751883801@GENIA Treebank@formal@@1@S@Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.@@@@1@12@@oe@16-12-2010
751883802@GENIA Treebank@formal@@1@S@Antioxidants have been proposed to be anti-atherosclerotic agents; however, the mechanisms underlying their beneficial effects are poorly understood.@@@@1@21@@oe@16-12-2010
751883803@GENIA Treebank@formal@@1@S@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).@@@@1@29@@oe@16-12-2010
751883804@GENIA Treebank@formal@@1@S@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).@@@@1@42@@oe@16-12-2010
751883805@GENIA Treebank@formal@@1@S@Agonist-induced monocytic cell adhesion, but not basal adhesion, was inhibited in a time- and concentration-dependent manner by alpha-tcp.@@@@1@21@@oe@16-12-2010
751883806@GENIA Treebank@formal@@1@S@The IC50 of alpha-tcp on an IL-1-induced response was 45 microM.@@@@1@12@@oe@16-12-2010
751883807@GENIA Treebank@formal@@1@S@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.@@@@1@40@@oe@16-12-2010
751883808@GENIA Treebank@formal@@1@S@Probucol (50 microM) and N-acetylcysteine (20 mM) also inhibited agonist-induced monocytic cell adhesion; whereas, several other antioxidants had no significant effect.@@@@1@28@@oe@16-12-2010
751883809@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
751883810@GENIA Treebank@formal@@1@S@Activation of the transcription factor NF-kappa B is reported to be necessary but not sufficient for E-selectin expression in EC.@@@@1@21@@oe@16-12-2010
751883811@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this transcription factor after cytokine stimulation.@@@@1@20@@oe@16-12-2010
751883812@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
751883813@GENIA Treebank@formal@@1@S@Our results point to a novel alternative mechanism of action of alpha-tcp.@@@@1@13@@oe@16-12-2010
751984501@GENIA Treebank@formal@@1@S@Inhibition of the differentiation of human myeloid cell lines by redox changes induced through glutathione depletion.@@@@1@17@@oe@16-12-2010
751984502@GENIA Treebank@formal@@1@S@We have investigated the effect of redox changes in vivo on the differentiation of two human myeloid cell lines, HL-60 and KG-1.@@@@1@24@@oe@16-12-2010
751984503@GENIA Treebank@formal@@1@S@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.@@@@1@37@@oe@16-12-2010
751984504@GENIA Treebank@formal@@1@S@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.@@@@1@37@@oe@16-12-2010
752009301@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
752009302@GENIA Treebank@formal@@1@S@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).@@@@1@62@@oe@16-12-2010
752009303@GENIA Treebank@formal@@1@S@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.@@@@1@48@@oe@16-12-2010
752009304@GENIA Treebank@formal@@1@S@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.@@@@1@57@@oe@16-12-2010
752009305@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
752009306@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
752009307@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
752009308@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
752009309@GENIA Treebank@formal@@1@S@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.@@@@1@23@@oe@16-12-2010
752009310@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
752009311@GENIA Treebank@formal@@1@S@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.@@@@1@33@@oe@16-12-2010
752091401@GENIA Treebank@formal@@1@S@CD14-mediated translocation of nuclear factor-kappa B induced by lipopolysaccharide does not require tyrosine kinase activity.@@@@1@16@@oe@16-12-2010
752091402@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
752091403@GENIA Treebank@formal@@1@S@CD14, a glycosylphosphatidylinositol-linked antigen, functions as an LPS signaling receptor.@@@@1@13@@oe@16-12-2010
752091404@GENIA Treebank@formal@@1@S@A critical issue concerns the mechanism by which CD14, which has no transmembrane domain, transduces its signal following LPS binding.@@@@1@23@@oe@16-12-2010
752091405@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
752091406@GENIA Treebank@formal@@1@S@Wild-type Chinese hamster ovary (CHO)-K1 cells can be activated by endotoxin to release arachidonate following transfection with human CD14 (CHO/CD14).@@@@1@26@@oe@16-12-2010
752091407@GENIA Treebank@formal@@1@S@Nuclear translocation of cytosolic NF-kappa B is correlated with a number of LPS-inducible responses.@@@@1@15@@oe@16-12-2010
752091408@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
752091409@GENIA Treebank@formal@@1@S@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.@@@@1@21@@oe@16-12-2010
752091410@GENIA Treebank@formal@@1@S@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.@@@@1@42@@oe@16-12-2010
752091411@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
752091412@GENIA Treebank@formal@@1@S@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.@@@@1@37@@oe@16-12-2010
752091413@GENIA Treebank@formal@@1@S@These results imply that TK activity is not obligatory for CD14-mediated signal transduction to occur in response to LPS.@@@@1@20@@oe@16-12-2010
752225701@GENIA Treebank@formal@@1@S@Regulation of CD14 expression during monocytic differentiation induced with 1 alpha,25-dihydroxyvitamin D3.@@@@1@13@@oe@16-12-2010
752225702@GENIA Treebank@formal@@1@S@CD14, a monocyte/macrophage receptor for the complex of LPS and LPS binding protein, is a differentiation marker for the monocyte/macrophage lineage.@@@@1@24@@oe@16-12-2010
752225703@GENIA Treebank@formal@@1@S@We have analyzed the regulation of CD14 expression during 1 alpha,25-dihydroxyvitamin D3 (VitD3)-induced monocytic differentiation.@@@@1@19@@oe@16-12-2010
752225704@GENIA Treebank@formal@@1@S@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.@@@@1@44@@oe@16-12-2010
752225705@GENIA Treebank@formal@@1@S@We have recently cloned the CD14 5' upstream sequence and demonstrated its tissue-specific promoter activity.@@@@1@16@@oe@16-12-2010
752225706@GENIA Treebank@formal@@1@S@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.@@@@1@46@@oe@16-12-2010
752225707@GENIA Treebank@formal@@1@S@This region contains two binding sites for the Sp1 transcription factor.@@@@1@12@@oe@16-12-2010
752225708@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
752225709@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
752225710@GENIA Treebank@formal@@1@S@These data demonstrate that VitD3 induces CD14 indirectly through some intermediary factor, and suggest a critical role for Sp1 in this process.@@@@1@24@@oe@16-12-2010
752230401@GENIA Treebank@formal@@1@S@Calcium signalling in T cells stimulated by a cyclophilin B-binding protein.@@@@1@12@@oe@16-12-2010
752230402@GENIA Treebank@formal@@1@S@The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor (TCR) that normally leads to T-cell activation.@@@@1@23@@oe@16-12-2010
752230403@GENIA Treebank@formal@@1@S@When bound to cyclophilin, cyclosporin A binds and inactivates the key signalling intermediate calcineurin.@@@@1@16@@oe@16-12-2010
752230404@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
752230405@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
752230406@GENIA Treebank@formal@@1@S@This protein, termed calcium-signal modulating cyclophilin ligand (CAML), acts downstream of the TCR and upstream of calcineurin by causing an influx of calcium.@@@@1@28@@oe@16-12-2010
752230407@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
752254801@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
752254802@GENIA Treebank@formal@@1@S@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).@@@@1@31@@oe@16-12-2010
752254803@GENIA Treebank@formal@@1@S@The antioxidant pyrrolidine dithiocarbamate (PDTC) specifically inhibits activation of nuclear factor-kappa B (NF-kappa B).@@@@1@19@@oe@16-12-2010
752254804@GENIA Treebank@formal@@1@S@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).@@@@1@45@@oe@16-12-2010
752254805@GENIA Treebank@formal@@1@S@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.@@@@1@46@@oe@16-12-2010
752254806@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
752254807@GENIA Treebank@formal@@1@S@Since HUVECs released superoxide anions in response to TNF, and H2O2 induces VCAM-1, PDTC may act as a radical scavenger.@@@@1@23@@oe@16-12-2010
752254808@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
752254809@GENIA Treebank@formal@@1@S@PDTC, apocynin, or SKF525a decreased adhesion of monocytic U937 cells to TNF-treated HUVECs (by 75% at 100 mumol/L PDTC).@@@@1@25@@oe@16-12-2010
752254810@GENIA Treebank@formal@@1@S@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.@@@@1@24@@oe@16-12-2010
752254811@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010
752350701@GENIA Treebank@formal@@1@S@Inducible binding to the c-fos serum response element during T cell activation is regulated by a phosphotyrosine-containing protein.@@@@1@19@@oe@16-12-2010
752350702@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
752350703@GENIA Treebank@formal@@1@S@Fos expression may be a pivotal event in converting ligand-receptor interactions at the membrane into functional modulation of cell phenotype.@@@@1@21@@oe@16-12-2010
752350704@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
752350705@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
752350706@GENIA Treebank@formal@@1@S@Band A contains the serum response factor plus additional factor(s).@@@@1@14@@oe@16-12-2010
752350707@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
752350708@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
752350709@GENIA Treebank@formal@@1@S@The phosphorylated tyrosine residue itself is important for the protein-protein interaction.@@@@1@12@@oe@16-12-2010
752451901@GENIA Treebank@formal@@1@S@MHC class II signaling in B-cell activation [see comments]@@@@1@11@@oe@16-12-2010
752451902@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
752451903@GENIA Treebank@formal@@1@S@These signals contribute to the expression of co-stimulatory activity by APCs and have important consequences for cell effector function.@@@@1@20@@oe@16-12-2010
752451904@GENIA Treebank@formal@@1@S@MHC class II molecules also serve as receptors for B-cell stimulation by microbial superantigens.@@@@1@15@@oe@16-12-2010
752451905@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
752476201@GENIA Treebank@formal@@1@S@Steel factor affects SCL expression during normal erythroid differentiation.@@@@1@10@@oe@16-12-2010
752476202@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
752476203@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
752476204@GENIA Treebank@formal@@1@S@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.@@@@1@41@@oe@16-12-2010
752476205@GENIA Treebank@formal@@1@S@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.@@@@1@33@@oe@16-12-2010
752476206@GENIA Treebank@formal@@1@S@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.@@@@1@33@@oe@16-12-2010
752476207@GENIA Treebank@formal@@1@S@The role of SCL in Steel factor-induced erythroid proliferation was then examined.@@@@1@13@@oe@16-12-2010
752476208@GENIA Treebank@formal@@1@S@In BFU-E-derived colonies cultured with Steel factor, colony size was significantly increased compared to control.@@@@1@17@@oe@16-12-2010
752476209@GENIA Treebank@formal@@1@S@In day 7 and day 10 erythroid precursors cultured with Steel factor, SCL protein was increased significantly compared to control.@@@@1@22@@oe@16-12-2010
752476210@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
752476211@GENIA Treebank@formal@@1@S@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.@@@@1@42@@oe@16-12-2010
752570101@GENIA Treebank@formal@@1@S@Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B.@@@@1@11@@oe@16-12-2010
752570102@GENIA Treebank@formal@@1@S@The B cell-associated surface molecule CD40 functions to regulate B cell responses.@@@@1@13@@oe@16-12-2010
752570103@GENIA Treebank@formal@@1@S@Cross-linking CD40 on B cells can lead to homotypic cell adhesion, IL-6 production, and, in combination with cytokines, to Ig isotype switching.@@@@1@27@@oe@16-12-2010
752570104@GENIA Treebank@formal@@1@S@Tyrosine kinase activity is increased shortly after engagement of this receptor.@@@@1@12@@oe@16-12-2010
752570105@GENIA Treebank@formal@@1@S@Little is known about how the very early events induced by CD40 cross-linking link to cellular responses.@@@@1@18@@oe@16-12-2010
752570106@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
752570107@GENIA Treebank@formal@@1@S@The activation is rapid and is mediated through a tyrosine kinase-dependent pathway.@@@@1@13@@oe@16-12-2010
752570108@GENIA Treebank@formal@@1@S@The complexes detected in electrophoretic mobility shift assays contain p50, p65 (RelA), c-Rel, and most likely other components.@@@@1@24@@oe@16-12-2010
752570109@GENIA Treebank@formal@@1@S@By using transient transfection assays, we found that cross-linking CD40 supports NF-kappa B-dependent gene expression.@@@@1@17@@oe@16-12-2010
752570110@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
752639801@GENIA Treebank@formal@@1@S@Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B signal transduction pathway.@@@@1@14@@oe@16-12-2010
752639802@GENIA Treebank@formal@@1@S@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.@@@@1@49@@oe@16-12-2010
752639803@GENIA Treebank@formal@@1@S@These initial pathways culminate in a common pathway through which all of the stimulating agents ultimately signal NF-kappa B activation.@@@@1@21@@oe@16-12-2010
752639804@GENIA Treebank@formal@@1@S@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.@@@@1@45@@oe@16-12-2010
752639805@GENIA Treebank@formal@@1@S@We propose the common pathway as the simplest way of accounting for the common requirements and properties of the signaling pathway.@@@@1@22@@oe@16-12-2010
752639806@GENIA Treebank@formal@@1@S@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 don'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.@@@@1@75@@oe@16-12-2010
752639807@GENIA Treebank@formal@@1@S@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.@@@@1@68@@oe@16-12-2010
752866801@GENIA Treebank@formal@@1@S@Interleukin-2 induces tyrosine phosphorylation and nuclear translocation of stat3 in human T lymphocytes.@@@@1@14@@oe@16-12-2010
752866802@GENIA Treebank@formal@@1@S@An early biochemical event associated with T cell activation through the interleukin-2 receptor (IL-2R) is tyrosine phosphorylation of several intracellular substrates.@@@@1@24@@oe@16-12-2010
752866803@GENIA Treebank@formal@@1@S@The exact mechanism by which IL-2 regulates transcription of different genes is presently unknown.@@@@1@15@@oe@16-12-2010
752866804@GENIA Treebank@formal@@1@S@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.@@@@1@38@@oe@16-12-2010
752866805@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
752866806@GENIA Treebank@formal@@1@S@Apart from stat3, another cytoplasmic protein was tyrosine phosphorylated and subsequently translocated to the nucleus in response to IL-2.@@@@1@21@@oe@16-12-2010
752866807@GENIA Treebank@formal@@1@S@This protein had an apparent molecular mass of 84 kDa and was not recognized by stat3 or stat1 mAb or antisera.@@@@1@22@@oe@16-12-2010
752866808@GENIA Treebank@formal@@1@S@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.@@@@1@33@@oe@16-12-2010
752866809@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
753023901@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
753023902@GENIA Treebank@formal@@1@S@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.@@@@1@40@@oe@16-12-2010
753023903@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
753023904@GENIA Treebank@formal@@1@S@The response of LFA-3 to TaxI induction was, on the other hand, relatively slow and weak, and might be indirect.@@@@1@24@@oe@16-12-2010
753023905@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
753023906@GENIA Treebank@formal@@1@S@The mechanism of down-regulation of ICAM-I or LFA-I in 4 ATL cell lines was next examined.@@@@1@17@@oe@16-12-2010
753023907@GENIA Treebank@formal@@1@S@ICAM-I mRNA was quite low in MT-I, but no genomic changes were found.@@@@1@15@@oe@16-12-2010
753023908@GENIA Treebank@formal@@1@S@The CAT reporter with the ICAM-I promoter was inactive in MT-I.@@@@1@12@@oe@16-12-2010
753023909@GENIA Treebank@formal@@1@S@Finally, combined treatment of MT-I with 5-azacytidine and IFN-gamma induced re-expression of ICAM-I.@@@@1@15@@oe@16-12-2010
753023910@GENIA Treebank@formal@@1@S@Collectively, (a) transcriptional factor(s) necessary for expression of ICAM-I gene may be repressed in MT-I through DNA methylation.@@@@1@25@@oe@16-12-2010
753023911@GENIA Treebank@formal@@1@S@Three other ATL cell lines (TL-OmI, H582, HuT102) were found to have little mRNA for the LFA-I beta chain (CD18).@@@@1@27@@oe@16-12-2010
753023912@GENIA Treebank@formal@@1@S@H582 and HuT102 were also negative for the LFA-I alpha chain (CDIIa) mRNA.@@@@1@16@@oe@16-12-2010
753023913@GENIA Treebank@formal@@1@S@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.@@@@1@40@@oe@16-12-2010
753228201@GENIA Treebank@formal@@1@S@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.@@@@1@24@@oe@16-12-2010
753228202@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
753228203@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
753228204@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
753228205@GENIA Treebank@formal@@1@S@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.@@@@1@53@@oe@16-12-2010
753228206@GENIA Treebank@formal@@1@S@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.@@@@1@45@@oe@16-12-2010
753228207@GENIA Treebank@formal@@1@S@The adherence-dependent increase in I kappa B alpha/MAD-3 mRNA levels was also not a consequence of mRNA stabilization events.@@@@1@20@@oe@16-12-2010
753228208@GENIA Treebank@formal@@1@S@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.@@@@1@43@@oe@16-12-2010
753228209@GENIA Treebank@formal@@1@S@Taken together, our data suggest that two interactive mechanisms regulate monocytic I kappa B alpha/MAD-3 mRNA levels.@@@@1@19@@oe@16-12-2010
753228210@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
753228211@GENIA Treebank@formal@@1@S@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.@@@@1@45@@oe@16-12-2010
753429301@GENIA Treebank@formal@@1@S@E2F-1 and a cyclin-like DNA repair enzyme, uracil-DNA glycosylase, provide evidence for an autoregulatory mechanism for transcription.@@@@1@20@@oe@16-12-2010
753429302@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
753429303@GENIA Treebank@formal@@1@S@We demonstrate, through the deletion of the human UDG promoter sequences, that expression of E2F-1 activates the UDG promoter through several E2F sites.@@@@1@26@@oe@16-12-2010
753429304@GENIA Treebank@formal@@1@S@The major putative downstream site for E2F, located in the first exon, serves as a target for E2F-1/DP1 complex binding in vitro.@@@@1@25@@oe@16-12-2010
753429305@GENIA Treebank@formal@@1@S@We also provide evidence for the functional relationship between the cyclin-like UDG gene product and E2F.@@@@1@17@@oe@16-12-2010
753429306@GENIA Treebank@formal@@1@S@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.@@@@1@24@@oe@16-12-2010
753429307@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
753429308@GENIA Treebank@formal@@1@S@This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription, likely through E2F.@@@@1@22@@oe@16-12-2010
753429309@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
753466301@GENIA Treebank@formal@@1@S@Aspirin inhibits nuclear factor-kappa B mobilization and monocyte adhesion in stimulated human endothelial cells.@@@@1@15@@oe@16-12-2010
753466302@GENIA Treebank@formal@@1@S@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).@@@@1@37@@oe@16-12-2010
753466303@GENIA Treebank@formal@@1@S@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).@@@@1@44@@oe@16-12-2010
753466304@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
753466305@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
753466306@GENIA Treebank@formal@@1@S@Aspirin appeared to prevent VCAM-1 transcription, since it dose-dependently inhibited induction of VCAM-1 mRNA by TNF.@@@@1@18@@oe@16-12-2010
753466307@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
753466308@GENIA Treebank@formal@@1@S@These effects of aspirin were not related to the inhibition of cyclooxygenase activity, since indomethacin was ineffective.@@@@1@19@@oe@16-12-2010
753466309@GENIA Treebank@formal@@1@S@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.@@@@1@40@@oe@16-12-2010
753768701@GENIA Treebank@formal@@1@S@Growth regulation and cellular changes during differentiation of human prostatic cancer LNCaP cells as induced by T lymphocyte-conditioned medium.@@@@1@21@@oe@16-12-2010
753768702@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
753768703@GENIA Treebank@formal@@1@S@Addition of CM caused a greater than 70% reduction of cell proliferation by cell counting and cell cycle.@@@@1@20@@oe@16-12-2010
753768704@GENIA Treebank@formal@@1@S@These cells showed G1 phase arrest and the clonogenicity was reduced.@@@@1@12@@oe@16-12-2010
753768705@GENIA Treebank@formal@@1@S@The growth-modulating effect was dose-dependent and not due to cell lysis or apoptosis.@@@@1@14@@oe@16-12-2010
753768706@GENIA Treebank@formal@@1@S@The binding of androgen to androgen receptor on these cells showed approximately 50% reduction, underlining a proliferation reduction mechanism.@@@@1@22@@oe@16-12-2010
753768707@GENIA Treebank@formal@@1@S@The prostate-specific antigen (PSA) was downregulated to approximately 75% during the process.@@@@1@16@@oe@16-12-2010
753768708@GENIA Treebank@formal@@1@S@Cell morphology showed dendritic processes extending from cytoplasm and other neuroendocrine cell characteristics.@@@@1@14@@oe@16-12-2010
753768709@GENIA Treebank@formal@@1@S@The expression of several cytoskeleton and intracellular proteins increased as determined by immunostaining on slides and by ELISA procedures.@@@@1@20@@oe@16-12-2010
753768710@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
753768711@GENIA Treebank@formal@@1@S@From these cellular changes, we can infer that the cell growth was modulated along with induction of terminal differentiation.@@@@1@21@@oe@16-12-2010
753768712@GENIA Treebank@formal@@1@S@Activated T cells were demonstrated to be important in providing the modulating activity.@@@@1@14@@oe@16-12-2010
753768713@GENIA Treebank@formal@@1@S@This growth modulator was semipurified and had an estimated molecular weight 13,000 to 24,000 Da.@@@@1@16@@oe@16-12-2010
753768714@GENIA Treebank@formal@@1@S@The activity was determined to be distinct from TGF, TNF, and some commonly known lymphokines.@@@@1@18@@oe@16-12-2010
753768715@GENIA Treebank@formal@@1@S@The interaction between lymphoid and prostatic cells in growth and development is described.@@@@1@14@@oe@16-12-2010
753776201@GENIA Treebank@formal@@1@S@Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion.@@@@1@14@@oe@16-12-2010
753776202@GENIA Treebank@formal@@1@S@Signal integration and NF-kappa B translocation [see comments]@@@@1@10@@oe@16-12-2010
753776203@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
753776204@GENIA Treebank@formal@@1@S@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.@@@@1@43@@oe@16-12-2010
753776205@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
753776206@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
753776207@GENIA Treebank@formal@@1@S@These results demonstrate that P-selectin, through its ligands on monocytes, may locally regulate cytokine secretion in inflamed tissues.@@@@1@21@@oe@16-12-2010
754057801@GENIA Treebank@formal@@1@S@Danazol decreases transcription of estrogen receptor gene in human monocytes.@@@@1@11@@oe@16-12-2010
754057802@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
754057803@GENIA Treebank@formal@@1@S@2. Danazol did not alter the degradation rate of ER mRNA in monocytes.@@@@1@14@@oe@16-12-2010
754057804@GENIA Treebank@formal@@1@S@3. Danazol decreased the transcription rate of ER gene to approximately 50% in monocytes in a run-on assay.@@@@1@20@@oe@16-12-2010
754057805@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
754094201@GENIA Treebank@formal@@1@S@Cross-linking of CD30 induces HIV expression in chronically infected T cells.@@@@1@12@@oe@16-12-2010
754094202@GENIA Treebank@formal@@1@S@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.@@@@1@43@@oe@16-12-2010
754094203@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
754094204@GENIA Treebank@formal@@1@S@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.@@@@1@23@@oe@16-12-2010
754094205@GENIA Treebank@formal@@1@S@Furthermore, cross-linking of CD30 leads to NF-kappa B activation and enhanced HIV transcription.@@@@1@15@@oe@16-12-2010
754094206@GENIA Treebank@formal@@1@S@Thus, CD30-CD30L interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of TNF.@@@@1@21@@oe@16-12-2010
754094207@GENIA Treebank@formal@@1@S@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.@@@@1@33@@oe@16-12-2010
754179401@GENIA Treebank@formal@@1@S@Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells.@@@@1@11@@oe@16-12-2010
754179402@GENIA Treebank@formal@@1@S@A possible signaling role for the Syk tyrosine kinase.@@@@1@10@@oe@16-12-2010
754179403@GENIA Treebank@formal@@1@S@Activation of cytoplasmic tyrosine kinases is an important aspect of signal transduction mediated by integrins.@@@@1@16@@oe@16-12-2010
754179404@GENIA Treebank@formal@@1@S@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.@@@@1@41@@oe@16-12-2010
754179405@GENIA Treebank@formal@@1@S@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.@@@@1@57@@oe@16-12-2010
754179406@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
754179407@GENIA Treebank@formal@@1@S@The components tyrosine phosphorylated subsequent to cell adhesion include paxillin, pp125FAK, and the SH2 domain containing tyrosine kinase Syk.@@@@1@22@@oe@16-12-2010
754179408@GENIA Treebank@formal@@1@S@In contrast, integrin ligation with antibodies induces tyrosine phosphorylation of Syk but not of FAK or paxillin.@@@@1@19@@oe@16-12-2010
754179409@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
754179410@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
754198701@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
754198702@GENIA Treebank@formal@@1@S@2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits murine and human B lymphocyte immunoglobulin production through an unknown mechanism.@@@@1@17@@oe@16-12-2010
754198703@GENIA Treebank@formal@@1@S@This study investigated the effect of TCDD on expression of the CD19 gene in a human B lymphocyte cell line.@@@@1@21@@oe@16-12-2010
754198704@GENIA Treebank@formal@@1@S@Northern blot analysis showed that TCDD treatment decreased steady state levels of CD19 mRNA by 67% in the IM-9 cell line.@@@@1@23@@oe@16-12-2010
754198705@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
754198706@GENIA Treebank@formal@@1@S@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.@@@@1@42@@oe@16-12-2010
754198707@GENIA Treebank@formal@@1@S@These results suggest that the AhR could interfere with BSAP-stimulated CD19 gene transcription by competition for a common DNA binding site.@@@@1@22@@oe@16-12-2010
754228601@GENIA Treebank@formal@@1@S@Nitric oxide decreases cytokine-induced endothelial activation.@@@@1@7@@oe@16-12-2010
754228602@GENIA Treebank@formal@@1@S@Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines.@@@@1@13@@oe@16-12-2010
754228603@GENIA Treebank@formal@@1@S@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).@@@@1@43@@oe@16-12-2010
754228604@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
754228605@GENIA Treebank@formal@@1@S@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.@@@@1@49@@oe@16-12-2010
754228606@GENIA Treebank@formal@@1@S@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).@@@@1@32@@oe@16-12-2010
754228607@GENIA Treebank@formal@@1@S@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.@@@@1@22@@oe@16-12-2010
754228608@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
754228609@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
754259101@GENIA Treebank@formal@@1@S@Distinct signaling properties identify functionally different CD4 epitopes.@@@@1@9@@oe@16-12-2010
754259102@GENIA Treebank@formal@@1@S@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.@@@@1@24@@oe@16-12-2010
754259103@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
754259104@GENIA Treebank@formal@@1@S@We demonstrate that CD4 triggering delivers signals capable of activating the NF-AT transcription factor which is required for interleukin-2 gene expression.@@@@1@22@@oe@16-12-2010
754259105@GENIA Treebank@formal@@1@S@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.@@@@1@43@@oe@16-12-2010
754259106@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
754259107@GENIA Treebank@formal@@1@S@The results identify functionally distinct epitopes on the CD4 coreceptor involved in activation of the Ras/protein kinase C and calcium pathways.@@@@1@22@@oe@16-12-2010
754307601@GENIA Treebank@formal@@1@S@Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein.@@@@1@15@@oe@16-12-2010
754307602@GENIA Treebank@formal@@1@S@Endothelial cells stimulated by LPS express E-selectin, which plays an important role in mediating neutrophil adhesion during inflammation.@@@@1@20@@oe@16-12-2010
754307603@GENIA Treebank@formal@@1@S@E-selectin is induced within 1-2 h, peaks at 4-6 h, and gradually returns to basal level by 24 h.@@@@1@22@@oe@16-12-2010
754307604@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
754307605@GENIA Treebank@formal@@1@S@Delayed administration of rBPI21 also affected LPS-mediated activation of the nuclear factor, NF-kappa B.@@@@1@16@@oe@16-12-2010
754307606@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
754307607@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
754311201@GENIA Treebank@formal@@1@S@Does thyroidectomy, radioactive iodine therapy, or antithyroid drug treatment alter reactivity of patients' T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases?@@@@1@28@@oe@16-12-2010
754311202@GENIA Treebank@formal@@1@S@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).@@@@1@58@@oe@16-12-2010
754311203@GENIA Treebank@formal@@1@S@Twenty subjects matched for age and sex without known thyroid disease served as controls.@@@@1@15@@oe@16-12-2010
754311204@GENIA Treebank@formal@@1@S@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.@@@@1@59@@oe@16-12-2010
754311205@GENIA Treebank@formal@@1@S@Reactivity to TSHR peptides before surgery was heterogeneous and spanned the entire extracellular domain.@@@@1@15@@oe@16-12-2010
754311206@GENIA Treebank@formal@@1@S@Six to 8 weeks after subtotal thyroidectomy, the number of patients' PBMC responding to any peptide and the average number of recognized peptides decreased.@@@@1@27@@oe@16-12-2010
754311207@GENIA Treebank@formal@@1@S@A further decrease in the T cell reactivity to TSHR peptides was observed 3-6 months after surgery.@@@@1@18@@oe@16-12-2010
754311208@GENIA Treebank@formal@@1@S@The responses of PBMC from Graves' patients before RAI therapy were less than those in the presurgical group.@@@@1@20@@oe@16-12-2010
754311209@GENIA Treebank@formal@@1@S@Six to 8 weeks after RAI therapy, the number of patients responding to any peptide and the average number of recognized peptides increased.@@@@1@25@@oe@16-12-2010
754311210@GENIA Treebank@formal@@1@S@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.@@@@1@33@@oe@16-12-2010
754311211@GENIA Treebank@formal@@1@S@Responses of PBMC from patients with GD, maintained euthyroid on ATD, were lower than those before surgery or RAI therapy.@@@@1@23@@oe@16-12-2010
754311212@GENIA Treebank@formal@@1@S@The reactivity of T cell lines in different groups reflected a pattern similar to PBMC after treatment.@@@@1@18@@oe@16-12-2010
754311213@GENIA Treebank@formal@@1@S@TSHR antibody and microsomal antibody levels decreased after surgery, but increased after RAI therapy.@@@@1@16@@oe@16-12-2010
754311214@GENIA Treebank@formal@@1@S@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.@@@@1@40@@oe@16-12-2010
754311215@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
754311216@GENIA Treebank@formal@@1@S@The increased T cell response after RAI therapy is probably epitope specific, rather than a response to the whole TSHR molecule.@@@@1@23@@oe@16-12-2010
754311217@GENIA Treebank@formal@@1@S@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.@@@@1@39@@oe@16-12-2010
754351201@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
754351202@GENIA Treebank@formal@@1@S@IL-10 affects monocytes and T cells by driving the progression of immune responsiveness such that Th2 lymphocyte-mediated effects predominate.@@@@1@20@@oe@16-12-2010
754351203@GENIA Treebank@formal@@1@S@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 heterodimers varies between the two cell types.@@@@1@50@@oe@16-12-2010
754351204@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
754351205@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
754351206@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
754351501@GENIA Treebank@formal@@1@S@Costimulation of human CD4+ T cells with LFA-3 and B7 induce distinct effects on AP-1 and NF-kappa B transcription factors.@@@@1@21@@oe@16-12-2010
754351502@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
754351503@GENIA Treebank@formal@@1@S@We now demonstrate that B7, but not LFA-3, strongly costimulated IL-2 transcription and mRNA expression in CD4+ T cells.@@@@1@22@@oe@16-12-2010
754351504@GENIA Treebank@formal@@1@S@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.@@@@1@23@@oe@16-12-2010
754351505@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
754351506@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
754351507@GENIA Treebank@formal@@1@S@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.@@@@1@21@@oe@16-12-2010
754351508@GENIA Treebank@formal@@1@S@The level of Oct-1 binding proteins remained similar in all samples.@@@@1@12@@oe@16-12-2010
754351509@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
754351510@GENIA Treebank@formal@@1@S@The AP-1 binding proteins contained c-Jun, Jun-D, and Fra-1, but marginal amounts of Jun-B and c-Fos.@@@@1@20@@oe@16-12-2010
754351511@GENIA Treebank@formal@@1@S@Our results indicate distinct effects of B7 and LFA-3 costimulation on the activity of AP-1 and NF-kappa B.@@@@1@19@@oe@16-12-2010
754351512@GENIA Treebank@formal@@1@S@These may partly account for the differential effects of B7 and LFA-3 costimulation on IL-2 expression.@@@@1@17@@oe@16-12-2010
754400101@GENIA Treebank@formal@@1@S@Interleukin 2 signaling involves the phosphorylation of Stat proteins.@@@@1@10@@oe@16-12-2010
754400102@GENIA Treebank@formal@@1@S@One of the most important cytokines involved in immune response regulation is interleukin 2 (IL-2), a potent activator of the proliferation and function of T lymphocytes and natural killer cells.@@@@1@34@@oe@16-12-2010
754400103@GENIA Treebank@formal@@1@S@The mechanisms by which the effects of IL-2 are propagated within cells are not understood.@@@@1@16@@oe@16-12-2010
754400104@GENIA Treebank@formal@@1@S@While the binding of IL-2 to its receptor was recently shown to lead to the activation of two kinases, Jak-1 and Jak-3, subsequent steps in the signaling pathway to the nucleus that lead to the activation of specific genes had not been characterized.@@@@1@46@@oe@16-12-2010
754400105@GENIA Treebank@formal@@1@S@Since many cytokines that activate Jak kinases also lead to the tyrosine phosphorylation and activation of members of the Stat family of transcription factors, the ability of IL-2 to trigger Stat phosphorylation was examined.@@@@1@36@@oe@16-12-2010
754400106@GENIA Treebank@formal@@1@S@Exposure of activated human T lymphocytes or of a natural killer cell line (NKL) to IL-2 leads to the phosphorylation of Stat1 alpha, Stat1 beta, and Stat3, as well as of two Stat-related proteins, p94 and p95.@@@@1@44@@oe@16-12-2010
754400107@GENIA Treebank@formal@@1@S@p94 and p95 share homology with Stat1 at the phosphorylation site and in the Src homology 2 (SH2) domain, but otherwise are immunologically distinct from Stat1.@@@@1@30@@oe@16-12-2010
754400108@GENIA Treebank@formal@@1@S@These Stat proteins were found to translocate to the nucleus and to bind to a specific DNA sequence.@@@@1@19@@oe@16-12-2010
754400109@GENIA Treebank@formal@@1@S@These findings suggest a mechanism by which IL-2 binding to its receptor may activate specific genes involved in immune cell function.@@@@1@22@@oe@16-12-2010
754546701@GENIA Treebank@formal@@1@S@Regulation of granulocyte-macrophage colony-stimulating factor and E-selectin expression in endothelial cells by cyclosporin A and the T-cell transcription factor NFAT.@@@@1@21@@oe@16-12-2010
754546702@GENIA Treebank@formal@@1@S@Nuclear factor of activated T cells (NFAT) was originally described as a T-cell-specific transcription factor athat supported the activation of cytokine gene expression and mediated the immunoregulatory effects of cyclosporin A (CsA).@@@@1@37@@oe@16-12-2010
754546703@GENIA Treebank@formal@@1@S@As we observed that activated endothelial cells also expressed NFAT, we tested the antiinflammatory properties of CsA in endothelial cells.@@@@1@22@@oe@16-12-2010
754546704@GENIA Treebank@formal@@1@S@Significantly, CsA completely suppressed the induction of NFAT in endothelial cells and inhibited the activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene regulatory elements that use NFAT by 60%.@@@@1@33@@oe@16-12-2010
754546705@GENIA Treebank@formal@@1@S@CsA similarly mediated a reduction of up to 65% in GM-CSF mRNA and protein expression in activated endothelial cells.@@@@1@21@@oe@16-12-2010
754546706@GENIA Treebank@formal@@1@S@CsA also suppressed E-selectin, but not vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells, even though the E-selectin promoter is activated by NF-kappa B rather than NFAT.@@@@1@33@@oe@16-12-2010
754546707@GENIA Treebank@formal@@1@S@Hence, induction of cell surface expression of this leukocyte adhesion molecule by tumor necrosis factor (TNF)-alpha was reduced by 40% in the presence of CsA, and this was reflected by a 29% decrease in neutrophil adhesion.@@@@1@44@@oe@16-12-2010
754546708@GENIA Treebank@formal@@1@S@The effects of CsA on endothelial cells were also detected at the chromatin structure level, as DNasel hypersensitive sites within both the GM-CSF enhancer and the E-selectin promoter were suppressed by CsA.@@@@1@34@@oe@16-12-2010
754546709@GENIA Treebank@formal@@1@S@This represents the first report of NFAT in endothelial cells and suggests mechanisms by which CsA could function as an antiinflammatory agent.@@@@1@23@@oe@16-12-2010
754568001@GENIA Treebank@formal@@1@S@Direct demonstration of NFATp dephosphorylation and nuclear localization in activated HT-2 cells using a specific NFATp polyclonal antibody.@@@@1@19@@oe@16-12-2010
754568002@GENIA Treebank@formal@@1@S@Nuclear factor of activated T cells (NFAT) regulates transcription of a number of cytokine genes, and NFAT DNA binding activity is stimulated following T cell activation.@@@@1@30@@oe@16-12-2010
754568003@GENIA Treebank@formal@@1@S@Several lines of evidence have suggested that NFAT is a substrate for calcineurin, a serine/threonine phosphatase.@@@@1@18@@oe@16-12-2010
754568004@GENIA Treebank@formal@@1@S@Using a polyclonal antibody to murine NFATp, Western blot analysis of various mouse tissues demonstrated that the 110-130-kDa NFATp protein was highly expressed in thymus and spleen.@@@@1@29@@oe@16-12-2010
754568005@GENIA Treebank@formal@@1@S@Treatment of immunoprecipitated NFATp from untreated HT-2 cells with calcineurin resulted in the dephosphorylation of NFATp, demonstrating that NFATp is an in vitro substrate for calcineurin.@@@@1@28@@oe@16-12-2010
754568006@GENIA Treebank@formal@@1@S@NFATp immunoprecipitated from 32P-labeled HT-2 cells migrated as an approximately 120-kDa protein that was localized to the cytosol of the cells.@@@@1@22@@oe@16-12-2010
754568007@GENIA Treebank@formal@@1@S@Treatment of the cells with ionomycin resulted in a decrease in the molecular weight of NFATp and a loss of 32P, consistent with NFATp dephosphorylation.@@@@1@27@@oe@16-12-2010
754568008@GENIA Treebank@formal@@1@S@The dephosphorylation of NFATp was accompanied by localization of the protein to the nuclear fraction.@@@@1@16@@oe@16-12-2010
754568009@GENIA Treebank@formal@@1@S@Both of these events were blocked by preincubation of the cells with FK506, a calcineurin inhibitor, consistent with the hypothesis that NFATp is a calcineurin substrate in cells.@@@@1@31@@oe@16-12-2010
755431501@GENIA Treebank@formal@@1@S@Temperature-induced down-regulation of the glucocorticoid receptor in peripheral blood mononuclear leucocyte in patients with sepsis or septic shock.@@@@1@19@@oe@16-12-2010
755431502@GENIA Treebank@formal@@1@S@OBJECTIVE: Activation of the hypothalamic-pituitary-adrenal axis is of vital importance during critical illness.@@@@1@15@@oe@16-12-2010
755431503@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
755431504@GENIA Treebank@formal@@1@S@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.@@@@1@48@@oe@16-12-2010
755431505@GENIA Treebank@formal@@1@S@SUBJECTS: Fifteen patients (age 25-79) with sepsis or septic shock who were admitted to an intensive care unit were studied.@@@@1@24@@oe@16-12-2010
755431506@GENIA Treebank@formal@@1@S@The control group consisted of 24 healthy laboratory employees.@@@@1@10@@oe@16-12-2010
755431507@GENIA Treebank@formal@@1@S@MEASUREMENTS: The binding capacity and affinity of the glucocorticoid receptors were measured and compared to clinical data and the plasma cortisol concentrations.@@@@1@24@@oe@16-12-2010
755431508@GENIA Treebank@formal@@1@S@RESULTS: Hypercortisolaemia, in vitro, resulted in a decreased affinity and a decreased binding capacity of the glucocorticoid receptor.@@@@1@22@@oe@16-12-2010
755431509@GENIA Treebank@formal@@1@S@In vitro, hyperthermia as well as variations in the cellular composition did not influence the glucocorticoid receptor.@@@@1@19@@oe@16-12-2010
755431510@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
755431511@GENIA Treebank@formal@@1@S@However, a decreased affinity of the glucocorticoid receptor was observed.@@@@1@12@@oe@16-12-2010
755431512@GENIA Treebank@formal@@1@S@There was a weak but significant negative correlation between body temperature and the number of glucocorticoid receptors in the patient group.@@@@1@22@@oe@16-12-2010
755431513@GENIA Treebank@formal@@1@S@There was no relation between circulating cortisol concentrations and glucocorticoid receptor affinity and number.@@@@1@15@@oe@16-12-2010
755431514@GENIA Treebank@formal@@1@S@CONCLUSIONS: There is no obvious regulation of the number of glucocorticoid receptors by plasma cortisol concentrations in vivo.@@@@1@20@@oe@16-12-2010
755431515@GENIA Treebank@formal@@1@S@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.@@@@1@47@@oe@16-12-2010
755438901@GENIA Treebank@formal@@1@S@Signalling via CD28 of human naive neonatal T lymphocytes.@@@@1@10@@oe@16-12-2010
755438902@GENIA Treebank@formal@@1@S@Accessory molecules play a crucial role in the development of the T cell response to antigenic challenge.@@@@1@18@@oe@16-12-2010
755438903@GENIA Treebank@formal@@1@S@We have examined the role of CD28 in modulating the 'naive' neonatal T cell response to anti-CD2-mediated activation.@@@@1@21@@oe@16-12-2010
755438904@GENIA Treebank@formal@@1@S@To compare the role of CD28, neonatal and adult T cells were stimulated with a pair of mitogenic anti-CD2 antibodies in the presence or absence of anti-CD28 MoAb.@@@@1@30@@oe@16-12-2010
755438905@GENIA Treebank@formal@@1@S@With anti-CD2 alone, neonatal T cells proliferated slightly but produced no detectable IL-2, whereas adult T cells proliferated vigorously, with significant IL-2 production.@@@@1@27@@oe@16-12-2010
755438906@GENIA Treebank@formal@@1@S@Costimulation with anti-CD28 MoAb greatly enhanced the proliferative response of neonatal T cells to levels equivalent to those of adult T cells, whereas adult T cells showed only slight increases.@@@@1@32@@oe@16-12-2010
755438907@GENIA Treebank@formal@@1@S@Although IL-2 secretion was increased in the presence of anti-CD28 MoAb, neonatal T cell IL-2 production remained lower than in adults.@@@@1@23@@oe@16-12-2010
755438908@GENIA Treebank@formal@@1@S@In contrast, enhancement of IL-2 mRNA expression in neonates was similar to adult levels.@@@@1@16@@oe@16-12-2010
755438909@GENIA Treebank@formal@@1@S@Anti-CD28 MoAb costimulation increased NF kappa B levels in neonates, albeit to levels lower than that of adults.@@@@1@20@@oe@16-12-2010
755438910@GENIA Treebank@formal@@1@S@The cellular mechanism governing the diminished proliferative response of neonatal T lymphocytes to anti-CD2 may therefore be due to decreased NF kappa B induction, reduced IL-2 mRNA expression and deficient IL-2 production.@@@@1@34@@oe@16-12-2010
755438911@GENIA Treebank@formal@@1@S@Although anti-CD28 MoAb costimulation enhances all of the above signals, NF kappa B and IL-2 levels remain lower than in adults, suggesting the need for further activation requirements in the neonate.@@@@1@34@@oe@16-12-2010
755988101@GENIA Treebank@formal@@1@S@Evidence for normal vitamin D receptor messenger ribonucleic acid and genotype in absorptive hypercalciuria.@@@@1@15@@oe@16-12-2010
755988102@GENIA Treebank@formal@@1@S@Absorptive hypercalciuria (a stone-forming condition) is characterized by gut hyperabsorption of calcium, hypercalciuria, and reduced bone density.@@@@1@22@@oe@16-12-2010
755988103@GENIA Treebank@formal@@1@S@Inasmuch as these features implicate enhanced calcitriol action in gut and bone, we analyzed the vitamin D receptor (VDR) gene to ascertain whether an abnormality of this gene marks patients with intestinal hyperabsorption of calcium.@@@@1@39@@oe@16-12-2010
755988104@GENIA Treebank@formal@@1@S@We have compared the frequency of a restriction fragment length polymorphism (Bsm I) associated with different alleles of the VDR gene in a group of 33 well characterized absorptive hypercalciuric patients and a group of 36 normal race- and age-matched control subjects.@@@@1@45@@oe@16-12-2010
755988105@GENIA Treebank@formal@@1@S@There was no difference between the distribution of the VDR alleles in the patient population when compared with the normal population.@@@@1@22@@oe@16-12-2010
755988106@GENIA Treebank@formal@@1@S@The coding region of VDR messenger RNA was also normal, as determined by both DNA sequence analysis and chemical mismatch cleavage analysis of copy DNA from 11 index absorptive hypercalciuric patients.@@@@1@33@@oe@16-12-2010
755988107@GENIA Treebank@formal@@1@S@On the basis of these results, we propose that the enhanced intestinal calcium absorption invariably seen in absorptive hypercalciuria and attendant symptoms of this disorder are not attributable to mutations of the VDR and are not linked to a common VDR genotype.@@@@1@44@@oe@16-12-2010
755988601@GENIA Treebank@formal@@1@S@Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated human T lymphocytes.@@@@1@14@@oe@16-12-2010
755988602@GENIA Treebank@formal@@1@S@Although evidence indicates that dehydroepiandrosterone (DHEA) exerts direct physiological effects, its mechanism of action remains unknown.@@@@1@20@@oe@16-12-2010
755988603@GENIA Treebank@formal@@1@S@DHEA binding sites were examined using a whole-cell binding assay in a human T lymphoid cell line, PEER, revealing that a single class of high-affinity binding sites for DHEA (dissociation constant = 7.4 +/- 0.53 nmol/L, mean +/- SE, n = 4) was greatly increased when treated with DHEA, phorbol-12-myristate-13-acetate, and the Ca2+ ionophore A23187.@@@@1@64@@oe@16-12-2010
755988604@GENIA Treebank@formal@@1@S@Bound [3H]DHEA was displaced sensitively by DHEA and secondarily by dihydrotestosterone, but not effectively by other steroids, including DHEA sulfate.@@@@1@23@@oe@16-12-2010
755988605@GENIA Treebank@formal@@1@S@These results not only indicate the existence of a DHEA receptor, but also suggest that T cells become susceptible to regulation by DHEA during the process of signal-induced activation.@@@@1@31@@oe@16-12-2010
756541501@GENIA Treebank@formal@@1@S@Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-kappa B/Rel transcription factors.@@@@1@21@@oe@16-12-2010
756541502@GENIA Treebank@formal@@1@S@CD4+ macrophages in tissues such as lung, skin, and lymph nodes, promyelocytic cells in bone marrow, and peripheral blood monocytes serve as important targets and reservoirs for human immunodeficiency virus type 1 (HIV-1) replication.@@@@1@41@@oe@16-12-2010
756541503@GENIA Treebank@formal@@1@S@HIV-1-infected myeloid cells are often diminished in their ability to participate in chemotaxis, phagocytosis, and intracellular killing.@@@@1@20@@oe@16-12-2010
756541504@GENIA Treebank@formal@@1@S@HIV-1 infection of myeloid cells can lead to the expression of surface receptors associated with cellular activation and/or differentiation that increase the responsiveness of these cells to cytokines secreted by neighboring cells as well as to bacteria or other pathogens.@@@@1@41@@oe@16-12-2010
756541505@GENIA Treebank@formal@@1@S@Enhancement of HIV-1 replication is related in part to increased DNA-binding activity of cellular transcription factors such as NF-kappa B.@@@@1@21@@oe@16-12-2010
756541506@GENIA Treebank@formal@@1@S@NF-kappa B binds to the HIV-1 enhancer region of the long terminal repeat and contributes to the inducibility of HIV-1 gene expression in response to multiple activating agents.@@@@1@29@@oe@16-12-2010
756541507@GENIA Treebank@formal@@1@S@Phosphorylation and degradation of the cytoplasmic inhibitor I kappa B alpha are crucial regulatory events in the activation of NF-kappa B DNA-binding activity.@@@@1@24@@oe@16-12-2010
756541508@GENIA Treebank@formal@@1@S@Both N- and C-terminal residues of I kappa B alpha are required for inducer-mediated degradation.@@@@1@16@@oe@16-12-2010
756541509@GENIA Treebank@formal@@1@S@Chronic HIV-1 infection of myeloid cells leads to constitutive NF-kappa B DNA-binding activity and provides an intranuclear environment capable of perpetuating HIV-1 replication.@@@@1@24@@oe@16-12-2010
756541510@GENIA Treebank@formal@@1@S@Increased intracellular stores of latent NF-kappa B may also result in rapid inducibility of NF-kappa B-dependent cytokine gene expression.@@@@1@20@@oe@16-12-2010
756541511@GENIA Treebank@formal@@1@S@In response to secondary pathogenic infections or antigenic challenge, cytokine gene expression is rapidly induced, enhanced, and sustained over prolonged periods in HIV-1-infected myeloid cells compared with uninfected cells.@@@@1@33@@oe@16-12-2010
756541512@GENIA Treebank@formal@@1@S@Elevated levels of several inflammatory cytokines have been detected in the sera of HIV-1-infected individuals.@@@@1@16@@oe@16-12-2010
756541513@GENIA Treebank@formal@@1@S@Secretion of myeloid cell-derived cytokines may both increase virus production and contribute to AIDS-associated disorders.@@@@1@16@@oe@16-12-2010
756567501@GENIA Treebank@formal@@1@S@The DNA-binding properties of two heat shock factors, HSF1 and HSF3, are induced in the avian erythroblast cell line HD6.@@@@1@23@@oe@16-12-2010
756567502@GENIA Treebank@formal@@1@S@Avian cells express three heat shock transcription factor (HSF) genes corresponding to a novel factor, HSF3, and homologs of mouse and human HSF1 and HSF2.@@@@1@30@@oe@16-12-2010
756567503@GENIA Treebank@formal@@1@S@Analysis of the biochemical and cell biological properties of these HSFs reveals that HSF3 has properties in common with both HSF1 and HSF2 and yet has features which are distinct from both.@@@@1@33@@oe@16-12-2010
756567504@GENIA Treebank@formal@@1@S@HSF3 is constitutively expressed in the erythroblast cell line HD6, the lymphoblast cell line MSB, and embryo fibroblasts, and yet its DNA-binding activity is induced only upon exposure of HD6 cells to heat shock.@@@@1@38@@oe@16-12-2010
756567505@GENIA Treebank@formal@@1@S@Acquisition of HSF3 DNA-binding activity in HD6 cells is accompanied by oligomerization from a non-DNA-binding dimer to a DNA-binding trimer, whereas the effect of heat shock on HSF1 is oligomerization of an inert monomer to a DNA-binding trimer.@@@@1@40@@oe@16-12-2010
756567506@GENIA Treebank@formal@@1@S@Induction of HSF3 DNA-binding activity is delayed compared with that of HSF1.@@@@1@13@@oe@16-12-2010
756567507@GENIA Treebank@formal@@1@S@As occurs for HSF1, heat shock leads to the translocation of HSF3 to the nucleus.@@@@1@17@@oe@16-12-2010
756567508@GENIA Treebank@formal@@1@S@HSF exhibits the properties of a transcriptional activator, as judged from the stimulatory activity of transiently overexpressed HSF3 measured by using a heat shock element-containing reporter construct and as independently assayed by the activity of a chimeric GAL4-HSF3 protein on a GAL4 reporter construct.@@@@1@46@@oe@16-12-2010
756567509@GENIA Treebank@formal@@1@S@These results reveal that HSF3 is negatively regulated in avian cells and acquires DNA-binding activity in certain cells upon heat shock.@@@@1@22@@oe@16-12-2010
756568301@GENIA Treebank@formal@@1@S@N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in response to inducers of NF-kappa B activity.@@@@1@20@@oe@16-12-2010
756568302@GENIA Treebank@formal@@1@S@The proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B.@@@@1@30@@oe@16-12-2010
756568303@GENIA Treebank@formal@@1@S@Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity, such as phorbol myristate acetate or lipopolysaccharide.@@@@1@52@@oe@16-12-2010
756568304@GENIA Treebank@formal@@1@S@In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein.@@@@1@37@@oe@16-12-2010
756568305@GENIA Treebank@formal@@1@S@By expressing mutant forms of the human protein in this cell line, we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha.@@@@1@36@@oe@16-12-2010
756568306@GENIA Treebank@formal@@1@S@Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation.@@@@1@32@@oe@16-12-2010
756568307@GENIA Treebank@formal@@1@S@Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein.@@@@1@57@@oe@16-12-2010
756568308@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010
756572201@GENIA Treebank@formal@@1@S@A central role for a single c-Myb binding site in a thymic locus control region.@@@@1@16@@oe@16-12-2010
756572202@GENIA Treebank@formal@@1@S@Locus control regions (LCRs) are powerful assemblies of cis elements that organize the actions of cell-type-specific trans-acting factors.@@@@1@21@@oe@16-12-2010
756572203@GENIA Treebank@formal@@1@S@A 2.3-kb LCR in the human adenosine deaminase (ADA) gene first intron, which controls expression in thymocytes, is composed of a 200-bp enhancer domain and extended flanking sequences that facilitate activation from within chromatin.@@@@1@39@@oe@16-12-2010
756572204@GENIA Treebank@formal@@1@S@Prior analyses have demonstrated that the enhancer contains a 28-bp core region and local adjacent augmentative cis elements.@@@@1@19@@oe@16-12-2010
756572205@GENIA Treebank@formal@@1@S@We now show that the core contains a single critical c-Myb binding site.@@@@1@14@@oe@16-12-2010
756572206@GENIA Treebank@formal@@1@S@In both transiently cotransfected human cells and stable chromatin-integrated yeast cells, c-Myb strongly transactivated reporter constructs that contained polymerized core sequences.@@@@1@23@@oe@16-12-2010
756572207@GENIA Treebank@formal@@1@S@c-Myb protein was strongly evident in T lymphoblasts in which the enhancer was active and was localized within discrete nuclear structures.@@@@1@22@@oe@16-12-2010
756572208@GENIA Treebank@formal@@1@S@Fetal murine thymus exhibited a striking concordance of endogenous c-myb expression with that of mouse ADA and human ADA LCR-directed transgene expression.@@@@1@23@@oe@16-12-2010
756572209@GENIA Treebank@formal@@1@S@Point mutation of the c-Myb site within the intact 2.3-kb LCR severely attenuated enhancer activity in transfections and LCR activity in transgenic thymocytes.@@@@1@24@@oe@16-12-2010
756572210@GENIA Treebank@formal@@1@S@Within the context of a complex enhancer and LCR, c-Myb can act as an organizer of thymocyte-specific gene expression via a single binding site.@@@@1@26@@oe@16-12-2010
756573201@GENIA Treebank@formal@@1@S@Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor.@@@@1@23@@oe@16-12-2010
756573202@GENIA Treebank@formal@@1@S@T-lymphocyte proliferation is suppressed by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D3, and is associated with a decrease in interleukin 2 (IL-2), gamma interferon, and granulocyte-macrophage colony-stimulating factor mRNA levels.@@@@1@41@@oe@16-12-2010
756573203@GENIA Treebank@formal@@1@S@We report here that 1,25(OH)2D3-mediated repression in Jurkat cells is cycloheximide resistant, suggesting that it is a direct transcriptional repressive effect on IL-2 expression by the vitamin D3 receptor (VDR).@@@@1@34@@oe@16-12-2010
756573204@GENIA Treebank@formal@@1@S@We therefore examined vitamin D3-mediated repression of activated IL-2 expression by cotransfecting Jurkat cells with IL-2 promoter/reporter constructs and a VDR overexpression vector and by DNA binding.@@@@1@29@@oe@16-12-2010
756573205@GENIA Treebank@formal@@1@S@We delineated an element conferring both DNA binding by the receptor in vitro and 1,25(OH)2D3-mediated repression in vivo to a short 40-bp region encompassing an important positive regulatory element, NF-AT-1, which is bound by a T-cell-specific transcription factor, NFATp, as well as by AP-1.@@@@1@49@@oe@16-12-2010
756573206@GENIA Treebank@formal@@1@S@VDR DNA-binding mutants were unable to either bind to this element in vitro or repress in vivo; the VDR DNA-binding domain alone, however, bound the element but also could not repress IL-2 expression.@@@@1@37@@oe@16-12-2010
756573207@GENIA Treebank@formal@@1@S@These results indicate that DNA binding by VDR is necessary but not sufficient to mediate IL-2 repression.@@@@1@18@@oe@16-12-2010
756573208@GENIA Treebank@formal@@1@S@By combining partially purified proteins in vitro, we observed the loss of the bound NFATp/AP-1-DNA complex upon inclusion of VDR or VDR-retinoid X receptor.@@@@1@27@@oe@16-12-2010
756573209@GENIA Treebank@formal@@1@S@Order of addition and off-rate experiments indicate that the VDR-retinoid X receptor heterodimer blocks NFATp/AP-1 complex formation and then stably associates with the NF-AT-1 element.@@@@1@27@@oe@16-12-2010
756573210@GENIA Treebank@formal@@1@S@This direct inhibition by a nuclear hormone receptor of transcriptional activators of the IL-2 gene may provide a mechanistic explanation of how vitamin derivatives can act as potent immunosuppressive agents.@@@@1@31@@oe@16-12-2010
756573601@GENIA Treebank@formal@@1@S@PU.1 (Spi-1) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene.@@@@1@18@@oe@16-12-2010
756573602@GENIA Treebank@formal@@1@S@Growth factor receptors play an important role in hematopoiesis.@@@@1@10@@oe@16-12-2010
756573603@GENIA Treebank@formal@@1@S@In order to further understand the mechanisms directing the expression of these key regulators of hematopoiesis, we initiated a study investigating the transcription factors activating the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha gene.@@@@1@40@@oe@16-12-2010
756573604@GENIA Treebank@formal@@1@S@Here, we demonstrate that the human GM-CSF receptor alpha promoter directs reporter gene activity in a tissue-specific fashion in myelomonocytic cells, which correlates with its expression pattern as analyzed by reverse transcription PCR.@@@@1@36@@oe@16-12-2010
756573605@GENIA Treebank@formal@@1@S@The GM-CSF receptor alpha promoter contains an important functional site between positions -53 and -41 as identified by deletion analysis of reporter constructs.@@@@1@24@@oe@16-12-2010
756573606@GENIA Treebank@formal@@1@S@We show that the myeloid and B cell transcription factor PU.1 binds specifically to this site.@@@@1@17@@oe@16-12-2010
756573607@GENIA Treebank@formal@@1@S@Furthermore, we demonstrate that a CCAAT site located upstream of the PU.1 site between positions -70 and -54 is involved in positive-negative regulation of the GM-CSF receptor alpha promoter activity.@@@@1@32@@oe@16-12-2010
756573608@GENIA Treebank@formal@@1@S@C/EBP alpha is the major CCAAT/enhancer-binding protein (C/EBP) form binding to this site in nuclear extracts of U937 cells.@@@@1@22@@oe@16-12-2010
756573609@GENIA Treebank@formal@@1@S@Point mutations of either the PU.1 site or the C/EBP site that abolish the binding of the respective factors result in a significant decrease of GM-CSF receptor alpha promoter activity in myelomonocytic cells only.@@@@1@35@@oe@16-12-2010
756573610@GENIA Treebank@formal@@1@S@Furthermore, we demonstrate that in myeloid and B cell extracts, PU.1 forms a novel, specific, more slowly migrating complex (PU-SF) when binding the GM-CSF receptor alpha promoter PU.1 site.@@@@1@36@@oe@16-12-2010
756573611@GENIA Treebank@formal@@1@S@This is the first demonstration of a specific interaction with PU.1 on a myeloid PU.1 binding site.@@@@1@18@@oe@16-12-2010
756573612@GENIA Treebank@formal@@1@S@The novel complex is distinct from that described previously as binding to B cell enhancer sites and can be formed by addition of PU.1 to extracts from certain nonmyeloid cell types which do not express PU.1, including T cells and epithelial cells, but not from erythroid cells.@@@@1@50@@oe@16-12-2010
756573613@GENIA Treebank@formal@@1@S@Furthermore, we demonstrate that the PU-SF complex binds to PU.1 sites found on a number of myeloid promoters, and its formation requires an intact PU.1 site adjacent to a single-stranded region.@@@@1@34@@oe@16-12-2010
756573614@GENIA Treebank@formal@@1@S@Expression of PU.1 in nonmyeloid cells can activate the GM-CSF receptor alpha promoter.@@@@1@14@@oe@16-12-2010
756573615@GENIA Treebank@formal@@1@S@Deletion of the amino-terminal region of PU.1 results in a failure to form the PU-SF complex and in a concomitant loss of transactivation, suggesting that formation of the PU-SF complex is of functional importance for the activity of the GM-CSF receptor alpha promoter.@@@@1@45@@oe@16-12-2010
756573616@GENIA Treebank@formal@@1@S@Finally, we demonstrate that C/EBP alpha can also active the GM-CSF receptor alpha promoter in nonmyeloid cells.@@@@1@19@@oe@16-12-2010
756573617@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 400 WORDS)@@@@1@7@@oe@16-12-2010
756581101@GENIA Treebank@formal@@1@S@An interferon-gamma activation sequence mediates the transcriptional regulation of the IgG Fc receptor type IC gene by interferon-gamma.@@@@1@19@@oe@16-12-2010
756581102@GENIA Treebank@formal@@1@S@Expression of the IgG Fc receptor type I (Fc gamma RI) on myeloid cells is dramatically increased by treatment with interferon-gamma (IFN-gamma).@@@@1@27@@oe@16-12-2010
756581103@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
756581104@GENIA Treebank@formal@@1@S@Treatment of U937 with IFN-gamma for 9 hr in the presence of cycloheximide led to super-induction of Fc gamma RI expression.@@@@1@22@@oe@16-12-2010
756581105@GENIA Treebank@formal@@1@S@Nuclear run-on analysis revealed that the rate of Fc gamma RI transcription was increased by IFN-gamma.@@@@1@17@@oe@16-12-2010
756581106@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
756581107@GENIA Treebank@formal@@1@S@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.@@@@1@59@@oe@16-12-2010
756581108@GENIA Treebank@formal@@1@S@A 17-bp sequence between positions -51 and -35 conferred IFN-gamma responsiveness on a heterologous promoter.@@@@1@16@@oe@16-12-2010
756581109@GENIA Treebank@formal@@1@S@Double-stranded GIRE sequence, but not a scrambled sequence, was specifically bound by nuclear proteins from IFN-gamma treated U937 cells.@@@@1@22@@oe@16-12-2010
756581110@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
756581111@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
756581112@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
756997601@GENIA Treebank@formal@@1@S@Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis [see comments]@@@@1@20@@oe@16-12-2010
756997602@GENIA Treebank@formal@@1@S@Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents.@@@@1@11@@oe@16-12-2010
756997603@GENIA Treebank@formal@@1@S@They inhibit synthesis of almost all known cytokines and of several cell surface molecules required for immune function, but the mechanism underlying this activity has been unclear.@@@@1@29@@oe@16-12-2010
756997604@GENIA Treebank@formal@@1@S@Here it is shown that glucocorticoids are potent inhibitors of nuclear factor kappa B (NF-kappa B) activation in mice and cultured cells.@@@@1@25@@oe@16-12-2010
756997605@GENIA Treebank@formal@@1@S@This inhibition is mediated by induction of the I kappa B alpha inhibitory protein, which traps activated NF-kappa B in inactive cytoplasmic complexes.@@@@1@25@@oe@16-12-2010
756997606@GENIA Treebank@formal@@1@S@Because NF-kappa B activates many immunoregulatory genes in response to pro-inflammatory stimuli, the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids.@@@@1@30@@oe@16-12-2010
757268201@GENIA Treebank@formal@@1@S@Pathogenesis of atherosclerosis.@@@@1@4@@oe@16-12-2010
757268202@GENIA Treebank@formal@@1@S@The earliest lesion in the development of an atherosclerotic plaque is the fatty streak.@@@@1@15@@oe@16-12-2010
757268203@GENIA Treebank@formal@@1@S@This chronic inflammatory reaction results from a sequence of events that begins with the trapping of low density lipoprotein (LDL) in the subendothelial space of the artery wall.@@@@1@31@@oe@16-12-2010
757268204@GENIA Treebank@formal@@1@S@The trapped LDL is seeded with oxidative species released by the overlying endothelium, and lipid oxidation is initiated within the LDL particle.@@@@1@24@@oe@16-12-2010
757268205@GENIA Treebank@formal@@1@S@Some of the lipids that result lead to the activation of NFkB-like transcription factors that cause the expression of genes whose protein products mediate monocyte binding, monocyte chemotaxis into the subendothelial space, and conversion into macrophages.@@@@1@39@@oe@16-12-2010
757268206@GENIA Treebank@formal@@1@S@At least 1 major gene modulates the oxidation of LDL lipids and/or the biologic response to these lipids.@@@@1@19@@oe@16-12-2010
757268207@GENIA Treebank@formal@@1@S@The inverse relation between high density lipoprotein (HDL) and atherosclerotic events may in part be due to enzymes associated with HDL that destroy the biologically active lipids generated in LDL.@@@@1@33@@oe@16-12-2010
757556501@GENIA Treebank@formal@@1@S@HMG-I binds to GATA motifs: implications for an HPFH syndrome.@@@@1@12@@oe@16-12-2010
757556502@GENIA Treebank@formal@@1@S@We have examined binding of the nuclear protein HMG-I to the human gamma-globin promoter.@@@@1@15@@oe@16-12-2010
757556503@GENIA Treebank@formal@@1@S@We find that HMG-I binds preferentially to the more 3' of a pair of GATA motifs in the gamma-globin promoter; this paired motif is bound by the erythroid factor GATA-1.@@@@1@32@@oe@16-12-2010
757556504@GENIA Treebank@formal@@1@S@A naturally occurring mutation (-175 T-C) in the area bound by HMG-I results in overexpression of gamma-globin in adult red blood cells (HPFH) and up-regulation of the gamma-globin promoter in in vitro expression assays; HMG-I does not bind to this mutant sequence.@@@@1@48@@oe@16-12-2010
757556505@GENIA Treebank@formal@@1@S@A survey of GATA motifs from other globin cis-elements demonstrates HMG-I binding to most of them.@@@@1@17@@oe@16-12-2010
757556506@GENIA Treebank@formal@@1@S@These findings implicate HMG-I in the HPFH phenotype; we speculate that it may participate in the formation of multiprotein complexes that regulate globin gene expression.@@@@1@27@@oe@16-12-2010
757630101@GENIA Treebank@formal@@1@S@Expression of the nucleoside diphosphate kinase in human skin cancers: an immunohistochemical study.@@@@1@15@@oe@16-12-2010
757630102@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
757630103@GENIA Treebank@formal@@1@S@However, the relationship remains controversial according to the tumor cell types and experimental system, with conflicting results from different research groups.@@@@1@24@@oe@16-12-2010
757630104@GENIA Treebank@formal@@1@S@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.@@@@1@54@@oe@16-12-2010
757630105@GENIA Treebank@formal@@1@S@The expression of NDP kinase was intense in KA and SCC compared with BCC.@@@@1@15@@oe@16-12-2010
757630106@GENIA Treebank@formal@@1@S@However, the difference of NDP kinase expression between KA and SCC was not statistically significant.@@@@1@17@@oe@16-12-2010
757630107@GENIA Treebank@formal@@1@S@And there was no statistically significant difference in NDP kinase expression between SCC with metastasis and SCC without metastasis.@@@@1@20@@oe@16-12-2010
757630108@GENIA Treebank@formal@@1@S@Our results contradict the hypothesis concerning the possible role of nm23 gene as a metastatic suppressor gene in human skin cancer.@@@@1@22@@oe@16-12-2010
757630109@GENIA Treebank@formal@@1@S@The mechanism of overexpression in various tumor cell types and its biological significance in cutaneous carcinogenesis remain to be determined.@@@@1@21@@oe@16-12-2010
757825001@GENIA Treebank@formal@@1@S@Cloning a cDNA from human NK/T cells which codes for a protein with high proline content.@@@@1@17@@oe@16-12-2010
757825002@GENIA Treebank@formal@@1@S@A cDNA clone, B4-2, was isolated from a natural killer (NK) minus T cell subtractive library.@@@@1@21@@oe@16-12-2010
757825003@GENIA Treebank@formal@@1@S@The B4-2 clone coded for an mRNA of 2061 bp in length.@@@@1@13@@oe@16-12-2010
757825004@GENIA Treebank@formal@@1@S@It encodes a deduced 327 aa protein with a calculated molecular mass of 35.2 kDa.@@@@1@16@@oe@16-12-2010
757825005@GENIA Treebank@formal@@1@S@Searching of B4-2 DNA and protein sequences against various databases revealed no high homology to other sequences.@@@@1@18@@oe@16-12-2010
757825006@GENIA Treebank@formal@@1@S@However, B4-2 has an unusually high proline content (13%), contains a putative nuclear targeting sequence, and has several SPXX motifs which are frequently found in gene regulatory proteins.@@@@1@35@@oe@16-12-2010
757825007@GENIA Treebank@formal@@1@S@One of the stretches of prolines in B4-2 closely resembles the ligand for proteins with SH3 domains.@@@@1@18@@oe@16-12-2010
757825008@GENIA Treebank@formal@@1@S@Northern hybridization data showed that B4-2 is not a lymphoid specific gene and is expressed in a hepatoma cell line and also weakly transcribed or absent in a variety of other cells.@@@@1@33@@oe@16-12-2010
757825009@GENIA Treebank@formal@@1@S@A polyclonal antiserum raised against recombinant B4-2 recognizes a 32-34 kDa protein in lymphocytes.@@@@1@15@@oe@16-12-2010
757898001@GENIA Treebank@formal@@1@S@IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and MRNA stability.@@@@1@16@@oe@16-12-2010
757898002@GENIA Treebank@formal@@1@S@The induction of cytokine expression in monocytes/macrophages by bacterial endotoxin or lipopolysaccharide is a critical, highly regulated host defence response.@@@@1@22@@oe@16-12-2010
757898003@GENIA Treebank@formal@@1@S@The augmentation of LPS responses by interferon gamma (IFN-gamma), referred to as priming, is well established.@@@@1@21@@oe@16-12-2010
757898004@GENIA Treebank@formal@@1@S@However, the mechanism(s) by which priming occurs is poorly defined.@@@@1@15@@oe@16-12-2010
757898005@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
757898006@GENIA Treebank@formal@@1@S@Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation.@@@@1@14@@oe@16-12-2010
757898007@GENIA Treebank@formal@@1@S@IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response.@@@@1@14@@oe@16-12-2010
757898008@GENIA Treebank@formal@@1@S@Priming occurred after several hours of treatment, and the primed state was induced by either IFN-gamma or GM-CSF, but not M-CSF.@@@@1@24@@oe@16-12-2010
757898009@GENIA Treebank@formal@@1@S@Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS.@@@@1@18@@oe@16-12-2010
757898010@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
757898011@GENIA Treebank@formal@@1@S@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).@@@@1@26@@oe@16-12-2010
757898012@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
757898013@GENIA Treebank@formal@@1@S@Finally, primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89.@@@@1@16@@oe@16-12-2010
757898014@GENIA Treebank@formal@@1@S@H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed cells, but had no effect on primed monocytes following LPS stimulation.@@@@1@22@@oe@16-12-2010
757898015@GENIA Treebank@formal@@1@S@(ABSTRACT TRUNCATED AT 250 WORDS)@@@@1@7@@oe@16-12-2010
757932801@GENIA Treebank@formal@@1@S@The myeloid zinc finger gene, MZF-1, regulates the CD34 promoter in vitro.@@@@1@15@@oe@16-12-2010
757932802@GENIA Treebank@formal@@1@S@MZF-1 is a C2H2 zinc finger gene encoding a putative transcriptional regulator of myeloid differentiation.@@@@1@16@@oe@16-12-2010
757932803@GENIA Treebank@formal@@1@S@The MZF-1 protein contains 13 C2H2 zinc fingers arranged in bipartite DNA binding domains containing zinc fingers through 4 and, in the carboxy-terminus, 5 through 13.@@@@1@29@@oe@16-12-2010
757932804@GENIA Treebank@formal@@1@S@We previously identified the DNA consensus binding site recognized by the two DNA binding domains.@@@@1@16@@oe@16-12-2010
757932805@GENIA Treebank@formal@@1@S@To assess the transcription regulatory function of MZF-1, the full-length MZF-1 coding region was fused to the DNA binding domain of the yeast transactivator GAL4.@@@@1@27@@oe@16-12-2010
757932806@GENIA Treebank@formal@@1@S@The expression vector was cotransfected with the chloramphenicol acetyl transferase (CAT) reporter gene regulated by the thymidine kinase promoter containing GAL4 DNA binding sites into NIH 3T3, 293, K562, and Jurkat cell lines.@@@@1@39@@oe@16-12-2010
757932807@GENIA Treebank@formal@@1@S@MZF-1 represses CAT reporter gene expression via GAL4 binding sites in the nonhematopoietic cell lines NIH 3T3 and 293.@@@@1@20@@oe@16-12-2010
757932808@GENIA Treebank@formal@@1@S@In contrast, MZF-1 activates CAT reporter gene expression in the hematopoietic cell lines K562 and Jurkat.@@@@1@18@@oe@16-12-2010
757932809@GENIA Treebank@formal@@1@S@The MZF-1 binding sites are present in the promoters of several genes expressed during myeloid differentiation, including the CD34 promoter.@@@@1@22@@oe@16-12-2010
757932810@GENIA Treebank@formal@@1@S@MZF-1 transcriptional regulation of this physiologically relevant promoter was assessed in both hematopoietic and nonhematopoietic cell lines.@@@@1@18@@oe@16-12-2010
757932811@GENIA Treebank@formal@@1@S@Recombinant MZF-1 protein specifically binds to the consensus binding sites in the CD34 promoter in mobility shift assays.@@@@1@19@@oe@16-12-2010
757932812@GENIA Treebank@formal@@1@S@MZF-1 expression vectors were cotransfected with the luciferase reporter plasmids regulated by the CD34 promoter into both nonhematopoietic and hematopoietic cell lines.@@@@1@23@@oe@16-12-2010
757932813@GENIA Treebank@formal@@1@S@As with the heterologous DNA binding domain, MZF-1 represses reporter gene expression in nonhematopoietic cell lines and activates expression in hematopoietic cell lines.@@@@1@25@@oe@16-12-2010
757932814@GENIA Treebank@formal@@1@S@Activation of CD34 expression in hematopoietic cell lines is dependent on the presence of intact MZF-1 binding sites.@@@@1@19@@oe@16-12-2010
757932815@GENIA Treebank@formal@@1@S@The cell type-specific regulation of the CD34 promoter by MZF-1 suggests the presence of tissue-specific regulators/adapters or differential MZF-1 modifications that determine MZF-1 transcriptional regulatory function.@@@@1@27@@oe@16-12-2010
757939901@GENIA Treebank@formal@@1@S@The human TCF-1 gene encodes a nuclear DNA-binding protein uniquely expressed in normal and neoplastic T-lineage lymphocytes.@@@@1@18@@oe@16-12-2010
757939902@GENIA Treebank@formal@@1@S@The TCF-1 gene encodes a putative transcription factor with affinity for a sequence motif occurring in a number of T-cell enhancers.@@@@1@22@@oe@16-12-2010
757939903@GENIA Treebank@formal@@1@S@TCF-1 mRNA was originally found to be expressed in a T cell-specific fashion within a set of human and mouse cell lines.@@@@1@23@@oe@16-12-2010
757939904@GENIA Treebank@formal@@1@S@In contrast, expression reportedly occurs in multiple nonlymphoid tissues during murine embryogenesis.@@@@1@14@@oe@16-12-2010
757939905@GENIA Treebank@formal@@1@S@We have now raised a monoclonal antibody to document expression and biochemistry of the human TCF-1 protein.@@@@1@18@@oe@16-12-2010
757939906@GENIA Treebank@formal@@1@S@As expected, the TCF-1 protein was detectable only in cell lines of T lineage.@@@@1@16@@oe@16-12-2010
757939907@GENIA Treebank@formal@@1@S@Its expression was always restricted to the nucleus.@@@@1@9@@oe@16-12-2010
757939908@GENIA Treebank@formal@@1@S@Immunohistochemistry on a panel of human tissues revealed that the TCF-1 protein was found exclusively in thymocytes and in CD3+ T cells in peripheral lymphoid tissues.@@@@1@27@@oe@16-12-2010
757939909@GENIA Treebank@formal@@1@S@Western blotting yielded a set of bands ranging from 25 kD to 55 kD, resulting from extensive alternative splicing.@@@@1@21@@oe@16-12-2010
757939910@GENIA Treebank@formal@@1@S@The TCF-1 protein was detectable in all samples of a set of 22 T-cell malignancies of various stages of maturation, but was absent from a large number of other hematologic neoplasms.@@@@1@33@@oe@16-12-2010
757939911@GENIA Treebank@formal@@1@S@These observations imply a T cell-specific function for TCF-1, a notion corroborated by recent observations on Tcf-1 knock-out mice.@@@@1@21@@oe@16-12-2010
757939912@GENIA Treebank@formal@@1@S@In addition, these results indicate that nuclear TCF-1 expression can serve as a pan-T-lineage marker in the diagnosis of lymphoid malignancies.@@@@1@23@@oe@16-12-2010
757940501@GENIA Treebank@formal@@1@S@Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T-cell lymphotropic virus type 1 Tax.@@@@1@27@@oe@16-12-2010
757940502@GENIA Treebank@formal@@1@S@L-selectin is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium.@@@@1@21@@oe@16-12-2010
757940503@GENIA Treebank@formal@@1@S@Upon cellular activation, expression of the L-selectin gene is downregulated at both the protein and mRNA levels.@@@@1@19@@oe@16-12-2010
757940504@GENIA Treebank@formal@@1@S@To understand the mechanism of leukemic cell infiltration into organs, we studied the expression and regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia (ATL) patients and investigated the response of the L-selectin promoter to human T-cell lymphotropic virus type 1 (HTLV-1) Tax, which is a viral transcriptional transactivator.@@@@1@59@@oe@16-12-2010
757940505@GENIA Treebank@formal@@1@S@Flow cytometry showed that L-selectin was expressed on fresh ATL cells along with other activation antigens.@@@@1@17@@oe@16-12-2010
757940506@GENIA Treebank@formal@@1@S@Northern blot analysis showed that ATL cells overexpressed that L-selectin mRNA and that the level was aberrantly upregulated after PMA stimulation.@@@@1@22@@oe@16-12-2010
757940507@GENIA Treebank@formal@@1@S@Studies using in situ hybridization showed expression of the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL patients.@@@@1@24@@oe@16-12-2010
757940508@GENIA Treebank@formal@@1@S@Intravenous injection of a rat T-cell line that overexpresses L-selectin showed increased organ infiltration.@@@@1@15@@oe@16-12-2010
757940509@GENIA Treebank@formal@@1@S@The induction of Tax expression in JPX9 cells resulted in about a twofold increase in the mRNA expression levels compared with the basal level.@@@@1@25@@oe@16-12-2010
757940510@GENIA Treebank@formal@@1@S@Chloramphenicol acetyltransferase (CAT) assay after transient cotransfection showed about a fivefold transactivation of the L-selectin promoter by Tax.@@@@1@21@@oe@16-12-2010
757940511@GENIA Treebank@formal@@1@S@The serum level of the shed form of L-selectin was significantly increased in ATL patients (mean +/- SD, 4,215.4 +/- 4,111 ng/mL) compared with those of asymptomatic carriers and healthy blood donors (mean +/- SD, 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL, respectively).@@@@1@53@@oe@16-12-2010
757940512@GENIA Treebank@formal@@1@S@These results indicated that ATL cells constitutively overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax.@@@@1@19@@oe@16-12-2010
757940513@GENIA Treebank@formal@@1@S@The overexpression of L-selectin, as well as of inflammatory cytokines, by ATL cells may provide a basis for ATL cells to attach the vascular endothelium, leading to transmigration and organ infitration.@@@@1@35@@oe@16-12-2010
758452001@GENIA Treebank@formal@@1@S@The DNA and steroid binding domains of the glucocorticoid receptor are not altered in mononuclear cells of treated CLL patients.@@@@1@21@@oe@16-12-2010
758452002@GENIA Treebank@formal@@1@S@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.@@@@1@33@@oe@16-12-2010
758452003@GENIA Treebank@formal@@1@S@The receptor was tested immunocytochemically, in steroid binding assays, and by a mutation screening (denaturing gradient gel electrophoresis) of the receptor-cDNA.@@@@1@26@@oe@16-12-2010
758452004@GENIA Treebank@formal@@1@S@The receptor concentration, as measured by staining and steroid binding test, varied considerably but showed no clear correlation to clinical response.@@@@1@24@@oe@16-12-2010
758452005@GENIA Treebank@formal@@1@S@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.@@@@1@41@@oe@16-12-2010
758452006@GENIA Treebank@formal@@1@S@In one individual who had not been treated before analysis a silent mutation was found in one receptor allele.@@@@1@20@@oe@16-12-2010
758452007@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
758452008@GENIA Treebank@formal@@1@S@This conclusion is discussed in relation to the mechanism of corticoid resistance in mouse and human lymphoma cells in culture.@@@@1@21@@oe@16-12-2010
758550501@GENIA Treebank@formal@@1@S@The normal cell cycle activation program is exploited during the infection of quiescent B lymphocytes by Epstein-Barr virus.@@@@1@19@@oe@16-12-2010
758550502@GENIA Treebank@formal@@1@S@B lymphocytes in the peripheral circulation are maintained in a non-proliferative state.@@@@1@13@@oe@16-12-2010
758550503@GENIA Treebank@formal@@1@S@Antigen recognition stimulates limited proliferation, whereas infection with Epstein-Barr virus (EBV) results in continual proliferation and the outgrowth of immortal cell lines.@@@@1@26@@oe@16-12-2010
758550504@GENIA Treebank@formal@@1@S@Because it is not clear at which point in cell cycle the peripheral B lymphocytes are arrested, we characterized the expression of several cell cycle-associated genes in quiescent and stimulated cells.@@@@1@33@@oe@16-12-2010
758550505@GENIA Treebank@formal@@1@S@We show that the expression of four cell genes, cdc-2, cyclin E, CD23, and cyclin D2, are up-regulated approximately 100-fold as a result of EBV-mediated immortalization.@@@@1@32@@oe@16-12-2010
758550506@GENIA Treebank@formal@@1@S@Because these genes play a positive role in cell proliferation, we suggest that this regulatory switch contributes to controlling entry into the cell cycle.@@@@1@26@@oe@16-12-2010
758550507@GENIA Treebank@formal@@1@S@Transient stimulation of quiescent B lymphocytes with either a cocktail of anti-CD40, anti-IgM, and IL4, or EBV results in the rapid expression of the same four genes, suggesting that, after infection, EBV exploits the normal program of B-lymphocyte cell cycle activation.@@@@1@48@@oe@16-12-2010
758706101@GENIA Treebank@formal@@1@S@BCL-6 and the molecular pathogenesis of B-cell lymphoma.@@@@1@9@@oe@16-12-2010
758706102@GENIA Treebank@formal@@1@S@The results presented identify the first genetic lesion associated with DLCL, the most clinically relevant form of NHL.@@@@1@20@@oe@16-12-2010
758706103@GENIA Treebank@formal@@1@S@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.@@@@1@54@@oe@16-12-2010
758706104@GENIA Treebank@formal@@1@S@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.@@@@1@41@@oe@16-12-2010
758706105@GENIA Treebank@formal@@1@S@In addition to contributing to the understanding of DLCL pathogenesis, the identification of BCL-6 lesions may have relevant clinical implications.@@@@1@22@@oe@16-12-2010
758706106@GENIA Treebank@formal@@1@S@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).@@@@1@31@@oe@16-12-2010
758706107@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
758706108@GENIA Treebank@formal@@1@S@Furthermore, the BCL-6 rearrangements can be used to identify and monitor the malignant clone with sensitive PCR-based techniques.@@@@1@20@@oe@16-12-2010
758706109@GENIA Treebank@formal@@1@S@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).@@@@1@40@@oe@16-12-2010
758832601@GENIA Treebank@formal@@1@S@Prolactin and interleukin-2 receptors in T lymphocytes signal through a MGF-STAT5-like transcription factor.@@@@1@14@@oe@16-12-2010
758832602@GENIA Treebank@formal@@1@S@The cell surface receptors for PRL and interleukin-2 (IL-2) are structurally distinct, but share regulatory tasks in T lymphocytes.@@@@1@23@@oe@16-12-2010
758832603@GENIA Treebank@formal@@1@S@They can stimulate proliferation and activate transcription of over-lapping sets of genes of T cells.@@@@1@16@@oe@16-12-2010
758832604@GENIA Treebank@formal@@1@S@PRL and IL-2 receptor activation are both linked to the Jak/Stat (signal transducer and activator of transcription) pathway.@@@@1@21@@oe@16-12-2010
758832605@GENIA Treebank@formal@@1@S@We investigated the ability of PRL and IL-2 to activate Stat proteins in different T cell lines.@@@@1@18@@oe@16-12-2010
758832606@GENIA Treebank@formal@@1@S@The DNA binding specificities, the reactivities toward Stat-specific antisera, and the mol wt of IL-2- and PRL-induced DNA-binding proteins in Nb2 and C196 T cell lines were investigated.@@@@1@31@@oe@16-12-2010
758832607@GENIA Treebank@formal@@1@S@A comparison with the Stat proteins induced by interferon-gamma, PRL, and IL-6 in T47D mammary tumor cells was made.@@@@1@22@@oe@16-12-2010
758832608@GENIA Treebank@formal@@1@S@We found that these parameters were indistinguishable for one of the PRL- and IL-2-induced factors.@@@@1@16@@oe@16-12-2010
758832609@GENIA Treebank@formal@@1@S@A transcription factor closely related to mammary gland factor-Stat5 is rapidly activated upon interaction of IL-2 and PRL with their respective receptors.@@@@1@23@@oe@16-12-2010
758832610@GENIA Treebank@formal@@1@S@Activation of a second protein related to Stat1 was also observed.@@@@1@12@@oe@16-12-2010
758832611@GENIA Treebank@formal@@1@S@Our results emphasize the role of PRL as a regulator of the immune response and indicate that the Stat factors mammary gland factor-Stat5 and Stat1 play a role in the regulation of gene expression during T cell development.@@@@1@39@@oe@16-12-2010
758908501@GENIA Treebank@formal@@1@S@CD30 ligation induces nuclear factor-kappa B activation in human T cell lines.@@@@1@13@@oe@16-12-2010
758908502@GENIA Treebank@formal@@1@S@CD30 is a recently described member of the tumor necrosis factor/nerve growth factor receptor superfamily.@@@@1@16@@oe@16-12-2010
758908503@GENIA Treebank@formal@@1@S@In this report, we show that following incubation of L540 cells (Hodgkin's disease-derived, T cell-like, CD30+ cells) with the agonistic anti-CD30 monoclonal antibodies (mAb) M44 and M67, two nuclear factor (NF)-kappa B DNA binding activities were induced in nuclear extracts, as determined in gel retardation assays.@@@@1@60@@oe@16-12-2010
758908504@GENIA Treebank@formal@@1@S@The effect of the mAb towards NF-kappa B activation was rapid, as it occurred within 20 min, and was sustained for up to 6 h.@@@@1@28@@oe@16-12-2010
758908505@GENIA Treebank@formal@@1@S@By comparison, an isotype-matched antibody had no effect on NF-kappa B activation.@@@@1@14@@oe@16-12-2010
758908506@GENIA Treebank@formal@@1@S@Moreover, in human T helper (Th) clones functionally characterized as being of the type 0, type 1 and type 2 (28%, < 1% und 93% CD30+, respectively), the extent of CD30-mediated NF-kappa B activation correlated with the proportion of CD30+ cells.@@@@1@54@@oe@16-12-2010
758908507@GENIA Treebank@formal@@1@S@In all cell lines investigated, the NF-kappa B complexes induced following CD30 engagement were shown to contain p50 NF-kappa B1, p65 RelA, and possibly other transcription factors.@@@@1@31@@oe@16-12-2010
758908508@GENIA Treebank@formal@@1@S@Collectively, our results demonstrate that nuclear translocation and activation of NF-kappa B rank among the short-term cellular responses elicited following CD30 ligation.@@@@1@24@@oe@16-12-2010
759024901@GENIA Treebank@formal@@1@S@Constitutive NF-kappa B activation, enhanced granulopoiesis, and neonatal lethality in I kappa B alpha-deficient mice.@@@@1@18@@oe@16-12-2010
759024902@GENIA Treebank@formal@@1@S@Transcription factors belonging to the NF-kappa B family are controlled by inhibitory I kappa B proteins, mainly I kappa B alpha and I kappa B beta.@@@@1@28@@oe@16-12-2010
759024903@GENIA Treebank@formal@@1@S@Apparently normal at birth, I kappa B alpha-/- mice exhibit severe runting, skin defects, and extensive granulopoiesis postnatally, typically dying by 8 days.@@@@1@28@@oe@16-12-2010
759024904@GENIA Treebank@formal@@1@S@Hematopoietic tissues from these mice display elevated levels of both nuclear NF-kappa B and mRNAs of some, but not all, genes thought to be regulated by NF-kappa B.@@@@1@31@@oe@16-12-2010
759024905@GENIA Treebank@formal@@1@S@NF-kappa B elevation results in these phenotypic abnormalities because mice lacking both I kappa B alpha and the p50 subunit of NF-kappa B show a dramatically delayed onset of abnormalities.@@@@1@31@@oe@16-12-2010
759024906@GENIA Treebank@formal@@1@S@In contrast to hematopoietic cells, I kappa B alpha-/- embryonic fibroblasts show minimal constitutive NF-kappa B, as well as normal signal-dependent NF-kappa B activation that is concomitant with I kappa B beta degradation.@@@@1@36@@oe@16-12-2010
759024907@GENIA Treebank@formal@@1@S@Our results indicate that I kappa b beta, but not I kappa B alpha, is required for the signal-dependent activation of NF-kappa B in fibroblasts.@@@@1@28@@oe@16-12-2010
759024908@GENIA Treebank@formal@@1@S@However, I kappa B alpha is required for the postinduction repression of NF-kappa B in fibroblasts.@@@@1@18@@oe@16-12-2010
759024909@GENIA Treebank@formal@@1@S@These results define distinct roles for the two forms of I kappa B and demonstrate the necessity for stringent control of NF-kappa B.@@@@1@24@@oe@16-12-2010
759066601@GENIA Treebank@formal@@1@S@Vitamin E therapy of acute CCl4-induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding.@@@@1@21@@oe@16-12-2010
759066602@GENIA Treebank@formal@@1@S@Oxidative stress, with reactive oxygen intermediate formation, may represent a common mechanism by which liver injury is induced by diverse etiologies.@@@@1@24@@oe@16-12-2010
759066603@GENIA Treebank@formal@@1@S@Oxidative stress enhances nuclear factor kappa B (NF-kappa B) activity, and NF-kappa B activity has been shown to enhance the expression of cytotoxic cytokines.@@@@1@28@@oe@16-12-2010
759066604@GENIA Treebank@formal@@1@S@Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice.@@@@1@20@@oe@16-12-2010
759066605@GENIA Treebank@formal@@1@S@This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of alpha-tocopherol.@@@@1@18@@oe@16-12-2010
759066606@GENIA Treebank@formal@@1@S@Alpha-tocopherol treatment of the mice given the CCl4 also reduced the NF-kappa B binding to levels approaching those found in normal mice.@@@@1@23@@oe@16-12-2010
759066607@GENIA Treebank@formal@@1@S@In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced NF-kappa B binding and an increase in tumor necrosis factor-alpha (TNF-alpha) messenger RNA levels.@@@@1@30@@oe@16-12-2010
759066608@GENIA Treebank@formal@@1@S@Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-kappa B binding activity in comparison with the binding of normal livers.@@@@1@25@@oe@16-12-2010
759066609@GENIA Treebank@formal@@1@S@These data demonstrate that abolishing acute hepatic injury with alpha-tocopherol, a free radical scavenger, also eliminated increased NF-kappa B binding.@@@@1@23@@oe@16-12-2010
759066610@GENIA Treebank@formal@@1@S@It is tempting to speculate that enhanced NF-kappa B expression caused by free radical production/oxidative stress may modulate liver injury, perhaps through an effect on cytotoxic cytokine synthesis.@@@@1@30@@oe@16-12-2010
759109101@GENIA Treebank@formal@@1@S@Attenuation of gamma interferon-induced tyrosine phosphorylation in mononuclear phagocytes infected with Leishmania donovani: selective inhibition of signaling through Janus kinases and Stat1.@@@@1@24@@oe@16-12-2010
759109102@GENIA Treebank@formal@@1@S@The induction of gene transcription in response to gamma interferon is impaired in mononuclear phagocytes infected with Leishmania donovani, and the mechanisms involved are not fully understood.@@@@1@29@@oe@16-12-2010
759109103@GENIA Treebank@formal@@1@S@The changes in gene expression brought about by gamma interferon are thought to involve transient increases in the activities of cellular protein tyrosine kinases, including the Janus kinases Jak1 and Jak2, leading to tyrosine phosphorylation of the transcription factor Stat1.@@@@1@43@@oe@16-12-2010
759109104@GENIA Treebank@formal@@1@S@To investigate the mechanisms accounting for the impaired responses to gamma interferon, a model system for examining overall changes in protein tyrosine phosphorylation, activation of Jak1 and Jak2 and phosphorylation of Stat1 was developed in phorbol 12-myristate 13-acetate-differentiated U-937 cells.@@@@1@43@@oe@16-12-2010
759109105@GENIA Treebank@formal@@1@S@Analysis of whole-cell lysates by antiphosphotyrosine immunoblotting showed that incubation with gamma interferon brought about specific increases in phosphotyrosine labeling of several proteins.@@@@1@24@@oe@16-12-2010
759109106@GENIA Treebank@formal@@1@S@Increased labeling of these proteins occurred to similar extents in control cells and in cells that had been infected with L. donovani for 16 h.@@@@1@26@@oe@16-12-2010
759109107@GENIA Treebank@formal@@1@S@Jak1, Jak2, and Stat1 were immunoprecipitated from control and interferon-treated cells, and tyrosine phosphorylation of these proteins, detected by antiphosphotyrosine immunoblotting was used to measured their activation.@@@@1@32@@oe@16-12-2010
759109108@GENIA Treebank@formal@@1@S@Tyrosine phosphorylation of Jak1, Jak2, and Stat1 increased markedly, in a dose-dependent manner, in U-937 cells incubated with gamma interferon.@@@@1@25@@oe@16-12-2010
759109109@GENIA Treebank@formal@@1@S@In contrast, in cells infected with L. donovani, tyrosine phosphorylation of Jak1, Jak2, and Stat1 was markedly impaired.@@@@1@23@@oe@16-12-2010
759109110@GENIA Treebank@formal@@1@S@This effect was dependent upon the duration of exposure to L. donovani and was maximal and complete at 16 h.@@@@1@21@@oe@16-12-2010
759109111@GENIA Treebank@formal@@1@S@Results similar to those observed with U-937 cells were also obtained with human peripheral blood monocytes.@@@@1@17@@oe@16-12-2010
759109112@GENIA Treebank@formal@@1@S@These findings indicate that infection of human mononuclear phagocytes with L. donovani leads to impaired gamma interferon-mediated tyrosine phosphorylation and selective effects on the Jak-Stat1 pathway.@@@@1@27@@oe@16-12-2010
759109113@GENIA Treebank@formal@@1@S@Unresponsiveness to gamma interferon for activation of this pathway may explain impaired transcriptional responses in leishmania-infected cells.@@@@1@18@@oe@16-12-2010
759109501@GENIA Treebank@formal@@1@S@Nonopsonic phagocytosis of Pseudomonas aeruginosa by macrophages and polymorphonuclear leukocytes requires the presence of the bacterial flagellum.@@@@1@18@@oe@16-12-2010
759109502@GENIA Treebank@formal@@1@S@Whereas the mechanism of nonopsonic phagocytosis of Pseudomonas aeruginosa has been described, the bacterial ligands required are poorly understood.@@@@1@21@@oe@16-12-2010
759109503@GENIA Treebank@formal@@1@S@To identify the requisite bacterial ligands, studies with isogenic mutants of P. aeruginosa PAK lacking pili, flagella, and the RpoN sigma factor were undertaken.@@@@1@28@@oe@16-12-2010
759109504@GENIA Treebank@formal@@1@S@The RpoN mutant, lacking pili, flagella, and nonpilus adhesins, bound poorly and was resistant to ingestion by both macrophages and neutrophils.@@@@1@26@@oe@16-12-2010
759109505@GENIA Treebank@formal@@1@S@Pili were not absolutely required for binding or phagocytosis of P. aeruginosa.@@@@1@13@@oe@16-12-2010
759109506@GENIA Treebank@formal@@1@S@The presence of a flagellum was not required for binding of P. aeruginosa to macrophages but was critical for the subsequent internalization of the bacterium, suggesting that this factor or a surface ligand associated with its assembly was responsible for stimulation of nonopsonic phagocytosis.@@@@1@46@@oe@16-12-2010
759259801@GENIA Treebank@formal@@1@S@Mutually exclusive interaction of a novel matrix attachment region binding protein and the NF-muNR enhancer repressor.@@@@1@17@@oe@16-12-2010
759259802@GENIA Treebank@formal@@1@S@Implications for regulation of immunoglobulin heavy chain expression.@@@@1@9@@oe@16-12-2010
759259803@GENIA Treebank@formal@@1@S@The immunoglobulin heavy chain (IgH) intronic enhancer stimulates transcription from functional promoters in B lymphocytes but not other cell types.@@@@1@23@@oe@16-12-2010
759259804@GENIA Treebank@formal@@1@S@The observation that binding sites for the nuclear factor-mu negative regulator (NF-muNR) enhancer repressor overlap nuclear matrix attachment regions (MARs) in this enhancer has lead to the hypothesis that the cell type specificity of the enhancer might be controlled by regulating nuclear matrix attachment (Scheuermann, R. H., and Chen, U. (1989) Genes & Dev. 3, 1255-1266).@@@@1@69@@oe@16-12-2010
759259805@GENIA Treebank@formal@@1@S@To understand the role of MARs in IgH enhancer regulation, we have identified a novel MAR-binding protein, MAR-BP1, from soluble nuclear matrix preparations based on its ability to bind to the MARs associated with the IgH enhancer.@@@@1@41@@oe@16-12-2010
759259806@GENIA Treebank@formal@@1@S@Purified MAR-BP1 migrates as a 33-kDa protein, and it can be found in nuclear matrix preparations from a number of different types of lymphoid cell lines.@@@@1@28@@oe@16-12-2010
759259807@GENIA Treebank@formal@@1@S@Although specific binding sites have been difficult to localize by chemical or enzymatic footprinting procedures, NF-muNR binding sites are critical for efficient MAR-BP1 binding.@@@@1@26@@oe@16-12-2010
759259808@GENIA Treebank@formal@@1@S@Indeed, binding of the IgH enhancer to either intact nuclear matrix preparations or to MAR-BP1 is mutually exclusive to NF-muNR binding.@@@@1@23@@oe@16-12-2010
759259809@GENIA Treebank@formal@@1@S@These results are consistent with a model for cell-type specific regulation in which binding of the NF-muNR repressor to the IgH enhancer prevents nuclear matrix attachment in inappropriate cells by interfering with MAR-BP1/enhancer interaction.@@@@1@35@@oe@16-12-2010
759267101@GENIA Treebank@formal@@1@S@Identification of essential GATA and Ets binding motifs within the promoter of the platelet glycoprotein Ib alpha gene.@@@@1@19@@oe@16-12-2010
759267102@GENIA Treebank@formal@@1@S@Platelet glycoprotein (GP) Ib-IX-V is a multisubunit adhesion receptor that supports platelet attachment to thrombogenic surfaces at sites of vascular injury.@@@@1@24@@oe@16-12-2010
759267103@GENIA Treebank@formal@@1@S@The congenital absence of the receptor results in a bleeding disorder associated with "giant" platelets, a condition linking the expression of the complex to platelet morphogenesis.@@@@1@30@@oe@16-12-2010
759267104@GENIA Treebank@formal@@1@S@To understand better the expression of the GP Ib-IX-V complex, studies were undertaken to define the essential genetic elements supporting the expression of the alpha-subunit of the complex (GP Ib alpha).@@@@1@35@@oe@16-12-2010
759267105@GENIA Treebank@formal@@1@S@GP Ib alpha promoter activity was evaluated by transfection of human erythroleukemia cells with reporter plasmids coding for the enzyme, luciferase.@@@@1@23@@oe@16-12-2010
759267106@GENIA Treebank@formal@@1@S@Studies were initiated with a fragment extending 2,738 nucleotides 5' to the transcription start site and lead to the identification of 253 nucleotides retaining full promoter activity in human erythroleukemia cells.@@@@1@32@@oe@16-12-2010
759267107@GENIA Treebank@formal@@1@S@In cells of nonhematopoietic lineage, human endothelial and HeLa cells, the GP Ib alpha promoter activity was no greater than background levels obtained with promoterless constructs.@@@@1@29@@oe@16-12-2010
759267108@GENIA Treebank@formal@@1@S@Gel shift assays and site-directed mutagenesis studies defined essential GATA and Ets binding motifs 93 and 150 nucleotides upstream of the transcription start site, a finding which further substantiates these elements as important determinants of megakaryocytic gene expression.@@@@1@40@@oe@16-12-2010
759267109@GENIA Treebank@formal@@1@S@The results define essential cis-acting elements responsible for the expression of GP Ib alpha and provide insights into molecular events coinciding with the release of normal platelets into the bloodstream.@@@@1@31@@oe@16-12-2010
759267601@GENIA Treebank@formal@@1@S@Multiple proteins interact with the nuclear inhibitory protein repressor element in the human interleukin-3 promoter.@@@@1@16@@oe@16-12-2010
759267602@GENIA Treebank@formal@@1@S@T cell expression of interleukin 3 (IL-3) is directed by positive and negative cis-acting DNA elements clustered within 300 base pairs of the transcriptional start site.@@@@1@29@@oe@16-12-2010
759267603@GENIA Treebank@formal@@1@S@A strong repressor element, termed nuclear inhibitory protein (NIP), was previously mapped to a segment of the IL-3 promoter between nucleotides -271 and -250.@@@@1@29@@oe@16-12-2010
759267604@GENIA Treebank@formal@@1@S@Functional characterization of this element demonstrates that it can mediate repression when linked in cis to a heterologous promoter.@@@@1@20@@oe@16-12-2010
759267605@GENIA Treebank@formal@@1@S@DNA binding experiments were carried out to characterize the repressor activity.@@@@1@12@@oe@16-12-2010
759267606@GENIA Treebank@formal@@1@S@Using varying conditions, three distinct complexes were shown to interact specifically with the NIP region, although only one correlates with repressor activity.@@@@1@25@@oe@16-12-2010
759267607@GENIA Treebank@formal@@1@S@Complex 1 results from binding of a ubiquitous polypeptide that recognizes the 3' portion of this sequence and is not required for repression.@@@@1@24@@oe@16-12-2010
759267608@GENIA Treebank@formal@@1@S@Complex 2 corresponds to binding of transcription factor (upstream stimulatory factor) to an E-box motif in the 5' portion of the NIP region.@@@@1@26@@oe@16-12-2010
759267609@GENIA Treebank@formal@@1@S@DNA binding specificity of complex 3 overlaps with that of upstream stimulatory factor but is clearly distinct.@@@@1@18@@oe@16-12-2010
759267610@GENIA Treebank@formal@@1@S@To determine which of the latter two complexes represents NIP activity, we incorporated small alterations into the NIP site of an IL-3 promoter-linked reporter construct and examined their effects on NIP-mediated repression.@@@@1@34@@oe@16-12-2010
759267611@GENIA Treebank@formal@@1@S@Functional specificity for repression matches the DNA binding specificity of complex 3; both repressor activity and complex 3 binding require the consensus sequence CTCACNTNC.@@@@1@26@@oe@16-12-2010
759313601@GENIA Treebank@formal@@1@S@Correlation of differentiation-inducing activity of retinoids on human leukemia cell lines HL-60 and NB4.@@@@1@15@@oe@16-12-2010
759313602@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
759313603@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
759445601@GENIA Treebank@formal@@1@S@Activation of the signal transducer and transcription (STAT) signaling pathway in a primary T cell response.@@@@1@19@@oe@16-12-2010
759445602@GENIA Treebank@formal@@1@S@Critical role for IL-6.@@@@1@5@@oe@16-12-2010
759445603@GENIA Treebank@formal@@1@S@The T cell activation is initiated by interaction of specific Ags with TCR, followed by activation of intracellular biochemical events leading to activation of several genes.@@@@1@28@@oe@16-12-2010
759445604@GENIA Treebank@formal@@1@S@The activation of signal transducer and activator of transcription (STAT) proteins in a primary TCR-mediated activation of T cells have been explored.@@@@1@25@@oe@16-12-2010
759445605@GENIA Treebank@formal@@1@S@In purified human peripheral blood T cells, nuclear STAT proteins were activated approximately 3 h after activation by cross-linked anti-CD3 Abs.@@@@1@23@@oe@16-12-2010
759445606@GENIA Treebank@formal@@1@S@These STAT proteins were detected by using the IFN-gamma-activated sequence (GAS) and related oligonucleotides as probes in electrophoretic mobility shift assay.@@@@1@24@@oe@16-12-2010
759445607@GENIA Treebank@formal@@1@S@Analysis of the nuclear extracts with anti-STAT Abs indicated that they contained STAT-3 and additional proteins crossreactive with the STAT family.@@@@1@22@@oe@16-12-2010
759445608@GENIA Treebank@formal@@1@S@The induction of STAT activity was inhibited completely by pretreatment with either cycloheximide or cyclosporin A, thus indicating that the induction was due to a secondary factor produced by the activated T cells.@@@@1@35@@oe@16-12-2010
759445609@GENIA Treebank@formal@@1@S@As neutralizing anti-IL-6 Abs effectively down-regulated the early induction of STAT proteins and as exogenously added IL-6 rapidly activated DNA binding similar to TCR-mediated bindings, it can be concluded that IL-6 is the factor responsible for the activation of STAT proteins in a primary T cell response.@@@@1@49@@oe@16-12-2010
759446801@GENIA Treebank@formal@@1@S@Regulation of IkB alpha phosphorylation by PKC- and Ca(2+)-dependent signal transduction pathways.@@@@1@13@@oe@16-12-2010
759446802@GENIA Treebank@formal@@1@S@The Ca(2+)-dependent phosphatase calcineurin, a target of FK506 and CsA, synergizes with PKC-induced activation of nuclear factor (NF)-kappa B in T cell lines.@@@@1@29@@oe@16-12-2010
759446803@GENIA Treebank@formal@@1@S@We have investigated whether this synergy is present in other cell types and the mechanism(s) by which these two pathways lead to NF-kappa B activation.@@@@1@29@@oe@16-12-2010
759446804@GENIA Treebank@formal@@1@S@While this synergy is present in other cell types, in the monocytic cell line U937 calcineurin is also sufficient to activate NF-kappa B.@@@@1@25@@oe@16-12-2010
759446805@GENIA Treebank@formal@@1@S@Having previously shown that Ca(2+)- and PKC-dependent pathways synergize by accelerating the degradation of IkB alpha, we focused on the regulation of IkB alpha phosphorylation.@@@@1@28@@oe@16-12-2010
759446806@GENIA Treebank@formal@@1@S@While PKC-dependent pathways sequentially result in the phosphorylation and in an incomplete degradation of IkB alpha in T cell lines, co-activation of Ca(2+)-dependent pathways accelerates the rate of IkB alpha phosphorylation and results in its complete degradation.@@@@1@39@@oe@16-12-2010
759446807@GENIA Treebank@formal@@1@S@Activation of Ca(2+)-dependent pathways alone do not result in the phosphorylation and/or degradation of IkB alpha in Jurkat T or in U937 cells.@@@@1@24@@oe@16-12-2010
759446808@GENIA Treebank@formal@@1@S@Treatment of T cells with the selective PKC inhibitor GF109203X abrogates the PMA-induced IkB alpha phosphorylation/degradation irrespective of activation of Ca(2+)-dependent pathways, but not the phosphorylation and degradation of IkB alpha induced by TNF-alpha, a PKC-independent stimulus.@@@@1@40@@oe@16-12-2010
759446809@GENIA Treebank@formal@@1@S@Contrary to the interaction with PKC, Ca(2+)-dependent pathways synergize with TNF-alpha not at the level of IkB alpha phosphorylation, but at the level of its degradation.@@@@1@29@@oe@16-12-2010
759446810@GENIA Treebank@formal@@1@S@These results indicate that Ca(2+)-dependent pathways, including the phosphatase calcineurin, participate in the regulation of NF-kappa B in a cell specific fashion and synergize with PKC-dependent and -independent pathways at the level of IkB alpha phosphorylation and degradation.@@@@1@41@@oe@16-12-2010
759448901@GENIA Treebank@formal@@1@S@Triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) induces nuclear translocation of NF-kappa B (p50/p65) in human monocytes and enhances viral replication in HIV-infected monocytic cells.@@@@1@35@@oe@16-12-2010
759448902@GENIA Treebank@formal@@1@S@Monocyte/macrophages may harbor HIV in a nonproductive fashion for prolonged periods of time.@@@@1@14@@oe@16-12-2010
759448903@GENIA Treebank@formal@@1@S@Viral gene expression may be reactivated by stimulation of the cells with LPS or cytokines such as TNF-alpha in vitro.@@@@1@21@@oe@16-12-2010
759448904@GENIA Treebank@formal@@1@S@The effect of LPS and TNF-alpha is mediated by their ability to induce nuclear translocation of the DNA-binding heterodimer NF-kappa B (p50/p65), which binds to a specific sequence in the HIV-long terminal repeat.@@@@1@38@@oe@16-12-2010
759448905@GENIA Treebank@formal@@1@S@The present study demonstrates that triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) enhances viral replication in HIV-infected human monocytic cells.@@@@1@27@@oe@16-12-2010
759448906@GENIA Treebank@formal@@1@S@Monocytic cell lines and normal peripheral blood monocytes were infected with HIV-1 in vitro and cultured in the presence or absence of F(ab')2 fragments of monoclonal anti-CR1 or anti-CR3 Abs or with C3 fragments.@@@@1@35@@oe@16-12-2010
759448907@GENIA Treebank@formal@@1@S@Stimulation of CR1 or CR3 induces a two- to fourfold increase in the amount of cell-associated and released p24 Ag in cell cultures that was equivalent to that observed in control cultures triggered with LPS.@@@@1@36@@oe@16-12-2010
759448908@GENIA Treebank@formal@@1@S@We further observed that stimulation of CR1 or CR3 induces the nuclear translocation of NF-kappa B p50/p65 in infected cells.@@@@1@22@@oe@16-12-2010
759448909@GENIA Treebank@formal@@1@S@Translocation of NF-kappa B p50/p65 was also observed following stimulation of CR1 or CR3 of uninfected peripheral blood monocytes from HIV-seronegative donors.@@@@1@24@@oe@16-12-2010
759448910@GENIA Treebank@formal@@1@S@The amount of protein translocated was similar to that observed when cells were stimulated with rhTNF-alpha.@@@@1@17@@oe@16-12-2010
759448911@GENIA Treebank@formal@@1@S@TNF-alpha did not mediate the translocation of NF-kappa B p50/p65 induced by triggering of complement receptors.@@@@1@18@@oe@16-12-2010
759448912@GENIA Treebank@formal@@1@S@Taken together, these observations suggest that HIV gene expression may be activated in infected monocytes through interaction of the cells with complement-opsonized particles and that enhanced viral replication is associated with C3 receptor-mediated nuclear translocation of the NF-kappa B complex.@@@@1@42@@oe@16-12-2010
759454001@GENIA Treebank@formal@@1@S@Nuclear factor-IL6 activates the human IL-4 promoter in T cells.@@@@1@11@@oe@16-12-2010
759454002@GENIA Treebank@formal@@1@S@Positive regulatory element I (PRE-I) is a strong enhancer element essential for expression of the human IL-4 gene.@@@@1@21@@oe@16-12-2010
759454003@GENIA Treebank@formal@@1@S@To identify transcription factors binding to PRE-I, we screened a cDNA expression library from Jurkat T cells and isolated a cDNA encoding nuclear factor (NF)-IL6 (also known as C/EBP beta).@@@@1@37@@oe@16-12-2010
759454004@GENIA Treebank@formal@@1@S@NF-IL6 mRNA was found in human Jurkat T cells and in the mouse Th2 clone D10, but not in Th1 clone 29.@@@@1@24@@oe@16-12-2010
759454005@GENIA Treebank@formal@@1@S@rNF-IL6 expressed in bacteria was shown to specifically bind to PRE-I.@@@@1@12@@oe@16-12-2010
759454006@GENIA Treebank@formal@@1@S@PRE-I forms multiple DNA-protein complexes with nuclear extracts from Jurkat cells.@@@@1@12@@oe@16-12-2010
759454007@GENIA Treebank@formal@@1@S@Some of these complexes were demonstrated to contain NF-IL6 by using anti-C/EBP beta Abs.@@@@1@15@@oe@16-12-2010
759454008@GENIA Treebank@formal@@1@S@Overexpression of NF-IL6 enhanced expression of the chloramphenicol acetyl transferase reporter gene linked to the PRE-I-thymidine kinase or the human IL-4 promoter more than 10-fold in Jurkat cells.@@@@1@29@@oe@16-12-2010
759454009@GENIA Treebank@formal@@1@S@Promoter deletion studies revealed two additional NF-IL6 binding sites located at positions -44 to -36 (C/EBP proximal) and -87 to -79 (C/EBP medial), respectively.@@@@1@30@@oe@16-12-2010
759454010@GENIA Treebank@formal@@1@S@Our results demonstrate that NF-IL6 is involved in transcriptional activation of the human IL-4 promoter in T cells.@@@@1@19@@oe@16-12-2010
760211401@GENIA Treebank@formal@@1@S@The activation of the Jak-STAT 1 signaling pathway by IL-5 in eosinophils.@@@@1@13@@oe@16-12-2010
760211402@GENIA Treebank@formal@@1@S@The intracellular signal transduction of IL-5 in eosinophils is unknown.@@@@1@11@@oe@16-12-2010
760211403@GENIA Treebank@formal@@1@S@The objective of this study was to investigate the involvement of the newly discovered Jak-STAT pathway in the IL-5 signal transduction mechanism.@@@@1@23@@oe@16-12-2010
760211404@GENIA Treebank@formal@@1@S@Eosinophils were purified from peripheral blood by discontinuous Percoll gradients and stimulated with IL-5.@@@@1@15@@oe@16-12-2010
760211405@GENIA Treebank@formal@@1@S@The involvement of Jak 2 was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation.@@@@1@16@@oe@16-12-2010
760211406@GENIA Treebank@formal@@1@S@The activation of Jak 2 was studied by autophosphorylation of the immunoprecipitated kinase.@@@@1@14@@oe@16-12-2010
760211407@GENIA Treebank@formal@@1@S@Jak 2 was tyrosine phosphorylated within 1 to 3 min after stimulation of eosinophils with IL-5.@@@@1@17@@oe@16-12-2010
760211408@GENIA Treebank@formal@@1@S@Further, the immunoprecipitated Jak 2 obtained from IL-5-stimulated cells underwent autophosphorylation.@@@@1@13@@oe@16-12-2010
760211409@GENIA Treebank@formal@@1@S@Jak 2 coprecipitated with the beta-subunit of the IL-5 receptor, suggesting a physical association of the kinase with the receptor.@@@@1@22@@oe@16-12-2010
760211410@GENIA Treebank@formal@@1@S@The nuclear factor STAT-1 (p91) was investigated by immunoprecipitation followed by immunoblotting for tyrosine phosphorylation.@@@@1@18@@oe@16-12-2010
760211411@GENIA Treebank@formal@@1@S@STAT-1 was tyrosine phosphorylated within 15 min of IL-5 stimulation.@@@@1@11@@oe@16-12-2010
760211412@GENIA Treebank@formal@@1@S@The presence of STAT-1 in the nuclear extract was studied by electrophoretic mobility shift assay.@@@@1@16@@oe@16-12-2010
760211413@GENIA Treebank@formal@@1@S@IL-5 induced two proteins that bound to the gamma-activating sequence.@@@@1@11@@oe@16-12-2010
760211414@GENIA Treebank@formal@@1@S@In the presence of an anti-STAT-1 Ab, the band was supershifted.@@@@1@13@@oe@16-12-2010
760211415@GENIA Treebank@formal@@1@S@Thus, we demonstrated that IL-5 activated the Jak 2-STAT 1 signaling pathway in eosinophils.@@@@1@16@@oe@16-12-2010
760211416@GENIA Treebank@formal@@1@S@We speculate that the Jak 2-STAT 1 pathway may be involved in the activation of IL-5-inducible genes in eosinophils.@@@@1@20@@oe@16-12-2010
760428301@GENIA Treebank@formal@@1@S@Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I.@@@@1@11@@oe@16-12-2010
760428302@GENIA Treebank@formal@@1@S@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).@@@@1@29@@oe@16-12-2010
760428303@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
760428304@GENIA Treebank@formal@@1@S@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.@@@@1@40@@oe@16-12-2010
760428305@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
760599001@GENIA Treebank@formal@@1@S@Positive and negative regulation of granulocyte-macrophage colony-stimulating factor promoter activity by AML1-related transcription factor, PEBP2.@@@@1@17@@oe@16-12-2010
760599002@GENIA Treebank@formal@@1@S@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.@@@@1@33@@oe@16-12-2010
760599003@GENIA Treebank@formal@@1@S@There are at least two genes, alpha A and alpha B, encoding the alpha subunit.@@@@1@18@@oe@16-12-2010
760599004@GENIA Treebank@formal@@1@S@alpha B is the mouse homologue of human AML1 gene detected at the breakpoints of t(8;21) and t(3;21) myeloid leukemias.@@@@1@31@@oe@16-12-2010
760599005@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
760599006@GENIA Treebank@formal@@1@S@PEBP2 alpha A1, alpha B1, and alpha B2 proteins bound the PEBP2 site within the mouse GM-CSF promoter.@@@@1@21@@oe@16-12-2010
760599007@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
760599008@GENIA Treebank@formal@@1@S@In contrast, the promoter activity was suppressed by alpha B2.@@@@1@12@@oe@16-12-2010
760599009@GENIA Treebank@formal@@1@S@Coexpression of alpha B1 and alpha B2 showed that the promoter activity could be determined by the alpha B1/alpha B2 ratio.@@@@1@22@@oe@16-12-2010
760599010@GENIA Treebank@formal@@1@S@Jurkat cell extract contained PEBP2 site-binding protein(s) that cross-reacted with antimouse alpha A1 antibodies.@@@@1@18@@oe@16-12-2010
760599011@GENIA Treebank@formal@@1@S@Northern blot analysis indicated the expression of human PEBP2 alpha A, alpha B (AML1), and beta genes in Jurkat cells.@@@@1@25@@oe@16-12-2010
760599012@GENIA Treebank@formal@@1@S@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.@@@@1@41@@oe@16-12-2010
760599601@GENIA Treebank@formal@@1@S@Heterogeneous expression of Epstein-Barr virus latent proteins in endemic Burkitt's lymphoma.@@@@1@13@@oe@16-12-2010
760599602@GENIA Treebank@formal@@1@S@Epstein-Barr virus (EBV)-infected cells may sustain three distinct forms of virus latency.@@@@1@16@@oe@16-12-2010
760599603@GENIA Treebank@formal@@1@S@In lymphoblastoid cell lines, six EBV-encoded nuclear antigens (EBNA1, 2, 3A, 3B, 3C, -LP), three latent membrane proteins (LMP1, 2A, 2B), and two nuclear RNAs (EBERs) are expressed.@@@@1@45@@oe@16-12-2010
760599604@GENIA Treebank@formal@@1@S@This form of latency, termed latency III, is also encountered in some posttransplant lymphoproliferative disorders.@@@@1@18@@oe@16-12-2010
760599605@GENIA Treebank@formal@@1@S@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).@@@@1@44@@oe@16-12-2010
760599606@GENIA Treebank@formal@@1@S@We have studied the expression of EBV proteins in 17 cases of EBV-positive endemic BL by immunohistology.@@@@1@18@@oe@16-12-2010
760599607@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
760599608@GENIA Treebank@formal@@1@S@Also, the BZLF1 trans-activator protein was expressed in a few tumor cells in 6 cases, indicating entry into the lytic cycle.@@@@1@24@@oe@16-12-2010
760599609@GENIA Treebank@formal@@1@S@A phenotypic drift from latency I to latency III has been observed previously in some BL cell lines.@@@@1@19@@oe@16-12-2010
760599610@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
760599701@GENIA Treebank@formal@@1@S@Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia?@@@@1@18@@oe@16-12-2010
760599702@GENIA Treebank@formal@@1@S@A pediatric oncology group study.@@@@1@6@@oe@16-12-2010
760599703@GENIA Treebank@formal@@1@S@Almost 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL) have tumor-specific rearrangements of the TAL1 gene.@@@@1@21@@oe@16-12-2010
760599704@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
760599705@GENIA Treebank@formal@@1@S@Hence, it has been proposed that ectopic expression of TAL1 promotes the development of T-ALL.@@@@1@17@@oe@16-12-2010
760599706@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
760599707@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
760599708@GENIA Treebank@formal@@1@S@Monoallelic expression of TAL1 was observed in the leukemic cells of all patients (8 of 8) bearing a TAL1 gene rearrangement.@@@@1@24@@oe@16-12-2010
760599709@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
760599710@GENIA Treebank@formal@@1@S@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).@@@@1@43@@oe@16-12-2010
760905301@GENIA Treebank@formal@@1@S@The peri-kappa B site mediates human immunodeficiency virus type 2 enhancer activation in monocytes but not in T cells.@@@@1@20@@oe@16-12-2010
760905302@GENIA Treebank@formal@@1@S@Human immunodeficiency virus type 2 (HIV-2), like HIV-1, causes AIDS and is associated with AIDS cases primarily in West Africa.@@@@1@25@@oe@16-12-2010
760905303@GENIA Treebank@formal@@1@S@HIV-1 and HIV-2 display significant differences in nucleic acid sequence and in the natural history of clinical disease.@@@@1@19@@oe@16-12-2010
760905304@GENIA Treebank@formal@@1@S@Consistent with these differences, we have previously demonstrated that the enhancer/promoter region of HIV-2 functions quite differently from that of HIV-1.@@@@1@23@@oe@16-12-2010
760905305@GENIA Treebank@formal@@1@S@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.@@@@1@70@@oe@16-12-2010
760905306@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
760905307@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
760905308@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
760905309@GENIA Treebank@formal@@1@S@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.@@@@1@63@@oe@16-12-2010
760905310@GENIA Treebank@formal@@1@S@Further, while specific constitutive binding to the peri-kappa B site is seen in monocytes, stimulation with phorbol esters induces additional, specific binding.@@@@1@26@@oe@16-12-2010
760905311@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
761266101@GENIA Treebank@formal@@1@S@Inhibitory action of nm23 proteins on induction of erythroid differentiation of human leukemia cells.@@@@1@15@@oe@16-12-2010
761266102@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
761266103@GENIA Treebank@formal@@1@S@nm23 genes encode proteins that participate in tumor metastasis regulation and in various fundamental cellular processes, although their mechanisms of action are still unknown.@@@@1@26@@oe@16-12-2010
761266104@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
761266105@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
761266106@GENIA Treebank@formal@@1@S@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.@@@@1@37@@oe@16-12-2010
761266107@GENIA Treebank@formal@@1@S@The erythroid differentiation of HEL cells was inhibited by recombinant human nm23-H1, -H2, mouse nm23-M1, and -M2 proteins.@@@@1@22@@oe@16-12-2010
761266108@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
761266109@GENIA Treebank@formal@@1@S@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.@@@@1@63@@oe@16-12-2010
761313501@GENIA Treebank@formal@@1@S@A conserved motif in the promoters of several cytokines expressed by human Th2-type lymphocytes.@@@@1@15@@oe@16-12-2010
761313502@GENIA Treebank@formal@@1@S@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)].@@@@1@36@@oe@16-12-2010
761313503@GENIA Treebank@formal@@1@S@It contains a core sequence CTTGG ... CCAAG which is present as part of larger palindromic sequences in each gene.@@@@1@21@@oe@16-12-2010
761313504@GENIA Treebank@formal@@1@S@This suggest that they may interact with a new family of trans-acting factors.@@@@1@14@@oe@16-12-2010
761313505@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
761313506@GENIA Treebank@formal@@1@S@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.@@@@1@46@@oe@16-12-2010
761313507@GENIA Treebank@formal@@1@S@In different genes, the core sequences are separated by integer numbers of helical turns.@@@@1@16@@oe@16-12-2010
761313508@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
761313801@GENIA Treebank@formal@@1@S@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.@@@@1@23@@oe@16-12-2010
761313802@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
761313803@GENIA Treebank@formal@@1@S@IL-5 also stimulates GTP binding to p21ras.@@@@1@8@@oe@16-12-2010
761313804@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
761313805@GENIA Treebank@formal@@1@S@Jak2 kinase has been shown to phosphorylate STAT nuclear proteins.@@@@1@11@@oe@16-12-2010
761313806@GENIA Treebank@formal@@1@S@The activation of STAT nuclear factors was studied by electrophoretic mobility shift assay using a gamma activation site (GAS) probe.@@@@1@23@@oe@16-12-2010
761313807@GENIA Treebank@formal@@1@S@We found that IL-5 induces two GAS-binding proteins in eosinophils, one of which is STAT1.@@@@1@17@@oe@16-12-2010
761313808@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
761349001@GENIA Treebank@formal@@1@S@Hematopoietic lineage commitment: role of transcription factors.@@@@1@9@@oe@16-12-2010
761349002@GENIA Treebank@formal@@1@S@This review focuses on the roles of transcription factors in hematopoietic lineage commitment.@@@@1@14@@oe@16-12-2010
761349003@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
761349004@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
761349005@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
761827701@GENIA Treebank@formal@@1@S@E1A gene expression induces susceptibility to killing by NK cells following immortalization but not adenovirus infection of human cells.@@@@1@20@@oe@16-12-2010
761827702@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
761827703@GENIA Treebank@formal@@1@S@Only stably transfected target cells exhibited cytolytic susceptibility, despite expression of equivalent levels of E1A proteins in Ad-infected targets.@@@@1@21@@oe@16-12-2010
761827704@GENIA Treebank@formal@@1@S@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.@@@@1@42@@oe@16-12-2010
761827705@GENIA Treebank@formal@@1@S@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.@@@@1@53@@oe@16-12-2010
762219101@GENIA Treebank@formal@@1@S@Thapsigargin induces IL-2 receptor alpha-chain in human peripheral and Jurkat T cells via a protein kinase C-independent mechanism.@@@@1@19@@oe@16-12-2010
762219102@GENIA Treebank@formal@@1@S@Thapsigargin (TG), an inhibitor of Ca(2+)-ATPase, depletes intracellular Ca2+ stores and induces a sustained Ca2+ influx without altering phosphatidyl inositol levels.@@@@1@26@@oe@16-12-2010
762219103@GENIA Treebank@formal@@1@S@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).@@@@1@33@@oe@16-12-2010
762219104@GENIA Treebank@formal@@1@S@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.@@@@1@24@@oe@16-12-2010
762219105@GENIA Treebank@formal@@1@S@A similar increase in IL-2R alpha by TG was also observed in human peripheral T cells.@@@@1@17@@oe@16-12-2010
762219106@GENIA Treebank@formal@@1@S@Further, like PMA, TG markedly induced NF kappa B in Jurkat T cells.@@@@1@16@@oe@16-12-2010
762219107@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
762219108@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
762219109@GENIA Treebank@formal@@1@S@In toto, these results suggest that TG induces IL-2R alpha in human T cells through a PKC-independent pathway.@@@@1@20@@oe@16-12-2010
762382801@GENIA Treebank@formal@@1@S@A functional T-cell receptor signaling pathway is required for p95vav activity.@@@@1@12@@oe@16-12-2010
762382802@GENIA Treebank@formal@@1@S@Stimulation of the T-cell antigen receptor (TCR) induces activation of multiple tyrosine kinases, resulting in phosphorylation of numerous intracellular substrates.@@@@1@24@@oe@16-12-2010
762382803@GENIA Treebank@formal@@1@S@One substrate is p95vav, which is expressed exclusively in hematopoietic and trophoblast cells.@@@@1@15@@oe@16-12-2010
762382804@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
762382805@GENIA Treebank@formal@@1@S@The role of p95vav in TCR-mediated signaling processes is unclear.@@@@1@11@@oe@16-12-2010
762382806@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
762382807@GENIA Treebank@formal@@1@S@Furthermore, p95vav synergizes with TCR stimulation in inducing NFAT- and interleukin-2-dependent transcription.@@@@1@14@@oe@16-12-2010
762382808@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
762382809@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
762382810@GENIA Treebank@formal@@1@S@We further demonstrate that the p95vav-induced NFAT activation is not mimicked by Ras activation, though its function is dependent upon Ras and Raf.@@@@1@25@@oe@16-12-2010
762382811@GENIA Treebank@formal@@1@S@Furthermore, the activating function of p95vav is blocked by FK506, suggesting that its activity also depends on calcineurin.@@@@1@21@@oe@16-12-2010
762382812@GENIA Treebank@formal@@1@S@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.@@@@1@37@@oe@16-12-2010
762382813@GENIA Treebank@formal@@1@S@However, overexpression of p95vav does not appear to influence TCR-induced protein tyrosine phosphorylation or increases in cytoplasmic free calcium.@@@@1@21@@oe@16-12-2010
762382814@GENIA Treebank@formal@@1@S@Taken together, our data suggest that p95vav plays an important role at an yet unidentified proximal position in the TCR signaling cascade.@@@@1@24@@oe@16-12-2010
762915701@GENIA Treebank@formal@@1@S@Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites.@@@@1@20@@oe@16-12-2010
762915702@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
762915703@GENIA Treebank@formal@@1@S@In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated.@@@@1@22@@oe@16-12-2010
762915704@GENIA Treebank@formal@@1@S@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.@@@@1@58@@oe@16-12-2010
762915705@GENIA Treebank@formal@@1@S@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).@@@@1@44@@oe@16-12-2010
762915706@GENIA Treebank@formal@@1@S@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.@@@@1@50@@oe@16-12-2010
762915707@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
762915708@GENIA Treebank@formal@@1@S@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.@@@@1@24@@oe@16-12-2010
762915709@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
762950801@GENIA Treebank@formal@@1@S@Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression.@@@@1@19@@oe@16-12-2010
762950802@GENIA Treebank@formal@@1@S@The class II major histocompatibility complex gene HLA-DRA is expressed in B cells, activated T lymphocytes, and in antigen-presenting cells.@@@@1@23@@oe@16-12-2010
762950803@GENIA Treebank@formal@@1@S@In addition, HLA-DRA gene expression is inducible in a variety of cell types by interferon-gamma (IFN-gamma).@@@@1@20@@oe@16-12-2010
762950804@GENIA Treebank@formal@@1@S@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.@@@@1@50@@oe@16-12-2010
762950805@GENIA Treebank@formal@@1@S@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.@@@@1@37@@oe@16-12-2010
762950806@GENIA Treebank@formal@@1@S@Thus, Oct-2A and HMG I/Y may synergize to activate HLA-DRA expression in B cells.@@@@1@16@@oe@16-12-2010
762950807@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
762950808@GENIA Treebank@formal@@1@S@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.@@@@1@37@@oe@16-12-2010
763557201@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
763557202@GENIA Treebank@formal@@1@S@The major histocompatibility (MHC) class II genes encode cell surface proteins that bind antigenic peptide for presentation to T-cells.@@@@1@22@@oe@16-12-2010
763557203@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
763557204@GENIA Treebank@formal@@1@S@Retinoblastoma protein (RB) is a tumor suppressor and functions as a transcriptional repressor by binding and inactivating the transactivator E2F-I.@@@@1@23@@oe@16-12-2010
763557205@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
763557206@GENIA Treebank@formal@@1@S@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.@@@@1@36@@oe@16-12-2010
763557207@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
763557208@GENIA Treebank@formal@@1@S@A second E2F-I binding protein, most likely DP-I, was also apparently normal in both class II-positive and -negative B-cell lines.@@@@1@23@@oe@16-12-2010
763557209@GENIA Treebank@formal@@1@S@We also examined the IFN-gamma induction of CIITA in RB-defective lines.@@@@1@12@@oe@16-12-2010
763557210@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
763557211@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
763557212@GENIA Treebank@formal@@1@S@Thus, the block in MHC class II inducibility in RB-defective cells is not due to a block in CIITA inducibility.@@@@1@22@@oe@16-12-2010
763598501@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
763598502@GENIA Treebank@formal@@1@S@Evidence for the involvement of Janus kinase 3 and interleukin-4 Stat.@@@@1@12@@oe@16-12-2010
763598503@GENIA Treebank@formal@@1@S@Germ line C transcripts can be induced by IL-4 in the human B cell line, BL-2.@@@@1@18@@oe@16-12-2010
763598504@GENIA Treebank@formal@@1@S@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.@@@@1@38@@oe@16-12-2010
763598505@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
763598506@GENIA Treebank@formal@@1@S@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.@@@@1@62@@oe@16-12-2010
763598507@GENIA Treebank@formal@@1@S@Congruous with the involvement of a Stat protein, IL-4 induced robust Janus kinase 3 (JAK3) activity in BL-2 cells.@@@@1@23@@oe@16-12-2010
763598508@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
763598509@GENIA Treebank@formal@@1@S@These results show that IL-4 NAF is IL-4 Stat, which is activated by JAK3 in response to IL-4 receptor engagement.@@@@1@22@@oe@16-12-2010
763617901@GENIA Treebank@formal@@1@S@Latent membrane protein-1 induces cyclin D2 expression, pRb hyperphosphorylation, and loss of TGF-beta 1-mediated growth inhibition in EBV-positive B cells.@@@@1@23@@oe@16-12-2010
763617902@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
763617903@GENIA Treebank@formal@@1@S@These regulators are targeted by negative growth regulatory signals, such as that provided by TGF-beta.@@@@1@17@@oe@16-12-2010
763617904@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
763617905@GENIA Treebank@formal@@1@S@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.@@@@1@47@@oe@16-12-2010
763617906@GENIA Treebank@formal@@1@S@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.@@@@1@44@@oe@16-12-2010
763617907@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
763617908@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
763619201@GENIA Treebank@formal@@1@S@Multiple signals are required for function of the human granulocyte-macrophage colony-stimulating factor gene promoter in T cells.@@@@1@18@@oe@16-12-2010
763619202@GENIA Treebank@formal@@1@S@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.@@@@1@33@@oe@16-12-2010
763619203@GENIA Treebank@formal@@1@S@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.@@@@1@40@@oe@16-12-2010
763619204@GENIA Treebank@formal@@1@S@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).@@@@1@57@@oe@16-12-2010
763619205@GENIA Treebank@formal@@1@S@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.@@@@1@48@@oe@16-12-2010
763619206@GENIA Treebank@formal@@1@S@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.@@@@1@39@@oe@16-12-2010
763619207@GENIA Treebank@formal@@1@S@Although the binding of this complex is not cyclosporin-sensitive, promoter induction is inhibited by cyclosporin treatment.@@@@1@18@@oe@16-12-2010
763619208@GENIA Treebank@formal@@1@S@A second weak inducible complex resembling nuclear factor of activated T cells (NF-AT) was also observed binding to the hCLEO region.@@@@1@24@@oe@16-12-2010
763619209@GENIA Treebank@formal@@1@S@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.@@@@1@43@@oe@16-12-2010
763619210@GENIA Treebank@formal@@1@S@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.@@@@1@41@@oe@16-12-2010
763619211@GENIA Treebank@formal@@1@S@Co-expression of Ras and calcineurin, however, did not activate the GM-CSF promoter, but required the additional expression of NF-kappa B p65.@@@@1@25@@oe@16-12-2010
763619212@GENIA Treebank@formal@@1@S@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.@@@@1@39@@oe@16-12-2010
763697701@GENIA Treebank@formal@@1@S@C/EBP proteins activate transcription from the human immunodeficiency virus type 1 long terminal repeat in macrophages/monocytes.@@@@1@17@@oe@16-12-2010
763697702@GENIA Treebank@formal@@1@S@Three binding sites for C/EBP proteins are found in the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) (V.M. Tesmer, A.Rajadhyaksha, J.Babin, and M.Bina, Proc.Natl.Acad.Sci. USA 90:7298-7302, 1993).@@@@1@44@@oe@16-12-2010
763697703@GENIA Treebank@formal@@1@S@We have determined the functional role of C/EBP proteins and C/EBP sites in regulating transcription from the HIV- 1 LTR in monocytes/macrophages.@@@@1@22@@oe@16-12-2010
763697704@GENIA Treebank@formal@@1@S@Inhibition of endogenous C/EBP proteins, using either an excess of C/EBP binding sites or a trans- dominant negative inhibitor, demonstrated that C/EBP proteins are required for basal and activated levels of HIV-1 LTR transcription in the promonocytic cell line U937.@@@@1@42@@oe@16-12-2010
763697705@GENIA Treebank@formal@@1@S@Northern (RNA) blots and binding assays showed that NF-IL6 is the only known C/EBP family member which is increased when U937 cells are activated.@@@@1@27@@oe@16-12-2010
763697706@GENIA Treebank@formal@@1@S@Mutational analyses of the HIV-1 LTR showed that one C/EBP site is required for normal LTR transcription both before and after cellular activation and that the two 3' C/EBP sites are functionally equivalent.@@@@1@34@@oe@16-12-2010
763697707@GENIA Treebank@formal@@1@S@However, transcription from crippled HIV-1 LTRs lacking C/EBP sites can still be induced following activation of U937 cells.@@@@1@20@@oe@16-12-2010
763697708@GENIA Treebank@formal@@1@S@Several models are suggested for how elevated NF-IL6 may participate in an autostimulatory loop involving HIV infection, macrophage activation, cytokine expression, and HIV replication.@@@@1@28@@oe@16-12-2010
763780901@GENIA Treebank@formal@@1@S@An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes.@@@@1@12@@oe@16-12-2010
763780902@GENIA Treebank@formal@@1@S@Lymphocytes are particularly susceptible to DNA damage-induced apoptosis, a response which may serve as a form of 'altruistic suicide' to counter their intrinsic high potential for mutation and clonal expansion.@@@@1@34@@oe@16-12-2010
763780903@GENIA Treebank@formal@@1@S@The tumour suppressor p53 has been shown to regulate this type of apoptosis in thymocytes, but an as yet unknown, p53-independent pathway(s) appears to mediate the same event in mitogen-activated mature T lymphocytes.@@@@1@39@@oe@16-12-2010
763780904@GENIA Treebank@formal@@1@S@Here we show DNA damage-induced apoptosis in these T lymphocytes is dependent on the antioncogenic transcription factor interferon regulatory factor (IRF)-1.@@@@1@25@@oe@16-12-2010
763780905@GENIA Treebank@formal@@1@S@Thus two different anti-onco-genic transcription factors, p53 and IRF-1, are required for distinct apoptotic pathways in T lymphocytes.@@@@1@21@@oe@16-12-2010
763780906@GENIA Treebank@formal@@1@S@We also show that mitogen induction of the interleukin-1 beta converting enzyme (ICE) gene, a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, is IRF-1-dependent.@@@@1@32@@oe@16-12-2010
763780907@GENIA Treebank@formal@@1@S@Ectopic overexpression of IRF-1 results in the activation of the endogenous gene for ICE and enhances the sensitivity of cells to radiation-induced apoptosis.@@@@1@24@@oe@16-12-2010
763817301@GENIA Treebank@formal@@1@S@Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity.@@@@1@13@@oe@16-12-2010
763817302@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
763817303@GENIA Treebank@formal@@1@S@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.@@@@1@24@@oe@16-12-2010
763817304@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
763817305@GENIA Treebank@formal@@1@S@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.@@@@1@32@@oe@16-12-2010
763817306@GENIA Treebank@formal@@1@S@These results suggest that the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter activity in a chromatin-dependent manner.@@@@1@19@@oe@16-12-2010
763817307@GENIA Treebank@formal@@1@S@We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation.@@@@1@20@@oe@16-12-2010
763817308@GENIA Treebank@formal@@1@S@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.@@@@1@42@@oe@16-12-2010
763818601@GENIA Treebank@formal@@1@S@Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes.@@@@1@13@@oe@16-12-2010
763818602@GENIA Treebank@formal@@1@S@Interleukin 12 (IL-12) is an important immunoregulatory cytokine whose receptor is a member of the hematopoietin receptor superfamily.@@@@1@21@@oe@16-12-2010
763818603@GENIA Treebank@formal@@1@S@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.@@@@1@39@@oe@16-12-2010
763818604@GENIA Treebank@formal@@1@S@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.@@@@1@40@@oe@16-12-2010
763818605@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
763818606@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
763818607@GENIA Treebank@formal@@1@S@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.@@@@1@25@@oe@16-12-2010
763820901@GENIA Treebank@formal@@1@S@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.@@@@1@27@@oe@16-12-2010
763820902@GENIA Treebank@formal@@1@S@Chronic myelogenous leukemia evolves in two clinically distinct stages: a chronic and a blast crisis phase.@@@@1@18@@oe@16-12-2010
763820903@GENIA Treebank@formal@@1@S@The molecular changes associated with chronic phase to blast crisis transition are largely unknown.@@@@1@15@@oe@16-12-2010
763820904@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
763820905@GENIA Treebank@formal@@1@S@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.@@@@1@63@@oe@16-12-2010
763820906@GENIA Treebank@formal@@1@S@DR-nm23 mRNA is preferentially expressed at early stages of myeloid differentiation of highly purified CD34+ cells.@@@@1@17@@oe@16-12-2010
763820907@GENIA Treebank@formal@@1@S@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.@@@@1@38@@oe@16-12-2010
763820908@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
764030101@GENIA Treebank@formal@@1@S@Transcription factors as targets for oxidative signalling during lymphocyte activation.@@@@1@11@@oe@16-12-2010
764030102@GENIA Treebank@formal@@1@S@We previously have demonstrated a requirement for oxidative events during cell cycle entry in T lymphocytes and have hypothesised that reactive oxygen species may act as intracellular signalling agents during lymphocyte activation.@@@@1@33@@oe@16-12-2010
764030103@GENIA Treebank@formal@@1@S@In the current study, cysteamine, an aminothiol compound with antioxidant activity, has been used to further investigate the role of oxidative signalling during lymphocyte activation.@@@@1@29@@oe@16-12-2010
764030104@GENIA Treebank@formal@@1@S@Treatment of normal human peripheral blood lymphocytes with cysteamine in vitro was found to inhibit proliferation in a dose-dependent manner, with essentially complete inhibition occurring at a dose of 400 microM.@@@@1@33@@oe@16-12-2010
764030105@GENIA Treebank@formal@@1@S@This inhibitory effect was limited to the first 2 h after mitogenic activation, localizing the time-frame of action of cysteamine to within the commitment period.@@@@1@27@@oe@16-12-2010
764030106@GENIA Treebank@formal@@1@S@It therefore was of interest to establish which, if any, commitment events were affected by oxidative signalling during cell cycle entry.@@@@1@24@@oe@16-12-2010
764030107@GENIA Treebank@formal@@1@S@Taking the IL-2 gene as a candidate, we examined the effect of cysteamine treatment on early gene expression during lymphocyte activation, and on the activity of transcription factors AP-1, NF-kappa B, NF-AT and Oct1, whose functions are required for expression of the IL-2 mRNA.@@@@1@50@@oe@16-12-2010
764030108@GENIA Treebank@formal@@1@S@Cysteamine treatment inhibited both expression of the IL-2 mRNA and secretion of IL-2 into the culture medium.@@@@1@18@@oe@16-12-2010
764030109@GENIA Treebank@formal@@1@S@The inhibitory effect of cysteamine may be mediated at least in part by an effect on transcription factor function, as the DNA binding activities of AP-1 and NF-kappa B extracted from mitogen-stimulated cells were significantly inhibited by cysteamine treatment.@@@@1@41@@oe@16-12-2010
764030110@GENIA Treebank@formal@@1@S@Interestingly, Oct1 and NF-AT DNA binding activity were not affected by cysteamine treatment, suggesting that oxidative signalling processes operate in a selective manner.@@@@1@26@@oe@16-12-2010
764030111@GENIA Treebank@formal@@1@S@The identification of regulatory proteins, such as transcription factors, as molecular targets for oxidative signalling provides further evidence to implicate oxidative signalling as being intimately involved in the G0 to G1 phase transition in T lymphocytes.@@@@1@39@@oe@16-12-2010
764030201@GENIA Treebank@formal@@1@S@Regulation of c-jun mRNA expression by hydroxyurea in human K562 cells during erythroid differentiation [published erratum appears in Biochim Biophys Acta 1995 Dec 27;1264(3):409]@@@@1@33@@oe@16-12-2010
764030202@GENIA Treebank@formal@@1@S@Hydroxyurea (HU) is an antitumor agent which also induces hemoglobinization during erythroid differentiation.@@@@1@16@@oe@16-12-2010
764030203@GENIA Treebank@formal@@1@S@In addition, HU stimulates the synthesis of fetal hemoglobin in sickle cell anemia patients.@@@@1@16@@oe@16-12-2010
764030204@GENIA Treebank@formal@@1@S@To further understand its mechanism of action, we investigated the effects of HU on regulation of c-jun expression prior to the onset of erythroid differentiation of K562 cells.@@@@1@30@@oe@16-12-2010
764030205@GENIA Treebank@formal@@1@S@HU induced a dose-dependent stimulation of c-jun synthesis.@@@@1@9@@oe@16-12-2010
764030206@GENIA Treebank@formal@@1@S@The levels of c-jun mRNA was elevated 4 to 7.5-fold by HU within 2 h.@@@@1@16@@oe@16-12-2010
764030207@GENIA Treebank@formal@@1@S@This was followed by a gradual decline to the basal level by 24 h.@@@@1@15@@oe@16-12-2010
764030208@GENIA Treebank@formal@@1@S@Both nuclear run-on and actinomycin D pulse experiments strongly indicate that HU regulates c-jun mRNA expression by increasing the rate of synthesis as well as stabilizing the c-jun mRNA.@@@@1@30@@oe@16-12-2010
764030209@GENIA Treebank@formal@@1@S@In addition, the level of jun protein was elevated by 2 to 5-fold within 4 h in HU treated cells.@@@@1@22@@oe@16-12-2010
764030210@GENIA Treebank@formal@@1@S@Furthermore, concentrations of HU below 250 microM slightly increased the 5X AP-1/CAT activity.@@@@1@15@@oe@16-12-2010
764030211@GENIA Treebank@formal@@1@S@These results strongly suggest that HU induces both transcriptional and post-transcription regulation of c-jun during erythroid differentiation.@@@@1@18@@oe@16-12-2010
764131901@GENIA Treebank@formal@@1@S@Characterization of 5' end of human thromboxane receptor gene.@@@@1@10@@oe@16-12-2010
764131902@GENIA Treebank@formal@@1@S@Organizational analysis and mapping of protein kinase C--responsive elements regulating expression in platelets.@@@@1@16@@oe@16-12-2010
764131903@GENIA Treebank@formal@@1@S@Platelet thromboxane receptors are acutely and reversibly upregulated after acute myocardial infarction.@@@@1@13@@oe@16-12-2010
764131904@GENIA Treebank@formal@@1@S@To determine if platelet thromboxane receptors are under transcriptional control, we isolated and characterized human genomic DNA clones containing the 5' flanking region of the thromboxane receptor gene.@@@@1@30@@oe@16-12-2010
764131905@GENIA Treebank@formal@@1@S@The exon-intron structure of the 5' portion of the thromboxane receptor gene was determined initially by comparing the nucleotide sequence of the 5' flanking genomic clone with that of a novel human uterine thromboxane receptor cDNA that extended the mRNA 141 bp further upstream than the previously identified human placental cDNA.@@@@1@52@@oe@16-12-2010
764131906@GENIA Treebank@formal@@1@S@A major transcription initiation site was located in three human tissues approximately 560 bp upstream from the translation initiation codon and 380 bp upstream from any previously identified transcription initiation site.@@@@1@32@@oe@16-12-2010
764131907@GENIA Treebank@formal@@1@S@The thromboxane receptor gene has neither a TATA nor a CAAT consensus site.@@@@1@14@@oe@16-12-2010
764131908@GENIA Treebank@formal@@1@S@Promoter function of the 5' flanking region of the thromboxane receptor gene was evaluated by transfection of thromboxane receptor gene promoter/chloramphenicol acetyltransferase (CAT) chimera plasmids into platelet-like K562 cells.@@@@1@32@@oe@16-12-2010
764131909@GENIA Treebank@formal@@1@S@Thromboxane receptor promoter activity, as assessed by CAT expression, was relatively weak but was significantly enhanced by phorbol ester treatment.@@@@1@23@@oe@16-12-2010
764131910@GENIA Treebank@formal@@1@S@Functional analysis of 5' deletion constructs in transfected K562 cells and gel mobility shift localized the major phorbol ester-responsive motifs in the thromboxane receptor gene promoter to a cluster of activator protein-2 (AP-2) binding consensus sites located approximately 1.8 kb 5' from the transcription initiation site.@@@@1@49@@oe@16-12-2010
764131911@GENIA Treebank@formal@@1@S@These studies are the first to determine the structure and organization of the 5' end of the thromboxane receptor gene and demonstrate that thromboxane receptor gene expression can be regulated by activation of protein kinase C via induction of an AP-2-like nuclear factor binding to upstream promoter elements.@@@@1@49@@oe@16-12-2010
764131912@GENIA Treebank@formal@@1@S@These findings strongly suggest that the mechanism for previously described upregulation of platelet thromboxane receptors after acute myocardial infarction is increased thromboxane receptor gene transcription in platelet-progenitor cells.@@@@1@29@@oe@16-12-2010
764169201@GENIA Treebank@formal@@1@S@IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase.@@@@1@16@@oe@16-12-2010
764169202@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
764169203@GENIA Treebank@formal@@1@S@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.@@@@1@37@@oe@16-12-2010
764169204@GENIA Treebank@formal@@1@S@Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity, followed by the activation of phospholipase A2 and 5-lipoxygenase.@@@@1@25@@oe@16-12-2010
764169205@GENIA Treebank@formal@@1@S@Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-kappa B activation.@@@@1@19@@oe@16-12-2010
764169206@GENIA Treebank@formal@@1@S@These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway.@@@@1@19@@oe@16-12-2010
764190301@GENIA Treebank@formal@@1@S@Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor behavior.@@@@1@19@@oe@16-12-2010
764190302@GENIA Treebank@formal@@1@S@OBJECTIVE: To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters, as well as on the androgen receptor status, in hirsute women.@@@@1@33@@oe@16-12-2010
764190303@GENIA Treebank@formal@@1@S@DESIGN: Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide, three times per day for 12 months.@@@@1@27@@oe@16-12-2010
764190304@GENIA Treebank@formal@@1@S@Barrier or intrauterine contraception was used during the study in sexually active women.@@@@1@14@@oe@16-12-2010
764190305@GENIA Treebank@formal@@1@S@Safety parameters were assessed throughout the study.@@@@1@8@@oe@16-12-2010
764190306@GENIA Treebank@formal@@1@S@Hirsutism, graded by the modified Ferriman-Gallwey score, and hormonal parameters were evaluated basally and at 4-month intervals during treatment.@@@@1@22@@oe@16-12-2010
764190307@GENIA Treebank@formal@@1@S@Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy.@@@@1@18@@oe@16-12-2010
764190308@GENIA Treebank@formal@@1@S@In addition, the concentration of androgen receptors in mononuclear leukocytes was measured, in both the follicular and luteal phases of the menstrual cycle, basally and after 4 months of flutamide treatment.@@@@1@35@@oe@16-12-2010
764190309@GENIA Treebank@formal@@1@S@RESULTS: Flutamide was well tolerated in all women, with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy.@@@@1@28@@oe@16-12-2010
764190310@GENIA Treebank@formal@@1@S@Hirsutism markedly improved in all women during the treatment (Ferriman-Gallwey score after 1 year: 4.1 +/- 0.5 versus 14.1 +/- 0.9).@@@@1@25@@oe@16-12-2010
764190311@GENIA Treebank@formal@@1@S@A reduction of serum androgens was found, whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH.@@@@1@30@@oe@16-12-2010
764190312@GENIA Treebank@formal@@1@S@Cycles remained ovulatory.@@@@1@4@@oe@16-12-2010
764190313@GENIA Treebank@formal@@1@S@Before treatment, the number of androgen receptors was higher in the luteal than in the follicular phase.@@@@1@19@@oe@16-12-2010
764190314@GENIA Treebank@formal@@1@S@This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug.@@@@1@14@@oe@16-12-2010
764190315@GENIA Treebank@formal@@1@S@CONCLUSIONS: Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function.@@@@1@18@@oe@16-12-2010
764190316@GENIA Treebank@formal@@1@S@Androgen receptor blockade might be potentiated by a reduction of serum androgens.@@@@1@13@@oe@16-12-2010
764190317@GENIA Treebank@formal@@1@S@Flutamide affects androgen receptor behavior during the menstrual cycle.@@@@1@10@@oe@16-12-2010
764190318@GENIA Treebank@formal@@1@S@The meaning of this finding remains to be elucidated .@@@@1@10@@oe@16-12-2010
764261501@GENIA Treebank@formal@@1@S@HIV-1 envelope glycoproteins induce activation of activated protein-1 in CD4+ T cells [published erratum appears in J Biol Chem 1995 Dec 1;270(48):29038]@@@@1@31@@oe@16-12-2010
764261502@GENIA Treebank@formal@@1@S@Activation of CD4 positive T cells is a primary requirement for human immunodeficiency virus (HIV) entry, efficient HIV replication, and progression to AIDS,@@@@1@28@@oe@16-12-2010
764261503@GENIA Treebank@formal@@1@S@Utilizing CD4 positive T cell lines and purified T cells from normal individuals, we have demonstrated that native envelope glycoproteins of HIV, gp 160, can induce activation of transcription factor, activated protein-1 (AP-1).@@@@1@40@@oe@16-12-2010
764261504@GENIA Treebank@formal@@1@S@The stimulatory effects of gp160 are mediated through the CD4 molecule, since treatment of gp160 with soluble CD4-IgG abrogates its activity, and CD4 negative T cell lines fail to be stimulated with gp160.@@@@1@36@@oe@16-12-2010
764261505@GENIA Treebank@formal@@1@S@Immunoprecipitation of the gp 160-induced nuclear extracts with polyclonal antibodies to Fos and Jun proteins indicates that AP-1 complex is comprised of members of these family of proteins.@@@@1@29@@oe@16-12-2010
764261506@GENIA Treebank@formal@@1@S@The gp160-induced AP-1 complex is dependent upon protein tyrosine phosphorylation and is protein synthesis-independent.@@@@1@15@@oe@16-12-2010
764261507@GENIA Treebank@formal@@1@S@This stimulation can also be abolished by inhibitors of protein kinase C, but it is unaffected by calcium channel blocker or cyclosporine A.@@@@1@25@@oe@16-12-2010
764261508@GENIA Treebank@formal@@1@S@This gp160 treatment adversely affects the functional capabilities of T cells: pre-treatment of CD4+ T cells with gp160 for 4 h at 37 degrees C inhibited anti-CD3-induced interleukin-2 secretion.@@@@1@31@@oe@16-12-2010
764261509@GENIA Treebank@formal@@1@S@Effects similar to gp160 were seen with anti-CD4 mAb.@@@@1@10@@oe@16-12-2010
764261510@GENIA Treebank@formal@@1@S@The aberrant activation of AP-1 by gp160 in CD4 positive T cells could result in up-regulation of cytokines containing AP-1 sites, e.g. interleukin-3 and granulocyte macrophage colony-stimulating factor, and concurrently lead to T cell unresponsiveness by inhibiting interleukin-2 secretion.@@@@1@42@@oe@16-12-2010
764301501@GENIA Treebank@formal@@1@S@Cellular and molecular mechanisms of IFN-gamma production induced by IL-2 and IL-12 in a human NK cell line.@@@@1@19@@oe@16-12-2010
764301502@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
764301503@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
764301504@GENIA Treebank@formal@@1@S@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.@@@@1@46@@oe@16-12-2010
764301505@GENIA Treebank@formal@@1@S@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.@@@@1@43@@oe@16-12-2010
764301506@GENIA Treebank@formal@@1@S@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.@@@@1@35@@oe@16-12-2010
764301507@GENIA Treebank@formal@@1@S@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.@@@@1@46@@oe@16-12-2010
764301508@GENIA Treebank@formal@@1@S@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.@@@@1@28@@oe@16-12-2010
764301509@GENIA Treebank@formal@@1@S@In contrast, IL-12 induction of IFN-gamma cytoplasmic mRNA appears to only partially depend on activation of protein kinase C.@@@@1@21@@oe@16-12-2010
764301510@GENIA Treebank@formal@@1@S@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.@@@@1@26@@oe@16-12-2010
764301511@GENIA Treebank@formal@@1@S@It also was observed that suppression of cytokine gene expression by these agents was independent of the inhibition of proliferation.@@@@1@21@@oe@16-12-2010
764301512@GENIA Treebank@formal@@1@S@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.@@@@1@37@@oe@16-12-2010
764301513@GENIA Treebank@formal@@1@S@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.@@@@1@47@@oe@16-12-2010
764520801@GENIA Treebank@formal@@1@S@Infection and replication of Tat- human immunodeficiency viruses: genetic analyses of LTR and tat mutations in primary and long-term human lymphoid cells.@@@@1@24@@oe@16-12-2010
764520802@GENIA Treebank@formal@@1@S@Tat is an essential regulatory protein for the replication of human immunodeficiency virus (HIV).@@@@1@17@@oe@16-12-2010
764520803@GENIA Treebank@formal@@1@S@Mutations in the tat gene have been shown to block HIV replication in human T cells.@@@@1@17@@oe@16-12-2010
764520804@GENIA Treebank@formal@@1@S@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.@@@@1@50@@oe@16-12-2010
764520805@GENIA Treebank@formal@@1@S@It is possible that Tat is also needed for other functions during HIV replication.@@@@1@15@@oe@16-12-2010
764520806@GENIA Treebank@formal@@1@S@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.@@@@1@40@@oe@16-12-2010
764520807@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
764520808@GENIA Treebank@formal@@1@S@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.@@@@1@24@@oe@16-12-2010
764520809@GENIA Treebank@formal@@1@S@Large amounts of viral RNA and particles were synthesized in infections established using the tat mutants that contain modified LTRs.@@@@1@21@@oe@16-12-2010
764520810@GENIA Treebank@formal@@1@S@However, this efficient propagation of the LTR-modified tat mutants was restricted to some lymphoid cell lines that have been transformed with other viruses.@@@@1@25@@oe@16-12-2010
764520811@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
764520812@GENIA Treebank@formal@@1@S@Direct sequencing of the viral genomes and reinfection kinetics showed no evidence of wild-type reversion even after prolonged infection with the Tat- virus.@@@@1@24@@oe@16-12-2010
764520813@GENIA Treebank@formal@@1@S@The implications for in vivo HIV-1 replication and potential application of this system to the study of alternative Tat function are discussed.@@@@1@23@@oe@16-12-2010
764523701@GENIA Treebank@formal@@1@S@Restoration of the Epstein-Barr virus ZEBRA protein's capacity to disrupt latency by the addition of heterologous activation regions.@@@@1@20@@oe@16-12-2010
764523702@GENIA Treebank@formal@@1@S@The ZEBRA protein has a unique biological function among herpesviral proteins.@@@@1@12@@oe@16-12-2010
764523703@GENIA Treebank@formal@@1@S@It is responsible for the disruption of Epstein-Barr virus (EBV) latency and the induction of the lytic cycle.@@@@1@21@@oe@16-12-2010
764523704@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
764523705@GENIA Treebank@formal@@1@S@We have employed the ZEBRA/EBV biological system to test whether a heterologous activation domain can substitute for another activation domain (the ZEBRA domain).@@@@1@26@@oe@16-12-2010
764523706@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
764523707@GENIA Treebank@formal@@1@S@Both chimeras were found to transactivate model and native promoters at equivalent or better levels than ZEBRA itself.@@@@1@19@@oe@16-12-2010
764523708@GENIA Treebank@formal@@1@S@Activation was not target- or cell-type dependent, nor was it dependent on the presence of virus.@@@@1@18@@oe@16-12-2010
764523709@GENIA Treebank@formal@@1@S@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.@@@@1@30@@oe@16-12-2010
764523710@GENIA Treebank@formal@@1@S@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.@@@@1@29@@oe@16-12-2010
764700101@GENIA Treebank@formal@@1@S@Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down's syndrome.@@@@1@17@@oe@16-12-2010
764700102@GENIA Treebank@formal@@1@S@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.@@@@1@31@@oe@16-12-2010
764700103@GENIA Treebank@formal@@1@S@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.@@@@1@34@@oe@16-12-2010
764700104@GENIA Treebank@formal@@1@S@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.@@@@1@38@@oe@16-12-2010
764700105@GENIA Treebank@formal@@1@S@We also found that mRNAs encoding GATA-1 and GATA-2 are expressed in all these cases.@@@@1@16@@oe@16-12-2010
764700106@GENIA Treebank@formal@@1@S@These results suggest that M7 blasts and TMD blasts correspond to the erythroid/megakaryocytic bipotential progenitor cells.@@@@1@17@@oe@16-12-2010