA-DRA mRNA": "RNA" } }, { "input_text": "Helenalin , an anti-inflammatory sesquiterpene lactone from Arnica , selectively inhibits transcription factor NF-kappaB [ see comments ]", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "Alcoholic extracts prepared form Arnicae flos , the collective name for flowerheads from Arnica montana and A. chamissonis ssp. foliosa , are used therapeutically as anti-inflammatory remedies .", "target_text": {} }, { "input_text": "The active ingredients mediating the pharmacological effect are mainly sesquiterpene lactones , such as helenalin , 11alpha,13-dihydrohelenalin , chamissonolid and their ester derivatives .", "target_text": {} }, { "input_text": "While these compounds affect various cellular processes , current data do not fully explain how sesquiterpene lactones exert their anti-inflammatory effect .", "target_text": {} }, { "input_text": "We show here that helenalin , and , to a much lesser degree , 11alpha,13-dihydrohelenalin and chamissonolid , inhibit activation of transcription factor NF-kappaB .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "This difference in efficacy , which correlates with the compounds ' anti-inflammatory potency in vivo , may be explained by differences in structure and conformation .", "target_text": {} }, { "input_text": "NF-kappaB , which resides in an inactive , cytoplasmic complex in unstimulated cells , is activated by phosphorylation and degradation of its inhibitory subunit , IkappaB .", "target_text": { "NF-kappaB": "protein", "cytoplasmic complex": "protein", "unstimulated cells": "cell_line", "inhibitory subunit": "protein", "IkappaB": "protein" } }, { "input_text": "Helenalin inhibits NF-kappaB activation in response to four different stimuli in T-cells , B-cells and epithelial cells and abrogates kappaB -driven gene expression .", "target_text": { "NF-kappaB": "protein", "T-cells": "cell_type", "B-cells": "cell_type", "epithelial cells": "cell_type", "kappaB": "protein" } }, { "input_text": "This inhibition is selective , as the activity of four other transcription factors , Oct-1 , TBP , Sp1 and STAT 5 was not affected .", "target_text": { "transcription factors": "protein", "Oct-1": "protein", "TBP": "protein", "Sp1": "protein", "STAT 5": "protein" } }, { "input_text": "We show that inhibition is not due to a direct modification of the active NF-kappaB heterodimer .", "target_text": { "NF-kappaB": "protein", "NF-kappaB heterodimer": "protein" } }, { "input_text": "Rather , helenalin modifies the NF-kappaB/ IkappaB complex , preventing the release of IkappaB .", "target_text": { "IkappaB": "protein", "NF-kappaB/ IkappaB complex": "protein" } }, { "input_text": "These data suggest a molecular mechanism for the anti-inflammatory effect of sesquiterpene lactones , which differs from that of other nonsteroidal anti-inflammatory drugs ( NSAIDs ) , indomethacin and acetyl salicylic acid .", "target_text": {} }, { "input_text": "The tax protein of human T-cell leukemia virus type 1 mediates the transactivation of the c-sis/platelet-derived growth factor-B promoter through interactions with the zinc finger transcription factors Sp1 and NGFI-A/Egr-1 .", "target_text": { "tax protein": "protein", "c-sis/platelet-derived growth factor-B promoter": "DNA", "transcription factors": "protein", "zinc finger transcription factors": "protein", "Sp1": "protein", "NGFI-A/Egr-1": "protein" } }, { "input_text": "Transcriptional up-regulation of the c-sis/platelet-derived growth factor-B ( PDGF-B ) proto-oncogene by the Tax protein of human T-cell leukemia virus type 1 has been implicated as one possible mechanism of cellular transformation by human T-cell leukemia virus type 1 .", "target_text": { "c-sis/platelet-derived growth factor-B": "protein", "PDGF-B": "protein", "c-sis/platelet-derived growth factor-B ( PDGF-B ) proto-oncogene": "DNA", "Tax protein": "protein" } }, { "input_text": "In previous work , we identified an essential site in the c-sis/PDGF-B promoter , Tax-responsive element 1 ( TRE1 ) , necessary for transactivation by Tax .", "target_text": { "c-sis/PDGF-B": "protein", "c-sis/PDGF-B promoter": "DNA", "Tax-responsive element 1": "DNA", "TRE1": "DNA", "Tax": "protein" } }, { "input_text": "We also identified Sp1 , Sp3 , and NGFI-A/Egr-1 as the primary nuclear transcription factors binding to TRE1 which mediate Tax responsiveness .", "target_text": { "Sp1": "protein", "NGFI-A/Egr-1": "protein", "transcription factors": "protein", "primary nuclear transcription factors": "protein", "TRE1": "DNA", "Tax": "protein" } }, { "input_text": "In the present work , we have investigated the mechanism ( s ) whereby Tax transactivates the c-sis/PDGF-B proto-oncogene .", "target_text": { "Tax": "protein", "c-sis/PDGF-B": "protein", "c-sis/PDGF-B proto-oncogene": "DNA" } }, { "input_text": "In vitro transcription assays showed that Tax was able to significantly increase the transcriptional activity of a template containing the -257 to +74 region of the c-sis/PDGF-B promoter .", "target_text": { "Tax": "protein", "-257 to +74 region": "DNA", "c-sis/PDGF-B": "protein", "c-sis/PDGF-B promoter": "DNA" } }, { "input_text": "Electrophoretic mobility shift assay analysis showed that Tax increased the DNA binding activity of both Sp1 and NGFI-A/Egr-1 using a TRE1 probe .", "target_text": { "Tax": "protein", "Sp1": "protein", "NGFI-A/Egr-1": "protein", "TRE1": "DNA", "TRE1 probe": "DNA" } }, { "input_text": "Analysis of Tax mutants showed that two mutants , IEXC29S and IEXL320G , were unable to significantly transactivate the c-sis/PDGF-B promoter .", "target_text": { "Tax": "protein", "Tax mutants": "protein", "IEXC29S": "protein", "IEXL320G": "protein", "c-sis/PDGF-B": "protein", "c-sis/PDGF-B promoter": "DNA" } }, { "input_text": "Finally , co-immunoprecipitation analysis revealed that Tax is able to stably bind to both Sp1 and NGFI-A/Egr-1 .", "target_text": { "Tax": "protein", "Sp1": "protein", "NGFI-A/Egr-1": "protein" } }, { "input_text": "Interestingly , co-immunoprecipitation analysis also revealed that Tax mutant IEXC29S is unable to interact with NGFI-A/Egr-1 , whereas Tax mutant IEXL320G is able to interact with NGFI-A/Egr-1 .", "target_text": { "Tax": "protein", "IEXC29S": "protein", "NGFI-A/Egr-1": "protein", "IEXL320G": "protein" } }, { "input_text": "Nuclear localization of RelB is associated with effective antigen-presenting cell function .", "target_text": { "RelB": "protein" } }, { "input_text": "Dendritic cells ( DC ) are potent APCs that enter resting tissues as precursors and , after Ag exposure , differentiate and migrate to draining lymph nodes .", "target_text": { "Dendritic cells": "cell_type", "DC": "cell_type", "APCs": "cell_type" } }, { "input_text": "The phenotype of RelB knockout mice implicates this member of the NF kappa B/Rel family in DC differentiation .", "target_text": { "RelB": "protein", "NF kappa B/Rel family": "protein", "DC": "cell_type" } }, { "input_text": "To further elucidate the role of RelB in DC differentiation , mRNA , intracellular protein expression , and DNA binding activity of RelB were examined in immature and differentiated human DC , as well as other PB mononuclear cell populations .", "target_text": { "RelB": "protein", "DC": "cell_type", "mRNA": "RNA", "human DC": "cell_type", "PB mononuclear cell populations": "cell_type" } }, { "input_text": "RelB protein and mRNA were detected constitutively in lymphocytes and in activated monocytes , differentiated DC , and monocyte-derived DC .", "target_text": { "RelB": "protein", "mRNA": "RNA", "lymphocytes": "cell_type", "activated monocytes": "cell_type", "DC": "cell_type", "differentiated DC": "cell_type", "monocyte-derived DC": "cell_line" } }, { "input_text": "Immunohistochemical staining demonstrated RelB within the differentiated lymph node interdigitating DC and follicular DC , but not undifferentiated DC in normal skin .", "target_text": { "RelB": "protein", "DC": "cell_type", "differentiated lymph node interdigitating DC": "cell_type", "follicular DC": "cell_type", "undifferentiated DC": "cell_type" } }, { "input_text": "Active nuclear RelB was detected by supershift assay only in differentiated DC derived from either PB precursors or monocytes and in activated B cells .", "target_text": { "RelB": "protein", "DC": "cell_type", "PB precursors": "cell_type", "monocytes": "cell_type", "activated B cells": "cell_type" } }, { "input_text": "These RelB + APC were potent stimulators of the MLR .", "target_text": { "RelB": "protein", "RelB + APC": "cell_type", "MLR": "protein" } }, { "input_text": "The data indicate that RelB expression is regulated both transcriptionally and post-translationally in myeloid cells .", "target_text": { "RelB": "protein", "myeloid cells": "cell_type" } }, { "input_text": "Within the nucleus , RelB may specifically transactivate genes that are critical for APC function .", "target_text": { "RelB": "protein", "APC": "cell_type" } }, { "input_text": "NF-AT activation induced by a CAML -interacting member of the tumor necrosis factor receptor superfamily .", "target_text": { "NF-AT": "protein", "CAML": "protein", "tumor necrosis factor receptor superfamily": "protein" } }, { "input_text": "Activation of the nuclear factor of activated T cells transcription factor ( NF-AT ) is a key event underlying lymphocyte action .", "target_text": { "nuclear factor of activated T cells": "protein", "transcription factor": "protein", "NF-AT": "protein" } }, { "input_text": "The CAML ( calcium-modulator and cyclophilin ligand ) protein is a coinducer of NF-AT activation when overexpressed in Jurkat T cells .", "target_text": { "CAML ( calcium-modulator and cyclophilin ligand ) protein": "protein", "NF-AT": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "A member of the tumor necrosis factor receptor superfamily was isolated by virtue of its affinity for CAML .", "target_text": { "tumor necrosis factor receptor superfamily": "protein", "CAML": "protein" } }, { "input_text": "Cross-linking of this lymphocyte-specific protein , designated TACI ( transmembrane activator and CAML -interactor ) , on the surface of transfected Jurkat cells with TACI -specific antibodies led to activation of the transcription factors NF-AT , AP-1 , and NFkappaB .", "target_text": { "lymphocyte-specific protein": "protein", "TACI": "protein", "CAML": "protein", "transmembrane activator and CAML -interactor": "protein", "transfected Jurkat cells": "cell_line", "TACI -specific antibodies": "protein", "transcription factors": "protein", "NF-AT": "protein", "AP-1": "protein", "NFkappaB": "protein" } }, { "input_text": "TACI -induced activation of NF-AT was specifically blocked by a dominant-negative CAML mutant , thus implicating CAML as a signaling intermediate .", "target_text": { "TACI": "protein", "NF-AT": "protein", "CAML": "protein", "dominant-negative CAML mutant": "protein" } }, { "input_text": "Rel/NF-kappa B transcription factors and the control of apoptosis .", "target_text": { "Rel/NF-kappa B": "protein", "transcription factors": "protein" } }, { "input_text": "The process of apoptosis is used to eliminate unwanted cells from a wide variety of organisms .", "target_text": { "unwanted cells": "cell_type" } }, { "input_text": "Various extracellular signals , often converging in common intracellular pathways , can induce apoptosis in a cell-type-specific fashion .", "target_text": {} }, { "input_text": "Recent work from several laboratories has demonstrated that Rel/NF-kappa B transcription factors regulate apoptosis in many cell types .", "target_text": { "Rel/NF-kappa B": "protein", "transcription factors": "protein" } }, { "input_text": "In most cells , Rel/NF-kappa B transcription factors appear to mediate survival signals that protect cells from apoptosis ; however , under some circumstances , activation of these factors may also promote apoptosis .", "target_text": { "Rel/NF-kappa B": "protein", "transcription factors": "protein" } }, { "input_text": "A thiol antioxidant regulates IgE isotype switching by inhibiting activation of nuclear factor-kappaB .", "target_text": { "IgE isotype": "protein", "nuclear factor-kappaB": "protein" } }, { "input_text": "The binding site for nuclear factor-kappaB ( NF-kappaB ) is present at the promoter region of the germline Cepsilon gene , but there is little information on whether this factor is involved in regulating IgE synthesis by human B cells .", "target_text": { "binding site": "DNA", "nuclear factor-kappaB": "protein", "NF-kappaB": "protein", "promoter region": "DNA", "germline Cepsilon gene": "DNA", "IgE": "protein", "human B cells": "cell_type" } }, { "input_text": "Accordingly , we studied the role of NF-kappaB in germline Cepsilon transcription by using two human Burkitt 's lymphoma B cell lines , DND39 and DG75 .", "target_text": { "NF-kappaB": "protein", "germline": "DNA", "human Burkitt 's lymphoma B cell lines": "cell_line", "DND39": "cell_line", "DG75": "cell_line" } }, { "input_text": "In both cell lines , n-acetyl-L-cysteine ( NAC ) , a potent thiol antioxidant , inhibited the triggering of the nuclear expression of NF-kappaB by IL-4 and by anti-CD40 monoclonal antibody .", "target_text": { "cell lines": "cell_line", "NF-kappaB": "protein", "IL-4": "protein", "anti-CD40 monoclonal antibody": "protein" } }, { "input_text": "Although IL-4 activated signal transducers and activators of transcription ( STAT ) 6 in addition to NF-kappaB , NAC treatment or the transfection of decoy oligodeoxynucleotides for NF-kappaB or STAT6 only partly blocked IL-4 -induced germline Cepsilon transcription .", "target_text": { "IL-4": "protein", "signal transducers and activators of transcription ( STAT ) 6": "protein", "NF-kappaB": "protein", "STAT6": "protein", "germline": "DNA" } }, { "input_text": "However , these two decoy oligodeoxynucleotides together almost completely abrogated IL-4 -induced germline Cepsilon transcription .", "target_text": { "IL-4": "protein", "germline": "DNA" } }, { "input_text": "Of note , CD40 -mediated enhancement of IL-4 -driven germline Cepsilon transcription was markedly decreased by NAC or by a decoy oligodeoxynucleotide for NF-kappaB .", "target_text": { "CD40": "protein", "IL-4": "protein", "germline": "DNA", "NF-kappaB": "protein" } }, { "input_text": "The effect of NAC was also examined on deletional switch recombination underlying the isotype switch to IgE .", "target_text": { "IgE": "protein" } }, { "input_text": "NAC inhibited the generation of Smu/Sepsilon switch fragments in normal human B cells costimulated with IL-4 and anti-CD40 monoclonal antibody .", "target_text": { "Smu/Sepsilon switch fragments": "protein", "human B cells": "cell_type", "IL-4": "protein", "anti-CD40 monoclonal antibody": "protein" } }, { "input_text": "It also abolished IL-4 -induced upregulation of CD40 but promoted upregulation of CD23 .", "target_text": { "IL-4": "protein", "CD40": "protein" } }, { "input_text": "These results suggest that coordination of NF-kappaB and STAT6 may be required for induction of germline Cepsilon transcription by IL-4 , and that CD40 -mediated NF-kappaB activation may be important in regulating both enhancement of germline Cepsilon transcription and class switching to IgE .", "target_text": { "NF-kappaB": "protein", "STAT6": "protein", "germline": "DNA", "IL-4": "protein", "CD40": "protein", "IgE": "protein" } }, { "input_text": "Pathogenesis .", "target_text": {} }, { "input_text": "There are many hypotheses concerning the pathogenesis of endometriosis , though no single theory can explain all cases .", "target_text": {} }, { "input_text": "It is likely that several mechanisms are involved .", "target_text": {} }, { "input_text": "Early studies concentrated on the histogenesis of the endometriotic lesion .", "target_text": {} }, { "input_text": "Recent evidence has implicated components of the immune system in the pathogenesis of endometriosis .", "target_text": {} }, { "input_text": "This review considers the evidence for different theories of the histogenesis of endometriosis and discusses possible immune factors that may be involved in the pathophysiology of the disease .", "target_text": {} }, { "input_text": "ATF1 and CREB trans-activate a cell cycle regulated histone H4 gene at a distal nuclear matrix associated promoter element .", "target_text": { "ATF1": "protein", "CREB": "protein", "histone H4": "protein", "cell cycle regulated histone H4 gene": "DNA", "distal nuclear matrix associated promoter element": "DNA" } }, { "input_text": "Proteins of the ATF/ CREB class of transcription factors stimulate gene expression of several cell growth-related genes through protein kinase A-related cAMP response elements .", "target_text": { "CREB": "protein", "transcription factors": "protein", "cell growth-related genes": "DNA", "protein kinase A-related cAMP response elements": "DNA" } }, { "input_text": "The promoter activity of cell cycle regulated histone H4 genes is regulated by at least four principal cis-acting elements which mediate G1/S phase control and/or enhancement of transcription during the cell cycle .", "target_text": { "cell cycle regulated histone H4 genes": "DNA", "principal cis-acting elements": "DNA" } }, { "input_text": "Using protein-DNA interaction assays we show that the H4 promoter contains two ATF/ CREB recognition motifs which interact with CREB , ATF1 , and ATF2 but not with ATF4/CREB2 .", "target_text": { "H4 promoter": "DNA", "CREB": "protein", "ATF1": "protein", "ATF2": "protein", "ATF4/CREB2": "protein" } }, { "input_text": "One ATF/CRE motif is located in the distal promoter at the nuclear matrix-associated Site IV , and the second motif is present in the proximal promoter at Site I .", "target_text": { "ATF/CRE motif": "DNA", "distal promoter": "DNA", "nuclear matrix-associated Site IV": "DNA", "proximal promoter": "DNA", "Site I": "DNA" } }, { "input_text": "Both ATF/CRE motifs overlap binding sequences for the multifunctional YY1 transcription factor , which has previously been shown to be nuclear matrix associated .", "target_text": { "ATF/CRE motifs": "DNA", "binding sequences": "DNA", "multifunctional YY1 transcription factor": "protein" } }, { "input_text": "Subnuclear fractionation reveals that there are two ATF1 isoforms which appear to differ with respect to DNA binding activity and partition selectively between nuclear matrix and nonmatrix compartments , consistent with the role of the nuclear matrix in regulating gene expression .", "target_text": { "ATF1": "protein", "ATF1 isoforms": "protein" } }, { "input_text": "Site-directed mutational studies demonstrate that Site I and Site IV together support ATF1- and CREB- induced trans-activation of the H4 promoter .", "target_text": { "Site I": "DNA", "Site IV": "DNA", "H4 promoter": "DNA" } }, { "input_text": "Thus , our data establish that ATF/CREB factors functionally modulate histone H4 gene transcription at distal and proximal promoter elements .", "target_text": { "ATF/CREB factors": "protein", "histone H4 gene": "DNA" } }, { "input_text": "Is celiac disease due to molecular mimicry between gliadin peptide -HLA class II molecule -T cell interactions and those of some unidentified superantigen ?", "target_text": { "-HLA class II molecule": "protein", "unidentified superantigen": "protein" } }, { "input_text": "This paper presents a new hypothesis for the etiology and pathogenesis of celiac disease ( CD ) .", "target_text": {} }, { "input_text": "It is our contention that CD is triggered by the binding of one or more gliadin peptides to CD -associated HLA class II molecules .", "target_text": { "CD -associated HLA class II molecules": "protein" } }, { "input_text": "Furthermore , we propose that these putative CD peptides bind to oligosaccharide residues on HLA class II molecules distal to the peptide-binding groove invoking recognition and binding by specialized subsets of gamma delta T cell receptor-bearing lymphocytes .", "target_text": { "HLA class II molecules": "protein", "peptide-binding groove": "protein", "gamma delta T cell receptor-bearing lymphocytes": "cell_type" } }, { "input_text": "The binding of these gamma delta T cells serves as a signal for abrogation of oral tolerance to ingested proteins setting in motion a series of immune responses directed against the small intestinal epithelium of CD patients .", "target_text": { "gamma delta T cells": "cell_type", "ingested proteins": "protein" } }, { "input_text": "CD patients are victimized by this self-distructed immune response because of inheritance of certain combinations of HLA-DQ and DR haplotypes .", "target_text": {} }, { "input_text": "Dimers encoded by HLA-DR haplotypes may be the primary restriction elements for lectin-like , gliadin peptides while the degree of immune suppression ( or lack thereof ) to ingested gliadins is governed by inherited HLA-DQ haplotypes .", "target_text": { "HLA-DR": "protein", "primary restriction elements": "DNA", "HLA-DQ": "DNA" } }, { "input_text": "Finally , we speculate that molecular mimicry between one or more gliadin peptides and some , as yet unidentified , bacterial or viral superantigen plays a role in disease pathogenesis .", "target_text": {} }, { "input_text": "Epstein-Barr virus latent membrane protein-1 triggers AP-1 activity via the c-Jun N-terminal kinase cascade .", "target_text": { "latent membrane protein-1": "protein", "AP-1": "protein", "c-Jun": "protein" } }, { "input_text": "The Epstein-Barr virus latent membrane protein-1 ( LMP-1 ) is an integral membrane protein which transforms fibroblasts and is essential for EBV-mediated B-cell immortalization .", "target_text": { "latent membrane protein-1": "protein", "LMP-1": "protein", "integral membrane protein": "protein", "fibroblasts": "cell_type" } }, { "input_text": "LMP-1 has been shown to trigger cellular NF-kappa B activity which , however , can not fully explain the oncogenic potential of LMP-1 .", "target_text": { "LMP-1": "protein", "NF-kappa B": "protein" } }, { "input_text": "Here we show that LMP-1 induces the activity of the AP-1 transcription factor , a dimer of Jun/Jun or Jun/Fos proteins .", "target_text": { "LMP-1": "protein", "AP-1": "protein", "AP-1 transcription factor": "protein", "Jun/Jun": "protein", "Jun/Fos": "protein", "Jun/Jun or Jun/Fos proteins": "protein" } }, { "input_text": "LMP-1 effects on AP-1 are mediated through activation of the c-Jun N-terminal kinase ( JNK ) cascade , but not the extracellular signal-regulated kinase ( Erk ) pathway .", "target_text": { "LMP-1": "protein", "AP-1": "protein", "c-Jun": "protein", "JNK": "protein", "extracellular signal-regulated kinase": "protein", "Erk": "protein" } }, { "input_text": "Consequently , LMP-1 triggers the activity of the c-Jun N-terminal transactivation domain which is known to be activated upon JNK -mediated phosphorylation .", "target_text": { "LMP-1": "protein", "c-Jun": "protein", "c-Jun N-terminal transactivation domain": "protein", "JNK": "protein" } }, { "input_text": "Deletion analysis indicates that the 55 C-terminal amino acids of the LMP-1 molecule , but not its TRAF interaction domain , are essential for AP-1 activation .", "target_text": { "C-terminal amino acids": "protein", "LMP-1": "protein", "LMP-1 molecule": "protein", "TRAF interaction domain": "protein", "AP-1": "protein" } }, { "input_text": "JNK -mediated transcriptional activation of AP-1 is the direct output of LMP -1-triggered signaling , as shown by an inducible LMP-1 mutant .", "target_text": { "JNK": "protein", "AP-1": "protein", "LMP": "protein", "LMP-1": "protein", "LMP-1 mutant": "protein" } }, { "input_text": "Using a tetracycline-regulated LMP-1 allele , we demonstrate that JNK is also an effector of non-cytotoxic LMP-1 signaling in B cells , the physiological target cells of EBV .", "target_text": { "LMP-1": "protein", "tetracycline-regulated LMP-1 allele": "DNA", "JNK": "protein", "B cells": "cell_type" } }, { "input_text": "In summary , our data reveal a novel effector of LMP-1 , the SEK/ JNK / c-Jun / AP-1 pathway , which contributes to our understanding of the immortalizing and transforming potential of LMP-1 .", "target_text": { "LMP-1": "protein", "JNK": "protein", "c-Jun": "protein", "AP-1": "protein" } }, { "input_text": "Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water .", "target_text": {} }, { "input_text": "1 . In this study we hypothesized that in individuals with certain genetic makeup , MTBE , benzene or their metabolites act as adducts and may induce programmed cell death .", "target_text": {} }, { "input_text": "2 . Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene -contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene , for a period of 5 to 8 years .", "target_text": {} }, { "input_text": "For comparison , we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene .", "target_text": {} }, { "input_text": "3 . Peripheral blood lymphocytes ( PBL ) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry .", "target_text": { "Peripheral blood lymphocytes": "cell_type", "PBL": "cell_type", "apoptotic cells": "cell_type" } }, { "input_text": "4 . When apoptotic lymphocytes from exposed individuals were compared to apoptotic lymphocytes from the control group , statistically-significant differences between each mean group were detected ( 26.4 +/- 1.8 and 12.1 +/- 1.3 , respectively ) , indicating an increased rate of apoptosis in 80.5 % of exposed individuals ( P < 0.0001 , Mann-Whitney U-Test ) .", "target_text": { "apoptotic lymphocytes": "cell_type" } }, { "input_text": "MTBE and benzene -induced apoptosis is attributed to a discrete block within the cell cycle progression .", "target_text": {} }, { "input_text": "Because cell cycle analysis showed that in PBL from chemically- exposed individuals , between 20-50 % of cells were accumulated at the S-G2/M boundaries .", "target_text": { "PBL": "cell_type" } }, { "input_text": "5 . One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B ( NF-kappa B ) .", "target_text": { "signaling molecules": "protein", "nuclear factor Kappa-B": "protein", "NF-kappa B": "protein" } }, { "input_text": "NF-kappa B was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Indeed , addition of inhibitors of NF-kappa B activation pyrrolidine dithiocarbamate ( PDTC ) , to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40 % .", "target_text": { "NF-kappa B": "protein", "lymphocytes": "cell_type" } }, { "input_text": "This reversal of apoptosis almost to the control level by inhibitor of NF-kappa B activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death .", "target_text": { "NF-kappa B": "protein", "signaling molecule": "protein" } }, { "input_text": "Purification and characterization of the human SR 31747A-binding protein .", "target_text": { "human SR 31747A-binding protein": "protein" } }, { "input_text": "A nuclear membrane protein related to yeast sterol isomerase .", "target_text": { "nuclear membrane protein": "protein", "yeast sterol isomerase": "protein" } }, { "input_text": "SR 31747A , defined as a sigma ligand , is a novel immunosuppressive agent that blocks proliferation of human and mouse lymphocytes .", "target_text": {} }, { "input_text": "Using a radiolabeled chemical probe , we here purified a target of SR 31747A and called it SR 31747A -binding protein ( SR-BP ) .", "target_text": { "SR 31747A -binding protein": "protein", "SR-BP": "protein" } }, { "input_text": "Purified SR-BP retained its binding properties and migrated on SDS-polyacrylamide gel as a Mr 28,000 protein .", "target_text": { "SR-BP": "protein", "Purified SR-BP": "protein", "Mr 28,000 protein": "protein" } }, { "input_text": "Cloning of the cDNA encoding human SR-BP shows an open reading frame for a 223-amino acid protein , which is homologous to the recently cloned sigma 1 receptor .", "target_text": { "cDNA": "DNA", "SR-BP": "protein", "human SR-BP": "protein", "open reading frame": "DNA", "223-amino acid protein": "protein", "sigma 1 receptor": "protein" } }, { "input_text": "Interestingly , the deduced amino acid sequence was found to be related to fungal C8-C7 sterol isomerase , encoded by the ERG2 gene .", "target_text": { "amino acid sequence": "protein", "fungal C8-C7 sterol isomerase": "protein", "ERG2 gene": "DNA" } }, { "input_text": "The ERG2 gene product has been identified recently as the molecular target of SR 31747A that mediates antiproliferative effects of the drug in yeast .", "target_text": { "ERG2 gene": "DNA", "ERG2 gene product": "protein" } }, { "input_text": "Northern blot analysis of SR-BP gene expression revealed a single transcript of 2 kilobases which was widely expressed among organs , with the highest abundance in liver and the lowest abundance in brain .", "target_text": { "SR-BP": "protein", "2 kilobases": "RNA" } }, { "input_text": "Subcellular localization analysis in various cells , using a specific monoclonal antibody raised against SR-BP , demonstrated that this protein was associated with the nuclear envelope .", "target_text": { "specific monoclonal antibody": "protein", "SR-BP": "protein" } }, { "input_text": "When studying the binding of SR 31747A on membranes from yeast expressing SR-BP , we found a pharmacological profile of sigma 1 receptors ; binding was displaced by (+)-pentazocine , haloperidol , and (+)-SKF 10,047 , with (+)-SKF 10, 047 being a more potent competitor than (-)-SKF 10,047 .", "target_text": { "SR-BP": "protein", "sigma 1 receptors": "protein" } }, { "input_text": "Scatchard plot analysis revealed Kd values of 7.1 nM and 0.15 nM for (+)-pentazocine and SR 31747A , respectively , indicating an affinity of SR-BP 50-fold higher for SR 31747A than for pentazocine .", "target_text": { "SR-BP": "protein" } }, { "input_text": "Additionally , we showed that pentazocine , a competitive inhibitor of SR 31747A binding , also prevents the immunosuppressive effect of SR 31747A .", "target_text": {} }, { "input_text": "Taken together , these findings strongly suggest that SR-BP represents the molecular target for SR 31747A in mammalian tissues , which could be critical for T cell proliferation .", "target_text": { "SR-BP": "protein" } }, { "input_text": "Phospholipase C gamma 1 overexpression and activation induced by interferon beta in human T lymphocytes : an ISGF3 -independent response .", "target_text": { "Phospholipase C gamma 1": "protein", "interferon beta": "protein", "human T lymphocytes": "cell_type", "ISGF3": "protein" } }, { "input_text": "Interferons exert their antiviral , antiproliferative and immunoregulatory activities by stimulating the expression of several genes .", "target_text": { "Interferons": "protein", "immunoregulatory": "protein" } }, { "input_text": "Such genes disclose a common element within their promoters , defined Interferon Stimulated Response Element ( ISRE ) , which binds a nuclear factor ( s ) translocated from the cytoplasm to the nucleus ( ISGF3 ) after the binding of interferon ( IFN ) to the specific receptor .", "target_text": { "promoters": "DNA", "Interferon Stimulated Response Element": "DNA", "ISRE": "DNA", "nuclear factor": "protein", "ISGF3": "protein", "interferon": "protein", "IFN": "protein" } }, { "input_text": "Here we report the induction of the synthesis and of the hydrolytic activity of phospholipase C gamma 1 ( PLC gamma 1 ) in human T lymphocytes by IFN-beta .", "target_text": { "phospholipase C gamma 1": "protein", "PLC gamma 1": "protein", "human T lymphocytes": "cell_type", "IFN-beta": "protein" } }, { "input_text": "The increased level of PLC gamma 1 becomes evident after 90 min of IFN-beta treatment and is still detectable after 24 h .", "target_text": { "PLC gamma 1": "protein", "IFN-beta": "protein" } }, { "input_text": "Neither the PLC gamma 1 overexpression induced by IFN nor the increased hydrolytic activity of the enzyme appear to be affected by pretreatment of the cells with the protein tyrosine kinase inhibitor genistein , which is known to prevent the association of ISGF3 components .", "target_text": { "PLC gamma 1": "protein", "IFN": "protein", "enzyme": "protein", "tyrosine kinase": "protein", "ISGF3": "protein" } }, { "input_text": "These results suggest that in human T lymphocytes IFN-beta can activate other transcription factor ( s ) distinct from ISGF3 to regulate PLC gamma 1 expression .", "target_text": { "human T lymphocytes": "cell_type", "IFN-beta": "protein", "transcription factor": "protein", "ISGF3": "protein", "PLC gamma 1": "protein" } }, { "input_text": "In addition , the ability of this enzyme to hydrolyse PIP2 , also in the presence of genistein , implies the possibility that this enzyme can exert its hydrolytic activity independently of protein tyrosine kinase activation .", "target_text": { "enzyme": "protein", "protein tyrosine kinase": "protein" } }, { "input_text": "Negative regulation by HLA-DO of MHC class II -restricted antigen processing .", "target_text": { "HLA-DO": "protein", "MHC class II": "protein" } }, { "input_text": "HLA-DM is a major histocompatibility complex ( MHC ) class II-like molecule that facilitates antigen processing by catalyzing the exchange of invariant chain-derived peptides ( CLIP ) from class II molecules for antigenic peptides .", "target_text": { "HLA-DM": "protein", "major histocompatibility complex ( MHC ) class II-like molecule": "protein", "class II molecules": "protein" } }, { "input_text": "HLA-DO is a second class II-like molecule that physically associates with HLA-DM in B cells .", "target_text": { "HLA-DO": "protein", "class II-like molecule": "protein", "HLA-DM": "protein", "B cells": "cell_type" } }, { "input_text": "HLA-DO was shown to block HLA-DM function .", "target_text": { "HLA-DO": "protein", "HLA-DM": "protein" } }, { "input_text": "Purified HLA-DM -DO complexes could not promote peptide exchange in vitro .", "target_text": { "HLA-DM": "protein", "HLA-DM -DO complexes": "protein" } }, { "input_text": "Expression of HLA-DO in a class II+ and DM+ , DO- human T cell line caused the accumulation of class II- CLIP complexes , indicating that HLA-DO blocked DM function in vivo and suggesting that HLA-DO is an important modulator of class II-restricted antigen processing .", "target_text": { "HLA-DO": "protein", "class II+ and DM+ , DO- human T cell line": "cell_line", "class II- CLIP complexes": "protein" } }, { "input_text": "Vitamin D receptor : no evidence for allele-specific mRNA stability in cells which are heterozygous for the Taq I restriction enzyme polymorphism .", "target_text": { "Vitamin D receptor": "protein", "Taq I restriction enzyme": "protein" } }, { "input_text": "Allelic variations of the vitamin D receptor ( VDR ) gene have been associated with the risk of developing prostate cancer in men and osteoporosis in postmenopausal women .", "target_text": { "vitamin D receptor": "protein", "VDR": "protein", "vitamin D receptor ( VDR ) gene": "DNA" } }, { "input_text": "Three RFLPs ( TaqI , ApaI , BsmI ) define two common haplotypes : BAt and baT .", "target_text": { "RFLPs": "DNA", "TaqI": "DNA", "ApaI": "DNA", "BsmI": "DNA" } }, { "input_text": "None of these polymorphisms change the translated protein .", "target_text": { "polymorphisms": "DNA", "translated protein": "protein" } }, { "input_text": "Since sequence variations in the 3' UTR of VDR have been linked to the different haplotypes , investigators have proposed that the stability of VDR mRNA is influenced by allelic variations .", "target_text": { "sequence variations": "DNA", "3' UTR": "DNA", "VDR": "protein", "VDR mRNA": "RNA" } }, { "input_text": "Indirect evidence suggested that allele T is less stable than allele t .", "target_text": { "allele T": "DNA", "allele t": "DNA" } }, { "input_text": "In this study , we used a RT-PCR based approach to compare the stability of the big T and small t allele in normal heterozygous lymphocytes and the heterozygous cell lines NB4 ( myeloid leukemia ) and PC-3 and DU 145 ( prostate cancers ) .", "target_text": { "normal heterozygous lymphocytes": "cell_type", "heterozygous cell lines": "cell_line", "NB4": "cell_line", "PC-3": "cell_line", "DU 145": "cell_line" } }, { "input_text": "In all three cases , we did not find a significant difference in stability .", "target_text": {} }, { "input_text": "Interestingly , we consistently observed 30 % less RT-PCR product derived from the small t allele mRNA in steady state , a finding which also speaks against a higher stability of the small t allele mRNA .", "target_text": { "RT-PCR product": "DNA", "small t allele mRNA": "RNA" } }, { "input_text": "These results indicate a variation in transcriptional regulation rather than mRNA stability between the alleles .", "target_text": { "alleles": "DNA" } }, { "input_text": "We hypothesize that an unknown gene or genes in linkage with the polymorphisms is ( are ) responsible for the relationship between risk of prostate cancer and VDR polymorphisms .", "target_text": { "polymorphisms": "DNA", "VDR": "protein" } }, { "input_text": "Replication of human immunodeficiency virus-1 in primary human T cells is dependent on the autocrine secretion of tumor necrosis factor through the control of nuclear factor-kappa B activation .", "target_text": { "primary human T cells": "cell_type", "tumor necrosis factor": "protein", "nuclear factor-kappa B": "protein" } }, { "input_text": "Tumor necrosis factor ( TNF ) -alpha controls T-cell activation and is a major inducer of human immunodeficiency virus ( HIV ) -1 replication in chronically infected cells .", "target_text": { "Tumor necrosis factor ( TNF ) -alpha": "protein", "chronically infected cells": "cell_type" } }, { "input_text": "Therefore , we have investigated its role in primary cultures of HIV-infected human T lymphocytes by using neutralizing anti-TNF-alpha antibodies or TNF-alpha .", "target_text": { "HIV-infected human T lymphocytes": "cell_type", "anti-TNF-alpha antibodies": "protein", "TNF-alpha": "protein" } }, { "input_text": "Primary resting T lymphocytes produced TNF-alpha and supported HIV replication after T-cell receptor activation .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "Addition of neutralizing anti- TNF-alpha antibodies drastically reduced p24 antigen release and prevented CD4+ cell depletion associated with infection .", "target_text": { "TNF-alpha": "protein", "anti- TNF-alpha antibodies": "protein", "p24 antigen": "protein", "CD4+": "protein" } }, { "input_text": "Anti- TNF-alpha also prevented nuclear factor-kappa B ( NF-kappa B ) activation , and a good correlation between this inhibition and inhibition of HIV replication was observed .", "target_text": { "TNF-alpha": "protein", "Anti- TNF-alpha": "protein", "nuclear factor-kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "Moreover , supplementing the cultures with high doses of IL-2 reverted anti- TNF-alpha inhibition of cell proliferation but did not affect the inhibition of HIV p24 antigen release or NF-kappa B activation in the same cultures .", "target_text": { "TNF-alpha": "protein", "p24 antigen": "protein", "NF-kappa B": "protein" } }, { "input_text": "Moreover , anti- TNF-alpha inhibited HIV-1 long terminal repeat ( LTR ) -driven transcription of a reporter gene in primary T cells in response to activation , either in the presence or the absence of HIV-1 Tat .", "target_text": { "TNF-alpha": "protein", "anti- TNF-alpha": "protein", "HIV-1 long terminal repeat": "DNA", "LTR": "DNA", "reporter gene": "DNA", "primary T cells": "cell_type", "HIV-1 Tat": "protein" } }, { "input_text": "Our results support an important role for autocrine TNF-alpha secretion in controlling HIV replication in primary T cells because of its ability to maintain NF-kappa B elevated in the nucleus of T cells .", "target_text": { "TNF-alpha": "protein", "primary T cells": "cell_type", "NF-kappa B": "protein", "T cells": "cell_type" } }, { "input_text": "Hypoxia enhances induction of endothelial ICAM-1 : role for metabolic acidosis and proteasomes .", "target_text": { "endothelial ICAM-1": "protein", "proteasomes": "protein" } }, { "input_text": "Intercellular adhesion molecule 1 ( ICAM-1 ) is an important molecule in promotion of polymorphonuclear neutrophil transendothelial migration during inflammation .", "target_text": { "Intercellular adhesion molecule 1": "protein", "ICAM-1": "protein" } }, { "input_text": "Coincident with many inflammatory diseases is tissue hypoxia .", "target_text": {} }, { "input_text": "Thus we hypothesized that combinations of hypoxia and inflammatory stimuli may differentially regulate expression of endothelial ICAM-1 .", "target_text": { "ICAM-1": "protein", "endothelial ICAM-1": "protein" } }, { "input_text": "Human endothelial cells were exposed to hypoxia in the presence or absence of added lipopolysaccharide ( LPS ) and examined for expression of functional ICAM-1 .", "target_text": { "Human endothelial cells": "cell_type", "ICAM-1": "protein" } }, { "input_text": "Although hypoxia alone did not induce ICAM-1 , the combination of LPS and hypoxia enhanced ( 3 +/- 0.4-fold over normoxia ) ICAM-1 expression .", "target_text": { "ICAM-1": "protein" } }, { "input_text": "Combinations of hypoxia and LPS significantly increased lymphocyte binding , and such increases were inhibited by addition of anti- ICAM-1 antibodies or antisense oligonucleotides .", "target_text": { "ICAM-1": "protein", "anti- ICAM-1 antibodies": "protein" } }, { "input_text": "Hypoxic endothelia showed a > 10-fold increase in sensitivity to inhibitors of proteasome activation , and combinations of hypoxia and LPS enhanced proteasome -dependent cytoplasmic-to-nuclear localization of the nuclear transcription factor-kappa B p65 ( Rel A ) subunit .", "target_text": { "proteasome": "protein", "nuclear transcription factor-kappa B p65 ( Rel A ) subunit": "protein" } }, { "input_text": "Such proteasome activation correlated with hypoxia -evoked decreases in both extracellular and intracellular pH .", "target_text": { "proteasome": "protein" } }, { "input_text": "We conclude from these studies that endothelial hypoxia provides a novel , proteasome -dependent stimulus for ICAM-1 induction .", "target_text": { "proteasome": "protein", "ICAM-1": "protein" } }, { "input_text": "Differanisole A , a novel antitumor antibiotic , enhances growth inhibition and differentiation of human myeloid leukemia cells induced by 9-cis retinoic acid .", "target_text": { "human myeloid leukemia cells": "cell_type" } }, { "input_text": "Differanisole A , 3,5-dichloro-2-hydroxy-4-methoxy-6-n-propylbenzoic acid , inhibited growth of human myeloid leukemia cells .", "target_text": { "human myeloid leukemia cells": "cell_type" } }, { "input_text": "The compound induced G1 arrest and granulocytic differentiation of HL-60 cells , although the differentiation-inducing effect was modest .", "target_text": { "HL-60 cells": "cell_line" } }, { "input_text": "Differanisole A and 9-cis retinoic acid ( 9cisRA ) synergistically inhibited the growth and induced functional and morphologic differentiation of HL-60 and NB4 cells , whereas the combined treatment with differanisole A and all-trans retinoic acid or 1alpha,25-dihydroxyvitamin D3 was less effective .", "target_text": {} }, { "input_text": "Similar results were obtained in primary culture of leukemia cells from a patient with acute promyelocytic leukemia .", "target_text": { "leukemia cells": "cell_type" } }, { "input_text": "The synergistic effect on growth inhibition and induction of differentiation required simultaneous treatment with differanisole A and 9cisRA .", "target_text": {} }, { "input_text": "Differanisole A and an RXR-specific ligand ( Ro47-5944 ) cooperatively inhibited the cell growth , while the combined effect of differanisole A and an RAR-specific ligand Am80 was just additive .", "target_text": {} }, { "input_text": "Differanisole A in combination with 9cisRA may have implications for therapy of acute promyelocytic leukemia patients .", "target_text": {} }, { "input_text": "The activation of the JAK2 /STAT5 pathway is commonly involved in signaling through the human IL-5 receptor .", "target_text": { "JAK2": "protein", "/STAT5": "protein", "human IL-5 receptor": "protein" } }, { "input_text": "The JAK ( Janus kinase ) family of protein tyrosine kinases and the STATs ( signal transducers and activators of transcription ) have been shown to be activated in response to a number of cytokines and growth factors .", "target_text": { "Janus kinase": "protein", "JAK ( Janus kinase ) family": "protein", "protein tyrosine kinases": "protein", "STATs": "protein", "signal transducers and activators of transcription": "protein", "cytokines": "protein", "growth factors": "protein" } }, { "input_text": "In this study , we evaluated the activation of JAK /STAT pathway upon human interleukin-5 ( hIL-5 ) stimulation of two different hIL-5 -responsive cell lines , hIL-5 receptor alpha-subunit ( hIL-5R alpha ) cDNA-transfected TF-1 ( TF-h5R alpha ) and butyric-acid -treated YY-1 ( YY-Bu ) , and peripheral eosinophils .", "target_text": { "JAK": "protein", "/STAT": "protein", "human interleukin-5": "protein", "hIL-5": "protein", "hIL-5 -responsive cell lines": "cell_line", "hIL-5 receptor alpha-subunit": "protein", "hIL-5R alpha": "protein", "hIL-5 receptor alpha-subunit ( hIL-5R alpha ) cDNA-transfected TF-1": "cell_line", "TF-h5R alpha": "cell_line", "butyric-acid -treated YY-1": "cell_line", "YY-Bu": "cell_line", "peripheral eosinophils": "cell_line" } }, { "input_text": "Immunoprecipitation and electrophoretic mobility shift analysis revealed that tyrosine phosphorylation of JAK2 and activation of STAT5 were induced upon stimulation with hIL-5 in all three cell types , while STAT1 activation was only observed in eosinophils .", "target_text": { "JAK2": "protein", "STAT5": "protein", "hIL-5": "protein", "STAT1": "protein", "eosinophils": "cell_type" } }, { "input_text": "These results indicate that JAK2 /STAT5 activation is a common JAK /STAT pathway for hIL-5 -mediated signal in these cells .", "target_text": { "JAK2": "protein", "/STAT5": "protein", "JAK": "protein", "/STAT": "protein", "hIL-5": "protein" } }, { "input_text": "Dysregulation of monocytic nuclear factor-kappa B by oxidized low-density lipoprotein .", "target_text": { "nuclear factor-kappa B": "protein", "monocytic nuclear factor-kappa B": "protein", "low-density lipoprotein": "protein" } }, { "input_text": "Nuclear factor-kappa B ( NF-kappa B ) /Rel transcription factors may be involved in atherosclerosis , as is suggested by the presence of activated NF-kappa B in human atherosclerotic lesions .", "target_text": { "NF-kappa B": "protein", "Nuclear factor-kappa B ( NF-kappa B ) /Rel transcription factors": "protein" } }, { "input_text": "The aim of the present study was to investigate the effects of oxidized LDL ( oxLDL ) on the NF-kappa B system in human THP-1 monocytic cells as well as adherent monocytes .", "target_text": { "oxidized LDL": "protein", "oxLDL": "protein", "NF-kappa B": "protein", "THP-1 monocytic cells": "cell_line", "adherent monocytes": "cell_type" } }, { "input_text": "Our results demonstrate that short-term incubation of these cells with oxLDL activated p50/p65 containing NF-kappa B dimers and induced the expression of the target gene IL-8 .", "target_text": { "oxLDL": "protein", "oxLDL activated p50/p65": "protein", "NF-kappa B": "protein", "NF-kappa B dimers": "protein", "target gene IL-8": "DNA" } }, { "input_text": "This activation of NF-kappa B was inhibited by the antioxidant and H2O2 scavenger pyrrolidine dithiocarbamate and the proteasome inhibitor PSI .", "target_text": { "NF-kappa B": "protein", "proteasome": "protein" } }, { "input_text": "The oxLDL -induced NF-kappa B activation was accompanied by an initial depletion of I kappa B-alpha followed by a slight transient increase in the level of this inhibitor protein .", "target_text": { "oxLDL": "protein", "NF-kappa B": "protein", "I kappa B-alpha": "protein" } }, { "input_text": "In contrast , long-term treatment with oxLDL prevented the lipopolysaccharide -induced depletion of I kappa B-alpha , accompanied by an inhibition of both NF-kappa B activation and the expression of tumor necrosis factor-alpha and interleukin-1 beta genes .", "target_text": { "oxLDL": "protein", "I kappa B-alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "These observations provide additional evidence that oxLDL is a potent modulator of gene expression and suggest that ( dys ) regulation of NF-kappa B /Rel is likely to play an important role in atherogenesis .", "target_text": { "oxLDL": "protein", "NF-kappa B": "protein", "NF-kappa B /Rel": "protein" } }, { "input_text": "Suppression of nuclear factor kappa B and CD18 -mediated leukocyte adhesion to the corneal endothelium by dexamethasone .", "target_text": { "nuclear factor kappa B": "protein", "CD18": "protein" } }, { "input_text": "PURPOSE : To demonstrate that leukocyte adhesion to cultured corneal endothelial cells is mediated by the CD18 antigen , and to determine whether dexamethasone directly suppresses adhesion by inhibiting activation of nuclear factor kappa B ( NFkappaB ) .", "target_text": { "cultured corneal endothelial cells": "cell_line", "CD18": "protein", "CD18 antigen": "protein", "nuclear factor kappa B": "protein", "NFkappaB": "protein" } }, { "input_text": "METHODS : Cultured bovine corneal endothelium was stimulated for 6 hours by 40 micron/ml tumor necrosis factor alpha ( TNFalpha ) .", "target_text": { "tumor necrosis factor alpha": "protein", "TNFalpha": "protein" } }, { "input_text": "Dexamethasone was added 1 hour before TNFalpha stimulation in the dexamethasone group .", "target_text": { "TNFalpha": "protein" } }, { "input_text": "After stimulation , neutrophils separated from a healthy human volunteer were added with or without anti- CD18 antibody .", "target_text": { "CD18": "protein", "anti- CD18 antibody": "protein" } }, { "input_text": "The culture plate was settled for 15 minutes at 37 degrees C , and then neutrophils were activated by N-formyl-methionyl-leucyl-phenylalanine for 5 minutes .", "target_text": { "neutrophils": "cell_type" } }, { "input_text": "Nonadherent neutrophils were removed by sealing and inverting the culture well .", "target_text": { "neutrophils": "cell_type" } }, { "input_text": "The intracellular localization of NFkappaB after TNFalpha simulation was determined by confocal immunocytochemistry using an anti-p65 antibody .", "target_text": { "NFkappaB": "protein", "TNFalpha": "protein", "anti-p65 antibody": "protein" } }, { "input_text": "RESULTS : Neutrophil adhesion to cultured corneal endothelial cells increased significantly on exposure to TNFalpha ( 451.4+/-45.4 cells/mm2 , n = 16 ) compared to control ( 156.7+/-27.3 cells/mm2 , n = 16 , P < 0.01 ) .", "target_text": { "cultured corneal endothelial cells": "cell_line", "TNFalpha": "protein" } }, { "input_text": "This increased adhesion was suppressed by the addition of anti- CD18 antibody ( 157.6+/-25.1 cells/mm2 , n = 8 , P < 0.01 ) and by pretreatment with 10(-7) M dexamethasone ( 207.9+/-31.5 cells/mm2 , n = 10 , P < 0.01 ) .", "target_text": { "CD18": "protein", "anti- CD18 antibody": "protein" } }, { "input_text": "Immunocytochemistry 60 minutes after stimulation revealed that NFkappaB was located in the cytoplasm in unstimulated cells ; however , the addition of TNFalpha caused NFkappaB to translocate into the nucleus .", "target_text": { "NFkappaB": "protein", "unstimulated cells": "cell_type", "TNFalpha": "protein" } }, { "input_text": "Pretreatment with dexamethasone tapered NFkappaB translocation into the nucleus .", "target_text": { "NFkappaB": "protein" } }, { "input_text": "CONCLUSIONS : Leukocyte adhesion to the corneal endothelium was shown to be mediated by CD18 expressed on activated leukocytes .", "target_text": { "CD18": "protein", "activated leukocytes": "cell_type" } }, { "input_text": "Pretreatment of the endothelium with dexamethasone inhibited leukocyte adhesion ; this may be due in part to the suppression of NFkappaB entry into the nucleus .", "target_text": { "NFkappaB": "protein" } }, { "input_text": "Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans .", "target_text": { "neutrophil gelatinase-associated lipocalin": "protein" } }, { "input_text": "Neutrophil gelatinase-associated lipocalin ( NGAL ) is a 25-kDa lipocalin first identified as a protein stored in specific granules of the human neutrophil .", "target_text": { "Neutrophil gelatinase-associated lipocalin": "protein", "NGAL": "protein", "25-kDa lipocalin": "protein", "human neutrophil": "cell_type" } }, { "input_text": "The protein is believed to bind small lipophilic substances such as bacterial derived formylpeptides and lipopolysaccharides ( LPS ) and might function as a modulator of inflammation .", "target_text": {} }, { "input_text": "To characterize the regulation of NGAL further , we have cloned and sequenced a 5869-bp region of the NGAL gene including 1695 bp of the 5' nontranscribed region and a 3696-bp coding region encompassing seven exons and six introns .", "target_text": { "NGAL": "protein", "5869-bp region": "DNA", "NGAL gene": "DNA", "5' nontranscribed region": "DNA", "3696-bp coding region": "DNA", "seven exons and six introns": "DNA" } }, { "input_text": "The transcriptional start sites were identified by an RNase protection assay .", "target_text": { "transcriptional start sites": "DNA", "RNase": "protein" } }, { "input_text": "The NGAL gene is highly homologous to the mouse gene 24p3 .", "target_text": { "NGAL": "protein", "mouse gene 24p3": "DNA" } }, { "input_text": "NGAL was expressed in bone marrow and in tissues that are prone to exposure to microorganisms .", "target_text": { "NGAL": "protein" } }, { "input_text": "Potential cis-acting elements were identified in the promoter region of the NGAL gene by computer analysis and include binding sites for CTF/CBP , the hematopoietic transcription factors GATA-1 and PU.1 , and the LPS -inducible factor NF-kappa B .", "target_text": { "cis-acting elements": "DNA", "promoter region": "DNA", "NGAL": "protein", "NGAL gene": "DNA", "binding sites": "DNA", "CTF/CBP": "protein", "hematopoietic transcription factors": "protein", "GATA-1": "protein", "PU.1": "protein", "NF-kappa B": "protein", "LPS -inducible factor NF-kappa B": "protein" } }, { "input_text": "Human neutrophils express GH-N gene transcripts and the pituitary transcription factor Pit-1b .", "target_text": { "neutrophils": "cell_type", "Human neutrophils": "cell_type", "GH-N gene": "DNA", "GH-N gene transcripts": "RNA", "pituitary transcription factor": "protein", "Pit-1b": "protein" } }, { "input_text": "Since GH stimulates the development and function of granulocytes , we investigated the expression of GH in granulocyte subsets .", "target_text": { "GH": "protein", "granulocytes": "cell_type", "granulocyte subsets": "cell_type" } }, { "input_text": "By immunocytochemistry , 25 +/- 7 % of the human neutrophils were shown to express immunoreactive GH , whereas eosinophils were negative .", "target_text": { "neutrophils": "cell_type", "human neutrophils": "cell_type", "GH": "protein", "immunoreactive GH": "protein", "eosinophils": "cell_type" } }, { "input_text": "Reversed transcription ( RT ) -PCR analysis demonstrated GH mRNA in neutrophils .", "target_text": { "GH": "protein", "GH mRNA": "RNA", "neutrophils": "cell_type" } }, { "input_text": "Restriction analysis revealed that neutrophils express the GH-N gene but not the GH-V gene .", "target_text": { "neutrophils": "cell_type", "GH-N gene": "DNA", "GH-V gene": "DNA" } }, { "input_text": "Furthermore , we demonstrated by western blot analysis that neutrophils express an alternatively spliced variant of the pituitary transcription factor Pit-1 , designated Pit-1b .", "target_text": { "neutrophils": "cell_type", "pituitary transcription factor": "protein", "Pit-1": "protein", "Pit-1b": "protein" } }, { "input_text": "The ability of BHRF1 to inhibit apoptosis is dependent on stimulus and cell type .", "target_text": { "BHRF1": "protein" } }, { "input_text": "The development of resistance to host defense mechanisms such as tumor necrosis factor ( TNF ) - and Fas- mediated apoptosis of transformed or virus-infected cells may be a critical component in the development of disease .", "target_text": { "transformed": "cell_type", "virus-infected cells": "cell_type" } }, { "input_text": "To find genes that protect cells from apoptosis , we used an expression cloning strategy and identified BHRF1 , an Epstein-Barr virus ( EBV ) early-lytic-cycle protein with distant homology to Bcl-2 , as an anti- apoptosis protein .", "target_text": { "BHRF1": "protein", "Epstein-Barr virus ( EBV ) early-lytic-cycle protein": "protein", "Bcl-2": "protein", "anti- apoptosis protein": "protein" } }, { "input_text": "Expression of BHRF1 in MCF-Fas cells conferred nearly complete resistance against both anti-Fas antibody and TNF-mediated apoptosis .", "target_text": { "BHRF1": "protein", "MCF-Fas cells": "cell_line", "anti-Fas antibody": "protein" } }, { "input_text": "In addition , BHRF1 protected these cells from monocyte-mediated killing but failed to protect them from killing mediated by lymphokine-activated killer cells .", "target_text": { "BHRF1": "protein", "lymphokine-activated killer cells": "cell_type" } }, { "input_text": "The ability of BHRF1 to protect MCF-Fas cells from apoptosis induced by various stimuli was identical to that of Bcl-2 and Bcl-xL .", "target_text": { "BHRF1": "protein", "MCF-Fas cells": "cell_line", "Bcl-2": "protein", "Bcl-xL": "protein" } }, { "input_text": "Moreover , the mechanism of action of BHRF1 resembled that of Bcl-2 and Bcl-xL as it inhibited TNF- and anti-Fas- induced activation of two enzymes participating in the apoptosis pathway , cytosolic phospholipase A2 and caspase-3/CPP32 , but did not interfere with the activation of NF-kappaB -like transcription factors .", "target_text": { "BHRF1": "protein", "Bcl-2": "protein", "Bcl-xL": "protein", "cytosolic phospholipase A2": "protein", "caspase-3/CPP32": "protein", "NF-kappaB": "protein", "NF-kappaB -like transcription factors": "protein" } }, { "input_text": "A putative function of BHRF1 in EBV -infected epithelial cells may be to protect virus-infected cells from TNF- and/or anti-Fas- induced cell death in order to maximize virus production .", "target_text": { "BHRF1": "protein", "EBV -infected epithelial cells": "cell_type" } }, { "input_text": "Surprisingly , expression of neither BHRF1 nor Bcl-2 in a B-cell line , BJAB , protected the cells from anti-Fas-mediated apoptosis even though they increased the survival of serum-starved cells .", "target_text": { "BHRF1": "protein", "Bcl-2": "protein", "B-cell line": "cell_line", "BJAB": "cell_line", "serum-starved cells": "cell_type" } }, { "input_text": "Thus , the protective role of BHRF1 against apoptosis resembles that of Bcl-2 in being cell type specific and dependent on the apoptotic stimulus .", "target_text": { "BHRF1": "protein", "Bcl-2": "protein" } }, { "input_text": "Genomic organization , sequence , and transcriptional regulation of the human eotaxin gene .", "target_text": { "human eotaxin gene": "DNA" } }, { "input_text": "Eotaxin is an eosinophil specific beta-chemokine assumed to be involved in eosinophilic inflammatory diseases such as atopic dermatitis , allergic rhinitis , asthma and parasitic infections .", "target_text": { "Eotaxin": "protein", "eosinophil specific beta-chemokine": "protein" } }, { "input_text": "Its expression is stimulus- and cell-specific .", "target_text": {} }, { "input_text": "We here describe the genomic organisation ( 3 exons of 132 , 112 and 542 bp and 2 introns of 1211 and 378 bp ) and sequence including 3 kb of DNA from the immediate 5' upstream region of the human eotaxin gene .", "target_text": { "exons": "DNA", "introns": "DNA", "5' upstream region": "DNA", "human eotaxin gene": "DNA" } }, { "input_text": "Among the regulatory promoter elements potentially regulating eotaxin gene expression and/or mediating the effects of anti-inflammatory drugs we identified consensus sequences known to interact with nuclear factors like NF-IL6 , AP-1 , a NF-kappa-B like consensus sequence and gamma-interferon- as well as glucocorticoid response elements .", "target_text": { "regulatory promoter elements": "DNA", "eotaxin gene": "DNA", "consensus sequences": "DNA", "nuclear factors": "protein", "NF-IL6": "protein", "AP-1": "protein", "NF-kappa-B like consensus sequence": "DNA" } }, { "input_text": "Differential interaction of nuclear factors with the leukocyte-specific pp52 promoter in B and T cells .", "target_text": { "nuclear factors": "protein", "leukocyte-specific pp52 promoter": "DNA" } }, { "input_text": "The leukocyte-specific , cytoskeleton-binding pp52 ( LSP-1 , WP-34 ) protein is widely expressed in multiple leukocyte lineages , including B and T lymphocytes , granulocytes , and macrophages .", "target_text": { "granulocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "We previously detected a tissue-specific promoter preceding the exon encoding the N terminus of the pp52 leukocyte protein .", "target_text": { "tissue-specific promoter": "DNA", "N terminus": "protein", "pp52 leukocyte protein": "protein" } }, { "input_text": "Here we describe the functional characterization of this promoter and identification of the factors in B and T cells that regulate its activity .", "target_text": {} }, { "input_text": "The pp52 promoter contains an initiator specifying the unique 5' terminus of pp52 mRNA , tandem pairs of Ets and SP1 motifs , and a lone C/EBP motif .", "target_text": { "pp52 promoter": "DNA", "5' terminus": "DNA", "pp52 mRNA": "RNA", "lone C/EBP motif": "DNA" } }, { "input_text": "All these motifs are essential and collectively control transcriptional activity .", "target_text": {} }, { "input_text": "DNA binding studies and Ab supershift assays revealed that different combinations of factors interact with these motifs in B cells vs T cells .", "target_text": { "B cells": "cell_type", "T cells": "cell_type" } }, { "input_text": "The Ets motifs are preferentially bound by PU-1 in B cell extracts from all stages of development , whereas a different Ets family member reacts with these motifs in T cell extracts .", "target_text": { "Ets motifs": "DNA", "PU-1": "protein", "Ets family member": "protein" } }, { "input_text": "The C/EBP motif is bound by Ig/EBP-1 in pre-B cell and T cell extracts , but is replaced by nuclear factor-IL-6beta or a nuclear factor-IL-6beta -Ig/EBP-1 heterodimer in plasmacytoma cell extracts .", "target_text": { "C/EBP motif": "DNA", "Ig/EBP-1": "protein", "nuclear factor-IL-6beta": "protein", "-Ig/EBP-1": "protein", "nuclear factor-IL-6beta -Ig/EBP-1 heterodimer": "protein" } }, { "input_text": "Despite its reported role as a negative regulator of transcription , Ig/EBP-1 appears to exert a stimulatory effect on this promoter .", "target_text": { "Ig/EBP-1": "protein", "promoter": "DNA" } }, { "input_text": "These findings reveal the features controlling the pp52 promoter in B and T cells and provide the foundation for determining the regulation of this promoter in other leukocyte lineages .", "target_text": { "pp52 promoter": "DNA", "promoter": "DNA", "leukocyte lineages": "cell_type" } }, { "input_text": "Regulation of B-cell commitment to plasma cells or to memory B cells .", "target_text": { "plasma cells": "cell_type", "B cells": "cell_type", "memory B cells": "cell_type" } }, { "input_text": "During humoral immune responses , B-lymphocyte activation is followed by differentiation along either the plasma cell pathway or the memory B-cell pathway .", "target_text": {} }, { "input_text": "Recent studies suggest that CD40-CD40 ligand , OX-OX40 ligand , a group of cytokines and intracellular transcriptional factors may all contribute to B-lymphocyte differentiation control .", "target_text": { "CD40-CD40 ligand": "protein", "OX-OX40 ligand": "protein", "cytokines": "protein" } }, { "input_text": "Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity .", "target_text": { "Transcription factor": "protein", "human immunodeficiency virus type 1 transcription start site": "DNA" } }, { "input_text": "When transcriptionally active , the human immunodeficiency virus ( HIV ) promoter contains a nucleosome-free region encompassing both the promoter /enhancer region and a large region ( 255 nucleotides [ nt ] ) downstream of the transcription start site .", "target_text": { "promoter": "DNA", "promoter /enhancer region": "DNA", "255 nucleotides": "DNA", "transcription start site": "DNA" } }, { "input_text": "We have previously identified new binding sites for transcription factors downstream of the transcription start site ( nt 465 to 720 ) : three AP-1 sites ( I , II , and III ) , an AP3-like motif ( AP3-L ) , a downstream binding factor ( DBF ) site , and juxtaposed Sp1 sites .", "target_text": { "transcription factors": "protein", "transcription start site": "DNA", "nt 465 to 720": "DNA", "AP-1 sites": "DNA", "AP3-like motif": "DNA", "AP3-L": "DNA", "downstream binding factor ( DBF ) site": "DNA", "juxtaposed Sp1 sites": "DNA" } }, { "input_text": "Here , we show that the DBF site is an interferon-responsive factor ( IRF ) binding site and that the AP3-L motif binds the T-cell-specific factor NF-AT .", "target_text": { "DBF site": "DNA", "interferon-responsive factor ( IRF ) binding site": "DNA", "AP3-L": "DNA", "AP3-L motif": "DNA", "T-cell-specific factor": "protein", "NF-AT": "protein" } }, { "input_text": "Mutations that abolish the binding of each factor to its cognate site are introduced in an infectious HIV-1 molecular clone to study their effect on HIV-1 transcription and replication .", "target_text": {} }, { "input_text": "Individual mutation of the DBF or AP3-L site as well as the double mutation AP-1(III)/ AP3-L did not affect HIV-1 replication compared to that of the wild-type virus .", "target_text": { "AP3-L": "DNA", "mutation AP-1(III)/ AP3-L": "DNA" } }, { "input_text": "In contrast , proviruses carrying mutations in the Sp1 sites were totally defective in terms of replication .", "target_text": { "Sp1 sites": "DNA" } }, { "input_text": "Virus production occurred with slightly delayed kinetics for viruses containing combined mutations in the AP-1(III) , AP3-L , and DBF sites and in the AP3-L and DBF-sites , whereas viruses mutated in the AP-1(I,II,III) and AP3-L sites and in the AP-1(I,II,III) , AP3-L , and DBF sites exhibited a severely defective replicative phenotype .", "target_text": { "AP-1(III)": "DNA", "AP3-L": "DNA", "DBF sites": "DNA", "DBF-sites": "DNA", "AP-1(I,II,III)": "DNA", "AP3-L sites": "DNA" } }, { "input_text": "No RNA-packaging defect could be measured for any of the mutant viruses as determined by quantification of their HIV genomic RNA .", "target_text": { "HIV genomic RNA": "RNA" } }, { "input_text": "Measurement of the transcriptional activity of the HIV-1 promoter after transient transfection of the HIV-1 provirus DNA or of long terminal repeat-luciferase constructs showed a positive correlation between the transcriptional and the replication defects for most mutants .", "target_text": { "HIV-1 promoter": "DNA", "HIV-1 provirus DNA": "DNA", "long terminal repeat-luciferase constructs": "DNA" } }, { "input_text": "Glucocorticoid receptor regulates expression of L-selectin and CD11/CD18 on human neutrophils [ see comments ]", "target_text": { "Glucocorticoid receptor": "protein", "L-selectin": "protein", "CD11/CD18": "protein", "human neutrophils": "cell_type" } }, { "input_text": "BACKGROUND : Recent studies have raised the hypothesis that glucocorticoids could diminish the ability of endothelial cells to direct leukocyte traffic into inflamed tissues by inhibiting expression of the adhesion molecules endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 .", "target_text": { "endothelial cells": "cell_type", "adhesion molecules": "protein", "endothelial-leukocyte adhesion molecule-1": "protein", "intercellular adhesion molecule-1": "protein" } }, { "input_text": "The aim of the present study was to investigate whether glucocorticoids also regulate the expression of L-selectin and CD11/CD18 integrins on human neutrophil granulocytes .", "target_text": { "L-selectin": "protein", "CD11/CD18": "protein", "integrins": "protein", "granulocytes": "cell_type", "human neutrophil granulocytes": "cell_type" } }, { "input_text": "METHODS AND RESULTS : Incubation of human whole blood with platelet-activating factor ( PAF , 1 mumol/L ) evoked downregulation of L-selectin and upregulation of CD11/CD18 adhesion receptors on neutrophils as measured by flow cytometry .", "target_text": { "platelet-activating factor": "protein", "PAF": "protein", "L-selectin": "protein", "CD11/CD18": "protein", "adhesion receptors": "protein" } }, { "input_text": "While dexamethasone ( 0.1 nmol/L to 100 mumol/L ) did not affect expression of adhesion molecules on resting neutrophils , it attenuated the PAF -induced changes in L-selectin and CD18 expression in a time- and concentration-dependent fashion with IC50 values of 31 and 13 nmol/L , respectively .", "target_text": { "adhesion molecules": "protein", "resting neutrophils": "cell_type", "PAF": "protein", "L-selectin": "protein", "CD18": "protein" } }, { "input_text": "These effects of dexamethasone were completely aborted by RU-486 ( 10 mumol/L ) , which blocks transcriptional activation of the glucocorticoid receptor , and by the protein synthesis inhibitor cycloheximide ( 35.5 mumol/L ) .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Dexamethasone , up to a concentration of 1 mumol/L , neither affected significantly the release of granule enzymes nor interfered with PAF binding to its membrane receptors .", "target_text": { "granule enzymes": "protein", "PAF": "protein", "membrane receptors": "protein" } }, { "input_text": "CONCLUSIONS : Our results show that glucocorticoids at clinically relevant concentrations exert specific actions on expression of adhesion molecules on activated neutrophils , which are mediated through ligation of glucocorticoid receptors and induction of protein synthesis , and suggest a novel mechanism by which anti-inflammatory corticosteroids may inhibit leukocyte accumulation .", "target_text": { "adhesion molecules": "protein", "activated neutrophils": "cell_type", "glucocorticoid receptors": "protein" } }, { "input_text": "The immediate-early gene product Egr-1 regulates the human interleukin-2 receptor beta-chain promoter through noncanonical Egr and Sp1 binding sites .", "target_text": { "Egr-1": "protein", "interleukin-2 receptor": "protein", "human interleukin-2 receptor beta-chain promoter": "DNA" } }, { "input_text": "The interleukin-2 IL-2 receptor beta-chain ( IL-2Rbeta ) is an essential component of the receptors for IL-2 and IL-15 .", "target_text": { "interleukin-2 IL-2 receptor beta-chain": "protein", "IL-2Rbeta": "protein", "IL-2": "protein", "IL-15": "protein" } }, { "input_text": "Although IL-2Rbeta is constitutively expressed by lymphocytes , its expression can be further induced by a number of stimuli , including phorbol 12-myristate 13-acetate ( PMA ) .", "target_text": { "IL-2Rbeta": "protein" } }, { "input_text": "We have now characterized factors that bind to an enhancer region located between nucleotides -170 and -139 of the human IL-2Rbeta promoter .", "target_text": { "nucleotides -170 and -139": "DNA", "IL-2Rbeta": "protein", "IL-2Rbeta promoter": "DNA" } }, { "input_text": "Both Sp1 and Sp3 bound to the 5' portion of this region , whereas a PMA -inducible factor ( PIF ) mainly bound to its 3' portion and bound to the Sp binding motifs as well .", "target_text": { "Sp1": "protein", "Sp3": "protein", "5' portion": "DNA", "PMA -inducible factor": "protein", "PIF": "protein", "3' portion": "DNA", "Sp binding motifs": "DNA" } }, { "input_text": "In Jurkat T cells , induction of PIF DNA binding activity was rapidly induced , required de novo protein synthesis , and was sustained at a high level for at least 23 h .", "target_text": { "T cells": "cell_type", "Jurkat T cells": "cell_line", "PIF": "protein" } }, { "input_text": "Interestingly , PIF was constitutively activated in human T-cell leukemia virus type 1 -transformed MT-2 cells .", "target_text": { "PIF": "protein", "human T-cell leukemia virus type 1 -transformed MT-2 cells": "cell_line" } }, { "input_text": "In this paper , we demonstrate that PIF is Egr-1 based on its recognition by anti- Egr-1 antisera in gel mobility shift assays , even though the IL-2Rbeta DNA binding motif differed substantially from the canonical Egr-1 binding site .", "target_text": { "PIF": "protein", "Egr-1": "protein", "IL-2Rbeta": "protein", "IL-2Rbeta DNA binding motif": "DNA", "Egr-1 binding site": "DNA" } }, { "input_text": "In addition , Egr-1 bound to the Sp binding site .", "target_text": { "Egr-1": "protein", "Sp binding site": "DNA" } }, { "input_text": "In Jurkat cells , both sites were required for maximal IL-2Rbeta promoter activity , and in HeLaS3 cells , transfection of Egr-1 could drive activity of a reporter construct containing both sites .", "target_text": { "Jurkat cells": "cell_line", "IL-2Rbeta": "protein", "Egr-1": "protein" } }, { "input_text": "Moreover , Sp1 and Egr-1 could form a complex with kinetics that correlated with the production of Egr-1 in Jurkat cells upon PMA stimulation .", "target_text": { "Sp1": "protein", "Egr-1": "protein", "Jurkat cells": "cell_line" } }, { "input_text": "Thus , Sp1 and Egr-1 physically and functionally cooperate to mediate maximal IL-2Rbeta promoter activity .", "target_text": { "Sp1": "protein", "Egr-1": "protein", "IL-2Rbeta promoter": "DNA" } }, { "input_text": "Overexpression of HSF2-beta inhibits hemin -induced heat shock gene expression and erythroid differentiation in K562 cells .", "target_text": { "HSF2-beta": "protein", "hemin": "protein", "K562 cells": "cell_line" } }, { "input_text": "Acquisition of heat shock factor 2 ( HSF2 ) DNA binding activity is accompanied by induced transcription of heat shock genes in hemin-treated K562 cells undergoing erythroid differentiation .", "target_text": { "heat shock genes": "DNA", "K562 cells": "cell_line" } }, { "input_text": "Previous studies revealed that HSF2 consists of two alternatively spliced isoforms , HSF2-alpha and HSF2-beta , whose relative abundance is developmentally regulated and varies between different tissues .", "target_text": { "HSF2": "protein", "HSF2-alpha": "protein", "HSF2-beta": "protein" } }, { "input_text": "To investigate whether the molar ratio of HSF2-alpha and HSF2-beta isoforms is crucial for the activation of HSF2 and whether the HSF2 isoforms play functionally distinct roles during the hemin-mediated erythroid differentiation , we generated cell clones expressing different levels of HSF2-alpha and HSF2-beta .", "target_text": { "HSF2-alpha": "protein", "HSF2-beta": "protein", "HSF2": "protein" } }, { "input_text": "We show that in parental K562 cells , the HSF2-alpha isoform is predominantly expressed and HSF2 can be activated upon hemin treatment .", "target_text": { "K562 cells": "cell_line", "HSF2-alpha": "protein", "HSF2-alpha isoform": "protein", "HSF2": "protein" } }, { "input_text": "In contrast , when HSF2-beta is expressed at levels exceeding those of endogenous HSF2-alpha , the hemin-induced DNA binding activity and transcription of heat shock genes are repressed , whereas overexpression of HSF2-alpha results in an enhanced hemin response .", "target_text": { "HSF2-beta": "protein", "HSF2-alpha": "protein", "endogenous HSF2-alpha": "protein", "heat shock genes": "DNA", "hemin": "protein" } }, { "input_text": "Furthermore , the hemin -induced accumulation of globin , known as a marker of erythroid differentiation , is decreased in cells overexpressing HSF2-beta .", "target_text": { "hemin": "protein", "globin": "protein", "HSF2-beta": "protein" } }, { "input_text": "We suggest that HSF2-beta acts as a negative regulator of HSF2 activity during hemin-mediated erythroid differentiation of K562 cells .", "target_text": { "HSF2-beta": "protein", "HSF2": "protein", "K562 cells": "cell_line" } }, { "input_text": "Sequential development of structural and functional alterations in T cells from tumor-bearing mice .", "target_text": { "T cells": "cell_type" } }, { "input_text": "The TCR alpha beta or -gamma delta chains bind the peptide ligand , whereas the associated CD3 delta epsilon gamma and TCR zeta subunits couple the TCR to intracellular signal transduction components .", "target_text": { "CD3 delta epsilon gamma": "protein", "TCR zeta subunits": "protein", "TCR": "protein" } }, { "input_text": "Recently , several groups have described marked alterations in signal transduction elements in T cells from cancer patients or in mice bearing tumor for a few weeks ( > 26 days ) .", "target_text": { "T cells": "cell_type" } }, { "input_text": "The sequence in which these alterations develop is unknown .", "target_text": {} }, { "input_text": "The aim of this study was to explore the kinetics of the development of alterations in signal transduction molecules ( TCR zeta chain , NF kappaB family proteins , and tyrosine kinase p56 ( lck ) ) in mice bearing MC38 colon adenocarcinoma .", "target_text": { "TCR zeta chain": "protein", "NF kappaB family proteins": "protein", "tyrosine kinase p56 ( lck )": "protein" } }, { "input_text": "The results demonstrate that alterations in NF kappaB family proteins , specifically the failure of p65 translocation to the nucleus , occur earlier and more frequently than the decrease in zeta-chain .", "target_text": { "NF kappaB family proteins": "protein", "p65": "protein", "zeta-chain": "protein" } }, { "input_text": "These defects are paralleled by an impaired ability to produce Th1 cytokines ( IL-2 and IFN-gamma ) .", "target_text": { "cytokines": "protein", "Th1 cytokines": "protein", "IL-2": "protein", "IFN-gamma": "protein" } }, { "input_text": "These initial changes are followed by the eventual loss of TCR zeta chain and p56 ( lck ) and a marked decrease in cytotoxic function .", "target_text": { "TCR zeta chain": "protein", "p56 ( lck )": "protein" } }, { "input_text": "An increased rate of lysosomal degradation is one of the mechanisms responsible for the loss of zeta-chain .", "target_text": { "zeta-chain": "protein" } }, { "input_text": "HLA-DMA and HLA-DMB gene expression functions through the conserved S-X-Y region .", "target_text": { "S-X-Y region": "DNA" } }, { "input_text": "The MHC class II homologous proteins HLA-DMA and HLA-DMB function in the loading of peptides onto class II molecules .", "target_text": { "MHC class II homologous proteins": "protein", "HLA-DMA": "protein", "HLA-DMB": "protein", "class II molecules": "protein" } }, { "input_text": "Like the class II genes , the HLA-DM genes contain upstream regulatory sequences similar to the S-X-Y regulatory region as well as additional putative regulatory sites .", "target_text": { "class II genes": "DNA", "HLA-DM genes": "DNA", "S-X-Y regulatory region": "DNA" } }, { "input_text": "To determine whether the DM genes are regulated in a similar manner as class II genes , a series of in vivo and in vitro analyses was performed .", "target_text": { "DM genes": "DNA", "class II genes": "DNA" } }, { "input_text": "Deletion analysis showed that expression from the DM promoters is dependent on the conserved S-X-Y region .", "target_text": { "DM promoters": "DNA", "S-X-Y region": "DNA" } }, { "input_text": "The class II-specific transcription factors RFX and CIITA are also required for expression , as cell lines deficient in these factors failed to allow transcription from the DM promoters .", "target_text": { "transcription factors": "protein", "class II-specific transcription factors": "protein", "RFX": "protein", "CIITA": "protein", "DM promoters": "DNA" } }, { "input_text": "In addition , in vivo footprint analysis showed the putative X and Y boxes to be occupied by transcription factors in wild-type B cells , but not in RFX -deficient B cells .", "target_text": { "transcription factors": "protein", "B cells": "cell_type", "wild-type B cells": "cell_type", "RFX": "protein", "RFX -deficient B cells": "cell_line" } }, { "input_text": "In astrocytes , IFN-gamma treatment induced increased occupancy of these sites .", "target_text": { "astrocytes": "cell_type", "IFN-gamma": "protein" } }, { "input_text": "None of the other putative regulatory sites was occupied in vivo , indicating that they may not be functional .", "target_text": {} }, { "input_text": "Finally , gel shift analysis showed synergistic complex formation between proteins that bind to the putative X boxes of the DM genes , as is found for the DRA gene .", "target_text": { "X boxes": "DNA", "DRA gene": "DNA" } }, { "input_text": "Therefore , the DM genes share a common mechanism of regulation with the class II genes .", "target_text": { "DM genes": "DNA", "class II genes": "DNA" } }, { "input_text": "Effect of adenovirus 2 on cellular gene activation in blood-derived monocytes and macrophages .", "target_text": { "blood-derived monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "We have investigated the effect of adenovirus 2 ( Ad2 ) infection on human monocytes and monocyte-derived macrophages with regard to expression of TNF-alpha and IL-1 beta .", "target_text": { "human monocytes": "cell_type", "macrophages": "cell_type", "monocyte-derived macrophages": "cell_type", "TNF-alpha": "protein", "IL-1 beta": "protein" } }, { "input_text": "In monocytes , the virus was bound to the surface without being internalized .", "target_text": {} }, { "input_text": "On the other hand , Ad2 was internalized by macrophages .", "target_text": { "macrophages": "cell_type" } }, { "input_text": "No virus replication and no transcription of the Ad2 early genes was observed in either of the cells .", "target_text": { "Ad2 early genes": "DNA" } }, { "input_text": "Ad2 infection induced transient increase in the mRNA levels for TNF-alpha and IL-1 beta in both monocytes and in macrophages , although the kinetics of the transcription was slightly different .", "target_text": { "mRNA": "RNA", "TNF-alpha": "protein", "IL-1 beta": "protein", "monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "The production of both cytokines , measured by ELISA tests , was enhanced in monocytes .", "target_text": { "cytokines": "protein", "monocytes": "cell_type" } }, { "input_text": "In macrophages , a slight enhancement of TNF-alpha production was seen , whereas IL-1 beta was not detected .", "target_text": { "macrophages": "cell_type", "TNF-alpha": "protein", "IL-1 beta": "protein" } }, { "input_text": "The data indicate that cellular genes might be activated by Ad2 virus infection in nonpermissive cells where no viral gene products could be detected .", "target_text": { "cellular genes": "DNA", "viral gene products": "protein" } }, { "input_text": "Structure and function analysis of the human myeloid cell nuclear differentiation antigen promoter : evidence for the role of Sp1 and not of c-Myb or PU.1 in myelomonocytic lineage-specific expression .", "target_text": { "human myeloid cell nuclear differentiation antigen promoter": "DNA", "Sp1": "protein", "c-Myb": "protein", "PU.1": "protein" } }, { "input_text": "The human myeloid nuclear differentiation antigen ( MNDA ) is expressed specifically in maturing cells of the myelomonocytic lineage and in monocytes and granulocytes .", "target_text": { "human myeloid nuclear differentiation antigen": "protein", "MNDA": "protein", "maturing cells": "cell_type", "monocytes": "cell_type", "granulocytes": "cell_type" } }, { "input_text": "Epitope enhancement was used to confirm the strict lineage- and stage-specific expression of MNDA in bone marrow as well as in other paraffin-embedded fixed tissues .", "target_text": { "MNDA": "protein" } }, { "input_text": "A 1-kb region of the gene that includes 5' flanking sequence was reported earlier to contain functional promoter activity and was specifically demethylated in expressing cells in contrast to null cells .", "target_text": { "1-kb region": "DNA", "5' flanking sequence": "DNA", "expressing cells": "cell_type", "null cells": "cell_type" } }, { "input_text": "Further analysis has revealed that this 1-kb fragment promotes higher reporter gene activity in MNDA -expressing cells than non-expressing cells , indicating cell-specific differences in transactivation .", "target_text": { "1-kb fragment": "DNA", "MNDA": "protein", "-expressing cells": "cell_type", "non-expressing cells": "cell_type" } }, { "input_text": "This sequence contains consensus elements consistent with myeloid-specific gene expression , including a PU.1 consensus site near the major transcription start site and a cluster of c-Myb sites located several hundred bases upstream of this region .", "target_text": { "consensus elements": "DNA", "PU.1 consensus site": "DNA", "transcription start site": "DNA", "c-Myb sites": "DNA" } }, { "input_text": "However , analysis of deletion mutants localized nearly all of the promoter activity to a short region ( -73 to -16 ) that did not include the cluster of c-Myb sites .", "target_text": { "deletion mutants": "DNA", "-73 to -16": "DNA", "c-Myb sites": "DNA" } }, { "input_text": "A 4-bp mutation of the core Sp1 consensus element ( GC box ) ( -20 ) reduced overall promoter activity of the 1-kb fragment .", "target_text": { "core Sp1 consensus element": "DNA", "GC box": "DNA", "1-kb fragment": "DNA" } }, { "input_text": "Mutation of the PU.1 site did not significantly affect promoter activity .", "target_text": { "PU.1 site": "DNA" } }, { "input_text": "Only a small region ( -35 to +22 ) including the Sp1 element and transcription start site , but not the PU.1 site was footprinted .", "target_text": { "Sp1 element": "DNA", "transcription start site": "DNA", "PU.1 site": "DNA" } }, { "input_text": "The 4-bp mutation of the core Sp1 consensus element abolished footprinting at the site and an antibody super-shift reaction showed that Sp1 is one of the factors binding the consensus site .", "target_text": { "Sp1 consensus element": "DNA", "Sp1": "protein", "consensus site": "DNA" } }, { "input_text": "The Sp1 site also co-localizes with a DNase I hypersensitive site .", "target_text": { "Sp1": "protein", "Sp1 site": "DNA", "DNase I hypersensitive site": "DNA" } }, { "input_text": "The results indicate that DNA methylation , chromatin structure , and transactivation at an Sp1 site contribute to the highly restricted expression of this myelomonocytic lineage specific gene .", "target_text": { "chromatin": "DNA", "Sp1": "protein", "Sp1 site": "DNA", "myelomonocytic lineage specific gene": "DNA" } }, { "input_text": "Critical cytoplasmic domains of human interleukin-9 receptor alpha chain in interleukin -9-mediated cell proliferation and signal transduction .", "target_text": { "cytoplasmic domains": "protein", "human interleukin-9 receptor alpha chain": "protein", "interleukin": "protein" } }, { "input_text": "Interleukin-9 receptor ( IL-9R ) complex consists of a ligand-specific alpha chain and IL-2R gamma chain .", "target_text": { "Interleukin-9 receptor ( IL-9R ) complex": "protein", "ligand-specific alpha chain": "protein", "IL-2R gamma chain": "protein" } }, { "input_text": "In this study , two regions in the cytoplasmic domain of human IL-9Ralpha were found to be important for IL-9 -mediated cell growth .", "target_text": { "cytoplasmic domain": "protein", "human IL-9Ralpha": "protein", "IL-9": "protein" } }, { "input_text": "A membrane-proximal region that contains the BOX1 consensus sequence is required for IL-9 -induced cell proliferation and tyrosine phosphorylation of Janus kinases ( JAKs ) .", "target_text": { "membrane-proximal region": "protein", "BOX1 consensus sequence": "protein", "IL-9": "protein", "Janus kinases": "protein", "JAKs": "protein" } }, { "input_text": "Deletion of this region or internal deletion of the BOX1 motif abrogated IL-9 -induced cell proliferation and signal transduction .", "target_text": { "BOX1 motif": "protein", "IL-9": "protein" } }, { "input_text": "However , substitution of the Pro-X-Pro in the BOX1 motif with Ala-X-Ala failed to abolish IL-9 -induced cell proliferation but decreased IL-9 -mediated tyrosine phosphorylation of JAK kinases , insulin receptor substrate-2 , and signal transducer and activator of transcription 3 ( STAT3 ) and expression of c-myc and junB .", "target_text": { "Pro-X-Pro": "protein", "BOX1 motif": "protein", "Ala-X-Ala": "protein", "IL-9": "protein", "JAK kinases": "protein", "insulin receptor substrate-2": "protein", "signal transducer and activator of transcription 3": "protein", "STAT3": "protein", "c-myc": "DNA", "junB": "DNA" } }, { "input_text": "Another important region is downstream of the BOX1 motif and contains a STAT3 binding motif YLPQ .", "target_text": { "BOX1 motif": "protein", "STAT3": "protein", "STAT3 binding motif": "DNA", "YLPQ": "DNA" } }, { "input_text": "Deletion of this region significantly impaired IL-9 -induced cell growth , activation of JAK kinases , insulin receptor substrate-2 , and STAT3 and expression of early response genes .", "target_text": { "IL-9": "protein", "JAK kinases": "protein", "insulin receptor substrate-2": "protein", "STAT3": "protein", "early response genes": "DNA" } }, { "input_text": "A point mutation changing YLPQ into YLPA greatly reduced IL-9 -induced activation of STAT3 and expression of c-myc but did not affect cell proliferation .", "target_text": { "YLPQ": "DNA", "YLPA": "DNA", "IL-9": "protein", "STAT3": "protein", "c-myc": "DNA" } }, { "input_text": "These results suggest that cooperation or cross-talk of signaling molecules associated with different domains of IL-9Ralpha other than STAT3 is essential for IL-9 -mediated cell growth .", "target_text": { "IL-9Ralpha": "protein", "STAT3": "protein", "IL-9": "protein" } }, { "input_text": "Bcl-2 protein inhibits bufalin -induced apoptosis through inhibition of mitogen-activated protein kinase activation in human leukemia U937 cells .", "target_text": { "Bcl-2 protein": "protein", "mitogen-activated protein kinase": "protein", "human leukemia U937 cells": "cell_line" } }, { "input_text": "In a previous study , we demonstrated that bufalin , which is an active principle of Chinese medicine , chan'su , caused apoptosis in human leukemia U937 cells by anomalous activation of mitogen-activated protein kinase ( MAPK ) via the signaling pathway of Ras , Raf-1 , and MAPK kinase-1 .", "target_text": { "human leukemia U937 cells": "cell_line", "mitogen-activated protein kinase": "protein", "MAPK": "protein", "Ras": "protein", "Raf-1": "protein", "MAPK kinase-1": "protein" } }, { "input_text": "Here , we report the effect of overexpression of bcl-2 in U937 cells on the signaling pathway of apoptosis that is induced by bufalin .", "target_text": { "bcl-2": "protein", "U937 cells": "cell_line" } }, { "input_text": "The results indicated that the apoptosis induced by bufalin in U937 cells was significantly inhibited by overexpression of the Bcl-2 protein .", "target_text": { "U937 cells": "cell_line", "Bcl-2 protein": "protein" } }, { "input_text": "No significant difference was detected in the activation of MAPK kinase-1 that is induced by bufalin in wild-type or Bcl-2-overexpressed U937 cells ; however , the activation of MAPK by bufalin was significantly attenuated in the cells overexpressing Bcl-2 .", "target_text": { "MAPK": "protein", "MAPK kinase-1": "protein", "U937 cells": "cell_line", "Bcl-2-overexpressed U937 cells": "cell_type", "Bcl-2": "protein" } }, { "input_text": "Bufalin treatment activated activator protein-1 transcriptional activity ; however , this activation was decreased to 40 % in bcl-2 -overexpressed U937 cells .", "target_text": { "activated activator protein-1": "protein", "bcl-2": "protein", "U937 cells": "cell_line" } }, { "input_text": "These results indicate that Bcl-2 acts downstream of MAPK kinase-1 but upstream of MAPK and suggest that , in the signaling pathway of the apoptotic process induced by bufalin , the transcriptional activity of activator protein-1 may be down-regulated through the inhibition of MAPK activity by Bcl-2 .", "target_text": { "Bcl-2": "protein", "MAPK": "protein", "MAPK kinase-1": "protein", "activator protein-1": "protein" } }, { "input_text": "Pancreatic islet expression studies and polymorphic DNA markers in the genes encoding hepatocyte nuclear factor -3alpha , -3beta , -3gamma , -4gamma , and -6 .", "target_text": {} }, { "input_text": "The genes encoding the functionally related hepatocyte nuclear factors HNF-1alpha and HNF-4alpha play a critical role in normal pancreatic beta-cell function .", "target_text": { "hepatocyte nuclear factors": "protein", "HNF-1alpha": "protein", "HNF-4alpha": "protein" } }, { "input_text": "Mutations in these liver -enriched transcription factors result in two forms of early-onset type 2 diabetes ( maturity-onset diabetes of the young [ MODY ] ) , MODY3 and MODY1 , which are characterized by impaired glucose-stimulated insulin secretion , early disease onset , and autosomal dominant inheritance .", "target_text": { "liver -enriched transcription factors": "protein" } }, { "input_text": "The transcriptional hierarchy of HNFs suggests that other proteins of the regulatory cascade might be responsible for other forms of MODY and/or late-onset type 2 diabetes .", "target_text": {} }, { "input_text": "In this study , we show that HNF -3alpha , -3beta , -3gamma , -4gamma , and -6 are expressed in pancreatic beta-cells .", "target_text": { "pancreatic beta-cells": "cell_type" } }, { "input_text": "We report the identification and characterization of simple tandem repeat DNA polymorphisms in the genes encoding HNF-3alpha , -3beta , -3gamma , -4gamma , and -6 and the mapping of HNF-6 to chromosome bands 15q21.1-21.2 by fluorescence in situ hybridization .", "target_text": { "simple tandem repeat DNA polymorphisms": "DNA", "HNF-3alpha": "protein", "-3beta": "protein", "-3gamma": "protein", "-4gamma": "protein", "-6": "protein", "HNF-6": "protein", "chromosome bands": "DNA", "15q21.1-21.2": "DNA" } }, { "input_text": "These markers will be useful to study the role of genetic variation in these genes in the pathogenesis of type 2 diabetes .", "target_text": {} }, { "input_text": "Induction of nuclear factor kappa B/Rel nuclear activity in human peripheral blood T lymphocytes by anti-HLA class I monoclonal antibodies .", "target_text": { "nuclear factor kappa B/Rel": "protein", "human peripheral blood T lymphocytes": "cell_type", "anti-HLA class I monoclonal antibodies": "protein" } }, { "input_text": "Monoclonal antibodies against either monomorphic or polymorphic determinants of class I antigen induced in PBMC and highly purified T lymphocytes the nuclear activity of NF-kappa B/Rel complexes .", "target_text": { "class I antigen": "protein", "PBMC": "cell_type", "purified T lymphocytes": "cell_type", "NF-kappa B/Rel complexes": "protein" } }, { "input_text": "These included both p50/p50 and p50/p65 dimers , recognized by specific antibodies in EMSA .", "target_text": { "p50/p50": "protein", "p50/p65 dimers": "protein", "specific antibodies": "protein" } }, { "input_text": "The induced complexes were detectable in extracts of cells incubated with anti-class I monoclonal antibody ( mAb ) for 1.5 h ; the induction was maximal at 5 h , persistent at 16 h and no longer observed at 40 h .", "target_text": { "complexes": "protein", "anti-class I monoclonal antibody": "protein", "mAb": "protein" } }, { "input_text": "The mAb failed to induce NF-kappa B/Rel nuclear activity in cells incubated in the presence of 3,4-dichloroisocoumarin , an inhibitor of I kappa B-alpha degradation .", "target_text": { "mAb": "protein", "NF-kappa B/Rel": "protein", "I kappa B-alpha": "protein" } }, { "input_text": "Together , these results suggest that class I triggering can induce the activity of NF-kappa B/Rel nuclear activity in peripheral blood T lymphocytes , thereby modulating the expression of genes regulated by these transcription factors .", "target_text": { "NF-kappa B/Rel": "protein", "peripheral blood T lymphocytes": "cell_type", "transcription factors": "protein" } }, { "input_text": "Anti-Ehrlichia chaffeensis antibody complexed with E. chaffeensis induces potent proinflammatory cytokine mRNA expression in human monocytes through sustained reduction of IkappaB-alpha and activation of NF-kappaB .", "target_text": { "Anti-Ehrlichia chaffeensis antibody": "protein", "proinflammatory cytokine mRNA": "RNA", "human monocytes": "cell_type", "IkappaB-alpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "Ehrlichia chaffeensis is an obligatory intracellular bacterium that infects monocytes and macrophages and is the etiologic agent of human ehrlichiosis in the United States .", "target_text": { "monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "Our previous studies showed that the exposure of human monocytes to E. chaffeensis induces the expression of interleukin-1beta ( IL-1beta ) , IL-8 , and IL-10 genes in vitro but not the expression of tumor necrosis factor alpha ( TNF-alpha ) and IL-6 mRNAs .", "target_text": { "monocytes": "cell_type", "human monocytes": "cell_type", "interleukin-1beta": "protein", "IL-1beta": "protein", "IL-8": "protein", "IL-10": "protein", "IL-10 genes": "DNA" } }, { "input_text": "In this study , the effect of anti- E. chaffeensis antibody complexed with E. chaffeensis on the expression of major proinflammatory cytokines in human monocytes was examined .", "target_text": { "anti- E. chaffeensis antibody": "protein", "major proinflammatory cytokines": "protein", "human monocytes": "cell_type" } }, { "input_text": "Human monocytic cell line THP-1 was treated with E. chaffeensis which had been preincubated with human anti- E. chaffeensis serum for 2 h , and the levels of cytokine mRNAs were evaluated by competitive reverse transcription-PCR .", "target_text": { "Human monocytic cell line THP-1": "cell_line", "cytokine mRNAs": "RNA" } }, { "input_text": "Anti- E. chaffeensis antibody complexed with E. chaffeensis significantly enhanced mRNA expression of IL-1beta in THP-1 cells .", "target_text": { "Anti- E. chaffeensis antibody": "protein", "IL-1beta": "protein", "THP-1 cells": "cell_line" } }, { "input_text": "The expression of TNF-alpha and IL-6 mRNAs was also induced .", "target_text": {} }, { "input_text": "The levels of secreted IL-1beta , TNF-alpha , and IL-6 during 24 h of stimulation were comparable to those induced by Escherichia coli lipopolysaccharide at 1 microg/ml .", "target_text": { "IL-1beta": "protein", "TNF-alpha": "protein", "IL-6": "protein" } }, { "input_text": "Fab fragment of anti- E. chaffeensis immunoglobulin G complexed with E. chaffeensis did not induce any of these three cytokines , indicating that ehrlichial binding is required for IL-1beta mRNA expression and that binding of the immune complex to the Fc gamma receptor is required for TNF-alpha and IL-6 mRNA expression and enhanced IL-1beta mRNA expression .", "target_text": { "anti- E. chaffeensis immunoglobulin G": "protein", "IL-1beta": "protein", "IL-1beta mRNA": "RNA", "immune complex": "protein", "Fc gamma receptor": "protein", "TNF-alpha": "protein", "IL-6": "protein", "IL-6 mRNA": "RNA" } }, { "input_text": "Furthermore , prolonged degradation of IkappaB-alpha and activation of NF-kappaB were demonstrated in THP-1 cells exposed to anti- E. chaffeensis serum and E. chaffeensis .", "target_text": { "IkappaB-alpha": "protein", "NF-kappaB": "protein", "THP-1 cells": "cell_line" } }, { "input_text": "This result implies that development of anti- E. chaffeensis antibody in patients can result in the production of major proinflammatory cytokines , which may play an important role in the pathophysiology of ehrlichiosis and immune responses to it .", "target_text": { "anti- E. chaffeensis antibody": "protein", "major proinflammatory cytokines": "protein" } }, { "input_text": "The class II trans-activator CIITA interacts with the TBP-associated factor TAFII32 .", "target_text": { "CIITA": "protein", "class II trans-activator CIITA": "protein", "TAFII32": "protein", "TBP-associated factor TAFII32": "protein" } }, { "input_text": "The class II trans- activator ( CIITA ) is the main transcriptional co-activator for the expression of MHC class II proteins .", "target_text": { "class II trans- activator": "protein", "CIITA": "protein", "MHC class II proteins": "protein" } }, { "input_text": "Its N-terminal 125 amino acids function as an independent transcriptional activation domain .", "target_text": { "N-terminal 125 amino acids": "protein", "independent transcriptional activation domain": "protein" } }, { "input_text": "Analyses of the primary amino acid sequence of the activation domain predict the presence of three alpha-helices , each with a high proportion of acidic residues .", "target_text": { "primary amino acid sequence": "protein", "activation domain": "protein", "alpha-helices": "protein" } }, { "input_text": "Using site-directed mutagenesis , we found that two of these predicted alpha-helices are required for full transcriptional activation by CIITA .", "target_text": { "alpha-helices": "protein", "CIITA": "protein" } }, { "input_text": "Moreover , a CIITA protein in which both functional alpha-helices have been deleted displays a dominant negative phenotype .", "target_text": { "CIITA": "protein", "CIITA protein": "protein", "alpha-helices": "protein" } }, { "input_text": "This activation domain of CIITA interacts with the 32 kDa subunit of the general transcription complex TFIID , TAFII32 .", "target_text": { "activation domain": "protein", "CIITA": "protein", "32 kDa subunit": "protein", "general transcription complex": "protein", "TFIID": "protein", "TAFII32": "protein" } }, { "input_text": "Decreased transcriptional activation by N-terminal deletions of CIITA is correlated directly with their reduced binding to TAFII32 .", "target_text": { "N-terminal deletions": "protein", "CIITA": "protein", "TAFII32": "protein" } }, { "input_text": "We conclude that interactions between TAFII32 and CIITA are responsible for activation of class II genes .", "target_text": { "TAFII32": "protein", "CIITA": "protein", "class II genes": "DNA" } }, { "input_text": "Characterization of interleukin-10 receptor expression on B-cell chronic lymphocytic leukemia cells .", "target_text": { "interleukin-10 receptor": "protein", "B-cell chronic lymphocytic leukemia cells": "cell_line" } }, { "input_text": "B-cell chronic lymphocytic leukemia ( B-CLL ) cells accumulate in vivo in the G0/G1 phase of the cell cycle , suggesting that their malignant expansion is due , at least in part , to a delay in cell death .", "target_text": { "B-cell chronic lymphocytic leukemia ( B-CLL ) cells": "cell_line" } }, { "input_text": "However , the cellular or molecular factors responsible for a delay in B-CLL cell death are unknown .", "target_text": { "molecular factors": "protein" } }, { "input_text": "B-CLL cells do express receptors for interferon-alpha ( IFN-alpha ) and IFN-gamma , and activation of both has been shown to promote B-CLL survival in vitro by preventing apoptosis .", "target_text": { "interferon-alpha": "protein", "IFN-alpha": "protein", "IFN-gamma": "protein" } }, { "input_text": "The interleukin-10 ( IL-10 ) receptor is another member of the IFN receptor family , but its ligand , IL-10 , has been reported to induce apoptosis in B-CLL cells .", "target_text": { "interleukin-10 ( IL-10 ) receptor": "protein", "IFN receptor family": "protein", "IL-10": "protein", "B-CLL cells": "cell_line" } }, { "input_text": "In the current study , we undertook a biochemical analysis of IL-10 receptor expression on freshly isolated B-CLL cells and characterized the functional responsiveness of IL-10 binding to its constitutively expressed receptor .", "target_text": { "IL-10 receptor": "protein", "B-CLL cells": "cell_line", "IL-10": "protein", "constitutively expressed receptor": "protein" } }, { "input_text": "We show that B-CLL cells bind IL-10 with significant specificity and express between 47 and 127 IL-10 receptor sites per cell , with a dissociation constant in the range of 168 to 426 x 10(-12) mol/L .", "target_text": { "B-CLL cells": "cell_line", "IL-10": "protein", "IL-10 receptor": "protein" } }, { "input_text": "Ligand binding and activation of the IL-10 receptor expressed on B-CLL cells results in the phosphorylation of signal transducer and activator of transcription 1 ( STAT1 ) and STAT3 proteins .", "target_text": { "IL-10 receptor": "protein", "B-CLL cells": "cell_line", "signal transducer and activator of transcription 1": "protein", "STAT1": "protein", "STAT3": "protein" } }, { "input_text": "This pattern of STAT protein phosphorylation is identical to IL-10 receptor activation on normal cells and similar to IFN-alpha ( STAT1 and STAT3 ) and IFN-gamma ( STAT1 ) receptor activation in CLL .", "target_text": { "STAT protein": "protein", "IL-10 receptor": "protein", "normal cells": "cell_type", "IFN-alpha": "protein", "STAT1": "protein", "STAT3": "protein", "IFN-gamma": "protein", "CLL": "cell_line" } }, { "input_text": "Further , in consecutive samples of fresh blood obtained from patients with B-CLL cells , the addition of IL-10 inhibited B-CLL proliferation , enhanced B-CLL differentiation , but did not induce apoptosis .", "target_text": { "B-CLL cells": "cell_line", "IL-10": "protein", "B-CLL": "cell_line" } }, { "input_text": "Indeed , IL-10 , like IFN-gamma , was able to significantly reduce the amount of B-CLL cell death caused by hydrocortisone-induced apoptosis .", "target_text": { "IL-10": "protein", "IFN-gamma": "protein" } }, { "input_text": "We conclude that cytokines , which signal through the interferon family of receptors , have comparable functional effects on B-CLL cells .", "target_text": { "cytokines": "protein", "interferon family": "protein", "B-CLL cells": "cell_line" } }, { "input_text": "Involvement of the N-terminal region of the human mineralocorticoid receptor hormone-binding domain in agonist and antagonist binding as revealed by a new monoclonal antibody .", "target_text": { "N-terminal region": "protein", "human mineralocorticoid receptor hormone-binding domain": "protein", "new monoclonal antibody": "protein" } }, { "input_text": "To gain a better understanding of the mechanism of binding to the human mineralocorticoid receptor ( hMR ) , we developed a new monoclonal antibody ( mAb ) raised against the hormone-binding domain ( HBD ) .", "target_text": { "human mineralocorticoid receptor": "protein", "hMR": "protein", "monoclonal antibody": "protein", "mAb": "protein", "hormone-binding domain": "protein", "HBD": "protein" } }, { "input_text": "For this purpose , mice were immunized with a fusion protein including the sequence Thr729-Lys984 of hMR .", "target_text": { "fusion protein": "protein", "Thr729-Lys984": "protein", "hMR": "protein" } }, { "input_text": "After ELISA screening , mAb 18C7 was selected for its specificity towards the HBD .", "target_text": { "mAb 18C7": "protein", "HBD": "protein" } }, { "input_text": "This antibody recognized both the denatured and native MR forms , as well as the hetero-oligomeric MR form and the transformed MR state .", "target_text": { "native MR forms": "protein", "hetero-oligomeric MR form": "protein", "transformed MR state": "protein" } }, { "input_text": "By using several HBD subfragments , the mAb 18C7 epitope was located in the N-terminal region of the HBD from Thr729 to Leu765 .", "target_text": { "HBD subfragments": "protein", "mAb 18C7": "protein", "mAb 18C7 epitope": "protein", "N-terminal region": "protein", "HBD": "protein", "Thr729 to Leu765": "protein" } }, { "input_text": "We then studied the effect of the antibody on aldosterone and progesterone binding to the hMR .", "target_text": { "hMR": "protein" } }, { "input_text": "When 18C7 was incubated with liganded MR , it was able to partly displace ( 20 % ) the hormone from its binding site .", "target_text": { "18C7": "protein", "liganded MR": "protein" } }, { "input_text": "When 18C7 was incubated with MR before aldosterone or progesterone , the antibody inhibited 75-80 % of the binding .", "target_text": { "18C7": "protein", "MR": "protein" } }, { "input_text": "The effect of 18C7 on the binding was similar with both hormones .", "target_text": { "18C7": "protein" } }, { "input_text": "A sucrose gradient analysis indicated the simultaneous presence of two kinds of receptor complexes : the steroid-MR complex and the antibody-MR complex .", "target_text": { "steroid-MR complex": "protein", "antibody-MR complex": "protein" } }, { "input_text": "After its associated proteins , especially the heat-shock protein hsp90 , had been cross-linked with the hMR by dimethylpimelimidate , 18C7 was still able to react with the receptor .", "target_text": { "heat-shock protein hsp90": "protein", "hMR": "protein", "18C7": "protein" } }, { "input_text": "Our results indicated that the epitope recognized by 18C7 was directly implicated in hormone binding .", "target_text": { "epitope": "protein", "18C7": "protein" } }, { "input_text": "The lack of steroid binding of HBD mutants with the Thr729-Leu765 sequence deleted [ Jalaguier , Mesnier , Leger and Auzou ( 1996 ) J.Steroid Biochem.Mol.Biol.57 , 43-50 ] supports this hypothesis .", "target_text": { "HBD": "protein", "Thr729-Leu765 sequence": "protein" } }, { "input_text": "Because of the similar behaviours of aldosterone and progesterone , we conclude that the N-terminal Thr729-Leu765 region of the HBD is similarly involved in the binding of both hormones .", "target_text": { "N-terminal Thr729-Leu765 region": "protein", "HBD": "protein" } }, { "input_text": "Molecular cloning of SLAP-130 , an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases .", "target_text": { "SLAP-130": "protein", "SLP-76-associated substrate": "protein", "T cell antigen receptor-stimulated protein tyrosine kinases": "protein" } }, { "input_text": "Previous work has demonstrated that SLP-76 , a Grb2-associated tyrosine -phosphorylated protein , augments Interleukin-2 promoter activity when overexpressed in the Jurkat T cell line .", "target_text": { "SLP-76": "protein", "Grb2-associated tyrosine -phosphorylated protein": "protein", "Interleukin-2 promoter": "DNA", "Jurkat T cell line": "cell_line" } }, { "input_text": "This activity requires regions of SLP-76 that mediate protein-protein interactions with other molecules in T cells , suggesting that SLP-76 -associated proteins also function to regulate signal transduction .", "target_text": { "SLP-76": "protein", "T cells": "cell_type" } }, { "input_text": "Here we describe the molecular cloning of SLAP-130 , a SLP-76 -associated phosphoprotein of 130 kDa .", "target_text": { "SLAP-130": "protein", "SLP-76": "protein", "SLP-76 -associated phosphoprotein": "protein" } }, { "input_text": "We demonstrate that SLAP-130 is hematopoietic cell-specific and associates with the SH2 domain of SLP-76 .", "target_text": { "SLAP-130": "protein", "SH2 domain": "protein", "SLP-76": "protein" } }, { "input_text": "Additionally , we show that SLAP-130 is a substrate of the T cell antigen receptor-induced protein tyrosine kinases .", "target_text": { "SLAP-130": "protein", "T cell antigen receptor-induced protein": "protein", "tyrosine kinases": "protein" } }, { "input_text": "Interestingly , we find that in contrast to SLP-76 , overexpression of SLAP-130 diminishes T cell antigen receptor -induced activation of the interleukin-2 promoter in Jurkat T cells and interferes with the augmentation of interleukin-2 promoter activity seen when SLP-76 is overexpressed in these cells .", "target_text": { "SLP-76": "protein", "SLAP-130": "protein", "T cell antigen receptor": "protein", "interleukin-2 promoter": "DNA", "Jurkat T cells": "cell_line" } }, { "input_text": "These data suggest that SLP-76 recruits a negative regulator , SLAP-130 , as well as positive regulators of signal transduction in T cells .", "target_text": { "SLP-76": "protein", "SLAP-130": "protein", "T cells": "cell_type" } }, { "input_text": "Molecular actions of prolactin in the immune system .", "target_text": {} }, { "input_text": "The immunoregulatory properties of prolactin , a pituitary peptide hormone , have received renewed attention .", "target_text": { "immunoregulatory": "protein" } }, { "input_text": "The prolactin receptor , a member of the hematopoietin/cytokine receptor superfamily , is ubiquitously expressed by cells in the immune system .", "target_text": { "prolactin receptor": "protein", "hematopoietin/cytokine receptor superfamily": "protein" } }, { "input_text": "Certain subpopulations of lymphocytes synthesize and secrete biologically active prolactin , which suggests that prolactin can act as an autocrine and/or paracrine factor to modulate the activities of cells of the immune system .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "This review focuses on the molecular actions of prolactin in the immune system .", "target_text": {} }, { "input_text": "Emphasis is given to recent information about the molecular mechanisms of prolactin receptor signal transduction , and the signaling molecules and prolactin -inducible target genes that participate in these responses .", "target_text": { "signaling molecules": "protein", "prolactin -inducible target genes": "DNA" } }, { "input_text": "In particular , the prolactin -inducible interferon regulatory factor-1 gene and its roles in mediating diverse immune responses .", "target_text": { "prolactin -inducible interferon regulatory factor-1 gene": "DNA" } }, { "input_text": "Transcriptional regulation during myelopoiesis .", "target_text": {} }, { "input_text": "The coordinated production of all blood cells from a common stem cell is a highly regulated process involving successive stages of commitment and differentiation .", "target_text": { "blood cells": "cell_type", "common stem cell": "cell_type" } }, { "input_text": "From analyses of mice deficient in transcription factor genes and from the characterizations of chromosome breakpoints in human leukemias , it has become evident that transcription factors are important regulators of hematopoiesis .", "target_text": { "transcription factor genes": "DNA", "chromosome breakpoints": "DNA", "transcription factors": "protein" } }, { "input_text": "During myelopoiesis , which includes the development of granulocytic and monocytic lineages , transcription factors from several families are active , including AML1/CBF beta , C/EBP , Ets , c-Myb , HOX , and MZF-1 .", "target_text": { "transcription factors": "protein", "AML1/CBF beta": "DNA", "C/EBP": "DNA", "Ets": "DNA", "c-Myb": "DNA", "HOX": "DNA", "MZF-1": "DNA" } }, { "input_text": "Few of these factors are expressed exclusively in myeloid cells ; instead it appears that they cooperatively regulate transcription of myeloid-specific genes .", "target_text": { "myeloid cells": "cell_type", "myeloid-specific genes": "DNA" } }, { "input_text": "Here we discuss recent advances in transcriptional regulation during myelopoiesis .", "target_text": {} }, { "input_text": "Activation of transcription factor NF-kappa B by phagocytic stimuli in human neutrophils .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Phagocytosis represents an important physiological trigger for the inducible expression of several genes in human neutrophils .", "target_text": { "human neutrophils": "cell_type" } }, { "input_text": "Here , we report that a DNA-binding activity primarily consisting of the classical NF-kappa B heterodimer , p50/RelA , is induced in phagocytosing neutrophils .", "target_text": { "NF-kappa B": "protein", "NF-kappa B heterodimer": "protein", "p50/RelA": "protein", "phagocytosing neutrophils": "cell_type" } }, { "input_text": "Under these conditions , NF-kappa B activation was found to be a rapid and transient response , reaching a maximum by 10-15 min , and returning to near-basal levels by 30 min .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "In neutrophils undergoing the phagocytosis of opsonized yeasts , the onset of NF-kappa B activation was paralleled by a decline in immunoreactive I kappa B-alpha protein levels , and the cellular I kappa B -alpha pool was replenished by 30 min , in agreement with our gel shift data .", "target_text": { "NF-kappa B": "protein", "I kappa B-alpha": "protein", "I kappa B": "protein" } }, { "input_text": "We conclude that NF-kappa B activation could constitute one of the mechanisms whereby the expression of kappa B-responsive genes is enhanced in phagocytosing neutrophils .", "target_text": { "NF-kappa B": "protein", "kappa B-responsive genes": "DNA", "phagocytosing neutrophils": "cell_type" } }, { "input_text": "To our knowledge , this represents the first demonstration that phagocytic stimuli can induce NF-kappa B activation in human neutrophils .", "target_text": { "NF-kappa B": "protein", "human neutrophils": "cell_type" } }, { "input_text": "Induction of human immunodeficiency virus type 1 expression in monocytic cells by Cryptococcus neoformans and Candida albicans .", "target_text": { "monocytic cells": "cell_type" } }, { "input_text": "Because candidiasis and cryptococcosis are common in human immunodeficiency virus ( HIV ) -infected persons , the effect of Cryptococcus neoformans and Candida albicans on HIV expression in monocytic cells was examined .", "target_text": { "monocytic cells": "cell_type" } }, { "input_text": "Stimulation of the latently HIV-infected myelomonocytic cell line OM-10.1 with C. neoformans and C. albicans in the presence of pooled human serum caused a ratio-dependent increase in HIV production .", "target_text": { "HIV-infected myelomonocytic cell line": "cell_line" } }, { "input_text": "Induction of HIV by C. neoformans was enhanced by anti-capsular antibody , while induction by both organisms was inhibited by anti-TNF-alpha antibody .", "target_text": { "anti-capsular antibody": "protein", "anti-TNF-alpha antibody": "protein" } }, { "input_text": "In THP-1 cells transfected with HIV plasmid constructs , both organisms induced transcription from the HIV long terminal repeat that was dependent on intact NF-kappaB binding sequences .", "target_text": { "HIV plasmid constructs": "DNA", "HIV long terminal repeat": "DNA", "NF-kappaB": "protein", "NF-kappaB binding sequences": "DNA" } }, { "input_text": "Thus , C. neoformans and C. albicans enhance HIV expression in monocytic cells through a TNF-alpha- and NF-kappaB- dependent mechanism .", "target_text": { "monocytic cells": "cell_type" } }, { "input_text": "In HIV -infected patients , such enhancement may further impair host immunity and could accelerate the course of HIV disease .", "target_text": {} }, { "input_text": "Nuclear levels of NF-kappaB correlate with syncytium-forming capacity of 8e51 cells , expressing a defective HIV virus .", "target_text": { "NF-kappaB": "protein", "8e51 cells": "cell_line" } }, { "input_text": "The double NF-kappaB site identified in the LTR of the human immunodeficiency virus-1 ( HIV-1 ) has been demonstrated to be necessary for efficient viral transcription .", "target_text": { "double NF-kappaB site": "DNA", "LTR": "DNA" } }, { "input_text": "In this report we present the characterisation of NF-kappaB subunits engaged in complexes binding to the HIV-1 NF-kappaB site in human 8e51 T-cells , that harbour a defective HIV-1 .", "target_text": { "NF-kappaB subunits": "protein", "HIV-1 NF-kappaB site": "DNA", "human 8e51 T-cells": "cell_line" } }, { "input_text": "At least four different specific NF-kappaB complexes are present in the nucleus of these cells .", "target_text": { "NF-kappaB complexes": "protein" } }, { "input_text": "With the use of specific antibodies we have determined the composition of each complex using electrophoretic mobility shift assays .", "target_text": { "specific antibodies": "protein" } }, { "input_text": "The results show the presence of several NF-kappaB family members , with the transactivating RelA being engaged in multiple complexes .", "target_text": { "NF-kappaB family members ,": "protein", "RelA": "protein" } }, { "input_text": "The importance of NF-kappaB complexes in viral functions has been established comparing the level of NF-kappaB DNA-binding complexes with syncytia-forming activity of 8e51 cells .", "target_text": { "NF-kappaB complexes": "protein", "8e51 cells": "cell_line" } }, { "input_text": "In fact , 8e51 cells that had almost lost their syncytia-forming capacity were found to contain at least 10 times less active NF-kappaB DNA-binding complex than the actively fusing cells .", "target_text": { "8e51 cells": "cell_line", "NF-kappaB DNA-binding complex": "protein", "actively fusing cells": "cell_type" } }, { "input_text": "The correlation is specific as the level of at least three other transcription factors did not change .", "target_text": { "transcription factors": "protein" } }, { "input_text": "c-Myb and Ets proteins synergize to overcome transcriptional repression by ZEB .", "target_text": { "c-Myb": "DNA", "Ets proteins": "protein", "ZEB": "protein" } }, { "input_text": "The Zfh family of zinc finger/homeodomain proteins was first identified in Drosophila where it is required for differentiation of tissues such as the central nervous system and muscle .", "target_text": { "Zfh family": "protein", "zinc finger/homeodomain proteins": "protein" } }, { "input_text": "ZEB , a vertebrate homolog of Zfh-1 , binds a subset of E boxes and blocks myogenesis through transcriptional repression of muscle genes .", "target_text": { "ZEB": "protein", "Zfh-1": "protein", "E boxes": "DNA", "muscle genes": "DNA" } }, { "input_text": "We present evidence here that ZEB also has an important role in controlling hematopoietic gene transcription .", "target_text": { "ZEB": "protein", "hematopoietic gene": "DNA" } }, { "input_text": "Two families of transcription factors that are required for normal hematopoiesis are c-Myb and Ets .", "target_text": { "transcription factors": "protein", "c-Myb": "protein", "Ets": "protein" } }, { "input_text": "These factors act synergistically to activate transcription , and this synergy is required for transcription of at least several important hematopoietic genes .", "target_text": { "hematopoietic genes": "DNA" } }, { "input_text": "ZEB blocks the activity of c-Myb and Ets individually , but together the factors synergize to resist this repression .", "target_text": { "ZEB": "protein", "c-Myb": "protein", "Ets": "protein" } }, { "input_text": "Such repression imposes a requirement for both c-Myb and Ets for transcriptional activity , providing one explanation for why synergy between these factors is important .", "target_text": { "c-Myb": "protein", "Ets": "protein" } }, { "input_text": "The balance between repression by ZEB and transcriptional activation by c-Myb /Ets provides a flexible regulatory mechanism for controlling gene expression in hematopoietic cells .", "target_text": { "ZEB": "protein", "c-Myb": "protein", "/Ets": "protein", "hematopoietic cells": "cell_type" } }, { "input_text": "We demonstrate that one target of this positive/negative regulation in vivo is the alpha4 integrin , which play a key role in normal hematopoiesis and function of mature leukocytes .", "target_text": { "alpha4 integrin": "protein", "mature leukocytes": "cell_type" } }, { "input_text": "Comparison of the transactivation domains of Stat5 and Stat6 in lymphoid cells and mammary epithelial cells .", "target_text": { "transactivation domains": "protein", "Stat5": "protein", "Stat6": "protein", "lymphoid cells": "cell_type", "mammary epithelial cells": "cell_type" } }, { "input_text": "Stat ( signal transducers and activators of transcription ) and Jak ( Janus kinases ) proteins are central components in the signal transduction events in hematopoietic and epithelial cells .", "target_text": { "Stat": "protein", "signal transducers and activators of transcription": "protein", "Jak": "protein", "Janus kinases": "protein" } }, { "input_text": "They are rapidly activated by various cytokines , hormones , and growth factors .", "target_text": { "cytokines": "protein" } }, { "input_text": "Upon ligand binding and cytokine receptor dimerization , Stat proteins are phosphorylated on tyrosine residues by Jak kinases .", "target_text": { "cytokine receptor": "protein", "Stat proteins": "protein", "Jak kinases": "protein" } }, { "input_text": "Activated Stat proteins form homo- or heterodimers , translocate to the nucleus , and induce transcription from responsive genes .", "target_text": { "Stat proteins": "protein" } }, { "input_text": "Stat5 and Stat6 are transcription factors active in mammary epithelial cells and immune cells .", "target_text": { "Stat5": "protein", "Stat6": "protein", "transcription factors": "protein", "epithelial cells": "cell_type", "mammary epithelial cells": "cell_type" } }, { "input_text": "Prolactin activates Stat5 , and interleukin-4 ( IL-4 ) activates Stat6 .", "target_text": { "Stat5": "protein", "interleukin-4": "protein", "IL-4": "protein", "Stat6": "protein" } }, { "input_text": "Both cytokines are able to stimulate cell proliferation , differentiation , and survival .", "target_text": { "cytokines": "protein" } }, { "input_text": "We investigated the transactivation potential of Stat6 and found that it is not restricted to lymphocytes .", "target_text": { "Stat6": "protein" } }, { "input_text": "IL-4 -dependent activation of Stat6 was also observed in HC11 mammary epithelial cells .", "target_text": { "IL-4": "protein", "Stat6": "protein", "mammary epithelial cells": "cell_type", "HC11 mammary epithelial cells": "cell_line" } }, { "input_text": "In these cells , Stat6 activation led to the induction of the beta-casein gene promoter .", "target_text": { "Stat6": "protein", "beta-casein gene promoter": "DNA" } }, { "input_text": "The induction of this promoter was confirmed in COS7 cells .", "target_text": { "COS7 cells": "cell_line" } }, { "input_text": "The glucocorticoid receptor was able to further enhance IL-4 -induced gene transcription through the action of Stat6 .", "target_text": { "glucocorticoid receptor": "protein", "IL-4": "protein", "Stat6": "protein" } }, { "input_text": "Deletion analysis of the carboxyl-terminal region of Stat6 and recombination of this region with a heterologous DNA binding domain allowed the delimitation and characterization of the transactivation domain of Stat6 .", "target_text": { "carboxyl-terminal region": "protein", "Stat6": "protein", "heterologous DNA binding domain": "protein" } }, { "input_text": "The potencies of the transactivation domains of Stat5 , Stat6 , and viral protein VP16 were compared .", "target_text": { "transactivation domains": "protein", "Stat5": "protein", "Stat6": "protein", "viral protein VP16": "protein" } }, { "input_text": "Stat6 had a transactivation domain which was about 10-fold stronger than that of Stat5 .", "target_text": { "Stat6": "protein", "Stat5": "protein" } }, { "input_text": "In pre-B cells ( Ba/F3 ) , the transactivation domain of Stat6 was IL-4 regulated , independently from its DNA binding function .", "target_text": { "pre-B cells": "cell_type", "Stat6": "protein", "IL-4": "protein" } }, { "input_text": "ETS1 , NFkappaB and AP1 synergistically transactivate the human GM-CSF promoter .", "target_text": { "ETS1": "protein", "NFkappaB": "protein", "AP1": "protein", "human GM-CSF promoter": "DNA" } }, { "input_text": "Activation of helper T cells results in coordinate expression of a number of cytokines involved in differentiation , proliferation and activation of the haematopoietic system .", "target_text": { "helper T cells": "cell_type", "cytokines": "protein" } }, { "input_text": "Granulocyte-macrophage colony stimulating factor ( GM-CSF ) is one such cytokine , whose increased expression results mostly from increases in transcription .", "target_text": { "Granulocyte-macrophage colony stimulating factor": "protein", "GM-CSF": "protein", "cytokine": "protein" } }, { "input_text": "Cis-acting elements with NFkappaB , AP1 and ETS -like binding motifs have been identified in the promoter region of the GM-CSF gene , and are important or essential for transcriptional activity following T cell activation .", "target_text": { "Cis-acting elements": "DNA", "GM-CSF": "protein", "GM-CSF gene": "DNA" } }, { "input_text": "ETS1 is a transcription factor of the ETS family that is expressed in T cells .", "target_text": { "ETS1": "protein", "transcription factor": "protein", "ETS family": "protein", "T cells": "cell_type" } }, { "input_text": "We have previously shown that ETS1 can transactivate GM-CSF in Jurkat T cells , but only after the cells have been stimulated by treatment with PMA and ionomycin , agents that mimic T cell activation .", "target_text": { "ETS1": "protein", "GM-CSF": "protein", "T cells": "cell_type", "Jurkat T cells": "cell_line" } }, { "input_text": "Thus we proposed that ETS1 , which is expressed constitutively in Jurkat cells , may act in concert with PMA/ionomycin inducible factors .", "target_text": { "ETS1": "protein", "Jurkat cells": "cell_line", "PMA/ionomycin inducible factors": "protein" } }, { "input_text": "Here we show that ETS1 can transactivate a GM-CSF reporter construct in unstimulated Jurkat cells , providing that either NFkappaB or AP1 transcription factors are supplied by co-transfection .", "target_text": { "ETS1": "protein", "GM-CSF": "protein", "GM-CSF reporter construct": "DNA", "Jurkat cells": "cell_line", "NFkappaB": "protein", "AP1": "protein", "transcription factors": "protein" } }, { "input_text": "We confirm that binding of endogenous NFkappaB and AP1 is induced following PMA /ionomycin treatment of T cells .", "target_text": { "NFkappaB": "protein", "AP1": "protein", "T cells": "cell_type" } }, { "input_text": "Transactivation by ETS1 , NFkappaB and AP1 is synergistic , and mutation of the individual binding sites reveals that the transcriptional activities of these factors are interdependent .", "target_text": { "ETS1": "protein", "NFkappaB": "protein", "AP1": "protein" } }, { "input_text": "Our results suggest that constitutive ETS1 , and inducible NFkappaB and AP1 , cooperate as part of a higher order transcriptional complex in activated T cells .", "target_text": { "ETS1": "protein", "NFkappaB": "protein", "AP1": "protein", "transcriptional complex": "protein", "T cells": "cell_type" } }, { "input_text": "Abnormal T lymphocyte development induced by targeted overexpression of IkappaB alpha .", "target_text": { "T lymphocyte": "cell_type", "IkappaB alpha": "protein" } }, { "input_text": "A role in thymic maturation for factors of the NF-kappaB family has long been suspected , but not yet proven .", "target_text": { "NF-kappaB family": "protein" } }, { "input_text": "Transgenic mice with a lymphocyte-specific defect in NF-kappaB activation were produced by targeted expression of human IkappaB alpha .", "target_text": { "NF-kappaB": "protein", "IkappaB alpha": "protein" } }, { "input_text": "The thymic cellularity of these mice was significantly decreased .", "target_text": {} }, { "input_text": "The proportion of mature , TCRhigh thymocytes of the alphabeta lineage was reduced , and the remaining TCRhigh population contained an unusually high proportion of double-positive cells .", "target_text": { "TCRhigh thymocytes": "cell_type", "alphabeta lineage": "cell_type", "TCRhigh population": "cell_type", "double-positive cells": "cell_line" } }, { "input_text": "This defect in maturation resulted in a transgene dose-dependent reduction in peripheral T lymphocytes , with the CD8 lineage being more severely affected .", "target_text": { "peripheral T lymphocytes": "cell_type", "CD8 lineage": "cell_type" } }, { "input_text": "These data provide direct evidence for the involvement of NF-kappaB /Rel family proteins in late stages of T lymphocyte development , coincident with positive and negative selection .", "target_text": { "NF-kappaB": "protein", "NF-kappaB /Rel family proteins": "protein", "T lymphocyte": "cell_type" } }, { "input_text": "CD40 is a functional activation antigen and B7-independent T cell costimulatory molecule on normal human lung fibroblasts .", "target_text": { "CD40": "protein", "activation antigen": "protein", "B7-independent T cell costimulatory molecule": "protein", "human lung fibroblasts": "cell_type" } }, { "input_text": "CD40 is an important signaling and activation Ag found on certain bone marrow-derived cells .", "target_text": { "CD40": "protein", "bone marrow-derived cells": "cell_type" } }, { "input_text": "Recently , CD40 also has been shown to be expressed by mesenchymal cells , including human fibroblasts .", "target_text": { "CD40": "protein", "mesenchymal cells": "cell_type", "human fibroblasts": "cell_type" } }, { "input_text": "Little is known about the role of CD40 in fibroblasts .", "target_text": { "CD40": "protein", "fibroblasts": "cell_type" } }, { "input_text": "The current study investigates the hypothesis that CD40 expressed on lung fibroblasts is an activation structure and mechanism for interaction with hemopoietic cells .", "target_text": { "CD40": "protein", "lung fibroblasts": "cell_type", "hemopoietic cells": "cell_type" } }, { "input_text": "Communication between resident tissue fibroblasts and T cells is necessary for normal wound healing , and can be pathologic , resulting in tissue fibrosis .", "target_text": { "fibroblasts": "cell_type", "T cells": "cell_type" } }, { "input_text": "Signaling through CD40 with soluble CD40 ligand stimulated fibroblast activation , as evidenced by mobilization of nuclear factor-kappaB and by induction of the proinflammatory and chemoattractant cytokines IL-6 and IL-8 .", "target_text": { "CD40": "protein", "cytokines": "protein", "IL-6": "protein", "IL-8": "protein" } }, { "input_text": "IFN-gamma-primed lung fibroblasts costimulate T lymphocyte proliferation utilizing CD40 , but not the well-studied costimulatory molecules B7-1 and B7-2 .", "target_text": { "fibroblasts": "cell_type", "IFN-gamma-primed lung fibroblasts": "cell_line", "CD40": "protein", "costimulatory molecules": "protein", "B7-1": "protein", "B7-2": "protein" } }, { "input_text": "Data reported herein support the hypothesis that cognate interactions between tissue fibroblasts and infiltrating T lymphocytes , via the CD40 /CD40L pathway , augment inflammation and may promote fibrogenesis by activating both cell types .", "target_text": { "tissue fibroblasts": "cell_type", "CD40": "protein", "/CD40L": "protein" } }, { "input_text": "Biphasic control of NF-kappa B activation induced by the triggering of HLA-DR antigens expressed on B cells .", "target_text": { "NF-kappa B": "protein", "HLA-DR antigens": "protein", "B cells": "cell_type" } }, { "input_text": "The regulation of NF-kappa B activation following the triggering of HLA-DR antigens by mAb L243 has been studied at various times in Raji cells .", "target_text": { "NF-kappa B": "protein", "HLA-DR antigens": "protein", "mAb L243": "protein", "Raji cells": "cell_line" } }, { "input_text": "Electrophoretic mobility shift assays demonstrated a strong increase of NF-kappa B DNA binding after triggering of HLA-DR antigens .", "target_text": { "NF-kappa B": "protein", "HLA-DR antigens": "protein" } }, { "input_text": "Using TNF-alpha-activity neutralizing antibodies , the authors demonstrated that the upregulation of NF-kappa B was found to depend , at later time point , on an autocrine effect of TNF-alpha secreted following triggering of HLA-DR antigens .", "target_text": { "TNF-alpha-activity neutralizing antibodies": "protein", "NF-kappa B": "protein", "TNF-alpha": "protein", "HLA-DR antigens": "protein" } }, { "input_text": "In contrast , it was found to be TNF-alpha independent in the early time point .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "Moreover , the upregulation of NF-kappa B binding activity is regulated by the triggering of selected epitopes of HLA-DR antigens .", "target_text": { "NF-kappa B": "protein", "epitopes": "protein", "HLA-DR antigens": "protein" } }, { "input_text": "In fact , mAb L243 but not the staphylococcal superantigens , staphylococcal exotoxin toxic shock syndrome toxin-I or staphylococcal enterotoxin B , regulate the NF-kappa B binding activity .", "target_text": { "mAb L243": "protein", "staphylococcal superantigens": "protein", "staphylococcal exotoxin toxic shock syndrome toxin-I": "protein", "staphylococcal enterotoxin B": "protein", "NF-kappa B": "protein" } }, { "input_text": "Regulation of inosine-5'-monophosphate dehydrogenase type II gene expression in human T cells .", "target_text": { "inosine-5'-monophosphate dehydrogenase": "protein", "inosine-5'-monophosphate dehydrogenase type II": "protein", "human T cells": "cell_type" } }, { "input_text": "Role for a novel 5' palindromic octamer sequence .", "target_text": { "5' palindromic octamer sequence": "DNA" } }, { "input_text": "Expression of the gene encoding human inosine- 5'-monophosphate dehydrogenase ( IMPDH ) type II , an enzyme catalyzing the rate-limiting step in the generation of guanine nucleotides , is increased more than 10-fold in activated peripheral blood T lymphocytes and is required for T cell activation .", "target_text": { "human inosine- 5'-monophosphate dehydrogenase ( IMPDH ) type II": "protein", "enzyme": "protein", "activated peripheral blood T lymphocytes": "cell_type" } }, { "input_text": "We have examined the 5'-regulatory sequences that are important for the transcriptional regulation of this gene in T cells .", "target_text": { "5'-regulatory sequences": "DNA", "T cells": "cell_type" } }, { "input_text": "DNase I mapping of genomic DNA identified a hypersensitive element near the transcription initiation site .", "target_text": { "DNase I": "protein", "genomic DNA": "DNA", "hypersensitive element": "DNA", "transcription initiation site": "DNA" } }, { "input_text": "Fine mapping by in vivo footprinting demonstrated five transcription factor binding sites that are occupied in both resting and activated peripheral blood T lymphocytes ; these are tandem CRE motifs , a Sp1 site , an overlapping Egr-1/ Sp1 site , and a novel palindromic octamer sequence ( POS ) .", "target_text": { "activated peripheral blood T lymphocytes": "cell_type", "tandem CRE motifs": "DNA", "Sp1 site": "DNA", "Egr-1/ Sp1 site": "DNA", "palindromic octamer sequence": "DNA", "POS": "DNA" } }, { "input_text": "The tandem CRE and POS sites are of major functional importance as judged by mutational and electrophoretic mobility shift analyses .", "target_text": {} }, { "input_text": "These data provide evidence that expression of the human IMPDH type II gene is predominantly regulated by the nuclear factors ATF-2 and an as yet unidentified POS -binding protein .", "target_text": { "human IMPDH type II gene": "DNA", "nuclear factors": "protein", "ATF-2": "protein", "POS": "DNA", "POS -binding protein": "protein" } }, { "input_text": "Additional major protein-DNA interactions do not occur within the promoter region after T lymphocyte activation , indicating a requirement for additional protein-protein interactions and/or post-translational modifications of pre-bound transcription factors to account for the observed increase in IMPDH type II gene expression .", "target_text": { "pre-bound transcription factors": "protein" } }, { "input_text": "Distinct mechanisms for N-acetylcysteine inhibition of cytokine-induced E-selectin and VCAM-1 expression .", "target_text": { "cytokine-induced E-selectin": "protein", "VCAM-1": "protein" } }, { "input_text": "We have examined the effects of N-acetyl-L-cysteine ( NAC ) , a well-characterized , thiol-containing antioxidant , on agonist-induced monocytic cell adhesion to endothelial cells ( EC ) .", "target_text": { "endothelial cells": "cell_type", "EC": "cell_type" } }, { "input_text": "NAC inhibited interleukin-1 ( IL-1 beta ) -induced , but not basal , adhesion with 50 % inhibition at approximately 20 mM .", "target_text": { "interleukin-1": "protein", "IL-1 beta": "protein" } }, { "input_text": "Monocytic cell adhesion to EC in response to tumor necrosis factor-alpha ( TNF-alpha ) , lipopolysaccharide ( LPS ) , alpha-thrombin , or phorbol 12-myristate 13-acetate ( PMA ) was similarly inhibited by NAC .", "target_text": { "EC": "cell_type", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "alpha-thrombin": "protein" } }, { "input_text": "Unlike published studies with pyrrolidinedithiocarbamate , which specifically inhibited vascular cell adhesion molecule 1 ( VCAM-1 ) , NAC inhibited IL-1 beta -induced mRNA and cell surface expression of both E-selectin and VCAM-1 .", "target_text": { "vascular cell adhesion molecule 1": "protein", "VCAM-1": "protein", "IL-1 beta": "protein", "IL-1 beta -induced mRNA": "RNA", "E-selectin": "protein" } }, { "input_text": "NAC had no effect on the half-life of E-selectin or VCAM-1 mRNA .", "target_text": {} }, { "input_text": "Although NAC reduced nuclear factor-kappa B ( NF-kappa B ) activation in EC as measured by gel-shift assays using an oligonucleotide probe corresponding to the consensus NF-kappa B binding sites of the VCAM-1 gene ( VCAM- NF-kappa B ) , the antioxidant had no appreciable effect when an oligomer corresponding to the consensus NF-kappa B binding site of the E-selectin gene ( E-selectin -NF-kappa B ) was used .", "target_text": { "nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "EC": "cell_type", "oligonucleotide probe": "DNA", "NF-kappa B binding sites": "DNA", "VCAM-1": "protein", "VCAM-1 gene": "DNA", "VCAM- NF-kappa B": "protein", "consensus NF-kappa B binding site": "DNA", "E-selectin": "protein", "E-selectin gene": "DNA", "-NF-kappa B": "protein" } }, { "input_text": "Because NF-kappa B has been reported to be redox sensitive , we studied the effects of NAC on the EC redox environment .", "target_text": { "NF-kappa B": "protein", "EC": "cell_type" } }, { "input_text": "NAC caused an expected dramatic increase in the reduced glutathione ( GSH ) levels in EC .", "target_text": { "EC": "cell_type" } }, { "input_text": "In vitro studies demonstrated that whereas the binding affinity of NF-kappa B to the VCAM- NF-kappa B oligomer peaked at a GSH -to-oxidized glutathione ( GSSG ) ratio of approximately 200 and decreased at higher ratios , the binding to the E-selectin -NF-kappa B oligomer appeared relatively unaffected even at ratios > 400 , i.e. , those achieved in EC treated with 40 mM NAC .", "target_text": { "NF-kappa B": "protein", "VCAM- NF-kappa B oligomer": "DNA", "E-selectin": "protein", "-NF-kappa B": "protein", "E-selectin -NF-kappa B oligomer": "DNA", "EC": "cell_type" } }, { "input_text": "These results suggest that NF-kappa B binding to its consensus sequences in the VCAM-1 and E-selectin gene exhibits marked differences in redox sensitivity , allowing for differential gene expression regulated by the same transcription factor .", "target_text": { "NF-kappa B": "protein", "VCAM-1": "protein", "E-selectin": "protein", "E-selectin gene": "DNA" } }, { "input_text": "Our data also demonstrate that NAC increases the GSH -to- GSSG ratio within the EC suggesting one possible mechanism through which this antioxidant inhibits agonist-induced monocyte adhesion to EC .", "target_text": { "EC": "cell_type" } }, { "input_text": "Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor alpha ( RAR alpha ) and PLZF-RAR alpha fusion proteins on retinoic acid signalling .", "target_text": { "acute promyelocytic leukemia PML-retinoic acid receptor alpha": "protein", "RAR alpha": "protein", "PLZF-RAR alpha fusion proteins": "protein" } }, { "input_text": "Fusion proteins involving the retinoic acid receptor alpha ( RAR alpha ) and the PML or PLZF nuclear protein are the genetic markers of acute promyelocytic leukemias ( APLs ) .", "target_text": { "receptor alpha": "protein", "RAR alpha": "protein", "PML": "protein", "PLZF nuclear protein": "protein" } }, { "input_text": "APLs with the PML-RAR alpha or the PLZF-RAR alpha fusion protein are phenotypically indistinguishable except that they differ in their sensitivity to retinoic acid ( RA ) -induced differentiation : PML-RAR alpha blasts are sensitive to RA and patients enter disease remission after RA treatment , while patients with PLZF-RAR alpha do not .", "target_text": { "PML-RAR alpha": "protein", "PLZF-RAR alpha": "protein", "PLZF-RAR alpha fusion protein": "protein" } }, { "input_text": "We here report that ( i ) like PML-RAR alpha expression , PLZF-RAR alpha expression blocks terminal differentiation of hematopoietic precursor cell lines ( U937 and HL-60 ) in response to different stimuli ( vitamin D3 , transforming growth factor beta1 , and dimethyl sulfoxide ) ; ( ii ) PML-RAR alpha , but not PLZF-RAR alpha , increases RA sensitivity of hematopoietic precursor cells and restores RA sensitivity of RA-resistant hematopoietic cells ; ( iii ) PML-RAR alpha and PLZF-RAR alpha have similar RA binding affinities ; and ( iv ) PML-RAR alpha enhances the RA response of RA target genes ( those for RAR beta , RAR gamma , and transglutaminase type II [ TGase ] ) in vivo , while PLZF-RAR alpha expression has either no effect ( RAR beta ) or an inhibitory activity ( RAR gamma and type II TGase ) .", "target_text": { "PML-RAR alpha": "protein", "PLZF-RAR alpha": "protein", "U937": "cell_line", "HL-60": "cell_line", "hematopoietic precursor cells": "cell_type", "RA-resistant hematopoietic cells": "cell_type", "RA target genes": "DNA", "RAR beta": "protein", "RAR gamma": "protein", "transglutaminase type II": "protein", "TGase": "protein", "type II TGase": "protein" } }, { "input_text": "These data demonstrate that PML-RAR alpha and PLZF-RAR alpha have similar ( inhibitory ) effects on RA-independent differentiation and opposite ( stimulatory or inhibitory ) effects on RA -dependent differentiation and that they behave in vivo as RA -dependent enhancers or inhibitors of RA -responsive genes , respectively .", "target_text": { "PML-RAR alpha": "protein", "PLZF-RAR alpha": "protein", "RA -dependent enhancers": "DNA", "RA -responsive genes": "DNA" } }, { "input_text": "Their different activities on the RA signalling pathway might underlie the different responses of PML-RAR alpha and PLZF-RAR alpha APLs to RA treatment .", "target_text": { "PML-RAR alpha": "protein", "PLZF-RAR alpha": "protein" } }, { "input_text": "The PLZF-RAR alpha fusion protein contains an approximately 120-amino-acid N-terminal motif ( called the POZ domain ) , which is also found in a variety of zinc finger proteins and a group of poxvirus proteins and which mediates protein-protein interactions .", "target_text": { "PLZF-RAR alpha": "protein", "PLZF-RAR alpha fusion protein": "protein", "120-amino-acid N-terminal motif": "protein", "POZ domain": "protein", "poxvirus proteins": "protein" } }, { "input_text": "Deletion of the PLZF POZ domain partially abrogated the inhibitory effect of PLZF-RAR alpha on RA-induced differentiation and on RA-mediated type II TGase up-regulation , suggesting that POZ-mediated protein interactions might be responsible for the inhibitory transcriptional activities of PLZF-RAR alpha .", "target_text": { "POZ domain": "protein", "PLZF POZ domain": "protein", "PLZF-RAR alpha": "protein", "type II TGase": "protein" } }, { "input_text": "A human homologue of the Drosophila Toll protein signals activation of adaptive immunity [ see comments ]", "target_text": { "Drosophila Toll protein": "protein" } }, { "input_text": "Induction of the adaptive immune response depends on the expression of co-stimulatory molecules and cytokines by antigen-presenting cells .", "target_text": { "co-stimulatory molecules": "protein", "cytokines": "protein", "antigen-presenting cells": "cell_type" } }, { "input_text": "The mechanisms that control the initial induction of these signals upon infection are poorly understood .", "target_text": {} }, { "input_text": "It has been proposed that their expression is controlled by the non-clonal , or innate , component of immunity that preceded in evolution the development of an adaptive immune system in vertebrates .", "target_text": {} }, { "input_text": "We report here the cloning and characterization of a human homologue of the Drosophila toll protein ( Toll ) which has been shown to induce the innate immune response in adult Drosophila .", "target_text": { "human homologue": "protein", "Drosophila toll protein": "protein", "Toll": "protein" } }, { "input_text": "Like Drosophila Toll , human Toll is a type I transmembrane protein with an extracellular domain consisting of a leucine-rich repeat ( LRR ) domain , and a cytoplasmic domain homologous to the cytoplasmic domain of the human interleukin ( IL ) -1 receptor .", "target_text": { "Toll": "protein", "human Toll": "protein", "LRR": "protein", "leucine-rich repeat ( LRR ) domain": "protein", "cytoplasmic domain": "protein", "human interleukin ( IL ) -1 receptor": "protein" } }, { "input_text": "Both Drosophila Toll and the IL-1 receptor are known to signal through the NF-kappaB pathway .", "target_text": { "Toll": "protein", "NF-kappaB": "protein" } }, { "input_text": "We show that a constitutively active mutant of human Toll transfected into human cell lines can induce the activation of NF-kappaB and the expression of NF-kappaB -controlled genes for the inflammatory cytokines IL-1 , IL-6 and IL-8 , as well as the expression of the co-stimulatory molecule B7.1 , which is required for the activation of naive T cells .", "target_text": { "Toll": "protein", "human Toll": "protein", "NF-kappaB": "protein", "NF-kappaB -controlled genes": "DNA", "cytokines": "protein", "inflammatory cytokines": "protein", "IL-1": "protein", "IL-6": "protein", "IL-8": "protein", "co-stimulatory molecule": "protein", "B7.1": "protein", "T cells": "cell_type", "naive T cells": "cell_type" } }, { "input_text": "Role of ascorbate in the activation of NF-kappaB by tumour necrosis factor-alpha in T-cells .", "target_text": { "NF-kappaB": "protein", "tumour necrosis factor-alpha": "protein", "T-cells": "cell_type" } }, { "input_text": "The first product of ascorbate oxidation , the ascorbate free radical ( AFR ) , acts in biological systems mainly as an oxidant , and through its role in the plasma membrane redox system exerts different effects on the cell .", "target_text": {} }, { "input_text": "We have investigated the role of ascorbate , AFR and dehydroascorbate ( DHA ) in the activation of the NF-kappaB transcription factor in Jurkat T-cells stimulated by tumour necrosis factor-alpha ( TNF-alpha ) .", "target_text": { "NF-kappaB": "protein", "NF-kappaB transcription factor": "protein", "Jurkat T-cells": "cell_line", "tumour necrosis factor-alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "Here we show , by electrophoretic mobility shift assays , that ascorbate increases the binding of NF-kappaB to DNA in TNF-alpha -stimulated Jurkat cells .", "target_text": { "NF-kappaB": "protein", "TNF-alpha": "protein", "TNF-alpha -stimulated Jurkat cells": "cell_line" } }, { "input_text": "The ability of ascorbate to enhance cytoplasmic inhibitory IkBalpha protein degradation correlates completely with its capacity to induce NF-kappaB binding to DNA and to potentiate NF-kappaB -mediated transactivation of the HIV-1 long terminal repeat promoter in TNF-alpha -stimulated Jurkat cells but not in cells stimulated with PMA plus ionomycin .", "target_text": { "IkBalpha protein": "protein", "NF-kappaB": "protein", "HIV-1 long terminal repeat promoter": "DNA", "TNF-alpha": "protein", "TNF-alpha -stimulated Jurkat cells": "cell_line" } }, { "input_text": "AFR behaves like ascorbate , while DHA and ascorbate phosphate do not affect TNF-alpha -mediated NF-kappaB activation .", "target_text": { "TNF-alpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "These results provide new evidence for a possible relationship between the activation of the electron-transport system at the plasma membrane by ascorbate or its free radical and redox-dependent gene transcription in T-cells .", "target_text": { "T-cells": "cell_type" } }, { "input_text": "Human cytomegalovirus induces interleukin-8 production by a human monocytic cell line , THP-1 , through acting concurrently on AP-1- and NF-kappaB- binding sites of the interleukin-8 gene .", "target_text": { "interleukin-8": "protein", "human monocytic cell line": "cell_line", "THP-1": "cell_line", "interleukin-8 gene": "DNA" } }, { "input_text": "Cytomegalovirus ( CMV ) infection induced interleukin-8 ( IL-8 ) gene transcription in a human monocytic cell line , THP-1 cells , leading to IL-8 secretion .", "target_text": { "interleukin-8": "protein", "IL-8": "protein", "human monocytic cell line": "cell_line", "THP-1 cells": "cell_line" } }, { "input_text": "The functional analysis of the IL-8 gene revealed that both AP-1- and NF-kappaB factor- binding elements were involved in conferring the responsiveness to CMV .", "target_text": { "IL-8": "protein", "IL-8 gene": "DNA" } }, { "input_text": "Moreover , electrophoretic mobility shift assays demonstrated that CMV induced the formation of NF-kappaB and AP-1 complexes .", "target_text": { "NF-kappaB": "protein", "AP-1 complexes": "protein" } }, { "input_text": "These results suggest that CMV activates these transcriptional factors , resulting in IL-8 gene expression .", "target_text": { "transcriptional factors": "protein", "IL-8": "protein" } }, { "input_text": "Construction and biological characterization of an interleukin-12 fusion protein ( Flexi-12 ) : delivery to acute myeloid leukemic blasts using adeno-associated virus .", "target_text": { "interleukin-12 fusion protein": "protein", "Flexi-12": "protein", "acute myeloid leukemic blasts": "cell_type" } }, { "input_text": "Interleukin-12 ( IL-12 ) is a cytokine that exhibits pleiotropic effects on lymphocytes and natural killer cells and has been shown to have promise for the immunotherapy of cancer .", "target_text": { "Interleukin-12": "protein", "IL-12": "protein", "cytokine": "protein", "lymphocytes": "cell_type", "natural killer cells": "cell_type" } }, { "input_text": "The combination of the immune costimulatory molecule B7.1 and IL-12 has been shown to be synergistic for T cell activation .", "target_text": { "immune costimulatory molecule": "protein", "B7.1": "protein", "IL-12": "protein" } }, { "input_text": "By transfecting tumor cells with both IL-12 and B7.1 cDNAs , it may be possible to use these modified targets as vaccines .", "target_text": {} }, { "input_text": "A major obstacle in designing a vector to deliver these genes results from the structure of IL-12 .", "target_text": { "IL-12": "protein" } }, { "input_text": "Functional IL-12 is a heterodimer composed of two distinct subunits that are encoded by separate genes on different chromosomes .", "target_text": { "IL-12": "protein", "heterodimer": "protein" } }, { "input_text": "Production of functional IL-12 requires the coordinated expression of both genes .", "target_text": { "IL-12": "protein", "functional IL-12": "protein" } }, { "input_text": "This presents several problems in vectors , particularly those in which additional genes , either a co-stimulatory gene or a selectable marker , are inserted .", "target_text": { "co-stimulatory gene": "DNA" } }, { "input_text": "Therefore , we have constructed a single cDNA that encodes a single-chain protein , called Flexi-12 , which retains all of the biological characteristics of recombinant IL-12 ( rIL-12 ) .", "target_text": { "cDNA": "DNA", "single-chain protein": "protein", "Flexi-12": "protein", "IL-12": "protein", "rIL-12": "protein" } }, { "input_text": "The monomeric polypeptide Flexi-12 is able to induce the proliferation of phytohemagglutinin ( PHA ) blasts , induce PHA blasts to secrete interferon-gamma ( IFN-gamma ) and additionally , by preincubation , enhance the killing of K562 targets by PBLs .", "target_text": { "Flexi-12": "protein", "phytohemagglutinin": "protein", "PHA": "protein", "phytohemagglutinin ( PHA ) blasts": "cell_line", "PHA blasts": "cell_line", "interferon-gamma": "protein", "IFN-gamma": "protein", "PBLs": "cell_type" } }, { "input_text": "These phenomena are in a dose-dependent manner comparable to that seen with rIL-12 .", "target_text": { "rIL-12": "protein" } }, { "input_text": "We have also shown that tyrosine phosphorylation of the STAT 4 transcription factor , which has been shown to be unique to the IL-12 signaling pathway , occurs with Flexi-12 at levels similar to those seen with rIL-12 .", "target_text": { "STAT 4 transcription factor": "protein", "IL-12": "protein", "Flexi-12": "protein", "rIL-12": "protein" } }, { "input_text": "We have packaged Flexi-12 into a recombinant adeno-associated virus ( AAV ) and used this vector to infect acute myeloid leukemic ( AML ) blasts .", "target_text": { "Flexi-12": "protein", "acute myeloid leukemic ( AML ) blasts": "cell_type" } }, { "input_text": "Infected AML blasts produced between 2 and 6 ng of IL-12/10 ( 6 ) cells per ml per 48 hr .", "target_text": { "AML blasts": "cell_type" } }, { "input_text": "These studies also confirm that AAV is an efficient delivery vehicle for cytokines to leukemic cells .", "target_text": { "cytokines": "protein" } }, { "input_text": "Direct analysis of these modified cells acting as tumor vaccines is underway .", "target_text": {} }, { "input_text": "Plasma sialyltransferase levels in psychiatric disorders as a possible indicator of HPA axis function .", "target_text": { "sialyltransferase": "protein" } }, { "input_text": "A dysfunction in the regulation of the hypothalamic-pituitary-adrenal ( HPA ) axis , possibly attributed to a change in glucocorticoid receptor ( GR ) functionality , has been implicated in depression .", "target_text": { "glucocorticoid receptor": "protein", "GR": "protein" } }, { "input_text": "We have measured both lymphocyte GR receptor binding parameters and plasma sialyltransferase activity , as a biochemical marker of GR function , in two groups of patients suffering from depression or schizophrenia and in a group of age- and sex-matched controls .", "target_text": { "lymphocyte GR": "protein", "sialyltransferase": "protein", "GR": "protein" } }, { "input_text": "While there was a significant increase in plasma cortisol levels in the depressed group , there were no changes in the lymphocyte GR binding parameters ( K ( m ) and Bmax ) .", "target_text": { "GR": "protein" } }, { "input_text": "There was , however , a significant decrease in the plasma sialyltransferase : cortisol ratio in the depressed group suggesting an inability of the raised cortisol levels to induce enzyme expression and this ratio may provide a useful biochemical marker of cortisol receptor function .", "target_text": { "sialyltransferase": "protein", "plasma sialyltransferase :": "protein" } }, { "input_text": "Although there was an increase in the plasma activity of the alpha 2,6 sialyltransferase isozyme in the schizophrenic group , no other changes were determined .", "target_text": { "sialyltransferase": "protein", "alpha 2,6 sialyltransferase isozyme": "protein" } }, { "input_text": "Therefore , while the total plasma sialyltransferase : cortisol ratio reflects HPA axis function , alterations in specific isozyme activity may also be associated with other CNS disease states .", "target_text": { "sialyltransferase": "protein", "plasma sialyltransferase": "protein" } }, { "input_text": "Regulation of CD95 ( Fas ) ligand expression by TCR -mediated signaling events .", "target_text": { "CD95 ( Fas ) ligand": "protein", "TCR": "protein" } }, { "input_text": "Stimulation of mature peripheral T cells by TCR engagement results in activation of signals that drive induction of cytokine gene expression and clonal expansion .", "target_text": { "mature peripheral T cells": "cell_type", "TCR": "protein", "cytokine": "protein" } }, { "input_text": "However , under some conditions , engagement of the TCR leads instead to apoptosis .", "target_text": { "TCR": "protein" } }, { "input_text": "Recent studies demonstrate that TCR -stimulated apoptosis requires expression of CD95 ligand on activated T cells followed by an interaction between CD95 ligand and the CD95 receptor also expressed on this population .", "target_text": { "TCR": "protein", "CD95 ligand": "protein", "activated T cells": "cell_type", "CD95 receptor": "protein" } }, { "input_text": "The experiments reported in this study were designed to address the signaling events triggered by TCR engagement that are important for regulating CD95 ligand gene expression .", "target_text": { "TCR": "protein", "CD95 ligand": "protein" } }, { "input_text": "To approach this , we generated a luciferase reporter construct containing elements of the CD95 ligand promoter .", "target_text": { "luciferase": "protein", "luciferase reporter construct": "DNA", "CD95 ligand": "protein" } }, { "input_text": "Using a previously described mutant of the Jurkat T cell line , we show that proximal signaling events dependent on the presence of the CD45 tyrosine phosphatase are required for TCR -stimulated CD95 ligand expression .", "target_text": { "Jurkat T cell line": "cell_line", "CD45 tyrosine phosphatase": "protein", "TCR": "protein", "CD95 ligand": "protein" } }, { "input_text": "Transient transfection studies demonstrate further that TCR -stimulated activation of the Ras signaling pathway is required for optimal activation of CD95 ligand .", "target_text": { "TCR": "protein", "Ras": "protein", "CD95 ligand": "protein" } }, { "input_text": "Next , in an effort to determine critical transcription factors that regulate CD95 ligand expression , we demonstrate a cyclosporin A-sensitive nuclear factor-AT response element in the promoter region of this gene that is critical for optimal CD95 ligand reporter activity in stimulated T cells .", "target_text": { "transcription factors": "protein", "CD95 ligand": "protein", "cyclosporin A-sensitive nuclear factor-AT response element": "DNA", "promoter region": "DNA", "stimulated T cells": "cell_type" } }, { "input_text": "Together , these studies begin a dissection of the biochemical events that lead to expression of CD95 ligand , a required step for TCR -induced apoptosis .", "target_text": { "CD95 ligand": "protein", "TCR": "protein" } }, { "input_text": "Reactive oxygen species and antioxidants in inflammatory diseases .", "target_text": {} }, { "input_text": "This paper aims to review the role of free radical-induced tissue damage and antioxidant defence mechanisms in inflammatory diseases that involve pathogenic processes similar to the periodontal diseases .", "target_text": {} }, { "input_text": "There is a clearly defined and substantial role for free radicals or reactive oxygen species ( ROS ) in periodontitis , but little research has been performed in this area .", "target_text": {} }, { "input_text": "This paper reviews the considerable data available relating ROS activity and antioxidant defence to inflammatory diseases and attempts to draw parallels with periodontitis , in an effort to stimulate more periodontal research in this important area .", "target_text": {} }, { "input_text": "The recent discovery of the transcription factor nuclear factor kappa B ( NF-kappa B ) is reviewed and several potential pathways for cytokine -induced periodontal tissue damage , mediated by NF-kappa B1 are discussed .", "target_text": { "transcription factor nuclear factor kappa B": "protein", "NF-kappa B": "protein", "cytokine": "protein", "NF-kappa B1": "protein" } }, { "input_text": "Emphasis is placed on cytokines that have been studied in periodontitis , principally TNF-alpha , IL-1 , IL-6 , IL-8 and beta-interferon .", "target_text": { "cytokines": "protein", "TNF-alpha": "protein", "IL-1": "protein", "IL-6": "protein", "IL-8": "protein", "beta-interferon": "protein" } }, { "input_text": "The link between cellular production of such important mediators of inflammation and the antioxidant ( AO ) thiols , cysteine and reduced glutathione ( GSH ) , is discussed and it is hypothesised that NF-kappa B antagonists may offer important therapeutic benefits .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Mutations in the TSC2 gene : analysis of the complete coding sequence using the protein truncation test ( PTT ) .", "target_text": { "TSC2 gene": "DNA" } }, { "input_text": "Mutations in the TSC2 gene on chromosome 16p13.3 are responsible for approximately 50 % of familial tuberous sclerosis ( TSC ) .", "target_text": { "TSC2 gene": "DNA", "chromosome 16p13.3": "DNA" } }, { "input_text": "The gene has 41 small exons spanning 45 kb of genomic DNA and encoding a 5.5 kb mRNA .", "target_text": { "41 small exons": "DNA", "45 kb": "DNA", "genomic DNA": "DNA", "5.5 kb mRNA": "RNA" } }, { "input_text": "Large germline deletions of TSC2 occur in < 5 % of cases , and a number of small intragenic mutations have been described .", "target_text": { "TSC2": "DNA" } }, { "input_text": "We analysed mRNA from 18 unrelated cases of TSC for TSC2 mutations using the protein truncation test ( PTT ) .", "target_text": { "TSC2 mutations": "DNA" } }, { "input_text": "Three cases were predicted to be TSC2 mutations on the basis of linkage analysis or because a hamartoma from the patient showed loss of heterozygosity for 16p13.3 markers .", "target_text": { "TSC2 mutations": "DNA", "16p13.3 markers": "DNA" } }, { "input_text": "Three overlapping PCR products , covering the complete coding sequence of mRNA , were generated from lymphoblastoid cell lines , translated into 35S-methionine labelled protein , and analysed by SDS-PAGE .", "target_text": { "PCR products": "DNA", "mRNA": "RNA", "lymphoblastoid cell lines": "cell_line", "35S-methionine labelled protein": "protein" } }, { "input_text": "PCR products showing PTT shifts were directly sequenced , and mutations confirmed by restriction enzyme digestion where possible .", "target_text": { "PCR products": "DNA" } }, { "input_text": "Six PTT shifts were identified .", "target_text": {} }, { "input_text": "Five of these were caused by mutations predicted to produce a truncated protein : ( i ) a sporadic case showed a 32 bp deletion in exon 11 , and a mutant mRNA without exon 11 was produced ; the normal exon 10 was also spliced out ; ( ii ) a sporadic case had a 1 bp deletion in exon 12 ( 1634delT ) ; ( iii ) a TSC2 -linked mother and daughter pair had a G --> T transversion in exon 23 ( G2715T ) introducing a cryptic splice site causing a 29 bp truncation of mRNA from exon 23 ; ( iv ) a sporadic case showed a 2 bp deletion in exon 36 ; ( v ) a sporadic case showed a 1 bp insertion disrupting the donor splice site of exon 37 ( 5007+2insA ) , resulting in the use of an upstream exonic cryptic splice site to cause a 29 bp truncation of mRNA from exon 37 .", "target_text": { "truncated protein": "protein", "32 bp deletion": "DNA", "exon 11": "RNA", "mutant mRNA": "RNA", "1 bp deletion": "DNA", "exon 12": "RNA", "1634delT": "RNA", "TSC2": "DNA", "TSC2 -linked mother and daughter pair": "RNA", "exon 23": "RNA", "G2715T": "RNA", "2 bp deletion": "DNA", "exon 36": "RNA", "1 bp insertion": "DNA", "exon 37": "RNA", "5007+2insA": "RNA", "upstream exonic cryptic splice site": "RNA", "29 bp truncation": "RNA", "mRNA": "RNA" } }, { "input_text": "In one case , the PTT shift was explained by in-frame splicing out of exon 10 , in the presence of a normal exon 10 genomic sequence .", "target_text": { "exon 10": "RNA", "normal exon 10 genomic sequence": "DNA" } }, { "input_text": "Alternative splicing of exon 10 of the TSC2 gene may be a normal variant .", "target_text": { "exon 10": "RNA", "TSC2 gene": "DNA" } }, { "input_text": "Three 3rd base substitution polymorphisms were also detected during direct sequencing of PCR products .", "target_text": { "PCR products": "DNA" } }, { "input_text": "Confirmed mutations were identified in 28 % of the families studied and on the assumption that half of the sporadic cases should have TSC2 mutations , a crude estimate of the detection rate would be 60 % .", "target_text": { "TSC2 mutations": "DNA" } }, { "input_text": "This compares favourably with other screening methods used for TSC2 , notably SSCP , and since PTT involves much less work it may be the method of choice .", "target_text": { "TSC2": "DNA" } }, { "input_text": "alpha-Tocopheryl succinate inhibits monocytic cell adhesion to endothelial cells by suppressing NF-kappa B mobilization .", "target_text": { "endothelial cells": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "The adherence of monocytes to activated endothelium is an early event in atherogenesis .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "Because antioxidants have been considered to be of antiatherosclerotic potential , we investigated the effects of alpha-tocopherol ( TCP ) and its acetate and succinate esters on monocyte adhesion to cytokine-stimulated human umbilical vein endothelial cells ( HUVEC ) .", "target_text": { "endothelial cells": "cell_type", "cytokine-stimulated human umbilical vein endothelial cells": "cell_line", "HUVEC": "cell_line" } }, { "input_text": "Endothelial cells were treated with TCP , alpha-tocopherol acetate ( TCP acetate ) , or alpha-tocopheryl succinate ( TCP succinate ) before stimulation with tumor necrosis factor-alpha ( TNF-alpha ; 10 U/ml , 6 h ) or interleukin-1 beta ( IL-1 beta ; 10 U/ml , 6 h ) .", "target_text": { "Endothelial cells": "cell_type", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "interleukin-1 beta": "protein", "IL-1 beta": "protein" } }, { "input_text": "Cytokine-stimulated cell surface expression of vascular cell adhesion molecule-1 ( VCAM-1 , CD106 ) and E-selectin ( ELAM-1 , CD62E ) , but not of intercellular adhesion molecule-1 ( ICAM-1 , CD54 ) , was time- and dose- dependently inhibited by TCP succinate but not by TCP or TCP acetate .", "target_text": { "vascular cell adhesion molecule-1": "protein", "VCAM-1": "protein", "CD106": "protein", "E-selectin": "protein", "ELAM-1": "protein", "CD62E": "protein", "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "CD54": "protein" } }, { "input_text": "TCP succinate ( 200 microM , 24 h ) reduced TNF-induced VCAM-1 and E-selectin expression from a specific mean fluorescence intensity of 151 +/- 28 to 12 +/- 4 channels and from 225 +/- 38 to 79 +/- 21 channels , respectively .", "target_text": { "VCAM-1": "protein", "TNF-induced VCAM-1": "protein", "E-selectin": "protein" } }, { "input_text": "Succinate alone had no effect .", "target_text": {} }, { "input_text": "Decreased adhesion molecule expression was associated with a reduction of monocytic cell adhesion .", "target_text": { "adhesion molecule": "protein" } }, { "input_text": "TCP succinate ( 20 microM , 72 h ) , but not TCP ( 200 microM , 72 h ) , reduced U-937 cell adhesion to TNF-alpha -stimulated ( 10 U/ml , 6 h ) HUVEC by 30 % ( P < 0.025 ) and to IL-1 beta -stimulated HUVEC by 56 % ( P < 0.010 ) .", "target_text": { "U-937 cell": "cell_line", "TNF-alpha": "protein", "HUVEC": "cell_line", "TNF-alpha -stimulated ( 10 U/ml , 6 h ) HUVEC": "cell_line", "IL-1 beta": "protein", "IL-1 beta -stimulated HUVEC": "cell_line" } }, { "input_text": "Electrophoretic mobility-shift assays of HUVEC nuclear proteins revealed a decrease in TNF-alpha -stimulated nuclear factor-kappa B ( NF-kappa B ) activation after pretreatment of HUVEC with TCP succinate but not with TCP , TCP acetate , or succinate alone .", "target_text": { "HUVEC": "cell_line", "nuclear proteins": "protein", "TNF-alpha": "protein", "TNF-alpha -stimulated nuclear factor-kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "In conclusion , we demonstrate that the vitamin E derivative TCP succinate prevents monocytic cell adhesion to cytokine-stimulated endothelial cells by inhibiting the activation of NF-kappa B , further emphasizing the antiatherosclerotic potential of lipid soluble antioxidants .", "target_text": { "endothelial cells": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "The product of the murine homolog of the Drosophila extra sex combs gene displays transcriptional repressor activity .", "target_text": { "murine homolog": "DNA", "Drosophila extra sex combs gene": "DNA", "transcriptional repressor": "protein" } }, { "input_text": "The heterogeneous nuclear ribonucleoprotein K protein represents a novel class of proteins that may act as docking platforms that orchestrate cross-talk among molecules involved in signal transduction and gene expression .", "target_text": { "heterogeneous nuclear ribonucleoprotein K protein": "protein" } }, { "input_text": "Using a fragment of K protein as bait in the yeast two-hybrid screen , we isolated a cDNA that encodes a protein whose primary structure has extensive similarity to the Drosophila melanogaster extra sex combs ( esc ) gene product , Esc , a putative silencer of homeotic genes .", "target_text": { "K protein": "protein", "cDNA": "DNA", "Drosophila melanogaster extra sex combs ( esc ) gene product": "protein", "Esc": "protein", "homeotic genes": "DNA" } }, { "input_text": "The cDNA that we isolated is identical to the cDNA of the recently positionally cloned mouse embryonic ectoderm development gene , eed .", "target_text": { "cDNA": "DNA", "mouse embryonic ectoderm development gene": "DNA" } }, { "input_text": "Like Esc , Eed contains six WD-40 repeats in the C-terminal half of the protein and is thought to repress homeotic gene expression during mouse embryogenesis .", "target_text": { "Esc": "protein", "Eed": "protein", "WD-40 repeats": "protein", "C-terminal half": "protein" } }, { "input_text": "Eed binds to K protein through a domain in its N terminus , but interestingly , this domain is not found in the Drosophila Esc .", "target_text": { "Eed": "protein", "K protein": "protein", "N terminus": "protein", "Esc": "protein" } }, { "input_text": "Gal4- Eed fusion protein represses transcription of a reporter gene driven by a promoter that contains Gal4-binding DNA elements .", "target_text": { "Eed": "protein", "Gal4- Eed fusion protein": "protein", "Gal4-binding DNA elements": "DNA" } }, { "input_text": "Eed also represses transcription when recruited to a target promoter by Gal4- K protein .", "target_text": { "Eed": "protein", "K protein": "protein", "Gal4- K protein": "protein" } }, { "input_text": "Point mutations within the eed gene that are responsible for severe embryonic development abnormalities abolished the transcriptional repressor activity of Eed .", "target_text": { "transcriptional repressor": "protein", "Eed": "protein" } }, { "input_text": "Results of this study suggest that Eed -restricted homeotic gene expression during embryogenesis reflects the action of Eed as a transcriptional repressor .", "target_text": { "Eed": "protein", "transcriptional repressor": "protein" } }, { "input_text": "The Eed -mediated transcriptional effects are likely to reflect the interaction of Eed with multiple molecular partners , including K protein .", "target_text": { "Eed": "protein", "K protein": "protein" } }, { "input_text": "Interferons up-regulate STAT1 , STAT2 , and IRF family transcription factor gene expression in human peripheral blood mononuclear cells and macrophages .", "target_text": { "Interferons": "protein", "STAT1": "protein", "STAT2": "protein", "IRF": "protein", "human peripheral blood mononuclear cells": "cell_type", "macrophages": "cell_type" } }, { "input_text": "IFN signaling is mediated by binding of IFNs to their receptors and subsequent activation of Janus tyrosine kinase ( JAK ) - STAT signaling pathway .", "target_text": { "IFN": "protein", "IFNs": "protein", "JAK": "protein", "STAT": "protein" } }, { "input_text": "Stimulation of cells with IFN-alpha leads to the assembly of IFN-stimulated gene factor 3 transcription factor complex formed by STAT1 , STAT2 , and p48 protein .", "target_text": { "IFN-alpha": "protein", "IFN-stimulated gene factor 3 transcription factor complex": "protein", "STAT1": "protein", "STAT2": "protein", "p48 protein": "protein" } }, { "input_text": "IFN-gamma signaling is mediated by homodimeric STAT1 protein .", "target_text": { "IFN-gamma": "protein", "STAT1": "protein", "homodimeric STAT1 protein": "protein" } }, { "input_text": "Although these signaling molecules are expressed constitutively , there is also evidence of transcriptional regulation by IFNs .", "target_text": { "IFNs": "protein" } }, { "input_text": "We have characterized the expression of STAT and IFN regulatory factor ( IRF ) family transcription factors in primary human blood mononuclear cells and macrophages in response to IFN-alpha and IFN-gamma stimulation .", "target_text": { "STAT and IFN regulatory factor ( IRF ) family transcription factors": "protein", "primary human blood mononuclear cells": "cell_type", "macrophages": "cell_type" } }, { "input_text": "We show that IFN-alpha and IFN-gamma rapidly and efficiently enhanced STAT1 , STAT2 , p48 , and IRF-1 gene expression .", "target_text": { "IFN-alpha": "protein", "IFN-gamma": "protein", "STAT1": "protein", "STAT2": "protein", "p48": "protein", "IRF-1": "protein", "IRF-1 gene": "DNA" } }, { "input_text": "IFN-gamma induced IRF-1 gene expression more strongly than IFN-alpha .", "target_text": { "IFN-gamma": "protein", "IRF-1": "protein", "IRF-1 gene": "DNA", "IFN-alpha": "protein" } }, { "input_text": "Stimulation experiments in the presence of protein synthesis inhibitor , cycloheximide , suggested that these genes were activated directly by IFNs .", "target_text": { "IFNs": "protein" } }, { "input_text": "IRF-2 gene was apparently only weakly responsive to IFNs in these cells .", "target_text": { "IRF-2 gene": "DNA", "IFNs": "protein" } }, { "input_text": "When macrophages were pretreated with low doses of IFN-gamma and then stimulated with IFN-alpha , clearly enhanced formation of specific transcription factor complexes was detected .", "target_text": { "macrophages": "cell_type", "IFN-gamma": "protein", "IFN-alpha": "protein", "transcription factor": "protein" } }, { "input_text": "This suggests that higher intracellular levels of STAT1 , STAT2 , and p48 protein may result in enhanced signal transduction for cytokines utilizing these transcription factors .", "target_text": { "STAT1": "protein", "STAT2": "protein", "p48": "protein", "p48 protein": "protein", "cytokines": "protein", "transcription factors": "protein" } }, { "input_text": "The role of nuclear factor-kappa B in cytokine gene regulation .", "target_text": { "nuclear factor-kappa B": "protein", "cytokine gene": "DNA" } }, { "input_text": "Transcription factors are DNA-binding proteins that regulate gene expression .", "target_text": { "Transcription factors": "protein", "DNA-binding proteins": "protein" } }, { "input_text": "Nuclear factor-kappa B ( NF-kappa B ) is a critical transcription factor for maximal expression of many cytokines that are involved in the pathogenesis of inflammatory diseases , such as adult respiratory distress syndrome ( ARDS ) and sepsis syndrome .", "target_text": { "Nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "transcription factor": "protein", "cytokines": "protein" } }, { "input_text": "Activation and regulation of NF-kappa B are tightly controlled by a group of inhibitory proteins ( I kappa B ) that sequester NF-kappa B in the cytoplasm of immune/inflammatory effector cells .", "target_text": { "NF-kappa B": "protein", "inhibitory proteins": "protein", "I kappa B": "protein", "immune/inflammatory effector cells": "cell_type" } }, { "input_text": "NF-kappa B activation involves signaled phosphorylation , ubiquitination , and proteolysis of I kappa B .", "target_text": { "NF-kappa B": "protein", "I kappa B": "protein" } }, { "input_text": "Liberated NF-kappa B migrates to the nucleus , where it binds to specific promoter sites and activates gene transcription .", "target_text": { "NF-kappa B": "protein", "specific promoter sites": "DNA" } }, { "input_text": "The activation of NF-kappa B initiates both extracellular and intracellular regulatory events that result in autoregulation of the inflammatory cascade through modulation of NF-kappa B activation .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Recently , activation of NF-kappa B has been linked to ARDS and has been shown to be a critical proximal step in the initiation of neutrophilic inflammation in animal models .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Activation of NF-kappa B can be inhibited in vivo by treatment with antioxidants , corticosteroids , and the induction of endotoxin tolerance .", "target_text": { "NF-kappa B": "protein", "endotoxin": "protein" } }, { "input_text": "Identification of more specific and efficacious inhibitors of NF-kappa B activation might prove beneficial for the treatment of cytokine-mediated inflammatory diseases .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Chimeric oncoprotein E2a-Pbx1 induces apoptosis of hematopoietic cells by a p53 -independent mechanism that is suppressed by Bcl-2 .", "target_text": { "Chimeric oncoprotein": "protein", "E2a-Pbx1": "protein", "hematopoietic cells": "cell_type", "p53": "protein", "Bcl-2": "protein" } }, { "input_text": "The chimeric oncoprotein E2a-Pbx1 results from fusion of the E2A and PBX1 genes following t(1;19) chromosomal translocations in B cell precursor acute leukemias .", "target_text": { "chimeric oncoprotein": "protein", "E2a-Pbx1": "protein", "t(1;19) chromosomal translocations": "DNA" } }, { "input_text": "Experimentally B cell progenitors do not tolerate constitutive expression of E2a-Pbx1 which contrasts with transformation of several other cell types following its stable expression both in vitro and in vivo .", "target_text": { "B cell progenitors": "cell_type", "E2a-Pbx1": "protein" } }, { "input_text": "To further investigate the effects of E2a-Pbx1 on the B cell progenitors , we conditionally expressed E2a-Pbx1 under control of a metal response element in hematopoietic precursor cell lines in vitro .", "target_text": { "E2a-Pbx1": "protein", "B cell progenitors": "cell_type", "hematopoietic precursor cell lines": "cell_line" } }, { "input_text": "Inducible expression of E2a-Pbx1 resulted in cell death with the morphologic and molecular features of apoptosis .", "target_text": { "E2a-Pbx1": "protein" } }, { "input_text": "A structure-function analysis demonstrated that induction of apoptosis was not a dominant-negative effect of the E2a moiety but , rather , required the DNA-binding homeodomain of Pbx1 .", "target_text": { "E2a moiety": "protein", "DNA-binding homeodomain": "protein", "Pbx1": "protein" } }, { "input_text": "E2a- Pbx1 -induced apoptosis proceeded through a BCL2 -responsive checkpoint eventuating in PARP inactivation but did require p53 .", "target_text": { "Pbx1": "protein", "BCL2": "protein", "PARP": "protein", "p53": "protein" } }, { "input_text": "Constitutive expression of E2a- Pbx1 did not induce apoptosis or continued cycling of Rat-1 fibroblasts in low serum conditions .", "target_text": { "Pbx1": "protein", "E2a- Pbx1": "protein", "Rat-1 fibroblasts": "cell_line" } }, { "input_text": "These studies demonstrate that E2a- Pbx1 initiates programmed cell death of hematopoietic precursers by a mechanism that requires its chimeric transcriptional properties , but , unlike other nuclear oncoproteins , is independent of p53 .", "target_text": { "Pbx1": "protein", "E2a- Pbx1": "protein", "hematopoietic precursers": "cell_type", "nuclear oncoproteins": "protein", "p53": "protein" } }, { "input_text": "CCAAT/enhancer binding protein epsilon is preferentially up-regulated during granulocytic differentiation and its functional versatility is determined by alternative use of promoters and differential splicing .", "target_text": { "CCAAT/enhancer binding protein epsilon": "protein", "promoters": "DNA" } }, { "input_text": "CCAAT/enhancer binding protein ( C/EBP ) epsilon is a recently cloned member of the C/EBP family of transcription factors and is expressed exclusively in cells of hematopoietic origin .", "target_text": { "CCAAT/enhancer binding protein ( C/EBP ) epsilon": "protein", "C/EBP family": "protein", "transcription factors": "protein" } }, { "input_text": "The human C/EBPepsilon gene is transcribed by two alternative promoters , Palpha and Pbeta .", "target_text": { "human C/EBPepsilon gene": "DNA", "promoters": "DNA", "Palpha": "DNA", "Pbeta": "DNA" } }, { "input_text": "A combination of differential splicing and alternative use of promoters generates four mRNA isoforms , of 2.6 kb and 1.3-1.5 kb in size .", "target_text": { "promoters": "DNA", "mRNA": "RNA", "mRNA isoforms": "RNA" } }, { "input_text": "These transcripts can encode three proteins of calculated molecular mass 32.2 kDa , 27.8 kDa , and 14.3 kDa .", "target_text": { "32.2 kDa": "RNA", "27.8 kDa": "RNA", "14.3 kDa": "RNA" } }, { "input_text": "Accordingly , Western blots with antibodies specific for the DNA-binding domain , that is common to all forms , identify multiple proteins .", "target_text": { "antibodies": "protein" } }, { "input_text": "C/EBPepsilon mRNA was greatly induced during in vitro granulocytic differentiation of human primary CD34(+) cells .", "target_text": { "C/EBPepsilon mRNA": "RNA", "human primary CD34(+) cells": "cell_type" } }, { "input_text": "Retinoic acid treatment of HL60 promyelocytic leukemia cells for 24 hr induced C/EBPepsilon mRNA levels by 4-fold , while prolonged treatment gradually reduced mRNA expression to pretreatment levels .", "target_text": { "HL60 promyelocytic leukemia cells": "cell_line", "C/EBPepsilon mRNA": "RNA" } }, { "input_text": "Transient transfection experiments with expression vectors for two of the isoforms demonstrated that the 32.2-kDa protein is an activator of transcription of granulocyte colony-stimulating factor receptor promoter , while the 14.3-kDa protein is not .", "target_text": { "32.2-kDa protein": "protein", "granulocyte colony-stimulating factor receptor promoter": "DNA", "14.3-kDa protein": "protein" } }, { "input_text": "Thus , C/EBPepsilon is regulated in a complex fashion and may play a role in the regulation of genes involved in myeloid differentiation .", "target_text": { "C/EBPepsilon": "protein" } }, { "input_text": "Effects of TPA , bryostatin 1 , and retinoic acid on PO-B , AP-1 , and AP-2 DNA binding during HL-60 differentiation .", "target_text": { "TPA": "protein", "bryostatin 1": "protein", "PO-B": "protein", "AP-1": "protein", "AP-2": "protein" } }, { "input_text": "PO-B was originally characterized as a transcriptional regulatory factor of the pro-opiomelanocortin ( POMC ) gene ; however , it has become increasingly clear that this protein may be active in tissues outside the pituitary , since it is present in diverse cell types , including differentiated HL-60 promyelocytic leukemia cells .", "target_text": { "PO-B": "protein", "transcriptional regulatory factor": "protein", "pro-opiomelanocortin ( POMC ) gene": "DNA", "HL-60 promyelocytic leukemia cells": "cell_type" } }, { "input_text": "We previously showed that PO-B DNA-binding is progressively induced during differentiation of promyelomonocytic leukemic HL-60 cells to the macrophage-like lineage ( with phorbol esters ) .", "target_text": { "PO-B": "protein", "promyelomonocytic leukemic HL-60 cells": "cell_line", "macrophage-like lineage": "cell_type" } }, { "input_text": "We now report that PO-B DNA-binding in HL-60 cells is similarly induced during differentiation to the granulocytic lineage ( with either retinoic acid or dimethylsulfoxide ) .", "target_text": { "PO-B": "protein", "HL-60 cells": "cell_line", "granulocytic lineage": "cell_type" } }, { "input_text": "Either a genetic or pharmacologic blockade of HL-60 differentiation prohibited these inductive effects .", "target_text": {} }, { "input_text": "These studies have prompted our interest in the dynamics of other transcription factor changes during HL-60 differentiation .", "target_text": { "transcription factor": "protein" } }, { "input_text": "Of these , we observed that another transcription factor ( AP-1 ) is also robustly induced at the DNA-binding level during macrophage-like HL-60 differentiation , but not during granulocytic differentiation .", "target_text": { "transcription factor": "protein", "AP-1": "protein" } }, { "input_text": "Conversely , the DNA-binding of the transcription factor AP-2 was slightly reduced by TPA -induced HL-60 differentiation but unchanged during granulocyte differentiation .", "target_text": { "transcription factor": "protein", "AP-2": "protein", "TPA": "protein" } }, { "input_text": "From these data , we conclude that the induction of PO-B DNA binding is a general marker of HL-60 myelomonocytic differentiation , but that qualitative aspects of the induction of additional distinct transcription factors , such as AP-1 , may contribute to lineage-specific determinants of cell fate .", "target_text": { "PO-B": "protein", "transcription factors": "protein", "AP-1": "protein" } }, { "input_text": "A novel genetic system to isolate a dominant negative effector on DNA-binding activity of Oct-2 .", "target_text": { "dominant negative effector": "protein", "Oct-2": "protein" } }, { "input_text": "Recent studies have revealed that interactions between transcription factors play an important role in regulation of gene expression in eukaryotic cells .", "target_text": { "transcription factors": "protein", "eukaryotic cells": "cell_type" } }, { "input_text": "To isolate cDNA clones that dominantly inhibit the DNA-binding activity of Oct-2 , chosen as a representative factor , we have developed a novel screening system .", "target_text": { "Oct-2": "protein" } }, { "input_text": "This employs an Escherichia coli tester strain carrying a modified lac operon as a reporter gene , with the lac operator sequence replaced by an octamer sequence .", "target_text": { "modified lac operon": "DNA", "reporter gene": "DNA", "octamer sequence": "DNA" } }, { "input_text": "Oct-2 expressed in this tester strain represses the expression of the reporter gene and changes the phenotype of the cell from Lac+ to Lac- .", "target_text": { "Oct-2": "protein" } }, { "input_text": "Introduction of a cDNA expression library prepared from a human T-cell line into the Oct-2 -harboring tester strain allowed selection of three Lac+ clones out of 1 x 10(5) transformants .", "target_text": { "human T-cell line": "cell_line", "Oct-2": "protein" } }, { "input_text": "One of them , hT86 , encoding a putative zinc finger protein was found to derepress beta-galactosidase activity in the Oct-2 -harboring tester strain at the transcriptional level .", "target_text": { "putative zinc finger protein": "protein", "beta-galactosidase": "protein", "Oct-2": "protein" } }, { "input_text": "In gel mobility shift assays , hT86 attenuated the intensity of the retarded band composed of the octamer probe and Oct-2 , suggesting a dominant negative effect on the DNA-binding activity of Oct-2 .", "target_text": { "octamer probe": "DNA", "Oct-2": "protein" } }, { "input_text": "The strategy described here provides a new approach for studying protein-protein interactions that govern the complex regulation of gene expression .", "target_text": {} }, { "input_text": "Tap : a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation .", "target_text": { "Tap": "protein", "cellular protein": "protein", "lymphocyte": "cell_type" } }, { "input_text": "Tip of herpesvirus saimiri associates with Lck and down-regulates Lck -mediated activation .", "target_text": { "Lck": "protein" } }, { "input_text": "We identified a novel cellular Tip-associated protein ( Tap ) by a yeast two-hybrid screen .", "target_text": { "Tip-associated protein": "protein", "Tap": "protein" } }, { "input_text": "Tap associated with Tip following transient expression in COS-1 cells and stable expression in human Jurkat-T cells .", "target_text": { "Tap": "protein", "Tip": "protein", "COS-1 cells": "cell_line", "human Jurkat-T cells": "cell_line" } }, { "input_text": "Expression of Tip and Tap in Jurkat-T cells induced dramatic cell aggregation .", "target_text": { "Tip": "protein", "Tap": "protein", "Jurkat-T cells": "cell_line" } }, { "input_text": "Aggregation was likely caused by the up-regulated surface expression of adhesion molecules including integrin alpha , L-selectin , ICAM-3 , and H-CAM .", "target_text": { "adhesion molecules": "protein", "integrin alpha": "protein", "L-selectin": "protein", "ICAM-3": "protein", "H-CAM": "protein" } }, { "input_text": "Furthermore , NF-kappaB transcriptional factor of aggregated cells had approximately 40-fold higher activity than that of parental cells .", "target_text": { "NF-kappaB": "protein", "NF-kappaB transcriptional factor": "protein", "parental cells": "cell_type" } }, { "input_text": "Thus , Tap is likely to be an important cellular mediator of Tip function in T cell transformation by herpesvirus saimiri .", "target_text": { "Tap": "protein", "Tip": "protein" } }, { "input_text": "Human monocyte binding to fibronectin enhances IFN-gamma -induced early signaling events .", "target_text": { "Human monocyte": "cell_type", "fibronectin": "protein", "IFN-gamma": "protein" } }, { "input_text": "Leukocyte integrins are fundamentally important in modulating adhesion to extracellular matrix components and to other cells .", "target_text": { "Leukocyte integrins": "protein" } }, { "input_text": "This integrin-mediated adhesion controls leukocyte arrest and extravasation during the onset of inflammatory responses .", "target_text": {} }, { "input_text": "Moreover , integrin -ligand interactions trigger signaling pathways that may influence leukocyte phenotype and function at sites of inflammation .", "target_text": { "integrin": "protein" } }, { "input_text": "In the current studies , we evaluated the combinatorial effects of monocyte adhesion and IFN-gamma on intracellular signaling pathways .", "target_text": { "IFN-gamma": "protein" } }, { "input_text": "IFN-gamma triggers a well-defined signal transduction pathway , which although not directly stimulated by monocyte adherence to fibronectin or arginine-glycine-aspartate ( RGD ) -coated substrata , was enhanced significantly in these matrix-adherent cells .", "target_text": { "IFN-gamma": "protein", "fibronectin": "protein", "arginine-glycine-aspartate ( RGD ) -coated substrata": "protein", "matrix-adherent cells": "cell_type" } }, { "input_text": "Compared with monocytes in suspension or adherent on plastic surfaces , monocytes adherent to fibronectin or RGD exhibited a greater than threefold increase in steady state levels of IFN-gamma -induced mRNA for the high affinity Fc gammaRI receptor .", "target_text": { "fibronectin": "protein", "IFN-gamma": "protein", "IFN-gamma -induced mRNA": "RNA", "high affinity Fc gammaRI receptor": "protein" } }, { "input_text": "By electrophoretic mobility shift assays , this increase in mRNA was associated with a 5- to 10-fold increase in the STAT1-containing DNA-binding complex that binds to Fc gammaRI promoter elements .", "target_text": { "mRNA": "RNA", "STAT1-containing DNA-binding complex": "protein", "Fc gammaRI promoter elements": "DNA" } }, { "input_text": "Furthermore , the tyrosine phosphorylation of STAT1 and the tyrosine kinases JAK1 and JAK2 was enhanced significantly in RGD -adherent monocytes compared with control cells .", "target_text": { "STAT1": "protein", "tyrosine kinases": "protein", "JAK1": "protein", "JAK2": "protein", "RGD -adherent monocytes": "cell_type", "control cells": "cell_type" } }, { "input_text": "These results suggest a novel mechanism by which integrin -mediated cell adhesion can modulate the magnitude of cytokine -induced signal transduction pathways , thereby amplifying cellular events leading to monocyte activation and inflammation .", "target_text": { "integrin": "protein", "cytokine": "protein" } }, { "input_text": "Surfactant protein A activates NF-kappa B in the THP-1 monocytic cell line .", "target_text": { "Surfactant protein A": "protein", "NF-kappa B": "protein", "THP-1 monocytic cell line": "cell_line" } }, { "input_text": "The expression of many genes for which products are involved in inflammation is controlled by the transcriptional regulator nuclear factor ( NF ) -kappa B .", "target_text": { "transcriptional regulator nuclear factor ( NF ) -kappa B": "protein" } }, { "input_text": "Because surfactant protein ( SP ) A is involved in local host defense in the lung and alters immune cell function by modulating the expression of proinflammatory cytokines as well as surface proteins involved in inflammation , we hypothesized that SP-A exerts its action , at least in part , via activation of NF-kappa B .", "target_text": { "surfactant protein ( SP ) A": "protein", "proinflammatory cytokines": "protein", "surface proteins": "protein", "SP-A": "protein", "NF-kappa B": "protein" } }, { "input_text": "We used gel shift assays to determine whether SP-A activated NF-kappa B in the THP-1 cell line , a human monocytic cell line .", "target_text": { "SP-A": "protein", "NF-kappa B": "protein", "THP-1 cell line": "cell_line", "human monocytic cell line": "cell_line" } }, { "input_text": "Activation of NF-kappa B in THP-1 cells by SP-A doses as low as 1 microgram/ml occurred within 30 min of SP-A treatment , peaked at 60 min , and then declined .", "target_text": { "NF-kappa B": "protein", "THP-1 cells": "cell_line", "SP-A": "protein" } }, { "input_text": "This activation is inhibited by known inhibitors of NF-kappa B or by simultaneous treatment of the cells with surfactant lipids .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Moreover , the NF-kappa B inhibitors blocked SP-A -dependent increases in tumor necrosis factor-alpha mRNA levels .", "target_text": { "NF-kappa B": "protein", "NF-kappa B inhibitors": "protein", "SP-A": "protein", "tumor necrosis factor-alpha mRNA": "RNA" } }, { "input_text": "These observations suggest a mechanism by which SP-A plays a role in the pathogenesis of some lung conditions and point to potential therapeutic measures that could be used to prevent SP-A induced inflammation in the lung .", "target_text": { "SP-A": "protein" } }, { "input_text": "GABP factors bind to a distal interleukin 2 ( IL-2 ) enhancer and contribute to c-Raf -mediated increase in IL-2 induction .", "target_text": { "GABP factors": "protein", "distal interleukin 2 ( IL-2 ) enhancer": "DNA", "c-Raf": "protein", "IL-2": "protein" } }, { "input_text": "Triggering of the T-cell receptor-CD3 complex activates two major signal cascades in T lymphocytes , ( i ) Ca2+-dependent signal cascades and ( ii ) protein kinase cascades .", "target_text": { "T-cell receptor-CD3 complex": "protein", "T lymphocytes": "cell_type", "protein kinase": "protein" } }, { "input_text": "Both signal cascades contribute to the induction of the interleukin 2 ( IL-2 ) gene during T-cell activation .", "target_text": { "IL-2": "protein", "interleukin 2 ( IL-2 ) gene": "DNA" } }, { "input_text": "Prominent protein kinase cascades are those that activate mitogen-activated protein ( MAP ) kinases .", "target_text": { "protein kinase": "protein", "mitogen-activated protein ( MAP ) kinases": "protein" } }, { "input_text": "We show here that c-Raf , which is at the helm of the classic MAP- Erk cascade , contributes to IL-2 induction through a distal enhancer element spanning the nucleotides from positions -502 to -413 in front of the transcriptional start site of the IL-2 gene .", "target_text": { "c-Raf": "protein", "Erk": "protein", "IL-2": "protein", "distal enhancer element": "DNA", "IL-2 gene": "DNA" } }, { "input_text": "Induction of this distal IL-2 enhancer differs from induction of the proximal IL-2 promoter-enhancer , since it is induced by phorbol esters alone and independent from Ca2+ signals .", "target_text": { "IL-2": "protein", "IL-2 enhancer": "DNA", "distal IL-2 enhancer": "DNA", "proximal IL-2 promoter-enhancer": "DNA" } }, { "input_text": "In DNA-protein binding studies , we detected the binding of transcription factors GABP alpha and -beta to a dyad symmetry element ( DSE ) of the distal enhancer , which is formed by palindromic binding sites of Ets-like factors .", "target_text": { "transcription factors": "protein", "dyad symmetry element": "DNA", "DSE": "DNA", "distal enhancer": "DNA", "palindromic binding sites": "DNA", "Ets-like factors": "protein" } }, { "input_text": "Introduction of point mutations suppressing GABP binding to the DSE interfered with the induction of the distal enhancer and the entire IL-2 promoter-enhancer , while overexpression of both GABP factors enhanced the IL-2 promoter-enhancer induction .", "target_text": { "DSE": "DNA", "distal enhancer": "DNA", "IL-2": "protein", "IL-2 promoter-enhancer": "DNA", "GABP factors": "protein" } }, { "input_text": "Overexpression of BXB , a constitutive active version of c-Raf , and of further members of the Ras - Raf - Erk signal cascade exerted an increase of GABP -mediated promoter-enhancer induction .", "target_text": { "BXB": "protein", "c-Raf": "protein", "Ras": "protein", "Raf": "protein", "Erk": "protein", "GABP": "protein" } }, { "input_text": "In conjunction with previously published data on c-Raf -induced phosphorylation of GABP factors ( E.Flory , A. Hoffmeyer , U.Smola , U.R.Rapp , and J.T.Bruder , J.Virol.70 : 2260- 2268 , 1996 ) , these results indicate a contribution of GABP factors to the Raf -mediated enhancement of IL-2 induction during T-cell activation .", "target_text": { "c-Raf": "protein", "GABP factors": "protein", "Raf": "protein", "IL-2": "protein" } }, { "input_text": "Lipopolysaccharide induction of the tumor necrosis factor-alpha promoter in human monocytic cells .", "target_text": { "tumor necrosis factor-alpha": "protein", "tumor necrosis factor-alpha promoter": "DNA", "human monocytic cells": "cell_type" } }, { "input_text": "Regulation by Egr-1 , c-Jun , and NF-kappaB transcription factors .", "target_text": { "Egr-1": "protein", "c-Jun": "protein", "NF-kappaB": "protein", "transcription factors": "protein" } }, { "input_text": "Biosynthesis of tumor necrosis factor-alpha ( TNF-alpha ) is predominantly by cells of the monocytic lineage .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "monocytic lineage": "cell_type" } }, { "input_text": "This study examined the role of various cis-acting regulatory elements in the lipopolysaccharide ( LPS ) induction of the human TNF-alpha promoter in cells of monocytic lineage .", "target_text": { "cis-acting regulatory elements": "DNA", "TNF-alpha": "protein", "human TNF-alpha promoter": "DNA", "monocytic lineage": "cell_type" } }, { "input_text": "Functional analysis of monocytic THP-1 cells transfected with plasmids containing various lengths of TNF-alpha promoter localized enhancer elements in a region ( -182 to -37 base pairs ( bp ) ) that were required for optimal transcription of the TNF-alpha gene in response to LPS .", "target_text": { "THP-1 cells": "cell_line", "monocytic THP-1 cells": "cell_line", "plasmids": "DNA", "TNF-alpha": "protein", "TNF-alpha promoter": "DNA", "enhancer elements": "DNA", "-182 to -37 base pairs": "DNA", "TNF-alpha gene": "DNA" } }, { "input_text": "Two regions were identified : region I ( -182 to -162 bp ) contained an overlapping Sp1/ Egr-1 site , and region II ( -119 to -88 ) contained CRE and NF-kappaB ( designated kappaB3 ) sites .", "target_text": { "region I": "DNA", "-182 to -162 bp": "DNA", "Egr-1": "protein", "Sp1/ Egr-1 site": "DNA", "region II": "DNA", "-119 to -88": "DNA", "CRE": "DNA", "NF-kappaB": "protein", "NF-kappaB ( designated kappaB3 ) sites": "DNA" } }, { "input_text": "In unstimulated THP-1 , CRE -binding protein and , to a lesser extent , c-Jun complexes were found to bind to the CRE site .", "target_text": { "THP-1": "cell_line", "CRE": "DNA", "CRE -binding protein": "protein", "c-Jun complexes": "protein", "CRE site": "DNA" } }, { "input_text": "LPS stimulation increased the binding of c-Jun -containing complexes .", "target_text": { "c-Jun": "protein", "c-Jun -containing complexes": "protein" } }, { "input_text": "In addition , LPS stimulation induced the binding of cognate nuclear factors to the Egr-1 and kappaB3 sites , which were identified as Egr-1 and p50/p65 , respectively .", "target_text": { "nuclear factors": "protein", "Egr-1": "protein", "p50/p65": "protein" } }, { "input_text": "The CRE and kappaB3 sites in region II together conferred strong LPS responsiveness to a heterologous promoter , whereas individually they failed to provide transcriptional activation .", "target_text": { "region II": "DNA", "heterologous promoter": "DNA" } }, { "input_text": "Furthermore , increasing the spacing between the CRE and the kappaB3 sites completely abolished LPS induction , suggesting a cooperative interaction between c-Jun complexes and p50/p65 .", "target_text": { "CRE": "DNA", "kappaB3 sites": "DNA", "CRE and the kappaB3 sites": "DNA", "c-Jun": "protein", "c-Jun complexes": "protein", "p50/p65": "protein" } }, { "input_text": "These studies indicate that maximal LPS induction of the TNF-alpha promoter is mediated by concerted participation of at least two separate cis-acting regulatory elements .", "target_text": { "TNF-alpha": "protein", "TNF-alpha promoter": "DNA", "cis-acting regulatory elements": "DNA" } }, { "input_text": "Rescue by cytokines of apoptotic cell death induced by IL-2 deprivation of human antigen-specific T cell clones .", "target_text": { "cytokines": "protein", "IL-2": "protein", "human antigen-specific T cell clones": "cell_line" } }, { "input_text": "The control of cell survival and cell death is of central importance in tissues with high cell turnover such as the lymphoid system .", "target_text": {} }, { "input_text": "We have examined the effect of cytokines on IL-2 deprivation-induced apoptosis of human antigen-specific T helper clones with different cytokine production profiles .", "target_text": { "cytokines": "protein", "IL-2": "protein", "human antigen-specific T helper clones": "cell_line", "cytokine": "protein" } }, { "input_text": "We found that IL-2 , interferon-alpha ( IFN-alpha ) , and IFN-beta inhibited IL-2 deprivation apoptosis in Th0 , Th1 , and Th2 clones .", "target_text": { "IL-2": "protein", "interferon-alpha": "protein", "IFN-alpha": "protein", "IFN-beta": "protein" } }, { "input_text": "We also found that IL-2 protects T cell clones from IL-2 deprivation apoptosis accompanying active proliferation and enhanced expression of P53 , Rb and Bcl-xL proteins .", "target_text": { "IL-2": "protein", "T cell clones": "cell_line", "P53": "protein", "Rb": "protein", "Bcl-xL proteins": "protein" } }, { "input_text": "In contrast , IFN-alpha /beta rescued T cell clones from apoptosis without active proliferation , and expression of apoptosis -associated proteins tested so far was unaffected .", "target_text": { "IFN-alpha": "protein", "IFN-alpha /beta": "protein", "T cell clones": "cell_line", "apoptosis -associated proteins": "protein" } }, { "input_text": "This may be due to the fact that T cells treated with IL-2 contained those located in S + G2/M phases of the cell cycle , whereas the vast majority of T cells treated with IFN-alpha /beta were located in G0/G1 phase .", "target_text": { "T cells": "cell_type", "IL-2": "protein", "IFN-alpha": "protein", "IFN-alpha /beta": "protein" } }, { "input_text": "IFN-alpha /beta specifically induced tyrosine phosphorylation and translocation into nucleus of signal transducers and activators of transcription ( STAT ) 2 protein in the T cell clones .", "target_text": { "IFN-alpha": "protein", "IFN-alpha /beta": "protein", "signal transducers and activators of transcription ( STAT ) 2 protein": "protein", "T cell clones": "cell_line" } }, { "input_text": "In addition , over-expression of STAT2 by transfection of the cDNA prevented apoptosis of the T cell clones .", "target_text": { "STAT2": "protein", "T cell clones": "cell_line" } }, { "input_text": "Our present study shows that IFN -alpha and -beta mediate anti-apoptotic effect through other pathways than that of IL-2 in growth factor deprivation apoptosis .", "target_text": { "IL-2": "protein" } }, { "input_text": "Interleukin-10 inhibits interferon-gamma-induced intercellular adhesion molecule-1 gene transcription in human monocytes .", "target_text": { "Interleukin-10": "protein", "intercellular adhesion molecule-1": "protein", "intercellular adhesion molecule-1 gene": "DNA", "human monocytes": "cell_type" } }, { "input_text": "Interleukin-10 ( IL-10 ) is a potent monocyte regulatory cytokine that inhibits gene expression of proinflammatory mediators .", "target_text": { "Interleukin-10": "protein", "IL-10": "protein", "monocyte regulatory cytokine": "protein", "proinflammatory mediators": "protein" } }, { "input_text": "In this study , we investigated the mechanism by which IL-10 downregulates expression of intercellular adhesion molecule-1 ( ICAM-1 ) on the cell surface of normal human monocytes activated with interferon-gamma ( IFN-gamma ) .", "target_text": { "IL-10": "protein", "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "human monocytes": "cell_type", "normal human monocytes": "cell_type", "interferon-gamma": "protein", "IFN-gamma": "protein" } }, { "input_text": "IL-10 inhibition of IFN-gamma -induced ICAM-1 expression was apparent as early as 3 hours and was blocked by an anti- IL-10 antibody but not by an isotype-matched control antibody .", "target_text": { "IL-10": "protein", "IFN-gamma": "protein", "ICAM-1": "protein", "anti- IL-10 antibody": "protein", "isotype-matched control antibody": "protein" } }, { "input_text": "Northern blot analysis showed that IL-10 reduced the accumulation of ICAM-1 mRNA in IFN-gamma -stimulated monocytes .", "target_text": { "IL-10": "protein", "ICAM-1": "protein", "ICAM-1 mRNA": "RNA", "IFN-gamma": "protein", "IFN-gamma -stimulated monocytes": "cell_line" } }, { "input_text": "IL-10 inhibition of ICAM-1 steady-state mRNA was detected at 3 hours and remained at 24 hours .", "target_text": { "IL-10": "protein", "ICAM-1": "protein", "ICAM-1 steady-state mRNA": "RNA" } }, { "input_text": "Nuclear run-on transcription assays showed that IL-10 inhibited the rate of IFN-gamma -induced transcription of the ICAM-1 gene , and mRNA stability studies showed that IL-10 did not alter the half-life of IFN-gamma -induced ICAM-1 message .", "target_text": { "IL-10": "protein", "IFN-gamma": "protein", "ICAM-1": "protein", "ICAM-1 gene": "DNA", "IFN-gamma -induced ICAM-1 message": "RNA" } }, { "input_text": "Thus , IL-10 inhibits IFN-gamma -induced ICAM-1 expression in monocytes primarily at the level of gene transcription .", "target_text": { "IL-10": "protein", "IFN-gamma": "protein", "ICAM-1": "protein", "monocytes": "cell_type" } }, { "input_text": "Activation of IFN-gamma -responsive genes requires tyrosine phosphorylation of the transcriptional factor STAT-1alpha ( signal transducer and activator of transcription-1alpha ) .", "target_text": { "IFN-gamma": "protein", "IFN-gamma -responsive genes": "DNA", "STAT-1alpha": "protein", "signal transducer and activator of transcription-1alpha": "protein" } }, { "input_text": "However , IL-10 did not affect IFN-gamma -induced tyrosine phosphorylation of STAT-1alpha or alter STAT-1alpha binding to the IFN-gamma response element ( IRE ) in the ICAM-1 promoter .", "target_text": { "IL-10": "protein", "IFN-gamma": "protein", "STAT-1alpha": "protein", "IFN-gamma response element": "DNA", "IRE": "DNA", "ICAM-1": "protein", "ICAM-1 promoter": "DNA" } }, { "input_text": "Instead , IL-10 prevented IFN-gamma -induced binding activity at the NF-kappaB site of the tumor necrosis factor alpha ( TNF-alpha ) -responsive NF-kappaB /C-EBP composite element in the ICAM-1 promoter .", "target_text": { "IL-10": "protein", "IFN-gamma": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein", "tumor necrosis factor alpha ( TNF-alpha ) -responsive NF-kappaB /C-EBP composite element": "DNA", "ICAM-1": "protein", "ICAM-1 promoter": "DNA" } }, { "input_text": "These data indicate that IL-10 inhibits IFN-gamma -induced transcription of the ICAM-1 gene by a regulatory mechanism that may involve NF-kappaB .", "target_text": { "IL-10": "protein", "IFN-gamma": "protein", "ICAM-1": "protein", "ICAM-1 gene": "DNA", "NF-kappaB": "protein" } }, { "input_text": "Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5 .", "target_text": { "type II bare lymphocyte syndrome-associated transactivators": "protein", "CIITA": "protein", "RFX5": "protein" } }, { "input_text": "Two of the genes defective in the five complementation groups identified in the class II-negative bare lymphocyte syndrome or corresponding laboratory mutants have been cloned .", "target_text": {} }, { "input_text": "One gene encodes a protein , RFX5 , that is a member of the RFX family of DNA binding proteins .", "target_text": { "RFX5": "protein", "RFX family of DNA binding proteins": "protein" } }, { "input_text": "The other , CIITA , encodes a large protein with a defined acidic transcriptional activation domain ; this protein does not interact with DNA .", "target_text": { "CIITA": "protein", "acidic transcriptional activation domain": "protein" } }, { "input_text": "Expression plasmids encoding regions of RFX5 fused to the GAL4 DNA binding domain activated transcription from a reporter construct containing GAL4 sites in a cotransfection assay in the Raji human B cell line .", "target_text": { "plasmids": "DNA", "Expression plasmids": "DNA", "RFX5": "protein", "GAL4 DNA binding domain": "protein", "GAL4 sites": "DNA", "Raji human B cell line": "cell_line" } }, { "input_text": "However , these plasmids produced transcriptional activity in HeLa cells only in conjunction with interferon gamma stimulation , a condition in which expression of both CIITA and class II major histocompatibility complex surface proteins are induced.", "target_text": { "plasmids": "DNA", "HeLa cells": "cell_line", "interferon gamma": "protein", "CIITA": "protein", "surface proteins": "protein", "class II major histocompatibility complex surface proteins": "protein" } }, { "input_text": "Furthermore , these plasmids were not active in RJ2.2.5 , an in vitro mutagenized derivative of Raji in which both copies of CIITA are defective .", "target_text": { "plasmids": "DNA", "RJ2.2.5": "cell_line", "Raji": "cell_line", "CIITA": "protein" } }, { "input_text": "Transcriptional activation by the RFX5 fusion protein could be restored in RJ2.2.5 by cotransfection with a CIITA expression plasmid .", "target_text": { "RFX5": "protein", "RFX5 fusion protein": "protein", "RJ2.2.5": "cell_line", "CIITA": "protein", "CIITA expression plasmid": "DNA" } }, { "input_text": "Finally , a direct interaction between RFX5 and CIITA was detected with the yeast two-hybrid and far-Western blot assays .", "target_text": { "RFX5": "protein", "CIITA": "protein" } }, { "input_text": "Thus , RFX5 can activate transcription only in cooperation with CIITA .", "target_text": { "RFX5": "protein", "CIITA": "protein" } }, { "input_text": "RFX5 and CIITA associate to form a complex capable of activating transcription from class II major histocompatibility complex promoters .", "target_text": { "RFX5": "protein", "CIITA": "protein", "class II major histocompatibility complex promoters": "DNA" } }, { "input_text": "In this complex , promoter specificity is determined by the DNA binding domain of RFX5 and the general transcription apparatus is recruited by the acidic activation domain of CIITA .", "target_text": { "RFX5": "protein", "acidic activation domain": "protein", "CIITA": "protein" } }, { "input_text": "Involvement of phosphatidylinositol 3-kinase in NFAT activation in T cells .", "target_text": { "phosphatidylinositol 3-kinase": "protein", "NFAT": "protein", "T cells": "cell_type" } }, { "input_text": "Phosphatidylinositol 3-kinase ( PI3-K ) has been implicated in the regulation of cell proliferation in many cell types .", "target_text": { "Phosphatidylinositol 3-kinase": "protein", "PI3-K": "protein" } }, { "input_text": "We have previously shown that in T cells the PI3-K inhibitor , wortmannin , interferes with activation of the mitogen-activated kinase , Erk2 , after T cell receptor ( TcR ) stimulation .", "target_text": { "T cells": "cell_type", "PI3-K": "protein", "mitogen-activated kinase": "protein", "Erk2": "protein", "T cell receptor": "protein", "TcR": "protein" } }, { "input_text": "To further explore the involvement of PI3-K in T cell activation , we created a set of potentially dominant negative PI3-K constructs comprising individual or tandem domains of the regulatory p85 subunit and tested their effect on downstream signaling events like Erk2 activation and transcription from an NFAT ( nuclear factor of activated T cells ) element taken from the interleukin-2 promoter .", "target_text": { "PI3-K": "protein", "dominant negative PI3-K constructs": "DNA", "tandem domains": "DNA", "regulatory p85 subunit": "protein", "Erk2": "protein", "NFAT": "protein", "T cells": "cell_type", "nuclear factor of activated T cells": "protein", "NFAT ( nuclear factor of activated T cells ) element": "DNA", "interleukin-2 promoter": "DNA" } }, { "input_text": "Following TcR stimulation , activation of Erk2 was only inhibited by a previously described truncated form of p85 that can not bind the catalytic subunit , but not by other constructs of p85 .", "target_text": { "TcR": "protein", "Erk2": "protein", "truncated form of p85": "protein", "catalytic subunit": "protein", "p85": "protein" } }, { "input_text": "In contrast , several mutant p85 alleles had dramatic effects on NFAT activation .", "target_text": { "p85": "protein", "NFAT": "protein" } }, { "input_text": "Most interestingly , the N-terminal SH2 domain had an inhibitory effect , whereas a mutant p85 containing only the two SH2 domains enhanced basal NFAT activity in a Ras -dependent manner .", "target_text": { "N-terminal SH2 domain": "protein", "p85": "protein", "mutant p85": "protein", "two SH2 domains": "protein", "NFAT": "protein", "Ras": "protein" } }, { "input_text": "Ionomycin induced synergistic activation of NFAT in cells expressing p85 mutants that contained the C-terminal SH2 domain .", "target_text": { "NFAT": "protein", "p85": "protein", "p85 mutants": "protein", "C-terminal SH2 domain": "protein" } }, { "input_text": "Analysis of phosphotyrosine -containing proteins bound to truncated p85 constructs revealed cooperative binding of the two SH2 domains but no apparent differences between the N- and C- terminal SH2 domains .", "target_text": { "phosphotyrosine -containing proteins": "protein", "p85": "protein", "p85 constructs": "protein", "two SH2 domains": "protein" } }, { "input_text": "Wortmannin did not interfere with NFAT activation , although it inhibited PI3-K and Erk2 activation in the same experiment .", "target_text": { "NFAT": "protein", "PI3-K": "protein", "Erk2": "protein" } }, { "input_text": "These results suggest that PI3-K is involved in NFAT activation through a complex adaptor function of its regulatory subunit and that its lipid kinase activity is dispensable for this effect .", "target_text": { "PI3-K": "protein", "NFAT": "protein", "regulatory subunit": "protein", "lipid kinase": "protein" } }, { "input_text": "Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice .", "target_text": {} }, { "input_text": "Acute promyelocytic leukemia ( APL ) is associated with reciprocal chromosomal translocations involving the retinoic acid receptor alpha ( RARalpha ) locus on chromosome 17 .", "target_text": { "retinoic acid receptor alpha": "protein", "RARalpha": "protein", "retinoic acid receptor alpha ( RARalpha ) locus": "DNA", "chromosome 17": "DNA" } }, { "input_text": "In the majority of cases , RARalpha translocates and fuses with the promyelocytic leukemia ( PML ) gene located on chromosome 15 .", "target_text": { "RARalpha": "protein", "promyelocytic leukemia ( PML ) gene": "DNA", "chromosome 15": "DNA" } }, { "input_text": "The resulting fusion genes encode the two structurally unique PML/ RARalpha and RARalpha /PML fusion proteins as well as aberrant PML gene products , the respective pathogenetic roles of which have not been elucidated .", "target_text": { "fusion genes": "DNA", "RARalpha": "protein", "PML/ RARalpha": "protein", "RARalpha /PML fusion proteins": "protein", "aberrant PML gene products": "protein" } }, { "input_text": "We have generated transgenic mice in which the PML/ RARalpha fusion protein is specifically expressed in the myeloid-promyelocytic lineage .", "target_text": { "RARalpha": "protein", "PML/ RARalpha fusion protein": "protein", "myeloid-promyelocytic lineage": "cell_type" } }, { "input_text": "During their first year of life , all the PML/ RARalpha transgenic mice have an abnormal hematopoiesis that can best be described as a myeloproliferative disorder .", "target_text": { "RARalpha": "protein" } }, { "input_text": "Between 12 and 14 months of age , 10 % of them develop a form of acute leukemia with a differentiation block at the promyelocytic stage that closely mimics human APL even in its response to retinoic acid .", "target_text": {} }, { "input_text": "Our results are conclusive in vivo evidence that PML/ RARalpha plays a crucial role in the pathogenesis of APL .", "target_text": { "RARalpha": "protein", "PML/ RARalpha": "protein" } }, { "input_text": "Constitutive and inducible protein/DNA interactions of the interferon-gamma promoter in vivo in [ corrected ] CD45RA and CD45R0 T helper subsets [ published erratum appears in Eur J Immunol 1997 Jul ; 27 ( 7 ) : 1830 ]", "target_text": { "interferon-gamma promoter": "DNA" } }, { "input_text": "Interferon-gamma ( IFN-gamma ) is a key cytokine of T lymphocytes with major regulatory functions in the immune system .", "target_text": { "IFN-gamma": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "To determine and compare protein/DNA interactions at the native IFN-gamma locus in T cells , we analyzed the human IFN-gamma promoter by ligation-mediated polymerase chain reaction ( LM-PCR ) techniques .", "target_text": { "IFN-gamma": "protein", "T cells": "cell_type", "human IFN-gamma promoter": "DNA" } }, { "input_text": "Accordingly , Jurkat T cells and primary CD45RA and CD45R0 CD4+ T cell subsets isolated from peripheral blood using immunomagnetic beads were cultured and analyzed by LM-PCR .", "target_text": { "Jurkat T cells": "cell_line" } }, { "input_text": "Constitutive and inducible protein/DNA interactions of the IFN-gamma promoter in vivo were detected in all T cells tested .", "target_text": { "IFN-gamma": "protein", "IFN-gamma promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "Interestingly , an inducible footprint between -183 and -196 was consistently observed in Jurkat T cells and CD45RA and CD45R0 T helper subsets upon stimulation with phorbol 12-myristate 13-acetate + phytohemagglutinin ( PMA + PHA ) that was highly sensitive to treatment with corticosteroids .", "target_text": { "-183 and -196": "DNA", "Jurkat T cells": "cell_line", "phytohemagglutinin": "protein", "PHA": "protein" } }, { "input_text": "This novel target site , denoted the C-site , was shown by several criteria , including cell distribution studies , stimulation experiments , supershift assays , and cross-competition electrophoretic mobility shift assays to bind the transcription factor AP-1 .", "target_text": { "novel target site": "DNA", "C-site": "DNA", "transcription factor AP-1": "protein" } }, { "input_text": "Mutation of the C-site that prevented AP-1 binding to this site was sufficient strikingly to reduce inducible promoter activity in primary CD45R0 T cells .", "target_text": { "C-site": "DNA", "AP-1": "protein", "primary CD45R0 T cells": "cell_type" } }, { "input_text": "In summary , the data demonstrate that IFN-gamma gene transcription in primary T cells is regulated in vivo at the level of constitutive and inducible protein/DNA interactions .", "target_text": { "IFN-gamma": "protein", "T cells": "cell_type", "primary T cells": "cell_type" } }, { "input_text": "We propose a model where basal transcription is maintained by binding of various transcription factors to the IFN-gamma promoter , whereas PMA + PHA -inducible IFN-gamma transcription in CD45R0 T cells is associated with binding of AP-1 to the C-site .", "target_text": { "transcription factors": "protein", "IFN-gamma promoter": "DNA", "PHA": "protein", "IFN-gamma": "protein", "CD45R0 T cells": "cell_type", "AP-1": "protein", "C-site": "DNA" } }, { "input_text": "Activation domain requirements for disruption of Epstein-Barr virus latency by ZEBRA .", "target_text": { "ZEBRA": "protein" } }, { "input_text": "Latent infection of B lymphocytes by Epstein-Barr virus ( EBV ) can be disrupted by expression of the EBV ZEBRA protein .", "target_text": { "B lymphocytes": "cell_type", "ZEBRA": "protein", "EBV ZEBRA protein": "protein" } }, { "input_text": "ZEBRA , a transcriptional activator , initiates the EBV lytic cascade by activating viral gene expression .", "target_text": { "ZEBRA": "protein" } }, { "input_text": "ZEBRA is also indispensable for viral replication and binds directly to the EBV lytic origin of replication .", "target_text": { "ZEBRA": "protein" } }, { "input_text": "The studies described herein demonstrate that the activation domain .", "target_text": {} }, { "input_text": "ZEBRA activation can be replaced by a heterologous acidic , proline-rich , or glutamine-rich activation domain .", "target_text": { "ZEBRA": "protein" } }, { "input_text": "ZEBRA activation domain swap constructs retain ZEBRA 's native abilities to activate specific EBV promoters , to disrupt EBV latency , and to stimulate replication at the EBV lytic origin .", "target_text": { "ZEBRA": "protein", "EBV promoters": "DNA", "EBV lytic origin": "DNA" } }, { "input_text": "Additional work , employing sequential and internal deletions of ZEBRA 's N-terminal activation domain , indicates that its separate activities are not attributable to specific subdomains but are spread throughout its N terminus and therefore can not be inactivated by deleting localized regions .", "target_text": { "ZEBRA": "protein", "N-terminal activation domain": "protein", "subdomains": "protein", "N terminus": "protein" } }, { "input_text": "CholecystokininB receptor from human Jurkat lymphoblastic T cells is involved in activator protein-1 -responsive gene activation .", "target_text": { "CholecystokininB receptor": "protein", "human Jurkat lymphoblastic T cells": "cell_line", "activator protein-1": "protein" } }, { "input_text": "The aim of this study was to analyze the role of cholecystokinin ( CCK(B) ) receptor in human lymphoblastic Jurkat T cells .", "target_text": { "cholecystokinin ( CCK(B) ) receptor": "protein", "human lymphoblastic Jurkat T cells": "cell_line" } }, { "input_text": "We investigated the trophic effect resulting from activation of such a receptor by using the reporter gene strategy .", "target_text": { "reporter gene": "DNA" } }, { "input_text": "For this purpose , we transiently transfected Jurkat T cells with the reporter plasmid p [(TRE)3-tk-Luc] and found that CCK-8 was able to dose-dependently induce luciferase expression related to activator protein-1 ( AP-1 ) activation with a maximal response identical to that obtained with compounds known to activate AP-1 complex ( quantitatively , the same level of induction was obtained with 1 nM 12-O-tetradecanoylphorbol-13-acetate , 100 microM diacylglycerol , or 4 nM epidermal growth factor ) .", "target_text": { "Jurkat T cells": "cell_line", "reporter plasmid p [(TRE)3-tk-Luc]": "DNA", "luciferase": "protein", "activator protein-1": "protein", "AP-1": "protein", "AP-1 complex": "protein" } }, { "input_text": "The involvement of the CCK(B) receptor in such a stimulation was demonstrated by the inhibiting effect of the selective CCK(B) receptor antagonist PD-135,158 .", "target_text": { "CCK(B) receptor": "protein" } }, { "input_text": "This effect was confirmed in COS-7 cells transfected with the cDNA of CCK(B) receptor cloned from Jurkat T cells .", "target_text": { "CCK(B) receptor": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "To better understand the AP-1 -dependent luciferase expression in Jurkat T cells , we tested two specific inhibitors of serine/threonine phosphatases -1 and -2A : okadaic acid and calyculin A .", "target_text": { "AP-1": "protein", "luciferase": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "These compounds strongly increased the phorbol-12-myristate-13-acetate response , whereas we have not observed a contribution of phosphatase inhibitors on a CCK-8 -induced luciferase activity .", "target_text": { "luciferase": "protein" } }, { "input_text": "To confirm that CCK(B) receptors are involved in AP-1 response , we investigated the CCK-8 effect on interleukin-2 expression , a natural endogenous gene regulated by several factors , including AP-1 .", "target_text": { "CCK(B) receptors": "protein", "AP-1": "protein", "interleukin-2": "protein", "endogenous gene": "DNA" } }, { "input_text": "In Jurkat T cells activated by phorbol-12-myristate-13-acetate and phytohemagglutinin , CCK-8 induced IL-2 expression .", "target_text": { "Jurkat T cells": "cell_line", "phytohemagglutinin": "protein" } }, { "input_text": "This induction was abolished by PD-135,158 .", "target_text": {} }, { "input_text": "Our results indicate that CCK-8 exerts a trophic effect in Jurkat T cells through stimulation of CCK(B) receptors by modulation of expression of AP-1 -regulated genes .", "target_text": { "Jurkat T cells": "cell_line", "CCK(B) receptors": "protein", "AP-1": "protein", "AP-1 -regulated genes": "DNA" } }, { "input_text": "A conserved tissue-specific structure at a human T-cell receptor beta-chain core promoter .", "target_text": { "human T-cell receptor beta-chain core promoter": "DNA" } }, { "input_text": "The T-cell receptor ( TCR ) beta-chain promoters have been characterized as nonstructured basal promoters that carry a single conserved ubiquitous cyclic AMP-responsive element .", "target_text": { "T-cell receptor ( TCR ) beta-chain promoters": "DNA", "nonstructured basal promoters": "DNA", "ubiquitous cyclic AMP-responsive element": "DNA" } }, { "input_text": "Our investigation of the human TCR beta gene uncovers a surprisingly complex and tissue-specific structure at the TCR Vbeta 8.1 promoter .", "target_text": { "human TCR beta gene": "DNA", "TCR Vbeta 8.1 promoter": "DNA" } }, { "input_text": "The core of the promoter ( positions -42 to +11 ) is recognized by the lymphoid cell -specific transcription factors Ets-1 , LEF1 , and AML1 as well as by CREB/ATF-1 , as is demonstrated in gel shift and footprinting experiments .", "target_text": { "promoter": "DNA", "positions -42 to +11": "DNA", "lymphoid cell": "cell_type", "lymphoid cell -specific transcription factors": "protein", "Ets-1": "protein", "LEF1": "protein", "AML1": "protein", "CREB/ATF-1": "protein" } }, { "input_text": "With the exception of LEF1 , these factors activate transcription in T cells .", "target_text": { "LEF1": "protein", "T cells": "cell_type" } }, { "input_text": "Binding sites at the core region show little conservation with consensus sites .", "target_text": { "Binding sites": "DNA", "consensus sites": "DNA" } }, { "input_text": "Nonetheless , CREB , Ets-1 , and AML1 bind and activate cooperatively and very efficiently through the nonconsensus binding sites at the core promoter region .", "target_text": { "CREB": "protein", "Ets-1": "protein", "AML1": "protein", "nonconsensus binding sites": "DNA", "core promoter region": "DNA" } }, { "input_text": "Moderate ubiquitous activation is further induced by CREB/ATF and Sp1 factors through proximal upstream elements .", "target_text": { "proximal upstream elements": "DNA" } }, { "input_text": "The tissue-specific core promoter structure is apparently conserved in other T-cell-specifically expressed genes such as the CD4 gene .", "target_text": { "tissue-specific core promoter structure": "DNA", "T-cell-specifically expressed genes": "DNA", "CD4 gene": "DNA" } }, { "input_text": "Our observations suggest that both the enhancer and the promoter have a complex tissue-specific structure whose functional interplay potentiates T-cell-specific transcription .", "target_text": { "enhancer": "DNA", "promoter": "DNA", "complex tissue-specific structure": "DNA" } }, { "input_text": "The cytoplasmic domain of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) receptor alpha subunit is essential for both GM-CSF -mediated growth and differentiation .", "target_text": { "cytoplasmic domain": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "granulocyte-macrophage colony-stimulating factor ( GM-CSF ) receptor alpha subunit": "protein" } }, { "input_text": "Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) regulates differentiation , survival , and proliferation of colony-forming unit-granulocyte-macrophage progenitor cells .", "target_text": { "Granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "colony-forming unit-granulocyte-macrophage progenitor cells": "cell_line" } }, { "input_text": "The biologic actions of GM-CSF are mediated by binding to a specific receptor consisting of two chains designated as alpha and beta subunits .", "target_text": { "GM-CSF": "protein" } }, { "input_text": "We have demonstrated that the murine FDC-P1-derived cell line WT-19 transfected with the human GM-CSF receptor alpha and beta subunits ( GM-CSFR alpha and beta ) can be induced to differentiate by the addition of human GM-CSF ( hGM-CSF ) .", "target_text": { "murine FDC-P1-derived cell line": "cell_line", "WT-19": "cell_line", "GM-CSF": "protein", "human GM-CSF": "protein", "hGM-CSF": "protein" } }, { "input_text": "By expressing a series of GM-CSFRalpha mutants in WT19 cells , we have determined the amino acid domains of the GM-CSFRalpha cytoplasmic domain that regulate cell differentiation , proliferation , and survival .", "target_text": { "GM-CSFRalpha": "protein", "GM-CSFRalpha mutants": "protein", "WT19 cells": "cell_line", "amino acid domains": "protein", "cytoplasmic domain": "protein" } }, { "input_text": "We found that the membrane proximal proline-rich domain and adjacent 16 residues are essential for both hGM-CSF -dependent cell proliferation and differentiation .", "target_text": { "membrane proximal proline-rich domain": "protein", "adjacent 16 residues": "protein", "hGM-CSF": "protein" } }, { "input_text": "In contrast , the C-terminal region of the GM-CSFRalpha cytoplasmic domain was not necessary for cell differentiation mediated by hGM-CSF , but the removal of this region severely impaired the ability of hGM-CSF to support cell survival .", "target_text": { "C-terminal region": "protein", "cytoplasmic domain": "protein", "GM-CSFRalpha cytoplasmic domain": "protein", "hGM-CSF": "protein" } }, { "input_text": "While the activation of JAK2 , Shc , Erk , and STAT5 proteins correlated with hGM-CSF -mediated cell growth , cellular differentiation occurred in the absence of activation of these signal transduction pathways .", "target_text": { "JAK2": "protein", "Shc": "protein", "Erk": "protein", "STAT5 proteins": "protein", "hGM-CSF": "protein" } }, { "input_text": "gamma-Interferon -induced resistance to 1,25-(OH)2 D3 in human monocytes and macrophages : a mechanism for the hypercalcemia of various granulomatoses .", "target_text": { "gamma-Interferon": "protein", "human monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "The hypercalcemia of various granulomatoses is caused by endogenous 1,25-dihydroxyvitamin D [ 1,25-(OH)2D3 ] overproduction by disease-activated macrophages .", "target_text": { "macrophages": "cell_type" } }, { "input_text": "The inability of 1,25(OH)2D3 to suppress its synthesis in macrophages contrasts with the tight control of its production in macrophage precursors , peripheral blood monocytes ( PBM ) .", "target_text": { "macrophages": "cell_type", "peripheral blood monocytes": "cell_type", "PBM": "cell_type" } }, { "input_text": "We examined whether 1,25(OH)2D3 resistance develops as PBM differentiate to macrophages or with macrophage activation .", "target_text": { "PBM": "cell_type", "macrophages": "cell_type" } }, { "input_text": "Normal human pulmonary alveolar macrophages ( PAM ) are less sensitive to 1,25(OH)2D3 than PBM , despite similar vitamin D receptor content ; however , both PBM and PAM respond to exogenous 1,25-(OH)2D3 by inhibiting 1,25(OH)2D3 synthesis and inducing 1,25(OH)2D3 degradation through enhancement of 24-hydroxylase mRNA levels and activity .", "target_text": { "human pulmonary alveolar macrophages": "cell_type", "PAM": "cell_type", "PBM": "cell_type", "vitamin D receptor": "protein", "24-hydroxylase": "protein" } }, { "input_text": "The human monocytic cell line THP-1 mimics PAM in 1,25(OH)2D3 synthesis and sensitivity to exogenous 1,25(OH)2D3 .", "target_text": { "human monocytic cell line": "cell_line", "THP-1": "cell_line", "PAM": "cell_type" } }, { "input_text": "We utilized THP-1 cells to examine the response to 1,25(OH)2D3 with macrophage activation .", "target_text": { "THP-1 cells": "cell_line" } }, { "input_text": "Activation of THP-1 cells with gamma-interferon ( gamma-IFN ) enhances 1,25(OH)2D3 synthesis 30-fold , blocks 1,25-(OH)2D3 suppression of its synthesis , and reduces by 42.2 % 1,25-(OH)2D3 induction of its degradation .", "target_text": { "THP-1 cells": "cell_line", "gamma-interferon": "protein", "gamma-IFN": "protein" } }, { "input_text": "The antagonistic effects of gamma-IFN are not merely restricted to enzymatic activities .", "target_text": { "gamma-IFN": "protein" } }, { "input_text": "In THP-1 cells and in normal PBM , gamma-IFN inhibits 1,25-(OH)2D3 induction of 24-hydroxylase mRNA levels without reducing mRNA stability , suggesting gamma-IFN inhibition of 1,25(OH)2D3 transactivating function .", "target_text": { "THP-1 cells": "cell_line", "PBM": "cell_type", "gamma-IFN": "protein", "24-hydroxylase": "protein" } }, { "input_text": "These results explain 1,25(OH)2D3 overproduction in granulomatoses and demonstrate potent inhibition by gamma-IFN of 1,25(OH)2D3 action in immune cells .", "target_text": { "gamma-IFN": "protein", "immune cells": "cell_type" } }, { "input_text": "Molecular cloning and characterization of a cDNA , CHEMR1 , encoding a chemokine receptor with a homology to the human C-C chemokine receptor , CCR-4 .", "target_text": { "cDNA": "DNA", "CHEMR1": "DNA", "chemokine receptor": "protein", "human C-C chemokine receptor": "protein", "CCR-4": "protein" } }, { "input_text": "Chemokines refer to a rapidly expanding family of small cytokines whose primary function is recruitment of leukocytes to inflammatory sites .", "target_text": { "Chemokines": "protein", "cytokines": "protein" } }, { "input_text": "These are known to bind to seven-transmembrane-domain containing receptors .", "target_text": { "seven-transmembrane-domain containing receptors": "protein" } }, { "input_text": "A cDNA clone , CHEMR1 , resembling the typical G protein-coupled receptor , was isolated from a mouse cytotoxic T-lymphocyte ( CTL ) library .", "target_text": { "cDNA clone": "DNA", "CHEMR1": "DNA", "G protein-coupled receptor": "protein", "mouse cytotoxic T-lymphocyte ( CTL ) library": "DNA" } }, { "input_text": "Northern blot analysis in mouse cell lines suggests that its expression is found in a variety of cells , including T cells , B cells , and macrophages .", "target_text": { "T cells": "cell_type", "B cells": "cell_type", "macrophages": "cell_type" } }, { "input_text": "The CHEMR1 gene Scya3r2 is a single-copy gene whose open reading frame may be in a single exon and maps to the distal region of mouse Chr 9 where the mouse macrophage inflammatory protein-1alpha ( MIP-1alpha ) receptor gene Scya3r and two related C-C chemokine receptor-like genes reside .", "target_text": { "CHEMR1": "DNA", "CHEMR1 gene": "DNA", "Scya3r2": "DNA", "single-copy gene": "DNA", "mouse Chr 9": "DNA", "mouse macrophage inflammatory protein-1alpha": "protein", "MIP-1alpha": "protein", "mouse macrophage inflammatory protein-1alpha ( MIP-1alpha ) receptor gene": "DNA", "Scya3r": "DNA", "C-C chemokine receptor-like genes": "DNA" } }, { "input_text": "Amino acid sequence comparison shows that CHEMR1 is 84 % identical to human CCR-4 , indicating that CHEMR1 is likely to be a mouse CCR-4 .", "target_text": { "CHEMR1": "DNA", "CCR-4": "protein", "human CCR-4": "protein", "mouse CCR-4": "protein" } }, { "input_text": "Binding assays using 125I-labeled C-C chemokines in mammalian cells indicated that CHEMR1 did not bind MIP-1alpha , RANTES , or MIP-1beta , whereas CCR-1 binds MIP-1alpha and RANTES .", "target_text": { "125I-labeled C-C chemokines": "protein", "mammalian cells": "cell_type", "CHEMR1": "DNA", "CCR-1": "protein", "MIP-1alpha": "protein", "RANTES": "protein" } }, { "input_text": "Our result is different from the reported properties of human CCR-4 .", "target_text": { "CCR-4": "protein", "human CCR-4": "protein" } }, { "input_text": "This suggests that CHEMR1 may be a receptor for unidentified C-C chemokine or a low-affinity receptor for MIP-1alpha .", "target_text": { "CHEMR1": "DNA", "C-C chemokine": "protein", "MIP-1alpha": "protein" } }, { "input_text": "Transactivation by CIITA , the type II bare lymphocyte syndrome-associated factor , requires participation of multiple regions of the TATA box binding protein .", "target_text": { "CIITA": "protein", "type II bare lymphocyte syndrome-associated factor": "protein", "TATA box binding protein": "protein" } }, { "input_text": "CIITA is a positive regulator of class II major histocompatibility complex gene transcription that has been found to be defective in one of the five complementation groups of class II major histocompatibility complex -negative cell lines .", "target_text": { "CIITA": "protein", "class II major histocompatibility complex gene": "DNA", "class II major histocompatibility complex": "protein", "class II major histocompatibility complex -negative cell lines": "cell_line" } }, { "input_text": "Its N-terminal region is capable of activating transcription from a reporter gene when fused to a DNA binding domain .", "target_text": { "N-terminal region": "protein", "DNA binding domain": "protein" } }, { "input_text": "We have investigated the mechanism of transactivation mediated by the CIITA activation domain by studying its role in the process of transcription initiation and elongation .", "target_text": { "CIITA": "protein", "CIITA activation domain": "protein" } }, { "input_text": "Specifically the altered specificity TBP ( TATA box binding protein ) assay has been used to analyze the response of the CIITA activation domain to mutations in TBP known to disrupt its interaction with its associated general factors .", "target_text": { "TATA box binding protein": "protein", "CIITA": "protein", "CIITA activation domain": "protein", "TBP": "protein", "associated general factors": "protein" } }, { "input_text": "Transactivation by CIITA was extremely sensitive to a mutation in TBP that in yeast is known to abolish VP16 -mediated transcription but leaves basal transcription unaffected .", "target_text": { "CIITA": "protein", "TBP": "protein", "VP16": "protein" } }, { "input_text": "A TBP mutant defective in interaction with TBP -associated factor TAFII250 also failed to mediate transactivation through the CIITA activation domain .", "target_text": { "TBP": "protein", "TBP -associated factor": "protein", "TAFII250": "protein", "CIITA": "protein", "CIITA activation domain": "protein" } }, { "input_text": "Certain interactions between TBP and general factors that are specifically required for acidic activation domains were also required for CIITA -mediated transactivation to reach its full potential .", "target_text": { "TBP": "protein", "general factors": "protein", "acidic activation domains": "protein", "CIITA": "protein" } }, { "input_text": "Finally , like VP16 , CIITA was able to stimulate elongation of transcription .", "target_text": { "CIITA": "protein" } }, { "input_text": "Overall the mechanism of transactivation by the human B-cell-specific CIITA is very similar to that mediated by the herpes virus transactivator VP16 in the ways that have been tested .", "target_text": { "CIITA": "protein", "human B-cell-specific CIITA": "protein", "herpes virus transactivator": "protein", "VP16": "protein" } }, { "input_text": "Relief of cyclin A gene transcriptional inhibition during activation of human primary T lymphocytes via CD2 and CD28 adhesion molecules .", "target_text": { "cyclin A": "protein", "human primary T lymphocytes": "cell_type", "CD2": "protein", "CD28": "protein", "adhesion molecules": "protein" } }, { "input_text": "Cyclin A transcription is cell cycle regulated and induced by cell proliferative signals .", "target_text": { "Cyclin A": "protein" } }, { "input_text": "To understand the mechanisms underlined in this regulation in normal human cells , we have analysed in vivo protein-DNA interactions at the Cyclin A locus in primary T lymphocytes .", "target_text": { "Cyclin A": "protein", "primary T lymphocytes": "cell_type" } }, { "input_text": "Stimulation of purified T lymphocytes by a combination of monoclonal antibodies directed at CD2 and CD28 adhesion molecules gives rise to a long lasting proliferation in the absence of accessory cells .", "target_text": { "monoclonal antibodies": "protein", "CD2": "protein", "CD28": "protein", "adhesion molecules": "protein", "accessory cells": "cell_type" } }, { "input_text": "Cyclin A was observed after 4 days of costimulation with anti CD2 + CD28 whereas stimulation by anti CD2 or anti CD28 alone was not effective .", "target_text": { "Cyclin A": "protein", "CD2": "protein", "anti CD2": "protein", "CD28": "protein", "anti CD28": "protein" } }, { "input_text": "In vivo genomic DMS footprinting revealed upstream of the major transcription initiation sites , the presence of at least three protein binding sites , two of which were constitutively occupied .", "target_text": { "transcription initiation sites": "DNA", "protein binding sites": "DNA" } }, { "input_text": "They bind in vitro respectively ATF-1 and NF-Y proteins .", "target_text": { "ATF-1": "protein", "NF-Y proteins": "protein" } }, { "input_text": "The third site was occupied in quiescent cells or in cells stimulated by anti CD2 or anti CD28 alone .", "target_text": { "CD2": "protein", "anti CD2": "protein", "CD28": "protein", "anti CD28": "protein" } }, { "input_text": "The mitogenic combination of anti CD2 + anti CD28 released the footprint as cells were committed to proliferation .", "target_text": { "CD2": "protein", "anti CD2": "protein", "CD28": "protein", "anti CD28": "protein" } }, { "input_text": "Consistent with theses results , nuclear extracts prepared from quiescent cells formed a specific complex with this element , whereas extracts prepared from cells treated with anti CD2 + anti CD28 failed to do so after cells entered a proliferative state .", "target_text": { "CD2": "protein", "anti CD2": "protein", "CD28": "protein", "anti CD28": "protein" } }, { "input_text": "An enhancer-blocking element between alpha and delta gene segments within the human T cell receptor alpha/delta locus .", "target_text": { "enhancer-blocking element": "DNA", "human T cell receptor alpha/delta locus": "DNA" } }, { "input_text": "T cell receptor ( TCR ) alpha and delta gene segments are organized within a single genetic locus but are differentially regulated during T cell development .", "target_text": { "T cell receptor ( TCR ) alpha": "protein" } }, { "input_text": "An enhancer-blocking element ( BEAD-1 , for blocking element alpha/delta 1 ) was localized to a 2.0-kb region 3' of TCR delta gene segments and 5' of TCR alpha joining gene segments within this locus .", "target_text": { "enhancer-blocking element": "DNA", "BEAD-1": "DNA", "element alpha/delta 1": "DNA", "2.0-kb region": "DNA", "TCR delta gene segments": "DNA", "TCR alpha joining gene segments": "DNA" } }, { "input_text": "BEAD-1 blocked the ability of the TCR delta enhancer ( Edelta ) to activate a promoter when located between the two in a chromatin-integrated construct .", "target_text": { "BEAD-1": "DNA", "TCR delta enhancer": "DNA", "Edelta": "DNA", "chromatin-integrated construct": "DNA" } }, { "input_text": "We propose that BEAD-1 functions as a boundary that separates the TCR alpha/delta locus into distinct regulatory domains controlled by Edelta and the TCR alpha enhancer , and that it prevents Edelta from opening the chromatin of the TCR alpha joining gene segments for VDJ recombination at an early stage of T cell development .", "target_text": { "BEAD-1": "DNA", "TCR alpha/delta locus": "DNA", "regulatory domains": "DNA", "Edelta": "DNA", "TCR alpha enhancer": "DNA", "chromatin": "DNA", "TCR alpha": "DNA" } }, { "input_text": "Uncoupling of cell cycle arrest from the expression of monocytic differentiation markers in HL60 cell variants .", "target_text": { "HL60 cell variants": "cell_line" } }, { "input_text": "Differentiation generally leads to cell cycle arrest .", "target_text": {} }, { "input_text": "Human leukemia HL60 cells respond to the presence of 1,25-dihydroxyvitamin D3 ( 1,25D3 ) by expressing a number of markers of the monocyte/macrophage phenotype and become arrested predominantly in the G1 phase of the cell cycle .", "target_text": { "Human leukemia HL60 cells": "cell_line" } }, { "input_text": "We have recently reported a series ( A ) of 1,25D3 -resistant variants of HL60 cells which proliferate in the presence of 1,25D3 and do not express differentiation markers ( Exp. Cell Res. 224 , 312 , 1996 ) .", "target_text": { "HL60 cells": "cell_line" } }, { "input_text": "We now describe another series ( B ) of such variants , which differ from A series cells grown in similar concentrations of 1,25D3 in that they express the CD14 antigen and nonspecific esterase , characteristic of the monocyte , while continuing to proliferate and they develop hypotetraploid DNA ( 4C ) content at higher concentrations of ambient 1,25D3 than the A series cells .", "target_text": { "CD14 antigen": "protein", "esterase": "protein" } }, { "input_text": "Cells in the B series with 4C DNA content ( 100B and 200B ) also differed from the A series 4C cells by the absence of DNA binding by the full-length Sp1 transcription factor .", "target_text": { "A series 4C cells": "cell_line", "Sp1": "protein", "transcription factor": "protein" } }, { "input_text": "However , B series cells resembled the A series cells in exhibiting faster growth rates than the parental HL60 cells and showed high levels of vitamin D receptor and retinoid receptor X proteins .", "target_text": { "HL60 cells": "cell_line", "vitamin D receptor": "protein", "retinoid receptor X proteins": "protein" } }, { "input_text": "These results show that the initial steps in the 1,25D3 signaling pathway are intact in B series resistant cells and lead to the appearance of early markers of monocytic differentiation .", "target_text": {} }, { "input_text": "However , the progression to subsequent events which comprise terminal differentiation and cell cycle arrest is halted during the adaptation to the presence of 1,25D3 in these cells .", "target_text": {} }, { "input_text": "Thus , the availability of these variant cells should provide a system for studying the link between differentiation and cell cycle arrest .", "target_text": {} }, { "input_text": "Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of anti-Tat single-chain intrabodies and NF-kappa B antagonists .", "target_text": { "anti-Tat single-chain intrabodies": "protein" } }, { "input_text": "Human immunodeficiency virus type 1 ( HIV-1 ) Tat , an early regulatory protein that is critical for viral gene expression and replication , transactivates the HIV-1 long terminal repeat ( LTR ) via its binding to the transactivation response element ( TAR ) and , along with other cellular factors , increases viral transcription initiation and elongation .", "target_text": { "Human immunodeficiency virus type 1 ( HIV-1 ) Tat": "protein", "regulatory protein": "protein", "HIV-1 long terminal repeat": "DNA", "LTR": "DNA", "transactivation response element": "DNA", "TAR": "DNA" } }, { "input_text": "Tat also superactivates the HIV-1 promoter through a TAR -independent mechanism , including tumor necrosis factor alpha-induced and protein kinase C ( PKC ) -dependent activation of NF-kappa B , and inhibitors of Tat and NF-kappa B cooperatively down-regulate this Tat -mediated LTR superactivation .", "target_text": { "HIV-1 promoter": "DNA", "TAR": "DNA", "PKC": "protein", "NF-kappa B": "protein", "Tat": "protein", "LTR": "DNA" } }, { "input_text": "In this study , a combined pharmacologic and genetic strategy using two PKC ( NF-kappa B ) inhibitors , pentoxifylline ( PTX ) and Go-6976 , and a stably expressed anti- Tat single-chain intracellular antibody ( sFv intrabody ) was employed to obtain cooperative inhibition of both HIV-1 LTR -driven gene expression and HIV-1 replication .", "target_text": { "PKC": "protein", "NF-kappa B": "protein", "Tat": "protein", "anti- Tat single-chain intracellular antibody": "protein", "sFv intrabody": "protein", "LTR": "DNA" } }, { "input_text": "Treatment of cells with PTX and Go-6976 resulted in cooperative inhibition of both HIV-1 LTR -driven gene expression and HIV-1 replication .", "target_text": { "HIV-1 LTR": "DNA" } }, { "input_text": "In addition , the combined use of anti- Tat sFv intrabodies and the two NF-kappa B inhibitors retained the virus in the latent state for as long as 45 days .", "target_text": { "Tat": "protein", "anti- Tat sFv intrabodies": "protein", "NF-kappa B": "protein" } }, { "input_text": "The combined treatment resulted in more durable inhibition of HIV-1 replication than was seen with the NF-kappa B inhibitors alone or the anti- Tat sFv intrabodies alone .", "target_text": { "NF-kappa B": "protein", "Tat": "protein", "Tat sFv intrabodies": "protein" } }, { "input_text": "Together , these results suggest that in future clinical gene therapy trials , a combined pharmacologic and genetic strategy like the one reported here may improve the survival of transduced cells and prolong clinical benefit .", "target_text": { "transduced cells": "cell_line" } }, { "input_text": "Transcription factors in immune-mediated disease .", "target_text": { "Transcription factors": "protein" } }, { "input_text": "A large amount of detailed information about the intracellular proteins regulating NF-kappa B activation and the cellular response to NF-kappa B activation has emerged recently .", "target_text": { "intracellular proteins": "protein", "NF-kappa B": "protein" } }, { "input_text": "Several small molecules , an antisense oligonucleotide , and gene therapeutic agents that inhibit NF-kappa b activation have been described .", "target_text": { "antisense oligonucleotide": "DNA", "NF-kappa b": "protein" } }, { "input_text": "Despite this , there are still significant gaps in our understanding of this process and its consequences .", "target_text": {} }, { "input_text": "In contrast , the characterization of transcription factors selectively regulating cytokine production by CD4+ T cell subsets is at a very early stage .", "target_text": { "transcription factors": "protein", "CD4+ T cell subsets": "cell_type" } }, { "input_text": "Three interacting proteins have recently been shown to contribute to subset-restricted expression of the IL-4 gene .", "target_text": { "interacting proteins": "protein", "IL-4 gene": "DNA" } }, { "input_text": "There are other elements regulating IL-4 gene expression , however , and the relative importance of these recently identified proteins has yet to be determined .", "target_text": { "IL-4 gene": "DNA" } }, { "input_text": "Involvement of Rel , Fos , and Jun proteins in binding activity to the IL-2 promoter CD28 response element/ AP-1 sequence in human T cells .", "target_text": { "IL-2 promoter": "DNA", "AP-1": "protein", "IL-2 promoter CD28 response element/ AP-1 sequence": "DNA", "human T cells": "cell_type" } }, { "input_text": "CD28 is an important costimulatory molecule in the activation of human T cells .", "target_text": { "CD28": "protein", "costimulatory molecule": "protein", "human T cells": "cell_type" } }, { "input_text": "Costimulation of T cells through both the Ag receptor and CD28 leads to high level IL-2 production , which is vital to the development of an immune response in vivo .", "target_text": { "T cells": "cell_type", "CD28": "protein", "IL-2": "protein" } }, { "input_text": "Previous reports have suggested the CD28 stimulation contributes to the activation of the IL-2 promoter by up-regulating the activity of several transcription factors , including AP-1 and nuclear factor-kappaB ( NF-kappaB ) / Rel family members as well as an uncharacterized transcription factor called CD28 response complex .", "target_text": { "CD28": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "transcription factors": "protein", "AP-1": "protein", "nuclear factor-kappaB": "protein", "NF-kappaB": "protein", "Rel": "protein", "nuclear factor-kappaB ( NF-kappaB ) / Rel family members": "protein", "uncharacterized transcription factor": "protein" } }, { "input_text": "While several lines of investigation have suggested that NF-kappaB/Rel family members make up the CD28 response complex transcription factor , other work has not supported this conclusion .", "target_text": { "NF-kappaB/Rel family members": "protein", "CD28": "protein", "transcription factor": "protein" } }, { "input_text": "Recent studies suggest that the CD28 response element ( CD28RE ) does not function independently but works instead in conjunction with the adjacent promoter proximal AP-1 -binding site and this hypothesis is confirmed here .", "target_text": { "CD28": "protein", "CD28 response element": "DNA", "CD28RE": "DNA", "AP-1": "protein", "AP-1 -binding site": "DNA", "adjacent promoter proximal AP-1 -binding site": "DNA" } }, { "input_text": "Also in the current study , binding activity to the CD28RE /AP-1 sequence of the IL-2 promoter is evaluated .", "target_text": { "CD28RE": "DNA", "CD28RE /AP-1 sequence": "DNA", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Although four specific complexes can be detected binding to this sequence , only one of these complexes is specific for both the CD28RE and the adjacent AP-1 site .", "target_text": { "CD28RE": "DNA", "adjacent AP-1 site": "DNA" } }, { "input_text": "Of the NF-kappaB/Rel family members tested , this CD28RE /AP-1-specific complex contains predominantly c-Rel , despite the fact that both p50 and RelA can efficiently bind to the CD28RE .", "target_text": { "NF-kappaB/Rel family members": "protein", "CD28RE": "DNA", "CD28RE /AP-1-specific complex": "protein", "c-Rel": "protein", "p50": "protein", "RelA": "protein" } }, { "input_text": "c-Fos and c-Jun are also found in this CD28RE /AP-1-specific complex .", "target_text": { "c-Fos": "protein", "c-Jun": "protein", "CD28RE": "DNA", "CD28RE /AP-1-specific complex": "protein" } }, { "input_text": "These data indicate that functional complexes encompassing both the CD28RE and the AP-1-binding sites influence IL-2 promoter activity in CD28 -costimulated T cells .", "target_text": { "CD28RE": "DNA", "AP-1-binding sites": "DNA", "IL-2": "protein", "IL-2 promoter": "DNA", "CD28": "protein", "T cells": "cell_type" } }, { "input_text": "Inducible expression and phosphorylation of coactivator BOB.1/OBF.1 in T cells [ see comments ]", "target_text": { "coactivator BOB.1/OBF.1": "protein", "T cells": "cell_type" } }, { "input_text": "BOB.1/OBF.1 is a transcriptional coactivator that is constitutively expressed in B cells and interacts with the Oct1 and Oct2 transcription factors .", "target_text": { "BOB.1/OBF.1": "protein", "transcriptional coactivator": "protein", "B cells": "cell_type", "transcription factors": "protein" } }, { "input_text": "Upon activation of Jurkat T cells and primary murine thymocytes with phorbol esters and ionomycin , BOB.1/OBF.1 expression and transactivation function were induced .", "target_text": { "Jurkat T cells": "cell_line", "primary murine thymocytes": "cell_type", "BOB.1/OBF.1": "protein" } }, { "input_text": "BOB.1/OBF.1 was phosphorylated at Ser184 both in vivo and in vitro , and this modification was required for inducible activation .", "target_text": { "BOB.1/OBF.1": "protein" } }, { "input_text": "Mutation of Ser184 also diminished transactivation function in B cells , suggesting that the activating phosphorylation that is inducible in T cells is constitutively present in B cells .", "target_text": { "B cells": "cell_type", "T cells": "cell_type" } }, { "input_text": "Thus , BOB.1/OBF.1 is a transcriptional coactivator that is critically regulated by posttranslational modifications to mediate cell type-specific gene expression .", "target_text": { "BOB.1/OBF.1": "protein", "transcriptional coactivator": "protein" } }, { "input_text": "Increased expression of Gs(alpha) enhances activation of the adenylyl cyclase signal transduction cascade .", "target_text": { "Gs(alpha)": "protein", "adenylyl cyclase": "protein" } }, { "input_text": "Expression of the stimulatory G protein , G(S)alpha , can vary over a 3-fold range in human tissues and in rodent central nervous system .", "target_text": { "G protein": "protein", "G(S)alpha": "protein" } }, { "input_text": "In fact , the offspring of alcoholics have higher levels of G(S)alpha expression in certain tissues compared with the offspring of nonalcoholics .", "target_text": { "G(S)alpha": "protein" } }, { "input_text": "The aim of this research was to test the hypothesis that a causal relationship exists between the level of expression of G(S)alpha and induction of the adenylyl cyclase ( AC ) cascade .", "target_text": { "G(S)alpha": "protein", "adenylyl cyclase": "protein" } }, { "input_text": "The methodology employed transient transfection of HEK 293 cells with a cDNA for the 52-kDa form of G(S)alpha under regulation by inducible metallothionein promoters .", "target_text": { "HEK 293 cells": "cell_line", "G(S)alpha": "protein", "inducible metallothionein promoters": "DNA" } }, { "input_text": "Transfectants were exposed to varying concentrations ( 0-125 microM ) of zinc sulfate that produced a 3-fold range of membrane G(S)alpha expression .", "target_text": { "G(S)alpha": "protein" } }, { "input_text": "The range of G(S)alpha expression produced was found to mimic a physiologically relevant spectrum of G(S)alpha expression in membranes derived from human tissues and rat brain .", "target_text": { "G(S)alpha": "protein" } }, { "input_text": "It was observed that induction of G(S)alpha expression increased constitutive as well as stimulated cAMP accumulation .", "target_text": { "G(S)alpha": "protein" } }, { "input_text": "Moreover , induction of G(S)alpha expression increased events distal to the accumulation of cAMP including the phosphorylation of the transcription factor , cAMP response element binding protein and transcriptional activation of cAMP-dependent reporter genes .", "target_text": { "G(S)alpha": "protein", "cAMP response element binding protein": "protein", "cAMP-dependent reporter genes": "DNA" } }, { "input_text": "In summary , these studies show that the amount of G(S)alpha expression has a marked impact on the level of activity of the AC cascade from the membrane through to the nucleus .", "target_text": { "G(S)alpha": "protein" } }, { "input_text": "It is hypothesized that individuals who differ in G(S)alpha expression may also differ in the expression of certain cAMP -dependent genes .", "target_text": { "G(S)alpha": "protein", "cAMP -dependent genes": "DNA" } }, { "input_text": "Thrombin generation by apoptotic vascular smooth muscle cells .", "target_text": { "Thrombin": "protein", "apoptotic vascular smooth muscle cells": "cell_type" } }, { "input_text": "Thrombin activation requires assembly of a prothrombinase complex of activated coagulation factors on an anionic phospholipid surface , classically provided by activated platelets .", "target_text": { "Thrombin": "protein", "prothrombinase complex": "protein", "coagulation factors": "protein", "activated platelets": "cell_type" } }, { "input_text": "We have previously shown that anionic phosphatidylserine is exposed by rat vascular smooth muscle cells ( VSMCs ) undergoing apoptosis after serum withdrawal .", "target_text": { "rat vascular smooth muscle cells": "cell_type", "VSMCs": "cell_type" } }, { "input_text": "In this study , using a chromogenic assay , we have shown thrombin generation by apoptotic VSMCs expressing c-myc ( VSMC-myc ) with an area under the thrombin -generation curve ( AUC ) of 305 +/- 17 nmol x min/L and a peak thrombin ( PT ) of 154 +/- 9 nmol/L .", "target_text": { "thrombin": "protein", "VSMCs": "cell_type", "apoptotic VSMCs": "cell_type", "c-myc": "protein", "VSMC-myc": "cell_line" } }, { "input_text": "The thrombin -generating potential of the apoptotic VSMC-myc cells was greater than that of unactivated platelets ( P = .003 for AUC ; P = .0002 for PT ) and similar to calcium-ionophore activated platelets ( AUC of 332 +/- 15 nmol x min/L , P = .3 ; PT of 172 +/- 8 nmol/L , P = .2 ) .", "target_text": { "thrombin": "protein", "apoptotic VSMC-myc cells": "cell_line", "unactivated platelets": "cell_type", "activated platelets": "cell_type" } }, { "input_text": "Thrombin activation was also seen with apoptotic human VSMCs ( AUC of 211 +/- 8 nmol x min/L ; PT of 103 +/- 4 nmol/L ) and was inhibited by annexin V ( P < .0001 for AUC and PT ) .", "target_text": { "Thrombin": "protein", "VSMCs": "cell_type", "apoptotic human VSMCs": "cell_type" } }, { "input_text": "VSMC-myc cells maintained in serum generated less thrombin than after serum withdrawal ( P = .0002 for AUC and PT ) .", "target_text": { "VSMC-myc cells": "cell_line", "thrombin": "protein" } }, { "input_text": "VSMCs derived from human coronary atherosclerotic plaques that apoptose even in serum also generated thrombin ( AUC of 260 +/- 2 nmol x min/L ; PT of 128 +/- 4 nmol/L ) .", "target_text": { "VSMCs": "cell_type", "thrombin": "protein" } }, { "input_text": "We conclude that apoptotic VSMCs possess a significant thrombin -generating capacity secondary to phosphatidylserine exposure .", "target_text": { "VSMCs": "cell_type", "apoptotic VSMCs": "cell_type", "thrombin": "protein" } }, { "input_text": "Apoptotic cells within atherosclerotic plaques may allow local thrombin activation , thereby contributing to disease progression .", "target_text": { "thrombin": "protein" } }, { "input_text": "An isotype-specific activator of major histocompatibility complex ( MHC ) class II genes that is independent of class II transactivator .", "target_text": { "major histocompatibility complex ( MHC ) class II genes": "DNA", "class II transactivator": "protein" } }, { "input_text": "Patients with one type of major histocompatibility complex class II combined immunodeficiency have mutations in a gene termed class II transactivator ( CIITA ) , which coordinately controls the transcription of the three major human class II genes , HLA -DR , -DQ , and -DP .", "target_text": { "major histocompatibility complex class II": "protein", "class II transactivator": "protein", "CIITA": "protein", "human class II genes": "DNA" } }, { "input_text": "However , the experimentally derived B-lymphoblastoid cell line , clone 13 , expresses high levels of HLADQ in the absence of HLA-DR and HLA-DP , despite its mapping by complementation analysis to this group .", "target_text": { "B-lymphoblastoid cell line": "cell_line", "clone 13": "cell_line", "HLADQ": "protein", "HLA-DR": "DNA", "HLA-DP": "DNA" } }, { "input_text": "It was possible that one of the clone 13 CIITA alleles bore a mutation that allowed HLA-DQ , but not HLA -DR or -DP transcription .", "target_text": { "clone 13": "cell_line", "CIITA": "protein", "clone 13 CIITA alleles": "DNA", "HLA-DQ": "DNA" } }, { "input_text": "Alternatively , another factor , distinct from CIITA , might control HLA-DQ expression .", "target_text": { "CIITA": "protein", "HLA-DQ": "DNA" } }, { "input_text": "We report here that ectopic expression of CIITA cDNAs derived by reverse transcriptase polymerase chain reaction from clone 13 do not restore expression of HLA-DQ in another CIITA -deficient cell line , RJ2.2.5 .", "target_text": { "CIITA": "protein", "CIITA cDNAs": "DNA", "clone 13": "cell_line", "HLA-DQ": "DNA", "CIITA -deficient cell line": "cell_line", "RJ2.2.5": "cell_line" } }, { "input_text": "In addition , no CIITA protein is detectable in clone 13 nuclear extracts .", "target_text": { "CIITA": "protein", "clone 13": "cell_line" } }, { "input_text": "In contrast , somatic cell fusion between clone 13 and RJ2.2.5 restored expression of the HLA-DQ haplotype encoded by the RJ2.2.5 DQB gene .", "target_text": { "clone 13": "cell_line", "RJ2.2.5": "cell_line", "HLA-DQ": "DNA", "RJ2.2.5 DQB gene": "DNA" } }, { "input_text": "Taken together , these data demonstrate the existence of an HLA-DQ isotype-specific trans-acting factor , which functions independently of CIITA .", "target_text": { "HLA-DQ": "DNA", "HLA-DQ isotype-specific trans-acting factor": "protein", "CIITA": "protein" } }, { "input_text": "Homodimerization of the human interleukin 4 receptor alpha chain induces Cepsilon germline transcripts in B cells in the absence of the interleukin 2 receptor gamma chain .", "target_text": { "human interleukin 4 receptor alpha chain": "protein", "Cepsilon germline transcripts": "RNA", "B cells": "cell_type", "interleukin 2 receptor gamma chain": "protein" } }, { "input_text": "The cytokines interleukin ( IL ) -4 and IL-13 play a critical role in inducing Cepsilon germline transcripts and IgE isotype switching in human B cells .", "target_text": { "cytokines": "protein", "interleukin ( IL ) -4": "protein", "IL-13": "protein", "Cepsilon germline transcripts": "RNA", "IgE isotype": "protein", "B cells": "cell_type", "human B cells": "cell_type" } }, { "input_text": "The IL-4 receptor ( IL-4R ) in B cells is composed of two chains , the IL-4-binding IL-4Ralpha chain , which is shared with the IL-13R , and the IL-2Rgamma ( gammac ) chain , which is shared with IL-7R , IL-9R , and IL-15R .", "target_text": { "IL-4 receptor": "protein", "IL-4R": "protein", "B cells": "cell_type", "IL-4Ralpha chain": "protein", "IL-4-binding IL-4Ralpha chain": "protein", "IL-13R": "protein", "IL-2Rgamma ( gammac ) chain": "protein", "IL-7R": "protein", "IL-9R": "protein", "IL-15R": "protein" } }, { "input_text": "IL-4 induces Cepsilon germline transcripts and IgE isotype switching in B cells from patients with gammac chain deficiency .", "target_text": { "IL-4": "protein", "Cepsilon germline transcripts": "RNA", "IgE isotype": "protein", "B cells": "cell_type", "gammac chain": "protein" } }, { "input_text": "Induction of Cepsilon germline transcripts by IL-4 in B cells that lack the gammac chain may involve signaling via the IL-13R .", "target_text": { "Cepsilon germline transcripts": "RNA", "IL-4": "protein", "B cells": "cell_type", "gammac chain": "protein", "IL-13R": "protein" } }, { "input_text": "Alternatively , the IL-4Ralpha chain may transduce intracellular signals that lead to Cepsilon gene transcription independently of its association with other chains .", "target_text": { "IL-4Ralpha chain": "protein", "Cepsilon gene": "DNA" } }, { "input_text": "We show that ligand-induced homodimerization of chimeric surface receptors consisting of the extracellular and transmembrane domains of the erythropoietin receptor and of the intracellular domain of IL-4Ralpha induces Janus kinase 1 ( Jak1 ) activation , STAT6 activation , and Cepsilon germline transcripts in human B cell line BJAB .", "target_text": { "chimeric surface receptors": "protein", "erythropoietin receptor": "protein", "intracellular domain": "protein", "IL-4Ralpha": "protein", "Janus kinase 1": "protein", "Jak1": "protein", "STAT6": "protein", "Cepsilon germline transcripts": "RNA", "human B cell line BJAB": "cell_line" } }, { "input_text": "Disruption of the Jak1 -binding proline-rich Box1 region of IL-4Ralpha abolished signaling by this chimeric receptor .", "target_text": { "Jak1": "protein", "Jak1 -binding proline-rich Box1 region": "protein", "IL-4Ralpha": "protein", "chimeric receptor": "protein" } }, { "input_text": "Furthermore , B cells transfected with a chimeric CD8alpha/IL-4Ralpha receptor , which is expressed on the cell surface as a homodimer , constitutively expressed Cepsilon germline transcripts .", "target_text": { "B cells": "cell_type", "chimeric CD8alpha/IL-4Ralpha receptor": "protein", "homodimer": "protein", "Cepsilon germline transcripts": "RNA" } }, { "input_text": "These results suggest that homodimerization of the IL-4Ralpha chain is sufficient to transduce Jak1 -dependent intracellular signals that lead to IgE isotype switching .", "target_text": { "IL-4Ralpha": "protein", "IL-4Ralpha chain": "protein", "Jak1": "protein", "IgE isotype": "protein" } }, { "input_text": "Transcriptional activity and constitutive nuclear localization of the ETS protein Elf-1 .", "target_text": { "ETS protein": "protein", "Elf-1": "protein" } }, { "input_text": "Elf-1 is a lymphoid-specific transcription factor that belongs to the ETS protein family .", "target_text": { "Elf-1": "protein", "lymphoid-specific transcription factor": "protein", "ETS protein": "protein", "ETS protein family": "protein" } }, { "input_text": "It can bind to DNA target sequences within a variety of cytokine genes .", "target_text": { "cytokine genes": "DNA" } }, { "input_text": "We demonstrate that Elf-1 is constitutively localized in the nucleus which is dependent on the presence of amino acids 86-265 .", "target_text": { "Elf-1": "protein", "amino acids 86-265": "protein" } }, { "input_text": "Analysis of Gal4-Elf-1 fusion proteins revealed that the N-terminal 86 amino acids of Elf-1 contain a transcriptional activation domain , the activity of which is attenuated by an internal repression domain .", "target_text": { "Gal4-Elf-1 fusion proteins": "protein", "Elf-1": "protein", "transcriptional activation domain": "protein", "internal repression domain": "protein" } }, { "input_text": "Furthermore , Elf-1 interacts specifically with the E74 target sequence and can stimulate transcription driven by the E74 site independent of mitogenic signaling .", "target_text": { "Elf-1": "protein", "E74 target sequence": "DNA", "E74 site": "DNA" } }, { "input_text": "Thus , Elf-1 is able to stimulate gene transcription which may be required for the development and activity of lymphocytes .", "target_text": { "Elf-1": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Characterization of peripheral blood T-lymphocytes transduced with HTLV-I Tax mutants with different trans-activating phenotypes .", "target_text": { "peripheral blood T-lymphocytes": "cell_type", "HTLV-I Tax mutants": "protein" } }, { "input_text": "Tax1 , a transcriptional trans-activator of the Human T-cell leukemia virus type I ( HTLV-I ) , induces the expression of many cellular genes through interaction with at least three distinct cellular transcription factors ; CREB/ATF , NF-kappaB , and SRF .", "target_text": { "Tax1": "protein", "transcriptional trans-activator": "protein", "transcription factors": "protein", "cellular transcription factors": "protein", "CREB/ATF": "protein", "NF-kappaB": "protein", "SRF": "protein" } }, { "input_text": "This Tax1 -induced activation of cellular genes is considered to be a critical event in T-cell transformation by HTLV-I .", "target_text": { "Tax1": "protein", "cellular genes": "DNA" } }, { "input_text": "To elucidate the role of each Tax1 -inducible transcriptional pathway in T-cell transformation , we introduced Tax1 mutants with different trans-activating phenotypes into peripheral blood lymphocytes ( PBL ) by retroviral vectors .", "target_text": { "Tax1": "protein", "Tax1 mutants": "protein", "lymphocytes": "cell_type", "peripheral blood lymphocytes": "cell_type", "PBL": "cell_type" } }, { "input_text": "Analysis of these PBLs revealed that activation of the NF-kappaB pathway is sufficient to promote the growth response to IL-2 .", "target_text": { "PBLs": "cell_type", "NF-kappaB": "protein", "IL-2": "protein" } }, { "input_text": "However , for the clonal expansion of CD4+ T-cells , which is a characteristic result of HTLV-I infection , activation of the CREB/ATF and SRF pathways is also required .", "target_text": { "CD4+ T-cells": "cell_type" } }, { "input_text": "Epstein-Barr virus binding to CD21 activates the initial viral promoter via NF-kappaB induction .", "target_text": { "CD21": "protein", "viral promoter": "DNA", "NF-kappaB": "protein" } }, { "input_text": "Epstein-Barr virus ( EBV ) , an oncogenic human herpesvirus , binds to and infects normal human B lymphocytes via CD21 , the CR2 complement receptor .", "target_text": { "normal human B lymphocytes": "cell_type", "CD21": "protein", "CR2 complement receptor": "protein" } }, { "input_text": "Studies of the mechanisms that enable EBV to infect nonactivated , noncycling B cells provide compelling evidence for a sequence of events in which EBV binding to CD21 on purified resting human B cells rapidly activates the NF-kappaB transcription factor , which , in turn , binds to and mediates transcriptional activation of Wp , the initial viral latent gene promoter .", "target_text": { "noncycling B cells": "cell_type", "CD21": "protein", "resting human B cells": "cell_type", "NF-kappaB": "protein", "transcription factor": "protein", "viral latent gene promoter": "DNA" } }, { "input_text": "Thus , EBV binding to its cellular receptor on resting B cells triggers an NF-kappaB -dependent intracellular signaling pathway which is required for infection .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo .", "target_text": { "AP-1": "protein" } }, { "input_text": "Some of the most potent antiinflammatory and immunosuppressive agents are synthetic glucocorticoids .", "target_text": {} }, { "input_text": "However , major side effects severely limit their therapeutic use .", "target_text": {} }, { "input_text": "The development of improved glucocorticoid-based drugs will require the separation of beneficial from deleterious effects .", "target_text": {} }, { "input_text": "One possibility toward this goal is to try to dissociate two main activities of glucocorticoids , i.e. transactivation and transrepression .", "target_text": {} }, { "input_text": "Screening of a library of compounds using transactivation and AP-1 transrepression models in transiently transfected cells identified dissociated glucocorticoids , which exert strong AP-1 inhibition but little or no transactivation .", "target_text": { "AP-1": "protein" } }, { "input_text": "Importantly , despite high ligand binding affinity , the prototypic dissociated compound , RU24858 , acted as a weak agonist and did not efficiently antagonize dexamethasone-induced transcription in transfected cells .", "target_text": { "transfected cells": "cell_type" } }, { "input_text": "Similar results were obtained in hepatic HTC cells for the transactivation of the endogenous tyrosine amino transferase gene ( TAT ) , which encodes one of the enzymes involved in the glucocorticoid-dependent stimulation of neoglucogenesis .", "target_text": { "hepatic HTC cells": "cell_line", "endogenous tyrosine amino transferase gene": "DNA", "TAT": "DNA" } }, { "input_text": "To investigate whether dissociated glucocorticoids retained the antiinflammatory and immunosuppressive potential of classic glucocorticoids , several in vitro and in vivo models were used .", "target_text": {} }, { "input_text": "Indeed , secretion of the proinflammatory lymphokine interleukin-1beta was severely inhibited by dissociated glucocorticoids in human monocytic THP 1 cells .", "target_text": { "interleukin-1beta": "protein", "proinflammatory lymphokine interleukin-1beta": "protein", "human monocytic THP 1 cells": "cell_line" } }, { "input_text": "Moreover , in two in vivo models , these compounds exerted an antiinflammatory and immunosuppressive activity as potent as that of the classic glucocorticoid prednisolone .", "target_text": {} }, { "input_text": "These results may lead to an improvement of antiinflammatory and immunosuppressive therapies and provide a novel concept for drug discovery .", "target_text": {} }, { "input_text": "In vivo footprinting and mutational analysis of the proximal CD19 promoter reveal important roles for an SP1/Egr-1 binding site and a novel site termed the PyG box .", "target_text": { "proximal CD19 promoter": "DNA", "SP1/Egr-1 binding site": "DNA", "PyG box": "DNA" } }, { "input_text": "CD19 expression begins at the pro-B cell stage of B cell development .", "target_text": { "CD19": "protein" } }, { "input_text": "As such it serves as a good prototype for B cell-specific genes whose expression begins shortly after lineage commitment .", "target_text": { "B cell-specific genes": "DNA" } }, { "input_text": "To understand the molecular mechanisms controlling CD19 gene expression , we isolated and functionally characterized the CD19 promoter using in vivo footprinting , gel shift assays , and transfection studies .", "target_text": { "CD19": "protein", "CD19 promoter": "DNA" } }, { "input_text": "Reporter constructs spanning portions of the promoter identified a region between -85 and -200 that produced high levels of reporter gene activity in lymphoid cells .", "target_text": { "region between -85 and -200": "DNA", "lymphoid cells": "cell_type" } }, { "input_text": "In vivo footprinting identified protected regions over the known high affinity B cell lineage-specific activator protein ( BSAP ) site , the low affinity BSAP site , a SP1/Egr-1 site termed the CD19 GC box , and two novel sites named the AT box and PyG box .", "target_text": { "B cell lineage-specific activator protein": "protein", "B cell lineage-specific activator protein ( BSAP ) site": "DNA", "low affinity BSAP site": "DNA", "SP1/Egr-1 site": "DNA", "CD19 GC box": "DNA", "AT box": "DNA", "PyG box": "DNA" } }, { "input_text": "Phorbol ester treatment of a pre-B cell line up-regulated CD19 expression , induced Egr-1 , and enhanced the footprint over the GC box .", "target_text": { "pre-B cell line": "cell_line", "CD19": "protein", "Egr-1": "protein" } }, { "input_text": "Gel shift assays demonstrated SP1 and Egr-1 binding to the CD19 GC box , while unknown nuclear proteins bound the PyG and AT boxes .", "target_text": { "Egr-1": "protein", "CD19 GC box": "DNA" } }, { "input_text": "Mutations in the AT box or in the BSAP sites did not affect CD19 reporter construct activity , while a mutation of the GC box reduced it modestly , and a PyG box mutation reduced it dramatically .", "target_text": { "AT box": "DNA", "BSAP": "protein", "BSAP sites": "DNA", "CD19": "protein", "reporter construct": "DNA", "GC box": "DNA", "PyG box": "DNA" } }, { "input_text": "BSAP failed to trans-activate CD19 promoter constructs in B cells or non-B cells , suggesting that cis elements such as the PyG and GC boxes are also necessary for high level CD19 promoter expression .", "target_text": { "BSAP": "protein", "CD19": "protein", "CD19 promoter": "DNA", "CD19 promoter constructs": "DNA", "B cells": "cell_type", "non-B cells": "cell_type" } }, { "input_text": "EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes .", "target_text": { "EBF": "protein", "E47": "protein", "endogenous immunoglobulin surrogate light chain genes": "DNA" } }, { "input_text": "Early B cell factor ( EBF ) and E47 participate in the transcriptional control of early B lymphocyte differentiation .", "target_text": { "Early B cell factor": "protein", "EBF": "protein", "E47": "protein" } }, { "input_text": "With the aim of identifying genetic targets for these transcription factors , we stably transfected cDNAs encoding EBF or a covalent homodimer of E47 , individually or together , into immature hematopoietic Ba/F3 cells , which lack both factors .", "target_text": { "transfected cDNAs": "DNA", "EBF": "protein", "E47": "protein", "immature hematopoietic Ba/F3 cells": "cell_line" } }, { "input_text": "In combination , EBF and E47 induce efficient expression of the endogenous immunoglobulin surrogate light chain genes , lambda5 and VpreB , whereas other pre-B cell-specific genes remain silent .", "target_text": { "EBF": "protein", "E47": "protein", "endogenous immunoglobulin surrogate light chain genes": "DNA", "lambda5": "DNA", "VpreB": "DNA", "pre-B cell-specific genes": "DNA" } }, { "input_text": "Multiple functionally important EBF and E47 binding sites were identified in the lambda5 promoter/enhancer region , indicating that lambda5 is a direct genetic target for these transcription factors .", "target_text": { "lambda5": "DNA", "lambda5 promoter/enhancer region": "DNA", "transcription factors": "protein" } }, { "input_text": "Taken together , these data suggest that EBF and E47 synergize to activate expression of a subset of genes that define an early stage of the B cell lineage .", "target_text": { "EBF": "protein", "E47": "protein", "B cell lineage": "cell_type" } }, { "input_text": "Cytokines : shared receptors , distinct functions .", "target_text": { "Cytokines": "protein", "receptors": "protein" } }, { "input_text": "That the signal transduction pathways used by the cytokines IL-2 and IL-15 are identical would suggest that these cytokines have redundant roles in lymphoid development ; instead , IL-2 is the guardian of thymus-derived T-cell homeostasis , while interleukin-15 promotes extrathymic development of T and NK cells .", "target_text": { "cytokines": "protein", "IL-2": "protein", "IL-15": "protein", "interleukin-15": "protein" } }, { "input_text": "The IL-4 receptor alpha-chain cytoplasmic domain is sufficient for activation of JAK-1 and STAT6 and the induction of IL-4 -specific gene expression .", "target_text": { "IL-4": "protein", "IL-4 receptor alpha-chain": "protein", "IL-4 receptor alpha-chain cytoplasmic domain": "protein", "JAK-1": "protein", "STAT6": "protein" } }, { "input_text": "The common gamma-chain ( gamma(c) ) is a functional component of the IL-4R , yet cells lacking gamma(c) are able to respond to IL-4 .", "target_text": { "common gamma-chain": "protein", "gamma(c)": "protein", "IL-4R": "protein", "IL-4": "protein" } }, { "input_text": "This has led to the suggestion that a surrogate gamma'-chain , which can interact with the IL-4R alpha chain to mediate signaling , is expressed on cells lacking gamma(c) .", "target_text": { "surrogate gamma'-chain": "protein", "IL-4R alpha chain": "protein", "gamma(c)": "protein" } }, { "input_text": "An alternative possibility is that in the absence of gamma(c) , the IL-4R alpha chain is able to transduce signals by homodimerization .", "target_text": { "gamma(c)": "protein", "IL-4R alpha chain": "protein" } }, { "input_text": "To test this latter possibility , a chimeric receptor containing the extracellular domain of c-kit ( the stem cell factor ( SCF ) receptor ) and the cytoplasmic and transmembrane domains of the IL-4R alpha chain was generated .", "target_text": { "chimeric receptor": "protein", "extracellular domain": "protein", "c-kit": "protein", "stem cell factor ( SCF ) receptor": "protein", "IL-4R": "protein", "IL-4R alpha chain": "protein" } }, { "input_text": "Treatment of cells expressing the chimeric receptor kit/IL-4R alpha with SCF induces activation of the IL-4R alpha-associated kinase JAK-1 and the transcription factor STAT6 .", "target_text": { "chimeric receptor": "protein", "kit/IL-4R alpha": "protein", "SCF": "protein", "IL-4R": "protein", "IL-4R alpha-associated kinase": "protein", "JAK-1": "protein", "transcription factor": "protein", "STAT6": "protein" } }, { "input_text": "However , tyrosine phosphorylation of JAK-3 , which associates with gamma(c) , is not induced by SCF in these cells .", "target_text": { "JAK-3": "protein", "gamma(c)": "protein", "SCF": "protein" } }, { "input_text": "SCF -mediated ligation of kit/IL-4R alpha is sufficient to elicit IL-4 -specific gene expression , including up-regulation of CD23 and synthesis of germ-line epsilon transcripts .", "target_text": { "SCF": "protein", "kit/IL-4R alpha": "protein", "IL-4": "protein", "CD23": "protein", "germ-line epsilon transcripts": "RNA" } }, { "input_text": "In the T cell line CTLL2 , ligation of kit/IL-4R alpha induces cellular proliferation .", "target_text": { "T cell line CTLL2": "cell_line", "kit/IL-4R alpha": "protein" } }, { "input_text": "Finally , in JAK-1 -deficient HeLa cells , STAT6 activation by IL-4 is completely abolished .", "target_text": { "JAK-1": "protein", "JAK-1 -deficient HeLa cells": "cell_line", "STAT6": "protein", "IL-4": "protein" } }, { "input_text": "Together , these data demonstrate that the IL-4R alpha cytoplasmic domain is sufficient to activate JAK-1 and STAT6 and to induce expression of IL-4 target genes , thus identifying a mechanism by which IL-4 signaling can proceed in the absence of JAK-3 and gamma(c) .", "target_text": { "IL-4R alpha cytoplasmic domain": "protein", "JAK-1": "protein", "STAT6": "protein", "IL-4": "protein", "IL-4 target genes": "DNA", "JAK-3": "protein", "gamma(c)": "protein" } }, { "input_text": "Histamine modulates the expression of c-fos through cyclic AMP production via the H2 receptor in the human promonocytic cell line U937 .", "target_text": { "c-fos": "DNA", "H2 receptor": "protein", "human promonocytic cell line U937": "cell_line" } }, { "input_text": "We examined the effects of histamine and its agonists on the expression of the c-fos and c-myc proto-oncogenes at the transcriptional and translational levels in the human promonocytic U937 cell line .", "target_text": { "human promonocytic U937 cell line": "cell_line" } }, { "input_text": "Histamine transiently increased cAMP and c-fos expression through H2 receptors .", "target_text": { "c-fos": "DNA", "H2 receptors": "protein" } }, { "input_text": "Dibutyryl cAMP also increased c-fos mRNA and protein , and levels remained elevated even after 12 hr of treatment .", "target_text": { "c-fos": "DNA", "c-fos mRNA": "RNA", "protein": "protein" } }, { "input_text": "Dose-dependence studies using histamine and dimaprit showed that the EC50 values for cAMP production and c-fos increase were similar , suggesting that cAMP might be involved in c-fos induction via H2 receptors .", "target_text": { "c-fos": "DNA", "H2 receptors": "protein" } }, { "input_text": "Furthermore , studies carried out using H7 , a protein kinase A /protein kinase C inhibitor , blocked c-fos induction , whereas no effect was observed with bisindolylmaleimide , a specific protein kinase C inhibitor .", "target_text": { "H7": "protein", "protein kinase A": "protein", "/protein kinase C": "protein", "protein kinase A /protein kinase C inhibitor": "protein", "c-fos": "DNA", "protein kinase C": "protein" } }, { "input_text": "No modification of c-myc expression could be detected on treatment with histamine or its analogues .", "target_text": { "c-myc": "DNA" } }, { "input_text": "Nevertheless , dibutyryl cAMP induced a down-regulation of the levels of this proto-oncogene .", "target_text": { "proto-oncogene": "DNA" } }, { "input_text": "In addition , dibutyryl cAMP inhibited cell growth in a dose-dependent manner , whereas histamine failed to affect proliferation and differentiation of U937 cells .", "target_text": { "U937 cells": "cell_line" } }, { "input_text": "Cells pretreated with dimaprit showed a decrease in the cAMP response to subsequent addition of H2 agonists , whereas the cAMP response to prostaglandin E2 remained unaltered .", "target_text": {} }, { "input_text": "This homologous mechanism of H2 receptor desensitization was time dependent .", "target_text": { "H2 receptor": "protein" } }, { "input_text": "These results indicate that histamine activates several mechanisms involved in the induction of differentiation , such as cAMP and c-fos production , but fails to promote differentiation of U937 cells , apparently due to the rapid desensitization of H2 receptors .", "target_text": { "c-fos": "DNA", "U937 cells": "cell_line", "H2 receptors": "protein" } }, { "input_text": "Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets .", "target_text": { "cytokine": "protein", "leukocytes": "cell_type", "thrombin-stimulated platelets": "cell_type" } }, { "input_text": "BACKGROUND : Activated platelets tether and activate myeloid leukocytes .", "target_text": { "Activated platelets": "cell_type", "leukocytes": "cell_type", "myeloid leukocytes": "cell_type" } }, { "input_text": "To investigate the potential relevance of this mechanism in acute myocardial infarction ( AMI ) , we examined cytokine induction by leukocyte-platelet adhesion and the occurrence of leukocyte-platelet conjugates in patients with AMI .", "target_text": { "cytokine": "protein" } }, { "input_text": "METHODS AND RESULTS : We obtained peripheral venous blood samples in 20 patients with AMI before and daily for 5 days after direct percutaneous transluminal coronary angioplasty ( PTCA ) and in 20 patients undergoing elective PTCA .", "target_text": {} }, { "input_text": "Throughout the study period , CD41 immunofluorescence of leukocytes ( flow cytometry ) revealed increased leukocyte-platelet adhesion in patients with AMI compared with control patients ( mean +/- SE of fluorescence [ channels ] before PTCA : 77 +/- 16 versus 35 +/- 9 ; P = .003 ) .", "target_text": { "leukocytes": "cell_type" } }, { "input_text": "In vitro , thrombin-stimulated fixed platelets bound to neutrophils and monocytes .", "target_text": { "thrombin-stimulated fixed platelets": "cell_type", "neutrophils": "cell_type", "monocytes": "cell_type" } }, { "input_text": "Within 2 hours , this resulted in increased mRNA for interleukin ( IL ) , 1 beta , IL-8 , and monocyte chemoattractant protein ( MCP ) -1 in unfractionated leukocytes .", "target_text": { "interleukin ( IL ) , 1 beta": "protein", "IL-8": "protein", "monocyte chemoattractant protein ( MCP ) -1": "protein", "leukocytes": "cell_type" } }, { "input_text": "After 4 hours , IL-1 beta and IL-8 concentration of the cell-free supernatant had increased by 268 +/- 36 % and 210 +/- 7 % , respectively , and cellular MCP-1 content had increased by 170 +/- 8 % .", "target_text": { "IL-1 beta": "protein", "IL-8": "protein", "MCP-1": "protein" } }, { "input_text": "Addition of activated platelets to adherent monocytes had a similar effect and was associated with nuclear factor-kappa B activation .", "target_text": { "activated platelets": "cell_type", "monocytes": "cell_type", "nuclear factor-kappa B": "protein" } }, { "input_text": "Inhibition of binding by anti-P selectin antibodies reduced the effect of activated platelets on cytokine production .", "target_text": { "anti-P selectin antibodies": "protein", "activated platelets": "cell_type", "cytokine": "protein" } }, { "input_text": "CONCLUSIONS : In patients with AMI , leukocyte-platelet adhesion is increased .", "target_text": {} }, { "input_text": "Binding of activated platelets induces IL-1 beta , IL-8 , and MCP-1 in leukocytes .", "target_text": { "activated platelets": "cell_type", "IL-1 beta": "protein", "IL-8": "protein", "MCP-1": "protein", "leukocytes": "cell_type" } }, { "input_text": "Our findings suggest that leukocyte-platelet adhesion contributes to the regulation of inflammatory responses in AMI .", "target_text": {} }, { "input_text": "Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus -induced cytotoxic T cell response .", "target_text": { "early lytic cycle proteins": "protein" } }, { "input_text": "Epstein-Barr virus ( EBV ) , a human gamma-herpesvirus , can establish both nonproductive ( latent ) and productive ( lytic ) infections .", "target_text": {} }, { "input_text": "Although the CD8+ cytotoxic T lymphocyte ( CTL ) response to latently infected cells is well characterized , very little is known about T cell controls over lytic infection ; this imbalance in our understanding belies the importance of virus-replicative lesions in several aspects of EBV disease pathogenesis .", "target_text": { "latently infected cells": "cell_type" } }, { "input_text": "The present work shows that the primary CD8+ CTL response to EBV in infectious mononucleosis patients contains multiple lytic antigen-specific reactivities at levels at least as high as those seen against latent antigens ; similar reactivities are also detectable in CTL memory .", "target_text": { "latent antigens": "protein" } }, { "input_text": "Clonal analysis revealed individual responses to the two immediate early proteins BZLF1 and BRLF1 , and to three ( BMLF1 , BMRF1 , and BALF2 ) of the six early proteins tested .", "target_text": { "immediate early proteins": "protein", "BZLF1": "protein", "BRLF1": "protein", "BMLF1": "protein", "BMRF1": "protein", "BALF2": "protein", "early proteins": "protein" } }, { "input_text": "In several cases , the peptide epitope and HLA-restricting determinant recognized by these CTLs has been defined , one unusual feature being the number of responses restricted through HLA-C alleles .", "target_text": { "CTLs": "cell_type", "HLA-C alleles": "DNA" } }, { "input_text": "The work strongly suggests that EBV -replicative lesions are subject to direct CTL control in vivo and that immediate early and early proteins are frequently the immunodominant targets .", "target_text": {} }, { "input_text": "This contrasts with findings in alpha- and beta- herpesvirus systems ( herpes simplex , cytomegalovirus ) where viral interference with the antigen-processing pathway during lytic infection renders immediate early and early proteins much less immunogenic .", "target_text": {} }, { "input_text": "The unique capacity of gamma-herpesvirus to amplify the viral load in vivo through a latent growth-transforming infection may have rendered these agents less dependent upon viral replication as a means of successfully colonizing their hosts .", "target_text": {} }, { "input_text": "Triggering of HLA-DR antigens differentially modulates tumor necrosis factor alpha release by B cells at distinct stage of maturation .", "target_text": { "HLA-DR antigens": "protein", "tumor necrosis factor alpha": "protein", "B cells": "cell_type" } }, { "input_text": "Triggering of HLA class II antigens by the anti-HLA-DR monoclonal antibody ( mAb ) L243 significantly ( P < 0.05 ) and differentially enhanced the release of tumor necrosis factor alpha ( TNF-alpha ) by the non-Hodgkin 's lymphoma cells Ri-I , Ci-I , and Sc-I , which are at a distinct stage of B-cell differentiation , and by the more mature Burkitt lymphoma cell Raji ; in contrast , it did not induce TNF-alpha release by the pre-B leukemia cells Nalm-6 and BV173 .", "target_text": { "HLA class II antigens": "protein", "anti-HLA-DR monoclonal antibody": "protein", "mAb": "protein", "anti-HLA-DR monoclonal antibody ( mAb ) L243": "protein", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein", "non-Hodgkin 's lymphoma cells": "cell_type", "Ri-I": "cell_line", "Ci-I": "cell_line", "Sc-I": "cell_line", "Burkitt lymphoma cell Raji": "cell_line", "pre-B leukemia cells": "cell_type", "Nalm-6": "cell_line", "BV173": "cell_line" } }, { "input_text": "TNF-alpha release peaked at 24 h and decreased thereafter , and it was dose dependent and preceded by an increase of TNF-alpha mRNA detectable after 3 h of stimulation with mAb L243 .", "target_text": { "TNF-alpha": "protein", "TNF-alpha mRNA": "RNA", "mAb L243": "protein" } }, { "input_text": "Secreted TNF-alpha mediated the enhancement of nuclear factor kappa B ( NF-kappa B ) and activator protein-1 ( AP-1 ) binding activity ; in fact , the triggering of HLA-DR antigens in the presence of antihuman TNF-alpha -neutralizing antibodies did not upregulate NF-kappa B and AP-1 .", "target_text": { "TNF-alpha": "protein", "nuclear factor kappa B": "protein", "NF-kappa B": "protein", "AP-1": "protein", "HLA-DR antigens": "protein", "antihuman TNF-alpha -neutralizing antibodies": "protein" } }, { "input_text": "In contrast , released TNF-alpha was not responsible for the homotypic aggregation of Ri-I , Ci-I , Sc-I , and Raji cells induced by mAb L243 , and it did not affect the proliferation of B cells investigated .", "target_text": { "TNF-alpha": "protein", "Ri-I": "cell_line", "Ci-I": "cell_line", "Sc-I": "cell_line", "Raji cells": "cell_line", "mAb L243": "protein", "B cells": "cell_type" } }, { "input_text": "Altogether , our data demonstrate that : ( a ) the ability of B cells to release TNF-alpha after triggering of HLA-DR antigens depends on their stage of differentiation ; ( b ) levels of released TNF-alpha seem to correlate with the stage of B-cell maturation but do not correlate with the amounts of cell surface HLA-DR antigens ; ( c ) secreted TNF-alpha regulates the levels of expression of NF-kappa B and AP-1 by an autocrine loop ; and ( d ) intracellular signals mediating TNF-alpha release by B cells are distinct from those regulating homotypic aggregation and proliferation .", "target_text": { "B cells": "cell_type", "TNF-alpha": "protein", "HLA-DR antigens": "protein", "cell surface HLA-DR antigens": "protein", "NF-kappa B": "protein", "AP-1": "protein" } }, { "input_text": "Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene .", "target_text": { "Transcription factor GATA-3": "protein", "interleukin-5 gene": "DNA" } }, { "input_text": "Interleukin-5 ( IL-5 ) , which is produced by CD4(+) T helper 2 ( Th2 ) cells , but not by Th1 cells , plays a key role in the development of eosinophilia in asthma .", "target_text": { "Interleukin-5": "protein", "IL-5": "protein", "CD4(+) T helper 2 ( Th2 ) cells": "cell_type", "Th1 cells": "cell_type" } }, { "input_text": "Despite increasing evidence that the outcome of many diseases is determined by the ratio of the two subsets of CD4(+) T helper cells , Th1 and Th2 , the molecular basis for Th1- and Th2- specific gene expression remains to be elucidated .", "target_text": { "CD4(+) T helper cells": "cell_type", "Th1": "cell_type", "Th2": "cell_type" } }, { "input_text": "We previously established a critical role for the transcription factor GATA-3 in IL-5 promoter activation in EL-4 cells , which express both Th1- and Th2- type cytokines .", "target_text": { "transcription factor": "protein", "GATA-3": "protein", "IL-5": "protein", "IL-5 promoter": "DNA", "EL-4 cells": "cell_line" } }, { "input_text": "Our studies reported here demonstrate that GATA-3 is critical for expression of the IL-5 gene in bona fide Th2 cells .", "target_text": { "GATA-3": "protein", "IL-5": "protein", "bona fide Th2 cells": "cell_type" } }, { "input_text": "Whereas mutations in the GATA-3 site abolished antigen- or cAMP- stimulated IL-5 promoter activation in Th2 cells , ectopic expression of GATA-3 in Th1 cells or in a non-lymphoid , non- IL-5 -producing cell line activated the IL-5 promoter .", "target_text": { "GATA-3": "protein", "Th1 cells": "cell_type", "IL-5": "protein", "non-lymphoid , non- IL-5 -producing cell line": "cell_line", "IL-5 promoter": "DNA" } }, { "input_text": "During the differentiation of naive CD4(+) T cells isolated from T cell receptor transgenic mice , GATA-3 gene expression was up-regulated in developing Th2 cells , but was down-regulated in Th1 cells , and antigen- or cAMP-activated Th2 cells ( but not Th1 cells ) expressed the GATA-3 protein .", "target_text": { "naive CD4(+) T cells": "cell_type", "GATA-3": "protein", "Th2 cells": "cell_type", "Th1 cells": "cell_type", "antigen- or cAMP-activated Th2 cells": "cell_type", "GATA-3 protein": "protein" } }, { "input_text": "Thus , GATA-3 may play an important role in the balance between Th1 and Th2 subsets in immune responses .", "target_text": { "GATA-3": "protein", "Th1": "cell_type", "Th2 subsets": "cell_type" } }, { "input_text": "Inhibition of GATA-3 activity has therapeutic potential in the treatment of asthma and other hypereosinophilic diseases .", "target_text": { "GATA-3": "protein" } }, { "input_text": "A shortened life span of EKLF-/- adult erythrocytes , due to a deficiency of beta-globin chains , is ameliorated by human gamma-globin chains .", "target_text": { "EKLF-/- adult erythrocytes": "cell_type", "beta-globin chains": "protein", "human gamma-globin chains": "protein" } }, { "input_text": "Using homologous recombination , both EKLF alleles in murine embryonic stem ( ES ) cells were inactivated .", "target_text": { "EKLF alleles": "DNA", "murine embryonic stem ( ES ) cells": "cell_line" } }, { "input_text": "These EKLF-/- ES cells were capable of undergoing in vitro differentiation to form definitive erythroid colonies that were similar in size and number to those formed by wild-type ES cells .", "target_text": { "EKLF-/- ES cells": "cell_line", "wild-type ES cells": "cell_type" } }, { "input_text": "However , the EKLF-/- colonies were poorly hemoglobinized and enucleated erythrocytes in these colonies contained numerous Heinz bodies .", "target_text": { "EKLF-/- colonies": "cell_line", "enucleated erythrocytes": "cell_type" } }, { "input_text": "Reverse transcriptase-polymerase chain reaction ( RT-PCR ) analyses revealed that adult and embryonic globin genes were appropriately regulated , with the exception of beta h1-globin , which continued to be expressed at a very low level .", "target_text": { "embryonic globin genes": "DNA", "beta h1-globin": "protein" } }, { "input_text": "The ratio of adult beta-globin/alpha-globin mRNA in the mutant ES cells was 1/15 of that in wild-type ES cells .", "target_text": { "adult beta-globin/alpha-globin mRNA": "RNA", "mutant ES cells": "cell_line", "wild-type ES cells": "cell_type" } }, { "input_text": "When the EKLF-/- cells were injected into blastocysts , they did not contribute at a detectable level to the mature erythrocyte compartment of the chimeric animals , based on analysis of glucose phosphate isomerase-1 ( GPI-1 ) isozymes and hemoglobins that distinguish ES cell-derived erythrocytes from host blastocyst-derived erythrocytes .", "target_text": { "EKLF-/- cells": "cell_line", "glucose phosphate isomerase-1 ( GPI-1 ) isozymes": "protein", "ES cell-derived erythrocytes": "cell_type", "blastocyst-derived erythrocytes": "cell_type" } }, { "input_text": "In contrast , semiquantitative RT-PCR analysis of RNA from reticulocytes of the same chimeric animals suggested that the ES cell-derived reticulocytes were present at a level of 6 % to 8 % .", "target_text": { "reticulocytes": "cell_type", "ES cell-derived reticulocytes": "cell_type" } }, { "input_text": "This indicated that the EKLF-/- erythrocytes in adult animals must be short-lived , apparently due to the imbalance of beta- versus alpha- globin chains , leading to the precipitation of excess alpha-globin chains to form Heinz bodies .", "target_text": { "EKLF-/- erythrocytes": "cell_line", "alpha-globin chains": "protein" } }, { "input_text": "Consistent with this hypothesis , the short life span was ameliorated by introduction into the EKLF-/- ES cells of a human LCR/gamma-globin gene , as evidenced by the presence of ES cell-derived reticulocytes as well as mature erythrocytes in the blood of the chimeric animals .", "target_text": { "EKLF-/- ES cells": "cell_line", "human LCR/gamma-globin gene": "DNA", "reticulocytes": "cell_type", "ES cell-derived reticulocytes": "cell_type", "mature erythrocytes": "cell_type" } }, { "input_text": "RP1 , a new member of the adenomatous polyposis coli-binding EB1-like gene family , is differentially expressed in activated T cells .", "target_text": { "RP1": "DNA", "adenomatous polyposis coli-binding EB1-like gene family": "DNA", "activated T cells": "cell_type" } }, { "input_text": "Cross-linking of the CD3 and CD28 molecules on T lymphocytes represents one of the most effective signals for T lymphocyte activation and triggering of their cytotoxic effector function .", "target_text": { "T lymphocytes": "cell_type", "T lymphocyte": "cell_type" } }, { "input_text": "To identify genes that are expressed in T cells after stimulation , mRNA from T lymphocytes that had been activated by the simultaneous stimulation of the CD3 and CD28 trigger molecules was transcribed for a differential mRNA display analysis into cDNA and was compared with cDNA from CD28 - or CD3 -activated or resting lymphocytes .", "target_text": { "T cells": "cell_type", "T lymphocytes": "cell_type", "CD3": "protein", "CD28": "protein", "lymphocytes": "cell_type" } }, { "input_text": "Differential expression was confirmed subsequently by Northern blot analysis .", "target_text": {} }, { "input_text": "One of the cDNA fragments expressed specifically in CD3 - and CD28 -activated T cells was designated RP1 .", "target_text": { "cDNA fragments": "DNA", "CD3": "protein", "CD28": "protein", "T cells": "cell_type", "-activated T cells": "cell_type", "RP1": "DNA" } }, { "input_text": "The predictive protein-coding region of RP1 had a significant homology to members of the recently found adenomatous polyposis coli ( APC ) protein -binding EB1 gene family , which codes for yet unknown protein ( s ) .", "target_text": { "predictive protein-coding region": "DNA", "RP1": "DNA", "adenomatous polyposis coli ( APC ) protein": "protein", "adenomatous polyposis coli ( APC ) protein -binding EB1 gene family": "DNA" } }, { "input_text": "Bacterially expressed RP1 protein revealed specific binding to wild-type but not to mutated APC protein .", "target_text": { "RP1": "DNA", "RP1 protein": "protein", "wild-type": "protein", "mutated APC protein": "protein" } }, { "input_text": "The rapid up-regulation of RP1 mRNA in properly activated T cells suggests that this gene might belong to the immediate/early gene family , which controls the signal transduction cascade downstream of the TCR .", "target_text": { "RP1": "DNA", "RP1 mRNA": "RNA", "activated T cells": "cell_type", "immediate/early gene family": "DNA", "TCR": "protein" } }, { "input_text": "As the expression level of the RP1 gene in activated T cells and a spectrum of tumor-derived cell lines correlates with the proliferative status of the cells , members of the EB1-like gene family may not only be involved in the tumorigenesis of colorectal cancers but may also play a role in the proliferative control of normal cells .", "target_text": { "RP1": "DNA", "RP1 gene": "DNA", "activated T cells": "cell_type", "tumor-derived cell lines": "cell_line", "EB1-like gene family": "DNA", "normal cells": "cell_type" } }, { "input_text": "Cyclosporin A interferes with the inducible degradation of NF-kappa B inhibitors , but not with the processing of p105/ NF-kappa B1 in T cells .", "target_text": { "NF-kappa B": "protein", "NF-kappa B1": "protein", "T cells": "cell_type" } }, { "input_text": "The transcription factor NF-kappa B controls the induction of numerous cytokine promoters during the activation of T lymphocytes .", "target_text": { "transcription factor": "protein", "NF-kappa B": "protein", "cytokine promoters": "DNA", "T lymphocytes": "cell_type" } }, { "input_text": "Inhibition of T cell activation by the immunosuppressants cyclosporin A ( CsA ) and FK506 exerts a suppressive effect on the induction of these NF-kappa B -controlled cytokine promoters .", "target_text": { "NF-kappa B": "protein", "cytokine promoters": "DNA", "NF-kappa B -controlled cytokine promoters": "DNA" } }, { "input_text": "We show for human Jurkat T leukemia cells , as well as human and mouse primary T lymphocytes , that this inhibitory effect is accompanied by an impaired nuclear translocation of the Rel proteins c-Rel , RelA/p65 and NF-kappa B1/p50 , whereas the nuclear appearance of RelB remains unaffected .", "target_text": { "human Jurkat T leukemia cells": "cell_line", "Rel proteins": "protein", "c-Rel": "protein", "RelA/p65": "protein", "NF-kappa B1/p50": "protein", "RelB": "protein" } }, { "input_text": "CsA does not interfere with the synthesis of Rel proteins , but prevents the inducible degradation of cytosolic NF-kappa B inhibitors I kappa B alpha and I kappa B beta upon T cell activation .", "target_text": { "Rel proteins": "protein", "NF-kappa B": "protein", "cytosolic NF-kappa B inhibitors": "protein", "I kappa B alpha": "protein", "I kappa B beta": "protein" } }, { "input_text": "CsA neither inhibits the processing of the NF-kappa B1 precursor p105 to p50 , nor does it \" stabilize \" the C-terminal portion of p105 , I kappa B gamma , which is degraded during p105 processing to mature p50 .", "target_text": { "NF-kappa B1 precursor": "protein", "p105": "protein", "p50": "protein", "I kappa B gamma": "protein", "mature p50": "protein" } }, { "input_text": "These results indicate that CsA interferes with a specific event in the signal-induced degradation of I kappa B alpha and I kappa B beta , but does not affect the processing of NF-kappa B1/ p105 to p50 .", "target_text": { "I kappa B alpha": "protein", "I kappa B beta": "protein", "p105": "protein", "NF-kappa B1/ p105": "protein", "p50": "protein" } }, { "input_text": "Activation of nuclear factor-kappa B by beta-amyloid peptides and interferon-gamma in murine microglia .", "target_text": { "nuclear factor-kappa B": "protein", "interferon-gamma": "protein" } }, { "input_text": "An increasing body of evidence suggests that amyloid-beta ( A beta ) peptides and microglia are crucially involved in the pathogenesis of Alzheimer 's disease .", "target_text": { "microglia": "cell_type" } }, { "input_text": "In an effort to further elucidate the biological effects of A beta towards microglia , we investigated the ability of A beta peptides to activate nuclear factor ( NF ) -kappa B in the N9 murine microglial cell line .", "target_text": { "microglia": "cell_type", "nuclear factor ( NF ) -kappa B": "protein", "N9 murine microglial cell line": "cell_line" } }, { "input_text": "Co-stimulation of microglia with suboptimal concentrations of A beta ( 25-35 ) and 100 U/ml IFN gamma resulted in the detection of a specific NF-kappa B DNA-binding activity in nuclear extracts , as determined in gel mobility shift assays .", "target_text": { "microglia": "cell_type", "IFN gamma": "protein", "NF-kappa B": "protein" } }, { "input_text": "This response required at least 120 min to be evident and supershift experiments revealed that the NF-kappa B complex contains both RelA and p50 .", "target_text": { "NF-kappa B": "protein", "NF-kappa B complex": "protein", "RelA": "protein", "p50": "protein" } }, { "input_text": "Accordingly , immunoblot experiments showed that amongst NF-kappa B /Rel proteins , RelA and p50 are mobilized to the nucleus following microglial cell stimulation with A beta ( 25-35 ) plus IFN gamma .", "target_text": { "NF-kappa B": "protein", "/Rel proteins": "protein", "RelA": "protein", "p50": "protein", "IFN gamma": "protein" } }, { "input_text": "Higher concentrations of A beta ( 25-35 ) were effective by themselves in inducing NF-kappa B activation , both in the N9 microglial cell line and in rat primary microglia , as well as in human monocytes .", "target_text": { "NF-kappa B": "protein", "N9 microglial cell line": "cell_line", "microglia": "cell_type", "rat primary microglia": "cell_line", "human monocytes": "cell_type" } }, { "input_text": "For purposes of comparison , microglia were also stimulated with bacterial LPS , a known NF-kappa B inducer .", "target_text": { "microglia": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "As expected , LPS strongly induced the formation of two NF-kappa B DNA-binding activities , one of which was identified as RelA /p50 .", "target_text": { "NF-kappa B": "protein", "RelA": "protein", "/p50": "protein", "RelA /p50": "protein" } }, { "input_text": "The LPS response was also more rapid , as it was already evident by 40 min and remained sustained for up to 3 h .", "target_text": {} }, { "input_text": "Collectively , these findings indicate that NF-kappa B activation might constitute one of the mechanisms underlying the inducible expression of kappa B-dependent genes in microglia stimulated by A beta peptides and IFN gamma , or by LPS .", "target_text": { "NF-kappa B": "protein", "kappa B-dependent genes": "DNA", "microglia": "cell_type", "IFN gamma": "protein" } }, { "input_text": "Glucocorticoid -mediated repression of cytokine gene transcription in human arteritis-SCID chimeras .", "target_text": { "cytokine gene": "DNA", "arteritis-SCID chimeras": "protein" } }, { "input_text": "Giant cell arteritis ( GCA ) is a vasculitic syndrome that preferentially affects medium and large -sized arteries .", "target_text": {} }, { "input_text": "Glucocorticoid therapy resolves clinical symptoms within hours to days , but therapy has to be continued over several years to prevent disease relapses .", "target_text": {} }, { "input_text": "It is not known whether and how glucocorticoids affect the function of the inflammatory infiltrate or why the disease persists subclinically despite chronic treatment .", "target_text": {} }, { "input_text": "GCA is self-sustained in temporal arteries engrafted into SCID mice , providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo .", "target_text": {} }, { "input_text": "Administration of dexamethasone to temporal artery-SCID chimeras for 1 wk induced a partial suppression of T cell and macrophage function as indicated by the reduced tissue concentrations of IL-2 , IL-1beta , and IL-6 mRNA , and by the diminished expression of inducible NO synthase .", "target_text": { "temporal artery-SCID chimeras": "cell_line", "NO synthase": "protein" } }, { "input_text": "In contrast , synthesis of IFN-gamma mRNA was only slightly decreased , and expression of TGF-beta1 was unaffected .", "target_text": { "IFN-gamma mRNA": "RNA", "TGF-beta1": "protein" } }, { "input_text": "These findings correlated with activation of the IkappaBalpha gene and blockade of the nuclear translocation of NFkappaB in the xenotransplanted tissue .", "target_text": { "IkappaBalpha gene": "DNA", "NFkappaB": "protein" } }, { "input_text": "Dose-response experiments suggested that steroid doses currently used in clinical medicine are suboptimal in repressing NFkappaB -mediated cytokine production in the inflammatory lesions .", "target_text": { "NFkappaB": "protein", "cytokine": "protein" } }, { "input_text": "Chronic steroid therapy was able to deplete the T cell products IL-2 and IFN-gamma , whereas the activation of tissue-infiltrating macrophages was only partially affected .", "target_text": { "T cell products": "protein", "IL-2": "protein", "IFN-gamma": "protein", "tissue-infiltrating macrophages": "cell_type" } }, { "input_text": "IL-1beta transcription was abrogated ; in contrast , TGF-beta1 mRNA synthesis was steroid resistant .", "target_text": { "IL-1beta": "protein", "TGF-beta1": "protein", "TGF-beta1 mRNA": "RNA" } }, { "input_text": "The persistence of TGF-beta1-transcribing macrophages , despite paralysis of T cell function , may provide an explanation for the chronicity of the disease , and may identify a novel therapeutic target in this inflammatory vasculopathy .", "target_text": { "TGF-beta1-transcribing macrophages": "cell_type" } }, { "input_text": "Defective survival and activation of thymocytes in transgenic mice expressing a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV .", "target_text": { "thymocytes": "cell_type", "catalytically inactive form": "protein", "Ca2+/calmodulin-dependent protein kinase IV": "protein" } }, { "input_text": "We have generated transgenic mice that express a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV ( CaMKIV ) specifically in thymic T cells .", "target_text": { "catalytically inactive form": "protein", "Ca2+/calmodulin-dependent protein kinase IV": "protein", "CaMKIV": "protein", "thymic T cells": "cell_type" } }, { "input_text": "The presence of this protein results in a markedly reduced thymic cellularity , although the distribution of the remaining cells is normal based on evaluation of the CD4 and CD8 cell surface antigens that are used to gauge T cell development .", "target_text": { "CD4": "protein", "CD8": "protein", "cell surface antigens": "protein" } }, { "input_text": "Isolated thymic T cells from the transgenic mice also show a dramatically decreased survival rate when evaluated in culture under conditions that do not favor activation .", "target_text": { "thymic T cells": "cell_type" } }, { "input_text": "When challenged with an activating stimulus such as alpha- CD3 or a combination of phorbol ester plus ionophore , the cells are severely compromised in their ability to produce the cytokine interleukin-2 ( IL-2 ) .", "target_text": { "CD3": "protein", "alpha- CD3": "protein", "cytokine": "protein", "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "Reduction of IL-2 production is secondary to the inability to phosphorylate the cAMP response element binding protein , CREB , and induce expression of the immediate early genes such as Fos B that are required to transactivate the IL-2 promoter .", "target_text": { "IL-2": "protein", "cAMP response element binding protein": "protein", "CREB": "protein", "immediate early genes": "DNA", "Fos B": "DNA", "IL-2 promoter": "DNA" } }, { "input_text": "Because transgene expression was regulated by the proximal promoter of the murine lck gene and this promoter is inactivated in T cells that exit the thymus , the mutant hCaMKIV is not present in peripheral T cells .", "target_text": { "proximal promoter": "DNA", "murine lck gene": "DNA", "T cells": "cell_type", "mutant hCaMKIV": "protein", "peripheral T cells": "cell_type" } }, { "input_text": "Consequently , T lymphocytes present in the spleen can be activated normally in response to either stimulus mentioned above , demonstrating that the effects of the inactive CaMKIV on activation are reversible .", "target_text": { "T lymphocytes": "cell_type", "inactive CaMKIV": "protein" } }, { "input_text": "Our results suggest that CaMKIV may represent a physiologically relevant CREB kinase in T cells and that the enzyme is also required to ensure normal expansion of T cells in the thymus .", "target_text": { "CaMKIV": "protein", "CREB": "protein", "CREB kinase": "protein", "T cells": "cell_type" } }, { "input_text": "Whereas the pathway responsible for this latter role is yet to be elucidated , it is unlikely to include CREB phosphorylation .", "target_text": { "CREB": "protein" } }, { "input_text": "A new mouse gene , SRG3 , related to the SWI3 of Saccharomyces cerevisiae , is required for apoptosis induced by glucocorticoids in a thymoma cell line .", "target_text": { "mouse gene": "DNA", "SRG3": "DNA", "SWI3": "DNA", "thymoma cell line": "cell_line" } }, { "input_text": "We isolated a new mouse gene that is highly expressed in thymocytes , testis , and brain .", "target_text": { "mouse gene": "DNA", "thymocytes": "cell_type" } }, { "input_text": "This gene , SRG3 , showed a significant sequence homology to SWI3 , a yeast transcriptional activator , and its human homolog BAF155 .", "target_text": { "SRG3": "DNA", "SWI3": "DNA", "yeast transcriptional activator": "DNA", "BAF155": "DNA", "human homolog BAF155": "DNA" } }, { "input_text": "SRG3 encodes 1,100 amino acids and has 33-47 % identity with SWI3 protein over three regions .", "target_text": { "SRG3": "DNA", "SWI3": "DNA", "SWI3 protein": "protein" } }, { "input_text": "The SRG3 protein contains an acidic NH2 terminus , a myb-like DNA binding domain , a leucine-zipper motif , and a proline- and glutamine-rich region at its COOH terminus .", "target_text": { "SRG3": "DNA", "SRG3 protein": "protein", "acidic NH2 terminus": "protein", "myb-like DNA binding domain": "protein", "leucine-zipper motif": "protein", "proline- and glutamine-rich region": "protein", "COOH terminus": "protein" } }, { "input_text": "Rabbit antiserum raised against a COOH-terminal polypeptide of the SRG3 recognized a protein with an apparent molecular mass of 155 kD .", "target_text": { "SRG3": "DNA" } }, { "input_text": "The serum also detected a 170-kD protein that seems to be a mouse homologue of human BAF170 .", "target_text": { "170-kD protein": "protein", "human BAF170": "protein" } }, { "input_text": "Immunoprecipitation of cell extract with the antiserum against the mouse SRG3 also brought down a 195-kD protein that could be recognized by an antiserum raised against human SWI2 protein .", "target_text": { "SRG3": "DNA", "mouse SRG3": "protein", "195-kD protein": "protein", "human SWI2 protein": "protein" } }, { "input_text": "The results suggest that the SRG3 protein associates with a mouse SWI2 .", "target_text": { "SRG3": "DNA", "SRG3 protein": "protein", "mouse SWI2": "protein" } }, { "input_text": "The SRG3 protein is expressed about three times higher in thymocytes than in peripheral lymphocytes .", "target_text": { "SRG3": "DNA", "SRG3 protein": "protein", "thymocytes": "cell_type", "peripheral lymphocytes": "cell_type" } }, { "input_text": "The expression of anti-sense RNA to SRG3 mRNA in a thymoma cell line , S49.1 , reduced the expression level of the SRG3 protein , and decreased the apoptotic cell death induced by glucocorticoids .", "target_text": { "anti-sense RNA": "protein", "SRG3": "DNA", "SRG3 mRNA": "RNA", "thymoma cell line": "cell_line", "S49.1": "cell_line", "SRG3 protein": "protein" } }, { "input_text": "These results suggest that the SRG3 protein is involved in the glucocorticoid-induced apoptosis in the thymoma cell line .", "target_text": { "SRG3": "DNA", "SRG3 protein": "protein", "thymoma cell line": "cell_line" } }, { "input_text": "This implicates that the SRG3 may play an important regulatory role during T cell development in thymus .", "target_text": { "SRG3": "DNA" } }, { "input_text": "Transcriptional induction of collagenase-1 in differentiated monocyte-like ( U937 ) cells is regulated by AP-1 and an upstream C/EBP-beta site .", "target_text": { "collagenase-1": "protein", "differentiated monocyte-like ( U937 ) cells": "cell_line", "AP-1": "protein", "upstream C/EBP-beta site": "DNA" } }, { "input_text": "In this report , we demonstrate that the AP-1 site and a distal promoter element regulate transcriptional induction of collagenase-1 during monocytic differentiation .", "target_text": { "AP-1": "protein", "distal promoter element": "DNA", "collagenase-1": "protein" } }, { "input_text": "Chloramphenicol acetyltransferase expression constructs containing regions of the human collagenase-1 promoter were stably or transiently transfected into U937 cells , and reporter activity was assessed at various times after the onset of phorbol 12-myristate 13-acetate ( PMA ) -mediated differentiation .", "target_text": { "Chloramphenicol acetyltransferase": "protein", "Chloramphenicol acetyltransferase expression constructs": "DNA", "collagenase-1": "protein", "collagenase-1 promoter": "DNA", "human collagenase-1 promoter": "DNA", "U937 cells": "cell_line" } }, { "input_text": "Rapid and strong induction of promoter activity was lost in constructs with a mutant AP-1 element ; however , at 16-96 h post-PMA , the mutant collagenase-1 promoter displayed AP-1 independent PMA-mediated transactivation .", "target_text": { "mutant AP-1 element": "DNA", "collagenase-1": "protein", "collagenase-1 promoter": "DNA", "mutant collagenase-1 promoter": "DNA", "AP-1": "protein" } }, { "input_text": "The AP-1 mutant constructs also showed delayed transcriptional activation in PMA-treated fibroblasts .", "target_text": { "AP-1": "protein", "AP-1 mutant constructs": "DNA", "PMA-treated fibroblasts": "cell_line" } }, { "input_text": "Western and supershift analyses indicated that functional Jun and Fos proteins were present in nuclear extracts of PMA-differentiated U937 cells .", "target_text": { "U937 cells": "cell_line", "PMA-differentiated U937 cells": "cell_line" } }, { "input_text": "Promoter deletion constructs demonstrated the potential role of distal promoter sequences in regulating collagenase-1 transcription .", "target_text": { "distal promoter sequences": "DNA", "collagenase-1": "protein" } }, { "input_text": "In particular , Western , supershift , and promoter deletion analyses suggested a role for CCAAT/enhancer-binding protein-beta ( C/EBP-beta ) binding site between -2010 and -1954 in regulating transcription of collagenase-1 in monocytic cells .", "target_text": { "CCAAT/enhancer-binding protein-beta": "protein", "C/EBP-beta": "protein", "CCAAT/enhancer-binding protein-beta ( C/EBP-beta ) binding site": "DNA", "-2010 and -1954": "DNA", "collagenase-1": "protein", "monocytic cells": "cell_type" } }, { "input_text": "Our findings suggest that distinct regulatory elements , acting somewhat independently of each other , control expression of collagenase-1 .", "target_text": { "regulatory elements": "DNA", "collagenase-1": "protein" } }, { "input_text": "In addition , our data suggests that the rapid PMA-mediated induction of collagenase-1 transcription is controlled by a mechanism distinct from that regulating the sustained expression of this proteinase in activated macrophages .", "target_text": { "collagenase-1": "protein", "proteinase": "protein", "activated macrophages": "cell_type" } }, { "input_text": "Quantification of vitamin D receptor mRNA by competitive polymerase chain reaction in PBMC : lack of correspondence with common allelic variants .", "target_text": { "vitamin D receptor": "protein", "vitamin D receptor mRNA": "RNA", "PBMC": "cell_type", "common allelic variants": "DNA" } }, { "input_text": "It has been recently claimed that polymorphism for the vitamin D receptor ( VDR ) influences several aspects of calcium and bone metabolism .", "target_text": { "vitamin D receptor": "protein", "VDR": "protein" } }, { "input_text": "To evaluate the physiologic plausibility of these claims , we compared the abundance of the VDR mRNA in peripheral blood mononuclear cells ( PBMCs ) between different VDR genotypes using a quantitative reverse transcribed polymerase chain reaction-based method .", "target_text": { "VDR mRNA": "RNA", "peripheral blood mononuclear cells": "cell_type", "PBMCs": "cell_type", "VDR": "protein", "VDR genotypes": "protein" } }, { "input_text": "The method is based on the coamplification of VDR cDNA and an internal standard consisting of known concentrations of a human VDR CDNA mutated at a BglII restriction site ; the interassay coefficient of variation is 11 % .", "target_text": { "VDR cDNA": "DNA", "human VDR CDNA": "DNA", "BglII restriction site": "DNA" } }, { "input_text": "To validate the method , we made use of earlier receptor binding studies indicating that normal human monocytes and activated , but not resting , lymphocytes expressed the VDR .", "target_text": { "normal human monocytes": "cell_type", "lymphocytes": "cell_type", "VDR": "protein" } }, { "input_text": "The concentration of the VDR mRNA was 10(-8) to 10(-7) g/g of total RNA in cell-sorted monocytes and in in vitro activated lymphocytes , but only 10(-12) g/g of total mRNA in resting lymphocytes , establishing that the VDR mRNA determined by our method in PBMCs is due to constitutive expression in monocytes .", "target_text": { "VDR mRNA": "RNA", "RNA": "RNA", "cell-sorted monocytes": "cell_type", "lymphocytes": "cell_type", "in vitro activated lymphocytes": "cell_type", "total mRNA": "RNA", "PBMCs": "cell_type", "monocytes": "cell_type" } }, { "input_text": "Following an initial genotype screening of 85 normal volunteers by polymerase chain reaction or restriction fragment length polymorphism analysis , 14 individuals with the Bb genotype , 12 with the bb genotype , and 12 with the BB genotype were selected .", "target_text": { "restriction fragment length polymorphism": "DNA" } }, { "input_text": "The concentration of the VDR mRNA , corrected for the number of monocytes , was similar among the three genotype groups , as were the other variables examined : serum calcitriol , serum osteocalcin , and vertebral and hip bone density .", "target_text": { "VDR mRNA": "RNA", "monocytes": "cell_type", "serum calcitriol": "protein", "serum osteocalcin": "protein" } }, { "input_text": "We conclude that VDR polymorphism does not affect the abundance of the VDR mRNA .", "target_text": { "VDR": "RNA", "VDR mRNA": "RNA" } }, { "input_text": "Oncogenic forms of NOTCH1 lacking either the primary binding site for RBP-Jkappa or nuclear localization sequences retain the ability to associate with RBP-Jkappa and activate transcription .", "target_text": { "NOTCH1": "protein", "primary binding site": "DNA", "RBP-Jkappa": "protein", "nuclear localization sequences": "protein" } }, { "input_text": "Truncated forms of the NOTCH1 transmembrane receptor engineered to resemble mutant forms of NOTCH1 found in certain cases of human T cell leukemia/lymphoma ( T-ALL ) efficiently induce T-ALL when expressed in the bone marrow of mice .", "target_text": { "NOTCH1": "protein", "NOTCH1 transmembrane receptor": "protein" } }, { "input_text": "Unlike full-sized NOTCH1 , two such truncated forms of the protein either lacking a major portion of the extracellular domain ( DeltaE ) or consisting only of the intracellular domain ( ICN ) were found to activate transcription in cultured cells , presumably through RBP-Jkappa response elements within DNA .", "target_text": { "NOTCH1": "protein", "extracellular domain": "protein", "DeltaE": "protein", "intracellular domain": "protein", "ICN": "protein", "RBP-Jkappa": "protein" } }, { "input_text": "Both truncated forms also bound to the transcription factor RBP-Jkappa in extracts prepared from human and murine T-ALL cell lines .", "target_text": { "RBP-Jkappa": "protein", "transcription factor RBP-Jkappa": "protein" } }, { "input_text": "Transcriptional activation required the presence of a weak RBP-Jkappa -binding site within the NOTCH1 ankyrin repeat region of the intracellular domain .", "target_text": { "RBP-Jkappa": "protein", "RBP-Jkappa -binding site": "protein", "NOTCH1": "protein", "NOTCH1 ankyrin repeat region": "protein", "intracellular domain": "protein" } }, { "input_text": "Unexpectedly , a second , stronger RBP-Jkappa -binding site , which lies within the intracellular domain close to the transmembrane region and significantly augments association with RBP-Jkappa , was not needed for oncogenesis or for transcriptional activation .", "target_text": { "RBP-Jkappa": "protein", "RBP-Jkappa -binding site": "protein", "intracellular domain": "protein" } }, { "input_text": "While ICN appeared primarily in the nucleus , DeltaE localized to cytoplasmic and nuclear membranes , suggesting that intranuclear localization is not essential for oncogenesis or transcriptional activation .", "target_text": { "ICN": "protein", "DeltaE": "protein" } }, { "input_text": "In support of this interpretation , mutation of putative nuclear localization sequences decreased nuclear localization and increased transcriptional activation by membrane-bound DeltaE .", "target_text": { "nuclear localization sequences": "protein", "DeltaE": "protein", "membrane-bound DeltaE": "protein" } }, { "input_text": "Transcriptional activation by this mutant form of membrane-bound DeltaE was approximately equivalent to that produced by intranuclear ICN .", "target_text": { "DeltaE": "protein", "membrane-bound DeltaE": "protein", "ICN": "protein", "intranuclear ICN": "protein" } }, { "input_text": "These data are most consistent with NOTCH1 oncogenesis and transcriptional activation being independent of association with RBP-Jkappa at promoter sites .", "target_text": { "NOTCH1": "protein", "RBP-Jkappa": "protein", "promoter sites": "DNA" } }, { "input_text": "Sp family members preferentially interact with the promoter proximal repeat within the HTLV-I enhancer .", "target_text": { "Sp family members": "protein", "promoter proximal repeat": "DNA", "HTLV-I enhancer": "DNA" } }, { "input_text": "Human T cell lymphotropic virus type I ( HTLV-I ) encodes the transactivator protein , Tax , which facilitates viral transcription from three 21 bp repeated elements within the U3 region of the long terminal repeat ( LTR ) .", "target_text": { "transactivator protein": "protein", "Tax": "protein", "21 bp repeated elements": "DNA", "U3 region": "DNA", "long terminal repeat": "DNA", "LTR": "DNA" } }, { "input_text": "Examination of the basal factors interacting with the 21 bp repeat elements through electrophoretic mobility shift ( EMS ) analyses has demonstrated the formation of DNA-protein complexes common to each of the 21 bp repeats ( C1-C3 ) as well as three DNA-protein complexes specific to the promoter proximal ( pp ) repeat ( U1 ( U1A/U1B ) and U2 ; 1-4 ) .", "target_text": { "basal factors": "protein", "21 bp repeat elements": "DNA", "DNA-protein complexes": "protein", "21 bp repeats": "DNA", "C1-C3": "DNA", "promoter proximal ( pp ) repeat": "DNA", "U1": "DNA", "U1A/U1B": "DNA", "U2": "DNA" } }, { "input_text": "These studies have indicated that the individual repeats are not identical with respect to the cellular factors with which they interact .", "target_text": { "cellular factors": "protein" } }, { "input_text": "EMS analyses utilizing a series of mutated pp repeat elements demonstrate that the nucleotide sequence requirements for U1 ( U1A/U1B ) and U2 formation are separable from those required for C1-C3 formation .", "target_text": { "mutated pp repeat elements": "DNA", "U1": "DNA", "U1A/U1B": "DNA", "U2": "DNA", "C1-C3": "DNA" } }, { "input_text": "Competition EMS analyses utilizing Sp1 and CREB binding site oligonucleotides demonstrate that Sp family members are critical components of U1 ( U1A/U1B ) and U2 and that ATF/CREB family members are critical components of C1-C3 .", "target_text": { "Sp family members": "protein", "U1": "DNA", "U1A/U1B": "DNA", "U2": "DNA", "ATF/CREB family members": "protein", "C1-C3": "DNA" } }, { "input_text": "EMS supershift analyses have demonstrated that Sp1 is involved in U1A formation while Sp3 is involved in U1B and U2 formation .", "target_text": { "Sp1": "protein", "Sp3": "protein" } }, { "input_text": "EMS analyses performed with nuclear extracts from Tax -expressing Jurkat cells and HTLV-I -transformed peripheral blood mononuclear cells demonstrate that Tax prevents the formation of U1 ( U1A/U1B ) and U2 DNA-protein complexes .", "target_text": { "Tax": "protein", "Tax -expressing Jurkat cells": "cell_line", "HTLV-I -transformed peripheral blood mononuclear cells": "cell_type", "U1": "DNA", "U1A/U1B": "DNA", "U2": "DNA", "DNA-protein complexes": "protein" } }, { "input_text": "Therefore , Tax appears to inhibit the interaction of Sp family members with the pp repeat .", "target_text": { "Tax": "protein", "Sp family members": "protein", "pp repeat": "DNA" } }, { "input_text": "Based on these observations , it is possible that the interaction of Sp and ATF/CREB family members with the pp repeat during basal and Tax -mediated transcription may play a critical role in viral gene expression during the initial stages of virus infection or during activation of a latent infection .", "target_text": { "Sp": "protein", "ATF/CREB family members": "protein", "pp repeat": "DNA", "Tax": "protein" } }, { "input_text": "Lineage- and stage- specific expression of runt box polypeptides in primitive and definitive hematopoiesis .", "target_text": { "runt box polypeptides": "protein" } }, { "input_text": "Translocations involving the human CBFA2 locus have been associated with leukemia .", "target_text": { "human CBFA2 locus": "DNA" } }, { "input_text": "This gene , originally named AML1 , is a human homologue of the Drosophila gene runt that controls early events in fly embryogenesis .", "target_text": { "AML1": "DNA", "Drosophila gene runt": "DNA" } }, { "input_text": "To clarify the role of mammalian runt products in normal and leukemic hematopoiesis , we have studied their pattern of expression in mouse hematopoietic tissues in the adult and during ontogeny using an anti-runt box antiserum .", "target_text": { "mammalian runt products": "protein" } }, { "input_text": "In the adult bone marrow , we found expression of runt polypeptides in differentiating myeloid cells and in B lymphocytes .", "target_text": { "differentiating myeloid cells": "cell_type", "B lymphocytes": "cell_type" } }, { "input_text": "Within the erythroid lineage , runt expression is biphasic , clearly present in the erythroblasts of early blood islands and of the fetal liver , but absent in the adult .", "target_text": { "erythroid lineage": "cell_type", "erythroblasts": "cell_type" } }, { "input_text": "Biochemical analysis by Western blotting of fetal and adult hematopoietic populations shows several runt isoforms .", "target_text": { "runt isoforms": "protein" } }, { "input_text": "At least one of them appears to be myeloid specific .", "target_text": {} }, { "input_text": "Signal transducer and activator of transcription-3 ( STAT3 ) is constitutively activated in normal , self-renewing B-1 cells but only inducibly expressed in conventional B lymphocytes [ see comments ]", "target_text": { "Signal transducer and activator of transcription-3": "protein", "STAT3": "protein", "self-renewing B-1 cells": "cell_type", "B lymphocytes": "cell_type" } }, { "input_text": "Cytokine and growth factor receptor engagement leads to the rapid phosphorylation and activation of latent , cytosolic signal transducers and activators of transcription ( STAT ) proteins , which then translocate to the nucleus where they regulate transcriptional events from specific promoter sequences .", "target_text": { "Cytokine": "protein", "growth factor receptor": "protein", "cytosolic signal transducers and activators of transcription ( STAT ) proteins": "protein", "specific promoter sequences": "DNA" } }, { "input_text": "STAT3 expression in particular has been associated with Abl , Src , and HTLV-1 transformation of normal cells .", "target_text": { "STAT3": "protein", "Abl": "protein", "Src": "protein", "normal cells": "cell_type" } }, { "input_text": "B-1 lymphocytes are self-renewing , CD5+ B cells that display a propensity for malignant transformation and are the normal counterpart to human chronic lymphocytic leukemias .", "target_text": { "B-1 lymphocytes": "cell_type", "CD5+ B cells": "cell_type" } }, { "input_text": "Further , B-1 cells are characterized by aberrant intracellular signaling , including hyperresponsiveness to phorbol ester PKC agonists .", "target_text": { "B-1 cells": "cell_type" } }, { "input_text": "Here we demonstrate that B-1 lymphocytes constitutively express nuclear activated STAT3 , which is not expressed by unmanipulated conventional ( B-2 ) lymphocytes .", "target_text": { "B-1 lymphocytes": "cell_type", "STAT3": "protein", "nuclear activated STAT3": "protein", "unmanipulated conventional ( B-2 ) lymphocytes": "cell_type" } }, { "input_text": "In contrast , STAT3 activation is induced in B-2 cells after antigen receptor engagement in a delayed fashion ( after 3 h ) .", "target_text": { "STAT3": "protein", "B-2 cells": "cell_type" } }, { "input_text": "Induction of STAT3 is inhibited by both the serine/threonine protein kinase inhibitor H-7 and the immunosuppressive drug rapamycin and requires de novo protein synthesis , demonstrating novel coupling between sIg and STAT proteins that differs from the classical paradigm for STAT induction by cytokine receptors .", "target_text": { "STAT3": "protein", "sIg": "protein", "STAT proteins": "protein", "STAT": "protein", "cytokine receptors": "protein" } }, { "input_text": "The inability of prolonged stimulation of conventional B-2 cells with anti-Ig , a treatment sufficient to induce CD5 expression , to result in sustained STAT3 activation suggests that STAT3 is a specific nuclear marker for B-1 cells .", "target_text": { "B-2 cells": "cell_type", "anti-Ig": "protein", "CD5": "protein", "STAT3": "protein", "B-1 cells": "cell_type" } }, { "input_text": "Thus , STAT3 may play a role in B cell antigen-specific signaling responses , and its constitutive activation is associated with a normal cell population exhibiting intrinsic proliferative behavior .", "target_text": { "STAT3": "protein" } }, { "input_text": "Significance of quantitative analysis of AML1 /ETO transcripts in peripheral blood stem cells from t(8;21) acute myelogenous leukemia .", "target_text": { "AML1": "DNA", "AML1 /ETO transcripts": "RNA", "peripheral blood stem cells": "cell_type" } }, { "input_text": "Autologous peripheral blood stem cell transplantation ( PBSCT ) is replacing autologous bone marrow transplantation ( BMT ) in the treatment of leukemia .", "target_text": { "peripheral blood stem cell": "cell_type" } }, { "input_text": "One of the potential advantages of autologous PBSCT is the possibility that peripheral blood stem cells ( PBSC ) are less likely to be contaminated by leukemic cells than bone marrow grafts .", "target_text": { "peripheral blood stem cells": "cell_type", "PBSC": "cell_type", "leukemic cells": "cell_type" } }, { "input_text": "However , the major problem still remains the high incidence of leukemic relapse following autologous PBSCT , which may be caused by the reinfusion of PBSC contaminated by leukemic cells .", "target_text": { "PBSC": "cell_type", "leukemic cells": "cell_type" } }, { "input_text": "Recently , we have developed a quantitative assay using competitive reverse transcriptase polymerase chain reaction that estimates the number of AML1 /ETO transcripts in t(8;21) acute myelogenous leukemia ( AML ) , in order to determine the degree of leukemic cell contamination in PBSC harvests , and to monitor minimal residual disease ( MRD ) quantitatively in patients with t(8;21) AML .", "target_text": { "reverse transcriptase polymerase": "protein", "AML1": "DNA", "AML1 /ETO transcripts": "RNA", "PBSC": "cell_type" } }, { "input_text": "Our data indicate that although PBSC harvests collected after consolidation chemotherapy are contaminated by leukemic cells , the degree of leukemic cell contamination decreases with repeated cycles of chemotherapy .", "target_text": { "PBSC": "cell_type", "leukemic cells": "cell_type" } }, { "input_text": "Furthermore , the MRD in PBSC harvests is less than in the corresponding bone marrow obtained on the day of the PBSC collection .", "target_text": { "PBSC": "cell_type" } }, { "input_text": "There appears to be no relationship between the number of AML1 /ETO transcripts found in the infused PBSC harvests and the incidence of leukemic relapse following autologous PBSCT in our study .", "target_text": { "AML1": "DNA", "AML1 /ETO transcripts": "RNA", "PBSC": "cell_type" } }, { "input_text": "However , a substantial decrease of AML1 /ETO transcripts was seen following autologous PBSCT .", "target_text": { "AML1": "DNA", "AML1 /ETO transcripts": "RNA" } }, { "input_text": "Thus , the quantitative analysis of AML1 /ETO transcripts may be clinically useful in patients with t(8;21) AML .", "target_text": { "AML1": "DNA", "AML1 /ETO transcripts": "RNA" } }, { "input_text": "Upregulation of c-Fos in activated T lymphoid and monocytic cells by human immunodeficiency virus-1 Tat protein .", "target_text": { "c-Fos": "protein", "human immunodeficiency virus-1 Tat protein": "protein" } }, { "input_text": "The regulatory Tat protein of the human immunodeficiency virus type-1 ( HIV-1 ) is essential for viral replication and also shows pleiotropic activities on various cell functions .", "target_text": { "regulatory Tat protein": "protein" } }, { "input_text": "To get further insights into the molecular mechanisms underlying the biological activity of Tat , we investigated the effect of endogenous and exogenous Tat protein on c-fos gene expression in T lymphoblastoid ( Jurkat ) and monocytic ( U937 ) cell lines , as well as in primary peripheral blood mononuclear cells ( PBMC ) .", "target_text": { "Tat": "protein", "Tat protein": "protein", "primary peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "Transient cotransfection of tat cDNA in sense orientation ( tat/S ) , together with a plasmid containing the c-fos promoter ( FC3 , from - 711 to +42 ) in front of the bacterial chloramphenicol acetyltransferase ( CAT ) gene significantly enhanced CAT activity in Jurkat cells activated by the addition of 15 % fetal calf serum ( FCS ) or 5 micrograms/mL phytohemagglutinin plus 10(-7) mol/L phorbol myristate acetate ( PMA ) and U937 cells activated by 15 % FCS or 10(-7) mol/L PMA .", "target_text": { "tat cDNA": "DNA", "tat/S": "DNA", "plasmid": "DNA", "c-fos promoter": "DNA", "FC3": "DNA", "711 to +42": "DNA", "chloramphenicol acetyltransferase": "protein", "bacterial chloramphenicol acetyltransferase ( CAT ) gene": "DNA", "CAT": "protein", "Jurkat cells": "cell_line", "phytohemagglutinin": "protein", "U937 cells": "cell_line" } }, { "input_text": "This effect was specifically due to Tat , since Jurkat and U937 cells cotransfected either with tat cDNA in antisense orientation ( tat/AS ) , tat carrying a mutation in the aminoacid cys22-gly22 ( tat 22/S ) or with the backbone vector alone ( pRPneo-SL3 ) did not show any significant difference in c-fos promoter activity as compared to cells transfected with FC3 plasmid alone .", "target_text": { "Tat": "protein", "Jurkat": "cell_line", "U937 cells": "cell_line", "tat cDNA": "DNA", "tat/AS": "DNA", "tat": "DNA", "aminoacid cys22-gly22": "protein", "tat 22/S": "DNA", "backbone vector alone": "DNA", "pRPneo-SL3": "DNA", "c-fos promoter": "DNA", "FC3 plasmid": "DNA" } }, { "input_text": "By using deletion mutants of the c-fos promoter , we found that the minimal DNA sequence required for Tat activity was located between nucleotides -404/-220 and that the serum responsive element ( SRE , -317/-288 ) , present within this region , was still responsive to Tat .", "target_text": { "c-fos promoter": "DNA", "minimal DNA sequence": "DNA", "Tat": "protein", "nucleotides -404/-220": "DNA", "serum responsive element": "DNA", "SRE": "DNA", "-317/-288": "DNA" } }, { "input_text": "A single point mutation in the SRE completely abrogated the responsiveness to tat/S .", "target_text": { "single point mutation": "DNA", "SRE": "DNA", "tat/S": "DNA" } }, { "input_text": "Exogenous recombinant Tat protein was also able to upregulate c-fos promoter activity in serum-activated Jurkat and U937 cells , as well as endogenous c-fos mRNA expression and c-Fos protein synthesis in both serum-activated cell lines and primary PBMC .", "target_text": { "Tat": "protein", "recombinant Tat protein": "protein", "c-fos promoter": "DNA", "U937 cells": "cell_line", "c-fos mRNA": "RNA", "c-Fos": "protein", "serum-activated cell lines": "cell_line", "PBMC": "cell_type", "primary PBMC": "cell_type" } }, { "input_text": "c-Fos protein was shown essential for an optimal transactivation of the HIV-1 long terminal repeat ( LTR ) by Tat : incubation of Jurkat cells with antisense , but not sense , c-fos oligonucleotides significantly reduced either the Tat -enhanced expression of an LTR-CAT reporter construct or the levels of gag p24 in the culture supernatants of Jurkat cells and PBMC acutely infected with HIV-1 .", "target_text": { "c-Fos": "protein", "long terminal repeat": "DNA", "LTR": "DNA", "Tat": "protein", "Jurkat cells": "cell_line", "LTR-CAT reporter construct": "DNA", "gag p24": "protein", "PBMC": "cell_type" } }, { "input_text": "Our data suggest that the c-fos upregulation mediated by Tat might play a significant role in the control of viral gene transactivation .", "target_text": { "c-fos": "DNA", "Tat": "protein" } }, { "input_text": "Cytokine signal networks and a new era in biomedical research .", "target_text": { "Cytokine signal networks": "protein" } }, { "input_text": "Elucidation of the biochemical nature of the signal transduction pathway that regulate transcription and replication is the focus of attention in molecular biology .", "target_text": {} }, { "input_text": "This research may make feasible manipulation of growth and differentiation of mammalian cells , which in turn would have profound implication in biomedical research on cell and gene therapy , and development of pharmaceutical products .", "target_text": { "mammalian cells": "cell_type" } }, { "input_text": "Cytokines control growth , differentiation , death , and function of cells of lymphocytic , hemopoietic systems , and together with nerve cells provide a pertinent model to study intercellular communications and intercellular signal networks .", "target_text": { "Cytokines": "protein", "nerve cells": "cell_type" } }, { "input_text": "This review outlines general features of signal transduction and several aspects of cytokine networks are discussed with emphasis on : transcriptional regulation of Th1 and Th2-specific cytokine genes in T cells , the roles of cytokines and their receptors in growth and differentiation of hemopoietic cells , and the manipulation of cytokine networks .", "target_text": { "cytokine networks": "protein", "cytokine genes": "DNA", "T cells": "cell_type", "cytokines": "protein", "hemopoietic cells": "cell_type" } }, { "input_text": "Regulation of the tissue factor gene in human monocytic cells .", "target_text": { "tissue factor gene": "DNA", "monocytic cells": "cell_type", "human monocytic cells": "cell_type" } }, { "input_text": "Role of AP-1 , NF-kappa B/Rel , and Sp1 proteins in uninduced and lipopolysaccharide -induced expression .", "target_text": { "AP-1": "protein", "NF-kappa B/Rel": "protein", "Sp1": "protein" } }, { "input_text": "Tissue factor ( TF ) expression by peripheral blood monocytes during sepsis initiates intravascular thrombosis .", "target_text": { "Tissue factor": "protein", "peripheral blood monocytes": "cell_type" } }, { "input_text": "Bacterial lipopolysaccharide ( LPS ) rapidly induces TF gene transcription in monocytes .", "target_text": { "TF gene": "DNA", "monocytes": "cell_type" } }, { "input_text": "The human TF promoter contains binding sites for the transcription factors AP-1 , c-Rel/p65 , Egr-1 , and Sp1 .", "target_text": { "human TF promoter": "DNA", "AP-1": "protein", "c-Rel/p65": "protein", "Egr-1": "protein", "Sp1": "protein" } }, { "input_text": "NF-kappa B/Rel proteins have been shown to physically interact with both AP-1 and Sp1 proteins .", "target_text": { "NF-kappa B/Rel": "protein", "NF-kappa B/Rel proteins": "protein" } }, { "input_text": "In this study , we investigated the role of these transcription factors in uninduced and LPS -induced TF gene expression in human monocytic THP-1 cells .", "target_text": { "transcription factors": "protein", "TF gene": "DNA", "human monocytic THP-1 cells": "cell_type" } }, { "input_text": "Deletional analysis indicated that five Sp1 sites mediated basal expression in uninduced cells .", "target_text": { "Sp1": "protein", "Sp1 sites": "DNA", "uninduced cells": "cell_type" } }, { "input_text": "The two AP-1 sites bound c-Fos /c-Jun heterodimers in both unstimulated and LPS-stimulated cells .", "target_text": { "AP-1": "protein", "AP-1 sites": "DNA", "c-Fos": "protein", "c-Fos /c-Jun heterodimers": "protein" } }, { "input_text": "Maximal LPS induction of the TF promoter required the two AP-1 sites and the kappa B site within the LPS response element .", "target_text": { "TF promoter": "DNA", "AP-1": "protein", "kappa B site": "DNA", "LPS response element": "DNA" } }, { "input_text": "Disruption of the conserved spacing between the proximal AP-1 site and the kappa B site abolished LPS induction .", "target_text": { "AP-1": "protein", "proximal AP-1 site": "DNA", "kappa B site": "DNA" } }, { "input_text": "Replacement of the two AP-1 sites with intrinsically bent DNA partially restored LPS induction , suggesting an additional structural role for the AP-1 sites .", "target_text": { "AP-1": "protein", "AP-1 sites": "DNA" } }, { "input_text": "Synergistic transactivation of the LPS response element in Drosophila Schneider cells by coexpression of c-Fos , c-Jun , c-Rel , and p65 or c-Jun and p65 required the transactivation domains of c-Jun and p65 .", "target_text": { "LPS response element": "DNA", "Drosophila Schneider cells": "cell_line", "c-Fos": "protein", "c-Jun": "protein", "c-Rel": "protein", "p65": "protein", "transactivation domains": "protein" } }, { "input_text": "These data indicated that c-Fos /c-Jun , c-Rel /p65 , and Sp1 regulate TF gene expression in human monocytic cells .", "target_text": { "c-Fos": "protein", "/c-Jun": "protein", "c-Rel": "protein", "/p65": "protein", "Sp1": "protein", "TF gene": "DNA", "monocytic cells": "cell_type", "human monocytic cells": "cell_type" } }, { "input_text": "Inhibitory effect of growth hormone on TNF-alpha secretion and nuclear factor-kappaB translocation in lipopolysaccharide -stimulated human monocytes .", "target_text": { "TNF-alpha": "protein", "nuclear factor-kappaB": "protein", "lipopolysaccharide -stimulated human monocytes": "cell_type" } }, { "input_text": "Several studies have pointed to a link between immune and endocrine systems , including a regulatory function of GH on monocyte activation .", "target_text": {} }, { "input_text": "The present study demonstrates that human THP-1 promonocytic cells , engineered by gene transfer to constitutively produce human growth hormone ( hGH ) , secreted depressed amounts of TNF-alpha in response to challenge by LPS .", "target_text": { "THP-1 promonocytic cells": "cell_line", "TNF-alpha": "protein" } }, { "input_text": "The effect of GH appears to occur in an autocrine fashion , since the inhibitory effect on TNF-alpha secretion by constitutive GH production could be abolished in the presence of anti-hGH mAb .", "target_text": { "TNF-alpha": "protein", "anti-hGH mAb": "protein" } }, { "input_text": "The GH -induced inhibitory effect was also observed using normal human monocytes and monocyte-derived macrophages .", "target_text": { "normal human monocytes": "cell_type", "monocyte-derived macrophages": "cell_type" } }, { "input_text": "Inhibition of TNF-alpha production by THP-1-hGH-transfected cells cultured in the presence of LPS is dependent on a selective pathway , since no inhibition of TNF-alpha production was observed when cells were cultured in the presence of PMA .", "target_text": { "TNF-alpha": "protein", "THP-1-hGH-transfected cells": "cell_line" } }, { "input_text": "Inhibition of TNF-alpha secretion by LPS -stimulated THP-1-hGH cells was associated with a decrease in nuclear translocation of nuclear factor-kappaB .", "target_text": { "TNF-alpha": "protein", "LPS -stimulated THP-1-hGH cells": "cell_line", "nuclear factor-kappaB": "protein" } }, { "input_text": "The capacity of GH to inhibit LPS -induced TNF-alpha production by monocytes without altering other pathways leading to TNF-alpha production may be of potential relevance in septic shock , since GH is available for clinical use .", "target_text": { "TNF-alpha": "protein", "monocytes": "cell_type" } }, { "input_text": "Nuclear factor-kappaB activation in human monocytes stimulated with lipopolysaccharide is inhibited by fibroblast conditioned medium and exogenous PGE2 .", "target_text": { "Nuclear factor-kappaB": "protein", "human monocytes": "cell_type" } }, { "input_text": "The nuclear factor kappaB ( NF-kappaB ) is thought to be crucially involved in the gene activation of several cytokines , including tumor necrosis factor alpha ( TNF ) .", "target_text": { "nuclear factor kappaB": "protein", "NF-kappaB": "protein", "cytokines": "protein", "tumor necrosis factor alpha": "protein", "TNF": "protein" } }, { "input_text": "Previously , we showed that fibroblast conditioned medium ( FCM ) is able to inhibit both TNF mRNA accumulation and protein release in peripheral blood-derived human monocytes ( PBM ) stimulated with lipopolysaccharide ( LPS ) .", "target_text": { "TNF mRNA": "RNA", "human monocytes": "cell_type", "peripheral blood-derived human monocytes": "cell_line", "PBM": "cell_line" } }, { "input_text": "In this study we have investigated the effect of FCM on the LPS -induced DNA-binding activity of NF-kappaB , by means of electrophoretic shift assay ( EMSA ) .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "We provide evidence that FCM strongly inhibits the LPS -induced NF-kappaB activation in PBM .", "target_text": { "NF-kappaB": "protein", "PBM": "cell_line" } }, { "input_text": "Furthermore , we show that exogenous PGE2 mimics the NF-kappaB inhibitory effect of FCM .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "On the other hand , FCM produced in the presence of indomethacin does not inhibit NF-kappaB activation by LPS .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Our results lend further support to the hypothesis that inflammatory and immune responses of monocytes/macrophages may be modulated at the molecular level by signals originating from tissue structural cells such as fibroblasts .", "target_text": { "monocytes/macrophages": "cell_type", "tissue structural cells": "cell_type", "fibroblasts": "cell_type" } }, { "input_text": "Human neutrophil elastase proteolytically activates the platelet integrin alphaIIbbeta3 through cleavage of the carboxyl terminus of the alphaIIb subunit heavy chain .", "target_text": { "Human neutrophil elastase": "protein", "platelet integrin": "protein", "alphaIIbbeta3": "protein", "carboxyl terminus": "protein", "alphaIIb subunit heavy chain": "protein" } }, { "input_text": "Involvement in the potentiation of platelet aggregation .", "target_text": {} }, { "input_text": "Neutrophil elastase ( NE ) and cathepsin G are two serine proteinases released concomitantly by stimulated polymorphonuclear neutrophils .", "target_text": { "Neutrophil elastase": "protein", "NE": "protein", "cathepsin G": "protein", "serine proteinases": "protein", "polymorphonuclear neutrophils": "cell_type" } }, { "input_text": "We previously demonstrated that while NE by itself does not activate human platelets , it strongly enhances the weak aggregation induced by a threshold concentration of cathepsin G ( threshold of cathepsin G ) ( Renesto , P. , and Chignard , M. ( 1993 ) Blood 82 , 139-144 ) .", "target_text": { "NE": "protein", "human platelets": "cell_type", "cathepsin G": "protein" } }, { "input_text": "The aim of this study was to delineate the molecular mechanisms involved in this potentiation process .", "target_text": {} }, { "input_text": "Two main pieces of data prompted us to focus on the activation of the platelet fibrinogen receptor , the alphaIIbbeta3 integrin .", "target_text": { "platelet fibrinogen receptor": "protein", "alphaIIbbeta3": "protein", "alphaIIbbeta3 integrin": "protein" } }, { "input_text": "First , previous studies have shown this integrin to be particularly prone to proteolytic regulation of its function .", "target_text": { "integrin": "protein" } }, { "input_text": "Second , we found that the potentiating activity of NE on the threshold of cathepsin G -induced platelet aggregation was strictly dependent on the presence of exogenous fibrinogen .", "target_text": { "NE": "protein", "cathepsin G": "protein", "exogenous fibrinogen": "protein" } }, { "input_text": "Using flow cytometry analysis , NE was shown to trigger a time-dependent binding of PAC-1 and AP-5 , two monoclonal antibodies specific for the activated and ligand-occupied conformers of alphaIIbbeta3 .", "target_text": { "NE": "protein", "PAC-1": "protein", "AP-5": "protein", "monoclonal antibodies": "protein", "alphaIIbbeta3": "protein" } }, { "input_text": "Furthermore , the potentiated aggregation was shown to result from an increased capacity of platelets to bind fibrinogen .", "target_text": {} }, { "input_text": "Indeed , the combination of NE and threshold of cathepsin G increased the binding of PAC-1 approximately 5.5-fold over basal values measured on nontreated platelets , whereas this binding raised only by approximately 3-fold in threshold of cathepsin G -stimulated platelets ( p < 0.05 ) .", "target_text": { "NE": "protein", "cathepsin G": "protein", "PAC-1": "protein", "nontreated platelets": "cell_type", "cathepsin G -stimulated platelets": "cell_type" } }, { "input_text": "By contrast , phosphatidic acid accumulation , pleckstrin phosphorylation , and calcium mobilization produced by the combination of NE and threshold of cathepsin G were not significantly different from those measured with threshold of cathepsin G alone ( p > 0.05 ) , indicating that the phospholipase C /protein kinase C pathway is not involved in the potentiation of aggregation .", "target_text": { "NE": "protein", "cathepsin G": "protein", "phospholipase C": "protein", "/protein kinase C": "protein" } }, { "input_text": "The foregoing data , as well as the requirement of catalytically active NE to trigger alphaIIbbeta3 activation and potentiate threshold of cathepsin G -initiated platelet aggregation , led us to examine whether the structure of this integrin was affected by NE .", "target_text": { "NE": "protein", "alphaIIbbeta3": "protein", "cathepsin G": "protein", "integrin": "protein" } }, { "input_text": "Immunoblot and flow cytometry analysis revealed a limited proteolysis of the carboxyl terminus of the alphaIIb subunit heavy chain ( alphaIIbH ) , as judged by the disappearance of the epitope for the monoclonal antibody PMI-1 .", "target_text": { "carboxyl terminus": "protein", "alphaIIb subunit heavy chain": "protein", "alphaIIbH": "protein", "monoclonal antibody PMI-1": "protein" } }, { "input_text": "Mass spectrometry studies performed on a synthetic peptide mapping over the cleavage domain of alphaIIbH predicted the site of proteolysis as located between Val837 and Asp838 .", "target_text": { "cleavage domain": "protein", "alphaIIbH": "protein" } }, { "input_text": "Treatment by NE of ATP-depleted platelets or Chinese hamster ovary cells expressing human recombinant alphaIIbbeta3 clearly established that activation of the integrin was independent of signal transduction events and was concomitant with the proteolysis of alphaIIbH .", "target_text": { "NE": "protein", "ATP-depleted platelets": "cell_type", "Chinese hamster ovary cells": "cell_line", "alphaIIbbeta3": "protein", "human recombinant alphaIIbbeta3": "protein", "integrin": "protein", "alphaIIbH": "protein" } }, { "input_text": "AP-1 derived from mature monocytes and astrocytes preferentially interacts with the HTLV-I promoter central 21 bp repeat .", "target_text": { "AP-1": "protein", "mature monocytes": "cell_type", "astrocytes": "cell_type", "HTLV-I promoter": "DNA", "21 bp repeat": "DNA" } }, { "input_text": "Characterization of the cellular transcription factors interacting with the human T cell lymphotropic virus type I ( HTLV-I ) long terminal repeat ( LTR ) is essential to dissecting the mechanisms involved in viral transcription that may be pertinent to the oncogenic and neuropathogenic processes associated with HTLV-I infection in both the immune and nervous systems .", "target_text": { "transcription factors": "protein", "human T cell lymphotropic virus type I ( HTLV-I ) long terminal repeat": "DNA", "LTR": "DNA" } }, { "input_text": "Electrophoretic mobility shift ( EMS ) analyses utilizing oligonucleotides homologous to each of the 21 bp repeat elements reacted with nuclear extracts derived from cell lines of lymphocytic , monocytic , neuronal , and glial cell origin have demonstrated differential binding of cellular factors to the three 21 bp repeats ( 1-4 ) .", "target_text": { "21 bp repeat": "DNA", "21 bp repeat elements": "DNA", "cell lines": "cell_line", "cellular factors": "protein", "21 bp repeats": "DNA" } }, { "input_text": "ATF/CREB and Sp family members interacted with the 21 bp repeats to form DNA-protein complexes common to all cell types examined .", "target_text": { "ATF/CREB": "protein", "Sp family members": "protein", "21 bp repeats": "DNA", "DNA-protein complexes": "protein" } }, { "input_text": "However , a unique DNA-protein complex was detected when the promoter central 21 bp repeat was reacted with nuclear extracts derived from either the U-373 MG glioblastoma cell line or the THP-1 mature monocytic cell line .", "target_text": { "DNA-protein complex": "protein", "21 bp repeat": "DNA", "U-373 MG glioblastoma cell line": "cell_line", "THP-1 mature monocytic cell line": "cell_line" } }, { "input_text": "Based on nucleotide sequence requirements and immunoreactivity , we demonstrate that this DNA-protein complex is comprised of the AP-1 components , Fos and Jun .", "target_text": { "DNA-protein complex": "protein", "AP-1": "protein", "Fos": "protein", "Jun": "protein" } }, { "input_text": "HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28 .", "target_text": { "naive CD4 T cells": "cell_type", "CD3/CD28": "protein" } }, { "input_text": "In this report , we demonstrate that the T cell tropic strain of HIV , LAI , does not replicate in naive CD4 T cells stimulated by cross-linking CD3 and CD28 .", "target_text": { "naive CD4 T cells": "cell_type", "CD3": "protein", "CD28": "protein" } }, { "input_text": "In contrast , LAI replicates well in memory CD4 T cells stimulated in the same way .", "target_text": { "memory CD4 T cells": "cell_type" } }, { "input_text": "Unlike this physiologically relevant stimulation , PHA stimulates productive LAI replication in both naive and memory T cells .", "target_text": { "PHA": "protein" } }, { "input_text": "These studies were conducted with highly purified ( FACS-isolated ) subsets of CD4 T cells identified by expression of both CD45RA and CD62L .", "target_text": { "CD4 T cells": "cell_type", "CD45RA": "protein", "CD62L": "protein" } }, { "input_text": "Remixing of purified T cells showed that naive T cells do not suppress LAI replication in memory T cells and that memory T cells do not restore LAI expression in naive T cells .", "target_text": { "purified T cells": "cell_type", "naive T cells": "cell_type", "memory T cells": "cell_type" } }, { "input_text": "The suppression of productive LAI replication in naive T cells is not due to differential expression of viral coreceptors , nor is it due to inhibition of activation of the important HIV transcription factors , nuclear factor-kappaB and activator protein-1 .", "target_text": { "naive T cells": "cell_type", "viral coreceptors": "protein", "transcription factors": "protein", "nuclear factor-kappaB": "protein", "activator protein-1": "protein" } }, { "input_text": "The inherent resistance of naive T cells to productive HIV infection , coupled with their proliferative advantage as demonstrated here , provides a sound basis for proposed clinical therapies using ex vivo expansion and reinfusion of CD4 T cells from HIV -infected adults .", "target_text": { "naive T cells": "cell_type", "CD4 T cells": "cell_type" } }, { "input_text": "A PMLRARalpha transgene initiates murine acute promyelocytic leukemia .", "target_text": { "PMLRARalpha transgene": "DNA" } }, { "input_text": "The malignant cells of acute promyelocytic leukemia ( APL ) contain a reciprocal chromosomal translocation that fuses the promyelocytic leukemia gene ( PML ) with the retinoic acid receptor alpha gene ( RAR alpha ) .", "target_text": { "malignant cells": "cell_type", "promyelocytic leukemia gene": "DNA", "retinoic acid receptor alpha gene": "DNA", "RAR alpha": "protein" } }, { "input_text": "To test the hypothesis that the chimera PMLRAR alpha plays a role in leukemogenesis , we expressed a PMLRAR alpha cDNA in myeloid cells of transgenic mice .", "target_text": { "chimera PMLRAR alpha": "protein", "PMLRAR alpha cDNA": "DNA", "myeloid cells": "cell_type" } }, { "input_text": "PMLRAR alpha transgenic mice exhibited impaired neutrophil maturation early in life , which progressed at a low frequency over the course of several months to overt APL .", "target_text": {} }, { "input_text": "Both the preleukemic state and the leukemia could be transplanted to nontransgenic mice , and the transplanted preleukemia could progress to APL .", "target_text": {} }, { "input_text": "The APL recapitulated features of the human disease , including a response to retinoic acid .", "target_text": {} }, { "input_text": "Retinoic acid caused the leukemic cells to differentiate in vitro and in vivo , eliciting remissions of both the preleukemic state and APL in mice .", "target_text": { "leukemic cells": "cell_type" } }, { "input_text": "Our results demonstrate that PMLRAR alpha impairs neutrophil differentiation and initiates the development of APL .", "target_text": { "PMLRAR alpha": "protein" } }, { "input_text": "The transgenic mice described here provide an apparently accurate model for human APL that includes clear evidence of tumor progression .", "target_text": {} }, { "input_text": "The model should be useful for exploring the molecular pathogenesis of APL and the mechanisms of the therapeutic response to retinoic acid , as well as for preclinical studies of therapeutic regimens .", "target_text": {} }, { "input_text": "DNA methylation changes in hematologic malignancies : biologic and clinical implications .", "target_text": {} }, { "input_text": "DNA methylation changes are among the most common detectable abnormalities in human neoplasia .", "target_text": {} }, { "input_text": "Hypermethylation within the promoters of selected genes appears to be especially common in all types of human hematopoietic neoplasms , and is usually associated with inactivation of the involved gene ( s ) .", "target_text": { "promoters": "DNA", "human hematopoietic neoplasms": "cell_type" } }, { "input_text": "Such hypermethylation-associated silencing of gene expression has been shown for several genes regulating the growth and differentiation of hematopoietic cells , including the estrogen receptor ( ER ) gene , P15 , P16 and others .", "target_text": { "hematopoietic cells": "cell_type", "estrogen receptor ( ER ) gene": "DNA" } }, { "input_text": "Hypermethylation within the promoters of some genes appear to be an early event in the pathogenesis of neoplasia ( ER , P15 ) , while other genes seem to become methylated during the progression of leukemias ( HIC1 , c-abl ) .", "target_text": { "promoters": "DNA", "ER": "DNA", "P15": "DNA" } }, { "input_text": "The high prevalence of promoter methylation suggests that this molecular abnormality can be used to monitor disease activity during therapy .", "target_text": {} }, { "input_text": "In addition , new technology allows the sensitive identification of gene hypermethylation in a background of normal cells , suggesting possible new strategies for the detection of minimal residual disease .", "target_text": { "normal cells": "cell_type" } }, { "input_text": "Finally , reactivation of tumor-suppressor gene expression through pharmacologic inhibition of DNA methyltransferase and resultant DNA demethylation appears to be a promising new avenue of therapy in acute leukemia .", "target_text": { "DNA methyltransferase": "protein" } }, { "input_text": "Redox regulation of the mitogen-activated protein kinase pathway during lymphocyte activation .", "target_text": { "mitogen-activated protein kinase": "protein" } }, { "input_text": "We have previously demonstrated an obligatory requirement for intracellular reactive oxygen species generation during T lymphocyte activation , and have proposed that intracellular reactive oxygen species may act as signalling agents in the regulation of certain cellular processes , for example , during cell cycle entry .", "target_text": {} }, { "input_text": "To test this hypothesis , we have been interested to determine which , if any , cell cycle entry events are affected by oxidative signalling .", "target_text": {} }, { "input_text": "In earlier studies , we have identified the transcription factors NF-kappa B and AP-1 as molecular targets for oxidative signalling processes during cell cycle entry , and have shown that oxidative signalling is involved in the regulation of early changes in gene expression during the G0 to G1 phase transition .", "target_text": { "transcription factors": "protein", "NF-kappa B": "protein", "AP-1": "protein" } }, { "input_text": "To extend these initial observations , we have examined the effect of antioxidant treatment on the activity of the mitogen-activated protein kinases erk1 and erk2 , as members of a signal transduction pathway known to directly regulate transcription factor function .", "target_text": { "mitogen-activated protein kinases": "protein", "erk1": "protein", "erk2": "protein" } }, { "input_text": "Using as a probe cysteamine , an aminothiol compound with both antioxidant and antiproliferative activity , we have identified erk2 , a key element of the MAP kinase pathway , as being responsive to oxidative signalling during lymphocyte activation .", "target_text": { "erk2": "protein" } }, { "input_text": "These observations provide further evidence to suggest a role for intracellular oxidant generation as a regulatory mechanism during cell cycle entry , and establish a link between oxidative signalling and other aspects of the intracellular signalling network that is activated in response to mitogenic stimulation .", "target_text": {} }, { "input_text": "Physical and functional interaction between the human T-cell lymphotropic virus type 1 Tax1 protein and the CCAAT binding protein NF-Y .", "target_text": { "human T-cell lymphotropic virus type 1 Tax1 protein": "protein", "CCAAT binding protein": "protein", "NF-Y": "protein" } }, { "input_text": "Tax1 , a potent activator of human T-cell lymphotropic virus type 1 ( HTLV-1 ) transcription , has been shown to modulate expression of many cellular genes .", "target_text": { "Tax1": "protein", "cellular genes": "DNA" } }, { "input_text": "Tax1 does not bind DNA directly but regulates transcription through protein-protein interactions with sequence-specific transcription factors .", "target_text": { "Tax1": "protein", "transcription factors": "protein", "sequence-specific transcription factors": "protein" } }, { "input_text": "Using the yeast two-hybrid system to screen for proteins which interact with Tax1 , we isolated the B subunit of the CCAAT binding protein NF-Y from a HeLa cDNA library .", "target_text": { "Tax1": "protein", "B subunit": "protein", "CCAAT binding protein": "protein", "NF-Y": "protein", "HeLa cDNA library": "DNA" } }, { "input_text": "The interaction of Tax1 with NF-YB was specific in that NF-YB did not interact with a variety of other transcription factors , including human immunodeficiency virus Tat , human papillomavirus E6 , and Bicoid , or with the M7 ( amino acids 29CP-AS ) Tax1 mutant .", "target_text": { "Tax1": "protein", "NF-YB": "protein", "transcription factors": "protein", "human immunodeficiency virus Tat": "protein", "human papillomavirus E6": "protein", "Bicoid": "protein", "M7 ( amino acids 29CP-AS ) Tax1 mutant": "protein" } }, { "input_text": "However , NF-YB did interact with the C-terminal Tax1 mutants M22 ( 130TL-AS ) and M47 ( 319LL-RS ) .", "target_text": { "NF-YB": "protein", "Tax1": "protein", "C-terminal Tax1 mutants": "protein", "M22": "protein", "130TL-AS": "protein", "M47": "protein", "319LL-RS": "protein" } }, { "input_text": "We also show that in vitro-translated NF-YB specifically bound to a glutathione S-transferase- Tax1 fusion protein .", "target_text": { "NF-YB": "protein", "Tax1": "protein", "glutathione S-transferase- Tax1 fusion protein": "protein" } }, { "input_text": "Further , Tax1 coimmunoprecipitated with NF-Y from nuclear extracts of HTLV-1-transformed cells , providing evidence for in vivo interaction of Tax1 and NF-YB .", "target_text": { "Tax1": "protein", "NF-Y": "protein", "HTLV-1-transformed cells": "cell_type", "NF-YB": "protein" } }, { "input_text": "We further demonstrate that Tax1 specifically activated the NF-Y -responsive DQbeta promoter , as well as a minimal promoter which contains only the Y-box element .", "target_text": { "Tax1": "protein", "NF-Y": "protein", "NF-Y -responsive DQbeta promoter": "DNA", "minimal promoter": "DNA", "Y-box element": "DNA" } }, { "input_text": "In addition , mutation of the Y-box element alone abrogated Tax1 -mediated activation .", "target_text": { "Y-box element": "DNA", "Tax1": "protein" } }, { "input_text": "Taken together , these data indicate that Tax1 interacts with NF-Y through the B subunit and that this interaction results in activation of the major histocompatibility complex class II promoter .", "target_text": { "Tax1": "protein", "NF-Y": "protein", "B subunit": "protein", "major histocompatibility complex class II promoter": "DNA" } }, { "input_text": "Through activation of this and other NF-Y driven promoters , the Tax1 -NF-Y interaction may play a critical role in causing cellular transformation and HTLV-1 pathogenesis .", "target_text": { "NF-Y": "protein", "promoters": "DNA", "Tax1": "protein", "-NF-Y": "protein" } }, { "input_text": "High levels of the DNA-binding activity of E2F in adult T-cell leukemia and human T-cell leukemia virus type I -infected cells : possible enhancement of DNA-binding of E2F by the human T-cell leukemia virus I transactivating protein , Tax .", "target_text": { "E2F": "protein", "human T-cell leukemia virus type I -infected cells": "cell_type", "human T-cell leukemia virus I transactivating protein": "protein", "Tax": "protein" } }, { "input_text": "Transcription factor E2F binds to cellular promoters of certain growth- and cell cycle- controlling genes and forms distinct heteromeric complexes with other nuclear proteins .", "target_text": { "Transcription factor": "protein", "E2F": "protein", "cellular promoters": "DNA", "heteromeric complexes": "protein", "nuclear proteins": "protein" } }, { "input_text": "It has therefore been proposed that E2F is involved in cellular proliferation control .", "target_text": { "E2F": "protein" } }, { "input_text": "Human T-cell leukemia virus type I ( HTLV-I ) is an etiological agent of adult T-cell leukemia ( ATL ) .", "target_text": {} }, { "input_text": "We show here by mobility-shift assay that E2F -containing DNA-binding complexes were detected in HTLV-I -infected T-cell lines and leukemic cells obtained from ATL patients but not in an uninfected T-cell line , Jurkat , and normal peripheral blood mononuclear cells .", "target_text": { "E2F": "protein", "E2F -containing DNA-binding complexes": "protein", "HTLV-I -infected T-cell lines": "cell_line", "leukemic cells": "cell_type", "uninfected T-cell line": "cell_line", "Jurkat": "cell_line", "normal peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "The Tax protein , encoded by HTLV-I , is a potent transcription activator of viral and several cellular genes .", "target_text": { "Tax": "protein", "Tax protein": "protein", "cellular genes": "DNA" } }, { "input_text": "We demonstrate that expression of Tax can induce the E2F -containing DNA-binding complexes in Jurkat T cells .", "target_text": { "Tax": "protein", "E2F": "protein", "E2F -containing DNA-binding complexes": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "Thus , Tax , through enhancement of the DNA-binding activity of E2F , may be capable of regulating cellular gene expression implicated in the proliferation and transformation of T cells in ATL .", "target_text": { "Tax": "protein", "E2F": "protein", "T cells": "cell_type" } }, { "input_text": "This activity may be relevant to the mechanisms whereby HTLV-I which does not contain oncogenes induces neoplasia .", "target_text": { "oncogenes": "DNA" } }, { "input_text": "Dissociation of the Jak kinase pathway from G-CSF receptor signaling in neutrophils .", "target_text": { "Jak kinase": "protein", "G-CSF receptor": "protein" } }, { "input_text": "Activation of the granulocyte colony-stimulating factor receptor ( G-CSFR ) induces rapid tyrosine phosphorylation of multiple intracellular substrates in proliferating cells and nonproliferating , terminally differentiated neutrophils .", "target_text": { "granulocyte colony-stimulating factor receptor": "protein", "G-CSFR": "protein", "intracellular substrates": "protein", "proliferating cells": "cell_type", "nonproliferating , terminally differentiated neutrophils": "cell_type" } }, { "input_text": "The kinases that couple ligand binding to tyrosine phosphorylation of cellular substrates by the G-CSFR with activation of specific functional programs are largely unknown .", "target_text": { "cellular substrates": "protein" } }, { "input_text": "In this study , we examined early signaling events in proliferating and terminally differentiated cells following G-CSF stimulation to determine whether identical signaling cascades are activated .", "target_text": { "proliferating": "cell_type", "terminally differentiated cells": "cell_type", "G-CSF": "protein" } }, { "input_text": "In murine Ba/F3 cells transfected with the human G-CSFR and NFS-60 cells constitutively expressing the murine G-CSFR , G-CSF induced tyrosine phosphorylation and activation of Jak1 , Jak2 , and Tyk2 .", "target_text": { "murine Ba/F3 cells": "cell_line", "human G-CSFR": "protein", "NFS-60 cells": "cell_line", "murine G-CSFR": "protein", "G-CSF": "protein", "Jak1": "protein", "Jak2": "protein", "Tyk2": "protein" } }, { "input_text": "Tyrosine phosphorylation of Stat3 and , to a lesser extent , Stat1 was also detected following G-CSF stimulation .", "target_text": { "Stat3": "protein", "Stat1": "protein", "G-CSF": "protein" } }, { "input_text": "Using a mitogenically incompetent human G-CSFR mutant in which Pro639 and Pro641 were substituted by alanine , the box 1 PDP motif was found to be required for activation of Jak kinases , tyrosine phosphorylation of the G-CSFR , and recruitment of Stat proteins .", "target_text": { "human G-CSFR": "protein", "mitogenically incompetent human G-CSFR mutant": "protein", "box 1 PDP motif": "protein", "Jak kinases": "protein", "G-CSFR": "protein", "Stat proteins": "protein" } }, { "input_text": "Notably , no activation of Jak1 , Jak2 , Tyk2 , Stat1 , or Stat3 was observed in neutrophils following G-CSF stimulation .", "target_text": { "Jak1": "protein", "Jak2": "protein", "Tyk2": "protein", "Stat1": "protein", "Stat3": "protein", "neutrophils": "cell_type", "G-CSF": "protein" } }, { "input_text": "In addition , there was no detectable activation in neutrophils of the recently cloned Jak3 kinase , which has been reported to be expressed at high levels as myeloid cells undergo terminal neutrophilic maturation .", "target_text": { "neutrophils": "cell_type", "Jak3 kinase": "protein", "myeloid cells": "cell_type" } }, { "input_text": "These results indicate a lack of involvement of Jak kinases in signaling by the G-CSFR in neutrophils , and suggest utilization of alternative signal transduction pathways distinct from those in proliferating cells .", "target_text": { "Jak kinases": "protein", "G-CSFR": "protein", "neutrophils": "cell_type", "proliferating cells": "cell_type" } }, { "input_text": "Activation of the Jak -Stat pathway correlates with proliferative signaling by the G-CSFR and requires the membrane-proximal box 1 PXP motif , which is conserved in members of the cytokine receptor superfamily .", "target_text": { "Jak": "protein", "-Stat": "protein", "G-CSFR": "protein", "membrane-proximal box 1 PXP motif": "protein", "cytokine receptor superfamily": "protein" } }, { "input_text": "Impaired induction of c-fos/c-jun genes and of transcriptional regulatory proteins binding distinct c-fos/c-jun promoter elements in activated human T cells during aging .", "target_text": { "c-fos/c-jun genes": "DNA", "transcriptional regulatory proteins": "protein", "c-fos/c-jun promoter elements": "DNA", "activated human T cells": "cell_type" } }, { "input_text": "The activation of transcriptional factor c-Fos/c-Jun AP-1 is essential for normal T cell responsiveness and is often impaired in T cells during aging .", "target_text": { "transcriptional factor": "protein", "AP-1": "protein", "T cell": "cell_type", "T cells": "cell_type" } }, { "input_text": "In the present study , we investigated whether aberrancies in the regulation of c-fos/c-jun at the mRNA or protein level might underlie the age-associated impairments of AP-1 in human T cells .", "target_text": { "c-fos/c-jun": "DNA", "AP-1": "protein", "human T cells": "cell_type" } }, { "input_text": "Whereas T cells from young subjects stimulated with cross-linked anti-CD3epsilon mAb OKT3 plus PMA or with the lectin PHA plus PMA demonstrated considerable increases in c-Fos protein expression , the expression of c-Fos but not c-Jun was markedly reduced in stimulated T cells from certain elderly subjects .", "target_text": { "T cells": "cell_type", "cross-linked anti-CD3epsilon mAb": "protein", "OKT3": "protein", "lectin": "protein", "PHA": "protein", "c-Fos": "protein", "c-Jun": "protein" } }, { "input_text": "In addition , RNase protection assays revealed that anti-CD3/ PMA -stimulated T cells from a substantial proportion of elderly subjects exhibited decreased levels of c-fos and/or c-jun mRNA compared to T cells from young subjects .", "target_text": { "RNase": "protein", "PMA -stimulated T cells": "cell_type", "T cells": "cell_type" } }, { "input_text": "Using electrophoretic mobility shift assays , the levels of nuclear regulatory proteins recognizing the AP-1 consensus TRE motif , the proximal c-jun TRE-like promoter element , and the c-fos serum response element ( SRE ) were determined in resting and stimulated T cells .", "target_text": { "nuclear regulatory proteins": "protein", "AP-1": "protein", "AP-1 consensus TRE motif": "DNA", "proximal c-jun TRE-like promoter element": "DNA", "c-fos serum response element": "DNA", "SRE": "DNA" } }, { "input_text": "Although the stimulation of T cells from young subjects resulted in coordinated increases of nuclear protein complexes binding the AP-1 TRE , c-jun TRE , and c-fos SRE DNA sequence motifs , age-related reductions in the activation of AP-1 were accompanied by decreased levels of c-jun TRE and c-fos SRE binding complexes .", "target_text": { "T cells": "cell_type", "nuclear protein complexes": "protein", "AP-1": "protein", "AP-1 TRE": "DNA", "c-jun TRE": "DNA", "SRE": "DNA", "c-fos SRE DNA sequence motifs": "DNA" } }, { "input_text": "Furthermore , the nuclear protein complexes binding the SRE motif induced in activated T cells of young and elderly subjects contained serum response factor and Elk-1 pointing toward age-related defects in the activation of transcriptional regulatory proteins distinct from c-jun/ AP-1 .", "target_text": { "nuclear protein complexes": "protein", "SRE": "DNA", "SRE motif": "DNA", "activated T cells": "cell_type", "serum response factor": "protein", "Elk-1": "protein", "transcriptional regulatory proteins": "protein", "AP-1": "protein", "c-jun/ AP-1": "protein" } }, { "input_text": "These results suggest that underlying aberrancies in the induction of c-fos/c-jun as well as their nuclear regulatory proteins may contribute to the age-related impairments of AP-1 activation in human T cells .", "target_text": { "c-fos/c-jun": "DNA", "nuclear regulatory proteins": "protein", "AP-1": "protein", "human T cells": "cell_type" } }, { "input_text": "Retinoic acid -induced modulation of IL-2 mRNA production and IL-2 receptor expression on T cells .", "target_text": { "IL-2": "protein", "IL-2 mRNA": "RNA", "T cells": "cell_type" } }, { "input_text": "BACKGROUND : Retinoic acid ( RA ) has important immune-modulating effects on both T and B cell function .", "target_text": {} }, { "input_text": "Our laboratory has shown that RA can enhance in vitro polyclonal B cell immunoglobulin ( Ig ) response .", "target_text": { "immunoglobulin": "protein" } }, { "input_text": "Investigating cytokines known to affect B cell differentiation , we have recently shown that IL-6 production is augmented by RA .", "target_text": { "cytokines": "protein", "IL-6": "protein" } }, { "input_text": "In the present study we have examined the immune modulating effects of RA on IL-2 mRNA , another important cytokine for B cell immunoglobulin production , the expression of IL-2 receptors on T cells , and the RA nuclear receptors .", "target_text": { "IL-2": "protein", "IL-2 mRNA": "RNA", "cytokine": "protein", "immunoglobulin": "protein", "IL-2 receptors": "protein", "T cells": "cell_type", "RA nuclear receptors": "protein" } }, { "input_text": "METHODS : Purified T cells were obtained from adenoidal tissues , and incubated with RA ( 10(-7) M ) or DMSO solvent/media control for 0 , 6-8 , and 24 h .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Total mRNA was extracted from T cells , and using RT-PCR , changes in the production of IL-2 and RA receptors ( RAR ) - alpha , beta , gamma mRNA were determined .", "target_text": { "mRNA": "RNA", "T cells": "cell_type", "IL-2": "protein", "RA receptors": "protein", "RAR": "protein", "alpha": "RNA", "beta": "RNA", "gamma mRNA": "RNA" } }, { "input_text": "The effects of RA on IL-2-alpha receptor expression was determined by flow cytometry on T cells .", "target_text": { "T cells": "cell_type" } }, { "input_text": "CONCLUSION : These studies suggest that RA can augment IL-2 mRNA production by T cells with a possible paracrine effect on IL-2R-alpha expression .", "target_text": { "IL-2": "protein", "IL-2 mRNA": "RNA", "T cells": "cell_type", "IL-2R-alpha": "protein" } }, { "input_text": "These changes appear to be mediated by RAR-alpha .", "target_text": { "RAR-alpha": "protein" } }, { "input_text": "Thus , IL-2 may be another important cytokine modulated by RA in the immune response .", "target_text": { "IL-2": "protein", "cytokine": "protein" } }, { "input_text": "Involvement of an SAF-like transcription factor in the activation of serum amyloid A gene in monocyte/macrophage cells by lipopolysaccharide .", "target_text": { "SAF-like transcription factor": "protein", "serum amyloid A gene": "DNA", "monocyte/macrophage cells": "cell_type" } }, { "input_text": "Serum amyloid A ( SAA ) has been linked to atherosclerosis because of its ability to remodel high-density lipoprotein by the depletion of apolipoprotein A1 , its ability to bind cholesterol , and its presence in the atherosclerotic plaques of coronary and carotid arteries .", "target_text": { "Serum amyloid A": "protein", "SAA": "protein" } }, { "input_text": "In the present study , we investigated the induction mechanism of SAA gene in THP-1 monocyte/macrophage cells which play a critical role in the development of atherosclerotic fatty streak and plaque formation .", "target_text": { "SAA": "protein", "SAA gene": "DNA", "monocyte/macrophage cells": "cell_type", "THP-1 monocyte/macrophage cells": "cell_line" } }, { "input_text": "We and others have shown that SAA gene is induced in monocyte/macrophage cells by lipopolysaccharide ( LPS ) .", "target_text": { "SAA": "protein", "monocyte/macrophage cells": "cell_type" } }, { "input_text": "By promoter function analysis , we show that the SAA promoter sequence between -280 and -226 can confer LPS responsiveness .", "target_text": { "SAA": "protein", "SAA promoter sequence": "DNA" } }, { "input_text": "Gel electrophoretic mobility shift assay detected an induced DNA-binding activity in these cells in response to LPS .", "target_text": {} }, { "input_text": "Characterization of the DNA-binding protein by UV cross-linking , Southwestern blot , and antibody ablation/supershift assays revealed that it is similar to a recently reported nuclear factor designated SAF .", "target_text": { "DNA-binding protein": "protein", "nuclear factor": "protein", "SAF": "protein" } }, { "input_text": "These results demonstrated that LPS -mediated SAA gene induction in monocyte/macrophage cells is primarily due to the induction of SAF activity .", "target_text": { "SAA": "protein", "monocyte/macrophage cells": "cell_type", "SAF": "protein" } }, { "input_text": "Cytomegalovirus immediate early genes upregulate interleukin-6 gene expression .", "target_text": { "Cytomegalovirus immediate early genes": "DNA", "interleukin-6": "protein" } }, { "input_text": "BACKGROUND : The immediate early genes ( IE ) of human cytomegalovirus ( CMV ) can be expressed in monocytic cells and are known to regulate viral and cellular genes .", "target_text": { "immediate early genes": "DNA", "IE": "DNA", "monocytic cells": "cell_type" } }, { "input_text": "Interleukin-6 ( IL-6 ) plays a central role in numerous inflammatory and immune processes .", "target_text": { "Interleukin-6": "protein", "IL-6": "protein" } }, { "input_text": "Interleukin-6 levels are increased in lung transplant patients clinically diagnosed with CMV pneumonitis .", "target_text": { "Interleukin-6": "protein" } }, { "input_text": "The regulation of IL-6 is dependent on various stimuli that include lipopolysaccharide ( LPS ) , viruses , and other cytokines .", "target_text": { "IL-6": "protein", "cytokines": "protein" } }, { "input_text": "These studies examined the ability of CMV IE gene products to modulate IL-6 production .", "target_text": { "IL-6": "protein" } }, { "input_text": "METHODS : THP-1 cells , a monocytic cell line , were transfected with the CMV IE genes .", "target_text": { "THP-1 cells": "cell_line", "monocytic cell line": "cell_line", "CMV IE genes": "DNA" } }, { "input_text": "Interleukin-6 protein and IL-6 mRNA were measured in control and CMV immediate early transfected cells .", "target_text": { "Interleukin-6": "protein", "IL-6": "protein", "IL-6 mRNA": "RNA", "CMV immediate early transfected cells": "cell_type" } }, { "input_text": "Cotransfection of CMV IE genes and IL-6 chloramphenicol acetyl transferase ( CAT ) or IL-6 luciferase constructs were used to study IL-6 promoter activity .", "target_text": { "CMV IE genes": "DNA", "IL-6": "protein" } }, { "input_text": "RESULTS : Interleukin-6 protein and mRNA production were significantly increased in cells transfected with the CMV IE genes and stimulated with LPS compared to LPS -stimulated control cells .", "target_text": { "Interleukin-6": "protein", "Interleukin-6 protein": "protein", "CMV IE genes": "DNA", "LPS -stimulated control cells": "cell_line" } }, { "input_text": "Cytomegalovirus IE gene products significantly enhanced LPS stimulation of IL-6 promoter activity in both IL-6 CAT and IL-6 luciferase assays .", "target_text": { "Cytomegalovirus IE gene products": "protein", "IL-6": "protein", "IL-6 promoter": "DNA" } }, { "input_text": "A deletion construct that contains a NF-kappa B site but is missing the multiple response region demonstrated a continued increase in IL-6 luciferase activity in LPS -stimulated CMV transfected cells .", "target_text": { "NF-kappa B": "protein", "NF-kappa B site": "DNA", "IL-6": "protein", "luciferase": "protein", "LPS -stimulated CMV transfected cells": "cell_line" } }, { "input_text": "CONCLUSION : Cytomegalovirus immediate early gene products significantly enhanced expression of IL-6 in LPS -stimulated cells .", "target_text": { "Cytomegalovirus immediate early gene products": "protein", "IL-6": "protein" } }, { "input_text": "The increase in IL-6 luciferase activity occurs in the absence of the multiple response region , the area of the IL-6 promoter responsive to IL-1 , TNF alpha , cyclic amp , and phorbol 12-myristate 13-acetate .", "target_text": { "IL-6": "protein", "luciferase": "protein", "IL-6 promoter": "DNA", "IL-1": "protein", "TNF alpha": "protein" } }, { "input_text": "The ability of CMV IE gene products to enhance IL-6 production may play an important role in immune inflammatory states associated with CMV infection .", "target_text": { "CMV IE gene products": "protein", "IL-6": "protein" } }, { "input_text": "Induction of relA ( p65 ) and I kappa B alpha subunit expression during differentiation of human peripheral blood monocytes to macrophages .", "target_text": { "relA ( p65 )": "protein", "I kappa B alpha subunit": "protein", "human peripheral blood monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "We evaluated the expression and DNA binding activity of nuclear factor ( NF ) -kappa B subunits in human peripheral blood monocytes and in monocyte-derived macrophages ( MDMs ) .", "target_text": { "nuclear factor ( NF ) -kappa B subunits": "protein", "human peripheral blood monocytes": "cell_type", "macrophages": "cell_type", "monocyte-derived macrophages": "cell_type", "MDMs": "cell_type" } }, { "input_text": "Constitutive DNA binding activity consisting of p50 homodimers was detected in nuclear extracts from both cell types .", "target_text": { "p50 homodimers": "protein" } }, { "input_text": "An additional complex composed of p50/RelA ( p65 ) heterodimers appeared only in nuclear extracts from 7-day MDMs .", "target_text": { "p50/RelA ( p65 ) heterodimers": "protein", "MDMs": "cell_type" } }, { "input_text": "Immunoblot analysis showed that the p50 subunit was constitutively expressed in monocytes and MDMs .", "target_text": { "monocytes": "cell_type", "MDMs": "cell_type" } }, { "input_text": "In contrast , the RelA ( p65 ) subunit was barely detectable in monocytes , but its level increased markedly in MDMs .", "target_text": { "RelA ( p65 ) subunit": "protein", "monocytes": "cell_type", "MDMs": "cell_type" } }, { "input_text": "Analysis of RelA ( p65 ) mRNA revealed that the stability of RelA ( p65 ) mRNA was significantly higher in MDMs , compared with monocytes .", "target_text": { "RelA ( p65 ) mRNA": "RNA", "MDMs": "cell_type", "monocytes": "cell_type" } }, { "input_text": "In MDMs , an upregulation of I kappa B alpha synthesis as well as the appearance of a novel M(r) 40,000 form of I kappa B alpha were also observed .", "target_text": { "MDMs": "cell_type", "I kappa B alpha": "protein" } }, { "input_text": "These results suggest that macrophage differentiation results in the expression of active p50/RelA ( p65 ) heterodimers with the capacity to activate target gene expression .", "target_text": { "p50/RelA ( p65 ) heterodimers": "protein" } }, { "input_text": "The parallel induction of I kappa B alpha synthesis may allow for the continuous presence of a cytoplasmic reservoir of p50/RelA ( p65 ) complexes that are readily available for inducer-mediated stimulation .", "target_text": { "I kappa B alpha": "protein", "p50/RelA ( p65 ) complexes": "protein" } }, { "input_text": "Nuclear Rel-A and c-Rel protein complexes are differentially distributed within human thymocytes .", "target_text": { "human thymocytes": "cell_type" } }, { "input_text": "Nuclear factor-kappa B ( NF-kappa B ) /Rel proteins are inducible transcriptional regulators of numerous cellular genes .", "target_text": { "NF-kappa B": "protein", "Nuclear factor-kappa B ( NF-kappa B ) /Rel proteins": "protein", "transcriptional regulators": "protein", "cellular genes": "DNA" } }, { "input_text": "They are particularly abundant in lymphoid tissues and are thought to be critical for the transcription of genes involved in immune and inflammatory responses .", "target_text": {} }, { "input_text": "We have reported previously that a nuclear NF-kappa B activity was present in freshly extracted human thymocytes in the absence of in vitro treatment of these cells .", "target_text": { "NF-kappa B": "protein", "human thymocytes": "cell_type" } }, { "input_text": "In the present report , we identified NF-kappa B proteins extracted from human thymocyte nuclei as being p50/p65 and p50/c-Rel complexes .", "target_text": { "NF-kappa B": "protein", "NF-kappa B proteins": "protein" } }, { "input_text": "Immunochemical and immunofluorescent staining of thymus sections using specific Abs allowed visualization of nuclear NF-kappa B proteins in both thymocytes and nonthymocyte cells .", "target_text": { "specific Abs": "protein", "NF-kappa B": "protein", "nuclear NF-kappa B proteins": "protein", "thymocytes": "cell_type", "nonthymocyte cells": "cell_type" } }, { "input_text": "This detection suggested a preferential activation of p50/c-Rel in medullary thymocytes , whereas p50/p65 was present in both cortical and medullary regions of human thymus lobules .", "target_text": { "p50/c-Rel": "protein", "thymocytes": "cell_type", "medullary thymocytes": "cell_type", "p50/p65": "protein" } }, { "input_text": "However , the intensity of p65 labeling was much higher in several thymocytes from the medulla .", "target_text": { "p65": "protein", "thymocytes": "cell_type" } }, { "input_text": "p65 , p50 , and c-Rel activities were found in both CD4- and CD8- positive thymocytes .", "target_text": {} }, { "input_text": "These observations suggest that p65 and c-Rel complexes play distinct roles in gene expression and that both forms of NF-kappa B play critical roles during late stages of the intrathymic maturation of T cells .", "target_text": { "NF-kappa B": "protein", "T cells": "cell_type" } }, { "input_text": "ALY , a context-dependent coactivator of LEF-1 and AML-1 , is required for TCRalpha enhancer function .", "target_text": { "ALY": "protein", "context-dependent coactivator": "protein", "LEF-1": "protein", "AML-1": "protein", "TCRalpha enhancer": "DNA" } }, { "input_text": "LEF-1 is a transcription factor that participates in the regulation of the T-cell receptor alpha ( TCR alpha ) enhancer by facilitating the assembly of multiple proteins into a higher order nucleoprotein complex .", "target_text": { "LEF-1": "protein", "T-cell receptor alpha ( TCR alpha ) enhancer": "DNA", "multiple proteins": "protein", "nucleoprotein complex": "protein" } }, { "input_text": "The function of LEF-1 is dependent , in part , on the HMG domain that induces a sharp bend in the DNA helix , and on an activation domain that stimulates transcription only in a specific context of other enhancer-binding proteins .", "target_text": { "LEF-1": "protein", "HMG domain": "protein", "activation domain": "protein", "enhancer-binding proteins": "protein" } }, { "input_text": "With the aim of gaining insight into the function of context-dependent activation domains , we cloned ALY , a novel LEF-1 -interacting protein .", "target_text": { "context-dependent activation domains": "protein", "ALY": "protein", "LEF-1": "protein", "LEF-1 -interacting protein": "protein" } }, { "input_text": "ALY is a ubiquitously expressed , nuclear protein that specifically associates with the activation domains of LEF-1 and AML-1 ( CBF alpha2 , PEBP2 alpha ( B ) , which is another protein component of the TCR alpha enhancer complex .", "target_text": { "ALY": "protein", "activation domains": "protein", "LEF-1": "protein", "AML-1": "protein", "CBF alpha2": "protein", "PEBP2 alpha": "protein", "TCR alpha enhancer complex": "protein" } }, { "input_text": "In addition , ALY can increase DNA binding by both LEF-1 and AML proteins .", "target_text": { "ALY": "protein", "LEF-1": "protein", "AML proteins": "protein" } }, { "input_text": "Overexpression of ALY stimulates the activity of the TCR alpha enhancer complex reconstituted in transfected nonlymphoid HeLa cells , whereas down-regulation of ALY by anti-sense oligonucleotides virtually eliminates TCR alpha enhancer activity in T cells .", "target_text": { "ALY": "protein", "TCR alpha enhancer complex": "protein", "transfected nonlymphoid HeLa cells": "cell_line", "TCR alpha enhancer": "DNA", "T cells": "cell_type" } }, { "input_text": "Similar to LEF-1 , ALY can stimulate transcription in the context of the TCR alpha enhancer but apparently not when tethered to DNA through an heterologous DNA-binding domain .", "target_text": { "LEF-1": "protein", "ALY": "protein", "TCR alpha enhancer": "DNA", "heterologous DNA-binding domain": "protein" } }, { "input_text": "We propose that ALY mediates context-dependent transcriptional activation by facilitating the functional collaboration of multiple proteins in the TCR alpha enhancer complex .", "target_text": { "ALY": "protein", "multiple proteins": "protein", "TCR alpha enhancer": "DNA", "TCR alpha enhancer complex": "protein" } }, { "input_text": "AML1a but not AML1b inhibits erythroid differentiation induced by sodium butyrate and enhances the megakaryocytic differentiation of K562 leukemia cells .", "target_text": { "AML1a": "protein", "AML1b": "protein", "K562 leukemia cells": "cell_type" } }, { "input_text": "AML1 may play a role in growth and differentiation of cells along erythroid and/or megakaryocytic lineages , because a significant level of the AML1 gene is expressed in these cells .", "target_text": { "AML1": "protein" } }, { "input_text": "We overexpressed AML1a ( without the transcription-activating domain ) and AML1b ( with the domain ) proteins in K562 leukemia cells , which can be induced to differentiate into hemoglobin-producing cells and megakaryocytes .", "target_text": { "AML1a": "protein", "transcription-activating domain": "protein", "AML1b": "protein", "K562 leukemia cells": "cell_type", "hemoglobin-producing cells": "cell_type", "megakaryocytes": "cell_type" } }, { "input_text": "The AML1a -transfected K562 cells had a reduced capacity to differentiate in the presence of sodium n-butyrate but not in the presence of other inducers , such as hemin , 1-beta-D-arabinofuranosylcytosine , and herbimycin A .", "target_text": { "AML1a": "protein", "AML1a -transfected K562 cells": "cell_line" } }, { "input_text": "The AML1 antisense oligodeoxynucleotide but not the sense oligomer recovered its differentiation-inducing capacity in the presence of butyrate .", "target_text": { "AML1": "protein" } }, { "input_text": "On the other hand , AML1b conferred a similar differentiation-inducing capacity upon K562 cells transfected with vector alone .", "target_text": { "AML1b": "protein", "K562 cells": "cell_line" } }, { "input_text": "AML1a expression was associated with enhanced sensitivity to megakaryocytic differentiation induced by phorbol ester .", "target_text": { "AML1a": "protein" } }, { "input_text": "These results provide evidence that AML1 proteins play a role in erythroid and megakaryocytic differentiation .", "target_text": { "AML1": "protein" } }, { "input_text": "Identification of sequence alterations in the upstream regulatory region of the estrogen receptor gene in an ER-negative breast cancer cell line .", "target_text": { "upstream regulatory region": "DNA", "estrogen receptor gene": "DNA", "ER-negative breast cancer cell line": "cell_line" } }, { "input_text": "Given the important role of the estrogen receptor ( ER ) in the development and physiology of the breast , it is essential to delineate the mechanisms responsible for its failed expression in some breast tumors .", "target_text": { "estrogen receptor": "protein", "ER": "protein" } }, { "input_text": "We have cloned and sequenced a portion of the ER upstream regulatory region from the ER -positive MCF-7 and the ER -negative MDA-MB-231 breast cancer cell lines to determine if sequence alterations in this region account for the ER -negative phenotype of some tumors .", "target_text": { "ER": "protein", "upstream regulatory region": "DNA", "ER -positive MCF-7": "cell_line", "ER -negative MDA-MB-231 breast cancer cell lines": "cell_line" } }, { "input_text": "From this , we identified a number of variations between the sequences , two of which were determined to be associated with a 50 % decrease in CAT activity .", "target_text": { "CAT": "protein" } }, { "input_text": "Suppression by azelastine hydrochloride of NF-kappa B activation involved in generation of cytokines and nitric oxide .", "target_text": { "NF-kappa B": "protein", "cytokines": "protein" } }, { "input_text": "The influence of the anti-allergy agent azelastine hydrochloride ( Azeptin ) on NF-kappa B activation associated with the generation of cytokines and nitric oxide ( NO ) was investigated in various kinds of human and mouse cells .", "target_text": { "NF-kappa B": "protein", "cytokines": "protein" } }, { "input_text": "Azeptin dose-dependently suppressed both DNA and protein synthesis in human gingival fibroblasts ( HF ) and also suppressed blastogenesis of human peripheral blood lymphocytes ( PBL ) . Generation of tumor necrosis factor-alpha , interleukin 1-beta , granulocyte-macrophage colony-stimulating factor and interleukin-6 from 10(-5) M Azeptin -treated PBL and human monocytes ( HM ) was decreased to approximately 1/3 to 2/3 of the control levels .", "target_text": { "human gingival fibroblasts": "cell_type", "HF": "cell_type", "human peripheral blood lymphocytes": "cell_type", "PBL": "cell_type", "tumor necrosis factor-alpha": "protein", "interleukin 1-beta": "protein", "granulocyte-macrophage colony-stimulating factor": "protein", "interleukin-6": "protein", "human monocytes": "cell_type", "HM": "cell_type" } }, { "input_text": "In parallel with the decreased cytokine generation , each cytokine mRNA was less expressed in the presence of 10(-5) M Azeptin .", "target_text": { "cytokine": "protein", "cytokine mRNA": "RNA" } }, { "input_text": "In addition , both inducible nitric oxide synthase -mRNA level and NO generation in mouse peritoneal macrophages were suppressed by 10(-5) M Azeptin .", "target_text": { "nitric oxide synthase": "protein", "mouse peritoneal macrophages": "cell_type" } }, { "input_text": "Being compatible with those results , Azeptin ( 10(-5) M ) suppressed activation of NF-kappa B in PBL , HM and HF .", "target_text": { "NF-kappa B": "protein", "PBL": "cell_type", "HF": "cell_type" } }, { "input_text": "These results appear to indicate that suppression of cytokine and NO generation by Azeptin results at least partially from the inhibition of NF-kappa B activation .", "target_text": { "cytokine": "protein", "NF-kappa B": "protein" } }, { "input_text": "Differential interaction of nuclear factors with the PRE-I enhancer element of the human IL-4 promoter in different T cell subsets .", "target_text": { "PRE-I enhancer element": "DNA", "human IL-4 promoter": "DNA", "T cell subsets": "cell_type" } }, { "input_text": "The immunomodulatory cytokine IL-4 affects cells of most hemopoietic lineages .", "target_text": { "cytokine": "protein", "IL-4": "protein", "hemopoietic lineages": "cell_type" } }, { "input_text": "IL-4 is secreted by activated Th2 but not Th1 cells and plays a major role in the immune response by modulating the differentiation of naive Th cells toward the Th2 phenotype .", "target_text": { "IL-4": "protein", "Th2": "cell_type", "Th1 cells": "cell_type", "naive Th cells": "cell_type", "Th2 phenotype": "cell_type" } }, { "input_text": "We have previously identified an enhancer element , PRE-I , that is essential for the function of the human IL-4 promoter .", "target_text": { "enhancer element": "DNA", "PRE-I": "DNA", "IL-4": "protein", "human IL-4 promoter": "DNA" } }, { "input_text": "To investigate the mechanisms responsible for tissue-specific expression of the IL-4 gene , we analyzed nuclear factors binding to the PRE-I site and compared the binding activities of these factors to the IL-4 promoter of Th1 and Th2 cells .", "target_text": { "IL-4": "protein", "nuclear factors": "protein", "PRE-I site": "DNA" } }, { "input_text": "We show that PRE-I interacts with PMA - and PMA / ionomycin -inducible , cyclosporin A -sensitive nuclear factors .", "target_text": { "PRE-I": "DNA", "nuclear factors": "protein" } }, { "input_text": "Using anti-C/EBPbeta ( NF-IL6 ) , anti-C/EBPdelta ( NF-IL6beta ) , anti-NF-ATc , anti-NF-ATp , anti-Fos , and anti-Jun Abs we demonstrate that the previously identified PRE-I binding factor POS-1 is composed of different transcription factors in different Th cell subsets .", "target_text": { "anti-C/EBPbeta": "protein", "NF-IL6": "protein", "anti-C/EBPdelta": "protein", "NF-IL6beta": "protein", "anti-NF-ATc": "protein", "anti-NF-ATp": "protein", "anti-Fos": "protein", "anti-Jun Abs": "protein", "PRE-I": "DNA", "PRE-I binding factor": "protein", "POS-1": "protein", "transcription factors": "protein" } }, { "input_text": "In the IL-4 -producing Th0-like human Jurkat and mouse EL-4 cells , POS-1 ( designated POS-1a ) contains NF-IL6beta and Jun .", "target_text": { "IL-4": "protein", "IL-4 -producing Th0-like human Jurkat": "cell_line", "mouse EL-4 cells": "cell_line", "POS-1": "protein", "POS-1a": "protein", "NF-IL6beta": "protein", "Jun": "protein" } }, { "input_text": "In the mouse Th2 D10 cells and in the human Th2 clones , POS-1 ( designated POS-1b ) contains NF-IL6beta , Jun , and NF-ATc/p .", "target_text": { "mouse Th2 D10 cells": "cell_line", "human Th2 clones": "cell_line", "POS-1": "protein", "POS-1b": "protein", "NF-IL6beta": "protein", "Jun": "protein", "NF-ATc/p": "protein" } }, { "input_text": "In contrast , POS-1 was not found in nuclear extracts of human Th1 clones .", "target_text": { "POS-1": "protein", "human Th1 clones": "cell_line" } }, { "input_text": "These findings suggest that PRE-I may play a role in the differential regulation of IL-4 gene expression levels .", "target_text": { "PRE-I": "DNA", "IL-4": "protein", "IL-4 gene": "DNA" } }, { "input_text": "Regulation of human epsilon germline transcription : role of B-cell-specific activator protein .", "target_text": { "germline": "DNA", "B-cell-specific activator protein": "protein" } }, { "input_text": "Germline transcripts initiate from promoters upstream of the immunoglobulin switch region , and are necessary to target the appropriate switch region for recombination and switching .", "target_text": { "Germline transcripts": "protein", "promoters": "DNA", "immunoglobulin switch region": "DNA" } }, { "input_text": "Different cytokines activate transcription at the appropriate germline promoter .", "target_text": { "cytokines": "protein", "germline promoter": "DNA" } }, { "input_text": "Because binding sites for B-cell-specific activator protein ( BSAP ) are located upstream of several switch regions in the immunoglobulin heavy chain gene cluster , BSAP might play a role in the regulation of germline transcription and isotype switching .", "target_text": { "binding sites": "DNA", "B-cell-specific activator protein": "protein", "BSAP": "protein", "immunoglobulin heavy chain gene cluster": "DNA", "germline": "DNA" } }, { "input_text": "We investigated whether BSAP plays a role in the transcriptional regulation of the epsilon germline promoter in human B cells .", "target_text": { "BSAP": "protein", "germline promoter": "DNA", "human B cells": "cell_type" } }, { "input_text": "Our results showed that BSAP plays a role in both IL-4 -dependent induction and CD40 -mediated upregulation of human epsilon germline transcription .", "target_text": { "BSAP": "protein", "IL-4": "protein", "CD40": "protein", "germline": "DNA" } }, { "input_text": "BSAP is unique among the transcription factors that regulate epsilon germline expression , because it is B cell specific , and is at the merging point of two signalling pathways that are critical for IgE switching .", "target_text": { "BSAP": "protein", "transcription factors": "protein", "germline": "DNA", "IgE": "protein" } }, { "input_text": "Experimental expression in mice and spontaneous expression in human SLE of polyomavirus T-antigen .", "target_text": { "polyomavirus T-antigen": "protein" } }, { "input_text": "A molecular basis for induction of antibodies to DNA and eukaryotic transcription factors .", "target_text": { "antibodies": "protein", "transcription factors": "protein", "eukaryotic transcription factors": "protein" } }, { "input_text": "We have previously demonstrated that experimental expression of the polyomavirus transcription factor T-antigen has the potential to induce anti-DNA antibodies in mice .", "target_text": { "polyomavirus transcription factor T-antigen": "protein", "anti-DNA antibodies": "protein" } }, { "input_text": "Two sets of independent evidences are presented here that demonstrate a biological relevance for this model .", "target_text": {} }, { "input_text": "First , we describe results demonstrating that mice inoculated with T-antigen-expressing plasmids produced antibodies , not only to T-antigen and DNA , but also to the DNA-binding eukaryotic transcription factors TATA-binding protein ( TBP ) , and to the cAMP-response-element-binding protein ( CREB ) .", "target_text": { "T-antigen-expressing plasmids": "DNA", "antibodies": "protein", "T-antigen": "protein", "transcription factors": "protein", "DNA-binding eukaryotic transcription factors": "protein", "TATA-binding protein": "protein", "TBP": "protein", "cAMP-response-element-binding protein": "protein", "CREB": "protein" } }, { "input_text": "Secondly , we investigated whether polyomavirus reactivation occurs in SLE patients , and whether antibodies to T-antigen , DNA , and to TBP and CREB are linked to such events .", "target_text": { "antibodies": "protein", "T-antigen": "protein", "DNA": "DNA", "TBP": "protein", "CREB": "protein" } }, { "input_text": "Both within and among these SLE patients , frequent polyomavirus reactivations were observed that could not be explained by certain rearrangements of the noncoding control regions , nor by corticosteroid treatment .", "target_text": {} }, { "input_text": "Linked to these events , antibodies to T-antigen , DNA , TBP , and CREB were detected , identical to what we observed in mice .", "target_text": { "antibodies": "protein", "T-antigen": "protein", "DNA": "DNA", "TBP": "protein", "CREB": "protein" } }, { "input_text": "Antibodies recognizing double-stranded DNA were confined to patients with frequent polyomavirus reactivations .", "target_text": {} }, { "input_text": "The results described here indicate that cognate interaction of B cells recognizing DNA or DNA-associated proteins and T cells recognizing T antigen had taken place as a consequence of complex formation between T ag and DNA in vivo in the context of polyomavirus reactivations .", "target_text": { "DNA-associated proteins": "protein", "T cells": "cell_type", "T antigen": "protein", "T ag": "protein", "DNA": "DNA" } }, { "input_text": "Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells .", "target_text": { "Jak3": "protein", "CD40": "protein", "B cells": "cell_type" } }, { "input_text": "CD40 is a receptor that is critical for the survival , growth , differentiation , and isotype switching of B lymphocytes .", "target_text": { "CD40": "protein", "B lymphocytes": "cell_type" } }, { "input_text": "Although CD40 lacks intrinsic tyrosine kinase activity , its ligation induces protein tyrosine phosphorylation , which is necessary for several CD40 -mediated events .", "target_text": { "CD40": "protein" } }, { "input_text": "We show that engagement of CD40 induces tyrosine phosphorylation and activation of Jak3 as well as of STAT3 .", "target_text": { "CD40": "protein", "Jak3": "protein", "STAT3": "protein" } }, { "input_text": "Jak3 is constitutively associated with CD40 , and this interaction requires a proline-rich sequence in the membrane-proximal region of CD40 .", "target_text": { "Jak3": "protein", "CD40": "protein", "proline-rich sequence": "protein", "membrane-proximal region": "protein" } }, { "input_text": "Deletion of this sequence abolishes the capacity of CD40 to induce expression of CD23 , ICAM-1 , and lymphotoxin-alpha genes in B cells .", "target_text": { "CD40": "protein", "CD23": "protein", "ICAM-1": "protein", "lymphotoxin-alpha genes": "DNA", "B cells": "cell_type" } }, { "input_text": "These results indicate that signaling through Jak3 is activated by CD40 and plays an important role in CD40 -mediated functions .", "target_text": { "Jak3": "protein", "CD40": "protein" } }, { "input_text": "Transcription factors required for lymphoid lineage commitment .", "target_text": { "Transcription factors": "protein" } }, { "input_text": "Intimate interactions between multipotential hemopoietic stem cells and their microenvironment work towards redefining the identity and the differentiative fate of these primitive cells .", "target_text": { "hemopoietic stem cells": "cell_type", "primitive cells": "cell_type" } }, { "input_text": "Molecular cues delivered by the microenvironment frequently act in an instructive fashion by initiating intracellular signaling pathways that ultimately target a select group of transcription factors .", "target_text": { "transcription factors": "protein" } }, { "input_text": "These transcriptional regulators in turn trigger a cascade of genetic changes that ultimately determine the course of the cells during differentiation .", "target_text": {} }, { "input_text": "Gene inactivation studies on the PU.1 , Ikaros and GATA-3 genes have revealed that their encoded factors are essential for the earliest commitment step into the B and T lymphoid lineages .", "target_text": {} }, { "input_text": "Interleukin-4 signaling in B lymphocytes from patients with X-linked severe combined immunodeficiency .", "target_text": { "Interleukin-4": "protein", "B lymphocytes": "cell_type" } }, { "input_text": "Interleukin-4 ( IL-4 ) is an important cytokine for B and T lymphocyte function and mediates its effects via a receptor that contains gammac .", "target_text": { "Interleukin-4": "protein", "IL-4": "protein", "gammac": "protein" } }, { "input_text": "B cells derived from patients with X-linked severe combined immunodeficiency ( X-SCID ) are deficient in gammac and provide a useful model in which to dissect the role of this subunit in IL-4 -mediated signaling .", "target_text": { "B cells": "cell_type", "IL-4": "protein" } }, { "input_text": "We found that although IL-4 stimulation of X-SCID B cells did not result in Janus tyrosine kinase-3 ( JAK3 ) phosphorylation , other IL-4 substrates including JAK1 and IRS-1 were phosphorylated .", "target_text": { "IL-4": "protein", "X-SCID B cells": "cell_type", "Janus tyrosine kinase-3": "protein", "JAK3": "protein", "IL-4 substrates": "protein", "JAK1": "protein", "IRS-1": "protein" } }, { "input_text": "Additionally , we detected signal transducers and activators of transcription 6 ( STAT6 ) tyrosine phosphorylation and DNA binding activity in X-SCID B cells with a wide range of gammac mutations .", "target_text": { "signal transducers and activators of transcription 6": "protein", "STAT6": "protein", "X-SCID B cells": "cell_type", "gammac": "protein" } }, { "input_text": "However , reconstitution of these X-SCID B cells with gammac enhanced IL-4 -mediated responses including STAT6 phosphorylation and DNA binding activity and resulted in increased CD23 expression .", "target_text": { "X-SCID B cells": "cell_type", "gammac": "protein", "IL-4": "protein", "STAT6": "protein", "CD23": "protein" } }, { "input_text": "Thus , gammac is not necessary to trigger IL-4 -mediated responses in B cells , but its presence is important for optimal IL-4 -signaling .", "target_text": { "gammac": "protein", "IL-4": "protein", "B cells": "cell_type" } }, { "input_text": "These results suggest that two distinct IL-4 signaling pathways exist .", "target_text": { "IL-4": "protein" } }, { "input_text": "Cell-to-cell contact activates the long terminal repeat of human immunodeficiency virus 1 through its kappaB motif .", "target_text": { "long terminal repeat": "DNA", "kappaB motif": "DNA" } }, { "input_text": "Cell-to-cell contact between peripheral blood lymphocytes and transfected human colonic carcinoma cell line HT29 activates transcription of the long terminal repeats ( LTR ) of human immunodeficiency virus .", "target_text": { "peripheral blood lymphocytes": "cell_type", "transfected human colonic carcinoma cell line HT29": "cell_line", "long terminal repeats": "DNA", "LTR": "DNA" } }, { "input_text": "HIV-1 LTR transcription is controlled by a complex array of virus-encoded and cellular proteins .", "target_text": { "HIV-1 LTR": "DNA" } }, { "input_text": "Using various constructs expressing a lacZ reporter gene under the control of the intact or three deleted forms of HIV-1 LTR , we obtained evidence that the kappaB regulatory elements located in the U3 region are involved in cell-to-cell activation of HIV-1 LTR .", "target_text": { "lacZ reporter gene": "DNA", "HIV-1 LTR": "DNA", "kappaB regulatory elements": "DNA", "U3 region": "DNA" } }, { "input_text": "Cell-to-cell contact activates in vitro binding of the nuclear factor kappaB ( NF-kappaB ) p50/p65 heterodimer to an HIV-1 kappaB oligonucleotide .", "target_text": { "nuclear factor kappaB": "protein", "NF-kappaB": "protein", "nuclear factor kappaB ( NF-kappaB ) p50/p65 heterodimer": "protein" } }, { "input_text": "Cell-to-cell contact activation of NF-kappaB was only partially inhibited by 100 microM pyrrolidine dithiocarbamate and was not correlated with a significant decrease of cellular inhibitor kappaB alpha .", "target_text": { "NF-kappaB": "protein", "cellular inhibitor kappaB alpha": "protein" } }, { "input_text": "NF-kappaB nuclear activation was not detectable before 1 h after cell contact and was dependent on protein synthesis .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Identification of nucleotide sequences that regulate transcription of the MCF13 murine leukemia virus long terminal repeat in activated T cells .", "target_text": { "nucleotide sequences": "DNA", "long terminal repeat": "DNA", "T cells": "cell_type" } }, { "input_text": "The region downstream of the enhancer ( DEN ) of the long terminal repeat of the mink cell focus-forming murine leukemia virus is important for viral pathogenicity .", "target_text": { "enhancer": "DNA", "DEN": "DNA", "long terminal repeat": "DNA" } }, { "input_text": "Another important activity of DEN is its control of transcription in activated T cells , and we have determined that an NF-kappaB site is critical for this activity .", "target_text": { "DEN": "DNA", "activated T cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "Possible role of nuclear factor-kappa B activity in germline C epsilon transcription in a human Burkitt lymphoma B cell line .", "target_text": { "nuclear factor-kappa B": "protein", "germline": "DNA", "human Burkitt lymphoma B cell line": "cell_line" } }, { "input_text": "Nuclear factor-kappa B ( NF-kappa B ) plays a broad role in gene regulation , but it is not evident whether NF-kappa B acts as a messenger system for germline C epsilon transcription .", "target_text": { "Nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "germline": "DNA" } }, { "input_text": "We report here that the signaling cascade triggered by interleukin-4 ( IL-4 ) or anti- CD40 monoclonal antibody ( mAb ) participates in NF-kappa B activation responsible for germline C epsilon transcription in a human Burkitt lymphoma B cell line , DND39 .", "target_text": { "interleukin-4": "protein", "IL-4": "protein", "CD40": "protein", "anti- CD40 monoclonal antibody": "protein", "mAb": "protein", "NF-kappa B": "protein", "germline": "DNA", "human Burkitt lymphoma B cell line": "cell_line", "DND39": "cell_line" } }, { "input_text": "Both IL-4 and anti- CD40 mAb induced activation of phosphatidylinositol 3-kinase ( PI3-kinase ) , translocation of a zeta isoform of protein kinase C , and nuclear expression of NF-kappa B .", "target_text": { "IL-4": "protein", "CD40": "protein", "CD40 mAb": "protein", "phosphatidylinositol 3-kinase": "protein", "PI3-kinase": "protein", "protein kinase C": "protein", "NF-kappa B": "protein" } }, { "input_text": "All such events were abrogated by treatment with LY294002 , a specific inhibitor of PI3-kinase .", "target_text": { "PI3-kinase": "protein" } }, { "input_text": "In addition , N-acetyl-L-cysteine ( NAC ) , a potent antioxidant , decreased NF-kappa B activation caused by IL-4 , anti- CD40 mAb , or their combination .", "target_text": { "NF-kappa B": "protein", "IL-4": "protein", "CD40": "protein", "anti- CD40 mAb": "protein" } }, { "input_text": "NAC was also effective in diminishing germline C epsilon transcription , and its potency was higher in cultures costimulated with IL-4 and anti- CD40 mAb than in those stimulated with IL-4 alone .", "target_text": { "germline": "DNA", "IL-4": "protein", "CD40": "protein", "anti- CD40 mAb": "protein" } }, { "input_text": "These results indicate that IL-4 and ligation of CD40 induce NF-kappa B expression via at least a mechanism dependent on the PI3-kinase pathway and suggest that NF-kappa B sensitive to NAC may play a role in regulating germline C epsilon transcription .", "target_text": { "IL-4": "protein", "CD40": "protein", "NF-kappa B": "protein", "PI3-kinase": "protein", "germline": "DNA" } }, { "input_text": "Differentiation of U-937 promonocytic cells by etoposide and ICRF-193 , two antitumour DNA topoisomerase II inhibitors with different mechanisms of action .", "target_text": { "U-937 promonocytic cells": "cell_line", "DNA topoisomerase II": "protein" } }, { "input_text": "We have compared the action on U-937 human promonocytic leukemia cells of two DNA topoisomerase II inhibitors , namely the epipodophyllotoxin etoposide and the bisdioxopiperazine ICRF-193 .", "target_text": { "U-937 human promonocytic leukemia cells": "cell_line", "DNA topoisomerase II": "protein" } }, { "input_text": "One hour pulse-treatment with 3 microM etoposide caused topoisomerase associated , primary DNA breakage , which was rapidly followed by apoptosis .", "target_text": { "topoisomerase": "protein" } }, { "input_text": "By contrast , these effects were not observed upon pulse-treatment with 6 microM ICRF-193 .", "target_text": {} }, { "input_text": "However , continuous treatments with subcytotoxic concentrations of etoposide ( 0.15 microM ) and ICRF-193 ( 0.3 microM ) produced several similar effects , namely decreased cell proliferation , accumulation of cells at G2 , increase in cell mass , and induction of differentiation .", "target_text": {} }, { "input_text": "Under these conditions , etoposide produced a biphasic activation of protein kinase C , which consisted in an early transient activation ( from hours 1 to 6 ) of the membrane-bound enzyme followed by a later activation ( hour 48 ) of the total , membrane-bound and cytosolic enzyme .", "target_text": { "protein kinase C": "protein", "membrane-bound enzyme": "protein" } }, { "input_text": "By contrast , ICRF-193 only provoked a late activation ( from hours 72 to 96 ) of the total enzyme .", "target_text": {} }, { "input_text": "When used at differentiation-inducing concentrations , both topoisomerase inhibitors caused a great stimulation of AP-1 binding activity , with maximum value at hour 12 in etoposide -treated cells and at hour 48 in ICRF-193 -treated cells .", "target_text": { "topoisomerase": "protein", "AP-1": "protein", "ICRF-193 -treated cells": "cell_type" } }, { "input_text": "By contrast , the binding activity of the NF-kappa ( B ) and EGR-1 transcription factors was little affected .", "target_text": { "NF-kappa ( B )": "protein", "EGR-1": "protein", "transcription factors": "protein" } }, { "input_text": "It is concluded that topoisomerase II inhibitors may induce the differentiation of promonocytic cells , independently of their capacity to cause DNA strand breaks .", "target_text": {} }, { "input_text": "However , there are other effects , such as the early activation of protein kinase C , which are probably derived from the production of primary DNA breakage by some anti- topoisomerase drugs .", "target_text": { "protein kinase C": "protein", "topoisomerase": "protein" } }, { "input_text": "GATA-1 DNA binding activity is down-regulated in late S phase in erythroid cells .", "target_text": { "GATA-1": "protein", "erythroid cells": "cell_type" } }, { "input_text": "We have set out to test a model for tissue-specific gene expression that relies on the early replication of expressed genes to sequester limiting activating transcription factors .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Using an erythroid cell line , we have tested the changes in the DNA binding activity of the lineage-restricted transcription factor GATA-1 through the cell cycle .", "target_text": { "erythroid cell line": "cell_line", "lineage-restricted transcription factor": "protein", "GATA-1": "protein" } }, { "input_text": "We find that GATA-1 activity is low in G1 , peaks in mid-S phase , and then decreases in G2/M .", "target_text": { "GATA-1": "protein" } }, { "input_text": "In contrast , the binding activities of two ubiquitous transcription factors , Oct1 and Sp1 , remain high in G2/M .", "target_text": { "transcription factors": "protein", "Oct1": "protein", "Sp1": "protein" } }, { "input_text": "GATA-1 protein and mRNA vary in a similar manner through the cell cycle , suggesting that the expression of the gene or the stability of its message is regulated .", "target_text": { "GATA-1": "protein", "mRNA": "RNA" } }, { "input_text": "Although a number of transcription factors involved in the control of the cell cycle or DNA replication have been shown to peak in S phase , this is the first example of a lineage-restricted transcription factor displaying S phase -specific DNA binding activity .", "target_text": { "transcription factors": "protein", "lineage-restricted transcription factor": "protein" } }, { "input_text": "One interpretation of these data leads to a model in which the peak in GATA-1 DNA binding amplifies the effect of early replication on the activation of erythroid-specific genes at the same time as preventing activation of non-erythroid genes containing GATA-responsive elements .", "target_text": { "GATA-1": "protein", "erythroid-specific genes": "DNA", "non-erythroid genes": "DNA", "GATA-responsive elements": "DNA" } }, { "input_text": "These results may also relate to recent data implicating GATA-1 function in apoptosis and cell cycle progression", "target_text": { "GATA-1": "protein" } }, { "input_text": "Activation of the NF-kappaB pathway by inflammatory stimuli in human neutrophils .", "target_text": { "NF-kappaB": "protein", "human neutrophils": "cell_type" } }, { "input_text": "Activated neutrophils have the ability to upregulate the expression of many genes , in particular those encoding cytokines and chemokines , and to subsequently release the corresponding proteins .", "target_text": { "Activated neutrophils": "cell_type", "cytokines": "protein", "chemokines": "protein" } }, { "input_text": "Although little is known to date concerning the regulation of gene transcription in neutrophils , it is noteworthy that many of these genes depend on the activation of transcription factors , such as NF-kappaB , for inducible expression .", "target_text": { "neutrophils": "cell_type", "transcription factors": "protein", "NF-kappaB": "protein" } }, { "input_text": "We therefore investigated whether NF-kappaB /Rel proteins are expressed in human neutrophils , as well as their fate on cell activation .", "target_text": { "NF-kappaB": "protein", "NF-kappaB /Rel proteins": "protein", "neutrophils": "cell_type", "human neutrophils": "cell_type" } }, { "input_text": "We now report that dimers consisting of p50 NFkappaB1 , p65 RelA , and/or c-Rel are present in neutrophils and that the greater part of these protein complexes is physically associated with cytoplasmic IkappaB-alpha in resting cells .", "target_text": { "p50 NFkappaB1": "protein", "p65 RelA": "protein", "c-Rel": "protein", "neutrophils": "cell_type", "protein complexes": "protein", "cytoplasmic IkappaB-alpha": "protein" } }, { "input_text": "Following neutrophil stimulation with proinflammatory agonists ( such as lipopolysaccharide [ LPS ] , tumor necrosis factor-alpha [ TNF-alpha ] , and fMet-Leu-Phe ) that induce the production of cytokines and chemokines in these cells , NF-kappaB /Rel proteins translocated to nuclear fractions , resulting in a transient induction of NF-kappaB DNA binding activity , as determined in gel mobility shift assays .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "cytokines": "protein", "chemokines": "protein", "NF-kappaB": "protein", "NF-kappaB /Rel proteins": "protein" } }, { "input_text": "The onset of both processes was found to be closely paralleled by , and dependent on , IkappaB-alpha degradation .", "target_text": { "IkappaB-alpha": "protein" } }, { "input_text": "Proinflammatory neutrophil stimuli also promoted the accumulation of IkappaB-alpha mRNA transcripts , resulting in the reexpression of the IkappaB-alpha protein .", "target_text": { "Proinflammatory neutrophil": "cell_type", "IkappaB-alpha mRNA transcripts": "RNA", "IkappaB-alpha protein": "protein" } }, { "input_text": "To our knowledge , this constitutes the first indication that NF-kappaB activation may underlie the action of proinflammatory stimuli towards human neutrophil gene expression and , as such , adds a new facet to our understanding of neutrophil biology .", "target_text": { "NF-kappaB": "protein", "neutrophil biology": "cell_type" } }, { "input_text": "Two distinct pathways of interleukin-5 synthesis in allergen-specific human T-cell clones are suppressed by glucocorticoids .", "target_text": { "interleukin-5": "protein", "allergen-specific human T-cell clones": "cell_line" } }, { "input_text": "Glucocorticoids ( GC ) have long been used as the most effective agents for the treatment of allergic diseases accompanied by eosinophilia such as chronic asthma and atopic dermatitis .", "target_text": {} }, { "input_text": "The development of chronic eosinophilic inflammation is dependent on interleukin-5 ( IL-5 ) , a selective eosinophil-activating factor , produced by helper T cells .", "target_text": { "interleukin-5": "protein", "IL-5": "protein", "selective eosinophil-activating factor": "protein", "helper T cells": "cell_type" } }, { "input_text": "To delineate the regulatory mechanisms of human IL-5 synthesis , we established allergen-specific CD4+ T-cell clones from asthmatic patients .", "target_text": { "IL-5": "protein", "allergen-specific CD4+ T-cell clones": "cell_line" } }, { "input_text": "GC efficiently suppressed IL-5 synthesis of T-cell clones activated via either T-cell receptor ( TCR ) or IL-2 receptor ( IL-2R ) .", "target_text": { "IL-5": "protein", "T-cell receptor": "protein", "TCR": "protein", "IL-2 receptor": "protein", "IL-2R": "protein" } }, { "input_text": "Induction of IL-5 mRNA upon TCR and IL-2R stimulation was totally inhibited by dexamethasone .", "target_text": { "IL-5": "protein", "IL-5 mRNA": "RNA", "TCR": "protein", "IL-2R": "protein" } }, { "input_text": "Human IL-5 promoter/enhancer-luciferase gene construct transfected to T-cell clones was transcribed on either TCR or IL-2R stimulation and was clearly downregulated by dexamethasone , indicating that the approximately 500-bp human IL-5 gene segment located 5' upstream of the coding region contains activation-inducible enhancer elements responsible for the regulation by GC .", "target_text": { "IL-5": "protein", "T-cell clones": "cell_line", "TCR": "protein", "IL-2R": "protein", "500-bp human IL-5 gene segment": "DNA", "5' upstream": "DNA", "activation-inducible enhancer elements": "DNA" } }, { "input_text": "Electrophoretic mobility shift assay analysis suggested that AP-1 and NF-kappaB are among the possible targets of GC actions on TCR -stimulated T cells .", "target_text": { "AP-1": "protein", "NF-kappaB": "protein", "TCR": "protein", "TCR -stimulated T cells": "cell_type" } }, { "input_text": "NF-AT and NF-kappaB were not significantly induced by IL-2 stimulation .", "target_text": { "NF-AT": "protein", "NF-kappaB": "protein", "IL-2": "protein" } }, { "input_text": "Our results showing that GC suppressed IL-5 production by human CD4+ T cells activated by two distinct stimuli , TCR and IL-2R stimulation , underscore the efficacy of GC in the treatment of allergic diseases via suppression of T-cell IL-5 synthesis .", "target_text": { "IL-5": "protein", "human CD4+ T cells": "cell_type", "TCR": "protein", "IL-2R": "protein" } }, { "input_text": "Itk , a T cell-specific tyrosine kinase , is required for CD2-mediated interleukin-2 promoter activation in the human T cell line Jurkat .", "target_text": { "Itk": "protein", "T cell-specific tyrosine kinase": "protein", "CD2-mediated interleukin-2 promoter": "DNA", "human T cell line Jurkat": "cell_line" } }, { "input_text": "We investigated the functional role of Itk , a member of the cytoplasmic tyrosine kinase Tec family , in T cell activation .", "target_text": { "Itk": "protein", "cytoplasmic tyrosine kinase Tec family": "protein" } }, { "input_text": "Stimulation of either CD2 or T cell receptor ( TCR ) /CD3 on Tcells by monoclonal antibody-mediated cross-linking induced tyrosine phosphorylation of Itk , which was maximal as early as 1 min after stimulation .", "target_text": { "CD2": "protein", "TCR": "protein", "Itk": "protein" } }, { "input_text": "The tyrosine kinase activity in the anti- Itk immunoprecipitate was significantly activated upon these stimulations .", "target_text": { "Itk": "protein" } }, { "input_text": "Interleukin-2 ( IL-2 ) promoter activity stimulated by cross-linking of CD2 , TCR /CD3 , and CD28 with antibodies was significantly reduced by transient expression of an Itk mutant lacking the kinase activity .", "target_text": { "IL-2": "protein", "CD2": "protein", "TCR": "protein", "CD28": "protein", "antibodies": "protein", "Itk": "protein", "Itk mutant": "protein" } }, { "input_text": "The reduction paralleled a decrease in tyrosine phosphorylation of endogenous wild-type Itk .", "target_text": { "Itk": "protein", "endogenous wild-type Itk": "protein" } }, { "input_text": "Stimulation of CD2 or TCR/CD3 induced activation of the nuclear factor of activated T cells ( NFAT ) , the binding site of which is included in the IL-2 gene promoter .", "target_text": { "CD2": "protein", "TCR/CD3": "protein", "nuclear factor of activated T cells": "protein", "NFAT": "protein", "binding site": "DNA", "IL-2": "protein", "IL-2 gene promoter": "DNA" } }, { "input_text": "The activation of NFAT was also impaired by expression of the Itk mutant .", "target_text": { "NFAT": "protein", "Itk": "protein", "Itk mutant": "protein" } }, { "input_text": "These results demonstrate that Itk plays a role in IL-2 production , indicating a critical involvement of Itk in the initial stage of T cell activation by mediating signals from the TCR/CD3 complex , CD2 , and CD28 .", "target_text": { "Itk": "protein", "IL-2": "protein", "TCR/CD3 complex": "protein", "CD2": "protein", "CD28": "protein" } }, { "input_text": "Expression of LAZ3/BCL6 in follicular center ( FC ) B cells of reactive lymph nodes and FC-derived non-Hodgkin lymphomas .", "target_text": { "LAZ3/BCL6": "protein" } }, { "input_text": "Chromosomal translocation resulting in abnormal expression of the LAZ3/BCL6 gene in B cells has been implicated in the tumorigenesis of non-Hodgkin lymphoma ( NHL ) .", "target_text": { "LAZ3/BCL6": "protein", "LAZ3/BCL6 gene": "DNA", "B cells": "cell_type" } }, { "input_text": "Therefore we studied the expression pattern of LAZ3/BCL6 by in situ hybridization with synthetic oligonucleotide probes in frozen tissue sections from five reactive lymph nodes and 38 B cell and non-B NHL .", "target_text": { "LAZ3/BCL6": "protein" } }, { "input_text": "In addition , we investigated the expression of LAZ3/BCL6 by Northern blot analysis on multiple human tissues .", "target_text": { "LAZ3/BCL6": "protein" } }, { "input_text": "The LAZ3/BCL6 transcript was found in a variety of tissues , including skeletal muscle , peripheral blood leukocytes , and weakly in normal lymph nodes .", "target_text": { "LAZ3/BCL6": "protein", "LAZ3/BCL6 transcript": "RNA", "peripheral blood leukocytes": "cell_type" } }, { "input_text": "In the tumor samples , expression of LAZ3/BCL6 was observed in 68 % of all B cell NHL and none of the non-B lymphomas .", "target_text": { "LAZ3/BCL6": "protein" } }, { "input_text": "All cases of follicular , mixed small and large cell lymphomas showed LAZ3/BCL6 expression confined to the neoplastic follicles .", "target_text": { "LAZ3/BCL6": "protein" } }, { "input_text": "A follicular expression pattern was also found in all non-malignant reactive lymph nodes .", "target_text": {} }, { "input_text": "Hence , the expression of LAZ3/BCL6 does not correlate to malignancy , but reflects the origin of B cells from the germinal centers .", "target_text": { "LAZ3/BCL6": "protein", "B cells": "cell_type" } }, { "input_text": "Jak1 expression is required for mediating interleukin-4-induced tyrosine phosphorylation of insulin receptor substrate and Stat6 signaling molecules .", "target_text": { "Jak1": "protein", "Stat6": "protein", "signaling molecules": "protein" } }, { "input_text": "The Jak1 , Jak2 , Jak3 , and Fes tyrosine kinases have been demonstrated to undergo tyrosine phosphorylation in response to interleukin ( IL ) -4 stimulation in different cell systems .", "target_text": { "interleukin ( IL ) -4": "protein" } }, { "input_text": "However , it is not clear which , if any , of these kinases are responsible for initiating IL-4-induced tyrosine phosphorylation of intracellular substrates in vivo .", "target_text": { "intracellular substrates": "protein" } }, { "input_text": "In the present study , we have utilized a mutant Jak1 -deficient HeLa cell line , E1C3 , and its parental Jak1 -expressing counterpart , 1D4 , to analyze the role of Jak1 in mediating IL-4-induced tyrosine phosphorylation events .", "target_text": { "Jak1": "protein", "mutant Jak1 -deficient HeLa cell line": "cell_line", "E1C3": "cell_line", "parental Jak1 -expressing counterpart": "cell_line", "1D4": "cell_line" } }, { "input_text": "IL-4 treatment rapidly induced tyrosine phosphorylation of insulin receptor substrate ( IRS ) -1 and IRS-2 in 1D4 but not in E1C3 cells .", "target_text": { "insulin receptor substrate ( IRS ) -1": "protein", "IRS-2": "protein", "1D4": "cell_line", "E1C3 cells": "cell_line" } }, { "input_text": "IL-4 -mediated tyrosine phosphorylation of Stat6 was pronounced in 1D4 cells , while no IL-4 -induced Stat6 phosphorylation was detected in E1C3 cells .", "target_text": { "IL-4": "protein", "Stat6": "protein", "1D4 cells": "cell_line", "E1C3 cells": "cell_line" } }, { "input_text": "IL-4 also induced Stat6 DNA binding activity from lysates of 1D4 but not E1C3 cells utilizing a radiolabeled immunoglobulin heavy chain germline epsilon promotor sequence ( Iepsilon ) in an electrophoretic mobility shift assay .", "target_text": { "IL-4": "protein", "Stat6": "protein", "1D4": "cell_line", "E1C3 cells": "cell_line", "radiolabeled immunoglobulin heavy chain germline epsilon promotor sequence": "DNA", "Iepsilon": "DNA" } }, { "input_text": "Reconstitution of Jak1 expression in E1C3 cells restored the ability of IL-4 to induce IRS and Stat6 tyrosine phosphorylation .", "target_text": { "Jak1": "protein", "E1C3 cells": "cell_line", "IL-4": "protein", "IRS": "DNA", "Stat6": "protein" } }, { "input_text": "These results provide evidence that Jak1 expression is required for mediating tyrosine phosphorylation and activation of crucial molecules involved in IL-4 signal transduction .", "target_text": { "Jak1": "protein", "IL-4": "protein" } }, { "input_text": "Oxidant-regulation of gene expression in the chronically inflamed intestine .", "target_text": {} }, { "input_text": "It is becoming increasingly apparent that the chronic gut inflammation observed in the idiopathic inflammatory bowel diseases ( e.g. ulcerative colitis , Crohn 's disease ) is associated with enhanced production of leukocyte-derived oxidants .", "target_text": {} }, { "input_text": "Oxidants such as hydrogen peroxide are known to activate certain transcription factors such as nuclear transcription factor kappa beta .", "target_text": { "transcription factors": "protein", "nuclear transcription factor kappa beta": "protein" } }, { "input_text": "Nuclear transcription factor kB ( NF-kappa B ) is a ubiquitous transcription factor and pleiotropic regulator of numerous genes involved in the immune and inflammatory responses .", "target_text": { "Nuclear transcription factor kB": "protein", "NF-kappa B": "protein", "ubiquitous transcription factor": "protein", "pleiotropic regulator": "protein" } }, { "input_text": "This transcription factor is activated via the selective phosphorylation , ubiquination and degradation of its inhibitor protein I-kB thereby allowing translocation of NF-kappa B into the nucleus where it upregulates the transcription of a variety of adhesion molecules ( e.g. ICAM-1 , VCAM-1 ) , cytokines ( TNF , IL-1 , IL-6 ) and enzymes ( iNOS ) .", "target_text": { "transcription factor": "protein", "inhibitor protein I-kB": "protein", "NF-kappa B": "protein", "adhesion molecules": "protein", "ICAM-1": "protein", "VCAM-1": "protein", "cytokines": "protein", "TNF": "protein", "IL-1": "protein", "IL-6": "protein", "enzymes": "protein", "iNOS": "protein" } }, { "input_text": "The proteolytic degradation of the post-translationally modified I-kappa B is known to be mediated by the 26S proteasome complex .", "target_text": { "I-kappa B": "protein", "26S proteasome complex": "protein" } }, { "input_text": "Based upon work from our laboratory , we propose that inhibition of NF-kappa B activation produces significant anti inflammatory activity which may be mediated by the inhibition of transcription of certain pro-inflammatory mediators and adhesion molecules .", "target_text": { "NF-kappa B": "protein", "pro-inflammatory mediators": "protein", "adhesion molecules": "protein" } }, { "input_text": "Generation of cytotoxic T lymphocytes against immunorecessive epitopes after multiple immunizations with adenovirus vectors is dependent on haplotype .", "target_text": { "cytotoxic T lymphocytes": "cell_type", "immunorecessive epitopes": "protein" } }, { "input_text": "Currently , adenovirus ( Ad ) is being considered as a vector for the treatment of cystic fibrosis as well as other diseases .", "target_text": {} }, { "input_text": "However , the cytotoxic T lymphocyte ( CTL ) response to Ad could limit the effectiveness of such approaches .", "target_text": { "cytotoxic T lymphocyte": "cell_type", "CTL": "cell_type" } }, { "input_text": "Since the CTL response to virus infection is often focused on one or a few immunodominant epitopes , one approach to circumvent this response is to create vectors that lack these immunodominant epitopes .", "target_text": { "CTL": "cell_type", "immunodominant epitopes": "protein" } }, { "input_text": "The effectiveness of this approach was tested by immunizing mice with human group C adenoviruses .", "target_text": {} }, { "input_text": "Three mouse strains ( C57BL/10SnJ [ H-2b ] , C3HeB/FeJ [ H-2k ] , and BALB/cByJ [ H-2d ] ) were immunized with wild-type Ad or Ad vectors lacking the immunodominant antigen ( s ) , and the CTL responses were measured .", "target_text": { "immunodominant antigen": "protein", "CTL": "cell_type" } }, { "input_text": "In C57BL/10 ( B10 ) mice , a single inoculation intraperitoneally ( i.p. ) led to the recognition of an immunodominant antigen in E1A .", "target_text": { "immunodominant antigen": "protein", "E1A": "DNA" } }, { "input_text": "When B10 mice were inoculated multiple times either i.p.", "target_text": {} }, { "input_text": "or intranasally with wild-type Ad or an Ad vector lacking most of the E1 region , subdominant epitopes outside this region were recognized .", "target_text": { "E1 region": "DNA" } }, { "input_text": "In contrast , C3H mice inoculated with wild-type Ad recognized an epitope mapping within E1B . When inoculated twice with Ad vectors lacking both E1A and E1B , no immunorecessive epitopes were recognized .", "target_text": { "E1B": "DNA", "E1A": "DNA", "immunorecessive epitopes": "protein" } }, { "input_text": "The immune response to Ad in BALB/c mice was more complex .", "target_text": {} }, { "input_text": "CTLs from BALB/c mice inoculated i.p. with wild-type Ad recognized E1B in the context of the major histocompatibility complex ( MHC ) class I Dd allele and a region outside E1 associated with the Kd allele .", "target_text": { "CTLs": "cell_type", "E1B": "DNA", "major histocompatibility complex": "protein", "MHC": "protein", "major histocompatibility complex ( MHC ) class I Dd allele": "DNA", "E1": "DNA", "Kd allele": "DNA" } }, { "input_text": "When BALB/c mice were inoculated with E1 -deleted Ad vectors , only the immunodominant Kd-restricted epitope was recognized , and Dd-restricted CTLs did not develop .", "target_text": { "E1": "DNA", "immunodominant Kd-restricted epitope": "protein", "CTLs": "cell_type" } }, { "input_text": "This report indicates that the emergence of CTLs against immunorecessive epitopes following multiple administrations of Ad vectors lacking immunodominant antigens is dependent on haplotype and could present an obstacle to gene therapy in an MHC -diverse human population .", "target_text": { "CTLs": "cell_type", "immunorecessive epitopes": "protein", "MHC": "protein" } }, { "input_text": "Characterization of the human platelet/endothelial cell adhesion molecule-1 promoter : identification of a GATA-2 binding element required for optimal transcriptional activity .", "target_text": { "human platelet/endothelial cell adhesion molecule-1 promoter": "DNA", "GATA-2": "protein", "GATA-2 binding element": "DNA" } }, { "input_text": "Platelet/endothelial cell adhesion molecule-1 ( PECAM-1 ) is a 130-kD member of the Ig gene superfamily that is expressed on platelets , endothelial cells , and certain leukocyte subsets .", "target_text": { "Platelet/endothelial cell adhesion molecule-1": "protein", "PECAM-1": "protein", "130-kD member": "protein", "Ig gene superfamily": "DNA", "platelets": "cell_type", "endothelial cells": "cell_type", "leukocyte subsets": "cell_type" } }, { "input_text": "To examine the factors controlling vascular-specific expression of PECAM-1 , we cloned the 5'-flanking region of the PECAM-1 gene and analyzed its transcriptional activity .", "target_text": { "PECAM-1": "protein", "5'-flanking region": "DNA", "PECAM-1 gene": "DNA" } }, { "input_text": "5'-Rapid amplification of cDNA ends ( 5'-RACE ) analysis showed that transcription initiation occurred at several closely spaced nearby sites originating approximately 204 bp upstream from the translation start site .", "target_text": { "cDNA ends": "DNA", "5'-RACE": "DNA", "204 bp upstream": "DNA", "translation start site": "DNA" } }, { "input_text": "Analysis of the sequence immediately upstream from the transcription initiation site ( TIS ) showed no canonical TATA or CAAT elements , however an initiator element commonly found in TATA -less promoters encompassed the TIS .", "target_text": { "transcription initiation site": "DNA", "TIS": "DNA", "TATA": "DNA", "CAAT elements": "DNA", "TATA -less promoters": "DNA" } }, { "input_text": "5'-serially truncated PECAM-1 promoter segments cloned in front of a luciferase reporter drove transcription in both a lineage- and orientation-specific manner .", "target_text": { "PECAM-1 promoter segments": "DNA", "5'-serially truncated PECAM-1 promoter segments": "DNA", "luciferase reporter": "DNA" } }, { "input_text": "Putative cis-acting control elements present within a 300-bp core promoter included two ets sites , an Sp1 site , tandem E-box domains , two GATA-associated sites ( CACCC ) , an AP-2 binding site , and a GATA element at -24 .", "target_text": { "cis-acting control elements": "DNA", "300-bp core promoter": "DNA", "ets sites": "DNA", "Sp1 site": "DNA", "E-box domains": "DNA", "GATA-associated sites": "DNA", "AP-2": "protein", "AP-2 binding site": "DNA", "GATA element": "DNA", "-24": "DNA" } }, { "input_text": "Mutational analysis showed that optimal transcriptional activity required the GATA sequence at position -24 , and gel-shift assays further showed that the GATA-2 transcription factor , but not GATA-1 , bound to this region of the PECAM-1 promoter .", "target_text": { "GATA sequence": "DNA", "-24": "DNA", "GATA-2": "protein", "GATA-2 transcription factor": "protein", "GATA-1": "protein", "PECAM-1 promoter": "DNA" } }, { "input_text": "Understanding the cis- and trans acting factors that regulate the tissue-specific expression of PECAM-1 should increase our understanding of the mechanisms by which vascular-specific gene expression is achieved .", "target_text": { "PECAM-1": "protein" } }, { "input_text": "A negative regulatory region containing a glucocorticosteroid response element ( nGRE ) in the human interleukin-1beta gene .", "target_text": { "glucocorticosteroid response element": "DNA", "nGRE": "DNA", "human interleukin-1beta gene": "DNA" } }, { "input_text": "Interleukin-1 beta ( IL-1beta ) is one of the most important inflammatory mediators in human inflammatory and immunological diseases .", "target_text": { "Interleukin-1 beta": "protein", "IL-1beta": "protein", "inflammatory mediators": "protein" } }, { "input_text": "The regulation of human IL-1beta gene expression has been studied for several years , and a few regulatory elements have been discovered in the promoter region .", "target_text": { "IL-1beta": "protein", "human IL-1beta": "protein", "regulatory elements": "DNA", "promoter region": "DNA" } }, { "input_text": "However , little is known about negative regulation of IL-1beta expression at the transcriptional level , which may play an important role in anti-inflammatory and immunosuppressive effects .", "target_text": { "IL-1beta": "protein" } }, { "input_text": "We have identified a negative regulatory element located in the region between -685 and -395 .", "target_text": { "negative regulatory element": "DNA", "-685 and -395": "DNA" } }, { "input_text": "Within this region , a 19-bp nuclear factor binding site ( -570 to -552 ) was characterized by DNase I footprinting and electromobility shift assay .", "target_text": { "19-bp nuclear factor binding site": "DNA", "-570 to -552": "DNA", "DNase I": "protein" } }, { "input_text": "A consensus sequence for a negative glucocorticoid response element ( nGRE ) and a transcription activator protein-2 binding site were noted within this footprint .", "target_text": { "consensus sequence": "DNA", "negative glucocorticoid response element": "DNA", "nGRE": "DNA", "transcription activator protein-2 binding site": "DNA" } }, { "input_text": "Functional studies showed a 2.5-fold increase in promoter activity when this 19-bp binding site was deleted in the reporter constructs IL-1beta /CAT and IL-1beta /SV40 promoter /CAT .", "target_text": { "19-bp binding site": "DNA", "reporter constructs": "DNA", "IL-1beta": "protein", "/CAT": "protein", "/SV40 promoter": "DNA" } }, { "input_text": "Dexamethasone ( 10(-8) M ) repressed chloramphenicol acetyltransferase ( CAT ) production by 75 % in the wild-type fragment but not in a deletion mutant lacking the 19-bp site .", "target_text": { "chloramphenicol acetyltransferase": "protein", "CAT": "protein", "wild-type fragment": "DNA", "deletion mutant": "DNA", "19-bp site": "DNA" } }, { "input_text": "A protein of about 150 kD that bound to this negative regulatory sequence was identified by UV cross-linking .", "target_text": { "150 kD": "protein", "negative regulatory sequence": "DNA" } }, { "input_text": "This is the first description of a negative regulatory region responsive to glucocorticoids in a cytokine gene .", "target_text": { "negative regulatory region": "DNA", "cytokine gene": "DNA" } }, { "input_text": "Interaction of transcription factors RFX1 and MIBP1 with the gamma motif of the negative regulatory element of the hepatitis B virus core promoter .", "target_text": { "transcription factors": "protein", "RFX1": "protein", "MIBP1": "protein", "gamma motif": "DNA", "negative regulatory element": "DNA", "hepatitis B virus core promoter": "DNA" } }, { "input_text": "The negative regulatory element ( NRE ) of the hepatitis B virus ( HBV ) core promoter contains three subregions which act synergistically to suppress core promoter activity .", "target_text": { "negative regulatory element": "DNA", "NRE": "DNA", "hepatitis B virus ( HBV ) core promoter": "DNA" } }, { "input_text": "One of these subregions , NRE gamma , is active in both HeLa cervical carcinoma cells and Huh7 hepatoma cells and was found to be bound by a protein factor present in both cell types .", "target_text": { "NRE gamma": "DNA", "HeLa cervical carcinoma cells": "cell_line", "Huh7 hepatoma cells": "cell_line" } }, { "input_text": "Here we show that the transcription factor RFX1 can bind to NRE gamma and transactivate the core promoter through this site .", "target_text": { "transcription factor": "protein", "RFX1": "protein", "NRE gamma": "DNA", "core promoter": "DNA" } }, { "input_text": "Mutations which abrogated the gene-suppressive activity of NRE gamma prevented RFX1 from binding to NRE gamma .", "target_text": { "NRE gamma": "DNA", "RFX1": "protein" } }, { "input_text": "In addition , RFX1 can bind simultaneously , most likely as a heterodimer , with the transcription factor MIBP1 to NRE gamma .", "target_text": { "RFX1": "protein", "heterodimer": "protein", "transcription factor": "protein", "MIBP1": "protein", "NRE gamma": "DNA" } }, { "input_text": "In the absence of a cloned MIBP1 gene for further studies , we hypothesize that RFX1 acts with MIBP1 to negatively regulate the core promoter activity through the NRE gamma site .", "target_text": { "MIBP1": "protein", "MIBP1 gene": "DNA", "RFX1": "protein", "NRE gamma": "DNA", "NRE gamma site": "DNA" } }, { "input_text": "The ability of RFX1 to transactivate the core promoter raises the possibility that RFX1 may play a dual role in regulating HBV gene expression", "target_text": { "RFX1": "protein", "core promoter": "DNA" } }, { "input_text": "Use of arsenic trioxide ( As2O3 ) in the treatment of acute promyelocytic leukemia ( APL ) : II .", "target_text": {} }, { "input_text": "Clinical efficacy and pharmacokinetics in relapsed patients .", "target_text": {} }, { "input_text": "The therapeutic effect of arsenic trioxide ( As2O3 ) in the treatment of acute promyelocytic leukemia ( APL ) was evaluated among 15 APL patients at relapse after all-trans retinoic acid ( ATRA ) induced and chemotherapy maintained complete remission ( CR ) .", "target_text": {} }, { "input_text": "As2O3 was administered intravenously at the dose of 10 mg/d .", "target_text": {} }, { "input_text": "Clinical CR was achieved in nine of 10 ( 90 % ) patients treated with As2O3 alone and in the remaining five patients treated by the combination of As2O3 and low-dose chemotherapeutic drugs or ATRA .", "target_text": {} }, { "input_text": "During the treatment with As2O3 , there was no bone marrow depression and only limited side effects were encountered .", "target_text": {} }, { "input_text": "Pharmacokinetic studies , which were performed in eight patients , showed that after a peak level of 5.54 micromol/L to 7.30 micromol/L , plasma arsenic was rapidly eliminated , and the continuous administration of As2O3 did not alter its pharmacokinetic behaviors .", "target_text": {} }, { "input_text": "In addition , increased amounts of arsenic appeared in the urine , with a daily excretion accounting for approximately 1 % to 8 % of the total daily dose administered .", "target_text": {} }, { "input_text": "Arsenic contents in hair and nail were increased , and the peak content of arsenic could reach 2.5 to 2.7 microg/g tissue at CR .", "target_text": {} }, { "input_text": "On the other hand , a decline of the arsenic content in hair and nail was observed after withdrawal of the drug .", "target_text": {} }, { "input_text": "We conclude that As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy .", "target_text": {} }, { "input_text": "Nucleolin is one component of the B cell-specific transcription factor and switch region binding protein , LR1 .", "target_text": { "Nucleolin": "protein", "B cell-specific transcription factor": "protein", "switch region binding protein": "protein", "LR1": "protein" } }, { "input_text": "LR1 is a B cell-specific , sequence-specific DNA binding activity that regulates transcription in activated B cells .", "target_text": { "LR1": "protein", "activated B cells": "cell_type" } }, { "input_text": "LR1 also binds Ig heavy chain switch region sequences and may function in class switch recombination .", "target_text": { "LR1": "protein", "Ig heavy chain": "protein" } }, { "input_text": "LR1 contains two polypeptides , of 106 kDa and 45 kDa , and here we report that the 106-kDa component of LR1 is nucleolin .", "target_text": { "LR1": "protein", "106-kDa component": "protein", "nucleolin": "protein" } }, { "input_text": "This identification , initially made by microsequence analysis , was verified by showing that ( i ) LR1 -DNA binding activity increased in B cells transfected with a nucleolin cDNA expression construct ; ( ii ) LR1 -DNA binding activity was recognized by antibodies raised against recombinant human nucleolin ; and ( iii ) in B cells transfected with epitope-tagged nucleolin expression constructs , the LR1 -DNA complex was recognized by the anti-tag antibody .", "target_text": { "LR1": "protein", "B cells": "cell_type", "nucleolin": "protein", "nucleolin cDNA expression construct": "DNA", "recombinant human nucleolin": "protein", "epitope-tagged nucleolin expression constructs": "DNA", "LR1 -DNA complex": "protein", "anti-tag antibody": "protein" } }, { "input_text": "Nucleolin is an abundant nucleolar protein which is believed to play a role in rDNA transcription or organization , or rRNA processing .", "target_text": { "Nucleolin": "protein", "abundant nucleolar protein": "protein", "rDNA": "DNA", "rRNA": "RNA" } }, { "input_text": "Homology between nucleolin and histone H1 suggests that nucleolin may alter DNA organization in response to cell cycle controls , and the nucleolin component of LR1 may therefore function to organize switch regions before , during , or after switch recombination .", "target_text": { "nucleolin": "protein", "histone H1": "protein", "LR1": "protein", "switch regions": "DNA" } }, { "input_text": "The demonstration that nucleolin is a component of a B cell-specific complex that binds switch region sequences suggests that the G-rich switch regions may have evolved from rDNA .", "target_text": { "nucleolin": "protein", "B cell-specific complex": "protein", "switch regions": "DNA", "G-rich switch regions": "DNA", "rDNA": "DNA" } }, { "input_text": "Glucocorticoid -resistance in peripheral-blood lymphocytes does not correlate with number of affinity of glucocorticoid-receptors in chronic renal failure patients .", "target_text": { "peripheral-blood lymphocytes": "cell_type", "glucocorticoid-receptors": "protein" } }, { "input_text": "Glucocorticoid ( GC ) resistance in patients with chronic renal failure ( CRF ) seriously impairs successive GC therapy after renal transplantation .", "target_text": {} }, { "input_text": "We examined the relationship between GC -receptor ( GC-R ) parameters in peripheral-blood mononuclear cells ( PBMC ) and PBMC resistance to GC in 21 CRF patients and 18 healthy subjects .", "target_text": { "peripheral-blood mononuclear cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "Each subject group was divided into two subgroups according to PBMC sensitivity to prednisolone in a mitogen assay procedure ; i.e. , sensitive ( IC50 < 381 ng/mL ) and resistant ( IC50 > 381 ng/mL ) groups .", "target_text": { "PBMC": "cell_type" } }, { "input_text": "In healthy subjects , the mean GC-R Bmax and Kd in quiescent PBMC of the GC -sensitive group were 2.89 +/- 1.23 fmol/10(6) cells and 4.00 +/- 2.24 nM , respectively .", "target_text": { "GC-R": "protein", "PBMC": "cell_type" } }, { "input_text": "The Bmax in these subjects significantly increased to 6.61 +/- 2.02 ( 257.7 +/- 107.8 % ) after 24 h stimulation with concanavalin A ( p < 0.01 ) , while the Kd change was not significant .", "target_text": {} }, { "input_text": "The GC-R Bmax and Kd in quiescent PBMC of the GC -resistant group were 5.33 +/- 1.37 fmol/10(6) cells and 3.20 +/- 1.39 nM , respectively .", "target_text": { "GC-R": "protein", "PBMC": "cell_type" } }, { "input_text": "Both of these parameters , however , did not change significantly after mitogen stimulation .", "target_text": { "mitogen": "protein" } }, { "input_text": "There was a significant negative correlation between IC50S of prednisolone and increase-ratios ( post/pre ratio ) of Bmax after mitogen stimulation ( p < 0.05 ) .", "target_text": { "mitogen": "protein" } }, { "input_text": "In CRF patients , Bmax and Kd in quiescent PBMC of the GC -sensitive group were 6.04 +/- 2.35 fmol/10(6) cells and 3.49 +/- 1.72 nM , respectively , while those in PBMC of the GC -resistant group were 5.13 +/- 2.31 fmol/10(6) cells and 4.04 +/- 1.62 nM , respectively .", "target_text": { "PBMC": "cell_type" } }, { "input_text": "The Bmax and Kd were not significantly changed after mitogen stimulation in both subgroups of CRF .", "target_text": { "mitogen": "protein" } }, { "input_text": "Moreover , in contrast to healthy subjects , there was no correlation between IC50 and GC-R parameters in CRF .", "target_text": { "GC-R": "protein" } }, { "input_text": "We concluded that , in healthy subjects , decreased PBMC capacity to amplify GC-R numbers in response to mitogen is correlated with GC resistance , whereas in CRF patients the resistant mechanism is not correlated with GC-R parameters .", "target_text": { "PBMC": "cell_type", "GC-R": "protein", "mitogen": "protein" } }, { "input_text": "An unknown event might be involved in GC -resistance of CRF .", "target_text": {} }, { "input_text": "Alteration of a single serine in the basic domain of the Epstein-Barr virus ZEBRA protein separates its functions of transcriptional activation and disruption of latency .", "target_text": { "basic domain": "protein", "Epstein-Barr virus ZEBRA protein": "protein" } }, { "input_text": "The ZEBRA protein from Epstein-Barr virus ( EBV ) activates a switch from the latent to the lytic expression program of the virus .", "target_text": { "ZEBRA protein": "protein" } }, { "input_text": "ZEBRA , a member of the bZIP family of DNA-binding proteins , is a transcriptional activator capable of inducing expression from viral lytic cycle promoters .", "target_text": { "ZEBRA": "protein", "bZIP family": "protein", "DNA-binding proteins": "protein", "viral lytic cycle promoters": "DNA" } }, { "input_text": "It had previously been thought that ZEBRA 's capacity to disrupt EBV latency resided primarily in its ability to activate transcription of genes that encode products required for lytic replication .", "target_text": { "ZEBRA": "protein" } }, { "input_text": "We generated a point mutant of ZEBRA , Z ( S186A ) , that was not impaired in its ability to activate transcription ; however , this mutation abolished its ability to initiate the viral lytic cascade .", "target_text": { "ZEBRA": "protein", "Z ( S186A )": "protein" } }, { "input_text": "The mutant , containing a serine -to- alanine substitution in the DNA-binding domain of the protein , bound to several known ZEBRA -binding sites and activated transcription from reporters bearing known ZEBRA -responsive promoters but did not disrupt latency in EBV -infected cell lines .", "target_text": { "DNA-binding domain": "protein", "ZEBRA": "protein", "ZEBRA -binding sites": "DNA", "ZEBRA -responsive promoters": "DNA", "EBV -infected cell lines": "cell_line" } }, { "input_text": "Therefore , initiation of the EBV lytic cycle by the ZEBRA protein requires a function in addition to transcriptional activation ; a change of serine 186 to alanine in the DNA-binding domain of ZEBRA abolished this additional function and uncovered a new role for the ZEBRA protein in disruption of EBV latency .", "target_text": { "ZEBRA": "protein", "ZEBRA protein": "protein", "DNA-binding domain": "protein" } }, { "input_text": "The additional function that is required for initiation of the lytic viral life cycle is likely to require phosphorylation of serine 186 of the ZEBRA protein , which may influence either DNA recognition or transcriptional activation of lytic viral promoters in a chromatinized viral episome .", "target_text": { "ZEBRA": "protein", "ZEBRA protein": "protein", "lytic viral promoters": "DNA", "chromatinized viral episome": "DNA" } }, { "input_text": "Immune hyperactivation of HIV-1 -infected T cells mediated by Tat and the CD28 pathway .", "target_text": { "HIV-1 -infected T cells": "cell_type", "Tat": "protein", "CD28": "protein" } }, { "input_text": "Human immunodeficiency virus-type 1 ( HIV-1 ) infection is characterized by a chronic state of immune hyperactivation in patients .", "target_text": {} }, { "input_text": "Infection of human peripheral blood lymphocytes with HIV-1 in vitro resulted in increased interleukin-2 ( IL-2 ) secretion in response to T cell activation via the CD3 and CD28 receptors .", "target_text": { "human peripheral blood lymphocytes": "cell_type" } }, { "input_text": "Expression of the HIV-1 transactivator Tat recapitulated this phenotype and was associated with increased IL-2 secretion in response to costimulation with CD3 plus CD28 .", "target_text": { "HIV-1 transactivator": "protein", "Tat": "protein", "IL-2": "protein", "CD3": "protein", "CD28": "protein" } }, { "input_text": "IL-2 superinduction by Tat occurred at the transcriptional level , was mediated by the CD28 -responsive element in the IL-2 promoter , and was exclusively dependent on the 29 amino acids encoded by the second exon of Tat .", "target_text": { "IL-2": "protein", "Tat": "protein", "CD28": "protein", "CD28 -responsive element": "DNA", "IL-2 promoter": "DNA", "29 amino acids": "protein", "second exon of Tat": "DNA" } }, { "input_text": "Response to intranasal fluticasone propionate in perennial allergic rhinitis not associated with glucocorticoid receptor characteristics .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "BACKGROUND : The reduction of symptoms due to treatment with corticosteroids varies among patients with perennial rhinitis .", "target_text": {} }, { "input_text": "Most patients will respond but a few patients respond less to these drugs .", "target_text": {} }, { "input_text": "OBJECTIVE : To investigate the association in reduction of symptoms due to glucocorticoids and glucocorticoid receptor characteristics in patients with perennial allergic rhinitis , in vitro glucocorticoid receptor binding studies were performed with peripheral blood mononuclear cells using dexamethasone and in vitro production of mediators were measured .", "target_text": { "glucocorticoid receptor": "protein", "peripheral blood mononuclear cells": "cell_type", "mediators": "protein" } }, { "input_text": "METHODS : During a double-blind placebo-controlled crossover study , 200 micrograms fluticasone propionate aqueous nasal spray ( in the active treatment period ) and placebo ( in the placebo treatment period ) were administered twice daily for 2 weeks to 22 patients allergic to house dust mite .", "target_text": {} }, { "input_text": "At the end of both treatment periods symptoms were scored after allergen provocation ( 100 , 1000 , 10000 BU/mL ) and during the 9.5 hours after this challenge .", "target_text": {} }, { "input_text": "Receptor binding studies with dexamethasone were performed with peripheral blood mononuclear cells .", "target_text": { "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Leukotriene B4 produced by monocytes in vitro and soluble interleukin-2 receptor released by lymphocytes in vitro and cortisol levels in plasma were determined .", "target_text": { "monocytes": "cell_type", "interleukin-2 receptor": "protein", "lymphocytes": "cell_type" } }, { "input_text": "RESULTS : No significant partial correlations of the number of the peripheral blood mononuclear cell glucocorticoid receptors ( 6821 +/- 5669 binding sites per cell ) and the affinity ( Kd : 16.5 +/- 13.51 nmol/L ) for the glucocorticoid receptors with the symptom score ( placebo : 4.3 +/- 2.45 pts ; fluticasone : 2.4 +/- 1.55 pts ) after active treatment were found .", "target_text": { "peripheral blood mononuclear cell": "cell_type", "glucocorticoid receptors": "protein", "peripheral blood mononuclear cell glucocorticoid receptors": "protein" } }, { "input_text": "Also no significant partial correlations of the levels of leukotriene B4 ( 45.6 +/- 105.3 ng/10(6) cells ) produced by monocytes in vitro , soluble interleukin-2 receptor ( 734 +/- 237 ng/10(6) cells ) released by lymphocytes in vitro and cortisol levels ( 571 +/- 236 ng/mL ) in plasma with the symptom score after active treatment were found .", "target_text": { "monocytes": "cell_type", "interleukin-2 receptor": "protein", "lymphocytes": "cell_type" } }, { "input_text": "CONCLUSIONS : The reduction of symptoms due to topical fluticasone propionate in patients with rhinitis and allergy to house dust mite is not correlated with the characteristics of the glucocorticoid receptor .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Constitutive expression of p50 homodimer in freshly isolated human monocytes decreases with in vitro and in vivo differentiation : a possible mechanism influencing human immunodeficiency virus replication in monocytes and mature macrophages .", "target_text": { "p50 homodimer": "protein", "freshly isolated human monocytes": "cell_type", "monocytes": "cell_type" } }, { "input_text": "Human immunodeficiency virus type 1 ( HIV-1 ) replicates more efficiently in vitro in differentiated macrophages than in freshly isolated monocytes .", "target_text": { "differentiated macrophages": "cell_type", "monocytes": "cell_type", "freshly isolated monocytes": "cell_type" } }, { "input_text": "We investigated whether this may be partly explained by changes in expression of NF-kappaB with monocyte differentiation .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "We demonstrated that constitutive expression of NF-kappaB in primary human monocytes changed significantly with differentiation in vitro to monocyte-derived macrophages ( MDMs ) and differentiation in vivo to alveolar macrophages ( AMs ) .", "target_text": { "NF-kappaB": "protein", "primary human monocytes": "cell_type", "monocyte-derived macrophages": "cell_type", "MDMs": "cell_type", "alveolar macrophages": "cell_type", "AMs": "cell_type" } }, { "input_text": "Freshly isolated monocytes constitutively expressed high levels of transcriptionally inactive p50 homodimer which decreased with time in culture in favor of the transcriptionally active p50/p65 and p50/RelB heterodimers .", "target_text": { "p50 homodimer": "protein", "transcriptionally inactive p50 homodimer": "protein" } }, { "input_text": "As in MDMs , AMs constitutively expressed p50/p65 and p50/RelB although at lower levels .", "target_text": { "MDMs": "cell_type", "AMs": "cell_type", "p50/p65": "protein", "p50/RelB": "protein" } }, { "input_text": "HIV infection of fresh monocytes failed to induce p50/p65 as seen in MDMs .", "target_text": { "monocytes": "cell_type", "p50/p65": "protein", "MDMs": "cell_type" } }, { "input_text": "The replacement of p50 homodimers with transcriptionally active heterodimers following time in culture may partially explain the progressive increase in susceptibility of monocytes to HIV infection during in vitro culture .", "target_text": { "p50 homodimers": "protein", "monocytes": "cell_type" } }, { "input_text": "The change in NF-kappaB components with monocyte differentiation in vivo may also explain the different transcriptional activities of these cell populations in HIV -infected individuals .", "target_text": { "NF-kappaB": "protein", "NF-kappaB components": "protein" } }, { "input_text": "NF-kappa B -independent suppression of HIV expression by ascorbic acid .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Ascorbic acid ( ascorbate or vitamin C ) has been shown to suppress the induction of HIV in latently infected T lymphocytic cells following stimulation with a tumor promoter ( PMA ) and inflammatory cytokine ( TNF-alpha ) .", "target_text": { "latently infected T lymphocytic cells": "cell_type", "inflammatory cytokine": "protein", "TNF-alpha": "protein" } }, { "input_text": "To assess whether this inhibition was mediated via modulation of the cellular transcription factor , NF-kappa B , we carried out gel shift analysis on nuclear extracts prepared under different conditions of cell stimulation in the presence or absence of ascorbate , N-acetylcysteine ( NAC ) , or zidovudine ( AZT ) .", "target_text": { "cellular transcription factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "Pretreatment of ACH-2 T cells by NAC followed by stimulation with PMA , TNF-alpha , or hydrogen peroxide ( H2O2 ) resulted in strong suppression of NF-kappa B activation .", "target_text": { "ACH-2 T cells": "cell_line", "TNF-alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "In contrast , neither ascorbate nor AZT affected NF-kappa B activity under all three induction conditions in the ACH-2 cell line .", "target_text": { "NF-kappa B": "protein", "ACH-2 cell line": "cell_line" } }, { "input_text": "Ascorbate and AZT also had no effect on NF-kappa B activation following TNF-alpha- or PMA- induced stimulation of U1 promonocytic cells .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "These results suggest that the molecular mechanism of HIV inhibition by ascorbate is not mediated via NF-kappa B inhibition , unlike that seen with other antioxidants .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "A T cell-specific enhancer in the interleukin-3 locus is activated cooperatively by Oct and NFAT elements within a DNase I-hypersensitive site .", "target_text": { "T cell-specific enhancer": "DNA", "interleukin-3 locus": "DNA", "DNase I-hypersensitive site": "DNA" } }, { "input_text": "Interleukin-3 ( IL-3 ) is a cytokine that is expressed primarily in activated T cells .", "target_text": { "Interleukin-3": "protein", "IL-3": "protein", "cytokine": "protein", "activated T cells": "cell_type" } }, { "input_text": "Here we identified an inducible T cell-specific enhancer 14 kb upstream of the IL-3 gene that responded to activation of T cell receptor signaling pathways .", "target_text": { "T cell-specific enhancer": "DNA", "IL-3": "protein", "IL-3 gene": "DNA", "T cell receptor": "protein" } }, { "input_text": "The IL-3 enhancer spanned an inducible cyclosporin A -sensitive DNase I-hypersensitive site found only in T cells .", "target_text": { "IL-3": "protein", "DNase I-hypersensitive site": "DNA", "cyclosporin A -sensitive DNase I-hypersensitive site": "DNA", "T cells": "cell_type" } }, { "input_text": "Four NFAT-like elements exist within the enhancer .", "target_text": { "NFAT-like elements": "DNA" } }, { "input_text": "The two most active NFAT-like elements were located at the center of the DNase I-hypersensitive site .", "target_text": { "NFAT-like elements": "DNA", "DNase I-hypersensitive site": "DNA" } }, { "input_text": "One of these NFAT-like elements encompassed overlapping Oct- and NFATp/c- binding sites , which functioned in a highly synergistic manner .", "target_text": { "NFAT-like elements": "DNA" } }, { "input_text": "We suggest that the T cell- specific expression of the IL-3 gene is partly controlled through the enhancer by cooperation between Oct and NFAT family proteins .", "target_text": { "IL-3": "protein", "IL-3 gene": "DNA" } }, { "input_text": "Adenovirus E1B 19K protein is required for efficient DNA replication in U937 cells .", "target_text": { "Adenovirus E1B 19K protein": "protein", "U937 cells": "cell_line" } }, { "input_text": "The adenovirus E1B 19K gene plays an essential role in transformation of primary rodent cells in cooperation with E1A and in the inhibition of apoptosis during lytic infection .", "target_text": { "adenovirus E1B 19K gene": "DNA", "primary rodent cells": "cell_type", "E1A": "protein" } }, { "input_text": "It has been shown that this E1B 19K protein is not necessary for viral DNA replication in human cell lines , such as HeLa and KB .", "target_text": { "E1B 19K protein": "protein", "human cell lines": "cell_line", "HeLa": "cell_line", "KB": "cell_line" } }, { "input_text": "We reported here that the E1B 19K mutant viruses were unable to replicate efficiently in a monocyte cell line , U937 .", "target_text": { "E1B 19K": "protein", "monocyte cell line": "cell_line", "U937": "cell_line" } }, { "input_text": "Viral DNA synthesis and late gene expression were found to be defective in U937 cells infected with E1B 19K mutants compared with wild-type virus .", "target_text": { "U937 cells": "cell_line", "E1B 19K": "protein" } }, { "input_text": "Early viral RNA splicing patterns also differ between wild-type and dl337-infected cells .", "target_text": {} }, { "input_text": "Furthermore , the defect in viral replication could be complemented by dl312 virus defective in E1A expression 4 days after infection with E1B mutants , suggesting persistence of the E1B mutant genome in the infected cells despite defective onset of the late phase of replication .", "target_text": { "E1A": "protein", "E1B mutant genome": "DNA" } }, { "input_text": "These results imply that E1B 19K is required for efficient viral DNA replication in U937 cells .", "target_text": { "E1B 19K": "protein", "U937 cells": "cell_line" } }, { "input_text": "Inefficient DNA replication is also found in another monocyte cell line , THP-1", "target_text": { "monocyte cell line": "cell_line", "THP-1": "cell_line" } }, { "input_text": "Activation of Ras and mitogen-activated protein kinase pathway by terminal complement complexes is G protein dependent .", "target_text": { "mitogen-activated protein kinase": "protein", "terminal complement complexes": "protein", "G protein": "protein" } }, { "input_text": "Assembly of terminal complement complexes ( TCC ) C5b-7 , C5b-8 , and C5b-9 on target cells during acute and chronic inflammation induces hydrolysis of plasma membrane phospholipids and heterotrimeric G protein activation .", "target_text": { "terminal complement complexes": "protein", "TCC": "protein", "C5b-7": "protein", "C5b-8": "protein", "C5b-9": "protein", "G protein": "protein" } }, { "input_text": "TCC also stimulate a variety of cellular activities , which include cytokine synthesis , proto-oncogene activation , and mitotic signaling .", "target_text": { "TCC": "protein", "cytokine": "protein", "proto-oncogene": "DNA" } }, { "input_text": "Now we report that sublytic TCC induced Ras , Raf-1 , and extracellular signal-regulated kinase ( ERK ) 1 activation in JY25 B cell line .", "target_text": { "TCC": "protein", "Ras": "protein", "Raf-1": "protein", "extracellular signal-regulated kinase ( ERK ) 1": "protein" } }, { "input_text": "When cells were exposed to C5b-9 , GTP-bound Ras in anti- C5b-9 immunoprecipitates was increased 3.2-fold at 2 min , while GTP-bound Ras in anti- Ras immunoprecipitates was increased 2-fold at 10 min .", "target_text": { "C5b-9": "protein", "Ras": "protein", "GTP-bound Ras": "protein", "anti- C5b-9 immunoprecipitates": "protein", "anti- Ras immunoprecipitates": "protein" } }, { "input_text": "Both C5b-9 and C5b-7 , but not C5b6 , increased Raf-1 kinase activity maximum 3.3-fold at 2 min and 2.8-fold at 5 min , respectively .", "target_text": { "C5b-9": "protein", "C5b-7": "protein", "C5b6": "protein", "Raf-1": "protein" } }, { "input_text": "ERK1 activity was 2-fold increased by C5b-9 at 2 min and by C5b-7 at 10 min , over the C5b6 level .", "target_text": { "ERK1": "protein", "C5b-9": "protein", "C5b-7": "protein", "C5b6": "protein" } }, { "input_text": "The role of mitogen-activated protein kinase ( MAPK ) pathway on TCC -inducible mitotic signaling was evaluated by assessing DNA synthesis and activator protein 1 ( AP-1 ) DNA-binding activity .", "target_text": { "mitogen-activated protein kinase": "protein", "MAPK": "protein", "TCC": "protein", "activator protein 1": "protein", "AP-1": "protein" } }, { "input_text": "The MAPK/ERK-specific inhibitor PD 098,059 abolished the C5b-9 -induced DNA synthesis .", "target_text": { "C5b-9": "protein" } }, { "input_text": "Involvement of G protein in the activation of MAPK pathway by TCC was indicated by inhibition of Raf-1 and ERK1 kinase activity , as well as the DNA synthesis by pretreatment of cells with pertussis toxin .", "target_text": { "G protein": "protein", "MAPK": "protein", "TCC": "protein", "Raf-1": "protein", "ERK1": "protein", "pertussis toxin": "protein" } }, { "input_text": "Overexpression of beta-adrenergic receptor kinase 1 carboxyl-terminal peptide in JY25 cells also inhibited Raf-1 and ERK1 activity , indicating a direct involvement of G betagamma subunits in the signal transduction generated through activation of MAPK pathway by TCC assembly in the plasma membrane .", "target_text": { "JY25 cells": "cell_line", "Raf-1": "protein", "ERK1": "protein", "MAPK": "protein", "TCC": "protein" } }, { "input_text": "Spontaneous occurrence of early region 1A reiteration mutants of type 5 adenovirus in persistently infected human T-lymphocytes .", "target_text": { "persistently infected human T-lymphocytes": "cell_type" } }, { "input_text": "Mutants of type 5 adenovirus ( Ad5 ) with reiterated DNA sequences in the E1a region appeared in a human T-lymphocyte cell line , Molt-4 , persistently infected with H5sub304 , a deletion/substitution mutant that has a wild-type phenotype in viral replication .", "target_text": { "reiterated DNA sequences": "DNA", "E1a region": "DNA", "human T-lymphocyte cell line": "cell_line", "Molt-4": "cell_line" } }, { "input_text": "Endonuclease analyses and DNA sequencing revealed DNA reiteration in each mutant .", "target_text": { "Endonuclease": "protein" } }, { "input_text": "In the four representative mutants investigated , the DNA reiterations all started within a six-base-pair consensus sequence , G ( or C ) CTGTG , located in the second exon of the E1a region ( at nt 1333 , 1367 , or 1419 ) .", "target_text": { "DNA reiterations": "DNA", "six-base-pair consensus sequence": "DNA", "exon": "DNA", "E1a region": "DNA" } }, { "input_text": "There was not any DNA homology between the breakpoints in the second exon and the inserting sequences ( starting at nt 532 , 710 , or 792 ) .", "target_text": { "exon": "DNA", "inserting sequences": "DNA" } }, { "input_text": "Northern analyses suggested that the reiterated splicing sites of the representative mutants were all used in RNA splicing , and the closest donor and recipient joints were used most frequently .", "target_text": { "reiterated splicing sites": "DNA" } }, { "input_text": "These observations imply that during persistent infection Ad5 underwent spontaneous mutations by sequence-specific breakage and nonhomologous end-end joining recombination events .", "target_text": {} }, { "input_text": "These E1a reiteration mutants could be propagated in HeLa , A549 , and KB cells ; they were genetically stable ; and they killed CREF cells at a strikingly high frequency .", "target_text": { "HeLa": "cell_line", "A549": "cell_line", "KB cells": "cell_line", "CREF cells": "cell_line" } }, { "input_text": "Preliminary observations tend to correlate this CREF cell killing with the accumulation of the early viral proteins and/or viral DNA in the infected cells .", "target_text": { "early viral proteins": "protein", "viral DNA": "DNA", "infected cells": "cell_type" } }, { "input_text": "This degree of cell damage was not observed in Ad5wt or H5sub304 infection of CREF cells .", "target_text": { "CREF cells": "cell_line" } }, { "input_text": "The observed E1a reiterations provide a model to gain insight into understanding the evolutionary events of some , if not all , adenovirus types during many years of symbiotic , persistent relationship in human tonsils and adenoids and possibly other lymphoid organs .", "target_text": { "E1a reiterations": "DNA" } }, { "input_text": "Preferential presentation of herpes simplex virus T-cell antigen by HLA DQA1*0501/DQB1*0201 in comparison to HLA DQA1*0201/DQB1*0201 .", "target_text": { "herpes simplex virus T-cell antigen": "protein", "HLA DQA1*0501/DQB1*0201": "protein", "HLA DQA1*0201/DQB1*0201": "protein" } }, { "input_text": "The HLA DQA1 locus is polymorphic .", "target_text": { "HLA DQA1 locus": "DNA" } }, { "input_text": "Haplotypes containing HLA DQA1*0501 , but not HLA DQA1*0201 , together with HLA DQB1*0201 are associated with Grave 's disease and celiac sprue .", "target_text": { "HLA DQA1*0501": "DNA", "HLA DQA1*0201": "DNA", "HLA DQB1*0201": "DNA" } }, { "input_text": "In this report , we demonstrate a functional correlate of DQA1 polymorphism .", "target_text": {} }, { "input_text": "T cells infiltrating a herpes simplex virus ( HSV ) lesion from a HLA DQ 2,7 individual yielded a virus-specific CD4+ clone restricted by DQ2 .", "target_text": { "T cells": "cell_type", "virus-specific CD4+ clone": "cell_line", "DQ2": "protein" } }, { "input_text": "Presentation of viral peptide and protein segregated with DQA1 allele , because cell lines bearing DQA1*0501/DQB1*0201 heterodimers presented antigen in proliferation and cytotoxicity assays much more efficiently than cell lines bearing DQA1*0201/DQB1*0201 .", "target_text": { "DQA1 allele": "DNA", "DQA1*0501/DQB1*0201 heterodimers": "protein", "cell lines": "cell_line", "DQA1*0201/DQB1*0201": "protein" } }, { "input_text": "Binding of viral peptide to cell lines bearing DQA1*0201 , in comparison to DQA1*0501 , was only moderately reduced and may not explain this effect .", "target_text": { "DQA1*0201": "protein", "DQA1*0501": "protein" } }, { "input_text": "Truncation and substitution analyses of peptide binding and T-cell activation were performed to determine which viral peptide residues contacting TCR might therefore be presented in an altered conformation by DQA1*0201/DQB1*0201 .", "target_text": { "TCR": "protein", "DQA1*0201/DQB1*0201": "protein" } }, { "input_text": "Residues 432 , 435 , 437 , 438 , and 440 ( position P1 , P4 , P6 , P7 , and P9 ) contributed to DQ2 binding , whereas residues 431 , 433 , 434 , and 436 ( positions P 1 , P2 , P3 , and P5 ) contributed to TCR contact .", "target_text": { "DQ2": "protein", "TCR": "protein" } }, { "input_text": "Differential presentation of peptide by HLA DQ2 heterodimers varying at the DQA1 locus may have relevance to host defense and the pathogenesis of HLA DQ2 -associated autoimmune diseases .", "target_text": { "HLA DQ2 heterodimers": "protein", "DQA1 locus": "DNA", "DQ2": "protein" } }, { "input_text": "Inhibitor ( IK ) of IFN-gamma induced HLA class II antigens expression also inhibits HLA class II constitutive expression in the human Raji B cell line .", "target_text": { "IFN-gamma": "protein", "HLA class II antigens": "protein", "HLA class II": "protein", "human Raji B cell line": "cell_line" } }, { "input_text": "The expression of major histocompatibility complex ( MHC ) class II antigens is constitutive in professional antigen presenting cells ( APCs ) but can also be induced by interferon-gamma ( IFN-gamma ) on the majority of the non professional APCs ( e.g. fibroblasts ) .", "target_text": { "major histocompatibility complex ( MHC ) class II antigens": "protein", "professional antigen presenting cells": "cell_type", "APCs": "cell_type", "interferon-gamma": "protein", "IFN-gamma": "protein", "professional APCs": "cell_type", "fibroblasts": "cell_type" } }, { "input_text": "We have recently characterised a new factor called IK which is an efficient inhibitor of IFN-gamma induction of MHC class II antigens expression .", "target_text": { "IK": "protein", "IFN-gamma": "protein", "MHC class II antigens": "protein" } }, { "input_text": "Here , we demonstrate a novel role for IK in MHC class II expression since over-expression of this protein by stable transfection into human B cells led to a total disappearance of constitutive MHC class II mRNA expression .", "target_text": { "IK": "protein", "MHC class II": "protein", "MHC class II mRNA": "RNA" } }, { "input_text": "The class II transactivator ( CIITA ) is necessary for both constitutive and IFN-gamma induced MHC class II expressions .", "target_text": { "class II transactivator": "DNA", "CIITA": "DNA", "IFN-gamma": "protein", "MHC class II": "protein" } }, { "input_text": "Examination of CIITA mRNA in IK stably transfected clones revealed a marked reduction of CIITA mRNA transcription .", "target_text": { "CIITA": "DNA", "CIITA mRNA": "RNA", "IK": "protein" } }, { "input_text": "Taken together these results demonstrate that the IK protein plays a key role in the constitutive expression of MHC class II antigens and that inhibition induced by IK is upstream of CIITA in this regulatory pathway .", "target_text": { "IK": "protein", "IK protein": "protein", "MHC class II antigens": "protein", "CIITA": "DNA" } }, { "input_text": "Selective expression of an interleukin-12 receptor component by human T helper 1 cells .", "target_text": { "interleukin-12 receptor component": "protein", "human T helper 1 cells": "cell_type" } }, { "input_text": "Interleukin-12 ( IL-12 ) , a heterodimeric cytokine produced by activated monocytes and dendritic cells , plays a crucial role in regulating interferon ( IFN ) -gamma production and in the generation of IFN-gamma -producing T helper 1 ( Th1 ) cells .", "target_text": { "Interleukin-12": "protein", "IL-12": "protein", "heterodimeric cytokine": "protein", "interferon ( IFN ) -gamma": "protein", "IFN-gamma": "protein", "IFN-gamma -producing T helper 1 ( Th1 ) cells": "cell_type" } }, { "input_text": "Here we show that the IL-12 receptor ( IL-12R ) beta 2 subunit , a recently cloned binding and signal transducing component of the IL-12R , is expressed on human Th1 but not Th2 clones and is induced during differentiation of human naive cells along the Th1 but not the Th2 pathway .", "target_text": { "IL-12": "protein", "IL-12 receptor": "protein", "IL-12R": "protein", "IL-12 receptor ( IL-12R ) beta 2 subunit": "protein", "human naive cells": "cell_type" } }, { "input_text": "IL-12 and type I but not type II interferons induce expression of the IL-12R beta 2 chain during in vitro T cell differentiation after antigen receptor triggering .", "target_text": { "IL-12": "protein", "IL-12R": "protein", "IL-12R beta 2 chain": "protein" } }, { "input_text": "The selective expression and regulation of the IL-12R beta 2 subunit may help to understand the basis of Th1/Th2 differentiation and may provide therapeutic options for altering the Th1/Th2 balance in several immuno-pathological conditions such as autoimmune diseases and allergies .", "target_text": { "IL-12R": "protein", "IL-12R beta 2 subunit": "protein" } }, { "input_text": "The T cell activation factor NF-ATc positively regulates HIV-1 replication and gene expression in T cells .", "target_text": { "T cell activation factor": "protein", "NF-ATc": "protein", "T cells": "cell_type" } }, { "input_text": "Clinical deterioration in human immunodeficiency virus type 1 ( HIV-1 ) infection is associated with increased levels of viral replication and burden in the peripheral blood and lymphoid organs .", "target_text": {} }, { "input_text": "T cell activation and ensuing cellular gene activation can be critical for HIV-1 replication .", "target_text": {} }, { "input_text": "The hypothesis that the nuclear factor of activated T cells ( NF-AT ) may influence HIV-1 replication is therefore compelling given the tight correlation of HIV-1 transcriptional induction to T cell activation .", "target_text": { "nuclear factor of activated T cells": "protein", "NF-AT": "protein" } }, { "input_text": "We report that certain NF-AT ( Rel ) family members productively bind the kappaB regulatory elements , synergize with NF-kappaB and Tat in transcriptional activation of HIV-1 , and enhance HIV-1 replication in T cells .", "target_text": { "NF-AT ( Rel ) family members": "protein", "kappaB regulatory elements": "DNA", "NF-kappaB": "protein", "Tat": "protein", "T cells": "cell_type" } }, { "input_text": "These results link regulatory factors critical to T cell commitment directly to HIV-1 replication .", "target_text": { "regulatory factors": "protein" } }, { "input_text": "Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 ( Th2 ) cells but not in Th1 cells .", "target_text": { "NFAT": "protein", "CD4+ T helper 2 ( Th2 ) cells": "cell_type", "Th1 cells": "cell_type" } }, { "input_text": "Transcriptional factors of the NFAT family play an important role in regulating the expression of several cytokine genes during the immune response , such as the genes for interleukin 2 ( IL-2 ) and IL-4 , among others .", "target_text": { "Transcriptional factors": "protein", "NFAT": "protein", "NFAT family": "protein", "cytokine genes": "DNA", "interleukin 2": "protein", "IL-2": "protein", "IL-4": "protein" } }, { "input_text": "Upon antigen stimulation , precursor CD4+ T helper ( pTh ) cells proliferate and differentiate into two populations of effector cells ( eTh1 and eTh2 ) , each one expressing a specific pattern of cytokines that distinguishes them from their precursors .", "target_text": { "CD4+ T helper ( pTh ) cells": "cell_type", "effector cells": "cell_type", "eTh1": "cell_type", "eTh2": "cell_type", "cytokines": "protein" } }, { "input_text": "eTh2 cells are the major source of IL-4 , while gamma interferon is produced by eTh1 cells .", "target_text": { "eTh2 cells": "cell_type", "IL-4": "protein", "gamma interferon": "protein", "eTh1 cells": "cell_type" } }, { "input_text": "Here we have used reporter transgenic mice to show that DNA binding and transcriptional activities of NFAT are transiently induced during the differentiation of pTh cells into either eTh1 or eTh2 cells to mediate the expression of IL-2 as a common growth factor in both pathways .", "target_text": { "NFAT": "protein", "pTh cells": "cell_type", "eTh1": "cell_type", "eTh2 cells": "cell_type", "IL-2": "protein" } }, { "input_text": "However , although NFAT DNA binding is similarly induced in both eTh1 and eTh2 cells upon antigen stimulation , only the NFAT complexes present in eTh2 cells are able to mediate high-level transcription , and relatively little NFAT transcriptional activity was induced in eTh1 cells .", "target_text": { "NFAT": "protein", "eTh1": "cell_type", "eTh2 cells": "cell_type", "NFAT complexes": "protein", "eTh1 cells": "cell_type" } }, { "input_text": "In contrast to activated pTh cells , neither eTh1 nor eTh2 cells produced significant IL-2 upon stimulation , but the high levels of NFAT transcriptional activities directly correlate with the IL-4 production induced in response to antigen stimulation in eTh2 cells .", "target_text": { "pTh cells": "cell_type", "eTh1": "cell_type", "eTh2 cells": "cell_type", "IL-2": "protein", "NFAT": "protein", "IL-4": "protein" } }, { "input_text": "These data suggest that activated NFAT is involved in the effector function of eTh2 cells and that the failure of eTh1 cells to produce IL-4 in response to an antigen is due , at least partially , to a failure to induce high-level transcription of the IL-4 gene by NFAT .", "target_text": { "NFAT": "protein", "eTh2 cells": "cell_type", "eTh1 cells": "cell_type", "IL-4": "protein", "IL-4 gene": "DNA" } }, { "input_text": "Regulation of NFAT could be therefore a critical element in the polarization to eTh1 or eTh2 .", "target_text": { "NFAT": "protein", "eTh1": "cell_type", "eTh2": "cell_type" } }, { "input_text": "Activation of the transcription factor NF-kappaB in lipopolysaccharide -stimulated U937 cells .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein", "lipopolysaccharide -stimulated U937 cells": "cell_line" } }, { "input_text": "During the course of serious bacterial infections , lipopolysaccharide ( LPS ) interacts with monocyte/macrophage receptors , resulting in the generation of inflammatory cytokines .", "target_text": { "monocyte/macrophage receptors": "protein", "cytokines": "protein", "inflammatory cytokines": "protein" } }, { "input_text": "Transcription factor NF-kappaB is crucial in activating the transcription of genes encoding proinflammatory cytokines .", "target_text": { "Transcription factor": "protein", "NF-kappaB": "protein", "cytokines": "protein", "proinflammatory cytokines": "protein" } }, { "input_text": "In this paper , we demonstrate that the activation of NF-kappaB by LPS in a promonocytic cell line ( U937 ) followed a rather slow kinetics , depending on the rate of IkappaB-alpha inhibitor hydrolysis .", "target_text": { "NF-kappaB": "protein", "promonocytic cell line": "cell_line", "U937": "cell_line", "IkappaB-alpha": "protein" } }, { "input_text": "No degradation of p105 and p100 inhibitors was observed under these conditions .", "target_text": {} }, { "input_text": "The transduction pathway leading to NF-kappaB activation in U937 cells involved the intracellular generation of reactive oxygen species ( ROS ) , as demonstrated by the concomitant inhibitory effects of antioxidants on NF-kappaB activation and the emission of a fluorescent probe reacting intracellularly with hydrogen peroxide .", "target_text": { "NF-kappaB": "protein", "U937 cells": "cell_line" } }, { "input_text": "This ROS pathway was also characterized by the use of other inhibitors .", "target_text": {} }, { "input_text": "This finding indicates that phospholipase A2 and 5-lipoxygenase are also involved .", "target_text": { "phospholipase A2": "protein", "5-lipoxygenase": "protein" } }, { "input_text": "However , the NF-kappaB activation pathway involving the acidic sphingomyelinase of the endolysosomial membrane did not seem to participate in the LPS -induced NF-kappaB activation in U937 cells .", "target_text": { "NF-kappaB": "protein", "acidic sphingomyelinase": "protein", "U937 cells": "cell_line" } }, { "input_text": "c-Rel is a target of pentoxifylline -mediated inhibition of T lymphocyte activation .", "target_text": { "c-Rel": "protein" } }, { "input_text": "The possible clinical use of the methyl xanthine derivative , pentoxifylline ( PF ) , for the treatment of T cell-dependent diseases is being noted with increasing interest .", "target_text": {} }, { "input_text": "In this paper , we studied the molecular consequences of PF treatment during lymphocyte activation .", "target_text": {} }, { "input_text": "We found that in T cells , anti-CD3-induced c-Rel expression was blocked by PF , whereas the induction of other NF-kappaB family members was not significantly affected .", "target_text": { "T cells": "cell_type", "c-Rel": "protein", "NF-kappaB": "protein", "NF-kappaB family members": "protein" } }, { "input_text": "However , induction of NF-AT , which has the same signaling requirements as c-Rel induction , was not inhibited by PF .", "target_text": { "NF-AT": "protein", "c-Rel": "protein" } }, { "input_text": "Among genes that respond to these transcription factors , IL-2 mRNA induction was suppressed by PF , whereas IL-2R ( alpha ) chain mRNA induction was not affected .", "target_text": { "transcription factors": "protein", "IL-2": "protein", "IL-2 mRNA": "RNA", "IL-2R ( alpha ) chain": "protein", "IL-2R ( alpha ) chain mRNA": "RNA" } }, { "input_text": "These observations implicated c-Rel as an IL-2 promoter factor , for which experimental support was obtained from transient transfection experiments .", "target_text": { "c-Rel": "protein", "IL-2": "protein", "IL-2 promoter factor": "protein" } }, { "input_text": "In contrast with the observation in T cells , c-Rel induction was not blocked by PF in B cells .", "target_text": { "T cells": "cell_type", "c-Rel": "protein", "B cells": "cell_type" } }, { "input_text": "The greater selectivity of PF , compared with FK506 , at both the molecular and cellular levels may prove advantageous in manipulating T cell responses in vivo .", "target_text": {} }, { "input_text": "V3 loop of human immunodeficiency virus type 1 suppresses interleukin 2 -induced T cell growth [ published erratum appears in AIDS Res Hum Retroviruses 1997 May 1 ; 13 ( 7 ) : 633 ]", "target_text": { "V3 loop": "protein", "interleukin 2": "protein" } }, { "input_text": "We tested the effect of three linear or two loop peptides derived from the V3 region of the HTLV-III BH10 clone or the SF2 strain of human immunodeficiency virus type 1 on IL-2 -driven T cell proliferation .", "target_text": { "V3 region": "protein", "IL-2": "protein" } }, { "input_text": "V3-BH10 , which consists of 42 amino acids and has a loop structure , suppressed IL-2 -driven proliferation of all IL-2 -dependent cells [ Kit225 , ED-40515(+) , KT-3 , 7-day PHA-blasts , and fresh peripheral blood mononuclear cells ] tested , whereas it did not suppress the cell growth of IL-2 -independent cell lines ( Hut102 , Molt-4 , and Jurkat ) .", "target_text": { "V3-BH10": "protein", "42 amino acids": "protein", "loop structure": "protein", "IL-2": "protein", "IL-2 -dependent cells": "cell_line", "Kit225": "cell_line", "ED-40515(+)": "cell_line", "KT-3": "cell_line", "7-day PHA-blasts": "cell_line", "fresh peripheral blood mononuclear cells": "cell_type", "IL-2 -independent cell lines": "cell_line", "Hut102": "cell_line", "Molt-4": "cell_line", "Jurkat": "cell_line" } }, { "input_text": "This suppressive effect was also seen in IL-2 -driven cell growth of CD8-positive lymphocytes purified from 7-day PHA-blasts , indicating that CD4 molecules were not required for the suppression .", "target_text": { "IL-2": "protein", "CD8-positive lymphocytes": "cell_type", "7-day PHA-blasts": "cell_type", "CD4 molecules": "protein" } }, { "input_text": "The treatment with anti- V3 loop monoclonal antibody ( 902 antibody ) completely abolished the suppressive effect of V3-BH10 .", "target_text": { "V3 loop": "protein", "anti- V3 loop monoclonal antibody": "protein", "902 antibody": "protein", "V3-BH10": "protein" } }, { "input_text": "In addition , V3-BH10 generated the arrest of Kit225 cells and also purified CD8-positive lymphocytes in G1 phase in the presence of IL-2 .", "target_text": { "V3-BH10": "protein", "Kit225 cells": "cell_line", "purified CD8-positive lymphocytes": "cell_line", "IL-2": "protein" } }, { "input_text": "Neither chromatin condensation nor DNA fragmentation was detected in Kit225 cells cultured with V3-BH10 and IL-2 .", "target_text": { "chromatin": "DNA", "Kit225 cells": "cell_line", "V3-BH10": "protein", "IL-2": "protein" } }, { "input_text": "V3-BH10 neither blocked radiolabeled IL-2 binding to IL-2 receptors nor affected tyrosyl phosphorylation of several cellular proteins ( p120 , p98 , p96 , p54 , and p38 ) , which is immediately induced by IL-2 stimulation .", "target_text": { "V3-BH10": "protein", "IL-2": "protein", "IL-2 receptors": "protein", "cellular proteins": "protein", "p120": "protein", "p98": "protein", "p96": "protein", "p54": "protein", "p38": "protein" } }, { "input_text": "However , V3-BH10 enhanced IL-2 -induced mRNA expression of c-fos but not c-myc or junB .", "target_text": { "V3-BH10": "protein", "IL-2": "protein", "-induced mRNA": "RNA", "c-fos": "DNA", "c-myc": "DNA", "junB": "DNA" } }, { "input_text": "Thus , the binding of V3 loop of gp120 to the cell surface molecule ( s ) appears to affect intracellular IL-2 signaling , which leads to the suppression of IL-2 -induced T cell growth", "target_text": { "V3 loop": "protein", "gp120": "protein", "IL-2": "protein" } }, { "input_text": "A negative role for phosphoinositide 3-kinase in T-cell antigen receptor function .", "target_text": { "phosphoinositide 3-kinase": "protein", "T-cell antigen receptor": "protein" } }, { "input_text": "BACKGROUND : A delicate balance between positive and negative regulatory mechanisms during T-cell activation determines the specificity and magnitude of an immune response .", "target_text": {} }, { "input_text": "Phosphoinositide 3-kinase ( PI 3-kinase ) is activated by a diverse set of receptors that determine T-cell function , including the T-cell antigen receptor ( TCR ) , the costimulatory receptor CD28 , and negative regulators of T-cell activation such as CTLA-4 .", "target_text": { "Phosphoinositide 3-kinase": "protein", "PI 3-kinase": "protein", "T-cell antigen receptor": "protein", "TCR": "protein", "costimulatory receptor CD28": "protein", "negative regulators": "protein", "CTLA-4": "protein" } }, { "input_text": "PI 3-kinase is also regulated by the haematopoietic cytokines that determine T-cell differentiation and lymphocyte proliferation .", "target_text": { "PI 3-kinase": "protein", "lymphocyte": "cell_type" } }, { "input_text": "PI 3-kinase can thus dynamically influence the outcome of the immune reactions at various stages .", "target_text": { "PI 3-kinase": "protein" } }, { "input_text": "In this study , we investigated the importance of PI 3-kinase in TCR -directed T-cell activation using activated or inhibitory versions of PI 3-kinase .", "target_text": { "PI 3-kinase": "protein", "TCR": "protein" } }, { "input_text": "RESULTS : Certain aspects of TCR responses such as the induction of transcriptional activity of AP1 and serum response factor were not affected by expression of the mutant forms of PI 3-kinase .", "target_text": { "TCR": "protein", "AP1": "protein", "serum response factor": "protein", "PI 3-kinase": "protein" } }, { "input_text": "We found , however , that PI 3-kinase profoundly influenced the transactivation capacity of ' nuclear factor of activated T cells ' ( NF-AT ) elicited by the TCR : expression of an activated form of PI 3-kinase inhibited TCR -mediated NF-AT responses , whereas expression of a dominant negative mutant of PI 3-kinase potently enhanced TCR -controlled NF-AT induction .", "target_text": { "PI 3-kinase": "protein", "nuclear factor of activated T cells": "protein", "NF-AT": "protein", "TCR": "protein" } }, { "input_text": "These effects of PI 3-kinase were not mediated by previously identified PI 3-kinase effectors , such as protein kinase B , a positive regulator of PI 3-kinase , or the GTPase Rac , and are therefore likely to involve a novel , as yet unknown , effector molecule .", "target_text": { "PI 3-kinase": "protein", "PI 3-kinase effectors": "protein", "protein kinase B": "protein", "positive regulator": "protein", "GTPase": "protein", "Rac": "protein", "GTPase Rac": "protein", "effector molecule": "protein" } }, { "input_text": "CONCLUSIONS : Our results establish that PI 3-kinase can both positively and negatively regulate T-cell function , and uncover a previously unrecognized function for PI 3-kinase in T cells as a selective negative regulator of TCR -signalling events and therefore as a determinant of T-cell homeostasis .", "target_text": { "PI 3-kinase": "protein", "T cells": "cell_type", "TCR": "protein" } }, { "input_text": "The Pax-5 gene is alternatively spliced during B-cell development .", "target_text": { "Pax-5 gene": "DNA" } }, { "input_text": "The transcription factor Pax-5 is expressed during the early stages of B-cell differentiation and influences the expression of several B-cell-specific genes .", "target_text": { "transcription factor": "protein", "transcription factor Pax-5": "protein", "B-cell-specific genes": "DNA" } }, { "input_text": "In addition to the existing isoform ( Pax-5 , which we have named Pax-5a ) , we have isolated three new isoforms , Pax-5b , Pax-5d , and Pax-5e , from murine spleen and B-lymphoid cell lines using library screenings and polymerase chain reaction amplification .", "target_text": { "Pax-5": "protein", "Pax-5a": "protein", "Pax-5b": "protein", "Pax-5d": "protein", "Pax-5e": "protein", "B-lymphoid cell lines": "cell_line" } }, { "input_text": "Isoforms Pax-5b and Pax-5e have spliced out their second exon , resulting in proteins with only a partial DNA-binding domain .", "target_text": { "Pax-5b": "protein", "Pax-5e": "protein", "DNA-binding domain": "protein" } }, { "input_text": "Isoforms Pax-5d and Pax-5e have deleted the 3'-region , which encodes the transactivating domain , and replaced it with a novel sequence .", "target_text": { "Pax-5e": "protein", "3'-region": "protein" } }, { "input_text": "The existence of alternative Pax-5 transcripts was confirmed using RNase protection assays .", "target_text": { "Pax-5": "protein", "Pax-5 transcripts": "RNA", "RNase": "protein" } }, { "input_text": "Furthermore , Pax-5a and Pax-5b proteins were detected using Western blot analysis .", "target_text": { "Pax-5a": "protein", "Pax-5b": "protein", "Pax-5b proteins": "protein" } }, { "input_text": "Pax-5a was detectable in pro- , pre- , and mature B-cell lines , but not in two plasmacytomas ; Pax-5b was shown to be present at low levels in mature B-cell lines and , unexpectedly , in one plasma cell line , but not in pro-B-cell or T-cell lines .", "target_text": { "Pax-5a": "protein", "Pax-5b": "protein", "mature B-cell lines": "cell_line" } }, { "input_text": "Mobility shift assays showed that in vitro translated Pax-5a and Pax-5d , but not Pax-5b or Pax-5e , could interact with a B-cell-specific activator protein-binding site on the blk promoter .", "target_text": { "Pax-5a": "protein", "Pax-5d": "protein", "Pax-5b": "protein", "Pax-5e": "protein", "B-cell-specific activator protein-binding site": "DNA", "blk promoter": "DNA" } }, { "input_text": "Using this assay , we also showed that Pax-5d was present in nuclear extracts of some ( but not all ) B-lymphoid lines and interacts with the B-cell-specific activator protein-binding site .", "target_text": { "Pax-5d": "protein", "B-lymphoid lines": "cell_line", "B-cell-specific activator protein-binding site": "DNA" } }, { "input_text": "The pattern of differential expression of alternatively spliced Pax-5 isoforms suggests that they may be important regulators of transcription during B-cell maturation .", "target_text": { "alternatively spliced Pax-5 isoforms": "protein", "regulators of transcription": "protein" } }, { "input_text": "Reconstitution of T cell antigen receptor-induced Erk2 kinase activation in Lck-negative JCaM1 cells by Syk .", "target_text": { "Erk2 kinase": "protein", "Lck-negative JCaM1 cells": "cell_line", "Syk": "protein" } }, { "input_text": "The two related protein- tyrosine kinases Syk and Zap are rapidly phosphorylated on tyrosine residues and enzymatically activated upon crosslinking of the T cell antigen receptor .", "target_text": { "protein- tyrosine kinases": "protein", "Syk": "protein", "Zap": "protein", "T cell antigen receptor": "protein" } }, { "input_text": "We have previously reported that the activation of Syk is less dependent on the Src family kinase Lck than the activation of Zap .", "target_text": { "Syk": "protein", "Src family kinase": "protein", "Lck": "protein", "Zap": "protein" } }, { "input_text": "Here we report that overexpression of Syk in the Lck -negative JCaM1 cells enabled the T cell antigen receptor /CD3 complex to induce a normal activation of the mitogen-activated protein kinase ( MAPK ) pathway and expression of a nuclear factor of activated T cells reporter construct .", "target_text": { "Syk": "protein", "Lck": "protein", "Lck -negative JCaM1 cells": "cell_line", "T cell antigen receptor": "protein", "T cell antigen receptor /CD3 complex": "protein", "mitogen-activated protein kinase": "protein", "MAPK": "protein", "T cells": "cell_type", "nuclear factor of activated T cells": "protein" } }, { "input_text": "In contrast , Zap and other protein- tyrosine kinases were unable to reconstitute these signaling pathways when expressed at the same levels .", "target_text": { "Zap": "protein", "protein- tyrosine kinases": "protein" } }, { "input_text": "In parallel , Syk was phosphorylated on tyrosine , while Zap was not .", "target_text": { "Syk": "protein", "Zap": "protein" } }, { "input_text": "The Syk -mediated T cell antigen receptor -induced MAPK activation was detectable within 1 min of receptor stimulation and peaked at 3-5 min .", "target_text": { "Syk": "protein", "T cell antigen receptor": "protein", "MAPK": "protein" } }, { "input_text": "The capacity of Syk to reconstitute the MAPK response required the catalytic activity of Syk , an intact autophosphorylation site ( Y518 and Y519 ) , both Src homology 2 domains and it was blocked by the inhibitory N17-mutated dominant-negative Ras construct .", "target_text": { "Syk": "protein", "MAPK": "protein", "autophosphorylation site": "protein", "Src homology 2 domains": "protein", "inhibitory N17-mutated dominant-negative Ras construct": "protein" } }, { "input_text": "A Y341 --> F mutant of Syk , which is deficient in its interaction with phospholipase Cy1 and Vav , was less efficient than wild-type Syk .", "target_text": { "F mutant": "protein", "Syk": "protein", "phospholipase Cy1": "protein", "Vav": "protein", "wild-type Syk": "protein" } }, { "input_text": "Our results suggest that Syk , in contrast to Zap , can transduce signals from the T cell antigen receptor independently of Lck .", "target_text": { "Syk": "protein", "Zap": "protein", "T cell antigen receptor": "protein", "Lck": "protein" } }, { "input_text": "Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation .", "target_text": { "transcription factor": "protein", "MEF2C": "protein", "p38": "protein", "MAP kinase p38": "protein" } }, { "input_text": "For cells of the innate immune system to mount a host defence response to infection , they must recognize products of microbial pathogens such as lipopolysaccharide ( LPS ) , the endotoxin secreted by Gram-negative bacteria .", "target_text": {} }, { "input_text": "These cellular responses require intracellular signalling pathways , such as the four MAP kinase ( MAPK ) pathways .", "target_text": { "MAP kinase": "protein", "MAPK": "protein" } }, { "input_text": "In mammalian cells the MAPK p38 is thought to play an important role in the regulation of cellular responses during infection through its effects on the expression of proinflammatory molecules .", "target_text": { "MAPK p38": "protein", "proinflammatory molecules": "protein" } }, { "input_text": "One means of understanding the role of p38 in these responses is to identify proteins with functions regulated by p38 -catalysed phosphorylation .", "target_text": { "p38": "protein" } }, { "input_text": "Here we demonstrate a link between the p38 pathway and a member of the myocyte-enhancer factor 2 ( MEF2 ) group of transcription factors .", "target_text": { "p38": "protein", "myocyte-enhancer factor 2 ( MEF2 ) group": "protein", "transcription factors": "protein" } }, { "input_text": "We found that in monocytic cells , LPS increases the transactivation activity of MEF2C through p38 -catalysed phosphorylation .", "target_text": { "monocytic cells": "cell_type", "MEF2C": "protein", "p38": "protein" } }, { "input_text": "One consequence of MEF2C activation is increased c-jun gene transcription .", "target_text": { "MEF2C": "protein", "c-jun gene": "DNA" } }, { "input_text": "Our results show that p38 may influence host defence and inflammation by maintaining the balance of c-Jun protein consumed during infection .", "target_text": { "p38": "protein", "c-Jun protein": "protein" } }, { "input_text": "Cellular redox status influences both cytotoxic and NF-kappa B activation in natural killer cells .", "target_text": { "natural killer cells": "cell_type" } }, { "input_text": "The role of cellular redox status in both cytotoxic activity and NF-kappa B activation in natural killer ( NK ) cells was investigated .", "target_text": { "NF-kappa B": "protein", "natural killer ( NK ) cells": "cell_type" } }, { "input_text": "The results indicate that stimulation of NK cells , either freshly isolated from peripheral blood lymphocytes ( PBL ) or long-term cultured NK clones , with specific cell targets results in an increased binding activity of NF-kappa B and AP-1 transcription factors measured by gel retardation .", "target_text": { "NK cells": "cell_type", "peripheral blood lymphocytes": "cell_type", "PBL": "cell_type", "long-term cultured NK clones": "cell_line", "NF-kappa B": "protein", "AP-1": "protein", "transcription factors": "protein" } }, { "input_text": "Pretreatment of NK cells with the antioxidant pyrrolidine dithiocarbarmate ( PDTC ) leads to the inhibition of NF-kappa B activation but the AP-1 binding to DNA was superinduced .", "target_text": { "NK cells": "cell_type", "NF-kappa B": "protein", "AP-1": "protein" } }, { "input_text": "The inhibition of NF-kappa B by PDTC paralleled with an inhibition of spontaneous cytotoxicity mediated by NK cells .", "target_text": { "NF-kappa B": "protein", "NK cells": "cell_type" } }, { "input_text": "Moreover , the inhibitors of serine proteases , N-alpha-tosyl-L-lysine chloromethyl ketone and N-alpha-tosyl-L-phenylalanine chloromethyl ketone , also blocked the cytolytic activity of NK cells against the sensitive target K562 .", "target_text": { "serine proteases": "protein", "NK cells": "cell_type", "K562": "cell_line" } }, { "input_text": "In contrast , NK activity was not affected by pretreatment of the effector cells with the proteasome inhibitor N-acetyl-leu-leu-norleucinal which selectively inhibits NF-kappa B activation .", "target_text": { "proteasome": "protein", "NF-kappa B": "protein" } }, { "input_text": "Altogether , these results support the hypothesis that the activation of NK cells involved transcriptional and post-transcriptional events , and that reactive intermediates may play an important role in the molecular processes related with the generation of a cytotoxic response by NK cells .", "target_text": { "NK cells": "cell_type" } }, { "input_text": "The predominant E2F complex in human primary haemopoietic cells and in AML blasts contains E2F-4 , DP-1 and p130 .", "target_text": { "E2F complex": "protein", "human primary haemopoietic cells": "cell_type", "AML blasts": "cell_type", "E2F-4": "protein", "DP-1": "protein", "p130": "protein" } }, { "input_text": "The E2F family of transcription factors are thought to play an important role in the control of cell cycle progression .", "target_text": { "E2F family": "protein", "transcription factors": "protein" } }, { "input_text": "There is now also increasing evidence that some family members may act as oncogenes or tumour suppressor genes .", "target_text": { "oncogenes": "DNA", "tumour suppressor genes": "DNA" } }, { "input_text": "The characterization of these proteins in human primary haemopoietic cells and acute myeloid leukaemia ( AML ) blasts may thus give an insight to the molecular mechanisms governing proliferation and leukaemogenesis in these cells .", "target_text": { "human primary haemopoietic cells": "cell_type", "acute myeloid leukaemia ( AML ) blasts": "cell_type" } }, { "input_text": "Therefore we analysed the expression of E2F -DNA binding activity and the constituent proteins found in the complexes in human primary haemopoietic cells of various lineages .", "target_text": { "E2F": "protein", "human primary haemopoietic cells": "cell_type" } }, { "input_text": "We also studied blasts from 18 patients with acute myeloid leukaemia ( AML ) .", "target_text": {} }, { "input_text": "On electromobility shift assays ( EMSA ) a single E2F-DNA binding complex was detected in T cells , B cells and monocytes which was shown to contain E2F-4 , DP-1 and p130 , indicating that all quiescent haemopoietic cells have the same complex .", "target_text": { "E2F-DNA binding complex": "protein", "T cells": "cell_type", "B cells": "cell_type", "monocytes": "cell_type", "E2F-4": "protein", "DP-1": "protein", "p130": "protein", "quiescent haemopoietic cells": "cell_type" } }, { "input_text": "Examination of 18 AML samples by EMSA revealed the presence of E2F binding and no gross abnormalities were detected .", "target_text": { "E2F": "protein" } }, { "input_text": "An E2F-4 /p130 complex was detected in representative samples of all FAB types analysed .", "target_text": { "E2F-4": "protein", "/p130": "protein", "E2F-4 /p130 complex": "protein", "FAB": "protein" } }, { "input_text": "Thus abnormalities of E2F function are unlikely to play a primary pathogenic role in AML .", "target_text": { "E2F": "protein" } }, { "input_text": "Characterization of a mutant cell line that does not activate NF-kappaB in response to multiple stimuli .", "target_text": { "mutant cell line": "cell_line", "NF-kappaB": "protein" } }, { "input_text": "Numerous genes required during the immune or inflammation response as well as the adhesion process are regulated by nuclear factor kappaB ( NF-kappaB ) .", "target_text": { "nuclear factor kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "Associated with its inhibitor , I kappaB , NF-kappaB resides as an inactive form in the cytoplasm .", "target_text": { "I kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "Upon stimulation by various agents , I kappaB is proteolyzed and NF-kappaB translocates to the nucleus , where it activates its target genes .", "target_text": { "I kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "The transduction pathways that lead to I kappaB inactivation remain poorly understood .", "target_text": { "I kappaB": "protein" } }, { "input_text": "In this study , we have characterized a cellular mutant , the 70/Z3-derived 1.3E2 murine pre-B cell line , that does not activate NF-kappaB in response to several stimuli .", "target_text": { "70/Z3-derived 1.3E2 murine pre-B cell line": "cell_line", "NF-kappaB": "protein" } }, { "input_text": "We demonstrate that upon stimulation by lipopolysaccharide , Taxol , phorbol myristate acetate , interleukin-1 , or double-stranded RNA , I kappaB alpha is not degraded , as a result of an absence of induced phosphorylation on serines 32 and 36 .", "target_text": { "interleukin-1": "protein", "double-stranded RNA": "RNA", "I kappaB": "protein", "I kappaB alpha": "protein" } }, { "input_text": "Neither a mutation in I kappaB alpha nor a mutation in p50 or relA , the two major subunits of NF-kappaB in this cell line , accounts for this phosphorylation defect .", "target_text": { "I kappaB": "protein", "I kappaB alpha": "protein", "p50": "protein", "relA": "protein", "NF-kappaB": "protein" } }, { "input_text": "As well as culminating in the inducible phosphorylation of I kappaB alpha on serines 32 and 36 , all the stimuli that are inactive on 1.3E2 cells exhibit a sensitivity to the antioxidant pyrrolidine dithiocarbamate ( PDTC ) .", "target_text": { "I kappaB": "protein", "1.3E2 cells": "cell_line" } }, { "input_text": "In contrast , stimuli such as hyperosmotic shock or phosphatase inhibitors , which use PDTC -insensitive pathways , induce I kappaB alpha degradation in 1.3E2 .", "target_text": { "I kappaB": "protein", "1.3E2": "cell_line" } }, { "input_text": "Analysis of the redox status of 1.3E2 does not reveal any difference from wild-type 70Z/3 .", "target_text": { "1.3E2": "cell_line", "wild-type 70Z/3": "cell_line" } }, { "input_text": "We also report that the human T-cell leukemia virus type 1 ( HTLV-1 ) -derived Tax trans-activator induces NF-kappaB activity in 1.3E2 , suggesting that this viral protein does not operate via the defective pathway .", "target_text": { "Tax": "protein", "human T-cell leukemia virus type 1 ( HTLV-1 ) -derived Tax trans-activator": "protein", "NF-kappaB": "protein", "1.3E2": "cell_line" } }, { "input_text": "Finally , we show that two other I kappaB molecules , I kappaB beta and the recently identified I kappaB epsilon , are not degraded in the 1.3E2 cell line following stimulation .", "target_text": { "I kappaB": "protein", "I kappaB molecules": "protein", "I kappaB beta": "protein", "I kappaB epsilon": "protein", "1.3E2": "cell_line" } }, { "input_text": "Our results demonstrate that 1.3E2 is a cellular transduction mutant exhibiting a defect in a step that is required by several different stimuli to activate NF-kappaB .", "target_text": { "1.3E2": "cell_line", "cellular transduction mutant": "protein", "NF-kappaB": "protein" } }, { "input_text": "In addition , this analysis suggests a common step in the signaling pathways that trigger I kappaB alpha , I kappaB beta , and I kappaB epsilon degradation .", "target_text": { "I kappaB": "protein", "I kappaB alpha": "protein", "I kappaB beta": "protein", "I kappaB epsilon": "protein" } }, { "input_text": "Involvement of Egr-1 /RelA synergy in distinguishing T cell activation from tumor necrosis factor-alpha -induced NF-kappa B1 transcription .", "target_text": { "Egr-1": "protein", "/RelA": "protein", "tumor necrosis factor-alpha": "protein", "NF-kappa B1": "protein" } }, { "input_text": "NF-kappa B is an important transcription factor required for T cell proliferation and other immunological functions .", "target_text": { "NF-kappa B": "protein", "transcription factor": "protein" } }, { "input_text": "The NF-kappa B1 gene encodes a 105-kD protein that is the precursor of the p50 component of NF-kappa B .", "target_text": { "NF-kappa B1 gene": "DNA", "105-kD protein": "protein", "p50": "protein", "p50 component": "protein", "NF-kappa B": "protein" } }, { "input_text": "Previously , we and others have demonstrated that NF-kappa B regulates the NF-kappa B1 gene .", "target_text": { "NF-kappa B": "protein", "NF-kappa B1 gene": "DNA" } }, { "input_text": "In this manuscript we have investigated the molecular mechanisms by which T cell lines stimulated with phorbol 12-myristate 13-acetate ( PMA ) and phytohemagglutin ( PHA ) display significantly higher levels of NF-kappa B1 encoding transcripts than cells stimulated with tumor necrosis factor-alpha , despite the fact that both stimuli activate NF-kappa B .", "target_text": { "T cell lines": "cell_line", "phytohemagglutin": "protein", "PHA": "protein", "NF-kappa B1": "protein", "transcripts": "RNA", "tumor necrosis factor-alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "Characterization of the NF-kappa B1 promoter identified an Egr-1 site which was found to be essential for both the PMA / PHA -mediated induction as well as the synergistic activation observed after the expression of the RelA subunit of NF-kappa B and Egr-1 .", "target_text": { "NF-kappa B1 promoter": "DNA", "Egr-1 site": "DNA", "PHA": "protein", "NF-kappa B": "protein", "Egr-1": "protein" } }, { "input_text": "Furthermore , Egr-1 induction was required for endogenous NF-kappa B1 gene expression , since PMA / PHA -stimulated T cell lines expressing antisense Egr-1 RNA were inhibited in their ability to upregulate NF-kappa B1 transcription .", "target_text": { "Egr-1": "protein", "NF-kappa B1": "DNA", "PHA": "protein", "T cell lines": "cell_line", "PHA -stimulated T cell lines": "cell_line", "Egr-1 RNA": "RNA" } }, { "input_text": "Our studies indicate that transcriptional synergy mediated by activation of both Egr-1 and NF-kappa B may have important ramifications in T cell development by upregulating NF-kappa B1 gene expression .", "target_text": { "Egr-1": "protein", "NF-kappa B": "protein", "NF-kappa B1": "DNA" } }, { "input_text": "The synthesis and immunogenicity of varicella-zoster virus glycoprotein E and immediate-early protein ( IE62 ) expressed in recombinant herpes simplex virus-1 .", "target_text": { "varicella-zoster virus glycoprotein E": "protein", "immediate-early protein": "protein", "IE62": "protein" } }, { "input_text": "In order to evaluate the conditions for optimal expression and immunogenicity of varicella-zoster virus ( VZV ) proteins in a herpes simplex virus-1 ( HSV-1 ) vector , we selected the VZV glycoprotein E ( gE ) , encoded by ORF 68 and the VZV product of ORF 62 , an immediate-early major tegument protein ( IE62 ) .", "target_text": { "varicella-zoster virus ( VZV ) proteins": "protein", "VZV glycoprotein E": "protein", "gE": "protein", "ORF 68": "DNA", "VZV product": "protein", "ORF 62": "DNA", "immediate-early major tegument protein": "protein", "IE62": "protein" } }, { "input_text": "Three HSV/VZV recombinants were generated : ( 1 ) VZV gE protein coding sequences along with the promoter region were inserted into the thymidine kinase ( TK ) gene of HSV-1 strain KOS ; ( 2 ) VZV gE expressed from the HSV-1 ICP4 promoter was inserted into the glycoprotein C ( gC ) gene of HSV-1 strain F ; and ( 3 ) VZV IE62 protein coding sequences under the control of the HSV-1 ICP4 promoter were inserted into the gC gene of HSV-1 strain F .", "target_text": { "HSV/VZV recombinants": "DNA", "VZV gE protein": "protein", "VZV gE protein coding sequences": "DNA", "promoter region": "protein", "thymidine kinase ( TK ) gene": "DNA", "VZV gE": "protein", "HSV-1 ICP4 promoter": "DNA", "glycoprotein C ( gC ) gene": "DNA", "IE62": "protein", "VZV IE62 protein coding sequences": "DNA", "gC gene": "DNA" } }, { "input_text": "Immunoblot analysis and immunoperoxidase staining of infected cell monolayers demonstrated vector expression of VZV proteins .", "target_text": { "VZV proteins": "protein" } }, { "input_text": "Following intracranial inoculation in mice , both VZV gE-HSV ( TK ) and VZV IE62-HSV ( gC ) induced an IgG response against VZV gE or VZV IE62 .", "target_text": { "VZV gE-HSV": "protein", "TK": "protein", "VZV IE62-HSV": "protein", "gC": "protein", "IgG": "protein", "VZV gE": "protein", "VZV IE62": "protein" } }, { "input_text": "When tested in cytotoxicity assays using T-lymphocytes from VZV immune human donors , the range of precursor frequencies for T-lymphocytes that recognized VZV gE or VZV IE62 was similar whether these proteins were expressed by HSV-1 or a vaccinia vector .", "target_text": { "T-lymphocytes": "cell_type", "VZV gE": "protein", "VZV IE62": "protein" } }, { "input_text": "These experiments demonstrate that HSV-1 is a competent vector for expression of these VZV proteins and support the feasibility of engineering a combined vaccine for these closely related alpha-herpesviruses .", "target_text": { "VZV proteins": "protein" } }, { "input_text": "Constitutive dephosphorylation and activation of a member of the nuclear factor of activated T cells , NF-AT1 , in Tax-expressing and type I human T-cell leukemia virus-infected human T cells .", "target_text": { "nuclear factor of activated T cells": "protein", "NF-AT1": "protein" } }, { "input_text": "The tax gene product of the type I human T-cell leukemia virus ( HTLV-I ) transactivates interleukin-2 ( IL-2 ) gene through activation of an enhancer termed CD28 responsive element ( CD28RE ) .", "target_text": { "IL-2": "protein", "interleukin-2 ( IL-2 ) gene": "DNA", "CD28 responsive element": "DNA", "CD28RE": "DNA" } }, { "input_text": "Tax activation of the CD28RE is partially mediated by a member of the nuclear factor of activated T cells , NF-AT1 .", "target_text": { "Tax": "protein", "CD28RE": "DNA", "nuclear factor of activated T cells": "protein", "NF-AT1": "protein" } }, { "input_text": "We have previously shown that NF-AT1 is constitutively active in Jurkat T cells stably transfected with the Tax cDNA , although the underlying molecular mechanism and physiological relevance of this finding remain unclear .", "target_text": { "NF-AT1": "protein", "Jurkat T cells": "cell_line", "Tax": "protein", "Tax cDNA": "DNA" } }, { "input_text": "In this report , we demonstrate that the active form of NF-AT1 is also present in the nuclei of HTLV-I -transformed T cells that express the Tax protein .", "target_text": { "NF-AT1": "protein", "HTLV-I -transformed T cells": "cell_type", "Tax": "protein", "Tax protein": "protein" } }, { "input_text": "Interestingly , the constitutive activation of NF-AT1 in these T cells is associated with its dephosphorylation .", "target_text": { "NF-AT1": "protein", "T cells": "cell_type" } }, { "input_text": "Furthermore , the dephosphorylated NF-AT1 can be rapidly rephosphorylated when the cells are incubated with cyclosporin A , an immunosuppressant inhibiting the serine /threonine phosphatase calcineurin .", "target_text": { "NF-AT1": "protein", "serine /threonine phosphatase": "protein", "calcineurin": "protein" } }, { "input_text": "These results suggest that activation of NF-AT1 in Tax-expressing and HTLV-I-transformed T cells results from its dephosphorylation , which in turn may be due to deregulation of calcineurin", "target_text": { "NF-AT1": "protein", "calcineurin": "protein" } }, { "input_text": "Expression of NFAT-family proteins in normal human T cells .", "target_text": { "NFAT-family proteins": "protein", "normal human T cells": "cell_type" } }, { "input_text": "NFAT proteins constitute a family of transcription factors involved in mediating signal transduction .", "target_text": { "NFAT proteins": "protein", "transcription factors": "protein" } }, { "input_text": "Using a panel of specific antisera in immunoprecipitation assays , we found that NFATp ( 135 kDa ) is constitutively expressed in normal human T cells , while synthesis of NFATc ( predominant form of 86 kDa ) is induced by ionomycin treatment .", "target_text": { "NFATp": "protein", "135 kDa": "protein", "normal human T cells": "cell_type", "NFATc": "protein", "86 kDa": "protein" } }, { "input_text": "NFAT4/x was very weakly expressed in unstimulated cells , and its level did not increase upon treatment with activating agents .", "target_text": { "NFAT4/x": "protein" } }, { "input_text": "NFAT3 protein was not observed under any conditions .", "target_text": { "NFAT3 protein": "protein" } }, { "input_text": "Higher-molecular-weight species of NFATc ( of 110 and 140 kDa ) were also detected .", "target_text": { "Higher-molecular-weight species": "protein", "NFATc": "protein" } }, { "input_text": "In addition , translation of NFATc mRNA apparently initiates at two different AUG codons , giving rise to proteins that differ in size by 36 amino acids .", "target_text": { "NFATc": "protein", "NFATc mRNA": "RNA", "AUG codons": "DNA" } }, { "input_text": "Additional size heterogeneity of both NFATc and NFATp results from phosphorylation .", "target_text": { "NFATc": "protein", "NFATp": "protein" } }, { "input_text": "In contrast to ionomycin treatment , exposure of cells to phorbol myristate acetate ( PMA ) plus anti-CD28 did not induce NFATc , indicating that under these conditions , interleukin-2 synthesis by these cells is apparently independent of NFATc .", "target_text": { "anti-CD28": "protein", "NFATc": "protein", "interleukin-2": "protein" } }, { "input_text": "In DNA binding assays , both PMA plus anti-CD28 and PMA plus ionomycin resulted in nuclear NFAT .", "target_text": { "anti-CD28": "protein", "nuclear NFAT": "protein" } }, { "input_text": "Surprisingly , the PMA - ionomycin -induced synthesis of NFATc that was detected by immunoprecipitation was not mirrored in the DNA binding assays : nearly all of the activity was due to NFATp .", "target_text": { "NFATc": "protein", "NFATp": "protein" } }, { "input_text": "This is the first study of expression of all family members at the protein level in normal human T cells .", "target_text": { "normal human T cells": "cell_type" } }, { "input_text": "Of the GATA-binding proteins , only GATA-4 selectively regulates the human IL-5 gene promoter in IL-5 producing cells which express multiple GATA-binding proteins .", "target_text": { "GATA-binding proteins": "protein", "GATA-4": "protein", "human IL-5 gene promoter": "DNA", "IL-5 producing cells": "cell_type", "multiple GATA-binding proteins": "protein" } }, { "input_text": "Interleukin-5 ( IL-5 ) is produced by T lymphocytes and known to support B cell growth and eosinophilic differentiation of the progenitor cells .", "target_text": { "Interleukin-5": "protein", "IL-5": "protein", "T lymphocytes": "cell_type", "progenitor cells": "cell_type" } }, { "input_text": "Using ATL-16T cells which express IL-5 mRNA , we have identified a region , within the human IL-5 gene promoter , that regulates IL-5 gene transcription .", "target_text": { "ATL-16T cells": "cell_line", "IL-5": "protein", "IL-5 mRNA": "RNA", "human IL-5 gene promoter": "DNA", "IL-5 gene": "DNA" } }, { "input_text": "This cis-acting sequence contains the core binding motif , (A/T)GATA(A/G) , for GATA-binding family proteins and thus suggests the involvement of these family members .", "target_text": { "cis-acting sequence": "DNA", "core binding motif": "DNA", "GATA-binding family proteins": "protein" } }, { "input_text": "In this report , we describe the cloning of human GATA-4 ( hGATA-4 ) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region .", "target_text": { "GATA-4": "protein", "human GATA-4": "protein", "hGATA-4": "protein", "-70 GATA site": "DNA", "IL-5": "protein", "IL-5 proximal promoter region": "DNA" } }, { "input_text": "By promoter deletion and mutation analyses , we established this region as a positive regulatory element .", "target_text": { "positive regulatory element": "DNA" } }, { "input_text": "Cotransfection experiments revealed that both hGATA-4 and PMA /A23187 stimulation are necessary for the IL-5 promoter activation .", "target_text": { "hGATA-4": "protein", "IL-5": "protein", "IL-5 promoter": "DNA" } }, { "input_text": "The requirement of another regulatory element called CLE0 , which lies downstream of the -70 GATA site , was also demonstrated .", "target_text": { "regulatory element": "DNA", "CLE0": "DNA", "-70 GATA site": "DNA" } }, { "input_text": "ATL-16T cells express mRNA of three GATA-binding proteins , hGATA-2 , hGATA-3 and hGATA-4 , and each of them has a potential to bind to the consensus (A/T)GATA(G/ A) motif .", "target_text": { "ATL-16T cells": "cell_line", "mRNA": "RNA", "GATA-binding proteins": "protein", "hGATA-2": "protein", "hGATA-3": "protein", "hGATA-4": "protein", "consensus (A/T)GATA(G/ A) motif": "DNA" } }, { "input_text": "However , using ATL-16T nuclear extract , we demonstrated that GATA-4 is the only GATA-binding protein that forms specific DNA-protein complex with the -70 GATA site .", "target_text": { "GATA-4": "protein", "GATA-binding protein": "protein", "DNA-protein complex": "protein", "-70 GATA site": "DNA" } }, { "input_text": "The electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity to the -70 GATA site among the three GATA-binding proteins .", "target_text": { "COS cells": "cell_line", "GATA-binding proteins": "protein", "GATA-4": "protein", "-70 GATA site": "DNA" } }, { "input_text": "When the transactivation ability was compared among the three , GATA-4 showed the highest activity .", "target_text": { "GATA-4": "protein" } }, { "input_text": "These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed .", "target_text": { "GATA-4": "protein", "IL-5": "protein", "IL-5 gene": "DNA", "GATA-binding proteins": "protein" } }, { "input_text": "Control of NFATx1 nuclear translocation by a calcineurin -regulated inhibitory domain .", "target_text": { "NFATx1": "protein", "calcineurin": "protein", "calcineurin -regulated inhibitory domain": "protein" } }, { "input_text": "The nuclear factor of activated T cells ( NFAT ) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of several cytokine genes .", "target_text": { "nuclear factor of activated T cells": "protein", "NFAT": "protein", "cytokine gene": "DNA", "T cells": "cell_type", "cis-acting elements": "DNA", "promoters": "DNA", "cytokine genes": "DNA" } }, { "input_text": "NFATx1 , which is preferentially expressed in the thymus and peripheral blood leukocytes , is one of four members of the NFAT family of transcription factors .", "target_text": { "NFATx1": "protein", "peripheral blood leukocytes": "cell_type", "NFAT": "protein", "NFAT family": "protein", "transcription factors": "protein" } }, { "input_text": "We have performed domain analysis of NFATx1 by examining the effects of deletion mutations .", "target_text": { "NFATx1": "protein" } }, { "input_text": "We found that NFATx1 DNA binding activity and interaction with AP-1 polypeptides were dependent on its central Rel similarity region and that transcriptional activation was reduced by deletions of either its N-terminal domain or its C-terminal domain , suggesting the presence of intrinsic transcriptional activation motifs in both regions .", "target_text": { "NFATx1": "protein", "central Rel similarity region": "protein", "N-terminal domain": "protein", "C-terminal domain": "protein", "intrinsic transcriptional activation motifs": "protein" } }, { "input_text": "We also identified a potent inhibitory sequence within its N-terminal domain .", "target_text": { "inhibitory sequence": "protein", "N-terminal domain": "protein" } }, { "input_text": "We show that the inactivation of the inhibition was dependent on the activity of calcineurin , a calcium-calmodulin-dependent phosphatase .", "target_text": { "calcineurin": "protein", "calcium-calmodulin-dependent phosphatase": "protein" } }, { "input_text": "We also show that calcineurin associated with the N-terminal domain of NFATx1 at multiple docking sites and caused a reduction of size , indicative of dephosphorylation , in NFATx1 .", "target_text": { "calcineurin": "protein", "N-terminal domain": "protein", "NFATx1": "protein", "multiple docking sites": "protein" } }, { "input_text": "We have mapped the inhibitory activity to less than 60 residues , containing motifs that are conserved in all NFAT proteins .", "target_text": { "60 residues": "protein", "NFAT proteins": "protein" } }, { "input_text": "Finally , we demonstrate that deletion in NFATx1 of the mapped 60 residues leads to its nuclear translocation independent of calcium signaling .", "target_text": { "NFATx1": "protein", "60 residues": "protein" } }, { "input_text": "Our results support the model proposing that the N-terminal domain confers calcium -signaling dependence on NFATx1 transactivation activity by regulating its intracellular localization through a protein module that associates with calcineurin and is a target of its phosphatase activity .", "target_text": { "N-terminal domain": "protein", "NFATx1": "protein", "calcineurin": "protein", "phosphatase": "protein" } }, { "input_text": "Neuronal ( type I ) nitric oxide synthase regulates nuclear factor kappaB activity and immunologic ( type II ) nitric oxide synthase expression .", "target_text": { "Neuronal ( type I ) nitric oxide synthase": "protein", "nuclear factor kappaB": "protein", "immunologic ( type II ) nitric oxide synthase": "protein" } }, { "input_text": "Nitric oxide subserves diverse physiologic roles in the nervous system .", "target_text": {} }, { "input_text": "NO is produced from at least three different NO synthase ( NOS ) isoforms : neuronal NOS ( nNOS ) , endothelial NOS , and immunologic NOS ( iNOS ) .", "target_text": { "NO synthase ( NOS ) isoforms": "protein", "neuronal NOS": "protein", "nNOS": "protein", "endothelial NOS": "protein", "immunologic NOS": "protein", "iNOS": "protein" } }, { "input_text": "We show that nNOS is the predominant isoform constitutively expressed in glia .", "target_text": { "nNOS": "protein", "glia": "cell_type" } }, { "input_text": "NO derived from nNOS in glia inhibits the transcription factor nuclear factor kappaB ( NF kappaB ) as NOS inhibitors enhance basal NF kappaB activation .", "target_text": { "nNOS": "protein", "glia": "cell_type", "transcription factor": "protein", "nuclear factor kappaB": "protein", "NF kappaB": "protein" } }, { "input_text": "Pyrrolidine dithiocarbamate ( PDTC ) is an inhibitor of NF kappaB in most cells ; however , we show that PDTC is also a potent scavenger of NO through formation of mononitrosyl iron complexes with PDTC .", "target_text": { "NF kappaB": "protein" } }, { "input_text": "In Jurkat cells , a human T-cell lymphoma cell line , tumor necrosis factor-alpha ( TNF-alpha ) induces NF kappaB activation that is inhibited by PDTC .", "target_text": { "Jurkat cells": "cell_line", "T-cell lymphoma cell line": "cell_line", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein", "NF kappaB": "protein" } }, { "input_text": "Contrary to the results in Jurkat cells , PDTC did not inhibit tumor necrosis factor-alpha -induced NF kappaB activation in astrocytes ; instead PDTC itself induces NF kappaB activation in astrocytes , and this may be related to scavenging of endogenously produced NO by the PDTC iron complex .", "target_text": { "Jurkat cells": "cell_line", "tumor necrosis factor-alpha": "protein", "NF kappaB": "protein", "astrocytes": "cell_type" } }, { "input_text": "In astrocytes PDTC also dramatically induces the NF kappaB - dependent enzyme , iNOS , supporting the physiologic relevance of endogenous NO regulation of NF kappaB .", "target_text": { "astrocytes": "cell_type", "NF kappaB": "protein", "NF kappaB - dependent enzyme": "protein", "iNOS": "protein" } }, { "input_text": "NF kappaB activation in glia from mice lacking nNOS responds more rapidly to PDTC compared with astrocytes from wild-type mice .", "target_text": { "NF kappaB": "protein", "glia": "cell_type", "nNOS": "protein", "astrocytes": "cell_type" } }, { "input_text": "Our data suggest that nNOS in astrocytes regulates NF kappaB activity and iNOS expression , and indicate a novel regulatory role for nNOS in tonically suppressing central nervous system , NF kappaB -regulated genes .", "target_text": { "nNOS": "protein", "astrocytes": "cell_type", "NF kappaB": "protein", "iNOS": "protein", "NF kappaB -regulated genes": "DNA" } }, { "input_text": "Involvement of Stat3 in interleukin-6 -induced IgM production in a human B-cell line .", "target_text": { "Stat3": "protein", "interleukin-6": "protein", "IgM": "protein", "human B-cell line": "cell_line" } }, { "input_text": "Interleukin-6 ( IL-6 ) is an important B-cell growth and differentiation factor .", "target_text": { "Interleukin-6": "protein", "IL-6": "protein", "B-cell growth and differentiation factor": "protein" } }, { "input_text": "IL-6 treatment of the human lymphoblastoid cell line , SKW6.4 , leads to increased IgM production .", "target_text": { "IL-6": "protein", "human lymphoblastoid cell line": "cell_line", "SKW6.4": "cell_line", "IgM": "protein" } }, { "input_text": "We have previously shown that IL-6 induces activation of JAK1 and JAK2 in human B cell lines .", "target_text": { "IL-6": "protein", "JAK1": "protein", "JAK2": "protein", "human B cell lines": "cell_line" } }, { "input_text": "A chimeric IL-6 receptor , comprised of the intracellular tail of the IL-6 receptor subunit gp130 fused to the extracellular domain of the epidermal growth factor ( EGF ) receptor , was stably transfected into SKW6.4 cells .", "target_text": { "IL-6": "protein", "IL-6 receptor": "protein", "intracellular tail": "protein", "IL-6 receptor subunit": "protein", "gp130": "protein", "extracellular domain": "protein", "epidermal growth factor ( EGF ) receptor": "protein", "SKW6.4 cells": "cell_line" } }, { "input_text": "EGF treatment induced IgM production in cells transfected with an intact gp130 cytoplasmic tail , but not in untransfected cells or cells transfected with a cytoplasmic tail lacking all four signal transducers and activators of transcription ( Stat ) binding sites .", "target_text": { "IgM": "protein", "gp130 cytoplasmic tail": "protein", "untransfected cells": "cell_line", "cytoplasmic tail": "protein", "signal transducers and activators of transcription": "protein", "Stat": "protein", "signal transducers and activators of transcription ( Stat ) binding sites": "protein" } }, { "input_text": "Moreover , EGF treatment induced Stat3 phosphorylation in cells transfected with the intact chimeric EGF-gp130 receptor along with induction of DNA-mobility shift of a classical interferon-gamma-activated site .", "target_text": { "Stat3": "protein", "chimeric EGF-gp130 receptor": "protein", "classical interferon-gamma-activated site": "DNA" } }, { "input_text": "To define further the relation between Stat3 activation and enhanced IgM production , we determined the effect of chimeric gp130 on the transcriptional activation of a genetic element linked to immunoglobulin production , namely the immunoglobulin heavy chain enhancer ( IgH-enhancer ) .", "target_text": { "Stat3": "protein", "IgM": "protein", "immunoglobulin": "protein", "immunoglobulin heavy chain enhancer": "DNA", "IgH-enhancer": "DNA" } }, { "input_text": "Parental as well as transfected SKW6.4 cells were transiently transfected with an IgH-enhancer -luciferase construct .", "target_text": { "SKW6.4 cells": "cell_line", "IgH-enhancer": "DNA", "IgH-enhancer -luciferase construct": "DNA" } }, { "input_text": "The transcriptional activity of the IgH-luciferase construct was induced upon ligation of the full-length chimeric receptor but not by truncated gp130 receptors .", "target_text": { "IgH-luciferase construct": "DNA", "full-length chimeric receptor": "protein", "truncated gp130 receptors": "protein" } }, { "input_text": "Moreover , the gp130 -induced activity of this reporter gene was abrogated by Stat3EE , a mutant Stat3 incapable of binding DNA .", "target_text": { "gp130": "protein", "reporter gene": "DNA", "Stat3EE": "protein", "Stat3": "protein" } }, { "input_text": "These results indicate that IL-6 -induced B-cell differentiation , as measured by IgM production , may be controlled by Stat3 proteins .", "target_text": { "IL-6": "protein", "IgM": "protein", "Stat3": "protein", "Stat3 proteins": "protein" } }, { "input_text": "T-lymphocytes from individuals with filarial inflammatory disease have increased transendothelial migration in vitro .", "target_text": { "T-lymphocytes": "cell_type" } }, { "input_text": "The in vitro transendothelial migration of circulating filarial antigen-specific T-cells was examined in Wuchereria banerofti infection .", "target_text": { "circulating filarial antigen-specific T-cells": "cell_type" } }, { "input_text": "Circulating T-cells from individuals with filaria-induced lymphatic pathology ( LP ) had significantly greater migration through unstimulated HUVEC monolayers than did T-cells from asymptomatic infected ( MF ) individuals ( P = 0.04 ) .", "target_text": { "Circulating T-cells": "cell_type", "HUVEC monolayers": "cell_type" } }, { "input_text": "In contrast to the MF individuals where no effect was seen , transendothelial migration of 48-hr filarial antigen stimulated T-cells from LP individuals was significantly ( P = 0.01 ) greater than migration of 48-hr media-stimulated T-cells .", "target_text": { "filarial antigen stimulated T-cells": "cell_type", "media-stimulated T-cells": "cell_type" } }, { "input_text": "In six of seven patients examined , inhibition of the VLA-4/ VCAM-1 pathway resulted in greater than 50 % inhibition of transendothelial migration of T-cells .", "target_text": { "VCAM-1": "protein", "T-cells": "cell_type" } }, { "input_text": "Transcriptional regulation of the ferritin heavy-chain gene : the activity of the CCAAT binding factor NF-Y is modulated in heme-treated Friend leukemia cells and during monocyte-to-macrophage differentiation .", "target_text": { "ferritin heavy-chain gene": "DNA", "CCAAT binding factor": "protein", "NF-Y": "protein", "CCAAT binding factor NF-Y": "protein", "heme-treated Friend leukemia cells": "cell_line" } }, { "input_text": "The ferritin H-chain gene promoter regulation was analyzed in heme-treated Friend leukemia cells ( FLCs ) and during monocyte-to-macrophage differentiation .", "target_text": { "ferritin H-chain gene promoter": "DNA", "heme-treated Friend leukemia cells": "cell_line", "FLCs": "cell_line" } }, { "input_text": "In the majority of cell lines studied , the regulation of ferritin expression was exerted mostly at the translational level .", "target_text": { "cell lines": "cell_line", "ferritin": "protein" } }, { "input_text": "However , in differentiating erythroid cells , which must incorporate high levels of iron to sustain hemoglobin synthesis , and in macrophages , which are involved in iron storage , transcriptional regulation seemed to be a relevant mechanism .", "target_text": { "differentiating erythroid cells": "cell_type", "hemoglobin": "protein", "macrophages": "cell_type" } }, { "input_text": "We show here that the minimum region of the ferritin H-gene promoter that is able to confer transcriptional regulation by heme in FLCs to a reporter gene is 77 nucleotides upstream of the TATA box .", "target_text": { "ferritin": "protein", "ferritin H-gene": "DNA", "ferritin H-gene promoter": "DNA", "FLCs": "cell_line", "reporter gene": "DNA", "77 nucleotides upstream": "DNA", "TATA box": "DNA" } }, { "input_text": "This cis element binds a protein complex referred to as HRF ( heme-responsive factor ) , which is greatly enhanced both in heme-treated FLCs and during monocyte-to-macrophage differentiation .", "target_text": { "cis element": "DNA", "HRF": "protein", "heme-responsive factor": "protein", "FLCs": "cell_line" } }, { "input_text": "The CCAAT element present in reverse orientation in this promoter region of the ferritin H-chain gene is necessary for binding and for gene activity , since a single point mutation is able to abolish the binding of HRF and the transcriptional activity in transfected cells .", "target_text": { "CCAAT element": "DNA", "ferritin": "protein", "ferritin H-chain gene": "DNA", "HRF": "protein", "transfected cells": "cell_line" } }, { "input_text": "By competition experiments and supershift assays , we identified the induced HRF as containing at least the ubiquitous transcription factor NF-Y .", "target_text": { "HRF": "protein", "transcription factor": "protein", "NF-Y": "protein" } }, { "input_text": "NF-Y is formed by three subunits , A , B , and C , all of which are necessary for DNA binding .", "target_text": { "NF-Y": "protein", "subunits": "protein", "A": "protein", "B": "protein", "C": "protein" } }, { "input_text": "Cotransfection with a transdominant negative mutant of the NF-YA subunit abolishes the transcriptional activation by heme , indicating that NF-Y plays an essential role in this activation .", "target_text": { "transdominant negative mutant": "protein", "NF-YA subunit": "protein", "heme": "protein", "NF-Y": "protein" } }, { "input_text": "We have also observed a differential expression of the NF-YA subunit in heme-treated and control FLCs and during monocyte-to-macrophage differentiation .", "target_text": { "NF-YA subunit": "protein", "FLCs": "cell_line" } }, { "input_text": "Concomitant downregulation of IgH 3' enhancer activity and c-myc expression in a plasmacytoma x fibroblast environment : implications for dysregulation of translocated c-myc .", "target_text": { "IgH 3' enhancer": "DNA", "c-myc": "DNA" } }, { "input_text": "Regulation of immunoglobulin heavy chain ( IgH ) gene expression is controlled by a B cell-specific promoter , intronic enhancer and additional B cell-specific enhancer elements identified recently in the 3' end of the IgH locus .", "target_text": { "immunoglobulin heavy chain ( IgH ) gene": "DNA", "B cell-specific promoter": "DNA", "intronic enhancer": "DNA", "B cell-specific enhancer elements": "DNA", "IgH locus": "DNA" } }, { "input_text": "One of the latter elements , the IgH 3' enhancer , is of particular interest : ( 1 ) it is B cell-specific and active only in late B cell development ; ( 2 ) in rodent plasmacytomas and in some human Burkitt 's lymphomas it is part of a locus control region ( LCR ) that is involved in deregulation of the c-myc oncogene as a result of translocation into the IgH locus ; and ( 3 ) it has been implicated in the mechanisms that control Ig gene class switch recombination .", "target_text": { "IgH 3' enhancer": "DNA", "locus control region": "DNA", "LCR": "DNA", "c-myc": "DNA", "c-myc oncogene": "DNA", "IgH locus": "DNA", "Ig gene class": "DNA" } }, { "input_text": "We have used a somatic cell hybridization approach to genetically analyse regulation of the activity of the IgH 3' enhancer .", "target_text": { "IgH 3' enhancer": "DNA" } }, { "input_text": "When mouse MPC11 plasmacytoma cells , in which the IgH 3' enhancer is active , are fused with fibroblasts , Ig expression is extinguished at the level of transcription .", "target_text": { "mouse MPC11 plasmacytoma cells": "cell_line", "IgH 3' enhancer": "DNA", "fibroblasts": "cell_type" } }, { "input_text": "Here we show that in a MPC11 plasmacytoma x fibroblast environment , the IgH 3' enhancer is transcriptionally inactive .", "target_text": { "MPC11 plasmacytoma x fibroblast environment": "cell_line", "IgH 3' enhancer": "DNA" } }, { "input_text": "Furthermore , we demonstrate that binding of several B cell-specific transcription factors , essential for IgH 3' enhancer activity , is lacking , which may explain 3' enhancer inactivity , although the binding of repressors can not be excluded .", "target_text": { "transcription factors": "protein", "B cell-specific transcription factors": "protein", "IgH 3' enhancer": "DNA" } }, { "input_text": "Moreover , the high expression level of c-myc , characteristic of the parental MPC11 cells carrying the t(12;15) translocation , is down-regulated in the hybrids to that in unfused fibroblasts .", "target_text": { "c-myc": "DNA", "MPC11 cells": "cell_line", "t(12;15) translocation": "DNA", "fibroblasts": "cell_type" } }, { "input_text": "Therefore , inactivation of the IgH 3' enhancer is a multifactorial process affecting several transcription factors that control the cell-specific and developmental activity of the enhancer .", "target_text": { "IgH 3' enhancer": "DNA", "transcription factors": "protein", "enhancer": "DNA" } }, { "input_text": "Activation of the NF-kappaB transcription factor in a T-lymphocytic cell line by hypochlorous acid .", "target_text": { "NF-kappaB": "protein", "transcription factor": "protein", "T-lymphocytic cell line": "cell_line" } }, { "input_text": "Reactive oxygen species ( ROS ) such as hydrogen peroxide serve as second messengers in the induction of the transcription factor NF-kappaB , and hence in the activation and replication of human immunodeficiency virus type 1 ( HIV-1 ) in human cells .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein", "human cells": "cell_type" } }, { "input_text": "During inflammatory reactions , many oxidative species are produced , one of which is hypochlorous acid ( HOCl ) , which is responsible for the microbicidal effects of activated human polymorphonuclear leukocytes .", "target_text": { "human polymorphonuclear leukocytes": "cell_type" } }, { "input_text": "Treatment of a T-lymphocytic cell line with micromolar concentrations of HOCl promoted the appearance of transcription factor NF-kappaB ( the heterodimer p50/p65 ) in the nucleus of the cells , even in the absence of de novo protein synthesis .", "target_text": { "T-lymphocytic cell line": "cell_line", "transcription factor": "protein", "NF-kappaB": "protein", "heterodimer p50/p65": "protein" } }, { "input_text": "Western blot analysis of the NF-kappaB inhibitory subunits ( IkappaB ) demonstrated that both IkappaB -alpha proteolysis and p105 processing were induced by the treatment .", "target_text": { "NF-kappaB": "protein", "NF-kappaB inhibitory subunits": "protein", "IkappaB": "protein", "p105": "protein" } }, { "input_text": "NF-kappaB activation was very effective when cells were subjected to hyperthermia before being treated with HOCl .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Various antioxidants , such as pyrrolidine dithiocarbamate , p-bromophenacyl-bromide and nordihydroguaiaretic acid could strongly reduce NF-kappaB translocation , demonstrating the importance of oxidative species in the transduction mechanism .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Moreover , ACH-2 cells treated with HOCl or H2O2 released tumour necrosis factor-alpha ( TNF-alpha ) in the supernatants .", "target_text": { "ACH-2 cells": "cell_line", "tumour necrosis factor-alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "The importance of TNF-alpha release in NF-kappaB induction by HOCl or H2O2 was demonstrated by the fact that : ( 1 ) the nuclear appearance of NF-kappaB was promoted in untreated cells ; and ( 2 ) synergism between TNF-alpha and HOCl was detected .", "target_text": { "TNF-alpha": "protein", "NF-kappaB": "protein", "untreated cells": "cell_line" } }, { "input_text": "Collectively , these results suggest that HOCl should be considered as an oxidative species capable of inducing NF-kappaB in a T-lymphocytic cell line through a transduction mechanism involving ROS , and having a long-distance effect through subsequent TNF-alpha release .", "target_text": { "NF-kappaB": "protein", "T-lymphocytic cell line": "cell_line", "TNF-alpha": "protein" } }, { "input_text": "Rapid Ca2+-mediated activation of Rap1 in human platelets .", "target_text": { "Rap1": "protein", "human platelets": "cell_type" } }, { "input_text": "Rap1 is a small , Ras-like GTPase whose function and regulation are still largely unknown .", "target_text": { "Rap1": "protein", "Ras-like GTPase": "protein" } }, { "input_text": "We have developed a novel assay to monitor the active , GTP-bound form of Rap1 based on the differential affinity of Rap1GTP and Rap1GDP for the Rap binding domain of RalGDS ( RBD ) .", "target_text": { "GTP-bound form": "protein", "Rap1": "protein", "Rap1GTP": "protein", "Rap1GDP": "protein", "Rap binding domain": "protein", "RalGDS": "protein", "RBD": "protein" } }, { "input_text": "Stimulation of blood platelets with alpha-thrombin or other platelet activators caused a rapid and strong induction of Rap1 that associated with RBD in vitro .", "target_text": { "blood platelets": "cell_type", "alpha-thrombin": "protein", "Rap1": "protein", "RBD": "protein" } }, { "input_text": "Binding to RBD increased from undetectable levels in resting platelets to > 50 % of total Rap1 within 30 s after stimulation .", "target_text": { "RBD": "protein", "resting platelets": "cell_type", "Rap1": "protein" } }, { "input_text": "An increase in the intracellular Ca2+ concentration is both necessary and sufficient for Rap1 activation since it was induced by agents that increase intracellular Ca2+ and inhibited by a Ca2+ -chelating agent .", "target_text": { "Rap1": "protein" } }, { "input_text": "Neither inhibition of translocation of Rap1 to the cytoskeleton nor inhibition of platelet aggregation affected thrombin -induced activation of Rap1 .", "target_text": { "Rap1": "protein", "thrombin": "protein" } }, { "input_text": "In contrast , prostaglandin I2 ( PGI2 ) , a strong negative regulator of platelet function , inhibited agonist-induced as well as Ca2+ -induced activation of Rap1 .", "target_text": { "platelet": "cell_type", "Rap1": "protein" } }, { "input_text": "From our results , we conclude that Rap1 activation in platelets is an important common event in early agonist-induced signalling , and that this activation is mediated by an increased intracellular Ca2+ concentration", "target_text": { "Rap1": "protein", "platelets": "cell_type" } }, { "input_text": "Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells .", "target_text": { "human immunodeficiency virus enhancer": "DNA", "T cells": "cell_type" } }, { "input_text": "The transcriptional regulatory elements of many inducible T-cell genes contain adjacent or overlapping binding sites for the Ets and NF-kappaB/NFAT families of transcription factors .", "target_text": { "transcriptional regulatory elements": "DNA", "inducible T-cell genes": "DNA", "overlapping binding sites": "DNA", "transcription factors": "protein" } }, { "input_text": "Similar arrays of functionally important NF-kappaB/NFAT and Ets binding sites are present in the transcriptional enhancers of human immunodeficiency viruses types 1 and 2 ( HIV-1 and HIV-2 ) , suggesting that this pattern of nuclear protein binding sites reflects an evolutionarily conserved mechanism for regulating inducible T-cell gene expression that has been co-opted during HIV evolution .", "target_text": { "transcriptional enhancers": "DNA", "nuclear protein binding sites": "DNA" } }, { "input_text": "Despite these findings , the molecular mechanisms by which Ets and NF-kappaB/NFAT proteins cooperatively regulate inducible T-cell gene expression remained unknown .", "target_text": {} }, { "input_text": "In the studies described in this report , we demonstrated a physical interaction between multiple Ets and NF-kappaB/NFAT proteins both in vitro and in activated normal human T cells .", "target_text": { "T cells": "cell_type", "activated normal human T cells": "cell_type" } }, { "input_text": "This interaction is mediated by the Ets domain of Ets proteins and the C-terminal region of the Rel homology domains of NF-kappaB/NFAT proteins .", "target_text": { "Ets domain": "DNA", "Ets proteins": "protein", "NF-kappaB/NFAT proteins": "protein" } }, { "input_text": "In addition , the Ets - NF-kappaB / NFAT interaction requires the presence of DNA binding sites for both proteins , as it is abolished by the DNA intercalating agents propidium iodide and ethidium bromide and enhanced by the presence of synthetic oligonucleotides containing binding sites for Ets and NF-kappaB proteins .", "target_text": { "Ets": "protein", "NF-kappaB": "protein", "NFAT": "protein", "DNA binding sites": "DNA", "binding sites": "DNA", "NF-kappaB proteins": "protein" } }, { "input_text": "A dominant-negative mutant of NF-kappaB p50 that binds DNA but fails to interact with Ets proteins inhibits the synergistic activation of the HIV-1 and HIV-2 enhancers by NF-kappaB ( p50 + p65 ) and Ets-1 , suggesting that physical interaction between Ets and NF-kappaB proteins is required for the transcriptional activity of the HIV-1 and HIV-2 enhancers .", "target_text": { "NF-kappaB p50": "protein", "Ets proteins": "protein", "NF-kappaB": "protein", "p50": "protein", "p65": "protein", "Ets-1": "protein", "Ets": "protein", "NF-kappaB proteins": "protein" } }, { "input_text": "Taken together , these findings suggest that evolutionarily conserved physical interactions between Ets and NF-kappaB/NFAT proteins are important in regulating the inducible expression of T-cell genes and viruses .", "target_text": { "T-cell genes": "DNA" } }, { "input_text": "These interactions represent a potential target for the development of novel immunosuppressive and antiviral therapies .", "target_text": {} }, { "input_text": "An acute myeloid leukemia gene , AML1 , regulates transcriptional activation and hemopoietic myeloid cell differentiation antagonistically by two alternative spliced forms .", "target_text": { "acute myeloid leukemia gene": "DNA", "AML1": "DNA" } }, { "input_text": "The AML1 gene on chromosome 21 is disrupted in the (8;21)(q22;q22) and (3;21)(q26;q22) translocations associated with myelogenous leukemias and encodes a DNA-binding protein .", "target_text": { "AML1 gene": "DNA", "chromosome 21": "DNA", "DNA-binding protein": "protein" } }, { "input_text": "From AML1 gene , two representative forms of proteins , AML1a and AML1b , are produced by an alternative splicing .", "target_text": { "AML1 gene": "DNA", "AML1a": "protein", "AML1b": "protein" } }, { "input_text": "Both forms have DNA-binding domain , but AML1a lacks a putative transcriptional activation domain which AML1b has .", "target_text": { "DNA-binding domain": "protein", "AML1a": "protein", "AML1b": "protein" } }, { "input_text": "Here we demonstrate that AML1a , which solely has no effects as a transcriptional regulator , dominantly suppresses transcriptional activation by AML1b , and that AML1a exhibits the higher affinity for DNA-binding than AML1b .", "target_text": { "AML1a": "protein", "AML1b": "protein" } }, { "input_text": "Furthermore a dominant negative form of AML1 , AML1a , totally suppressed granulocytic differentiation otherwise induced by granulocyte colony-stimulating factor when AML1a was overexpressed in 32Dc13 murine myeloid cells .", "target_text": { "dominant negative form": "protein", "AML1": "protein", "AML1a": "protein", "granulocyte colony-stimulating factor": "protein", "32Dc13 murine myeloid cells": "cell_type" } }, { "input_text": "Such differentiation block by AML1a was canceled by the concomitant overexpression of AML1b .", "target_text": { "AML1a": "protein", "AML1b": "protein" } }, { "input_text": "These data strongly suggest that a transcriptionally active form of AML1 is essential for the myeloid cell differentiation .", "target_text": { "AML1": "protein" } }, { "input_text": "In addition , we observed an altered expression level of AML1 along with the myeloid differentiation in several hemopoietic cell lines .", "target_text": { "AML1": "protein", "hemopoietic cell lines": "cell_line" } }, { "input_text": "In these cases , at least , the AML1 expression level is a potential regulator for myeloid cell differentiation .", "target_text": { "AML1": "protein" } }, { "input_text": "Nuclear factor-kappa B potently up-regulates the promoter activity of RANTES , a chemokine that blocks HIV infection .", "target_text": { "Nuclear factor-kappa B": "protein", "RANTES": "protein" } }, { "input_text": "The complex network of cytokines that are involved in inflammatory and immunoregulatory responses plays a critical role in the pathogenesis of HIV infection .", "target_text": { "cytokines": "protein" } }, { "input_text": "RANTES ( regulated upon activation , normal T cell expressed and secreted ) is a cytokine that belongs to the beta-chemokine family ; it is chemoattractant for CD4+/CD45RO T cells , it is produced by various cell types including CD8+ and CD4+ T cells as well as monocytes/macrophages , and has recently been shown to suppress replication of macrophage-tropic strains of HIV in CD4+ T cells .", "target_text": { "RANTES": "protein", "regulated upon activation , normal T cell expressed and secreted": "protein", "cytokine": "protein", "beta-chemokine family": "protein", "CD4+/CD45RO T cells": "cell_type", "monocytes/macrophages": "cell_type", "CD4+ T cells": "cell_type" } }, { "input_text": "To investigate the molecular mechanisms of RANTES expression , the RANTES promoter region was analyzed by transient expression and gel-mobility shift assays .", "target_text": { "RANTES": "protein", "RANTES promoter region": "DNA" } }, { "input_text": "We demonstrate that : 1 ) RANTES promoter activity is up-regulated by PMA plus ionomycin , coexpression of the p65 subunit of nuclear factor ( NF ) -kappa B , the proinflammatory cytokines TNF-alpha and IL-1 beta , and the CD28 costimulatory pathway ; 2 ) the RANTES promoter region contains four NF-kappa B binding sites at positions -30 , -44 , -213 , and -579 relative to the transcription start site ; 3 ) one site ( -213 ) is an NF-AT ( nuclear factor of activated T cells ) binding site that also has weak affinity to NF-kappa B , and the most distal site ( -579 ) also serves as a CD28-responsive element ; and 4 ) mutation on any of those NF-kappa B sites or coexpression of I kappa B alpha ( cytoplasmic inhibitor of NF-kappa B ) markedly reduced the promoter activity .", "target_text": { "RANTES": "protein", "p65 subunit": "protein", "nuclear factor ( NF ) -kappa B": "protein", "proinflammatory cytokines": "protein", "TNF-alpha": "protein", "IL-1 beta": "protein", "CD28": "protein", "RANTES promoter region": "DNA", "NF-kappa B": "protein", "binding sites": "DNA", "NF-kappa B binding sites": "DNA", "transcription start site": "DNA", "NF-AT": "protein", "nuclear factor of activated T cells": "protein", "NF-AT ( nuclear factor of activated T cells ) binding site": "DNA", "CD28-responsive element": "DNA", "NF-kappa B sites": "DNA", "I kappa B alpha": "protein", "cytoplasmic inhibitor of NF-kappa B": "protein" } }, { "input_text": "Thus , NF-kappa B , a potent transcriptional activator of HIV expression , is also involved in the expression of RANTES , a chemokine that blocks infection by macrophage-tropic strains of HIV .", "target_text": { "NF-kappa B": "protein", "RANTES": "protein", "chemokine": "protein" } }, { "input_text": "Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3 -mediated survival of pro-B lymphocytes .", "target_text": { "NFIL3/E4BP4 transcription factor": "protein", "interleukin 3": "protein", "pro-B lymphocytes": "cell_type" } }, { "input_text": "The E2A-HLF ( hepatic leukemia factor ) oncoprotein , generated in pro-B lymphocytes by fusion of the trans-activation domain of E2A to the basic region/leucine zipper ( bZIP ) domain of HLF , functions as an anti-apoptotic transcription factor in leukemic cell transformation .", "target_text": { "E2A-HLF ( hepatic leukemia factor ) oncoprotein": "protein", "pro-B lymphocytes": "cell_type", "trans-activation domain": "protein", "E2A": "protein", "bZIP": "protein", "basic region/leucine zipper ( bZIP ) domain": "protein", "HLF": "protein", "anti-apoptotic transcription factor": "protein" } }, { "input_text": "When introduced into interleukin 3 ( IL-3 ) -dependent mouse pro-B lymphocytes , E2A-HLF prevents apoptosis induced by growth factor deprivation , suggesting that IL-3 mediates cell survival through activation of a transcription factor whose activity can be constitutively replaced by the chimeric oncoprotein .", "target_text": { "interleukin 3": "protein", "IL-3": "protein", "pro-B lymphocytes": "cell_type", "E2A-HLF": "protein", "growth factor": "protein", "transcription factor": "protein", "chimeric oncoprotein": "protein" } }, { "input_text": "We considered four bZIP transcription factors as candidates for this putative IL-3 -regulated factor , each of which binds avidly to the DNA consensus sequence recognized by E2A-HLF and is related to the Caenorhabditis elegans CES-2 ( cell death specification protein ) neuron-specific mediator of cell death .", "target_text": { "transcription factors": "protein", "bZIP transcription factors": "protein", "IL-3": "protein", "IL-3 -regulated factor": "protein", "DNA consensus sequence": "DNA", "E2A-HLF": "protein", "Caenorhabditis elegans CES-2": "protein", "cell death specification protein": "protein", "neuron-specific mediator of cell death": "protein" } }, { "input_text": "The expression and binding activity of the Nfil3 protein ( also called E4bp4 ) , but not of Hlf , Dbp , or Tef , was found to be regulated by IL-3 in mouse pro-B cell lines ( Baf-3 and FL5.12 ) .", "target_text": { "Nfil3 protein": "protein", "E4bp4": "protein", "Hlf": "protein", "Dbp": "protein", "Tef": "protein", "IL-3": "protein", "mouse pro-B cell lines": "cell_line", "Baf-3": "cell_line", "FL5.12": "cell_line" } }, { "input_text": "Northern blot analysis showed that Nfil3/ E4bp4 is regulated as a \" delayed-early \" IL-3 -responsive gene , requiring de novo protein synthesis .", "target_text": { "E4bp4": "protein", "Nfil3/ E4bp4": "protein", "IL-3": "protein", "\" delayed-early \" IL-3 -responsive gene": "DNA" } }, { "input_text": "In the absence of IL-3 , enforced expression of the human NFIL3/E4BP4 cDNA promoted the survival but not the growth of IL-3 -dependent pro-B cells .", "target_text": { "IL-3": "protein", "human NFIL3/E4BP4 cDNA": "DNA", "IL-3 -dependent pro-B cells": "cell_type" } }, { "input_text": "Our results implicate NFIL3/E4BP4 ( nuclear factor regulated by IL-3 /adenovirus E4 promoter binding protein ) in a distinct growth factor-regulated signaling pathway that is responsible for the survival of early B-cell progenitors , and whose alteration by E2A-HLF leads to childhood B lineage leukemia .", "target_text": { "NFIL3/E4BP4": "protein", "IL-3": "protein", "nuclear factor regulated by IL-3 /adenovirus E4 promoter binding protein": "protein", "early B-cell progenitors": "cell_type", "E2A-HLF": "protein" } }, { "input_text": "Detection of adenovirus DNA in peripheral blood mononuclear cells by polymerase chain reaction assay .", "target_text": { "adenovirus DNA": "DNA", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Adenovirus can establish persistent infections which may reactivate and cause disease in immunocompromised hosts .", "target_text": {} }, { "input_text": "Lymphocytes have been postulated to serve as a site of adenoviral persistence based upon the ability to isolate adenovirus from tonsils and to detect adenovirus DNA by Southern blot hybridization in peripheral blood mononuclear cells ( PBMC ) .", "target_text": { "Lymphocytes": "cell_type", "adenovirus DNA": "DNA", "peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "To test this hypothesis , a more sensitive and specific polymerase chain reaction ( PCR ) assay was developed to detect adenovirus DNA .", "target_text": { "adenovirus DNA": "DNA" } }, { "input_text": "Two sets of nested primers were designed to conserved sequences in the adenovirus E1A and hexon genes .", "target_text": { "nested primers": "DNA", "adenovirus E1A": "protein", "hexon": "protein" } }, { "input_text": "The E1A and hexon primers amplified DNA from representative adenoviral serotypes in all six adenoviral groups ( A-F ) .", "target_text": { "E1A": "protein", "hexon": "protein" } }, { "input_text": "Both primers detected a single copy of the adenovirus type 2 genome but were less sensitive for the group B type 35 .", "target_text": { "adenovirus type 2 genome": "DNA" } }, { "input_text": "None of 33 PBMC specimens from healthy adults and only one of 40 pediatric samples was positive ( at a low level ) for adenovirus DNA by nested PCR assay .", "target_text": { "PBMC": "cell_type", "adenovirus DNA": "DNA" } }, { "input_text": "In comparison , PBMC from two children with fatal adenoviral infection were both strongly positive for adenovirus DNA .", "target_text": { "PBMC": "cell_type", "adenovirus DNA": "DNA" } }, { "input_text": "It is concluded that , in contrast to a previous study , PBMC are not a common site of persistent group C adenoviral infection .", "target_text": { "PBMC": "cell_type" } }, { "input_text": "In addition , assay of PBMC by the adenovirus -specific PCR may help detect early invasive disease and warrants further evaluation .", "target_text": { "PBMC": "cell_type" } }, { "input_text": "Common and distinct intracellular signaling pathways in human neutrophils utilized by platelet activating factor and FMLP .", "target_text": { "human neutrophils": "cell_type", "platelet activating factor": "protein", "FMLP": "protein" } }, { "input_text": "Stimulation of human neutrophils with chemoattractants FMLP or platelet activating factor ( PAF ) results in different but overlapping functional responses .", "target_text": { "human neutrophils": "cell_type", "chemoattractants": "protein", "FMLP": "protein", "platelet activating factor": "protein", "PAF": "protein" } }, { "input_text": "We questioned whether these differences might reflect patterns of intracellular signal transduction .", "target_text": {} }, { "input_text": "Stimulation with either PAF or FMLP resulted in equivalent phosphorylation and activation of the mitogen-activated protein kinase ( MAPk ) homologue 38-kD murine MAP kinase homologous to HOG-1 ( p38 ) MAPk .", "target_text": { "PAF": "protein", "FMLP": "protein", "mitogen-activated protein kinase": "protein", "MAPk": "protein", "mitogen-activated protein kinase ( MAPk ) homologue": "protein", "38-kD murine MAP kinase": "protein", "HOG-1 ( p38 ) MAPk": "protein" } }, { "input_text": "Neither FMLP nor PAF activated c-jun NH2-terminal MAPk ( JNKs ) .", "target_text": { "FMLP": "protein", "PAF": "protein", "c-jun NH2-terminal MAPk": "protein", "JNKs": "protein" } }, { "input_text": "Under identical conditions , FMLP but not PAF , resulted in significant p42/44 ( ERK ) MAPk activation .", "target_text": { "FMLP": "protein", "PAF": "protein", "p42/44 ( ERK ) MAPk": "protein" } }, { "input_text": "Both FMLP and PAF activated MAP kinase kinase-3 ( MKK3 ) , a known activator of p38 MAPk .", "target_text": { "FMLP": "protein", "PAF": "protein", "PAF activated MAP kinase kinase-3": "protein", "MKK3": "protein", "p38 MAPk": "protein" } }, { "input_text": "Both MAP ERK kinase kinase-1 ( MEKK1 ) and Raf are activated strongly by FMLP , but minimally by PAF .", "target_text": { "MAP ERK kinase kinase-1": "protein", "MEKK1": "protein", "Raf": "protein", "FMLP": "protein", "PAF": "protein" } }, { "input_text": "Pertussis toxin blocked FMLP -induced activation of the p42/44 ( ERK ) MAPk cascade , but not that of p38 MAPk .", "target_text": { "Pertussis toxin": "protein", "FMLP": "protein", "p42/44 ( ERK ) MAPk": "protein", "p38 MAPk": "protein" } }, { "input_text": "A specific p38 MAPk inhibitor ( SK&F 86002 ) blocked superoxide anion production in response to FMLP and reduced adhesion and chemotaxis in response to PAF or FMLP .", "target_text": { "p38 MAPk": "protein", "FMLP": "protein", "PAF": "protein" } }, { "input_text": "These results demonstrate distinct patterns of intracellular signaling for two chemoattractants and suggest that selective activation of intracellular signaling cascades may underlie different patterns of functional responses .", "target_text": { "chemoattractants": "protein" } }, { "input_text": "Cloning of the novel human myeloid-cell-specific C/EBP-epsilon transcription factor .", "target_text": { "novel human myeloid-cell-specific C/EBP-epsilon transcription factor": "protein" } }, { "input_text": "Chicken NF-M transcription factor , in cooperation with either c-Myb or v-Myb , is active in the combinatorial activation of myeloid-cell-specific genes in heterologous cell types , such as embryonic fibroblasts .", "target_text": { "Chicken NF-M transcription factor": "protein", "c-Myb": "protein", "v-Myb": "protein", "myeloid-cell-specific genes": "DNA", "heterologous cell types": "cell_type", "embryonic fibroblasts": "cell_type" } }, { "input_text": "In humans , similar effects were observed with homologous members of the CCAAT/enhancer-binding protein ( C/EBP ) family of transcriptional regulators , especially the human homolog of chicken NF-M , C/EBP-beta ( NF-IL6 ) .", "target_text": { "CCAAT/enhancer-binding protein ( C/EBP ) family": "protein", "transcriptional regulators": "protein", "chicken NF-M": "protein", "C/EBP-beta": "protein", "NF-IL6": "protein" } }, { "input_text": "However , the NF-IL6 gene is expressed in a variety of nonmyeloid cell types and is strongly inducible in response to inflammatory stimuli , making it an unlikely candidate to have an exclusive role as a combinatorial differentiation switch during myelopoiesis in human cells .", "target_text": { "NF-IL6": "protein", "NF-IL6 gene": "DNA", "human cells": "cell_type" } }, { "input_text": "By using a reverse transcription-PCR-based approach and a set of primers specific for the DNA-binding domains of highly homologous members of the C/EBP family of transcriptional regulators , we have cloned a novel human gene encoding a member of the C/EBP gene family , identified as the human homolog of CRP1 , C/EBP-epsilon .", "target_text": { "DNA-binding domains": "DNA", "C/EBP family": "protein", "transcriptional regulators": "protein", "novel human gene": "DNA", "C/EBP gene family": "DNA", "CRP1": "protein", "C/EBP-epsilon": "protein" } }, { "input_text": "A 1.2-kb cDNA encoding full-length human C/EBP-epsilon was cloned from a promyelocyte-late myeloblast-derived lambda gt11 library .", "target_text": { "1.2-kb cDNA": "DNA", "human C/EBP-epsilon": "DNA", "promyelocyte-late myeloblast-derived lambda gt11 library": "DNA" } }, { "input_text": "Molecular analysis of the cDNA and genomic clones indicated the presence of two exons encoding a protein with an apparent molecular mass of 32 kDa and a pI of 9.5 .", "target_text": { "exons": "DNA" } }, { "input_text": "Primer extension analysis of C/EBP-epsilon mRNA detected a single major transcription start site approximately 200 bp upstream of the start codon .", "target_text": { "C/EBP-epsilon": "protein", "C/EBP-epsilon mRNA": "RNA", "transcription start site": "DNA", "start codon": "DNA" } }, { "input_text": "The putative promoter area is similar to those of several other myeloid-cell-specific genes in that it contains no TATAAA box but has a number of purine-rich stretches with multiple sites for the factors of the Ets family of transcriptional regulators .", "target_text": { "TATAAA box": "DNA", "purine-rich stretches": "DNA", "Ets family": "protein", "transcriptional regulators": "protein" } }, { "input_text": "Northern blot analyses indicated a highly restricted mRNA expression pattern , with the strongest expression occurring in promyelocyte and late-myeloblast-like cell lines .", "target_text": {} }, { "input_text": "Western blot and immunoprecipitation studies using rabbit anti-C/EBP-epsilon antibodies raised against the N-terminal portion of C/EBP-epsilon ( amino acids 1 to 115 ) showed that C/EBP-epsilon is a 32-kDa nuclear phosphoprotein .", "target_text": { "rabbit anti-C/EBP-epsilon antibodies": "protein", "N-terminal portion": "protein", "C/EBP-epsilon": "protein", "amino acids 1 to 115": "protein", "32-kDa nuclear phosphoprotein": "protein" } }, { "input_text": "The human C/EBP-epsilon protein exhibited strong and specific binding to double-stranded DNA containing consensus C/EBP sites .", "target_text": { "C/EBP-epsilon": "protein", "double-stranded DNA containing consensus C/EBP sites": "DNA" } }, { "input_text": "Cotransfection of the C/EBP-epsilon sense and antisense expression constructs together with chloramphenicol acetyltransferase reporter vectors containing myeloid-cell-specific c-mim and human myeloperoxidase promoters suggested a role for C/EBP-epsilon transcription factor in the regulation of a subset of myeloid-cell-specific genes .", "target_text": { "C/EBP-epsilon": "protein", "chloramphenicol acetyltransferase": "protein", "chloramphenicol acetyltransferase reporter vectors": "DNA", "transcription factor": "protein", "myeloid-cell-specific genes": "DNA" } }, { "input_text": "Transient tranfection of a promyelocyte cell line ( NB4 ) with a C/EBP-epsilon expression plasmid increased cell growth by sevenfold , while antisense C/EBP-epsilon caused a fivefold decrease in clonal growth of these cells .", "target_text": { "promyelocyte cell line": "cell_line", "NB4": "cell_line", "C/EBP-epsilon": "protein", "C/EBP-epsilon expression plasmid": "DNA" } }, { "input_text": "The tumour associated cell surface antigen A6H is costimulatory for human CD4+ but not CD8+ T cells .", "target_text": { "tumour associated cell surface antigen": "protein", "A6H": "protein" } }, { "input_text": "The A6H monoclonal antibody ( mAb ) recognizes a 120,000-140,000 MW antigen that is expressed at similar densities on 85-90 % of human CD4+ and CD8+ T cells and on renal cell carcinomas .", "target_text": { "A6H": "protein", "A6H monoclonal antibody": "protein", "120,000-140,000 MW antigen": "protein" } }, { "input_text": "The binding of the A6H mAb induced a costimulatory signal in anti-CD3 activated T cells .", "target_text": { "A6H mAb": "protein", "anti-CD3 activated T cells": "cell_line" } }, { "input_text": "In the present report , we show that A6H costimulated cell proliferation and cytokine production in purified CD4+ T cells .", "target_text": { "A6H": "protein", "cytokine": "protein", "CD4+ T cells": "cell_type" } }, { "input_text": "Unexpectedly , the CD8+ T-cell subpopulation failed to respond .", "target_text": { "CD8+ T-cell subpopulation": "cell_type" } }, { "input_text": "CD4+ T cells costimulated with the A6H mAb upregulated CD80 , CD86 , CD71 , interleukin-2 ( IL-2 ) R alpha , IL-2R beta and IL-2R gamma , while no corresponding up-regulation of these cell surface molecules was seen in CD8+ T cells .", "target_text": { "CD4+ T cells": "cell_type", "A6H mAb": "protein", "CD80": "protein", "CD86": "protein", "CD71": "protein", "interleukin-2 ( IL-2 ) R alpha": "protein", "IL-2R beta": "protein", "IL-2R gamma": "protein", "cell surface molecules": "protein", "CD8+ T cells": "cell_type" } }, { "input_text": "In order to investigate the nature of the A6H mAb costimulus at the transcriptional level we have examined induction of the transcription factors OCT-1 , AP-1 and NF-kappa B which are known to be transcriptional regulators of several cytokine and cytokine receptor genes , including the IL-2 and IL-2R genes .", "target_text": { "A6H mAb": "protein", "transcription factors": "protein", "OCT-1": "protein", "AP-1": "protein", "NF-kappa B": "protein", "transcriptional regulators": "protein", "cytokine": "protein" } }, { "input_text": "Co-ligation of the A6H antigen and the CD3 complex induced expression of the transcription factor AP-1 in CD4+ T cells , whereas no increase in NF-kappa B and octamer-binding ( Oct ) proteins was seen compared to T cells stimulated with anti-CD3 alone .", "target_text": { "A6H": "protein", "CD3 complex": "protein", "transcription factor": "protein", "AP-1": "protein", "CD4+ T cells": "cell_type", "NF-kappa B": "protein", "octamer-binding ( Oct ) proteins": "protein", "T cells": "cell_type", "anti-CD3": "protein" } }, { "input_text": "Furthermore , no induction of AP-1 was seen in A6H costimulated CD8+ T cells .", "target_text": { "AP-1": "protein", "A6H": "protein", "CD8+ T cells": "cell_type" } }, { "input_text": "These results suggests that both proximal steps in CD8+ T-cell activation as well as the later phases are unresponsive to A6H ligation .", "target_text": { "A6H": "protein" } }, { "input_text": "Molecular differences of the A6H molecule or distinct regulation of the A6H transduced AP-1 activation pathway may exist in CD4+ and CD8+ T cell subpopulations .", "target_text": { "A6H": "protein", "A6H molecule": "protein", "AP-1": "protein" } }, { "input_text": "Cloning and expression of the glucocorticoid receptor from the squirrel monkey ( Saimiri boliviensis boliviensis ) , a glucocorticoid-resistant primate .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "New World primates such as the squirrel monkey have elevated cortisol levels and glucocorticoid resistance .", "target_text": {} }, { "input_text": "We have shown that the apparent binding affinity of the glucocorticoid receptor in squirrel monkey lymphocytes is 5-fold lower than that in human lymphocytes ( apparent Kd , 20.9 +/- 1.8 and 4.3 +/- 0.2 nmol/L , respectively ; n = 3 ) , consistent with previous studies in mononuclear leukocytes isolated from the two species .", "target_text": { "glucocorticoid receptor": "protein", "squirrel monkey lymphocytes": "cell_type", "human lymphocytes": "cell_type", "mononuclear leukocytes": "cell_type" } }, { "input_text": "As a first step in understanding the mechanism of decreased binding affinity in New World primates , we used reverse transcription-PCR to clone the glucocorticoid receptor from squirrel monkey liver and have compared the sequence to receptor sequences obtained from owl monkey liver , cotton-top tamarin B95-8 cells , and human lymphocytes .", "target_text": { "glucocorticoid receptor": "protein", "cotton-top tamarin B95-8 cells": "cell_line", "human lymphocytes": "cell_type" } }, { "input_text": "The squirrel monkey glucocorticoid receptor is approximately 97 % identical in nucleotide and amino acid sequence to the human receptor .", "target_text": { "glucocorticoid receptor": "protein", "human receptor": "protein" } }, { "input_text": "The ligand-binding domain ( amino acids 528-777 ) of the squirrel monkey glucocorticoid receptor contains four amino acid differences ( Ser551 to Thr , Ser616 to Ala , Ala618 to Ser , and Ile761 to Leu ) , all of which are present in owl monkey and cotton-top tamarin receptors .", "target_text": { "ligand-binding domain": "protein", "amino acids 528-777": "protein", "glucocorticoid receptor": "protein" } }, { "input_text": "The DNA-binding domain ( amino acids 421-486 ) is completely conserved among human , squirrel monkey , owl monkey , and cotton-top tamarin receptors .", "target_text": { "DNA-binding domain": "protein", "amino acids 421-486": "protein" } }, { "input_text": "Twenty-two differences from the human sequence were found in the N-terminal region ( amino acids 1-421 ) of the squirrel monkey receptor .", "target_text": { "N-terminal region": "protein", "amino acids 1-421": "protein" } }, { "input_text": "None of the substitutions in the ligand-binding domain matched mutations known to influence binding affinity in other species .", "target_text": { "ligand-binding domain": "protein" } }, { "input_text": "To determine whether the substitutions per se were responsible for decreased affinity , squirrel monkey and human glucocorticoid receptors were expressed in the TNT Coupled Reticulocyte Lysate System .", "target_text": { "human glucocorticoid receptors": "protein" } }, { "input_text": "Expressions of human and squirrel monkey glucocorticoid receptors and a squirrel monkey receptor in which Phe774 was mutated to Leu ( F774L ) were similar .", "target_text": { "glucocorticoid receptors": "protein", "squirrel monkey receptor": "protein" } }, { "input_text": "When expressed in the TNT System , squirrel monkey and human glucocorticoid receptors had similar , high affinity binding for dexamethasone ( apparent Kd , 5.9 +/- 1.2 and 4.3 +/- 0.5 nmol/L , respectively ; n = 3 ) , whereas the squirrel monkey F774L receptor had lower affinity binding ( apparent Kd , 20.4 +/- 2.0 nmol/L ; n = 3 ) .", "target_text": { "glucocorticoid receptors": "protein", "human glucocorticoid receptors": "protein", "squirrel monkey F774L receptor": "protein" } }, { "input_text": "Thus , substitutions within the ligand-binding domain of the squirrel monkey glucocorticoid receptor can not account for the decreased binding affinity of these receptors in squirrel monkey cells .", "target_text": { "ligand-binding domain": "protein", "glucocorticoid receptor": "protein", "squirrel monkey cells": "cell_type" } }, { "input_text": "Rather , the binding affinity is probably influenced by the expression of cytosolic factors that affect glucocorticoid receptor function .", "target_text": { "cytosolic factors": "protein", "glucocorticoid receptor": "protein" } }, { "input_text": "Shared gamma(c) subunit within the human interleukin-7 receptor complex .", "target_text": { "gamma(c) subunit": "protein", "human interleukin-7 receptor complex": "protein" } }, { "input_text": "A molecular basis for the pathogenesis of X-linked severe combined immunodeficiency .", "target_text": {} }, { "input_text": "Genetic evidence suggests that mutations in the gamma(c) receptor subunit cause X-linked severe combined immunodeficiency ( X-SCID ) .", "target_text": { "gamma(c) receptor subunit": "protein" } }, { "input_text": "The gamma(c) subunit can be employed in receptor complexes for IL -2 , -4 , -7 , -9 , and -15 , and the multiple signaling defects that would result from a defective gamma(c) chain in these receptors are proposed to cause the severe phenotype of X-SCID patients .", "target_text": { "gamma(c) subunit": "protein", "receptor complexes": "protein", "gamma(c) chain": "protein" } }, { "input_text": "Interestingly , gene disruption of either IL-7 or the IL-7 receptor ( IL-7R ) alpha subunit in mice leads to immunological defects that are similar to human X-SCID .", "target_text": { "IL-7": "protein", "IL-7 receptor ( IL-7R ) alpha subunit": "protein" } }, { "input_text": "These observations suggest the functional importance of gamma(c) in the IL-7R complex .", "target_text": { "gamma(c)": "protein", "IL-7R complex": "protein" } }, { "input_text": "In the present study , structure/function analyses of the IL-7R complex using a chimeric receptor system demonstrated that gamma(c) is indeed critical for IL-7R function .", "target_text": { "IL-7R complex": "protein", "chimeric receptor": "protein", "gamma(c)": "protein", "IL-7R": "protein" } }, { "input_text": "Nonetheless , only a limited portion of the cytoplasmic domain of gamma(c) is necessary for IL-7R signal transduction .", "target_text": { "cytoplasmic domain": "protein", "gamma(c)": "protein", "IL-7R": "protein" } }, { "input_text": "Furthermore , replacement of the gamma(c) cytoplasmic domain by a severely truncated erythropoeitin receptor does not affect measured IL-7R signaling events .", "target_text": { "gamma(c)": "protein", "cytoplasmic domain": "protein", "severely truncated erythropoeitin receptor": "protein", "IL-7R": "protein" } }, { "input_text": "These findings support a model in which gamma(c) serves primarily to activate signal transduction by the IL-7R complex , while IL-7R alpha determines specific signaling events through its association with cytoplasmic signaling molecules .", "target_text": { "gamma(c)": "protein", "IL-7R complex": "protein", "IL-7R alpha": "protein", "cytoplasmic signaling molecules": "protein" } }, { "input_text": "Finally , these studies are consistent with the hypothesis that the molecular pathogenesis of X-SCID is due primarily to gamma(c) -mediated defects in the IL-7 /IL-7R system", "target_text": { "gamma(c)": "protein", "IL-7": "protein", "/IL-7R": "protein" } }, { "input_text": "S-allyl cysteine inhibits activation of nuclear factor kappa B in human T cells .", "target_text": { "nuclear factor kappa B": "protein", "human T cells": "cell_type" } }, { "input_text": "Reactive oxygen species are involved in signal transduction pathways leading to nuclear factor kappa B ( NF-kappa B ) activation which has been implicated in the regulation of gene transcription .", "target_text": { "nuclear factor kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "We recently reported that a garlic compound , S-allyl cysteine ( SAC ) , protects bovine pulmonary artery endothelial cells from oxidant injury induced by hydrogen peroxide ( H2O2 ) .", "target_text": { "bovine pulmonary artery endothelial cells": "cell_type" } }, { "input_text": "In this study we determined the effects of SAC on NF-kappa B activation in human T lymphocytes ( Jurkat cells ) induced by tumor necrosis factor alpha ( TNF- alpha ) and H2O2 .", "target_text": { "NF-kappa B": "protein", "human T lymphocytes": "cell_type", "Jurkat cells": "cell_line", "tumor necrosis factor alpha": "protein", "TNF- alpha": "protein" } }, { "input_text": "Activated NF-kappa B in nuclear extracts was measured by an electrophoretic mobility shift assay using 32P-labeled probe .", "target_text": { "NF-kappa B": "protein", "32P-labeled probe": "DNA" } }, { "input_text": "SAC consistently exhibited a dose-dependent inhibition of NF-kappa B activation induced by both TNF-alpha and H2O2 .", "target_text": { "NF-kappa B": "protein", "TNF-alpha": "protein" } }, { "input_text": "Supershift with specific antibodies to NF-kappa B subunits confirmed that the inducible retarded bands observed in the EMSA and p65-p50 heterodimer of the NF-kappa B /Rel protein .", "target_text": { "NF-kappa B subunits": "protein", "p65-p50 heterodimer": "protein", "NF-kappa B": "protein", "NF-kappa B /Rel protein": "protein" } }, { "input_text": "Our data suggest that SAC may act via antioxidant mechanisms to block NF-kappa B activation in Jurkat cells .", "target_text": { "NF-kappa B": "protein", "Jurkat cells": "cell_line" } }, { "input_text": "Elf-2 , a rhombotin-2 binding ets transcription factor : discovery and potential role in T cell leukemia .", "target_text": { "Elf-2": "protein", "rhombotin-2 binding ets transcription factor": "protein" } }, { "input_text": "Rhombotin-2 ( RBTN-2 ) is a proto-oncogene only in the context of T lymphocytes .", "target_text": { "Rhombotin-2": "DNA", "RBTN-2": "DNA", "proto-oncogene": "DNA", "T lymphocytes": "cell_type" } }, { "input_text": "We postulated that the oncogenic effect of RBTN-2 in T cells is likely mediated by binding protein ( s ) with T cell-specific expression .", "target_text": { "RBTN-2": "protein", "binding protein": "protein" } }, { "input_text": "By screening a T cell cDNA library , we identified a novel ets transcription factor that binds RBTN-2 .", "target_text": { "cDNA library": "DNA", "novel ets transcription factor": "protein", "RBTN-2": "protein" } }, { "input_text": "This protein was named elf-2 because its DNA-binding domain is virtually identical to that of ets family member elf-1 .", "target_text": { "elf-2": "protein", "DNA-binding domain": "protein", "ets family member": "protein", "elf-1": "protein" } }, { "input_text": "Northern analyses showed similar levels of two elf-2 transcripts ( 3.5 kb and 3.8 kb ) in all tissues except thymus .", "target_text": { "elf-2": "protein", "elf-2 transcripts": "RNA" } }, { "input_text": "Thymocytes expressed four- to 10-fold greater amounts of the 3.5 kb transcript than other tissues .", "target_text": { "Thymocytes": "cell_type", "3.5 kb transcript": "RNA" } }, { "input_text": "Sequence analyses of cDNA clones indicated that these transcripts encode proteins differing only at their amino termini , and likely represent alternatively spliced isoforms .", "target_text": { "cDNA clones": "DNA", "amino termini": "protein" } }, { "input_text": "These isoforms ( elf-2a and elf-2b ) contain identical RBTN-2 binding regions and DNA-binding domains .", "target_text": { "elf-2a": "protein", "elf-2b": "protein", "RBTN-2": "protein", "RBTN-2 binding regions": "protein", "DNA-binding domains": "protein" } }, { "input_text": "Elf-2b lacks a putative transactivation domain .", "target_text": { "Elf-2b": "protein", "putative transactivation domain": "protein" } }, { "input_text": "The expression patterns suggest that RBTN-2 normally interacts equally with elf-2a and elf-2b .", "target_text": { "RBTN-2": "protein", "elf-2a": "protein", "elf-2b": "protein" } }, { "input_text": "In contrast , when RBTN-2 is inappropriately expressed in T cells , RBTN-2 would interact predominantly with elf-2b ; this interaction may lead to T cell proliferation .", "target_text": { "RBTN-2": "protein", "T cells": "cell_type", "elf-2b": "protein" } }, { "input_text": "Transcription factor effects on chromosome constitution of cell hybrids .", "target_text": { "Transcription factor": "protein", "cell hybrids": "cell_line" } }, { "input_text": "When immunoglobulin ( Ig ) -secreting plasmacytomas are fused to a T-cell lymphoma , Ig gene expression ceases in greater than 95 % of the resulting hybrids .", "target_text": { "immunoglobulin ( Ig ) -secreting plasmacytomas": "cell_line", "T-cell lymphoma": "cell_type", "Ig gene": "DNA" } }, { "input_text": "In the rare hybrids that continue to express Ig , all other tested B lymphocyte-specific genes also remain active .", "target_text": { "B lymphocyte-specific genes": "DNA" } }, { "input_text": "The low frequency with which these Ig-expressing hybrids are recovered , along with the fact that cell fusions can lead to chromosome loss , led us to propose that this rare phenotype was due to loss of a T-cell-derived chromosome encoding a factor or factors with gene silencing activity .", "target_text": { "Ig-expressing hybrids": "cell_line", "T-cell-derived chromosome encoding a factor": "protein" } }, { "input_text": "To identify the relevant chromosome , we have used a polymerase chain reaction ( PCR ) -assisted method of chromosome mapping to analyze both Ig-silenced ( common ) and Ig-expressing ( rare ) hybrids .", "target_text": {} }, { "input_text": "Although no single chromosome was found to correlate with Ig gene silencing , we discovered that the two types of hybrids had undergone distinct patterns of chromosome loss .", "target_text": { "Ig gene": "DNA" } }, { "input_text": "Moreover , we found that ectopic expression of a B-cell-specific transcription factor ( Oct-2 ) dramatically altered both the phenotype and chromosome constitution of hybrids arising in these cell fusions .", "target_text": { "B-cell-specific transcription factor": "protein", "Oct-2": "protein" } }, { "input_text": "Reactivation of Kaposi 's sarcoma -associated herpesvirus infection from latency by expression of the ORF 50 transactivator , a homolog of the EBV R protein .", "target_text": { "ORF 50 transactivator": "protein", "EBV R protein": "protein" } }, { "input_text": "Kaposi 's sarcoma ( KS ) -associated herpesvirus ( KSHV ) , or human herpesvirus 8 , is a lymphotropic virus strongly linked to several AIDS-related neoplasms .", "target_text": {} }, { "input_text": "The primary reservoir of infection consists of latently infected B lymphocytes and possibly other mononuclear cells .", "target_text": { "B lymphocytes": "cell_type", "mononuclear cells": "cell_type" } }, { "input_text": "Viral reactivation from latency and spread from this lymphoid reservoir is presumably required for development of nonlymphoid tumors like KS .", "target_text": {} }, { "input_text": "Here we show that deregulated expression of a single viral gene , ORF 50 , which encodes a transactivator able to selectively upregulate delayed-early viral genes , suffices to disrupt latency and induce the lytic gene cascade in latently infected B cells .", "target_text": { "viral gene": "DNA", "ORF 50": "DNA", "delayed-early viral genes": "DNA", "latently infected B cells": "cell_type" } }, { "input_text": "The identification of this gene opens the way to studies of the physiologic mechanisms controlling reactvation of KSHV from latency .", "target_text": {} }, { "input_text": "Copyright 1998 Academic Press .", "target_text": {} }, { "input_text": "Nuclear factor of activated T cells and AP-1 are insufficient for IL-2 promoter activation : requirement for CD28 up-regulation of RE/AP .", "target_text": { "T cells": "cell_type", "Nuclear factor of activated T cells": "protein", "AP-1": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "CD28": "protein", "RE/AP": "protein" } }, { "input_text": "IL-2 gene transcription in T cells requires both TCR and costimulatory signals .", "target_text": { "IL-2": "protein", "T cells": "cell_type" } }, { "input_text": "IL-2 promoter activation in Jurkat T cells stimulated with superantigen presented by Raji B cells requires CD28 activation .", "target_text": { "IL-2": "protein", "IL-2 promoter": "DNA", "Jurkat T cells": "cell_line", "Raji B cells": "cell_line", "CD28": "protein" } }, { "input_text": "The addition of rCTLA4Ig , which blocks CD28 binding to its ligand , to the cultures decreased IL-2 promoter activation by > 80 % .", "target_text": { "CD28": "protein", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "Interestingly , CTLA4Ig did not significantly inhibit the activation of either NF of activated T cells ( NFAT ) or AP-1 reporters .", "target_text": { "NF of activated T cells": "protein", "NFAT": "protein", "AP-1": "protein", "AP-1 reporters": "DNA" } }, { "input_text": "Therefore , activation of NFAT and AP-1 is insufficient for IL-2 promoter activation .", "target_text": { "NFAT": "protein", "AP-1": "protein", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "In contrast , an RE/AP reporter was blocked by CTLA4Ig by > 90 % .", "target_text": { "RE/AP": "protein" } }, { "input_text": "Thus , the requirement for CD28 in IL-2 promoter activation appears to be due to RE/AP and not the NFAT or AP-1 sites .", "target_text": { "CD28": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "RE/AP": "protein" } }, { "input_text": "In addition , these data suggest that transcriptional activation of RE/AP is not mediated by NFAT , because activation of a NFAT reporter is not affected by the addition of CTLA4Ig .", "target_text": { "RE/AP": "protein", "NFAT": "protein" } }, { "input_text": "The control of lytic replication of Epstein-Barr virus in B lymphocytes ( Review ) .", "target_text": { "B lymphocytes": "cell_type" } }, { "input_text": "Uncontrolled replication of a virus , which is harmful to the host is also disadvantageous to the virus .", "target_text": {} }, { "input_text": "Most viruses can not compete with the various immune mechanisms and become eliminated in the course of infection .", "target_text": {} }, { "input_text": "Therefore , only the time between infection and eradication remains for these viruses to proliferate .", "target_text": {} }, { "input_text": "A few viruses , like the Herpesviruses or the papillomaviruses , however , have developed a sophisticated strategy for persisting lifelong , usually asymptomatically in the host , hiding from the immune system and producing infectious progeny at the same time .", "target_text": {} }, { "input_text": "This strategy depends on a separation of latency and the lytic replication , either by time due to differentiation-dependent mechanisms or by spatial separation as the result of different host cell types .", "target_text": {} }, { "input_text": "Both are true for the Epstein-Barr virus ( EBV ) .", "target_text": {} }, { "input_text": "B cells and epithelial cells have a pivotal role in the life cycle of the virus .", "target_text": { "B cells": "cell_type", "epithelial cells": "cell_type" } }, { "input_text": "The former can become latently infected and are thought to be the virus reservoir in vivo , whereas the latter were shown to be permissive for lytic replication .", "target_text": {} }, { "input_text": "However , replication of EBV in vivo is controlled primarily by host immune mechanisms selecting for cells that are not permissive for viral replication as the result of a particular set of transcription factors .", "target_text": { "transcription factors": "protein" } }, { "input_text": "These factors control the activity of the regulatory immediate-early genes and , in addition , lytic and latent cycle regulatory genes negatively interfere with each other and thus link cellular and viral gene regulatory mechanisms .", "target_text": { "regulatory immediate-early genes": "DNA", "viral gene": "DNA" } }, { "input_text": "Disturbance of both the immune surveillance as well as viral gene regulation may result in EBV -associated disease .", "target_text": { "viral gene": "DNA" } }, { "input_text": "Adaptor function for the Syk kinases-interacting protein 3BP2 in IL-2 gene activation .", "target_text": { "Syk kinases-interacting protein": "protein", "3BP2": "protein", "IL-2": "protein" } }, { "input_text": "Syk-family tyrosine kinases are essential for lymphocyte development and activation .", "target_text": { "Syk-family tyrosine kinases": "protein" } }, { "input_text": "Using a yeast two-hybrid screen to identify Syk kinases-interacting proteins ( SKIPs ) , we isolated 3BP2 , an Abl SH3-interacting protein of unknown function .", "target_text": { "Syk kinases-interacting proteins": "protein", "SKIPs": "protein", "3BP2": "protein", "Abl SH3-interacting protein": "protein" } }, { "input_text": "3BP2 was selectively expressed in hematopoietic/lymphoid tissues and bound via its SH2 domain activated Syk-family kinases in mammalian cells , including in antigen receptor-stimulated T cells .", "target_text": { "3BP2": "protein", "SH2 domain activated Syk-family kinases": "protein", "mammalian cells": "cell_type", "antigen receptor-stimulated T cells": "cell_type" } }, { "input_text": "In addition to Zap-70 , the 3BP2 SH2 domain associated in vitro with LAT , Grb2 , PLCgamma1 , and Cbl from activated T cell lysates .", "target_text": { "Zap-70": "protein", "3BP2": "protein", "3BP2 SH2 domain": "protein", "LAT": "protein", "Grb2": "protein", "PLCgamma1": "protein", "Cbl": "protein" } }, { "input_text": "Transient 3BP2 overexpression induced transcriptional activation of the IL-2 promoter and its NFAT or AP-1 elements .", "target_text": { "3BP2": "protein", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "This activity was dependent on the SH2 and pleckstrin-homology domains of 3BP2 , and required functional Syk kinases , Ras , and calcineurin .", "target_text": { "SH2": "protein", "pleckstrin-homology domains": "protein", "3BP2": "protein", "Syk kinases": "protein", "Ras": "protein", "calcineurin": "protein" } }, { "input_text": "Thus , 3BP2 is an important adaptor that may couple activated Zap-70 /Syk to a LAT -containing signaling complex involved in TCR-mediated gene transcription .", "target_text": { "3BP2": "protein", "Zap-70": "protein", "Zap-70 /Syk": "protein", "LAT": "protein", "LAT -containing signaling complex": "protein" } }, { "input_text": "In vitro suppression of programmed cell death of B cells by tissue inhibitor of metalloproteinases-1 .", "target_text": { "B cells": "cell_type", "metalloproteinases-1": "protein" } }, { "input_text": "Cellular pathways for induction of programmed cell death ( PCD ) have been identified , but little is known about specific extracellular matrix processes that may affect apoptosis along those pathways .", "target_text": {} }, { "input_text": "In this study , a series of Burkitt 's lymphoma ( BL ) cell lines were assayed for their expression of tissue inhibitor of metalloproteinases ( TIMP ) -1 .", "target_text": { "Burkitt 's lymphoma ( BL ) cell lines": "cell_line", "tissue inhibitor of metalloproteinases ( TIMP ) -1": "protein" } }, { "input_text": "Results indicate that TIMP-1 -positive BL lines show resistance to cold-shock-induced apoptosis .", "target_text": { "TIMP-1": "protein", "TIMP-1 -positive BL lines": "cell_line" } }, { "input_text": "Furthermore , recombinant TIMP-1 , but not TIMP-2 or a synthetic metalloproteinase inhibitor ( BB-94 ) , confers resistance to apoptosis induced by both CD95-dependent and -independent ( cold shock , serum deprivation , and gamma-radiation ) pathways in TIMP-1 -negative BL lines .", "target_text": { "TIMP-1": "protein", "TIMP-2": "protein", "TIMP-1 -negative BL lines": "cell_line" } }, { "input_text": "TIMP-1 suppression of PCD is not due to metalloproteinase inhibition , as reduction and alkylation of the TIMP-1 did not abolish this activity .", "target_text": { "TIMP-1": "protein", "metalloproteinase": "protein" } }, { "input_text": "Retroviral induction of TIMP-1 not only resulted in cell survival but also in continued DNA synthesis for up to 5 d in the absence of serum , while controls underwent apoptosis .", "target_text": { "TIMP-1": "protein" } }, { "input_text": "This resistance to apoptosis is reversed by anti- TIMP-1 antibodies , demonstrating that secreted TIMP-1 is active in blocking apoptosis .", "target_text": { "TIMP-1": "protein", "anti- TIMP-1 antibodies": "protein" } }, { "input_text": "Furthermore , TIMP-1 upregulation induced expression of Bcl-XL but not Bcl-2 as well as decreased NF-kappaB activity as compared with controls .", "target_text": { "TIMP-1": "protein", "Bcl-XL": "protein", "Bcl-2": "protein", "NF-kappaB": "protein" } }, { "input_text": "These results demonstrate that TIMP-1 suppresses apoptosis in B cells and suggests a novel activity for TIMP-1 in tissue homeostasis .", "target_text": { "TIMP-1": "protein", "B cells": "cell_type" } }, { "input_text": "Spi-1/PU.1 proto-oncogene induces opposite effects on monocytic and erythroid differentiation of K562 cells .", "target_text": { "Spi-1/PU.1": "DNA", "proto-oncogene": "DNA", "K562 cells": "cell_line" } }, { "input_text": "Spi-1/PU.1 is a hematopoietic transcription factor of the Ets family .", "target_text": { "Spi-1/PU.1": "protein", "hematopoietic transcription factor": "protein", "Ets family": "protein" } }, { "input_text": "To analyze the effects of ectopic expression of spi-1 on the proliferation/differentiation of human myeloid leukemia cells , K562 cells were stably transfected with a spi-1 expression vector .", "target_text": { "spi-1": "protein", "human myeloid leukemia cells": "cell_type", "K562 cells": "cell_line", "spi-1 expression vector": "DNA" } }, { "input_text": "The transfected cell lines expressed elevated levels of spi-1 mRNA and protein and high Spi-1 -DNA binding activity .", "target_text": { "transfected cell lines": "cell_line", "spi-1": "protein", "spi-1 mRNA": "RNA", "Spi-1": "protein" } }, { "input_text": "The spi-1 transfected cells showed reduced growth rates and reduced clonogenic cell growth .", "target_text": { "spi-1": "protein", "spi-1 transfected cells": "cell_line" } }, { "input_text": "When the erythroid and monocytic differentiation markers were analyzed , spi-1 overexpression resulted in opposite effects : erythroid differentiation was significantly inhibited in spi-1 transfectants , while spi-1 overexpression increased the monocytic differentiation of cells .", "target_text": { "spi-1": "protein", "spi-1 transfectants": "cell_line" } }, { "input_text": "These results indicate a differential role of Spi-1 on the differentiation of human myeloid leukemia cells .", "target_text": { "Spi-1": "DNA", "human myeloid leukemia cells": "cell_line" } }, { "input_text": "Copyright 1998 Academic Press .", "target_text": {} }, { "input_text": "In vivo function of an interleukin 2 receptor beta chain ( IL-2Rbeta ) / IL-4Ralpha cytokine receptor chimera potentiates allergic airway disease .", "target_text": { "interleukin 2 receptor beta chain": "protein", "( IL-2Rbeta ) / IL-4Ralpha cytokine receptor chimera": "protein" } }, { "input_text": "Strength of T cell receptor ( TCR ) signaling , coreceptors , costimulation , antigen-presenting cell type , and cytokines all play crucial roles in determining the efficiency with which type 2 T lymphocytes ( Th2 , Tc2 ) develop from uncommitted precursors .", "target_text": { "T cell receptor": "protein", "TCR": "protein", "coreceptors": "protein", "antigen-presenting cell type": "cell_type", "T lymphocytes": "cell_type", "type 2 T lymphocytes": "cell_type", "Th2": "cell_type", "Tc2": "cell_type", "uncommitted precursors": "protein" } }, { "input_text": "To investigate in vivo regulatory mechanisms that control the population of type 2 T cells and disease susceptibility , we have created lines of transgenic mice in which expression of a chimeric cytokine receptor ( the mouse interleukin 2 receptor beta chain [ IL-2Rbeta ] extracellular domain fused to the cytoplasmic tail of IL-4Ralpha ) is targeted to the T lymphoid lineage using the proximal lck promoter .", "target_text": { "type 2 T cells": "cell_type", "chimeric cytokine receptor": "protein", "interleukin 2 receptor beta chain": "protein", "mouse interleukin 2 receptor beta chain": "protein", "IL-2Rbeta": "protein", "mouse interleukin 2 receptor beta chain [ IL-2Rbeta ] extracellular domain": "protein", "cytoplasmic tail": "protein", "IL-4Ralpha": "protein", "T lymphoid lineage": "cell_type", "proximal lck promoter": "DNA" } }, { "input_text": "This chimera transduced IL-4 -specific signals in response to IL-2 binding and dramatically enhanced type 2 responses ( IL-4 , IL-5 , and immunoglobulin E production ) upon in vitro TCR stimulation or in vivo antigen challenge .", "target_text": { "IL-4": "protein", "IL-2": "protein", "IL-5": "protein", "immunoglobulin E": "protein", "TCR": "protein" } }, { "input_text": "Thus , type 2 effector function was augmented by IL-4 signals transduced through a chimeric receptor expressed in a T cell-specific manner .", "target_text": { "IL-4": "protein", "chimeric receptor": "protein" } }, { "input_text": "This influence was sufficient for establishment of antigen-induced allergic airway hyperresponsiveness on a disease-resistant background", "target_text": {} }, { "input_text": "Differentiation-dependent expression of a human carboxylesterase in monocytic cells and transcription factor binding to the promoter .", "target_text": { "human carboxylesterase": "protein", "monocytic cells": "cell_type", "transcription factor": "protein", "promoter": "DNA" } }, { "input_text": "Carboxylesterases play an important role in defense and clearance mechanisms of the monocyte/macrophage system .", "target_text": { "Carboxylesterases": "protein" } }, { "input_text": "During the differentiation process of cells from the monocytic cell line THP-1 we observed a transient transcriptional upregulation of a human carboxylesterase analyzed by means of Northern blots .", "target_text": { "monocytic cell line THP-1": "cell_line", "human carboxylesterase": "protein" } }, { "input_text": "In PMA-treated THP-1 cells we could detect three major transcription initiation sites as revealed by Nuclease Protection Assay carried out with two overlapping antisense RNA probes .", "target_text": { "PMA-treated THP-1 cells": "cell_line", "transcription initiation sites": "DNA", "overlapping antisense RNA probes": "RNA" } }, { "input_text": "We have recently cloned the carboxylesterase upstream sequence and showed its basal promoter activity in CHO cells .", "target_text": { "carboxylesterase upstream sequence": "DNA", "basal promoter": "DNA", "CHO cells": "cell_line" } }, { "input_text": "Using electrophoretic mobility shift analysis we demonstrated that the promoter region spanning base pairs -1 to -275 , which contains several putative binding sites for transcription factors , is bound by nuclear factors Sp1 and IRBP but not by C/EBPs .", "target_text": { "promoter region": "DNA", "base pairs -1 to -275": "DNA", "transcription factors": "protein", "nuclear factors": "protein", "Sp1": "protein", "IRBP": "protein", "C/EBPs": "protein" } }, { "input_text": "Taken together these data indicate that carboxylesterase gene transcription in THP-1 cells starts at multiple initiation sites and that Sp1 and IRBP may be critical factors for modulating the differentiation-dependent transcription of this human carboxylesterase gene .", "target_text": { "THP-1 cells": "cell_line", "Sp1": "protein", "IRBP": "protein", "human carboxylesterase": "protein", "human carboxylesterase gene": "DNA" } }, { "input_text": "The role of the Ikaros gene in lymphocyte development and homeostasis .", "target_text": { "Ikaros gene": "DNA" } }, { "input_text": "The Ikaros gene , which encodes a family of hemopoietic-specific zinc finger proteins , is described as a central regulator of lymphocyte differentiation .", "target_text": { "Ikaros gene": "DNA", "hemopoietic-specific zinc finger proteins": "protein" } }, { "input_text": "During fetal development , it is required at the earliest stage of T cell and B cell specification .", "target_text": {} }, { "input_text": "In the adult , however , lymphoid lineages rely on Ikaros at distinct phases of their development .", "target_text": { "lymphoid lineages": "cell_type", "Ikaros": "DNA" } }, { "input_text": "Its activity is essential for the generation of B cell but not of T cell precursors , although the differentiation of the latter is not normal .", "target_text": { "B cell": "cell_type", "T cell precursors": "cell_type" } }, { "input_text": "A significant increase in CD4 thymocytes and their immediate precursors is detected , and because these cells lack markers that correlate with positive selection , a deregulation in their maturation process is suggested .", "target_text": { "CD4 thymocytes": "cell_type" } }, { "input_text": "Furthermore , Ikaros-null thymocytes hyperproliferate in response to T cell receptor ( TCR ) signaling ; within days after their appearance in the thymus , clonally expanding populations are detected .", "target_text": { "Ikaros-null thymocytes": "cell_type", "T cell receptor": "protein", "TCR": "protein" } }, { "input_text": "Deregulated TCR -mediated responses and the fast kinetics of tumor development in these mutant thymocytes implicate Ikaros as a central tumor suppressor gene for the T cell lineage .", "target_text": { "TCR": "protein", "mutant thymocytes": "cell_type", "central tumor suppressor gene": "DNA", "T cell lineage": "cell_type" } }, { "input_text": "In addition , lack of natural killer cells and selective defects in gamma delta T cells and dendritic antigen-presenting cells point to Ikaros as an essential factor for the establishment of early branchpoints of the T cell pathway .", "target_text": { "natural killer cells": "cell_type", "gamma delta T cells": "cell_type", "dendritic antigen-presenting cells": "cell_type", "Ikaros": "protein" } }, { "input_text": "The dominant interference activity of Ikaros isoforms unable to bind DNA and their effects in lymphocyte development suggest that Ikaros works in concert with other factors .", "target_text": { "Ikaros": "protein", "Ikaros isoforms": "protein" } }, { "input_text": "The role of Aiolos , a lymphoid-restricted and structurally related gene , in lymphoid differentiation is discussed .", "target_text": { "Aiolos": "DNA" } }, { "input_text": "A model is proposed that defines Ikaros as the backbone of a complex regulatory protein network that controls cell fate decisions and regulates homeostasis in the hemo-lymphoid system .", "target_text": { "Ikaros": "protein", "complex regulatory protein network": "protein" } }, { "input_text": "Changes in this regulatory network may reflect differentiation and proliferation adjustments made in hemo-lymphoid progenitors and precursors as they give rise to the cells of our immune system .", "target_text": { "hemo-lymphoid progenitors": "cell_type", "precursors": "cell_type" } }, { "input_text": "STAT1 pathway is involved in activation of caprine arthritis-encephalitis virus long terminal repeat in monocytes .", "target_text": { "STAT1": "protein", "arthritis-encephalitis virus long terminal repeat": "DNA", "monocytes": "cell_type" } }, { "input_text": "The caprine arthritis-encephalitis virus ( CAEV ) long terminal repeat ( LTR ) is activated by gamma interferon ( IFN-gamma ) in promonocytic cells .", "target_text": { "caprine arthritis-encephalitis virus ( CAEV ) long terminal repeat": "DNA", "LTR": "DNA", "gamma interferon": "protein", "IFN-gamma": "protein", "promonocytic cells": "cell_type" } }, { "input_text": "We have previously shown that a 70-bp element is necessary and sufficient for the response of the CAEV LTR to this cytokine .", "target_text": { "70-bp element": "DNA", "CAEV LTR": "DNA", "cytokine": "protein" } }, { "input_text": "At the 5' end , this 70-bp IFN-gamma response element contains sequence similarity to the gamma activated site ( GAS ) .", "target_text": { "5' end": "DNA", "IFN-gamma": "protein", "70-bp IFN-gamma response element": "DNA", "gamma activated site": "DNA", "GAS": "DNA" } }, { "input_text": "Here we demonstrate that the putative GAS element in the CAEV LTR binds specifically to a cellular factor induced by IFN-gamma in promonocytic cells .", "target_text": { "GAS element": "DNA", "CAEV LTR": "DNA", "cellular factor": "protein", "IFN-gamma": "protein", "promonocytic cells": "cell_type" } }, { "input_text": "Substitution mutations in this consensus sequence eliminate binding of the inducible factor .", "target_text": { "consensus sequence": "DNA", "inducible factor": "protein" } }, { "input_text": "The GAS element from the 70-bp motif is sufficient to confer responsiveness to IFN-gamma using a heterologous minimal promoter .", "target_text": { "GAS element": "DNA", "70-bp motif": "DNA", "IFN-gamma": "protein" } }, { "input_text": "Consistent with the binding data , the same mutations in the GAS element eliminate responsiveness to IFN-gamma in the context of both a functional CAEV LTR and a heterologous promoter .", "target_text": { "GAS element": "DNA", "IFN-gamma": "protein", "CAEV LTR": "DNA", "heterologous promoter": "DNA" } }, { "input_text": "The cellular factor that binds to the GAS element is present from 5 min to 14 h after stimulation with IFN-gamma .", "target_text": { "GAS element": "DNA", "IFN-gamma": "protein" } }, { "input_text": "Binding of the nuclear factor to the GAS element in the CAEV LTR is inhibited by antibody directed against STAT1 ( p91/84 ) .", "target_text": { "GAS element": "DNA", "CAEV LTR": "DNA", "STAT1": "protein", "p91/84": "protein" } }, { "input_text": "Thus , the GAS sequence in the CAEV LTR is essential for the response to IFN-gamma and a STAT1 -like factor binds to this site .", "target_text": { "CAEV LTR": "DNA", "IFN-gamma": "protein", "STAT1": "protein", "STAT1 -like factor": "protein" } }, { "input_text": "The STAT-1 signaling pathway provides at least one mechanism for activation of the CAEV LTR by IFN-gamma in monocytes .", "target_text": { "CAEV LTR": "DNA", "IFN-gamma": "protein", "monocytes": "cell_type" } }, { "input_text": "These data are the first demonstration of a role for a STAT family member in the regulation of a viral promoter .", "target_text": { "STAT family member": "protein", "viral promoter": "DNA" } }, { "input_text": "1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with renal insufficiency .", "target_text": { "1,25-Dihydroxyvitamin D3 receptors": "DNA", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "A reduced expression of the vitamin D receptor ( VDR ) in parathyroid glands of uremic animals and humans has been observed .", "target_text": { "vitamin D receptor": "protein" } }, { "input_text": "Similar results have been obtained by our own group in peripheral blood mononuclear cells ( PBMC ) from patients with secondary hyperparathyroidism to chronic renal failure .", "target_text": { "peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "However , the reasons for these changes are not clear .", "target_text": {} }, { "input_text": "In the present study , we have investigated the specific uptake of [3H]1,25(OH)2D3 by PBMC of 11 women with advanced chronic renal failure ( A-CRF ) , 6 women with mild-moderate renal insufficiency ( M-CRF ) , and 23 healthy women .", "target_text": { "PBMC": "cell_type" } }, { "input_text": "The mean dissociation constant ( KD ) was similar in both groups of patients and in healthy women ( A-CRF : 0.7 +/- 0.5 x 10(-10) M ; M-CRF : 1.1 +/- 0.9 x 10(-10) M ; controls : 1.0 +/- 0.6 x 10(-10) M ) .", "target_text": {} }, { "input_text": "However , VDR concentration was significantly decreased in A-CRF ( 0.8 +/- 0.5 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in controls , p < 0.001 ) , whereas no changes were seen in M-CRF ( 1.7 +/- 0.7 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in controls ) .", "target_text": { "VDR": "protein" } }, { "input_text": "No correlation was seen between VDR and serum calcitriol or PTH levels , when considering both groups of patients together or separately .", "target_text": { "VDR": "protein" } }, { "input_text": "Conversely , a significant negative correlation was found between VDR and serum creatinine values when A-CRF and M-CRF were considered altogether ( r = -0.63 ; p < 0.01 ) .", "target_text": { "VDR": "protein" } }, { "input_text": "Treatment with two different schedules of oral calcitriol ( five patients with 0.5 microgram/day for 1 month and four patients with 2 micrograms/day for 7 days ) did not change VDR concentrations .", "target_text": { "VDR": "protein" } }, { "input_text": "We conclude that the low levels of serum 1,25(OH)2D3 of uremia are not responsible for the decrease in VDR concentration found in these patients .", "target_text": { "VDR": "protein" } }, { "input_text": "Transcription factor binding to the core promoter of the human monoamine oxidase B gene in the cerebral cortex and in blood cells .", "target_text": { "Transcription factor": "protein", "core promoter": "DNA", "human monoamine oxidase B gene": "DNA", "blood cells": "cell_type" } }, { "input_text": "Many studies show that monoamine oxidase B in blood cells is a biological marker for personality characteristics such as sensation seeking .", "target_text": { "monoamine oxidase B": "protein", "blood cells": "cell_type" } }, { "input_text": "The mechanism underlying this association is so far not explored .", "target_text": {} }, { "input_text": "In the present study we have performed electrophoretic mobility-shift assays to investigate the pattern of protein binding to a 150 bp fragment of the proximal 5'-flanking region of the human monoamine oxidase B gene .", "target_text": { "150 bp fragment": "DNA", "proximal 5'-flanking region": "DNA", "monoamine oxidase B": "protein", "human monoamine oxidase B gene": "DNA" } }, { "input_text": "We compared the pattern using nuclear extracts from human brain and lymphocytes .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "Interestingly , a correlation was observed between monoamine oxidase B enzyme activity in blood cells ( platelets ) and the binding pattern of two uncharacterized transcription factors .", "target_text": { "monoamine oxidase B": "protein", "blood cells": "cell_type", "platelets": "cell_type", "transcription factors": "protein" } }, { "input_text": "These data are well in line with the long-standing notion that interindividual differences in platelet monoamine oxidase may represent differences in expression of the enzyme rather than genotypic variation .", "target_text": { "platelet monoamine oxidase": "protein" } }, { "input_text": "Enhanced differentiation of HL-60 leukemia cells to macrophages induced by ciprofibrate .", "target_text": { "HL-60 leukemia cells": "cell_line", "macrophages": "cell_type" } }, { "input_text": "Ciprofibrate , an hypolipidaemic peroxisome proliferator , induced differentiation of HL-60 cells .", "target_text": { "HL-60 cells": "cell_line" } }, { "input_text": "The effect was greatly potentiated by phorbol 12-myristate 13-acetate at a concentration where neither phorbol ester nor ciprofibrate alone had any effect on these cells .", "target_text": {} }, { "input_text": "As occurs for HL-60 cell differentiation induced by high phorbol ester concentration , the ciprofibrate -induced phorbol ester -dependent differentiation of HL-60 cells proceeded through the monocytic/macrophage pathway and induced the phosphorylation of proteins with similar molecular weights suggesting that increased protein kinase C activity may be involved in the effect .", "target_text": { "HL-60 cells": "cell_line", "protein kinase C": "protein" } }, { "input_text": "The peroxisome proliferator-activated receptor ( PPARalpha ) transcription factor is expressed in HL-60 cells , but no changes were observed in its expression upon HL-60 cell differentiation .", "target_text": { "transcription factor": "protein", "HL-60 cells": "cell_line" } }, { "input_text": "The involvement of multiple tumor necrosis factor receptor ( TNFR ) -associated factors in the signaling mechanisms of receptor activator of NF-kappaB , a member of the TNFR superfamily .", "target_text": { "tumor necrosis factor receptor ( TNFR ) -associated factors": "protein", "receptor activator": "protein", "NF-kappaB": "protein", "TNFR superfamily": "protein" } }, { "input_text": "Receptor activator of NF-kappaB ( RANK ) is a recently identified member of the tumor necrosis factor receptor superfamily and is expressed on activated T cells and dendritic cells .", "target_text": { "NF-kappaB": "protein", "Receptor activator of NF-kappaB": "protein", "RANK": "protein", "tumor necrosis factor receptor superfamily": "protein", "activated T cells": "cell_type", "dendritic cells": "cell_type" } }, { "input_text": "Its cognate ligand ( RANKL ) plays significant roles in the activation of dendritic cell function and osteoclast differentiation .", "target_text": { "cognate ligand": "protein", "RANKL": "protein" } }, { "input_text": "We demonstrate here the interaction of RANK with tumor necrosis factor receptor-associated factors ( TRAFs ) 1 , 2 , 3 , 5 , and 6 both in vitro and in cells .", "target_text": { "RANK": "protein", "TRAFs": "protein" } }, { "input_text": "Mapping of the structural requirements for TRAF /RANK interaction revealed multiple TRAF binding sites clustered in two distinct domains in the RANK cytoplasmic tail .", "target_text": { "TRAF": "protein", "/RANK": "protein", "TRAF binding sites": "protein", "RANK": "protein", "RANK cytoplasmic tail": "protein" } }, { "input_text": "These TRAF binding domains were shown to be functionally important for the RANK -dependent induction of NF-kappaB and c-Jun NH2-terminal kinase activities .", "target_text": { "TRAF binding domains": "protein", "RANK": "protein", "NF-kappaB": "protein", "c-Jun": "protein", "NH2-terminal kinase": "protein" } }, { "input_text": "Site-directed mutagenesis demonstrated that these TRAF binding sites exhibited selective binding for different TRAF proteins .", "target_text": { "TRAF": "protein", "TRAF binding sites": "protein", "TRAF proteins": "protein" } }, { "input_text": "In particular , TRAF6 interacted with membrane-proximal determinants distinct from those binding TRAFs 1 , 2 , 3 , and 5 .", "target_text": { "TRAF6": "protein", "membrane-proximal determinants": "protein" } }, { "input_text": "When this membrane-proximal TRAF6 interaction domain was deleted , RANK -mediated NF-kappaB signaling was completely inhibited while c-Jun NH2-terminal kinase activation was partially inhibited .", "target_text": { "TRAF6": "protein", "membrane-proximal TRAF6 interaction domain": "protein", "RANK": "protein", "NF-kappaB": "protein", "c-Jun NH2-terminal kinase": "protein" } }, { "input_text": "An NH2-terminal truncation mutant of TRAF6 inhibited RANKL -mediated NF-kappaB activation , but failed to affect constitutive signaling induced by receptor overexpression , revealing a selective role for TRAF6 in ligand-induced activation events .", "target_text": { "NH2-terminal truncation mutant": "protein", "TRAF6": "protein", "RANKL": "protein", "NF-kappaB": "protein" } }, { "input_text": "Stat6 inhibits human interleukin-4 promoter activity in T cells .", "target_text": { "Stat6": "protein", "interleukin-4 promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "The differentiation of naive T-helper ( Th ) cells into cytokine -secreting effector Th cells requires exposure to multiple signals , including exogenous cytokines .", "target_text": { "naive T-helper ( Th ) cells": "cell_type", "cytokine": "protein", "cytokine -secreting effector Th cells": "cell_type", "exogenous cytokines": "protein" } }, { "input_text": "Interleukin-4 ( IL-4 ) plays a major role in this process by promoting the differentiation of IL-4 -secreting Th2 cells .", "target_text": { "Interleukin-4": "protein", "IL-4": "protein" } }, { "input_text": "In Th2 cells , IL-4 gene expression is tightly controlled at the level of transcription by the coordinated binding of multiple transcription factors to regulatory elements in the proximal promoter region .", "target_text": { "IL-4": "protein", "transcription factors": "protein", "promoter region": "DNA" } }, { "input_text": "Nuclear factor of activated T cell ( NFAT ) family members play a critical role in regulating IL-4 transcription and interact with up to five sequences ( termed P0 through P4 ) in the IL-4 promoter .", "target_text": { "Nuclear factor of activated T cell ( NFAT ) family members": "protein", "IL-4": "protein", "IL-4 promoter": "DNA" } }, { "input_text": "The molecular mechanisms by which IL-4 induces expression of the IL-4 gene are not known , although the IL-4 -activated transcription factor signal transducer and activator of transcription 6 ( Stat6 ) is required for this effect .", "target_text": { "IL-4": "protein", "IL-4 gene": "DNA", "transcription factor": "protein", "IL-4 -activated transcription factor signal transducer and activator of transcription 6": "protein", "Stat6": "protein" } }, { "input_text": "We report here that Stat6 interacts with three binding sites in the human IL-4 promoter by electrophoretic mobility shift assays .", "target_text": { "Stat6": "protein", "human IL-4 promoter": "DNA" } }, { "input_text": "These sites overlap the P1 , P2 , and P4 NFAT elements .", "target_text": {} }, { "input_text": "To investigate the role of Stat6 in regulating IL-4 transcription , we used Stat6 -deficient Jurkat T cells with different intact IL-4 promoter constructs in cotransfection assays .", "target_text": { "Stat6": "protein", "IL-4": "protein", "T cells": "cell_type", "IL-4 promoter": "DNA", "IL-4 promoter constructs": "DNA" } }, { "input_text": "We show that , whereas a multimerized response element from the germline IgE promoter was highly induced by IL-4 in Stat6 -expressing Jurkat cells , the intact human IL-4 promoter was repressed under similar conditions .", "target_text": { "multimerized response element": "DNA", "germline IgE promoter": "DNA", "IL-4": "protein", "Stat6": "protein", "Stat6 -expressing Jurkat cells": "cell_type", "IL-4 promoter": "DNA", "human IL-4 promoter": "DNA" } }, { "input_text": "We conclude that the function of Stat6 is highly dependent on promoter context and that this factor promotes IL-4 gene expression in an indirect manner .", "target_text": { "Stat6": "protein", "IL-4": "protein" } }, { "input_text": "Epithelial cell-initiated inflammation plays a crucial role in early tissue damage in amebic infection of human intestine .", "target_text": {} }, { "input_text": "BACKGROUND & AIMS : Entamoeba histolytica infection of the intestine can induce severe gut inflammation .", "target_text": {} }, { "input_text": "The aims of this study were to assess the role of the host inflammatory response in the tissue damage observed with amebiasis and the role of the intestinal epithelial cell in initiating that response .", "target_text": { "intestinal epithelial cell": "cell_type" } }, { "input_text": "METHODS : E. histolytica infection was established in human intestinal xenografts in severe combined immunodeficient ( SCID-HU-INT ) mice .", "target_text": {} }, { "input_text": "Human intestinal epithelial cell inflammatory responses to amebic infection were inhibited by the intraluminal administration of an antisense oligonucleotide to the human p65 subunit of nuclear factor kappaB , and the role of neutrophils in tissue damage observed with amebiasis was studied by depleting neutrophils from SCID-HU-INT mice .", "target_text": { "intestinal epithelial cell": "cell_type", "human p65 subunit": "protein", "nuclear factor kappaB": "protein", "neutrophils": "cell_type" } }, { "input_text": "RESULTS : Administration of the antisense oligonucleotide blocked the production of human interleukin 1beta and interleukin 8 by intestinal epithelial cells and inhibited neutrophil influx into the E. histolytica -infected intestinal xenografts .", "target_text": { "human interleukin 1beta": "protein", "interleukin 8": "protein", "intestinal epithelial cells": "cell_type" } }, { "input_text": "Inhibition of the gut inflammatory response by the antisense oligonucleotide or the depletion of neutrophils from SCID-HU- INT mice blocked the increase in intestinal permeability observed with amebic infection .", "target_text": { "neutrophils": "cell_type" } }, { "input_text": "CONCLUSIONS : Intestinal epithelial cells initiate an inflammatory response with resulting neutrophil-mediated tissue damage in response to E. histolytica infection ; this inflammatory cascade can be blocked by inhibiting the transcription of genes regulated by nuclear factor kappaB .", "target_text": { "Intestinal epithelial cells": "cell_type", "nuclear factor kappaB": "protein" } }, { "input_text": "Triptolide induces apoptotic death of T lymphocyte .", "target_text": { "T lymphocyte": "cell_type" } }, { "input_text": "Extract of Tripterygium wilfordii Hook . f ( TWHf ) has immunosuppressive activity and has been used as anti-inflammatory agent in traditional Chinese medicine for centuries .", "target_text": {} }, { "input_text": "Recent studies have demonstrated that triptolide is the major active component in the extract that inhibits antigen or mitogen -induced T cell proliferation .", "target_text": { "mitogen": "protein" } }, { "input_text": "In attempting to investigate its effect on activation of T lymphocytes , we found triptolide induces apoptotic death of T cell hybridomas and peripheral T cells but not that of thymocytes .", "target_text": { "T lymphocytes": "cell_type", "T cell hybridomas": "cell_line", "peripheral T cells": "cell_type", "thymocytes": "cell_type" } }, { "input_text": "The triptolide -induced apoptosis is accompanied by increase of DEVD-cleavable caspases activity and degradation of caspase substrate poly ( ADP-ribose ) polymerase ( PARP ) .", "target_text": { "caspases": "protein", "caspase substrate poly ( ADP-ribose ) polymerase": "protein", "PARP": "protein" } }, { "input_text": "A specific inhibitor of caspases , zVAD-FMK , prevents triptolide -induced PARP degradation and DNA fragmentation but not growth arrest .", "target_text": { "caspases": "protein", "PARP": "protein" } }, { "input_text": "Furthermore , enforced expression of Bcl-2 inhibited triptolide -induced degradation of PARP and apoptosis .", "target_text": { "Bcl-2": "protein", "PARP": "protein" } }, { "input_text": "These results indicate that triptolide induces T cell apoptosis through activating caspases , and suggest the growth arrest and apoptotic effect of triptolide may contribute to the immunosuppressive activity of TWHf extract", "target_text": { "caspases": "protein" } }, { "input_text": "A novel transcription factor regulates expression of the vacuolar H+-ATPase B2 subunit through AP-2 sites during monocytic differentiation .", "target_text": { "transcription factor": "protein", "H+-ATPase B2 subunit": "protein", "vacuolar H+-ATPase B2 subunit": "protein", "AP-2 sites": "DNA" } }, { "input_text": "During monocyte-to-macrophage differentiation , the cellular content of vacuolar H+-ATPase ( V-ATPase ) increases more than 4-fold .", "target_text": { "vacuolar H+-ATPase": "protein", "V-ATPase": "protein" } }, { "input_text": "We have shown previously that amplified expression of the B2 subunit of the V-ATPase occurs solely by increased transcription , and that the 5'-untranslated region of the B2 gene , containing multiple consensus binding sites for the transcription factors AP-2 and Sp1 , is required for this expression .", "target_text": { "B2 subunit": "protein", "V-ATPase": "protein", "5'-untranslated region": "DNA", "B2 gene": "DNA", "consensus binding sites": "DNA", "transcription factors": "protein", "AP-2": "protein", "Sp1": "protein" } }, { "input_text": "The present study demonstrates that AP-2 binding sequences are essential for increased transcription from the B2 promoter during monocyte-macrophage differentiation and that AP-2 , expressed exogenously in THP-1 and other cells , activates transcription from the B2 promoter .", "target_text": { "AP-2": "protein", "AP-2 binding sequences": "DNA", "B2 promoter": "DNA", "THP-1": "cell_line" } }, { "input_text": "In mobility shift assays , a nuclear factor from THP-1 and U-937 cells was identified that binds to several AP-2 response elements within the B2 promoter , but does not react with AP-2 antibodies , and has a DNA sequence binding affinity profile that differs from AP-2 .", "target_text": { "nuclear factor": "protein", "THP-1": "cell_line", "U-937 cells": "cell_line", "AP-2": "protein", "AP-2 response elements": "DNA", "B2 promoter": "DNA", "AP-2 antibodies": "protein", "DNA sequence": "DNA" } }, { "input_text": "These findings suggest that a novel AP-2 -like transcription factor is responsible for V-ATPase B subunit amplification during monocyte differentiation .", "target_text": { "AP-2": "protein", "transcription factor": "protein", "AP-2 -like transcription factor": "protein", "V-ATPase": "protein", "V-ATPase B subunit": "protein" } }, { "input_text": "c-Jun and GST-pi expression in human plasma cells .", "target_text": { "human plasma cells": "cell_type" } }, { "input_text": "Bone marrow samples from 33 patients affected by MM and MGUS , and 8 patients not affected by lymphoproliferative diseases were studied for expression of c-Jun ( a component of the transcription factor AP-1 ) and glutathione-S-transferase pi ( GST-pi ) using immunocytochemical methods .", "target_text": { "c-Jun": "protein", "transcription factor": "protein", "AP-1": "protein", "glutathione-S-transferase pi": "protein", "GST-pi": "protein" } }, { "input_text": "A high and frequent expression of these two proteins was found both in MM and MGUS patients ( 31/33 patients positive for c-Jun and 29/33 patients positive for GST-pi ) and in controls not affected by monoclonal gammopathy ( 7/8 patients positive for both c-Jun and GST-pi ) .", "target_text": { "c-Jun": "protein", "GST-pi": "protein" } }, { "input_text": "No statistically significant correlation was found between c-Jun- and GST-pi- positive plasma cells .", "target_text": {} }, { "input_text": "The expression of these two proteins was not related to clinical or laboratory data .", "target_text": {} }, { "input_text": "Our results seem to confirm a possible role of the transcriptional complex AP-1 in activating GST-pi promoter in human plasma cells .", "target_text": { "transcriptional complex": "protein", "AP-1": "protein", "GST-pi": "protein", "GST-pi promoter": "DNA", "human plasma cells": "cell_type" } }, { "input_text": "Activation of signaling pathways and prevention of apoptosis by cytokines in eosinophils .", "target_text": { "cytokines": "protein", "eosinophils": "cell_type" } }, { "input_text": "Inhibition of apoptosis in eosinophils by cytokines such as IL-5 and GM-CSF may play an important role in the pathogenesis of allergic and parasitic disorders .", "target_text": { "eosinophils": "cell_type", "cytokines": "protein", "IL-5": "protein", "GM-CSF": "protein" } }, { "input_text": "Recently , there has been some progress in the understanding of the signal transduction pathways activated by these cytokines in eosinophils .", "target_text": { "cytokines": "protein", "eosinophils": "cell_type" } }, { "input_text": "The IL-3 , IL-5 and GM-CSF receptors share a common signal transducer that possesses no intrinsic kinase domain .", "target_text": { "IL-3": "protein", "IL-5": "protein", "GM-CSF receptors": "protein", "common signal transducer": "protein", "intrinsic kinase domain": "protein" } }, { "input_text": "It has been shown that eosinophil stimulation by these cytokines is associated with increases in tyrosine phosphorylation of several cellular substrates .", "target_text": { "cytokines": "protein" } }, { "input_text": "In the past few years , there has been some progress in defining the tyrosine kinases that are activated by the IL-3 / IL-5 / GM-CSF receptor beta-subunit in eosinophils .", "target_text": { "IL-3": "protein", "IL-5": "protein", "GM-CSF": "protein", "IL-3 / IL-5 / GM-CSF receptor beta-subunit": "protein", "eosinophils": "cell_type" } }, { "input_text": "This review will concentrate on this topic and on its role for the regulation of eosinophil apoptosis .", "target_text": {} }, { "input_text": "Requirement of GATA-1 and p45 NF-E2 expression in butyric acid -induced erythroid differentiation .", "target_text": { "GATA-1": "protein", "p45 NF-E2": "protein" } }, { "input_text": "Butyric acid ( BA ) is known to induce overexpression of fetal hemoglobin and then erythroid differentiation .", "target_text": { "fetal hemoglobin": "protein" } }, { "input_text": "Therefore , BA is currently under clinical investigation as a potential therapy for the treatment of sickle cell disease and cancer .", "target_text": {} }, { "input_text": "Nevertheless , the molecular mechanisms involved in BA -induced differentiation remain largely unknown .", "target_text": {} }, { "input_text": "Previous reports have shown that BA -induced overexpression of erythroid genes occurred at the transcriptional level , suggesting the involvement of erythroid transcription factors .", "target_text": { "erythroid genes": "DNA", "transcription factors": "protein", "erythroid transcription factors": "protein" } }, { "input_text": "Here , we intend to demonstrate the requirement of GATA-1 and NF-E2 transcription factors in the BA -induced erythroid differentiation of human leukemic K562 cells .", "target_text": { "GATA-1": "protein", "NF-E2": "protein", "transcription factors": "protein", "human leukemic K562 cells": "cell_line" } }, { "input_text": "Time-course experiments showed that nuclear levels of GATA-1 and p45 NF-E2 proteins increased during BA treatment .", "target_text": { "GATA-1": "protein", "NF-E2": "protein", "p45 NF-E2": "protein" } }, { "input_text": "Moreover , antisense oligodeoxynucleotides targeting either GATA-1 or p45 NF-E2 proteins inhibited both protein expression and BA -induced differentiation .", "target_text": { "GATA-1": "protein", "p45 NF-E2": "protein" } }, { "input_text": "In contrast , BA -induced cell growth inhibition was not affected .", "target_text": {} }, { "input_text": "These results provide the first direct evidence for the requirement of GATA-1 and NF-E2 in BA -induced differentiation process .", "target_text": { "GATA-1": "protein", "NF-E2": "protein" } }, { "input_text": "Characterisation of regulatory sequences at the Epstein-Barr virus BamHI W promoter .", "target_text": { "Epstein-Barr virus BamHI W promoter": "DNA" } }, { "input_text": "Epstein-Barr virus , a human gammaherpesvirus , possesses a unique set of latent genes whose constitutive expression in B cells leads to cell growth transformation .", "target_text": { "latent genes": "DNA", "B cells": "cell_type" } }, { "input_text": "The initiation of this growth transforming infection depends on a viral promoter in BamHI W ( Wp ) whose regulation is poorly understood .", "target_text": { "viral promoter": "DNA" } }, { "input_text": "Using Wp reporter constructs in in vitro transfection assays , we found that Wp was 11- to 190-fold more active in B cell than in non-B cell lines and that three regions of the promoter ( termed UAS1 , UAS2 , and UAS3 ) contributed to transcriptional activation .", "target_text": { "Wp reporter constructs": "DNA", "B cell": "cell_line", "non-B cell lines": "cell_line", "promoter": "DNA", "UAS1": "DNA", "UAS2": "DNA", "UAS3": "DNA" } }, { "input_text": "The upstream regions UAS3 ( -1168 to -440 ) and UAS2 ( -352 to -264 ) both functioned in a cell lineage-independent manner and were together responsible for the bulk of Wp activity in non-B cells ; mutational analysis indicated the importance of a YY1 binding site in UAS2 in that context .", "target_text": { "UAS3": "DNA", "-1168 to -440": "DNA", "UAS2": "DNA", "-352 to -264": "DNA", "non-B cells": "cell_type", "YY1 binding site": "DNA" } }, { "input_text": "By contrast , UAS1 ( -140 to -87 ) was B cell specific and was the key determinant of the promoter 's increased activity in B cell lines .", "target_text": { "UAS1": "DNA", "-140 to -87": "DNA", "B cell lines": "cell_line" } }, { "input_text": "Mutational analysis of UAS1 sequences combined with in vitro bandshift assays revealed the presence of three binding sites for cellular factors in this region .", "target_text": { "UAS1": "DNA", "UAS1 sequences": "DNA", "binding sites": "DNA", "cellular factors": "protein" } }, { "input_text": "When mutations that abolished factor binding in bandshift assays were introduced into a Wp reporter construct , the loss of any one of the three UAS1 binding sites was sufficient to reduce promoter activity by 10- to 30-fold in B cells .", "target_text": { "Wp reporter construct": "DNA", "UAS1": "DNA", "binding sites": "DNA", "UAS1 binding sites": "DNA", "B cells": "cell_type" } }, { "input_text": "From sequence analysis , two of these appear to be novel transcription factor binding sites , whereas the third was identified as a cyclic AMP response element ( CRE ) .", "target_text": { "transcription factor": "protein", "binding sites": "DNA", "cyclic AMP response element": "DNA", "CRE": "DNA" } }, { "input_text": "Our data indicate that this CRE interacts with CREB and ATF1 proteins present in B cell nuclear extracts and that this interaction is important for Wp activity .", "target_text": { "CRE": "DNA" } }, { "input_text": "In situ RT-PCR detection of Epstein-Barr virus immediate-early transcripts in CD4+ and CD8+ T lymphocytes .", "target_text": { "Epstein-Barr virus immediate-early transcripts": "RNA" } }, { "input_text": "AIDS -related Epstein-Barr virus ( EBV ) -associated T cell lymphomas are emerging as a new , distinct histopathological entity .", "target_text": {} }, { "input_text": "The pathway whereby EBV infects T cells as well as the initial EBV transcriptional program in T cells has not been established .", "target_text": { "T cells": "cell_type" } }, { "input_text": "In order to shed light on the early events of the EBV infection of T cells , we have used in situ reverse transcription based polymerase chain reaction ( RT-PCR ) to study the initial EBV transcriptional program in homogeneous CD4+ and CD8+ lymphocytes .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Following EBV infection , Epstein-Barr nuclear antigen ( EBNA ) expression could be detected in T rosetting CD4+ and CD8+ T lymphocytes .", "target_text": { "EBNA": "protein" } }, { "input_text": "Only a few cells showed viral capsid antigen ( VCA ) .", "target_text": { "viral capsid antigen": "protein", "VCA": "protein" } }, { "input_text": "EBV immediate-early gene transcripts ( BZLF1 , BRLF1 , and BMLF1 ) encoded in the BamHI Z , R , and M fragments could be detected by in situ RT-PCR in the EBV producer cell line B95.8 .", "target_text": { "EBV immediate-early gene transcripts": "RNA", "BZLF1": "RNA", "BRLF1": "RNA", "BMLF1": "RNA" } }, { "input_text": "Both BZLF1 and BRLF1 immediate-early transcripts , but not BMLF1 transcript , could be detected in individual CD4+ and CD8+ T cells infected with EBV .", "target_text": { "BMLF1": "RNA", "BMLF1 transcript": "RNA" } }, { "input_text": "Demonstration of EBV mRNA transcripts encoding immediate-early transcriptional transactivators in EBV -infected T cells provides the first evidence for a possible mechanism whereby EBV could contribute to T cell proliferation and EBV -associated T cell malignancies .", "target_text": { "EBV mRNA transcripts": "RNA", "immediate-early transcriptional transactivators": "protein", "T cells": "cell_type", "EBV -infected T cells": "cell_type" } }, { "input_text": "The linkage between T-cell and dendritic cell development in the mouse thymus .", "target_text": {} }, { "input_text": "Thymic dendritic cells ( DC ) mediate negative selection at a relatively late stage of the T-cell developmental pathway .", "target_text": { "Thymic dendritic cells": "cell_type", "DC": "cell_type" } }, { "input_text": "We present evidence that the development of thymic DC and of T-lineage cells is linked via a common precursor at an early stage of thymocyte development .", "target_text": { "thymic DC": "cell_type", "T-lineage cells": "cell_type" } }, { "input_text": "T-lineage precursor populations from the adult mouse thymus , prior to T-cell receptor gene rearrangement , display a capacity to produce DC as well as T cells in the thymus , and are very efficient precursors of DC in culture .", "target_text": { "DC": "cell_type", "T cells": "cell_type" } }, { "input_text": "These lymphoid/ DC precursors have little capacity to form myeloid cells , indicating that thymic DC are a lymphoid-related rather than myeloid-related lineage .", "target_text": { "DC": "cell_type", "lymphoid/ DC precursors": "cell_type", "myeloid cells": "cell_type", "thymic DC": "cell_type", "myeloid-related lineage": "cell_type" } }, { "input_text": "In contrast to myeloid-related DC , granulocyte-macrophage colony-stimulating factor is not required for the development of these lymphoid-related DC in vivo or in vitro .", "target_text": { "DC": "cell_type", "myeloid-related DC": "cell_type", "granulocyte-macrophage colony-stimulating factor": "protein", "lymphoid-related DC": "cell_type" } }, { "input_text": "DC can develop in mutant mice lacking mature T cells , provided the common precursors are present .", "target_text": { "DC": "cell_type", "T cells": "cell_type", "mature T cells": "cell_type" } }, { "input_text": "However , in mutant mice lacking functional Ikaros transcription factors , there are deficiencies in lymphoid precursor cells , in mature lymphoid cells and in DC .", "target_text": { "Ikaros": "protein", "transcription factors": "protein", "lymphoid precursor cells": "cell_type", "mature lymphoid cells": "cell_type", "DC": "cell_type" } }, { "input_text": "Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells .", "target_text": { "T cells": "cell_type", "nuclear factor of activated T cells": "protein" } }, { "input_text": "Post HIV-1 entry , productive HIV-1 infection of primary T cells requires overcoming several cellular blocks to provirus establishment and replication .", "target_text": { "T cells": "cell_type", "primary T cells": "cell_type" } }, { "input_text": "Activation of unknown host intracellular events overcomes such inhibitory steps and is concomitant with HIV-1 replication .", "target_text": {} }, { "input_text": "We show that the transcription factor NFATc was sufficient as a cellular factor to induce a highly permissive state for HIV-1 replication in primary CD4+ T cells .", "target_text": { "transcription factor": "protein", "NFATc": "protein", "primary CD4+ T cells": "cell_type" } }, { "input_text": "NFATc overcame a blockade at reverse transcription and permitted active HIV-1 replication .", "target_text": { "NFATc": "protein" } }, { "input_text": "Pharmacologic blockade of endogenous NFAT activity by FK506 or CsA inhibited synthesis of reverse transcription and also potently blocked HIV-1 replication .", "target_text": { "endogenous NFAT": "protein" } }, { "input_text": "T cells therefore can become competent for HIV-1 replication by control of regulated host factors such as the NFATc transcription factor .", "target_text": { "T cells": "cell_type", "regulated host factors": "protein", "NFATc": "protein", "transcription factor": "protein" } }, { "input_text": "The host mechanisms regulated by such permissivity factors are potential targets for anti- HIV-1 therapy .", "target_text": {} }, { "input_text": "Regulation of NF-kappa B , AP-1 , NFAT , and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50 .", "target_text": { "NF-kappa B": "protein", "AP-1": "protein", "NFAT": "protein", "STAT1": "protein", "T lymphocytes": "cell_type", "nuclear localization sequence": "protein", "NF-kappa B p50": "protein" } }, { "input_text": "Activation of T lymphocytes by Ags or cytokines results in translocation of the transcription factors NF-kappa B , AP-1 , NFAT , and STAT from the cytoplasm into the nucleus .", "target_text": { "T lymphocytes": "cell_type", "Ags": "protein", "cytokines": "protein", "transcription factors": "protein", "NF-kappa B": "protein", "AP-1": "protein", "NFAT": "protein", "STAT": "protein" } }, { "input_text": "The first step in the nuclear import process is recognition of a nuclear localization sequence ( NLS ) within the karyophilic protein by a cytoplasmic receptor such as the importin ( karyopherin ) -alpha subunit .", "target_text": { "nuclear localization sequence": "protein", "NLS": "protein", "karyophilic protein": "protein", "cytoplasmic receptor": "protein", "importin ( karyopherin ) -alpha subunit": "protein" } }, { "input_text": "The NLSs of NF-kappa B , AP-1 , and NFAT differ and the NLS of STAT1 has not yet been identified .", "target_text": { "NLSs": "protein", "NF-kappa B": "protein", "AP-1": "protein", "NFAT": "protein", "NLS": "protein", "STAT1": "protein" } }, { "input_text": "Herein we demonstrate that the inducible nuclear import of NF-kappa B , AP-1 , NFAT , and STAT1 in Jurkat T lymphocytes is significantly inhibited by a cell-permeable peptide carrying the NLS of the NF-kappa B p50 subunit .", "target_text": { "NF-kappa B": "protein", "AP-1": "protein", "NFAT": "protein", "STAT1": "protein", "Jurkat T lymphocytes": "cell_line", "NLS": "protein", "NF-kappa B p50 subunit": "protein" } }, { "input_text": "NLS peptide-mediated disruption of the nuclear import of these transcription factors results in inhibition of I kappa B alpha and IL-2 gene expression , processes dependent on NF-kappa B or the combination of NF-kappa B , AP-1 , and NFAT .", "target_text": { "NLS": "protein", "transcription factors": "protein", "NF-kappa B": "protein", "AP-1": "protein", "NFAT": "protein" } }, { "input_text": "Further , we show that inhibitory NLS peptide interacts in vitro with a cytoplasmic NLS receptor complex comprised of the Rch1/importin ( karyopherin ) -beta heterodimer expressed in Jurkat T cells .", "target_text": { "NLS": "protein", "cytoplasmic NLS receptor complex": "protein", "Rch1/importin ( karyopherin ) -beta heterodimer": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "Taken together , these data indicate that the inducible nuclear import of NF-kappa B , AP-1 , NFAT , and STAT1 in Jurkat T cells can be regulated by NLS peptide delivered noninvasively to the cytoplasm of Jurkat T cells to target members of the importin ( karyopherin ) -alpha beta NLS receptor complex .", "target_text": { "NF-kappa B": "protein", "AP-1": "protein", "NFAT": "protein", "STAT1": "protein", "Jurkat T cells": "cell_line", "NLS": "protein", "importin ( karyopherin ) -alpha beta": "protein", "NLS receptor complex": "protein" } }, { "input_text": "Membrane-associated lymphotoxin on natural killer cells activates endothelial cells via an NF-kappaB -dependent pathway .", "target_text": { "Membrane-associated lymphotoxin": "protein", "natural killer cells": "cell_type", "endothelial cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "BACKGROUND : Inhibition of complement in small animal models of xenotransplantation has demonstrated graft infiltration with natural killer ( NK ) cells and monocytes associated with endothelial cell ( EC ) activation .", "target_text": { "natural killer ( NK ) cells": "cell_type", "endothelial cell": "cell_type", "EC": "cell_type" } }, { "input_text": "We have previously demonstrated that human NK cells activate porcine EC in vitro , which results in adhesion molecule expression and cytokine secretion .", "target_text": { "human NK cells": "cell_type", "EC": "cell_type", "adhesion molecule": "protein", "cytokine": "protein" } }, { "input_text": "In this study , we used the NK cell line NK92 to define the molecular and cellular basis of NK cell-mediated EC activation .", "target_text": { "NK cell line NK92": "cell_line", "EC": "cell_type" } }, { "input_text": "METHODS : EC were transfected with either reporter constructs containing the luciferase gene driven either by E-selectin or interleukin ( IL ) -8 promoters or a synthetic NF-kappaB -dependent promoter .", "target_text": { "EC": "cell_type", "luciferase": "protein", "luciferase gene": "DNA", "NF-kappaB": "protein", "NF-kappaB -dependent promoter": "DNA" } }, { "input_text": "In addition , a dominant-negative mutant tumor necrosis factor receptor I ( TNFRI ) expression vector was co-transfected in inhibition studies .", "target_text": { "dominant-negative mutant tumor necrosis factor receptor I ( TNFRI ) expression vector": "DNA" } }, { "input_text": "Forty-eight hours after transfection , EC were stimulated with NK cells or NK cell membrane extracts for 7 hr and activation was measured by a luciferase assay .", "target_text": { "EC": "cell_type", "NK cells": "cell_type", "NK cell membrane extracts": "cell_type", "luciferase": "protein" } }, { "input_text": "RESULTS : Co-culture of NK cells with transfected EC enhanced E-selectin , IL-8 , and NF-kappaB -dependent promoter activity .", "target_text": { "NK cells": "cell_type", "EC": "cell_type", "E-selectin": "protein", "IL-8": "protein", "NF-kappaB": "protein" } }, { "input_text": "NK cell membrane extracts retained the capacity to activate EC and induced nuclear translocation of NF-kappaB ( p50 and p65 ) .", "target_text": { "EC": "cell_type", "NF-kappaB": "protein", "p50": "protein", "p65": "protein" } }, { "input_text": "Western blotting of NK cell and membrane extracts detected the presence of Lymphotoxin-alpha ( LTalpha ) but not tumor necrosis factor-alpha .", "target_text": { "NK cell": "cell_type", "Lymphotoxin-alpha": "protein", "LTalpha": "protein", "tumor necrosis factor-alpha": "protein" } }, { "input_text": "Furthermore , LTalpha was secreted in NK: EC co- cultures .", "target_text": { "LTalpha": "protein", "EC": "cell_type", "NK: EC co- cultures": "cell_line" } }, { "input_text": "Co-transfection with dominant-negative mutant TNFRI inhibited EC activation by NK cell membrane extracts and by NK cells by 80 % and 47 % , respectively .", "target_text": { "dominant-negative mutant TNFRI": "protein", "EC": "cell_type", "NK cells": "cell_type" } }, { "input_text": "The same pattern of inhibition was observed using anti-human LT sera .", "target_text": {} }, { "input_text": "CONCLUSIONS : Human NK cell membrane-bound LT signals across species via TNFRI , leading to NF-kappaB nuclear translocation and transcription of E-selectin and IL-8 , which results in EC activation .", "target_text": { "TNFRI": "protein", "NF-kappaB": "protein", "E-selectin": "protein", "IL-8": "protein", "EC": "cell_type" } }, { "input_text": "The discrepancy in the degree of inhibition by membrane extracts and NK cells with mutant TNFRI suggests that additional pathways are utilized by NK cells to activate EC", "target_text": { "NK cells": "cell_type", "mutant TNFRI": "protein", "EC": "cell_type" } }, { "input_text": "Ras -dependent , Ca2+ -stimulated activation of nuclear factor of activated T cells by a constitutively active Cbl mutant in T cells .", "target_text": { "Ras": "protein", "nuclear factor of activated T cells": "protein", "Cbl mutant": "protein", "T cells": "cell_type" } }, { "input_text": "T cell receptor ( TCR ) stimulation induces rapid tyrosine phosphorylation of cellular proteins , including Cbl , a protooncogene product whose function remains unclear .", "target_text": { "T cell receptor": "protein", "TCR": "protein", "cellular proteins": "protein", "Cbl": "protein", "protooncogene product": "protein" } }, { "input_text": "As a first step toward elucidating the function of Cbl in TCR -initiated signaling , we evaluated the ability of wild-type Cbl or a transforming Cbl mutant ( 70Z/3 ) to induce transcriptional activation of a nuclear factor of activated T cells ( NFAT ) element derived from the interleukin 2 ( IL2 ) promoter in transiently cotransfected Jurkat-TAg T cells .", "target_text": { "Cbl": "protein", "TCR": "protein", "wild-type Cbl": "protein", "Cbl mutant": "protein", "T cells": "cell_type", "nuclear factor of activated T cells": "protein", "NFAT": "protein", "nuclear factor of activated T cells ( NFAT ) element": "DNA", "interleukin 2": "protein", "IL2": "protein", "interleukin 2 ( IL2 ) promoter": "DNA", "Jurkat-TAg T cells": "cell_line" } }, { "input_text": "70Z/3 , but not Cbl , caused NFAT activation which was significantly enhanced by stimulation with calcium ionophore , and was drastically reduced by cyclosporin A pretreatment .", "target_text": { "70Z/3": "protein", "Cbl": "protein", "NFAT": "protein" } }, { "input_text": "A point mutation of a potential phosphatidylinositol 3-kinase ( PI3-K ) binding site ( Y731EAM to Y731EAC ) in 70Z/3 disrupted the association of PI3-K with 70Z/3 , but did not reduce the induction of NFAT activity , suggesting that the interaction between Cbl and PI3-K is not required in the 70Z/3 -mediated induction of NFAT .", "target_text": { "phosphatidylinositol 3-kinase": "protein", "PI3-K": "protein", "phosphatidylinositol 3-kinase ( PI3-K ) binding site": "DNA", "Y731EAM": "DNA", "Y731EAC": "DNA", "70Z/3": "protein", "NFAT": "protein", "Cbl": "protein" } }, { "input_text": "Additional mapping studies indicated that defined deletions of C-terminal 70Z/3 sequences affected to a variable degree its ability to stimulate NFAT activity .", "target_text": { "70Z/3": "protein", "NFAT": "protein" } }, { "input_text": "Strikingly , deletion of 346 C-terminal residues augmented this activity , whereas removal of 20 additional residues abolished it .", "target_text": { "346 C-terminal residues": "protein" } }, { "input_text": "Coexpression of dominant negative Ras abrogated the basal or ionomycin-stimulated , 70Z/3 -mediated NFAT activation , suggesting a functional Ras is required for this activation .", "target_text": { "dominant negative Ras": "protein", "70Z/3": "protein", "NFAT": "protein", "functional Ras": "protein" } }, { "input_text": "These results implicate Cbl in Ras -dependent signaling pathways which lead to NFAT activation .", "target_text": { "Cbl": "protein", "Ras": "protein", "NFAT": "protein" } }, { "input_text": "Requirement of prestimulated THP-1 monocytic cells for endothelial cell activation .", "target_text": { "prestimulated THP-1 monocytic cells": "cell_line", "endothelial cell": "cell_type" } }, { "input_text": "Involvement of TNF alpha .", "target_text": {} }, { "input_text": "Blood monocytes spontaneously activate endothelial cells in culture , leading to adhesion of monocytic cells onto the endothelial surface and overproduction of endothelial proteins such as von Willebrand factor ( vWf ) and plasminogen activator inhibitor type 1 ( PAI-1 ) .", "target_text": { "Blood monocytes": "cell_type", "endothelial cells": "cell_type", "monocytic cells": "cell_type", "von Willebrand factor": "protein", "vWf": "protein", "plasminogen activator inhibitor type 1": "protein", "PAI-1": "protein" } }, { "input_text": "To overcome the difficulty in obtaining quiescent monocytes , we studied the ability of promonocytic THP-1 cells to activate endothelial cells .", "target_text": { "quiescent monocytes": "cell_type", "promonocytic THP-1 cells": "cell_line", "endothelial cells": "cell_type" } }, { "input_text": "Lipopolysaccharide ( LPS ) -prestimulated and untreated THP-1 cells were cocultured with resting human umbilical vein endothelial cells ( HUVEC ) for 3 and 24 h in the presence of colimycin to neutralize LPS traces .", "target_text": { "THP-1 cells": "cell_line", "endothelial cells": "cell_type", "resting human umbilical vein endothelial cells": "cell_type", "HUVEC": "cell_type" } }, { "input_text": "Addition of untreated THP-1 cells had little effect on HUVEC adhesiveness .", "target_text": { "THP-1 cells": "cell_line", "HUVEC": "cell_type" } }, { "input_text": "Addition of prestimulated THP-1 cells was followed by a noticeable adhesion after 3 h which reversed to basal values within 24 h .", "target_text": { "THP-1 cells": "cell_line" } }, { "input_text": "Under these conditions HUVEC adhesion molecules , E-selectin , VCAM-1 and ICAM-1 , were increased at 3 h with only ICAM-1 remaining overexpressed at 24 h .", "target_text": { "HUVEC": "cell_type", "HUVEC adhesion molecules": "protein", "E-selectin": "protein", "VCAM-1": "protein", "ICAM-1": "protein" } }, { "input_text": "Diffusible endothelial proteins such as soluble E-selectin , PAI-1 and vWf to a minimal extent , increased in supernatants from HUVEC cocultured for 24 h with prestimulated THP-1 cells .", "target_text": { "endothelial proteins": "protein", "Diffusible endothelial proteins": "protein", "E-selectin": "protein", "PAI-1": "protein", "vWf": "protein", "HUVEC": "cell_type", "THP-1 cells": "cell_line" } }, { "input_text": "In those cocultures , TNF alpha concentrations peaked at 3 h whereas IL-1 beta levels progressively rose until 24 h .", "target_text": { "TNF alpha": "protein" } }, { "input_text": "Addition of an anti- TNF alpha antibody decreased by 40 % E-selectin and ICAM-1 induction and suppressed PAI-1 overproduction with a weak effect on vWf .", "target_text": { "TNF alpha": "protein", "anti- TNF alpha antibody": "protein", "E-selectin": "protein", "ICAM-1": "protein", "PAI-1": "protein", "vWf": "protein" } }, { "input_text": "An anti-IL-1 beta antibody had negligible effects on HUVEC adhesion molecules , PAI-1 or vWf production .", "target_text": { "anti-IL-1 beta antibody": "protein", "HUVEC": "cell_type", "HUVEC adhesion molecules": "protein", "PAI-1": "protein", "vWf": "protein" } }, { "input_text": "These results provide evidence that promonocytic THP-1 cells require prestimulation in order to activate HUVEC and that TNF alpha contributes to this phenomenon .", "target_text": { "promonocytic THP-1 cells": "cell_line", "HUVEC": "cell_type", "TNF alpha": "protein" } }, { "input_text": "Engagement of the Lewis X antigen ( CD15 ) results in monocyte activation .", "target_text": {} }, { "input_text": "We previously reported that monocyte adhesion to tumor necrosis factor-alpha ( TNF-alpha ) -treated endothelial cells increased expression of tissue factor and CD36 on monocytes .", "target_text": { "TNF-alpha": "protein", "endothelial cells": "cell_type", "tumor necrosis factor-alpha ( TNF-alpha ) -treated endothelial cells": "cell_line", "CD36": "protein" } }, { "input_text": "Using immunological cross-linking to mimic receptor engagement by natural ligands , we now show that CD15 ( Lewis X ) , a monocyte counter-receptor for endothelial selectins may participate in this response .", "target_text": { "monocyte counter-receptor": "protein", "endothelial selectins": "protein" } }, { "input_text": "We used cytokine production as a readout for monocyte activation and found that CD15 cross-linking induced TNF-alpha release from peripheral blood monocytes and cells from the monocytic cell line MM6 .", "target_text": { "TNF-alpha": "protein", "peripheral blood monocytes": "cell_type", "monocytic cell line MM6": "cell_line" } }, { "input_text": "Quantitative reverse transcriptase -polymerase chain reaction ( RT-PCR ) showed an increase in steady-state TNF-alpha mRNA after 3 to 4 hours of cross-linking .", "target_text": { "reverse transcriptase": "protein", "TNF-alpha": "protein", "TNF-alpha mRNA": "RNA" } }, { "input_text": "CD15 cross-linking also concomitantly increased interleukin-1 beta ( IL-1 beta ) mRNA , while no apparent change was observed in the levels of beta-actin mRNA , indicating specificity .", "target_text": { "interleukin-1 beta": "protein", "IL-1 beta": "protein", "interleukin-1 beta ( IL-1 beta ) mRNA": "RNA", "beta-actin mRNA": "RNA" } }, { "input_text": "To examine transcriptional regulation of cytokine genes by CD15 engagement , a CAT plasmid reporter construct containing IL-1 beta promoter/enhancer sequences was introduced into MM6 .", "target_text": { "cytokine genes": "DNA", "IL-1 beta": "protein", "IL-1 beta promoter/enhancer sequences": "DNA", "MM6": "cell_line" } }, { "input_text": "Subsequent cross-linking of CD15 increased CAT activity .", "target_text": { "CAT": "protein" } }, { "input_text": "CD15 engagement by monoclonal antibody also attenuated IL-1 beta transcript degradation , demonstrating that signaling via CD15 also had posttranscriptional effects .", "target_text": { "monoclonal antibody": "protein", "IL-1 beta": "protein" } }, { "input_text": "Nuclear extracts of anti- CD15 cross-linked cells demonstrated enhanced levels of the transcriptional factor activator protein-1 , minimally changed nuclear factor-kappa B , and did not affect SV40 promoter specific protein-1 .", "target_text": { "CD15 cross-linked cells": "cell_type", "transcriptional factor activator protein-1": "protein", "nuclear factor-kappa B": "protein", "SV40 promoter": "DNA", "SV40 promoter specific protein-1": "protein" } }, { "input_text": "We conclude that engagement of CD15 on monocytes results in monocyte activation .", "target_text": {} }, { "input_text": "In addition to its well-recognized adhesive role , CD15 may function as an important signaling molecule capable of initiating proinflammatory events in monocytes that come into contact with activated endothelium .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "CD2 signalling induces phosphorylation of CREB in primary lymphocytes .", "target_text": { "CD2": "protein", "CREB": "protein", "primary lymphocytes": "cell_type" } }, { "input_text": "Promoter sequences responsive to cyclic AMP ( cAMP ) are found in a number of cellular genes , and bind transcription factors of the cAMP response element binding protein ( CREB ) / activating transcription factor-1 ( ATF-1 ) family .", "target_text": { "cellular genes": "DNA", "transcription factors": "protein", "cAMP response element binding protein": "protein", "CREB": "protein", "CREB ) / activating transcription factor-1 ( ATF-1 ) family": "protein" } }, { "input_text": "We have used a human T-lymphotropic virus type 1 ( HTLV-1 ) model of cAMP response element ( CRE ) transcription to investigate the influence of lymphocyte activation on transcription from homologous regions in the viral promoter .", "target_text": { "cAMP response element": "DNA", "CRE": "DNA", "viral promoter": "DNA" } }, { "input_text": "We previously demonstrated increased HTLV-1 transcription following CD2 but not CD3 receptor cross-linking .", "target_text": {} }, { "input_text": "We hypothesized that this increased viral transcription was mediated , in part , through the phosphorylation of CREB .", "target_text": { "CREB": "protein" } }, { "input_text": "Therefore , we investigated CD2 and CD3 receptor -mediated signalling in primary human peripheral blood mononuclear cells ( PBMC ) .", "target_text": { "CD2": "protein", "CD3": "protein", "CD3 receptor": "protein", "primary human peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "CD2 , but not CD3 , cross-linking increased cAMP detected by competitive enzyme-linked immunosorbent assay ( ELISA ) approximately fourfold .", "target_text": { "CD2": "protein", "CD3": "protein" } }, { "input_text": "CD2 cross-linking concurrently increased phosphorylation of CREB detected by immunoblot assay eightfold .", "target_text": { "CD2": "protein", "CREB": "protein" } }, { "input_text": "Consistent with post-translational regulation , no change in total level of CREB protein was observed .", "target_text": { "CREB": "protein" } }, { "input_text": "Phosphorylation of CREB occurred through a herbimycin A and Rp-cAMP- sensitive pathway , suggesting phosphorylation required antecedent activation of both protein tyrosine kinases ( PTK ) and protein kinase A ( PKA ) .", "target_text": { "CREB": "protein", "protein tyrosine kinases": "protein", "PTK": "protein", "protein kinase A": "protein", "PKA": "protein" } }, { "input_text": "Both CD2 and CD3 cross-linking increased binding of nuclear proteins to a radiolabelled CRE oligonucleotide probe in electrophoretic mobility shift assays suggesting that lymphocyte activation enhances binding independently of phosphorylation of CREB at serine 133 .", "target_text": { "CD2": "protein", "CD3": "protein", "nuclear proteins": "protein", "CREB": "protein" } }, { "input_text": "These data indicate specific modulation of the CREB /ATF-1 family of transcription factors by the CD2 signalling pathway and suggest CD2 receptor modulation of CRE -mediated transcription following ligand engagement ( e.g. cell-to-cell contact ) .", "target_text": { "CREB": "protein", "CREB /ATF-1 family": "protein", "transcription factors": "protein", "CD2": "protein", "CRE": "DNA" } }, { "input_text": "X-rays -induced secretion of cellular factor ( s ) that enhance ( s ) HIV-1 promoter transcription in various non-irradiated transfected cell lines .", "target_text": { "cellular factor": "protein", "HIV-1 promoter": "DNA", "non-irradiated transfected cell lines": "cell_line" } }, { "input_text": "Various cellular stress agents like ionizing radiation exposure could activate human immunodeficiency virus type 1 ( HIV- 1 ) replication or reporter gene expression .", "target_text": { "reporter gene": "DNA" } }, { "input_text": "In addition , extracellular factor ( s ) released by X-ray-treated human colonic carcinoma cell line ( HT29 ) might activate the long terminal repeat ( LTR ) of HIV-1 in non-irradiated HT29 cells .", "target_text": { "extracellular factor": "protein", "X-ray-treated human colonic carcinoma cell line": "cell_line", "HT29": "cell_line", "long terminal repeat": "DNA", "LTR": "DNA", "non-irradiated HT29 cells": "cell_line" } }, { "input_text": "In the present report we show that in various transiently or stably transfected cell lines , X-ray irradiation up-regulates HIV-1 LTR transcription through the kappaB regulatory elements .", "target_text": { "stably transfected cell lines": "cell_line", "HIV-1 LTR": "DNA", "kappaB regulatory elements": "protein" } }, { "input_text": "A factor ( s ) , which is processed by and acts upon a variety of cell types , was detected by addition to non-irradiated cells of either X-ray -treated cells or a conditioned medium taken from irradiated cultures .", "target_text": { "non-irradiated cells": "cell_type", "X-ray -treated cells": "cell_line", "irradiated cultures": "cell_line" } }, { "input_text": "The magnitude of responsiveness is cell type dependent .", "target_text": {} }, { "input_text": "In addition , X-ray activation of HIV-1 LTR in transiently or stably transfected cell lines is inhibited by a potent antioxidant drug , pyrrolidine dithiocarbamate and by another drug , known for its role in the trapping of growth factors , suramin .", "target_text": { "HIV-1 LTR": "DNA", "cell lines": "cell_line", "growth factors": "protein" } }, { "input_text": "The importance of these observations in the pathophysiology of patients with AIDS-related cancers treated by radiotherapy remains to be established .", "target_text": {} }, { "input_text": "Activation of the human delta-globin gene promoter in primary adult erythroid cells .", "target_text": { "human delta-globin gene promoter": "DNA", "primary adult erythroid cells": "cell_type" } }, { "input_text": "Restoration of the CCAAT box or insertion of an erythroid Kruppel-like factor ( EKLF ) binding site in the delta promoter activates its expression in several erythroid cell lines .", "target_text": { "CCAAT box": "DNA", "erythroid Kruppel-like factor ( EKLF ) binding site": "DNA", "delta promoter": "DNA", "erythroid cell lines": "cell_line" } }, { "input_text": "We extended these studies using a novel primary human adult erythroid cell ( hAEC ) system to investigate these effects at the late erythroblast stage .", "target_text": { "primary human adult erythroid cell": "cell_line", "hAEC": "cell_line", "primary human adult erythroid cell ( hAEC ) system": "cell_line", "late erythroblast stage": "cell_type" } }, { "input_text": "Restoration of the CCAAT box at -70 bp , or insertion of an EKLF binding site at -85 bp or -95 bp in the promoter significantly increased delta globin gene expression in hAEC .", "target_text": { "CCAAT box": "DNA", "-70 bp": "DNA", "EKLF binding site": "DNA", "-85 bp": "DNA", "-95 bp": "DNA", "promoter": "DNA" } }, { "input_text": "Our results demonstrate that the altered CCAAT box ( CCAAC ) and the lack of an EKLF binding site in delta-globin contribute to its low level of expression in the hAEC model as well .", "target_text": { "CCAAT box": "DNA", "EKLF binding site": "DNA", "delta-globin": "protein", "hAEC model": "cell_line" } }, { "input_text": "Constitutive association of JAK1 and STAT5 in pro-B cells is dissolved by interleukin-4 -induced tyrosine phosphorylation of both proteins .", "target_text": { "JAK1": "protein", "STAT5": "protein", "pro-B cells": "cell_type", "interleukin-4": "protein" } }, { "input_text": "The bipartite human interleukin-4 ( IL-4 ) receptor was functionally expressed in murine pro-B cells and activated by human IL-4 to evoke intracellular signaling .", "target_text": { "interleukin-4": "protein", "IL-4": "protein", "bipartite human interleukin-4 ( IL-4 ) receptor": "protein", "pro-B cells": "cell_type", "murine pro-B cells": "cell_type", "human IL-4": "protein" } }, { "input_text": "Mutual association of signal transducing proteins within the receptor complex was then studied in dependence of ligand stimulation .", "target_text": { "signal transducing proteins": "protein" } }, { "input_text": "Besides ligand-induced receptor heterodimerization and contacts of the two IL-4 receptor subunits alpha and gamma with Janus kinases JAK1 and JAK3 a prominent constitutive binding between JAK1 and signal transducer and activator of transcription STAT5 was detected .", "target_text": { "Janus kinases": "protein", "JAK1": "protein", "JAK3": "protein", "signal transducer and activator of transcription": "protein", "STAT5": "protein" } }, { "input_text": "Since both these proteins become phosphorylated in response to IL-4 receptor stimulation , the influence of tyrosine phosphorylation on their mutual contact was analyzed .", "target_text": { "IL-4 receptor": "protein" } }, { "input_text": "Association of JAK1 and STAT5 was found to occur exclusively between unphosphorylated proteins .", "target_text": { "JAK1": "protein", "STAT5": "protein", "unphosphorylated proteins": "protein" } }, { "input_text": "Activation of human macrophages by mechanical ventilation in vitro .", "target_text": { "human macrophages": "cell_type" } }, { "input_text": "Positive-pressure mechanical ventilation supports gas exchange in patients with respiratory failure but is also responsible for significant lung injury .", "target_text": {} }, { "input_text": "In this study , we have developed an in vitro model in which isolated lung cells can be submitted to a prolonged cyclic pressure-stretching strain resembling that of conventional mechanical ventilation .", "target_text": { "lung cells": "cell_type", "prolonged cyclic pressure-stretching strain": "cell_line" } }, { "input_text": "In this model , cells cultured on a Silastic membrane were elongated up to 7 % of their initial diameter , corresponding to a 12 % increase in cell surface .", "target_text": {} }, { "input_text": "The lung macrophage was identified as the main cellular source for critical inflammatory mediators such as tumor necrosis factor-alpha , the chemokines interleukin ( IL ) -8 and -6 , and matrix metalloproteinase-9 in this model system of mechanical ventilation .", "target_text": { "lung macrophage": "cell_type", "inflammatory mediators": "protein", "tumor necrosis factor-alpha": "protein", "chemokines": "protein", "matrix metalloproteinase-9": "protein" } }, { "input_text": "These mediators were measured in supernatants from ventilated alveolar macrophages , monocyte-derived macrophages , and promonocytic THP-1 cells .", "target_text": { "ventilated alveolar macrophages": "cell_type", "monocyte-derived macrophages": "cell_type", "promonocytic THP-1 cells": "cell_line" } }, { "input_text": "Nuclear factor-kappaB was found to be activated in ventilated macrophages .", "target_text": { "Nuclear factor-kappaB": "protein", "ventilated macrophages": "cell_type" } }, { "input_text": "Synergistic proinflammatory effects of mechanical stress and molecules such as bacterial endotoxin were observed , suggesting that mechanical ventilation might be particularly deleterious in preinjured or infected lungs .", "target_text": { "bacterial endotoxin": "protein" } }, { "input_text": "Dexamethasone prevented IL-8 and tumor necrosis factor-alpha secretion in ventilated macrophages .", "target_text": { "IL-8": "protein", "tumor necrosis factor-alpha": "protein", "ventilated macrophages": "cell_type" } }, { "input_text": "Mechanical ventilation induced low levels of IL-8 secretion by alveolar type II-like cells .", "target_text": { "IL-8": "protein", "alveolar type II-like cells": "cell_type" } }, { "input_text": "Other lung cell types such as endothelial cells , bronchial cells , and fibroblasts failed to produce IL-8 in response to a prolonged cyclic pressure-stretching load .", "target_text": { "endothelial cells": "cell_type", "bronchial cells": "cell_type", "fibroblasts": "cell_type", "IL-8": "protein" } }, { "input_text": "This model is of particular value for exploring physical stress-induced signaling pathways , as well as for testing the effects of novel ventilatory strategies or adjunctive substances aimed at modulating cell activation induced by mechanical ventilation .", "target_text": {} }, { "input_text": "Signaling pathways mediated by the TNF- and cytokine- receptor families target a common cis-element of the IFN regulatory factor 1 promoter .", "target_text": { "cis-element": "DNA", "IFN regulatory factor 1 promoter": "DNA" } }, { "input_text": "CD40 activation of B cells is strongly influenced by the presence of cytokines .", "target_text": { "CD40": "protein", "B cells": "cell_type", "cytokines": "protein" } }, { "input_text": "However , the molecular basis for the interplay between these distinct stimuli is not clearly delineated .", "target_text": {} }, { "input_text": "IFN regulatory factor 1 ( IRF-1 ) is a transcription factor activated by either CD40 or cytokines .", "target_text": { "IFN regulatory factor 1": "protein", "IRF-1": "protein", "transcription factor": "protein", "CD40": "protein", "cytokines": "protein" } }, { "input_text": "We have found that these different sets of signals target a common cis-acting element in the promoter of this gene , the IRF-1 gamma -activated site ( GAS ) .", "target_text": { "IRF-1": "protein", "IRF-1 gamma": "protein", "IRF-1 gamma -activated site": "DNA", "GAS": "DNA" } }, { "input_text": "Targeting of the IRF-1 GAS is not confined to activation via CD40 but extends to other stimuli that mimic the CD40 signaling cascade , like TNF-alpha and EBV .", "target_text": { "IRF-1 GAS": "DNA", "CD40": "protein", "TNF-alpha": "protein" } }, { "input_text": "In contrast to induction of STATs by cytokines , the IRF-1 GAS -binding complex activated by CD40 , TNF-alpha , or EBV contains Rel proteins , specifically p50 and p65 .", "target_text": { "STATs": "protein", "cytokines": "protein", "IRF-1 GAS": "DNA", "CD40": "protein", "TNF-alpha": "protein", "Rel proteins": "protein", "p50": "protein", "p65": "protein" } }, { "input_text": "In this system , simultaneous exposure to CD40L together with either IL-4 or IFN-gamma does not lead to the activation of novel Rel/STAT complexes .", "target_text": { "CD40L": "protein", "IL-4": "protein", "IFN-gamma": "protein", "Rel/STAT complexes": "protein" } }, { "input_text": "Given the importance of IRF-1 in a variety of biologic functions from proliferation to apoptosis , our findings support the notion that modulation of IRF-1 levels may be a critical control point in B cell activation .", "target_text": { "IRF-1": "protein" } }, { "input_text": "Differential effects of protein kinase C inhibitors on fibronectin -induced interleukin-beta gene transcription , protein synthesis and secretion in human monocytic cells .", "target_text": { "protein kinase C": "protein", "fibronectin": "protein", "interleukin-beta": "protein", "interleukin-beta gene": "DNA", "monocytic cells": "cell_type", "human monocytic cells": "cell_type" } }, { "input_text": "Human monocytic cells express interleukin-1beta ( IL-1beta ) when stimulated with the extracellular matrix glycoprotein , fibronectin ( FN ) .", "target_text": { "Human monocytic cells": "cell_type", "interleukin-1beta": "protein", "IL-1beta": "protein", "extracellular matrix glycoprotein": "protein", "fibronectin": "protein", "FN": "protein" } }, { "input_text": "Protein kinase C ( PKC ) activation is considered important for this process ; however , the metabolic steps at which PKC acts upon to mediate the FN -induced IL-1beta response remain unclear .", "target_text": { "Protein kinase C": "protein", "PKC": "protein", "FN": "protein", "IL-1beta": "protein" } }, { "input_text": "We performed an analysis of the mechanisms by which two PKC inhibitors , Calphostin C and Staurosporine , prevent the FN -induced IL-1beta response .", "target_text": { "PKC": "protein", "FN": "protein", "IL-1beta": "protein" } }, { "input_text": "Both inhibitors blocked the secretion of IL-1beta protein into the media of peripheral blood mononuclear cells exposed to FN .", "target_text": { "IL-1beta": "protein", "IL-1beta protein": "protein", "peripheral blood mononuclear cells": "cell_type", "FN": "protein" } }, { "input_text": "Immunoprecipitation analysis revealed that unde3r these circumstances , Calphostin C inhibited the production of IL-1beta protein , whereas Staurosporine allowed protein production , but inhibited its secretion .", "target_text": { "IL-1beta": "protein", "IL-1beta protein": "protein" } }, { "input_text": "To determine the mechanisms responsible for these differences , we turned to human U937 promonocytic cells .", "target_text": { "human U937 promonocytic cells": "cell_line" } }, { "input_text": "U937 cells transfected with the human full-length IL-1beta promoter connected to a luciferase reporter gene were submitted to transcription assays , Northern blotting , and DNA electrophoresis mobility gel shift assays .", "target_text": { "IL-1beta": "protein", "full-length IL-1beta promoter": "DNA", "luciferase": "protein", "luciferase reporter gene": "DNA" } }, { "input_text": "These studies revealed that Calphostin C inhibited the nuclear translocation of the transcription factor activator protein-1 ( AP-1 ) which is considered necessary for FN induction of IL-1beta gene transcription , and prevented the transcription of the IL-1beta gene .", "target_text": { "transcription factor": "protein", "transcription factor activator protein-1": "protein", "AP-1": "protein", "FN": "protein", "IL-1beta": "protein", "IL-1beta gene": "DNA" } }, { "input_text": "In contrast , Staurosporine alone induced AP-1 translocation and stimulation of the gene .", "target_text": { "AP-1": "protein" } }, { "input_text": "Overall , our data indicate that Calphostin C prevents the transcription of the IL-1beta gene thereby inhibiting protein synthesis .", "target_text": { "IL-1beta gene": "DNA" } }, { "input_text": "Based on the high specificity of this compound for PKC , we conclude that PKC is necessary for FN -induced IL-1beta protein production .", "target_text": { "PKC": "protein", "FN": "protein", "IL-1beta": "protein" } }, { "input_text": "In contrast , Staurosporine prevented secretion of IL-1beta by unknown mechanisms", "target_text": { "IL-1beta": "protein" } }, { "input_text": "The carboxyl-terminal cytoplasmic domain of CD36 is required for oxidized low-density lipoprotein modulation of NF-kappaB activity by tumor necrosis factor-alpha .", "target_text": { "carboxyl-terminal cytoplasmic domain": "protein", "CD36": "protein", "NF-kappaB": "protein", "tumor necrosis factor-alpha": "protein" } }, { "input_text": "The binding of oxidized low-density lipoprotein ( Ox LDL ) by monocyte -macrophages causes pleiotropic effects , including changes in gene expression , and is thought to represent an early event in atherogenesis .", "target_text": { "monocyte": "cell_type", "-macrophages": "cell_type" } }, { "input_text": "The integral membrane glycoprotein CD36 appears to play a physiological role in binding and uptake of Ox LDL by monocyte- macrophages , although the molecular events associated with CD36 -Ox LDL interaction are unknown .", "target_text": { "CD36": "protein", "glycoprotein CD36": "protein", "macrophages": "cell_type", "monocyte- macrophages": "cell_type" } }, { "input_text": "To approach this issue , we used CD36 transfected Chinese hampster ovary ( CHO ) cells , exposed them to Ox LDL , and determined changes in the activity of the transcription factor NF-kappaB .", "target_text": { "CD36": "protein", "Chinese hampster ovary ( CHO ) cells": "cell_type", "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "We report here that Ox LDL enhanced DNA binding activity of nuclear extracts to an NF-kappaB sequence following activation of CD36 -producing CHO cells with the proinflammatory cytokine tumor necrosis factor-alpha ( TNF-alpha ) .", "target_text": { "NF-kappaB": "protein", "NF-kappaB sequence": "DNA", "CD36": "protein", "CD36 -producing CHO cells": "cell_line", "proinflammatory cytokine": "protein", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "This enhanced DNA binding activity was inhibited by coincubation of CD36 transfected cells with the human CD36 -specific antibody OKM5 .", "target_text": { "CD36": "protein", "human CD36 -specific antibody": "protein", "OKM5": "protein" } }, { "input_text": "We also determined that activation of NF-kappaB DNA binding activity required an intact carboxyl-terminal cytoplasmic segment on CD36 .", "target_text": { "NF-kappaB": "protein", "carboxyl-terminal cytoplasmic segment": "protein", "CD36": "protein" } }, { "input_text": "Our results support the idea that human CD36 mediates signal transduction events in response to Ox LDL .", "target_text": { "CD36": "protein", "human CD36": "protein" } }, { "input_text": "TRAMP , a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas ( Apo-1/CD95 ) .", "target_text": { "TRAMP": "protein", "apoptosis-mediating receptor": "protein", "tumor necrosis factor receptor 1": "protein", "Fas": "protein", "Apo-1/CD95": "protein" } }, { "input_text": "A novel member of the tumor necrosis factor ( TNF ) receptor family , designated TRAMP , has been identified .", "target_text": { "tumor necrosis factor ( TNF ) receptor family": "protein", "TRAMP": "protein" } }, { "input_text": "The structural organization of the 393 amino acid long human TRAMP is most homologous to TNF receptor 1 .", "target_text": { "TRAMP": "protein", "393 amino acid long human TRAMP": "protein", "TNF receptor 1": "protein" } }, { "input_text": "TRAMP is abundantly expressed on thymocytes and lymphocytes .", "target_text": { "TRAMP": "protein", "thymocytes": "cell_type", "lymphocytes": "cell_type" } }, { "input_text": "Its extracellular domain is composed of four cysteine-rich domains , and the cytoplasmic region contains a death domain known to signal apoptosis .", "target_text": { "cysteine-rich domains": "protein", "cytoplasmic region": "protein", "death domain": "protein" } }, { "input_text": "Overexpression of TRAMP leads to two major responses , NF-kappaB activation and apoptosis .", "target_text": { "TRAMP": "protein", "NF-kappaB": "protein" } }, { "input_text": "TRAMP -induced cell death is inhibited by an inhibitor of ICE-like proteases , but not by Bcl-2 .", "target_text": { "TRAMP": "protein", "ICE-like proteases": "protein", "Bcl-2": "protein" } }, { "input_text": "In addition , TRAMP does not appear to interact with any of the known apoptosis -inducing ligands of the TNF family .", "target_text": { "TRAMP": "protein", "apoptosis -inducing ligands": "protein", "TNF family": "protein" } }, { "input_text": "The state of maturation of monocytes into macrophages determines the effects of IL-4 and IL-13 on HIV replication .", "target_text": { "monocytes": "cell_type", "macrophages": "cell_type", "IL-4": "protein", "IL-13": "protein" } }, { "input_text": "The molecular mechanisms of the effects of IL-4 and IL-13 on HIV infection in human monocytes as they matured into monocyte-derived macrophages over 7 days were investigated using HIV-1 ( BaL ) , and low passage clinical strains .", "target_text": { "IL-4": "protein", "IL-13": "protein", "human monocytes": "cell_type", "monocyte-derived macrophages": "cell_type" } }, { "input_text": "IL-4 and IL-13 up-regulated the expression of both genomic and spliced HIV mRNA in monocytes cultured on Teflon , as determined by Northern analysis and p24 Ag assay .", "target_text": { "IL-4": "protein", "IL-13": "protein", "HIV mRNA": "RNA", "monocytes": "cell_type", "p24 Ag": "protein" } }, { "input_text": "Using a nuclear run-on assay , IL-4 stimulation was shown to enhance transcription by two- to threefold .", "target_text": { "IL-4": "protein" } }, { "input_text": "IL-4 stimulated nuclear factor-kappaB nuclear translocation and binding before enhancement of HIV RNA expression .", "target_text": { "IL-4": "protein", "nuclear factor-kappaB": "protein", "HIV RNA": "RNA" } }, { "input_text": "Conversely , IL-4 and IL-13 markedly and significantly inhibited HIV replication at the transcriptional level in monocyte-derived macrophages , and this occurred whether these cytokines were added before or after HIV infection .", "target_text": { "IL-4": "protein", "IL-13": "protein", "monocyte-derived macrophages": "cell_type", "cytokines": "protein" } }, { "input_text": "The reversal from stimulation to inhibition occurred after 3 to 5 days of adherence to plastic .", "target_text": {} }, { "input_text": "IL-4 had no significant effect on HIV reverse transcription .", "target_text": { "IL-4": "protein" } }, { "input_text": "The effect of both cytokines on the monocyte maturation/differentiation ( CD11b , CD13 , and CD26 ) and other macrophage markers ( CD14 and CD68 ) was examined .", "target_text": { "cytokines": "protein", "CD11b": "protein", "CD13": "protein", "CD26": "protein", "macrophage markers": "protein", "CD14": "protein", "CD68": "protein" } }, { "input_text": "IL-4 enhanced CD11b , but inhibited CD26 expression and delayed CD13 loss .", "target_text": { "IL-4": "protein", "CD11b": "protein", "CD26": "protein", "CD13": "protein" } }, { "input_text": "IL-13 had similar effects on CD11b and CD13 , but no effect on CD26 .", "target_text": { "IL-13": "protein", "CD11b": "protein", "CD13": "protein", "CD26": "protein" } }, { "input_text": "Hence , these cytokines do not simply enhance monocyte differentiation , but have complex and slightly divergent effects that impact on HIV replication probably through cell signaling pathways and nuclear factor-kappaB translocation .", "target_text": { "cytokines": "protein", "nuclear factor-kappaB": "protein" } }, { "input_text": "Mice lacking the transcription factor CIITA -- a second look .", "target_text": { "transcription factor": "protein", "CIITA": "protein" } }, { "input_text": "We have generated a second line of mice lacking a transcription factor thought to be a critical regulator of MHC class II gene expression , CIITA ( for class II transactivator ) .", "target_text": { "transcription factor": "protein", "MHC class II gene": "DNA", "CIITA": "protein", "transactivator": "protein" } }, { "input_text": "Our and the previously published lines differ in the deletion that was engineered and by the fact that we removed the neomycin-resistance promoter and structural gene via the cre-loxP recombination system .", "target_text": { "neomycin-resistance promoter": "DNA", "structural gene": "DNA" } }, { "input_text": "Characterization of our line led to two new findings .", "target_text": {} }, { "input_text": "First , a substantial number of cells can express class II molecules in the absence of CIITA , albeit at 5-fold reduced levels , most notably dendritic cells in s.c. lymph nodes ; therefore , the CIITA gene can not be an absolute ' master gene ' controlling the expression of class II molecules , as had been thought .", "target_text": { "class II molecules": "protein", "CIITA": "protein", "dendritic cells": "cell_type", "CIITA gene": "DNA", "master gene": "DNA" } }, { "input_text": "Second , in contrast to recent results on human cell lines , CIITA is not critically involved in the IFN-gamma -induced up-regulation of MHC class I genes .", "target_text": { "human cell lines": "cell_line", "CIITA": "protein", "IFN-gamma": "protein", "MHC class I genes": "DNA" } }, { "input_text": "Interleukin-10 stabilizes inhibitory kappaB-alpha in human monocytes .", "target_text": { "Interleukin-10": "protein", "kappaB-alpha": "protein", "human monocytes": "cell_type" } }, { "input_text": "Interleukin-10 ( IL-10 ) protects animals from lethal endotoxemia .", "target_text": { "Interleukin-10": "protein", "IL-10": "protein" } }, { "input_text": "This beneficial effect is mediated , in part , by inhibition of inflammatory cytokine production , including tumor necrosis factor-alpha ( TNF-alpha ) .", "target_text": { "inflammatory cytokine": "protein", "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "Evidence suggests that IL-10 may inhibit activation of the transcription factor nuclear factor-kappaB ( NF-kappaB ) through an unknown mechanism .", "target_text": { "IL-10": "protein", "transcription factor": "protein", "nuclear factor-kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "NF-kappaB activation in response to inflammatory signals is dependent upon degradation of its associated inhibitory peptide , inhibitory kappaB-alpha ( IkappaB-alpha ) .", "target_text": { "NF-kappaB": "protein", "inhibitory kappaB-alpha": "protein", "IkappaB-alpha": "protein" } }, { "input_text": "We hypothesized that IL-10 prevents human monocyte NF-kappaB activation and resultant TNF-alpha production by stabilization of IkappaB-alpha .", "target_text": { "IL-10": "protein", "NF-kappaB": "protein", "TNF-alpha": "protein", "IkappaB-alpha": "protein" } }, { "input_text": "The purpose of this study was to determine the effect of IL-10 on lipopolysaccharide ( LPS ) -induced human monocyte TNF-alpha production , NF-kappaB activation , and IkappaB-alpha degradation .", "target_text": { "IL-10": "protein", "TNF-alpha": "protein", "NF-kappaB": "protein", "IkappaB-alpha": "protein" } }, { "input_text": "Monocytes were isolated from human donors .", "target_text": {} }, { "input_text": "Cells were stimulated with endotoxin ( LPS , 100 ng/mL ) with and without human IL-10 ( 10 ng/mL ) .", "target_text": { "endotoxin": "protein", "IL-10": "protein" } }, { "input_text": "Following stimulation , TNF-alpha was measured in cell supernatants by ELISA , NF-kappaB activity by electrophoretic mobility shift assay , and IkappaB-alpha levels by Western blot .", "target_text": { "TNF-alpha": "protein", "NF-kappaB": "protein", "IkappaB-alpha": "protein" } }, { "input_text": "We observed that after LPS stimulation of human monocytes , TNF-alpha increased to 798+/-67 pg/mL ( p < .001 versus control ) .", "target_text": { "human monocytes": "cell_type", "TNF-alpha": "protein" } }, { "input_text": "IL-10 attenuated LPS -stimulated TNF-alpha production ( 297+/-54 ; p < .001 versus LPS alone ) .", "target_text": { "IL-10": "protein", "TNF-alpha": "protein" } }, { "input_text": "After LPS stimulation in human monocytes , IkappaB-alpha protein levels decreased , and NF-kappaB DNA binding increased .", "target_text": { "human monocytes": "cell_type", "IkappaB-alpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "IL-10 pretreatment prevented LPS -induced decreases in IkappaB-alpha protein levels and attenuated NF-kappaB DNA binding .", "target_text": { "IL-10": "protein", "IkappaB-alpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "IL-10 appears to prevent activation of NF-kappaB by preserving IkappaB-alpha protein levels , leading to a reduction in TNF-alpha release .", "target_text": { "IL-10": "protein", "NF-kappaB": "protein", "IkappaB-alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "Down-regulation of human granzyme B expression by glucocorticoids .", "target_text": { "granzyme B": "protein" } }, { "input_text": "Dexamethasone inhibits binding to the Ikaros and AP-1 regulatory elements of the granzyme B promoter .", "target_text": { "Ikaros": "protein", "AP-1 regulatory elements": "DNA", "granzyme B promoter": "DNA" } }, { "input_text": "The serine protease granzyme B is an essential component of the granule exocytosis pathway , a major apoptotic mechanism used by cytotoxic T lymphocytes and natural killer cells to induce target cell apoptosis .", "target_text": { "serine protease granzyme B": "protein", "lymphocytes": "cell_type", "cytotoxic T lymphocytes": "cell_type", "natural killer cells": "cell_type" } }, { "input_text": "Granzyme B gene transcription is induced in activated lymphocytes upon antigenic stimulation , and several regulatory regions including CBF , AP-1 , and Ikaros binding sites have been shown to be essential in the control of granzyme B promoter activation .", "target_text": { "lymphocytes": "cell_type", "regulatory regions": "DNA", "CBF": "protein", "AP-1": "protein", "Ikaros": "protein", "Ikaros binding sites": "DNA", "granzyme B promoter": "DNA" } }, { "input_text": "Dexamethasone , a glucocorticoid that is widely used as an immunomodulatory and anti-inflammatory agent , inhibits granzyme B mRNA transcript in phytohemagglutinin -activated peripheral blood mononuclear cells .", "target_text": { "granzyme B mRNA transcript": "RNA", "phytohemagglutinin": "protein", "phytohemagglutinin -activated peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Transfection of a reporter construct containing the -148 to +60 region of the human granzyme B promoter demonstrated that this region was the target for dexamethasone repression .", "target_text": { "-148 to +60 region": "DNA", "granzyme B promoter": "DNA" } }, { "input_text": "Mutation of Ikaros or AP-1 binding sites in the context of the granzyme B promoter demonstrated that both sites participate in dexamethasone -mediated inhibition of the granzyme B promoter activity .", "target_text": { "Ikaros": "protein", "AP-1 binding sites": "DNA", "granzyme B promoter": "DNA" } }, { "input_text": "Electromobility shift assay revealed that dexamethasone abolished the binding of nuclear transcription factors to the Ikaros binding site and reduced AP-1 binding activity .", "target_text": { "nuclear transcription factors": "protein", "Ikaros": "protein", "Ikaros binding site": "DNA", "AP-1": "protein" } }, { "input_text": "These results indicate that dexamethasone is able to abrogate the transcriptional activity of the human granzyme B gene promoter by inhibiting the binding of nuclear factors at the AP-1 and Ikaros sites .", "target_text": { "human granzyme B gene promoter": "DNA", "nuclear factors": "protein" } }, { "input_text": "Glucocorticoid receptors on mononuclear leukocytes in polycystic ovary syndrome .", "target_text": { "Glucocorticoid receptors": "protein", "mononuclear leukocytes": "cell_type" } }, { "input_text": "OBJECTIVE : Many studies have suggested that there is a possible hormonal dysregulation of hypothalamic-pituitary-adrenal ( HPA ) axis and an increased cortisol clearance in patients with polycystic ovary syndrome ( PCOS ) .", "target_text": {} }, { "input_text": "Therefore in this study , we have examined the role of glucocorticoid receptor/s ( GR ) characteristics in the developing of these abnormalities in patients with PCOS .", "target_text": { "glucocorticoid receptor/s": "protein", "GR": "protein" } }, { "input_text": "METHOD : For this purpose , the number and affinity of GR in peripheral mononuclear leukocytes ( MNL ) of 10 patients with PCOS and 10 healthy women ( controls ) were determined .", "target_text": { "GR": "protein", "mononuclear leukocytes": "cell_type" } }, { "input_text": "RESULTS : There were no significant differences in the number ( 6500+/-1001 sites/cell and 6352+/-1697 sites/cell , respectively ; P > 0.05 ) and affinity ( 3.93+/-0.89 nM and 4.49+/-0.71 nM , respectively ; P > 0.05 ) of GR between the PCOS patients and the controls .", "target_text": { "GR": "protein" } }, { "input_text": "CONCLUSIONS : These results suggest that the alterations in the HPA axis and in the cortisol metabolism observed in PCOS are not related to GR deficiency .", "target_text": { "GR": "protein" } }, { "input_text": "Heterogeneous expression of the lipocalin NGAL in primary breast cancers .", "target_text": { "lipocalin NGAL": "protein" } }, { "input_text": "We have previously shown that neu oncogene-initiated rat mammary carcinomas uniquely over-express neu-related lipocalin ( NRL ) , a member of the calycin protein superfamily .", "target_text": { "neu-related lipocalin": "protein", "NRL": "protein", "calycin protein superfamily": "protein" } }, { "input_text": "Here , we characterize the putative human homolog of NRL , neutrophil gelatinase-associated lipocalin ( NGAL ) .", "target_text": { "putative human homolog": "protein", "NRL": "protein", "neutrophil gelatinase-associated lipocalin": "protein", "NGAL": "protein" } }, { "input_text": "ngal gene expression was found at moderate levels in only 2 of 17 human tissues examined , breast and lung .", "target_text": {} }, { "input_text": "When breast cancers were examined for NGAL mRNA and protein levels , they were found to exhibit heterogeneous expression .", "target_text": {} }, { "input_text": "NGAL levels varied in these tumors from undetectable to exceeding those in normal breast parenchyma .", "target_text": { "NGAL": "protein" } }, { "input_text": "Immuno-histochemical analysis confirmed the presence of NGAL within breast carcinoma cells but detected only low levels of this protein in normal ductal epithelium .", "target_text": { "NGAL": "protein", "breast carcinoma cells": "cell_type" } }, { "input_text": "In contrast , large amounts of the protein were localized to the lumen of normal breast ducts in the vicinity of NGAL -expressing tumors .", "target_text": { "NGAL": "protein" } }, { "input_text": "Interestingly , unlike NRL in rat mammary carcinomas , no significant association between NGAL expression and HER-2/neu activation was found in human breast tumors .", "target_text": { "NRL": "protein", "NGAL": "protein", "HER-2/neu": "protein" } }, { "input_text": "In contrast , a significant correlation between NGAL expression in breast cancer was found with several other markers of poor prognosis , including estrogen and progesterone receptor -negative status and high proliferation ( S-phase fraction ) .", "target_text": { "NGAL": "protein", "progesterone receptor": "protein" } }, { "input_text": "NGAL levels were stratified as high or low in breast cancers from a cohort of node-positive patients with known outcome .", "target_text": { "NGAL": "protein" } }, { "input_text": "No significant association between NGAL expression and disease-free or overall survival was observed .", "target_text": { "NGAL": "protein" } }, { "input_text": "BASH , a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius .", "target_text": { "BASH": "protein", "novel signaling molecule": "protein", "B cells": "cell_type" } }, { "input_text": "The bursa of Fabricius is a gut-associated lymphoid organ that is essential for the generation of a diversified B cell repertoire in the chicken .", "target_text": { "B cell repertoire": "cell_type" } }, { "input_text": "We describe here a novel gene preferentially expressed in bursal B cells .", "target_text": { "B cells": "cell_type", "bursal B cells": "cell_type" } }, { "input_text": "The gene encodes an 85-kDa protein , designated BASH ( B cell adaptor containing SH2 domain ) , that contains N-terminal acidic domains with SH2 domain-binding phosphotyrosine-based motifs , a proline -rich domain , and a C-terminal SH2 domain .", "target_text": { "85-kDa protein": "protein", "BASH": "protein", "B cell adaptor containing SH2 domain": "protein", "N-terminal acidic domains": "protein", "SH2 domain-binding phosphotyrosine-based motifs": "protein", "proline -rich domain": "protein", "C-terminal SH2 domain": "protein" } }, { "input_text": "BASH shows a substantial sequence similarity to SLP-76 , an adaptor protein functioning in TCR -signal transduction .", "target_text": { "BASH": "protein", "SLP-76": "protein", "TCR": "protein" } }, { "input_text": "BASH becomes tyrosine -phosphorylated with the B cell Ag receptor ( BCR ) cross-link or by coexpression with Syk and Lyn and associates with signaling molecules including Syk and a putative chicken Shc homologue .", "target_text": { "BASH": "protein", "B cell Ag receptor": "protein", "BCR": "protein", "Syk": "protein", "Lyn": "protein", "signaling molecules": "protein", "putative chicken Shc homologue": "protein" } }, { "input_text": "Overexpression of BASH results in suppression of the NF-AT activation induced by BCR -cross-linking .", "target_text": { "BASH": "protein", "NF-AT": "protein", "BCR": "protein" } }, { "input_text": "These findings suggest that BASH is involved in BCR -mediated signal transduction and could play a critical role in B cell development in the bursa .", "target_text": { "BASH": "protein", "BCR": "protein" } }, { "input_text": "Granulocyte colony-stimulating factor activates a 72-kDa isoform of STAT3 in human neutrophils .", "target_text": { "Granulocyte colony-stimulating factor": "protein", "72-kDa isoform": "protein", "STAT3": "protein", "human neutrophils": "cell_type" } }, { "input_text": "Granulocyte colony-stimulating factor ( G-CSF ) signaling involves activation of STATs , proteins that serve the dual function of signal transduction and activation of transcription .", "target_text": { "Granulocyte colony-stimulating factor": "protein", "G-CSF": "protein", "STATs": "protein" } }, { "input_text": "We previously demonstrated that G-CSF activated a distinct Stat3-like protein in immature and mature normal myeloid cells , StatG .", "target_text": { "G-CSF": "protein", "Stat3-like protein": "protein", "StatG": "protein" } }, { "input_text": "StatG in normal immature human myeloid cells , i.e. adult CD34+ bone marrow cells , was composed of Stat3beta .", "target_text": { "StatG": "protein", "normal immature human myeloid cells": "cell_type", "adult CD34+ bone marrow cells": "cell_type", "Stat3beta": "protein" } }, { "input_text": "This investigation was undertaken to determine the composition of StatG in mature normal human myeloid cells , i.e. polymorphonuclear neutrophilic granulocytes ( PMN ) .", "target_text": { "StatG": "protein", "mature normal human myeloid cells": "cell_type", "polymorphonuclear neutrophilic granulocytes": "cell_type", "PMN": "cell_type" } }, { "input_text": "These studies revealed that the major protein in extracts of PMN activated by G-CSF to bind the high-affinity serum-inducible element ( hSIE ) is a 72-kDa protein that cross-reacts with Stat3 monoclonal antibody , which we have designated Stat3gamma .", "target_text": { "major protein": "protein", "PMN": "cell_type", "G-CSF": "protein", "high-affinity serum-inducible element": "DNA", "hSIE": "DNA", "72-kDa protein": "protein", "Stat3 monoclonal antibody": "protein", "Stat3gamma": "protein" } }, { "input_text": "Stat3gamma is derived from Stat3alpha by limited proteolysis and lacks the carboxyl-terminal portion of Stat3alpha .", "target_text": { "Stat3gamma": "protein", "Stat3alpha": "protein", "carboxyl-terminal portion": "protein" } }, { "input_text": "Because this region of Stat3alpha is involved in transcriptional activation , our findings suggest the possibility that Stat3gamma may be transcriptionally inactive and may compete with Stat3alpha for Stat3 binding sites in these terminally differentiated myeloid cells", "target_text": { "Stat3alpha": "protein", "Stat3gamma": "protein", "Stat3": "protein", "Stat3 binding sites": "DNA", "terminally differentiated myeloid cells": "cell_type" } }, { "input_text": "Association between expression of intercellular adhesion molecule-1 and integration of human T-cell-leukemia virus type 1 in adult T-cell leukemia cells .", "target_text": { "intercellular adhesion molecule-1": "protein", "adult T-cell leukemia cells": "cell_type" } }, { "input_text": "It is known that the expression levels of intercellular adhesion molecule-1 ( ICAM-1 ) in adult T cell leukemia ( ATL ) cells are high , whereas those in T-lymphoid cells are not .", "target_text": { "intercellular adhesion molecule-1": "protein", "ICAM-1": "protein", "adult T cell leukemia ( ATL ) cells": "cell_type", "T-lymphoid cells": "cell_type" } }, { "input_text": "In order to investigate the factors that influence the induction of ICAM-1 molecules , Northern blot analysis to measure the expression level of ICAM-1 mRNAs and Southern blot hybridization to analyze the integration of human T-cell-leukemia virus type 1 ( HTLV-1 ) provirus were done .", "target_text": { "ICAM-1": "protein", "ICAM-1 mRNAs": "RNA" } }, { "input_text": "The levels of ICAM-1 mRNA expression of ATL cells were generally higher than those of T-lymphoid cells .", "target_text": { "ICAM-1": "protein", "ICAM-1 mRNA": "RNA", "ATL cells": "cell_line", "T-lymphoid cells": "cell_type" } }, { "input_text": "However , ILT-mat cells and ATL16T(-) cells , although they were ATL cells , showed rather low surface ICAM-1 expression and ICAM-1 mRNA expression .", "target_text": { "ILT-mat cells": "cell_line", "ATL16T(-) cells": "cell_line", "ATL cells": "cell_line", "ICAM-1": "protein", "ICAM-1 mRNA": "RNA" } }, { "input_text": "Southern blot hybridization showed that only two and four bands were found in ILT-mat and ATL16T(-) cells , respectively , whereas > 10 bands were detected in other ATL cells .", "target_text": { "ILT-mat": "cell_line", "ATL16T(-) cells": "cell_line", "ATL cells": "cell_line" } }, { "input_text": "These results suggest that monoclonal integration of HTLV-1 provirus to the genome of T cell , especially the number of integration sites , is one of the factors for induction of ICAM-1 molecules .", "target_text": { "T cell": "cell_type", "ICAM-1": "protein", "ICAM-1 molecules": "protein" } }, { "input_text": "Heat-shock and cadmium chloride increase the vimentin mRNA and protein levels in U-937 human promonocytic cells .", "target_text": { "Heat-shock": "protein", "U-937 human promonocytic cells": "cell_line" } }, { "input_text": "Heat-shock for 2 hours at 42 degrees C , or the administration for 3 hours of 100 or 150 microM cadmium chloride , inhibited the subsequent proliferation activity , induced the expression of functional differentiation markers , and caused an increase in the amount of the stress-responsive HSP70 protein in U-937 human promonocytic cells .", "target_text": { "Heat-shock": "protein", "subsequent proliferation activity": "cell_line", "differentiation markers": "protein", "stress-responsive HSP70 protein": "protein", "U-937 human promonocytic cells": "cell_line" } }, { "input_text": "In addition , both heat and cadmium produced an increase in the amount of the intermediate filament protein vimentin , as determined by immunoblot and immunofluorescence assays .", "target_text": { "intermediate filament protein": "protein", "vimentin": "protein" } }, { "input_text": "By contrast , the amounts of actin and beta-tubulin were not significantly altered .", "target_text": { "actin": "protein", "beta-tubulin": "protein" } }, { "input_text": "The amount of vimentin mRNA was also increased during recovery from stress , indicating that vimentin expression was not exclusively regulated at the protein level .", "target_text": { "vimentin": "protein", "vimentin mRNA": "RNA" } }, { "input_text": "Although cadmium caused an early , transient stimulation of c-jun and c-fos expression and AP-1 binding activity , heat-shock failed to alter both protooncogene expression and transcription factor binding , indicating that the stress-induced vimentin increase was not the result of AP-1 -mediated transcriptional activation .", "target_text": { "c-jun": "DNA", "c-fos": "DNA", "AP-1": "protein", "protooncogene": "DNA", "vimentin": "protein" } }, { "input_text": "Finally , it was observed that the rate of decay of vimentin mRNA upon actinomycin D administration was decreased in heat- and cadmium- pretreated cells in comparison to untreated cells .", "target_text": { "vimentin": "protein", "vimentin mRNA": "RNA", "untreated cells": "cell_type" } }, { "input_text": "These results indicate that stress treatments cause an increase in vimentin levels in promonocytic cells , which may be explained at least in part by transcript stabilization .", "target_text": { "vimentin": "protein", "promonocytic cells": "cell_type" } }, { "input_text": "Ovarian and breast cytotoxic T lymphocytes can recognize peptides from the amino enhancer of split protein of the Notch complex .", "target_text": { "cytotoxic T lymphocytes": "cell_type", "Notch complex": "protein" } }, { "input_text": "In this study we investigated recognition by ovarian tumor associated lymphocyte ( OVTAL ) , and breast tumor associated lymphocytes ( BRTAL ) , of peptides corresponding to the sequence 125-135 of the Aminoenhancer of split ( AES ) protein .", "target_text": { "ovarian tumor associated lymphocyte": "cell_type", "OVTAL": "cell_type", "breast tumor associated lymphocytes": "cell_type", "BRTAL": "cell_type", "125-135 of the Aminoenhancer of split ( AES ) protein": "protein" } }, { "input_text": "Three of these peptides designated as G75:AES1/2 ( 128-135 ) , G60: AES1/2 ( 127-137 ) and G61: AES1/2 ( 125-133 ) correspond to the wildtype AES sequence , while the fourth G76:GPLTPLPV , AES1/2 ( 128-135 ) corresponds to a variant sequence of the peptide G75 with the N-terminal Leu substituted to glycine .", "target_text": { "128-135": "protein", "127-137": "protein", "125-133": "protein", "wildtype AES sequence": "DNA", "AES1/2 ( 128-135 )": "protein" } }, { "input_text": "These sequences were chosen for study because mass-spectrometric analysis ( MS ) of a CTL active HPLC peptide fraction eluted from immunoaffinity precipitated HLA-A2 molecule , revealed : ( a ) the presence of an ion with a mass-to-charge ratio ( m/z ) of 793 which was more abundant than other ions of similar masses ; ( b ) the tentatively reconstituted sequence of the ion 793 matched the sequence of peptide G76 .", "target_text": { "CTL": "cell_type", "immunoaffinity precipitated HLA-A2 molecule": "protein" } }, { "input_text": "We found that AES peptides G75 ( 128-135 ) and G76 ( 128-135 ) ( L128G ) reconstituted CTL recognition at concentrations ranging between 200-500 nM .", "target_text": { "128-135": "protein" } }, { "input_text": "These concentrations are lower than concentrations reported to activate effector function of CTL recognizing other epithelial tumor Ag .", "target_text": { "epithelial tumor Ag": "protein" } }, { "input_text": "Furthermore , analysis with cloned CD8+ T cells indicated that G75 and G76 were not cross-reactive specificities , suggesting a key role for the N-terminal residues of the variant peptide in dictating specificities .", "target_text": { "CD8+ T cells": "cell_type", "N-terminal residues": "protein" } }, { "input_text": "Since the AES proteins are part of a set of transcriptional repressors encoded by the Enhancer of split [ E(spl) ] genes , and since these repressors are activated to suppress cell differentiation in response to Notch receptors signalling , the AES peptides may represent a novel class of self-antigens that deserve further consideration as tumor Ag in epithelial cancers .", "target_text": { "AES proteins": "protein", "Enhancer of split [ E(spl) ] genes": "DNA", "Notch receptors": "protein", "self-antigens": "protein", "tumor Ag": "protein" } }, { "input_text": "Induction of the pro-myelocytic leukaemia gene by type I and type II interferons .", "target_text": { "pro-myelocytic leukaemia gene": "DNA" } }, { "input_text": "The physiological role of the pro-myelocytic leukaemia ( PML ) gene product is poorly defined .", "target_text": { "PML": "DNA", "pro-myelocytic leukaemia ( PML ) gene product": "protein" } }, { "input_text": "Among other functions , PML is involved in haematopoietic differentiation and in control of cell growth and tumorigenesis .", "target_text": { "PML": "DNA" } }, { "input_text": "We investigated the regulation of human PML expression by interferons ( IFNs ) and IL-1 in various human haematopoietic lines ( U937 , THP1 , HL60 , NB4 ) , in human diploid fibroblasts and in human peripheral blood leukocytes .", "target_text": { "PML": "DNA", "interferons": "protein", "IFNs": "protein", "IL-1": "protein", "human haematopoietic lines": "cell_line", "U937": "cell_line", "THP1": "cell_line", "HL60": "cell_line", "NB4": "cell_line", "human diploid fibroblasts": "cell_type", "human peripheral blood leukocytes": "cell_type" } }, { "input_text": "Cytokine-induced modulation of PML expression was assessed by Northern blot analyses , flow cytometry studies and in situ immunolabelling .", "target_text": { "PML": "DNA" } }, { "input_text": "Our data show that IFNs and IL-1 upregulate PML transcript and protein expression in a time and dose-dependent manner .", "target_text": { "IFNs": "protein", "IL-1": "protein" } }, { "input_text": "In situ immunolabelling revealed that upregulation of protein expression by IFN-alpha is a consequence of a marked increase in both the number and the intensity of the staining of so-called PML nuclear bodies .", "target_text": { "IFN-alpha": "protein", "PML": "DNA", "PML nuclear bodies": "protein" } }, { "input_text": "Our data suggest that stimulation of PML expression by interferons and IL-1 may account for upregulation of PML proteins observed in inflammatory tissues and in proliferative states .", "target_text": { "PML": "DNA", "interferons": "protein", "IL-1": "protein", "PML proteins": "protein" } }, { "input_text": "The position of the ZEBRA activation domain does not influence its biological activity .", "target_text": { "ZEBRA activation domain": "protein" } }, { "input_text": "Epstein-Barr virus ( EBV ) is a human herpesvirus which latently infects B lymphocytes .", "target_text": { "B lymphocytes": "cell_type" } }, { "input_text": "EBV encodes a unique transcriptional activator , known as ZEBRA , which can disrupt viral latency in B cells and induce lytic viral replication .", "target_text": { "ZEBRA": "protein", "B cells": "cell_type" } }, { "input_text": "Furthermore , ZEBRA has been shown to bind at the EBV origin of lytic replication , and is necessary for viral DNA replication to occur .", "target_text": { "ZEBRA": "protein" } }, { "input_text": "Previously we demonstrated that heterologous activation domains can fully substitute for the ZEBRA activation domain .", "target_text": { "heterologous activation domains": "protein", "ZEBRA": "protein", "ZEBRA activation domain": "protein" } }, { "input_text": "Here we extend those results by showing that the position of the ZEBRA activation domain or a heterologous replacement domain does not influence its ability to function in the disruption of EBV latency .", "target_text": { "ZEBRA": "protein", "ZEBRA activation domain": "protein" } }, { "input_text": "In this study three novel clones were constructed in which the ZEBRA activation region was repositioned to the carboxy terminus of the protein .", "target_text": { "ZEBRA": "protein", "ZEBRA activation region": "protein", "carboxy terminus": "protein" } }, { "input_text": "These mutants were used to demonstrate that the ability of ZEBRA 's wild type domain to function in the complex biological process of virus activation is not compromised by altering its position within the protein .", "target_text": { "ZEBRA": "protein", "ZEBRA 's wild type domain": "protein" } }, { "input_text": "The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity .", "target_text": { "glucocorticoid receptor": "protein", "human mononuclear leukocyte": "cell_type" } }, { "input_text": "Glucocorticoid receptors ( GR ) and 3-O-methyl-D glucose ( 3-O-MG ) transport were determined in mononuclear leukocytes ( MNL ) from 11 abdominal obese subjects , 10 pituitary-dependent Cushing 's syndrome ( Cushing 's disease ) and 10 healthy controls .", "target_text": { "Glucocorticoid receptors": "protein", "GR": "protein", "mononuclear leukocytes": "cell_type", "MNL": "cell_type" } }, { "input_text": "Using a whole-cell competitive binding assay and 3H-dexamethasone as tracer , MNL of abdominal obese subjects were found to have 4855 +/- 1389 sites/cell which was significantly lower ( p < 0.05 ) than controls ( 6234 +/- 1568 sites/cell ) , although no significant difference was found in the mean serum cortisol level .", "target_text": { "MNL": "cell_type" } }, { "input_text": "Their mean Kd ( affinity ) was also significantly lower than that found in the healthy controls ( obese Kd : 2.92 +/- 0.84 nmol/l , control Kd : 4.55 +/- 0.67 nM , p < 0.05 ) .", "target_text": {} }, { "input_text": "On the other hand , the receptor characteristics in Cushing 's disease patients were within the normal range .", "target_text": {} }, { "input_text": "At the same time , 3-O-MG transport was determined in the same subjects .", "target_text": {} }, { "input_text": "In Cushing 's disease , 3-O-MG transport was within the normal range , whereas in abdominal obesity this value was significantly lower than the healthy controls ( abdominal obese : 31.90 +/- 8.20 ; control : 46.26 +/- 12.91 fmol/10(6) cell , min , p < 0.05 ) .", "target_text": {} }, { "input_text": "We also found a positive correlation between 3-O-MG transport and GR binding capacity in abdominal subjects ( r = 0.89 , p < 0.001 ) , however we did not find such a correlation in Cushing 's disease ( r = 0.60 , p > 0.05 ) .", "target_text": { "GR": "protein" } }, { "input_text": "These results indicated that , in abdominal obesity , the GR binding capacity in MNL is influenced by the changes in glucose transport .", "target_text": { "GR": "protein", "MNL": "cell_type" } }, { "input_text": "Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma .", "target_text": { "Interleukin-10": "protein", "transforming growth factor-beta": "protein", "transforming growth factor-beta promoter": "DNA", "transforming growth factor-beta promoter polymorphisms": "DNA" } }, { "input_text": "Interleukin-10 ( IL-10 ) and transforming growth factor beta ( TGF-beta ) are inhibitory for B and T cells , IgE production , and mast cell proliferation , and they induce apoptosis in eosinophils .", "target_text": { "Interleukin-10": "protein", "IL-10": "protein", "transforming growth factor beta": "protein", "TGF-beta": "protein", "IgE": "protein", "eosinophils": "cell_type" } }, { "input_text": "These cytokines are therefore candidate genes which could contribute to the development of asthma or allergies .", "target_text": { "cytokines": "protein" } }, { "input_text": "We investigated the hypothesis that polymorphic nucleotides within the IL-10 and TGF-beta gene promoters would link to the expression of allergies and asthma .", "target_text": {} }, { "input_text": "DNA taken from families with an asthmatic proband was examined for base exchanges by single-stranded conformational polymorphism ( SSCP ) .", "target_text": {} }, { "input_text": "We demonstrated the presence of a polymorphism in the promoter region of the IL-10 gene and four in the TGF-beta gene promoters ( 3 in TGF-beta1 and 1 in TGF-beta2 ) .", "target_text": { "promoter region": "DNA", "IL-10": "protein", "IL-10 gene": "DNA", "TGF-beta": "protein", "TGF-beta gene promoters": "DNA", "TGF-beta1": "DNA", "TGF-beta2": "DNA" } }, { "input_text": "The IL-10 gene polymorphism was a C -to- A exchange 571 base pairs upstream from the translation start site and was present between consensus binding sequences for Sp1 and elevated total serum .", "target_text": { "IL-10": "protein", "571 base pairs upstream": "DNA", "translation start site": "DNA", "consensus binding sequences": "DNA", "Sp1": "protein" } }, { "input_text": "This polymorphism was associated with elevated total serum IgE in subjects heterozygotic or homozygotic for this base exchange ( p < 0.009 ) .", "target_text": { "IgE": "protein", "total serum IgE": "protein" } }, { "input_text": "The base exchange at -509 ( from the transcription initiation site ) in the TGF-beta promoter also linked to elevated total IgE ( p < 0.01 ) .", "target_text": { "TGF-beta promoter": "DNA", "IgE": "protein" } }, { "input_text": "This polymorphism represented a C -to- T base exchange which induced a YY1 consensus sequence and is present in a region of the promoter associated with negative transcription regulation .", "target_text": { "YY1 consensus sequence": "DNA" } }, { "input_text": "Tpl-2 induces IL-2 expression in T-cell lines by triggering multiple signaling pathways that activate NFAT and NF-kappaB .", "target_text": { "Tpl-2": "protein", "IL-2": "protein", "T-cell lines": "cell_line", "NFAT": "protein", "NF-kappaB": "protein" } }, { "input_text": "The Tpl-2 kinase activates the nuclear factor of activated T cells ( NFAT ) and induces IL-2 expression in T-cell lines .", "target_text": { "Tpl-2": "protein", "Tpl-2 kinase": "protein", "nuclear factor of activated T cells": "protein", "NFAT": "protein", "IL-2": "protein", "T-cell lines": "cell_line" } }, { "input_text": "Here we show that the activation of the IL-2 promoter by Tpl-2 is inhibited by mutant signaling molecules that inhibit the mitogen-activated protein kinase ( MAPK ) or the calcineurin /NFAT pathways and is promoted by combinations of signaling molecules that activate these pathways .", "target_text": { "IL-2": "protein", "IL-2 promoter": "DNA", "Tpl-2": "protein", "mutant signaling molecules": "protein", "mitogen-activated protein kinase": "protein", "MAPK": "protein", "calcineurin": "protein", "/NFAT": "protein", "signaling molecules": "protein" } }, { "input_text": "We , therefore , conclude that signals generated by the convergence of the MAPK and the calcineurin /NFAT pathway are necessary and sufficient for the activation of the IL-2 promoter by Tpl-2 .", "target_text": { "MAPK": "protein", "calcineurin": "protein", "/NFAT": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "Tpl-2": "protein" } }, { "input_text": "The activation of both the IL-2 promoter and an NFAT -driven minimal promoter were shown to depend on signals transduced by Raf1 .", "target_text": { "IL-2 promoter": "DNA", "NFAT": "protein", "NFAT -driven minimal promoter": "DNA", "Raf1": "protein" } }, { "input_text": "However , it was only the IL-2 promoter whose activation by Tpl-2 was fully blocked by the dominant negative mutant MEK1S218/222A and the MEK1/MEK2 inhibitor PD098059 .", "target_text": { "IL-2": "protein", "IL-2 promoter": "DNA", "Tpl-2": "protein", "MEK1S218/222A": "protein", "dominant negative mutant MEK1S218/222A": "protein" } }, { "input_text": "Since the activation of NFAT is MAPK -dependent these findings suggested that the activation of MAPK by Tpl-2 is either independent or only partially dependent on MEK1 and MEK2 .", "target_text": { "NFAT": "protein", "MAPK": "protein", "Tpl-2": "protein", "MEK1": "protein", "MEK2": "protein" } }, { "input_text": "In addition , they suggested that the activation of the IL-2 promoter is under the control of not only NFAT but also a second factor whose activation is MEK -dependent .", "target_text": { "IL-2": "protein", "IL-2 promoter": "DNA", "NFAT": "protein", "MEK": "protein" } }, { "input_text": "Experiments in COS-1 and EL-4 cells confirmed both hypotheses and revealed that the second factor activated by Tpl-2 is NF-kappaB .", "target_text": { "COS-1": "cell_line", "EL-4 cells": "cell_line", "Tpl-2": "protein", "NF-kappaB": "protein" } }, { "input_text": "While the activation of the IL-2 promoter and an NFAT -driven minimal promoter by Tpl-2 was fully blocked by the dominant negative mutant NFAT delta418 , it was only partially blocked by the calcineurin inhibitor cyclosporin A suggesting that the Tpl-2 -mediated NFAT activation is under the control of a combination of calcineurin- dependent and independent pathways .", "target_text": { "IL-2": "protein", "IL-2 promoter": "DNA", "NFAT": "protein", "NFAT -driven minimal promoter": "DNA", "Tpl-2": "protein", "dominant negative mutant": "protein", "NFAT delta418": "protein", "calcineurin": "protein" } }, { "input_text": "Both pathways were fully blocked by Bcl-2 or Bcl-X(L) .", "target_text": { "Bcl-2": "protein", "Bcl-X(L)": "protein" } }, { "input_text": "Differential activation of functionally distinct STAT5 proteins by IL-5 and GM-CSF during eosinophil and neutrophil differentiation from human CD34+ hematopoietic stem cells .", "target_text": { "STAT5 proteins": "protein", "IL-5": "protein", "GM-CSF": "protein", "human CD34+ hematopoietic stem cells": "cell_line" } }, { "input_text": "Interleukin-5 ( IL-5 ) and granulocyte macrophage-colony stimulating factor ( GM-CSF ) are important cytokines for the proliferation , differentiation , and activation of myeloid lineages .", "target_text": { "Interleukin-5": "protein", "IL-5": "protein", "granulocyte macrophage-colony stimulating factor": "protein", "GM-CSF": "protein", "cytokines": "protein", "myeloid lineages": "cell_type" } }, { "input_text": "The JAK /STAT pathway is one of the signaling pathways implicated in mediating biological responses induced by these cytokines .", "target_text": { "JAK": "protein", "/STAT": "protein", "cytokines": "protein" } }, { "input_text": "Previous studies have demonstrated that these cytokines predominantly activate an 80 kDa STAT5 isoform in mature granulocytes .", "target_text": { "cytokines": "protein", "80 kDa STAT5 isoform": "protein" } }, { "input_text": "To better understand the role of STAT proteins during growth and differentiation of granulocytes , we evaluated differentiation of human CD34+ hematopoietic stem cells ex vivo toward eosinophils and neutrophils .", "target_text": { "human CD34+ hematopoietic stem cells": "cell_line", "eosinophils": "cell_type" } }, { "input_text": "Bandshift experiments showed that in an early stage of both differentiation pathways ( 14 days ) , the 94 kDa STAT5B protein was activated by both IL-5 ( eosinophil lineage ) and GM-CSF ( neutrophil lineage ) .", "target_text": { "STAT5B protein": "protein", "IL-5": "protein", "eosinophil lineage": "cell_type", "GM-CSF": "protein", "neutrophil lineage": "cell_type" } }, { "input_text": "However , during maturation of both lineages ( days 21 and 28 ) , increased expression of a functionally distinct 80 kDa STAT5 isoform was observed , resulting in heterodimer DNA-binding complexes containing both the 94 and 80 kDa STAT5 proteins .", "target_text": { "80 kDa STAT5 isoform": "protein", "heterodimer DNA-binding complexes": "protein", "STAT5 proteins": "protein" } }, { "input_text": "The finding that functionally distinct isoforms of STAT5 are activated during the early and late differentiation stages of granulocytes suggests that they might be involved in regulating different biological functions in these cells .", "target_text": { "STAT5": "protein" } }, { "input_text": "The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development .", "target_text": { "HOX11": "protein", "T-cell oncogenic protein HOX11": "protein", "Aldh1": "protein", "NIH 3T3 cells": "cell_line" } }, { "input_text": "Hox11 is a homeobox gene essential for spleen formation in mice , since atrophy of the anlage of a developing spleen occurs in early embryonic development in Hox11 null mice .", "target_text": { "Hox11": "DNA", "homeobox gene": "DNA" } }, { "input_text": "HOX11 is also expressed in a subset of T-cell acute leukemias after specific chromosomal translocations .", "target_text": { "HOX11": "protein" } }, { "input_text": "Since the protein has a homeodomain and can activate transcription , it probably exerts at least some of its effects in vivo by regulation of target genes .", "target_text": { "homeodomain": "DNA", "target genes": "DNA" } }, { "input_text": "Representational difference analysis has been used to isolate cDNA clones corresponding to mRNA species activated following stable expression of HOX11 in NIH 3T3 cells .", "target_text": { "cDNA clones": "DNA", "mRNA species": "RNA", "HOX11": "protein", "NIH 3T3 cells": "cell_line" } }, { "input_text": "The gene encoding the retinoic acid-synthesizing enzyme aldehyde dehydrogenase 1 ( Aldh1 ) , initially called Hdg-1 , was found to be ectopically activated by HOX11 in this system .", "target_text": { "retinoic acid-synthesizing enzyme": "protein", "aldehyde dehydrogenase 1": "protein", "Aldh1": "protein", "Hdg-1": "protein", "HOX11": "protein" } }, { "input_text": "Study of Aldh1 gene expression during spleen development showed that the presence of Aldh1 mRNA inversely correlated with Hox11 .", "target_text": { "Aldh1": "protein", "Aldh1 mRNA": "RNA", "Hox11": "protein" } }, { "input_text": "Hox11 null mouse embryos have elevated Aldh1 mRNA in spleen primordia prior to atrophy , while Aldh1 seems to be repressed by Hox11 during organogenesis of the spleens of wild-type mice .", "target_text": { "Hox11": "protein", "Aldh1": "protein", "Aldh1 mRNA": "RNA" } }, { "input_text": "This result suggests that expression of Aldh1 protein is negatively regulated by Hox11 and that abnormal expression of Aldh1 in Hox11 null mice may cause loss of splenic precursor cells by aberrant retinoic acid metabolism", "target_text": { "Aldh1": "protein", "Aldh1 protein": "protein", "Hox11": "protein", "splenic precursor cells": "cell_type" } }, { "input_text": "Role of the X2 box in activated transcription from the DRA promoter in B cells .", "target_text": { "X2 box": "DNA", "DRA promoter": "DNA", "B cells": "cell_type" } }, { "input_text": "We investigated the function of the evolutionary conserved X2 box in the promoter of the HLA-DRA gene from the human major histocompatibility complex ( MHC ) in resting and activated B cells .", "target_text": { "X2 box": "DNA", "promoter": "DNA", "HLA-DRA gene": "DNA", "human major histocompatibility complex": "protein", "MHC": "protein", "B cells": "cell_type" } }, { "input_text": "NF-X2 , which contains members of the AP-1/ATF/CREB families of transcription factors , interacts with the X2 box ( 5'-TGCGTCA-3' ) from positions -97 to -91 in the DRA promoter .", "target_text": { "NF-X2": "DNA", "AP-1/ATF/CREB families": "protein", "transcription factors": "protein", "X2 box": "DNA", "DRA promoter": "DNA" } }, { "input_text": "In resting Raji cells , little to no binding to the X2 box was observed .", "target_text": { "Raji cells": "cell_line", "X2 box": "DNA" } }, { "input_text": "In sharp contrast , in B cells treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate ( TPA ) , strong interactions between the X2 box and NF-X2 containing c-Fos were observed .", "target_text": { "B cells": "cell_type", "X2 box": "DNA", "NF-X2": "DNA", "c-Fos": "protein" } }, { "input_text": "As determined by transient expression and RNA analyses , the activation of protein kinase C ( PKC ) also increased rates of transcription from the wild-type DRA promoter but not from a DRA promoter bearing clustered point mutations in the X2 box .", "target_text": { "DRA promoter": "DNA", "X2 box": "DNA" } }, { "input_text": "Since the co-expression with a dominant negative c-Fos abolished the responsiveness to TPA , we conclude that activated transcription of the DRA gene depends on interactions between the X2 box and NF-X2 , which contains c-Fos .", "target_text": { "c-Fos": "protein", "DRA gene": "DNA", "X2 box": "DNA", "NF-X2": "DNA" } }, { "input_text": "Thymocytes control the CD4 gene differently from mature T lymphocytes .", "target_text": { "CD4 gene": "DNA", "mature T lymphocytes": "cell_type" } }, { "input_text": "We analyzed the activity of the enhancer , the promoter and the silencer of the human CD4 gene during T cell development using transgenic mice .", "target_text": { "enhancer": "DNA", "promoter": "DNA", "silencer": "DNA", "CD4 gene": "DNA", "human CD4 gene": "DNA" } }, { "input_text": "Immunofluorescence studies on thymic populations of mice carrying transgenes in various combinations of these regulatory DNA elements revealed that thymocytes control the CD4 gene in a different manner than mature peripheral T lymphocytes .", "target_text": { "thymic populations": "cell_type", "regulatory DNA elements": "DNA", "thymocytes": "cell_type", "CD4 gene": "DNA", "peripheral T lymphocytes": "cell_type" } }, { "input_text": "The 5'-positive regulatory unit , consisting of the promoter and the 5' enhancer , is already active at the CD4 - CD8 -double-negative ( DN ) stage of development .", "target_text": { "5'-positive regulatory unit": "DNA", "promoter": "DNA", "5' enhancer": "DNA", "CD4": "protein", "CD8": "protein" } }, { "input_text": "However , its activity becomes lower in the double-positive and a fraction of the CD4+ CD8int/- cell population , indicating that an additional enhancer , located in either the first or the third intron of the CD4 gene , is required for CD4 gene expression in this population .", "target_text": { "CD4+ CD8int/- cell population": "cell_type", "CD4 gene": "DNA" } }, { "input_text": "The other studied regulatory element is the minimal CD4 silencer which inhibits CD4 gene expression in peripheral CD8 T lymphocytes .", "target_text": { "regulatory element": "DNA", "minimal CD4 silencer": "DNA", "CD4 gene": "DNA", "peripheral CD8 T lymphocytes": "cell_type" } }, { "input_text": "This silencer is inactive in the most immature DN thymocytes , which probably use a distinct silencer mechanism to down-regulate CD4 gene expression .", "target_text": { "thymocytes": "cell_type", "immature DN thymocytes": "cell_type", "CD4 gene": "DNA" } }, { "input_text": "Unexpectedly , the CD4 silencer is also active in CD4+ CD8int/- cells of the thymus , implying that an anti-silencer may be required to resume CD4 expression in this cell population .", "target_text": { "CD4 silencer": "DNA", "CD4+ CD8int/- cells": "cell_type", "CD4": "protein" } }, { "input_text": "Altogether , the CD4 gene is regulated by several positive and negative regulatory mechanisms which come into play in a developmentally coordinated manner .", "target_text": { "CD4": "protein", "CD4 gene": "DNA" } }, { "input_text": "[ Induction of apoptosis in lymphocytes by glucocorticoids : between physiology and pharmacology ]", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "Glucocorticoids are physiological molecules that are also extensively used in clinics as anti-inflammatory , immunosuppressive or anti-tumoral agents .", "target_text": {} }, { "input_text": "Glucocorticoids can induce apoptosis on normal lymphoid cells and play a key role in the physiology of thymic selection .", "target_text": { "normal lymphoid cells": "cell_type" } }, { "input_text": "In clinics these molecules are also used for their potencies in inducing apoptosis of malignant lymphoid cells .", "target_text": { "malignant lymphoid cells": "cell_type" } }, { "input_text": "Glucocorticoids are mediating their effects after binding to an intracellular receptor belonging to the steroid receptor superfamily : the glucocorticoid receptor ( GR ) .", "target_text": { "intracellular receptor": "protein", "steroid receptor superfamily": "protein", "glucocorticoid receptor": "protein", "GR": "protein" } }, { "input_text": "Once activated , the GR , can mediate his effects through direct binding on the DNA or via protein/protein interactions with transcription factors .", "target_text": { "GR": "protein", "transcription factors": "protein" } }, { "input_text": "Depending on the type of lymphocytes , the mechanism of apoptosis induced by glucocorticoids fall roughly in two categories : induction of \" death genes \" by the activated GR ( I kappa B , c-jun ) or repression of survival factors ( AP-1 , c-Myc ) .", "target_text": { "lymphocytes": "cell_type", "GR": "protein", "I kappa B": "protein", "c-jun": "protein", "survival factors": "protein", "AP-1": "protein", "c-Myc": "protein" } }, { "input_text": "In the case of thymic selection the mechanism is more subtle depending on the mutual repression of Nur77 and GR .", "target_text": { "Nur77": "protein", "GR": "protein" } }, { "input_text": "Direct suppression of Stat1 function during adenoviral infection .", "target_text": { "Stat1": "protein" } }, { "input_text": "The action of adenoviral E1A oncoprotein on host immune-response genes has been attributed to interaction with p300/CBP-type transcriptional coactivators in competition with endogenous transcription factors such as signal transducer and activator of transcription ( STAT ) proteins .", "target_text": { "adenoviral E1A oncoprotein": "protein", "host immune-response genes": "DNA", "p300/CBP-type transcriptional coactivators": "protein", "transcription factors": "protein", "endogenous transcription factors": "protein", "signal transducer and activator of transcription ( STAT ) proteins": "protein" } }, { "input_text": "However , we show that mutant forms of E1A that no longer bind p300/CBP can still interact directly with Stat1 ( via E1A N-terminal and Stat1 C-terminal residues ) and block IFNgamma-driven , Stat1 -dependent gene activation and consequent function during early-phase infection in the natural host cell .", "target_text": { "E1A": "protein", "p300/CBP": "protein", "Stat1": "protein", "natural host cell": "cell_type" } }, { "input_text": "The results provide a distinct and more specific mechanism for E1A -mediated immune suppression and an alternative model of IFNgamma -driven enhanceosome formation that may allow for other adaptors ( in addition to p300/CBP ) to link Stat1 to the basal transcription complex .", "target_text": { "E1A": "protein", "IFNgamma": "protein", "p300/CBP": "protein", "Stat1": "protein", "basal transcription complex": "protein" } }, { "input_text": "Effect of environmental estrogens on IL-1beta promoter activity in a macrophage cell line .", "target_text": { "IL-1beta": "protein", "IL-1beta promoter": "DNA", "macrophage cell line": "cell_line" } }, { "input_text": "Environmental estrogens or estrogen disrupters have recently received a great deal of attention because of their potential health impact on reproductive tissues .", "target_text": {} }, { "input_text": "Few , if any , studies have been made on the impact of these compounds on the immune system .", "target_text": {} }, { "input_text": "We sought to determine the activities of various environmental estrogens on the modulation of the interleukin-1beta ( IL-1beta ) gene in a model monocytic cell line , hER + IL-1beta -CAT+ .", "target_text": { "interleukin-1beta": "protein", "IL-1beta": "protein", "interleukin-1beta ( IL-1beta ) gene": "DNA", "model monocytic cell line": "cell_line", "hER + IL-1beta -CAT+": "cell_line" } }, { "input_text": "This cell line stably transfected with the human estrogen receptor , and an IL-1beta promoter construct fused to the CAT reporter gene allows us to monitor the effect of estrogenic compounds on IL-1beta promoter activity .", "target_text": { "human estrogen receptor": "protein", "IL-1beta": "protein", "IL-1beta promoter": "DNA", "CAT reporter gene": "DNA" } }, { "input_text": "17beta-estradiol ( E2 ) markedly enhanced lipopolysaccharide - ( LPS ) induced IL-1beta promoter -driven CAT activity in a dose-dependent manner .", "target_text": { "IL-1beta": "protein", "IL-1beta promoter": "DNA", "CAT": "protein" } }, { "input_text": "The mycotoxins alpha-zearalenol and zearalenone both exhibited full agonist activity , but at lower potencies , with EC50 values of 1.8 and 54 nM , respectively , compared with E2 at 0.5 nM .", "target_text": {} }, { "input_text": "In addition , genistein was a very low-potency agonist , having an EC50 of 1.5 microM .", "target_text": {} }, { "input_text": "Similar to the E2 response , the slope factors for alpha-zearalenol , zearalenone , and genistein were close to 3.0 , suggesting positive cooperativity in the estrogenic response .", "target_text": {} }, { "input_text": "The activity of the mycotoxins appeared to be mediated through the estrogen receptor , since both the antiestrogens H1285 and ICI 182 , 780 effectively inhibited their agonist activity in a dose-dependent manner .", "target_text": {} }, { "input_text": "Representative environmental estrogenic compounds both from plant and industrial sources were also tested .", "target_text": {} }, { "input_text": "Unlike the mycoestrogens , none of the compounds , with the exception of genistein , synergized with LPS to enhance IL-1beta promoter activity .", "target_text": { "IL-1beta": "protein", "IL-1beta promoter": "DNA" } }, { "input_text": "When tested for antiestrogenic activity , the industrial compound 4-octylphenol was able to antagonize the response to E2 ; however , the response was three orders of magnitude less potent than H 1285 .", "target_text": {} }, { "input_text": "Naringenin , a plant flavonoid , showed little or no ability to antagonize the response to E2 .", "target_text": {} }, { "input_text": "Overall , the results show that some environmental estrogens that display agonist activity in reproductive tissue also have an effect on IL-1 gene expression in hemopoietic-derived tissue .", "target_text": { "IL-1 gene": "DNA" } }, { "input_text": "Isolation and utilization of human dendritic cells from peripheral blood to assay an in vitro primary immune response to varicella-zoster virus peptides .", "target_text": { "human dendritic cells": "cell_type" } }, { "input_text": "A human dendritic cell-based assay used to monitor a T cell proliferation response to viral peptides in vitro is described .", "target_text": {} }, { "input_text": "Dendritic cells and autologous CD4 + T cells were isolated from peripheral blood by a series of density-gradient centrifugations or magnetic bead separations ( or both ) .", "target_text": { "Dendritic cells": "cell_type", "CD4": "protein", "autologous CD4 + T cells": "cell_type" } }, { "input_text": "Peptides corresponding to residues of the immediate early protein , IE62 , of varicella-zoster virus ( VZV ) were used as stimulating antigens , and persons with no history of varicella and no humoral or cellular immunity to VZV served as naive donors for the assays .", "target_text": { "immediate early protein": "protein", "IE62": "protein", "stimulating antigens": "protein" } }, { "input_text": "Three VZV -susceptible donors were tested , and all demonstrated an in vitro response to multiple VZV peptides .", "target_text": {} }, { "input_text": "This assay has potential as a screen to establish the immunogenicity of viral antigens in vitro using T cells from naive donors .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Xenogeneic human serum promotes leukocyte adhesion to porcine endothelium under flow conditions , possibly through the activation of the transcription factor NF-kappa B .", "target_text": { "transcription factor NF-kappa B": "protein" } }, { "input_text": "Endothelial cell activation and leukocyte infiltration are a consistent feature of discordant xenograft rejection .", "target_text": {} }, { "input_text": "Here we evaluated whether xenogeneic serum , as a source of xenoreactive natural antibodies and complement , induced endothelial cell activation with consequent leukocyte adhesion under flow conditions .", "target_text": { "xenoreactive natural antibodies": "protein" } }, { "input_text": "Porcine aortic endothelial cells ( PAEC ) were incubated for 1 hr 30 min or 5 hr with 10 % homologous porcine serum ( control ) or 10 % xenogeneic human serum and then perfused with total human leukocytes in a parallel plate flow chamber under laminar flow ( 1.5 dynes/cm2 ) .", "target_text": { "Porcine aortic endothelial cells": "cell_line", "PAEC": "cell_line", "human leukocytes": "cell_type" } }, { "input_text": "Adherent cells were counted by digital image analysis .", "target_text": {} }, { "input_text": "Xenogeneic human serum significantly ( P < 0.01 ) increased the number of adherent leukocytes as compared with porcine serum .", "target_text": { "adherent leukocytes": "cell_type" } }, { "input_text": "A similar adhesive response was elicited by TNF alpha ( 100 U/ml ) , one of the most potent inducers of endothelial cell adhesive properties , here used as positive control .", "target_text": { "endothelial cell": "cell_type" } }, { "input_text": "In order to elucidate possible mechanisms underlying endothelial cell activation by xenogeneic serum , we focussed on transcription factor NF-kappa B , a central regulator for the induction of different genes , including adhesive molecules and chemoattractants .", "target_text": { "endothelial cell": "cell_type", "NF-kappa B": "protein", "transcription factor NF-kappa B": "protein", "adhesive molecules": "protein", "chemoattractants": "protein" } }, { "input_text": "By confocal fluorescence microscopy , we observed a positive staining for NF-kappa B ( p65 subunit ) in the nuclei of PAEC exposed for 1 hr 30 min to human serum , which indicated NF-kappa B activation in this setting .", "target_text": { "NF-kappa B": "protein", "p65 subunit": "protein", "PAEC": "cell_line" } }, { "input_text": "At variance , in PAEC incubated with the homologous serum , NF-kappa B was strictly localized in the cell cytoplasm .", "target_text": { "PAEC": "cell_line", "NF-kappa B": "protein" } }, { "input_text": "Treatment of PAEC exposed to xenogeneic serum with the NF-kappa B inhibitors pyrrolidinedithiocarbamate ( PDTC , 25 microM ) and tosyl-phechloromethylketone ( TPCK , 25 microM ) significantly ( P < 0.01 ) reduced leukocyte adhesion in respect to PAEC treated with human serum alone .", "target_text": { "PAEC": "cell_line", "NF-kappa B": "protein" } }, { "input_text": "Findings that xenogeneic serum promotes leukocyte-endothelium interaction possibly through NF-kappa B activation might be relevant for designing future therapeutic strategies aimed at prolonging xenograft survival .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Anaphylatoxins C5a and C3a induce nuclear factor kappaB activation in human peripheral blood monocytes .", "target_text": { "Anaphylatoxins": "protein", "C5a": "protein", "C3a": "protein", "nuclear factor kappaB": "protein", "human peripheral blood monocytes": "cell_type" } }, { "input_text": "The anaphylatoxins C5a and C3a are involved in the regulation of cytokine production .", "target_text": { "anaphylatoxins": "protein", "C5a": "protein", "C3a": "protein" } }, { "input_text": "In this study the capability of C5a and C3a to induce transcription factor activation was examined .", "target_text": { "C5a": "protein", "C3a": "protein" } }, { "input_text": "C5a and C3a stimulation of human peripheral blood monocytes resulted in nuclear expression of a DNA binding activity with specificity to the kappaB sequence .", "target_text": { "C5a": "protein", "C3a": "protein", "human peripheral blood monocytes": "cell_type", "kappaB sequence": "DNA" } }, { "input_text": "The p50 and p65 proteins , constituents of the prototypic nuclear factor kappaB , were identified as components of the DNA-protein complexes by anti-peptide antibodies in gel supershift assays .", "target_text": { "nuclear factor kappaB": "protein", "anti-peptide antibodies": "protein" } }, { "input_text": "C5a induced kappaB binding activity was detected 15 min after agonist stimulation , peaked at 30-40 min , and remained detectable at 2 h .", "target_text": { "C5a": "protein", "kappaB": "protein" } }, { "input_text": "Binding to kappaB sequence was accompanied by an initial decrease and subsequent increase in the cytoplasmic IkappaBalpha levels , as detected by Western blotting using an anti- IkappaBalpha antibody .", "target_text": { "kappaB sequence": "DNA", "IkappaBalpha": "protein", "anti- IkappaBalpha antibody": "protein" } }, { "input_text": "Pertussis toxin treatment markedly decreased kappaB binding activities induced by both C5a and C3a , whereas cholera toxin displayed no inhibitory effect .", "target_text": { "kappaB": "protein", "C5a": "protein", "C3a": "protein", "cholera toxin": "protein" } }, { "input_text": "Neither of the two toxins affected kappaB binding activity induced by TNFalpha in the same cells .", "target_text": { "kappaB": "protein", "TNFalpha": "protein" } }, { "input_text": "These results imply a potential role of the anaphylatoxins C5a and C3a in regulating leukocytes gene expression through G protein-coupled transcription factor activation .", "target_text": { "anaphylatoxins": "protein", "C5a": "protein", "C3a": "protein" } }, { "input_text": "Thrombopoietin and its receptor .", "target_text": { "Thrombopoietin": "protein" } }, { "input_text": "Thrombopoietin ( TPO ) , the primary physiological regulator of platelet production , was initially thought to be a lineage-specific factor acting predominantly on megakaryocytopoiesis .", "target_text": { "Thrombopoietin": "protein", "TPO": "protein" } }, { "input_text": "Detailed studies establish that this cytokine mediates biological effects on a broad spectrum of hematopoietic progenitor cells , including stem cells .", "target_text": { "hematopoietic progenitor cells": "cell_type", "stem cells": "cell_type" } }, { "input_text": "TPO is a hormone constitutively produced mainly by the liver and kidney .", "target_text": { "TPO": "protein" } }, { "input_text": "Plasma TPO levels are regulated by the platelet and megakaryocyte mass through Mpl receptor binding , internalization and degradation .", "target_text": { "TPO": "protein", "Mpl receptor": "protein" } }, { "input_text": "The Mpl receptor is a member of the hematopoietin receptor superfamily lacking intrinsic kinase activity .", "target_text": { "Mpl receptor": "protein", "hematopoietin receptor superfamily": "protein" } }, { "input_text": "Upon ligand-induced Mpl homodimerization , the major signaling events for proliferation are mediated through the JAK2 /STAT5 pathway , while differentiation might occur through a prolonged activation of the MAPK pathway .", "target_text": { "JAK2": "protein", "/STAT5": "protein", "MAPK": "protein" } }, { "input_text": "Preclinical and clinical studies demonstrate the potential use of TPO in a variety of contexts , but it is too early to evaluate its benefit in reducing platelet transfusion .", "target_text": { "TPO": "protein" } }, { "input_text": "TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3 .", "target_text": { "TAL1": "protein", "LIM-only proteins": "protein", "retinaldehyde dehydrogenase 2": "protein", "GATA3": "protein" } }, { "input_text": "Previously , we have shown that TAL1 and the LIM-only protein gene ( LMO ) are regularly coactivated in T-cell acute lymphoblastic leukemia ( T-ALL ) .", "target_text": { "TAL1": "protein", "LIM-only protein gene": "DNA", "LMO": "DNA" } }, { "input_text": "This observation is likely to relate to the findings that TAL1 and LMO are highly synergistic in T-cell tumorigenesis in double- transgenic mice .", "target_text": { "TAL1": "protein", "LMO": "protein" } }, { "input_text": "To understand the molecular mechanisms of functional synergy between TAL1 and LMO in tumorigenesis and transcriptional regulation , we tried to identify downstream target genes regulated by TAL1 and LMO by a subtractive PCR method .", "target_text": { "TAL1": "protein", "LMO": "protein", "downstream target genes": "DNA" } }, { "input_text": "One of the isolated genes , that for retinaldehyde dehydrogenase 2 ( RALDH2 ) , was regularly expressed in most of the T-ALL cell lines that coexpressed TAL1 and LMO .", "target_text": { "retinaldehyde dehydrogenase 2": "protein", "RALDH2": "protein", "T-ALL cell lines": "cell_line", "TAL1": "protein", "LMO": "protein" } }, { "input_text": "Exogenously transfected TAL1 and LMO , but not either alone , induced RALDH2 expression in a T-ALL cell line , HPB-ALL , not expressing endogeneous TAL1 or LMO .", "target_text": { "TAL1": "protein", "LMO": "protein", "RALDH2": "protein", "T-ALL cell line": "cell_line", "HPB-ALL": "cell_line" } }, { "input_text": "The RALDH2 transcripts in T-ALL were , however , mostly initiated within the second intron .", "target_text": { "RALDH2": "protein", "RALDH2 transcripts": "RNA", "second intron": "RNA" } }, { "input_text": "Promoter analysis revealed that a GATA site in a cryptic promoter in the second intron was essential and sufficient for the TAL1- and LMO- dependent transcriptional activation , and GATA3 binds to this site .", "target_text": { "GATA site": "DNA", "cryptic promoter": "DNA", "second intron": "DNA", "GATA3": "protein" } }, { "input_text": "In addition , forced expression of GATA3 potentiated the induction of RALDH2 by TAL1 and LMO , and these three factors formed a complex in vivo .", "target_text": { "GATA3": "protein", "RALDH2": "protein", "TAL1": "protein", "LMO": "protein" } }, { "input_text": "Furthermore , a TAL1 mutant not binding to DNA also activated the transcription of RALDH2 in the presence of LMO and GATA3 .", "target_text": { "TAL1": "protein", "RALDH2": "protein", "LMO": "protein", "GATA3": "protein" } }, { "input_text": "Collectively , we have identified the RALDH2 gene as a first example of direct transcriptional target genes regulated by TAL1 and LMO in T-ALL .", "target_text": { "RALDH2": "protein", "RALDH2 gene": "DNA", "transcriptional target genes": "DNA", "TAL1": "protein", "LMO": "protein" } }, { "input_text": "In this case , TAL1 and LMO act as cofactors for GATA3 to activate the transcription of RALDH2", "target_text": { "TAL1": "protein", "LMO": "protein", "GATA3": "protein", "RALDH2": "protein" } }, { "input_text": "Glucocorticoid receptors in human peripheral blood mononuclear cells in relation to age and to sport activity .", "target_text": { "Glucocorticoid receptors": "protein", "human peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Glucocorticoid receptors ( GR ) are ubiquitous molecules and are present also in the hippocampus and in several other nervous and immune tissues .", "target_text": { "Glucocorticoid receptors": "protein", "GR": "protein" } }, { "input_text": "Peripheral blood mononuclear cells ( PBMCs ) are a good model for studies of GR in humans .", "target_text": { "Peripheral blood mononuclear cells": "cell_type", "PBMCs": "cell_type", "GR": "protein" } }, { "input_text": "Glucocorticoids are important for maintaining cellular and humoral homeostasis and are key mediators of neuroendocrine-immune regulatory interactions .", "target_text": {} }, { "input_text": "The increase of cortisol is immunosuppressive and reduces GR concentration both in nervous and immune systems .", "target_text": { "GR": "protein" } }, { "input_text": "Variation of glucocorticoids in healthy aged subjects and athletes has been shown .", "target_text": {} }, { "input_text": "Prompted by these results , we have investigated in man a possible relationship between GR binding capacity in the PBMCs and age , in relation also to plasma testosterone and cortisol .", "target_text": { "GR": "protein", "PBMCs": "cell_type" } }, { "input_text": "The same parameters have been examined in a group of soccer players for comparison with the sedentary group .", "target_text": {} }, { "input_text": "GR binding capacity was higher in younger subjects than in older ones , and lower in the group of athletes than in the younger and older sedentary subjects .", "target_text": { "GR": "protein" } }, { "input_text": "In the sedentary group a negative correlation was present between GR binding capacity and age .", "target_text": { "GR": "protein" } }, { "input_text": "Plasma cortisol was higher and testosterone lower in the athletes ; they were negatively correlated in athletes and positively correlated in the sedentary subjects .", "target_text": {} }, { "input_text": "The results for athletes agree with their lower anabolic/catabolic balance .", "target_text": {} }, { "input_text": "The mechanism of reduced GR levels in relation to age and sport activity could involve a loss or an involution of receptor synthesis .", "target_text": { "GR": "protein" } }, { "input_text": "However other possibilities , such as altered distribution of lymphocyte subpopulations with different receptor concentrations and with different cytokine production , can not be excluded .", "target_text": { "cytokine": "protein" } }, { "input_text": "Several neuroendocrine-immune interactions could be responsible for reduced GR levels with age and sport activity in man .", "target_text": { "GR": "protein" } }, { "input_text": "Glycation-dependent , reactive oxygen species-mediated suppression of the insulin gene promoter activity in HIT cells .", "target_text": { "HIT cells": "cell_type" } }, { "input_text": "Prolonged poor glycemic control in non-insulin-dependent diabetes mellitus patients often leads to a decline in insulin secretion from pancreatic beta cells , accompanied by a decrease in the insulin content of the cells .", "target_text": { "pancreatic beta cells": "cell_type" } }, { "input_text": "As a step toward elucidating the pathophysiological background of the so-called glucose toxicity to pancreatic beta cells , we induced glycation in HIT-T15 cells using a sugar with strong deoxidizing activity , D-ribose , and examined the effects on insulin gene transcription .", "target_text": { "pancreatic beta cells": "cell_type", "HIT-T15 cells": "cell_type" } }, { "input_text": "The results of reporter gene analyses revealed that the insulin gene promoter is more sensitive to glycation than the control beta-actin gene promoter ; approximately 50 and 80 % of the insulin gene promoter activity was lost when the cells were kept for 3 d in the presence of 40 and 60 mM D-ribose , respectively .", "target_text": { "reporter gene": "DNA", "insulin gene promoter": "DNA", "beta-actin gene promoter": "DNA" } }, { "input_text": "In agreement with this , decrease in the insulin mRNA and insulin content was observed in the glycation-induced cells .", "target_text": { "insulin mRNA": "RNA", "glycation-induced cells": "cell_type" } }, { "input_text": "Also , gel mobility shift analyses using specific antiserum revealed decrease in the DNA-binding activity of an insulin gene transcription factor , PDX-1/IPF1/STF-1 .", "target_text": { "insulin gene transcription factor": "protein", "PDX-1/IPF1/STF-1": "protein" } }, { "input_text": "These effects of D-ribose seemed almost irreversible but could be prevented by addition of 1 mM aminoguanidine or 10 mM N-acetylcysteine , thus suggesting that glycation and reactive oxygen species , generated through the glycation reaction , serve as mediators of the phenomena .", "target_text": {} }, { "input_text": "These observations suggest that protein glycation in pancreatic beta cells , which occurs in vivo under chronic hyperglycemia , suppresses insulin gene transcription and thus can explain part of the beta cell glucose toxicity .", "target_text": { "pancreatic beta cells": "cell_type" } }, { "input_text": "Nuclear factor-kappa B activity in T cells from patients with rheumatic diseases : a preliminary report .", "target_text": { "Nuclear factor-kappa B": "protein", "T cells": "cell_type" } }, { "input_text": "OBJECTIVE : The NF-kappa B/Rel family of transcription factors regulates the expression of many genes involved in the immune or inflammatory response at the transcriptional level .", "target_text": { "NF-kappa B/Rel family": "protein", "transcription factors": "protein" } }, { "input_text": "The aim of this study was to determine whether distinctive patterns of NF-kappa B activation are seen in different forms of joint disease .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "METHODS : The DNA binding activity of these nucleoproteins was examined in purified synovial and peripheral T cells from patients with various chronic rheumatic diseases ( 12 : four with rheumatoid arthritis ; five with spondyloarthropathies ; and three with osteoarthritis ) .", "target_text": { "nucleoproteins": "protein" } }, { "input_text": "RESULTS : Electrophoretic mobility shift assays disclosed two specific complexes bound to a NF-kappa B specific 32P-labelled oligonucleotide in nucleoproteins extracted from purified T cells isolated from synovial fluid and peripheral blood of patients with rheumatoid arthritis .", "target_text": { "NF-kappa B": "protein", "nucleoproteins": "protein", "purified T cells": "cell_type" } }, { "input_text": "The complexes consisted of p50/p50 homodimers and p50/p65 heterodimers .", "target_text": { "complexes": "protein", "p50/p50 homodimers": "protein" } }, { "input_text": "Increased NF-kappa B binding to DNA in synovial T cells was observed relative to peripheral T cells .", "target_text": { "NF-kappa B": "protein", "synovial T cells": "cell_type" } }, { "input_text": "In non-rheumatoid arthritis , binding of NF-kappa B in synovial T cells was exclusively mediated by p50/p50 homodimers .", "target_text": { "NF-kappa B": "protein", "synovial T cells": "cell_type", "p50/p50 homodimers": "protein" } }, { "input_text": "CONCLUSION : Overall , the results suggest that NF-kappa B may play a central part in the activation of infiltrating T cells in chronic rheumatoid arthritis .", "target_text": { "NF-kappa B": "protein", "infiltrating T cells": "cell_type" } }, { "input_text": "The activation of this nuclear factor is qualitatively different in rheumatoid synovial T cells to that in other forms of non-rheumatoid arthritis ( for example , osteoarthritis , spondyloarthropathies ) .", "target_text": { "synovial T cells": "cell_type", "rheumatoid synovial T cells": "cell_type" } }, { "input_text": "X chromosome inactivation patterns in normal females .", "target_text": { "X chromosome": "DNA" } }, { "input_text": "Since one of the two X chromosomes is randomly inactivated at an early stage of female embryonic development , X-linked markers have been used to study the origin and development of various neoplastic disorders in affected heterozygous women ; clonality assays have provided a useful tool to the understanding of the mechanisms underlying the development of neoplasia .", "target_text": { "X chromosomes": "DNA", "X-linked markers": "protein" } }, { "input_text": "Recently , a technique of clonal analysis has been devised that takes advantage of a highly polymorphic short tandem repeat within the X-linked human androgen receptor ( AR ) gene , resulting in a heterozygosity rate approaching 90 % .", "target_text": { "short tandem repeat": "DNA", "X-linked human androgen receptor ( AR ) gene": "DNA" } }, { "input_text": "The rapid expansion of the number of women now suitable for X inactivation analysis has however given rise to new controversies , one of the more troublesome being the possibility of a modification of the pattern of X- chromosome inactivation pattern in blood cells of elderly women .", "target_text": { "X- chromosome": "DNA", "blood cells": "cell_type" } }, { "input_text": "In the present study we analyze with the AR assay a group of 166 healthy females aged between 8 and 94 years , with no history of genetic or neoplastic familial disorders .", "target_text": {} }, { "input_text": "We failed to find any correlation between age and X- chromosome inactivation pattern ( r = 0.17 ) , even subdividing the subjects in different age groups according to the criteria used by other researchers , and therefore reaffirm that , when tested for with well-standardized and accurate criteria , extremely unbalanced inactivation of the X chromosome is a truly uncommon phenomenon in normal women .", "target_text": { "X- chromosome": "DNA", "X chromosome": "DNA" } }, { "input_text": "Copyright 1998 Academic Press .", "target_text": {} }, { "input_text": "The role of Stat4 in species-specific regulation of Th cell development by type I IFNs .", "target_text": { "Stat4": "protein", "type I IFNs": "protein" } }, { "input_text": "Type I IFNs ( IFN-alpha/beta ) , in addition to IL-12 , have been shown to play an important role in the differentiation of human , but not mouse , Th cells .", "target_text": { "Type I IFNs": "protein", "IFN-alpha/beta": "protein", "IL-12": "protein", "Th cells": "cell_type" } }, { "input_text": "We show here that IFN-alpha/beta act directly on human T cells to drive Th1 development , bypassing the need for IL-12 -induced signaling , whereas IFN-alpha can not substitute IL-12 for mouse Th1 development .", "target_text": { "IFN-alpha/beta": "protein", "human T cells": "cell_type", "IL-12": "protein", "IFN-alpha": "protein" } }, { "input_text": "The molecular basis for this species specificity is that IFN-alpha /beta activate Stat4 in differentiating human , but not mouse , Th cells .", "target_text": { "IFN-alpha": "protein", "IFN-alpha /beta": "protein", "Stat4": "protein", "Th cells": "cell_type" } }, { "input_text": "Unlike IL-12 , which acts only on Th1 cells , IFN-alpha /beta can activate Stat4 not only in human Th1 , but also in Th2 cells .", "target_text": { "IL-12": "protein", "Th1 cells": "cell_type", "IFN-alpha": "protein", "IFN-alpha /beta": "protein", "Stat4": "protein", "human Th1": "cell_type", "Th2 cells": "cell_type" } }, { "input_text": "However , restimulation of human Th2 lines and clones in the presence of IFN-alpha does not induce the production of IFN-gamma .", "target_text": { "human Th2 lines": "cell_line", "IFN-alpha": "protein", "IFN-gamma": "protein" } }, { "input_text": "These results suggest that activation of Stat4 , which is necessary for the differentiation of naive T cells into polarized Th1 cells , is not sufficient to induce phenotype reversal of human Th2 cells .", "target_text": { "Stat4": "protein", "naive T cells": "cell_type", "Th1 cells": "cell_type", "human Th2 cells": "cell_type" } }, { "input_text": "Molecular cloning of FKHRL1P2 , a member of the developmentally regulated fork head domain transcription factor family .", "target_text": { "FKHRL1P2": "protein", "fork head domain transcription factor family": "protein" } }, { "input_text": "Here we report the expression of a fork head domain protein in human T helper cells .", "target_text": { "fork head domain protein": "protein", "human T helper cells": "cell_type" } }, { "input_text": "We cloned and characterized a fork head cDNA from human T helper cell mRNA using differential display RT-PCR .", "target_text": { "fork head cDNA": "DNA", "human T helper cell mRNA": "RNA" } }, { "input_text": "The cDNA contains a 546-nucleotide ( nt ) open reading frame ( ORF ) that codes for the carboxyl-terminal 180 amino acids ( aa ) of the recently identified fkhrl1 gene .", "target_text": { "546-nucleotide ( nt ) open reading frame": "DNA", "ORF": "DNA", "carboxyl-terminal 180 amino acids": "protein", "fkhrl1 gene": "DNA" } }, { "input_text": "This ORF does not contain the characteristic DNA-binding domain found in members of the forkhead protein family .", "target_text": { "ORF": "DNA", "DNA-binding domain": "DNA", "forkhead protein family": "protein" } }, { "input_text": "In-vitro transcription/translation of this cDNA expressed a protein of approximately 20 kDa .", "target_text": { "cDNA": "DNA" } }, { "input_text": "We have generated antibodies that specifically immunoprecipitated the in-vitro-translated 20-kDa protein .", "target_text": { "in-vitro-translated 20-kDa protein": "protein" } }, { "input_text": "This antibody also recognizes in human T lymphocytes a 70-kDa protein corresponding in size to that predicted for the fkhrl1 gene product .", "target_text": { "human T lymphocytes": "cell_type", "fkhrl1 gene": "DNA" } }, { "input_text": "The mRNA levels for fkhrl1 is elevated in T helper-induced lymphocytes in comparison to PHA-stimulated T lymphocytes .", "target_text": { "fkhrl1": "DNA", "T helper-induced lymphocytes": "cell_type", "PHA-stimulated T lymphocytes": "cell_line" } }, { "input_text": "Further characterization of FKHRL1 and its related family members should shed light on the transcriptional mechanisms of this fork head gene subfamily and their role in T helper cell differentiation and regulation of cell growth .", "target_text": { "FKHRL1": "DNA", "fork head gene subfamily": "DNA" } }, { "input_text": "Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism .", "target_text": { "GATA-3": "protein" } }, { "input_text": "Recently , the transcription factor GATA-3 was shown to be selectively expressed in Th2 but not Th1 cells and to augment Th2-specific cytokines .", "target_text": { "transcription factor": "protein", "GATA-3": "protein", "Th1 cells": "cell_type", "Th2-specific cytokines": "protein" } }, { "input_text": "Here , we show that loss of GATA-3 expression by developing Th1 cells requires IL-12 signaling through Stat4 and does not simply result from an absence of IL-4 .", "target_text": { "GATA-3": "protein", "Th1 cells": "cell_type", "IL-12": "protein", "Stat4": "protein", "IL-4": "protein" } }, { "input_text": "Moreover , we demonstrate a novel role for GATA-3 in directly repressing Th1 development distinct from its positive actions on Th2-specific cytokines .", "target_text": { "GATA-3": "protein", "Th2-specific cytokines": "protein" } }, { "input_text": "GATA-3 inhibits Th1 cytokines by a cell-intrinsic mechanism that is not dependent on IL-4 and that may involve repression of IL-12 signaling .", "target_text": { "GATA-3": "protein", "Th1 cytokines": "protein", "IL-4": "protein", "IL-12": "protein" } }, { "input_text": "Thus , GATA-3 expression and IL-12 signaling are mutually antagonistic , which facilitates rapid dominance of one pathway during early Th development , producing a stable divergence in cytokine profiles .", "target_text": { "GATA-3": "protein", "IL-12": "protein", "cytokine": "protein" } }, { "input_text": "Conserved elements containing NF-E2 and tandem GATA binding sites are required for erythroid-specific chromatin structure reorganization within the human beta-globin locus control region .", "target_text": { "Conserved elements": "DNA", "erythroid-specific chromatin structure": "DNA", "human beta-globin locus control region": "DNA" } }, { "input_text": "Proper expression of the genes of the human beta-globin gene locus requires the associated locus control region ( LCR ) .", "target_text": { "human beta-globin gene locus": "DNA", "locus control region": "DNA", "LCR": "DNA" } }, { "input_text": "Structurally , the LCR is defined by the presence of four domains of erythroid-specific chromatin structure .", "target_text": { "LCR": "DNA", "erythroid-specific chromatin structure": "DNA" } }, { "input_text": "These domains , which have been characterized as DNase I hypersensitive sites ( HSs ) , comprise the active elements of the LCR .", "target_text": { "DNase I hypersensitive sites": "DNA", "HSs": "DNA", "LCR": "DNA" } }, { "input_text": "The major focus of this research is to define the cis -acting elements which are required for the formation of these domains of unique chromatin structure .", "target_text": { "cis -acting elements": "DNA", "chromatin structure": "DNA" } }, { "input_text": "Our previous investigations on the formation of LCR HS4 demonstrated that NF-E2 and tandem , inverted GATA binding sites are required for the formation of the native HS .", "target_text": { "LCR HS4": "DNA", "native HS": "DNA" } }, { "input_text": "Similarly arranged NF-E2 and tandem GATA sites are present within the core regions of the other human LCR HSs and are evolutionarily conserved .", "target_text": { "core regions": "DNA", "human LCR HSs": "DNA" } }, { "input_text": "Using site-directed mutagenesis of human HSs 2 and 3 we have tested the hypothesis that these NF-E2 and GATA sites are common requirements for the formation of all LCR HSs .", "target_text": { "LCR HSs": "DNA" } }, { "input_text": "We find that mutation of these elements , and particularly the GATA elements , results in a decrease or complete loss of DNase I hypersensitivity .", "target_text": { "GATA elements": "DNA", "DNase I": "protein" } }, { "input_text": "These data imply the presence of common structural elements within the core of each LCR HS which are required for erythroid-specific chromatin structure reorganization .", "target_text": { "LCR HS": "DNA", "erythroid-specific chromatin structure": "DNA" } }, { "input_text": "Cloning of ARE-containing genes by AU-motif-directed display .", "target_text": { "ARE-containing genes": "DNA" } }, { "input_text": "A procedure suitable for cloning labile mRNAs that contain AU motifs is presented ( AU-DD ) .", "target_text": { "cloning labile mRNAs": "RNA", "AU motifs": "RNA", "AU-DD": "RNA" } }, { "input_text": "These motifs are regulatory sequences within the so-called AU-rich elements ( AREs ) often found in 3' untranslated regions of genes such as cytokines , proto-oncogenes , and transcription factors .", "target_text": { "regulatory sequences": "DNA", "AU-rich elements": "DNA", "AREs": "DNA", "3' untranslated regions": "DNA", "cytokines": "protein", "proto-oncogenes": "DNA", "transcription factors": "protein" } }, { "input_text": "AU-DD is an AU-motif-directed differential display that permits the identification of ARE-containing genes differentially expressed after cell activation .", "target_text": { "AU-DD": "DNA", "AU-motif-directed differential display": "DNA", "ARE-containing genes": "DNA" } }, { "input_text": "It has been applied to peripheral blood monocytes and a T cell clone to isolate 59 cDNA fragments associated to activation .", "target_text": { "peripheral blood monocytes": "cell_type", "T cell clone": "cell_line", "59 cDNA fragments": "DNA" } }, { "input_text": "Fourteen percent of isolated fragments belong to already known genes that certainly are cytokines and transduction/ transcription factors .", "target_text": { "cytokines": "protein", "transcription factors": "protein", "transduction/ transcription factors": "protein" } }, { "input_text": "The remaining 86 % correspond to unknown genes of which 92 % have been confirmed to be differentially expressed .", "target_text": { "genes": "DNA" } }, { "input_text": "These data demonstrate the efficiency of the system and support the notion that numerous genes falling into those categories remain unidentified and that they can be cloned by this method .", "target_text": { "genes": "DNA" } }, { "input_text": "Copyright 1998 Academic Press .", "target_text": {} }, { "input_text": "Transcription factor NF-kappaB regulation of renal fibrosis during ureteral obstruction .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Irrespective of the etiology , many kidney diseases result in inflammation and fibrosis of the tubulointerstitium , with the subsequent loss of renal function .", "target_text": {} }, { "input_text": "To initiate any disease process or for any disease process to progress , there must be changes in the transcription of genes within the affected tissue .", "target_text": {} }, { "input_text": "The nuclear factor-kappa B ( NF-kappaB ) family of transcription factors regulates genes involved in inflammation , cell proliferation , and cell differentiation .", "target_text": { "nuclear factor-kappa B": "protein", "NF-kappaB": "protein", "nuclear factor-kappa B ( NF-kappaB ) family": "protein", "transcription factors": "protein" } }, { "input_text": "This review discusses the NF-kappaB transcription factor family in general and the association of NF-kappaB activation with cellular/molecular events of renal inflammation and fibrosis", "target_text": { "NF-kappaB": "protein", "transcription factor": "protein", "NF-kappaB transcription factor family": "protein" } }, { "input_text": "Expression of transcription factors during sodium phenylacetate induced erythroid differentiation in K562 cells .", "target_text": { "transcription factors": "protein", "K562 cells": "cell_line" } }, { "input_text": "During 15 days of treatment of K562 cells with sodium phenylacetate , we observed an increase in the cellular hemoglobin concentration with a similar increase in the expression of gamma-globin mRNA .", "target_text": { "K562 cells": "cell_line", "hemoglobin": "protein", "gamma-globin mRNA": "RNA" } }, { "input_text": "Morphological studies demonstrated characteristic features of erythroid differentiation and maturation .", "target_text": {} }, { "input_text": "At the same time there was no change in the level of expression of the cell surface antigenes CD33 , CD34 , CD45 , CD71 and glycophorin A .", "target_text": { "cell surface antigenes": "protein", "CD33": "protein", "CD34": "protein", "CD45": "protein", "CD71": "protein", "glycophorin A": "protein" } }, { "input_text": "Likewise , the level of expression of the erythroid transcription factors GATA-1 , GATA-2 , NF-E2 , SCL and RBTN2 , all expressed in untreated K562 cells , did not increase during sodium phenylacetate induced erythroid differentiation .", "target_text": { "transcription factors": "protein", "erythroid transcription factors": "protein", "GATA-1": "protein", "GATA-2": "protein", "NF-E2": "protein", "SCL": "protein", "RBTN2": "protein", "K562 cells": "cell_line" } }, { "input_text": "The expression of the nuclear factors Evi-1 and c-myb , known to inhibit erythroid differentiation , did not decrease .", "target_text": { "nuclear factors": "protein", "Evi-1": "protein", "c-myb": "protein" } }, { "input_text": "We conclude that sodium phenylacetate treatment of K562 cells increases gamma-globin mRNA and induces cell maturation as judged by morphology without affecting the expression of the erythroid transcription factors , some of which are known to be involved in the regulation of beta-like globin genes .", "target_text": { "K562 cells": "cell_line", "gamma-globin mRNA": "RNA", "transcription factors": "protein", "erythroid transcription factors": "protein", "beta-like globin genes": "DNA" } }, { "input_text": "Isolation of a B-cell-specific promoter for the human class II transactivator .", "target_text": { "B-cell-specific promoter": "DNA", "human class II transactivator": "protein" } }, { "input_text": "The class II transactivator ( CIITA ) is essential for the expression of major histocompatibility complex ( MHC ) class II antigens .", "target_text": { "class II transactivator": "protein", "CIITA": "protein", "major histocompatibility complex ( MHC ) class II antigens": "protein" } }, { "input_text": "The tissular patterns of CIITA and MHC class II gene expression are tightly correlated : CIITA mRNA is highly expressed in B cells , and is induced by interferon gamma ( IFN-gamma ) in macrophage and epithelial cell lines .", "target_text": { "CIITA mRNA": "RNA", "B cells": "cell_type", "interferon gamma": "protein", "IFN-gamma": "protein" } }, { "input_text": "We first isolated two overlapping cosmids encoding human CIITA which , when co-transfected , are able to restore MHC class II expression in a B-lymphoblastoid cell line ( B-LCL ) defective for CIITA .", "target_text": { "cosmids": "DNA", "human CIITA": "protein", "MHC class II": "protein", "B-lymphoblastoid cell line": "cell_line", "B-LCL": "cell_line", "CIITA": "protein" } }, { "input_text": "Subsequently , a 1.8 kilobase ( kb ) fragment of the CIITA promoter was isolated and sequenced .", "target_text": { "1.8 kilobase ( kb ) fragment": "DNA", "CIITA promoter": "DNA" } }, { "input_text": "A motif presenting a strong similarity to an initiator was detected , as well as putative binding sites for Sp1 , GATA-2 , LyF-1 , ets-1 , AP1 , and MZF1 transcription factors , and two GAS motifs .", "target_text": { "putative binding sites": "DNA", "Sp1": "protein", "GATA-2": "protein", "LyF-1": "protein", "ets-1": "protein", "AP1": "protein", "MZF1": "protein", "transcription factors": "protein", "GAS motifs": "DNA" } }, { "input_text": "When introduced in front of a luciferase reporter gene , this promoter is able to direct a high luciferase activity in a human B-LCL .", "target_text": { "luciferase reporter gene": "DNA", "luciferase": "protein", "human B-LCL": "cell_line" } }, { "input_text": "In contrast , luciferase expression was not stimulated after IFN-gamma treatment when the construct was transfected in macrophage or in epithelial cell lines .", "target_text": { "luciferase": "protein", "IFN-gamma": "protein", "epithelial cell lines": "cell_line" } }, { "input_text": "However , an induction of the human CIITA gene was observed in mouse macrophage and fibrosarcoma cell lines , when the cells were transfected with a cosmid containing the human CIITA gene , but lacking the 1.8 kb promoter described above .", "target_text": { "human CIITA gene": "DNA", "cosmid": "DNA", "1.8 kb promoter": "DNA" } }, { "input_text": "Taken together , these data suggest the existence of an intragenic promoter driving an IFN-gamma -inducible expression of CIITA .", "target_text": { "IFN-gamma": "protein", "CIITA": "protein" } }, { "input_text": "Phenotypic and functional studies of leukocytes in human endometrium and endometriosis .", "target_text": { "leukocytes": "cell_type" } }, { "input_text": "The aetiology of endometriosis , a common and disabling disorder , is presently unknown , although immune dysfunction could allow ectopic endometrial fragments to survive outside the uterine cavity .", "target_text": {} }, { "input_text": "These studies investigate the relationship between leukocyte populations , steroid hormone receptor expression , proliferative activity , bcl-2 expression and apoptosis in eutopic and ectopic endometrium from women with endometriosis or adenomyosis at different phases of the menstrual cycle .", "target_text": { "leukocyte populations": "cell_type", "steroid hormone receptor": "protein", "bcl-2": "protein" } }, { "input_text": "Significantly increased oestrogen receptor expression , bcl-2 expression and numbers of CD8+ leukocytes were found in ectopic compared with eutopic endometrium in endometriosis , and CD56+ endometrial granulated lymphocytes ( eGLs ) were significantly reduced in ectopic endometrium .", "target_text": { "oestrogen receptor": "protein", "bcl-2": "protein", "leukocytes": "cell_type" } }, { "input_text": "Apoptotic cells were rarely found in control and subject endometria .", "target_text": { "Apoptotic cells": "cell_type" } }, { "input_text": "In contrast with endometriosis , adenomyotic lesions showed identical steroid hormone receptor expression , proliferative activity , bcl-2 expression and leukocyte subpopulations to eutopic endometrium , indicating different aetiologies for these disorders .", "target_text": { "steroid hormone receptor": "protein", "bcl-2": "protein" } }, { "input_text": "The unusual CD56+ CD16- eGLs present in large numbers in late secretory phase eutopic endometrium were highly purified ( > 98 % ) by immunomagnetic separation .", "target_text": { "CD56+ CD16- eGLs": "cell_type" } }, { "input_text": "Except for a negligible cytotoxic activity of eGLs from early proliferative samples , cytotoxic activity of eGLs from non-pregnant endometrium during the menstrual cycle was comparable with those in peripheral blood , predominantly CD56+ CD16+ natural killer cells .", "target_text": { "eGLs": "cell_type", "CD56+ CD16+ natural killer cells": "cell_type" } }, { "input_text": "eGLs from non-pregnant endometrium and early pregnancy showed a variable proliferative response to 5 and 100 U/ml interleukin-2 over 48-h and 120-h time courses .", "target_text": { "eGLs": "cell_type", "interleukin-2": "protein" } }, { "input_text": "eGLs are evidently functionally important in the eutopic endometrium .", "target_text": { "eGLs": "cell_type" } }, { "input_text": "Their absence in endometriotic lesions together with increased CD+8 T-cell numbers and increased oestrogen receptor and bcl-2 expression may have significant effects on the development and progression of endometriosis .", "target_text": { "CD+8 T-cell": "cell_type", "oestrogen receptor": "protein", "bcl-2": "protein" } }, { "input_text": "Regulation of interleukin-1beta transcription by Epstein-Barr virus involves a number of latent proteins via their interaction with RBP .", "target_text": { "interleukin-1beta": "protein", "latent proteins": "protein", "RBP": "protein" } }, { "input_text": "Epstein-Barr virus ( EBV ) infects B cells , resulting in the outgrowth of immortalised lymphoblastoid cell lines ( LCLs ) .", "target_text": { "B cells": "cell_type", "immortalised lymphoblastoid cell lines": "cell_line", "LCLs": "cell_line" } }, { "input_text": "Here , we demonstrate through the use of intracellular staining that interleukin-1beta ( IL-1beta ) is expressed in LCLs and investigate the influence of the individual latent proteins on the expression of IL-1beta .", "target_text": { "interleukin-1beta": "protein", "IL-1beta": "protein", "LCLs": "cell_line", "latent proteins": "protein" } }, { "input_text": "Using RT-PCR , IL-1beta was shown to be up-regulated in EBV-transformed LCLs as well as in group III Burkitt 's lymphoma ( BL ) cell lines , compared with group I BL cell lines .", "target_text": { "IL-1beta": "protein", "LCLs": "cell_line", "EBV-transformed LCLs": "cell_line", "group III Burkitt 's lymphoma ( BL ) cell lines": "cell_line", "group I BL cell lines": "cell_line" } }, { "input_text": "The up-regulation of IL-1beta message could be mediated by the latent membrane protein-1 , EBV nuclear proteins 2 , 3 , 4 , and 6 genes .", "target_text": { "IL-1beta": "protein", "latent membrane protein-1": "protein" } }, { "input_text": "Electrophoretic mobility shift assays ( EMSAs ) demonstrated that the -300 region of the IL-1beta promoter , which contains a nuclear factor-kappaB ( NF-kappaB ) binding site , contained a functional RBP binding site .", "target_text": { "IL-1beta": "protein", "nuclear factor-kappaB": "protein", "NF-kappaB": "protein", "nuclear factor-kappaB ( NF-kappaB ) binding site": "DNA", "functional RBP binding site": "DNA" } }, { "input_text": "Binding of RBP to this site could be inhibited by addition of EBV nuclear proteins 3 and 6 , suggesting that these proteins displace RBP from its recognition sequence , removing transcriptional repression and allowing gene transcription to occur .", "target_text": { "RBP": "protein", "recognition sequence": "DNA" } }, { "input_text": "In group I BL cells , containing low levels of NF-kappaB , only RBP binding was observed in EMSAs , whereas NF-kappaB binding could be demonstrated in EBV-transformed B cell lines containing high levels of activated NF-kappaB .", "target_text": { "group I BL cells": "cell_line", "NF-kappaB": "protein", "RBP": "protein", "EBV-transformed B cell lines": "cell_line" } }, { "input_text": "In addition , the expression of latent membrane protein-1 led to activation of NF-kappaB that was capable of binding the IL-1beta promoter .", "target_text": { "latent membrane protein-1": "protein", "NF-kappaB": "protein", "IL-1beta": "protein", "IL-1beta promoter": "DNA" } }, { "input_text": "The study demonstrates that EBV can up-regulate IL-1beta expression , possibly by using RBP , NF-kappaB , or both .", "target_text": { "IL-1beta": "protein", "RBP": "protein", "NF-kappaB": "protein" } }, { "input_text": "Copyright 1998 Academic Press .", "target_text": {} }, { "input_text": "CD27 /CD70 interaction augments IgE secretion by promoting the differentiation of memory B cells into plasma cells .", "target_text": { "CD27": "protein", "IgE": "protein", "memory B cells": "cell_type", "plasma cells": "cell_type" } }, { "input_text": "The induction of IgE switching in B cells requires several signals given by cytokines and cell contact-delivered signals .", "target_text": { "IgE": "protein", "B cells": "cell_type", "cytokines": "protein" } }, { "input_text": "Here , we investigated the role of CD27 /CD70 interaction in B cell IgE synthesis .", "target_text": { "CD27": "protein", "IgE": "protein" } }, { "input_text": "The addition of CD27 ligand ( CD70 ) transfectants to B cell cultures increased the IgE synthesis synergistically in the presence of IL-4 plus anti-CD40 mAb ( anti-CD40 ) .", "target_text": { "B cell cultures": "cell_line", "IgE": "protein", "IL-4": "protein", "anti-CD40 mAb": "protein", "anti-CD40": "protein" } }, { "input_text": "The effect of CD70 transfectants was dose dependent and was completely blocked by anti-CD70 mAb .", "target_text": { "CD70 transfectants": "cell_line", "anti-CD70 mAb .": "protein" } }, { "input_text": "CD27+ B cells had the ability to produce IgE , which was increased by contact with CD70 transfectants , whereas CD27- B cells did not produce IgE .", "target_text": { "CD27+ B cells": "cell_type", "IgE": "protein" } }, { "input_text": "CD27 /CD70 interaction enhanced B cell proliferation in the presence of IL-4 or IL-4 plus anti-CD40 .", "target_text": { "CD27": "protein", "B cell": "cell_type", "IL-4": "protein", "anti-CD40": "protein" } }, { "input_text": "The augmentation of B cell proliferation by CD70 transfectants was apparent in CD27+ B cells , but was mild in CD27- B cells .", "target_text": { "CD27+ B cells": "cell_type", "CD27- B cells": "cell_type" } }, { "input_text": "The helper activity for IgE synthesis by the CD27 /CD70 interaction did not contribute to the enhancement of germline epsilon transcripts .", "target_text": { "IgE": "protein", "CD27": "protein", "germline epsilon transcripts": "RNA" } }, { "input_text": "Flow cytometric and morphological analyses demonstrated that the addition of CD70 transfectants to B cell cultures remarkably promoted differentiation into plasma cells in the presence of IL-4 and CD40 signaling .", "target_text": { "B cell cultures": "cell_line", "plasma cells": "cell_type", "IL-4": "protein", "CD40": "protein" } }, { "input_text": "Finally , CD27 cross-linking resulted in the up-regulation of positive regulatory domain I-binding factor-1 .", "target_text": { "CD27": "protein", "positive regulatory domain I-binding factor-1": "protein" } }, { "input_text": "Taken together , our findings indicate that signaling via CD27 on B cells induces IgE synthesis , in cooperation with IL-4 and CD40 signaling , by promoting the generation of plasma cells through up-regulation of positive regulatory domain I-binding factor-1 .", "target_text": { "CD27": "protein", "B cells": "cell_type", "IgE": "protein", "IL-4": "protein", "CD40": "protein", "plasma cells": "cell_type", "positive regulatory domain I-binding factor-1": "protein" } }, { "input_text": "Human immunodeficiency virus type-1 transcription : role of the 5'-untranslated leader region ( review ) .", "target_text": {} }, { "input_text": "Human immunodeficiency virus type-1 ( HIV-1 ) transcription is dependent on the interaction of host-cell transcription factors with cis-regulatory DNA elements within the viral long terminal repeat ( LTR ) .", "target_text": { "transcription factors": "protein", "host-cell transcription factors": "protein", "cis-regulatory DNA elements": "DNA", "viral long terminal repeat": "DNA", "LTR": "DNA" } }, { "input_text": "Much attention has focused on the series of sequence elements upstream of the transcriptional initiation site in the U3 region of the LTR including the Sp1 and NF-kappaB binding sites .", "target_text": { "transcriptional initiation site": "DNA", "U3 region": "DNA", "LTR": "DNA", "Sp1": "protein", "NF-kappaB": "protein", "binding sites": "DNA" } }, { "input_text": "Recent studies , however , demonstrate that the transcribed 5'-untranslated leader region ( 5'-UTR ) also contains important transcriptional elements .", "target_text": { "5'-untranslated leader region": "DNA", "5'-UTR": "DNA", "transcriptional elements": "DNA" } }, { "input_text": "These regulatory elements situated downstream of transcription interact with constitutive and inducible transcription factors , mediate transmission of cellular activation signals , and are important for efficient HIV-1 transcription and replication .", "target_text": { "regulatory elements": "DNA", "transcription factors": "protein" } }, { "input_text": "The 5'-UTR contains binding sites for the transcription factors AP-1 , NF-kappaB , NF-AT , IRF , and Sp1 .", "target_text": { "5'-UTR": "DNA", "binding sites": "DNA", "transcription factors": "protein", "NF-kappaB": "protein", "NF-AT": "protein", "IRF": "protein", "Sp1": "protein" } }, { "input_text": "Mutations in these binding sites can interfere with the viral response to cell activation signals , decrease LTR transcription , and inhibit viral replication .", "target_text": { "binding sites": "DNA", "LTR": "DNA" } }, { "input_text": "The 5'-UTR also interacts with a specific nucleosome that is rapidly displaced during transcriptional activation of the latent provirus .", "target_text": { "5'-UTR": "DNA", "nucleosome": "protein" } }, { "input_text": "We propose that the inducible transcription factor binding sites in the 5'-UTR comprise a downstream enhancer domain that can function independent of , or in concert with , the LTR promoter to rapidly increase latent proviral transcription in response to cell activation signals .", "target_text": { "binding sites": "DNA", "inducible transcription factor binding sites": "DNA", "5'-UTR": "DNA", "downstream enhancer domain": "DNA", "LTR": "DNA", "LTR promoter": "DNA" } }, { "input_text": "In this review , we describe the host-cell transcription factors that interact with the 5'-UTR and discuss their role in the transcriptional regulation of HIV-1 gene expression .", "target_text": { "transcription factors": "protein", "host-cell transcription factors": "protein", "5'-UTR": "DNA" } }, { "input_text": "Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76 .", "target_text": { "linker protein": "protein", "SLP-76": "protein" } }, { "input_text": "Tyrosine phosphorylation of linker proteins enables the T cell antigen receptor ( TCR ) -associated protein tyrosine kinases to phosphorylate and regulate effector molecules that generate second messengers .", "target_text": { "linker proteins": "protein", "T cell antigen receptor ( TCR ) -associated protein tyrosine kinases": "protein", "effector molecules": "protein", "second messengers": "protein" } }, { "input_text": "We demonstrate here that the SLP-76 linker protein interacts with both nck , an adaptor protein , and Vav , a guanine nucleotide exchange factor for Rho-family GTPases .", "target_text": { "SLP-76": "protein", "nck": "protein", "adaptor protein": "protein", "Vav": "protein", "guanine nucleotide exchange factor": "protein", "Rho-family GTPases": "protein" } }, { "input_text": "The assembly of this tri-molecular complex permits the activated Rho-family GTPases to regulate target effectors that interact through nck .", "target_text": { "tri-molecular complex": "protein", "Rho-family GTPases": "protein", "nck": "protein" } }, { "input_text": "In turn , assembly of this complex mediates the enzymatic activation of the p21-activated protein kinase 1 and facilitates actin polymerization .", "target_text": { "p21-activated protein kinase 1": "protein", "actin": "protein" } }, { "input_text": "Hence , phosphorylation of linker proteins not only bridges the TCR-associated PTK , ZAP-70 , with downstream effector proteins , but also provides a scaffold to integrate distinct signaling complexes to regulate T cell function .", "target_text": { "linker proteins": "protein", "TCR-associated PTK": "protein", "ZAP-70": "protein", "signaling complexes": "protein", "T cell": "cell_type" } }, { "input_text": "Interleukin-12 expression in B cells by transformation with Epstein-Barr virus .", "target_text": { "Interleukin-12": "protein", "B cells": "cell_type" } }, { "input_text": "Although interleukin ( IL ) -12 was originally purified from an Epstein-Barr ( EBV ) -transformed B cell line and the high correlation of EBV infection and IL-12 expression has been suggested , no study has reported whether EBV infection is directly linked to IL-12 expression .", "target_text": { "interleukin ( IL ) -12": "protein", "Epstein-Barr ( EBV ) -transformed B cell line": "cell_line", "IL-12": "protein" } }, { "input_text": "To address this issue , we have investigated IL-12 expression in B cells during in vitro transformation with EBV .", "target_text": { "IL-12": "protein", "B cells": "cell_type" } }, { "input_text": "Human peripheral B cells became capable of constitutively producing p40 by in vitro transformation with EBV , coincident with the expression of latent membrane protein 1 ( LMP1 ) of EBV .", "target_text": { "Human peripheral B cells": "cell_type", "latent membrane protein 1": "protein", "LMP1": "protein" } }, { "input_text": "These B cells expressed p40 and p35 mRNA , and phorbol myristate acetate ( PMA ) stimulation strongly enhanced p40 and p70 production .", "target_text": { "B cells": "cell_type" } }, { "input_text": "Furthermore , transfection with LMP1 expression vector into a human B lymphoma cell line , Daudi , led to p40 production with nuclear factor ( NF ) -kappaB activation .", "target_text": { "LMP1": "protein", "LMP1 expression vector": "DNA", "human B lymphoma cell line": "cell_line", "Daudi": "cell_line", "p40": "protein", "nuclear factor ( NF ) -kappaB": "protein" } }, { "input_text": "These results suggest that transformation of primary B cells with EBV induces IL-12 expression potentially through LMP1 expression .", "target_text": { "primary B cells": "cell_type", "IL-12": "protein", "LMP1": "protein" } }, { "input_text": "Copyright 1998 Academic Press .", "target_text": {} }, { "input_text": "The human gene encoding the lectin-type oxidized LDL receptor ( OLR1 ) is a novel member of the natural killer gene complex with a unique expression profile .", "target_text": { "human gene": "DNA", "lectin-type oxidized LDL receptor": "protein", "OLR1": "protein", "natural killer gene complex": "protein" } }, { "input_text": "LOX-1 is an endothelial receptor for oxidized low-density lipoprotein that plays essential roles in atherogenesis .", "target_text": { "LOX-1": "protein", "endothelial receptor": "protein", "oxidized low-density lipoprotein": "protein" } }, { "input_text": "LOX-1 has the highest homology with C-type lectin receptors expressed on natural killer cells .", "target_text": { "LOX-1": "protein", "C-type lectin receptors": "protein", "natural killer cells": "cell_type" } }, { "input_text": "In the present study , we cloned and characterized the human LOX-1 gene ( HGMW-approved symbol OLR1 ) .", "target_text": { "human LOX-1 gene": "DNA", "OLR1": "protein", "HGMW-approved symbol OLR1": "protein" } }, { "input_text": "The gene structure of LOX-1 resembles that of the natural killer cell receptors .", "target_text": { "LOX-1": "protein", "natural killer cell receptors": "protein" } }, { "input_text": "Fluorescence in situ hybridization and analyses of a yeast artificial chromosome contig revealed that the human LOX-1 gene is located in the natural killer gene complex on chromosome 12p12-p13 , where the genes of the natural killer cell receptors cluster .", "target_text": { "LOX-1": "protein", "human LOX-1 gene": "DNA", "natural killer gene complex": "protein", "chromosome 12p12-p13": "DNA", "natural killer cell receptors": "protein" } }, { "input_text": "In contrast , the expression pattern of LOX-1 is different from that of the natural killer cell receptors ; LOX-1 is expressed in vascular-rich organs , but not in lymphocytes .", "target_text": { "LOX-1": "protein", "natural killer cell receptors": "protein", "lymphocytes": "cell_type" } }, { "input_text": "A 1753-bp fragment of the 5' flanking region of the LOX-1 gene had a functional promoter activity .", "target_text": { "1753-bp fragment": "DNA", "5' flanking region": "DNA", "LOX-1": "protein", "LOX-1 gene": "DNA" } }, { "input_text": "This region contains binding sites for several transcription factors , including the STAT family and NF-IL6 , and the expression of LOX-1 was upregulated by several cytokines .", "target_text": { "binding sites": "DNA", "transcription factors": "protein", "STAT family": "protein", "NF-IL6": "protein", "LOX-1": "protein", "cytokines": "protein" } }, { "input_text": "These results demonstrate that the human LOX-1 gene is a new member of the natural killer gene complex with a unique expression profile .", "target_text": { "LOX-1": "protein", "human LOX-1 gene": "DNA", "natural killer gene complex": "protein" } }, { "input_text": "Copyright 1998 Academic Press .", "target_text": {} }, { "input_text": "Transcriptional regulation of the beta-casein gene by cytokines : cross-talk between STAT5 and other signaling molecules .", "target_text": { "beta-casein": "protein", "beta-casein gene": "DNA", "cytokines": "protein", "STAT5": "protein", "signaling molecules": "protein" } }, { "input_text": "The beta-casein promoter has been widely used to monitor the activation of STAT ( signal transducer and activator of transcription ) 5 since STAT5 was originally found as a mediator of PRL-inducible beta-casein expression .", "target_text": { "beta-casein": "protein", "beta-casein promoter": "DNA", "STAT ( signal transducer and activator of transcription ) 5": "protein", "STAT5": "protein" } }, { "input_text": "However , not only is expression of the beta-casein gene regulated by STAT5 but it is also affected by other molecules such as glucocorticoid and Ras .", "target_text": { "beta-casein": "protein", "beta-casein gene": "DNA", "STAT5": "protein", "Ras": "protein" } }, { "input_text": "In this report , we describe the transcriptional regulation of the beta-casein gene by cytokines in T cells .", "target_text": { "beta-casein": "protein", "beta-casein gene": "DNA", "cytokines": "protein", "T cells": "cell_type" } }, { "input_text": "We have found that the beta-casein gene is expressed in a cytotoxic T cell line , CTLL-2 , in response to interleukin-2 ( IL-2 ) , which activates STAT5 .", "target_text": { "beta-casein": "protein", "beta-casein gene": "DNA", "cytotoxic T cell line": "cell_line", "CTLL-2": "cell_line", "interleukin-2": "protein", "IL-2": "protein", "STAT5": "protein" } }, { "input_text": "While IL-4 does not activate STAT5 , it induces expression of STAT5 -regulated genes in CTLL-2 , i.e. beta-casein , a cytokine-inducible SH2-containing protein ( CIS ) , and oncostatin M ( OSM ) , suggesting that STAT6 activated by IL-4 substitutes for the function of STAT5 in T cells .", "target_text": { "IL-4": "protein", "STAT5": "protein", "STAT5 -regulated genes": "DNA", "CTLL-2": "cell_line", "beta-casein": "protein", "cytokine-inducible SH2-containing protein": "protein", "CIS": "protein", "oncostatin M": "protein", "OSM": "protein", "T cells": "cell_type" } }, { "input_text": "IL-2 -induced beta-casein expression was enhanced by dexamethasone , and this synergistic effect of Dexamethasone requires the sequence between -155 and -193 in the beta-casein promoter .", "target_text": { "IL-2": "protein", "beta-casein": "protein", "-155 and -193": "DNA", "beta-casein promoter": "DNA" } }, { "input_text": "Coincidentally , a deletion of this region enhanced the IL-2 -induced expression of beta-casein .", "target_text": { "IL-2": "protein", "beta-casein": "protein" } }, { "input_text": "Expression of an active form of Ras , Ras(G12V) , suppressed the IL-2 -induced beta-casein and OSM gene expression , and the negative effect of Ras is mediated by the region between -105 and -193 in the beta-casein promoter .", "target_text": { "Ras": "protein", "Ras(G12V)": "protein", "IL-2": "protein", "beta-casein": "protein", "OSM": "protein", "-105 and -193": "DNA", "beta-casein promoter": "DNA" } }, { "input_text": "In apparent contradiction , expression of a dominant negative form of Ras , RasN17 , also inhibited IL-2 -induced activation of the promoter containing the minimal beta-casein STAT5 element as well as the promoters of CIS and OSM .", "target_text": { "Ras": "protein", "RasN17": "protein", "IL-2": "protein", "beta-casein": "protein", "STAT5": "protein", "beta-casein STAT5 element": "DNA", "CIS": "protein", "OSM": "protein" } }, { "input_text": "In addition , Ras(G12V) complemented signaling by an erythropoietin receptor mutant defective in Ras activation and augmented the activation of the beta-casein promoter by the mutant erythropoietin receptor signaling , suggesting a possible role of Ras in Stat5 -mediated gene expression .", "target_text": { "Ras(G12V)": "protein", "erythropoietin receptor mutant": "protein", "Ras": "protein", "beta-casein": "protein", "beta-casein promoter": "DNA", "mutant erythropoietin receptor": "protein", "Stat5": "protein" } }, { "input_text": "These results collectively reveal a complex interaction of STAT5 with other signaling pathways and illustrate that regulation of gene expression requires integration of opposing signals", "target_text": { "STAT5": "protein" } }, { "input_text": "GATA-3 represses gp91phox gene expression in eosinophil-committed HL-60-C15 cells .", "target_text": { "GATA-3": "protein", "gp91phox gene": "DNA", "eosinophil-committed HL-60-C15 cells": "cell_line" } }, { "input_text": "To study the regulatory mechanism of gp91phox gene expression in eosinophils , we transiently transfected eosinophil-committed HL-60-C15 cells with gp91phox promoter constructs , and identified a negative element from bp -267 to -246 of the gp91phox gene , the deletion of which caused an 83 % increase in promoter activity .", "target_text": { "gp91phox gene": "DNA", "eosinophil-committed HL-60-C15 cells": "cell_line", "gp91phox promoter constructs": "DNA", "negative element": "DNA", "-267 to -246": "DNA" } }, { "input_text": "Electrophoresis mobility shift assays demonstrated GATA-3 binds to the GATA consensus site from bp -256 to -250 .", "target_text": { "GATA-3": "protein", "GATA consensus site": "DNA", "-256 to -250 .": "DNA" } }, { "input_text": "An 81 % increment in promoter activity was obtained when a mutation was introduced in the GATA-3 binding site of the bp -267 to +12 construct , which is comparable to that of the bp -245 to +12 construct .", "target_text": { "GATA-3": "protein", "GATA-3 binding site": "DNA", "bp -267 to +12 construct": "DNA", "bp -245 to +12 construct": "DNA" } }, { "input_text": "We therefore conclude that GATA-3 specifically binding to the GATA site negatively regulates the expression of the gene in HL-60-C15 cells .", "target_text": { "GATA-3": "protein", "GATA site": "DNA", "HL-60-C15 cells": "cell_line" } }, { "input_text": "Uncoupling activation-dependent HS1 phosphorylation from nuclear factor of activated T cells transcriptional activation in Jurkat T cells : differential signaling through CD3 and the costimulatory receptors CD2 and CD28 .", "target_text": { "HS1": "protein", "nuclear factor of activated T cells": "protein", "Jurkat T cells": "cell_line", "CD3": "protein", "CD2": "protein", "CD28": "protein" } }, { "input_text": "CD3 , CD2 , and CD28 are functionally distinct receptors on T lymphocytes .", "target_text": { "CD3": "protein", "CD2": "protein", "CD28": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Engagement of any of these receptors induces the rapid tyrosine phosphorylation of a shared group of intracellular signaling proteins , including Vav , Cbl , p85 phosphoinositide 3-kinase , and the Src family kinases Lck and Fyn .", "target_text": { "intracellular signaling proteins": "protein", "Vav": "protein", "Cbl": "protein", "p85 phosphoinositide 3-kinase": "protein", "Src family kinases": "protein", "Lck": "protein", "Fyn": "protein" } }, { "input_text": "Ligation of CD3 also induces the tyrosine phosphorylation of HS1 , a 75-kDa hematopoietic cell-specific intracellular signaling protein of unknown function .", "target_text": { "CD3": "protein", "HS1": "protein", "75-kDa hematopoietic cell-specific intracellular signaling protein": "protein" } }, { "input_text": "We have examined changes in HS1 phosphorylation after differential stimulation of CD3 , CD2 , and CD28 to elucidate its role in T cells and to further delineate the signaling pathways recruited by these receptors .", "target_text": { "HS1": "protein", "CD3": "protein", "CD2": "protein", "CD28": "protein", "T cells": "cell_type" } }, { "input_text": "Unlike ligation of CD3 , stimulation with anti- CD28 mAb or CHO cells expressing the CD28 ligands CD80 or CD86 did not lead to tyrosine phosphorylation of HS1 in Jurkat T cells .", "target_text": { "CD3": "protein", "CD28": "protein", "anti- CD28 mAb": "protein", "CHO cells": "cell_line", "CD28 ligands": "protein", "CD80": "protein", "CD86": "protein", "HS1": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "Additionally , no tyrosine phosphorylation of HS1 was induced by mitogenic pairs of anti- CD2 mAbs capable of activating the transcription factor NFAT ( nuclear factor of activated T cells ) .", "target_text": { "HS1": "protein", "mitogenic pairs": "cell_type", "CD2": "protein", "anti- CD2 mAbs": "protein", "transcription factor NFAT": "protein", "nuclear factor of activated T cells": "protein" } }, { "input_text": "Costimulation through CD28 and/or CD2 did not modulate the CD3 -dependent phosphorylation of HS1 .", "target_text": { "CD28": "protein", "CD2": "protein", "CD3": "protein", "HS1": "protein" } }, { "input_text": "In vivo studies indicated that CD3 -induced HSI phosphorylation was dependent upon both the Src family tyrosine kinase Lck and the tyrosine phosphatase CD45 , did not require MEK1 kinase activity , and was regulated by protein kinase C activation .", "target_text": { "CD3": "protein", "HSI": "protein", "Src family tyrosine kinase": "protein", "Lck": "protein", "tyrosine phosphatase": "protein", "CD45": "protein", "MEK1": "protein", "protein kinase C": "protein" } }, { "input_text": "Thus , although CD3 , CD28 , and CD2 activate many of the same signaling molecules , they differed in their capacity to induce the tyrosine phosphorylation of HSI .", "target_text": { "CD3": "protein", "CD28": "protein", "signaling molecules": "protein", "HSI": "protein" } }, { "input_text": "Furthermore , activation-dependent tyrosine phosphorylation of HS1 was not required for NFAT transcriptional activation .", "target_text": { "HS1": "protein", "NFAT": "protein" } }, { "input_text": "c-fos and c-jun mRNA expression in activated cord and adult lymphocytes : an analysis by Northern hybridization .", "target_text": {} }, { "input_text": "BACKGROUND AND OBJECTIVES : To further analyze the neonatal immune response to an antigenic challenge such as blood transfusion , c-fos and c-jun mRNA expression were analyzed in twelve in-vitro-stimulated normal cord blood and ten in-vitro-stimulated normal adult peripheral blood lymphocyte samples .", "target_text": { "in-vitro-stimulated normal adult peripheral blood lymphocyte samples": "cell_type" } }, { "input_text": "MATERIALS AND METHODS : Lymphocyte samples were stimulated by either the mitogen phytohemagglutinin ( PHA ) or the monoclonal antibody alphaCD3 .", "target_text": { "Lymphocyte samples": "cell_type", "mitogen phytohemagglutinin": "protein", "PHA": "protein", "alphaCD3": "protein" } }, { "input_text": "Proliferation rate and Northern blot hybridization were employed .", "target_text": {} }, { "input_text": "RESULTS : Cord lymphocytes revealed a greater proliferation rate with PHA and alphaCD3 than adult lymphocytes ( p = 0.0081 and 0.0023 , respectively ) .", "target_text": { "PHA": "protein", "alphaCD3": "protein" } }, { "input_text": "In addition , Northern blot analysis of cord and adult samples revealed similar maximal increases in c-fos ( 99+/-15 and 126+/-11 % , p = 0.0126 ) and c-jun ( 123+/-9 and 185+/-38 % , p = 0.0291 ) mRNA expression , respectively , as early as 15 min post- alphaCD3 stimulation .", "target_text": { "c-fos": "RNA", "c-jun ( 123+/-9 and 185+/-38 % , p = 0.0291 ) mRNA": "RNA", "alphaCD3": "protein" } }, { "input_text": "Adult lymphocytes showed an equivalent increase in mRNA expression of c-fos and c-jun ( 140+/-25 and 155+/-31 % ) at 30 min post- PHA stimulation , while cord lymphocyte maximum c-fos and c-jun expression ( 82+/-6 and 142+/-12 % ) occurred at 15 min post- PHA stimulation ( c-fos , p = 0.0354 ; c-jun , p = 0.0112 ) .", "target_text": { "c-fos": "DNA", "c-jun": "DNA", "PHA": "protein", "cord lymphocyte": "cell_type" } }, { "input_text": "CONCLUSION : Although cord lymphocyte proliferation rates were significantly greater than those of adult lymphocytes following stimulation , lymphocyte activation , as analyzed by c-fos and c-jun mRNA expression , appears similar in both cord and adult samples .", "target_text": { "cord lymphocyte": "cell_type" } }, { "input_text": "We conclude that cord lymphocyte activation exhibits an adult-type profile .", "target_text": {} }, { "input_text": "Fcgamma receptor -mediated mitogen-activated protein kinase activation in monocytes is independent of Ras .", "target_text": { "Fcgamma receptor": "protein", "mitogen-activated protein kinase": "protein", "monocytes": "cell_type", "Ras": "protein" } }, { "input_text": "Receptors for the Fc portion of immunoglobulin molecules ( FcR ) present on leukocyte cell membranes mediate a large number of cellular responses that are very important in host defense , including phagocytosis , cell cytotoxicity , production and secretion of inflammatory mediators , and modulation of the immune response .", "target_text": { "Fc portion": "protein", "immunoglobulin molecules": "protein", "FcR": "protein", "inflammatory mediators": "protein" } }, { "input_text": "Cross-linking of FcR with immune complexes leads , first to activation of protein- tyrosine kinases .", "target_text": { "FcR": "protein", "immune complexes": "protein", "protein- tyrosine kinases": "protein" } }, { "input_text": "The molecular events that follow and that transduce signals from these receptors to the nucleus are still poorly defined .", "target_text": {} }, { "input_text": "We have investigated the signal transduction pathway from Fc receptors that leads to gene activation and production of cytokines in monocytes .", "target_text": { "Fc receptors": "protein", "cytokines": "protein", "monocytes": "cell_type" } }, { "input_text": "Cross-linking of FcR , on the THP-1 monocytic cell line , by immune complexes resulted in both activation of the transcription factor NF-kappaB and interleukin 1 production .", "target_text": { "FcR": "protein", "THP-1 monocytic cell line": "cell_line", "immune complexes": "protein", "transcription factor": "protein", "NF-kappaB": "protein", "interleukin 1": "protein" } }, { "input_text": "These responses were completely blocked by tyrosine kinase inhibitors .", "target_text": { "tyrosine kinase": "protein" } }, { "input_text": "In contrast , expression of dominant negative mutants of Ras and Raf-1 , in these cells , did not have any effect on FcR -mediated nuclear factor activation , suggesting that the mitogen-activated protein kinase ( MAPK ) signaling pathway was not used by these receptors .", "target_text": { "dominant negative mutants": "protein", "Ras": "protein", "Raf-1": "protein", "FcR": "protein", "nuclear factor": "protein", "mitogen-activated protein kinase": "protein", "MAPK": "protein" } }, { "input_text": "However , MAPK activation was easily detected by in vitro kinase assays , after FcR cross-linking with immune complexes .", "target_text": { "MAPK": "protein", "FcR": "protein", "immune complexes": "protein" } }, { "input_text": "Using the specific MAPK /extracellular signal-regulated kinase kinase ( MAPK kinase ) inhibitor PD98059 , we found that MAPK activation is necessary for FcR -dependent activation of the nuclear factor NF-kappaB .", "target_text": { "MAPK": "protein", "FcR": "protein", "nuclear factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "These results strongly suggest that the signaling pathway from Fc receptors leading to expression of different genes important to leukocyte biology , initiates with tyrosine kinases and requires MAPK activation ; but in contrast to other tyrosine kinase receptors , FcR -mediated MAPK activation does not involve Ras and Raf .", "target_text": { "Fc receptors": "protein", "tyrosine kinases": "protein", "MAPK": "protein", "tyrosine kinase receptors": "protein", "FcR": "protein", "Ras": "protein", "Raf": "protein" } }, { "input_text": "BCL-6 mutations in normal germinal center B cells : evidence of somatic hypermutation acting outside Ig loci .", "target_text": { "BCL-6": "protein", "normal germinal center B cells": "cell_type", "Ig loci": "DNA" } }, { "input_text": "The molecular mechanism involved in the process of antigen-driven somatic hypermutation of Ig genes is unknown , but it is commonly believed that this mechanism is restricted to the Ig loci .", "target_text": { "Ig genes": "DNA", "Ig loci": "DNA" } }, { "input_text": "B cell lymphomas commonly display multiple somatic mutations clustering in the 5'-regulatory region of BCL-6 , a proto-oncogene encoding for a POZ/Zinc finger transcriptional repressor expressed in germinal center ( GC ) B cells and required for GC formation .", "target_text": { "B cell lymphomas": "cell_type", "5'-regulatory region": "DNA", "BCL-6": "protein", "proto-oncogene": "DNA", "POZ/Zinc finger transcriptional repressor": "protein", "germinal center ( GC ) B cells": "cell_type" } }, { "input_text": "To determine whether BCL-6 mutations represent a tumor-associated phenomenon or reflect a physiologic mechanism , we screened single human tonsillar GC B cells for mutations occurring in the BCL-6 5'-noncoding region and in the Ig variable heavy chain sequences .", "target_text": { "BCL-6": "protein", "human tonsillar GC B cells": "cell_type", "BCL-6 5'-noncoding region": "DNA", "Ig variable heavy chain sequences": "DNA" } }, { "input_text": "Thirty percent of GC B cells , but not naive B cells , displayed mutations in the 742 bp region analyzed within the first intron of BCL-6 ( overall frequency : 5 x 10(-4)/bp ) .", "target_text": { "GC B cells": "cell_type", "naive B cells": "cell_type", "742 bp region": "DNA", "BCL-6": "protein" } }, { "input_text": "Accordingly , an expanded survey in lymphoid malignancies showed that BCL-6 mutations are restricted to B cell tumors displaying GC or post-GC phenotype and carrying mutated Ig variable heavy chain sequences .", "target_text": { "BCL-6": "protein", "mutated Ig variable heavy chain sequences": "DNA" } }, { "input_text": "These results indicate that the somatic hypermutation mechanism active in GC B cells physiologically targets non-Ig sequences .", "target_text": { "GC B cells": "cell_type", "non-Ig sequences": "DNA" } }, { "input_text": "The AD1 and AD2 transactivation domains of E2A are essential for the antiapoptotic activity of the chimeric oncoprotein E2A-HLF .", "target_text": { "AD1": "protein", "AD2": "protein", "E2A": "protein", "chimeric oncoprotein": "protein", "E2A-HLF": "protein" } }, { "input_text": "The chimeric oncoprotein E2A-HLF , generated by the t(17;19) chromosomal translocation in pro-B-cell acute lymphoblastic leukemia , incorporates the transactivation domains of E2A and the basic leucine zipper ( bZIP ) DNA-binding and protein dimerization domain of HLF ( hepatic leukemic factor ) .", "target_text": { "chimeric oncoprotein": "protein", "E2A-HLF": "protein", "t(17;19) chromosomal translocation": "DNA", "transactivation domains": "protein", "E2A": "protein", "HLF": "protein", "hepatic leukemic factor": "protein" } }, { "input_text": "The ability of E2A-HLF to prolong the survival of interleukin-3 ( IL-3 ) -dependent murine pro-B cells after IL-3 withdrawal suggests that it disrupts signaling pathways normally responsible for cell suicide , allowing the cells to accumulate as transformed lymphoblasts .", "target_text": { "E2A-HLF": "protein", "interleukin-3": "protein", "IL-3": "protein", "interleukin-3 ( IL-3 ) -dependent murine pro-B cells": "cell_line", "transformed lymphoblasts": "cell_type" } }, { "input_text": "To determine the structural motifs that contribute to this antiapoptotic effect , we constructed a panel of E2A-HLF mutants and programmed their expression in IL-3 -dependent murine pro-B cells ( FL5.12 line ) , using a zinc-inducible vector .", "target_text": { "E2A-HLF": "protein", "E2A-HLF mutants": "protein", "IL-3": "protein", "IL-3 -dependent murine pro-B cells": "cell_line", "FL5.12 line": "cell_line" } }, { "input_text": "Neither the E12 nor the E47 product of the E2A gene nor the wild-type HLF protein was able to protect the cells from apoptosis induced by IL-3 deprivation .", "target_text": { "E12": "protein", "E47": "protein", "E2A": "protein", "E2A gene": "DNA", "wild-type HLF protein": "protein", "IL-3": "protein" } }, { "input_text": "Surprisingly , different combinations of disabling mutations within the HLF bZIP domain had little effect on the antiapoptotic property of the chimeric protein , so long as the amino-terminal portion of E2A remained intact .", "target_text": { "HLF bZIP domain": "protein", "chimeric protein": "protein", "E2A": "protein" } }, { "input_text": "In the context of a bZIP domain defective in DNA binding , mutants retaining either of the two transactivation domains of E2A were able to extend cell survival after growth factor deprivation .", "target_text": { "bZIP domain": "protein", "transactivation domains": "protein", "E2A": "protein", "growth factor": "protein" } }, { "input_text": "Thus , the block of apoptosis imposed by E2A-HLF in pro-B lymphocytes depends critically on the transactivating regions of E2A .", "target_text": { "E2A-HLF": "protein", "pro-B lymphocytes": "cell_type", "transactivating regions": "protein", "E2A": "protein" } }, { "input_text": "Since neither DNA binding nor protein dimerization through the bZIP domain of HLF is required for this effect , we propose mechanisms whereby protein-protein interactions with the amino-terminal region of E2A allow the chimera to act as a transcriptional cofactor to alter the expression of genes regulating the apoptotic machinery in pro-B cells .", "target_text": { "bZIP domain": "protein", "HLF": "protein", "E2A": "protein", "chimera": "protein", "pro-B cells": "cell_type" } }, { "input_text": "Induction of Mn SOD in human monocytes without inflammatory cytokine production by a mutant endotoxin .", "target_text": { "Mn SOD": "protein", "human monocytes": "cell_type", "inflammatory cytokine": "protein", "mutant endotoxin": "protein" } }, { "input_text": "Endotoxin selectively induces monocyte Mn superoxide dismutase ( SOD ) without affecting levels of Cu , Zn SOD , catalase , or glutathione peroxidase .", "target_text": { "Endotoxin": "protein", "monocyte Mn superoxide dismutase": "protein", "SOD": "protein", "Zn SOD": "protein", "catalase": "protein", "glutathione peroxidase": "protein" } }, { "input_text": "However , little is known about the structure-activity relationship and the mechanism by which endotoxin induces Mn SOD .", "target_text": { "Mn SOD": "protein" } }, { "input_text": "In this study we demonstrated that a mutant Escherichia coli endotoxin lacking myristoyl fatty acid at the 3' R-3-hydroxymyristate position of the lipid A moiety retained its full capacity to coagulate Limulus amoebocyte lysate compared with the wild-type E . coli endotoxin and markedly stimulated the activation of human monocyte nuclear factor-kappaB and the induction of Mn SOD mRNA and enzyme activity .", "target_text": { "human monocyte nuclear factor-kappaB": "protein", "Mn SOD": "protein", "Mn SOD mRNA": "RNA" } }, { "input_text": "However , in contrast to the wild-type endotoxin , it failed to induce significant production of tumor necrosis factor-alpha and macrophage inflammatory protein-1alpha by monocytes and did not induce the phosphorylation and nuclear translocation of mitogen-activated protein kinase .", "target_text": { "tumor necrosis factor-alpha": "protein", "macrophage inflammatory protein-1alpha": "protein", "monocytes": "cell_type", "mitogen-activated protein kinase": "protein" } }, { "input_text": "These results suggest that 1 ) lipid A myristoyl fatty acid , although it is important for the induction of inflammatory cytokine production by human monocytes , is not necessary for the induction of Mn SOD , 2 ) endotoxin -mediated induction of Mn SOD and inflammatory cytokines are regulated , at least in part , through different signal transduction pathways , and 3 ) failure of the mutant endotoxin to induce tumor necrosis factor-alpha production is , at least in part , due to its inability to activate mitogen-activated protein kinase .", "target_text": { "inflammatory cytokine": "protein", "human monocytes": "cell_type", "Mn SOD": "protein", "endotoxin": "protein", "cytokines": "protein", "mutant endotoxin": "protein", "tumor necrosis factor-alpha": "protein", "mitogen-activated protein kinase": "protein" } }, { "input_text": "Regulation of the vitellogenin gene B1 promoter after transfer into hepatocytes in primary cultures .", "target_text": { "vitellogenin gene B1 promoter": "DNA", "hepatocytes": "cell_type" } }, { "input_text": "The estrogen-dependent and tissue-specific regulation of the Xenopus laevis vitellogenin gene B1 promoter has been studied by lipid-mediated DNA transfer into Xenopus hepatocytes in primary culture .", "target_text": { "vitellogenin gene B1 promoter": "DNA", "hepatocytes": "cell_type", "Xenopus hepatocytes": "cell_type" } }, { "input_text": "Hepatocytes achieve an efficient hormonal control of this promoter through a functional interaction between the estrogen responsive elements and a promoter proximal region upstream of the TATA box , which is characterized by a high density of binding sites for the transcription factors CTF/NF-1 , C/EBP and HNF3 .", "target_text": { "estrogen responsive elements": "DNA", "promoter proximal region": "DNA", "TATA box": "DNA", "transcription factors": "protein", "CTF/NF-1": "protein", "C/EBP": "protein", "HNF3": "protein" } }, { "input_text": "DNA accessibility to restriction enzymes within the chromosomal copy of the vitellogenin gene B1 promoter shows that the estrogen responsive unit and the promoter proximal region are sensitive to digestion in uninduced and estrogen -induced hepatocytes but not in erythrocyte nuclei .", "target_text": { "restriction enzymes": "protein", "vitellogenin gene B1 promoter": "DNA", "estrogen responsive unit": "DNA", "promoter proximal region": "DNA", "hepatocytes": "cell_type", "estrogen -induced hepatocytes": "cell_type" } }, { "input_text": "Together , these findings support the notion that chromatin configuration as well as the interplay of promoter elements mediate proper hormone-dependent and tissue-specific expression of the B1 vitellogenin gene .", "target_text": { "chromatin": "DNA", "promoter elements": "DNA", "B1 vitellogenin gene": "DNA" } }, { "input_text": "Characterization of cytokine differential induction of STAT complexes in primary human T and NK cells .", "target_text": { "cytokine": "protein", "STAT complexes": "protein" } }, { "input_text": "Cytokines , IL-2 , IL-4 , IL-6 , IL-7 , IL-12 , and IL-15 are key regulators of human peripheral blood T and NK cell activation and differentiation but the precise mechanisms that give rise to their differential activities within these cells are not clear .", "target_text": { "Cytokines": "protein", "IL-2": "protein", "IL-4": "protein", "IL-6": "protein", "IL-7": "protein", "IL-12": "protein", "IL-15": "protein" } }, { "input_text": "Recent studies reveal that a family of transcription factors , signal transducers and activators of transcription ( STATs ) directly mediate many cytokine signals .", "target_text": { "transcription factors": "protein", "signal transducers and activators of transcription": "protein", "STATs": "protein", "cytokine": "protein" } }, { "input_text": "We analyzed the activation of STATs in primary human T and NK cells by a variety of specific cytokines .", "target_text": { "STATs": "protein", "cytokines": "protein" } }, { "input_text": "We demonstrate that IL-12 induces STAT4 only in freshly isolated primary NK cells , but not in primary T cells , consistent with the lack of the IL-12 receptor in resting T cells .", "target_text": { "IL-12": "protein", "STAT4": "protein", "NK cells": "cell_type", "primary NK cells": "cell_type", "primary T cells": "cell_type", "IL-12 receptor": "protein", "resting T cells": "cell_type" } }, { "input_text": "In contrast , IL-4 induces different C epsilon GAS DNA-protein binding complexes in both T and NK cells .", "target_text": { "IL-4": "protein", "C epsilon GAS DNA-protein binding complexes": "protein", "NK cells": "cell_type" } }, { "input_text": "Moreover , IL-4 costimulation with IL-2 or IL-12 does not alter their own preferential GAS -like DNA binding patterns when C epsilon- , Fc gamma RI- , and SIE GAS motif containing oligonucleotide probes are compared , suggesting that induction of GAS-like DNA-protein binding complexes by IL-2 , IL-4 , and IL-12 is highly selective and represents one important factor in determining specific gene activation .", "target_text": { "IL-4": "protein", "IL-2": "protein", "IL-12": "protein", "GAS": "DNA", "GAS-like DNA-protein binding complexes": "protein" } }, { "input_text": "In addition , IL-6 and IL-2 synergistically induce homo- and heterodimerized STAT1 alpha and STAT3 in both NK and T cells , consistent with their reported synergism in modulating perforin gene expression .", "target_text": { "IL-6": "protein", "IL-2": "protein", "STAT1 alpha": "protein", "STAT3": "protein", "perforin gene": "DNA" } }, { "input_text": "We further demonstrated that IL -2 , -7 , and -15 induce multiple STAT proteins , including STAT5a , STAT5b , STAT1 alpha , STAT3 , and another unidentified Fc gamma RI GAS DNA-binding protein .", "target_text": { "multiple STAT proteins": "protein", "STAT5a": "protein", "STAT5b": "protein", "STAT1 alpha": "protein", "STAT3": "protein", "Fc gamma RI GAS DNA-binding protein": "protein" } }, { "input_text": "Finally , we observed that activated STAT5a and STAT5b proteins form distinct Fc gamma RI GAS binding patterns in T and NK cells , suggesting that they might have different roles in gene regulation .", "target_text": { "STAT5a": "protein", "STAT5b": "protein" } }, { "input_text": "Our data provide evidence that the differential responses in gene expression and cell activation seen in primary NK and T cells on direct stimulation with different cytokines may be a direct result of distinct activation of STAT transcription factors .", "target_text": { "cytokines": "protein", "transcription factors": "protein", "STAT transcription factors": "protein" } }, { "input_text": "A regulatory element in the CD95 ( APO-1/Fas ) ligand promoter is essential for responsiveness to TCR -mediated activation .", "target_text": { "regulatory element": "DNA", "CD95": "protein", "APO-1/Fas": "protein", "CD95 ( APO-1/Fas ) ligand promoter": "DNA", "TCR": "protein" } }, { "input_text": "Expression of the CD95 ( APO-1/Fas ) ligand ( CD95L ) in activated T cells is a major cause of T cell activation-induced apoptosis .", "target_text": { "CD95": "protein", "APO-1/Fas": "protein", "CD95 ( APO-1/Fas ) ligand": "protein", "CD95L": "protein", "activated T cells": "cell_type" } }, { "input_text": "To study the molecular mechanisms of transcriptional control of CD95L expression in T cells , we investigated the human CD95L promoter in Jurkat T cells .", "target_text": { "CD95L": "protein", "T cells": "cell_type", "human CD95L promoter": "DNA", "Jurkat T cells": "cell_line" } }, { "input_text": "Deletion studies revealed that the CD95L proximal promoter sequence from -220 to the transcription start site is essential for T cell stimulation-induced expression of CD95L .", "target_text": { "CD95L": "protein", "CD95L proximal promoter sequence": "DNA", "-220": "DNA", "transcription start site": "DNA" } }, { "input_text": "In this study , we discovered a novel regulatory element located at -120 of the CD95L promoter which contains DNA binding sites for SP-1 and a yet unknown inducible factor .", "target_text": { "regulatory element": "DNA", "-120": "DNA", "CD95L": "protein", "CD95L promoter": "DNA", "DNA binding sites": "DNA", "SP-1": "protein", "inducible factor": "protein" } }, { "input_text": "Mutation analysis demonstrated that binding of the inducible factor to the -120 region is crucial for the biological function of the CD95L promoter upon T cell stimulation .", "target_text": { "-120 region": "DNA", "CD95L": "protein", "CD95L promoter": "DNA" } }, { "input_text": "The DNA sequence at -120 also contains two DNA motifs homologous to the binding site for NF-AT .", "target_text": { "-120": "DNA", "DNA motifs": "DNA", "NF-AT": "protein" } }, { "input_text": "NF-AT does not directly bind to this element .", "target_text": { "NF-AT": "protein" } }, { "input_text": "However , cotransfection studies with an NF-AT expression vector showed that NF-AT may confer a strong inducible activity to the CD95L promoter at this regulatory region .", "target_text": { "NF-AT": "protein", "NF-AT expression vector": "DNA", "CD95L": "protein", "CD95L promoter": "DNA", "regulatory region": "DNA" } }, { "input_text": "Our data also show that the immunosuppressive agent cyclosporin A down-regulates CD95L transcription by inhibiting the function of this positive regulatory element", "target_text": { "CD95L": "protein", "regulatory element": "DNA" } }, { "input_text": "A nongenomic mechanism for progesterone-mediated immunosuppression : inhibition of K+ channels , Ca2+ signaling , and gene expression in T lymphocytes .", "target_text": { "K+ channels": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "The mechanism by which progesterone causes localized suppression of the immune response during pregnancy has remained elusive .", "target_text": {} }, { "input_text": "Using human T lymphocytes and T cell lines , we show that progesterone , at concentrations found in the placenta , rapidly and reversibly blocks voltage-gated and calcium-activated K+ channels ( KV and KCa , respectively ) , resulting in depolarization of the membrane potential .", "target_text": { "T lymphocytes": "cell_type", "human T lymphocytes": "cell_type", "T cell lines": "cell_line", "KV": "protein", "KCa": "protein" } }, { "input_text": "As a result , Ca2+ signaling and nuclear factor of activated T cells ( NF-AT ) -driven gene expression are inhibited .", "target_text": { "nuclear factor of activated T cells": "protein", "NF-AT": "protein" } }, { "input_text": "Progesterone acts distally to the initial steps of T cell receptor ( TCR ) -mediated signal transduction , since it blocks sustained Ca2+ signals after thapsigargin stimulation , as well as oscillatory Ca2+ signals , but not the Ca2+ transient after TCR stimulation .", "target_text": { "T cell receptor": "protein", "TCR": "protein" } }, { "input_text": "K+ channel blockade by progesterone is specific ; other steroid hormones had little or no effect , although the progesterone antagonist RU 486 also blocked KV and KCa channels .", "target_text": { "KV": "protein", "KCa": "protein" } }, { "input_text": "Progesterone effectively blocked a broad spectrum of K+ channels , reducing both Kv1.3 and charybdotoxin-resistant components of KV current and KCa current in T cells , as well as blocking several cloned KV channels expressed in cell lines .", "target_text": { "K+ channels": "protein", "Kv1.3": "protein", "charybdotoxin-resistant components": "protein", "KV": "protein", "KCa": "protein", "T cells": "cell_type", "cloned KV channels": "protein", "cell lines": "cell_line" } }, { "input_text": "Progesterone had little or no effect on a cloned voltage-gated Na+ channel , an inward rectifier K+ channel , or on lymphocyte Ca2+ and Cl- channels .", "target_text": { "cloned voltage-gated Na+ channel": "protein", "K+ channel": "protein" } }, { "input_text": "We propose that direct inhibition of K+ channels in T cells by progesterone contributes to progesterone -induced immunosuppression .", "target_text": { "K+ channels": "protein", "T cells": "cell_type" } }, { "input_text": "A mouse carrying genetic defect in the choice between T and B lymphocytes .", "target_text": {} }, { "input_text": "Transgenic mice with human CD3epsilon gene have been shown to exhibit early arrest of T cell development in the thymus .", "target_text": { "human CD3epsilon gene": "DNA" } }, { "input_text": "The present study shows that , instead of T cells , B cells are generated in the thymus of a line , tg epsilon26 , of the human CD3epsilon transgenic mice .", "target_text": { "T cells": "cell_type", "B cells": "cell_type" } }, { "input_text": "The accumulation of mature B cells in the thymus was found only in tg epsilon26 mice , not in other human CD3epsilon transgenic mouse lines or other T cell-deficient mice , including CD3-epsilon knockout mice and TCR-beta/TCR-delta double knockout mice .", "target_text": { "mature B cells": "cell_type", "human CD3epsilon transgenic mouse lines": "cell_line" } }, { "input_text": "Hanging drop-mediated transfer into 2-deoxyguanosine-treated thymus lobes showed that lymphoid progenitor cells rather than thymus stromal cells were responsible for abnormal B cell development in tg epsilon26 thymus , and that tg epsilon26 fetal liver cells were destined to become B cells in normal thymus even in the presence of normal progenitor cells undergoing T cell development .", "target_text": { "lymphoid progenitor cells": "cell_type", "tg epsilon26": "protein", "tg epsilon26 fetal liver cells": "cell_type", "B cells": "cell_type", "normal progenitor cells": "cell_type" } }, { "input_text": "These results indicate that lymphoid progenitor cells in tg epsilon26 mice are genetically defective in thymic choice between T cells and B cells , generating B cells even in normal thymus environment .", "target_text": { "lymphoid progenitor cells": "cell_type", "tg epsilon26": "protein", "T cells": "cell_type", "B cells": "cell_type" } }, { "input_text": "Interestingly , tg epsilon26 thymocytes expressed GATA-3 and TCF-1 , but not LEF-1 and PEBP-2alpha , among T cell-specific transcription factors that are involved in early T cell development , indicating that GATA-3 and TCF-1 expressed during thymocyte development do not necessarily determine the cell fate into T cell lineage .", "target_text": { "tg epsilon26": "protein", "tg epsilon26 thymocytes": "cell_type", "GATA-3": "protein", "TCF-1": "protein", "LEF-1": "protein", "PEBP-2alpha": "protein", "T cell-specific transcription factors": "protein", "T cell lineage": "cell_type" } }, { "input_text": "Thus , tg epsilon26 mice provide a novel mouse model in that lineage choice between T and B lymphocytes is genetically defective .", "target_text": { "tg epsilon26": "protein" } }, { "input_text": "Downstream activation of a TATA-less promoter by Oct-2 , Bob1 , and NF-kappaB directs expression of the homing receptor BLR1 to mature B cells .", "target_text": { "TATA-less promoter": "DNA", "Oct-2": "protein", "NF-kappaB": "protein", "BLR1": "protein", "homing receptor BLR1": "protein", "mature B cells": "cell_type" } }, { "input_text": "The chemokine receptor , BLR1 , is a major regulator of the microenvironmental homing of B cells in lymphoid organs .", "target_text": { "chemokine receptor": "protein", "BLR1": "protein", "B cells": "cell_type" } }, { "input_text": "In vitro studies identify three essential elements of the TATA-less blr1 core promoter that confer cell type- and differentiation- specific expression in the B cells of both humans and mice , a functional promoter region ( -36 with respect to the transcription start site ) , a NF-kappaB motif ( +44 ) , and a noncanonical octamer motif ( +157 ) .", "target_text": { "TATA-less blr1 core promoter": "DNA", "B cells": "cell_type", "functional promoter region": "DNA", "transcription start site": "DNA", "NF-kappaB": "protein", "NF-kappaB motif": "DNA", "noncanonical octamer motif": "DNA" } }, { "input_text": "The importance of these sites was confirmed by in vivo studies in gene-targeted mice deficient of either Oct-2 , Bob1 , or both NF-kappaB subunits p50 and p52 .", "target_text": { "Oct-2": "protein", "Bob1": "protein", "NF-kappaB": "protein" } }, { "input_text": "In all of these animals , the expression of BLR1 was reduced or absent .", "target_text": { "BLR1": "protein" } }, { "input_text": "In mice deficient only of p52/ NF-kappaB , BLR1 expression was unaffected .", "target_text": { "NF-kappaB": "protein", "p52/ NF-kappaB": "protein", "BLR1": "protein" } }, { "input_text": "Thus our data demonstrate that BLR1 is a target gene for Oct-2 , Bob1 , and members of the NF-kappaB /Rel family and provides a link to the impaired B cell functions in mice deficient for these factors .", "target_text": { "BLR1": "protein", "Oct-2": "protein", "Bob1": "protein", "NF-kappaB": "protein", "NF-kappaB /Rel family": "protein" } }, { "input_text": "CD4 promoter transactivation by human herpesvirus 6 .", "target_text": { "CD4 promoter": "DNA" } }, { "input_text": "The observation that human herpesvirus 6 ( HHV-6 ) can induce CD4 gene transcription and expression in CD4(-) cells was reported several years ago ( P.Lusso , A.De Maria , M.Malnati , F.Lori , S.E.DeRocco , M. Baseler , and R.C.Gallo , Nature 349 : 533-535 , 1991 ) and subsequently confirmed ( P.Lusso , M.S.Malnati , A.Garzino-Demo , R.W.Crowley , E. O.Long , and R.C.Gallo , Nature 362 : 458-462 , 1993 ; G.Furlini , M. Vignoli , E.Ramazzotti , M.C.Re , G.Visani , and M.LaPlaca , Blood 87 : 4737-4745 , 1996 ) .", "target_text": { "CD4 gene": "DNA", "CD4(-) cells": "cell_line" } }, { "input_text": "Our objective was to identify the mechanisms underlying such phenomena .", "target_text": {} }, { "input_text": "Using reporter gene constructs driven by the CD4 promoter , we report that HHV-6 can efficiently transactivate such genetic elements .", "target_text": { "reporter gene constructs": "DNA", "CD4 promoter": "DNA", "genetic elements": "DNA" } }, { "input_text": "Activation of the CD4 promoter occurs in the presence of the viral DNA polymerase inhibitor phosphonoformic acid , which limits expression to the immediate-early and early classes of viral genes .", "target_text": { "CD4 promoter": "DNA" } }, { "input_text": "Using deletion mutants and specific CD4 promoter mutants , we identified an ATF/CRE binding site located at nucleotides -67 to -60 upstream of the CD4 gene transcription start site that is important for HHV-6 transactivation .", "target_text": { "CD4 promoter": "DNA", "CD4 promoter mutants": "DNA", "ATF/CRE binding site": "DNA", "nucleotides -67 to -60 upstream": "DNA", "CD4 gene": "DNA", "CD4 gene transcription start site": "DNA" } }, { "input_text": "The ATF/CRE site is also essential for CD4 promoter activation by forskolin , an activator of adenylate cyclase .", "target_text": { "ATF/CRE site": "DNA", "CD4 promoter": "DNA" } }, { "input_text": "Using electrophoretic mobility shift assays and specific antibodies , we showed that CREB-1 binds specifically to the -79 to -52 region of the CD4 promoter .", "target_text": { "CREB-1": "protein", "-79 to -52 region": "DNA", "CD4 promoter": "DNA" } }, { "input_text": "Last , we have identified two open reading frames ( ORFs ) of HHV-6 , U86 and U89 from the immediate-early locus A , that can transactivate the CD4 promoter in HeLa cells .", "target_text": { "open reading frames": "DNA", "ORFs": "DNA", "U86": "DNA", "U89": "DNA", "CD4 promoter": "DNA", "HeLa cells": "cell_line" } }, { "input_text": "However , transactivation of the CD4 promoter by ORFs U86 and U89 is independent of the CRE element , suggesting that additional HHV-6 ORFs are likely to contribute to CD4 gene activation .", "target_text": { "CD4 promoter": "DNA", "ORFs": "DNA", "U86": "DNA", "U89": "DNA", "CRE element": "DNA", "HHV-6 ORFs": "DNA", "CD4 gene": "DNA" } }, { "input_text": "Taken together , our results will help to understand the complex interactions occurring between HHV-6 and the CD4 promoter and provide additional information regarding the class of transcription factors involved in the control of CD4 gene expression .", "target_text": { "CD4 promoter": "DNA", "transcription factors": "protein", "CD4 gene": "DNA" } }, { "input_text": "The PEBP2betaMYH11 fusion created by Inv(16)(p13;q22) in myeloid leukemia impairs neutrophil maturation and contributes to granulocytic dysplasia .", "target_text": { "PEBP2betaMYH11": "protein", "Inv(16)(p13;q22)": "DNA" } }, { "input_text": "Chromosomal translocations involving the genes encoding the alpha and beta subunits of the Pebp2/Cbf transcription factor have been associated with human acute myeloid leukemia and the preleukemic condition , myelodysplasia .", "target_text": { "Pebp2/Cbf transcription factor": "protein" } }, { "input_text": "Inv(16)(p13;q22) fuses the gene encoding the beta subunit of Pebp2 to the MYH11 gene encoding a smooth muscle myosin heavy chain ( Smmhc ) .", "target_text": { "Inv(16)(p13;q22)": "DNA", "beta subunit": "protein", "Pebp2": "protein", "MYH11 gene": "DNA", "smooth muscle myosin heavy chain": "protein", "Smmhc": "protein" } }, { "input_text": "To examine the effect of the inv(16)(p13;q22) on myelopoiesis , we used the hMRP8 promoter element to generate transgenic mice expressing the Pebp2beta Smmhc chimeric fusion protein in myeloid cells .", "target_text": { "inv(16)(p13;q22)": "DNA", "hMRP8 promoter element": "DNA", "Pebp2beta": "protein", "Smmhc": "protein", "Smmhc chimeric fusion protein": "protein", "myeloid cells": "cell_type" } }, { "input_text": "Neutrophil maturation was impaired in PEBP2betaMYH11 transgenic mice .", "target_text": { "PEBP2betaMYH11": "protein" } }, { "input_text": "Although the transgenic mice had normal numbers of circulating neutrophils , their bone marrow contained increased numbers of immature neutrophilic cells , which exhibited abnormal characteristics .", "target_text": { "circulating neutrophils": "cell_type", "immature neutrophilic cells": "cell_type" } }, { "input_text": "In addition , PEBP2betaMYH11 inhibited neutrophilic differentiation in colonies derived from hematopoietic progenitors .", "target_text": { "PEBP2betaMYH11": "protein", "hematopoietic progenitors": "cell_type" } }, { "input_text": "Coexpression of both PEBP2betaMYH11 and activated NRAS induced a more severe phenotype characterized by abnormal nuclear morphology indicative of granulocytic dysplasia .", "target_text": { "PEBP2betaMYH11": "protein", "activated NRAS": "protein" } }, { "input_text": "These results show that PEBP2betaMYH11 can impair neutrophil development and provide evidence that alterations of Pebp2 can contribute to the genesis of myelodysplasia .", "target_text": { "PEBP2betaMYH11": "protein", "Pebp2": "protein" } }, { "input_text": "Human T cell leukemia virus-I ( HTLV-I ) Tax -mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state .", "target_text": { "Tax": "protein", "activated T cells": "cell_type" } }, { "input_text": "We have shown that an estradiol-dependent activation of human T cell leukemia virus-I Tax leads to the inhibition of cell proliferation and to the induction of apoptosis .", "target_text": { "Tax": "protein" } }, { "input_text": "The present study demonstrates that a hormone-dependent activation of Tax promotes an enhanced prooxidant state in stably transfected Jurkat cells as measured by changes in the intracellular levels of glutathione and H2O2 ; these changes are followed by apoptotic cell death .", "target_text": { "Tax": "protein", "Jurkat cells": "cell_line", "stably transfected Jurkat cells": "cell_line" } }, { "input_text": "Additional stimulation of the CD3 /TCR pathway enhances the oxidative and apoptotic effects .", "target_text": { "CD3": "protein", "/TCR": "protein" } }, { "input_text": "Both Tax -mediated apoptosis and oxidative stress can be potently suppressed by antioxidants , as is seen with the administration of recombinant thioredoxin ( adult T cell leukemia-derived factor ) or pyrrolidine dithiocarbamate .", "target_text": { "Tax": "protein", "thioredoxin": "protein", "recombinant thioredoxin": "protein", "adult T cell leukemia-derived factor": "protein" } }, { "input_text": "Hormone-induced Tax activation induces a long-lasting activation of NF-kappaB , which is a major target of reactive oxygen intermediates .", "target_text": { "Tax": "protein", "NF-kappaB": "protein" } }, { "input_text": "The long-term exposure of Jurkat cells to hormone eventually results in a selection of cell clones that have lost Tax activity .", "target_text": { "Jurkat cells": "cell_line", "cell clones": "cell_line", "Tax": "protein" } }, { "input_text": "A subsequent transfection of these apparently \" nonresponsive \" clones allows the recovery of Tax responses in these cells .", "target_text": { "\" nonresponsive \" clones": "cell_line", "Tax": "protein" } }, { "input_text": "Our observations indicate that changes in the intracellular redox status may be a determining factor in Tax -mediated DNA damage , apoptosis , and selection against the long-term expression of Tax function .", "target_text": { "Tax": "protein" } }, { "input_text": "An allosteric drug , o,o'-bismyristoyl thiamine disulfide , suppresses HIV-1 replication through prevention of nuclear translocation of both HIV-1 Tat and NF-kappa B .", "target_text": { "HIV-1 Tat": "protein", "NF-kappa B": "protein" } }, { "input_text": "The efficacy of o , o'-bismyristoyl thiamine disulfide ( BMT ) was examined in detail against HIV-1 laboratory isolates ( HTLV-IIIB , JRFL , and MN ) , primary isolates ( KMT and KMO ) , and simian immunodeficiency virus ( SIVmac251 ) in vitro .", "target_text": {} }, { "input_text": "BMT inhibited the replication of HIV-1 in both laboratory and primary isolates in vitro .", "target_text": {} }, { "input_text": "In addition , BMT exhibited antiviral activity against SIVmac251 .", "target_text": {} }, { "input_text": "Minimizing energy studies of BMT structure reveal that a trans-disulfide of thiamine ( holo drug ) disulfide ( TDS , protodrug ) is allosterically transited to the reactive twisted disulfide of BMT ( allo drug ) by o , o'-bismyristoyl esterification of TDS .", "target_text": {} }, { "input_text": "BMT inhibits nuclear translocation of both HIV-1 transactivator ( TAT ) and the cellular transcriptional nuclear factor-KB ( NF-kappa B ) , resulting in the suppression of HIV-1 replication .", "target_text": { "HIV-1 transactivator": "protein", "TAT": "protein", "cellular transcriptional nuclear factor-KB": "protein", "NF-kappa B": "protein" } }, { "input_text": "Glucocorticoid -induced apoptosis and regulation of NF-kappaB activity in human leukemic T cells .", "target_text": { "NF-kappaB": "protein", "human leukemic T cells": "cell_type" } }, { "input_text": "Glucocorticoid -induced apoptosis was investigated in glucocorticoid-sensitive 6TG1.1 and resistant ICR27TK.3 human leukemic T cells .", "target_text": { "glucocorticoid-sensitive 6TG1.1": "cell_line", "resistant ICR27TK.3": "cell_line", "human leukemic T cells": "cell_type" } }, { "input_text": "Following glucocorticoid treatment of 6TG1.1 cells , chromatin fragmentation was observed after a delay of 24 h .", "target_text": { "6TG1.1 cells": "cell_line", "chromatin": "DNA" } }, { "input_text": "Fragmentation was not observed in ICR27TK.3 cells containing mutant glucocorticoid receptors ( L753F ) that are activation-deficient but retain the ability to repress AP-1 activity .", "target_text": { "ICR27TK.3 cells": "cell_line", "mutant glucocorticoid receptors": "protein", "L753F": "cell_line", "AP-1": "protein" } }, { "input_text": "Nor was fragmentation observed after treatment with RU38486 , indicating that repression of AP-1 activity is not involved .", "target_text": { "AP-1": "protein" } }, { "input_text": "As described in other systems , fragmentation required ongoing protein synthesis .", "target_text": {} }, { "input_text": "However , inhibition of protein synthesis with cycloheximide anytime during the first 18 h of steroid treatment was as effective in blocking chromatin fragmentation as inhibition for the entire period , suggesting that synthesis of a component with a rapid turnover rate is required .", "target_text": {} }, { "input_text": "Dexamethasone treatment completely blocked 12-O-tetradecanoylphorbol 13-acetate induction of nuclear factor-kappaB ( NF-kappaB ) activity and elicited an increase in the amount of immunoreactive IkappaB alpha in sensitive 6TG1.1 cells but not in resistant ICR27TK.3 cells .", "target_text": { "nuclear factor-kappaB": "protein", "NF-kappaB": "protein", "immunoreactive IkappaB alpha": "protein", "6TG1.1 cells": "cell_line", "ICR27TK.3 cells": "cell_line" } }, { "input_text": "In addition , mild detergent treatment of cell extracts indicated that a substantial amount of cytoplasmic NF-kappaB is complexed with IkappaB alpha or some other inhibitory factor . These results suggest that induction of a labile inhibitory factor such as IkappaB alpha may contribute to glucocorticoid-induced apoptosis .", "target_text": { "NF-kappaB": "protein", "cytoplasmic NF-kappaB": "protein", "IkappaB alpha": "protein", "labile inhibitory factor": "protein" } }, { "input_text": "Inhibition of HIV-1 replication by combination of a novel inhibitor of TNF-alpha with AZT .", "target_text": { "TNF-alpha": "protein" } }, { "input_text": "The small molecule S9a was derived from an established tumor necrosis factor-alpha ( TNF-alpha ) inhibitor ( Canventol ) by replacement of the isopropylidine group with a phenyl ring .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF-alpha": "protein" } }, { "input_text": "S9a at 10 to 100 nM inhibited HIV production as potently as 3'-azido-3'-deoxythymidine ( AZT ) , an inhibitor of viral reverse transcriptase .", "target_text": { "viral reverse transcriptase": "protein" } }, { "input_text": "Furthermore , S9a and AZT in combination , at noncytoxic concentrations strongly inhibited HIV-1 replication that was more than additive and substantially prolonged the appearance of virus both in acutely infected CD4+ lymphocytes ( SupT ) in culture and in peripheral blood mononuclear cells ( PBMCs ) infected with a primary HIV-1 isolate .", "target_text": { "acutely infected CD4+ lymphocytes": "cell_type", "SupT": "cell_line", "peripheral blood mononuclear cells": "cell_type", "PBMCs": "cell_type" } }, { "input_text": "S9a inhibited TNF-alpha promoter-driven reporter gene activity .", "target_text": { "TNF-alpha": "protein", "reporter gene": "DNA" } }, { "input_text": "It was proposed that the mechanism of antiviral action of S9a was on the host cell , by blocking TNF-alpha transcription via a Tat -induced tar-independent loop , which decreases downstream NF-kappaB activation of HIV-1 long terminal repeat ( LTR ) .", "target_text": { "TNF-alpha": "protein", "Tat": "protein", "NF-kappaB": "protein", "HIV-1 long terminal repeat": "DNA", "LTR": "DNA" } }, { "input_text": "S9a was superior to the first generation compound Canventol , which was superior to the natural compound sarcophytol A , demonstrating that further structure-based enhancement of potency of these compounds is feasible .", "target_text": {} }, { "input_text": "This study suggests a therapeutic approach against AIDS by application of two drugs , one against a cellular and the other a viral target , which may provide an approach to the problem of frequent emergence of resistant variants to combinations of drugs that target only HIV genes .", "target_text": { "HIV genes": "DNA" } }, { "input_text": "Highly polarized HLA class II antigen processing and presentation by human intestinal epithelial cells .", "target_text": { "HLA class II antigen": "protein", "human intestinal epithelial cells": "cell_type" } }, { "input_text": "The high concentration of foreign antigen in the lumen of the gastrointestinal tract is separated from the underlying lymphocytes by a single cell layer of polarized epithelium .", "target_text": { "foreign antigen": "protein", "lumen": "cell_type", "lymphocytes": "cell_type" } }, { "input_text": "Intestinal epithelial cells can express HLA class II antigens and may function as antigen-presenting cells to CD4(+) T cells within the intestinal mucosa .", "target_text": { "Intestinal epithelial cells": "cell_type", "HLA class II antigens": "protein", "antigen-presenting cells to CD4(+) T cells": "cell_type" } }, { "input_text": "Using tetanus toxoid specific and HLA-DR-restricted T lymphocytes , we show that polarized intestinal epithelial cells directed to express HLA-DR molecules are able to initiate class II processing only after internalization of antigen from their apical surface .", "target_text": { "polarized intestinal epithelial cells": "cell_type", "HLA-DR molecules": "protein" } }, { "input_text": "Coexpression of the class II transactivator CIITA in these cells , which stimulates highly efficient class II processing without the characteristic decline in barrier function seen in polarized monolayers treated with the proinflammatory cytokine gamma-IFN , facilitates antigen processing from the basolateral surface .", "target_text": { "class II transactivator CIITA": "protein", "proinflammatory cytokine gamma-IFN": "protein" } }, { "input_text": "In both cases , peptide presentation to T cells via class II molecules was restricted to the basolateral surface .", "target_text": { "T cells": "cell_type", "class II molecules": "protein" } }, { "input_text": "These data indicate a highly polarized functional architecture for antigen processing and presentation by intestinal epithelial cells , and suggest that the functional outcome of antigen processing by the intestinal epithelium is both dependent on the cellular surface at which the foreign antigen is internalized and by the underlying degree of mucosal inflammation", "target_text": { "intestinal epithelial cells": "cell_type" } }, { "input_text": "Tobacco smoke induces coordinate activation of HSF and inhibition of NFkappaB in human monocytes : effects on TNFalpha release .", "target_text": { "HSF": "protein", "NFkappaB": "protein", "human monocytes": "cell_type", "TNFalpha": "protein" } }, { "input_text": "Tobacco smoke ( TS ) exposure is a major risk factor for human disease , and macrophages of healthy smokers have a depressed capacity to release cytokines , including tumor necrosis factor ( TNF ) alpha .", "target_text": { "macrophages": "cell_type", "cytokines": "protein", "tumor necrosis factor ( TNF ) alpha": "protein" } }, { "input_text": "TS induces the synthesis of heat shock ( HS ) /stress proteins ( HSP ) , and , in particular , of Hsp70 .", "target_text": { "heat shock ( HS ) /stress proteins": "protein", "HSP": "protein", "Hsp70": "protein" } }, { "input_text": "We determined whether Hsp70 induction by TS was mediated by the activation of the HS transcription factor , HSF .", "target_text": { "Hsp70": "protein", "HS transcription factor": "protein", "HSF": "protein" } }, { "input_text": "HSF activation has been shown to inhibit NFkappaB .", "target_text": { "HSF": "protein", "NFkappaB": "protein" } }, { "input_text": "Thus , we also determined the effects of TS on NFkappaB .", "target_text": { "NFkappaB": "protein" } }, { "input_text": "U937 cells and human peripheral blood monocytes were exposed to TS , binding activities of the respective transcription factors were analyzed , and Hsp70 expression and TNFalpha release were determined in parallel .", "target_text": { "U937 cells": "cell_line", "human peripheral blood monocytes": "cell_type", "transcription factors": "protein", "Hsp70": "protein", "TNFalpha": "protein" } }, { "input_text": "TS activated HSF , which was associated with Hsp70 overexpression and inhibition of NFkappaB binding activity and TNFalpha release .", "target_text": { "HSF": "protein", "Hsp70": "protein", "NFkappaB": "protein", "TNFalpha": "protein" } }, { "input_text": "The altered cytokine profile observed in smokers may relate to an HSF / Hsp70 -mediated inhibition of NFkappaB activity .", "target_text": { "cytokine profile": "protein", "HSF": "protein", "Hsp70": "protein", "NFkappaB": "protein" } }, { "input_text": "Copyright 1998 Academic Press .", "target_text": {} }, { "input_text": "[ Molecular mechanism of cytokine gene expression in Th1 and Th2 ]", "target_text": { "cytokine gene": "DNA", "Th1": "cell_line", "Th2": "cell_line" } }, { "input_text": "Upon activation by antigens , helper T cells differentiate into one of several subsets , characterized by their distinct cytokine -production patterns .", "target_text": { "antigens": "protein", "helper T cells": "cell_type", "cytokine": "protein" } }, { "input_text": "Among these subsets , Th1 cells are known to activate cellular immunity resulting in inflammatory response , whereas Th2 cells induce humoral and allergic responses and suppress inflammation .", "target_text": { "Th1 cells": "cell_line", "Th2 cells": "cell_line" } }, { "input_text": "Th1 and Th2 effector functions and their development are attributable to their distinct cytokine expression patterns .", "target_text": { "cytokine": "protein" } }, { "input_text": "Recent reports have demonstrated that differential expression of cell surface molecules , such as adhesion molecule and chemokine receptor , is involved in their recruitment into target tissues .", "target_text": { "adhesion molecule": "protein", "chemokine receptor": "protein" } }, { "input_text": "It is , therefore , suggested that clarification of the mechanisms of differential gene expression in Th1/Th2 should lead to rational strategies for manipulating pathological immune responses .", "target_text": { "Th1/Th2": "cell_line" } }, { "input_text": "Activation of helper T cells mediated by the T cell receptor induces a series of biochemical events .", "target_text": { "helper T cells": "cell_type" } }, { "input_text": "Among them , both the activation of PKC/Ras- and CaM/CN- mediated pathways play a central role in the signal transduction of cytokine gene expression .", "target_text": { "cytokine gene": "DNA" } }, { "input_text": "Closer examination using non-transformed murine Th1 and Th2 clones suggested that a balance between the activities of the two signaling pathways contributes to cytokine gene expression .", "target_text": { "cytokine gene": "DNA" } }, { "input_text": "We propose that one of the targets of PGE2 , whose effect distinguishes Th1 from Th2 , resides in the downstream PKC/Ras -mediated pathway .", "target_text": { "Th1": "cell_line", "PKC/Ras": "protein" } }, { "input_text": "Signalling into the T-cell nucleus : NFAT regulation .", "target_text": { "NFAT": "protein" } }, { "input_text": "The nuclear factor of activated T cells ( NFAT ) plays an important role in T-cell biology .", "target_text": { "nuclear factor of activated T cells": "protein", "NFAT": "protein" } }, { "input_text": "Activation of T cells results in the rapid calcineurin -dependent translocation of NFAT transcription factors from the cytoplasm to the nucleus .", "target_text": { "calcineurin": "protein", "NFAT": "protein", "transcription factors": "protein" } }, { "input_text": "This translocation process coupled to the subsequent active maintenance of NFAT in the nucleus compartment is critical for the induction of expression of several genes encoding cytokines and membrane proteins that modulate immune responses .", "target_text": { "NFAT": "protein", "cytokines": "protein", "membrane proteins": "protein" } }, { "input_text": "The molecular cloning of the NFAT family of transcription factors has facilitated rapid progress in the understanding of the signalling mechanisms that control the activity of NFAT .", "target_text": { "NFAT": "protein", "NFAT family": "protein", "transcription factors": "protein" } }, { "input_text": "Differential RNA display identifies novel genes associated with decreased vitamin D receptor expression .", "target_text": { "novel genes": "DNA", "vitamin D receptor": "protein" } }, { "input_text": "To characterize further the function of the intracellular vitamin D receptor ( VDR ) , we have developed stable transfectant variants of a vitamin D-responsive cell line ( U937 ) which express either decreased or increased numbers of VDR .", "target_text": { "vitamin D receptor": "protein", "intracellular vitamin D receptor": "protein", "VDR": "protein", "stable transfectant variants": "cell_line", "vitamin D-responsive cell line": "cell_line", "U937": "cell_line" } }, { "input_text": "In this study we have analyzed changes in gene expression associated with this variable VDR expression .", "target_text": { "VDR": "protein" } }, { "input_text": "Initial experiments indicated that a 50 % decrease in VDR levels was associated with a 2-fold increase in cell proliferation and a similar rise in c-myc mRNA expression .", "target_text": { "VDR": "protein", "c-myc mRNA": "RNA" } }, { "input_text": "Further studies were carried out using differential RNA display ( DD ) .", "target_text": {} }, { "input_text": "Sequence analysis of DD products revealed two cDNAs with identity to known gene products : the catalytic sub-unit of DNA-protein kinase ( DNA-PK(CS) ) , and the peroxisomal enzyme 17beta-hydroxysteroid dehydrogenase type IV ( 17beta-HSD IV ) .", "target_text": { "DD products": "protein", "cDNAs": "DNA", "known gene products": "protein", "catalytic sub-unit": "protein", "DNA-protein kinase": "protein", "catalytic sub-unit of DNA-protein kinase": "protein", "DNA-PK(CS)": "protein", "peroxisomal enzyme 17beta-hydroxysteroid dehydrogenase type IV": "protein", "17beta-HSD IV": "protein" } }, { "input_text": "Northern analysis confirmed that expression of both mRNAs was reduced in cells with decreased numbers of VDR .", "target_text": { "mRNAs": "RNA", "VDR": "protein" } }, { "input_text": "Down-regulation of 17beta-HSD IV mRNA expression was associated with enhanced estradiol inactivation by U937 cells , suggesting a link between estrogenic pathways and cell proliferation .", "target_text": { "17beta-HSD IV": "protein", "U937 cells": "cell_line" } }, { "input_text": "Further Northern analyses indicated that there was no significant change in 17beta-HSD IV or DNA-PK(CS) mRNA levels following treatment with 1,25(OH)2D3 , although expression of both genes varied with changes in cell proliferation .", "target_text": { "17beta-HSD IV": "protein", "DNA-PK(CS)": "protein", "DNA-PK(CS) mRNA": "RNA" } }, { "input_text": "These data suggest that , in addition to its established role as a hormone-dependent trans-activator , VDR may influence gene expression by ligand-independent mechanisms .", "target_text": { "hormone-dependent trans-activator": "protein", "VDR": "protein" } }, { "input_text": "Prostaglandin E2 Up-regulates HIV-1 long terminal repeat -driven gene activity in T cells via NF-kappaB -dependent and -independent signaling pathways .", "target_text": { "HIV-1 long terminal repeat": "DNA", "T cells": "cell_type" } }, { "input_text": "Replication of human immunodeficiency virus type-1 ( HIV-1 ) is highly dependent on the state of activation of the infected cells and is modulated by interactions between viral and host cellular factors .", "target_text": { "infected cells": "cell_type" } }, { "input_text": "Prostaglandin E2 ( PGE2 ) , a pleiotropic immunomodulatory molecule , is observed at elevated levels during HIV-1 infection as well as during the course of other pathogenic infections .", "target_text": { "pleiotropic immunomodulatory molecule": "protein" } }, { "input_text": "In 1G5 , a Jurkat-derived T cell line stably transfected with a luciferase gene driven by HIV-1 long terminal repeat ( LTR ) , we found that PGE2 markedly enhanced HIV-1 LTR -mediated reporter gene activity .", "target_text": { "1G5": "cell_line", "Jurkat-derived T cell line": "cell_line", "luciferase gene": "DNA", "HIV-1 long terminal repeat": "DNA", "LTR": "DNA", "HIV-1 LTR": "DNA", "reporter gene": "DNA" } }, { "input_text": "Experiments have been conducted to identify second messengers involved in this PGE2 -dependent up-regulating effect on the regulatory element of HIV-1 .", "target_text": { "second messengers": "protein" } }, { "input_text": "In this study , we present evidence indicating that signal transduction pathways induced by PGE2 necessitate the participation of cyclic AMP , protein kinase A , and Ca2+ .", "target_text": { "protein kinase A": "protein" } }, { "input_text": "Experiments conducted with different HIV-1 LTR -based vectors suggested that PGE2 -mediated activation effect on HIV-1 transcription was transduced via both NF-kappaB -dependent and -independent signaling pathways .", "target_text": { "HIV-1 LTR": "DNA", "HIV-1 LTR -based vectors": "DNA" } }, { "input_text": "The involvement of NF-kappaB in the PGE2 -dependent activating effect on HIV-1 transcription was further confirmed using a kappaB-regulated luciferase encoding vector and by electrophoretic mobility shift assays .", "target_text": { "NF-kappaB": "protein", "kappaB-regulated luciferase encoding vector": "DNA" } }, { "input_text": "Results from Northern blot and flow cytometric analyses , as well as the use of a selective antagonist indicated that PGE2 modulation of HIV-1 LTR -driven reporter gene activity in studied T lymphoid cells is transduced via the EP4 receptor subtype .", "target_text": { "HIV-1 LTR": "DNA", "reporter gene": "DNA", "T lymphoid cells": "cell_type", "EP4 receptor subtype": "protein" } }, { "input_text": "These results suggest that secretion of PGE2 by macrophages in response to infection or inflammatory activators could induce signaling events resulting in activation of proviral DNA present into T cells latently infected with HIV-1 .", "target_text": { "macrophages": "cell_type", "T cells": "cell_type" } }, { "input_text": "Activation of distinct transcription factors in neutrophils by bacterial LPS , interferon-gamma , and GM-CSF and the necessity to overcome the action of endogenous proteases .", "target_text": { "transcription factors": "protein", "neutrophils": "cell_type", "interferon-gamma": "protein", "GM-CSF": "protein", "endogenous proteases": "protein" } }, { "input_text": "Human neutrophils can be induced to actively transcribe a number of early-response genes , in particular those encoding cytokines , chemokines , and the high-affinity surface receptor for IgG , FcgammaRI .", "target_text": { "neutrophils": "cell_type", "early-response genes": "DNA", "cytokines": "protein", "chemokines": "protein", "IgG": "protein", "FcgammaRI": "protein" } }, { "input_text": "Although little is known to date about the regulation of gene transcription in neutrophils , several indications point to a role for distinct transcription factors , such as members of the NF-kappaB and STAT families .", "target_text": { "neutrophils": "cell_type", "transcription factors": "protein", "NF-kappaB": "protein", "STAT families": "protein" } }, { "input_text": "In this study , we investigated whether these transcription factors become activated under stimulatory conditions which are known to induce gene transcription in neutrophils .", "target_text": { "transcription factors": "protein", "neutrophils": "cell_type" } }, { "input_text": "Unexpectedly , we found that conventional procedures employed to prepare cellular extracts cause the release of proteolytic activities that are normally stored in intracellular granules , resulting in the degradation of various NF-kappaB /Rel and STAT proteins .", "target_text": { "NF-kappaB": "protein", "NF-kappaB /Rel": "protein", "STAT proteins": "protein" } }, { "input_text": "To circumvent this problem , we developed an alternative procedure which allowed us to show that in neutrophils , LPS and TNFalpha induce a NF-kappaB DNA-binding activity which essentially consists of p50/RelA dimers , and that IFNgamma promotes the binding of STAT1 homodimers to the IFNgamma response region of the FcgammaRI promoter .", "target_text": { "neutrophils": "cell_type", "TNFalpha": "protein", "NF-kappaB": "protein", "p50/RelA dimers": "protein", "IFNgamma": "protein", "STAT1 homodimers": "protein", "IFNgamma response region": "DNA", "FcgammaRI": "protein", "FcgammaRI promoter": "DNA" } }, { "input_text": "Moreover , we report that neutrophil stimulation with GM-CSF results in the formation of a STAT5 -containing DNA-binding activity .", "target_text": { "GM-CSF": "protein", "STAT5": "protein" } }, { "input_text": "Collectively , the current findings open new perspectives about mechanisms that are likely to regulate gene transcription in neutrophils .", "target_text": { "neutrophils": "cell_type" } }, { "input_text": "In addition , the procedure described herein could prove useful in other cell types that express high levels of endogenous proteases .", "target_text": { "endogenous proteases": "protein" } }, { "input_text": "Low CD3+CD28-induced interleukin-2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells .", "target_text": { "interleukin-2": "protein", "neonatal T cells": "cell_type" } }, { "input_text": "The capacity of neonatal T cells to secrete interleukin-2 ( IL-2 ) has been reported to be variable .", "target_text": { "neonatal T cells": "cell_type", "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "We analysed IL-2 production in purified neonatal and adult T cells using polyclonal activator phorbol ester + calcium ionophore ( PDBu + iono ) or receptor-mediated anti-CD3 /anti-CD3+ anti-CD28 stimulation .", "target_text": { "IL-2": "protein", "anti-CD3": "protein", "anti-CD28": "protein" } }, { "input_text": "PDBu + iono induced equally high IL-2 levels in both groups and , when stimulated with plate-bound anti-CD3 monoclonal antibody ( mAb ) , the IL-2 secretion by neonatal cells was undetectable and adult cells produced low amounts of IL-2 ( mean 331 +/- 86 pg/ml ) .", "target_text": { "IL-2": "protein", "anti-CD3 monoclonal antibody": "protein", "mAb": "protein", "neonatal cells": "cell_type", "adult cells": "cell_type" } }, { "input_text": "The addition of anti-CD28 mAb to anti-CD3-stimulated cells markedly increased IL-2 production in both cell types , but levels of IL-2 in neonatal T cells remained clearly lower than those of adult T cells ( respective mean values : 385 +/- 109 pg/ml and 4494 +/- 1199 pg/ml ) .", "target_text": { "anti-CD28 mAb": "protein", "anti-CD3-stimulated cells": "cell_line", "IL-2": "protein", "neonatal T cells": "cell_type", "adult T cells": "cell_type" } }, { "input_text": "As NF-kappa B is a critical transcription factor in the control of IL-2 expression , we next analysed its nuclear translocation in neonatal and adult T cells using the electrophoretic mobility shift assay and , because induction of reactive oxygen intermediates ( ROI ) is required for the activation of NF-kappa B , we also analysed levels of intracellular ROI in these cells using the ROI -reactive fluorochrome DCFH-DA and flow cytometry .", "target_text": { "NF-kappa B": "protein", "transcription factor": "protein", "IL-2": "protein" } }, { "input_text": "In neonatal T cells NF-kappa B activation and ROI formation after anti-CD3 stimulation were low compared with adult T cells and , although addition of anti-CD28 mAb increased induction of NF-kappa B and ROI formation , levels similar to those of adults were not achieved .", "target_text": { "neonatal T cells": "cell_type", "NF-kappa B": "protein", "anti-CD3": "protein", "adult T cells": "cell_type", "anti-CD28 mAb": "protein" } }, { "input_text": "After PDBu + iono stimulation , the cells showed similar ROI formation and IL-2 secretion .", "target_text": { "IL-2": "protein" } }, { "input_text": "Our results suggest that reduced IL-2 production by neonatal T cells is specific for anti-CD3 and anti-CD3 + anti-CD28 -mediated stimulation and that these activators can not effectively activate the ROI -NF-kappa B signalling pathway in neonatal T cells .", "target_text": { "IL-2": "protein", "neonatal T cells": "cell_type", "anti-CD3": "protein", "anti-CD28": "protein", "-NF-kappa B": "protein" } }, { "input_text": "CD30 is a CD40 -inducible molecule that negatively regulates CD40 -mediated immunoglobulin class switching in non-antigen-selected human B cells .", "target_text": { "CD30": "protein", "CD40": "protein", "CD40 -inducible molecule": "protein", "CD40 -mediated immunoglobulin": "protein", "non-antigen-selected human B cells": "cell_line" } }, { "input_text": "We used our monoclonal model of germinal center maturation , CL-01 B cells , to investigate the role of CD30 in human B cell differentiation .", "target_text": { "CL-01 B cells": "cell_type", "CD30": "protein" } }, { "input_text": "CL-01 cells are IgM + IgD + CD30 + and switch to IgG , IgA , and IgE when exposed to CD40L and IL-4 .", "target_text": { "CL-01 cells": "cell_line", "IgM": "protein", "IgD": "protein", "CD30": "protein", "IgG": "protein", "IgA": "protein", "IgE": "protein", "CD40L": "protein", "IL-4": "protein" } }, { "input_text": "Switching is hampered by CD30 coengagement , possibly through interference with the CD40 -mediated NF-kappaB -dependent transcriptional activation of downstream C(H) genes .", "target_text": { "CD30": "protein", "CD40": "protein", "NF-kappaB": "protein", "downstream C(H) genes": "DNA" } }, { "input_text": "The physiological relevance of this phenomenon is emphasized by similar CD30 -mediated effects in naive B cells .", "target_text": { "CD30": "protein", "naive B cells": "cell_type" } }, { "input_text": "Expression of CD30 by these cells is induced by CD40L but is inhibited by B cell receptor coengagement and/or exposure to IL-6 and IL-12 .", "target_text": { "CD30": "protein", "CD40L": "protein", "IL-6": "protein", "IL-12": "protein" } }, { "input_text": "Our data suggest that CD30 critically regulates the CD40 -mediated differentiation of non-antigen-selected human B cells .", "target_text": { "CD30": "protein", "CD40": "protein", "non-antigen-selected human B cells": "cell_line" } }, { "input_text": "Calcineurin and the biological effect of cyclosporine and tacrolimus .", "target_text": { "Calcineurin": "protein" } }, { "input_text": "The mechanism of the immunosuppressive effect of CyA and FK 506 can be monitored in vivo in humans .", "target_text": {} }, { "input_text": "The picture emerging is of a close relationship between drug concentrations and CN inhibition .", "target_text": {} }, { "input_text": "But many puzzles of the drugs remain .", "target_text": {} }, { "input_text": "What is the role of CyA in the activation of transforming growth factor-beta ( TGF-beta ) , particularly in relationship to nephrotoxicity and fibrogenesis ?", "target_text": { "transforming growth factor-beta": "protein", "TGF-beta": "protein" } }, { "input_text": "How important are the anti-inflammatory ( non T ) effects of CyA , and which cells do they operate in ?", "target_text": {} }, { "input_text": "Are there effects of CyA and FK 506 all attributable to CN inhibition , and how much of them are mediated through the NFATC family of transcription factors ?", "target_text": { "NFATC family": "protein", "transcription factors": "protein" } }, { "input_text": "Finally , it would be useful to know what the inhibitory effects of CyA are on tolerance and negative regulatory events .", "target_text": {} }, { "input_text": "Stimulation of B and T cells activates expression of transcription and differentiation factors .", "target_text": {} }, { "input_text": "During B and T cell differentiation and proliferation many genes are induced or repressed while certain genes are constitutively expressed .", "target_text": {} }, { "input_text": "To investigate processes related to B and T cell activation , the gene expression of stimulated and nonstimulated Ramos and Jurkat cells was studied using cDNA microarray technology .", "target_text": {} }, { "input_text": "Simultaneous analysis of close to 600 genes indicated highest increase in the expression of certain transcription , differentiation and proliferation factors .", "target_text": { "600 genes": "DNA" } }, { "input_text": "Many of these genes have not previously been shown to funcion in the stimulated lymphocytes .", "target_text": { "stimulated lymphocytes": "cell_type" } }, { "input_text": "Also genes encoding proteins involved in DNA replication , binding , transcription and translation were induced .", "target_text": {} }, { "input_text": "Large part of the activated genes were under very stringent regulation being expressed only after stimulation .", "target_text": { "activated genes": "DNA" } }, { "input_text": "The mechanism and function of the expressed genes during lymphocyte differentiation and in disorders is discussed .", "target_text": { "expressed genes": "DNA" } }, { "input_text": "Interleukin 2 and 15 activate Stat3alpha in human T lymphocytes .", "target_text": { "Stat3alpha": "protein", "human T lymphocytes": "cell_type" } }, { "input_text": "Signal transducer and activator of transcription 3 ( Stat3 ) has recently been shown to exist in two alternatively spliced isoforms , a short form , Stat3beta , and a longer form , Stat3alpha , displaying differences in transcriptional activity .", "target_text": { "Signal transducer and activator of transcription 3": "protein", "Stat3": "protein", "Stat3beta": "protein", "Stat3alpha": "protein" } }, { "input_text": "It is unknown which Stat3 isoform ( s ) is activated in response to interleukin ( IL ) -2 and IL-15 .", "target_text": { "Stat3": "protein", "Stat3 isoform": "protein", "interleukin ( IL ) -2": "protein", "IL-15": "protein" } }, { "input_text": "Here , cytokine -induced activation of Stat3 in previously activated CD4(+) human T cells was examined using Stat3 antibodies directed against different regions of Stat3 .", "target_text": { "cytokine": "protein", "Stat3": "protein", "CD4(+) human T cells": "cell_type" } }, { "input_text": "As determined by tyrosine phosphorylation , nuclear translocation and binding to an hSIE-oligonucleotide probe , IL-2 and IL-15 activated the slowly migrating isoform , Stat3alpha .", "target_text": { "IL-2": "protein", "IL-15": "protein", "Stat3alpha": "protein" } }, { "input_text": "In contrast , minimal or no activation of Stat3beta was observed , suggesting that IL-2 and IL-15 predominantly activate Stat3alpha in human CD4(+) T cells .", "target_text": { "Stat3beta": "protein", "IL-2": "protein", "IL-15": "protein", "Stat3alpha": "protein", "human CD4(+) T cells": "cell_type" } }, { "input_text": "In this way , diversity in the expression and activation of Stat3 proteins may provide additional means of regulating cytokine -induced T cell responses .", "target_text": { "Stat3": "protein", "Stat3 proteins": "protein", "cytokine": "protein" } }, { "input_text": "Copyright 1998 Academic Press .", "target_text": {} }, { "input_text": "Transcriptional regulation of lysosomal acid lipase in differentiating monocytes is mediated by transcription factors Sp1 and AP-2 .", "target_text": { "lysosomal acid lipase": "protein", "transcription factors": "protein", "Sp1": "protein", "AP-2": "protein" } }, { "input_text": "Human lysosomal acid lipase ( LAL ) is a hydrolase required for the cleavage of cholesteryl esters and triglycerides derived from plasma lipoproteins .", "target_text": { "lysosomal acid lipase": "protein", "LAL": "protein", "hydrolase": "protein" } }, { "input_text": "It is shown here that during monocyte to macrophage differentiation , the expression of LAL -mRNA is induced .", "target_text": { "LAL": "protein", "LAL -mRNA": "RNA" } }, { "input_text": "This induction is dependent on protein kinase C activity and protein synthesis .", "target_text": { "protein kinase C": "protein" } }, { "input_text": "The cell type-specific increase in LAL expression is further investigated in the THP-1 cell line with respect to transcriptional regulation .", "target_text": { "LAL": "protein", "THP-1 cell line": "cell_line" } }, { "input_text": "The human monocytic leukemia cell line THP-1 differentiates into macrophage-like cells when treated with phorbol esters .", "target_text": { "human monocytic leukemia cell line": "cell_line", "THP-1": "cell_line", "macrophage-like cells": "cell_type" } }, { "input_text": "In order to determine the cis-acting elements necessary for both basal and phorbol 12-myristate-13 acetate ( PMA ) -enhanced promoter activity , we performed deletion analysis and reporter gene assays .", "target_text": { "cis-acting elements": "DNA", "reporter gene": "DNA" } }, { "input_text": "A PMA responsive element has been identified between -182 bp and -107 bp upstream of the major transcription start site .", "target_text": { "PMA responsive element": "DNA", "-182 bp": "DNA", "-107 bp": "DNA", "major transcription start site": "DNA" } }, { "input_text": "Gel mobility shift assays demonstrated that binding of Sp1 and AP-2 to the LAL promoter is increased by PMA in THP-1 cells .", "target_text": { "Sp1": "protein", "AP-2": "protein", "LAL": "protein", "LAL promoter": "DNA", "THP-1 cells": "cell_line" } }, { "input_text": "Co-transfections with expression plasmids for Sp1 and AP-2 further emphasized the important role of these transcription factors in both basal and PMA -enhanced LAL expression .", "target_text": { "expression plasmids": "DNA", "Sp1": "protein", "AP-2": "protein", "transcription factors": "protein", "LAL": "protein" } }, { "input_text": "Our data suggest that differentiation dependent increase of lysosomal acid lipase ( LAL ) expression in THP-1 cells is mediated by a concerted action of Sp1 and AP-2 .", "target_text": { "lysosomal acid lipase": "protein", "LAL": "protein", "THP-1 cells": "cell_line", "Sp1": "protein", "AP-2": "protein" } }, { "input_text": "Relationship between IkappaBalpha constitutive expression , TNFalpha synthesis , and apoptosis in EBV-infected lymphoblastoid cells .", "target_text": { "IkappaBalpha": "protein", "TNFalpha": "protein", "EBV-infected lymphoblastoid cells": "cell_type" } }, { "input_text": "In order to understand the role of NF-kappaB in EBV transformation we have established stably transfected IkappaBalpha into lymphoblastoid cells .", "target_text": { "NF-kappaB": "protein", "IkappaBalpha": "protein", "lymphoblastoid cells": "cell_type" } }, { "input_text": "Two clones were obtained in which the loss of NF-kappaB binding activity correlated with the constitutive expression of the transgenic IkappaBalpha .", "target_text": { "NF-kappaB": "protein", "IkappaBalpha": "protein" } }, { "input_text": "Protein latency expression was determined by immunocytochemistry .", "target_text": {} }, { "input_text": "Expression of surface markers , intracytoplasmic content of cytokines cell cycle analysis after BrdU incorporation and DNA staining with propidium iodide were studied by flow cytometry .", "target_text": { "cytokines": "protein", "BrdU": "protein" } }, { "input_text": "Percentage of apoptotic cells was determined by in-situ labelling of DNA strand breaks .", "target_text": { "apoptotic cells": "cell_type" } }, { "input_text": "No significative changes in EBV latency nor in cell surface marker expression was found .", "target_text": {} }, { "input_text": "In contrast , intracytoplasmic TNFalpha levels were strongly reduced in transfected clones .", "target_text": { "TNFalpha": "protein", "transfected clones": "cell_line" } }, { "input_text": "Furthermore , 30 % of IkappaBalpha transfected cells were apoptotic after 8 h of TNFalpha treatment .", "target_text": { "IkappaBalpha": "protein", "IkappaBalpha transfected cells": "cell_line", "TNFalpha": "protein" } }, { "input_text": "This correlated with a strong reduction of BrdU incorporation after 24 h of TNFalpha treatment .", "target_text": { "TNFalpha": "protein" } }, { "input_text": "No effect was seen with non transfected cells or with cells transfected with a control plasmid .", "target_text": { "transfected cells": "cell_line" } }, { "input_text": "Our results suggest that the TNFalpha gene could be one of the targets of NF-kappaB in EBV infected cells and that NF-kappaB protects EBV -infected cells from apoptosis induced by TNFalpha , which may favour the proliferative effect of this cytokine .", "target_text": { "TNFalpha": "protein", "TNFalpha gene": "DNA", "NF-kappaB": "protein", "NF-kappaB protects EBV -infected cells": "cell_type", "cytokine": "protein" } }, { "input_text": "Seminoma in a postmenopausal woman with a Y;15 translocation in peripheral blood lymphocytes and a t(Y;15)/45,X Turner mosaic pattern in skin fibroblasts .", "target_text": { "Y;15 translocation": "DNA", "peripheral blood lymphocytes": "cell_type", "skin fibroblasts": "cell_type" } }, { "input_text": "We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses .", "target_text": {} }, { "input_text": "The patient was a phenotypic female with late onset menarche ( 18 years of age ) , who was amenorrhoeic for the first year , followed by menses of one to three days ' slight flow with dysmenorrhoea , but an otherwise normal menstrual history .", "target_text": {} }, { "input_text": "A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass .", "target_text": {} }, { "input_text": "Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46,X,-Y,t(Y;15)(q12;p13) .", "target_text": { "peripheral blood lymphocyte cultures": "cell_type" } }, { "input_text": "Cytogenetic examination of the patient 's younger brother , who had fathered three healthy children , showed an identical karyotype .", "target_text": {} }, { "input_text": "Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in skin samples from the patient 's elbow and genital regions , although there were no clinical stigmata of Turner syndrome .", "target_text": { "46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines": "cell_line" } }, { "input_text": "An androgen receptor binding assay of cultured genital skin fibroblasts was negative .", "target_text": { "skin fibroblasts": "cell_type", "cultured genital skin fibroblasts": "cell_line" } }, { "input_text": "Molecular analysis using Southern blot hybridisation , PCR , and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences , including the SRY ( sex determining region of the Y chromosome ) gene sequence .", "target_text": { "SRY ( sex determining region of the Y chromosome ) gene sequence": "DNA" } }, { "input_text": "These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female , although we can not exclude abnormalities of other genes related to sex differentiation .", "target_text": { "45,X cell line": "cell_line" } }, { "input_text": "Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid , cepharanthine , in chronically infected monocytic cells .", "target_text": { "chronically infected monocytic cells": "cell_type" } }, { "input_text": "Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have antiinflammatory , antiallergic , and immunomodulatory activities in vivo .", "target_text": {} }, { "input_text": "As several inflammatory cytokines and oxidative stresses are involved in the pathogenesis of HIV-1 infection , we investigated the inhibitory effects of cepharanthine on tumor necrosis factor alpha ( TNF-alpha ) - and phorbol 12-myristate 13-acetate ( PMA ) - induced HIV-1 replication in chronically infected cell lines .", "target_text": { "cytokines": "protein", "inflammatory cytokines": "protein", "TNF-alpha": "protein", "chronically infected cell lines": "cell_line" } }, { "input_text": "Two chronically HIV-1 -infected cell lines , U1 ( monocytic ) and ACH-2 ( T lymphocytic ) , were stimulated with TNF-alpha or PMA and cultured in the presence of various concentrations of the compound .", "target_text": { "chronically HIV-1 -infected cell lines": "cell_line", "U1": "cell_line", "ACH-2": "cell_line", "TNF-alpha": "protein" } }, { "input_text": "HIV-1 replication was determined by p24 antigen level .", "target_text": { "p24 antigen": "protein" } }, { "input_text": "The inhibitory effects of cepharanthine on HIV-1 long terminal repeat ( LTR ) -driven gene expression and nuclear factor kappaB ( NF-kappaB ) activation were also examined .", "target_text": { "HIV-1 long terminal repeat": "DNA", "LTR": "DNA", "nuclear factor kappaB": "protein", "NF-kappaB": "protein" } }, { "input_text": "Cepharanthine dose dependently inhibited HIV-1 replication in TNF-alpha- and PMA- stimulated U1 cells but not in ACH-2 cells .", "target_text": { "ACH-2 cells": "cell_line" } }, { "input_text": "Its 50 % effective and cytotoxic concentrations were 0.016 and 2.2 microg/ml in PMA -stimulated U1 cells , respectively .", "target_text": { "PMA -stimulated U1 cells": "cell_line" } }, { "input_text": "Cepharanthine was found to suppress HIV-1 LTR -driven gene expression through the inhibition of NF-kappaB activation .", "target_text": { "HIV-1 LTR": "DNA", "NF-kappaB": "protein" } }, { "input_text": "These results indicate that cepharanthine is a highly potent inhibitor of HIV-1 replication in a chronically infected monocytic cell line .", "target_text": { "chronically infected monocytic cell line": "cell_line" } }, { "input_text": "Since biscoclaurine alkaloids , containing cepharanthine as a major component , are widely used for the treatment of patients with various inflammatory diseases in Japan , cepharanthine should be further pursued for its chemotherapeutic potential in HIV-1 -infected patients .", "target_text": {} }, { "input_text": "NF-kappaB only partially mediates Epstein-Barr virus latent membrane protein 1 activation of B cells .", "target_text": { "NF-kappaB": "protein", "Epstein-Barr virus latent membrane protein 1": "protein" } }, { "input_text": "The latent membrane protein 1 ( LMP1 ) of Epstein-Barr virus ( EBV ) is required for EBV -induced immortalization of human B cells and causes tumorigenic transformation of cell lines .", "target_text": { "latent membrane protein 1": "protein", "LMP1": "protein", "human B cells": "cell_type", "cell lines": "cell_line" } }, { "input_text": "LMP1 expression induces phenotypic changes resembling B cell activation , such as cell size increase and up-regulation of cell surface activation markers .", "target_text": { "LMP1": "protein", "cell surface activation markers": "protein" } }, { "input_text": "LMP1 contains two domains that activate the transcription factor NF-kappaB , one through interactions with TRAF proteins and the other with the TRADD protein .", "target_text": { "LMP1": "protein", "transcription factor": "protein", "NF-kappaB": "protein", "TRAF proteins": "protein", "TRADD protein": "protein" } }, { "input_text": "The purpose of the present study was to investigate the importance of NF-kappaB induction in the up-regulation of the B cell activation markers ICAM-1 and CD71 by LMP1 .", "target_text": { "NF-kappaB": "protein", "ICAM-1": "protein", "CD71": "protein", "LMP1": "protein" } }, { "input_text": "This study shows that expression of LMP1 activates transcription from p50/p65- and c-Rel- responsive promoters , and that this activity can be completely inhibited by expression of a dominant inhibitory IkappaB mutant .", "target_text": { "LMP1": "protein", "inhibitory IkappaB mutant": "protein" } }, { "input_text": "ICAM-1 and CD71 are nevertheless up-regulated by LMP1 in primary B cells and cell lines expressing the dominant IkappaB .", "target_text": { "ICAM-1": "protein", "CD71": "protein", "LMP1": "protein", "primary B cells": "cell_type", "dominant IkappaB": "protein" } }, { "input_text": "Furthermore , LMP1 -induced cell size increase of primary B cells was unaffected by IkappaB expression .", "target_text": { "LMP1": "protein", "primary B cells": "cell_type", "IkappaB": "protein" } }, { "input_text": "It was concluded that even when LMP1 is unable to activate NF-kappaB , it is still capable of inducing certain characteristics of activated B cells , strongly suggesting that LMP1 can also activate cells independently of NF-kappaB .", "target_text": { "LMP1": "protein", "NF-kappaB": "protein", "activated B cells": "cell_type" } }, { "input_text": "Models of lineage switching in hematopoietic development : a new myeloid-committed eosinophil cell line ( YJ ) demonstrates trilineage potential .", "target_text": { "myeloid-committed eosinophil cell line": "cell_line", "YJ": "cell_line" } }, { "input_text": "A new human leukemia cell line with an eosinophilic phenotype , designated YJ , was established from the peripheral blood cells of a patient with chronic myelomonocytic leukemia ( CMMoL ) with eosinophilia .", "target_text": { "human leukemia cell line": "cell_line", "YJ": "cell_line", "peripheral blood cells": "cell_type" } }, { "input_text": "When cultured in RPMI 1640 medium containing 10 % fetal bovine serum , most YJ cells were myeloblastoid with a small number of the cells having eosinophilic granules .", "target_text": { "YJ cells": "cell_line" } }, { "input_text": "Cell surface markers in the YJ cells were positive for CD33 and were negative for CD34 , CD16 and CD23 .", "target_text": { "Cell surface markers": "protein", "YJ cells": "cell_line", "CD33": "protein", "CD34": "protein", "CD16": "protein", "CD23": "protein" } }, { "input_text": "The eosinophilic characteristics of YJ cells were confirmed by histochemical staining with Fast-Green/Neutral-Red and by the expression of mRNAs for eosinophil-associated granule proteins , eosinophil cationic protein ( ECP ) , eosinophil-derived neurotoxin ( EDN ) , eosinophil peroxidase ( EPO ) , and major basic protein ( MBP ) , and for the Charcot-Leyden crystal ( CLC ) protein .", "target_text": { "YJ cells": "cell_line", "mRNAs": "RNA", "eosinophil-associated granule proteins": "protein", "eosinophil cationic protein": "protein", "ECP": "protein", "eosinophil-derived neurotoxin": "protein", "EDN": "protein", "eosinophil peroxidase": "protein", "EPO": "protein", "major basic protein": "protein", "MBP": "protein", "Charcot-Leyden crystal ( CLC ) protein": "protein" } }, { "input_text": "The YJ cells could be induced towards monocytic differentiation by stimulation with phorbol 12-myristate 13-acetate ( PMA ) .", "target_text": { "YJ cells": "cell_line" } }, { "input_text": "The monocytic characteristics of YJ cells treated with PMA were confirmed by morphological analysis with alpha-naphthyl butyrate esterase staining , by CD14 expression , and by increased expression of Egr-1 mRNA .", "target_text": { "YJ cells": "cell_line", "CD14": "protein", "Egr-1 mRNA": "RNA" } }, { "input_text": "Furthermore , YJ cells could be differentiated towards the neutrophil lineage by stimulation with all-trans retinoic acid ( RA ) .", "target_text": { "YJ cells": "cell_line", "neutrophil lineage": "cell_type" } }, { "input_text": "YJ cells treated in vitro with 2 microM RA differentiated into metamyelocytes and band neutrophils , and increased the number of nitroblue tetrazolium ( NBT ) -positive cells and increased gp91phox mRNA expression .", "target_text": { "YJ cells": "cell_line", "metamyelocytes": "cell_type", "band neutrophils": "cell_type", "nitroblue tetrazolium ( NBT ) -positive cells": "cell_line", "gp91phox mRNA": "RNA" } }, { "input_text": "Thus , the YJ cell line exhibited eosinophilic characteristics , but was able to differentiate to the monocytic or neutrophilic lineages in response to PMA or RA , respectively .", "target_text": { "YJ cell line": "cell_line" } }, { "input_text": "The expression of genes for transcription factors involved in myeloid differentiation was evaluated by Northern blot analysis .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Increased expression of Egr-1 was observed with macrophage differentiation .", "target_text": { "Egr-1": "protein" } }, { "input_text": "In contrast , increased expressions of C/EBPbeta and MZF-1 mRNA occurred with neutrophilic differentiation .", "target_text": { "C/EBPbeta": "protein", "MZF-1": "protein", "MZF-1 mRNA": "RNA" } }, { "input_text": "The YJ cell line should be useful for elucidating the molecular mechanisms governing lineage switching from the eosinophil to monocytic or neutrophil lineages .", "target_text": { "YJ cell line": "cell_line", "eosinophil": "cell_type" } }, { "input_text": "Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury .", "target_text": { "Interleukin-6": "protein" } }, { "input_text": "Hemorrhagic shock ( HS ) initiates an inflammatory cascade that includes the production of cytokines and recruitment of neutrophils ( PMN ) and may progress to organ failure , inducing acute respiratory distress syndrome ( ARDS ) .", "target_text": { "cytokines": "protein", "neutrophils": "cell_type", "PMN": "cell_type" } }, { "input_text": "To examine the hypothesis that interleukin-6 ( IL-6 ) contributes to PMN infiltration and lung damage in HS , we examined the lungs of rats subjected to unresuscitated and resuscitated HS for the production of IL-6 and activation of Stat3 .", "target_text": { "interleukin-6": "protein", "IL-6": "protein", "Stat3": "protein" } }, { "input_text": "Using semiquantitative RT- PCR , we found a striking increase in IL-6 mRNA levels only in resuscitated HS , with peak levels observed 1 h after initiation of resuscitation .", "target_text": { "IL-6": "protein", "IL-6 mRNA": "RNA" } }, { "input_text": "Increased IL-6 protein expression was localized to bronchial and alveolar cells .", "target_text": { "IL-6": "protein" } }, { "input_text": "Electrophoretic mobility shift assay of protein extracts from shock lungs exhibited an increase in Stat3 activation with kinetics similar to IL-6 mRNA .", "target_text": { "Stat3": "protein", "IL-6": "protein", "IL-6 mRNA": "RNA" } }, { "input_text": "In situ DNA binding assay determined Stat3 activation predominantly within alveoli .", "target_text": { "Stat3": "protein" } }, { "input_text": "Intratracheal instillation of IL-6 alone into normal rats resulted in PMN infiltration into lung interstitium and alveoli , marked elevation of bronchoalveolar lavage cellularity , and increased wet-to-dry ratio .", "target_text": { "IL-6": "protein" } }, { "input_text": "These findings indicate that IL-6 production and Stat3 activation occur early in HS and may contribute to PMN-mediated lung injury , including ARDS after HS .", "target_text": { "IL-6": "protein", "Stat3": "protein" } }, { "input_text": "The MHC class II transactivator ( CIITA ) requires conserved leucine charged domains for interactions with the conserved W box promoter element .", "target_text": { "MHC class II transactivator": "protein", "CIITA": "protein", "leucine charged domains": "protein", "W box promoter element": "DNA" } }, { "input_text": "The class II transactivator CIITA is required for transcriptional activation of the major histocompatibility complex ( MHC ) class II genes .", "target_text": { "class II transactivator": "protein", "CIITA": "protein", "major histocompatibility complex ( MHC ) class II genes": "DNA" } }, { "input_text": "Aside from an N-terminal acidic transcriptional activation domain , little is known about how this factor functions .", "target_text": { "N-terminal acidic transcriptional activation domain": "DNA" } }, { "input_text": "Extensive mutagenesis of CIITA was undertaken to identify structural motifs required for function .", "target_text": { "CIITA": "protein" } }, { "input_text": "The ability of mutants to activate a reporter gene under the control of MHC class II conserved W-X-Y or X-Y regulatory elements was determined .", "target_text": { "MHC class II": "protein" } }, { "input_text": "Two mutants displayed differential activity between the two promoters , activating transcription with the W-X-Y but not the X-Y elements .", "target_text": { "promoters": "DNA" } }, { "input_text": "All mutants were tested for their ability to interfere with wild-type CIITA activity .", "target_text": { "CIITA": "protein" } }, { "input_text": "Five CIITA mutant constructions were able to down-regulate wild-type CIITA activity .", "target_text": { "CIITA": "protein", "CIITA mutant constructions": "DNA" } }, { "input_text": "Three of these mutants contained targeted disruptions of potential functional motifs : the acidic activation domain , a putative GTP -binding motif and two leucine charged domains ( LCD motifs ) .", "target_text": { "acidic activation domain": "protein", "GTP -binding motif": "protein", "leucine charged domains": "protein", "LCD motifs": "protein" } }, { "input_text": "The other two contained mutations in regions that do not have homology to described proteins .", "target_text": {} }, { "input_text": "The characterization of CIITA mutants that are able to discriminate between promoters with or without the W box strongly suggests that CIITA requires such interactions for function .", "target_text": { "CIITA": "protein", "CIITA mutants": "protein", "W box": "DNA" } }, { "input_text": "The identification of LCD motifs required for CIITA function brings to light a previously undefined role of these motifs in CIITA function .", "target_text": { "LCD motifs": "protein", "CIITA": "protein" } }, { "input_text": "The peroxisome proliferator-activated receptor alpha ( PPARalpha ) ligand WY 14,643 does not interfere with leukotriene B4 induced adhesion of neutrophils to endothelial cells .", "target_text": { "peroxisome proliferator-activated receptor alpha": "protein", "PPARalpha": "protein", "neutrophils": "cell_type", "endothelial cells": "cell_type" } }, { "input_text": "Peroxisome proliferator-activated receptors ( PPAR ) control discrete genes involved in fatty acid and lipid metabolism .", "target_text": { "Peroxisome proliferator-activated receptors": "protein", "PPAR": "protein" } }, { "input_text": "Recently , it was suggested that activation of the alpha isoform of PPAR by the potent proinflammatory mediator leukotriene B4 ( LTB4 ) enhanced degradation of this eicosanoid , offersuggesting a new aspect of down-regulation of inflammation .", "target_text": { "alpha isoform": "protein", "PPAR": "protein" } }, { "input_text": "Here , we studied whether PPARalpha activation ( by means of the selective agonist WY 14,643 ) of endothelial cells , pivotal in the regulation of inflammatory responses , interfered with LTB4 induced adhesion of PMN neutrophil granulocytes in vitro .", "target_text": { "PPARalpha": "protein", "endothelial cells": "cell_type", "PMN neutrophil granulocytes": "cell_type" } }, { "input_text": "When endothelial cells were treated with WY 14,643 prior to activation with LTB4 ( or fMLP , IL-1beta or TNFalpha , as controls ) we could not document any effect on the number of adhering PMN or duration of the response .", "target_text": { "endothelial cells": "cell_type", "fMLP": "protein", "IL-1beta": "protein", "TNFalpha": "protein", "adhering PMN": "cell_type" } }, { "input_text": "Thus , this study provides no evidence indicating a regulatory function of PPARalpha in LTB4 induced adhesive interactions between endothelial cells and neutrophils", "target_text": { "PPARalpha": "protein", "endothelial cells": "cell_type", "neutrophils": "cell_type" } }, { "input_text": "Interaction of sickle erythrocytes with endothelial cells in the presence of endothelial cell conditioned medium induces oxidant stress leading to transendothelial migration of monocytes .", "target_text": { "sickle erythrocytes": "cell_type", "endothelial cells": "cell_type", "monocytes": "cell_type" } }, { "input_text": "The abnormal adherence of sickle red blood cells ( SS RBC ) to endothelial cells has been thought to contribute to vascular occlusion , a major cause of morbidity in sickle cell disease ( SCD ) .", "target_text": { "sickle red blood cells": "cell_type", "SS RBC": "cell_type", "endothelial cells": "cell_type" } }, { "input_text": "We determined whether the interaction of SS RBC with cultured endothelial cells induced cellular oxidant stress that would culminate in expression of cell adhesion molecules ( CAMs ) involved in the adhesion and diapedesis of monocytes and the adherence of SS reticulocytes .", "target_text": { "SS RBC": "cell_type", "endothelial cells": "cell_type", "cell adhesion molecules": "protein", "CAMs": "protein", "monocytes": "cell_type", "SS reticulocytes": "cell_type" } }, { "input_text": "We showed that the interaction of SS RBC at 2 % concentration in the presence of multimers of von Willebrand factor ( vWf ) , derived from endothelial cell-derived conditioned medium ( E-CM ) with cultured human umbilical vein endothelial cells ( HUVEC ) , resulted in a fivefold increased formation of thiobarbituric acid-reactive substances ( TBARS ) and activation of the transcription factor NF-kB , both indicators of cellular oxidant stress .", "target_text": { "SS RBC": "cell_type", "von Willebrand factor": "protein", "vWf": "protein", "endothelial cells": "cell_type", "cultured human umbilical vein endothelial cells": "cell_line", "HUVEC": "cell_line", "transcription factor": "protein", "NF-kB": "protein" } }, { "input_text": "Normal RBC show none of these phenomena .", "target_text": { "Normal RBC": "cell_type" } }, { "input_text": "The oxidant stress-induced signaling resulted in an increased surface expression of a subset of CAMs , ICAM-1 , E-selectin , and VCAM-1 in HUVEC .", "target_text": { "CAMs": "protein", "ICAM-1": "protein", "E-selectin": "protein", "VCAM-1": "protein", "HUVEC": "cell_line" } }, { "input_text": "The addition of oxygen radical scavenger enzymes ( catalase , superoxide dismutase ) and antioxidant ( probucol ) inhibited these events .", "target_text": { "oxygen radical scavenger enzymes": "protein", "catalase": "protein", "superoxide dismutase": "protein" } }, { "input_text": "Additionally , preincubation of HUVEC with a synthetic peptide Arg-Gly-Asp ( RGD ) that prevents vWf -mediated adhesion of SS RBC reduced the surface expression of VCAM-1 and NF-kB activation .", "target_text": { "HUVEC": "cell_line", "vWf": "protein", "SS RBC": "cell_type", "VCAM-1": "protein", "NF-kB": "protein" } }, { "input_text": "Furthermore , SS RBC -induced oxidant stress resulted in a twofold increase in the transendothelial migration of both monocyte-like HL-60 cells and human peripheral blood monocytes , and approximately a sixfold increase in platelet-endothelial cell adhesion molecule-1 ( PECAM-1 ) phosphorylation , each of which was blocked by protein kinase C inhibitor and antioxidants .", "target_text": { "SS RBC": "cell_type", "monocyte-like HL-60 cells": "cell_line", "monocytes": "cell_type", "human peripheral blood monocytes": "cell_type", "platelet-endothelial cell adhesion molecule-1": "protein", "PECAM-1": "protein", "protein kinase C": "protein" } }, { "input_text": "These results suggest that the adherence/contact of SS RBC to endothelial cells in large vessel can generate enhanced oxidant stress leading to increased adhesion and diapedesis of monocytes , as well as heightened adherence of SS reticulocytes , indicating that injury/activation of endothelium can contribute to vaso-occlusion in SCD .", "target_text": { "SS RBC": "cell_type", "endothelial cells": "cell_type", "monocytes": "cell_type", "SS reticulocytes": "cell_type" } }, { "input_text": "Signal transduction abnormalities in T lymphocytes from patients with advanced renal carcinoma : clinical relevance and effects of cytokine therapy .", "target_text": { "T lymphocytes": "cell_type", "cytokine": "protein" } }, { "input_text": "Studies have demonstrated abnormalities of the CD3/T-cell antigen receptor ( TCR ) and pathways of signal transduction in T lymphocytes from animals and patients with advanced malignancy .", "target_text": { "CD3/T-cell antigen receptor": "protein", "TCR": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Diminished expression of TCRzeta and p56(lck) that are associated with the TCR and reduced nuclear localization of RelA containing nuclear factor kappaB ( NFkappaB ) complexes have been noted .", "target_text": { "TCRzeta": "protein", "p56(lck)": "protein", "TCR": "protein", "RelA": "protein", "NFkappaB": "protein", "RelA containing nuclear factor kappaB ( NFkappaB ) complexes": "protein" } }, { "input_text": "These defects have been described in T cells from patients with malignant melanoma , renal cell carcinoma ( RCC ) , ovarian cancer , and colorectal cancer .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Preliminary observations also indicate possible correlation with clinical variables such as stage in selected instances .", "target_text": {} }, { "input_text": "To further characterize altered expression of TCRzeta , p56(lck) , and impaired activation of NFkappaB , T lymphocytes were obtained from 65 patients with RCC , the majority of whom were receiving combination cytokine therapy [ interleukin ( IL ) -2 , IFN alpha -containing regimens ] and 37 control individuals .", "target_text": { "TCRzeta": "protein", "p56(lck)": "protein", "NFkappaB": "protein", "T lymphocytes": "cell_type", "cytokine": "protein", "interleukin ( IL ) -2": "protein", "IFN alpha": "protein" } }, { "input_text": "In 29 of these patients , levels of TCRzeta and p56(lck) were determined by Western blots of T-cell lysates and semiquantitated using densitometry .", "target_text": { "TCRzeta": "protein", "p56(lck)": "protein" } }, { "input_text": "Relative levels were then correlated with a series of clinical variables including response to therapy , performance status , survival , disease sites , age , and others .", "target_text": {} }, { "input_text": "In another group of 28 patients ( three individuals from the first group ) , the frequency of abnormal NFkappaB activation was studied using electrophoretic mobility shift assays after activation of T cells with phorbol myristate acetate/ionomycin or anti-CD3 monoclonal antibody .", "target_text": { "NFkappaB": "protein", "T cells": "cell_type", "anti-CD3 monoclonal antibody": "protein" } }, { "input_text": "Changes in these signaling molecules during cytokine treatment were also investigated .", "target_text": { "cytokine": "protein" } }, { "input_text": "TCRzeta and p56(lck) were detected in the peripheral blood T cells in 27 of 29 patients , and overall , reduced levels were noted visually in 12 of 29 ( 41 % ) and 13 of 29 ( 45 % ) individuals , respectively .", "target_text": { "TCRzeta": "protein", "p56(lck)": "protein", "peripheral blood T cells": "cell_type" } }, { "input_text": "When levels were semiquantitated using densitometry , significant decreases of TCRzeta ( P = 0.029 ) and p56(lck) ( P = 0.029 ) but not CD3epsilon ( P = 0.131 ) , compared with control levels , were found .", "target_text": { "TCRzeta": "protein", "p56(lck)": "protein", "CD3epsilon": "protein" } }, { "input_text": "In patients treated with IL-2/ IFN alpha -based therapy , relative levels of TCRzeta increased significantly ( P = 0.002 ) on day 15 of cycle one compared with the baseline .", "target_text": { "IFN alpha": "protein", "TCRzeta": "protein" } }, { "input_text": "Correlations of TCRzeta or p56(lck) levels with response or disease variables , except for lower TCRzeta levels ( P < 0.001 ) in the presence of bone metastases , were not found .", "target_text": { "TCRzeta": "protein", "p56(lck)": "protein" } }, { "input_text": "Abnormal NFkappaB activation after stimulation with phorbol myristate acetate/ionomycin and/or anti-CD3 monoclonal antibody was found in 59 % of patients ( 17 of 28 ) and was not accounted for by the advanced age of the study cohort .", "target_text": { "NFkappaB": "protein", "anti-CD3 monoclonal antibody": "protein" } }, { "input_text": "Activation of NFkappaB in peripheral blood T cells was inducible during cytokine therapy in four of six individuals who displayed impaired NFkappaB activity prior to therapy .", "target_text": { "NFkappaB": "protein", "peripheral blood T cells": "cell_type", "cytokine": "protein" } }, { "input_text": "Moreover , impaired activation of NFkappaB does not appear linked to a reduction of TCRzeta expression , because in five patients , normal TCRzeta levels were present although kappaB binding was not inducible .", "target_text": { "NFkappaB": "protein", "TCRzeta": "protein", "kappaB": "protein" } }, { "input_text": "In the majority of patients with advanced RCC , peripheral blood T cells express TCRzeta and p56(lck) , and in a subset , reduced levels of these TCRzeta associated molecules are seen that may increase during cytokine -based therapy .", "target_text": { "peripheral blood T cells": "cell_type", "TCRzeta": "protein", "p56(lck)": "protein", "TCRzeta associated molecules": "protein", "cytokine": "protein" } }, { "input_text": "Abnormal activation of NFkappaB is also present in > 50 % of patients and may also revert to normal during IL-2/ IFN alpha -based treatment .", "target_text": { "NFkappaB": "protein", "IFN alpha": "protein" } }, { "input_text": "This alteration in NFkappaB activation occurred in the presence of normal expression of TCRzeta -associated signaling elements .", "target_text": { "NFkappaB": "protein", "TCRzeta": "protein", "TCRzeta -associated signaling elements": "DNA" } }, { "input_text": "The clinical significance of these findings remains unclear .", "target_text": {} }, { "input_text": "Identification of transcription factors expressed during ATRA-induced neutrophil differentiation of HL60 cells .", "target_text": { "transcription factors": "protein", "HL60 cells": "cell_line" } }, { "input_text": "A recent clinical therapeutic initiative has been the use of chemical agents which induce the leukaemic cells to overcome their block in differentiation .", "target_text": { "leukaemic cells": "cell_type" } }, { "input_text": "In order to understand this block the cascade of molecular events needs to be characterized .", "target_text": {} }, { "input_text": "Haemopoietic differentiation is ultimately controlled at the level of gene transcription which is mediated by an array of transcription factors .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Many transcription factors contain similar structural protein sequences , and we have used an RT-PCR -based approach to isolate sequences , from transcription factor gene families which share similar domains .", "target_text": { "transcription factors": "protein", "structural protein sequences": "protein", "transcription factor": "protein" } }, { "input_text": "Degenerate primers corresponding to the TFIIIA zinc-finger consensus amino acid sequences and to the POU-homeodomain and POU-specific domain were used to amplify genes on the basis that they contained similarities in structural motifs shared within these families of transcription factors .", "target_text": { "TFIIIA zinc-finger": "protein", "TFIIIA zinc-finger consensus amino acid sequences": "DNA", "POU-homeodomain": "protein", "POU-specific domain": "protein", "transcription factors": "protein" } }, { "input_text": "A serum-independent HL60 cell line was induced towards the neutrophil lineage by treatment with all-trans retinoic acid ( ATRA ) for 24 h .", "target_text": { "HL60 cell line": "cell_line", "serum-independent HL60 cell line": "cell_line" } }, { "input_text": "CD38+ cells committed towards this lineage were enriched and a population of these cells treated with dihydroxyvitamin D3 to induce neutrophil maturation .", "target_text": { "CD38+ cells": "cell_type" } }, { "input_text": "RNA extracted from uninduced , ATRA -induced CD38+ cells , and vitamin D3 treated maturing cell cultures were amplified using the degenerate primers .", "target_text": { "CD38+ cells": "cell_type", "ATRA -induced CD38+ cells": "cell_line", "vitamin D3 treated maturing cell cultures": "cell_line" } }, { "input_text": "PCR fragments were cloned , sequenced , clustered into homologous groups , and the group sequences searched on the GenBank database .", "target_text": { "PCR fragments": "DNA" } }, { "input_text": "The Oct 1 transcription factor , and a very close homologue , KIAA0144 , was identified using the POU family primers .", "target_text": { "transcription factor": "protein", "KIAA0144": "DNA" } }, { "input_text": "The zinc-finger primers identified three zinc-finger genes .", "target_text": {} }, { "input_text": "The pattern of gene expression was suggested from the number of clones in each group at neutrophil commitment and maturation .", "target_text": {} }, { "input_text": "The differential expression of the genes in the zinc finger and POU families will lead to a better understanding of the cascade of gene expression which occurs following ATRA -induced differentiation .", "target_text": {} }, { "input_text": "GATA-3 -dependent enhancer activity in IL-4 gene regulation .", "target_text": { "GATA-3": "protein", "IL-4 gene": "DNA" } }, { "input_text": "Previously , we analyzed the proximal IL-4 promoter in directing Th2-specific activity .", "target_text": { "IL-4": "protein", "IL-4 promoter": "DNA", "proximal IL-4 promoter": "DNA" } }, { "input_text": "An 800-base pair proximal promoter conferred some Th2-selective expression in transgenic mice .", "target_text": { "800-base pair proximal promoter": "DNA" } }, { "input_text": "However , this region directed extremely low reporter mRNA levels relative to endogenous IL-4 mRNA , suggesting that full gene activity requires additional enhancer elements .", "target_text": { "IL-4": "protein", "IL-4 mRNA": "RNA", "enhancer elements": "DNA" } }, { "input_text": "Here , we analyzed large genomic IL-4 regions for enhancer activity and interaction with transcription factors .", "target_text": { "IL-4": "protein", "genomic IL-4 regions": "DNA", "transcription factors": "protein" } }, { "input_text": "The proximal IL-4 promoter is only moderately augmented by GATA-3 , but certain genomic regions significantly enhanced GATA-3 promoter transactivation .", "target_text": { "IL-4": "protein", "IL-4 promoter": "DNA", "GATA-3": "protein", "genomic regions": "DNA", "GATA-3 promoter": "DNA" } }, { "input_text": "Some enhancing regions contained consensus , GATA sites that bound Th2-specific complexes .", "target_text": { "GATA sites": "DNA", "Th2-specific complexes": "protein" } }, { "input_text": "However , retroviral transduction of GATA-3 into developing T cells induced IL-5 to full Th2 levels , but only partially restored IL-4 production .", "target_text": { "GATA-3": "protein", "developing T cells": "cell_type", "IL-5": "protein", "Th2": "protein", "IL-4": "protein" } }, { "input_text": "Thus , we propose that GATA-3 is permissive , but not sufficient , for full IL-4 enhancement and may act through GATA elements surrounding the IL-13 / IL-4 gene locus .", "target_text": { "GATA-3": "protein", "IL-4": "protein", "GATA elements": "DNA", "IL-13": "protein", "IL-4 gene": "DNA", "IL-13 / IL-4 gene locus": "DNA" } }, { "input_text": "Position effect of translocations involving the inactive X chromosome : physical linkage to XIC/XIST does not lead to long-range de novo inactivation in human differentiated cells .", "target_text": { "inactive X chromosome": "DNA", "XIC/XIST": "DNA", "human differentiated cells": "cell_type" } }, { "input_text": "Given the reported long-range cis-inactivating effect of the XIST gene in early embryonic development and the lack of requirement of X- chromosome-specific elements for propagating the inactive state , there exists the possibility of cis inactivation of autosomal material after de novo translocation to an inactive X chromosome ( Xi ) in differentiated cells .", "target_text": { "XIST gene": "DNA", "X- chromosome-specific elements": "DNA", "inactive X chromosome": "DNA", "Xi": "DNA", "differentiated cells": "cell_type" } }, { "input_text": "We have analyzed de novo radiation-induced translocations between the Xi and autosomes to study the maintenance and spreading of X-chromosome inactivation ( X inactivation ) in relation to the position of the X-inactivation center ( XIC ) /XIST in differentiated cells .", "target_text": { "Xi": "DNA", "autosomes": "DNA", "X-chromosome": "DNA", "( XIC ) /XIST": "DNA", "differentiated cells": "cell_type" } }, { "input_text": "Autosome/ Xi translocations were detected by fluorescence in situ hybridization ( FISH ) .", "target_text": { "Xi": "DNA" } }, { "input_text": "The activation status of the chromosomes involved in the translocation was determined by simultaneous immunocytogenetic studies using antibodies against either BrdU incorporated at late S phase or acetylated histone H4 .", "target_text": { "chromosomes": "DNA", "antibodies": "protein", "BrdU": "protein", "acetylated histone H4": "protein" } }, { "input_text": "The position of XIC/XIST in the reciprocal products of the translocation was determined by XIST-specific FISH and computer enhancement .", "target_text": { "XIC/XIST": "DNA" } }, { "input_text": "In other experiments , the Xq13 region carrying XIC/XIST was localized by computer enhancement of the DAPI banding pattern .", "target_text": { "Xq13 region": "DNA", "XIC/XIST": "DNA" } }, { "input_text": "Our study in differentiated cells provides a visual demonstration that physical separation from XIC/XIST does not result in reactivation of inactive X-chromosome material and that X inactivation is not spread to the translocated autosomes irrespective of the position of XIC/XIST .", "target_text": { "differentiated cells": "cell_type", "XIC/XIST": "DNA", "inactive X-chromosome": "DNA", "translocated autosomes": "DNA" } }, { "input_text": "This observation suggests that physical linkage to XIC/XIST does not lead to de novo inactivation of autosomal material .", "target_text": { "XIC/XIST": "DNA" } }, { "input_text": "Interleukin -4 and -13 induce upregulation of the murine macrophage 12/15-lipoxygenase activity : evidence for the involvement of transcription factor STAT6 .", "target_text": { "12/15-lipoxygenase activity": "protein", "transcription factor": "protein", "STAT6": "protein" } }, { "input_text": "When human monocytes or alveolar macrophages are cultured in the presence of interleukin ( IL ) -4 or IL-13 , the expression of the reticulocyte-type 15-lipoxygenase is induced .", "target_text": { "monocytes": "cell_type", "alveolar macrophages": "cell_type", "interleukin ( IL ) -4": "protein", "IL-13": "protein", "reticulocyte-type 15-lipoxygenase": "protein" } }, { "input_text": "In mice a 15-lipoxygenase is not expressed , but a leukocyte-type 12-lipoxygenase is present in peritoneal macrophages .", "target_text": { "15-lipoxygenase": "protein", "leukocyte-type 12-lipoxygenase": "protein", "peritoneal macrophages": "cell_type" } }, { "input_text": "To investigate whether both lipoxygenase isoforms exhibit a similar regulatory response toward cytokine stimulation , we studied the regulation of the leukocyte-type 12-lipoxygenase of murine peritoneal macrophages by interleukins and found that the activity of this enzyme is upregulated in a dose-dependent manner when the cells were cultured in the presence of the IL-4 or IL-13 but not by IL-10 .", "target_text": { "lipoxygenase isoforms": "protein", "cytokine": "protein", "leukocyte-type 12-lipoxygenase": "protein", "peritoneal macrophages": "cell_type", "murine peritoneal macrophages": "cell_type", "interleukins": "protein", "enzyme": "protein", "IL-4": "protein", "IL-13": "protein", "IL-10": "protein" } }, { "input_text": "When peripheral murine monocytes that do not express the lipoxygenase were treated with IL-4 expression of 12/15-lipoxygenase mRNA was induced , suggesting pretranslational control mechanisms .", "target_text": { "monocytes": "cell_type", "lipoxygenase": "protein", "IL-4": "protein", "12/15-lipoxygenase": "protein", "12/15-lipoxygenase mRNA": "RNA" } }, { "input_text": "In contrast , no upregulation of the lipoxygenase activity was observed when the macrophages were prepared from homozygous STAT6 -deficient mice .", "target_text": { "lipoxygenase": "protein", "macrophages": "cell_type", "STAT6": "protein" } }, { "input_text": "Peritoneal macrophages of transgenic mice that systemically overexpress IL-4 exhibited a threefold to fourfold higher 12-lipoxygenase activity than cells prepared from control animals .", "target_text": { "macrophages": "cell_type", "Peritoneal macrophages": "cell_type", "IL-4": "protein", "12-lipoxygenase": "protein" } }, { "input_text": "A similar upregulation of 12-lipoxygenase activity was detected in heart , spleen , and lung of the transgenic animals .", "target_text": { "12-lipoxygenase": "protein" } }, { "input_text": "Moreover , a strong induction of the enzyme was observed in red cells during experimental anemia in mice .", "target_text": { "red cells": "cell_type" } }, { "input_text": "The data presented here indicate that ( 1 ) the 12-lipoxygenase activity of murine macrophages is upregulated in vitro and in vivo by IL-4 and/or IL-13 , ( 2 ) this upregulation requires expression of the transcription factor STAT6 , and ( 3 ) the constitutive expression of the enzyme appears to be STAT6 independent .", "target_text": { "12-lipoxygenase": "protein", "IL-4": "protein", "IL-13": "protein", "transcription factor": "protein", "STAT6": "protein" } }, { "input_text": "The cytokine -dependent upregulation of the murine macrophage 12-lipoxygenase and its induction during experimental anemia suggests its close relatedness with the human reticulocyte-type 15-lipoxygenase despite their differences in the positional specificity of arachidonic acid oxygenation .", "target_text": { "cytokine": "protein", "12-lipoxygenase": "protein", "murine macrophage 12-lipoxygenase": "protein", "15-lipoxygenase": "protein", "reticulocyte-type 15-lipoxygenase": "protein", "human reticulocyte-type 15-lipoxygenase": "protein" } }, { "input_text": "Interferon-gamma-induced factor binding to the interleukin-4 -responsive element of CD23b promoter in human tonsillar mononuclear cells : role in transient up-regulation of the interleukin-4 -induced CD23b mRNA .", "target_text": { "Interferon-gamma-induced factor": "protein", "interleukin-4": "protein", "interleukin-4 -responsive element": "DNA", "CD23b promoter": "DNA", "human tonsillar mononuclear cells": "cell_type", "CD23b mRNA": "RNA", "interleukin-4 -induced CD23b mRNA": "RNA" } }, { "input_text": "Stimulation of human tonsillar mononuclear cells with interleukin-4 ( IL-4 ) and interferon-gamma ( IFN-gamma ) rapidly induced the activation of distinct nuclear factors with different mobilities , both of which bind the IL-4 response element ( IL-4RE ) of CD23b promoter as examined by electrophoretic mobility shift assays ( EMSA ) .", "target_text": { "human tonsillar mononuclear cells": "cell_type", "interleukin-4": "protein", "IL-4": "protein", "interferon-gamma": "protein", "IFN-gamma": "protein", "nuclear factors": "protein", "IL-4 response element": "DNA", "IL-4RE": "DNA", "CD23b promoter": "DNA" } }, { "input_text": "Co-treatment of IL-4 and IFN-gamma induced , in addition to the two distinct complexes , a new complex with an intermediate mobility .", "target_text": { "IL-4": "protein", "IFN-gamma": "protein" } }, { "input_text": "The IL-4 -induced complex reacted with anti- STAT ( signal transducers and activators of transcription ) 6 , resulting in a supershift whereas the formation of the IFN-gamma -induced complex was inhibited by anti- STAT 1 .", "target_text": { "IL-4": "protein", "IL-4 -induced complex": "protein", "STAT ( signal transducers and activators of transcription ) 6": "protein", "anti- STAT ( signal transducers and activators of transcription ) 6": "protein", "IFN-gamma": "protein", "IFN-gamma -induced complex": "protein", "STAT 1": "protein", "anti- STAT 1": "protein" } }, { "input_text": "The intermediate complex appeared to react with both anti- STAT 6 and anti- STAT 1 .", "target_text": { "STAT 6": "protein", "anti- STAT 6": "protein", "STAT 1": "protein", "anti- STAT 1": "protein" } }, { "input_text": "Although IFN-gamma alone did not induce CD23 mRNA transcription , Northern blot analysis revealed a transient up-regulation of the IL-4 -induced CD23 mRNA by IFN-gamma within 2 h of IFN-gamma treatment in these tonsillar cells .", "target_text": { "IFN-gamma": "protein", "CD23 mRNA": "RNA", "IL-4": "protein", "IL-4 -induced CD23 mRNA": "RNA", "tonsillar cells": "cell_type" } }, { "input_text": "The results suggest that the IL-4RE of the IL-4 -inducible gene can accommodate both IL-4- and IFN-gamma- activated factors , such as STAT 6 and STAT 1 , either in homodimeric or heterodimeric forms and the binding of these different proteins to the respective promoter may play a potential regulatory role in the IL-4 - inducible gene expression .", "target_text": { "IL-4RE": "DNA", "IL-4": "protein", "IL-4 -inducible gene": "DNA", "STAT 6": "protein", "STAT 1": "protein" } }, { "input_text": "A p56lck -independent pathway of CD2 signaling involves Jun kinase .", "target_text": { "p56lck": "protein", "CD2": "protein", "Jun kinase": "protein" } }, { "input_text": "The p56 Src family non-receptor tyrosine kinase has been shown to be critical for T lymphocyte differentiation and activation .", "target_text": { "p56 Src family non-receptor tyrosine kinase": "protein" } }, { "input_text": "Hence in the absence of p56 , T cell receptor triggered activation does not occur .", "target_text": { "p56": "protein", "T cell receptor": "protein" } }, { "input_text": "We now provide evidence for a CD2 -based signaling pathway which , in contrast to that of the T cell receptor , is independent of p56 .", "target_text": { "CD2": "protein", "T cell receptor": "protein", "p56": "protein" } }, { "input_text": "CD2 -mediated interleukin-2 production occurs via activation of Jun kinase in cell lines lacking p56 .", "target_text": { "CD2": "protein", "interleukin-2": "protein", "Jun kinase": "protein", "p56": "protein" } }, { "input_text": "Jun kinase then facilitates the binding of c-Jun/c-Fos heterodimers to the AP-1 consensus site and the subsequent transcriptional activity of the interleukin-2 promoter .", "target_text": { "Jun kinase": "protein", "c-Jun/c-Fos heterodimers": "protein", "AP-1 consensus site": "DNA", "interleukin-2": "protein", "interleukin-2 promoter": "DNA" } }, { "input_text": "These data elucidate differences between TCR and CD2 signaling pathways in the same T cells .", "target_text": { "TCR": "protein", "CD2": "protein", "T cells": "cell_type" } }, { "input_text": "Activation of E2F -mediated transcription by human T-cell leukemia virus type I Tax protein in a p16 ( INK4A ) -negative T-cell line .", "target_text": { "E2F": "protein", "human T-cell leukemia virus type I Tax protein": "protein", "p16 ( INK4A ) -negative T-cell line": "cell_line" } }, { "input_text": "The human T-cell leukemia virus type I ( HTLV-I ) is a causative agent of adult T-cell leukemia .", "target_text": {} }, { "input_text": "Although the exact mechanism by which HTLV-I contributes to leukemogenesis is still unclear , the Tax protein is thought to play a major role in this process .", "target_text": { "Tax protein": "protein" } }, { "input_text": "This 40-kDa polypeptide is able to interact with the tumor suppressor p16 ( INK4A ) .", "target_text": { "tumor suppressor": "protein", "p16 ( INK4A )": "protein" } }, { "input_text": "Consequently , Tax can activate the signaling pathway that lead to the release of E2F that in turn induces expression of factors required for cell cycle progression .", "target_text": { "Tax": "protein", "E2F": "protein" } }, { "input_text": "In this paper , we demonstrate that Tax can also activate E2F -mediated transcription independently of p16 ( INK4A ) .", "target_text": { "Tax": "protein", "E2F": "protein", "p16 ( INK4A )": "protein" } }, { "input_text": "Indeed , when Tax is coexpressed with the E2F-1 transcription factor in CEM T-cells , which lack expression of p16 ( INK4A ) , it strongly potentiates the E2F -dependent activation of a reporter construct driven by a promoter containing E2F binding sites .", "target_text": { "Tax": "protein", "E2F-1": "protein", "transcription factor": "protein", "CEM T-cells": "cell_line", "p16 ( INK4A )": "protein", "E2F": "protein", "E2F binding sites": "DNA" } }, { "input_text": "This stimulation is abrogated by mutations affecting the E2F -binding sites .", "target_text": { "E2F": "protein", "E2F -binding sites": "DNA" } }, { "input_text": "In addition , Tax also stimulates the transcription of the E2F-1 gene itself .", "target_text": { "Tax": "protein", "E2F-1": "protein", "E2F-1 gene": "DNA" } }, { "input_text": "Using Tax mutants that fail to activate either ATF - or NF-kappaB-dependent promoters and different 5' truncation mutants of the E2F-1 promoter , we show that the Tax -dependent transcriptional control of the E2F1 gene involves , at least in part , the ATF binding site located in the E2F-1 promoter .", "target_text": { "Tax": "protein", "ATF": "protein", "NF-kappaB-dependent promoters": "DNA", "5' truncation mutants": "DNA", "E2F-1": "protein", "E2F-1 promoter": "DNA", "E2F1 gene": "DNA", "ATF binding site": "DNA" } }, { "input_text": "Inducible nitric oxide : an autoregulatory feedback inhibitor of vascular inflammation .", "target_text": {} }, { "input_text": "Inducible nitric oxide ( iNO ) is produced at sites of vascular inflammation by resident and nonresident vascular wall cells , but its role in the inflammatory process is not known .", "target_text": { "vascular wall cells": "cell_type" } }, { "input_text": "In this study , we show that a novel function of iNO is to terminate inflammatory processes .", "target_text": {} }, { "input_text": "We find that iNO produced by murine macrophage-like cells , RAW264.7 , can inhibit cytokine -induced endothelial cell activation in a separated and mixed endothelial-RAW264.7 coculture system .", "target_text": { "murine macrophage-like cells": "cell_line", "RAW264.7": "cell_line", "cytokine": "protein", "endothelial-RAW264.7": "cell_line", "endothelial-RAW264.7 coculture system": "cell_line" } }, { "input_text": "Both iNO production and endothelial VCAM-1 expression were induced simultaneously with bacterial LPS and murine-specific IFN-gamma .", "target_text": { "VCAM-1": "protein", "IFN-gamma": "protein", "murine-specific IFN-gamma": "protein" } }, { "input_text": "Inhibition of iNO synthase ( iNOS ) activity with N omega-monomethyl-L-arginine in endothelial-RAW264.7 cocultures , stimulated with murine-specific IFN-gamma and LPS , decreased iNO production by 86 % , augmented VCAM-1 and iNOS expression in endothelial and RAW264.7 cells , respectively , and increased monocyte adhesion to the endothelial cell surface .", "target_text": { "iNO synthase": "protein", "iNOS": "protein", "endothelial-RAW264.7 cocultures": "cell_line", "IFN-gamma": "protein", "murine-specific IFN-gamma": "protein", "VCAM-1": "protein", "RAW264.7 cells": "cell_line" } }, { "input_text": "Transient transfection studies using various VCAM-1 promoter constructs demonstrated that inhibitory effects of iNO on VCAM-1 gene transcription were mediated , in part , by inhibitory effects of iNO on kappa B cis-acting elements .", "target_text": { "VCAM-1": "protein", "VCAM-1 promoter": "DNA", "kappa B cis-acting elements": "DNA" } }, { "input_text": "Immunofluorescence studies using an Ab to the RelA ( p65 ) subunit of nuclear factor-kappa B revealed that iNO inhibited the activation of nuclear factor-kappa B .", "target_text": { "RelA": "protein", "p65": "protein", "RelA ( p65 ) subunit": "protein", "factor-kappa B": "protein", "nuclear factor-kappa B": "protein" } }, { "input_text": "These studies indicate that iNO attenuates iNOS expression in macrophages and inhibits monocyte adhesion to endothelial cells , and suggest that endogenously derived iNO may be an important autoregulatory inhibitor of vascular inflammation", "target_text": { "iNOS": "protein", "macrophages": "cell_type", "endothelial cells": "cell_type" } }, { "input_text": "Detection of oestrogen receptor variants in endometrium , myometrium , leiomyoma and peripheral blood mononuclear cells : comparison to variants present in breast cancer .", "target_text": { "oestrogen receptor variants": "protein", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Oestradiol has mitogenic and regulatory effects on various organs and cells , mediated mainly by its nuclear receptor ( ER ) .", "target_text": { "nuclear receptor": "protein", "ER": "protein" } }, { "input_text": "The presence of aberrant ER forms in Oestrogen-dependent tumours has been discussed in correlation with tumour progression .", "target_text": { "ER": "protein" } }, { "input_text": "ER variants , generated by alternative splicing , have been detected in human breast cancer , but also in normal mammary glands , therefore their role in tumorigenesis has been questioned .", "target_text": { "ER": "protein" } }, { "input_text": "We have investigated , by the use of the reverse transcription polymerase chain reaction amplification technique , the possible existence of ER variants in other normal oestrogen target organs and cells , such as uterus ( myometrium and endometrium ) , in peripheral blood mononuclear cells and in a benign uterus tumour ( leiomyoma ) .", "target_text": { "ER": "protein", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "We have detected variant ER in these samples and have compared the variant profile to that observed in breast cancer .", "target_text": { "ER": "protein" } }, { "input_text": "All tissues and cells studied expressed both wild-type ER and variant species .", "target_text": { "ER": "protein", "wild-type ER": "protein", "variant species": "protein" } }, { "input_text": "Variant forms encompassed ER with deletions of exons 2 , 5 and 7 .", "target_text": { "ER": "protein" } }, { "input_text": "Variants with exon 5 deleted were detected only in peripheral blood mononuclear cells and in breast cancer .", "target_text": { "exon 5": "DNA", "peripheral blood mononuclear cells": "cell_type" } }, { "input_text": "Variants with exons 2 and 7 deleted were present in all specimens tested .", "target_text": {} }, { "input_text": "These results corroborate previous findings that the presence of ER variants is not a characteristic of breast cancer .", "target_text": { "ER": "protein" } }, { "input_text": "The physiological significance and possible clinical relevance of the variant ER forms remain to be elucidated .", "target_text": { "ER": "protein" } }, { "input_text": "p21ras initiates Rac-1 but not phosphatidyl inositol 3 kinase /PKB , mediated signaling pathways in T lymphocytes .", "target_text": { "p21ras": "protein", "Rac-1": "protein", "phosphatidyl inositol 3 kinase": "protein", "/PKB": "protein", "phosphatidyl inositol 3 kinase /PKB": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "p21ras is activated by the T cell antigen receptor ( TCR ) and then co-ordinates important signaling pathways for T lymphocyte activation .", "target_text": { "p21ras": "protein", "T cell antigen receptor": "protein", "TCR": "protein", "T lymphocyte": "protein" } }, { "input_text": "Effector pathways for this guanine nucleotide binding protein in T cells are mediated by the serine/threonine kinase Raf-1 and the Ras-related GTPase Rac-1 .", "target_text": { "guanine nucleotide binding protein": "protein", "T cells": "cell_type", "serine/threonine kinase": "protein", "Raf-1": "protein", "Ras-related GTPase": "protein", "Rac-1": "protein" } }, { "input_text": "In fibroblasts , an important effector for the Ras oncogene is Phosphatidylinositol 3-kinase ( PtdIns 3-kinase ) .", "target_text": { "fibroblasts": "cell_type", "Ras oncogene": "DNA", "Phosphatidylinositol 3-kinase": "protein", "PtdIns 3-kinase": "protein" } }, { "input_text": "Activation of this lipid kinase is able to induce critical Rac-1 signaling pathways and can couple p21ras to cell survival mechanisms via the serine /threonine kinase Akt/PKB .", "target_text": { "lipid kinase": "protein", "Rac-1": "protein", "p21ras": "protein", "serine /threonine kinase Akt/PKB": "protein" } }, { "input_text": "The role of PtdIns 3-kinase in Ras signaling in T cells has not been explored .", "target_text": { "PtdIns 3-kinase": "protein", "Ras": "protein", "T cells": "cell_type" } }, { "input_text": "In the present study , we examined the ability of PtdIns 3-kinase to initiate the Rac-1 signaling pathways important for T cell activation .", "target_text": { "PtdIns 3-kinase": "protein", "Rac-1": "protein" } }, { "input_text": "We also examined the possibility that Akt/PKB is regulated by Ras signaling pathways in T lymphocytes .", "target_text": { "Akt/PKB": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "The results show that Ras can initiate a Rac-1 mediated pathway that regulates the transcriptional function of AP-1 complexes .", "target_text": { "Ras": "protein", "Rac-1": "protein", "AP-1 complexes": "protein" } }, { "input_text": "PtdIns 3-kinase signals can not mimic p21ras and induce the Rac mediated responses of AP-1 transcriptional activation .", "target_text": { "PtdIns 3-kinase": "protein", "p21ras": "protein", "Rac": "protein", "AP-1": "protein" } }, { "input_text": "Moreover , neither TCR or Ras activation of AP-1 is dependent on PtdIns 3-kinase .", "target_text": { "TCR": "protein", "Ras": "protein", "AP-1": "protein", "PtdIns 3-kinase": "protein" } }, { "input_text": "PKB is activated in response to triggering of the T cell antigen receptor ; PtdIns 3-kinase activity is both required and sufficient for this TCR response .", "target_text": { "PKB": "protein", "T cell antigen receptor": "protein", "PtdIns 3-kinase": "protein", "TCR": "protein" } }, { "input_text": "In contrast , p21ras signals are unable to induce Akt/PKB activity in T cell nor is Ras function required for Akt/PKB activation in response to the TCR .", "target_text": { "p21ras": "protein", "Akt/PKB": "protein", "T cell": "cell_type", "Ras": "protein", "TCR": "protein" } }, { "input_text": "The present data thus highlight that PtdIns 3-kinase and Akt/PKB are not universal Ras effector molecules .", "target_text": { "PtdIns 3-kinase": "protein", "Akt/PKB": "protein", "Ras": "protein", "Ras effector molecules": "protein" } }, { "input_text": "Ras can initiate Rac-1 regulated signaling pathways in the context of T cell antigen receptor function independently of PtdIns 3-kinase activity .", "target_text": { "Ras": "protein", "Rac-1": "protein", "T cell antigen receptor": "protein", "PtdIns 3-kinase": "protein" } }, { "input_text": "Interleukin 1beta mediates the modulatory effects of monocytes on LNCaP human prostate cancer cells .", "target_text": { "Interleukin 1beta": "protein", "monocytes": "cell_type", "LNCaP human prostate cancer cells": "cell_type" } }, { "input_text": "Proliferative and secretory responses in androgen-sensitive prostate cancer LNCaP cells are regulated by steroid and peptide hormones and by differentiation-promoting substances .", "target_text": { "androgen-sensitive prostate cancer LNCaP cells": "cell_type" } }, { "input_text": "In the present study , we evaluated whether peripheral blood monocytes that exhibit anti-tumour activity in haematopoietic and solid tumours influence growth and secretion in the LNCaP cell line .", "target_text": { "monocytes": "cell_type", "peripheral blood monocytes": "cell_type", "LNCaP cell line": "cell_line" } }, { "input_text": "For this purpose , LNCaP cells were incubated with monocyte-conditioned medium ( MCM ) , and proliferation as well as expression of androgen receptor ( AR ) and secretion of prostate-specific antigen ( PSA ) were assessed .", "target_text": { "LNCaP cells": "cell_line", "androgen receptor": "protein", "AR": "protein", "prostate-specific antigen": "protein", "PSA": "protein" } }, { "input_text": "Conditioned medium from monocytes reduced proliferation in a dose-dependent manner .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "Incubation with 40 % MCM caused a 50 % reduction in cell proliferation .", "target_text": {} }, { "input_text": "AR protein decreased by 70 % and PSA levels in supernatants from LNCaP cells were reduced by approximately 80 % following treatment with MCM .", "target_text": { "AR": "protein", "AR protein": "protein", "PSA": "protein", "LNCaP cells": "cell_line" } }, { "input_text": "We focused on the contribution of two major products of activated monocytes , prostaglandin E2 and interleukin 1beta ( IL-1beta ) , to the MCM modulatory action .", "target_text": { "monocytes": "cell_type", "interleukin 1beta": "protein", "IL-1beta": "protein" } }, { "input_text": "LNCaP cells treated with prostaglandin E2 showed neither a reduction in proliferation nor a down-regulation of AR and PSA levels .", "target_text": { "LNCaP cells": "cell_line", "AR": "protein", "PSA": "protein" } }, { "input_text": "The effects of MCM on cellular proliferation , AR protein and PSA secretion were abolished by pretreatment of MCM with a neutralizing anti- IL-1beta antibody .", "target_text": { "AR protein": "protein", "PSA": "protein", "IL-1beta": "protein", "anti- IL-1beta antibody": "protein" } }, { "input_text": "In addition , recombinant IL-1beta was able to replace MCM for the inhibition of proliferation and down-regulation of AR and PSA proteins .", "target_text": { "IL-1beta": "protein", "AR": "protein", "PSA": "protein" } }, { "input_text": "LNCaP cells were shown to express the IL-1beta receptor type 1 , which transduces IL-1beta signal .", "target_text": { "LNCaP cells": "cell_line", "IL-1beta": "protein" } }, { "input_text": "Our findings reveal that monocyte-derived IL-1beta inhibits the proliferation of androgen-responsive prostate tumour cells and reduces AR and PSA levels .", "target_text": { "IL-1beta": "protein", "monocyte-derived IL-1beta": "protein", "androgen-responsive prostate tumour cells": "cell_type", "AR": "protein", "PSA": "protein" } }, { "input_text": "Differential responsiveness of the IL-5 and IL-4 genes to transcription factor GATA-3 .", "target_text": { "transcription factor GATA-3": "protein" } }, { "input_text": "The cytokines IL-4 and IL-5 are often coordinately produced by Th2 cells as in asthma .", "target_text": { "cytokines": "protein", "IL-4": "protein", "IL-5": "protein", "Th2 cells": "cell_line" } }, { "input_text": "However , it is unclear whether similar molecular mechanisms underlie transcription of the two genes .", "target_text": { "genes": "DNA" } }, { "input_text": "We have previously shown that the transcription factor GATA-3 is expressed in Th2 but not Th1 cells and is crucial for activation of the IL-5 promoter by different stimuli .", "target_text": { "transcription factor GATA-3": "protein", "IL-5": "protein", "IL-5 promoter": "DNA" } }, { "input_text": "In a different study , GATA-3 was shown to be sufficient for the expression of IL-4 and other Th2 cytokine genes .", "target_text": { "GATA-3": "protein", "IL-4": "protein", "Th2 cytokine genes": "DNA" } }, { "input_text": "Here , we show that ectopic expression of GATA-3 is sufficient to drive IL-5 but not IL-4 gene expression .", "target_text": { "GATA-3": "protein", "IL-5": "protein", "IL-4": "protein" } }, { "input_text": "Also , in Th2 cells , antisense GATA-3 RNA inhibits IL-5 but not IL-4 promoter activation .", "target_text": { "Th2 cells": "cell_line", "GATA-3": "protein", "IL-5": "protein", "IL-4": "protein" } }, { "input_text": "The induction of IL-5 gene expression by GATA-3 involves high affinity binding of GATA-3 to an inverted GATA repeat in the IL-5 promoter .", "target_text": { "IL-5": "protein", "IL-5 gene": "DNA", "GATA-3": "protein", "GATA repeat": "DNA", "IL-5 promoter": "DNA" } }, { "input_text": "The interleukin 2 receptor alpha chain /CD25 promoter is a target for nuclear factor of activated T cells .", "target_text": { "interleukin 2 receptor alpha chain": "protein", "/CD25": "protein", "interleukin 2 receptor alpha chain /CD25 promoter": "DNA", "nuclear factor of activated T cells": "protein" } }, { "input_text": "The expression of the murine interleukin ( IL ) -2 receptor alpha chain /CD25 is strongly induced at the transcriptional level after T cell activation .", "target_text": { "murine interleukin ( IL ) -2 receptor alpha chain": "protein", "murine interleukin ( IL ) -2 receptor alpha chain /CD25": "protein" } }, { "input_text": "We show here that nuclear factor of activated T cell ( NF-AT ) factors are involved in the control of CD25 promoter induction in T cells .", "target_text": { "nuclear factor of activated T cell ( NF-AT ) factors": "protein", "CD25": "protein", "CD25 promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "NF-ATp and NF-ATc bind to two sites around positions -585 and -650 located upstream of the proximal CD25 promoter .", "target_text": { "NF-ATp": "protein", "NF-ATc": "protein", "CD25": "protein", "CD25 promoter": "DNA", "proximal CD25 promoter": "DNA" } }, { "input_text": "Immediately 3' from these NF-AT motifs , nonconsensus sites are located for the binding of AP-1 -like factors .", "target_text": { "NF-AT motifs": "DNA", "nonconsensus sites": "DNA", "AP-1": "protein", "AP-1 -like factors": "protein" } }, { "input_text": "Mutations of sites that suppress NF-AT binding impair the induction and strong NF-ATp -mediated transactivation of the CD25 promoter in T cells .", "target_text": { "NF-AT": "protein", "NF-ATp": "protein", "CD25": "protein", "CD25 promoter": "DNA", "T cells": "cell_type" } }, { "input_text": "In T lymphocytes from NF-ATp -deficient mice , the expression of CD25 is severely impaired , leading to a delayed IL-2 receptor expression after T cell receptor ( TCR ) / CD3 stimulation .", "target_text": { "T lymphocytes": "cell_type", "NF-ATp": "protein", "CD25": "protein", "IL-2 receptor": "protein", "TCR": "protein", "CD3": "protein" } }, { "input_text": "Our data indicate an important role for NF-AT in the faithful expression of high affinity IL-2 receptors and a close link between the TCR -mediated induction of IL-2 and IL-2 receptor alpha chain promoters , both of which are regulated by NF-AT factors .", "target_text": { "NF-AT": "protein", "IL-2": "protein", "high affinity IL-2 receptors": "protein", "TCR": "protein", "IL-2 receptor alpha chain": "protein", "IL-2 receptor alpha chain promoters": "DNA", "NF-AT factors": "protein" } }, { "input_text": "A novel mutation in the coding sequence of the FY*B allele of the Duffy chemokine receptor gene is associated with an altered erythrocyte phenotype .", "target_text": { "FY*B allele": "DNA", "Duffy chemokine receptor gene": "DNA" } }, { "input_text": "The Duffy blood group system is of clinical and biological significance .", "target_text": {} }, { "input_text": "Antibodies to Duffy antigens are responsible for some cases of transfusion incompatibility and newborn hemolytic disease .", "target_text": { "Antibodies": "protein", "Duffy antigens": "protein" } }, { "input_text": "The Duffy protein is a receptor for the Plasmodium vivax erythrocyte-binding protein and is also a receptor for various chemokines ( thus renamed Duffy Antigen Receptor for Chemokines [ DARC ] ) .", "target_text": { "Duffy protein": "protein", "Plasmodium vivax erythrocyte-binding protein": "protein", "chemokines": "protein", "Duffy Antigen Receptor for Chemokines": "protein", "DARC": "protein" } }, { "input_text": "The two Duffy polymorphic antigens , Fya and Fyb ( coded by the FY*A and FY*B alleles ) , are present on erythrocyte membranes .", "target_text": { "Duffy polymorphic antigens": "protein", "Fya": "protein", "Fyb": "protein", "erythrocyte membranes": "protein" } }, { "input_text": "The Fy(a-b-) phenotype is the predominant one in populations of black people and also occurs in other populations , including some non-Ashkenazi Jewish groups .", "target_text": {} }, { "input_text": "The Fy(a-b-) phenotype has been associated with a mutation in the FY*B promoter at the GATA box that abolishes the expression of erythrocyte Duffy protein .", "target_text": { "FY*B promoter": "DNA", "GATA box": "DNA", "Duffy protein": "protein", "erythrocyte Duffy protein": "protein" } }, { "input_text": "We describe here a novel mutation , present in the FY*B coding sequence ( 271C --> T ) , that is associated with some Fy(b-) phenotypes among non-Ashkenazi Jews and among Brazilian blacks .", "target_text": { "FY*B coding sequence": "DNA" } }, { "input_text": "The mutation is present in Fy(b-) individuals , who have wild-type FY*B GATA and carry the previously described 304G --> A substitution .", "target_text": { "wild-type FY*B GATA": "DNA" } }, { "input_text": "The 271C --> T and 304G --> A can be identified by restriction enzyme-generated restriction fragment length polymorphisms .", "target_text": { "restriction enzyme-generated restriction fragment length polymorphisms": "DNA" } }, { "input_text": "The 271C --> T substitution represents a considerable change in chemical nature ( Arg91 --> Cys ) , one which may affect the antigenic determinants of DARC , and thus be of clinical significance .", "target_text": { "DARC": "protein" } }, { "input_text": "The mutation may have implications for some physiological roles of DARC and be of interest in malaria research and in studies of population genetics .", "target_text": { "DARC": "protein" } }, { "input_text": "Establishment and characterization of EBV-positive and EBV-negative primary effusion lymphoma cell lines harbouring human herpesvirus type-8 .", "target_text": {} }, { "input_text": "In this study we report on the establishment and characterization of two novel lymphoma cell lines ( CRO-AP/3 and CRO-AP/5 ) which carry infection by human herpesvirus type-8 ( HHV-8 ) and have derived from AIDS-related primary effusion lymphoma ( PEL ) .", "target_text": { "lymphoma cell lines": "cell_line", "CRO-AP/3": "cell_line", "CRO-AP/5": "cell_line", "PEL": "cell_line" } }, { "input_text": "These two cell lines are representative of different virologic subtypes of PEL , i.e. HHV-8 +/EBV- PEL in the case of CRO-AP/3 and HHV-8 +/EBV+ PEL in the case of CRO-AP/5 .", "target_text": { "cell lines": "cell_line", "PEL": "cell_line", "HHV-8 +/EBV- PEL": "cell_line", "CRO-AP/3": "cell_line", "CRO-AP/3 and HHV-8 +/EBV+ PEL": "cell_line", "CRO-AP/5": "cell_line" } }, { "input_text": "Consistent with the diagnosis of PEL , both CRO-AP/3 and CRO-AP/5 expressed indeterminate ( i.e. non-B , non-T ) phenotypes although immunogenotypic studies documented their B-cell origin .", "target_text": { "PEL": "cell_line", "CRO-AP/3": "cell_line", "CRO-AP/5": "cell_line", "B-cell origin": "cell_type" } }, { "input_text": "Both cell lines are devoid of genetic lesions of c-MYC , BCL-2 and p53 as well as gross rearrangements of BCL-6 .", "target_text": { "cell lines": "cell_line", "c-MYC": "protein", "BCL-2": "protein", "p53": "protein", "BCL-6": "protein" } }, { "input_text": "Detailed histogenetic characterization of these novel PEL cell lines suggests that PEL may derive from a post-germinal centre B cell which has undergone pre-terminal differentiation .", "target_text": { "PEL cell lines": "cell_line", "PEL": "cell_line", "post-germinal centre B cell": "cell_line" } }, { "input_text": "The CRO-AP/3 and CRO-AP/5 cell lines may provide a valuable model for clarifying the pathogenesis of PEL .", "target_text": { "CRO-AP/3": "cell_line", "CRO-AP/5 cell lines": "cell_line", "PEL": "cell_line" } }, { "input_text": "In particular , these cell lines may help understand the relative contribution of HHV-8 and EBV to PEL growth and development and may facilitate the identification of recurrent cytogenetic abnormalities highlighting putative novel cancer related loci relevant to PEL .", "target_text": { "cell lines": "cell_line", "PEL": "cell_line" } }, { "input_text": "Two-site interaction of nuclear factor of activated T cells with activated calcineurin .", "target_text": { "T cells": "cell_type", "nuclear factor of activated T cells": "protein", "calcineurin": "protein" } }, { "input_text": "Transcription factors belonging to the nuclear factor of activated T cells ( NFAT ) family regulate the expression of cytokine genes and other inducible genes during the immune response .", "target_text": { "Transcription factors": "protein", "nuclear factor of activated T cells": "protein", "nuclear factor of activated T cells ( NFAT ) family": "protein", "cytokine genes": "DNA" } }, { "input_text": "The functions of NFAT proteins are directly controlled by the calcium- and calmodulin- dependent phosphatase calcineurin .", "target_text": { "NFAT proteins": "protein", "calcineurin": "protein" } }, { "input_text": "Here we show that the binding of calcineurin to NFAT is substantially increased when calcineurin is activated with calmodulin and calcium .", "target_text": { "calcineurin": "protein", "NFAT": "protein", "calmodulin": "protein" } }, { "input_text": "FK506.FKBP12 drug-immunophilin complexes inhibited the interaction of NFAT with activated calcineurin much more effectively than they inhibited the interaction with inactive calcineurin , suggesting that part of the interaction with activated calcineurin involved the enzyme active site .", "target_text": { "NFAT": "protein", "calcineurin": "protein", "enzyme active site": "DNA" } }, { "input_text": "We have previously shown that NFAT is targeted to inactive calcineurin at a region distinct from the calcineurin active site ( Aramburu , J. , Garcia-Cozar , F. J. , Raghavan , A. , Okamura , H. , Rao , A. , and Hogan , P. G. ( 1998 ) Mol. Cell 1 , 627-637 ) ; this region is also involved in NFAT binding to activated calcineurin , since binding is inhibited by an NFAT peptide spanning the calcineurin docking site on NFAT .", "target_text": { "NFAT": "protein", "calcineurin": "protein", "calcineurin active site": "DNA" } }, { "input_text": "The interacting surfaces are located on the catalytic domain of the calcineurin A chain and on an 86-amino acid fragment of the NFAT regulatory domain .", "target_text": { "catalytic domain": "protein", "calcineurin": "protein", "calcineurin A chain": "protein", "86-amino acid fragment": "protein", "NFAT": "protein", "NFAT regulatory domain": "protein" } }, { "input_text": "NFAT binding to the calcineurin catalytic domain was inhibited by the calcineurin autoinhibitory domain and the RII substrate peptide , which bind in the calcineurin active site , as well as by the NFAT docking site peptide , which binds to a region of calcineurin distinct from the active site .", "target_text": { "NFAT": "protein", "calcineurin": "protein", "calcineurin catalytic domain": "protein", "calcineurin autoinhibitory domain": "protein", "calcineurin active site": "protein", "active site": "protein" } }, { "input_text": "We propose that , in resting cells , NFAT is targeted to a region of the calcineurin catalytic domain that does not overlap the calcineurin active site .", "target_text": { "resting cells": "cell_type", "NFAT": "protein", "calcineurin": "protein", "calcineurin catalytic domain": "protein", "calcineurin active site": "protein" } }, { "input_text": "Upon cell activation , displacement of the autoinhibitory domain by calmodulin binding allows NFAT to bind additionally to the calcineurin active site , thus positioning NFAT for immediate dephosphorylation at functional phosphoserine residues .", "target_text": { "autoinhibitory domain": "protein", "calmodulin": "protein", "NFAT": "protein", "calcineurin": "protein", "calcineurin active site": "protein" } }, { "input_text": "Nuclear factor-kappaB induction in CD45RO+ and CD45RA+ T cell subsets during aging .", "target_text": { "Nuclear factor-kappaB": "protein" } }, { "input_text": "An increase in the ratio of memory to naive T cells has been postulated to underlie immune hyporesponsiveness accompanying aging .", "target_text": {} }, { "input_text": "Our analyses of the induction of nuclear factor-kappaB ( NFkappaB ) in activated memory ( CD45RO+ ) and naive ( CD45RA+ ) T cell subsets from young and elderly donors has demonstrated that , regardless of donor age , memory T cells are not significantly altered in their responsiveness to TNF-alpha -mediated induction of NFkappaB .", "target_text": { "nuclear factor-kappaB": "protein", "NFkappaB": "protein", "memory T cells": "cell_type", "TNF-alpha": "protein" } }, { "input_text": "Although treatment with TNF-alpha induced nuclear localization of NFkappaB in both memory and naive T cell subsets , irrespective of the age of the donor , the levels of induced NFkappaB were significantly lower in both subsets of T cells obtained from the elderly , when compared to those in young .", "target_text": { "TNF-alpha": "protein", "NFkappaB": "protein", "T cells": "cell_type" } }, { "input_text": "Examination of IkappaB alpha regulation revealed that TNF-alpha -mediated degradation of IkappaB alpha in both memory and naive T cells from the elderly was severely impaired , thus contributing to the lowered induction of the observed NFkappaB .", "target_text": { "IkappaB alpha": "protein", "TNF-alpha": "protein", "NFkappaB": "protein" } }, { "input_text": "In addition , this age-related decrease in induction of nuclear NFkappaB correlated with decrease in intracellular IL-2 receptor expression and anti-CD3 -induced proliferation of both memory and naive T cells subsets .", "target_text": { "NFkappaB": "protein", "nuclear NFkappaB": "protein", "IL-2": "protein", "anti-CD3": "protein" } }, { "input_text": "Taken together , our results suggest that the age-related hyporesponsiveness can not be attributed to a skewing of the T cell population towards a memory phenotype in the elderly .", "target_text": {} }, { "input_text": "Cyclosporin A -resistant transactivation of the IL-2 promoter requires activity of okadaic acid-sensitive serine /threonine phosphatases .", "target_text": { "IL-2": "protein", "IL-2 promoter": "DNA", "okadaic acid-sensitive serine /threonine phosphatases": "protein" } }, { "input_text": "Expression of the IL-2 gene requires activation of T cells through stimulation of the TCR and costimulation through accessory receptors .", "target_text": { "IL-2": "protein", "IL-2 gene": "DNA", "T cells": "cell_type", "TCR": "protein", "accessory receptors": "protein" } }, { "input_text": "We have found recently that okadaic acid-sensitive Ser /Thr phosphatases are involved in a cyclosporin A -insensitive pathway that selectively transmits costimulatory signals .", "target_text": { "okadaic acid-sensitive Ser /Thr phosphatases": "protein" } }, { "input_text": "In this study , we analyzed whether activities of these phosphatases are necessary for the expression of the IL-2 gene .", "target_text": { "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "In both activated peripheral blood T lymphocytes and activated tumorigenic T cell lines , IL-2 gene expression was blocked at the transcriptional level by okadaic acid .", "target_text": { "T lymphocytes": "cell_type", "activated peripheral blood T lymphocytes": "cell_type", "activated tumorigenic T cell lines": "cell_line", "IL-2": "protein" } }, { "input_text": "The transcription factors active at the IL-2 promoter were differentially influenced : upon down-modulation of okadaic acid -sensitive phosphatases , transactivation by octamer , NF-kappa B , and NF of activated T cells proteins was abrogated , while transactivation by AP-1 proteins was even enhanced .", "target_text": { "transcription factors": "protein", "IL-2": "protein", "IL-2 promoter": "DNA", "okadaic acid -sensitive phosphatases": "protein", "NF-kappa B": "protein", "NF of activated T cells proteins": "protein", "AP-1": "protein", "AP-1 proteins was even enhanced .": "protein" } }, { "input_text": "YM268 increases the glucose uptake , cell differentiation , and mRNA expression of glucose transporter in 3T3-L1 adipocytes .", "target_text": { "glucose transporter": "protein", "3T3-L1 adipocytes": "cell_type" } }, { "input_text": "The purpose of this study was to examine the effects of bis[4-[2,4-dioxo-5-thiazolidinyl)methyl]phenyl] methane ( YM-268 ) , a thiazolidinedione derivative , on glucose uptake , adipocyte differentiation through peroxisome proliferator-activated receptor gamma ( PPARgamma ) , and phosphatidylinositol 3-kinase ( PI 3-kinase ) activity in cultured cells .", "target_text": { "adipocyte": "cell_type", "peroxisome proliferator-activated receptor gamma": "protein", "PPARgamma": "protein", "phosphatidylinositol 3-kinase": "protein", "PI 3-kinase": "protein", "cultured cells": "cell_line" } }, { "input_text": "YM268 and pioglitazone dose-dependently increased the 2-deoxyglucose uptake in 3T3-L1 cells .", "target_text": { "3T3-L1 cells": "cell_line" } }, { "input_text": "YM268 facilitated the insulin-stimulated triglyceride accumulation in 3T3-L1 adipocytes and increased the mRNA expression of fatty acid-binding protein .", "target_text": { "3T3-L1 adipocytes": "cell_type", "fatty acid-binding protein": "protein" } }, { "input_text": "YM268 , with and without insulin , increased the mRNA expression of glucose transporter isoforms such as GLUT1 and GLUT4 , indicating enhancement of adipocyte differentiation .", "target_text": { "glucose transporter": "protein", "GLUT1": "protein", "GLUT4": "protein", "adipocyte": "cell_type" } }, { "input_text": "Additionally , YM268 and pioglitazone showed activity of the PPARgamma ligand , a member of the nuclear receptor superfamily responsible for adipogenesis .", "target_text": { "PPARgamma": "protein", "PPARgamma ligand": "protein", "nuclear receptor superfamily": "protein" } }, { "input_text": "To examine the possible involvement of the increased activity of PI 3-kinase in YM268 -stimulated glucose uptake , the enzyme activity was estimated by measuring the phosphatidylinositol-3,4,5-trisphosphate ( PI-3,4,5-P3 ) concentration in human monocytic cells .", "target_text": { "PI 3-kinase": "protein", "human monocytic cells": "cell_type" } }, { "input_text": "Insulin dose-dependently increased the PI-3,4,5-P3 production but YM268 had no significant effect on the insulin -dependent and -independent PI 3-kinase activation .", "target_text": {} }, { "input_text": "These results indicate that the mechanism by which YM268 increased glucose uptake , may be accounted for in part by the enhancement of GLUT1 and GLUT4 expression through PPARgamma activation .", "target_text": { "GLUT1": "protein", "GLUT4": "protein", "PPARgamma": "protein" } }, { "input_text": "The nuclear receptor PPARgamma - bigger than fat .", "target_text": { "nuclear receptor": "protein", "PPARgamma": "protein" } }, { "input_text": "Work reported over the past year has provided insights into the mechanisms whereby ligand activation of the nuclear receptor peroxisome proliferator-activated receptor gamma ( PPARgamma ) regulates systemic glucose and lipid homeostasis .", "target_text": { "nuclear receptor peroxisome proliferator-activated receptor gamma": "protein", "PPARgamma": "protein" } }, { "input_text": "PPARgamma has also been implicated recently in the biology of monocytes and in cell-cycle regulation and cancer .", "target_text": { "PPARgamma": "protein" } }, { "input_text": "Polyunsaturated fatty acids and eicosanoids bind and activate PPARgamma , suggesting that these lipids may serve as hormonal regulators of a variety of biological processes .", "target_text": { "PPARgamma": "protein" } }, { "input_text": "The role of caspases in T cell development and the control of immune responses .", "target_text": {} }, { "input_text": "Apoptosis is responsible for the removal of potentially autoreactive or useless T cells during thymic selection and activated T cells in the periphery .", "target_text": { "activated T cells": "cell_type" } }, { "input_text": "Specific families of receptors , kinases , transcription factors , and cysteine proteases , termed caspases , are involved in the apoptotic cascade leading to proteolysis of specific substrates and to morphological changes associated with programmed cell death .", "target_text": { "receptors": "protein", "kinases": "protein", "transcription factors": "protein", "cysteine proteases": "protein", "termed caspases": "protein" } }, { "input_text": "Although common members of the apoptotic cascade are shared between different cell types , it appears that cell-specific factors can influence the response to a given apoptotic stimuli .", "target_text": { "cell-specific factors": "protein" } }, { "input_text": "Characterization and understanding of the basic mechanisms involved in the different pathways protecting or leading to cell death may provide novel ways to control inappropriate apoptosis involved in several diseases .", "target_text": {} }, { "input_text": "Cross-priming of CTL responses in vivo does not require antigenic peptides in the endoplasmic reticulum of immunizing cells .", "target_text": { "immunizing cells": "cell_type" } }, { "input_text": "It has been proposed that the cross-priming of CTL responses in vivo involves the transfer to host APCs of heat shock protein glycoprotein 96 -chaperoned antigenic peptides released from the endoplasmic reticulum ( ER ) of dying or infected cells .", "target_text": { "APCs": "cell_type", "heat shock protein glycoprotein 96": "protein" } }, { "input_text": "We have tested this possibility directly using TAP-deficient cell lines lacking antigenic ER peptides derived from two model Ags , the human adenovirus type 5 early regions E1A and E1B .", "target_text": { "TAP-deficient cell lines": "cell_line", "Ags": "protein" } }, { "input_text": "Although both proteins were well expressed , the cells were not recognized by E1A- or E1B- specific CTLs unless the relevant epitope was either provided exogenously as a synthetic peptide or targeted to the ER in a TAP-independent fashion .", "target_text": {} }, { "input_text": "Despite the absence of these ER peptides , the TAP1-/- cells were able to efficiently cross-prime E1A- and E1B- specific CTLs following immunization of syngeneic mice .", "target_text": { "TAP1-/- cells": "cell_type" } }, { "input_text": "These results indicate that , although purified peptide/glycoprotein 96 complexes are potent immunogens , the mechanism of CTL cross-priming in vivo does not depend upon antigenic peptides in the ER of immunizing cells .", "target_text": { "peptide/glycoprotein 96 complexes": "protein", "immunizing cells": "cell_type" } }, { "input_text": "A critical role of the p75 tumor necrosis factor receptor ( p75TNF-R ) in organ inflammation independent of TNF , lymphotoxin alpha , or the p55TNF-R .", "target_text": { "p75 tumor necrosis factor receptor": "protein", "p75TNF-R": "protein", "TNF": "protein", "lymphotoxin alpha": "protein", "p55TNF-R .": "protein" } }, { "input_text": "Despite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor ( p75TNF-R ) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis , inflammatory liver disease , pancreatitis , respiratory distress syndrome , or AIDS , the function of this receptor remains poorly defined in vivo .", "target_text": { "p75 tumor necrosis factor receptor": "protein", "p75TNF-R": "protein" } }, { "input_text": "We show here that at levels relevant to human disease , production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas , liver , kidney , and lung , and characterized by constitutively increased NF-kappaB activity in the peripheral blood mononuclear cell compartment .", "target_text": { "p75TNF-R": "protein", "human p75TNF-R": "protein", "NF-kappaB": "protein", "peripheral blood mononuclear cell": "cell_type" } }, { "input_text": "This process is shown to evolve independently of the presence of TNF , lymphotoxin alpha , or the p55TNF-R , although coexpression of a human TNF transgene accelerated pathology .", "target_text": { "TNF": "protein", "lymphotoxin alpha": "protein", "p55TNF-R": "protein", "human TNF transgene": "DNA" } }, { "input_text": "These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies .", "target_text": { "p75TNF-R": "protein" } }, { "input_text": "Expression status of BCL-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin 's disease .", "target_text": { "BCL-6": "protein", "syndecan-1": "protein" } }, { "input_text": "The tumor cells in most cases of Hodgkin 's disease ( HD ) have been recently recognized to originate from the B-cell lineage , but their precise differentiation stage is not fully clarified .", "target_text": { "tumor cells": "cell_type", "B-cell lineage": "cell_type" } }, { "input_text": "Recently , we have reported that the histogenesis of B-cell lymphomas may be assessed by monitoring the expression pattern of BCL-6 , a transcription factor expressed in germinal center ( GC ) B cells , and CD138/ syndecan-1 ( syn-1 ) , a proteoglycan associated with post-GC , terminal B-cell differentiation .", "target_text": { "B-cell lymphomas": "cell_type", "BCL-6": "protein", "transcription factor": "protein", "germinal center ( GC ) B cells": "cell_type", "syndecan-1": "protein", "CD138/ syndecan-1": "protein", "syn-1": "protein" } }, { "input_text": "In this study , we have applied these two markers to the study of HD histogenesis .", "target_text": {} }, { "input_text": "We have found that in nodular lymphocyte predominance HD ( NLPHD ) tumor cells consistently display the BCL-6 (+)/ syn-1 (-) phenotype , indicating their derivation from GC B cells .", "target_text": { "tumor cells": "cell_type", "BCL-6": "protein", "syn-1": "protein", "GC B cells": "cell_type" } }, { "input_text": "Conversely , classic HD ( CHD ) is heterogeneous because the tumor cells of a fraction of CHD display the BCL-6 (-)/ syn-1 (+) phenotype of post-GC B-cells , whereas another fraction of CHD is constituted by a mixture of tumor cells reflecting the GC ( BCL-6 (+)/ syn-1 (-) ) or post-GC ( BCL-6 (-)/ syn-1 (+) ) phenotypes .", "target_text": { "tumor cells": "cell_type", "BCL-6": "protein", "syn-1": "protein" } }, { "input_text": "BCL-6 (-)/ syn-1 (+) tumor cells of CHD are mostly found surrounded by T cells expressing CD40L , consistent with the observation that CD40 signaling downregulates BCL-6 expression .", "target_text": { "BCL-6": "protein", "syn-1": "protein", "tumor cells": "cell_type", "BCL-6 (-)/ syn-1 (+) tumor cells": "cell_line", "T cells": "cell_type", "CD40L": "protein", "CD40": "protein" } }, { "input_text": "These data indicate that tumor cells of NLPHD uniformly display a GC B-cell phenotype , whereas the phenotype of tumor cells of CHD appears to be modulated by the surrounding cellular background , particularly CD40L + reactive T cells .", "target_text": { "tumor cells": "cell_type", "CD40L": "protein", "T cells": "cell_type", "CD40L + reactive T cells": "cell_type" } }, { "input_text": "Molecular and cellular analysis of human immunodeficiency virus -induced apoptosis in lymphoblastoid T-cell-line-expressing wild-type and mutated CD4 receptors .", "target_text": { "receptors": "protein" } }, { "input_text": "We have previously shown that the presence of the CD4 cytoplasmic tail is critical for human immunodeficiency virus ( HIV ) -induced apoptosis ( J.Corbeil , M.Tremblay , and D.D.Richman , J.Exp.Med.183 : 39-48 , 1996 ) .", "target_text": { "CD4 cytoplasmic tail": "protein" } }, { "input_text": "We have pursued our investigation of the role of the CD4 transduction pathway in HIV-induced apoptosis .", "target_text": { "CD4": "protein" } }, { "input_text": "To do this , wild-type and mutant forms of the CD4 cytoplasmic tail were stably expressed in the lymphoblastoid T-cell line A2.01 .", "target_text": { "CD4": "protein", "CD4 cytoplasmic tail": "protein", "lymphoblastoid T-cell line": "cell_line", "A2.01": "cell_line" } }, { "input_text": "Apoptosis was prevented when CD4 truncated at residue 402 was expressed ; however , cells expressing mutated receptors that do not associate with p56(lck) ( mutated at the dicysteine motif and truncated at residue 418 ) but which conserved proximal domains of the cytoplasmic tail underwent apoptosis like wild- type CD4 .", "target_text": { "CD4": "protein", "p56(lck)": "protein", "dicysteine motif": "protein", "cytoplasmic tail": "protein", "wild- type CD4": "protein" } }, { "input_text": "The differences between wild-type and mutated receptors in the induction of apoptosis were not related to levels of p56(lck) or NF- kappaB activation .", "target_text": { "p56(lck)": "protein", "NF- kappaB": "protein" } }, { "input_text": "Initial signaling through the CD4 receptor played a major role in the sensitization of HIV-infected T cells to undergo apoptosis .", "target_text": { "CD4": "protein", "CD4 receptor": "protein", "HIV-infected T cells": "cell_type" } }, { "input_text": "Incubation of HIV-infected cells with monoclonal antibody ( MAb ) 13B8-2 , which binds to CD4 in a region critical for dimerization of the receptor , prevented apoptosis without inhibiting HIV replication .", "target_text": { "HIV-infected cells": "cell_type", "monoclonal antibody ( MAb ) 13B8-2": "protein", "CD4": "protein" } }, { "input_text": "Moreover , the apoptotic process was not related to Fas -Fas ligand interaction ; however , an antagonistic anti-Fas MAb ( ZB-4 ) enhanced apoptosis in HIV-infected cells without inducing apoptosis in uninfected cells .", "target_text": { "Fas": "protein", "-Fas ligand": "protein", "HIV-infected cells": "cell_type", "uninfected cells": "cell_type" } }, { "input_text": "These observations demonstrate that CD4 signaling mediates HIV-induced apoptosis by a mechanism independent of Fas -Fas ligand interaction , does not require p56(lck) signaling , and may involve a critical region for CD4 dimerization .", "target_text": { "CD4": "protein", "Fas": "protein", "-Fas ligand": "protein", "p56(lck)": "protein" } }, { "input_text": "p130 , p107 , and pRb are differentially regulated in proliferating cells and during cell cycle arrest by alpha-interferon .", "target_text": { "p130": "protein", "p107": "protein", "pRb": "protein", "proliferating cells": "cell_type", "alpha-interferon": "protein" } }, { "input_text": "We have determined how the phosphorylation of the retinoblastoma family ( pRb , p107 , and p130 ) is governed in individual cell cycle phases of Daudi B-cells during cell cycle exit triggered by alpha-interferon ( alpha-IFN ) .", "target_text": { "retinoblastoma family": "protein", "pRb": "protein", "p107": "protein", "p130": "protein", "Daudi B-cells": "cell_line", "alpha-interferon": "protein", "alpha-IFN": "protein" } }, { "input_text": "alpha-IFN causes dephosphorylation of pRb and loss of p130 phosphorylated Form 3 .", "target_text": { "alpha-IFN": "protein", "pRb": "protein", "p130": "protein", "p130 phosphorylated Form 3": "protein" } }, { "input_text": "However , the change in p130 phosphorylation in response to alpha-IFN occurs before dephosphorylation of pRb is complete because loss of p130 Form 3 occurs throughout the cell cycle prior to complete arrest in G1 , whereas pRb is dephosphorylated only in G1 .", "target_text": { "p130": "protein", "alpha-IFN": "protein", "pRb": "protein", "p130 Form 3": "protein" } }, { "input_text": "In contrast , p107 is dephosphorylated and is then depleted from cells as they exit the cell cycle .", "target_text": { "p107": "protein" } }, { "input_text": "p130 , predominantly in Form 1 , and hypophosphorylated pRb bind an E2F DNA binding site ; p130 complexes E2F-4 , whereas pRb binds both E2F-4 and E2F-1 .", "target_text": { "p130": "protein", "pRb": "protein", "hypophosphorylated pRb": "protein", "E2F DNA binding site": "DNA", "E2F-4": "protein", "E2F-1": "protein" } }, { "input_text": "The phosphorylated forms of E2F-4 that bind to the E2F DNA site are different from hyperphosphorylated E2F-4 , which predominates in primary hemopoietic cells in G0 .", "target_text": { "E2F-4": "protein", "E2F DNA site": "DNA", "primary hemopoietic cells": "cell_type" } }, { "input_text": "We conclude that although cell cycle arrest induced by alpha-IFN may be mediated in part by formation of a complex containing p130 and E2F-4 , alpha-IFN does not induce hyperphosphorylation of E2F-4 , which characterizes primary hemopoietic cells in G0 .", "target_text": { "alpha-IFN": "protein", "p130": "protein", "E2F-4": "protein", "primary hemopoietic cells": "cell_type" } }, { "input_text": "The transcription factors c-myb and C/EBP alpha regulate the monocytic/myeloic gene MRP14 .", "target_text": { "transcription factors": "protein", "c-myb": "protein", "C/EBP alpha": "protein", "monocytic/myeloic gene": "DNA", "MRP14": "DNA" } }, { "input_text": "The entry of microorganisms into the body induces inflammatory processes .", "target_text": {} }, { "input_text": "During this process a sequence of cellular , humoral , non-specific and specific actions are evoked to combat the infection .", "target_text": {} }, { "input_text": "Macrophages and granulocytes , which are developed from a common progenitor cell , are the cellular components of the specific and non-specific immunoreaction .", "target_text": { "Macrophages": "cell_type", "granulocytes": "cell_type" } }, { "input_text": "MRP14 ( Macrophage migration inhibitory related protein ) and MRP8 , two S-100 proteins contained in high concentrations in these cells are obviously essential for adhesion and migration of monocytes and granulocytes .", "target_text": { "MRP14": "DNA", "Macrophage migration inhibitory related protein": "protein", "MRP8": "protein", "S-100 proteins": "protein", "monocytes": "cell_type", "granulocytes": "cell_type" } }, { "input_text": "To investigate the transcriptional regulation of these genes we cotransfected constructs expressing CAT under control of the MRP14 promoter and expression constructs of C/EBP alpha and v-myb , two transcription factors involved in myeloid/monocytic differentiation .", "target_text": { "CAT": "protein", "MRP14": "protein", "MRP14 promoter": "DNA", "C/EBP alpha": "protein", "v-myb": "protein", "transcription factors": "protein" } }, { "input_text": "Transfection with C/EBP alpha revealed a massive enhancement of the MRP14 promoter in both , HL 60 cells ( granulocytic differentiated ) and L132 fibroblasts .", "target_text": { "C/EBP alpha": "protein", "MRP14": "protein", "MRP14 promoter": "DNA", "HL 60 cells": "cell_type", "L132 fibroblasts": "cell_type" } }, { "input_text": "In contrast , v-myb reduces MRP14 promoter activity .", "target_text": { "v-myb": "protein", "MRP14": "protein", "MRP14 promoter": "DNA" } }, { "input_text": "Northern blot analysis of L132 cells transfected with the C/EBP alpha expression vector demonstrate that C/EBP alpha is sufficient to enhance MRP14 expression in the context of the whole genome .", "target_text": { "L132 cells": "cell_type", "C/EBP alpha": "protein", "MRP14": "protein" } }, { "input_text": "A CD28 -associated signaling pathway leading to cytokine gene transcription and T cell proliferation without TCR engagement .", "target_text": { "CD28": "protein", "cytokine gene": "DNA", "TCR": "protein" } }, { "input_text": "Stimulation of resting human T cells with the CD28 -specific mAb BW 828 induces proliferation and cytokine synthesis without further requirement for TCR coengagement .", "target_text": { "resting human T cells": "cell_type", "CD28": "protein", "CD28 -specific mAb BW 828": "protein", "cytokine": "protein", "TCR": "protein" } }, { "input_text": "This observation prompted us to postulate that signal 2 ( costimulatory signal ) alone without signal 1 ( TCR signal ) can activate T cells .", "target_text": { "TCR": "protein", "T cells": "cell_type" } }, { "input_text": "To test whether this putative function of CD28 is mediated via a particular signaling pathway , we compared early signaling events initiated in resting T cells by the stimulatory mAb BW 828 with signals triggered by the nonstimulating CD28 mAb 9.3 .", "target_text": { "CD28": "protein", "T cells": "cell_type", "stimulatory mAb BW 828": "protein", "nonstimulating CD28 mAb 9.3": "protein" } }, { "input_text": "Stimulation of T cells with BW 828 induced an increase in intracellular Ca2+ , but did not lead to detectable activation of the protein kinases p56(lck) and c-Raf-1 .", "target_text": { "T cells": "cell_type", "BW 828": "protein", "protein kinases": "protein", "p56(lck)": "protein", "c-Raf-1": "protein" } }, { "input_text": "This pathway resulted in the induction of the transcription factors NF-kappa B , NF-AT , and proteins binding to the CD28 response element of the IL-2 promoter .", "target_text": { "transcription factors": "protein", "NF-kappa B": "protein", "NF-AT": "protein", "CD28": "protein", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "On the other hand , stimulation of T cells with mAb 9.3 increased the level of intracellular Ca2+ and triggered the activation of p56(lck) and c-Raf-1 , but was unable to induce the binding of transcription factors to the IL-2 promoter .", "target_text": { "T cells": "cell_type", "mAb 9.3": "protein", "p56(lck)": "protein", "c-Raf-1": "protein", "transcription factors": "protein", "IL-2": "protein", "IL-2 promoter": "DNA" } }, { "input_text": "In contrast to the differential signaling of BW 828 and 9.3 in resting T cells , the two mAbs exhibited a similar pattern of early signaling events in activated T cells and Jurkat cells ( p56(lck) activation , association of phosphatidylinositol 3-kinase with CD28 ) , indicating that the signaling capacity of CD28 changes with activation .", "target_text": { "BW 828": "protein", "9.3": "protein", "activated T cells": "cell_type", "Jurkat cells": "cell_type", "p56(lck)": "protein", "phosphatidylinositol 3-kinase": "protein", "CD28": "protein" } }, { "input_text": "These data support the view that stimulation through CD28 can induce some effector functions in T cells and suggest that this capacity is associated with a particular pattern of early signaling events", "target_text": { "CD28": "protein", "T cells": "cell_type" } }, { "input_text": "Decreased IL-12 production and Th1 cell development by acetyl salicylic acid -mediated inhibition of NF-kappaB .", "target_text": { "IL-12": "protein", "NF-kappaB": "protein" } }, { "input_text": "IL-12 is a 75-kDa heterodimeric cytokine composed of two covalently linked p35 and p40 chains .", "target_text": { "IL-12": "protein", "75-kDa heterodimeric cytokine": "protein" } }, { "input_text": "This pro-inflammatory cytokine plays a prominent role in the development of Th1 cell-mediated immune responses .", "target_text": { "pro-inflammatory cytokine": "protein" } }, { "input_text": "Th1 cell-mediated immune responses have been implicated in the pathogenesis of chronic inflammatory autoimmune diseases .", "target_text": {} }, { "input_text": "Thus , IL-12 appears to be a critical factor in the generation and maintenance of chronic inflammatory conditions .", "target_text": { "IL-12": "protein" } }, { "input_text": "In this study , we investigated the effects of a commonly prescribed anti-inflammatory drug , acetyl salicylic acid ( ASA ) , on IL-12 production and Th1 cell development .", "target_text": { "IL-12": "protein" } }, { "input_text": "ASA was found to inhibit secretion of the IL-12 heterodimer as well as p40 monomer by human monocytic cells .", "target_text": { "IL-12": "protein", "IL-12 heterodimer": "protein", "p40 monomer": "protein", "human monocytic cells": "cell_type" } }, { "input_text": "This was associated with the down-regulation of IL-12p40 mRNA expression .", "target_text": { "IL-12p40": "protein", "IL-12p40 mRNA": "RNA" } }, { "input_text": "Analysis of the regulation of the p40 gene promoter revealed that ASA inhibited NF-kappaB activation and binding to the p40-kappaB site in the p40 promoter , leading to transcriptional repression of the p40 gene .", "target_text": { "p40 gene promoter": "DNA", "NF-kappaB": "protein", "p40-kappaB": "protein", "p40-kappaB site": "DNA", "p40": "protein", "p40 promoter": "DNA", "p40 gene": "DNA" } }, { "input_text": "Addition of ASA to an in vitro T helper cell differentiation system , at concentrations compatible with plasma levels reached during anti-inflammatory therapy , resulted in reduced development of Th1 cells .", "target_text": { "Th1 cells": "cell_type" } }, { "input_text": "These results suggest that the inhibition of NF-kappaB activation by ASA leads to down-regulation of IL-12 production and inhibition of Th1 cell development .", "target_text": { "NF-kappaB": "protein", "IL-12": "protein" } }, { "input_text": "Attenuation of HLA-DR expression by mononuclear phagocytes infected with Mycobacterium tuberculosis is related to intracellular sequestration of immature class II heterodimers .", "target_text": { "HLA-DR": "protein", "mononuclear phagocytes": "cell_type", "immature class II heterodimers": "protein" } }, { "input_text": "MHC class II expression was examined in macrophages infected with Mycobacterium tuberculosis .", "target_text": { "MHC class II": "protein", "macrophages": "cell_type" } }, { "input_text": "IFN-gamma increased the surface expression of class II molecules in THP-1 cells and this was markedly reduced in cells infected with M. tuberculosis .", "target_text": { "IFN-gamma": "protein", "class II molecules": "protein", "THP-1 cells": "cell_line" } }, { "input_text": "Despite this effect , steady state levels of HLA-DRalpha , HLA-DRbeta , and invariant ( Ii ) chains were equivalent in control and infected cells .", "target_text": { "HLA-DRalpha": "protein", "HLA-DRbeta": "protein", "invariant ( Ii ) chains": "protein" } }, { "input_text": "Metabolic labeling combined with pulse-chase experiments and biochemical analysis showed that the majority of class II molecules in infected cells became resistant to endoglycosidase H , consistent with normal Golgi processing .", "target_text": { "class II molecules": "protein", "endoglycosidase H": "protein" } }, { "input_text": "However , results of intracellular staining and dual color confocal microscopy revealed a significant defect in transport of newly synthesized class II molecules through the endocytic compartment .", "target_text": { "class II molecules": "protein" } }, { "input_text": "Thus , compared with findings in control cells , class II molecules in infected cells colocalized to a minimal extent with a lysosomal-associated membrane protein-1 + endosomal compartment .", "target_text": { "class II molecules": "protein", "infected cells": "cell_type", "lysosomal-associated membrane protein-1": "protein" } }, { "input_text": "In addition , in contrast to control cells , class II molecules in infected cells failed to colocalize with endocytosed BSA under conditions where this marker is known to label late endosomes , lysosomes , and the MHC class II compartment .", "target_text": { "control cells": "cell_type", "class II molecules": "protein", "infected cells": "cell_type", "endocytosed BSA": "protein", "MHC class II": "protein" } }, { "input_text": "Consistent with defective transport along the endocytic pathway , the maturation of SDS-stable class II alphabeta dimers -- dependent upon removal of Ii chain and peptide loading of class II dimers in the MHC class II compartment -- was markedly impaired in M. tuberculosis -infected cells .", "target_text": { "SDS-stable class II alphabeta dimers": "protein", "Ii chain": "protein", "class II dimers": "protein", "MHC class II": "protein", "-infected cells": "cell_type" } }, { "input_text": "These findings indicate that defective transport and processing of class II molecules through the endosomal/lysosomal system is responsible for diminished cell surface expression of MHC class II molecules in cells infected with M. tuberculosis .", "target_text": { "class II molecules": "protein", "MHC class II molecules": "protein" } }, { "input_text": "Identification of upstream regulatory elements that repress expression of adult beta-like globin genes in a primitive erythroid environment .", "target_text": { "upstream regulatory elements": "DNA", "adult beta-like globin genes": "DNA" } }, { "input_text": "Our investigations have focused on localizing cis-elements responsible for the down regulation of the adult beta-like globin genes ( delta and beta ) in immature , or primitive erythroid tissues .", "target_text": { "cis-elements": "DNA", "adult beta-like globin genes": "DNA", "delta": "DNA", "beta": "DNA" } }, { "input_text": "We studied their activity after transfection into K562 cells , an erythroleukemia cell line with an embryonic-fetal phenotype .", "target_text": { "K562 cells": "cell_line", "erythroleukemia cell line": "cell_line" } }, { "input_text": "Analyzed DNA sequences included delta and beta 5' flanking regions extending from approximately -500 to +50bp ( promoter regions ) , truncated delta and beta 5' flanking regions extending from approximately -250 to +50 bp , and chimeric promoter constructions , which consisted of a distal delta or beta fragment fused to a proximal beta or delta sequence .", "target_text": { "DNA sequences": "DNA", "-500 to +50bp": "DNA", "promoter regions": "DNA", "beta 5' flanking regions": "DNA", "-250 to +50 bp": "DNA", "chimeric promoter constructions": "DNA" } }, { "input_text": "In CAT reporter constructions no appreciable level of CAT activity was supported by the beta globin promoter , and only low level activity by the delta promoter .", "target_text": { "CAT reporter constructions": "DNA", "CAT": "protein", "beta globin promoter": "DNA", "delta promoter": "DNA" } }, { "input_text": "Truncation of the beta globin promoter led to a 2-3 fold increase in promoter activity .", "target_text": { "beta globin promoter": "DNA" } }, { "input_text": "In contrast , deletion of the upstream portion of the delta promoter led to a 10 fold decrease in expression .", "target_text": { "upstream portion": "DNA", "delta promoter": "DNA" } }, { "input_text": "Coupling of the upstream beta globin sequence from approximately -500 to -250 bp to the truncated delta promoter fragment led to complete extinction of transcription activity , consistent with a negative regulatory effect of the beta globin gene upstream element ( s ) .", "target_text": { "upstream beta globin sequence": "DNA", "delta promoter": "DNA", "beta globin gene upstream element": "DNA" } }, { "input_text": "Fusion of the upstream portion of the delta promoter to the truncated beta globin promoter yielded a modest increase in promoter strength relative to the truncated beta gene promoter , indicating the presence of a positive transcriptional element ( s ) in the upstream delta globin regulatory region .", "target_text": { "upstream portion": "DNA", "delta promoter": "DNA", "beta globin promoter": "DNA", "truncated beta gene promoter": "DNA", "positive transcriptional element": "DNA", "upstream delta globin regulatory region": "DNA" } }, { "input_text": "Site-directed mutagenesis of binding sites for the repressor proteins BP1 and BP2 in the upstream portion of the beta globin gene flanking region led to a 4-6 fold increase in promoter activity .", "target_text": { "upstream portion": "DNA", "beta globin gene flanking region": "DNA" } }, { "input_text": "DNase I footprinting of the upstream delta-globin region revealed protected sequences corresponding to consensus binding sites for GATA-1 and BP2 .", "target_text": { "DNase I": "protein", "upstream delta-globin region": "DNA", "protected sequences": "DNA", "consensus binding sites": "DNA", "GATA-1": "protein", "BP2": "protein" } }, { "input_text": "These results confirm that sequences in the upstream promoter region of the adult beta globin gene contribute to its factor-mediated suppression early in development and then may modulate its expression at a later stage .", "target_text": { "upstream promoter region": "DNA", "adult beta globin gene": "DNA" } }, { "input_text": "Analysis of cytokine signaling in patients with extrinsic asthma and hyperimmunoglobulin E .", "target_text": { "cytokine": "protein" } }, { "input_text": "BACKGROUND : Recent data suggest that the regulation of class switching to IgE by cytokines is mediated by STAT transcription factors .", "target_text": { "IgE": "protein", "cytokines": "protein", "STAT transcription factors": "protein" } }, { "input_text": "The induction of IgE by IL-4 and IL-13 occurs through the activation of the intracellular signal-transducing protein Stat6 , whereas the inhibition of IgE class switching by interferon-y ( IFN-gamma ) occurs through the activation of Statl .", "target_text": { "IgE": "protein", "IL-4": "protein", "IL-13": "protein", "intracellular signal-transducing protein Stat6": "protein", "interferon-y": "protein", "IFN-gamma": "protein", "Statl": "protein" } }, { "input_text": "OBJECTIVE : We hypothesized that in extrinsic asthma or in cases of markedly elevated IgE ( ie , hyperimmunoglobulin E [ HIE ] ) increased levels of IgE may be associated with alterations in the cytokine levels or the activation of Stat6 .", "target_text": { "IgE": "protein", "cytokine": "protein", "Stat6": "protein" } }, { "input_text": "METHODS : PBMCs and sera from 8 patients with extrinsic asthma ( mean IgE , 285+/-100 IU/mL ) , 3 patients with HIE ( mean IgE , 7050+/-1122 IU/mL ) , and 14 nonatopic control subjects ( mean IgE , 112+/-28 IU/mL ) were analyzed .", "target_text": { "PBMCs": "cell_type", "IgE": "protein" } }, { "input_text": "RESULTS : The mean IL-4 level detected by ELISA was much greater in patients with HIE than control subjects ( 88.6+/-11.5 pg/mL vs 11.5+/-7.1 pg/mL , P = .005 ) , and increased IL-4 levels among patients with both asthma and HIE correlated with the increased IgE levels .", "target_text": { "IL-4": "protein", "IgE": "protein" } }, { "input_text": "In contrast , IL-13 levels were not elevated .", "target_text": { "IL-13": "protein" } }, { "input_text": "Levels of Stat6 protein present in PBMCs did not differ in the patients and control subjects .", "target_text": { "Stat6": "protein", "PBMCs": "cell_type" } }, { "input_text": "Examination of Stat6 DNA-binding activity demonstrated no activation of IL-4 signaling in patients with either HIE or acute asthma .", "target_text": { "Stat6": "protein", "IL-4": "protein" } }, { "input_text": "Interestingly , evidence for the presence of B cells that have already switched to IgE was seen in PBMCs of several patients with asthma or HIE .", "target_text": { "B cells": "cell_type", "IgE": "protein", "PBMCs": "cell_type" } }, { "input_text": "CONCLUSION : These results indicate that ( 1 ) IgE production in asthma and HIE usually is associated with elevated levels of IL-4 , but not IL-13 , in the peripheral blood ; ( 2 ) the increased sera IL-4 levels in asthma and HIE are not sufficient to induce Stat6 activation in PBMCs ; and ( 3 ) evidence of switch recombination to epsilon may be detected in isolated cases of elevated IgE .", "target_text": { "IgE": "protein", "IL-4": "protein", "IL-13": "protein", "Stat6": "protein", "PBMCs": "cell_type" } }, { "input_text": "This implies that high levels of IgE in these patients either results from B cells that have already undergone class switching , from Ig class switching that is localized to target tissues , or both .", "target_text": { "IgE": "protein", "B cells": "cell_type" } }, { "input_text": "Carboxyl-terminal 15-amino acid sequence of NFATx1 is possibly created by tissue-specific splicing and is essential for transactivation activity in T cells .", "target_text": { "Carboxyl-terminal 15-amino acid sequence": "protein", "NFATx1": "protein", "T cells": "cell_type" } }, { "input_text": "NFAT regulates transcription of a number of cytokine and other immunoregulatory genes .", "target_text": { "NFAT": "protein", "immunoregulatory genes": "DNA" } }, { "input_text": "We have isolated NFATx , which is one of four members of the NFAT family of transcription factors and is preferentially expressed in the thymus and peripheral blood leukocytes , and an isoform of NFATx , NFATx1 .", "target_text": { "NFATx": "protein", "NFAT family": "protein", "transcription factors": "protein", "peripheral blood leukocytes": "cell_type", "NFATx1": "protein" } }, { "input_text": "Here we provide evidence showing that 15 amino acids in the carboxyl-terminal end of NFATx1 are required for its maximum transactivation activity in Jurkat T cells .", "target_text": { "carboxyl-terminal end": "protein", "NFATx1": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "A fusion between these 15 amino acids and the GAL4 DNA binding domain was capable of transactivating reporters driven by the GAL4 DNA binding site .", "target_text": { "GAL4 DNA binding domain": "protein", "GAL4 DNA binding site": "DNA" } }, { "input_text": "Interestingly , this 15-amino acid transactivation sequence is well conserved in NFAT family proteins , although the sequences contiguous to the carboxyl-terminal regions of the NFAT family are much less conserved .", "target_text": { "15-amino acid transactivation sequence": "protein", "NFAT family": "protein", "NFAT family proteins": "protein", "carboxyl-terminal regions": "protein" } }, { "input_text": "We also report three additional isoforms of NFATx , designated NFATx2 , NFATx3 , and NFATx4 .", "target_text": { "NFATx": "protein", "NFATx2": "protein", "NFATx3": "protein", "NFATx4": "protein" } }, { "input_text": "This transactivation sequence is altered by tissue-specific alternative splicing in newly isolated NFATx isoforms , resulting in lower transactivation activity in Jurkat T cells .", "target_text": { "NFATx": "protein", "NFATx isoforms": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "NFATx1 is expressed predominantly in the thymus and peripheral blood leukocyte , while the skeletal muscle expressed primarily NFATx2 .", "target_text": { "NFATx1": "protein", "peripheral blood leukocyte": "cell_type", "NFATx2": "protein" } }, { "input_text": "In Jurkat cells , transcription from the NFAT site of the IL-2 promoter is activated strongly by NFATx1 but only weakly by NFATx2 .", "target_text": { "Jurkat cells": "cell_line", "NFAT site": "DNA", "IL-2 promoter": "DNA", "NFATx1": "protein", "NFATx2": "protein" } }, { "input_text": "These data demonstrate that the 15-amino acid sequence of NFATx1 is a major transactivation sequence required for induction of genes by NFATx1 in T cells and possibly regulates NFAT activity through tissue-specific alternative splicing .", "target_text": { "15-amino acid sequence": "protein", "NFATx1": "protein", "major transactivation sequence": "protein", "T cells": "cell_type", "NFAT": "protein" } }, { "input_text": "Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the beta-globin locus control region in vivo .", "target_text": { "Altered DNA-binding specificity mutants": "protein", "EKLF": "protein", "beta-globin locus control region": "DNA" } }, { "input_text": "The locus control region of the beta-globin cluster contains five DNase I hypersensitive sites ( 5'HS1-5 ) required for locus activation .", "target_text": { "locus control region": "DNA", "beta-globin cluster": "DNA", "DNase I hypersensitive sites": "DNA", "5'HS1-5": "DNA" } }, { "input_text": "5'HS3 contains six G-rich motifs that are essential for its activity .", "target_text": { "5'HS3": "DNA", "G-rich motifs": "DNA" } }, { "input_text": "Members of a protein family , characterized by three zinc fingers highly homologous to those found in transcription factor Sp1 , interact with these motifs .", "target_text": { "zinc fingers": "protein", "transcription factor Sp1": "protein" } }, { "input_text": "Because point mutagenesis can not distinguish between family members , it is not known which protein activates 5'HS3 .", "target_text": { "5'HS3": "DNA" } }, { "input_text": "We show that the function of such closely related proteins can be distinguished in vivo by matching point mutations in 5'HS3 with amino acid changes in the zinc fingers of Sp1 and EKLF .", "target_text": { "5'HS3": "DNA", "zinc fingers": "protein", "Sp1": "protein", "EKLF": "protein" } }, { "input_text": "Testing their activity in transgenic mice shows that EKLF is a direct activator of 5'HS3 .", "target_text": { "EKLF": "protein", "5'HS3": "DNA" } }, { "input_text": "The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes .", "target_text": { "Epstein-Barr virus Rta protein": "protein", "lytic cycle genes": "DNA", "B lymphocytes": "cell_type" } }, { "input_text": "The transition of Epstein-Barr virus ( EBV ) from latency into the lytic cycle is associated with the expression of two immediate-early viral genes , BZLF1 and BRLF1 .", "target_text": { "immediate-early viral genes": "DNA", "BZLF1": "DNA", "BRLF1": "DNA" } }, { "input_text": "Overexpression of ZEBRA , the product of BZLF1 , is sufficient to disrupt latency in B lymphocytes and epithelial cells by stimulating expression of lytic cycle genes , including BRLF1 .", "target_text": { "BZLF1": "DNA", "B lymphocytes": "cell_type", "epithelial cells": "cell_type", "lytic cycle genes": "DNA", "BRLF1": "DNA" } }, { "input_text": "The BRLF1 product Rta functions as a transcriptional activator in both B lymphocytes and epithelial cells .", "target_text": { "BRLF1": "DNA", "Rta": "protein", "BRLF1 product Rta": "protein", "B lymphocytes": "cell_type", "epithelial cells": "cell_type" } }, { "input_text": "However , Rta has recently been reported to disrupt latency in an epithelial specific manner ( S. Zalani , E. Holley-Guthrie , and S. Kenney , Proc. Natl. Acad. Sci. USA 93 : 9194-9199 , 1996 ) .", "target_text": { "Rta": "protein" } }, { "input_text": "Here we demonstrate that expression of Rta is also sufficient for disruption of latency in a permissive B-cell line .", "target_text": { "Rta": "protein", "permissive B-cell line": "cell_line" } }, { "input_text": "In HH514-16 cells , transfection of Rta leads to synthesis of ZEBRA , viral DNA replication , and late gene expression .", "target_text": { "HH514-16 cells": "cell_line", "Rta": "protein", "ZEBRA": "protein" } }, { "input_text": "However , Rta by itself is less potent than ZEBRA in the ability to activate most early and late lytic cycle genes .", "target_text": { "Rta": "protein", "ZEBRA": "protein", "lytic cycle genes": "DNA" } }, { "input_text": "In light of previous work implicating ZEBRA in the activation of Rta , we suggest a cooperative model for EBV entry into the lytic cycle .", "target_text": { "ZEBRA": "protein", "Rta": "protein" } }, { "input_text": "Expression of either BZLF1 or BRLF1 triggers expression of the other immediate-early factor , and together these activators act individually or in synergy on downstream targets to activate the viral lytic cycle .", "target_text": { "BZLF1": "DNA", "BRLF1": "DNA", "immediate-early factor": "protein", "downstream targets": "DNA" } }, { "input_text": "Transcription of a minimal promoter from the NF-IL6 gene is regulated by CREB/ATF and SP1 proteins in U937 promonocytic cells .", "target_text": { "minimal promoter": "DNA", "NF-IL6 gene": "DNA", "CREB/ATF": "protein", "SP1 proteins": "protein", "U937 promonocytic cells": "cell_line" } }, { "input_text": "NF-IL6 is an important transcriptional regulator of genes induced in activated monocytes/ macrophages , and NF-IL6 is the only CCAAT/enhancer-binding protein ( C/EBP ) family member whose steady-state mRNA levels increase upon activation of monocytes ( 1 ) .", "target_text": { "NF-IL6": "protein", "macrophages": "cell_type", "activated monocytes/ macrophages": "cell_type", "CCAAT/enhancer-binding protein ( C/EBP ) family": "protein", "monocytes": "cell_type" } }, { "input_text": "We show that increased transcription of the NF-IL6 gene is responsible , at least in part , for induction of NF-IL6 mRNA following activation of U937 promonocytic cells .", "target_text": { "NF-IL6": "protein", "NF-IL6 gene": "DNA", "NF-IL6 mRNA": "RNA", "U937 promonocytic cells": "cell_line" } }, { "input_text": "We have identified a 104-bp minimal promoter region of the NF-IL6 gene that is sufficient for basal and activation-dependent induction of transcription in U937 cells .", "target_text": { "104-bp minimal promoter region": "DNA", "NF-IL6 gene": "DNA", "U937 cells": "cell_line" } }, { "input_text": "This region contains binding sites for the cAMP response element-binding protein/activation transcription factor ( CREB/ATF ) and Sp1 families of transcription factors .", "target_text": { "cAMP response element-binding protein/activation transcription factor": "protein", "CREB/ATF": "protein", "Sp1": "protein", "transcription factors": "protein" } }, { "input_text": "Each site is functionally important and contributes independently to transcription of the NF-IL6 gene in U937 cells .", "target_text": { "NF-IL6": "protein", "NF-IL6 gene": "DNA", "U937 cells": "cell_line" } }, { "input_text": "CIITA B-cell-specific promoter suppression in MHC class II -silenced cell hybrids .", "target_text": { "CIITA": "protein", "B-cell-specific promoter": "DNA", "MHC class II": "protein", "MHC class II -silenced cell hybrids": "cell_line" } }, { "input_text": "In this study , various sets of somatic cell hybrids , generated by the fusion of epithelial cell lines with B-lymphoblastoid cell lines , were analyzed for the expression of major histocompatibility complex ( MHC ) class II antigens .", "target_text": { "somatic cell hybrids": "cell_line", "epithelial cell lines": "cell_line", "B-lymphoblastoid cell lines": "cell_line", "major histocompatibility complex ( MHC ) class II antigens": "protein" } }, { "input_text": "We first demonstrate , in human and mouse intraspecies hybrids , the coordinate suppression of MHC class II , Ii ( invariant chain ) and HLA-DM gene transcription , and the release of the silencing by the addition of interferon gamma .", "target_text": { "human and mouse intraspecies hybrids": "cell_line", "MHC class II": "protein", "Ii": "protein", "invariant chain": "protein", "HLA-DM gene": "DNA", "interferon gamma": "protein" } }, { "input_text": "Using interspecies hybrids , the segregation of human chromosomes allowed us to establish that MHC class II extinction is linked to the presence in the hybrids of the chromosomes from the epithelial fusion partner .", "target_text": { "human chromosomes": "DNA", "MHC class II": "protein", "chromosomes": "DNA", "epithelial fusion partner": "cell_type" } }, { "input_text": "Moreover , our data provide evidence that the expression pattern of MHC class II mRNA is correlated with that of the class II transactivator ( CIITA ) , suggesting that CIITA is the actual target of the silencing .", "target_text": { "MHC class II": "protein", "MHC class II mRNA": "RNA", "class II transactivator": "protein", "CIITA": "protein" } }, { "input_text": "To gain further insight into the suppression phenomenon we performed luciferase assays which show that silencing affects the activity of the B-cell-specific promoter of CIITA .", "target_text": { "B-cell-specific promoter": "DNA", "CIITA": "protein" } }, { "input_text": "These results therefore demonstrate that the MHC class II gene silencing in somatic cell hybrids is due to an active suppression of one of the promoters of the CIITA gene , mediated by the epithelial cell fusion partner .", "target_text": { "MHC class II": "protein", "somatic cell hybrids": "cell_line", "promoters": "DNA", "CIITA": "protein", "CIITA gene": "DNA", "epithelial cell fusion partner": "cell_type" } }, { "input_text": "Class II transactivator-independent endothelial cell MHC class II gene activation induced by lymphocyte adhesion .", "target_text": { "MHC class II": "protein" } }, { "input_text": "NK cells induce MHC class II molecules on the surface of allogeneic endothelial cells in an adhesion-dependent , IFN-gamma -independent manner .", "target_text": { "MHC class II": "protein", "IFN-gamma": "protein" } }, { "input_text": "Here , we demonstrate that NK cells induce HLA-DR on the surface of a mutant cell line that is defective in IFN-gamma -induced MHC class II expression .", "target_text": { "NK cells": "cell_line", "HLA-DR": "protein", "mutant cell line": "cell_line", "IFN-gamma": "protein", "MHC class II": "protein" } }, { "input_text": "RNA analysis in these cells and in a cell line that is defective in class II transactivator ( CIITA ) demonstrates that NK cell-induced HLA-DR alpha mRNA expression is also CIITA -independent .", "target_text": { "class II transactivator": "protein", "CIITA": "protein", "HLA-DR alpha": "protein", "HLA-DR alpha mRNA": "RNA" } }, { "input_text": "The Janus kinase-1-deficient cell line U4A expresses HLA-DR alpha mRNA in response to NK cell activation , and HLA-DR alpha promoter constructs transfected into these cells are induced by NK cells but not IFN-gamma .", "target_text": { "Janus kinase-1-deficient cell line U4A": "cell_line", "HLA-DR alpha": "protein", "HLA-DR alpha mRNA": "RNA", "HLA-DR alpha promoter": "DNA", "HLA-DR alpha promoter constructs": "DNA", "NK cells": "cell_line", "IFN-gamma": "protein" } }, { "input_text": "These data indicate that the IFN-gamma -independent component of the target cell HLA-DR expression induced by lymphocyte adhesion uses a signaling pathway that is distinct from the IFN-gamma -dependent mechanism and also suggest that CIITA is not required .", "target_text": { "IFN-gamma": "protein", "HLA-DR": "protein", "CIITA": "protein" } }, { "input_text": "Effects of overexpression of IL-1 receptor-associated kinase on NFkappaB activation , IL-2 production and stress-activated protein kinases in the murine T cell line EL4 .", "target_text": { "IL-1 receptor-associated kinase": "protein", "NFkappaB": "protein", "IL-2": "protein", "murine T cell line EL4": "cell_line" } }, { "input_text": "The association and activation of the IL-1 receptor-associated protein kinase ( IRAK ) to the IL-1 receptor complex is one of the earliest events detectable in IL-1 signal transduction .", "target_text": { "IL-1 receptor-associated protein kinase": "protein", "IRAK": "protein", "IL-1": "protein", "IL-1 receptor complex": "protein" } }, { "input_text": "We generated permanent clones of the murine T cell line EL4 6.1 overexpressing human ( h ) IRAK to evaluate the role of this kinase in IL-1 signaling .", "target_text": { "murine T cell line EL4 6.1": "cell_line", "IRAK": "protein", "human ( h ) IRAK": "protein", "IL-1": "protein" } }, { "input_text": "Overexpression of hIRAK enhanced IL-1 -stimulated activation of the transcription factor NFkappaB , whereas a truncated form ( N-IRAK ) specifically inhibited IL-1 -dependent NFkappaB activity .", "target_text": { "hIRAK": "protein", "IL-1": "protein", "NFkappaB": "protein", "transcription factor NFkappaB": "protein", "N-IRAK": "protein" } }, { "input_text": "In clones stably overexpressing hIRAK a weak constitutive activation of NFkappaB correlated with a low basal IL-2 production which was enhanced in an IL-1 -dependent manner .", "target_text": { "hIRAK": "protein", "NFkappaB": "protein", "IL-2": "protein", "IL-1": "protein" } }, { "input_text": "Compared to the parental cell line the dose-response curve of IL-1 -induced IL-2 production was shifted in both potency and efficacy .", "target_text": { "parental cell line": "cell_line", "IL-1": "protein", "IL-2": "protein" } }, { "input_text": "These results demonstrate that IRAK directly triggers NFkappaB -mediated gene expression in EL4 cells .", "target_text": { "IRAK": "protein", "NFkappaB": "protein", "EL4 cells": "cell_line" } }, { "input_text": "Qualitatively different effects were observed for the IL-1 -induced activation of stress-activated protein ( SAP ) kinases : permanent overexpression of IRAK did not affect the dose dependence but prolonged the kinetics of IL-1 -induced activation of SAP kinases , suggesting that this signaling branch may be regulated by distinct mechanisms .", "target_text": { "IL-1": "protein", "stress-activated protein ( SAP ) kinases": "protein", "IRAK": "protein", "SAP kinases": "protein" } }, { "input_text": "The role of protein kinase C signaling in activated DRA transcription .", "target_text": { "protein kinase C": "protein", "DRA": "DNA" } }, { "input_text": "Expression of human MHC HLA-DRA class II gene can be up-regulated in B cells by Ig cross-linking as well as by phorbol esters such as 12-O-tetradecanoyl phorbol 13-acetate ( TPA ) .", "target_text": { "human MHC HLA-DRA class II gene": "DNA", "B cells": "cell_type" } }, { "input_text": "Induced DRA expression involves activation of restricted protein kinase C ( PKC ) isoforms , resulting in activated activator protein-1 -dependent transcription .", "target_text": { "DRA": "DNA", "protein kinase C": "protein", "PKC": "protein", "restricted protein kinase C ( PKC ) isoforms": "protein", "protein-1": "protein" } }, { "input_text": "In this report expression profiles and activation of PKC were analyzed in human Raji B lymphoblastoid cells .", "target_text": { "PKC": "protein", "human Raji B lymphoblastoid cells": "cell_line" } }, { "input_text": "Transient transfection analysis with target plasmids containing either DRA promoter ( wild-type or mutated ) or TPA response elements demonstrated that pretreatment with the selective PKC inhibitor GF 109203X repressed TPA -mediated activation .", "target_text": { "target plasmids": "DNA", "DRA promoter": "DNA", "TPA response elements": "DNA", "PKC": "protein" } }, { "input_text": "Western analysis performed on cellular fractions of resting cells and of TPA -activated cells revealed abundant expression of classical PKC-alpha ( cPKC-alpha ) , cPKC-betaII , and atypical PKC-zeta isoforms and identified a sustained translocation of cPKC-alpha and cPKC-betaII from the cytosolic compartment to membranes .", "target_text": { "resting cells": "cell_type", "TPA -activated cells": "cell_type", "classical PKC-alpha": "protein", "cPKC-alpha": "protein", "cPKC-betaII": "protein", "atypical PKC-zeta isoforms": "protein" } }, { "input_text": "As expected , the distribution of atypical PKC-zeta was unaffected by TPA treatment and displayed an even distribution between cytosol and membranes .", "target_text": { "atypical PKC-zeta": "protein" } }, { "input_text": "This finding was confirmed by immunofluorescence microscopy .", "target_text": {} }, { "input_text": "The TPA -mediated translocation of cPKC-alpha and cPKC-betaII was not influenced by pretreatment with GF 109203X .", "target_text": { "cPKC-alpha": "protein", "cPKC-betaII": "protein" } }, { "input_text": "Finally , functional activation and translocation of PKC were investigated with a selective in vitro kinase assay .", "target_text": { "PKC": "protein" } }, { "input_text": "Together , these results show that activated HLA-DRA expression in response to TPA treatment is strictly dependent on PKC activation acting on the X2 box of the DRA promoter and that selective inhibition of PKC enzymatic activity does not influence subcellular localization of expressed PKC isoenzymes .", "target_text": { "HLA-DRA": "protein", "PKC": "protein", "X2 box": "DNA", "DRA promoter": "DNA", "PKC isoenzymes": "protein" } }, { "input_text": "Thus , the translocation event per se occurs independently of PKC activation in these cells .", "target_text": { "PKC": "protein" } }, { "input_text": "Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands [ see comments ]", "target_text": { "RNA polymerase II": "protein", "human cells": "cell_type" } }, { "input_text": "Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes .", "target_text": { "human cells": "cell_type" } }, { "input_text": "Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis .", "target_text": { "cellular DNA-binding transcription factors": "protein" } }, { "input_text": "Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-1 , lymphoid-enhancer binding factor 1 , and TATA-box binding protein .", "target_text": { "transcription factors": "protein", "Ets-1": "protein", "lymphoid-enhancer binding factor 1": "protein", "TATA-box": "DNA", "TATA-box binding protein": "protein" } }, { "input_text": "These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays .", "target_text": { "transcription factor": "protein" } }, { "input_text": "When used in combination , the polyamides inhibit virus replication by > 99 % in isolated human peripheral blood lymphocytes , with no detectable cell toxicity .", "target_text": { "isolated human peripheral blood lymphocytes": "cell_type" } }, { "input_text": "The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression , as well as a mechanism for the inhibition of viral replication .", "target_text": { "DNA sequences": "DNA", "RNA polymerase II promoters": "DNA" } }, { "input_text": "musculin : a murine basic helix-loop-helix transcription factor gene expressed in embryonic skeletal muscle .", "target_text": { "musculin": "DNA", "murine basic helix-loop-helix transcription factor gene": "DNA" } }, { "input_text": "We describe the embryonic expression of musculin , a new murine member of the bHLH family of transcription factors .", "target_text": { "musculin": "protein", "bHLH family": "protein", "transcription factors": "protein" } }, { "input_text": "Musculin protein is closely related to human ABF-1 , which is expressed in activated B cells , and to epicardin/capsulin/Pod-1 , which is expressed in branchial myoblasts , visceral and urogenital mesoderm and epicardium .", "target_text": { "human ABF-1": "protein", "B cells": "cell_type", "epicardin/capsulin/Pod-1": "protein", "branchial myoblasts": "cell_type" } }, { "input_text": "In situ hybridisation revealed musculin expression in embryos was largely restricted to the embryonic skeletal muscle lineage .", "target_text": { "musculin": "protein", "embryonic skeletal muscle lineage": "cell_type" } }, { "input_text": "While all skeletal muscles expressed the gene , only a subset of myocytes within each muscle were positive , indicating molecular heterogeneity within fetal muscle .", "target_text": {} }, { "input_text": "Copyright 1998 Elsevier Science Ireland Ltd .", "target_text": {} }, { "input_text": "All Rights Reserved .", "target_text": {} }, { "input_text": "Induction of T cell anergy by high concentrations of immunodominant native peptide is accompanied by IL-10 production and a block in JNK activity .", "target_text": { "IL-10": "protein", "JNK": "protein" } }, { "input_text": "The ability to induce anergy in antigen-specific T cells has potential therapeutic value for altering pathologic immune responses .", "target_text": { "antigen-specific T cells": "cell_type" } }, { "input_text": "This study was undertaken to further analyze changes in cytokine production and intracellular signaling during anergy induction using high concentrations of native peptide ligand of tetanus toxoid ( TT ) - and myelin basic protein ( MBP ) - specific human T cell lines .", "target_text": { "cytokine": "protein" } }, { "input_text": "The TT -selected T cell line could be rendered unresponsive to its dominant epitope in a dose-dependent manner ( IC50 = 0.03 microg/ml ) .", "target_text": { "TT -selected T cell line": "cell_line" } }, { "input_text": "The TT -selected line , as well as three T cell clones established from this line , continued to produce IFN-gamma and significantly increased IL-4 and IL-10 production when anergy was induced with high concentrations of the immunodominant epitope .", "target_text": { "TT -selected line": "cell_line", "IFN-gamma": "protein", "IL-4": "protein", "IL-10": "protein" } }, { "input_text": "JNK enzymatic activity was blocked in anergized T cells .", "target_text": { "JNK": "protein", "anergized T cells": "cell_line" } }, { "input_text": "The MBP -selected line could likewise be rendered unresponsive by incubation with supraoptimal concentrations of immunodominant peptide and anergy induction was accompanied by IL-10 release .", "target_text": { "MBP": "protein", "IL-10": "protein" } }, { "input_text": "Both T cell lines could be anergized by the autopresentation of native peptide since anergy was induced in cultures lacking fresh antigen-presenting cells .", "target_text": { "T cell lines": "cell_line", "antigen-presenting cells": "cell_type" } }, { "input_text": "This study shows that the mitogen-activated protein kinase cascade is blocked when anergy is induced to high concentrations of soluble peptide .", "target_text": { "mitogen-activated protein kinase": "protein" } }, { "input_text": "Copyright 1998 Academic Press .", "target_text": {} }, { "input_text": "Upregulation of interleukin 6 and granulocyte colony-stimulating factor receptors by transcription factor CCAAT enhancer binding protein alpha ( C/EBP alpha ) is critical for granulopoiesis .", "target_text": { "interleukin 6": "protein", "granulocyte colony-stimulating factor receptors": "protein", "transcription factor": "protein", "CCAAT enhancer binding protein": "protein", "CCAAT enhancer binding protein alpha": "protein", "C/EBP alpha": "protein" } }, { "input_text": "Cytokines stimulate granulopoiesis through signaling via receptors whose expression is controlled by lineage-specific transcription factors .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Previously , we demonstrated that granulocyte colony-stimulating factor ( G-CSF ) receptor mRNA was undetectable and granulocyte maturation blocked in CCAAT enhancer binding protein alpha ( C/EBPalpha ) -deficient mice .", "target_text": { "granulocyte colony-stimulating factor": "protein", "G-CSF": "protein", "granulocyte colony-stimulating factor ( G-CSF ) receptor mRNA": "RNA", "CCAAT enhancer binding protein": "protein", "CCAAT enhancer binding protein alpha": "protein", "C/EBPalpha": "protein" } }, { "input_text": "This phenotype is distinct from that of G-CSF receptor-/- mice , suggesting that other genes are likely to be adversely affected by loss of C/EBPalpha .", "target_text": { "C/EBPalpha": "protein" } }, { "input_text": "Here we demonstrate loss of interleukin 6 ( IL-6 ) receptor and IL-6-responsive colony-forming units ( CFU-IL6 ) in C/EBPalpha -/- mice .", "target_text": { "interleukin 6": "protein", "interleukin 6 ( IL-6 ) receptor": "protein", "IL-6-responsive colony-forming units": "protein", "CFU-IL6": "protein", "C/EBPalpha": "protein" } }, { "input_text": "The observed failure of granulopoiesis could be rescued by the addition of soluble IL-6 receptor and IL-6 or by retroviral transduction of G-CSF receptors , demonstrating that loss of both of these receptors contributes to the absolute block in granulocyte maturation observed in C/EBPalpha -deficient hematopoietic cells .", "target_text": { "IL-6": "protein", "IL-6 receptor": "protein", "G-CSF receptors": "protein", "C/EBPalpha": "protein", "C/EBPalpha -deficient hematopoietic cells": "cell_type" } }, { "input_text": "The results of these and other studies suggest that additional C/EBPalpha target genes , possibly other cytokine receptors , are also important for the block in granulocyte differentiation observed in vivo in C/EBPalpha -deficient mice .", "target_text": { "C/EBPalpha": "protein", "C/EBPalpha target genes": "DNA" } }, { "input_text": "Phosphatidylinositides bind to plasma membrane CD14 and can prevent monocyte activation by bacterial lipopolysaccharide .", "target_text": { "CD14": "protein", "plasma membrane CD14": "protein" } }, { "input_text": "Although bacterial lipopolysaccharides ( LPS ) and several other microbial agonists can bind to mCD14 ( membrane CD14 ) , a cell-surface receptor found principally on monocytes and neutrophils , host-derived mCD14 ligands are poorly defined .", "target_text": { "mCD14": "protein", "membrane CD14": "protein", "monocytes": "cell_type", "neutrophils": "cell_type" } }, { "input_text": "We report here that phosphatidylinositol ( PtdIns ) , phosphatidylinositol -4-phosphate , and other phosphatidylinositides can bind to mCD14 .", "target_text": { "mCD14": "protein" } }, { "input_text": "Phosphatidylserine ( PS ) , another anionic glycerophospholipid , binds to mCD14 with lower apparent affinity than does PtdIns .", "target_text": { "mCD14": "protein" } }, { "input_text": "LPS -binding protein , a lipid transfer protein found in serum , facilitates both PS - and PtdIns - mCD14 binding .", "target_text": { "LPS -binding protein": "protein", "mCD14": "protein" } }, { "input_text": "PtdIns binding to mCD14 can be blocked by anti-CD14 monoclonal antibodies that inhibit LPS -mCD14 binding , and PtdIns can inhibit both LPS -mCD14 binding and LPS -induced responses in monocytes .", "target_text": { "mCD14": "protein", "anti-CD14 monoclonal antibodies": "protein", "-mCD14": "protein", "monocytes": "cell_type" } }, { "input_text": "Serum-equilibrated PtdIns also binds to mCD14 -expressing cells , raising the possibility that endogenous PtdIns may modulate cellular responses to LPS and other mCD14 ligands in vivo .", "target_text": { "mCD14": "protein", "Serum-equilibrated PtdIns also binds to mCD14 -expressing cells": "cell_type" } }, { "input_text": "Protein kinase C regulates Fas ( CD95/APO-1 ) expression .", "target_text": { "Protein kinase C": "protein", "Fas": "protein", "CD95/APO-1": "protein" } }, { "input_text": "Fas ( CD95/APO-1 ) is a transmembrane protein of the TNF/neuron growth factor receptor family .", "target_text": { "Fas": "protein", "CD95/APO-1": "protein", "transmembrane protein": "protein", "TNF/neuron growth factor receptor family": "protein" } }, { "input_text": "Ligation of Fas by specific Abs or Fas ligand ( FasL/CD95 ligand ) induces rapid apoptotic cell death in a variety of cell types .", "target_text": { "Fas": "protein", "specific Abs": "protein", "Fas ligand": "protein", "FasL/CD95 ligand": "protein" } }, { "input_text": "Despite progress in understanding the death signals transduced from Fas , very little is known with regard to the mechanisms by which Fas expression is regulated .", "target_text": { "Fas": "protein" } }, { "input_text": "Using our previously established murine T cell hybridoma model A1.1 , we show that specific protein kinase C ( PKC ) inhibitors could block activation-induced Fas expression and apoptosis .", "target_text": { "murine T cell hybridoma model": "cell_line", "A1.1": "cell_line", "protein kinase C": "protein", "PKC": "protein", "Fas": "protein" } }, { "input_text": "The activation of PKC with PMA or 1-oleoyl-2-acetyl-sn-glycerol could mimic the TCR signal by inducing the expression of Fas but not FasL .", "target_text": { "PKC": "protein", "TCR": "protein", "Fas": "protein" } }, { "input_text": "PKC -dependent Fas expression was also observed in several murine and human tumor cell lines .", "target_text": { "PKC": "protein", "Fas": "protein" } }, { "input_text": "Since the inhibition of Ca2+ redistribution by an inhibitor of intracellular Ca2+ mobilization , 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride , inhibited TCR-induced FasL but not Fas , the expression of Fas appears to be independent of Ca2+ mobilization .", "target_text": { "TCR-induced FasL": "protein", "Fas": "protein" } }, { "input_text": "Significantly , expression of the newly identified Fas -regulatory gene , TDAG51 , was found to be dependent upon the activity of PKC .", "target_text": { "Fas": "protein", "Fas -regulatory gene": "DNA", "TDAG51": "DNA", "PKC": "protein" } }, { "input_text": "PKC activation only induced Fas expression in cells expressing wild-type TDAG51 .", "target_text": { "PKC": "protein", "Fas": "protein", "TDAG51": "DNA" } }, { "input_text": "Thus , Fas expression is likely mediated by PKC through TDAG51 .", "target_text": { "Fas": "protein", "PKC": "protein", "TDAG51": "DNA" } }, { "input_text": "Retinoic acid inhibits CD40 + interleukin-4 -mediated IgE production in vitro .", "target_text": { "CD40": "protein", "interleukin-4": "protein", "IgE": "protein" } }, { "input_text": "To elucidate the role of retinoic acid ( RA ) in anti- CD40 + interleukin-4 ( IL-4 ) -mediated B-cell activation , the effect of 10(-12) to 10(-6) mol/L RA was studied in anti-CD40 ( 1 microgram/mL ) + IL-4 ( 5 ng/mL ) -mediated proliferation and Ig synthesis by human peripheral blood mononuclear cells ( PBMC ) and B cells in healthy donors .", "target_text": { "CD40": "protein", "anti- CD40": "protein", "interleukin-4": "protein", "IL-4": "protein", "anti-CD40": "protein", "human peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type", "B cells": "cell_type" } }, { "input_text": "Anti-CD40 + IL-4 -mediated proliferation of PBMC and B cells was inhibited by RA in a dose-dependent manner , with maximal inhibition of 62 % +/- 5 % in PBMC and 55 % +/- 4.4 % in B cells by all-trans RA , and 58 % +/- 6.7 % and 51 % +/- 4.7 % , respectively by 13-cis RA .", "target_text": { "Anti-CD40": "protein", "IL-4": "protein", "PBMC": "cell_type", "B cells": "cell_type" } }, { "input_text": "IgE synthesis was even more markedly inhibited by RA starting at concentrations of > 10(-14) mol/L for B cells and > 10(-10) mol/L for PBMC .", "target_text": { "IgE": "protein", "B cells": "cell_type", "PBMC": "cell_type" } }, { "input_text": "Maximal inhibition of IgE production for B cells was at 10(-8) mol/L for all-trans RA ( 94 % +/- 1.8 % ) and 96 % +/- 3.2 % for 13-cis RA .", "target_text": { "IgE": "protein", "B cells": "cell_type" } }, { "input_text": "Low concentrations of RA inhibiting IgE synthesis ( 10(-10) mol/L ) affected neither B-cell proliferation nor the production of IgA , IgG , and IgM .", "target_text": { "IgE": "protein", "IgA": "protein", "IgG": "protein", "IgM": "protein" } }, { "input_text": "Elucidation of the mechanism involved in this inhibition of IgE production shows that epsilon germline transcription is decreased by RA , whereas production of interferon-gamma ( IFN-gamma ) was not enhanced in the presence of RA .", "target_text": { "IgE": "protein", "germline": "DNA", "interferon-gamma": "protein", "IFN-gamma": "protein" } }, { "input_text": "To differentiate whether the RA effect was mediated by RA receptors alpha , beta , and gamma , the expression of the retinoic acid receptors ( RAR ) was examined by reverse transcriptase -polymerase chain reaction ( RT-PCR ) .", "target_text": { "retinoic acid receptors": "protein", "RAR": "protein", "reverse transcriptase": "protein" } }, { "input_text": "The data show that unstimulated human peripheral B cells express mRNA of the RA receptor alpha , beta , and gamma .", "target_text": { "unstimulated human peripheral B cells": "cell_type" } }, { "input_text": "Using retinoids with different receptor binding specificity ( CD336 , CD437 , CD2019 , CD367 ) , dose-dependent inhibition of IgE synthesis was shown by all four derivates , but was most marked by an RA binding the alpha receptor with high specificity .", "target_text": { "IgE": "protein", "alpha receptor": "protein" } }, { "input_text": "Taken together , this study shows that RA inhibits IgE production of anti-CD40 + IL-4 -stimulated B cells in vitro .", "target_text": { "IgE": "protein", "anti-CD40": "protein", "IL-4": "protein", "anti-CD40 + IL-4 -stimulated B cells": "cell_line" } }, { "input_text": "Copyright 1998 by The American Society of Hematology .", "target_text": {} }, { "input_text": "Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha ( IKKalpha ) and IKKbeta cellular kinases .", "target_text": { "Tax": "protein", "NF-kappaB": "protein", "IkappaB kinase alpha": "protein", "IKKalpha": "protein", "IKKbeta": "protein", "cellular kinases": "protein" } }, { "input_text": "Tax corresponds to a 40-kDa transforming protein from the pathogenic retrovirus human T-cell leukemia virus type 1 ( HTLV-1 ) that activates nuclear expression of the NF-kappaB /Rel family of transcription factors by an unknown mechanism .", "target_text": { "Tax": "protein", "40-kDa transforming protein": "protein", "NF-kappaB": "protein", "NF-kappaB /Rel family": "protein", "transcription factors": "protein" } }, { "input_text": "Tax expression promotes N-terminal phosphorylation and degradation of IkappaB alpha , a principal cytoplasmic inhibitor of NF-kappaB .", "target_text": { "Tax": "protein", "IkappaB alpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "Our studies now demonstrate that HTLV-1 Tax activates the recently identified cellular kinases IkappaB kinase alpha ( IKKalpha ) and IKKbeta , which normally phosphorylate IkappaB alpha on both of its N-terminal regulatory serines in response to tumor necrosis factor alpha ( TNF-alpha ) and interleukin-1 ( IL-1 ) stimulation .", "target_text": { "Tax": "protein", "cellular kinases": "protein", "IkappaB kinase alpha": "protein", "IKKalpha": "protein", "IKKbeta": "protein", "IkappaB alpha": "protein", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein", "interleukin-1": "protein", "IL-1": "protein" } }, { "input_text": "In contrast , a mutant of Tax termed M22 , which does not induce NF-kappaB , fails to activate either IKKalpha or IKKbeta .", "target_text": { "Tax": "protein", "M22": "protein", "NF-kappaB": "protein", "IKKalpha": "protein", "IKKbeta": "protein" } }, { "input_text": "Furthermore , endogenous IKK enzymatic activity was significantly elevated in HTLV-1-infected and Tax-expressing T-cell lines .", "target_text": {} }, { "input_text": "Transfection of kinase-deficient mutants of IKKalpha and IKKbeta into either human Jurkat T or 293 cells also inhibits NF-kappaB -dependent reporter gene expression induced by Tax .", "target_text": { "IKKalpha": "protein", "IKKbeta": "protein", "NF-kappaB": "protein", "reporter gene": "DNA", "Tax": "protein" } }, { "input_text": "Similarly , a kinase-deficient mutant of NIK ( NF-kappaB -inducing kinase ) , which represents an upstream kinase in the TNF-alpha and IL-1 signaling pathways leading to IKKalpha and IKKbeta activation , blocks Tax induction of NF-kappaB .", "target_text": { "kinase-deficient mutant": "protein", "NIK": "protein", "NF-kappaB": "protein", "NF-kappaB -inducing kinase": "protein", "IKKalpha": "protein", "IKKbeta": "protein", "Tax": "protein" } }, { "input_text": "However , plasma membrane-proximal elements in these proinflammatory cytokine pathways are apparently not involved since dominant negative mutants of the TRAF2 and TRAF6 adaptors , which effectively block signaling through the cytoplasmic tails of the TNF-alpha and IL-1 receptors , respectively , do not inhibit Tax induction of NF-kappaB .", "target_text": { "plasma membrane-proximal elements": "DNA", "proinflammatory cytokine": "protein", "cytoplasmic tails": "protein", "TNF-alpha": "protein", "IL-1": "protein", "Tax": "protein", "NF-kappaB": "protein" } }, { "input_text": "Together , these studies demonstrate that HTLV-1 Tax exploits a distal part of the proinflammatory cytokine signaling cascade leading to induction of NF-kappaB .", "target_text": { "Tax": "protein", "proinflammatory cytokine": "protein", "NF-kappaB": "protein" } }, { "input_text": "The pathological alteration of this cytokine pathway leading to NF-kappaB activation by Tax may play a central role in HTLV-1 -mediated transformation of human T cells , clinically manifested as the adult T-cell leukemia", "target_text": { "NF-kappaB": "protein", "Tax": "protein", "human T cells": "cell_type" } }, { "input_text": "Role of IKK1 and IKK2 in lipopolysaccharide signaling in human monocytic cells .", "target_text": { "IKK1": "protein", "IKK2": "protein", "human monocytic cells": "cell_type" } }, { "input_text": "Mononuclear phagocytes play a major role in immune and inflammatory responses .", "target_text": { "Mononuclear phagocytes": "cell_type" } }, { "input_text": "Bacterial lipopolysaccharide ( LPS ) induces monocytes to express a variety of genes by activating the NF-kappaB/Rel transcription factor family .", "target_text": { "monocytes": "cell_type", "NF-kappaB/Rel": "protein", "NF-kappaB/Rel transcription factor family": "protein" } }, { "input_text": "Recently , we have reported that the tumor necrosis factor and interleukin 1 signaling pathways activate two kinases , IKK1 and IKK2 .", "target_text": { "tumor necrosis factor": "protein", "interleukin 1": "protein", "IKK1": "protein", "IKK2": "protein" } }, { "input_text": "Phosphorylation of the IkappaB cytoplasmic inhibitors , IkappaBalpha , IkappaBbeta , and IkappaBepsilon , by these kinases triggers proteolytic degradation and the release of NF-kappaB/Rel proteins into the nucleus .", "target_text": { "IkappaB": "protein", "IkappaB cytoplasmic inhibitors": "protein", "IkappaBalpha": "protein", "IkappaBbeta": "protein", "IkappaBepsilon": "protein", "NF-kappaB/Rel proteins": "protein" } }, { "input_text": "At present , the role of the IKKs in LPS signaling has not been investigated .", "target_text": {} }, { "input_text": "Here , we report that LPS induces IKK activity in human monocytes and THP-1 monocytic cells .", "target_text": { "IKK": "protein", "monocytes": "cell_type", "human monocytes": "cell_type", "THP-1 monocytic cells": "cell_line" } }, { "input_text": "The kinetics of activation of kinase activity in monocytic cells are relatively slow with maximal activity observed at 60 min , which coincides with the degradation of IkappaBs and the nuclear translocation of NF-kappaB .", "target_text": { "monocytic cells": "cell_type", "IkappaBs": "protein", "NF-kappaB": "protein" } }, { "input_text": "In transfection experiments , overexpression of wild type IKK1 , a dominant negative mutant IKK1 ( K44M ) , or wild type IKK2 did not affect LPS -induced kappaB -dependent transcription in monocytic cells .", "target_text": { "IKK1": "protein", "dominant negative mutant IKK1": "protein", "K44M": "protein", "IKK2": "protein", "wild type IKK2": "protein", "kappaB": "protein", "monocytic cells": "cell_type" } }, { "input_text": "In contrast , a dominant negative mutant of IKK2 inhibited LPS induction of kappaB -dependent transcription in a dose-dependent manner .", "target_text": { "IKK2": "protein", "kappaB": "protein" } }, { "input_text": "These results indicate that LPS induction of kappaB-dependent gene expression in human monocytic cells requires activation of IKK2 .", "target_text": { "monocytic cells": "cell_type", "human monocytic cells": "cell_type", "IKK2": "protein" } }, { "input_text": "IL-7 reconstitutes multiple aspects of v-Abl -mediated signaling .", "target_text": { "IL-7": "protein", "v-Abl": "protein" } }, { "input_text": "The mechanism by which early lymphoid cells are selectively transformed by v-Abl is currently unknown .", "target_text": { "early lymphoid cells": "cell_type", "v-Abl": "protein" } }, { "input_text": "Previous studies have shown constitutive activation of IL-4 and IL-7 signaling pathways , as measured by activation of Janus protein kinase ( JAK ) 1 , JAK3 , STAT5 , and STAT6 , in pre-B cells transformed by v-Abl .", "target_text": { "IL-4": "protein", "IL-7": "protein", "Janus protein kinase ( JAK ) 1": "protein", "JAK3": "protein", "STAT5": "protein", "STAT6": "protein", "pre-B cells": "cell_type", "v-Abl": "protein" } }, { "input_text": "To determine whether activation of these cytokine signaling pathways by v-Abl is important in the cellular events induced by the Abelson murine leukemia virus , the effects of IL-4 and IL-7 on pre-B cells transformed with a temperature-sensitive v-Abl mutant were examined .", "target_text": { "v-Abl": "protein", "IL-4": "protein", "IL-7": "protein", "pre-B cells": "cell_type", "v-Abl mutant": "protein", "temperature-sensitive v-Abl mutant": "protein" } }, { "input_text": "Whereas IL-4 had little or no effect , IL-7 delayed both the apoptosis and cell cycle arrest that occur upon v-Abl kinase inactivation .", "target_text": { "IL-4": "protein", "IL-7": "protein", "v-Abl": "protein" } }, { "input_text": "IL-7 also delayed the decreases in the levels of c-Myc , Bcl-2 , and Bcl-xL that occur upon loss of v-Abl kinase activity .", "target_text": { "IL-7": "protein", "c-Myc": "protein", "Bcl-2": "protein", "Bcl-xL": "protein", "v-Abl": "protein" } }, { "input_text": "IL-7 did not maintain v-Abl -mediated differentiation arrest of the pre-B cells , as activation of NF-kappaB and RAG gene transcription was unaffected by IL-7 .", "target_text": { "IL-7": "protein", "v-Abl": "protein", "pre-B cells": "cell_type", "NF-kappaB": "protein", "RAG gene": "DNA" } }, { "input_text": "These results identify a potential role for IL-7 signaling pathways in transformation by v-Abl while demonstrating that a combination of IL-4 and IL-7 signaling can not substitute for an active v-Abl kinase in transformed pre-B cells .", "target_text": { "IL-7": "protein", "v-Abl": "protein", "IL-4": "protein", "pre-B cells": "cell_type", "transformed pre-B cells": "cell_type" } }, { "input_text": "Differential regulation of coproporphyrinogen oxidase gene between erythroid and nonerythroid cells .", "target_text": { "coproporphyrinogen oxidase gene": "DNA" } }, { "input_text": "Coproporphyrinogen oxidase ( CPO ) catalyzes the sixth step of the heme biosynthetic pathway .", "target_text": { "Coproporphyrinogen oxidase": "protein", "CPO": "protein", "heme": "protein" } }, { "input_text": "To assess the tissue-specific regulation of the CPO gene promoter , mouse genomic DNA clones for CPO were isolated .", "target_text": { "CPO": "protein", "CPO gene promoter": "DNA", "mouse genomic DNA clones": "DNA" } }, { "input_text": "Structural analysis demonstrated that the mouse CPO gene spans approximately 11 kb and consists of seven exons , just like its human counterpart .", "target_text": { "CPO": "protein", "mouse CPO gene": "DNA", "seven exons": "DNA" } }, { "input_text": "Functional analysis of the promoter by transient transfection assays indicated that synergistic action between an SP-1 -like element at -21/-12 , a GATA site at -59/-54 , and a novel regulatory element , CPRE ( - GGACTACAG - ) at -49/-41 , is essential for the promoter activity in murine erythroleukemia ( MEL ) cells .", "target_text": { "SP-1": "protein", "SP-1 -like element": "DNA", "GATA site": "DNA", "novel regulatory element": "DNA", "CPRE": "DNA", "GGACTACAG": "DNA", "murine erythroleukemia ( MEL ) cells": "cell_type" } }, { "input_text": "In nonerythroid NIH3T3 cells , however , the GATA site is not required .", "target_text": { "nonerythroid NIH3T3 cells": "cell_line", "GATA site": "DNA" } }, { "input_text": "Gel mobility shift assays demonstrated that specific DNA-protein complexes can be formed with each element , and that there are cell-specific differences in factors , which bind to the SP-1 -like element between MEL and NIH3T3 cells .", "target_text": { "DNA-protein complexes": "protein", "SP-1": "protein", "SP-1 -like element": "DNA" } }, { "input_text": "These results provide evidence for differential regulation of the promoter function of CPO gene between erythroid and nonerythroid cells .", "target_text": { "CPO": "protein" } }, { "input_text": "Copyright 1998 by The American Society of Hematology", "target_text": {} }, { "input_text": "Tumor suppressor proteins as regulators of cell differentiation .", "target_text": { "Tumor suppressor proteins": "protein" } }, { "input_text": "The products of the tumor suppressor genes are considered to function as specific inhibitors of tumor cell growth .", "target_text": { "tumor suppressor genes": "DNA" } }, { "input_text": "In this communication , we present evidence to show that these proteins inhibit tumor cell proliferation by participating in the activation of tumor cell differentiation .", "target_text": {} }, { "input_text": "The ML-1 human myeloblastic leukemia cells used in this study proliferate when treated with insulin-like growth factor I and transferrin but differentiate to monocytes when exposed to tumor necrosis factor alpha or transforming growth factor beta1 , or to macrophage-like cells when treated with both these cytokines .", "target_text": { "ML-1 human myeloblastic leukemia cells": "cell_line", "insulin-like growth factor I": "protein", "transferrin": "protein", "monocytes": "cell_type", "tumor necrosis factor alpha": "protein", "transforming growth factor beta1": "protein", "macrophage-like cells": "cell_type", "cytokines": "protein" } }, { "input_text": "Initiation of proliferation but not of differentiation was followed by a 20- to 25-fold increase in the nuclear level of the DNA polymerase-associated processivity factor PCNA and of the proliferation-specific transcription factor E2F1 .", "target_text": { "PCNA": "protein", "DNA polymerase-associated processivity factor PCNA": "protein", "E2F1": "protein", "proliferation-specific transcription factor E2F1": "protein" } }, { "input_text": "In contrast , induction of differentiation but not of proliferation was followed by a 25- to 30-fold increase in the nuclear level of the tumor suppressor proteins p53 ( wild type ) , pRb , and p130/Rb2 and of the p53-dependent cyclin kinase inhibitor p21/Cip1 .", "target_text": { "tumor suppressor proteins p53": "protein", "pRb": "protein", "p130/Rb2": "protein", "p53-dependent cyclin kinase inhibitor": "protein", "p21/Cip1": "protein" } }, { "input_text": "p53 and p21/Cip1 , respectively , inhibit the expression and activation of PCNA , whereas p130 and pRb , respectively , inhibit the expression and activation of E2F1 .", "target_text": { "p53": "protein", "p21/Cip1": "protein", "PCNA": "protein", "p130": "protein", "pRb": "protein", "E2F1": "protein" } }, { "input_text": "As a result , G1-S-associated DNA and mRNA synthesis is inhibited , growth uncoupled from differentiation , and maturation enabled to proceed .", "target_text": { "G1-S-associated DNA": "DNA" } }, { "input_text": "Where this function of the tumor suppressor proteins is impaired , the capacity for differentiation is lost , which leads to the sustained proliferation that is characteristic of the cancer cell .", "target_text": { "tumor suppressor proteins": "protein", "cancer cell": "cell_type" } }, { "input_text": "Transcription factor activation in lymphokine activated killer cells and lymphocytes from patients receiving IL-2 immunotherapy .", "target_text": { "Transcription factor": "protein", "killer cells": "cell_type", "lymphocytes": "cell_type", "IL-2": "protein" } }, { "input_text": "Administration of the cytokine interleukin-2 ( IL-2 ) can result in therapeutic benefits for individuals with renal cell carcinoma and melanoma .", "target_text": { "cytokine interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "Here we report an analysis of the transcription factor families AP-1 , Sp1 , NF-kappaB , and signal transducers and activators of transcription ( STAT ) in cancer patients ' lymphocytes before and after IL-2 immunotherapy , as assessed by a gel-shift assay .", "target_text": { "NF-kappaB": "protein", "signal transducers and activators of transcription": "protein", "STAT": "protein", "lymphocytes": "cell_type", "cancer patients ' lymphocytes": "cell_type", "IL-2": "protein" } }, { "input_text": "An in vitro surrogate of IL-2 immunotherapy is the incubation of fresh peripheral blood mononuclear cells ( PBMC ) from healthy individuals in IL-2 for several days , resulting in the production of lymphokine -activated killer ( LAK ) activity in these cultures .", "target_text": { "IL-2": "protein", "fresh peripheral blood mononuclear cells": "cell_type", "PBMC": "cell_type", "lymphokine": "protein" } }, { "input_text": "One purpose of this study was to describe the profile of transcription factor activation in these different populations , and assess whether the patterns observed correlated with functional differences in these cells .", "target_text": {} }, { "input_text": "Prior to in vivo IL-2 administration , the typical binding pattern of transcription factors in PBMC from patients resembled that seen in fresh PBMC from healthy individuals .", "target_text": { "IL-2": "protein", "transcription factors": "protein", "PBMC": "cell_type" } }, { "input_text": "Over a 3-week course of IL-2 therapy , in most patients the binding patterns of AP-1 , Sp1 , and NF-kappaB proteins changed to resemble those seen in PBMC activated by IL-2 in vitro .", "target_text": { "IL-2": "protein", "AP-1": "protein", "Sp1": "protein", "NF-kappaB": "protein", "PBMC": "cell_type" } }, { "input_text": "However , the cells obtained from IL-2 -treated patients did not have low-level constitutive expression of STAT binding factors as did LAK cells .", "target_text": { "IL-2": "protein", "STAT binding factors": "protein", "LAK cells": "protein" } }, { "input_text": "When these patient cells were further stimulated by IL-2 in vitro , additional differences in STAT induction patterns were noted .", "target_text": { "IL-2": "protein", "STAT": "protein" } }, { "input_text": "These data provide further information on the molecular events occurring in immune cells generated through in vivo and in vitro administration of IL-2 , and further document that there is not a precise congruence between PBMC activated in vivo and in vitro by IL-2 .", "target_text": { "immune cells": "cell_type", "IL-2": "protein", "PBMC": "cell_type" } }, { "input_text": "Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells [ see comments ]", "target_text": { "Activated platelets": "cell_type", "monocyte chemotactic protein-1": "protein", "intercellular adhesion molecule-1": "cell_type", "endothelial cells": "cell_type" } }, { "input_text": "BACKGROUND : Platelet/endothelium interaction plays an important role in the pathophysiology of inflammation and atherosclerosis .", "target_text": {} }, { "input_text": "The role of platelets for monocyte chemotactic protein-1 ( MCP-1 ) secretion and surface expression of intercellular adhesion molecule-1 ( ICAM-1 ) on endothelial cells has been assessed .", "target_text": { "monocyte chemotactic protein-1": "protein", "MCP-1": "protein", "intercellular adhesion molecule-1": "cell_type", "ICAM-1": "protein", "endothelial cells": "cell_type" } }, { "input_text": "METHODS AND RESULTS : Monolayers of human umbilical vein endothelial cells were incubated with nonstimulated or ADP-activated platelets for 6 hours , and secretion of MCP-1 and surface expression of ICAM-1 were determined by ELISA and flow cytometry , respectively .", "target_text": { "endothelial cells": "cell_type", "human umbilical vein endothelial cells": "cell_type", "ADP-activated platelets": "cell_type", "MCP-1": "protein", "ICAM-1": "protein" } }, { "input_text": "In the presence of ADP-activated platelets , both MCP-1 secretion and ICAM-1 surface expression were significantly increased compared with nonstimulated platelets ( P < 0.02 ) .", "target_text": { "ADP-activated platelets": "cell_type", "MCP-1": "protein", "ICAM-1": "protein", "nonstimulated platelets": "cell_type" } }, { "input_text": "Activation of the transcription factor nuclear factor-kappaB ( NF-kappaB ) determined by electrophoretic mobility shift assay and kappaB -dependent transcriptional activity was enhanced in the presence of activated platelets .", "target_text": { "transcription factor nuclear factor-kappaB": "protein", "NF-kappaB": "protein", "kappaB": "protein", "activated platelets": "cell_type" } }, { "input_text": "In addition , ADP- activated platelets induced MCP-1 and ICAM-1 promoter-dependent transcription .", "target_text": { "activated platelets": "cell_type", "ADP- activated platelets": "cell_type" } }, { "input_text": "Liposomal transfection of a double-stranded kappaB phosphorothioate oligonucleotide , but not of the mutated form , inhibited MCP-1 secretion and surface expression of ICAM-1 on activated endothelium ( P < 0.05 ) .", "target_text": { "MCP-1": "protein", "ICAM-1": "protein" } }, { "input_text": "CONCLUSIONS : The present study indicates that activated platelets modulate chemotactic ( MCP-1 ) and adhesive ( ICAM-1 ) properties of endothelial cells via an NF-kappaB -dependent mechanism .", "target_text": { "activated platelets": "cell_type", "MCP-1": "protein", "ICAM-1": "protein", "endothelial cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "Platelet-induced activation of the NF-kappaB system might contribute to early inflammatory events in atherogenesis .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Retinoid X receptor and c-cerbA/thyroid hormone receptor regulate erythroid cell growth and differentiation .", "target_text": { "Retinoid X receptor": "protein", "c-cerbA/thyroid hormone receptor": "protein" } }, { "input_text": "Nuclear receptors are important regulators of erythroid cell development .", "target_text": { "Nuclear receptors": "protein" } }, { "input_text": "Here we investigated the impact of retinoid X receptor ( RXR ) , retinoic acid receptor ( RAR ) , and of the c-erbA/thyroid hormone ( T3 ) receptor ( c-erbA/TR ) on growth and differentiation of erythroid cells using an in vitro culture system of stem cell factor-dependent erythroid progenitors .", "target_text": { "retinoid X receptor": "protein", "RXR": "protein", "retinoic acid receptor": "protein", "RAR": "protein", "c-erbA/thyroid hormone ( T3 ) receptor": "protein", "c-erbA/TR": "protein", "erythroid cells": "cell_type", "stem cell factor-dependent erythroid progenitors": "cell_type" } }, { "input_text": "RXR , RAR , and c-erbA/TR -specific ligands were found to induce erythroid-specific gene expression and to accelerate erythroid differentiation in culture , with T3 being most effective .", "target_text": { "RXR": "protein", "RAR": "protein", "c-erbA/TR": "protein", "erythroid-specific gene": "DNA" } }, { "input_text": "Furthermore , while ligand-activated c-erbA/TR accelerated differentiation , unliganded c-erbA/TR effectively blocked differentiation and supported sustained progenitor growth in culture .", "target_text": { "c-erbA/TR": "protein" } }, { "input_text": "Thus , c-erbA/TR appears to act as a binary switch affecting erythroid cell fate : unliganded c-erbA/TR supports growth while ligand-activated c-erbA/TR induces differentiation .", "target_text": { "c-erbA/TR": "protein", "erythroid cell fate": "cell_type" } }, { "input_text": "Additionally , to determine the impact of RXR for erythroid cell development , dominant interfering mutant RXRs , lacking the transcriptional activator functions AF-1 and AF-2 , or AF-2 only , or the entire DNA-binding domain , were introduced into erythroid progenitor cells via recombinant retrovirus vectors and analyzed for RXR -specific effects .", "target_text": { "RXR": "protein", "mutant RXRs": "protein", "AF-1": "protein", "AF-2": "protein", "entire DNA-binding domain": "DNA", "erythroid progenitor cells": "cell_type" } }, { "input_text": "It was found that expression of wild-type RXR and of the RXR mutants devoid of AF-1 and/or AF-2 supported a transient outgrowth of erythroid cells .", "target_text": { "RXR": "protein", "wild-type RXR": "protein", "RXR mutants": "protein", "AF-1": "protein", "AF-2": "protein", "erythroid cells": "cell_type" } }, { "input_text": "In marked contrast , expression of the dominant interfering deltaDNA-binding domain RXR , containing a deletion of the entire DNA-binding domain , was incompatible with erythroid cell growth in vitro , suggesting a pivotal role of RXR for erythroid cell development .", "target_text": { "dominant interfering deltaDNA-binding domain": "protein", "RXR": "protein", "entire DNA-binding domain": "DNA" } }, { "input_text": "Peripheral T lymphocytes from women with breast cancer exhibit abnormal protein expression of several signaling molecules .", "target_text": { "lymphocytes": "cell_type", "Peripheral T lymphocytes": "cell_type", "several signaling molecules": "protein" } }, { "input_text": "We examined signaling molecules of peripheral blood T lymphocytes obtained from women with breast cancer .", "target_text": { "peripheral blood T lymphocytes": "cell_type" } }, { "input_text": "In 6 of 14 patients , T lymphocytes displayed an impaired ability to translocate NFeB p65 ( Rel-A ) following activation by anti-CD3 and IL-2 .", "target_text": { "T lymphocytes": "cell_type", "NFeB p65": "protein", "Rel-A": "protein", "IL-2": "protein" } }, { "input_text": "This observation was made despite normal cytoplasmic levels of the Rel-A protein .", "target_text": { "Rel-A protein": "protein" } }, { "input_text": "We also detected abnormally low levels of the signaling molecules T-cell receptor ( TCR ) -zeta , ZAP-70 and p56lck in 4 of 14 breast cancer patients , i.e. , defects in T-cell signaling molecules .", "target_text": { "signaling molecules": "protein", "T-cell receptor ( TCR ) -zeta": "protein", "ZAP-70": "protein", "p56lck": "protein", "T-cell signaling molecules": "protein" } }, { "input_text": "T lymphocytes from 6 of the 14 patients also exhibited an increased expression of the dual specificity phosphatase , map kinase phosphatase-1 ( MKP-1 ) .", "target_text": { "T lymphocytes": "cell_type", "specificity phosphatase": "protein", "map kinase phosphatase-1": "protein", "MKP-1": "protein" } }, { "input_text": "MKP-1 inactivates MAP kinase and therefore may interfere with the activation of c-jun and c-fos .", "target_text": { "MKP-1": "protein", "MAP kinase": "protein", "c-jun": "DNA", "c-fos": "DNA" } }, { "input_text": "Abnormalities of I or more signaling molecules were found in 9 of 14 patients ; however , only 3 patients had T cells that exhibited all 5 defects .", "target_text": { "signaling molecules": "protein", "T cells": "cell_type" } }, { "input_text": "Our data have implications for the detection of potentially dysfunctional T cells in patients with cancer .", "target_text": { "T cells": "cell_type" } }, { "input_text": "For example , the analysis of only 1 signaling molecule may allow patients with significant defects in T-cell signaling to go unnoticed .", "target_text": { "signaling molecule": "protein" } }, { "input_text": "Finally , despite impaired Rel-A translocation , T cells were capable of transcribing IL-2 .", "target_text": { "Rel-A": "protein", "T cells": "cell_type", "IL-2": "protein" } }, { "input_text": "Impairments in the translocation of Rel-B and c-Rel further suggest that the NFKB family members Rel-A , Rel-B and c-Rel are not required for the transcription of IL-2 in the peripheral T lymphocytes of patients with breast cancer .", "target_text": { "Rel-B": "protein", "c-Rel": "protein", "NFKB family members": "protein", "Rel-A": "protein", "IL-2": "protein", "T lymphocytes": "cell_type", "peripheral T lymphocytes": "cell_type" } }, { "input_text": "Specific glucocorticoid binding at different levels of human motor activity .", "target_text": {} }, { "input_text": "We studied the number of glucocorticoid receptors and dissociation constant in isolated human lymphocytes as well as blood concentrations of hormones produced by the hypothalamic-hypophyseal-adrenocortical system in three experimental series : at normal ( 17 subjects ) , decreased ( 10 subjects , a 360-d head-down bed rest ) and increased ( 8 subjects , physical exercise on bicycle ergometer ) levels of motor activity .", "target_text": { "glucocorticoid receptors": "protein", "isolated human lymphocytes": "cell_type" } }, { "input_text": "In the first series we found that the number of glucocorticoid receptors and dissociation constant did not depend on the season , on the age of subjects nor on cortisol concentrations in blood .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "In the second series we observed the following : at the end of the first month of bed rest the number of glucocorticoid receptors and receptor affinity significantly increased ; at the beginning of the third month of bed rest specific glucocorticoid binding significantly decreased and circadian rhythms of adrenocorticotropin and cortisol in blood varied markedly ; at the end of the sixth month of bed rest the number of glucocorticoid receptors returned to prebed rest levels and dissociation constant decreased .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "In the third series physical exercises that induced an activation of the hypothalamic-hypophyseal-adrenocortical system ( maximal physical exercises and prolonged submaximal exercises at 70 % of maximal oxygen uptake ) led to a significant increase in the number of glucocorticoid receptors without changes of dissociation constant .", "target_text": { "glucocorticoid receptors": "protein" } }, { "input_text": "These results indicate that both a decrease and an increase of human motor activity resulted in significant changes of specific glucocorticoid binding which were not influenced by changes of circulating hormone concentrations in blood but by some other factors affected by physical activity .", "target_text": {} }, { "input_text": "The small GTP -binding protein Rho potentiates AP-1 transcription in T cells .", "target_text": { "Rho": "protein", "small GTP -binding protein Rho": "protein", "AP-1": "protein", "T cells": "cell_type" } }, { "input_text": "The Rho family of small GTP -binding proteins is involved in the regulation of cytoskeletal structure , gene transcription , specific cell fate development , and transformation .", "target_text": { "Rho": "protein", "small GTP -binding proteins": "protein" } }, { "input_text": "We demonstrate in this report that overexpression of an activated form of Rho enhances AP-1 activity in Jurkat T cells in the presence of phorbol myristate acetate ( PMA ) , but activated Rho ( V14Rho ) has little or no effect on NFAT , Oct-1 , and NF-kappaB enhancer element activities under similar conditions .", "target_text": { "Rho": "protein", "AP-1": "protein", "Jurkat T cells": "cell_line", "V14Rho": "protein", "NFAT": "protein", "Oct-1": "protein", "NF-kappaB": "protein", "NF-kappaB enhancer element": "DNA" } }, { "input_text": "Overexpression of a V14Rho construct incapable of membrane localization ( CAAX deleted ) abolishes PMA -induced AP-1 transcriptional activation .", "target_text": { "V14Rho": "protein", "V14Rho construct": "DNA", "CAAX deleted": "DNA", "AP-1": "protein" } }, { "input_text": "The effect of Rho on AP-1 is independent of the mitogen-activated protein kinase pathway , as a dominant-negative MEK and a MEK inhibitor ( PD98059 ) did not affect Rho -induced AP-1 activity .", "target_text": { "Rho": "protein", "AP-1": "protein", "mitogen-activated protein kinase": "protein", "MEK": "protein", "dominant-negative MEK": "protein" } }, { "input_text": "V14Rho binds strongly to protein kinase Calpha ( PKCalpha ) in vivo ; however , deletion of the CAAX site on V14Rho severely diminished this association .", "target_text": { "V14Rho": "protein", "protein kinase Calpha": "protein", "PKCalpha": "protein", "CAAX site": "DNA" } }, { "input_text": "Evidence for a role for PKCalpha as an effector of Rho was obtained by the observation that coexpression of the N-terminal domain of PKCalpha blocked the effects of activated Rho plus PMA on AP-1 transcriptional activity .", "target_text": { "PKCalpha": "protein", "Rho": "protein", "N-terminal domain": "protein", "AP-1": "protein" } }, { "input_text": "These data suggest that Rho potentiates AP-1 transcription during T-cell activation", "target_text": { "Rho": "protein", "AP-1": "protein" } }, { "input_text": "Changes in PKC isoforms in human alveolar macrophages compared with blood monocytes .", "target_text": { "PKC isoforms": "protein", "human alveolar macrophages": "cell_type", "blood monocytes": "cell_type" } }, { "input_text": "Alveolar macrophages play an important role in host defense and in other types of inflammatory processes in the lung .", "target_text": {} }, { "input_text": "These cells exhibit many alterations in function compared with their precursor cells , blood monocytes .", "target_text": { "precursor cells": "cell_type", "blood monocytes": "cell_type" } }, { "input_text": "To evaluate a potential mechanism for these differences in function , we evaluated expression of protein kinase C ( PKC ) isoforms .", "target_text": { "protein kinase C": "protein", "PKC": "protein", "protein kinase C ( PKC ) isoforms": "protein" } }, { "input_text": "We found an increase in Ca2+ -dependent PKC isoforms in monocytes compared with alveolar macrophages .", "target_text": { "PKC": "protein", "PKC isoforms": "protein", "Ca2+ -dependent PKC isoforms": "protein" } }, { "input_text": "We also found differential expression of the Ca2+ -independent isoforms in alveolar macrophages compared with monocytes .", "target_text": { "Ca2+ -independent isoforms": "protein", "alveolar macrophages": "cell_type", "monocytes": "cell_type" } }, { "input_text": "One consequence of the activation of PKC can be increased expression of mitogen-activated protein ( MAP ) kinase pathways .", "target_text": { "PKC": "protein", "mitogen-activated protein ( MAP ) kinase": "protein" } }, { "input_text": "Therefore , we also evaluated activation of the MAP kinase extracellular signal-regulated kinase ( ERK ) 2 by the phorbol ester phorbol 12-myristate 13-acetate ( PMA ) .", "target_text": { "MAP kinase extracellular signal-regulated kinase": "protein", "ERK": "protein", "MAP kinase extracellular signal-regulated kinase ( ERK ) 2": "protein" } }, { "input_text": "PMA activated ERK2 kinase in both alveolar macrophages and monocytes ; however , monocytes consistently showed a significantly greater activation of ERK2 kinase by PMA compared with alveolar macrophages .", "target_text": { "ERK2 kinase": "protein", "alveolar macrophages": "cell_type", "monocytes": "cell_type" } }, { "input_text": "Another known consequence of the activation of PKC and subsequent activation of ERK kinase is activation of the transcription factor activator protein-1 ( AP-1 ) .", "target_text": { "PKC": "protein", "ERK kinase": "protein", "transcription factor activator protein-1": "protein", "AP-1": "protein" } }, { "input_text": "We evaluated the activation of AP-1 by PMA in both monocytes and macrophages .", "target_text": { "AP-1": "protein", "monocytes": "cell_type" } }, { "input_text": "We found very little detectable activation of AP-1 , as assessed in a gel shift assay , in alveolar macrophages , whereas monocytes showed a substantial activation of AP-1 by PMA .", "target_text": { "AP-1": "protein", "alveolar macrophages": "cell_type", "monocytes": "cell_type" } }, { "input_text": "These studies show that the differential expression of PKC isoforms in alveolar macrophages and blood monocytes is associated with important functional alterations in the cells .", "target_text": { "PKC": "protein", "PKC isoforms": "protein", "alveolar macrophages": "cell_type", "monocytes": "cell_type", "blood monocytes": "cell_type" } }, { "input_text": "Expression of gamma-IFN responsive genes in scavenger receptor over-expressing monocytes is associated with xanthomatosis .", "target_text": { "gamma-IFN responsive genes": "DNA", "monocytes": "cell_type", "over-expressing monocytes": "cell_type" } }, { "input_text": "We have recently described an inherited over-expression of the macrophage scavenger receptor ( SR ) in blood monocytes from members of a kindred , only two of whom displayed extensive xanthomatosis .", "target_text": { "macrophage scavenger receptor": "protein", "SR": "protein", "monocytes": "cell_type", "blood monocytes": "cell_type" } }, { "input_text": "Using mRNA differential display we demonstrated abnormally high expression of the signal transducer and activator of transcription ( STAT1alpha ) in monocytes from the proband II-2 .", "target_text": { "signal transducer and activator of transcription": "protein", "STAT1alpha": "protein", "monocytes": "cell_type", "proband II-2": "cell_line" } }, { "input_text": "Expression of gamma-interferon inducible protein 10 ( IP-10 ) , a STAT1alpha -responsive gene and mediator of inflammatory response , was also abnormally expressed in the monocytes from II-2 .", "target_text": { "gamma-interferon inducible protein 10": "protein", "IP-10": "protein", "STAT1alpha": "protein", "STAT1alpha -responsive gene": "DNA", "monocytes": "cell_type", "II-2": "cell_line" } }, { "input_text": "Over-expression of both genes was restricted to monocytes from II-2 and was not observed in monocytes from the clinically unaffected family members , unlike that of SR .", "target_text": { "monocytes": "cell_type", "II-2": "cell_line", "SR": "protein" } }, { "input_text": "Gel retardation assays with THP-1 cell extracts identified gamma-IFN inducible DNA binding activity to three potential STATI DNA binding elements in the human IP-10 promoter region from nucleotides - 245 to - 188 .", "target_text": { "THP-1 cell": "cell_line", "gamma-IFN": "protein", "STATI": "protein", "STATI DNA binding elements": "DNA", "IP-10": "protein", "human IP-10 promoter region": "DNA", "nucleotides - 245 to - 188": "DNA" } }, { "input_text": "Taken together these results suggest that gamma-interferon mediated cell activation is responsible for STAT1alpha -induced transcription of the IP-10 gene in THP-1 macrophages as well as in monocytes from II-2 .", "target_text": { "STAT1alpha": "protein", "IP-10": "protein", "THP-1 macrophages": "cell_line", "monocytes": "cell_type", "II-2": "cell_line" } }, { "input_text": "Analysis of monocytes from familial hypercholesterolemic ( FH ) subjects , who frequently develop xanthomatosis , revealed a significant number of subjects with elevated STAT1alpha and IP-10 expression .", "target_text": { "monocytes": "cell_type" } }, { "input_text": "Our data suggest that the inflammatory effects of gamma-IFN signaling could play a role in foam cell formation and xanthomatosis .", "target_text": { "gamma-IFN": "protein" } }, { "input_text": "Redox signals and NF-kappaB activation in T cells .", "target_text": { "NF-kappaB": "protein", "T cells": "cell_type" } }, { "input_text": "Accumulating data from a number of laboratories have recently indicated that the response of transcription factor NF-kappaB to alterations in the redox homeostasis of cells may play an important role in modulating immune function .", "target_text": { "transcription factor": "protein", "NF-kappaB": "protein" } }, { "input_text": "The activation of NF-kappaB has been recognized to regulate a number of genes necessary for normal T cell responses including IL-2 , IL-6 , IL-8 , and several T cell surface receptors .", "target_text": { "NF-kappaB": "protein", "IL-2": "protein", "IL-6": "protein", "IL-8": "protein", "T cell surface receptors": "protein" } }, { "input_text": "Diminished NF-kappaB activity has been shown to occur in T cells with aging , suggesting that impaired activation of NF-kappaB might occur during cellular senescence .", "target_text": { "NF-kappaB": "protein", "T cells": "cell_type" } }, { "input_text": "In addition , aberrancies in NF-kappaB activity have been implicated in the immunopathogenesis of diseases involving immune or inflammatory processes such as atherosclerosis and HIV-1 infection .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "The role of H2O2 and other reactive oxygen species ( ROS ) as an integratory secondary messenger for divergent T cell signals has been complicated by the fact that various T cell lines and peripheral blood T cells differ markedly in the levels of NF-kappaB activation induced by oxidant stress .", "target_text": { "T cell lines": "cell_line", "T cells": "cell_type", "peripheral blood T cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "Additionally , proposed pathways of NF-kappaB activation have been based on indirect evidence provided by experiments which used antioxidants to inhibit active NF-kappaB formation .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Further , complete activation of T cells requires at least two signals , one that stimulates an increase in intracellular calcium and one that stimulates enzymatic processes including kinases .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Similarly , substantial evidence indicates that full activation of NF-kappaB requires dual signals .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "The ability of H2O2 or other ROS to induce T cell signals and functional responses by these two mechanisms is reviewed and the specific response of NF-kappaB to redox changes in T cells is examined .", "target_text": { "NF-kappaB": "protein", "T cells": "cell_type" } }, { "input_text": "Data are also presented to suggest that the redox regulation in NF-kappaB activation may be relevant to immune-related diseases and to aging .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "Uncoupling of nonreceptor tyrosine kinases from PLC-gamma1 in an SLP-76-deficient T cell .", "target_text": { "tyrosine kinases": "protein", "PLC-gamma1": "protein" } }, { "input_text": "Activation of nonreceptor protein tyrosine kinases ( PTKs ) is essential for T cell receptor ( TCR ) responsiveness ; however , the function of individual PTK substrates is often uncertain .", "target_text": { "tyrosine kinases": "protein", "nonreceptor protein tyrosine kinases": "protein", "PTKs": "protein", "T cell receptor": "protein", "TCR": "protein", "PTK substrates": "protein" } }, { "input_text": "A mutant T cell line was isolated that lacked expression of SLP-76 ( SH2 domain-containing leukocyte protein of 76 kilodaltons ) , a hematopoietically expressed adaptor protein and PTK substrate .", "target_text": { "mutant T cell line": "cell_line", "SLP-76": "protein", "SH2 domain-containing leukocyte protein": "protein", "hematopoietically expressed adaptor protein": "protein", "PTK substrate": "protein" } }, { "input_text": "SLP-76 was not required for TCR -induced tyrosine phosphorylation of most proteins , but was required for optimal tyrosine phosphorylation and activation of phospholipase C-gamma1 ( PLC-gamma1 ) , as well as Ras pathway activation .", "target_text": { "SLP-76": "protein", "TCR": "protein", "phospholipase C-gamma1": "protein", "PLC-gamma1": "protein", "Ras": "protein" } }, { "input_text": "TCR -inducible gene expression was dependent on SLP-76 .", "target_text": { "TCR": "protein", "SLP-76": "protein" } }, { "input_text": "Thus , coupling of TCR-regulated PTKs to downstream signaling pathways requires SLP-76 .", "target_text": { "PTKs": "protein", "TCR-regulated PTKs": "protein", "SLP-76": "protein" } }, { "input_text": "A novel function of Stat1 and Stat3 proteins in erythropoietin -induced erythroid differentiation of a human leukemia cell line .", "target_text": { "Stat1": "protein", "Stat3": "protein", "erythropoietin": "protein", "human leukemia cell line": "cell_line" } }, { "input_text": "We recently determined that erythropoietin ( EPO ) activates 3 members of the signal transducer and activator of transcription ( STAT ) family , Stat1alpha , Stat3 , and Stat5 , in the human EPO -dependent cell lines , UT-7 and UT-7/ EPO ( Kirito et al , J Biol Chem 272 : 16507 , 1997 ) .", "target_text": { "erythropoietin": "protein", "EPO": "protein", "Stat1alpha": "protein", "Stat3": "protein", "Stat5": "protein", "human EPO -dependent cell lines": "cell_line", "UT-7": "cell_line", "UT-7/ EPO": "cell_line" } }, { "input_text": "In addition , we have shown that Stat1alpha , but not Stat3 , is involved in EPO -induced cellular proliferation .", "target_text": { "Stat1alpha": "protein", "Stat3": "protein", "EPO": "protein" } }, { "input_text": "In this study , we examined the roles of Stat1alpha and Stat3 in EPO -induced erythroid differentiation .", "target_text": { "Stat1alpha": "protein", "Stat3": "protein", "EPO": "protein" } }, { "input_text": "UT-7/GM was used as a model system , because this cell line can differentiate into erythroid-lineage cells with EPO treatment ( Komatsu et al , Blood 89 : 4021 , 1997 ) .", "target_text": { "UT-7/GM": "cell_line", "erythroid-lineage cells": "cell_type", "EPO": "protein" } }, { "input_text": "We found that EPO did not activate Stat1alpha or Stat3 in UT-7/GM cells .", "target_text": { "EPO": "protein", "Stat1alpha": "protein", "Stat3": "protein", "UT-7/GM cells": "cell_line" } }, { "input_text": "Transfection experiments showed that both Stat1alpha and Stat3 inhibited the induction by EPO of gamma-globin and erythroid-specific 5-aminolevulinate synthetase transcripts , resulting in a reduction of the percentage of hemoglobin-positive cells .", "target_text": { "Stat1alpha": "protein", "Stat3": "protein", "EPO": "protein", "hemoglobin-positive cells": "cell_type" } }, { "input_text": "Dominant negative forms of Stat1alpha or Stat3 promoted the EPO -induced erythroid differentiation of UT-7/GM cells , even in the presence of granulocyte-macrophage colony-stimulating factor , although this cytokine never induced erythroid differentiation of the parent UT-7/GM cells with or without EPO .", "target_text": { "Stat1alpha": "protein", "Stat3": "protein", "EPO": "protein", "UT-7/GM cells": "cell_line", "granulocyte-macrophage colony-stimulating factor": "protein", "parent UT-7/GM cells": "cell_line" } }, { "input_text": "A cell cycle analysis showed that the constitutive activation of Stat1alpha , but not Stat3 , shortened the period of G0/G1 prolongation caused by EPO stimulation .", "target_text": { "Stat1alpha": "protein", "Stat3": "protein", "EPO": "protein" } }, { "input_text": "Taken together , our data suggest that Stat1alpha and Stat3 act as negative regulators in EPO -induced erythroid differentiation .", "target_text": { "Stat1alpha": "protein", "Stat3": "protein", "EPO": "protein" } }, { "input_text": "Specifically , Stat1alpha may activate a cell cycle-associated gene ( s ) , leading to the entry of cells into the cell cycle .", "target_text": { "Stat1alpha": "protein", "cell cycle-associated gene": "DNA" } }, { "input_text": "Ro 09-2210 exhibits potent anti-proliferative effects on activated T cells by selectively blocking MKK activity .", "target_text": { "T cells": "cell_type", "MKK": "protein" } }, { "input_text": "By using high throughput screening of microbial broths , we have identified a compound , designated Ro 09-2210 , which is able to block anti-CD3 induced peripheral blood T cell activation with an IC50 = 40 nM .", "target_text": { "anti-CD3": "protein" } }, { "input_text": "Ro 09-2210 was also able to block antigen-induced IL-2 secretion with an IC50 = 30 nM , but was considerably less potent at blocking Ca2+ flux stimulated by anti-CD3 treatment .", "target_text": { "IL-2": "protein", "anti-CD3": "protein" } }, { "input_text": "To determine the mechanism of action of Ro 09-2210 , we set up a transient expression system in Jurkat T cells using a variety of reporter gene constructs and showed effective inhibition of phorbol ester / ionomycin -induced NF-AT activation and anti-CD3 induced NF-AT with IC50 = 7.7 and 10 nM , respectively .", "target_text": { "Jurkat T cells": "cell_line", "NF-AT": "protein" } }, { "input_text": "Ro 09-2210 was also able to inhibit phorbol ester / ionomycin -induced activation of AP1 with IC50 = < 10 nM .", "target_text": { "AP1": "protein" } }, { "input_text": "We further showed that Ro 09-2210 was unable to inhibit c-jun induced expression of AP1 -dependent reporter constructs ( IC50 > 500 nM ) , but was able to potently inhibit ras-induced AP1 activation ( IC50 = 20 nM ) .", "target_text": { "c-jun": "DNA", "AP1": "protein", "AP1 -dependent reporter constructs": "DNA" } }, { "input_text": "This suggested that Ro 09-2210 was inhibiting an activator of AP-1 which was upstream of c-jun and downstream of ras signaling .", "target_text": { "AP-1": "protein", "c-jun": "DNA", "ras": "protein" } }, { "input_text": "To investigate further , we then purified a number of different kinases , including PKC , PhK , ZAP-70 , ERK , and MEK 1 ( a MKK ) , and showed that Ro 09-2210 was a selective inhibitor of MEK1 in vitro ( IC50 = 59 nM ) .", "target_text": { "PKC": "protein", "PhK": "protein", "ZAP-70": "protein", "ERK": "protein", "MEK 1": "protein", "MKK": "protein", "MEK1": "protein" } }, { "input_text": "Coactivation by OCA-B : definition of critical regions and synergism with general cofactors .", "target_text": { "OCA-B": "protein" } }, { "input_text": "Molecular dissection of the B-cell-specific transcription coactivator OCA-B has revealed distinct regions important , respectively , for recruitment to immunoglobulin promoters through interaction with octamer-bound Oct-1 and for subsequent coactivator function .", "target_text": { "OCA-B": "protein", "immunoglobulin promoters": "DNA", "Oct-1": "protein", "octamer-bound Oct-1": "protein" } }, { "input_text": "Further analysis of general coactivator requirements showed that selective removal of PC4 from the essential USA fraction severely impairs Oct-1 and OCA-B function in a cell-free system reconstituted with partially purified factors .", "target_text": { "PC4": "protein" } }, { "input_text": "Full activity can be restored by the combined action of recombinant PC4 and the PC4 -depleted USA fraction , thus suggesting a joint requirement for PC4 and another , USA-derived component ( s ) for optimal function of Oct-1 /OCA-B in the reconstituted system .", "target_text": { "PC4": "protein", "Oct-1": "protein", "/OCA-B": "protein" } }, { "input_text": "Indeed , USA-derived PC2 was found to act synergistically with PC4 in reproducing the function of intact USA in the assay system .", "target_text": { "USA-derived PC2": "protein", "PC4": "protein" } }, { "input_text": "Consistent with the requirement for PC4 in the reconstituted system , OCA-B was found to interact directly with PC4 .", "target_text": { "PC4": "protein", "OCA-B": "protein" } }, { "input_text": "Surprisingly , however , removal of PC4 from the unfractionated nuclear extract has no detrimental effect on OCA-B / Oct-1 -dependent transcription .", "target_text": { "PC4": "protein", "OCA-B": "protein", "Oct-1": "protein" } }, { "input_text": "These results lead to a general model for the synergistic function of activation domains in Oct-1 and OCA-B ( mediated by the combined action of the multiple USA components ) and , further , suggest a functional redundancy in general coactivators .", "target_text": { "Oct-1": "protein", "OCA-B": "protein", "general coactivators": "protein" } }, { "input_text": "Activation of Stat-3 is involved in the induction of apoptosis after ligation of major histocompatibility complex class I molecules on human Jurkat T cells .", "target_text": { "Stat-3": "protein", "major histocompatibility complex class I molecules": "protein", "Jurkat T cells": "cell_line", "human Jurkat T cells": "cell_line" } }, { "input_text": "Activation of Janus tyrosine kinases ( Jak ) and Signal transducers and activators of transcription ( Stat ) after ligation of major histocompatibility complex class I ( MHC-I ) was explored in Jurkat T cells .", "target_text": { "tyrosine kinases": "protein", "Janus tyrosine kinases": "protein", "Jak": "protein", "Signal transducers and activators of transcription": "protein", "Stat": "protein", "major histocompatibility complex class I": "protein", "MHC-I": "protein", "Jurkat T cells": "cell_line" } }, { "input_text": "Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2 , but not Jak1 , Jak2 , and Jak3 .", "target_text": { "MHC-I": "protein", "Tyk2": "protein", "Jak1": "protein", "Jak2": "protein", "Jak3": "protein" } }, { "input_text": "In addition , the transcription factor Stat-3 was tyrosine phosphorylated in the cytoplasm and subsequently translocated to the cell nucleus .", "target_text": { "transcription factor": "protein", "Stat-3": "protein" } }, { "input_text": "Data obtained by electrophoretic mobility shift assay suggested that the activated Stat-3 protein associates with the human serum-inducible element ( hSIE ) DNA-probe derived from the interferon-gamma activated site ( GAS ) in the c-fos promoter , a common DNA sequence for Stat protein binding .", "target_text": { "activated Stat-3 protein": "protein", "hSIE": "DNA", "human serum-inducible element ( hSIE ) DNA-probe": "DNA", "interferon-gamma activated site": "DNA", "GAS": "DNA", "c-fos promoter": "DNA", "Stat protein": "protein" } }, { "input_text": "An association between hSIE and Stat-3 after MHC-I ligation was directly demonstrated by precipitating Stat-3 from nuclear extracts with biotinylated hSIE probe and avidin -coupled agarose .", "target_text": { "hSIE": "DNA", "Stat-3": "protein", "MHC-I": "protein", "hSIE probe": "DNA", "avidin": "protein" } }, { "input_text": "To investigate the function of the activated Stat-3 , Jurkat T cells were transiently transfected with a Stat-3 isoform lacking the transactivating domain .", "target_text": { "Stat-3": "protein", "Jurkat T cells": "cell_line", "Stat-3 isoform": "protein", "transactivating domain": "protein" } }, { "input_text": "This dominant-negative acting Stat-3 isoform significantly inhibited apoptosis induced by ligation of MHC-I .", "target_text": { "Stat-3": "protein", "dominant-negative acting Stat-3 isoform": "protein", "MHC-I": "protein" } }, { "input_text": "In conclusion , our data suggest the involvement of the Jak/Stat signal pathway in MHC-I -induced signal transduction in T cells .", "target_text": { "Jak/Stat": "protein", "MHC-I": "protein", "T cells": "cell_type" } }, { "input_text": "IL-2 -induced growth of CD8+ T cell prolymphocytic leukemia cells mediated by NF-kappaB induction and IL-2 receptor alpha expression .", "target_text": { "IL-2": "protein", "CD8+ T cell prolymphocytic leukemia cells": "cell_type", "NF-kappaB": "protein", "IL-2 receptor alpha": "protein" } }, { "input_text": "The binding of interleukin-2 ( IL-2 ) to its receptor on normal T cells induces nuclear expression of nuclear factor kappaB ( NF-kappaB ) , activation of the IL-2 receptor ( IL-2R ) alpha chain gene , and cell proliferation .", "target_text": { "interleukin-2": "protein", "IL-2": "protein", "T cells": "cell_type", "nuclear factor kappaB": "protein", "NF-kappaB": "protein", "IL-2 receptor": "protein", "IL-2 receptor ( IL-2R ) alpha chain": "protein", "IL-2 receptor ( IL-2R ) alpha chain gene": "DNA" } }, { "input_text": "In the present study , the role of IL-2R signaling in the growth of CD8+ T cell prolymphocytic leukemia ( T-PLL ) cells has been investigated .", "target_text": { "IL-2R": "protein", "CD8+ T cell prolymphocytic leukemia ( T-PLL ) cells": "cell_line" } }, { "input_text": "Flow cytometry revealed that primary leukemia cells from a patient with CD8+ T-PLL expressed IL-2R alpha and beta chains , and the cells showed a proliferative response and an increase in IL-2Ralpha expression on culture with exogeneous IL-2 .", "target_text": { "primary leukemia cells": "cell_type", "IL-2Ralpha": "protein", "IL-2": "protein" } }, { "input_text": "Northern blot analysis failed to detect IL-2 mRNA , suggesting that IL-2 may act in a paracrine manner in vivo .", "target_text": { "IL-2 mRNA": "RNA", "IL-2": "protein" } }, { "input_text": "Electrophoretic mobility-shift assays revealed that recombinant IL-2 increased NF-kappaB binding activity in nuclear extracts of the leukemia cells , and Northern blot analysis showed that IL-2 increased the abundance of mRNAs encoding the NF-kappaB components c-Rel and KBF1 in these cells .", "target_text": { "IL-2": "protein", "NF-kappaB": "protein", "leukemia cells": "cell_type", "c-Rel": "protein", "KBF1": "protein" } }, { "input_text": "IL-2 binding analysis demonstrated that IL-2 markedly increased the number of low affinity IL-2Rs on the leukemia cells , without an effect on the number of high-affinity IL-2Rs .", "target_text": { "IL-2": "protein", "IL-2Rs": "protein", "leukemia cells": "cell_type", "high-affinity IL-2Rs": "protein" } }, { "input_text": "These results show that IL-2 is capable of inducing the nuclear expression of NF-kappaB in primary CD8+ T-PLL cells , and that this effect is mediated , at least in part , at a pretranslational level", "target_text": { "IL-2": "protein", "NF-kappaB": "protein", "primary CD8+ T-PLL cells": "cell_line" } }, { "input_text": "Dimethyldithiocarbamate inhibits in vitro activation of primary human CD4+ T lymphocytes .", "target_text": { "primary human CD4+ T lymphocytes": "cell_type" } }, { "input_text": "Dithiocarbamates ( DTC ) , a diverse group of industrial and therapeutic chemicals , have been reported to inhibit , enhance or have no effect on the immune system .", "target_text": {} }, { "input_text": "These apparent inconsistencies reflect the complexity of the DTCs biological activities and are probably due in part to differences in dose , route of exposure , animal species used and/or specific compound tested .", "target_text": {} }, { "input_text": "The studies described herein were undertaken to investigate the immunotoxicity of one member of this family , dimethyldithiocarbamate ( DMDTC ) .", "target_text": {} }, { "input_text": "We demonstrate that 0.1-0.5 microM DMDTC inhibits TNF-alpha -induced activation of NF-kappaB in primary human CD4+ T cells .", "target_text": { "TNF-alpha": "protein", "NF-kappaB": "protein", "primary human CD4+ T cells": "cell_type" } }, { "input_text": "This inhibition is not accompanied by a loss in viability , and DMDTC -treated T cells retain other active signaling pathways throughout the exposure duration .", "target_text": { "DMDTC -treated T cells": "cell_type" } }, { "input_text": "The inhibition of NF-kappaB is apparently permanent as DMDTC -treated T cells did not regain normal TNF-alpha activation , even after 72 h in culture .", "target_text": { "NF-kappaB": "protein", "DMDTC -treated T cells": "cell_type", "TNF-alpha": "protein" } }, { "input_text": "DMDTC does not appear to alter NF-kappaB directly as pre-incubation of nuclear extracts with DMDTC does not diminish binding activity of this protein .", "target_text": { "NF-kappaB": "protein" } }, { "input_text": "We further demonstrate that 0.1-0.5 microM DMDTC inhibits intracellular IL-2 production and decreases surface expression of CD25 ( the alpha subunit of the IL-2 receptor ) in T cells stimulated with phorbol ester .", "target_text": { "IL-2": "protein", "CD25": "protein", "alpha subunit": "protein", "IL-2 receptor": "protein", "T cells": "cell_type" } }, { "input_text": "These data demonstrate that DMDTC is a potent immunosuppressive compound in vitro .", "target_text": {} }, { "input_text": "Human 15-lipoxygenase gene promoter : analysis and identification of DNA binding sites for IL-13-induced regulatory factors in monocytes .", "target_text": { "Human 15-lipoxygenase gene promoter": "DNA", "DNA binding sites": "DNA", "IL-13-induced regulatory factors": "protein", "monocytes": "cell_type" } }, { "input_text": "In order to study the transcriptional control of 15-LO expression , we have cloned and sequenced the human 15-LO promoter region .", "target_text": { "15-LO": "protein", "human 15-LO promoter region": "DNA" } }, { "input_text": "The 15-LO promoter is associated with a CpG island at the 5'-end of the gene , and sequence analysis reveals putative Sp1 and Ap2 binding site/s and absence of TATA or CAAT motifs .", "target_text": { "15-LO": "protein", "CpG island": "DNA", "5'-end": "DNA" } }, { "input_text": "Transcription is initiated at one major site .", "target_text": {} }, { "input_text": "Using deletion constructs , we have defined an active promoter region of 1056 bp .", "target_text": { "deletion constructs": "DNA", "active promoter region": "DNA" } }, { "input_text": "Gel-shift assays revealed that transcriptional factor ( s ) induced only in response to IL-13 treatment of human peripheral blood monocytes bind to the 15-LO promoter DNA .", "target_text": { "transcriptional factor": "protein", "IL-13": "protein", "human peripheral blood monocytes": "cell_type", "15-LO": "protein", "15-LO promoter DNA": "DNA" } }, { "input_text": "Two regions , DP1 ( -140 to -92 bp ) and DP2 ( -353 to -304 bp ) of the promoter were essential for transcription in HeLa cells and human peripheral monocytes .", "target_text": { "DP1": "DNA", "-140 to -92 bp": "DNA", "DP2": "DNA", "-353 to -304 bp": "DNA", "HeLa cells": "cell_line", "human peripheral monocytes": "cell_type" } }, { "input_text": "Hela nuclear extracts contained a specific nuclear factor ( s ) binding to 15-LO promoter DNA which are distinct from those derived from IL-13 -treated human peripheral monocyte nuclear extracts .", "target_text": { "specific nuclear factor ( s )": "protein", "15-LO": "protein", "15-LO promoter DNA": "DNA", "IL-13": "protein", "IL-13 -treated human peripheral monocyte": "cell_line" } }, { "input_text": "In addition , fluorescent in situ hybridization ( FISH ) results refined the previous localization of 15-LO to human chromosome 17p13.3 .", "target_text": { "15-LO": "protein", "human chromosome 17p13.3": "DNA" } }, { "input_text": "Ex vivo activation of tumor-draining lymph node T cells reverses defects in signal transduction molecules .", "target_text": { "T cells": "cell_type", "tumor-draining lymph node T cells": "cell_type", "signal transduction molecules": "protein" } }, { "input_text": "The adoptive transfer of tumor-draining lymph node ( LN ) T cells activated ex vivo with anti-CD3 and interleukin 2 ( IL-2 ) mediates the regression of the poorly immunogenic murine melanoma D5 .", "target_text": { "T cells": "cell_type", "anti-CD3": "protein", "interleukin 2": "protein", "IL-2": "protein" } }, { "input_text": "The efficacy of the activated LN cells is augmented when the sensitizing tumor is a genetically modified variant ( designated D5G6 ) that secretes granulocyte/macrophage-colony-stimulating factor .", "target_text": { "LN cells": "cell_type", "activated LN cells": "cell_type", "genetically modified variant": "cell_line", "D5G6": "cell_line", "granulocyte/macrophage-colony-stimulating factor": "protein" } }, { "input_text": "In contrast to anti-CD3/ IL-2 - activated LN cells , adoptive transfer of freshly isolated tumor-draining LN T cells has no therapeutic activity .", "target_text": { "IL-2": "protein", "LN cells": "cell_type", "activated LN cells": "cell_type", "anti-CD3/ IL-2 - activated LN cells": "cell_line", "tumor-draining LN T cells": "cell_type" } }, { "input_text": "To determine whether the acquisition of antitumor function during ex vivo activation is associated with modifications in signal transduction capacity , the protein tyrosine kinases p56lck and p59fyn and proteins of the NF-kappaB family were analyzed in tumor-draining LN T cells .", "target_text": { "tyrosine kinases": "protein", "p56lck": "protein", "p59fyn": "protein", "NF-kappaB family": "protein", "tumor-draining LN T cells": "cell_type" } }, { "input_text": "The levels of p56lck and p59fyn were lower in tumor-draining than in normal LN T cells and production of tyrosine -phosphorylated substrates was markedly depressed following anti-CD3 stimulation .", "target_text": { "p56lck": "protein", "p59fyn": "protein", "normal LN T cells": "cell_type", "tyrosine -phosphorylated substrates": "protein", "anti-CD3": "protein" } }, { "input_text": "After 5-day anti-CD3 /IL-2 activation , levels of p56lck and p59fyn and protein tyrosine kinase activity increased .", "target_text": { "anti-CD3": "protein", "/IL-2": "protein", "p56lck": "protein", "p59fyn": "protein" } }, { "input_text": "Interestingly , the levels of p56lck , p59fyn , and tyrosine kinase activity were higher in activated T cells derived from LN that drained D5G6 than they were in those from D5 tumors .", "target_text": { "p56lck": "protein", "p59fyn": "protein", "activated T cells": "cell_type" } }, { "input_text": "In contrast , the cytoplasmic levels of c-Rel and Rel A were normal in freshly isolated tumor-draining LN , as was nuclear kappaB DNA-binding activity induced by anti-CD3 mAb or phorbol myristate acetate .", "target_text": { "c-Rel": "protein", "Rel A": "protein", "kappaB": "protein", "anti-CD3": "protein", "anti-CD3 mAb": "protein" } }, { "input_text": "Stimulation of activated LN cells with D5 tumor cells induced the nuclear translocation of NF-kappaB .", "target_text": { "LN cells": "cell_type", "activated LN cells": "cell_type", "D5 tumor cells": "cell_type", "NF-kappaB": "protein" } }, { "input_text": "These findings indicate that the recovery of proteins mediating signal transduction through the T cell receptor/CD3 complex in LN T cells activated ex vivo was associated with the acquisition of antitumor function .", "target_text": { "T cell receptor/CD3 complex": "protein", "LN T cells": "cell_type" } }, { "input_text": "Suppression of human anti-porcine T-cell immune responses by major histocompatibility complex class II transactivator constructs lacking the amino terminal domain .", "target_text": { "major histocompatibility complex class II transactivator constructs": "DNA" } }, { "input_text": "BACKGROUND : The class II transactivator ( CIITA ) is a bi- or multifunctional domain protein that acts as a transcriptional activator and plays a critical role in the expression of MHC class II genes .", "target_text": { "class II transactivator": "protein", "CIITA": "protein", "bi- or multifunctional domain protein": "protein", "transcriptional activator": "protein", "MHC class II genes": "DNA" } }, { "input_text": "We have previously demonstrated that a mutated form of the human CIITA gene , coding for a protein lacking the amino terminal 151 amino acids , acts as a potent dominant-negative suppressor of HLA class II expression .", "target_text": { "CIITA": "protein", "human CIITA gene": "DNA", "amino terminal 151 amino acids": "protein", "HLA class II": "protein" } }, { "input_text": "Porcine MHC class II antigens are potent stimulators of direct T-cell recognition by human CD4+ T cells and are , therefore , likely to play an important role in the rejection responses to transgenic pig donors in clinical xenotransplantation .", "target_text": { "Porcine MHC class II antigens": "protein", "human CD4+ T cells": "cell_type" } }, { "input_text": "We were , therefore , interested in examining mutated CIITA constructs for their effect on porcine MHC class II expression .", "target_text": { "CIITA": "protein", "CIITA constructs": "DNA", "MHC class II": "protein" } }, { "input_text": "METHODS : Stable transfectants of the porcine vascular endothelial cell line PIEC with mutated CIITA constructs were tested for SLA-DR and SLA-DQ induction by recombinant porcine interferon-gamma .", "target_text": { "porcine vascular endothelial cell line": "cell_line", "PIEC": "cell_line", "CIITA": "protein", "CIITA constructs": "DNA", "SLA-DR": "protein", "SLA-DQ": "protein", "recombinant porcine interferon-gamma": "protein" } }, { "input_text": "Transient transfectants of the porcine B-cell line L23 with the mutated CIITA constructs were tested for the suppression of constitutive SLA-DR and SLA-DQ expression .", "target_text": { "porcine B-cell line L23": "cell_line", "CIITA": "protein", "CIITA constructs": "DNA" } }, { "input_text": "T-cell proliferation studies were performed using highly purified human CD4+ T cells .", "target_text": { "human CD4+ T cells": "cell_type" } }, { "input_text": "RESULTS : In preliminary studies , we demonstrated that transfection of the PIEC line with full-length human CIITA constructs resulted in strong expression of SLA-DR and SLA-DQ antigens , thus establishing the cross-species effectiveness of human CIITA in the pig .", "target_text": { "PIEC line": "cell_line", "CIITA": "protein", "CIITA constructs": "DNA", "SLA-DR": "protein", "SLA-DQ": "protein", "human CIITA": "protein" } }, { "input_text": "The mutated human CIITA constructs were , therefore , tested in the pig .", "target_text": { "CIITA": "protein", "mutated human CIITA constructs": "DNA" } }, { "input_text": "PIEC clones stably transfected with one of these constructs showed up to 99 % suppression of SLA-DR and SLA-DQ antigen induction and marked suppression of SLA-DRA mRNA induction .", "target_text": { "PIEC clones": "cell_line", "SLA-DR": "protein", "SLA-DQ": "protein", "SLA-DRA": "protein", "SLA-DRA mRNA": "RNA" } }, { "input_text": "Moreover , transient transfection of the porcine B-cell line L23 showed up to 90 % suppression of constitutive SLA-DR and SLA-DQ antigen expression in 5-8 days .", "target_text": { "porcine B-cell line L23": "cell_line" } }, { "input_text": "In functional studies , interferon-gamma -stimulated PIEC clones transfected with this mutated CIITA construct failed to stimulate purified human CD4+ T lymphocytes .", "target_text": { "interferon-gamma": "protein", "PIEC clones": "cell_line", "interferon-gamma -stimulated PIEC clones": "cell_line", "CIITA": "protein", "mutated CIITA": "protein", "human CD4+ T lymphocytes": "cell_type" } }, { "input_text": "CONCLUSION : Mutated human CIITA constructs are potent suppressors of porcine MHC class II expression .", "target_text": { "CIITA": "protein", "Mutated human CIITA constructs": "DNA", "MHC class II": "protein" } }, { "input_text": "Macrophages in human atheroma contain PPARgamma : differentiation-dependent peroxisomal proliferator-activated receptor gamma ( PPARgamma ) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro .", "target_text": { "Macrophages": "cell_type", "PPARgamma": "protein", "differentiation-dependent peroxisomal proliferator-activated receptor gamma": "protein", "MMP-9": "protein" } }, { "input_text": "Mononuclear phagocytes play an important role in atherosclerosis and its sequela plaque rupture in part by their secretion of matrix metalloproteinases ( MMPs ) , including MMP-9 .", "target_text": { "Mononuclear phagocytes": "cell_type", "matrix metalloproteinases": "protein", "MMPs": "protein", "MMP-9": "protein" } }, { "input_text": "Peroxisomal proliferator-activated receptor gamma ( PPARgamma ) , a transcription factor in the nuclear receptor superfamily , regulates gene expression in response to various activators , including 15-deoxy-delta12,14-prostaglandin J2 and the antidiabetic agent troglitazone .", "target_text": { "Peroxisomal proliferator-activated receptor gamma": "protein", "PPARgamma": "protein", "transcription factor": "protein" } }, { "input_text": "The role of PPARgamma in human atherosclerosis is unexplored .", "target_text": { "PPARgamma": "protein" } }, { "input_text": "We report here that monocytes/macrophages in human atherosclerotic lesions ( n = 12 ) express immunostainable PPARgamma .", "target_text": { "monocytes/macrophages": "cell_type", "PPARgamma": "protein", "immunostainable PPARgamma": "protein" } }, { "input_text": "Normal artery specimens ( n = 6 ) reveal minimal immunoreactive PPARgamma .", "target_text": { "PPARgamma": "protein", "minimal immunoreactive PPARgamma": "protein" } }, { "input_text": "Human monocytes and monocyte-derived macrophages cultured for 6 days in 5 % human serum expressed PPARgamma mRNA and protein by reverse transcription-polymerase chain reaction and Western blotting , respectively .", "target_text": { "Human monocytes": "cell_type", "monocyte-derived macrophages": "cell_type", "PPARgamma": "protein", "PPARgamma mRNA": "RNA" } }, { "input_text": "In addition , PPARgamma mRNA expression in U937 cells increased during phorbol 12-myristate 13 acetate -induced differentiation .", "target_text": { "PPARgamma": "protein", "PPARgamma mRNA": "RNA", "U937 cells": "cell_line" } }, { "input_text": "Stimulation of PPARgamma with troglitazone or 15-deoxy-delta12,14-prostaglandin J2 in human monocyte-derived macrophages inhibited MMP-9 gelatinolytic activity in a concentration-dependent fashion as revealed by zymography .", "target_text": { "PPARgamma": "protein", "monocyte-derived macrophages": "cell_type", "MMP-9": "protein" } }, { "input_text": "This inhibition correlates with decreased MMP-9 secretion as determined by Western blotting .", "target_text": { "MMP-9": "protein" } }, { "input_text": "Thus , PPARgamma is present in macrophages in human atherosclerotic lesions and may regulate expression and activity of MMP-9 , an enzyme implicated in plaque rupture .", "target_text": { "PPARgamma": "protein", "macrophages": "cell_type", "MMP-9": "protein" } }, { "input_text": "PPARgamma is likely to be an important regulator of monocyte/macrophage function with relevance for human atherosclerotic disease .", "target_text": { "PPARgamma": "protein" } }, { "input_text": "Erythropoietin induces tyrosine phosphorylation of Jak2 , STAT5A , and STAT5B in primary cultured human erythroid precursors .", "target_text": { "Erythropoietin": "protein", "Jak2": "protein", "STAT5A": "protein", "STAT5B": "protein", "primary cultured human erythroid precursors": "cell_type" } }, { "input_text": "We examined signaling by erythropoietin in highly purified human colony forming unit-erythroid cells , generated in vitro from CD34(+) cells .", "target_text": { "erythropoietin": "protein", "highly purified human colony forming unit-erythroid cells": "cell_type", "CD34(+) cells": "cell_type" } }, { "input_text": "We found that erythropoietin induces tyrosine phosphorylation of Jak2 , STAT5A , and STAT5B .", "target_text": { "erythropoietin": "protein", "Jak2": "protein", "STAT5A": "protein", "STAT5B": "protein" } }, { "input_text": "Tyrosine phosphorylation of Jak2 reaches a peak around 10 minutes after stimulation and is maximum at 5 U/mL of erythropoietin .", "target_text": { "Jak2": "protein", "erythropoietin": "protein" } }, { "input_text": "Tyrosine phosphorylation of STAT5 is accompanied by the translocation of activated STAT5 to the nucleus as shown by electrophoretic mobility shift assay ( EMSA ) using 32Pi-labeled STAT5 binding site in the beta-casein promoter .", "target_text": { "STAT5": "protein", "STAT5 binding site": "DNA", "beta-casein promoter": "DNA" } }, { "input_text": "Tyrosine phosphorylation STAT1 or STAT3 was not detected in human erythroid precursors after stimulation with erythropoietin .", "target_text": { "STAT1": "protein", "STAT3": "protein", "human erythroid precursors": "cell_type", "erythropoietin": "protein" } }, { "input_text": "Crkl , an SH2/SH3 adapter protein , becomes coimmunoprecipitated specifically with STAT5 from erythropoietin -stimulated erythroid cells ; although it was shown to become associated with c-Cbl in the studies using cell lines .", "target_text": { "Crkl": "protein", "SH2/SH3 adapter protein": "protein", "STAT5": "protein", "erythropoietin": "protein", "erythropoietin -stimulated erythroid cells": "cell_type", "c-Cbl": "protein", "cell lines": "cell_line" } }, { "input_text": "Thus , human erythroid precursors can be expanded in vitro in sufficient numbers and purity to allow its usage in signal transduction studies .", "target_text": { "human erythroid precursors": "cell_type" } }, { "input_text": "This report sets a basis for further studies on signaling in primary cultured human erythroid precursors , which in turn contribute to our better understanding in the differentiation processes of erythrocytes and their precursors .", "target_text": { "human erythroid precursors": "cell_type", "primary cultured human erythroid precursors": "cell_type", "erythrocytes": "cell_type" } }, { "input_text": "Oxidative stress suppresses transcription factor activities in stimulated lymphocytes .", "target_text": { "transcription factor": "protein", "stimulated lymphocytes": "cell_type" } }, { "input_text": "Effects of oxidative stress on stimulation-dependent signal transduction , leading to IL-2 expression , were studied .", "target_text": { "IL-2": "protein" } }, { "input_text": "Purified quiescent human blood T lymphocytes were subjected to : ( i ) acute exposure to hydrogen peroxide ; ( ii ) chronic exposure to hydrogen peroxide ; and ( iii ) acute exposure to ionizing radiation .", "target_text": { "Purified quiescent human blood T lymphocytes": "cell_type" } }, { "input_text": "The cells were then stimulated for 6 h .", "target_text": {} }, { "input_text": "DNA-binding activities ( determined by the electrophoretic mobility shift assay ) of three transcription factors : NFkappaB , AP-1 and NFAT , were abolished in the lymphocytes by all three modes of oxidative stress .", "target_text": { "transcription factors": "protein", "NFkappaB": "protein", "AP-1": "protein", "NFAT": "protein", "lymphocytes": "cell_type" } }, { "input_text": "The lymphocytes exhibited lipid peroxidation only upon exposure to the lowest level of hydrogen peroxide used ( 20 microM ) .", "target_text": { "lymphocytes": "cell_type" } }, { "input_text": "All three modes of oxidative stress induced catalase activity in the lymphocytes .", "target_text": { "catalase": "protein", "lymphocytes": "cell_type" } }, { "input_text": "The only exception was hydrogen peroxide at 20 microM , which did not induce catalase activity .", "target_text": { "catalase": "protein" } }, { "input_text": "We conclude that : ( i ) suppression of specific transcription factor functions can potentially serve as a marker of exposure to oxidative stress and its effects on human lymphocytes ; ( ii ) lipid peroxidation is only detectable in human lymphocytes upon exposure to weak oxidative stress which does not induce catalase activity ; ( iii ) therefore , transcription factor DNA-binding activities are more sensitive to oxidative stress than lipid peroxidation .", "target_text": { "transcription factor": "protein", "human lymphocytes": "cell_type", "catalase": "protein" } }, { "input_text": "IL-4 -dependent regulation of TGF-alpha and TGF-beta1 expression in human eosinophils .", "target_text": { "IL-4": "protein", "human eosinophils": "cell_type" } }, { "input_text": "TGFs play important roles in wound healing and carcinogenesis .", "target_text": { "TGFs": "protein" } }, { "input_text": "We have previously demonstrated that eosinophils infiltrating into different pathologic processes elaborate TGF-alpha and TGF-beta1 .", "target_text": { "eosinophils": "cell_type", "TGF-alpha": "protein", "TGF-beta1": "protein" } }, { "input_text": "Eosinophils infiltrating hamster cutaneous wounds were found to express TGFs sequentially .", "target_text": { "Eosinophils": "cell_type", "TGFs": "protein" } }, { "input_text": "In this study , we examined the biologic mediators that may regulate the expression of TGF -alpha and -beta1 by eosinophils .", "target_text": { "eosinophils": "cell_type" } }, { "input_text": "Eosinophils were isolated from the peripheral blood of healthy donors and cultured in the absence or presence of IL-3 , IL-4 , and IL-5 .", "target_text": { "Eosinophils": "cell_type", "IL-3": "protein", "IL-4": "protein", "IL-5": "protein" } }, { "input_text": "Cells were analyzed by in situ hybridization and immunohistochemistry .", "target_text": {} }, { "input_text": "Supernatants from these cultures were assayed for secreted TGF-alpha and TGF-beta1 using TGF -specific ELISAs .", "target_text": { "TGF-alpha": "protein", "TGF-beta1": "protein", "TGF": "protein" } }, { "input_text": "IL-3 , IL-4 , and IL-5 independently up-regulated TGF-beta1 mRNA and product expression by eosinophils in all donors .", "target_text": { "IL-3": "protein", "IL-4": "protein", "IL-5": "protein", "TGF-beta1": "protein", "TGF-beta1 mRNA": "RNA", "eosinophils": "cell_type" } }, { "input_text": "Interestingly , TGF-alpha production by eosinophils was up-regulated by IL-3 and IL-5 but was down-regulated by IL-4 .", "target_text": { "TGF-alpha": "protein", "eosinophils": "cell_type", "IL-3": "protein", "IL-5": "protein", "IL-4": "protein" } }, { "input_text": "Consistent with the ability of IL-4 to regulate eosinophil responses , IL-4 signaling molecules are present in human eosinophils .", "target_text": { "IL-4": "protein", "IL-4 signaling molecules": "protein", "eosinophils": "cell_type", "human eosinophils": "cell_type" } }, { "input_text": "The observation that IL-4 can differentially regulate the expression of TGF-alpha and TGF-beta1 suggests that IL-4 may serve as a physiologic molecular switch of TGF expression by the infiltrating eosinophils in wound healing and carcinogenesis .", "target_text": { "IL-4": "protein", "TGF-alpha": "protein", "TGF-beta1": "protein", "TGF": "protein", "eosinophils": "cell_type" } }, { "input_text": "MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11) : both rearrangements are associated with a poor prognosis .", "target_text": { "CALM": "DNA", "AF10": "DNA", "translocation t(10;11)": "DNA" } }, { "input_text": "The translocation t(10;11) (p13;q14) has been observed in acute lymphoblastic leukemia ( ALL ) as well as acute myeloid leukemia ( AML ) .", "target_text": { "translocation t(10;11)": "DNA", "translocation t(10;11) (p13;q14)": "DNA" } }, { "input_text": "A recent study showed a MLL/ AF10 fusion in all cases of AML with t(10;11) and various breakpoints on chromosome 11 ranging from q13 to q23 .", "target_text": { "AF10": "DNA", "MLL/ AF10 fusion": "DNA", "t(10;11)": "DNA", "chromosome 11": "DNA", "q13": "DNA", "q23": "DNA" } }, { "input_text": "We recently cloned CALM ( Clathrin Assembly Lymphoid Myeloid leukemia gene ) , the fusion partner of AF10 at 11q14 in the monocytic cell line U937 .", "target_text": { "CALM": "DNA", "Clathrin Assembly Lymphoid Myeloid leukemia gene": "DNA", "AF10": "DNA", "11q14": "DNA", "monocytic cell line U937": "cell_line" } }, { "input_text": "To further define the role of these genes in acute leukemias , 10 cases ( 9 AML and 1 ALL ) with cytogenetically proven t(10;11)(p12-14;q13-21) and well-characterized morphology , immunophenotype , and clinical course were analyzed .", "target_text": { "t(10;11)(p12-14;q13-21)": "DNA" } }, { "input_text": "Interphase fluorescence in situ hybridization ( FISH ) was performed with 2 YACs flanking the CALM region , a YAC contig of the MLL region , and a YAC spanning the AF10 breakpoint .", "target_text": { "YACs": "DNA", "CALM": "DNA", "CALM region": "DNA", "YAC contig": "DNA", "MLL region": "DNA", "YAC": "DNA", "AF10": "DNA" } }, { "input_text": "Rearrangement of at least one of these genes was detected in all cases with balanced t(10;11) .", "target_text": { "t(10;11)": "DNA" } }, { "input_text": "In 4 cases , including 3 AML with immature morphology ( 1 AML -M0 and 2 AML -M1 ) and 1 ALL , the signals of the CALM YACS were separated in interphase cells , indicating a translocation breakpoint within the CALM region .", "target_text": { "CALM": "DNA", "CALM YACS": "DNA", "CALM region": "DNA" } }, { "input_text": "MLL was rearranged in 3 AML with myelomonocytic differentiation ( 2 AML-M2 and 1 AML-M5 ) , including 1 secondary AML .", "target_text": {} }, { "input_text": "In all 3 cases , a characteristic immunophenotype was identified ( CD4+ , CD13 - , CD33+ , CD65s+ ) .", "target_text": { "CD4+": "protein", "CD13": "protein" } }, { "input_text": "AF-10 was involved in 5 of 6 evaluable cases , including 1 case without detectable CALM or MLL rearrangement .", "target_text": { "CALM": "DNA" } }, { "input_text": "In 2 complex translocations , none of the three genes was rearranged .", "target_text": {} }, { "input_text": "All cases had a remarkably poor prognosis , with a mean survival of 9.6 +/- 6.6 months .", "target_text": {} }, { "input_text": "For the 7 AML cases that were uniformly treated according to the AMLCG86/92 protocols , disease-free and overall survival was significantly worse than for the overall study group ( P = .03 and P = .01 , respectively ) .", "target_text": {} }, { "input_text": "We conclude that the t(10;11)(p13;q14) indicates CALM and MLL rearrangements in morphologically distinct subsets of acute leukemia and may be associated with a poor prognosis .", "target_text": { "t(10;11)(p13;q14)": "DNA" } }, { "input_text": "The role of E-proteins in B- and T- lymphocyte development .", "target_text": { "E-proteins": "protein" } }, { "input_text": "Department of lymphocytes from hematopoietic stem cells is controlled , in part , by the activity of transcriptional regulatory proteins .", "target_text": { "lymphocytes": "cell_type", "hematopoietic stem cells": "cell_type", "transcriptional regulatory proteins": "protein" } }, { "input_text": "In particular , one class of helix-loop-helix proteins , termed E-proteins , have been implicated in the regulation of gene expression during B-cell development .", "target_text": { "helix-loop-helix proteins": "protein", "E-proteins": "protein" } }, { "input_text": "Recent analysis of gene-targeted mice has allowed a direct assessment of the functional roles of several E-protein family members in hematopoiesis .", "target_text": { "several E-protein family members": "protein" } }, { "input_text": "In this review we describe the defects in B- and T- lymphocyte development in mice carrying targeted mutations in the E-protein genes and discuss our current understanding of the role of these proteins in lymphoid development", "target_text": { "E-protein genes": "DNA" } }, { "input_text": "Epstein-Barr virus-transforming protein latent infection membrane protein 1 activates transcription factor NF-kappaB through a pathway that includes the NF-kappaB -inducing kinase and the IkappaB kinases IKKalpha and IKKbeta .", "target_text": { "Epstein-Barr virus-transforming protein": "protein", "latent infection membrane protein 1": "protein", "NF-kappaB": "protein", "transcription factor NF-kappaB": "protein", "NF-kappaB -inducing kinase": "protein", "IkappaB kinases": "protein", "IKKalpha": "protein", "IKKbeta": "protein" } }, { "input_text": "The Epstein-Barr virus oncoprotein latent infection membrane protein 1 ( LMP1 ) is a constitutively aggregated pseudo-tumor necrosis factor receptor ( TNFR ) that activates transcription factor NF-kappaB through two sites in its C-terminal cytoplasmic domain .", "target_text": { "Epstein-Barr virus oncoprotein": "protein", "latent infection membrane protein 1": "protein", "LMP1": "protein", "pseudo-tumor necrosis factor receptor": "protein", "TNFR": "protein", "NF-kappaB": "protein", "transcription factor NF-kappaB": "protein", "C-terminal cytoplasmic domain": "protein" } }, { "input_text": "One site is similar to activated TNFRII in associating with TNFR -associated factors TRAF1 and TRAF2 , and the second site is similar to TNFRI in associating with the TNFRI death domain interacting protein TRADD .", "target_text": { "TNFRII": "protein", "TNFR": "protein", "TNFR -associated factors": "protein", "TRAF1": "protein", "TRAF2": "protein", "TNFRI": "protein", "TNFRI death domain": "protein", "TNFRI death domain interacting protein": "protein", "TRADD": "protein" } }, { "input_text": "TNFRI has been recently shown to activate NF-kappaB through association with TRADD , RIP , and TRAF2 ; activation of the NF-kappaB -inducing kinase ( NIK ) ; activation of the IkappaB alpha kinases ( IKKalpha and IKKbeta ) ; and phosphorylation of IkappaB alpha .", "target_text": { "TNFRI": "protein", "NF-kappaB": "protein", "TRADD": "protein", "RIP": "protein", "TRAF2": "protein", "NF-kappaB -inducing kinase": "protein", "NIK": "protein", "IkappaB alpha kinases": "protein", "IKKalpha": "protein", "IKKbeta": "protein", "IkappaB alpha": "protein" } }, { "input_text": "IkappaB alpha phosphorylation on Ser-32 and Ser-36 is followed by its degradation and NF-kappaB activation .", "target_text": { "IkappaB alpha": "protein", "NF-kappaB": "protein" } }, { "input_text": "In this report , we show that NF-kappaB activation by LMP1 or by each of its effector sites is mediated by a pathway that includes NIK , IKKalpha , and IKKbeta .", "target_text": { "NF-kappaB": "protein", "LMP1": "protein", "effector sites": "protein", "NIK": "protein", "IKKalpha": "protein", "IKKbeta": "protein" } }, { "input_text": "Dominant negative mutants of NIK , IKKalpha , or IKKbeta substantially inhibited NF-kappaB activation by LMP1 or by each of its effector sites .", "target_text": { "Dominant negative mutants": "protein", "NIK": "protein", "IKKalpha": "protein", "IKKbeta": "protein", "NF-kappaB": "protein", "LMP1": "protein", "effector sites": "protein" } }, { "input_text": "Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18- mediated function .", "target_text": { "MyD88 gene": "DNA" } }, { "input_text": "MyD88 , originally isolated as a myeloid differentiation primary response gene , is shown to act as an adaptor in interleukin-1 ( IL-1 ) signaling by interacting with both the IL-1 receptor complex and IL-1 receptor-associated kinase ( IRAK ) .", "target_text": { "MyD88": "protein", "primary response gene": "DNA", "interleukin-1": "protein", "IL-1": "protein", "IL-1 receptor complex": "protein", "IL-1 receptor-associated kinase": "protein", "IRAK": "protein" } }, { "input_text": "Mice generated by gene targeting to lack MyD88 have defects in T cell proliferation as well as induction of acute phase proteins and cytokines in response to IL-1 .", "target_text": { "MyD88": "protein", "cytokines": "protein", "IL-1": "protein" } }, { "input_text": "Increases in interferon-gamma production and natural killer cell activity in response to IL-18 are abrogated .", "target_text": { "interferon-gamma": "protein", "IL-18": "protein" } }, { "input_text": "In vivo Th1 response is also impaired .", "target_text": {} }, { "input_text": "Furthermore , IL-18 -induced activation of NF-kappaB and c-Jun N-terminal kinase ( JNK ) is blocked in MyD88 -/- Th1-developing cells .", "target_text": { "IL-18": "protein", "NF-kappaB": "protein", "c-Jun N-terminal kinase": "protein", "JNK": "protein", "MyD88": "protein", "MyD88 -/- Th1-developing cells": "cell_line" } }, { "input_text": "Taken together , these results demonstrate that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor .", "target_text": { "MyD88": "protein", "IL-1": "protein", "IL-1 receptor": "protein", "IL-18": "protein", "IL-18 receptor": "protein" } }, { "input_text": "Ciprofloxacin induces an immunomodulatory stress response in human T lymphocytes .", "target_text": { "human T lymphocytes": "cell_type" } }, { "input_text": "Exposure of cells to adverse environmental conditions invokes a genetically programmed series of events resulting in the induction of specific genes .", "target_text": { "specific genes": "DNA" } }, { "input_text": "The fluoroquinolone antibiotic ciprofloxacin has recently been reported to upregulate interleukin-2 ( IL-2 ) gene induction .", "target_text": { "interleukin-2": "protein", "IL-2": "protein" } }, { "input_text": "In the present investigation , the effect of ciprofloxacin at supratherapeutic concentrations on immediate-early ( < 2 h ) gene expression in primary human peripheral blood lymphocytes was studied with Northern blots .", "target_text": { "primary human peripheral blood lymphocytes": "cell_type" } }, { "input_text": "In addition , transcriptional activity of IL-2 and metallothionein enhancer and promoter regions and transcription factors AP-1 , NF-kappaB , and NF-AT were analyzed by chloramphenicol acetyltransferase ( CAT ) and electrophoretic mobility shift assays , respectively .", "target_text": { "IL-2": "protein", "transcription factors": "protein", "AP-1": "protein", "NF-kappaB": "protein", "NF-AT": "protein", "chloramphenicol acetyltransferase": "protein", "CAT": "protein" } }, { "input_text": "The concentration of c-fos , c-jun , c-myc , junB , and fra-1 mRNAs was increased in activated peripheral blood lymphocytes incubated with ciprofloxacin compared to that in untreated controls .", "target_text": { "peripheral blood lymphocytes": "cell_type" } }, { "input_text": "Ciprofloxacin increased CAT activity in stimulated lymphocytes transfected with plasmids containing either the IL-2 or metallothionein enhancer .", "target_text": { "CAT": "protein", "plasmids": "cell_type", "IL-2": "protein", "metallothionein": "protein", "metallothionein enhancer": "DNA" } }, { "input_text": "Furthermore , among the transcription factors tested , AP-1 activity was increased in stimulated purified T helper lymphocytes incubated with ciprofloxacin compared to drug-free controls .", "target_text": { "transcription factors": "protein", "AP-1": "protein", "stimulated purified T helper lymphocytes": "cell_type", "drug-free controls": "cell_type" } }, { "input_text": "Taken together , ciprofloxacin increased the levels of immediate-early transcripts , enhanced IL-2 and metallothionein promoter induction , and upregulated AP-1 concentrations in primary lymphocytes , reflecting a program commonly observed in mammalian stress responses .", "target_text": { "immediate-early transcripts": "RNA", "IL-2": "protein", "metallothionein": "protein", "AP-1": "protein", "primary lymphocytes": "cell_type" } }, { "input_text": "A novel retinoic acid receptor ( RAR ) -selective antagonist inhibits differentiation and apoptosis of HL-60 cells : implications of RARalpha -mediated signals in myeloid leukemic cells .", "target_text": { "retinoic acid receptor": "protein", "RAR": "protein", "HL-60 cells": "cell_line", "RARalpha": "protein", "myeloid leukemic cells": "cell_type" } }, { "input_text": "Retinoic acid ( RA ) induces HL-60 cells to differentiate terminally into mature granulocytes , which subsequently die by apoptosis .", "target_text": { "HL-60 cells": "cell_line", "mature granulocytes": "cell_type" } }, { "input_text": "The biological effects of RA are mediated by two distinct families of transcription factors : retinoic acid receptors ( RARs ) and retinoid X receptors ( RXRs ) .", "target_text": { "transcription factors": "protein", "retinoic acid receptors": "protein", "RARs": "protein", "retinoid X receptors": "protein", "RXRs": "protein" } }, { "input_text": "RARs and RXRs form heterodimers and regulate retinoid-mediated gene expression .", "target_text": { "RARs": "protein", "RXRs": "protein", "heterodimers": "protein" } }, { "input_text": "We have recently developed a novel RAR -selective antagonist ( ER27191 ) which prevents RAR activation by retinoids .", "target_text": { "RAR": "protein" } }, { "input_text": "Using this RAR-selective antagonist , and RXR and RAR agonist , we demonstrate the RAR -mediated signaling pathway is important for differentiation and apoptosis of myeloid leukemic cells .", "target_text": { "RXR": "protein", "RAR": "protein", "myeloid leukemic cells": "cell_type" } }, { "input_text": "Simple activation of RXRs is not sufficient to induce apoptosis of the cells .", "target_text": { "RXRs": "protein" } }, { "input_text": "Interestingly , the combination of the RAR-selective antagonist and 9-cis RA resulted in partial differentiation and apoptosis of HL-60 and NB4 cells , whereas the RAR antagonist completely blocked all-trans RA -induced differentiation and apoptosis of the cells .", "target_text": { "RAR": "protein" } }, { "input_text": "Additional experiments showed that levels of BCL-2 protein decreased during differentiation of myeloid leukemic cells .", "target_text": { "BCL-2 protein": "protein", "myeloid leukemic cells": "cell_type" } }, { "input_text": "Furthermore , HL-60 cells transduced with a bcl-2 expression vector showed the same differentiation response to retinoids as did parental HL-60 cells even though apoptosis was inhibited in these bcl-2-transduced cells , suggesting that differentiation and apoptosis are regulated independently in myeloid leukemic cells .", "target_text": { "HL-60 cells": "cell_line", "bcl-2 expression vector": "DNA", "parental HL-60 cells": "cell_line", "bcl-2-transduced cells": "cell_line", "myeloid leukemic cells": "cell_type" } }, { "input_text": "Thrombopoietin supports in vitro erythroid differentiation via its specific receptor c-Mpl in a human leukemia cell line .", "target_text": { "Thrombopoietin": "protein", "c-Mpl": "protein", "human leukemia cell line": "cell_line" } }, { "input_text": "Thrombopoietin ( TPO ) acts on megakaryopoiesis and erythropoiesis in vitro and in vivo .", "target_text": { "Thrombopoietin": "protein", "TPO": "protein" } }, { "input_text": "We isolated a novel subline , UT-7/GMT , from the human leukemia cell line UT-7/GM ( N. Komatsu , et al. , Blood , 89 : 4021-4033 , 1997 ) .", "target_text": { "UT-7/GMT": "cell_line", "human leukemia cell line": "cell_line", "human leukemia cell line UT-7/GM": "cell_line" } }, { "input_text": "A small population of UT-7/GM cells positively stained for hemoglobin ( Hb ) after a 7-day exposure to TPO .", "target_text": { "UT-7/GM cells": "cell_line", "hemoglobin": "protein", "Hb": "protein", "TPO": "protein" } }, { "input_text": "More than 50 % of TPO -treated UT-7/GMT cells positively stained for Hb .", "target_text": { "TPO": "protein", "TPO -treated UT-7/GMT cells": "cell_line", "Hb": "protein" } }, { "input_text": "Using UT-7/GMT cells , we examined how TPO promotes hemoglobinization .", "target_text": { "UT-7/GMT cells": "cell_line", "TPO": "protein" } }, { "input_text": "TPO induced tyrosine phosphorylation of the TPO receptor but not the erythropoietin ( EPO ) receptor .", "target_text": { "TPO": "protein", "EPO": "protein", "erythropoietin ( EPO ) receptor": "protein" } }, { "input_text": "There was no competition between TPO and EPO for binding to EPO receptor .", "target_text": { "TPO": "protein", "EPO": "protein", "EPO receptor": "protein" } }, { "input_text": "These findings suggest that TPO has a direct effect on hemoglobinization via a specific receptor on UT-7/GMT cells .", "target_text": { "TPO": "protein", "UT-7/GMT cells": "cell_line" } }, { "input_text": "Isoelectric focusing demonstrated that TPO induced fetal and adult Hb synthesis , whereas EPO induced embryonic , fetal , and adult Hb synthesis .", "target_text": { "TPO": "protein", "EPO": "protein" } }, { "input_text": "Thus , our data suggest that TPO has a distinct action on erythropoiesis .", "target_text": { "TPO": "protein" } }, { "input_text": "Role of GATA-1 in proliferation and differentiation of definitive erythroid and megakaryocytic cells in vivo .", "target_text": { "GATA-1": "protein" } }, { "input_text": "To elucidate the contributions of GATA-1 to definitive hematopoiesis in vivo , we have examined adult mice that were rendered genetically defective in GATA-1 synthesis ( Takahashi et al , J Biol Chem 272 : 12611 , 1997 ) .", "target_text": { "GATA-1": "protein" } }, { "input_text": "Because the GATA-1 gene is located on the X chromosome , which is randomly inactivated in every cell , heterozygous females can bear either an active wild-type or mutant ( referred to as GATA-1.05 ) GATA-1 allele , consequently leading to variable anemic severity .", "target_text": { "GATA-1": "protein", "GATA-1 gene": "DNA", "X chromosome": "DNA", "GATA-1.05": "DNA" } }, { "input_text": "These heterozygous mutant mice usually developed normally , but they began to die after 5 months .", "target_text": {} }, { "input_text": "These affected animals displayed marked splenomegaly , anemia , and thrombocytopenia .", "target_text": {} }, { "input_text": "Proerythroblasts and megakaryocytes massively accumulated in the spleens of the heterozygotes , and we showed that the neomycin resistance gene ( which is the positive selection marker in ES cells ) was expressed profusely in the abnormally abundant cells generated in the GATA-1.05 mutant females .", "target_text": { "Proerythroblasts": "cell_type", "megakaryocytes": "cell_type", "neomycin resistance gene": "DNA", "ES cells": "cell_type", "GATA-1.05": "protein" } }, { "input_text": "We also observed hematopoiesis outside of the bone marrow in the affected mutant mice .", "target_text": {} }, { "input_text": "These data suggest that a small number of GATA-1.05 mutant hematopoietic progenitor cells begin to proliferate vigorously during early adulthood , but because the cells are unable to terminally differentiate , this leads to progenitor proliferation in the spleen and consequently death .", "target_text": { "GATA-1.05": "protein", "GATA-1.05 mutant hematopoietic progenitor cells": "cell_line" } }, { "input_text": "Thus , GATA-1 plays important in vivo roles for directing definitive hematopoietic progenitors to differentiate along both the erythroid and megakaryocytic pathways .", "target_text": { "GATA-1": "protein", "hematopoietic progenitors": "cell_type" } }, { "input_text": "The GATA-1 heterozygous mutant mouse shows a phenotype that is analogous to human myelodysplastic syndrome and thus may serve as a useful model for this disorder .", "target_text": { "GATA-1": "protein" } }, { "input_text": "Differential regulation of the Janus kinase -STAT pathway and biologic function of IL-13 in primary human NK and T cells : a comparative study with IL-4 .", "target_text": { "Janus kinase": "protein", "-STAT": "protein", "IL-13": "protein", "IL-4": "protein" } }, { "input_text": "IL-13 , a cytokine similar to IL-4 , is a regulator of human B cell and monocyte functions .", "target_text": { "IL-13": "protein", "IL-4": "protein" } }, { "input_text": "Biologic effects of IL-13 on primary human NK and T cells have not been well defined .", "target_text": { "IL-13": "protein" } }, { "input_text": "We demonstrate that , in primary NK cells , IL-13 , but not IL-4 , may induce low levels of IFN-gamma secretion .", "target_text": { "primary NK cells": "cell_type", "IL-13": "protein", "IL-4": "protein", "IFN-gamma": "protein" } }, { "input_text": "When NK cells were costimulated with IL-13 and IL-2 , IL-13 generally resulted in two types of reactivity : IL-13 synergized with IL-2 to stimulate IFN-gamma production or it modestly inhibited IL-2 - mediated IFN-gamma production .", "target_text": { "NK cells": "cell_type", "IL-13": "protein", "IL-2": "protein", "IFN-gamma": "protein" } }, { "input_text": "In both types of donors , the effect of IL-13 on IL-2 -induced IFN-gamma production was in marked contrast to the strong inhibition seen with IL-4 in NK cells .", "target_text": { "IL-13": "protein", "IL-2": "protein", "IFN-gamma": "protein", "IL-4": "protein", "NK cells": "cell_type" } }, { "input_text": "Additionally , IL-13 suppresses IL-2-induced NK cytolytic and proliferative activities although less efficiently than IL-4 .", "target_text": { "IL-13": "protein", "IL-4": "protein" } }, { "input_text": "In T cells , IL-13 inhibits anti-CD3 mAb/IL-2- or PHA- mediated IFN-gamma production and enhances cytolytic potential .", "target_text": { "T cells": "cell_type", "IL-13": "protein" } }, { "input_text": "Furthermore , we demonstrate that IL-13 , like IL-4 , induces distinct STAT6-DNA binding complexes and tyrosine phosphorylation of STAT6 and Janus kinase 3 ( JAK3 ) in NK and T cells .", "target_text": { "IL-13": "protein", "IL-4": "protein", "STAT6-DNA binding complexes": "protein", "STAT6": "protein", "Janus kinase 3": "protein", "JAK3": "protein", "T cells": "cell_type" } }, { "input_text": "We observed that Abs directed against unique domains of STAT6 have differential effects on complexes in T cells but not in NK cells , suggesting different STAT6 isoforms .", "target_text": { "STAT6": "protein", "T cells": "cell_type", "NK cells": "cell_type", "STAT6 isoforms": "protein" } }, { "input_text": "These findings show that IL-13 and IL-4 have the ability to regulate NK and T cell activation and that IL- 13 is a potent regulator of STAT6 and JAK3 in these cell types .", "target_text": { "IL-13": "protein", "IL-4": "protein", "IL- 13": "protein", "STAT6": "protein", "JAK3": "protein" } }, { "input_text": "The human toll signaling pathway : divergence of nuclear factor kappaB and JNK /SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 ( TRAF6 ) .", "target_text": { "nuclear factor kappaB": "protein", "JNK": "protein", "/SAPK": "protein", "tumor necrosis factor receptor-associated factor 6": "protein", "TRAF6": "protein" } }, { "input_text": "The human homologue of Drosophila Toll ( hToll ) is a recently cloned receptor of the interleukin 1 receptor ( IL-1R ) superfamily , and has been implicated in the activation of adaptive immunity .", "target_text": { "Drosophila Toll": "protein", "hToll": "protein", "interleukin 1 receptor": "protein", "IL-1R": "protein", "interleukin 1 receptor ( IL-1R ) superfamily": "protein" } }, { "input_text": "Signaling by hToll is shown to occur through sequential recruitment of the adapter molecule MyD88 and the IL-1R-associated kinase .", "target_text": { "hToll": "protein", "adapter molecule": "protein", "MyD88": "protein", "IL-1R-associated kinase": "protein" } }, { "input_text": "Tumor necrosis factor receptor-activated factor 6 ( TRAF6 ) and the nuclear factor kappaB ( NF-kappaB ) -inducing kinase ( NIK ) are both involved in subsequent steps of NF-kappaB activation .", "target_text": { "Tumor necrosis factor receptor-activated factor 6": "protein", "TRAF6": "protein", "nuclear factor kappaB": "protein", "NF-kappaB": "protein", "nuclear factor kappaB ( NF-kappaB ) -inducing kinase": "protein", "NIK": "protein" } }, { "input_text": "Conversely , a dominant negative version of TRAF6 failed to block hToll -induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases , thus suggesting an early divergence of the two pathways .", "target_text": { "TRAF6": "protein", "hToll": "protein", "stress-activated protein kinase/c-Jun NH2-terminal kinases": "protein" } }, { "input_text": "Inhibition of nuclear factor kappaB activation attenuates apoptosis resistance in lymphoid cells .", "target_text": { "nuclear factor kappaB": "protein", "lymphoid cells": "cell_type" } }, { "input_text": "Death-inducing ligands ( DILs ) such as tumor necrosis factor alpha ( TNFalpha ) or the cytotoxic drug doxorubicin have been shown to activate a nuclear factor kappaB ( NFkappaB ) -dependent program that may rescue cells from apoptosis induction .", "target_text": { "Death-inducing ligands": "protein", "DILs": "protein", "tumor necrosis factor alpha": "protein", "TNFalpha": "protein", "nuclear factor kappaB": "protein", "NFkappaB": "protein" } }, { "input_text": "We demonstrate here that TRAIL ( TNF-related apoptosis -inducing ligand ) , a recently identified DIL , also activates NFkappaB in lymphoid cell lines in a kinetic similar to TNFalpha .", "target_text": { "TRAIL": "protein", "TNF-related apoptosis -inducing ligand": "protein", "DIL": "protein", "NFkappaB": "protein", "TNFalpha": "protein" } }, { "input_text": "NFkappaB activity is independent from FADD , caspases , and apoptosis induction .", "target_text": { "NFkappaB": "protein", "FADD": "protein", "caspases": "protein" } }, { "input_text": "To study the influence of NFkappaB activity on apoptosis mediated by TRAIL , CD95 , TNFalpha , or doxorubicin , NFkappaB activation was inhibited using the proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal or transient overexpression of mutant IkappaBalpha .", "target_text": { "NFkappaB": "protein", "TRAIL": "protein", "TNFalpha": "protein", "proteasome": "protein", "mutant IkappaBalpha": "protein" } }, { "input_text": "Sensitivity for induction of apoptosis was markedly increased by these treatments in apoptosis sensitive cell lines .", "target_text": { "cell lines": "cell_line" } }, { "input_text": "Moreover , both in cell lines and in primary leukemia cells that are resistant towards induction of apoptosis by DILs and doxorubicin , antagonization of NFkappaB activity partially restored apoptosis sensitivity .", "target_text": { "DILs": "protein", "NFkappaB": "protein" } }, { "input_text": "These data suggest that inhibition of NFkappaB activation may provide a molecular approach to increase apoptosis sensitivity in anticancer treatment .", "target_text": { "NFkappaB": "protein" } }, { "input_text": "Loss- and gain-of-function mutations reveal an important role of BSAP ( Pax-5 ) at the start and end of B cell differentiation .", "target_text": { "BSAP": "protein", "Pax-5": "protein" } }, { "input_text": "Pax-5 codes for the transcription factor BSAP which is expressed throughout B cell development except in terminally differentiated plasma cells .", "target_text": { "Pax-5": "protein", "transcription factor": "protein", "BSAP": "protein", "terminally differentiated plasma cells": "cell_type" } }, { "input_text": "Gene targeting experiments in the mouse revealed a differential dependency of fetal and adult B-lymphopoiesis on this transcription factor .", "target_text": { "transcription factor": "protein" } }, { "input_text": "BSAP is required for B-lineage commitment in the fetal liver and for progression beyond an early pro-B cell stage in adult bone marrow .", "target_text": { "BSAP": "protein" } }, { "input_text": "The characterization of Pax-5 -deficient pro-B cells demonstrated an important role of BSAP in the regulation of the CD19 , mb-1 ( Ig alpha ) and N-myc genes as well as in the developmental pathway controlling VH-to-DHJH recombination at the immunoglobulin heavy-chain ( IgH ) locus .", "target_text": { "Pax-5": "protein", "Pax-5 -deficient pro-B cells": "cell_type", "BSAP": "protein", "CD19": "protein", "mb-1": "protein", "Ig alpha": "protein", "N-myc genes": "DNA", "immunoglobulin heavy-chain": "protein", "IgH": "protein", "immunoglobulin heavy-chain ( IgH ) locus": "protein" } }, { "input_text": "The human PAX-5 gene was recently shown to participate together with the IgH locus in the chromosomal translocation t(9;14)(p13;q32) .", "target_text": { "human PAX-5 gene": "DNA", "IgH locus": "DNA", "t(9;14)(p13;q32)": "DNA" } }, { "input_text": "This translocation is characteristic of a small subset of non-Hodgkin lymphomas exhibiting plasmacytoid differentiation .", "target_text": {} }, { "input_text": "The translocated PAX-5 gene is deregulated by the insertion of IgH regulatory elements into its 5' region , which may contribute to tumorigenesis by interfering with the shut-down of PAX-5 transcription and thus with the completion of plasma cell differentiation", "target_text": { "translocated PAX-5 gene": "DNA", "IgH regulatory elements": "DNA", "5' region": "DNA", "PAX-5": "protein", "plasma cell": "cell_type" } }, { "input_text": "Acetylation and modulation of erythroid Kruppel-like factor ( EKLF ) activity by interaction with histone acetyltransferases .", "target_text": { "erythroid Kruppel-like factor": "protein", "EKLF": "protein", "histone acetyltransferases": "protein" } }, { "input_text": "Erythroid Kruppel-like factor ( EKLF ) is a red cell-specific transcriptional activator that is crucial for consolidating the switch to high levels of adult beta-globin expression during erythroid ontogeny .", "target_text": { "Erythroid Kruppel-like factor": "protein", "EKLF": "protein", "red cell-specific transcriptional activator": "protein", "beta-globin": "protein" } }, { "input_text": "EKLF is required for integrity of the chromatin structure at the beta-like globin locus , and it interacts with a positive-acting factor in vivo .", "target_text": { "EKLF": "protein", "chromatin structure": "DNA", "beta-like globin locus": "DNA", "positive-acting factor": "protein" } }, { "input_text": "We find that EKLF is an acetylated transcription factor , and that it interacts in vivo with CBP , p300 , and P/CAF .", "target_text": { "EKLF": "protein", "acetylated transcription factor": "protein", "CBP": "protein", "p300": "protein", "P/CAF": "protein" } }, { "input_text": "However , its interactions with these histone acetyltransferases are not equivalent , as CBP and p300 , but not P/CAF , utilize EKLF as a substrate for in vitro acetylation within its trans- activation region .", "target_text": { "histone acetyltransferases": "protein", "CBP": "protein", "p300": "protein", "P/CAF": "protein", "EKLF": "protein", "activation region": "protein" } }, { "input_text": "The functional effects of these interactions are that CBP and p300 , but not P/CAF , enhance EKLF 's transcriptional activation of the beta-globin promoter in erythroid cells .", "target_text": { "CBP": "protein", "p300": "protein", "P/CAF": "protein", "EKLF": "protein", "beta-globin promoter": "DNA", "erythroid cells": "cell_type" } }, { "input_text": "These results establish EKLF as a tissue-specific transcription factor that undergoes post-translational acetylation and suggest a mechanism by which EKLF is able to alter chromatin structure and induce beta-globin expression within the beta-like globin cluster .", "target_text": { "EKLF": "protein", "tissue-specific transcription factor": "protein", "chromatin": "DNA", "beta-globin": "protein", "beta-like globin cluster": "DNA" } }, { "input_text": "Recognition of herpes simplex virus type 2 tegument proteins by CD4 T cells infiltrating human genital herpes lesions .", "target_text": { "herpes simplex virus type 2 tegument proteins": "protein", "CD4 T cells": "cell_type" } }, { "input_text": "The local cellular immune response to herpes simplex virus ( HSV ) is important in the control of recurrent HSV infection .", "target_text": {} }, { "input_text": "The antiviral functions of infiltrating CD4-bearing T cells may include cytotoxicity , inhibition of viral growth , lymphokine secretion , and support of humoral and CD8 responses .", "target_text": { "infiltrating CD4-bearing T cells": "cell_type", "lymphokine": "protein" } }, { "input_text": "The antigens recognized by many HSV -specific CD4 T cells localizing to genital HSV -2 lesions are unknown .", "target_text": { "CD4 T cells": "cell_type", "HSV -specific CD4 T cells": "cell_type" } }, { "input_text": "T cells recognizing antigens encoded within map units 0 . 67 to 0.73 of HSV DNA are frequently recovered from herpetic lesions .", "target_text": { "T cells": "cell_type", "HSV DNA": "DNA" } }, { "input_text": "Expression cloning with this region of DNA now shows that tegument protein VP22 and the viral dUTPase , encoded by genes UL49 and UL50 , respectively , are T-cell antigens .", "target_text": { "tegument protein": "protein", "VP22": "protein", "viral dUTPase": "protein", "UL49": "DNA", "UL50": "DNA", "T-cell antigens": "protein" } }, { "input_text": "Separate epitopes in VP22 were defined for T-cell clones from each of three patients .", "target_text": { "epitopes": "protein", "VP22": "protein", "T-cell clones": "cell_line" } }, { "input_text": "Reactivity with the tegument protein encoded by UL21 was identified for an additional patient .", "target_text": { "tegument protein": "protein", "UL21": "DNA" } }, { "input_text": "Three new epitopes were identified in VP16 , a tegument protein associated with VP22 .", "target_text": { "VP16": "protein", "tegument protein": "protein", "VP22": "protein" } }, { "input_text": "Some tegument-specific CD4 T-cell clones exhibited cytotoxic activity against HSV -infected cells .", "target_text": { "T-cell clones": "cell_line", "tegument-specific CD4 T-cell clones": "cell_line", "HSV -infected cells": "cell_type" } }, { "input_text": "These results suggest that herpes simplex tegument proteins are processed for antigen presentation in vivo and are possible candidate compounds for herpes simplex vaccines .", "target_text": { "herpes simplex tegument proteins": "protein" } }, { "input_text": "Fibrinogen activates NF-kappa B transcription factors in mononuclear phagocytes .", "target_text": { "Fibrinogen": "protein", "NF-kappa B": "protein", "NF-kappa B transcription factors": "protein", "mononuclear phagocytes": "cell_type" } }, { "input_text": "Adhesion to extracellular matrices is known to modulate leukocyte activation , although the mechanisms are not fully understood .", "target_text": {} }, { "input_text": "Mononuclear phagocytes are exposed to fibrinous provisional matrix throughout migration into inflammatory foci , so this study was undertaken to determine whether fibrinogen triggers activation of NF-kappa B transcription factors .", "target_text": { "Mononuclear phagocytes": "cell_type", "NF-kappa B transcription factors": "protein" } }, { "input_text": "U937 cells differentiated with PMA in nonadherent culture were shown to express two fibrinogen-binding integrins , predominately CD11b/CD18 , and to a lesser extent , CD11c/CD18 .", "target_text": { "U937 cells": "cell_line", "nonadherent culture": "cell_line", "fibrinogen-binding integrins": "protein", "CD11b/CD18": "protein", "CD11c/CD18": "protein" } }, { "input_text": "Cells stimulated with fibrinogen ( 10-100 microg/ml ) /Mn2+ ( 50 microM ) for 2 h were examined by electrophoretic mobility shift assay .", "target_text": { "fibrinogen": "protein" } }, { "input_text": "NF-kappa B activation , minimal in unstimulated cells , was substantially up-regulated by fibrinogen .", "target_text": { "NF-kappa B": "protein", "unstimulated cells": "cell_type", "fibrinogen": "protein" } }, { "input_text": "Fibrinogen also caused activation of AP-1 , but not SP1 or cAMP response element-binding protein ( CREB ) factors .", "target_text": { "Fibrinogen": "protein", "AP-1": "protein", "SP1": "protein", "cAMP response element-binding protein ( CREB ) factors": "protein" } }, { "input_text": "Blocking mAbs against CD18 and CD11b abrogated fibrinogen -induced NF-kappa B activation .", "target_text": { "mAbs": "protein", "CD18": "protein", "CD11b": "protein", "fibrinogen": "protein", "NF-kappa B": "protein" } }, { "input_text": "To determine the effects on transcriptional regulation , U937 cells were transfected with a plasmid containing the HIV-1 enhancer ( bearing two NF-kappa B sites ) coupled to a chloramphenicol acetyltransferase ( CAT ) reporter .", "target_text": { "U937 cells": "cell_line", "HIV-1 enhancer": "DNA", "NF-kappa B": "protein", "NF-kappa B sites": "DNA", "chloramphenicol acetyltransferase": "protein", "CAT": "protein", "chloramphenicol acetyltransferase ( CAT ) reporter": "DNA" } }, { "input_text": "Cells were subsequently stimulated with 1 ) PMA for 24 h , inducing CAT activity by 2.6-fold , 2 ) fibrinogen /Mn2+ for 2 h , inducing CAT activity by 3.2-fold , or 3 ) costimulation with fibrinogen and PMA , inducing 5.7-fold the CAT activity induced by PMA alone .", "target_text": { "CAT": "protein", "fibrinogen": "protein" } }, { "input_text": "We conclude that contact with fibrinogen -derived proteins may contribute to mononuclear phagocyte activation by signaling through CD11b/CD18 , resulting in selective activation of transcriptional regulatory factors , including NF-kappa B .", "target_text": { "fibrinogen": "protein", "fibrinogen -derived proteins": "protein", "CD11b/CD18": "protein", "transcriptional regulatory factors": "protein", "NF-kappa B": "protein" } }, { "input_text": "Peripheral blood T cells and monocytes and B cell lines derived from patients with lupus express estrogen receptor transcripts similar to those of normal cells .", "target_text": { "T cells": "cell_type", "Peripheral blood T cells": "cell_type", "monocytes": "cell_type", "B cell lines": "cell_line", "normal cells": "cell_type" } }, { "input_text": "OBJECTIVE : To identify and characterize estrogen receptor ( ER ) transcripts expressed in immune cells of patients with systemic lupus erythematosus ( SLE ) and healthy donors .", "target_text": { "estrogen receptor ( ER ) transcripts": "RNA", "immune cells": "cell_type" } }, { "input_text": "METHODS : Peripheral blood monocytes and T cells were prepared from patients with SLE ( n = 6 ) and healthy donors ( n = 8 ) .", "target_text": { "Peripheral blood monocytes": "cell_type", "T cells": "cell_type" } }, { "input_text": "T cells were separated into CD4 and CD8 .", "target_text": { "T cells": "cell_type", "CD4": "cell_type", "CD8": "cell_type" } }, { "input_text": "Some monocytes and T cells were stimulated with estradiol , PMA , and ionomycin .", "target_text": { "monocytes": "cell_type", "T cells": "cell_type" } }, { "input_text": "Epstein-Barr virus-transformed B cell lines ( n = 7 ) and B cell hybridomas ( n = 2 ) established from patients with SLE and a healthy individual were used as a B cell source .", "target_text": { "B cell lines": "cell_line", "B cell hybridomas": "cell_line" } }, { "input_text": "These cells were examined for ER mRNA by reverse transcription nested polymerase chain reaction .", "target_text": { "ER mRNA": "RNA" } }, { "input_text": "Amplified cDNA were sequenced by standard methods .", "target_text": { "cDNA": "DNA" } }, { "input_text": "RESULTS : In all cells tested , ER mRNA was expressed without prior in vitro stimulation .", "target_text": { "ER mRNA": "RNA" } }, { "input_text": "Partial sequences from exons 1-8 were nearly identical to the published sequence of the human ER mRNA .", "target_text": { "exons 1-8": "DNA", "ER mRNA": "RNA", "human ER mRNA": "RNA" } }, { "input_text": "There were no notable differences in the ER transcripts between patients and healthy controls .", "target_text": { "ER transcripts": "RNA" } }, { "input_text": "Variant receptor transcripts lacking exon 5 or exon 7 , which encodes the hormone binding domain , were identified in the majority of the cells .", "target_text": { "exon 5": "DNA", "exon 7": "DNA" } }, { "input_text": "Precise deletion of the exons suggests that they are alternatively spliced transcripts .", "target_text": {} }, { "input_text": "Whether the detected transcripts are translated into functional receptor proteins remains to be determined .", "target_text": {} }, { "input_text": "In vitro stimulation did not affect ER mRNA expression .", "target_text": { "ER mRNA": "RNA" } }, { "input_text": "The presence of variants did not correlate with disease activity or medication .", "target_text": {} }, { "input_text": "CONCLUSION : Monocytes , T cells , and B cells in patients express transcripts of the normal wild type ER and the hormone binding domain variants in vivo .", "target_text": { "Monocytes": "cell_type", "T cells": "cell_type", "B cells": "cell_type", "wild type ER": "protein", "hormone binding domain variants": "protein" } }, { "input_text": "DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-kappa B and AP-1 .", "target_text": { "Fas ligand": "protein", "T lymphocytes": "cell_type", "NF-kappa B": "protein", "AP-1": "protein" } }, { "input_text": "Apoptosis induced by DNA damage and other stresses can proceed via expression of Fas ligand ( FasL ) and ligation of its receptor , Fas ( CD95 ) .", "target_text": { "Fas ligand": "protein", "FasL": "protein" } }, { "input_text": "We report that activation of the two transcription factors NF-kappa B and AP-1 is crucially involved in FasL expression induced by etoposide , teniposide , and UV irradiation .", "target_text": { "AP-1": "protein", "FasL": "protein" } }, { "input_text": "A nondegradable mutant of I kappa B blocked both FasL expression and apoptosis induced by DNA damage but not Fas ligation .", "target_text": { "I kappa B": "protein", "FasL": "protein", "Fas": "protein" } }, { "input_text": "These stimuli also induced the stress-activated kinase pathway ( SAPK /JNK ) , which was required for the maximal induction of apoptosis .", "target_text": { "SAPK": "protein", "/JNK": "protein" } }, { "input_text": "A 1.2 kb FasL promoter responded to DNA damage , as well as coexpression with p65 Rel or Fos/Jun .", "target_text": { "FasL": "protein", "FasL promoter": "DNA", "p65 Rel": "protein", "Fos/Jun": "protein" } }, { "input_text": "Mutations in the relevant NF-kappa B and AP-1 binding sites eliminated these responses .", "target_text": { "NF-kappa B": "protein", "AP-1": "protein", "AP-1 binding sites": "DNA" } }, { "input_text": "Thus , activation of NF-kappa B and AP-1 contributes to stress-induced apoptosis via the expression of FasL .", "target_text": { "NF-kappa B": "protein", "AP-1": "protein", "FasL": "protein" } }, { "input_text": "A small , nonpeptidyl mimic of granulocyte-colony-stimulating factor [ see commetns ]", "target_text": { "granulocyte-colony-stimulating factor": "protein" } }, { "input_text": "A nonpeptidyl small molecule SB 247464 , capable of activating granulocyte-colony-stimulating factor ( G-CSF ) signal transduction pathways , was identified in a high-throughput assay in cultured cells .", "target_text": { "granulocyte-colony-stimulating factor": "protein", "G-CSF": "protein", "cultured cells": "cell_type" } }, { "input_text": "Like G-CSF , SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated primary murine bone marrow cells to form granulocytic colonies in vitro .", "target_text": { "G-CSF": "protein", "multiple signaling proteins": "protein", "primary murine bone marrow cells": "cell_type", "granulocytic colonies": "cell_type" } }, { "input_text": "It also elevated peripheral blood neutrophil counts in mice .", "target_text": { "peripheral blood neutrophil": "cell_type" } }, { "input_text": "The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464 , suggesting that the compound acts by oligomerizing receptor chains .", "target_text": { "G-CSF": "protein", "murine G-CSF receptor": "protein", "oligomerizing receptor chains": "protein" } }, { "input_text": "The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand .", "target_text": {} }, { "input_text": "Minimal residual disease in acute myelogenous leukemia with PML/RAR alpha or AML1/ETO mRNA and phenotypic analysis of possible T and natural killer cells in bone marrow .", "target_text": { "PML/RAR alpha": "protein", "AML1/ETO": "protein" } }, { "input_text": "Here we studied minimal residual disease ( MRD ) of patients with acute myeloid leukemia ( AML ) who have PML/RAR alpha or AML1/ETO as well as the phenotypic analysis of lymphocyte subsets involved in antitumor immunity .", "target_text": { "PML/RAR alpha": "protein", "AML1/ETO": "protein", "lymphocyte subsets": "cell_type" } }, { "input_text": "Eight patients in long-term ( LT ; 3 to 15 years ) and 15 patients in short-term ( ST ; up to 3 years ) remission were studied .", "target_text": {} }, { "input_text": "Using the reverse transcription-polymerase chain reaction ( RT ) assay , the limit of detection was 10(-5) to 10(-6) for PML/RAR alpha transcript and 10(-4) to 10(-5) for the AML1/ETO transcript .", "target_text": { "PML/RAR alpha": "protein", "PML/RAR alpha transcript": "RNA", "AML1/ETO": "protein", "AML1/ETO transcript": "RNA" } }, { "input_text": "Simultaneously , T lymphocyte subsets and NK cells from the peripheral blood ( PB ) and bone marrow ( BM ) were investigated by flow cytometric analysis .", "target_text": { "T lymphocyte subsets": "cell_type", "NK cells": "cell_type" } }, { "input_text": "Four of the eight patients in LT and 7 of the 15 patients in ST remission were MRD -positive .", "target_text": {} }, { "input_text": "Although all MRD -positive patients in LT remission are still until now event-free , 3 of the 7 MRD -positive ( MRD + ) patients in ST remission soon relapsed .", "target_text": {} }, { "input_text": "The total populations of CD4 + , CD8 + and CD56 + [ possible T-cell and natural killer ( T/NK ) populations ] in the BM of ST patients and MRD +/LT patients were significantly ( p < .01 ) low .", "target_text": { "CD4": "protein", "CD8": "protein", "CD56": "protein", "T-cell": "cell_type", "natural killer": "cell_type", "T/NK": "cell_type" } }, { "input_text": "The CD8 + CD28 + population showed the same tendency ( p < .01-.02 ) .", "target_text": { "CD8": "protein", "CD28": "protein" } }, { "input_text": "The T/NK subsets in the BM of MRD -negative ( MRD - ) LT ( MRD -/LT ) patients showed similar numbers of cells as normal volunteers .", "target_text": { "T/NK subsets": "cell_type" } }, { "input_text": "Basically , the total percentage of the CD4 + , CD8 + and CD56 + cell populations in the BM was increased and in the following order : MRD -/LT patients , normal volunteers , MRD +/LT patients and MRD + or -/ST patients .", "target_text": { "CD4": "protein", "CD8": "protein", "CD56": "protein" } }, { "input_text": "The percentages of the T/NK-cell subsets in the PB were not significantly different among these groups .", "target_text": { "T/NK-cell subsets": "cell_type" } }, { "input_text": "Thus , the difference of the possible T/NK-cell phenotype in the BM may strongly influence clinical and molecular remission .", "target_text": { "T/NK-cell": "cell_type" } }, { "input_text": "These results still remain to be confirmed by further studies of the functional anti-tumor immunity of T/NK cells of AML in remission .", "target_text": { "T/NK cells": "cell_type" } }, { "input_text": "Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB -dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells .", "target_text": { "NF-kappaB": "protein", "long terminal repeat": "DNA", "T cells": "cell_type" } }, { "input_text": "Tuberculosis has emerged as an epidemic , extended by the large number of individuals infected with human immunodeficiency virus type 1 ( HIV-1 ) .", "target_text": {} }, { "input_text": "The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan ( ManLAM ) of Mycobacterium tuberculosis ( M. tuberculosis ) could activate transcription of HIV-1 in T cells with the use of an in vitro cell culture system .", "target_text": { "mycobacterial cell": "cell_type", "T cells": "cell_type" } }, { "input_text": "These experiments are of prime importance considering that CD4 -expressing T lymphocytes represent the major virus reservoir in the peripheral blood of infected individuals .", "target_text": { "CD4": "protein", "T lymphocytes": "cell_type", "CD4 -expressing T lymphocytes": "cell_type" } }, { "input_text": "Using the 1G5 cell line harbouring the luciferase reporter gene under the control of the HIV-1 LTR , it was first found that culture protein filtrates ( CFP ) from M. tuberculosis or purified ManLAM could activate HIV-1 LTR -dependent gene expression unlike similarly prepared CFP extracts devoid of ManLAM .", "target_text": { "1G5 cell line": "cell_line", "luciferase reporter gene": "DNA", "HIV-1 LTR": "DNA", "HIV-1 LTR -dependent gene": "DNA" } }, { "input_text": "The implication of protein tyrosine kinase ( s ) , protein kinase A and/or protein kinase C was highlighted by the abrogation of the ManLAM -mediated activation of HIV-1 LTR -driven gene expression using herbimycin A and H7 .", "target_text": { "protein tyrosine kinase ( s )": "protein", "protein kinase A": "protein", "protein kinase C": "protein", "HIV-1 LTR": "DNA", "HIV-1 LTR -driven gene": "DNA" } }, { "input_text": "It was also determined , using electrophoresis mobility shift assays , that M. tuberculosis ManLAM led to the nuclear translocation of the transcription factor NF-kappaB .", "target_text": { "NF-kappaB": "protein", "transcription factor NF-kappaB": "protein" } }, { "input_text": "M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type , but not the kappaB -mutated , HIV-1 LTR region .", "target_text": { "luciferase gene": "DNA", "kappaB": "DNA", "LTR": "DNA", "HIV-1 LTR region": "DNA", "wild-type , but not the kappaB -mutated , HIV-1 LTR region": "DNA" } }, { "input_text": "Finally , the ManLAM -mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of endogenous TNF-alpha .", "target_text": { "LTR": "DNA", "HIV-1 LTR": "DNA", "endogenous TNF-alpha": "protein" } }, { "input_text": "The results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells and could thus have the potential to influence the pathogenesis of HIV-1 infection .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Human immunodeficiency virus type 1 long terminal repeat quasispecies differ in basal transcription and nuclear factor recruitment in human glial cells and lymphocytes .", "target_text": { "long terminal repeat": "DNA", "Human immunodeficiency virus type 1 long terminal repeat": "DNA", "Human immunodeficiency virus type 1 long terminal repeat quasispecies": "DNA", "nuclear factor": "protein" } }, { "input_text": "The generation of genomic diversity during the course of infection has the potential to affect all aspects of HIV-1 replication , including expression of the proviral genome .", "target_text": { "proviral genome": "DNA" } }, { "input_text": "To gain a better understanding of the impact of long terminal repeat ( LTR ) sequence diversity on LTR -directed gene expression in cells of the central nervous system ( CNS ) and immune system , we amplified and cloned LTRs from proviral DNA in HIV-1 -infected peripheral blood .", "target_text": { "long terminal repeat": "DNA", "LTR": "DNA", "LTR -directed gene": "DNA", "LTRs": "DNA", "proviral DNA": "DNA", "HIV-1 -infected peripheral blood": "cell_type" } }, { "input_text": "Sequence analysis of nineteen LTRs cloned from 2 adult and 3 pediatric patients revealed an average of 33 nucleotide changes ( with respect to the sequence of the LAI LTR ) within the 455-bp U3 region .", "target_text": { "LTRs": "DNA", "LTR": "DNA", "LAI LTR": "DNA", "455-bp U3 region": "DNA" } }, { "input_text": "Transient expression analyses in cells of neuroglial and lymphocytic origin demonstrated that some of these LTRs had activities which varied significantly from the LAI LTR in U-373 MG cells ( an astrocytoma cell line ) as well as in Jurkat cells ( a CD4- positive lymphocyte cell line ) .", "target_text": { "LTRs": "DNA", "LTR": "DNA", "LAI LTR": "DNA", "U-373 MG cells": "cell_line", "astrocytoma": "cell_type", "astrocytoma cell line": "cell_line", "Jurkat cells": "cell_line", "lymphocyte": "cell_type", "CD4- positive lymphocyte cell line": "cell_line" } }, { "input_text": "While LTRs which demonstrated the highest activities in U-373 MG cells also yielded high activities in Jurkat cells , the LTRs were generally more active in Jurkat cells when compared to the LAI LTR .", "target_text": { "LTRs": "DNA", "U-373 MG cells": "cell_line", "Jurkat cells": "cell_line", "LTR": "DNA", "LAI LTR": "DNA" } }, { "input_text": "Differences in LTR sequence also resulted in differences in transcription factor recruitment to cis-acting sites within the U3 region of the LTR , as demonstrated by electrophoretic mobility shift assays .", "target_text": { "LTR": "DNA", "LTR sequence": "DNA", "cis-acting sites": "DNA", "U3 region": "DNA" } }, { "input_text": "In particular , naturally occurring sequence variation impacted transcription factor binding to an activating transcription factor/ cAMP response element binding ( ATF/CREB ) binding site ( located between the LEF-1 and distal NF-kappaB transcription factor binding sites ) that we identified in previous studies of the HIV-1 LTR .", "target_text": { "transcription factor": "protein", "activating transcription factor/ cAMP response element binding": "protein", "ATF/CREB": "protein", "activating transcription factor/ cAMP response element binding ( ATF/CREB ) binding site": "DNA", "LEF-1": "protein", "NF-kappaB": "protein", "LTR": "DNA", "HIV-1 LTR": "DNA" } }, { "input_text": "These findings suggest that LTR sequence changes can significantly affect basal LTR function and transcription factor recruitment , which may , in turn , alter the course of viral replication in cells of CNS and immune system origin .", "target_text": { "LTR": "DNA", "LTR sequence": "DNA", "transcription factor": "protein" } }, { "input_text": "HMG box containing transcription factors in lymphocyte differentiation .", "target_text": { "HMG box": "protein", "transcription factors": "protein", "lymphocyte": "cell_type" } }, { "input_text": "The identification of the mammalian sex-determining gene Sry has led to the discovery of a large family of related ( ' HMG box ' ) transcription factors that control developmental events in yeast , C. elegans , Drosophila and vertebrates .", "target_text": { "mammalian sex-determining gene Sry": "DNA", "HMG box": "protein", "transcription factors": "protein" } }, { "input_text": "In lymphocyte differentiation , several HMG box proteins play a decisive role .", "target_text": { "lymphocyte": "cell_type", "HMG box proteins": "protein" } }, { "input_text": "Sox-4 is important for very early B-cell differentiation , while TCF-1/LEF-1 play a crucial role in early thymocyte development .", "target_text": { "Sox-4": "protein", "TCF-1/LEF-1": "protein" } }, { "input_text": "TCF/LEF proteins have recently been found to constitute a downstream component of the Wingless/Wnt signal transduction pathway .", "target_text": { "TCF/LEF proteins": "protein" } }, { "input_text": "In flies , this pathway controls segment polarity ; in Xenopus it controls the definition of the body axis .", "target_text": {} }, { "input_text": "Deregulation of the pathway occurs in several human tumors .", "target_text": {} }, { "input_text": "These insights in the molecular events that are involved in TCF/LEF function in these organisms may eventually lead to the understanding of the function of these HMG box proteins in lymphoid development", "target_text": { "TCF/LEF": "protein", "HMG box proteins": "protein" } }, { "input_text": "Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes : application for diagnosis , genetic counseling , and therapy .", "target_text": { "androgen receptor": "protein", "androgen receptor gene": "DNA" } }, { "input_text": "Recent studies indicate that mutations in the androgen receptor gene are associated with androgen insensitivity syndromes , a heterogeneous group of related disorders involving defective sexual differentiation in karyotypic males .", "target_text": { "androgen receptor gene": "DNA" } }, { "input_text": "In this report , we address the possibility of rapid mutational analysis of the androgen receptor gene for initial diagnosis , genetic counseling , and molecular subclassification of affected patients and their families .", "target_text": { "androgen receptor": "protein", "androgen receptor gene": "DNA" } }, { "input_text": "DNA from peripheral blood leukocytes of six patients from five families with various degrees of androgen insensitivity was studied .", "target_text": { "DNA": "DNA", "peripheral blood leukocytes": "cell_type" } }, { "input_text": "Exons 2 to 8 of the androgen receptor gene were analyzed using a combination of single strand conformation polymorphism analysis and direct DNA sequencing .", "target_text": { "Exons 2 to 8": "DNA", "androgen receptor gene": "DNA" } }, { "input_text": "Female family members were also studied to identify heterozygote carriers .", "target_text": {} }, { "input_text": "Point mutations in the AR gene were identified in all six patients , and all mutations caused amino acid substitutions .", "target_text": { "AR gene": "DNA" } }, { "input_text": "One patient with incomplete androgen insensitivity was a mosaic for the mutation .", "target_text": {} }, { "input_text": "Four of the five mothers , as well as a young sister of one patient , were carriers of the mutation present in the affected child .", "target_text": {} }, { "input_text": "Our data show that new mutations may occur in the androgen receptor gene leading to sporadic androgen insensitivity syndrome .", "target_text": { "androgen receptor gene": "DNA" } }, { "input_text": "Molecular genetic characterization of the variant allele can serve as a primary tool for diagnosis and subsequent therapy , and can provide a basis for distinguishing heterozygous carriers in familial androgen resistance .", "target_text": { "variant allele": "DNA" } }, { "input_text": "The identification of carriers is of substantial clinical importance for genetic counseling .", "target_text": {} }, { "input_text": "Proliferation index as a prognostic marker in breast cancer .", "target_text": {} }, { "input_text": "BACKGROUND .", "target_text": {} }, { "input_text": "The proliferative activity of tumors has been extensively investigated with different approaches , among which the use of the monoclonal antibody Ki-67 represents an easy and reliable means of assessing cell proliferation .", "target_text": { "monoclonal antibody Ki-67": "protein" } }, { "input_text": "In this study , the proliferative activity of 129 primary breast cancers was investigated , and the results were related to prognosis .", "target_text": {} }, { "input_text": "METHODS .", "target_text": {} }, { "input_text": "Tumor samples , obtained from 129 patients who underwent surgery between January 1987 and December 1988 , were processed for staining by an immunohistochemical procedure ( avidin-biotin complex ) .", "target_text": { "avidin-biotin complex": "protein" } }, { "input_text": "The median time of observation was 42 months ( range , 31-55 months ) .", "target_text": {} }, { "input_text": "Life-table analysis ( Mantel-Cox ) was used to assess the probability of disease-free survival ( DFS ) and overall survival ( OS ) .", "target_text": {} }, { "input_text": "RESULTS .", "target_text": {} }, { "input_text": "Tumors with high Ki-67 proliferation indices ( > 20 % ) were associated with a higher 4-year probability of relapse of disease ( 55.3 % versus 79.1 % ; P = 0.003 ) and death ( 71 % versus 95.6 % ; P = 0.00005 ) when compared with tumors with low Ki-67 values .", "target_text": { "Ki-67": "protein" } }, { "input_text": "In addition , this proliferative parameter maintained its prognostic significance when the patients were stratified according to lymph node involvement , menopausal status , and nuclear estrogen receptor content .", "target_text": { "nuclear estrogen receptor": "protein" } }, { "input_text": "CONCLUSIONS .", "target_text": {} }, { "input_text": "Tumor proliferative activity as evaluated by the monoclonal antibody Ki-67 seems to be an effective indicator of prognosis in breast cancer for DFS and OS .", "target_text": { "monoclonal antibody Ki-67": "protein" } }, { "input_text": "Regulation of the Ets-related transcription factor Elf-1 by binding to the retinoblastoma protein .", "target_text": { "Ets-related transcription factor": "protein", "Elf-1": "protein", "retinoblastoma protein": "protein" } }, { "input_text": "The retinoblastoma gene product ( Rb ) is a nuclear phosphoprotein that regulates cell cycle progression .", "target_text": { "retinoblastoma gene product": "protein", "Rb": "protein", "nuclear phosphoprotein": "protein" } }, { "input_text": "Elf-1 is a lymphoid-specific Ets transcription factor that regulates inducible gene expression during T cell activation .", "target_text": { "Elf-1": "protein", "lymphoid-specific Ets transcription factor": "protein", "T cell": "cell_type" } }, { "input_text": "In this report , it is demonstrated that Elf-1 contains a sequence motif that is highly related to the Rb binding sites of several viral oncoproteins and binds to the pocket region of Rb both in vitro and in vivo .", "target_text": { "Elf-1": "protein", "Rb binding sites": "protein", "oncoproteins": "protein", "Rb": "protein" } }, { "input_text": "Elf-1 binds exclusively to the underphosphorylated form of Rb and fails to bind to Rb mutants derived from patients with retinoblastoma .", "target_text": { "Elf-1": "protein", "Rb": "protein", "Rb mutants": "protein" } }, { "input_text": "Co-immunoprecipitation experiments demonstrated an association between Elf-1 and Rb in resting normal human T cells .", "target_text": { "Elf-1": "protein", "Rb": "protein", "resting normal human T cells": "cell_type" } }, { "input_text": "After T cell activation , the phosphorylation of Rb results in the release of Elf-1 , which is correlated temporally with the activation of Elf-1 -mediated transcription .", "target_text": { "Rb": "protein", "Elf-1": "protein" } }, { "input_text": "Overexpression of a phosphorylation-defective form of Rb inhibited Elf-1 -dependent transcription during T cell activation .", "target_text": { "Rb": "protein", "Elf-1": "protein", "T cell": "cell_type" } }, { "input_text": "These results demonstrate that Rb interacts specifically with a lineage-restricted Ets transcription factor .", "target_text": { "Rb": "protein", "lineage-restricted Ets transcription factor": "protein" } }, { "input_text": "This regulated interaction may be important for the coordination of lineage-specific effector functions such as lymphokine production with cell cycle progression in activated T cells .", "target_text": { "lymphokine": "protein", "activated T cells": "cell_type" } }, { "input_text": "Human CD3-CD16+ natural killer cells express the hGATA-3 T cell transcription factor and an unrearranged 2.3-kb TcR delta transcript .", "target_text": { "Human CD3-CD16+ natural killer cells": "cell_line", "hGATA-3 T cell transcription factor": "protein", "2.3-kb TcR delta transcript": "protein" } }, { "input_text": "In this study we analyzed the T cell receptor ( TcR ) delta transcripts expressed by CD3-CD16+ cells and we investigated whether these cells expressed the hGATA-3 T cell transcription factor and the recombination-activating gene ( RAG ) -1 .", "target_text": { "T cell receptor ( TcR ) delta transcripts": "protein", "CD3-CD16+ cells": "cell_line", "hGATA-3 T cell transcription factor": "protein", "recombination-activating gene ( RAG ) -1": "DNA" } }, { "input_text": "Multiple TcR delta transcripts deriving from an unrearranged TcR delta gene were detected in both polyclonal and clonal CD3-CD16+ natural killer ( NK ) cell lines .", "target_text": { "TcR delta transcripts": "protein", "TcR delta gene": "DNA", "NK": "cell_type", "natural killer ( NK ) cell": "cell_type" } }, { "input_text": "Two unrearranged TcR delta transcripts had a size similar to that of the functional TcR delta mRNA ( 2.3 and 1.3 kb ) found in TcR gamma/delta+ T lymphocytes .", "target_text": { "TcR delta transcripts": "protein", "TcR delta mRNA": "RNA", "TcR gamma/delta+ T lymphocytes": "cell_line" } }, { "input_text": "Sequence analysis of nine different 2.3-kb cDNA clones obtained from NK-derived polyA+ RNA confirmed that they corresponded to an unrearranged TcR delta gene .", "target_text": { "TcR delta gene": "DNA" } }, { "input_text": "These cDNA were 2343 bp long and their transcription initiation site was located 814 bp upstream from the J delta 1 segment .", "target_text": { "814 bp upstream": "DNA", "J delta 1 segment": "DNA" } }, { "input_text": "The sequence located upstream of the J delta 1 segment corresponded to the previously reported germ-line sequence .", "target_text": { "J delta 1 segment": "DNA" } }, { "input_text": "The J delta 1 segment was correctly spliced to C delta ; in addition the four C delta exons were found to be already assembled .", "target_text": { "J delta 1 segment": "DNA", "C delta": "DNA" } }, { "input_text": "Two polyadenylation sites were present in the fourth C delta exon .", "target_text": { "fourth C delta exon": "DNA" } }, { "input_text": "However , only that located at the 3' end appeared to be utilized in the 2.3-kb cDNA .", "target_text": { "2.3-kb cDNA": "DNA" } }, { "input_text": "The expression of hGATA-3 , a T cell-specific factor known to be involved in the regulation of the transcription of TcR delta locus , was analyzed by Northern blot , in cultured NK cell population and clones ( but not in freshly derived cell populations ) .", "target_text": { "hGATA-3": "protein", "T cell-specific factor": "protein", "TcR delta locus": "DNA", "NK cell population": "cell_line" } }, { "input_text": "All NK clones and cell lines studied were found to express hGATA-3-specific mRNA , suggesting that hGATA-3 may be involved in the regulation of the unrearranged TcR delta gene expression in NK cells .", "target_text": { "NK clones": "cell_line", "hGATA-3-specific mRNA": "RNA", "hGATA-3": "protein", "TcR delta gene": "DNA", "NK cells": "cell_type" } }, { "input_text": "Finally , no transcription of the RAG-1 gene could be detected in all NK cell lines or clones analyzed .", "target_text": { "RAG-1 gene": "DNA", "NK cell lines": "cell_line" } }, { "input_text": "Negative transcriptional regulation of human interleukin 2 ( IL-2 ) gene by glucocorticoids through interference with nuclear transcription factors AP-1 and NF-AT .", "target_text": { "human interleukin 2": "protein", "IL-2": "protein", "human interleukin 2 ( IL-2 ) gene": "DNA", "nuclear transcription factors": "protein", "AP-1": "protein", "NF-AT": "protein" } }, { "input_text": "IL-2 gene transcription is affected by several nuclear proteins .", "target_text": { "IL-2 gene": "DNA", "nuclear proteins": "protein" } }, { "input_text": "We asked whether dexamethasone ( Dex ) and cyclosporin A ( CsA ) inhibit IL-2 gene transcription by interfering with the activity of nuclear proteins that bind to the IL-2 promoter .", "target_text": { "IL-2 gene": "DNA", "nuclear proteins": "protein" } }, { "input_text": "Nuclear extracts from primary human T lymphocytes were analyzed by electrophoretic DNA mobility shift assays .", "target_text": { "primary human T lymphocytes": "cell_type" } }, { "input_text": "Both Dex and CsA inhibited the binding of transcription factors AP-1 and NF-AT , but not of NF-kB and OCT-1/OAF , to their corresponding sites on the IL-2 gene promoter .", "target_text": { "AP-1": "protein", "NF-AT": "protein", "NF-kB": "protein", "OCT-1/OAF": "protein", "IL-2 gene promoter": "DNA" } }, { "input_text": "To correlate changes in nuclear factor binding in vitro with transcriptional activity in vivo and define the structural requirements for IL-2 promoter repression , we used transient DNA transfections .", "target_text": { "IL-2 promoter": "DNA" } }, { "input_text": "Jurkat cells were transfected with plasmids containing either the intact IL-2 promoter or its AP-1 , NF-AT , and NF-kB motifs .", "target_text": { "Jurkat cells": "cell_line", "plasmids": "DNA", "IL-2 promoter": "DNA" } }, { "input_text": "Dex inhibited the IL-2 promoter and the AP-1 , but not the NF-AT and NF-kB plasmids .", "target_text": { "IL-2 promoter": "DNA", "AP-1": "DNA", "NF-AT": "DNA", "NF-kB plasmids": "DNA" } }, { "input_text": "In contrast , CsA inhibited the IL-2 promoter and the NF-AT , but not the AP-1 and NF-kB plasmids .", "target_text": { "IL-2 promoter": "DNA", "NF-AT": "DNA", "AP-1": "DNA", "NF-kB plasmids": "DNA" } }, { "input_text": "These results suggest that in human T lymphocytes both Dex and CsA inhibited IL-2 gene transcription through interference with transcription factors AP-1 and NF-AT .", "target_text": { "human T lymphocytes": "cell_type", "IL-2 gene": "DNA", "transcription factors": "protein", "AP-1": "protein", "NF-AT": "protein" } }, { "input_text": "We propose that , while maximum inhibition may involve interaction with both transcription factors , AP-1 is the primary target of Dex .", "target_text": { "transcription factors": "protein", "AP-1": "protein" } }, { "input_text": "Nuclear factor kappa B , a mediator of lipopolysaccharide effects .", "target_text": { "Nuclear factor kappa B": "protein" } }, { "input_text": "Exposure of certain cell types to bacterial lipopolysaccharide ( LPS ) leads to activation of nuclear factor kappa B ( NF-kappa B ) , an inducible transcription factor .", "target_text": { "nuclear factor kappa B": "protein", "NF-kappa B": "protein", "inducible transcription factor": "protein" } }, { "input_text": "One of NF-kappa B 's unique properties is its posttranslational activation via release of an inhibitory subunit , called inhibitor of NF-kappa B ( I kappa B ) , from a sequestered cytoplasmic form .", "target_text": { "NF-kappa B": "protein", "inhibitory subunit": "protein", "inhibitor of NF-kappa B": "protein", "I kappa B": "protein", "sequestered cytoplasmic form": "protein" } }, { "input_text": "This event is also triggered under various other conditions of biomedical importance .", "target_text": {} }, { "input_text": "Other bacterial toxins , tumor necrosis factor-alpha ( TNF ) , interleukin-1 ( IL-1 ) , T cell mitogens , UV light , gamma rays and oxidative stress were reported to induce NF-kappa B .", "target_text": { "tumor necrosis factor-alpha": "protein", "TNF": "protein", "interleukin-1": "protein", "IL-1": "protein", "T cell mitogens": "protein", "NF-kappa B": "protein" } }, { "input_text": "The activated form of NF-kappa B , which is rapidly taken up into nuclei , initiates transcription from immediate early genes in a wide variety of cell types .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "Most of the target genes for NF-kappa B are of relevance for the immune response and can be grouped into those encoding cytokines , cell surface receptors , acute phase proteins and viral genomes , such as that of human immunodeficiency virus type 1 ( HIV-1 ) .", "target_text": { "NF-kappa B": "protein", "cytokines": "protein", "cell surface receptors": "protein", "acute phase proteins": "protein", "viral genomes": "DNA" } }, { "input_text": "We will discuss recent experimental evidences suggesting that LPS might share a pathway of NF-kappa B activation with other inducers of the factor .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "This common pathway may involve reactive oxygen intermediates ( ROI ) as messenger molecules .", "target_text": {} }, { "input_text": "[ The trend of molecular biology study on eosinophils ]", "target_text": { "eosinophils": "cell_type" } }, { "input_text": "Recently , many investigators have been interested in the study on eosinophil biology since genes association with eosinophils such as interleukin-5 or eosinophil granule proteins ( EPO , ECP , EDN , MBP , and CLC ) , were isolated .", "target_text": { "eosinophil": "cell_type", "eosinophils": "cell_type", "interleukin-5": "protein", "eosinophil granule proteins": "protein", "EPO": "protein", "ECP": "protein", "EDN": "protein", "MBP": "protein", "CLC": "protein" } }, { "input_text": "However , the molecular basis for the commitment of progenitors to the eosinophil lineage has not been determined .", "target_text": { "eosinophil lineage": "cell_type" } }, { "input_text": "The mechanism by which eosinophil-specific genes encoding primary and secondary granule proteins ( e.g. ECP , EDN , EPO , MBP , and CLC ) are expressed and regulated during eosinophilopoiesis is also unknown .", "target_text": { "eosinophil-specific genes": "DNA", "secondary granule proteins": "protein", "ECP": "protein", "EDN": "protein", "EPO": "protein", "MBP": "protein", "CLC": "protein" } }, { "input_text": "In this paper , I described the characterization of genes encoding eosinophil granule proteins and the mRNA expression of GATA-1 binding transcription factor during eosinophil differentiation .", "target_text": { "eosinophil granule proteins": "protein", "GATA-1 binding transcription factor": "protein" } }, { "input_text": "Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells ( NF-AT ) complex .", "target_text": { "lymphoid-specific nuclear factor": "protein", "activated T cells": "cell_type", "NF-AT": "protein" } }, { "input_text": "The lymphoid-specific transcription complex , NF-AT , is involved in early gene activation in T cells and is assembled from a pre-existing , T cell restricted cytoplasmic factor and an inducible ubiquitous nuclear component within 30 min after activation through the antigen receptor .", "target_text": { "lymphoid-specific transcription complex": "protein", "NF-AT": "protein", "T cells": "cell_type", "T cell restricted cytoplasmic factor": "protein", "ubiquitous": "protein", "nuclear component": "protein", "antigen receptor": "protein" } }, { "input_text": "Recent studies have implicated the family of AP1 factors as components of the murine NF-AT complex .", "target_text": { "AP1 factors": "protein", "murine NF-AT complex": "protein" } }, { "input_text": "Evidence is provided here that the nuclear component of human NF-AT contains the phorbol ester-inducible transcription factor AP1 ( Jun/Fos ) .", "target_text": { "human NF-AT": "protein", "phorbol ester-inducible transcription factor AP1": "protein", "Jun/Fos": "protein" } }, { "input_text": "We further characterize which AP1 family members can assume this role .", "target_text": { "AP1 family members": "protein" } }, { "input_text": "Antisera to Fos inhibits NF-AT DNA binding as does an oligonucleotide containing a binding site for AP1 .", "target_text": { "Fos": "protein", "NF-AT": "protein", "AP1": "protein", "binding site for AP1": "DNA" } }, { "input_text": "Constitutive expression in vivo of Fos , and to a lesser extent Fra-1 , eliminates the requirement for phorbol 12-myristate 13-acetate ( PMA ) stimulation , leaving NF-AT -directed transcription responsive to calcium ionophore alone .", "target_text": { "Fos": "protein", "Fra-1": "protein", "NF-AT": "protein" } }, { "input_text": "Overexpression of cJun or JunD , but not JunB , also eliminates the requirement for PMA , indicating that many but not all Jun- and Fos-related proteins functionally activate NF-AT -dependent transcription in the presence of the cytoplasmic component .", "target_text": { "cJun": "protein", "JunD": "protein", "JunB": "protein", "Jun- and Fos-related proteins": "protein", "NF-AT": "protein", "cytoplasmic component": "protein" } }, { "input_text": "NF-AT DNA binding can be reconstituted in vitro using semi-purified AP1 proteins mixed with cytosol from T lymphocytes .", "target_text": { "NF-AT": "protein", "semi-purified AP1 proteins": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "Fos proteins are not needed for this reconstitution , and although JunB is not functional , it can participate in the NF-AT DNA binding complex .", "target_text": { "JunB": "protein", "NF-AT DNA binding complex": "protein" } }, { "input_text": "Finally , we have partially purified the cytoplasmic component of NF-AT and show by elution and renaturation from SDS-polyacrylamide gel electrophoresis gels that it has a molecular mass between 94 and 116 kDa and may have multiple differentially modified forms .", "target_text": { "cytoplasmic component of NF-AT": "protein" } }, { "input_text": "Glucocorticoid receptors in mononuclear cells of patients with sepsis .", "target_text": { "Glucocorticoid receptors": "protein", "mononuclear cells": "cell_type" } }, { "input_text": "Glucocorticoid receptor ( GR ) hormone-binding activity was studied by a whole-cell method in mononuclear cells ( MNC ) from peripheral blood of 7 patients during the hemodynamic compensatory phase of sepsis .", "target_text": { "Glucocorticoid receptor": "protein", "GR": "protein", "mononuclear cells": "cell_type", "MNC": "cell_type" } }, { "input_text": "4 patients were receiving dopamine , which did not affect the GR count .", "target_text": { "GR": "protein" } }, { "input_text": "The patients ' plasma cortisol concentrations were normal or slightly elevated .", "target_text": {} }, { "input_text": "Despite a wide range , the mean GR count and affinity in MNC from septic patients did not differ from those in normal controls , suggesting that glucocorticoids could still be effective in the hemodynamic compensatory phase of sepsis .", "target_text": { "GR": "protein", "MNC": "cell_type" } }, { "input_text": "The impaired transcription factor AP-1 DNA binding activity in lymphocytes derived from subjects with some symptoms of premature aging .", "target_text": { "transcription factor AP-1": "protein", "lymphocytes": "cell_type" } }, { "input_text": "The study of human disorders known as premature aging syndromes may provide insight into the mechanisms of cellular senescence .", "target_text": {} }, { "input_text": "The main feature of cellular senescence in vitro is cessation of cell proliferation .", "target_text": {} }, { "input_text": "Down syndrome ( DS ) and neuronal ceroid-lypofuscinosis ( NCL ) are clinically characterized by the premature onset of numerous features normally associated with human aging .", "target_text": {} }, { "input_text": "Phytohemagglutinin stimulated lymphocytes derived from DS subjects showed a statistically significant diminished proliferation capacity in comparison with lymphocytes derived from NCL and healthy individuals .", "target_text": { "Phytohemagglutinin": "protein", "lymphocytes": "cell_type" } }, { "input_text": "We demonstrated , by applying the electrophoretic mobility shift assay , slightly impaired AP-1 DNA binding activity in NCL lymphocytes and strong in DS ones .", "target_text": { "AP-1": "protein", "NCL lymphocytes": "cell_type", "DS ones": "cell_type" } }, { "input_text": "Our results showed that the same molecular mechanisms of proliferation cessation could exist in fibroblasts characterized by replicative senescence and in lymphocytes derived from individuals with premature aging syndromes ( Down", "target_text": { "fibroblasts": "cell_type", "lymphocytes": "cell_type" } }, { "input_text": "Differential contribution of herpes simplex virus type 1 gene products and cellular factors to the activation of human immunodeficiency virus type 1 provirus .", "target_text": { "herpes simplex virus type 1 gene products": "protein", "cellular factors": "protein" } }, { "input_text": "We have previously reported that infection with herpes simplex virus type 1 ( HSV-1 ) activates expression of the human immunodeficiency virus type 1 ( HIV-1 ) provirus in T cells .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Activation of the HIV-1 provirus correlated with the activation of binding of 55- and 85- kDa proteins to the kappa B enhancer and binding of the 50-kDa HLP-1 protein to the LBP-1 sequences of the HIV-1 long terminal repeat .", "target_text": { "kappa B enhancer": "DNA", "50-kDa HLP-1 protein": "protein", "LBP-1 sequences": "DNA", "HIV-1 long terminal repeat": "DNA" } }, { "input_text": "Further examination of this system has shown that the inhibition of HSV-1 replication by the antiviral drug acyclovir does not inhibit HSV-1-mediated induction of HIV-1 provirus .", "target_text": {} }, { "input_text": "Surprisingly , the NF-kappa B and HLP-1 binding activities were substantially inhibited in acyclovir -treated cells .", "target_text": { "NF-kappa B": "protein", "acyclovir -treated cells": "cell_line" } }, { "input_text": "In the transient-transfection assay , ICP0 , but not ICP4 , activated the HIV-1 long terminal repeat promoter region and the effect of ICP0 was greatly enhanced in the presence of the NF-kappa B binding proteins , suggesting that induction of the HIV-1 provirus involves cooperation between the HSV-1-activated cellular factor , NF-kappa B , and the virus-encoded transactivator , ICP0 .", "target_text": { "ICP0": "protein", "ICP4": "protein", "HIV-1 long terminal repeat promoter region": "DNA", "NF-kappa B": "protein", "NF-kappa B binding proteins": "protein", "HSV-1-activated cellular factor": "protein", "virus-encoded transactivator": "protein" } }, { "input_text": "Transcriptional activation of the macrophage colony-stimulating factor gene by IL-2 is associated with secretion of bioactive macrophage colony-stimulating factor protein by monocytes and involves activation of the transcription factor NF-kappa B .", "target_text": { "macrophage colony-stimulating factor gene": "DNA", "IL-2": "protein", "macrophage colony-stimulating factor protein": "protein", "monocytes": "cell_type", "transcription factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "Human peripheral blood monocytes ( Mo ) constitutively display the beta-chain of the receptor for IL-2 , whereas expression of the IL-2R alpha-chain is not constitutive but inducible with IL-2 .", "target_text": { "Human peripheral blood monocytes": "cell_type", "Mo": "cell_type", "IL-2": "protein", "IL-2R alpha-chain": "protein" } }, { "input_text": "Here we report that binding of human IL-2 to its binding site leads to transcriptional activation of the macrophage CSF ( M-CSF ) gene in Mo resulting in accumulation of M-CSF mRNA and subsequent release of bioactive M-CSF protein as demonstrated by ELISA and inhibition of IL-2 induced release of an activity-stimulating growth of monocyte-type colonies by a neutralizing anti-M-CSF antibody .", "target_text": { "human IL-2": "protein", "M-CSF": "protein", "macrophage CSF ( M-CSF ) gene": "DNA", "Mo": "cell_type", "M-CSF mRNA": "RNA", "M-CSF protein": "protein", "IL-2": "protein", "monocyte-type colonies": "cell_line", "anti-M-CSF antibody": "protein" } }, { "input_text": "Transcriptional activation of the M-CSF gene by IL-2 is preceded by enhanced binding activity of the transcription factor NF-kappa B to its recognition sequence in the 5' regulatory enhancer region of the M-CSF gene .", "target_text": { "M-CSF gene": "DNA", "IL-2": "protein", "transcription factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "Moreover , using a heterologous promoter ( herpes thymidine kinase ) construct containing the NF-kappa B consensus sequence , it is shown that NF-kappa B binding by an IL-2 -induced monocyte-derived nuclear protein confers reporter gene ( human growth hormone ) activity .", "target_text": { "heterologous promoter": "DNA", "herpes thymidine kinase": "protein", "heterologous promoter ( herpes thymidine kinase ) construct": "DNA", "NF-kappa B": "protein", "NF-kappa B consensus sequence": "DNA", "IL-2": "protein", "IL-2 -induced monocyte-derived nuclear protein": "protein" } }, { "input_text": "Taken together , our findings indicate that IL-2 induces gene expression of M-CSF in human blood-derived Mo and provide evidence for involvement of NF-kappa B in transcriptional regulation of this gene .", "target_text": { "IL-2": "protein", "M-CSF": "protein", "Mo": "cell_type", "human blood-derived Mo": "cell_type", "NF-kappa B": "protein" } }, { "input_text": "Regulation of the interleukin-1 beta ( IL-1 beta ) gene by mycobacterial components and lipopolysaccharide is mediated by two nuclear factor-IL6 motifs .", "target_text": { "IL-1 beta": "protein", "interleukin-1 beta ( IL-1 beta ) gene": "DNA", "mycobacterial components": "protein", "nuclear factor-IL6 motifs": "DNA" } }, { "input_text": "The cytokines interleukin-1 beta ( IL-1 beta ) and tumor necrosis factor alpha ( TNF-alpha ) are released by mononuclear phagocytes in vitro after stimulation with mycobacteria and are considered to mediate pathophysiologic events , including granuloma formation and systemic symptoms .", "target_text": { "IL-1 beta": "protein", "TNF-alpha": "protein", "mononuclear phagocytes": "cell_type" } }, { "input_text": "We demonstrated that the Mycobacterium tuberculosis cell wall component lipoarabinomannan ( LAM ) is a very potent inducer of IL-1 beta gene expression in human monocytes and investigated the mechanism of this effect .", "target_text": { "IL-1 beta gene": "DNA", "human monocytes": "cell_type" } }, { "input_text": "We localized the LAM - , lipopolysaccharide ( LPS ) - , and TNF-alpha -inducible promoter activity to a -131/+15 ( positions -131 to +15 ) DNA fragment of the IL-1 beta gene by deletion analysis and chloramphenicol acetyltransferase assay .", "target_text": { "TNF-alpha": "protein", "-inducible promoter": "DNA", "IL-1 beta gene": "DNA", "chloramphenicol acetyltransferase": "protein" } }, { "input_text": "Within this DNA fragment , there were two novel 9-bp motifs ( -90/-82 and -40/-32 ) with high homology to the nuclear factor-IL6 ( NF-IL6 ) binding site .", "target_text": { "9-bp motifs": "DNA", "nuclear factor-IL6": "protein", "NF-IL6": "protein", "nuclear factor-IL6 ( NF-IL6 ) binding site": "DNA" } }, { "input_text": "Site-directed mutagenesis demonstrated that the two NF-IL-6 motifs could be independently activated by LAM , LPS , or TNF-alpha and that they acted in an orientation-independent manner .", "target_text": { "NF-IL-6 motifs": "DNA", "TNF-alpha": "protein" } }, { "input_text": "DNA mobility shift assay revealed specific binding of nuclear protein ( s ) from LAM- , LPS- , or TNF-alpha- stimulated THP-1 cells to the NF-IL6 motifs .", "target_text": { "nuclear protein": "protein", "NF-IL6 motifs": "DNA" } }, { "input_text": "We conclude that the two NF-IL6 sites mediate induction of IL-1 beta in response to the stimuli LAM , LPS , and TNF-alpha .", "target_text": { "NF-IL6 sites": "DNA", "IL-1 beta": "protein", "TNF-alpha": "protein" } }, { "input_text": "HIV-1 Nef protein inhibits the recruitment of AP-1 DNA-binding activity in human T-cells .", "target_text": { "HIV-1 Nef protein": "protein", "AP-1": "protein", "human T-cells": "cell_type" } }, { "input_text": "The human immunodeficiency virus type 1 long terminal repeat , HIV-1-LTR , contains binding sites for several cellular transcription factors which contribute to HIV-1 gene expression .", "target_text": { "human immunodeficiency virus type 1 long terminal repeat": "DNA", "HIV-1-LTR": "DNA", "HIV-1 gene": "DNA" } }, { "input_text": "Our previous studies on the function of the HIV-1-encoded Nef protein suggested that Nef may be an inhibitor HIV-1 transcription .", "target_text": { "HIV-1-encoded Nef protein": "protein", "Nef": "protein" } }, { "input_text": "To determine whether Nef affects the binding of cellular factors implicated in HIV-1 regulation , 32P-labeled oligonucleotides corresponding to the binding sites were incubated with nuclear extracts prepared from Nef-expressing T-cell lines that were not stimulated or were stimulated with T-cell mitogens .", "target_text": { "Nef": "protein", "cellular factors": "protein", "Nef-expressing T-cell lines": "cell_line", "T-cell mitogens": "protein" } }, { "input_text": "We found that Nef inhibited the recruitment of AP-1 DNA-binding activity in mitogen-stimulated human T-cells .", "target_text": { "Nef": "protein", "AP-1": "protein", "human T-cells": "cell_type" } }, { "input_text": "Additionally , Nef expressing cells were transiently transfected with a plasmid in which HIV-1 AP-1 DNA recognition sequences were cloned downstream of the chloramphenicol acetyltransferase ( CAT ) gene .", "target_text": { "Nef": "protein", "Nef expressing cells": "cell_line", "HIV-1 AP-1 DNA recognition sequences": "DNA", "chloramphenicol acetyltransferase": "protein", "CAT": "protein", "chloramphenicol acetyltransferase ( CAT ) gene": "DNA" } }, { "input_text": "Mitogen-mediated transcriptional activation of the CAT gene in this construct was inhibited in Nef -expressing cells but not in control cells .", "target_text": { "CAT gene": "DNA", "Nef": "protein", "Nef -expressing cells": "cell_line" } }, { "input_text": "These studies suggest that , by inhibiting AP-1 activation , Nef may play a role in regulating HIV-1 gene expression in infected T-cells .", "target_text": { "AP-1": "protein", "Nef": "protein", "HIV-1 gene": "DNA", "infected T-cells": "cell_type" } }, { "input_text": "Regulation of the beta-globin locus .", "target_text": { "beta-globin locus": "DNA" } }, { "input_text": "Transcription of the human beta-globin gene cluster depends upon upstream regulatory sequences , which are collectively termed the locus control region .", "target_text": { "human beta-globin gene cluster": "DNA", "upstream regulatory sequences": "DNA", "locus control region": "DNA" } }, { "input_text": "Recent studies have provided new insights into how the individual genes of the cluster are regulated through development .", "target_text": {} }, { "input_text": "The crux of transcriptional activation is how the locus control region communicates with the gene-proximal regulatory elements .", "target_text": { "locus control region": "DNA", "gene-proximal regulatory elements": "DNA" } }, { "input_text": "Enhancing effect of 17 beta-estradiol on human NK cell activity .", "target_text": {} }, { "input_text": "The in vitro effect of 17 beta-estradiol on NK activity was studied .", "target_text": {} }, { "input_text": "The proliferation and NK activity of YT-N17 ( a human NK-like cell line ) were enhanced by 17 beta-estradiol ( E2 ) , and the enhancement was blocked by tamoxifen ( Tx ) , an antagonist of E2 .", "target_text": { "YT-N17": "cell_line", "human NK-like cell line": "cell_line" } }, { "input_text": "On the contrary , other steroid hormones such as Tx , progesterone , and testosterone had no effect .", "target_text": {} }, { "input_text": "YT-N17 contained 11.8 fmol/mg protein of estrogen receptor ( mean of two independent assays ) , a value which was 5-10-fold higher than that of other hematopoietic cell lines .", "target_text": { "YT-N17": "cell_line", "estrogen receptor": "protein", "hematopoietic cell lines": "cell_line" } }, { "input_text": "An enhancement of NK activity by E2 was also seen in large granular lymphocytes obtained from normal subjects , and it was again suppressed by Tx .", "target_text": { "large granular lymphocytes": "cell_type" } }, { "input_text": "These data suggest that E2 is one of the activating factors for NK/LGL cells .", "target_text": { "NK/LGL cells": "cell_line" } }, { "input_text": "A serum response element and a binding site for NF-Y mediate the serum response of the human thrombospondin 1 gene .", "target_text": { "serum response element": "DNA", "NF-Y": "protein", "binding site for NF-Y": "DNA", "human thrombospondin 1 gene": "DNA" } }, { "input_text": "The expression of thrombospondin 1 ( TSP 1 ) , a member of the TSP gene family , is rapidly induced by growth factors .", "target_text": { "thrombospondin 1": "protein", "TSP 1": "protein", "TSP gene family": "DNA" } }, { "input_text": "We tested the ability of human TSP 1 -chloramphenicol acetyltransferase constructs to respond to serum in stably transfected NIH-3T3 cells .", "target_text": { "TSP 1": "protein", "-chloramphenicol acetyltransferase": "protein", "human TSP 1 -chloramphenicol acetyltransferase constructs": "DNA" } }, { "input_text": "Two transcriptional elements in the TSP 1 promoter , a distal element at -1280 and a proximal element at -65 , were required for the response of the human TSP 1 gene to serum .", "target_text": { "TSP 1": "protein" } }, { "input_text": "The distal element contains the 5'-CC(A + T)6GG-3' consensus sequence characteristic of a serum-response element ( SRE ) .", "target_text": {} }, { "input_text": "Deletions or mutations in this element reduced the serum response of the TSP 1 gene by 80-90 % .", "target_text": { "TSP 1 gene": "DNA" } }, { "input_text": "In gel-shift assays , the -1280 element and the c-fos SRE cross -competed , whereas their functional and binding mutants did not .", "target_text": { "-1280 element": "DNA", "c-fos SRE cross": "DNA", "binding mutants": "DNA" } }, { "input_text": "The proximal element contains the sequence 5'-GGCCAATGGG-3' , which closely resembles the consensus binding motif for the CCAAT-binding factor NF-Y ( CBF , CP1 , alpha CP1 ) .", "target_text": { "proximal element": "DNA", "CCAAT-binding factor": "DNA", "NF-Y": "protein", "CBF": "protein", "CP1": "protein", "alpha CP1": "protein" } }, { "input_text": "Deletions or mutations in this element also reduced the serum response by 80-90 % .", "target_text": {} }, { "input_text": "Methylation interference analysis of the -65 region identified a pattern of contacts with nuclear factors resembling that for NF-Y , and an NF-Y -binding site and the proximal TSP 1 element cross-competed in gel-shift assays , whereas their binding mutants did not .", "target_text": { "-65 region": "DNA", "nuclear factors": "protein", "NF-Y": "protein", "NF-Y -binding site": "DNA", "proximal TSP 1 element": "DNA", "binding mutants": "DNA" } }, { "input_text": "Finally , an abbreviated TSP 1 promoter/5'-flank , containing the SRE- and NF-Y- binding sites , mediated a serum response that was close in magnitude to that of the parent promoter .", "target_text": { "abbreviated TSP 1 promoter/5'-flank": "DNA", "parent promoter": "DNA" } }, { "input_text": "We conclude that the serum response of the human TSP 1 gene requires the coordinated function of an SRE- and NF-Y- binding site .", "target_text": { "TSP 1 gene": "DNA" } }, { "input_text": "Cell-type-specific transactivation of the parathyroid hormone-related protein gene promoter by the human T-cell leukemia virus type I ( HTLV-I ) tax and HTLV-II tax proteins .", "target_text": { "parathyroid hormone-related protein gene promoter": "DNA", "human T-cell leukemia virus type I ( HTLV-I ) tax": "protein", "HTLV-II tax proteins": "protein" } }, { "input_text": "The human T-cell leukemia virus type I ( HTLV-I ) and HTLV-II Tax proteins are potent transactivators of viral and cellular gene expression .", "target_text": { "transactivators": "protein" } }, { "input_text": "Using deletion mutants , the downstream parathyroid hormone-related protein ( PTHrP ) promoter is shown to be responsive to both HTLV-I and HTLV-II Tax as well as the AP1/c-jun proto-oncogene .", "target_text": { "deletion mutants": "DNA", "parathyroid hormone-related protein": "protein", "PTHrP": "protein", "parathyroid hormone-related protein ( PTHrP ) promoter": "DNA", "AP1/c-jun proto-oncogene": "DNA" } }, { "input_text": "Transactivation of PTHrP by Tax was seen in T cells but not in B-cell lines or fibroblasts .", "target_text": { "PTHrP": "protein", "Tax": "protein", "T cells": "cell_type", "B-cell lines": "cell_line", "fibroblasts": "cell_line" } }, { "input_text": "A carboxy terminal Tax deletion mutant was deficient in transactivation of both the PTHrP and IL2R alpha promoters but not the HTLV-I long terminal repeat ( LTR ) .", "target_text": { "carboxy terminal Tax deletion mutant": "DNA", "HTLV-I long terminal repeat": "DNA", "LTR": "DNA" } }, { "input_text": "Exogenous provision of NFkB rescued IL2R alpha expression but not the PTHrP promoter .", "target_text": { "NFkB": "protein", "IL2R": "protein", "PTHrP": "protein", "PTHrP promoter": "DNA" } }, { "input_text": "Thus , HTLV-I Tax , HTLV-II Tax , and c-jun transactivate PTHrP and may contribute to the pathogenesis of hypercalcemia in adult T-cell leukemia .", "target_text": { "HTLV-I Tax": "protein", "HTLV-II Tax": "protein", "c-jun": "protein", "PTHrP": "protein" } }, { "input_text": "Involvement of Alu sequences in the cell-specific regulation of transcription of the gamma chain of Fc and T cell receptors .", "target_text": { "Alu sequences": "DNA", "gamma chain": "protein", "Fc": "protein", "T cell receptors": "protein" } }, { "input_text": "The Fc epsilon RI-gamma chains are expressed in a variety of hematopoietic cells where they play a critical role in signal transduction .", "target_text": { "Fc epsilon RI-gamma chains": "protein", "hematopoietic cells": "cell_type" } }, { "input_text": "They are part of the high affinity IgE receptor in mast cells , basophils , Langerhans cells , and possibly other cells ; a component of the low affinity receptor for IgG ( Fc gamma RIIIA or CD16 ) in natural killer cells and macrophages ; and part of the T cell antigen receptor in subsets of T cells .", "target_text": { "high affinity IgE receptor": "protein", "mast cells": "cell_type", "basophils": "cell_type", "Langerhans cells": "cell_type", "IgG": "protein", "Fc gamma RIIIA": "protein", "CD16": "protein", "killer cells": "cell_type", "macrophages": "cell_type", "T cell antigen receptor": "protein", "T cells": "cell_type" } }, { "input_text": "Here we have investigated the transcriptional regulation of the gamma chain gene by analyzing the 2.5-kilobase sequence upstream of the transcription start site .", "target_text": { "gamma chain": "protein", "2.5-kilobase sequence": "DNA", "transcription start site": "DNA" } }, { "input_text": "This sequence contains a promoter specific to cells of hematopoietic lineage .", "target_text": { "promoter": "DNA", "cells of hematopoietic lineage": "cell_type" } }, { "input_text": "However , the tissue specificity of this promoter is only partial because it is active in all of the hematopoietic cells tested here , regardless of whether they constitutively express Fc epsilon RI- gamma chain transcripts .", "target_text": { "promoter": "DNA", "hematopoietic cells": "cell_type", "gamma chain": "protein" } }, { "input_text": "We have identified two adjacent cis-acting regulatory elements , both of which are part of an Alu repeat .", "target_text": {} }, { "input_text": "The first ( -445/-366 ) is a positive element active in both basophils and T cells .", "target_text": { "basophils": "cell_type", "T cells": "cell_type" } }, { "input_text": "The second ( -365/-264 ) binds to nuclear factors , which appear to be different in basophils and T cells , and acts as a negative element in basophils and as a positive one in T cells .", "target_text": { "nuclear factors": "protein", "basophils": "cell_type", "T cells": "cell_type" } }, { "input_text": "Thus , this Alu repeat ( 90 % identical to Alu consensus sequences ) has evolved to become both a positive and negative regulator .", "target_text": { "Alu repeat": "DNA", "Alu consensus sequences": "DNA" } }, { "input_text": "Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system .", "target_text": {} }, { "input_text": "1 . Blood cell receptors in volunteers with moderately increased body burdens .", "target_text": { "Blood cell receptors": "protein" } }, { "input_text": "Using monoclonal antibodies ( mAbs ) and flow cytometry , we studied a variety of surface receptors on lymphocyte subpopulations of workers with moderately increased body burdens of 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD ) and of other polychlorinated dibenzo-p-dioxins and dibenzofurans ( PCDD/PCDF ) , expressed here as International-Toxicity Equivalencies ( I-TE ) .", "target_text": { "monoclonal antibodies": "protein", "mAbs": "protein", "surface receptors": "protein", "lymphocyte subpopulations": "cell_type" } }, { "input_text": "The hypothesis to be tested was whether or not humans exhibit a similar susceptibility to PCDDs/PCDFs with respect to the surface receptors found previously to respond to small doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD ) in Callithrix jacchus .", "target_text": { "surface receptors": "protein" } }, { "input_text": "These are : helper-inducer ( memory ) T cells ( CD4+CD45R0+CD45RA-CD29highCD11a+ ) , CD20+ B cells , and cytotoxic T cells ( CD8+CD56+/CD57+ ) .", "target_text": { "T cells": "cell_type", "helper-inducer ( memory ) T cells": "cell_type", "CD4+CD45R0+CD45RA-CD29highCD11a+": "cell_type", "CD20+ B cells": "cell_type", "cytotoxic T cells": "cell_type", "CD8+CD56+/CD57+": "cell_type" } }, { "input_text": "Furthermore , 68 triple-labellings with mAbs were performed on the cells of each volunteer to possibly generate further hypotheses .", "target_text": { "mAbs": "protein" } }, { "input_text": "It was evaluated whether any of the variables might be used as a biomarker of effects for this class of compounds .", "target_text": {} }, { "input_text": "There were two main goals : ( 1 ) to evaluate whether workers with a moderately increased PCDD/PCDF -body burden [ 25-140 ppt TCDD or 104-522 ppt I-TE in blood fat ] exhibit changes in the surface receptors of white blood cells , as observed in previous studies in non-human primates , and ( 2 ) to clarify whether persons at the upper range [ 10-23 ppt TCDD or 30-90 ppt I-TE in blood fat ] of the body burden reference values of a not particularly exposed population show detectable deviations in these immunological variables , when compared with persons at the lower and medium range [ 1-3 ppt TCDD or 9-29 ppt I-TE ] of these body burden reference values .", "target_text": { "surface receptors": "protein", "white blood cells": "cell_type" } }, { "input_text": "Regression analysis of our data revealed slight trends for some of the biomarkers ( e.g. CD45R0+ ) .", "target_text": {} }, { "input_text": "With one exception , these were all increases .", "target_text": {} }, { "input_text": "None of the alterations observed are of medical relevance .", "target_text": {} }, { "input_text": "The slight increase in the percentage of CD4+CD45R0+ cells remained significant even after covariant analysis taking age-related changes into account .", "target_text": { "CD4+CD45R0+ cells": "cell_type" } }, { "input_text": "Altogether , the data do not provide any evidence to support an assumption that moderately increased body burdens of PCDDs/PCDFs in adults induce decreases in the cellular components of the human immune system .", "target_text": {} }, { "input_text": "Adult humans certainly are less susceptible to this action of PCDDs/PCDFs than adolescent Callithrix jacchus", "target_text": {} }, { "input_text": "Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone ( DHEA ) and an analog of DHEA .", "target_text": {} }, { "input_text": "The initial infection with human immunodeficiency virus type 1 ( HIV-1 ) in most individuals usually results in the establishment of a latent or chronic infection before eventual progression toward acquired immunodeficiency syndrome .", "target_text": {} }, { "input_text": "HIV-1 can also establish a latent or persistent infection in some T cell lines that show minimal constitutive virus expression .", "target_text": { "T cell lines": "cell_line" } }, { "input_text": "However , activation of the T cell lines leading to enhanced HIV-1 replication can be induced by antigens , mitogens , and cytokines ( tumor necrosis factor alpha [ TNF-alpha ] , interleukin 1 , and interleukin-2 ) .", "target_text": { "T cell lines": "cell_line", "antigens": "protein", "cytokines": "protein", "tumor necrosis factor alpha": "protein", "TNF-alpha": "protein", "interleukin 1": "protein", "interleukin-2": "protein" } }, { "input_text": "Various gene products from other viruses ( HTLV-1 , HSV , EBV , CMV , HBV , and HHV-6 ) can also enhance HIV-1 long terminal repeat ( LTR ) -driven reporter gene activity .", "target_text": { "long terminal repeat": "DNA", "LTR": "DNA", "reporter gene": "DNA" } }, { "input_text": "On the basis of these observations , it has been proposed that reactivation of latent HIV-1 harbored in chronically infected T lymphocytes , monocytes , or macrophages plays an important role in the pathogenesis of AIDS .", "target_text": { "chronically infected T lymphocytes": "cell_type", "monocytes": "cell_type", "macrophages": "cell_type" } }, { "input_text": "So far , there are no drugs or therapy available that can provide protection against HIV-1 latency reactivation .", "target_text": {} }, { "input_text": "ACH-2 , derived from a human T cell line ( CEM ) , is chronically infected with HIV-1 , with low levels of constitutive virus expression .", "target_text": { "ACH-2": "cell_line", "human T cell line": "cell_line", "CEM": "cell_line" } }, { "input_text": "ACH-2 can be converted to productive infection by stimulation of the cells with 12-O-tetradecanoylphorbol-13-acetate ( TPA ) , mitogen or cytokines ( TNF-alpha ) , or infection with HSV .", "target_text": { "ACH-2": "cell_line", "cytokines": "protein", "TNF-alpha": "protein" } }, { "input_text": "Therefore the ACH-2 cell line is a good candidate for studying the effects of drugs on HIV-1 activation .", "target_text": { "ACH-2": "cell_line" } }, { "input_text": "Previously , we have reported that DHEA and synthetic analogs of DHEA can be modest inhibitors of HIV-1 IIIB replication in phytohemagglutinin-stimulated peripheral blood lymphocyte cultures .", "target_text": { "phytohemagglutinin-stimulated peripheral blood lymphocyte cultures": "cell_line" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "Occurrence of a silencer of the interleukin-2 gene in naive but not in memory resting T helper lymphocytes .", "target_text": { "silencer": "DNA", "interleukin-2": "protein", "interleukin-2 gene": "DNA", "memory resting T helper lymphocytes": "cell_type" } }, { "input_text": "In the immune system the first activation of a naive T cell by antigen is a key step in the shaping of the peripheral T cell specificity repertoire and maintenance of self-tolerance .", "target_text": { "naive T cell": "cell_type" } }, { "input_text": "In the present study , analysis of the interleukin-2 ( IL-2 ) gene activation shows that naive human helper T cells ( cord blood CD4+ T cells , adult CD4+CD45RO- T cells ) regulate IL-2 transcription by a mechanism involving both a silencer and an activator acting on the purine-rich IL-2 promoter elements ( NF-AT binding sites ) .", "target_text": { "interleukin-2": "protein", "IL-2": "protein", "interleukin-2 ( IL-2 ) gene": "DNA", "naive human helper T cells": "cell_type", "cord blood CD4+ T cells": "cell_type", "adult CD4+CD45RO- T cells": "cell_type", "silencer": "DNA", "activator": "DNA", "purine-rich IL-2 promoter elements": "DNA", "NF-AT binding sites": "DNA" } }, { "input_text": "By contrast , memory cells , either in vitro activated helper T cells reverting to a resting state , or CD4+ T ( memory ) clones , or CD4+CD45RO+ T cells isolated ex vivo , no longer have a silencer .", "target_text": { "vitro activated helper T cells": "cell_line", "CD4+ T ( memory ) clones": "cell_line", "CD4+CD45RO+ T cells": "cell_line", "silencer": "DNA" } }, { "input_text": "Their IL-2 transcription seems to be controlled solely by the transition from inactive to active functional state of a positive transcription factor binding to these promoter elements as well as its cytoplasmic or nuclear location : in resting memory T cells the activator is located in the cytoplasm and is inactive , whereas in stimulated cells it is functional in promoting transcription and now resides in the nucleus .", "target_text": { "IL-2": "protein", "positive transcription factor": "protein", "resting memory T cells": "cell_type", "activator": "DNA", "stimulated cells": "cell_line" } }, { "input_text": "Thus , the regulation of the gene coding for the main T cell growth factor changes irreversibly after the first encounter of T cells with antigen .", "target_text": { "T cell growth factor": "protein" } }, { "input_text": "It is most likely that the presence of a silencer contributes to the more stringent activation requirements of naive CD4+ T cells .", "target_text": { "silencer": "DNA", "naive CD4+ T cells": "cell_type" } }, { "input_text": "Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils : potential role in gene transcription .", "target_text": { "mRNA": "RNA", "GATA-binding proteins": "protein", "human eosinophils": "cell_type", "basophils": "cell_type" } }, { "input_text": "The expression of the hematopoietic transcription factors GATA-1 , GATA-2 , and GATA-3 was studied in eosinophils and basophils .", "target_text": { "hematopoietic transcription factors": "protein", "GATA-1": "protein", "GATA-2": "protein", "GATA-3": "protein", "eosinophils": "cell_type", "basophils": "cell_type" } }, { "input_text": "Eosinophils express mRNA for GATA-1 , GATA-2 , and GATA-3 .", "target_text": { "Eosinophils": "cell_type", "mRNA": "RNA", "GATA-1": "protein", "GATA-2": "protein", "GATA-3": "protein" } }, { "input_text": "Basophils express GATA-2 and GATA-3 .", "target_text": { "Basophils": "cell_type", "GATA-2": "protein", "GATA-3": "protein" } }, { "input_text": "Treatment of HL-60 eosinophilic sublines with either interleukin-5 or butyric acid increased the expression of GATA-1 mRNA concomitant with the expression of eosinophil-specific genes , whereas levels of GATA-2 mRNA remained relatively constant .", "target_text": { "HL-60 eosinophilic sublines": "cell_line", "interleukin-5": "protein", "GATA-1": "protein", "GATA-1 mRNA": "RNA", "eosinophil-specific genes": "DNA", "GATA-2": "protein", "GATA-2 mRNA": "RNA" } }, { "input_text": "The presence of mRNA for these proteins in eosinophils and basophils suggests that gene transcription in these lineages may be regulated by GATA-binding proteins .", "target_text": { "mRNA": "RNA", "eosinophils": "cell_type", "basophils": "cell_type", "GATA-binding proteins": "protein" } }, { "input_text": "Oxidoreductive regulation of nuclear factor kappa B .", "target_text": { "nuclear factor kappa B": "protein" } }, { "input_text": "Involvement of a cellular reducing catalyst thioredoxin .", "target_text": { "thioredoxin": "protein" } }, { "input_text": "We have investigated an oxidoreductive regulatory pathway for the DNA binding activity of a pleiotropic cellular transcription factor , nuclear factor kappa B ( NF kappa B ) , has been investigated by using NF kappa B prepared from the nucleus and the cytosol of the primary human T lymphocytes .", "target_text": { "pleiotropic cellular transcription factor": "protein", "nuclear factor kappa B": "protein", "NF kappa B": "protein", "primary human T lymphocytes": "cell_type" } }, { "input_text": "We show that a cellular reducing catalyst thioredoxin ( Trx ) plays a major role in activation of the DNA binding of NF kappa B in vitro and stimulation of transcription from the NF kappa B -dependent gene expression .", "target_text": { "thioredoxin": "protein", "Trx": "protein", "NF kappa B": "protein" } }, { "input_text": "We demonstrate evidence suggesting that redox regulation of NF kappa B by Trx might be exerted at a step after dissociation of the inhibitory molecule I kappa B , a cytosolic-anchoring protein for NF kappa B .", "target_text": { "NF kappa B": "protein", "Trx": "protein", "I kappa B": "protein", "cytosolic-anchoring protein": "protein" } }, { "input_text": "To examine the effect of Trx in intact cells , we performed transient assay with a chloramphenicol acetyltransferase -expressing plasmid under the control of human immunodeficiency virus ( HIV ) long terminal repeat and an effector plasmid expressing human Trx .", "target_text": { "Trx": "protein", "chloramphenicol acetyltransferase": "protein", "chloramphenicol acetyltransferase -expressing plasmid": "DNA", "human immunodeficiency virus ( HIV ) long terminal repeat": "DNA", "effector plasmid": "DNA", "human Trx": "protein" } }, { "input_text": "The promoter activity from HIV long terminal repeat was greatly augmented by co-transfecting the Trx-expressing plasmid , whose effect was dependent on the NF kappa B -binding sites .", "target_text": { "HIV long terminal repeat": "DNA", "Trx-expressing plasmid": "DNA", "NF kappa B": "protein" } }, { "input_text": "These findings have suggested that cysteine residue ( s ) of NF kappa B might be involved in the DNA-recognition by NF kappa B and that the redox control mechanism mediated by Trx might have a regulatory role in the NF kappa B -mediated gene expression .", "target_text": { "NF kappa B": "protein", "Trx": "protein" } }, { "input_text": "These results may also provide a clue to understanding of the molecular process of AIDS pathogenesis and its possible biochemical intervention .", "target_text": {} }, { "input_text": "Synergism between the CD3 antigen- and CD2 antigen- derived signals .", "target_text": {} }, { "input_text": "Exploration at the level of induction of DNA-binding proteins and characterization of the inhibitory activity of cyclosporine .", "target_text": { "DNA-binding proteins": "protein" } }, { "input_text": "We have demonstrated earlier that the crosslinkage of the CD3/TCR complex with the CD2 antigen results in the proliferation of normal human T cells .", "target_text": { "CD3/TCR complex": "protein", "CD2 antigen": "protein", "normal human T cells": "cell_type" } }, { "input_text": "The effect of this synergism was perceptible at the level of induction of the IL-2 gene , a process critical for T cell growth .", "target_text": { "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "To further understand the molecular and nuclear basis for this synergism , we have explored the induction of DNA-binding proteins in highly purified normal human T cells signaled via the CD3 and/or CD2 proteins .", "target_text": { "DNA-binding proteins": "protein", "normal human T cells": "cell_type", "CD3": "protein", "CD2 proteins": "protein" } }, { "input_text": "The effect of transmembrane signaling of T cells with ionomycin , and/or sn-1 , 2 dioctanoyl glycerol , was also determined .", "target_text": { "T cells": "cell_type" } }, { "input_text": "The emergence of nuclear binding proteins was investigated using interleukin-2 sequence specific oligonucleotide probes in the electrophoretic mobility shift assay .", "target_text": { "nuclear binding proteins": "protein", "interleukin-2": "protein", "interleukin-2 sequence specific oligonucleotide probes": "DNA" } }, { "input_text": "Our studies demonstrate for the first time that CD3 antigen-derived signals and CD2 antigen -derived signals are synergistic in inducing the emergence of transcription factors that bind to the NF-AT1 , AP-1 , and NF-kB sites located in the promoter/enhancer region of the IL-2 gene .", "target_text": { "CD3": "protein", "CD2 antigen": "protein", "transcription factors": "protein", "promoter/enhancer region": "DNA", "IL-2": "protein" } }, { "input_text": "Moreover , cyclosporine , at concentrations readily accomplished in clinical practice , was found to inhibit the emergence of these DNA-binding proteins in normal human T cells signaled via cell surface proteins implicated in antigen-dependent T cell activation and in T cells stimulated by mobilization of cellular calcium and activation of protein kinase C .", "target_text": { "DNA-binding proteins": "protein", "T cells": "cell_type", "normal human T cells": "cell_type", "protein kinase C": "protein" } }, { "input_text": "Induced myeloid differentiation of K562 cells with downregulation of erythroid and megakaryocytic transcription factors : a novel experimental model for hemopoietic lineage restriction .", "target_text": { "K562 cells": "cell_line" } }, { "input_text": "The human erythroleukemia cell line K562 can be induced to differentiate along the erythroid and megakaryocytic lineages .", "target_text": { "human erythroleukemia cell line K562": "cell_line" } }, { "input_text": "Here we demonstrate that hexamethylene bisacetamide ( HMBA ) induced K562 cells to differentiate along a third pathway .", "target_text": { "K562 cells": "cell_line" } }, { "input_text": "This was accompanied by downregulation of two transcription factors normally expressed in erythroid , mast and megakaryocyte lineages .", "target_text": { "transcription factors": "protein" } }, { "input_text": "Northern analysis demonstrated coordinate downregulation of alpha globin and gamma globin in addition to the two lineage-restricted transcription factors , SCL and GATA-1 .", "target_text": { "alpha globin": "protein", "gamma globin": "protein", "transcription factors": "protein", "SCL": "protein", "GATA-1": "protein" } }, { "input_text": "Proliferation of the K562 cells was also suppressed .", "target_text": { "K562 cells": "cell_line" } }, { "input_text": "Clonal assay showed that the suppression was irreversible and appeared analogous to the commitment of murine erythroleukemia ( MEL ) cells to terminal differentiation .", "target_text": { "murine erythroleukemia ( MEL ) cells": "cell_line" } }, { "input_text": "In contrast to MEL cells , however , K562 cells acquired a macrophage-like morphology and exhibited a complete failure to generate benzidine-positive cells .", "target_text": { "MEL cells": "cell_line", "K562 cells": "cell_line", "benzidine-positive cells": "cell_line" } }, { "input_text": "Electron microscopy revealed a marked increase in granules resembling those specific for eosinophils .", "target_text": { "eosinophils": "cell_type" } }, { "input_text": "Surface marker analysis showed that HMBA-induced cells expressed reduced levels of glycophorin A , CD5 , CD7 and CD11b .", "target_text": { "HMBA-induced cells": "cell_line", "glycophorin A": "protein", "CD5": "protein", "CD7": "protein", "CD11b": "protein" } }, { "input_text": "No upregulation of megakaryocyte or lymphoid markers occurred .", "target_text": {} }, { "input_text": "Thus the response of K562 cells to HMBA may provide a useful experimental system for studying the molecular mechanisms responsible for downmodulation of lineage-restricted transcription factors during hemopoietic lineage commitment .", "target_text": { "K562 cells": "cell_line", "transcription factors": "protein" } }, { "input_text": "Activation of primary human T-lymphocytes through CD2 plus CD28 adhesion molecules induces long-term nuclear expression of NF-kappa B .", "target_text": { "primary human T-lymphocytes": "cell_type", "CD2 plus CD28 adhesion molecules": "protein", "NF-kappa B": "protein" } }, { "input_text": "Stimulation of highly purified human T-cells via CD2 and CD28 adhesion molecules induces and maintains proliferation for more than 3 weeks .", "target_text": { "highly purified human T-cells": "cell_type" } }, { "input_text": "This potent interleukin 2 ( IL-2 ) -dependent activation does not require monocytes or accessory cells .", "target_text": { "interleukin 2": "protein", "IL-2": "protein", "monocytes": "cell_type", "accessory cells": "cell_type" } }, { "input_text": "Long-lasting IL-2 receptivity is associated with high-level expression of the inducible IL-2 receptor alpha chain ( IL-2R alpha ) gene that is regulated at both transcriptional and posttranscriptional levels .", "target_text": { "IL-2": "protein", "IL-2 receptor alpha chain": "protein", "IL-2R alpha": "protein", "IL-2 receptor alpha chain ( IL-2R alpha ) gene": "DNA" } }, { "input_text": "Increase of IL-2R alpha gene transcription involves the enhanced binding of the transcription factor NF-kappa B to its consensus sequence in the 5'-regulatory region of the IL-2R alpha gene .", "target_text": { "IL-2R alpha": "protein", "IL-2R alpha gene": "DNA", "NF-kappa B": "protein", "consensus sequence": "DNA", "5'-regulatory region": "DNA" } }, { "input_text": "To dissect the molecular basis for the unusually persistent transcription of the IL-2R alpha gene , we analyzed nuclear NF-kappa B binding to a radiolabeled IL-2R alpha kappa B-specific oligonucleotide probe during the time course of CD2 + CD28 activation .", "target_text": { "IL-2R alpha": "protein", "IL-2R alpha gene": "DNA", "NF-kappa B": "protein", "CD2": "protein", "CD28": "protein" } }, { "input_text": "Resting T-cell nuclear extracts contained KBF1/p50 homodimer .", "target_text": { "KBF1/p50 homodimer": "protein" } }, { "input_text": "After stimulation , two new kappa B-specific complexes were identified as NF-kappa B p50-p65 heterodimer and putative c-Rel homodimer or c-Rel-p65 heterodimer .", "target_text": { "kappa B-specific complexes": "protein", "NF-kappa B": "protein", "p50-p65 heterodimer": "protein", "c-Rel homodimer": "protein", "c-Rel-p65 heterodimer": "protein" } }, { "input_text": "Both inducible complexes persisted for at least 3 weeks .", "target_text": {} }, { "input_text": "Their relative levels were very similar for the duration of proliferation .", "target_text": {} }, { "input_text": "In parallel , CD2 + CD28 activation triggered a significant intracellular thiol decrease , suggesting that oxygen radicals are involved in the signaling pathway of adhesion molecules .", "target_text": { "CD2": "protein", "CD28": "protein", "adhesion molecules": "protein" } }, { "input_text": "Finally , micromolar amounts of pyrrolidine dithiocarbamate , an oxygen radical scavenger that efficiently blocked the nuclear appearance of NF-kappa B in T-lymphocytes , also inhibited IL-2 secretion , IL-2R alpha cell surface expression , and T-cell proliferation .", "target_text": { "NF-kappa B": "protein", "T-lymphocytes": "cell_type", "IL-2": "protein", "IL-2R alpha": "protein" } }, { "input_text": "Together , these results suggest that NF-kappa B plays an important role in long-term activation of human primary T-lymphocytes via CD2 + CD28 .", "target_text": { "NF-kappa B": "protein", "T-lymphocytes": "cell_type", "human primary T-lymphocytes": "cell_type", "CD2": "protein", "CD28": "protein" } }, { "input_text": "Immobilization and recovery of fusion proteins and B-lymphocyte cells using magnetic separation .", "target_text": { "fusion proteins": "protein", "B-lymphocyte cells": "cell_type" } }, { "input_text": "A new approach to facilitate immobilization and affinity purification of recombinant proteins and selected human B lymphocytes has been developed .", "target_text": { "recombinant proteins": "protein", "human B lymphocytes": "cell_type" } }, { "input_text": "Using magnetic beads with attached DNA containing the Escherichia coli lac operator , fusion proteins comprising the DNA-binding lac repressor could be affinity-purified and recovered by gentle elution conditions , such as with a lactose analogue or by enzymatic means using either deoxyribonuclease ( DNase ) or restriction endonucleases .", "target_text": { "DNA": "DNA", "Escherichia coli lac operator": "DNA", "fusion proteins": "protein", "DNA-binding lac repressor": "DNA", "deoxyribonuclease": "protein", "DNase": "protein", "restriction endonucleases": "protein" } }, { "input_text": "The results show for the first time that a DNA-binding protein can be used for affinity purification of fusion proteins as exemplified by the specific and gentle recovery of beta-galactosidase and alkaline phosphatase from bacterial lysates using immunomagnetic separation .", "target_text": { "DNA-binding protein": "protein", "fusion proteins": "protein", "beta-galactosidase": "protein", "alkaline phosphatase": "protein" } }, { "input_text": "The approach was further extended to cell separation by the efficient recovery and elution of human CD37 B lymphocytes from peripheral blood .", "target_text": { "human CD37 B lymphocytes": "cell_line" } }, { "input_text": "ras protein activity is essential for T-cell antigen receptor signal transduction .", "target_text": { "ras protein": "protein", "T-cell antigen receptor": "protein" } }, { "input_text": "In a Jurkat cell model of T-cell activation an interleukin-2 promoter/reporter gene construct was activated by antigen receptor agonism in combination with the lymphokine interleukin-1 .", "target_text": { "Jurkat cell model": "cell_line", "interleukin-2": "protein", "interleukin-2 promoter/reporter gene construct": "DNA", "antigen receptor": "protein", "lymphokine": "protein", "interleukin-1": "protein" } }, { "input_text": "Antigen receptor signals could be mimicked by suboptimal activation of protein kinase C ( PKC ) with phorbol esters in combination with calcium mobilization by an ionophore .", "target_text": { "protein kinase C": "protein", "PKC": "protein" } }, { "input_text": "In cotransfection experiments , oncogenic rats obviated the need for PKC stimulation but did not replace either the calcium signal or interleukin-1 .", "target_text": { "PKC": "protein", "interleukin-1": "protein" } }, { "input_text": "Activated ras expression also replaced the requirement for PKC stimulation in activation of the T-cell transcription factor NF-AT .", "target_text": { "ras": "protein", "PKC": "protein", "T-cell transcription factor": "protein", "NF-AT": "protein" } }, { "input_text": "A dominant inhibitory ras mutant specifically blocked antigen receptor agonism , indicating that ras activity is required for antigen receptor signaling .", "target_text": { "dominant inhibitory ras mutant": "protein", "ras": "protein", "antigen receptor": "protein" } }, { "input_text": "In addition , an inhibitor of PKC blocked both activated ras and phorbol ester stimulation , suggesting a role for ras upstream of PKC .", "target_text": { "PKC": "protein", "ras": "protein" } }, { "input_text": "Expression of the Tat protein of HIV1 in human promonocytic U937 cells .", "target_text": { "Tat protein": "protein", "U937 cells": "cell_line", "human promonocytic U937 cells": "cell_line" } }, { "input_text": "Numerous studies have shown that , upon HIV1 infection , human promonocytic U937 cells were induced to differentiate , as indicated , for example , by increased expression of adhesion molecules .", "target_text": { "U937 cells": "cell_line", "human promonocytic U937 cells": "cell_line", "adhesion molecules": "protein" } }, { "input_text": "One of the viral proteins involved in this process might be the Tat protein .", "target_text": { "Tat protein": "protein" } }, { "input_text": "Indeed , this viral protein , which is essential for productive infection , has also been shown to display growth-stimulating properties and immunomodulatory activities .", "target_text": { "viral protein": "protein" } }, { "input_text": "In order to apprehend the role of the HIV1 tat gene in inducing the differentiation of HIV1 -infected U937 cells , we have successfully introduced this gene into U937 cells by infecting them with retroviral particles transducing tat .", "target_text": { "HIV1 tat gene": "DNA", "U937 cells": "cell_line", "HIV1 -infected U937 cells": "cell_line", "tat": "DNA" } }, { "input_text": "The effect of the Tat protein constitutively expressed by these cells upon their differentiation was then evaluated by looking for the expression of the c-fos and of the c-fms proto-oncogenes which are linked to the differentiation of myelomonoblastic cells .", "target_text": { "Tat protein": "protein", "c-fos": "DNA", "c-fms proto-oncogenes": "DNA", "myelomonoblastic cells": "cell_type" } }, { "input_text": "Northern blot analysis revealed in these cells , an increase in the transcription of these two proto-oncogenes , and this increase was amplified after treatment with phorbol myristate acetate .", "target_text": { "proto-oncogenes": "DNA" } }, { "input_text": "No such increase was observed in control U937 cells .", "target_text": { "U937 cells": "cell_line" } }, { "input_text": "These results indicate that , among HIV1 gene products , the Tat protein appears to trigger monocytic differentiation , and suggests that this viral protein directs progenitors of the monocyte/macrophage lineage towards a differentiation stage in which production of viral antigens and virions might be more efficient .", "target_text": { "HIV1 gene products": "protein", "Tat protein": "protein", "viral protein": "protein", "monocyte/macrophage lineage": "cell_type", "antigens": "protein", "viral antigens": "protein" } }, { "input_text": "Analysis of the preexisting and nuclear forms of nuclear factor of activated T cells .", "target_text": { "activated T cells": "cell_type", "nuclear factor of activated T cells": "protein" } }, { "input_text": "The nuclear factor of activated T cells ( NF-AT ) 3 is an inducible DNA-binding protein that is essential for transcriptional induction of the IL-2 gene during T cell activation .", "target_text": { "nuclear factor of activated T cells": "protein", "NF-AT": "protein", "DNA-binding protein": "protein", "IL-2": "protein", "IL-2 gene": "DNA" } }, { "input_text": "NF-AT is thought to consist of two components : a ubiquitous , inducible nuclear component that we have identified as Fos and Jun proteins , and a preexisting , T cell-specific component ( NF-ATp ) which is the target for the immunosuppressive agents cyclosporin A ( CsA ) and FK506 .", "target_text": { "NF-AT": "protein", "ubiquitous , inducible nuclear component": "protein", "Fos": "protein", "Jun": "protein", "Jun proteins": "protein", "T cell-specific component": "protein", "NF-ATp": "protein" } }, { "input_text": "We have previously shown that nuclear extracts from activated T cells form two inducible NF-AT complexes with an oligonucleotide corresponding to the distal NF-AT site of the murine IL-2 promoter , although hypotonic extracts of unstimulated T cells form a single complex containing NF-ATp .", "target_text": { "T cells": "cell_type", "activated T cells": "cell_type", "NF-AT complexes": "protein", "NF-AT": "protein", "distal NF-AT site": "DNA", "IL-2": "protein", "murine IL-2 promoter": "DNA", "NF-ATp": "protein" } }, { "input_text": "We show that the ability to detect NF-ATp in a gel shift assay , which is essential for purification and biochemical studies of this protein , is strikingly dependent on the precise sequence of the NF-AT oligonucleotide used as the labeled probe .", "target_text": { "NF-ATp": "protein", "NF-AT": "protein" } }, { "input_text": "Moreover we present evidence that the component that forms the faster-migrating ( \" lower \" ) nuclear NF-AT complex is derived by a calcium-dependent , cyclosporin-sensitive , posttranslational modification of NF-ATp , and that Fos and Jun proteins stabilize its interaction with DNA .", "target_text": { "nuclear NF-AT complex": "protein", "NF-ATp": "protein", "Fos": "protein", "Jun": "protein", "DNA": "DNA" } }, { "input_text": "The results are discussed in the context of a model relating the two nuclear NF-AT complexes to NF-ATp .", "target_text": { "NF-AT complexes": "protein", "NF-ATp": "protein" } }, { "input_text": "Cell cycle analysis of E2F in primary human T cells reveals novel E2F complexes and biochemically distinct forms of free E2F .", "target_text": { "E2F": "protein", "T cells": "cell_type", "primary human T cells": "cell_type", "novel E2F complexes": "protein" } }, { "input_text": "The transcription factor E2F activates the expression of multiple genes involved in cell proliferation , such as c-myc and the dihydrofolate reductase gene .", "target_text": { "transcription factor": "protein", "E2F": "protein", "genes": "DNA", "c-myc": "DNA", "dihydrofolate reductase gene": "DNA" } }, { "input_text": "Regulation of E2F involves its interactions with other cellular proteins , including the retinoblastoma protein ( Rb ) , the Rb-related protein p107 , cyclin A , and cdk2 .", "target_text": { "E2F": "protein", "cellular proteins": "protein", "retinoblastoma protein": "protein", "Rb": "protein", "Rb-related protein": "protein", "p107": "protein", "cyclin A": "protein", "cdk2": "protein" } }, { "input_text": "We undertook a detailed analysis of E2F DNA-binding activities and their cell cycle behavior in primary human T cells .", "target_text": { "E2F": "protein", "T cells": "cell_type" } }, { "input_text": "Three E2F DNA-binding activities were identified in resting ( G0 ) T cells with mobilities in gel shift assays distinct from those of previously defined E2F complexes .", "target_text": { "E2F": "protein", "T cells": "cell_type" } }, { "input_text": "One of these activities was found to be a novel , less abundant , Rb- E2F complex .", "target_text": { "E2F": "protein" } }, { "input_text": "The most prominent E2F activity in resting T cells ( termed complex X ) was abundant in both G0 and G1 but disappeared as cells entered S phase , suggesting a possible role in negatively regulating E2F function .", "target_text": { "E2F": "protein", "T cells": "cell_type" } }, { "input_text": "Complex X could be dissociated by adenovirus E1A with a requirement for an intact E1A conserved region 2 .", "target_text": { "Complex X": "protein", "E1A conserved region 2": "DNA" } }, { "input_text": "However , X failed to react with a variety of antibodies against Rb or p107 , implicating the involvement of an E1A-binding protein other than Rb or p107 .", "target_text": { "X": "protein", "Rb": "protein", "p107": "protein", "E1A-binding protein": "protein" } }, { "input_text": "In addition to these novel E2F complexes , three distinct forms of unbound ( free ) E2F were resolved in gel shift experiments .", "target_text": { "E2F": "protein", "novel E2F complexes": "protein" } }, { "input_text": "These species showed different cell cycle kinetics .", "target_text": {} }, { "input_text": "UV cross-linking experiments suggested that a distinct E2F DNA-binding protein is uniquely associated with the S-phase p107 complex and is not associated with Rb .", "target_text": { "E2F": "protein", "p107": "protein", "S-phase p107 complex": "protein", "Rb": "protein" } }, { "input_text": "Together , these results suggest that E2F consists of multiple , biochemically distinct DNA-binding proteins which function at different points in the cell cycle .", "target_text": { "E2F": "protein", "DNA-binding proteins": "protein" } }, { "input_text": "Defective translocation of protein kinase C in multidrug-resistant HL-60 cells confers a reversible loss of phorbol ester-induced monocytic differentiation .", "target_text": { "protein kinase C": "protein", "multidrug-resistant HL-60 cells": "cell_line" } }, { "input_text": "Previous studies have demonstrated that human HL-60 myeloid leukemia cells differentiate in response to phorbol esters .", "target_text": { "human HL-60 myeloid leukemia cells": "cell_line" } }, { "input_text": "This event is associated with induction of the c-jun early response gene and appearance of a monocytic phenotype .", "target_text": { "c-jun early response gene": "DNA" } }, { "input_text": "The present studies have examined the effects of vincristine-selected , multidrug resistance on 12-O-tetradecanoylphorbol-13-acetate ( TPA ) -induced HL-60 cell differentiation .", "target_text": {} }, { "input_text": "The results demonstrate that multidrug-resistant HL-60 cells , designated HL-60/vinc , fail to respond to TPA with an increase in c-jun transcripts or other phenotypic characteristics of monocytic differentiation .", "target_text": { "HL-60 cells": "cell_line", "multidrug-resistant HL-60 cells": "cell_line", "c-jun": "DNA", "c-jun transcripts": "RNA" } }, { "input_text": "By contrast , treatment of HL-60/vinc cells with okadaic acid , an inhibitor of serine /threonine protein phosphatases , induces c-jun transcription , growth arrest , and expression of the c-fms gene .", "target_text": { "HL-60/vinc cells": "cell_line", "serine /threonine protein phosphatases": "protein", "c-jun": "DNA", "c-fms gene": "DNA" } }, { "input_text": "Studies were also performed with an HL-60/vinc revertant ( HL-60/vinc/R ) line that has regained partial sensitivity to vincristine .", "target_text": { "HL-60/vinc revertant": "cell_line", "HL-60/vinc/R": "cell_line" } }, { "input_text": "The finding that HL-60/vinc/R cells respond to TPA with induction of a monocytic phenotype , but not c-jun expression , suggests that c-jun induction is not obligatory for monocytic differentiation .", "target_text": { "HL-60/vinc/R cells": "cell_line", "c-jun": "DNA" } }, { "input_text": "Other studies further demonstrate that the jun-B and fra-1 genes are induced by TPA in both HL-60/vinc and HL-60/vinc/R cells , whereas c-fos expression is attenuated in the HL-60/vinc line .", "target_text": { "jun-B": "DNA", "fra-1": "DNA", "genes": "DNA", "HL-60/vinc": "cell_line", "HL-60/vinc/R cells": "cell_line", "c-fos": "DNA" } }, { "input_text": "Since TPA activates protein kinase C ( PKC ) , we examined translocation of PKC from the cytosol to the membrane fraction .", "target_text": { "protein kinase C": "protein", "PKC": "protein" } }, { "input_text": "Although HL-60 and HL-60/vinc/R cells demonstrated translocation of PKC activity , this subcellular redistribution was undetectable in HL-60/vinc cells .", "target_text": { "HL-60": "cell_line", "HL-60/vinc/R cells": "cell_line", "PKC": "protein", "HL-60/vinc cells": "cell_line" } }, { "input_text": "Activity of the mitogen-activated protein kinase family with associated phosphorylation of c-Jun Y-peptide was markedly diminished in TPA -treated HL-60/vinc cells , but not in response to okadaic acid .", "target_text": { "mitogen-activated protein kinase family": "protein", "c-Jun Y-peptide": "protein", "HL-60/vinc cells": "cell_line", "TPA -treated HL-60/vinc cells": "cell_line" } }, { "input_text": "Taken together , these findings suggest that vincristine resistance confers insensitivity to TPA -induced differentiation and can include defects in PKC -mediated signaling events and induction of jun/fos early response gene expression .", "target_text": { "PKC": "protein", "jun/fos early response gene": "DNA" } }, { "input_text": "Molecular basis of a multiple lymphokine deficiency in a patient with severe combined immunodeficiency .", "target_text": { "lymphokine": "protein" } }, { "input_text": "We have previously reported that the T lymphocytes of a child with severe combined immunodeficiency are defective in the transcription of several lymphokine genes that include IL2 , IL3 , IL4 , and IL5 , which encode interleukins 2 , 3 , 4 , and 5 ( IL-2 , -3 , -4 , and -5 ) .", "target_text": { "T lymphocytes": "cell_type", "lymphokine": "protein", "genes": "DNA", "lymphokine genes": "DNA", "IL2": "DNA", "IL3": "DNA", "IL4": "DNA", "IL5": "DNA", "interleukins": "protein", "IL-2": "protein", "-3": "protein", "-4": "protein", "-5": "protein" } }, { "input_text": "To determine whether the defect in the patient 's T lymphocytes involved a trans-acting factor common to the affected lymphokine genes , we examined the ability of nuclear factors from the patient 's T lymphocytes to bind response elements present in the regulatory region of IL2 .", "target_text": { "T lymphocytes": "cell_type", "trans-acting factor": "protein", "lymphokine": "protein", "genes": "DNA", "lymphokine genes": "DNA", "nuclear factors": "protein", "regulatory region": "DNA", "IL2": "DNA" } }, { "input_text": "Nuclear factor NF-kB , activation protein 1 ( AP-1 ) , OCT-1 , and NF-IL-2B binding activity were normal .", "target_text": { "Nuclear factor NF-kB": "protein", "activation protein 1": "protein", "AP-1": "protein", "OCT-1": "protein", "NF-IL-2B": "protein" } }, { "input_text": "In contrast , the binding of the nuclear factor of activated T cells ( NF-AT ) to its response element in the IL2 enhancer and to an NF-AT -like response element present in the IL4 enhancer was abnormal .", "target_text": { "T cells": "cell_type", "activated T cells": "cell_type", "nuclear factor of activated T cells": "protein", "NF-AT": "protein", "IL2": "DNA", "IL2 enhancer": "DNA", "NF-AT -like response element": "DNA", "IL4 enhancer": "DNA" } }, { "input_text": "To ascertain whether the abnormal NF-AT binding activity was related to an impaired function , we transfected patient and control T lymphocytes with constructs containing the reporter gene encoding chloramphenicol acetyl transferase ( CAT ) under the control of the entire IL2 regulatory region or of multimers of individual enhancer sequences .", "target_text": { "NF-AT": "protein", "T lymphocytes": "cell_type", "chloramphenicol acetyl transferase": "protein", "CAT": "protein", "IL2": "DNA", "IL2 regulatory region": "DNA", "enhancer sequences": "DNA" } }, { "input_text": "CAT expression directed by the IL2 regulatory region or by a multimer of the NF-AT -binding site was markedly lower in the patient relative to controls .", "target_text": { "IL2": "DNA", "IL2 regulatory region": "DNA", "NF-AT": "protein", "NF-AT -binding site": "DNA" } }, { "input_text": "In contrast , CAT gene expression directed by a multimer of the OCT-1 proximal ( OCT-1p ) -binding site was equivalent in patient and controls .", "target_text": { "CAT gene": "DNA", "OCT-1 proximal ( OCT-1p ) -binding site": "DNA" } }, { "input_text": "These results indicate that an abnormality of/or influencing NF-AT may underlie the multiple lymphokine deficiency in this patient .", "target_text": { "NF-AT": "protein", "lymphokine": "protein" } }, { "input_text": "FK506 and ciclosporin : molecular probes for studying intracellular signal transduction .", "target_text": {} }, { "input_text": "The immunosuppressants ciclosporin and FK506 block the Ca(2+)-dependent signal-transduction pathway emanating from the T-cell receptor , thereby inhibiting the activation of helper T cells .", "target_text": { "T-cell receptor": "protein", "T cells": "cell_type", "helper T cells": "cell_type" } }, { "input_text": "Using these drugs as probes , chemists and biologists have uncovered several intracellular signalling molecules bridging the generation of second-messenger Ca2+ ions and the transcriptional activation of IL-2 , among which are calmodulin , calcineurin and the nuclear factor of activated T cells ( NF-AT ) .", "target_text": { "IL-2": "protein", "calmodulin": "protein", "calcineurin": "protein", "T cells": "cell_type", "activated T cells": "cell_type", "nuclear factor of activated T cells": "protein", "NF-AT": "protein" } }, { "input_text": "Hence , Ca2+ binds to calmodulin , leading to the binding of calmodulin to calcineurin ; the activated calcineurin , in turn , may dephosphorylate the cytoplasmic subunit of NF-AT , resulting in its translocation from the cytoplasm into the nucleus to form a competent transcriptional activator .", "target_text": { "calmodulin": "protein", "calcineurin": "protein", "NF-AT": "protein", "cytoplasmic subunit of NF-AT": "protein", "competent transcriptional activator": "protein" } }, { "input_text": "As described by Jun Liu , these drugs manifest their effects in an unprecedented fashion .", "target_text": { "Jun": "protein" } }, { "input_text": "They do not directly intercept intracellular signalling molecules .", "target_text": {} }, { "input_text": "Instead , they form tight complexes with two different classes of abundant cytosolic receptors called immunophilins upon entering the cell , and consequently inhibit their peptidyl prolyl cis-trans isomerase activities .", "target_text": { "cytosolic receptors": "protein", "immunophilins": "protein", "peptidyl prolyl cis-trans isomerase": "protein" } }, { "input_text": "The two structurally distinct immunophilin-drug complexes bind to , and inhibit , the phosphatase activity of calcineurin .", "target_text": { "immunophilin-drug complexes": "protein", "phosphatase": "protein", "calcineurin": "protein" } }, { "input_text": "p105 and p98 precursor proteins play an active role in NF-kappa B -mediated signal transduction .", "target_text": { "p105": "protein", "p98": "protein", "precursor proteins": "protein", "NF-kappa B": "protein" } }, { "input_text": "The Rel/ NF-kappa B family of transcription factors is composed of two distinct subgroups , proteins that undergo proteolytic processing and contain SWI6/ankyrin repeats in their carboxyl termini ( p105 , p98 ) , and those without such repeats that do not require processing ( p65 , c-Rel , RelB , and Dorsal ) .", "target_text": { "NF-kappa B": "protein", "Rel/ NF-kappa B family": "protein", "transcription factors": "protein", "SWI6/ankyrin repeats": "protein", "carboxyl termini": "protein", "p105": "protein", "p98": "protein", "p65": "protein", "c-Rel": "protein", "RelB": "protein", "Dorsal": "protein" } }, { "input_text": "We demonstrate that the p105 and p98 precursors share functional properties with the I kappa B proteins , which also contain SWI6/ankyrin repeats .", "target_text": { "p105": "protein", "p98": "protein", "I kappa B proteins": "protein", "SWI6/ankyrin repeats": "protein" } }, { "input_text": "Both p105 and p98 were found to form stable complexes with other Rel/ NF-kappa B family members , including p65 and c-Rel .", "target_text": { "p105": "protein", "p98": "protein", "NF-kappa B": "protein", "Rel/ NF-kappa B family members": "protein", "p65": "protein", "c-Rel": "protein" } }, { "input_text": "Association with the precursors is sufficient for cytoplasmic retention of either p65 or c-Rel , both of which are otherwise nuclear .", "target_text": { "p65": "protein", "c-Rel": "protein" } }, { "input_text": "These complexes undergo stimulus-responsive processing to produce active p50/ c-Rel and p55/ c-Rel complexes .", "target_text": { "c-Rel": "protein", "p50/ c-Rel": "protein", "p55/ c-Rel": "protein" } }, { "input_text": "These observations suggest a second pathway leading to NF-kappa B induction , in which processing of the precursors rather than phosphorylation of I kappa B plays a major role .", "target_text": { "NF-kappa B": "protein", "I kappa B": "protein" } }, { "input_text": "NF-kappa B controls expression of inhibitor I kappa B alpha : evidence for an inducible autoregulatory pathway .", "target_text": { "NF-kappa B": "protein", "I kappa B": "protein", "I kappa B alpha": "protein" } }, { "input_text": "The eukaryotic transcription factor nuclear factor-kappa B ( NF-kappa B ) participates in many parts of the genetic program mediating T lymphocyte activation and growth .", "target_text": { "transcription factor": "protein", "nuclear factor-kappa B": "protein", "NF-kappa B": "protein", "T lymphocyte": "cell_type" } }, { "input_text": "Nuclear expression of NF-kappa B occurs after its induced dissociation from its cytoplasmic inhibitor I kappa B alpha .", "target_text": { "NF-kappa B": "protein", "I kappa B alpha": "protein" } }, { "input_text": "Phorbol ester and tumor necrosis factor-alpha induction of nuclear NF-kappa B is associated with both the degradation of performed I kappa B alpha and the activation of I kappa B alpha gene expression .", "target_text": { "tumor necrosis factor-alpha": "protein", "NF-kappa B": "protein", "nuclear NF-kappa B": "protein", "I kappa B alpha": "protein", "I kappa B": "protein" } }, { "input_text": "Transfection studies indicate that the I kappa B alpha gene is specifically induced by the 65-kilodalton transactivating subunit of NF-kappa B .", "target_text": { "I kappa B alpha": "protein", "I kappa B alpha gene": "DNA", "65-kilodalton transactivating subunit": "protein", "NF-kappa B": "protein" } }, { "input_text": "Association of the newly synthesized I kappa B alpha with p65 restores intracellular inhibition of NF-kappa B DNA binding activity and prolongs the survival of this labile inhibitor .", "target_text": { "I kappa B alpha": "protein", "p65": "protein", "NF-kappa B": "protein" } }, { "input_text": "Together , these results show that NF-kappa B controls the expression of I kappa B alpha by means of an inducible autoregulatory pathway .", "target_text": { "NF-kappa B": "protein", "I kappa B": "protein" } }, { "input_text": "The human prointerleukin 1 beta gene requires DNA sequences both proximal and distal to the transcription start site for tissue-specific induction .", "target_text": { "human prointerleukin 1 beta": "protein", "human prointerleukin 1 beta gene": "DNA", "transcription start site": "DNA" } }, { "input_text": "In these studies , we have identified DNA sequences and specific protein interactions necessary for transcriptional regulation of the human prointerleukin 1 beta ( proIL-1 beta ) gene .", "target_text": { "DNA sequences": "DNA", "human prointerleukin 1 beta": "protein", "proIL-1 beta": "protein", "human prointerleukin 1 beta ( proIL-1 beta ) gene": "DNA" } }, { "input_text": "A cell-type-independent lipopolysaccharide ( LPS ) -responsive enhancer element located between -3757 and -2729 bp upstream from the transcription start site ( cap site ) consisted of at least six discrete subregions which were essential to the maximal induction by LPS in transfected monocytes .", "target_text": { "cell-type-independent lipopolysaccharide ( LPS ) -responsive enhancer element": "DNA", "-3757 and -2729 bp upstream": "DNA", "transcription start site": "DNA", "cap site": "DNA", "transfected monocytes": "cell_line" } }, { "input_text": "The enhancer also appeared to mediate phorbol myristate acetate induction in monocytes and IL-1 responsiveness in fibroblasts .", "target_text": { "monocytes": "cell_type", "IL-1": "protein", "fibroblasts": "cell_type" } }, { "input_text": "Deletion and base substitution mutations along with DNA binding studies demonstrated that the enhancer contained a minimum of three functional protein binding sequences , two of which appeared to be important for gene induction .", "target_text": { "protein binding sequences": "DNA" } }, { "input_text": "One of the essential proteins which bound to the enhancer was similar or identical to members of the C/EBP family of transcription factors required for both IL-1 - and LPS -specific induction of the IL-6 gene ( i.e. , the NF-IL6 proteins ) .", "target_text": { "C/EBP family": "protein", "transcription factors": "protein", "IL-1": "protein", "IL-6 gene": "DNA", "NF-IL6 proteins": "DNA" } }, { "input_text": "When ligated to the proIL-1 beta cap site -proximal region ( located between -131 to +12 ) , both the proIL-1 beta and the simian virus 40 enhancer elements functioned more efficiently in monocytes than in HeLa cells , which are not normally competent for IL-1 beta expression .", "target_text": { "proIL-1 beta": "protein", "cap site": "DNA", "proIL-1 beta cap site": "DNA", "-proximal region": "DNA", "monocytes": "cell_type", "HeLa cells": "cell_type", "IL-1 beta": "protein" } }, { "input_text": "When ligated to the murine c-fos promoter , however , the proIL-1 beta enhancer was inducible in phorbol myristate acetate -stimulated HeLa cells , suggesting the existence of a proIL-1 beta promoter-proximal requirement for tissue specificity .", "target_text": { "c-fos": "DNA", "murine c-fos promoter": "DNA", "proIL-1 beta": "protein", "proIL-1 beta enhancer": "DNA", "HeLa cells": "cell_type", "phorbol myristate acetate -stimulated HeLa cells": "cell_line" } }, { "input_text": "Lymphocytes from the site of disease suggest adenovirus is one cause of persistent or recurrent inflammatory arthritis .", "target_text": { "Lymphocytes": "cell_type" } }, { "input_text": "The assessment of synovial lymphocyte reactivity to adenovirus antigen stimulation was undertaken in patients with persistent or recurrent inflammatory arthritis .", "target_text": {} }, { "input_text": "The 3H-thymidine uptake procedure was employed , incorporating multiple microbiological antigens .", "target_text": { "microbiological antigens": "protein" } }, { "input_text": "Five patients were found with repeated maximal responses to adenovirus antigen ; in one of these adenovirus nucleotide sequences were present in a synovial biopsy specimen .", "target_text": { "adenovirus antigen": "protein", "adenovirus nucleotide sequences": "DNA" } }, { "input_text": "It is concluded that adenovirus may be one cause of persistent or recurrent inflammatory arthritis .", "target_text": {} }, { "input_text": "Expression of PILOT , a putative transcription factor , requires two signals and is cyclosporin A sensitive in T cells .", "target_text": { "PILOT": "protein", "transcription factor": "protein", "T cells": "cell_type" } }, { "input_text": "Few known genes ( IL-2 , members of the IL-8 family , interferon-gamma ) are induced in T cells only through the combined effect of phorbol myristic acetate ( PMA ) and a Ca(2+)-ionophore , and expression of only these genes can be fully suppressed by Cyclosporin A ( CyA ) .", "target_text": { "genes": "DNA", "IL-2": "protein", "IL-8 family": "DNA", "interferon-gamma": "DNA", "T cells": "cell_type" } }, { "input_text": "We have identified a putative transcription factor , designated PILOT , with an identical dual signal requirement for expression .", "target_text": { "transcription factor": "protein", "PILOT": "protein" } }, { "input_text": "Induction of the PILOT gene is detectable in human T cells 20 min following activation in the presence of cycloheximide and is fully suppressed by CyA .", "target_text": { "PILOT": "protein", "T cells": "cell_type" } }, { "input_text": "The PILOT protein has a calculated M(r) of 42.6 kDa and contains three zinc fingers of the C2H2-type at the carboxyl-terminus which are highly homologous to the zinc finger regions of the transcription factors EGR1 , EGR2 , and pAT 133 .", "target_text": { "PILOT": "protein", "zinc fingers": "protein", "C2H2-type": "protein", "carboxyl-terminus": "protein", "zinc finger regions": "protein", "transcription factors": "protein", "EGR1": "protein", "EGR2": "protein", "pAT 133": "protein" } }, { "input_text": "In contrast to T cells , in fibroblasts PILOT gene expression requires only one signal ( PMA ) and is not affected by CyA .", "target_text": { "T cells": "cell_type", "fibroblasts": "cell_type", "PILOT": "protein" } }, { "input_text": "This observation directly demonstrates the existence of a Ca2+ signal-dependent regulatory element obligatory for expression of some genes in T cells but not in fibroblasts .", "target_text": { "Ca2+ signal-dependent regulatory element": "protein", "genes": "DNA", "T cells": "cell_type", "fibroblasts": "cell_type" } }, { "input_text": "This differential expression model will be valuable in the dissection of the dual signal pathway in T cells and the effects of CyA upon it .", "target_text": { "T cells": "cell_type" } }, { "input_text": "Antisense oligonucleotides to the p65 subunit of NF-kappa B block CD11b expression and alter adhesion properties of differentiated HL-60 granulocytes .", "target_text": { "p65 subunit": "protein", "NF-kappa B": "protein", "CD11b": "protein", "HL-60 granulocytes": "cell_line" } }, { "input_text": "NF-kappa B is a pleiotropic regulator of a variety of genes implicated in the cellular response to injury .", "target_text": { "NF-kappa B": "protein", "pleiotropic regulator": "protein" } }, { "input_text": "This function has been attributed to the coordinated binding of subunits of NF-kappa B to distinct regions of the promoter elements of numerous genes , including cytokines , growth factor receptors , and adhesion molecules .", "target_text": { "NF-kappa B": "protein", "promoter elements": "DNA", "cytokines": "protein", "growth factor receptors": "protein", "adhesion molecules": "protein" } }, { "input_text": "Antisense phosphorothioate oligonucleotides to the p50 and p65 subunits of the NF-kappa B complex were used to define the physiologic role of this transcription factor in resting and stimulated granulocytes .", "target_text": { "p50": "protein", "p65 subunits": "protein", "NF-kappa B complex": "protein", "transcription factor": "protein" } }, { "input_text": "A reduction in the expression of p65 was produced by treatment with the phosphorothioate antisense oligodeoxynucleotide .", "target_text": { "p65": "protein" } }, { "input_text": "This reduction was accompanied by rapid changes in the cellular adhesion of dimethyl sulfoxide -differentiated HL-60 leukemia cells stimulated by 12-O-tetradecanoylphorbol 13-acetate ( TPA ) .", "target_text": { "dimethyl sulfoxide -differentiated HL-60 leukemia cells": "cell_line" } }, { "input_text": "These effects were characterized by a marked reduction in CD11b integrin expression on the surface of treated cells .", "target_text": { "CD11b": "protein", "integrin": "protein", "treated cells": "cell_line" } }, { "input_text": "Furthermore , the p65 antisense oligomer effectively abolished an upregulation of CD11b that was produced by formyl-met-leu-phe and TPA .", "target_text": { "p65": "protein", "CD11b": "protein" } }, { "input_text": "However , the p65 antisense phosphorothioate oligodeoxynucleotide had no significant effect on the production of reactive oxygen intermediates or on phagocytosis by these cells .", "target_text": { "p65": "protein" } }, { "input_text": "These findings indicate that antisense oligomers to p65 can be used to define the role of NF-kappa B in the activation pathways of neutrophils .", "target_text": { "p65": "protein", "NF-kappa B": "protein", "neutrophils": "cell_type" } }, { "input_text": "The p65 subunit of NF-kappa B regulates I kappa B by two distinct mechanisms .", "target_text": { "p65 subunit": "protein", "NF-kappa B": "protein", "I kappa B": "protein" } }, { "input_text": "Transcription factor NF-kappa B ( p50/p65 ) is generally localized to the cytoplasm by its inhibitor I kappa B .", "target_text": { "NF-kappa B": "protein", "p50/p65": "protein", "I kappa B": "protein" } }, { "input_text": "Overproduced I kappa B , free from NF-kappa B , is rapidly degraded .", "target_text": { "I kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "Overexpression of p65 increases endogenous I kappa B protein in both carcinoma and lymphoid cells by two mechanisms : protein stabilization and increased transcription of I kappa B mRNA .", "target_text": { "p65": "protein", "I kappa B": "protein", "I kappa B mRNA": "RNA" } }, { "input_text": "In contrast , p65 delta , a naturally occurring splice variant , fails to markedly augment I kappa B protein levels .", "target_text": { "p65 delta": "protein", "I kappa B": "protein" } }, { "input_text": "Both overexpressed p65 and coexpressed p50 are cytoplasmic , whereas p65 delta is partly nuclear , indicating that the I kappa B induced by p65 can maintain NF-kappa B in the cytoplasm .", "target_text": { "p65": "protein", "p50": "protein", "p65 delta": "protein", "I kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "Thus , p65 and I kappa B are linked in an autoregulatory loop , ensuring that NF-kappa B is held in the cytoplasm until cells are specifically induced to translocate it to the nucleus .", "target_text": { "p65": "protein", "I kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells .", "target_text": { "MAD3": "protein", "c-Rel": "protein", "NF-kappa B": "protein", "human monocytic THP-1 cells": "cell_line" } }, { "input_text": "Many effects of lipopolysaccharide ( LPS ) on gene expression , including that of human immunodeficiency virus ( HIV ) , in monocytic cells are mediated by activation of kappa B DNA-binding proteins .", "target_text": { "monocytic cells": "cell_type" } }, { "input_text": "However , the specific members of the NF-kappa B /Rel transcription factor family involved in the LPS response , and the mechanisms through which LPS -generated signals are transduced remain unclear .", "target_text": { "NF-kappa B": "protein", "transcription factor": "protein", "NF-kappa B /Rel transcription factor family": "protein" } }, { "input_text": "Here we show that LPS induces nuclear expression of c-Rel/p50 heterodimers as well as p50/p65 ( NF-kappa B ) kappa B DNA-binding complexes in human monocytic THP-1 cells .", "target_text": { "c-Rel/p50 heterodimers": "protein", "p50/p65": "protein", "NF-kappa B": "protein", "human monocytic THP-1 cells": "cell_line" } }, { "input_text": "Nuclear localization of these proteins occurred concomitantly with a rapid decrease in their cytosolic levels and was independent of phorbol ester-sensitive protein kinase C .", "target_text": { "phorbol ester-sensitive protein kinase C": "protein" } }, { "input_text": "Within 24 h following LPS stimulation there was a striking increase in the levels of c-Rel , p105 , and p50 in the cytosol .", "target_text": { "c-Rel": "protein", "p105": "protein", "p50": "protein" } }, { "input_text": "The increased levels of these proteins correlated with increases in the amounts of their mRNAs during LPS activation of THP-1 cells .", "target_text": { "mRNAs": "RNA", "THP-1 cells": "cell_line" } }, { "input_text": "LPS activation of THP-1 cells resulted in phosphorylation of MAD3 ( an I kappa B -like protein ) , a rapid increase in MAD3 mRNA , and an increase in MAD3 protein by 2 h .", "target_text": { "THP-1 cells": "cell_line", "MAD3": "protein", "I kappa B": "protein", "MAD3 mRNA": "RNA" } }, { "input_text": "Thus , LPS activation of human monocytic cells results in nuclear expression of c-Rel /p50 and p50/p65 ( NF-kappa B ) and induces phosphorylation of MAD3 .", "target_text": { "monocytic cells": "cell_type", "c-Rel": "protein", "c-Rel /p50": "protein", "p50/p65": "protein", "NF-kappa B": "protein", "MAD3": "protein" } }, { "input_text": "A chimeric type II / type I interleukin-1 receptor can mediate interleukin-1 induction of gene expression in T cells .", "target_text": { "interleukin-1": "protein", "chimeric type II / type I interleukin-1 receptor": "protein", "T cells": "cell_type" } }, { "input_text": "The type I interleukin-1 receptor ( IL-1R ) is capable of transducing a signal resulting in promoter activation in T cells .", "target_text": { "type I interleukin-1 receptor": "protein", "IL-1R": "protein", "T cells": "cell_type" } }, { "input_text": "This signal transduction is dependent on the cytoplasmic domain , which consists of 213 amino acids .", "target_text": { "cytoplasmic domain": "protein" } }, { "input_text": "In contrast to the type I receptor , the type II IL-1R has a small cytoplasmic tail , and it is not clear whether this receptor is a signal-transducing or a regulatory molecule .", "target_text": { "type I receptor": "protein", "IL-1R": "protein", "type II IL-1R": "protein", "cytoplasmic tail": "protein", "signal-transducing": "protein", "regulatory molecule": "protein" } }, { "input_text": "Here we report that the type II IL-1R does not mediate gene activation in Jurkat cells .", "target_text": { "IL-1R": "protein", "type II IL-1R": "protein", "Jurkat cells": "cell_line" } }, { "input_text": "However , a hybrid receptor composed of the extracellular and transmembrane regions of the human type II interleukin-1 fused to the cytoplasmic domain of the human type I IL-1R was capable of transducing a signal across the membrane resulting in a pattern of gene activation identical to that mediated by the type I IL-1R .", "target_text": { "human type II interleukin-1": "protein", "cytoplasmic domain": "protein", "IL-1R": "protein", "human type I IL-1R": "protein", "type I IL-1R": "protein" } }, { "input_text": "Our results indicated that the extracellular domain of the type II IL-1R was capable of functionally interacting with interleukin-1 and transmitting the resulting signal to a heterologous cytoplasmic domain .", "target_text": { "extracellular domain": "protein", "IL-1R": "protein", "type II IL-1R": "protein", "interleukin-1": "protein", "heterologous cytoplasmic domain": "protein" } }, { "input_text": "A mutation of the glucocorticoid receptor in primary cortisol resistance .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "The precise molecular abnormalities that cause primary cortisol resistance have not been completely described .", "target_text": {} }, { "input_text": "In a subject with primary cortisol resistance we have observed glucocorticoid receptors ( hGR ) with a decreased affinity for dexamethasone .", "target_text": { "glucocorticoid receptors": "protein", "hGR": "protein" } }, { "input_text": "We hypothesize that a mutation of the hGR glucocorticoid-binding domain is the cause of cortisol resistance .", "target_text": { "hGR": "protein", "hGR glucocorticoid-binding domain": "protein" } }, { "input_text": "Total RNA isolated from the index subject 's mononuclear leukocytes was used to produce first strand hGR cDNAs , and the entire hGR cDNA was amplified in segments and sequenced .", "target_text": { "mononuclear leukocytes": "cell_type", "hGR": "protein", "hGR cDNAs": "DNA", "hGR cDNA": "DNA" } }, { "input_text": "At nucleotide 2 , 317 we identified a homozygous A for G point mutation that predicts an isoleucine ( ATT ) for valine ( GTT ) substitution at amino acid 729 .", "target_text": {} }, { "input_text": "When the wild-type hGR and hGR -Ile 729 were expressed in COS-1 cells and assayed for [3H]-Dexamethasone binding , the dissociation constants were 0.799 +/- 0.068 and 1.54 +/- 0.06 nM ( mean +/- SEM ) ( P < 0.01 ) , respectively .", "target_text": { "hGR": "protein", "wild-type hGR": "protein", "hGR -Ile 729": "protein", "COS-1 cells": "cell_line" } }, { "input_text": "When the wild-type hGR and hGR -Ile 729 were expressed in CV-1 cells that were cotransfected with the mouse mammary tumor virus long terminal repeat fused to the chloramphenicol acetyl transferase ( CAT ) gene , the hGR -Ile 729 conferred a fourfold decrease in apparent potency on dexamethasone stimulation of CAT activity .", "target_text": { "hGR": "protein", "wild-type hGR": "protein", "hGR -Ile 729": "protein", "CV-1 cells": "cell_line", "mouse mammary tumor virus long terminal repeat": "DNA", "chloramphenicol acetyl transferase": "protein", "CAT": "protein", "chloramphenicol acetyl transferase ( CAT ) gene": "DNA" } }, { "input_text": "The isoleucine for valine substitution at amino acid 729 impairs the function of the hGR and is the likely cause of primary cortisol resistance in this subject .", "target_text": { "hGR": "protein" } }, { "input_text": "The transcriptionally active factors mediating the effect of the HTLV-I Tax transactivator on the IL-2R alpha kappa B enhancer include the product of the c-rel proto-oncogene .", "target_text": { "transcriptionally active factors": "protein", "HTLV-I Tax": "protein", "HTLV-I Tax transactivator": "protein", "IL-2R": "protein", "IL-2R alpha kappa B enhancer": "DNA", "c-rel proto-oncogene": "DNA" } }, { "input_text": "The transactivator HTLV-I Tax activates the promoter of the gene coding for the interleukin 2 alpha-chain receptor ( IL-2R alpha ) via a kappa B site that can bind several protein species of the rel family .", "target_text": { "HTLV-I Tax": "protein", "promoter": "DNA", "interleukin 2 alpha-chain receptor": "protein", "IL-2R alpha": "protein", "kappa B site": "DNA", "rel family": "protein" } }, { "input_text": "Tax1 strongly activates the enhancer activity of this motif , in both epithelial HeLa and lymphoid Jurkat cells .", "target_text": { "Tax1": "protein", "epithelial HeLa": "cell_line", "Jurkat cells": "cell_line" } }, { "input_text": "This activation was not observed in undifferentiated embryocarcinoma F9 cells .", "target_text": {} }, { "input_text": "Overexpression of the p50 , p65 and Rel proteins in these cells showed that significant activation of the IL-2R alpha kappa B site was observed only with Rel and Rel plus p65 .", "target_text": { "p50": "protein", "p65": "protein", "Rel proteins": "protein", "IL-2R alpha": "protein", "kappa B site": "DNA", "Rel": "protein" } }, { "input_text": "Moreover , whereas both Tax and phorbol 12-myristate 13-acetate ( PMA ) are able to efficiently induce the binding of NF-kappa B to the IL-2R alpha kappa B site , PMA is functionally inactive .", "target_text": { "Tax": "protein", "NF-kappa B": "protein", "IL-2R alpha": "protein", "kappa B site": "DNA", "IL-2R alpha kappa B site": "DNA" } }, { "input_text": "Using the DNA affinity precipitation assay , we observed that Tax1 is able to efficiently induce the binding of Rel , whereas PMA is not .", "target_text": { "Tax1": "protein" } }, { "input_text": "This established a clear difference between both stimuli , indicating that Rel is the functionally active factor .", "target_text": { "Rel": "protein", "functionally active factor": "protein" } }, { "input_text": "We conclude from these results that the functional activity of members of the rel family is regulated by their interaction with DNA and that Rel can be a potent transcriptional activator on specific kappa B sites .", "target_text": { "rel family": "protein", "Rel": "protein", "kappa B sites": "DNA" } }, { "input_text": "Transcriptional regulation of interleukin 3 ( IL3 ) in primary human T lymphocytes .", "target_text": { "interleukin 3": "protein", "IL3": "protein", "primary human T lymphocytes": "cell_type" } }, { "input_text": "Role of AP-1- and octamer- binding proteins in control of IL3 gene expression .", "target_text": { "IL3": "protein" } }, { "input_text": "We have investigated the molecular and biochemical basis for activation of interleukin 3 ( IL3 ) gene expression in primary human T lymphocytes following CD3 and CD2 receptor stimulation or activation by phytohemagglutinin plus phorbol 12-myristate 13-acetate .", "target_text": { "interleukin 3": "protein", "IL3": "protein", "primary human T lymphocytes": "cell_type", "phytohemagglutinin": "protein" } }, { "input_text": "Using transfection and reporter gene assays specifically designed for primary T lymphocytes in conjunction with gel retardation assays , Western blot analyses and UV cross-linking studies , we found that c-Jun , c-Fos , and octamer-binding proteins play a major role in transcriptional activation of the IL3 gene via their interaction with two specific regions contained within the IL3 5'-flanking sequence .", "target_text": { "primary T lymphocytes": "cell_type", "c-Jun": "protein", "c-Fos": "protein", "octamer-binding proteins": "protein", "IL3": "protein", "IL3 gene": "DNA", "IL3 5'-flanking sequence": "DNA" } }, { "input_text": "Additionally , the region between bases -107 and -59 of the IL3 promoter containing putative AP-2 and Sp1 binding motifs appears necessary for basal level expression of the IL3 gene .", "target_text": { "-107 and -59": "DNA", "IL3": "protein", "IL3 promoter": "DNA" } }, { "input_text": "The data also indicate that CD2 receptor activation and phytohemagglutinin plus phorbol 12-myristate 13-acetate stimulation augment T cell IL3 gene expression through the same cis- and trans-activating signals .", "target_text": { "CD2": "protein", "phytohemagglutinin": "protein", "IL3": "protein" } }, { "input_text": "These results should contribute to a better understanding of the regulation of IL3 gene expression in human T lymphocytes .", "target_text": { "IL3": "protein", "human T lymphocytes": "cell_type" } }, { "input_text": "Dimerization of NF-KB2 with RelA ( p65 ) regulates DNA binding , transcriptional activation , and inhibition by an I kappa B -alpha ( MAD-3 ) .", "target_text": { "NF-KB2": "protein", "RelA ( p65 )": "protein", "I kappa B": "protein", "I kappa B -alpha": "protein", "MAD-3": "protein" } }, { "input_text": "Inducible expression of human immunodeficiency virus ( HIV ) is regulated by a cellular transcription factor , nuclear factor kappa B ( NF-kappa B ) .", "target_text": { "transcription factor": "protein", "nuclear factor kappa B": "protein", "NF-kappa B": "protein" } }, { "input_text": "NF-kappa B is composed of distinct subunits ; five independent genes , NFKB1 ( p105 ) , NFKB2 ( p100 ) , RelA ( p65 ) , c-rel and relB , that encode related proteins that bind to kappa B DNA elements have been isolated .", "target_text": { "NF-kappa B": "protein", "NFKB1": "DNA", "p105": "protein", "NFKB2": "DNA", "p100": "protein", "RelA ( p65 )": "protein", "c-rel": "DNA", "relB": "DNA", "kappa B DNA elements": "DNA" } }, { "input_text": "We have previously found that NFKB2 ( p49/p52 ) acts in concert with RelA ( p65 ) to stimulate the HIV enhancer in Jurkat T-leukemia cells .", "target_text": { "NFKB2 ( p49/p52 )": "protein", "RelA ( p65 )": "protein", "HIV enhancer": "DNA", "T-leukemia cells": "cell_line" } }, { "input_text": "Here we examine the biochemical basis for the transcriptional regulation of HIV by NFKB2 .", "target_text": { "NFKB2": "protein" } }, { "input_text": "Using Scatchard analysis , we have determined the dissociation constants of homodimeric p49 and heterodimeric p49/p65 for binding to the HIV kappa B site .", "target_text": { "homodimeric p49": "protein", "heterodimeric p49/p65": "protein", "kappa B site": "DNA", "HIV kappa B site": "DNA" } }, { "input_text": "p49 has a approximately 18-fold-lower affinity for the HIV kappa B site ( KD = 69.1 pM ) than does the approximately 50-kDa protein NFKB1 ( p50 ) derived from p105 ( KD = 3.9 pM ) .", "target_text": { "p49": "protein", "kappa B site": "DNA", "NFKB1 ( p50 )": "protein", "p105": "protein" } }, { "input_text": "In contrast , the affinity of heterodimeric NFKB2 ( p49 ) / RelA ( p65 ) for this site is approximately 6-fold higher ( KD = 11.8 pM ) than that of p49 alone .", "target_text": { "NFKB2": "protein", "p49": "protein", "RelA ( p65 )": "protein", "heterodimeric NFKB2 ( p49 ) / RelA ( p65 )": "protein" } }, { "input_text": "Consistent with these findings , in vitro transcription was stimulated 18-fold by the addition of preformed , heterodimeric NFKB2 ( p49 ) / RelA ( p65 ) protein .", "target_text": { "NFKB2": "protein", "p49": "protein", "RelA ( p65 )": "protein", "heterodimeric NFKB2 ( p49 ) / RelA ( p65 ) protein": "protein" } }, { "input_text": "Transcriptional activation of the HIV enhancer was also subject to regulation by recently cloned I kappa B-alpha ( MAD-3 ) .", "target_text": { "I kappa B-alpha": "protein", "MAD-3": "protein" } }, { "input_text": "Recombinant I kappa B-alpha ( MAD-3 ) inhibited the DNA binding activity of p65 , p49/p65 , and p50/p65 but stimulated the binding of NFKB2 ( p49 ) or NFKB1 ( p50 ) .", "target_text": { "MAD-3": "protein", "p65": "protein", "p49/p65": "protein", "p50/p65": "protein", "NFKB2": "protein", "p49": "protein" } }, { "input_text": "Functional activation of an HIV reporter plasmid by p49/p65 in transiently transfected Jurkat T-leukemia cells was also inhibited by coexpression of MAD-3 .", "target_text": { "p49/p65": "protein", "T-leukemia cells": "cell_line", "transiently transfected Jurkat T-leukemia cells": "cell_line", "MAD-3": "protein" } }, { "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )", "target_text": {} }, { "input_text": "The c-rel protooncogene product represses NF-kappa B p65 -mediated transcriptional activation of the long terminal repeat of type 1 human immunodeficiency virus .", "target_text": { "c-rel protooncogene": "DNA", "c-rel protooncogene product": "protein", "NF-kappa B": "protein", "p65": "protein" } }, { "input_text": "The long terminal repeat ( LTR ) of the type 1 human immunodeficiency virus ( HIV-1 ) and the 5' regulatory region of the gene encoding the interleukin 2 receptor alpha subunit ( IL-2R alpha ) share functional kappa B enhancer elements involved in the regulation of these inducible transcription units during T-cell activation .", "target_text": { "long terminal repeat": "DNA", "LTR": "DNA", "5' regulatory region": "DNA", "interleukin 2 receptor alpha subunit": "protein", "IL-2R alpha": "protein", "kappa B enhancer elements": "DNA" } }, { "input_text": "These kappa B enhancer elements are recognized by a structurally related family of interactive proteins that includes p50 , p65 , and the product of the c-rel protooncogene ( c-Rel ) .", "target_text": { "kappa B enhancer elements": "DNA", "p50": "protein", "p65": "protein", "c-rel protooncogene": "DNA", "c-Rel": "protein" } }, { "input_text": "Recent biochemical studies have shown that p65 and p50 form the prototypical NF-kappa B complex , which is rapidly translocated from the cytoplasm to the nucleus during T-cell activation .", "target_text": { "p65": "protein", "p50": "protein", "NF-kappa B": "protein", "NF-kappa B complex": "protein" } }, { "input_text": "This intracellular signaling complex potently stimulates kappa B-directed transcription from either the HIV-1 LTR or the IL-2R alpha promoter via the strong transactivation domain present in p65 .", "target_text": { "HIV-1 LTR": "DNA", "IL-2R alpha": "protein", "IL-2R alpha promoter": "DNA", "p65": "protein" } }, { "input_text": "We now demonstrate that nuclear expression of human c-Rel , which is induced by either phorbol ester or tumor necrosis factor alpha with delayed kinetics relative to p65 , markedly represses p65 -mediated activation of these transcription units .", "target_text": { "c-Rel": "protein", "tumor necrosis factor alpha": "protein", "p65": "protein" } }, { "input_text": "These inhibitory effects of c-Rel correlate with its DNA-binding activity but not with its ability to heterodimerize with p50 , suggesting that c-Rel inhibition involves competition with p50 /p65 for occupancy of the kappa B enhancer element .", "target_text": { "c-Rel": "protein", "p50": "protein", "/p65": "protein", "p50 /p65": "protein" } }, { "input_text": "Together , these findings suggest that one function of c-Rel is as a physiologic repressor of the HIV-1 LTR and IL-2R alpha promoters , serving to efficiently counter the strong transcriptional activating effects of p65 .", "target_text": { "c-Rel": "protein", "HIV-1 LTR": "DNA", "IL-2R alpha": "protein", "p65": "protein" } }, { "input_text": "Ras oncogene transformation of human B lymphoblasts is associated with lymphocyte activation and with a block of differentiation .", "target_text": { "Ras oncogene": "DNA", "human B lymphoblasts": "cell_type" } }, { "input_text": "The p21ras small GTP binding proteins participate in signal transduction from cell surface receptors and affect neoplastic transformation and development in many different cell types .", "target_text": { "p21ras small GTP binding proteins": "protein" } }, { "input_text": "In the present study , we examined the relationship between ras transformation and differentiation of human B lymphocytes .", "target_text": { "human B lymphocytes": "cell_type" } }, { "input_text": "We show that the constitutive expression of the T24 Ha-ras oncogene in EBV-immortalized B lymphoblasts was associated with the induction of the interleukin 2 receptor alpha subunit , with an impaired immunoglobulin gene expression , altered adhesion properties and increased survival in serum-free medium .", "target_text": { "T24 Ha-ras oncogene": "DNA", "EBV-immortalized B lymphoblasts": "cell_line", "interleukin 2 receptor alpha subunit": "protein", "immunoglobulin gene": "DNA" } }, { "input_text": "Since induction of the IL-2 receptor alpha subunit is a hallmark of lymphocyte activation , we suggest that p21ras naturally triggers B cell activation .", "target_text": { "IL-2 receptor alpha subunit": "protein", "lymphocyte": "cell_type", "p21ras": "protein", "B cell": "cell_type" } }, { "input_text": "The ras-transformed lymphocytes displayed a fully functional IL-2r , as assessed by c-fos induction following treatment with IL-2 ; nevertheless , they were not growth stimulated by this lymphokine .", "target_text": { "ras-transformed lymphocytes": "cell_line", "IL-2r": "protein", "c-fos": "DNA", "IL-2": "protein", "lymphokine": "protein" } }, { "input_text": "The decreased expression of immunoglobulin genes indicates that the ras oncogene blocks terminal differentiation to plasma cells , possibly by inhibiting the activity of lymphocyte-specific transcription factors .", "target_text": { "immunoglobulin genes": "DNA", "ras oncogene": "DNA", "plasma cells": "cell_type", "lymphocyte-specific transcription factors": "protein" } }, { "input_text": "Somewhat unexpectedly , the constitutive p21ras activity did not cause an increased DNA binding of transcription factors PEA1 ( AP1 ) , PEA3 , Oct-2 or NF-kB", "target_text": { "p21ras": "protein", "transcription factors": "protein", "PEA1": "protein", "AP1": "protein", "PEA3": "protein", "Oct-2": "protein", "NF-kB": "protein" } }, { "input_text": "Comparative analysis of NFAT ( nuclear factor of activated T cells ) complex in human T and B lymphocytes .", "target_text": { "NFAT": "protein", "nuclear factor of activated T cells": "protein" } }, { "input_text": "Nuclear factor of activated T cells ( NFAT ) is a transcriptional activator that binds to sequences in the interleukin-2 ( IL-2 ) promoter and is thought to be largely responsible for the T cell-specific inducibility of IL-2 expression .", "target_text": { "NFAT": "protein", "transcriptional activator": "protein", "interleukin-2": "protein", "IL-2": "protein", "interleukin-2 ( IL-2 ) promoter": "DNA" } }, { "input_text": "Electrophoretic mobility shift assays ( EMSA ) showed that specific NFAT binding activity could also be induced in human B cells .", "target_text": { "NFAT": "protein", "human B cells": "cell_type" } }, { "input_text": "The B cell NFAT complex , however , was not functional , since it failed to activate transcription from an NFAT -driven chloramphenicol acetyltransferase ( CAT ) construct .", "target_text": { "NFAT": "protein", "NFAT complex": "protein", "B cell NFAT complex": "protein", "chloramphenicol acetyltransferase": "protein", "CAT": "protein", "NFAT -driven chloramphenicol acetyltransferase ( CAT ) construct": "DNA" } }, { "input_text": "Competition with an AP-1 motif or with anti-Jun and anti-Fos antibodies abolished binding to the NFAT motif in both T and B cells , indicating that Jun and Fos are critical for NFAT complex formation in both cell types .", "target_text": { "AP-1 motif": "DNA", "anti-Jun": "protein", "anti-Fos antibodies": "protein", "NFAT": "protein", "NFAT motif": "DNA", "NFAT complex": "protein" } }, { "input_text": "Purified recombinant Jun and Fos proteins failed to bind directly to the NFAT motif .", "target_text": { "NFAT": "protein", "NFAT motif": "DNA" } }, { "input_text": "However , when combined with unstimulated B or T cell extracts , full-length , but not truncated , Jun/Fos heterodimers were able to form an NFAT complex , indicating the presence of a constitutively expressed nuclear factor ( s ) in B and T cells necessary for the formation of the NFAT complex in both cell types .", "target_text": { "NFAT": "protein", "NFAT complex": "protein", "constitutively expressed nuclear factor": "protein" } }, { "input_text": "An NFAT oligonucleotide carrying mutations in the 5' purine-rich part of the NFAT sequence failed to form a complex and to compete with the wild type motif for NFAT complex formation in both T and B cells .", "target_text": { "NFAT": "protein", "5' purine-rich part": "DNA", "NFAT sequence": "DNA", "NFAT complex": "protein" } }, { "input_text": "We therefore propose a model whereby a core NFAT complex consisting of Jun , Fos , and a constitutive nuclear factor is formed in both T and B cells , but an additional factor and/or post-translational modification of a factor , missing in B cells , might be required for transactivation by NFAT .", "target_text": { "NFAT": "protein", "NFAT complex": "protein", "Jun": "protein", "Fos": "protein", "constitutive nuclear factor": "protein", "B cells": "cell_type" } }, { "input_text": "Differential autoregulation of glucocorticoid receptor expression in human T- and B- cell lines .", "target_text": { "glucocorticoid receptor": "protein" } }, { "input_text": "Regulation of glucocorticoid receptor ( GR ) expression by its cognate ligand was examined in the glucocorticoid-sensitive human leukemic T-cell line 6TG1.1 and in the human B-cell line IM-9 .", "target_text": { "glucocorticoid receptor": "protein", "glucocorticoid-sensitive human leukemic T-cell line 6TG1.1": "cell_line", "human B-cell line IM-9": "cell_line" } }, { "input_text": "In contrast to the decrease in GR mRNA seen in IM-9 cells after treatment with 1 microM dexamethasone for 16-18 h , treatment of 6TG1.1 cells resulted in an 8-fold increase in GR mRNA , as determined by Northern blot and RNase protection analysis , with a corresponding 3- to 4-fold increase in GR protein .", "target_text": { "GR mRNA": "RNA", "IM-9 cells": "cell_line", "6TG1.1 cells": "cell_line", "RNase": "protein", "GR protein": "protein" } }, { "input_text": "Half-maximal induction of GR mRNA and protein in 6TG1.1 cells was observed between 10-100 nM dexamethasone , and inclusion of 1 microM RU 38486 completely blocked the effects of 100 nM dexamethasone , demonstrating that positive autoregulation of GR expression in 6TG1.1 cells is a receptor-mediated response .", "target_text": { "GR mRNA": "RNA", "6TG1.1 cells": "cell_line", "GR": "protein" } }, { "input_text": "Positive autoregulation of GR expression was also observed in glucocorticoid-resistant CEM-C1 cells , which contain functional GR , but whose growth is unaffected by glucocorticoids .", "target_text": { "GR": "protein", "glucocorticoid-resistant CEM-C1 cells": "cell_line" } }, { "input_text": "Thus , positive autoregulation is neither a consequence nor the sole cause of growth arrest .", "target_text": {} }, { "input_text": "The degree of negative autoregulation in IM-9 cells and positive autoregulation in 6TG1.1 cells was unaffected by inhibition of protein synthesis with cycloheximide .", "target_text": { "IM-9 cells": "cell_line", "6TG1.1 cells": "cell_line" } }, { "input_text": "Measurement of GR mRNA turnover in 6TG1.1 cells treated with actinomycin-D revealed a half-life of 2.5 h , which was unaffected by dexamethasone treatment .", "target_text": { "GR mRNA": "RNA", "6TG1.1 cells": "cell_line" } }, { "input_text": "A similar half-life was determined in IM-9 cells and was also unaffected by steroid treatment .", "target_text": { "IM-9 cells": "cell_line" } }, { "input_text": "These results are consistent with the interpretation that glucocorticoid -mediated autoregulation of GR expression is a tissue-specific primary transcriptional response .", "target_text": {} }, { "input_text": "Induction of CD8 antigen and suppressor activity by glucocorticoids in a CEM human leukemic cell clone .", "target_text": { "CD8 antigen": "protein", "CEM human leukemic cell clone": "cell_line" } }, { "input_text": "The relationship between glucocorticoid effect and regulation of cell surface antigens was investigated in two models of leukemic cell lines , CEM C7 denoted ( r+ , ly+ ) and CEM C1 ( r+ , ly- ) .", "target_text": { "cell surface antigens": "protein", "leukemic cell lines": "cell_line", "CEM C7": "cell_line", "CEM C1": "cell_line" } }, { "input_text": "The reactivity of murine monoclonal antibodies , anti-CD4-FITC , anti-CD8-FITC , anti-CD2-FITC and anti-calla-FITC , were analyzed using flow cytometry .", "target_text": { "murine monoclonal antibodies": "protein", "anti-CD4-FITC": "protein", "anti-CD8-FITC": "protein", "anti-CD2-FITC": "protein", "anti-calla-FITC": "protein" } }, { "input_text": "The suppressor function was determined using [3H]thymidine incorporation into phytohemagglutinin -activated peripheral blood lymphocytes .", "target_text": { "phytohemagglutinin": "protein", "phytohemagglutinin -activated peripheral blood lymphocytes": "cell_line" } }, { "input_text": "Dexamethasone treatment of a human leukemic cell clone CEM C7 caused an increase in a subset of cells expressing the surface antigen CD8 , which is present on suppressor and cytotoxic T-lymphocytes .", "target_text": { "human leukemic cell clone CEM C7": "cell_line", "surface antigen CD8": "protein", "cytotoxic T-lymphocytes": "cell_type" } }, { "input_text": "By comparison , there was no modification of the expression of CD4 antigen , which is expressed at high levels in these cells .", "target_text": { "CD4 antigen": "protein" } }, { "input_text": "After two days of treatment with 5 x 10 ( -8 ) M dexamethasone , CEM C7 cells showed a two-fold increase in suppressor activity compared to untreated cells .", "target_text": { "CEM C7 cells": "cell_line" } }, { "input_text": "In contrast , there was no regulation by glucocorticoids of either the CD8 or CD4 antigens in the leukemic clone CEM C1 .", "target_text": { "CD8": "protein", "CD4 antigens": "protein", "leukemic clone CEM C1": "cell_line" } }, { "input_text": "Furthermore , no modification of the suppressor function in CEM C1 cells by dexamethasone was observed .", "target_text": { "CEM C1 cells": "cell_line" } }, { "input_text": "In the human leukemic cells studied here , the ability to induce CD8 antigen expression in a CD4+ cells correlates with the ability to induce cell lysis in a glucocorticoid receptor positive cell population .", "target_text": { "CD8 antigen": "protein", "CD4+ cells": "cell_line", "glucocorticoid receptor": "protein", "glucocorticoid receptor positive cell population": "cell_line" } }, { "input_text": "Adenovirus E1A inhibits IFN -induced resistance to cytolysis by natural killer cells .", "target_text": { "IFN": "protein", "natural killer cells": "cell_type" } }, { "input_text": "Infection of target cells with cytopathic viruses inhibits IFN induction of cytolytic resistance to NK cell-mediated cytolysis [ IFN -mediated cytoprotection ( IFN -MCP ) ] .", "target_text": { "target cells": "cell_type", "IFN": "protein" } }, { "input_text": "It has been thought that the virally induced inhibition of IFN -MCP is secondary to the shutdown of cellular macromolecular synthesis that accompanies cytopathic virus infections .", "target_text": { "IFN": "protein" } }, { "input_text": "Group C , adenovirus serotype 5 ( Ad5 ) infection inhibits both IFN -MCP and cellular protein synthesis .", "target_text": { "IFN": "protein", "cellular protein": "protein" } }, { "input_text": "This study determined if the Ad5-induced inhibition of IFN -MCP was independent of adenovirus ( Ad ) infection and secondary only to the expression of the Ad early region 1A gene ( E1A ) .", "target_text": { "IFN": "protein", "Ad early region 1A gene": "DNA", "E1A": "DNA" } }, { "input_text": "To test this hypothesis , 4-h NK cytolysis assays were performed on IFN-gamma-treated human cells infected with an Ad5 E1A deletion mutant , dl343 , or transfected with the Ad5 E1A gene .", "target_text": { "IFN-gamma-treated human cells": "cell_line", "E1A": "DNA", "Ad5 E1A gene": "DNA" } }, { "input_text": "IFN -MCP was not inhibited by infection with dl343 , despite the production of large amounts of both early ( E1B , p55 ) and late ( hexon ) Ad proteins .", "target_text": { "IFN": "protein", "E1B": "protein", "p55": "protein", "hexon": "protein", "Ad proteins": "protein" } }, { "input_text": "In contrast to E1A -negative , parental cell lines , IFN -MCP was blocked in Ad5 E1A -transfected epithelial and fibroblastic cell lines .", "target_text": { "E1A": "DNA", "E1A -negative , parental cell lines": "cell_line", "IFN": "protein", "E1A -transfected epithelial": "cell_line", "fibroblastic cell lines": "cell_line" } }, { "input_text": "Genetic mapping studies within the E1A gene demonstrated that expression of only the first exon of E1A was sufficient to inhibit IFN -MCP .", "target_text": { "E1A": "DNA", "E1A gene": "DNA", "IFN": "protein" } }, { "input_text": "DNA sequence homology of E1A genes between different Ad groups ( group A , Ad12 ; group C , Ad5 ) is limited almost entirely to three conserved regions located within the first exon of E1A .", "target_text": { "E1A": "DNA" } }, { "input_text": "Because IFN -MCP was also blocked in Ad12 E1A -transfected cell lines , expression of one or more of the E1A -conserved regions may be necessary to inhibit IFN -MCP .", "target_text": { "IFN": "protein", "E1A": "DNA", "Ad12 E1A -transfected cell lines": "cell_line", "E1A -conserved regions": "DNA" } }, { "input_text": "In summary , the expression of E1A gene products inhibited IFN -MCP independently of virus infection .", "target_text": { "E1A": "DNA", "E1A gene products": "protein", "IFN": "protein" } }, { "input_text": "E1A 's inhibition of IFN -MCP has the net effect of promoting the selective NK cell-mediated clearance of Ad-infected or Ad-transformed human cells .", "target_text": { "E1A": "DNA", "IFN": "protein", "Ad-transformed human cells": "cell_line" } }, { "input_text": "A protein of the AP-1 family is a component of nuclear factor of activated T cells .", "target_text": { "AP-1 family": "protein", "T cells": "cell_type", "nuclear factor of activated T cells": "protein" } }, { "input_text": "Nuclear factor of activated T cells ( NF-AT ) is a transcriptional activator involved in the induction of IL-2 gene expression .", "target_text": { "Nuclear factor of activated T cells": "protein", "NF-AT": "protein", "transcriptional activator": "protein", "IL-2": "protein" } }, { "input_text": "The response element for NF-AT is a sequence localized between -285/-254 in the IL-2 regulatory region .", "target_text": { "NF-AT": "protein", "-285/-254": "DNA", "IL-2": "protein", "IL-2 regulatory region": "DNA" } }, { "input_text": "The composition of NF-AT protein is still not fully elucidated .", "target_text": { "NF-AT": "protein" } }, { "input_text": "We demonstrate that , in normal human T cells , an AP-1 protein is a component of the NF-AT protein complex .", "target_text": { "T cells": "cell_type", "AP-1 protein": "protein", "NF-AT": "protein", "NF-AT protein complex": "protein" } }, { "input_text": "This was evidenced by the ability of the AP-1 site to compete with the NF-AT site for binding to NF-AT and by the capacity of immobilized anti- Jun and anti- Fos antibodies to deplete NF-AT -binding activity from nuclear extracts of activated T cells .", "target_text": { "AP-1 site": "DNA", "NF-AT": "protein", "Jun": "protein", "immobilized anti- Jun": "protein", "Fos": "protein", "anti- Fos": "protein", "T cells": "cell_type", "activated T cells": "cell_type" } }, { "input_text": "There was no detectable binding of in vitro translated Jun /Fos heterodimer ( AP-1 ) to the NF-AT sequence , and the NF-AT sequence was unable to inhibit the binding of Jun /Fos to the AP-1 sequence .", "target_text": { "Jun": "protein", "/Fos": "protein", "Jun /Fos heterodimer": "protein", "AP-1": "protein", "NF-AT": "protein", "NF-AT sequence": "DNA", "Jun /Fos": "protein", "AP-1 sequence": "DNA" } }, { "input_text": "The presence of an AP-1 protein in the NF-AT protein complex may regulate NF-AT -binding activity through protein-protein interaction .", "target_text": { "AP-1": "protein", "NF-AT": "protein" } }, { "input_text": "Interaction between NF-kappa B - and serum response factor -binding elements activates an interleukin-2 receptor alpha-chain enhancer specifically in T lymphocytes .", "target_text": { "NF-kappa B": "protein", "serum response factor": "protein", "interleukin-2": "protein", "interleukin-2 receptor alpha-chain enhancer": "DNA", "T lymphocytes": "cell_type" } }, { "input_text": "We find that a short enhancer element containing the NF-kappa B binding site from the interleukin-2 receptor alpha-chain gene ( IL-2R alpha ) is preferentially activated in T cells .", "target_text": { "NF-kappa B binding site": "DNA", "interleukin-2": "protein", "interleukin-2 receptor alpha-chain gene": "DNA", "IL-2R alpha": "protein", "T cells": "cell_type" } }, { "input_text": "The IL-2R alpha enhancer binds NF-kappa B poorly and is only weakly activated by the NF-kappa B site alone .", "target_text": { "IL-2R alpha": "protein", "IL-2R alpha enhancer": "DNA", "NF-kappa B": "protein", "NF-kappa B site": "DNA" } }, { "input_text": "Serum response factor ( SRF ) binds to a site adjacent to the NF-kappa B site in the IL-2R enhancer , and both sites together have strong transcriptional activity specifically in T cells .", "target_text": { "Serum response factor": "protein", "SRF": "protein", "NF-kappa B site": "DNA", "IL-2R enhancer": "DNA", "T cells": "cell_type" } }, { "input_text": "Surprisingly , the levels of SRF constitutively expressed in T cells are consistently higher than in other cell types .", "target_text": { "SRF": "protein", "T cells": "cell_type" } }, { "input_text": "Overexpression of SRF in B cells causes the IL-2R enhancer to function as well as it does in T cells , suggesting that the high level of SRF binding in T cells is functionally important .", "target_text": { "SRF": "protein", "B cells": "cell_type", "IL-2R enhancer": "DNA", "T cells": "cell_type" } }, { "input_text": "Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor , I kappa B-alpha .", "target_text": { "transcriptional activator": "protein", "NF-kappa B": "protein", "I kappa B-alpha": "protein" } }, { "input_text": "The NK-kappa B transcription factor complex is sequestered in the cytoplasm by the inhibitory protein I kappa B-alpha ( MAD-3 ) .", "target_text": { "NK-kappa B transcription factor complex": "protein", "I kappa B-alpha": "protein", "MAD-3": "protein" } }, { "input_text": "Various cellular stimuli relieve this inhibition by mechanisms largely unknown , leading to NF-kappa B nuclear localization and transactivation of its target genes .", "target_text": { "NF-kappa B": "protein" } }, { "input_text": "It is demonstrated here with human T lymphocytes and monocytes that different stimuli , including tumor necrosis factor alpha and phorbol 12-myristate 13-acetate , cause rapid degradation of I kappa B-alpha , with concomitant activation of NF-kappa B , followed by a dramatic increase in I kappa B-alpha mRNA and protein synthesis .", "target_text": { "T lymphocytes": "cell_type", "human T lymphocytes": "cell_type", "monocytes": "cell_type", "tumor necrosis factor alpha": "protein", "I kappa B-alpha": "protein", "NF-kappa B": "protein", "I kappa B-alpha mRNA": "RNA" } }, { "input_text": "Transfection studies reveal that the I kappa B-alpha mRNA and the encoded protein are potently induced by NF-kappa B and by homodimers of p65 and of c-Rel .", "target_text": { "I kappa B-alpha": "protein", "I kappa B-alpha mRNA": "RNA", "NF-kappa B": "protein", "p65": "protein", "c-Rel": "protein" } }, { "input_text": "We propose a model in which NF-kappa B and I kappa B-alpha mutually regulate each other in a cycle : saturating amounts of the inhibitory I kappa B-alpha protein are destroyed upon stimulation , allowing rapid activation of NF-kappa B .", "target_text": { "NF-kappa B": "protein", "I kappa B-alpha": "protein" } }, { "input_text": "Subsequently , I kappa B-alpha mRNA and protein levels are quickly induced by the activated NF-kappa B .", "target_text": { "I kappa B-alpha": "protein", "I kappa B-alpha mRNA": "RNA", "NF-kappa B": "protein" } }, { "input_text": "This resurgence of I kappa B-alpha protein acts to restore an equilibrium in which NF-kappa B is again inhibited .", "target_text": { "I kappa B-alpha": "protein", "NF-kappa B": "protein" } }, { "input_text": "Replication of type 1 human immunodeficiency viruses containing linker substitution mutations in the -201 to -130 region of the long terminal repeat .", "target_text": { "-201 to -130 region": "DNA", "long terminal repeat": "DNA" } }, { "input_text": "In previous transfection analyses using the chloramphenicol acetyltransferase reporter gene system , we determined that linker substitution ( LS ) mutations between -201 and -130 ( relative to the transcription start site ) of the human immunodeficiency virus type 1 long terminal repeat ( LTR ) caused moderate decreases in LTR transcriptional activity in a T-cell line ( S.L.Zeichner , J.Y.H. Kim , and J.C.Alwine , J.Virol.65 : 2436-2444 , 1991 ) .", "target_text": { "chloramphenicol acetyltransferase": "protein", "reporter gene": "DNA", "-201 and -130": "DNA", "long terminal repeat": "DNA", "LTR": "DNA", "T-cell line": "cell_line" } }, { "input_text": "In order to confirm the significance of this region in the context of viral replication , we constructed several of these LS mutations ( -201 to - 184 , -183 to -166 , -165 to -148 , and -148 to -130 ) in proviruses and prepared viral stocks by cocultivation of transfected RD cells with CEMx174 cells .", "target_text": { "-201 to - 184": "DNA", "-183 to -166": "DNA", "-165 to -148": "DNA", "-148 to -130": "DNA", "transfected RD cells": "cell_line", "CEMx174 cells": "cell_line" } }, { "input_text": "In addition , two mutations between -93 and -76 and between -75 and -58 were utilized , since they affect the nuclear factor kappa B ( NF-kappa B ) - and Sp1 -binding sites and were expected to diminish viral replication .", "target_text": { "-93 and -76": "DNA", "-75 and -58": "DNA", "nuclear factor kappa B": "protein", "NF-kappa B": "protein", "Sp1": "protein" } }, { "input_text": "Our results suggest that while transfection analyses offer an adequate approximation of the effects of the LS mutations , the analysis of viral replication using a mutant viral stock presents a more accurate picture , which is sometimes at variance with the transfection results .", "target_text": {} }, { "input_text": "Three mutants ( -201/-184 NXS , -165/-148 NXS , and -147/-130 NXS ) had effects on viral replication that were much more severe than the effects predicted from their performance in transfection analyses , and the effects of two LS mutations ( -201/-184 NXS and -183/-166 NXS ) were not predicted by their effects in transfection .", "target_text": {} }, { "input_text": "In addition , we observed cell type-specific permissiveness to replication of some mutant viruses .", "target_text": {} }, { "input_text": "In the cell types tested , the LS mutations indicated an apparent requirement not only for the intact NF-kappa B and SP1-binding sites but also for several regions between -201 and -130 not previously associated with viral infectivity .", "target_text": { "NF-kappa B": "protein", "SP1-binding sites": "DNA", "-201 and -130": "DNA" } }, { "input_text": "Transcription factor GATA-1 and erythroid development .", "target_text": { "Transcription factor": "protein", "GATA-1": "protein" } }, { "input_text": "In summary , we derived an experimental system that allows us to dissect the function of GATA-1 in red cell development at a genetic level .", "target_text": { "GATA-1": "protein", "red cell": "cell_type" } }, { "input_text": "We have established the essential nature of GATA-1 during both primitive and definitive erythropoiesis .", "target_text": { "GATA-1": "protein" } }, { "input_text": "By ablating the expression of the endogenous GATA-1 gene , we are in a position to introduce a variety of constructs that harbor subtle modifications in flanking or protein-coding sequences .", "target_text": { "GATA-1": "protein", "GATA-1 gene": "DNA", "protein-coding sequences": "DNA" } }, { "input_text": "We can now study regulatory regions and functional domains of the protein in the context of a true erythroid environment , experiments that have not been possible heretofore .", "target_text": {} }, { "input_text": "Although the assay involves the dramatic loss of red cell production , it should be possible to define important regulatory domains that can then be assayed using less stringent systems , such as cell-free extracts for in vitro transcription .", "target_text": {} }, { "input_text": "The ideal situation would be analyses conducted in GATA-1 -erythroid cells .", "target_text": { "GATA-1": "protein", "GATA-1 -erythroid cells": "cell_line" } }, { "input_text": "However , these cells have been impossible to generate given the requirement of GATA-1 for Epo receptor expression and red cell viability ( C. Simon and S. Orkin , unpublished observations ) .", "target_text": { "GATA-1": "protein", "Epo receptor": "protein", "red cell": "cell_type" } }, { "input_text": "It may be possible to produce such cells by first expressing the Epo receptor under the influence of a constitutive promoter and then targeting the GATA-1 gene .", "target_text": { "Epo receptor": "protein", "GATA-1": "protein", "GATA-1 gene": "DNA" } }, { "input_text": "If GATA-1 -red cells were available , the analyses would involve the actual transcription of or chromatin structure surrounding the globin genes .", "target_text": { "GATA-1": "protein", "GATA-1 -red cells": "cell_line", "globin genes": "DNA" } }, { "input_text": "Structure-function studies of the GATA-1 protein could be greatly simplified and a larger number of mutants studied .", "target_text": { "GATA-1": "protein" } }, { "input_text": "However , the ES cell system can be used as an alternative until targeted erythroleukemia cells become available .", "target_text": { "targeted erythroleukemia cells": "cell_line" } }, { "input_text": "Other applications involve the introduction of other GATA-binding protein family members to determine whether they rescue the mutation .", "target_text": { "GATA-binding protein family members": "protein" } }, { "input_text": "If they can not , chimeric proteins can be tested to identify which amino acids distinguish the different family members .", "target_text": { "chimeric proteins": "protein" } }, { "input_text": "We feel that these experiments are vital to understanding the function of GATA-1 during erythroid ontogeny .", "target_text": { "GATA-1": "protein" } }, { "input_text": "How does GATA-1 regulate red cell genes like globin or the Epo receptor ? Once we identify the functional domains of the GATA-binding proteins , we hope to learn what proteins GATA-1 binds to in the basic transcription machinery or in chromatin .", "target_text": { "GATA-1": "protein", "red cell genes": "DNA", "globin": "DNA", "Epo receptor": "protein", "GATA-binding proteins": "protein" } }, { "input_text": "Is GATA-1 necessary for globin gene switching ? GATA-1 may be modified differently during development so that the locus control region can interact with different globin promoters .", "target_text": { "GATA-1": "protein", "globin promoters": "DNA" } }, { "input_text": "We may find that one region of the protein is required for embryonic expression and another for adult globin gene expression .", "target_text": { "globin gene": "DNA" } }, { "input_text": "A human putative lymphocyte G0/G1 switch gene homologous to a rodent gene encoding a zinc-binding potential transcription factor .", "target_text": { "human putative lymphocyte G0/G1 switch gene": "DNA", "rodent gene": "DNA", "zinc-binding potential transcription factor": "protein" } }, { "input_text": "G0S24 is a member of a set of genes ( putative G0/G1 switch regulatory genes ) that are expressed transiently within 1-2 hr of the addition of lectin or cycloheximide to human blood mononuclear cells .", "target_text": { "G0S24": "DNA", "putative G0/G1 switch regulatory genes": "DNA", "lectin": "protein", "human blood mononuclear cells": "cell_type" } }, { "input_text": "Comparison of a full-length cDNA sequence with the corresponding genomic sequence reveals an open reading frame of 326 amino acids , distributed across two exons .", "target_text": { "full-length cDNA sequence": "DNA", "open reading frame": "DNA", "exons": "DNA" } }, { "input_text": "Potential phosphorylation sites include the sequence PSPTSPT , which resembles an RNA polymerase II repeat reported to be a target of the cell cycle control kinase cdc2 .", "target_text": { "phosphorylation sites": "protein", "PSPTSPT": "protein", "RNA polymerase II repeat": "protein", "cell cycle control kinase cdc2": "protein" } }, { "input_text": "Comparison of the derived protein sequence with those of rodent homologs allows classification into three groups .", "target_text": {} }, { "input_text": "Group 1 contains G0S24 and the rat and mouse TIS11 genes ( also known as TTP , Nup475 , and Zfp36 ) .", "target_text": { "G0S24": "DNA", "TTP": "DNA", "Nup475": "DNA", "Zfp36": "DNA" } }, { "input_text": "Members of this group have three tetraproline repeats .", "target_text": { "three tetraproline repeats": "protein" } }, { "input_text": "Groups 1 and 2 have a serine-rich region and an \" arginine element \" ( RRLPIF ) at the carboxyl terminus .", "target_text": { "serine-rich region": "protein", "arginine element": "protein", "RRLPIF": "protein", "carboxyl terminus": "protein" } }, { "input_text": "All groups contain cysteine- and histidine-rich putative zinc finger domains and a serine-phenylalanine \" SFS \" domain similar to part of the large subunit of eukaryotic RNA polymerase II .", "target_text": { "cysteine- and histidine-rich putative zinc finger domains": "protein", "serine-phenylalanine \" SFS \" domain": "protein", "eukaryotic RNA polymerase II": "protein" } }, { "input_text": "Comparison of group 1 human and mouse genomic sequences shows high conservation in the 5' flank and exons .", "target_text": { "5' flank": "DNA", "exons": "DNA" } }, { "input_text": "A CpG island suggests expression in the germ line .", "target_text": {} }, { "input_text": "G0S24 has potential sites for transcription factors in the 5' flank and intron ; these include a serum response element .", "target_text": { "G0S24": "DNA", "transcription factors": "protein", "5' flank": "DNA", "intron": "DNA", "serum response element": "DNA" } }, { "input_text": "Protein and genomic sequences show similarities with those of a variety of proteins involved in transcription , suggesting that the G0S24 product has a similar role .", "target_text": { "G0S24 product": "protein" } }, { "input_text": "Regulation of lymphoid-specific immunoglobulin mu heavy chain gene enhancer by ETS-domain proteins .", "target_text": { "immunoglobulin": "protein", "immunoglobulin mu heavy chain gene": "DNA", "enhancer": "DNA", "lymphoid-specific immunoglobulin mu heavy chain gene enhancer": "DNA" } }, { "input_text": "The enhancer for the immunoglobulin mu heavy chain gene ( IgH ) activates a heterologous gene at the pre-B cell stage of B lymphocyte differentiation .", "target_text": { "enhancer": "DNA", "immunoglobulin mu heavy chain gene": "DNA", "IgH": "protein", "heterologous gene": "DNA", "B lymphocyte": "cell_type" } }, { "input_text": "A lymphoid-specific element , microB , is necessary for enhancer function in pre-B cells .", "target_text": { "lymphoid-specific element": "DNA", "microB": "DNA", "enhancer": "DNA", "pre-B cells": "cell_type" } }, { "input_text": "A microB binding protein is encoded by the PU.1/Spi-1 proto-oncogene .", "target_text": { "microB": "DNA", "microB binding protein": "protein", "PU.1/Spi-1 proto-oncogene": "DNA" } }, { "input_text": "Another sequence element , microA , was identified in the mu enhancer that binds the product of the ets-1 proto-oncogene .", "target_text": { "sequence element": "DNA", "microA": "DNA", "mu enhancer": "DNA", "ets-1 proto-oncogene": "DNA" } }, { "input_text": "The microA motif was required for microB-dependent enhancer activity , which suggests that a minimal B cell-specific enhancer is composed of both the PU.1 and Ets-1 binding sites .", "target_text": { "microA": "DNA", "microB-dependent enhancer": "DNA", "minimal B cell-specific enhancer": "DNA", "PU.1": "protein", "Ets-1": "protein", "PU.1 and Ets-1 binding sites": "DNA" } }, { "input_text": "Co-expression of both PU.1 and Ets-1 in nonlymphoid cells trans-activated reporter plasmids that contained the minimal mu enhancer .", "target_text": { "PU.1": "protein", "Ets-1": "protein", "nonlymphoid cells": "cell_type", "trans-activated reporter plasmids": "DNA", "mu enhancer": "DNA" } }, { "input_text": "These results implicate two members of the Ets family in the activation of IgH gene expression .", "target_text": { "Ets family": "protein", "IgH": "protein", "IgH gene": "DNA" } }, { "input_text": "1,25-Dihydroxy vitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate synergistically induce monocytic cell differentiation : FOS and RB expression .", "target_text": { "monocytic cell": "cell_type", "FOS": "protein", "RB": "protein" } }, { "input_text": "1,25-dihydroxy vitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate ( TPA ) interact synergistically to induce monocytic differentiation of U937 histiocytic lymphoma cells .", "target_text": { "U937 histiocytic lymphoma cells": "cell_line" } }, { "input_text": "Addition of TPA causes an otherwise ineffective dose of 1,25-dihydroxy vitamin D3 to induce differentiation .", "target_text": {} }, { "input_text": "The induced differentiation depends on the simultaneous ( vs. sequential ) presence of both agents .", "target_text": {} }, { "input_text": "The kinetics of induced differentiation are consistent with a G1 specific cellular response to initiate the metabolic cascade culminating in cell differentiation .", "target_text": {} }, { "input_text": "The induced differentiation occurs with down-regulation of c-fos protein and an accompanying up-regulation of RB protein expression , consistent with a possible need for up-regulated RB expression to maintain a given differentiated phenotype and suppress transcriptional activators that might typically be associated with proliferation .", "target_text": { "c-fos protein": "protein", "RB protein": "protein", "RB": "protein", "transcriptional activators": "protein" } }, { "input_text": "Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner .", "target_text": { "GATA-2/estrogen receptor chimera": "protein" } }, { "input_text": "The GATA factors are a family of transcriptional regulatory proteins in eukaryotes that share extensive homology in their DNA-binding domains .", "target_text": { "GATA factors": "protein", "transcriptional regulatory proteins": "protein", "DNA-binding domains": "protein" } }, { "input_text": "One enigmatic aspect of GATA factor expression is that several GATA proteins , which ostensibly share the same DNA-binding site specificity , are coexpressed in erythroid cells .", "target_text": { "GATA factor": "protein", "GATA proteins": "protein", "DNA-binding site": "protein" } }, { "input_text": "To elucidate the roles of individual GATA factors in erythropoiesis , conditional alleles of GATA-1 , GATA-2 , and GATA-3 were prepared by fusing each of the factors to the hormone-binding domain of the human estrogen receptor ( ER ) .", "target_text": { "GATA factors": "protein", "GATA-1": "protein", "GATA-2": "protein", "GATA-3": "protein", "hormone-binding domain": "protein", "human estrogen receptor": "protein", "ER": "protein" } }, { "input_text": "These GATA/ER chimeric factors were shown to be hormone-inducible trans-activating proteins in transient transfection assays .", "target_text": { "GATA/ER chimeric factors": "protein", "hormone-inducible trans-activating proteins": "protein" } }, { "input_text": "When stably introduced into primary erythroblasts or conditionally transformed erythroid progenitors cells , exogenous GATA-2/ER promoted proliferation and inhibited terminal differentiation in an estrogen -dependent manner .", "target_text": { "primary erythroblasts": "cell_type", "conditionally transformed erythroid progenitors cells": "cell_line", "GATA-2/ER": "protein" } }, { "input_text": "These phenotypic effects are specifically attributable to the action of ectopically expressed GATA-2/ER because erythroblasts expressing exogenous GATA-2 are constitutively arrested in differentiation and because erythroid progenitors expressing either Gal/ER or GATA-3/ER do not display a hormone-responsive block in differentiation .", "target_text": { "GATA-2/ER": "protein", "GATA-2": "protein", "erythroid progenitors": "cell_line", "Gal/ER": "protein", "GATA-3/ER": "protein" } }, { "input_text": "Thus , the GATA-2 transcription factor appears to play a role in regulating the self-renewal capacity of early erythroid progenitor cells .", "target_text": { "GATA-2": "protein", "GATA-2 transcription factor": "protein", "early erythroid progenitor cells": "cell_type" } }, { "input_text": "Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock , yet succumb to L. monocytogenes infection .", "target_text": { "55 kd tumor necrosis factor receptor": "protein" } }, { "input_text": "The multiple biological activities of tumor necrosis factor ( TNF ) are mediated by two distinct cell surface receptors of 55 kd ( TNFRp55 ) and 75 kd ( TNFRp75 ) .", "target_text": { "tumor necrosis factor": "protein", "TNF": "protein", "cell surface receptors": "protein", "55 kd": "protein", "TNFRp55": "protein", "75 kd": "protein", "TNFRp75": "protein" } }, { "input_text": "Using gene targeting , we generated a TNFRp55 -deficient mouse strain .", "target_text": { "TNFRp55": "protein" } }, { "input_text": "Cells from TNFRp55-/-mutant mice lack expression of TNFRp55 but display normal numbers of high affinity TNFRp75 molecules .", "target_text": { "TNFRp55": "protein", "high affinity TNFRp75 molecules": "protein" } }, { "input_text": "Thymocyte development and lymphocyte populations are unaltered , and clonal deletion of potentially self-reactive T cells is not impaired .", "target_text": { "Thymocyte": "cell_type", "lymphocyte populations": "cell_type", "T cells": "cell_type", "self-reactive T cells": "cell_type" } }, { "input_text": "However , TNF signaling is largely abolished , as judged by the failure of TNF to induce NF-kappa B in T lymphocytes from TNFRp55 -deficient mice .", "target_text": { "TNF": "protein", "NF-kappa B": "protein", "T lymphocytes": "cell_type", "TNFRp55": "protein" } }, { "input_text": "The loss of TNFRp55 function renders mice resistant to lethal dosages of either lipopolysaccharides or S. aureus enterotoxin B .", "target_text": { "TNFRp55": "protein", "S. aureus enterotoxin B": "protein" } }, { "input_text": "In contrast , TNFRp55-deficient mice are severely impaired to clear L. monocytogenes and readily succumb to infection .", "target_text": {} }, { "input_text": "Thus , the 55 kd TNFR plays a decisive role in the host 's defense against microorganisms and their pathogenic factors .", "target_text": { "55 kd TNFR": "protein" } }, { "input_text": "Costimulation of peripheral blood T cell activation by human endothelial cells .", "target_text": { "peripheral blood T cell": "cell_type", "endothelial cells": "cell_type", "human endothelial cells": "cell_type" } }, { "input_text": "Enhanced IL-2 transcription correlates with increased c-fos synthesis and increased Fos content of AP-1 .", "target_text": { "IL-2": "protein", "c-fos": "protein", "Fos": "protein", "AP-1": "protein" } }, { "input_text": "Endothelial cells ( EC ) act as APC for resting PBL in vitro , and may have important roles in vivo in the pathogenesis of allograft rejection and delayed hypersensitivity .", "target_text": { "Endothelial cells": "cell_type", "EC": "cell_type", "PBL": "cell_type", "resting PBL": "cell_type" } }, { "input_text": "We previously reported that human umbilical vein EC provide costimulatory signals to PHA-stimulated PBL via CD2 : lymphocyte function-associated Ag-3 and an unidentified ligand pair , resulting in a three- to eight-fold enhancement of IL-2 production .", "target_text": { "EC": "cell_type", "human umbilical vein EC": "cell_type", "PBL": "cell_type", "PHA-stimulated PBL": "cell_type", "CD2 : lymphocyte function-associated Ag-3": "protein", "IL-2": "protein" } }, { "input_text": "The physiologic relevance of this increase was demonstrated by the proliferative advantage provided by EC to PBL suboptimally stimulated with mAb OKT3 .", "target_text": { "EC": "cell_type", "PBL": "cell_type", "mAb OKT3": "protein" } }, { "input_text": "We now report that EC costimulation causes increased levels of IL-2 mRNA as a result of increased IL-2 transcription in PBL .", "target_text": { "EC": "cell_type", "IL-2 mRNA": "RNA", "IL-2": "protein", "PBL": "cell_type" } }, { "input_text": "We therefore examined the effects of EC on T cell nuclear factors known to regulate IL-2 transcription , including c-jun and c-fos-two components of the transcription factor AP-1 , NFAT , and others .", "target_text": { "EC": "cell_type", "T cell nuclear factors": "protein", "IL-2": "protein", "c-jun": "protein", "c-fos-two components": "protein", "transcription factor": "protein", "AP-1": "protein", "NFAT": "protein" } }, { "input_text": "PBL constitutively express c-jun transcripts , and the level of c-jun mRNA is not altered by PHA activation in the absence or presence of EC .", "target_text": { "PBL": "cell_type", "c-jun": "protein", "c-jun transcripts": "protein", "c-jun mRNA": "RNA", "PHA": "protein", "EC": "cell_type" } }, { "input_text": "In contrast , c-fos mRNA is absent from resting T cells and is induced on PHA activation .", "target_text": { "c-fos mRNA": "RNA", "T cells": "cell_type", "PHA": "protein" } }, { "input_text": "EC alone do not induce c-fos mRNA but augment the level of c-fos mRNA in PHA-activated T cells by 3- to 10-fold .", "target_text": { "EC": "cell_type", "c-fos mRNA": "RNA", "T cells": "cell_type", "PHA-activated T cells": "cell_type" } }, { "input_text": "This effect is largely independent of the CD2 : lymphocyte function- associated Ag-3 pathway .", "target_text": {} }, { "input_text": "Gel-shift analysis reveals the constitutive presence of nuclear factors in resting PBL that bind to the proximal AP-1 site of the IL-2 promoter and that contain immunoreactive c-Jun but not c-Fos protein .", "target_text": { "PBL": "cell_type", "resting PBL": "cell_type", "proximal AP-1 site": "DNA", "IL-2 promoter": "DNA", "c-Jun": "protein", "c-Fos": "protein" } }, { "input_text": "In contrast , AP-1 from PHA-activated cells contains c-Jun and low levels of c-Fos .", "target_text": { "AP-1": "protein", "PHA-activated cells": "cell_type", "c-Jun": "protein", "c-Fos": "protein" } }, { "input_text": "Strikingly , costimulation with EC results in a dramatic increase ( up to 15-fold ) in the c-Fos content of AP-1 .", "target_text": { "EC": "cell_type", "c-Fos": "protein", "AP-1": "protein" } }, { "input_text": "Levels of other nuclear factors involved in IL-2 regulation were not altered by EC , although NFAT-DNA complexes migrated at a slightly different mobility .", "target_text": { "nuclear factors": "protein", "IL-2": "protein", "EC": "cell_type", "NFAT-DNA complexes": "protein" } }, { "input_text": "In summary , our data suggest that changes in the composition of transcription factor AP-1 is a key molecular mechanism for increasing IL-2 transcription and may underlie the phenomenon of costimulation by EC .", "target_text": { "transcription factor": "protein", "AP-1": "protein", "IL-2": "protein", "EC": "cell_type" } }, { "input_text": "Transcriptional activation of human zeta 2 globin promoter by the alpha globin regulatory element ( HS-40 ) : functional role of specific nuclear factor-DNA complexes .", "target_text": { "human zeta 2 globin promoter": "DNA", "alpha globin regulatory element": "DNA", "HS-40": "DNA", "nuclear factor-DNA complexes": "protein" } }, { "input_text": "We studied the functional interaction between human embryonic zeta 2 globin promoter and the alpha globin regulatory element ( HS-40 ) located 40 kb upstream of the zeta 2 globin gene .", "target_text": { "human embryonic zeta 2 globin promoter": "DNA", "alpha globin regulatory element": "DNA", "HS-40": "DNA", "40 kb upstream": "DNA", "zeta 2 globin gene": "DNA" } }, { "input_text": "It was shown by transient expression assay that HS-40 behaved as an authentic enhancer for high-level zeta 2 globin promoter activity in K562 cells , an erythroid cell line of embryonic and/or fetal origin .", "target_text": { "HS-40": "DNA", "enhancer": "DNA", "zeta 2 globin promoter": "DNA", "K562 cells": "cell_line" } }, { "input_text": "Although sequences located between -559 and -88 of the zeta 2 globin gene were dispensable for its expression on enhancerless plasmids , they were required for the HS-40 enhancer -mediated activity of the zeta 2 globin promoter .", "target_text": { "zeta 2 globin gene": "DNA", "enhancerless plasmids": "DNA", "HS-40": "DNA", "HS-40 enhancer": "DNA", "zeta 2 globin promoter": "DNA" } }, { "input_text": "Site-directed mutagenesis demonstrated that this HS-40 enhancer- zeta 2 globin promoter interaction is mediated by the two GATA-1 factor binding motifs located at -230 and -104 , respectively .", "target_text": { "HS-40": "DNA", "zeta 2 globin promoter": "DNA", "GATA-1 factor binding motifs": "DNA" } }, { "input_text": "The functional domains of HS-40 were also mapped .", "target_text": { "HS-40": "DNA" } }, { "input_text": "Bal 31 deletion mapping data suggested that one GATA-1 motif , one GT motif , and two NF-E2/AP1 motifs together formed the functional core of HS-40 in the erythroid-specific activation of the zeta 2 globin promoter .", "target_text": { "HS-40": "DNA", "zeta 2 globin promoter": "DNA" } }, { "input_text": "Site-directed mutagenesis further demonstrated that the enhancer function of one of the two NF-E2/AP1 motifs of HS-40 is mediated through its binding to NF-E2 but not AP1 transcription factor .", "target_text": { "enhancer": "DNA", "HS-40": "DNA", "NF-E2": "protein", "AP1 transcription factor": "protein" } }, { "input_text": "Finally , we did genomic footprinting of the HS-40 enhancer region in K562 cells , adult nucleated erythroblasts , and different nonerythroid cells .", "target_text": { "HS-40 enhancer region": "DNA", "K562 cells": "cell_line", "adult nucleated erythroblasts": "cell_line", "nonerythroid cells": "cell_type" } }, { "input_text": "All sequence motifs within the functional core of HS-40 , as mapped by transient expression analysis , appeared to bind a nuclear factor ( s ) in living K562 cells but not in nonerythroid cells .", "target_text": { "HS-40": "DNA", "nuclear factor": "protein", "K562 cells": "cell_line", "nonerythroid cells": "cell_type" } }, { "input_text": "On the other hand , only one of the apparently nonfunctional sequence motifs was bound with factors in vivo .", "target_text": { "nonfunctional sequence motifs": "DNA" } }, { "input_text": "In comparison to K562 , nucleated erythroblasts from adult human bone marrow exhibited a similar but nonidentical pattern of nuclear factor binding in vivo at the HS-40 region .", "target_text": { "K562": "cell_line", "nucleated erythroblasts": "cell_line", "nuclear factor": "protein", "HS-40": "DNA" } }, { "input_text": "These data suggest that transcriptional activation of human embryonic zeta 2 globin gene and the fetal/adult alpha globin genes is mediated by erythroid cell-specific and developmental stage-specific nuclear factor-DNA complexes which form at the enhancer ( HS-40 ) and the globin promoters .", "target_text": { "zeta 2 globin gene": "DNA", "human embryonic zeta 2 globin gene": "DNA", "fetal/adult alpha globin genes": "DNA", "nuclear factor-DNA complexes": "protein", "developmental stage-specific nuclear factor-DNA complexes": "protein", "enhancer": "DNA", "HS-40": "DNA", "globin promoters": "DNA" } }, { "input_text": "Transcriptional regulation of the pyruvate kinase erythroid-specific promoter .", "target_text": { "pyruvate kinase erythroid-specific promoter": "DNA" } }, { "input_text": "Mammal pyruvate kinases are encoded by two genes .", "target_text": { "Mammal pyruvate kinases": "protein" } }, { "input_text": "The L gene produces the erythroid ( R-PK ) or the hepatic ( L-PK ) isozymes by the alternative use of two promoters .", "target_text": { "L gene": "DNA", "erythroid": "protein", "R-PK": "protein", "L-PK": "protein", "hepatic ( L-PK ) isozymes": "protein", "promoters": "DNA" } }, { "input_text": "We report the characterization of the cis- and trans- acting elements involved in the tissue-specific activity of the L gene erythroid promoter .", "target_text": { "L gene erythroid promoter": "DNA" } }, { "input_text": "A R-PK DNA fragment extending from -870 to +54 relative to the cap site confers erythroid specificity to a reporter gene .", "target_text": { "R-PK DNA fragment": "DNA", "cap site": "DNA", "reporter gene": "DNA" } }, { "input_text": "Within this region , we define a minimal promoter ( -62 to +54 ) that displays erythroid-specific activity and contains two DNA binding sites .", "target_text": { "minimal promoter": "DNA" } }, { "input_text": "One , located at -50 , binds members of the CCACC/Sp1 family and the other , located at -20 , binds the erythroid factor GATA-1 .", "target_text": { "CCACC/Sp1 family": "protein", "erythroid factor GATA-1": "protein" } }, { "input_text": "Although the -20 GATA binding site ( AGATAA ) is also a potential TFIID binding site , it does not bind TFIID .", "target_text": { "GATA binding site": "DNA", "TFIID binding site": "DNA", "TFIID": "protein" } }, { "input_text": "Furthermore , the substitution of this GATA binding site by a canonical TFIID binding site suppresses the promoter activity .", "target_text": { "GATA binding site": "DNA", "TFIID": "protein", "TFIID binding site": "DNA" } }, { "input_text": "Mutations and deletions of both sites indicate that only the association of CCACC/Sp1 and GATA binding sites can drive efficient and tissue-specific expression of this R-PK minimal promoter .", "target_text": { "CCACC/Sp1": "protein", "GATA binding sites": "DNA", "R-PK": "protein", "minimal promoter": "DNA" } }, { "input_text": "Finally , by co-transfection experiments , we study the elements involved in the hGATA-1 transactivation of the R-PK promoter in HeLa cells .", "target_text": { "R-PK promoter": "DNA", "HeLa cells": "cell_line" } }, { "input_text": "Protease treatment of nuclear extracts distinguishes between class II MHC X1 box DNA-binding proteins in wild-type and class II-deficient B cells .", "target_text": { "class II MHC X1 box DNA-binding proteins": "protein" } }, { "input_text": "The X box region is critical for directing the expression of class II major histocompatibility complex genes in B lymphocytes .", "target_text": { "X box region": "DNA", "class II major histocompatibility complex genes": "DNA", "B lymphocytes": "cell_type" } }, { "input_text": "Although several class II promoter-specific DNA binding factors have been described , only the X box region factor , RFX , shows a genetic correlation with class II expression , being deficient in some B cell lines derived from patients with class II-deficient congenital immunodeficiency .", "target_text": { "class II promoter-specific DNA binding factors": "protein", "X box region": "DNA", "RFX": "protein", "B cell lines": "cell_line" } }, { "input_text": "To further evaluate the role of X box DNA-binding proteins in class II gene expression , the role of the X box region was examined in both class II-positive and -negative lymphoid cells .", "target_text": { "X box DNA-binding proteins": "protein", "class II gene": "DNA", "X box region": "DNA", "class II-positive": "cell_line", "-negative lymphoid cells": "cell_line" } }, { "input_text": "In addition to the wild-type B cell line Raji , two class II transcriptional mutant cell lines , SJO and RJ2.2.5 , and Jurkat , a class II negative T cell line , were examined .", "target_text": { "wild-type B cell line Raji": "cell_line", "two class II transcriptional mutant cell lines": "cell_line", "SJO": "cell_line", "RJ2.2.5": "cell_line", "Jurkat": "cell_line", "class II negative T cell line": "cell_line" } }, { "input_text": "In contrast to wild-type B cells , neither of the class II mutant cell lines could use the X box region to direct the expression of a transiently transfected reporter gene , indicating that the X box-dependent transcriptional pathway is defective in these cells .", "target_text": { "wild-type B cells": "cell_line", "class II mutant cell lines": "cell_line", "X box region": "DNA", "reporter gene": "DNA" } }, { "input_text": "The binding activity of the X1 box DNA-binding protein RFX was examined and found to be present in wild-type B cells and the mutant RJ2.2.5 but was absent in SJO and Jurkat .", "target_text": { "X1 box DNA-binding protein": "protein", "RFX": "protein", "wild-type B cells": "cell_line", "RJ2.2.5": "cell_line", "SJO": "cell_line", "Jurkat": "cell_line" } }, { "input_text": "However , other X1 box-specific activities were detected in all these cell lines .", "target_text": { "cell lines": "cell_line" } }, { "input_text": "To determine whether these different X1 box activities represented distinct DNA binding proteins or multimeric forms of the same factor ( s ) , protease treatment of the crude nuclear extracts followed by DNA-binding assays were carried out and demonstrated that B cell extracts contain at least two X1-specific factors .", "target_text": { "DNA binding proteins": "protein", "protease": "protein", "X1-specific factors": "protein" } }, { "input_text": "One of these cleaved products ( band 1 pk ) correlates with RFX activity .", "target_text": { "RFX": "protein" } }, { "input_text": "A similar comparison with protease-treated extracts prepared from Jurkat cells demonstrated the presence of the band 1pk activity despite an absence of the native RFX activity .", "target_text": { "Jurkat": "cell_line", "Jurkat cells": "cell_line", "RFX": "protein" } }, { "input_text": "In contrast , protease treatment and analysis of SJO extracts showed no detectable levels of the band 1pk activity .", "target_text": { "SJO": "cell_line" } }, { "input_text": "These results demonstrate that multiple X1 box-specific DNA-binding activities exist in all lymphoid cells , but the presence of an actively binding RFX species correlates with class II transcription .", "target_text": { "lymphoid cells": "cell_type", "RFX": "protein" } }, { "input_text": "Human immunodeficiency viruses containing heterologous enhancer/promoters are replication competent and exhibit different lymphocyte tropisms .", "target_text": { "heterologous enhancer/promoters": "DNA" } }, { "input_text": "The human immunodeficiency virus ( HIV ) type 1 long terminal repeat ( LTR ) contains binding sites for nuclear factor kappa B ( NF-kappa B ) and the constitutively expressed transcription factor Sp1 , both of which are highly conserved in HIV and simian immunodeficiency virus isolates .", "target_text": { "human immunodeficiency virus ( HIV ) type 1 long terminal repeat": "DNA", "LTR": "DNA", "nuclear factor kappa B": "protein", "NF-kappa B": "protein", "transcription factor Sp1": "protein" } }, { "input_text": "To delineate the effects of these motifs on the replicative capacity of HIV and to explore the possibility of extending the virus host range , known heterologous enhancer/promoters were inserted into the HIV-1 LTR in place of the NF-kappa B and Sp1 binding sites .", "target_text": { "heterologous enhancer/promoters": "DNA", "HIV-1 LTR": "DNA", "NF-kappa B": "protein", "Sp1 binding sites": "DNA" } }, { "input_text": "The effects of these substitutions on viral replication in transfected HeLa cells and on HIV infection of human peripheral blood lymphocytes or continuous T-leukemia cell lines were evaluated .", "target_text": { "HeLa cells": "cell_line", "human peripheral blood lymphocytes": "cell_type", "continuous T-leukemia cell lines": "cell_line" } }, { "input_text": "HIVs in which the NF- kappa B/Sp1 enhancer plus the downstream TATA element were replaced with heterologous enhancer/promoters were also constructed .", "target_text": { "NF- kappa B/Sp1 enhancer": "DNA", "downstream TATA element": "DNA", "heterologous enhancer/promoters": "DNA" } }, { "input_text": "Viruses containing the human cytomegalovirus immediate-early enhancer exhibited infectious kinetics similar to that of wild-type HIV in activated human peripheral blood lymphocytes and AA2 cells but replicated less efficiently in H9 and CEM cells .", "target_text": { "human cytomegalovirus immediate-early enhancer": "DNA", "activated human peripheral blood lymphocytes": "cell_type", "AA2 cells": "cell_line" } }, { "input_text": "These studies indicate that heterologous enhancer elements are capable of restoring Tat responsiveness to the HIV LTR in the context of directing reporter gene expression as well as in the production of infectious progeny virions .", "target_text": { "heterologous enhancer elements": "DNA", "Tat": "protein", "HIV LTR": "DNA", "reporter gene": "DNA" } }, { "input_text": "Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C signaling pathway in human B- lymphocyte precursors [ published erratum appears in Proc Natl Acad Sci U S A 1993 Apr 15 ; 90 ( 8 ) : 3775 ]", "target_text": { "protein kinase C": "protein", "human B- lymphocyte precursors": "cell_type" } }, { "input_text": "Ionizing radiation triggers a signal in human B-lymphocyte precursors that is intimately linked to an active protein-tyrosine kinase regulatory pathway .", "target_text": { "human B-lymphocyte precursors": "cell_type", "protein-tyrosine kinase": "protein" } }, { "input_text": "We show that in B-lymphocyte precursors , irradiation with gamma-rays leads to ( i ) stimulation of phosphatidylinositol turnover ; ( ii ) downstream activation by covalent modification of multiple serine-specific protein kinases , including protein kinase C ; and ( iii ) activation of nuclear factor kappa B .", "target_text": { "B-lymphocyte precursors": "cell_type", "serine-specific protein kinases": "protein", "protein kinase C": "protein", "nuclear factor kappa B": "protein" } }, { "input_text": "All of the radiation-induced signals were effectively prevented by the protein-tyrosine kinase inhibitors genistein and herbimycin A .", "target_text": { "protein-tyrosine kinase": "protein" } }, { "input_text": "Thus , tyrosine phosphorylation is an important and perhaps mandatory proximal step in the activation of the protein kinase C signaling cascade in human B-lymphocyte precursors .", "target_text": { "protein kinase C": "protein", "human B-lymphocyte precursors": "cell_type" } }, { "input_text": "Our report expands current knowledge of the radiation-induced signaling cascade by clarifying the chronological sequence of biochemical events that follow irradiation .", "target_text": {} }, { "input_text": "Tumor necrosis factor receptor expression and signal transduction in HIV-1 -infected cells .", "target_text": { "Tumor necrosis factor": "protein", "Tumor necrosis factor receptor": "protein", "HIV-1 -infected cells": "cell_type" } }, { "input_text": "OBJECTIVE : To examine the inter-relationship between HIV-1 infection and the cell surface receptors for tumor necrosis factor ( TNF ) -alpha , an immunoregulatory cytokine that can enhance HIV-1 replication .", "target_text": { "tumor necrosis factor ( TNF ) -alpha": "protein" } }, { "input_text": "DESIGN : Infected promyelocytic and promonocytic cells were examined because they normally express both types of TNF receptors .", "target_text": { "promyelocytic": "cell_type", "promonocytic cells": "cell_type", "TNF receptors": "protein" } }, { "input_text": "METHODS : TNF receptor surface expression was determined by specific monoclonal antibody recognition and flow cytometry , and signal transduction was detected by gel shift analysis .", "target_text": { "TNF": "protein", "monoclonal antibody": "protein" } }, { "input_text": "HIV-1 activation and expression was quantitated by reverse transcriptase assay .", "target_text": { "reverse transcriptase": "protein" } }, { "input_text": "RESULTS : In the OM-10.1 promyelocytic model of chronic infection , TNF-alpha-induced HIV-1 expression also resulted in a substantial increase in 75 kd TNF receptor ( TR75 ) expression although 55 kD TNF receptor ( TR55 ) levels were not dramatically altered .", "target_text": { "75 kd TNF receptor": "protein", "TR75": "protein", "55 kD TNF receptor": "protein", "TR55": "protein" } }, { "input_text": "A series of uninfected parental HL-60 subclones all reduced TR75 surface expression in response to TNF-alpha treatment .", "target_text": { "uninfected parental HL-60 subclones": "cell_line", "TR75": "protein", "TNF-alpha": "protein" } }, { "input_text": "Enhanced TR75 expression on OM-10.1 cells followed the same TNF-alpha -dose dependency as that observed for HIV-1 production .", "target_text": { "TR75": "protein", "TNF-alpha": "protein" } }, { "input_text": "An increase in TR75 expression was also evident during the peak of an acute HIV-1 infection of HL-60 promyelocytes .", "target_text": { "TR75": "protein", "HL-60 promyelocytes": "cell_line" } }, { "input_text": "Although TR55 expression was unaltered during TNF-alpha -induced HIV activation , this receptor was still involved in the viral activation process .", "target_text": { "TR55": "protein", "TNF-alpha": "protein" } }, { "input_text": "Antibody cross-linking of TR55 , in the absence of exogenous TNF-alpha , induced maximal HIV-1 expression , an up-modulation of surface TR75 , and nuclear NF-kappa B activity in OM-10.1 cultures .", "target_text": { "TR55": "protein", "exogenous TNF-alpha": "protein", "TR75": "protein", "NF-kappa B": "protein" } }, { "input_text": "Surprisingly , this was the case even when an antagonistic anti-TR55 antibody was used .", "target_text": { "antagonistic anti-TR55 antibody": "protein" } }, { "input_text": "Anti-TR55 antibody cross-linking in chronically infected U1 promonocytic cultures could only partially substitute for TNF-alpha-induced HIV-1 expression .", "target_text": { "Anti-TR55 antibody": "protein", "chronically infected U1 promonocytic cultures": "cell_line" } }, { "input_text": "CONCLUSIONS : Our results demonstrated that HIV-1 infection can selectively influence the surface expression of TNF receptors , potentially influencing its own expression and altering normal immunoregulatory signal transduction .", "target_text": { "TNF receptors": "protein", "immunoregulatory": "protein" } }, { "input_text": "Comparative mapping of SRY in the great apes .", "target_text": { "SRY": "DNA" } }, { "input_text": "Cytogenetic studies of the primate Y chromosomes have suggested that extensive rearrangements have occurred during evolution of the great apes .", "target_text": { "Y chromosomes": "DNA", "primate Y chromosomes": "DNA" } }, { "input_text": "We have used in situ hybridization to define these rearrangements at the molecular level .", "target_text": {} }, { "input_text": "pHU-14 , a probe including sequences from the sex determining gene SRY , hybridizes close to the early replicating pseudoautosomal segment in a telomeric or subtelomeric position of the Y chromosomes of all great apes .", "target_text": { "pHU-14": "DNA", "sex determining gene SRY": "DNA", "Y chromosomes": "DNA" } }, { "input_text": "The low copy repeat detected by the probe Fr35-II is obviously included in Y chromosomal rearrangements during hominid evolution .", "target_text": { "low copy repeat": "DNA", "Fr35-II": "DNA" } }, { "input_text": "These results , combined with previous studies , suggest that the Y chromosome in great apes has a conserved region including the pseudoautosomal region and the testis-determining region .", "target_text": { "pseudoautosomal region": "DNA" } }, { "input_text": "The rest of the Y chromosome has undergone several rearrangements in the different great apes .", "target_text": { "Y chromosome": "DNA" } }, { "input_text": "Calcium dependent activation of the NF-AT transcription factor by p59fyn .", "target_text": { "NF-AT transcription factor": "protein", "p59fyn": "protein" } }, { "input_text": "A reporter gene under the control of a T-cell antigen receptor element was activated in Jurkat cells by antigen receptor triggering or by a combination of phorbol myristate acetate , which activates protein kinase C , and a calcium ionophore .", "target_text": { "reporter gene": "DNA", "T-cell antigen receptor element": "DNA", "Jurkat cells": "cell_line", "protein kinase C": "protein" } }, { "input_text": "Both these signals were necessary for expression of the reporter gene .", "target_text": { "reporter gene": "DNA" } }, { "input_text": "When co-transfected with a construct capable of overexpressing the tyrosine kinase p59fyn , the reporter gene was activated by PMA alone .", "target_text": { "tyrosine kinase": "protein", "p59fyn": "protein", "reporter gene": "DNA", "PMA": "protein" } }, { "input_text": "Thus p59fyn could replace the calcium ionophore but not activation of protein kinase C .", "target_text": { "p59fyn": "protein", "protein kinase C": "protein" } }, { "input_text": "The activation by p59fyn plus PMA was blocked by EGTA and by the immunosuppressant drug cyclosporin A .", "target_text": { "p59fyn": "protein", "PMA": "protein" } }, { "input_text": "Dependence for the proliferative response to erythropoietin on an established erythroid differentiation program in a human hematopoietic cell line , UT-7 .", "target_text": { "erythropoietin": "protein", "human hematopoietic cell line": "cell_line", "UT-7": "cell_line" } }, { "input_text": "Erythroid differentiation involves the activation of a number of erythroid-specific genes , most of which , including the globin genes and the erythropoietin receptor ( Epo-R ) gene , are , at least in part , regulated by the transcription factor GATA-1 .", "target_text": { "globin genes": "DNA", "erythropoietin receptor": "protein", "Epo-R": "protein", "erythropoietin receptor ( Epo-R ) gene": "DNA", "transcription factor": "protein", "GATA-1": "protein" } }, { "input_text": "In order to understand the relationship , if any , between expression of GATA-1 , response to Epo and erythroid differentiation , we analyzed the expression of GATA-1 , Epo-R and globin genes in an Epo-dependent human cell line , UT-7 Epo .", "target_text": { "GATA-1": "protein", "Epo-R": "protein", "globin genes": "DNA", "UT-7": "cell_line" } }, { "input_text": "The results were compared to those obtained with the parental granulocyte-macrophage colony-stimulating factor ( GM-CSF ) -dependent cell line , UT-7 , which has a predominantly megakaryoblastic phenotype and is unable to proliferate continuously in the presence of Epo .", "target_text": { "granulocyte-macrophage colony-stimulating factor": "protein", "GM-CSF": "protein", "parental granulocyte-macrophage colony-stimulating factor ( GM-CSF ) -dependent cell line": "cell_line", "UT-7": "cell_line", "Epo": "protein" } }, { "input_text": "UT-7 Epo and UT-7 expressed similar levels of GATA-1 mRNA and binding activity .", "target_text": { "UT-7 Epo": "protein", "UT-7": "cell_line", "GATA-1": "protein", "GATA-1 mRNA": "RNA" } }, { "input_text": "The two lines also expressed comparable levels of Epo-R mRNA while the number of Epo -binding sites on UT-7 Epo cells was one-sixth the number of UT-7 cells ( 2400 +/- 3 vs. 13 , 800 +/- 300 ) .", "target_text": { "Epo-R mRNA": "RNA", "Epo": "protein", "UT-7 Epo cells": "cell_line", "UT-7 cells": "cell_line" } }, { "input_text": "This difference in the number of binding sites could be due to differences in cell surface ( UT-7 cells are 20 % smaller than the parental UT-7 cells ) or in receptor turnover .", "target_text": { "UT-7 cells": "cell_line" } }, { "input_text": "By Northern analysis , UT-7 cells expressed detectable levels of beta- and gamma-globin but not alpha-globin .", "target_text": { "UT-7 cells": "cell_line", "beta- and gamma-globin": "protein", "alpha-globin": "protein" } }, { "input_text": "In comparison , UT-7 Epo cells expressed alpha-globin and higher levels of gamma-globin ( 5-fold ) and beta-globin ( from barely to clearly detectable ) .", "target_text": { "UT-7 Epo cells": "cell_line", "gamma-globin": "protein", "beta-globin": "protein" } }, { "input_text": "Globin chains ( alpha , beta and gamma ) were clearly detectable by affinity chromatography in UT-7 Epo but not in UT-7 cells .", "target_text": { "Globin chains": "protein", "alpha": "protein", "beta": "protein", "gamma": "protein", "UT-7 Epo": "protein", "UT-7 cells": "cell_line" } }, { "input_text": "The frequency of the cells which expressed beta- and gamma- globin genes in the two cell populations was measured by immunofluorescence with beta- and gamma- specific antibodies .", "target_text": {} }, { "input_text": "The number of gamma-positive cells and their fluorescence intensity were higher in UT-7 Epo than in UT-7 cells ( 0 to 17 % barely positive cells and 23 to 40 % clearly positive cells , respectively ) , indicating that the increase in globin mRNA observed in UT-7 Epo is due to both an increase of gene expression per cell and an increase in numbers of cells containing gamma-globin .", "target_text": { "gamma-positive cells": "cell_line", "UT-7 Epo": "protein", "UT-7 cells": "cell_line", "globin mRNA": "RNA", "gamma-globin": "protein" } }, { "input_text": "The levels of GATA-1 , Epo-R and globin mRNA expressed were not affected by a 24-hour incubation of either cell line with Epo , GM-CSF or interleukin-3 ( IL-3 ) .", "target_text": { "GATA-1": "protein", "Epo-R": "protein", "globin mRNA": "RNA", "Epo": "protein", "GM-CSF": "protein", "interleukin-3": "protein", "IL-3": "protein" } }, { "input_text": "( ABSTRACT TRUNCATED AT 400 WORDS )", "target_text": {} }, { "input_text": "The Sp1 transcription factor binds the CD11b promoter specifically in myeloid cells in vivo and is essential for myeloid-specific promoter activity .", "target_text": { "transcription factor": "protein", "Sp1 transcription factor": "protein", "CD11b promoter": "DNA", "myeloid-specific promoter": "DNA" } }, { "input_text": "The myeloid integrin CD11b is expressed selectively on the surface of mature macrophages , monocytes , neutrophils , and natural killer cells .", "target_text": { "myeloid integrin CD11b": "protein", "mature macrophages": "cell_type", "monocytes": "cell_type", "neutrophils": "cell_type", "natural killer cells": "cell_type" } }, { "input_text": "Lineage-specific expression is controlled at the level of mRNA transcription .", "target_text": {} }, { "input_text": "Recent isolation of the CD11b promoter shows that 92 base pairs ( bp ) of 5'-flanking DNA are sufficient to direct myeloid-specific expression of a reporter gene .", "target_text": { "CD11b promoter": "DNA", "5'-flanking DNA": "DNA", "reporter gene": "DNA" } }, { "input_text": "To characterize regulatory sequences important for promoter activity , we performed linker scanning analysis of the 92-bp CD11b promoter and demonstrate that a sequence at bp -60 is essential for CD11b promoter activity .", "target_text": { "CD11b promoter": "DNA", "92-bp CD11b promoter": "DNA" } }, { "input_text": "We show that this sequence binds the transcription factor Sp1 in vitro and in vivo .", "target_text": { "transcription factor": "protein", "Sp1": "protein" } }, { "input_text": "In vivo the Sp1 site is bound only in myeloid ( U937 ) cells , not in cervical carcinoma ( HeLa ) cells .", "target_text": { "Sp1 site": "DNA", "U937": "cell_line", "myeloid ( U937 ) cells": "cell_line", "HeLa": "cell_line", "cervical carcinoma ( HeLa ) cells": "cell_line" } }, { "input_text": "In addition , the macrophage transcription factor PU.1 binds the CD11b promoter in vitro and in vivo close to the Sp1 site .", "target_text": { "transcription factor": "protein", "CD11b promoter": "DNA", "Sp1 site": "DNA" } }, { "input_text": "We propose a model in which binding of a myeloid-specific factor ( PU.1 ) allows a general factor ( Sp1 ) to bind in a tissue-specific fashion thereby contributing to the myeloid-specific expression of CD11b .", "target_text": { "myeloid-specific factor": "protein", "PU.1": "protein", "Sp1": "protein", "CD11b": "cell_line" } }, { "input_text": "Transcription factor jun-B is target of autoreactive T-cells in IDDM .", "target_text": { "Transcription factor jun-B": "protein", "autoreactive T-cells": "cell_type" } }, { "input_text": "Target antigens defined by autoantibodies in IDDM include insulin , a putative glycolipid that reacts with islet cell antibodies , and a 64,000-M(r) protein recently identified as glutamic acid decarboxylase .", "target_text": { "autoantibodies": "protein", "islet cell antibodies": "protein", "64,000-M(r) protein": "protein", "glutamic acid decarboxylase": "protein" } }, { "input_text": "In addition , some IDDM sera that contain antibodies to glutamic acid decarboxylase also coprecipitate a 38,000-M(r) protein from islets .", "target_text": { "antibodies": "protein", "glutamic acid decarboxylase": "protein", "38,000-M(r) protein": "protein" } }, { "input_text": "This study used a high titer anti-38,000-M(r) serum to screen bacteriophage lambda cDNA expression libraries and identified human islet and placental clones encoding jun-B , the nuclear transcription protein , of predicted 38,000 M(r) .", "target_text": { "bacteriophage lambda cDNA": "DNA", "human islet": "cell_type", "placental clones": "cell_line", "jun-B": "protein", "nuclear transcription protein": "protein" } }, { "input_text": "Peripheral blood T-cells exhibited significant proliferation in response to a recombinant fragment of jun-B ( amino acids 1-180 ) in 12 of 17 ( 71 % ) recent-onset IDDM subjects , 8 of 16 ( 50 % ) ICA-positive first-degree relatives of IDDM subjects who were at risk , 3 of 12 ( 25 % ) other autoimmune disease subjects , and 0 of 10 healthy control subjects .", "target_text": { "Peripheral blood T-cells": "cell_type", "jun-B": "protein" } }, { "input_text": "Proliferation to tetanus toxoid did not differ significantly between the groups .", "target_text": {} }, { "input_text": "Responses to jun-B were not related to age , sex , or human leukocyte antigen status .", "target_text": { "jun-B": "protein", "human leukocyte": "cell_type", "human leukocyte antigen": "protein" } }, { "input_text": "Thus , autoreactive T-cells identify a novel antigen , p38 jun-B , in IDDM and appear to indicate subjects at risk for the development of clinical disease .", "target_text": { "autoreactive T-cells": "cell_type", "novel antigen": "protein", "jun-B": "protein", "p38 jun-B": "protein" } }, { "input_text": "Stimulation of interleukin-1 alpha and interleukin-1 beta production in human monocytes by protein phosphatase 1 and 2A inhibitors .", "target_text": { "interleukin-1 alpha": "protein", "interleukin-1 beta": "protein", "human monocytes": "cell_type" } }, { "input_text": "Protein phosphatases 1 and 2A are important in regulating cellular functions by controlling the phosphorylation state of their substrates .", "target_text": {} }, { "input_text": "In human monocytes , the inhibitors of these phosphatases , okadaic acid and calyculin A , were found to increase the mRNA accumulation and cytokine production of interleukin-1 beta and interleukin-1 alpha .", "target_text": { "human monocytes": "cell_type", "phosphatases": "protein", "interleukin-1 beta": "protein", "interleukin-1 alpha": "protein" } }, { "input_text": "The increased mRNA accumulation was found to be primarily because of the increase in the transcription rate of the interleukin-1 genes .", "target_text": { "mRNA": "RNA", "interleukin-1 genes": "DNA" } }, { "input_text": "Stimulation of interleukin-1 gene transcription may be caused by the stimulation of transcription factor activities , including those of AP-1 , by these protein phosphatase inhibitors .", "target_text": { "interleukin-1 gene": "DNA", "transcription factor": "protein", "AP-1": "protein", "protein phosphatase": "protein" } }, { "input_text": "Okadaic acid increased the synthesis of the interleukin-1 beta precursor and mature forms and their secretion .", "target_text": { "interleukin-1 beta": "protein" } }, { "input_text": "This increased processing and secretion correlated with the stimulation of IL-1 beta convertase mRNA accumulation .", "target_text": { "IL-1 beta convertase": "protein", "IL-1 beta convertase mRNA": "RNA" } }, { "input_text": "The stimulation of interleukin-1 alpha production by okadaic acid was more modest than that of interleukin-1 beta .", "target_text": { "interleukin-1 alpha": "protein", "interleukin-1 beta": "protein" } }, { "input_text": "However , the phosphorylation of the precursor interleukin-1 alpha cytokine was increased .", "target_text": { "interleukin-1 alpha": "protein", "precursor interleukin-1 alpha cytokine": "protein" } }, { "input_text": "These results show that protein phosphatase 1 and 2A inhibitors exert multiple effects on cytokine production in human monocytes and suggest that these two phosphatases play important roles in regulating interleukin-1 production .", "target_text": { "human monocytes": "cell_type", "phosphatases": "protein", "interleukin-1": "protein" } }, { "input_text": "The interleukin 2 CD28-responsive complex contains at least three members of the NF kappa B family : c-Rel , p50 , and p65 .", "target_text": { "interleukin 2 CD28-responsive complex": "protein", "NF kappa B family": "protein", "c-Rel": "protein", "p50": "protein", "p65": "protein" } }, { "input_text": "Optimal activation of T cells requires at least two signals .", "target_text": { "T cells": "cell_type" } }, { "input_text": "One signal can be delivered by the antigen-specific T-cell receptor , and the second signal is provided by the costimulatory molecule ( s ) delivered by the antigen-presenting cell .", "target_text": { "antigen-specific T-cell receptor": "protein", "antigen-presenting cell": "cell_type" } }, { "input_text": "CD28 is a T-cell surface molecule and stimulation through this protein plays an important role in delivering the second activation signal .", "target_text": { "CD28": "protein", "T-cell surface molecule": "protein" } }, { "input_text": "In this report , we show that in human peripheral blood T cells , CD28 -mediated signal transduction involves the rel family proteins -- c-Rel , p50 , and p65 .", "target_text": { "human peripheral blood T cells": "cell_type", "CD28": "protein", "rel family proteins": "protein", "c-Rel": "protein", "p50": "protein", "p65": "protein" } }, { "input_text": "Treatment of peripheral blood T cells with phorbol 12-myristate 13-acetate ( PMA ) and anti-CD28 monoclonal antibody ( mAb ) results in augmentation of nuclear c-Rel , p50 , and p65 , and this augmentation can occur in the presence of the immunosuppressant cyclosporin A .", "target_text": { "peripheral blood T cells": "cell_type", "anti-CD28 monoclonal antibody": "protein", "mAb": "protein", "nuclear c-Rel": "protein", "p50": "protein", "p65": "protein" } }, { "input_text": "It is also shown in this report that , in response to PMA/anti-CD28 mAb or anti-CD3/anti-CD28 mAb , c-Rel , p50 , and p65 are associated with CD28 -responsive element present in the promoter of the human interleukin 2 gene .", "target_text": { "PMA/anti-CD28 mAb": "protein", "anti-CD3/anti-CD28 mAb": "protein", "c-Rel": "protein", "p50": "protein", "p65": "protein", "CD28": "protein", "CD28 -responsive element": "DNA", "promoter": "DNA", "human interleukin 2 gene": "DNA" } }, { "input_text": "The functional significance of c-Rel involvement in the CD28 -responsive complex is demonstrated by transient transfection analysis , where cotransfection of c-Rel augments the level of expression of a chloramphenicol acetyltransferase reporter gene linked to the CD28 -responsive element .", "target_text": { "c-Rel": "protein", "CD28": "protein", "CD28 -responsive complex": "protein", "chloramphenicol acetyltransferase": "protein", "reporter gene": "DNA", "chloramphenicol acetyltransferase reporter gene": "DNA", "CD28 -responsive element": "DNA" } }, { "input_text": "Expression of tal-1 and GATA-binding proteins during human hematopoiesis .", "target_text": { "tal-1": "protein", "GATA-binding proteins": "protein" } }, { "input_text": "Tal-1 rearrangements are associated with nearly 30 % of human T acute lymphoblastic leukemia .", "target_text": { "Tal-1": "protein" } }, { "input_text": "Tal-1 gene encodes a putative transcription factor with a basic helix-loop-helix domain and is known to be predominantly expressed in hematopoietic cells .", "target_text": { "Tal-1 gene": "DNA", "transcription factor": "protein", "basic helix-loop-helix domain": "protein", "hematopoietic cells": "cell_type" } }, { "input_text": "We investigated the pattern of tal-1 expression in purified human hematopoietic cells by in situ hybridization and reverse transcriptase polymerase chain reaction analysis .", "target_text": { "tal-1": "protein", "hematopoietic cells": "cell_type", "purified human hematopoietic cells": "cell_type", "reverse transcriptase polymerase": "protein" } }, { "input_text": "Both methods demonstrated that the tal-1 gene is expressed in megakaryocytes and erythroblasts as well as in basophilic granulocytes .", "target_text": { "tal-1": "protein", "basophilic granulocytes": "cell_type" } }, { "input_text": "In addition , our results indicate that the tal-1 1A promoter , which contains two consensus GATA-binding sites , is active mainly in these lineages .", "target_text": { "tal-1 1A promoter": "DNA", "GATA-binding sites": "DNA" } }, { "input_text": "Because the GATA-1 gene is known to transactivate several genes specific for the erythroid , megakaryocytic , and mastocytic/basophilic lineages , we studied GATA-1 expression in these purified hematopoietic cells .", "target_text": { "GATA-1 gene": "DNA", "GATA-1": "protein", "hematopoietic cells": "cell_type" } }, { "input_text": "We found that GATA-1 and tal-1 genes are coexpressed in these three lineages .", "target_text": {} }, { "input_text": "Remarkably , the expression of both genes is downmodulated during erythroid and megakaryocytic terminal maturation .", "target_text": {} }, { "input_text": "In immature hematopoietic cells , tal-1 and GATA-1 genes are coexpressed in committed progenitors cells ( CD34+/CD38(2+) ) , whereas they are not detectable in the most primitive cells ( CD34(2+)/CD38- ) .", "target_text": { "hematopoietic cells": "cell_type", "immature hematopoietic cells": "cell_type", "genes": "DNA", "committed progenitors cells": "cell_type", "CD34+/CD38(2+)": "cell_line", "primitive cells": "cell_type", "CD34(2+)/CD38-": "cell_line" } }, { "input_text": "In contrast , GATA-2 is strongly expressed in both most primitive and committed progenitors cells , whereas GATA-3 is mostly detected in most primitive ones .", "target_text": { "GATA-2": "protein", "GATA-3": "protein" } }, { "input_text": "Altogether our results strongly suggest that GATA-1 modulates the transcription of tal-1 during the differentiation of the erythroid , megakaryocytic , and basosophilic lineages .", "target_text": { "GATA-1": "protein", "tal-1": "protein" } }, { "input_text": "The lytic transition of Epstein-Barr virus is imitated by recombinant B-cells .", "target_text": { "recombinant B-cells": "cell_line" } }, { "input_text": "Lytic transition of Epstein-Barr virus ( EBV ) is initiated by distinct immediate early regulators of the viral cycle , in synchronization to temporary , permissive conditions during host cell differentiation .", "target_text": {} }, { "input_text": "We developed eukaryotic vectors suitable to imitate the processes involved in lytic transition in cell culture systems .", "target_text": {} }, { "input_text": "Two stable B cell lines were established : R59Z activator cells were used to induce lytic EBV expression in a constitutive manner by the production of the BZLF 1 trans-activator ( Zta ) .", "target_text": { "B cell lines": "cell_line", "R59Z activator cells": "cell_line", "BZLF 1 trans-activator": "protein", "Zta": "protein" } }, { "input_text": "R7-57 reporter cells , on the other hand , signaled induced activity of the lytic origin of EBV replication ( ori Lyt ) .", "target_text": { "R7-57 reporter cells": "cell_line", "lytic origin of EBV replication": "DNA", "ori Lyt": "DNA" } }, { "input_text": "Different modes , like chemical induction , lytic superinfection with EBV and single gene trans-activation converted the recombinant ori Lyt element in R7-57 reporter cells .", "target_text": { "ori Lyt": "DNA", "recombinant ori Lyt element": "DNA", "R7-57 reporter cells": "cell_line" } }, { "input_text": "BZLF 1 , transiently expressed in R7-57 reporter cells , was the only EBV trans-activator found , sufficient in inducing the viral lytic cycle .", "target_text": { "BZLF 1": "protein", "R7-57 reporter cells": "cell_line", "EBV trans-activator": "protein" } }, { "input_text": "Basing on these experiments , trans-cellular activation of EBV was tested by cocultivation of BZLF 1 -expressing R59Z activator cells with the R7-57 reporter line .", "target_text": { "BZLF 1": "protein", "BZLF 1 -expressing R59Z activator cells": "cell_type", "R7-57 reporter line": "cell_line" } }, { "input_text": "No lytic effect on the reporter cells could be measured , neither by cocultivation of activator cells nor by coincubation of BZLF 1 -containing cell lysates .", "target_text": { "activator cells": "cell_line", "BZLF 1": "protein" } }, { "input_text": "Latency breaking activity , however , was transferred from activator to reporter cells when active , exogenous virus was added .", "target_text": { "activator": "cell_line", "reporter cells": "cell_line" } }, { "input_text": "The cell system described in these experiments provides a tool for the detection of EBV reactivation and demonstrates the potential of the lytic regulatory gene BZLF 1", "target_text": { "regulatory gene BZLF 1": "DNA" } }, { "input_text": "Costimulation of cAMP and protein kinase C pathways inhibits the CD3 -dependent T cell activation and leads to a persistent expression of the AP-1 transcription factor .", "target_text": { "protein kinase C": "protein", "CD3": "protein", "AP-1": "protein", "AP-1 transcription factor": "protein" } }, { "input_text": "The effects mediated by a combined stimulation of cAMP - and protein kinase C ( PKC ) -dependent pathways have been investigated in different cellular systems , and it has been shown that they may complement each other in activating cell proliferation and differentiation .", "target_text": { "protein kinase C": "protein", "PKC": "protein" } }, { "input_text": "In this report , we show that upon the stimulation of both pathways T lymphocytes became refractory to activation via the CD3/T cell receptor ( TcR ) complex .", "target_text": { "T lymphocytes": "cell_type", "CD3/T cell receptor": "protein", "TcR": "protein" } }, { "input_text": "T cells preincubated with phorbol 12-myristate 13-acetate ( PMA ) and dibutyryl cAMP ( Bt2cAMP ) displayed a deficient proliferative ability in response to anti-CD3 mAb stimulation , whereas lymphocytes treated individually with either Bt2cAMP or PMA responded comparably to untreated samples .", "target_text": { "T cells": "cell_type", "anti-CD3 mAb": "protein", "lymphocytes": "cell_type" } }, { "input_text": "We detected an association between the reduced mitogenic response and low expression of both interleukin-2 ( IL-2 ) and the alpha chain ( CD25 ) of the IL-2 receptor ( IL-2R ) .", "target_text": { "interleukin-2": "protein", "IL-2": "protein", "alpha chain": "protein", "CD25": "protein", "IL-2 receptor": "protein", "IL-2R": "protein" } }, { "input_text": "Analysis of intracellular Ca2+ mobilization suggested that the CD3 / TcR -dependent signal transduction was impaired in PMA/Bt2cAMP-treated cells .", "target_text": { "CD3": "protein", "TcR": "protein", "PMA/Bt2cAMP-treated cells": "cell_line" } }, { "input_text": "Remarkably , we observed that these samples displayed a persistent expression of the c-fos protooncogene , associated to an increased AP-1 DNA-binding activity , whereas no variations of CREB or NF-kB were detected .", "target_text": { "c-fos protooncogene": "DNA", "AP-1": "protein", "CREB": "protein", "NF-kB": "protein" } }, { "input_text": "Neither Bt2cAMP nor PMA individually mediated these sustained effects , which therefore appear as a consequence of the interplay between both metabolic stimuli .", "target_text": {} }, { "input_text": "Altogether , the data provide the evidence that both pathways complement each other in regulating gene expression and , conversely , downregulate the TcR transduction mechanisms .", "target_text": { "TcR": "protein" } }, { "input_text": "The lymphotoxin promoter is stimulated by HTLV-I tax activation of NF-kappa B in human T-cell lines .", "target_text": { "lymphotoxin promoter": "DNA", "HTLV-I tax": "protein", "NF-kappa B": "protein", "human T-cell lines": "cell_line" } }, { "input_text": "The HTLV-I transcriptional activator tax was used to gain insight into the mechanism of lymphotoxin ( LT ; TNF-beta ) gene induction .", "target_text": { "HTLV-I transcriptional activator tax": "protein", "lymphotoxin": "protein", "LT": "protein", "TNF-beta": "protein", "lymphotoxin ( LT ; TNF-beta ) gene": "DNA" } }, { "input_text": "Tax-expressing cell lines produce LT biologic activity .", "target_text": { "Tax-expressing cell lines": "cell_line", "LT": "protein" } }, { "input_text": "An LT promoter ( LT-293 ) CAT construct that contained an NF-kappa B site was active in the LT-producing C81-66-45 cell line , which contains defective HTLV-I but expresses tax .", "target_text": { "LT promoter": "DNA", "LT-293": "DNA", "LT promoter ( LT-293 ) CAT construct": "DNA", "NF-kappa B site": "DNA", "LT-producing C81-66-45 cell line": "cell_line", "tax": "protein" } }, { "input_text": "The observation that a mutated LT-kappa B construct ( M1-CAT ) was inactive in C81-66-45 , confirmed the importance of NF-kappa B in LT gene expression .", "target_text": { "mutated LT-kappa B construct": "DNA", "M1-CAT": "DNA", "C81-66-45": "cell_line", "NF-kappa B": "protein", "LT": "protein" } }, { "input_text": "Tax was transfected into HTLV-I-negative human T-cell lines .", "target_text": { "Tax": "protein", "HTLV-I-negative human T-cell lines": "cell_line" } }, { "input_text": "Jurkat T cells stably expressing tax contained elevated levels of NF-kappa B that directly bound to the LT-kappa B site .", "target_text": { "Jurkat T cells": "cell_line", "tax": "protein", "NF-kappa B": "protein", "LT-kappa B site": "DNA" } }, { "input_text": "Tax co-transfected with reporter constructs into Jurkat cells maximally activated HTLV-I-LTR-CAT and kappa B-fos-CAT and also activated LT-293 to a lesser extent .", "target_text": { "Tax": "protein", "reporter constructs": "DNA", "Jurkat cells": "cell_line", "HTLV-I-LTR-CAT": "protein", "kappa B-fos-CAT": "protein", "LT-293": "DNA" } }, { "input_text": "In JM T cells , tax induced LT-293 activity by two- to four-fold , though there was no induction of M1-CAT .", "target_text": { "JM T cells": "cell_line", "tax": "protein", "LT-293": "DNA", "M1-CAT": "protein" } }, { "input_text": "The increase in LT-293 CAT activity mirrored the increase in LT biologic activity seen under these conditions .", "target_text": { "LT-293": "DNA", "CAT": "protein", "LT": "protein" } }, { "input_text": "These studies , the first to demonstrate induction of LT promoter activity over basal levels , indicate that HTLV-I tax causes low-level activation of both endogenous LT and the LT promoter , at least in part through activation of NF-kappa B .", "target_text": { "LT": "protein", "LT promoter": "DNA", "HTLV-I tax": "protein", "NF-kappa B": "protein" } }, { "input_text": "A concatenated form of Epstein-Barr viral DNA in lymphoblastoid cell lines induced by transfection with BZLF1 .", "target_text": { "Epstein-Barr viral DNA": "DNA", "lymphoblastoid cell lines": "cell_line", "BZLF1": "protein" } }, { "input_text": "The replicative form of Epstein-Barr virus ( EBV ) DNA was studied using two lymphoblastoid cell lines , X50-7 and 6F11 , which are latently infected by Epstein-Barr virus .", "target_text": { "lymphoblastoid cell lines": "cell_line" } }, { "input_text": "The lytic cycle of EBV infection was induced by transfection of the cells with the BRLF1/BZLF1 coding region of the P3HR-1 defective genome .", "target_text": { "BRLF1/BZLF1 coding region": "DNA", "P3HR-1 defective genome": "DNA" } }, { "input_text": "We combined two techniques to identify the productive replicative form of Epstein-Barr viral DNA in the lytic cycle-induced cells .", "target_text": { "Epstein-Barr viral DNA": "DNA", "lytic cycle-induced cells": "cell_line" } }, { "input_text": "Restriction enzyme analysis followed by Southern blot hybridization identified a significant increase in the fused fragment encompassing both ends of EBV DNA .", "target_text": { "EBV DNA": "DNA" } }, { "input_text": "This indicates an increase in either episomal DNA or concatameric linear DNA .", "target_text": { "episomal DNA": "DNA", "concatameric linear DNA": "DNA" } }, { "input_text": "Southern blot analysis of in situ lysing gels revealed that the cellular content of linear EBV DNA was also increased significantly after the initiation of the viral lytic cycle , while the amount of circular DNA remained approximately constant .", "target_text": { "EBV DNA": "DNA", "linear EBV DNA": "DNA" } }, { "input_text": "We propose from these results that the source of the fused fragment encompassing both ends of EBV DNA is a concatenated linear EBV DNA molecule , and that such a concatenated molecule most likely represents a replicative form of EBV DNA in productively infected cells .", "target_text": { "EBV DNA": "DNA", "concatenated linear EBV DNA molecule": "DNA" } }, { "input_text": "Expression levels of the thyrotropin receptor gene in autoimmune thyroid disease : coregulation with parameters of thyroid function and inverse relation to major histocompatibility complex classes I and II .", "target_text": { "thyrotropin receptor gene": "DNA" } }, { "input_text": "Using a human TSH receptor ( TSH-R ) cDNA probe , we investigated TSH-R transcript levels in 13 human thyroid fragments by Northern blot analysis ; 7 Graves ' disease , 2 Hashimoto 's disease , 3 endemic goiter , and 1 healthy thyroid gland were studied .", "target_text": { "human TSH receptor": "protein", "TSH-R": "protein", "human TSH receptor ( TSH-R ) cDNA probe": "DNA" } }, { "input_text": "TSH-R expression levels were variable , but displayed a close correlation to the expression of thyroid peroxidase ( r = 0.703 ; P < 0.05 ) , thyroglobulin ( r = 0.817 ; P < 0.01 ) , and the nuclear oncogene c-fos ( r = 0.935 ; P < 0.001 ) , but not c-myc .", "target_text": { "TSH-R": "protein", "thyroid peroxidase": "protein", "thyroglobulin": "protein", "nuclear oncogene c-fos": "DNA", "c-myc": "protein" } }, { "input_text": "Overall , TSH-R transcript levels were low or absent in those thyroids in which expression of the major histocompatibility complex class I or II ( MHC I or II ) was high , thus establishing an inverse relation ( MHC I , r = -0.791 ; P < 0.01 ; MHC II , r = -0.784 ; P < 0.01 ) .", "target_text": { "TSH-R": "protein", "MHC I": "protein", "MHC II": "protein" } }, { "input_text": "In situ hybridization showed that apart from lymphocytes , thyroid cells themselves were the source of MHC II transcripts .", "target_text": { "lymphocytes": "cell_type", "thyroid cells": "cell_type", "MHC II": "protein", "MHC II transcripts": "protein" } }, { "input_text": "gamma-Interferon expression was only detectable in 1 Hashimoto 's goiter .", "target_text": { "gamma-Interferon": "protein" } }, { "input_text": "Our findings suggest that next to lymphocyte infiltration , active regulatory events in the thyrocyte are responsible for the inverse relation between functional parameters ( TSH-R , thyroid peroxidase , thyroglobulin , and c-fos ) and immunological markers ( MHC I and II ) .", "target_text": { "thyrocyte": "cell_type", "TSH-R": "protein", "thyroid peroxidase": "protein", "thyroglobulin": "protein" } }, { "input_text": "Functional antagonism between vitamin D3 and retinoic acid in the regulation of CD14 and CD23 expression during monocytic differentiation of U-937 cells .", "target_text": { "U-937 cells": "cell_line" } }, { "input_text": "1,25 alpha-Dihydroxicholecalciferol ( VitD3 ) and retinoic acid ( RA ) are important regulators of the proliferation and differentiation of several cell types .", "target_text": {} }, { "input_text": "This paper describes how the expression of the monocyte-macrophage Ag , CD14 , and the low affinity Fc receptor for IgE , CD23 , were inversely regulated during VitD3 - and RA-induced monocytic differentiation of human U-937 monoblasts .", "target_text": { "monocyte-macrophage Ag": "protein", "CD14": "protein", "affinity Fc receptor": "protein", "IgE": "protein", "CD23": "protein", "human U-937 monoblasts": "cell_line" } }, { "input_text": "PMA induced the expression of both CD14 and CD23 mRNA and protein .", "target_text": { "CD14": "protein", "CD23 mRNA": "RNA" } }, { "input_text": "Exposure to VitD3 rapidly induced the de novo expression of CD14 mRNA and protein .", "target_text": { "CD14 mRNA": "RNA" } }, { "input_text": "The addition of cycloheximide completely blocked the VitD3 induction of CD14 mRNA expression , indicating that the induction was dependent on ongoing protein synthesis .", "target_text": { "CD14 mRNA": "RNA" } }, { "input_text": "While inducing CD14 expression , VitD3 concomitantly suppressed the basal , PMA- , and RA- inducible CD23 expression in a dose-dependent manner .", "target_text": { "CD14": "protein", "CD23": "protein" } }, { "input_text": "In contrast , U-937 cells induced by RA strongly increased their expression of CD23 mRNA and protein , whereas they completely lacked detectable CD14 cell surface or mRNA expression .", "target_text": { "U-937 cells": "cell_line", "CD23": "protein", "CD23 mRNA": "RNA" } }, { "input_text": "Furthermore , the VitD3 - and the PMA -induced CD14 expression was inhibited as a temporal consequence of the RA-induced differentiation .", "target_text": { "CD14": "protein" } }, { "input_text": "The results suggest that there exists a functional antagonism between VitD3 and RA that may have important implications for the regulation of certain immune and inflammatory responses through their inverse effects on CD14 and CD23 gene expression .", "target_text": {} }, { "input_text": "Cell-specific bifunctional role of Jun oncogene family members on glucocorticoid receptor -dependent transcription .", "target_text": { "Jun oncogene family members": "DNA", "glucocorticoid receptor": "protein" } }, { "input_text": "Interaction between protein kinase C ( PKC ) - and glucocorticoid receptor ( GR ) -mediated signaling is suggested by the ability of the PKC activating phorbol ester 12-O-tetradecanoylphorbol-13-acetate ( TPA ) to inhibit GR -dependent transcription of the mouse mammary tumor virus ( MMTV ) long terminal repeat ( LTR ) .", "target_text": { "protein kinase C": "protein", "PKC": "protein", "glucocorticoid receptor": "protein", "GR": "protein", "long terminal repeat": "DNA", "LTR": "DNA" } }, { "input_text": "Here we report that this interference is cell specific , as TPA augmented dexamethasone -induced transcriptional activation of the MMTV LTR in several T cell lines but was inhibitory in NIH-3T3 fibroblasts .", "target_text": { "MMTV LTR": "DNA", "T cell lines": "cell_line", "NIH-3T3 fibroblasts": "cell_line" } }, { "input_text": "TPA-GR synergism was determined to have occurred at the GR -responsive element ( GRE ) level by functional analysis of deletion mutants or synthetic GRE oligonucleotides driving chloramphenicol acetyl-transferase expression .", "target_text": { "GR": "protein", "GR -responsive element": "DNA", "GRE": "DNA", "deletion mutants": "DNA", "synthetic GRE oligonucleotides": "DNA", "chloramphenicol acetyl-transferase": "protein" } }, { "input_text": "Synergism required an intact GR DNA-binding domain , whereas amino- or carboxyl- terminal domains were dispensable .", "target_text": { "GR DNA-binding domain": "protein" } }, { "input_text": "The effect was abrogated by the PKC inhibitor staurosporine , suggesting a role for PKC .", "target_text": { "PKC": "protein" } }, { "input_text": "Increased c-jun , jun-B , and jun-D expression above basal levels and increased transcriptional activity of AP-1/TPA responsive elements fused to chloramphenicol acetyl-transferase vectors were observed in T cells treated with TPA alone or in combination with dexamethasone .", "target_text": { "c-jun": "protein", "jun-B": "protein", "jun-D": "protein", "AP-1/TPA responsive elements": "DNA", "chloramphenicol acetyl-transferase": "protein", "chloramphenicol acetyl-transferase vectors": "DNA", "T cells": "cell_type" } }, { "input_text": "The ability of Jun proteins to cooperate with GR in T cells has been investigated after transfection of c-jun , jun-B , or jun-D expression vectors , which augmented GR -dependent transcription from either MMTV LTR or GRE .", "target_text": { "Jun proteins": "protein", "GR": "protein", "T cells": "cell_type", "MMTV LTR": "DNA", "GRE": "DNA" } }, { "input_text": "Conversely , c-jun and jun-B transfection blunted GR -dependent transcription in HeLa cells .", "target_text": { "c-jun": "protein", "jun-B": "protein", "GR": "protein", "HeLa cells": "cell_line" } }, { "input_text": "The presence of c-fos had a negative influence on GR function and correlated with the cell-specific synergistic or antagonistic activity of Jun with respect to GR ; high basal expression of c-fos as well as AP-1 DNA binding and transcriptional activity were observed in HeLa cells , but not in T cells .", "target_text": { "c-fos": "protein", "GR": "protein", "Jun": "protein", "AP-1": "protein", "HeLa cells": "cell_line", "T cells": "cell_type" } }, { "input_text": "Furthermore overexpression of exogenous c-fos has an inhibitory effect on GR -dependent transcription from GRE in T cells .", "target_text": { "c-fos": "protein", "exogenous c-fos": "protein", "GR": "protein", "GRE": "DNA", "T cells": "cell_type" } }, { "input_text": "We propose that Jun plays a bifunctional role on GR -dependent transcriptional activation of GRE , selecting either synergistic or antagonistic activity depending on the cell-specific microenvironment .", "target_text": { "Jun": "protein", "GR": "protein", "GRE": "DNA" } }, { "input_text": "In this regard , intracellular levels of c-fos appear to be influential .", "target_text": { "c-fos": "protein" } }, { "input_text": "Cell type- and stage-specific expression of the CD20/B1 antigen correlates with the activity of a diverged octamer DNA motif present in its promoter .", "target_text": { "CD20/B1 antigen": "protein", "octamer DNA motif": "DNA", "promoter": "DNA" } }, { "input_text": "The CD20 ( B1 ) gene encodes a B cell-specific protein involved in the regulation of human B cell proliferation and differentiation .", "target_text": { "CD20 ( B1 ) gene": "DNA", "B cell-specific protein": "protein" } }, { "input_text": "Studies with 5' deletion CD20 promoter-CAT constructs have previously revealed two regions of the promoter between bases -186 and -280 and between bases -280 and -454 which contained positive regulatory elements .", "target_text": { "5' deletion CD20 promoter-CAT constructs": "DNA", "promoter": "DNA", "positive regulatory elements": "DNA" } }, { "input_text": "In this study we identified a sequence element present in the most proximal region located between bases -214 and -201 , TTCTTCTAATTAA , which is important in the high constitutive expression of CD20 in mature B cells and the induction of CD20 in pre-B cells .", "target_text": { "sequence element": "DNA", "CD20": "protein", "pre-B cells": "cell_type" } }, { "input_text": "This sequence element was referred to as the BAT box and its deletion significantly reduced the activity of a CD20 promoter-CAT construct in B cells .", "target_text": { "sequence element": "DNA", "BAT box": "DNA" } }, { "input_text": "Mobility shift assays with various mutant probes and B cell nuclear extracts demonstrated that the core sequence TAAT was essential for binding to this site .", "target_text": {} }, { "input_text": "Cross competition experiments with an octamer sequence from the Ig heavy chain promoter , the BAT box , and a TA-rich sequence present in the CD21 promoter revealed that all three sequences bound the same nuclear proteins suggesting that the BAT box binding proteins were Oct-1 and Oct-2 .", "target_text": { "BAT box": "DNA", "TA-rich sequence": "DNA", "CD21 promoter": "DNA", "nuclear proteins": "protein", "BAT box binding proteins": "protein", "Oct-1": "protein", "Oct-2": "protein" } }, { "input_text": "Southwestern blotting and UV cross-linking studies confirmed that the BAT box binding proteins were Oct-1 and Oct-2 .", "target_text": { "BAT box binding proteins": "protein", "Oct-1": "protein", "Oct-2": "protein" } }, { "input_text": "The affinity of the BAT box binding proteins for the BAT box was approximately 25-fold less than for the octamer sequence and the BAT box binding proteins dissociated from the BAT box 10-fold more rapidly than from the octamer sequence .", "target_text": { "BAT box binding proteins": "protein", "BAT box": "DNA", "octamer sequence": "DNA" } }, { "input_text": "Despite this lower affinity , a trimer of the BAT box sequence was as efficiently transactivated by an Oct-2 expression vector as was a trimer of the octamer sequence in HeLa cells .", "target_text": { "BAT box": "DNA", "BAT box sequence": "DNA", "Oct-2": "protein", "Oct-2 expression vector": "DNA", "octamer sequence": "DNA", "HeLa cells": "cell_line" } }, { "input_text": "The BAT box and Oct-2 were also implicated in the induction of CD20 in the pre-B cell line , PB-697 , via phorbol esters .", "target_text": { "BAT box": "DNA", "Oct-2": "protein", "CD20": "protein", "pre-B cell line": "cell_line", "PB-697": "cell_line" } }, { "input_text": "The induction of CD20 mRNA was temporally associated with induction of Oct-2 mRNA and a BAT box-deleted CD20-CAT construct , in contrast to the wild type , was poorly induced by phorbol esters .", "target_text": { "CD20 mRNA": "RNA", "Oct-2 mRNA": "RNA", "BAT box-deleted CD20-CAT construct": "DNA" } }, { "input_text": "Together these results suggest that the BAT box binding proteins are important in the B cell specific expression of CD20 and perhaps CD21 .", "target_text": { "BAT box binding proteins": "protein", "CD20": "protein", "CD21": "protein" } }, { "input_text": "Human CD4 lymphocytes specifically recognize a peptide representing the fusion region of the hybrid protein pml/RAR alpha present in acute promyelocytic leukemia cells .", "target_text": { "Human CD4 lymphocytes": "cell_type", "hybrid protein": "protein", "pml/RAR alpha": "protein", "acute promyelocytic leukemia cells": "cell_type" } }, { "input_text": "Fusion proteins present in leukemic cells frequently contain a new amino acid at the fusion point .", "target_text": { "Fusion proteins": "protein", "leukemic cells": "cell_type", "fusion point": "protein" } }, { "input_text": "We tested whether a peptide ( BCR1/25 ) encompassing the fusion region of the hybrid molecule pml/RAR alpha , which is selectively expressed by acute promyelocytic leukemia ( APL ) cells , can be recognized by human T lymphocytes in vitro .", "target_text": { "fusion region": "protein", "pml/RAR alpha": "protein", "acute promyelocytic leukemia ( APL ) cells": "cell_type", "T lymphocytes": "cell_type", "human T lymphocytes": "cell_type" } }, { "input_text": "CD4+ lymphocytes , at both polyclonal and clonal level , recognized peptide BCR1/25 in an HLA-DR -- restricted fashion on presentation by autologous antigen-presenting cell ( APC ) or by APC expressing the HLA-DR11 restricting molecule .", "target_text": { "CD4+ lymphocytes": "cell_type", "HLA-DR": "protein", "autologous antigen-presenting cell": "cell_type", "APC": "cell_type", "HLA-DR11 restricting molecule": "protein" } }, { "input_text": "Control peptides corresponding to the normal pml and RAR alpha proteins were not recognized .", "target_text": { "pml": "protein", "RAR alpha proteins": "protein" } }, { "input_text": "One clone ( DEG5 ) also exerted a high and specific cytotoxicity against autologous cells pulsed with BCR1/25 .", "target_text": { "DEG5": "cell_line", "autologous cells": "cell_line" } }, { "input_text": "The autologous DE LCL containing a transduced pml/RAR alpha fusion gene and expressing a bcr1 type of the pml/RAR alpha hybrid protein induced the proliferation of DE anti-BCR1/25 T cell clones .", "target_text": { "autologous DE LCL": "cell_line", "pml/RAR alpha": "protein", "pml/RAR alpha fusion gene": "DNA", "bcr1 type": "protein", "DE anti-BCR1/25 T cell clones": "cell_line" } }, { "input_text": "It is concluded that the bcr1 type-pml/RAR alpha fusion protein of APL contains an antigenic site , absent from the normal parent molecules and recognized by human CD4+ lymphocytes .", "target_text": { "bcr1 type-pml/RAR alpha fusion protein": "protein", "APL": "cell_line", "human CD4+ lymphocytes": "cell_line" } }, { "input_text": "The zinc finger transcription factor Egr-1 is essential for and restricts differentiation along the macrophage lineage .", "target_text": { "zinc finger": "protein", "zinc finger transcription factor": "protein", "Egr-1": "protein", "macrophage lineage": "cell_type" } }, { "input_text": "We have isolated cDNA clones of myeloid differentiation primary response ( MyD ) genes , activated in the absence of de novo protein synthesis following induction for differentiation along either the macrophage or granulocyte lineage in human myeloblastic leukemia HL-60 cells .", "target_text": { "cDNA clones": "DNA", "myeloid differentiation primary response ( MyD ) genes": "DNA", "macrophage": "cell_type", "granulocyte lineage": "cell_type", "myeloblastic leukemia HL-60 cells": "cell_line" } }, { "input_text": "One cDNA clone of a primary response gene , expressed upon macrophage differentiation , encoded for Egr-1 , a zinc finger transcription factor .", "target_text": { "cDNA clone": "DNA", "Egr-1": "protein", "zinc finger transcription factor": "protein" } }, { "input_text": "The Egr-1 gene was observed to be transcriptionally silent in HL-60 cells , but active in U-937 and M1 cells , the latter two being predetermined for macrophage differentiation .", "target_text": { "Egr-1 gene": "DNA", "HL-60 cells": "cell_line", "U-937": "cell_line", "M1 cells": "cell_line" } }, { "input_text": "Egr-1 antisense oligomers in the culture media blocked macrophage differentiation in both myeloid leukemia cell lines and normal myeloblasts .", "target_text": { "Egr-1": "protein", "myeloid leukemia cell lines": "cell_line", "myeloblasts": "cell_type" } }, { "input_text": "HL-60 cells constitutively expressing an Egr-1 transgene ( HL-60Egr-1 ) could be induced for macrophage , but not granulocyte , differentiation .", "target_text": { "HL-60 cells": "cell_line", "Egr-1 transgene": "DNA", "HL-60Egr-1": "DNA", "macrophage": "cell_type", "granulocyte": "cell_type" } }, { "input_text": "These observations indicate that expression of Egr-1 is essential for and restricts differentiation of myeloblasts along the macrophage lineage .", "target_text": { "Egr-1": "protein", "myeloblasts": "cell_type", "macrophage lineage": "cell_type" } }, { "input_text": "The Epstein-Barr virus nuclear antigen 2 interacts with an EBNA2 responsive cis-element of the terminal protein 1 gene promoter .", "target_text": { "Epstein-Barr virus nuclear antigen 2": "protein", "EBNA2 responsive cis-element": "DNA", "terminal protein 1 gene promoter": "DNA" } }, { "input_text": "The Epstein-Barr virus protein EBNA2 acts as a transcriptional activator of cellular and viral genes and plays a crucial role in the immortalization of human primary B-cells by EBV .", "target_text": { "Epstein-Barr virus protein EBNA2": "protein", "transcriptional activator": "protein", "human primary B-cells": "cell_type" } }, { "input_text": "We have shown previously that EBNA2 transactivates the promoters of the latent membrane antigens LMP , TP1 and TP2 .", "target_text": { "EBNA2": "protein", "latent membrane antigens": "protein", "LMP": "protein", "TP1": "protein", "TP2": "protein" } }, { "input_text": "The promoter of the TP1 gene was chosen as a model system to study the molecular mechanism of EBNA2 mediated transactivation .", "target_text": { "promoter": "DNA", "TP1 gene": "DNA", "EBNA2": "protein" } }, { "input_text": "To identify an EBNA2 dependent cis-acting element , various TP1 promoter-reporter gene constructs were transfected in the absence and presence of an EBNA2 expression vector into the established B-cell line BL41-P3HR1 .", "target_text": { "EBNA2": "protein", "EBNA2 dependent cis-acting element": "DNA", "TP1 promoter-reporter gene constructs": "DNA", "EBNA2 expression vector": "DNA", "B-cell line BL41-P3HR1": "cell_line" } }, { "input_text": "We were able to delineate an 81 bp EBNA2 responsive region between -258 and -177 relative to the TP1 RNA start site .", "target_text": { "EBNA2": "protein", "81 bp EBNA2 responsive region": "DNA", "TP1 RNA start site": "DNA" } }, { "input_text": "The element worked in either orientation and could mediate EBNA2 dependent transactivation on a heterologous promoter .", "target_text": { "EBNA2": "protein", "heterologous promoter": "DNA" } }, { "input_text": "Electrophoretic mobility shift assays revealed three specific protein-DNA complexes formed with sequences of the EBNA2 responsive element .", "target_text": { "protein-DNA complexes": "protein", "EBNA2": "protein", "EBNA2 responsive element": "DNA" } }, { "input_text": "Two of these were not cell type specific , but the third was detected only in EBNA2 positive cell extracts .", "target_text": { "EBNA2": "protein" } }, { "input_text": "Gel-shift analysis in the presence of EBNA2 specific monoclonal antibodies revealed that EBNA2 is a component of the third complex .", "target_text": { "EBNA2": "protein", "EBNA2 specific monoclonal antibodies": "protein" } }, { "input_text": "Thus , these experiments demonstrate that EBNA2 interacts with an EBNA2 responsive cis-element of the TP1 promoter", "target_text": { "EBNA2": "protein", "EBNA2 responsive cis-element": "DNA", "TP1 promoter": "DNA" } }, { "input_text": "Minimally modified low density lipoprotein -induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate .", "target_text": { "lipoprotein": "protein", "endothelial cells": "cell_type" } }, { "input_text": "We have previously shown that minimally oxidized LDL ( MM-LDL ) activated endothelial cells to increase their interaction with monocytes but not neutrophils , inducing monocyte but not neutrophil binding and synthesis of monocyte chemotactic protein-1 and monocyte colony-stimulating factor ( M-CSF ) .", "target_text": { "MM-LDL": "protein", "endothelial cells": "cell_type", "minimally oxidized LDL ( MM-LDL ) activated endothelial cells": "cell_line", "monocytes": "cell_type", "neutrophils": "cell_type", "monocyte chemotactic protein-1": "protein", "monocyte colony-stimulating factor": "protein", "M-CSF": "protein" } }, { "input_text": "In the present studies we have examined the signaling pathways by which this monocyte-specific response is induced .", "target_text": {} }, { "input_text": "Both induction of monocyte binding and mRNA levels for M-CSF by MM-LDL were not inhibited in protein kinase C-depleted endothelial cells .", "target_text": { "M-CSF": "protein", "MM-LDL": "protein", "endothelial cells": "cell_type" } }, { "input_text": "A number of our studies indicate that cAMP is the second messenger for the effects of MM-LDL cited above .", "target_text": { "MM-LDL": "protein" } }, { "input_text": "Incubation of endothelial cells with MM-LDL caused a 173 % increase in intracellular cAMP levels .", "target_text": { "endothelial cells": "cell_type", "MM-LDL": "protein" } }, { "input_text": "Agents which increased cAMP levels , including cholera toxin , pertussis toxin , dibutyryl cAMP , and isoproterenol mimicked the actions of MM-LDL .", "target_text": { "MM-LDL": "protein" } }, { "input_text": "Agents which elevated cAMP were also shown to activate NF kappa B , suggesting a role for this transcription factor in activation of monocyte-endothelial interactions .", "target_text": { "NF kappa B": "protein" } }, { "input_text": "Although endothelial leukocyte adhesion molecule ( ELAM ) mRNA synthesis can be regulated by NF kappa B , ELAM was not expressed and ELAM mRNA was only slightly elevated in response to MM-LDL .", "target_text": { "endothelial leukocyte adhesion molecule": "protein", "ELAM": "protein", "endothelial leukocyte adhesion molecule ( ELAM ) mRNA": "RNA", "NF kappa B": "protein", "ELAM mRNA": "RNA", "MM-LDL": "protein" } }, { "input_text": "We present evidence that induction of neutrophil binding by LPS is actually suppressed by agents that elevated cAMP levels .", "target_text": { "neutrophil": "cell_type" } }, { "input_text": "Human T cell transcription factor GATA-3 stimulates HIV-1 expression .", "target_text": { "Human T cell transcription factor": "protein", "GATA-3": "protein" } }, { "input_text": "A family of transcriptional activating proteins , the GATA factors , has been shown to bind to a consensus motif through a highly conserved C4 zinc finger DNA binding domain .", "target_text": { "GATA factors": "protein", "consensus motif": "DNA", "C4 zinc finger": "protein", "highly conserved C4 zinc finger DNA binding domain": "protein" } }, { "input_text": "One member of this multigene family , GATA-3 , is most abundantly expressed in T lymphocytes , a cellular target for human immunodeficiency virus type 1 ( HIV-1 ) infection and replication .", "target_text": { "GATA-3": "protein", "T lymphocytes": "cell_type" } }, { "input_text": "In vitro DNase I footprinting analysis revealed six hGATA-3 binding sites in the U3 region ( the transcriptional regulatory domain ) of the HIV-1 LTR .", "target_text": { "DNase I": "protein", "hGATA-3 binding sites": "DNA", "U3 region": "DNA", "transcriptional regulatory domain": "DNA", "HIV-1 LTR": "DNA" } }, { "input_text": "Cotransfection of an hGATA-3 expression plasmid with a reporter plasmid whose transcription is directed by the HIV-1 LTR resulted in 6- to 10-fold stimulation of LTR -mediated transcription , whereas site specific mutation of these GATA sites resulted in virtual abrogation of the activation by hGATA-3 .", "target_text": { "hGATA-3 expression plasmid": "DNA", "reporter plasmid": "DNA", "HIV-1 LTR": "DNA", "LTR": "DNA", "GATA sites": "DNA", "hGATA-3": "protein" } }, { "input_text": "Further , deletion of the hGATA-3 transcriptional activation domain abolished GATA-dependent HIV-1 trans-activation , showing that the stimulation of viral transcription observed is a direct effect of cotransfected hGATA-3 .", "target_text": { "hGATA-3": "protein", "hGATA-3 transcriptional activation domain": "DNA", "cotransfected hGATA-3": "protein" } }, { "input_text": "Introduction of the HIV-1 plasmids in which the GATA sites have been mutated into human T lymphocytes also caused a significant reduction in LTR -mediated transcription at both the basal level and in ( PHA- plus PMA- ) stimulated T cells .", "target_text": { "HIV-1 plasmids": "DNA", "GATA sites": "DNA", "T lymphocytes": "cell_type", "LTR": "DNA", "stimulated T cells": "cell_line" } }, { "input_text": "These observations suggest that in addition to its normal role in T lymphocyte gene regulation , hGATA-3 may also play a significant role in HIV-1 transcriptional activation .", "target_text": { "T lymphocyte": "cell_type", "hGATA-3": "protein" } }, { "input_text": "Cytokine modulation of HIV expression .", "target_text": {} }, { "input_text": "Cytokines , the peptide hormones which control the homeostasis of the immune system and also play a fundamental role in inflammatory and immune mediated reactions , have been involved at multiple levels in the pathogenesis of the acquired immune deficiency syndrome ( AIDS ) .", "target_text": { "Cytokines": "protein", "peptide hormones": "protein" } }, { "input_text": "Infection with the human immunodeficiency virus ( HIV ) has been shown to induce production of several cytokines both in vitro and in vivo .", "target_text": { "cytokines": "protein" } }, { "input_text": "Conversely , several cytokines modulate the levels of HIV expression in infected cells of both T lymphocytic and mononuclear phagocytic lineage .", "target_text": { "cytokines": "protein" } }, { "input_text": "Activated mononuclear cells , particularly B cells which are in a state of chronic activation in HIV infected individuals , release HIV -inductive cytokines and thus play a potentially important role in the pathogenesis of HIV infection .", "target_text": { "Activated mononuclear cells": "cell_type", "B cells": "cell_type", "cytokines": "protein", "HIV -inductive cytokines": "protein" } }, { "input_text": "Cloning and functional characterization of early B-cell factor , a regulator of lymphocyte-specific gene expression .", "target_text": { "early B-cell factor": "protein" } }, { "input_text": "Early B-cell factor ( EBF ) was identified previously as a tissue-specific and differentiation stage-specific DNA-binding protein that participates in the regulation of the pre-B and B lymphocyte-specific mb-1 gene .", "target_text": { "Early B-cell factor": "protein", "EBF": "protein", "DNA-binding protein": "protein" } }, { "input_text": "Partial amino acid sequences obtained from purified EBF were used to isolate cDNA clones , which by multiple criteria encode EBF .", "target_text": { "EBF": "protein", "cDNA clones": "DNA" } }, { "input_text": "The recombinant polypeptide formed sequence-specific complexes with the EBF -binding site in the mb-1 promoter .", "target_text": { "recombinant polypeptide": "protein", "EBF": "protein", "EBF -binding site": "DNA", "mb-1 promoter": "DNA" } }, { "input_text": "The cDNA hybridized to multiple transcripts in pre-B and B-cell lines , but transcripts were not detected at significant levels in plasmacytoma , T-cell , and nonlymphoid cell lines .", "target_text": { "cDNA": "DNA", "pre-B": "cell_line", "B-cell lines": "cell_line", "pre-B and B-cell lines": "cell_line", "plasmacytoma": "cell_line", "T-cell": "cell_line", "nonlymphoid cell lines": "cell_line" } }, { "input_text": "Expression of recombinant EBF in transfected nonlymphoid cells strongly activated transcription from reporter plasmids containing functional EBF -binding sites .", "target_text": { "EBF": "protein", "transfected nonlymphoid cells": "cell_line", "EBF -binding sites": "DNA" } }, { "input_text": "Analysis of DNA binding by deletion mutants of EBF identified an amino-terminal cysteine-rich DNA-binding domain lacking obvious sequence similarity to known transcription factors .", "target_text": { "EBF": "protein", "amino-terminal cysteine-rich DNA-binding domain": "protein", "transcription factors": "protein" } }, { "input_text": "DNA-binding assays with cotranslated wild-type and truncated forms of EBF indicated that the protein interacts with its site as a homodimer .", "target_text": { "EBF": "protein", "homodimer": "protein" } }, { "input_text": "Deletions delineated a carboxy-terminal dimerization region containing two repeats of 15 amino acids that show similarity with the dimerization domains of basic-helix-loop-helix proteins .", "target_text": { "carboxy-terminal dimerization region": "protein", "dimerization domains": "protein", "basic-helix-loop-helix proteins": "protein" } }, { "input_text": "Together , these data suggest that EBF represents a novel regulator of B lymphocyte-specific gene expression .", "target_text": { "EBF": "protein" } }, { "input_text": "Cell-specific expression of helix-loop-helix transcription factors encoded by the E2A gene .", "target_text": { "helix-loop-helix transcription factors": "protein", "E2A gene": "DNA" } }, { "input_text": "The E2A gene encodes transcription factors of the helix-loop-helix family that are implicated in cell-specific gene expression as part of dimeric complexes that interact with E box enhancer elements .", "target_text": { "E2A gene": "DNA", "transcription factors": "protein", "helix-loop-helix family": "protein", "dimeric complexes": "protein", "E box": "DNA", "E box enhancer elements": "DNA" } }, { "input_text": "It has previously been shown that transcripts of the E2A gene can be detected in a wide range of cell types .", "target_text": { "E2A gene": "DNA" } }, { "input_text": "We have now examined expression of the mouse E2A gene at the protein level using polyclonal antisera directed against distinct portions of the E2A protein to probe blots of cellular extracts .", "target_text": { "E2A gene": "DNA", "mouse E2A gene": "DNA", "E2A protein": "protein" } }, { "input_text": "A 73 kDa protein was identified by this analysis : this protein is highly enriched in cell lines of B lymphoid origin as compared to pancreatic beta-cells and fibroblast cells .", "target_text": { "73 kDa protein": "protein", "cell lines of B lymphoid origin": "cell_line", "pancreatic beta-cells": "cell_type", "fibroblast cells": "cell_type" } }, { "input_text": "The detection of this protein selectively in extracts of lymphoid cells correlates with the presence of the E box -binding activity LEF1/BCF1 in these cells ; this binding activity was previously shown to be efficiently recognized by antiserum directed against E2A gene products .", "target_text": { "lymphoid cells": "cell_type", "E box": "DNA", "LEF1/BCF1": "protein", "E2A gene": "DNA", "E2A gene products": "protein" } }, { "input_text": "Transfection of cells with full length E2A cDNA leads to appearance of protein co-migrating with the 73 kDa protein on SDS gel electrophoresis and co-migrating with LEF1/BCF1 on mobility shift analysis .", "target_text": { "E2A cDNA": "DNA", "73 kDa protein": "protein", "LEF1/BCF1": "protein" } }, { "input_text": "Our results are consistent with the view that the DNA-binding activity LEF1/BCF1 is a homodimer of E2A proteins ; the selective appearance of this putative cell-specific transcription factor in B lymphoid cells seems to be attributable , at least in part , to the elevated E2A protein concentrations in these cells .", "target_text": { "LEF1/BCF1": "protein", "homodimer of E2A proteins": "protein", "B lymphoid cells": "cell_type", "E2A protein": "protein" } }, { "input_text": "Hypertension in pregnancy .", "target_text": {} }, { "input_text": "Pregnancy-induced hypertension ( PIH ) is a frequent cause of maternal and neonatal morbidity and mortality .", "target_text": {} }, { "input_text": "In the present study we focused on the pathophysiology of PIH , mainly on the role of mineralocorticoids , reversed blood pressure patterns , and the resulting necessity of continuous monitoring of the preeclamptic mother .", "target_text": {} }, { "input_text": "Problems of antihypertensive therapy are discussed and the first results of a pilot study with Urapidil are presented .", "target_text": {} }, { "input_text": "To examine the role of mineralocorticoids in the pathophysiology of PIH , we studied plasma aldosterone and 18-hydroxy-corticosterone ( 18-OH-B ) levels in 25 women with PIH and in 25 healthy pregnant women .", "target_text": {} }, { "input_text": "Furthermore , we evaluated the mineralocorticoid receptor ( MR ) count in mononuclear leukocytes in the 2 groups .", "target_text": { "mineralocorticoid receptor": "protein", "MR": "protein", "mononuclear leukocytes": "cell_type" } }, { "input_text": "The MR-count was significantly decreased in the PIH -group .", "target_text": {} }, { "input_text": "The values of plasma aldosterone and 18-OH-B were also low .", "target_text": {} }, { "input_text": "These results can not be explained by receptor down-regulation due to higher level of mineralocorticoids of the zona glomerulosa .", "target_text": {} }, { "input_text": "Perhaps deoxycorticosterone or a hitherto unknown mineralocorticoid is responsible for the hypertension and altered MR -status .", "target_text": { "MR": "protein" } }, { "input_text": "The first results of continuous blood pressure measurements with a noninvasive , real-time blood pressure monitor ( Finapres ) are presented .", "target_text": {} }, { "input_text": "The comparison of the obtained values with intraarterial measurements demonstrates a good correlation between the two methods .", "target_text": {} }, { "input_text": "We also report on the first experiences with Urapidil in the treatment of hypertension in severe preeclampsia .", "target_text": {} }, { "input_text": "The data show that hypertension in preeclamptic women can be treated by Urapidil without side effects or reflex-tachycardia .", "target_text": {} }, { "input_text": "Further studies will have to prove if Urapidil is suited for prepartal treatment of PIH as well .", "target_text": {} }, { "input_text": "Suppression of a cellular differentiation program by phorbol esters coincides with inhibition of binding of a cell-specific transcription factor ( NF-E2 ) to an enhancer element required for expression of an erythroid-specific gene .", "target_text": { "cell-specific transcription factor": "protein", "NF-E2": "protein", "enhancer element": "DNA", "erythroid-specific gene": "DNA" } }, { "input_text": "Induction by hemin increases , while induction with 12-O-tetradecanoylphorbol-13-acetate ( TPA ) represses , erythroid-specific gene expression in the human cell line K562 .", "target_text": { "erythroid-specific gene": "DNA", "human cell line K562": "cell_line" } }, { "input_text": "We analyzed the effects of hemin or TPA induction on the binding and activity of transcription factors at a regulatory element found within the transcriptional regulatory sequences of many erythroid-specific genes .", "target_text": { "transcription factors": "protein", "regulatory element": "DNA", "transcriptional regulatory sequences": "DNA", "erythroid-specific genes": "DNA" } }, { "input_text": "TPA induction increases the binding of ubiquitous AP-1 factors to this element .", "target_text": { "ubiquitous AP-1 factors": "protein" } }, { "input_text": "TPA induction inhibits the binding of the lineage limited transcription factor NF-E2 to this transcriptional control element .", "target_text": { "lineage limited transcription factor": "protein", "NF-E2": "protein", "transcriptional control element": "DNA" } }, { "input_text": "Hemin induction of K562 cells does not facilitate the binding of NF-E2 to its recognition site .", "target_text": { "K562 cells": "cell_line", "NF-E2": "protein", "recognition site": "DNA" } }, { "input_text": "Hemin induction appears to nonspecifically increase the expression of transiently transfected genes in K562 cells .", "target_text": { "K562 cells": "cell_line" } }, { "input_text": "Beyond this nonspecific increase in gene expression , hemin induction acts to increase the activity of the lineage limited transcription factor NF-E2 .", "target_text": { "hemin": "protein", "lineage limited transcription factor": "protein" } }, { "input_text": "The divergent effects of hemin and TPA on gene expression in K562 cells are mediated , in part , by their contrasting effects on the transcription factor NF-E2 .", "target_text": { "K562 cells": "cell_line", "transcription factor": "protein", "NF-E2": "protein" } }, { "input_text": "Interleukin-3 expression by activated T cells involves an inducible , T-cell-specific factor and an octamer binding protein .", "target_text": { "Interleukin-3": "protein", "activated T cells": "cell_type", "T-cell-specific factor": "protein", "octamer binding protein": "protein" } }, { "input_text": "Interleukin-3 ( IL-3 ) is exclusively expressed by activated T and natural killer cells , a function that is tightly controlled both in a lineage-specific and in a stimulation-dependent manner .", "target_text": { "Interleukin-3": "protein", "IL-3": "protein", "activated T": "cell_type", "natural killer cells": "cell_type" } }, { "input_text": "We have investigated the protein binding characteristics and functional importance of the ACT-1-activating region of the IL-3 promoter .", "target_text": { "ACT-1-activating region": "DNA", "IL-3": "protein" } }, { "input_text": "This region binds an inducible , T-cell-specific factor over its 5' end , a site that is necessary for the expression of IL-3 in the absence of other upstream elements .", "target_text": { "T-cell-specific factor": "protein", "5' end": "DNA", "IL-3": "protein" } }, { "input_text": "Over its 3' end , it binds a factor that is ubiquitously and constitutively expressed .", "target_text": { "3' end": "DNA" } }, { "input_text": "This factor is Oct-1 or an immunologically related octamer-binding protein , and it plays a role in coordinating the activity of several regulatory elements .", "target_text": { "Oct-1": "protein", "immunologically related octamer-binding protein": "protein", "regulatory elements": "DNA" } }, { "input_text": "These characteristics make the ACT-1 site analogous to the activating ARRE-1 site in the IL-2 promoter .", "target_text": { "ACT-1 site": "DNA", "ARRE-1 site": "DNA", "IL-2 promoter": "DNA" } }, { "input_text": "Furthermore , and despite a lack of sequence homology , the promoters of IL-3 and IL-2 share an organizational pattern of regulatory elements that is likely to be important for the T-cell-specific expression of these genes .", "target_text": { "IL-3": "protein", "IL-2": "protein" } }, { "input_text": "Interleukin-4 inhibits the lipopolysaccharide-induced expression of c-jun and c-fos messenger RNA and activator protein-1 binding activity in human monocytes .", "target_text": { "Interleukin-4": "protein", "activator protein-1": "protein", "human monocytes": "cell_type" } }, { "input_text": "We studied the effect of interleukin-4 ( IL-4 ) on the lipopolysaccharide ( LPS ) induction of two immediate early genes c-fos and c-jun .", "target_text": { "interleukin-4": "protein", "IL-4": "protein", "c-fos": "DNA", "c-jun": "DNA" } }, { "input_text": "These genes encode proteins that form the dimeric complex activator protein-1 ( AP-1 ) , which is active as a transcriptional factor .", "target_text": { "dimeric complex": "protein", "activator protein-1": "protein", "AP-1": "protein", "transcriptional factor": "protein" } }, { "input_text": "Maximal accumulation of either c-fos and c-jun messenger RNA ( mRNA ) occurred 30 minutes after LPS addition .", "target_text": {} }, { "input_text": "When cells were treated with IL-4 for 5 hours before LPS activation , both the c-fos and the c-jun mRNA expression was decreased .", "target_text": { "IL-4": "protein" } }, { "input_text": "The inhibition of c-fos and c-jun expression by IL-4 in LPS-treated cells was shown to be due to a lower transcription rate of the c-fos and c-jun genes .", "target_text": { "c-fos": "DNA", "IL-4": "protein", "LPS-treated cells": "cell_type", "c-jun genes": "DNA", "c-fos and c-jun genes": "DNA" } }, { "input_text": "IL-4 did not affect the stability of the c-fos and c-jun transcripts .", "target_text": { "IL-4": "protein", "c-fos": "protein", "c-jun transcripts": "protein" } }, { "input_text": "Finally , using electrophoretic mobility shift assays , evidence was obtained that IL-4 inhibits LPS-induced expression of AP-1 protein .", "target_text": { "IL-4": "protein", "AP-1": "protein" } }, { "input_text": "These data indicate that IL-4 suppresses the induction of transcription factors in human activated monocytes .", "target_text": { "IL-4": "protein", "transcription factors": "protein", "monocytes": "cell_type", "human activated monocytes": "cell_type" } }, { "input_text": "Transient pseudohypoaldosteronism in obstructive renal disease with transient reduction of lymphocytic aldosterone receptors .", "target_text": { "lymphocytic aldosterone receptors": "protein" } }, { "input_text": "Results in two affected infants .", "target_text": {} }, { "input_text": "We report two patients with transient pseudohypoaldosteronism due to obstructive renal disease .", "target_text": {} }, { "input_text": "Both patients presented with a salt-losing episode simulating adrenal insufficiency .", "target_text": {} }, { "input_text": "In one patient , transient reduction of aldosterone receptors could be documented , while in the second patient the clinical and biochemical parameters were consistent with transient pseudohypoaldosteronism .", "target_text": { "aldosterone receptors": "protein" } }, { "input_text": "Aldosterone receptors were normal in both patients", "target_text": { "Aldosterone receptors": "protein" } }, { "input_text": "Aldosterone-specific membrane receptors and rapid non-genomic actions of mineralocorticoids .", "target_text": { "Aldosterone-specific membrane receptors": "protein" } }, { "input_text": "Functional studies in extrarenal , non-epithelial cells such as smooth muscle cells and more recently circulating human lymphocytes have provided increasing evidence that aldosterone produces not only classical genomic effects , but also rapid , non-genomic effects on transmembrane electrolyte movements .", "target_text": { "extrarenal , non-epithelial cells": "cell_type", "smooth muscle cells": "cell_type", "human lymphocytes": "cell_type", "circulating human lymphocytes": "cell_type" } }, { "input_text": "These involve activation of the sodium/proton exchanger of the cell membrane at very low , physiological concentrations of aldosterone with an acute onset within 1-2 min .", "target_text": { "sodium/proton exchanger": "protein" } }, { "input_text": "A second messenger cascade involved is the inositol 1,4,5-trisphosphate /calcium pathway which responds over the same rapid time course .", "target_text": {} }, { "input_text": "Such changes clearly can not be explained by genomic mechanisms , which are responsible for later effects than the membrane related rapid responses .", "target_text": {} }, { "input_text": "The mechanisms underlying these rapid effects of aldosterone on electrolytes have been extensively studied in human lymphocytes , which thus may represent valuable tools in the delineation of the receptor-effector mechanisms involved .", "target_text": { "human lymphocytes": "cell_type" } }, { "input_text": "The unique characteristics of this new pathway for steroid action include its rapid time course , 10,000-fold selectivity for aldosterone over cortisol and the ineffectiveness of spironolactones , classical mineralocorticoid antagonists , as antagonists of the response .", "target_text": {} }, { "input_text": "Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells .", "target_text": { "Human immunodeficiency virus type 1 Nef protein": "protein", "NF-kappa B": "protein", "human T cells": "cell_type" } }, { "input_text": "Human immunodeficiency virus type 1 ( HIV-1 ) can establish a persistent and latent infection in CD4+ T lymphocytes ( W.C.Greene , N.Engl.J. Med.324 : 308-317 , 1991 ; S.M.Schnittman , M.C.Psallidopoulos , H.C. Lane , L.Thompson , M.Baseler , F.Massari , C.H.Fox , N.P.Salzman , and A.S.Fauci , Science 245 : 305-308 , 1989 ) .", "target_text": { "CD4+ T lymphocytes": "cell_type" } }, { "input_text": "Production of HIV-1 from latently infected cells requires host cell activation by T-cell mitogens ( T.Folks , D.M.Powell , M.M.Lightfoote , S.Benn , M.A. Martin , and A.S.Fauci , Science 231 : 600-602 , 1986 ; D.Zagury , J. Bernard , R.Leonard , R.Cheynier , M.Feldman , P.S.Sarin , and R.C. Gallo , Science 231 : 850-853 , 1986 ) .", "target_text": { "T-cell mitogens": "protein" } }, { "input_text": "This activation is mediated by the host transcription factor NF-kappa B [ G.Nabel and D.Baltimore , Nature ( London ) 326 : 711-717 , 1987 ] .", "target_text": { "host transcription factor": "protein", "NF-kappa B": "protein" } }, { "input_text": "We report here that the HIV-1 -encoded Nef protein inhibits the induction of NF-kappa B DNA-binding activity by T- cell mitogens .", "target_text": { "HIV-1 -encoded Nef protein": "protein", "NF-kappa B": "protein", "T- cell mitogens": "protein" } }, { "input_text": "However , Nef does not affect the DNA-binding activity of other transcription factors implicated in HIV-1 regulation , including SP-1 , USF , URS , and NF-AT .", "target_text": { "Nef": "protein", "transcription factors": "protein", "SP-1": "protein", "USF": "protein", "URS": "protein", "NF-AT": "protein" } }, { "input_text": "Additionally , Nef inhibits the induction of HIV-1- and interleukin 2- directed gene expression , and the effect on HIV-1 transcription depends on an intact NF-kappa B -binding site .", "target_text": { "Nef": "protein", "NF-kappa B": "protein", "NF-kappa B -binding site": "DNA" } }, { "input_text": "These results indicate that defective recruitment of NF-kappa B may underlie Nef 's negative transcriptional effects on the HIV-1 and interleukin 2 promoters .", "target_text": { "NF-kappa B": "protein", "Nef": "protein" } }, { "input_text": "Further evidence suggests that Nef inhibits NF-kappa B induction by interfering with a signal derived from the T-cell receptor complex .", "target_text": { "Nef": "protein", "NF-kappa B": "protein", "T-cell receptor complex": "protein" } } ]