983774501@GENIA Treebank@formal@@1@S@Interleukin-12 expression in B cells by transformation with Epstein-Barr virus.@@@@1@11@@oe@16-12-2010 983774502@GENIA Treebank@formal@@1@S@Although interleukin (IL)-12 was originally purified from an Epstein-Barr (EBV)-transformed B cell line and the high correlation of EBV infection and IL-12 expression has been suggested, no study has reported whether EBV infection is directly linked to IL-12 expression.@@@@1@47@@oe@16-12-2010 983774503@GENIA Treebank@formal@@1@S@To address this issue, we have investigated IL-12 expression in B cells during in vitro transformation with EBV.@@@@1@20@@oe@16-12-2010 983774504@GENIA Treebank@formal@@1@S@Human peripheral B cells became capable of constitutively producing p40 by in vitro transformation with EBV, coincident with the expression of latent membrane protein 1 (LMP1) of EBV.@@@@1@32@@oe@16-12-2010 983774505@GENIA Treebank@formal@@1@S@These B cells expressed p40 and p35 mRNA, and phorbol myristate acetate (PMA) stimulation strongly enhanced p40 and p70 production.@@@@1@24@@oe@16-12-2010 983774506@GENIA Treebank@formal@@1@S@Furthermore, transfection with LMP1 expression vector into a human B lymphoma cell line, Daudi, led to p40 production with nuclear factor (NF)-kappaB activation.@@@@1@30@@oe@16-12-2010 983774507@GENIA Treebank@formal@@1@S@These results suggest that transformation of primary B cells with EBV induces IL-12 expression potentially through LMP1 expression.@@@@1@19@@oe@16-12-2010 983774508@GENIA Treebank@formal@@1@S@Copyright 1998 Academic Press.@@@@1@5@@oe@16-12-2010 983800001@GENIA Treebank@formal@@1@S@Conserved elements containing NF-E2 and tandem GATA binding sites are required for erythroid-specific chromatin structure reorganization within the human beta-globin locus control region.@@@@1@24@@oe@16-12-2010 983800002@GENIA Treebank@formal@@1@S@Proper expression of the genes of the human beta-globin gene locus requires the associated locus control region (LCR).@@@@1@21@@oe@16-12-2010 983800003@GENIA Treebank@formal@@1@S@Structurally, the LCR is defined by the presence of four domains of erythroid-specific chromatin structure.@@@@1@17@@oe@16-12-2010 983800004@GENIA Treebank@formal@@1@S@These domains, which have been characterized as DNase I hypersensitive sites (HSs), comprise the active elements of the LCR.@@@@1@24@@oe@16-12-2010 983800005@GENIA Treebank@formal@@1@S@The major focus of this research is to define the cis -acting elements which are required for the formation of these domains of unique chromatin structure.@@@@1@26@@oe@16-12-2010 983800006@GENIA Treebank@formal@@1@S@Our previous investigations on the formation of LCR HS4 demonstrated that NF-E2 and tandem, inverted GATA binding sites are required for the formation of the native HS.@@@@1@29@@oe@16-12-2010 983800007@GENIA Treebank@formal@@1@S@Similarly arranged NF-E2 and tandem GATA sites are present within the core regions of the other human LCR HSs and are evolutionarily conserved.@@@@1@24@@oe@16-12-2010 983800008@GENIA Treebank@formal@@1@S@Using site-directed mutagenesis of human HSs 2 and 3 we have tested the hypothesis that these NF-E2 and GATA sites are common requirements for the formation of all LCR HSs.@@@@1@31@@oe@16-12-2010 983800009@GENIA Treebank@formal@@1@S@We find that mutation of these elements, and particularly the GATA elements, results in a decrease or complete loss of DNase I hypersensitivity.@@@@1@26@@oe@16-12-2010 983800010@GENIA Treebank@formal@@1@S@These data imply the presence of common structural elements within the core of each LCR HS which are required for erythroid-specific chromatin structure reorganization.@@@@1@25@@oe@16-12-2010 983806101@GENIA Treebank@formal@@1@S@Anaphylatoxins C5a and C3a induce nuclear factor kappaB activation in human peripheral blood monocytes.@@@@1@15@@oe@16-12-2010 983806102@GENIA Treebank@formal@@1@S@The anaphylatoxins C5a and C3a are involved in the regulation of cytokine production.@@@@1@14@@oe@16-12-2010 983806103@GENIA Treebank@formal@@1@S@In this study the capability of C5a and C3a to induce transcription factor activation was examined.@@@@1@17@@oe@16-12-2010 983806104@GENIA Treebank@formal@@1@S@C5a and C3a stimulation of human peripheral blood monocytes resulted in nuclear expression of a DNA binding activity with specificity to the kappaB sequence.@@@@1@25@@oe@16-12-2010 983806105@GENIA Treebank@formal@@1@S@The p50 and p65 proteins, constituents of the prototypic nuclear factor kappaB, were identified as components of the DNA-protein complexes by anti-peptide antibodies in gel supershift assays.@@@@1@30@@oe@16-12-2010 983806106@GENIA Treebank@formal@@1@S@C5a induced kappaB binding activity was detected 15 min after agonist stimulation, peaked at 30-40 min, and remained detectable at 2 h.@@@@1@25@@oe@16-12-2010 983806107@GENIA Treebank@formal@@1@S@Binding to kappaB sequence was accompanied by an initial decrease and subsequent increase in the cytoplasmic IkappaBalpha levels, as detected by Western blotting using an anti-IkappaBalpha antibody.@@@@1@29@@oe@16-12-2010 983806108@GENIA Treebank@formal@@1@S@Pertussis toxin treatment markedly decreased kappaB binding activities induced by both C5a and C3a, whereas cholera toxin displayed no inhibitory effect.@@@@1@23@@oe@16-12-2010 983806109@GENIA Treebank@formal@@1@S@Neither of the two toxins affected kappaB binding activity induced by TNFalpha in the same cells.@@@@1@17@@oe@16-12-2010 983806110@GENIA Treebank@formal@@1@S@These results imply a potential role of the anaphylatoxins C5a and C3a in regulating leukocytes gene expression through G protein-coupled transcription factor activation.@@@@1@24@@oe@16-12-2010 984092401@GENIA Treebank@formal@@1@S@Tpl-2 induces IL-2 expression in T-cell lines by triggering multiple signaling pathways that activate NFAT and NF-kappaB.@@@@1@18@@oe@16-12-2010 984092402@GENIA Treebank@formal@@1@S@The Tpl-2 kinase activates the nuclear factor of activated T cells (NFAT) and induces IL-2 expression in T-cell lines.@@@@1@22@@oe@16-12-2010 984092403@GENIA Treebank@formal@@1@S@Here we show that the activation of the IL-2 promoter by Tpl-2 is inhibited by mutant signaling molecules that inhibit the mitogen-activated protein kinase (MAPK) or the calcineurin/NFAT pathways and is promoted by combinations of signaling molecules that activate these pathways.@@@@1@44@@oe@16-12-2010 984092404@GENIA Treebank@formal@@1@S@We, therefore, conclude that signals generated by the convergence of the MAPK and the calcineurin/NFAT pathway are necessary and sufficient for the activation of the IL-2 promoter by Tpl-2.@@@@1@32@@oe@16-12-2010 984092405@GENIA Treebank@formal@@1@S@The activation of both the IL-2 promoter and an NFAT-driven minimal promoter were shown to depend on signals transduced by Raf1.@@@@1@22@@oe@16-12-2010 984092406@GENIA Treebank@formal@@1@S@However, it was only the IL-2 promoter whose activation by Tpl-2 was fully blocked by the dominant negative mutant MEK1S218/222A and the MEK1/MEK2 inhibitor PD098059.@@@@1@27@@oe@16-12-2010 984092407@GENIA Treebank@formal@@1@S@Since the activation of NFAT is MAPK-dependent these findings suggested that the activation of MAPK by Tpl-2 is either independent or only partially dependent on MEK1 and MEK2.@@@@1@29@@oe@16-12-2010 984092408@GENIA Treebank@formal@@1@S@In addition, they suggested that the activation of the IL-2 promoter is under the control of not only NFAT but also a second factor whose activation is MEK-dependent.@@@@1@30@@oe@16-12-2010 984092409@GENIA Treebank@formal@@1@S@Experiments in COS-1 and EL-4 cells confirmed both hypotheses and revealed that the second factor activated by Tpl-2 is NF-kappaB.@@@@1@21@@oe@16-12-2010 984092410@GENIA Treebank@formal@@1@S@While the activation of the IL-2 promoter and an NFAT-driven minimal promoter by Tpl-2 was fully blocked by the dominant negative mutant NFAT delta418, it was only partially blocked by the calcineurin inhibitor cyclosporin A suggesting that the Tpl-2-mediated NFAT activation is under the control of a combination of calcineurin-dependent and independent pathways.@@@@1@55@@oe@16-12-2010 984092411@GENIA Treebank@formal@@1@S@Both pathways were fully blocked by Bcl-2 or Bcl-X(L).@@@@1@10@@oe@16-12-2010 984296301@GENIA Treebank@formal@@1@S@Heterogeneous expression of the lipocalin NGAL in primary breast cancers.@@@@1@11@@oe@16-12-2010 984296302@GENIA Treebank@formal@@1@S@We have previously shown that neu oncogene-initiated rat mammary carcinomas uniquely over-express neu-related lipocalin (NRL), a member of the calycin protein superfamily.@@@@1@26@@oe@16-12-2010 984296303@GENIA Treebank@formal@@1@S@Here, we characterize the putative human homolog of NRL, neutrophil gelatinase-associated lipocalin (NGAL).@@@@1@18@@oe@16-12-2010 984296304@GENIA Treebank@formal@@1@S@ngal gene expression was found at moderate levels in only 2 of 17 human tissues examined, breast and lung.@@@@1@21@@oe@16-12-2010 984296305@GENIA Treebank@formal@@1@S@When breast cancers were examined for NGAL mRNA and protein levels, they were found to exhibit heterogeneous expression.@@@@1@20@@oe@16-12-2010 984296306@GENIA Treebank@formal@@1@S@NGAL levels varied in these tumors from undetectable to exceeding those in normal breast parenchyma.@@@@1@16@@oe@16-12-2010 984296307@GENIA Treebank@formal@@1@S@Immuno-histochemical analysis confirmed the presence of NGAL within breast carcinoma cells but detected only low levels of this protein in normal ductal epithelium.@@@@1@24@@oe@16-12-2010 984296308@GENIA Treebank@formal@@1@S@In contrast, large amounts of the protein were localized to the lumen of normal breast ducts in the vicinity of NGAL-expressing tumors.@@@@1@24@@oe@16-12-2010 984296309@GENIA Treebank@formal@@1@S@Interestingly, unlike NRL in rat mammary carcinomas, no significant association between NGAL expression and HER-2/neu activation was found in human breast tumors.@@@@1@25@@oe@16-12-2010 984296310@GENIA Treebank@formal@@1@S@In contrast, a significant correlation between NGAL expression in breast cancer was found with several other markers of poor prognosis, including estrogen and progesterone receptor-negative status and high proliferation (S-phase fraction).@@@@1@36@@oe@16-12-2010 984296311@GENIA Treebank@formal@@1@S@NGAL levels were stratified as high or low in breast cancers from a cohort of node-positive patients with known outcome.@@@@1@21@@oe@16-12-2010 984296312@GENIA Treebank@formal@@1@S@No significant association between NGAL expression and disease-free or overall survival was observed.@@@@1@14@@oe@16-12-2010 984384001@GENIA Treebank@formal@@1@S@Activation of human macrophages by mechanical ventilation in vitro.@@@@1@10@@oe@16-12-2010 984384002@GENIA Treebank@formal@@1@S@Positive-pressure mechanical ventilation supports gas exchange in patients with respiratory failure but is also responsible for significant lung injury.@@@@1@20@@oe@16-12-2010 984384003@GENIA Treebank@formal@@1@S@In this study, we have developed an in vitro model in which isolated lung cells can be submitted to a prolonged cyclic pressure-stretching strain resembling that of conventional mechanical ventilation.@@@@1@32@@oe@16-12-2010 984384004@GENIA Treebank@formal@@1@S@In this model, cells cultured on a Silastic membrane were elongated up to 7% of their initial diameter, corresponding to a 12% increase in cell surface.@@@@1@31@@oe@16-12-2010 984384005@GENIA Treebank@formal@@1@S@The lung macrophage was identified as the main cellular source for critical inflammatory mediators such as tumor necrosis factor-alpha, the chemokines interleukin (IL)-8 and -6, and matrix metalloproteinase-9 in this model system of mechanical ventilation.@@@@1@41@@oe@16-12-2010 984384006@GENIA Treebank@formal@@1@S@These mediators were measured in supernatants from ventilated alveolar macrophages, monocyte-derived macrophages, and promonocytic THP-1 cells.@@@@1@19@@oe@16-12-2010 984384007@GENIA Treebank@formal@@1@S@Nuclear factor-kappaB was found to be activated in ventilated macrophages.@@@@1@11@@oe@16-12-2010 984384008@GENIA Treebank@formal@@1@S@Synergistic proinflammatory effects of mechanical stress and molecules such as bacterial endotoxin were observed, suggesting that mechanical ventilation might be particularly deleterious in preinjured or infected lungs.@@@@1@29@@oe@16-12-2010 984384009@GENIA Treebank@formal@@1@S@Dexamethasone prevented IL-8 and tumor necrosis factor-alpha secretion in ventilated macrophages.@@@@1@12@@oe@16-12-2010 984384010@GENIA Treebank@formal@@1@S@Mechanical ventilation induced low levels of IL-8 secretion by alveolar type II-like cells.@@@@1@14@@oe@16-12-2010 984384011@GENIA Treebank@formal@@1@S@Other lung cell types such as endothelial cells, bronchial cells, and fibroblasts failed to produce IL-8 in response to a prolonged cyclic pressure-stretching load.@@@@1@27@@oe@16-12-2010 984384012@GENIA Treebank@formal@@1@S@This model is of particular value for exploring physical stress-induced signaling pathways, as well as for testing the effects of novel ventilatory strategies or adjunctive substances aimed at modulating cell activation induced by mechanical ventilation.@@@@1@37@@oe@16-12-2010 984536201@GENIA Treebank@formal@@1@S@Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells.@@@@1@17@@oe@16-12-2010 984536202@GENIA Treebank@formal@@1@S@Post HIV-1 entry, productive HIV-1 infection of primary T cells requires overcoming several cellular blocks to provirus establishment and replication.@@@@1@22@@oe@16-12-2010 984536203@GENIA Treebank@formal@@1@S@Activation of unknown host intracellular events overcomes such inhibitory steps and is concomitant with HIV-1 replication.@@@@1@17@@oe@16-12-2010 984536204@GENIA Treebank@formal@@1@S@We show that the transcription factor NFATc was sufficient as a cellular factor to induce a highly permissive state for HIV-1 replication in primary CD4+ T cells.@@@@1@28@@oe@16-12-2010 984536205@GENIA Treebank@formal@@1@S@NFATc overcame a blockade at reverse transcription and permitted active HIV-1 replication.@@@@1@13@@oe@16-12-2010 984536206@GENIA Treebank@formal@@1@S@Pharmacologic blockade of endogenous NFAT activity by FK506 or CsA inhibited synthesis of reverse transcription and also potently blocked HIV-1 replication.@@@@1@22@@oe@16-12-2010 984536207@GENIA Treebank@formal@@1@S@T cells therefore can become competent for HIV-1 replication by control of regulated host factors such as the NFATc transcription factor.@@@@1@22@@oe@16-12-2010 984536208@GENIA Treebank@formal@@1@S@The host mechanisms regulated by such permissivity factors are potential targets for anti-HIV-1 therapy.@@@@1@15@@oe@16-12-2010 984551701@GENIA Treebank@formal@@1@S@Stat6 inhibits human interleukin-4 promoter activity in T cells.@@@@1@10@@oe@16-12-2010 984551702@GENIA Treebank@formal@@1@S@The differentiation of naive T-helper (Th) cells into cytokine-secreting effector Th cells requires exposure to multiple signals, including exogenous cytokines.@@@@1@24@@oe@16-12-2010 984551703@GENIA Treebank@formal@@1@S@Interleukin-4 (IL-4) plays a major role in this process by promoting the differentiation of IL-4-secreting Th2 cells.@@@@1@20@@oe@16-12-2010 984551704@GENIA Treebank@formal@@1@S@In Th2 cells, IL-4 gene expression is tightly controlled at the level of transcription by the coordinated binding of multiple transcription factors to regulatory elements in the proximal promoter region.@@@@1@32@@oe@16-12-2010 984551705@GENIA Treebank@formal@@1@S@Nuclear factor of activated T cell (NFAT) family members play a critical role in regulating IL-4 transcription and interact with up to five sequences (termed P0 through P4) in the IL-4 promoter.@@@@1@37@@oe@16-12-2010 984551706@GENIA Treebank@formal@@1@S@The molecular mechanisms by which IL-4 induces expression of the IL-4 gene are not known, although the IL-4-activated transcription factor signal transducer and activator of transcription 6 (Stat6) is required for this effect.@@@@1@37@@oe@16-12-2010 984551707@GENIA Treebank@formal@@1@S@We report here that Stat6 interacts with three binding sites in the human IL-4 promoter by electrophoretic mobility shift assays.@@@@1@21@@oe@16-12-2010 984551708@GENIA Treebank@formal@@1@S@These sites overlap the P1, P2, and P4 NFAT elements.@@@@1@13@@oe@16-12-2010 984551709@GENIA Treebank@formal@@1@S@To investigate the role of Stat6 in regulating IL-4 transcription, we used Stat6-deficient Jurkat T cells with different intact IL-4 promoter constructs in cotransfection assays.@@@@1@27@@oe@16-12-2010 984551710@GENIA Treebank@formal@@1@S@We show that, whereas a multimerized response element from the germline IgE promoter was highly induced by IL-4 in Stat6-expressing Jurkat cells, the intact human IL-4 promoter was repressed under similar conditions.@@@@1@35@@oe@16-12-2010 984551711@GENIA Treebank@formal@@1@S@We conclude that the function of Stat6 is highly dependent on promoter context and that this factor promotes IL-4 gene expression in an indirect manner.@@@@1@26@@oe@16-12-2010 984648101@GENIA Treebank@formal@@1@S@Adaptor function for the Syk kinases-interacting protein 3BP2 in IL-2 gene activation.@@@@1@13@@oe@16-12-2010 984648102@GENIA Treebank@formal@@1@S@Syk-family tyrosine kinases are essential for lymphocyte development and activation.@@@@1@11@@oe@16-12-2010 984648103@GENIA Treebank@formal@@1@S@Using a yeast two-hybrid screen to identify Syk kinases-interacting proteins (SKIPs), we isolated 3BP2, an Abl SH3-interacting protein of unknown function.@@@@1@26@@oe@16-12-2010 984648104@GENIA Treebank@formal@@1@S@3BP2 was selectively expressed in hematopoietic/lymphoid tissues and bound via its SH2 domain activated Syk-family kinases in mammalian cells, including in antigen receptor-stimulated T cells.@@@@1@27@@oe@16-12-2010 984648105@GENIA Treebank@formal@@1@S@In addition to Zap-70, the 3BP2 SH2 domain associated in vitro with LAT, Grb2, PLCgamma1, and Cbl from activated T cell lysates.@@@@1@27@@oe@16-12-2010 984648106@GENIA Treebank@formal@@1@S@Transient 3BP2 overexpression induced transcriptional activation of the IL-2 promoter and its NFAT or AP-1 elements.@@@@1@17@@oe@16-12-2010 984648107@GENIA Treebank@formal@@1@S@This activity was dependent on the SH2 and pleckstrin-homology domains of 3BP2, and required functional Syk kinases, Ras, and calcineurin.@@@@1@24@@oe@16-12-2010 984648108@GENIA Treebank@formal@@1@S@Thus, 3BP2 is an important adaptor that may couple activated Zap-70/Syk to a LAT-containing signaling complex involved in TCR-mediated gene transcription.@@@@1@23@@oe@16-12-2010 984648201@GENIA Treebank@formal@@1@S@Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76.@@@@1@15@@oe@16-12-2010 984648202@GENIA Treebank@formal@@1@S@Tyrosine phosphorylation of linker proteins enables the T cell antigen receptor (TCR)-associated protein tyrosine kinases to phosphorylate and regulate effector molecules that generate second messengers.@@@@1@29@@oe@16-12-2010 984648203@GENIA Treebank@formal@@1@S@We demonstrate here that the SLP-76 linker protein interacts with both nck, an adaptor protein, and Vav, a guanine nucleotide exchange factor for Rho-family GTPases.@@@@1@29@@oe@16-12-2010 984648204@GENIA Treebank@formal@@1@S@The assembly of this tri-molecular complex permits the activated Rho-family GTPases to regulate target effectors that interact through nck.@@@@1@20@@oe@16-12-2010 984648205@GENIA Treebank@formal@@1@S@In turn, assembly of this complex mediates the enzymatic activation of the p21-activated protein kinase 1 and facilitates actin polymerization.@@@@1@22@@oe@16-12-2010 984648206@GENIA Treebank@formal@@1@S@Hence, phosphorylation of linker proteins not only bridges the TCR-associated PTK, ZAP-70, with downstream effector proteins, but also provides a scaffold to integrate distinct signaling complexes to regulate T cell function.@@@@1@36@@oe@16-12-2010 984649501@GENIA Treebank@formal@@1@S@Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism.@@@@1@12@@oe@16-12-2010 984649502@GENIA Treebank@formal@@1@S@Recently, the transcription factor GATA-3 was shown to be selectively expressed in Th2 but not Th1 cells and to augment Th2-specific cytokines.@@@@1@24@@oe@16-12-2010 984649503@GENIA Treebank@formal@@1@S@Here, we show that loss of GATA-3 expression by developing Th1 cells requires IL-12 signaling through Stat4 and does not simply result from an absence of IL-4.@@@@1@29@@oe@16-12-2010 984649504@GENIA Treebank@formal@@1@S@Moreover, we demonstrate a novel role for GATA-3 in directly repressing Th1 development distinct from its positive actions on Th2-specific cytokines.@@@@1@23@@oe@16-12-2010 984649505@GENIA Treebank@formal@@1@S@GATA-3 inhibits Th1 cytokines by a cell-intrinsic mechanism that is not dependent on IL-4 and that may involve repression of IL-12 signaling.@@@@1@23@@oe@16-12-2010 984649506@GENIA Treebank@formal@@1@S@Thus, GATA-3 expression and IL-12 signaling are mutually antagonistic, which facilitates rapid dominance of one pathway during early Th development, producing a stable divergence in cytokine profiles.@@@@1@31@@oe@16-12-2010 984729201@GENIA Treebank@formal@@1@S@Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma.@@@@1@12@@oe@16-12-2010 984729202@GENIA Treebank@formal@@1@S@Interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta) are inhibitory for B and T cells, IgE production, and mast cell proliferation, and they induce apoptosis in eosinophils.@@@@1@35@@oe@16-12-2010 984729203@GENIA Treebank@formal@@1@S@These cytokines are therefore candidate genes which could contribute to the development of asthma or allergies.@@@@1@17@@oe@16-12-2010 984729204@GENIA Treebank@formal@@1@S@We investigated the hypothesis that polymorphic nucleotides within the IL-10 and TGF-beta gene promoters would link to the expression of allergies and asthma.@@@@1@24@@oe@16-12-2010 984729205@GENIA Treebank@formal@@1@S@DNA taken from families with an asthmatic proband was examined for base exchanges by single-stranded conformational polymorphism (SSCP).@@@@1@21@@oe@16-12-2010 984729206@GENIA Treebank@formal@@1@S@We demonstrated the presence of a polymorphism in the promoter region of the IL-10 gene and four in the TGF-beta gene promoters (3 in TGF-beta1 and 1 in TGF-beta2).@@@@1@32@@oe@16-12-2010 984729207@GENIA Treebank@formal@@1@S@The IL-10 gene polymorphism was a C-to-A exchange 571 base pairs upstream from the translation start site and was present between consensus binding sequences for Sp1 and elevated total serum.@@@@1@31@@oe@16-12-2010 984729208@GENIA Treebank@formal@@1@S@This polymorphism was associated with elevated total serum IgE in subjects heterozygotic or homozygotic for this base exchange (p < 0.009).@@@@1@24@@oe@16-12-2010 984729209@GENIA Treebank@formal@@1@S@The base exchange at -509 (from the transcription initiation site) in the TGF-beta promoter also linked to elevated total IgE (p < 0.01).@@@@1@28@@oe@16-12-2010 984729210@GENIA Treebank@formal@@1@S@This polymorphism represented a C-to-T base exchange which induced a YY1 consensus sequence and is present in a region of the promoter associated with negative transcription regulation.@@@@1@28@@oe@16-12-2010 984733701@GENIA Treebank@formal@@1@S@Accessing Epstein-Barr virus-specific T-cell memory with peptide-loaded dendritic cells.@@@@1@10@@oe@16-12-2010 984733702@GENIA Treebank@formal@@1@S@The conventional means of studying Epstein-Barr virus (EBV)-induced cytotoxic T-lymphocyte (CTL) memory, by in vitro stimulation with the latently infected autologous lymphoblastoid cell line (LCL), has important limitations.@@@@1@38@@oe@16-12-2010 984733703@GENIA Treebank@formal@@1@S@First, it gives no information on memory to lytic cycle antigens; second, it preferentially amplifies the dominant components of latent antigen-specific memory at the expense of key subdominant reactivities.@@@@1@33@@oe@16-12-2010 984733704@GENIA Treebank@formal@@1@S@Here we describe an alternative approach, based on in vitro stimulation with epitope peptide-loaded dendritic cells (DCs), which allows one to probe the CTL repertoire for any individual reactivity of choice; this method proved significantly more efficient than stimulation with peptide alone.@@@@1@48@@oe@16-12-2010 984733705@GENIA Treebank@formal@@1@S@Using this approach we first show that reactivities to the immunodominant and subdominant lytic cycle epitopes identified by T cells during primary EBV infection are regularly detectable in the CTL memory of virus carriers; this implies that in such carriers chronic virus replication remains under direct T-cell control.@@@@1@50@@oe@16-12-2010 984733706@GENIA Treebank@formal@@1@S@We further show that subdominant latent cycle reactivities to epitopes in the latent membrane protein LMP2, though rarely undetectable in LCL-stimulated populations, can be reactivated by DC stimulation and selectively expanded as polyclonal CTL lines; the adoptive transfer of such preparations may be of value in targeting certain EBV-positive malignancies.@@@@1@54@@oe@16-12-2010 984970901@GENIA Treebank@formal@@1@S@Glucocorticoid receptors on mononuclear leukocytes in polycystic ovary syndrome.@@@@1@10@@oe@16-12-2010 984970902@GENIA Treebank@formal@@1@S@OBJECTIVE: Many studies have suggested that there is a possible hormonal dysregulation of hypothalamic-pituitary-adrenal (HPA) axis and an increased cortisol clearance in patients with polycystic ovary syndrome (PCOS).@@@@1@34@@oe@16-12-2010 984970903@GENIA Treebank@formal@@1@S@Therefore in this study, we have examined the role of glucocorticoid receptor/s (GR) characteristics in the developing of these abnormalities in patients with PCOS.@@@@1@28@@oe@16-12-2010 984970904@GENIA Treebank@formal@@1@S@METHOD: For this purpose, the number and affinity of GR in peripheral mononuclear leukocytes (MNL) of 10 patients with PCOS and 10 healthy women (controls) were determined.@@@@1@34@@oe@16-12-2010 984970905@GENIA Treebank@formal@@1@S@RESULTS: There were no significant differences in the number (6500+/-1001 sites/cell and 6352+/-1697 sites/cell, respectively; P > 0.05) and affinity (3.93+/-0.89 nM and 4.49+/-0.71 nM, respectively; P > 0.05) of GR between the PCOS patients and the controls.@@@@1@48@@oe@16-12-2010 984970906@GENIA Treebank@formal@@1@S@CONCLUSIONS: These results suggest that the alterations in the HPA axis and in the cortisol metabolism observed in PCOS are not related to GR deficiency.@@@@1@27@@oe@16-12-2010 984988001@GENIA Treebank@formal@@1@S@Constitutive association of JAK1 and STAT5 in pro-B cells is dissolved by interleukin-4-induced tyrosine phosphorylation of both proteins.@@@@1@19@@oe@16-12-2010 984988002@GENIA Treebank@formal@@1@S@The bipartite human interleukin-4 (IL-4) receptor was functionally expressed in murine pro-B cells and activated by human IL-4 to evoke intracellular signaling.@@@@1@25@@oe@16-12-2010 984988003@GENIA Treebank@formal@@1@S@Mutual association of signal transducing proteins within the receptor complex was then studied in dependence of ligand stimulation.@@@@1@19@@oe@16-12-2010 984988004@GENIA Treebank@formal@@1@S@Besides ligand-induced receptor heterodimerization and contacts of the two IL-4 receptor subunits alpha and gamma with Janus kinases JAK1 and JAK3 a prominent constitutive binding between JAK1 and signal transducer and activator of transcription STAT5 was detected.@@@@1@38@@oe@16-12-2010 984988005@GENIA Treebank@formal@@1@S@Since both these proteins become phosphorylated in response to IL-4 receptor stimulation, the influence of tyrosine phosphorylation on their mutual contact was analyzed.@@@@1@25@@oe@16-12-2010 984988006@GENIA Treebank@formal@@1@S@Association of JAK1 and STAT5 was found to occur exclusively between unphosphorylated proteins.@@@@1@14@@oe@16-12-2010 985085001@GENIA Treebank@formal@@1@S@The linkage between T-cell and dendritic cell development in the mouse thymus.@@@@1@13@@oe@16-12-2010 985085002@GENIA Treebank@formal@@1@S@Thymic dendritic cells (DC) mediate negative selection at a relatively late stage of the T-cell developmental pathway.@@@@1@20@@oe@16-12-2010 985085003@GENIA Treebank@formal@@1@S@We present evidence that the development of thymic DC and of T-lineage cells is linked via a common precursor at an early stage of thymocyte development.@@@@1@27@@oe@16-12-2010 985085004@GENIA Treebank@formal@@1@S@T-lineage precursor populations from the adult mouse thymus, prior to T-cell receptor gene rearrangement, display a capacity to produce DC as well as T cells in the thymus, and are very efficient precursors of DC in culture.@@@@1@41@@oe@16-12-2010 985085005@GENIA Treebank@formal@@1@S@These lymphoid/DC precursors have little capacity to form myeloid cells, indicating that thymic DC are a lymphoid-related rather than myeloid-related lineage.@@@@1@23@@oe@16-12-2010 985085006@GENIA Treebank@formal@@1@S@In contrast to myeloid-related DC, granulocyte-macrophage colony-stimulating factor is not required for the development of these lymphoid-related DC in vivo or in vitro.@@@@1@25@@oe@16-12-2010 985085007@GENIA Treebank@formal@@1@S@DC can develop in mutant mice lacking mature T cells, provided the common precursors are present.@@@@1@18@@oe@16-12-2010 985085008@GENIA Treebank@formal@@1@S@However, in mutant mice lacking functional Ikaros transcription factors, there are deficiencies in lymphoid precursor cells, in mature lymphoid cells and in DC.@@@@1@27@@oe@16-12-2010 985207001@GENIA Treebank@formal@@1@S@The involvement of multiple tumor necrosis factor receptor (TNFR)-associated factors in the signaling mechanisms of receptor activator of NF-kappaB, a member of the TNFR superfamily.@@@@1@30@@oe@16-12-2010 985207002@GENIA Treebank@formal@@1@S@Receptor activator of NF-kappaB (RANK) is a recently identified member of the tumor necrosis factor receptor superfamily and is expressed on activated T cells and dendritic cells.@@@@1@30@@oe@16-12-2010 985207003@GENIA Treebank@formal@@1@S@Its cognate ligand (RANKL) plays significant roles in the activation of dendritic cell function and osteoclast differentiation.@@@@1@20@@oe@16-12-2010 985207004@GENIA Treebank@formal@@1@S@We demonstrate here the interaction of RANK with tumor necrosis factor receptor-associated factors (TRAFs) 1, 2, 3, 5, and 6 both in vitro and in cells.@@@@1@33@@oe@16-12-2010 985207005@GENIA Treebank@formal@@1@S@Mapping of the structural requirements for TRAF/RANK interaction revealed multiple TRAF binding sites clustered in two distinct domains in the RANK cytoplasmic tail.@@@@1@24@@oe@16-12-2010 985207006@GENIA Treebank@formal@@1@S@These TRAF binding domains were shown to be functionally important for the RANK-dependent induction of NF-kappaB and c-Jun NH2-terminal kinase activities.@@@@1@22@@oe@16-12-2010 985207007@GENIA Treebank@formal@@1@S@Site-directed mutagenesis demonstrated that these TRAF binding sites exhibited selective binding for different TRAF proteins.@@@@1@16@@oe@16-12-2010 985207008@GENIA Treebank@formal@@1@S@In particular, TRAF6 interacted with membrane-proximal determinants distinct from those binding TRAFs 1, 2, 3, and 5.@@@@1@22@@oe@16-12-2010 985207009@GENIA Treebank@formal@@1@S@When this membrane-proximal TRAF6 interaction domain was deleted, RANK-mediated NF-kappaB signaling was completely inhibited while c-Jun NH2-terminal kinase activation was partially inhibited.@@@@1@24@@oe@16-12-2010 985207010@GENIA Treebank@formal@@1@S@An NH2-terminal truncation mutant of TRAF6 inhibited RANKL-mediated NF-kappaB activation, but failed to affect constitutive signaling induced by receptor overexpression, revealing a selective role for TRAF6 in ligand-induced activation events.@@@@1@33@@oe@16-12-2010 985221101@GENIA Treebank@formal@@1@S@The control of lytic replication of Epstein-Barr virus in B lymphocytes (Review).@@@@1@15@@oe@16-12-2010 985221102@GENIA Treebank@formal@@1@S@Uncontrolled replication of a virus, which is harmful to the host is also disadvantageous to the virus.@@@@1@19@@oe@16-12-2010 985221103@GENIA Treebank@formal@@1@S@Most viruses cannot compete with the various immune mechanisms and become eliminated in the course of infection.@@@@1@19@@oe@16-12-2010 985221104@GENIA Treebank@formal@@1@S@Therefore, only the time between infection and eradication remains for these viruses to proliferate.@@@@1@16@@oe@16-12-2010 985221105@GENIA Treebank@formal@@1@S@A few viruses, like the Herpesviruses or the papillomaviruses, however, have developed a sophisticated strategy for persisting lifelong, usually asymptomatically in the host, hiding from the immune system and producing infectious progeny at the same time.@@@@1@42@@oe@16-12-2010 985221106@GENIA Treebank@formal@@1@S@This strategy depends on a separation of latency and the lytic replication, either by time due to differentiation-dependent mechanisms or by spatial separation as the result of different host cell types.@@@@1@33@@oe@16-12-2010 985221107@GENIA Treebank@formal@@1@S@Both are true for the Epstein-Barr virus (EBV).@@@@1@11@@oe@16-12-2010 985221108@GENIA Treebank@formal@@1@S@B cells and epithelial cells have a pivotal role in the life cycle of the virus.@@@@1@17@@oe@16-12-2010 985221109@GENIA Treebank@formal@@1@S@The former can become latently infected and are thought to be the virus reservoir in vivo, whereas the latter were shown to be permissive for lytic replication.@@@@1@29@@oe@16-12-2010 985221110@GENIA Treebank@formal@@1@S@However, replication of EBV in vivo is controlled primarily by host immune mechanisms selecting for cells that are not permissive for viral replication as the result of a particular set of transcription factors.@@@@1@35@@oe@16-12-2010 985221111@GENIA Treebank@formal@@1@S@These factors control the activity of the regulatory immediate-early genes and, in addition, lytic and latent cycle regulatory genes negatively interfere with each other and thus link cellular and viral gene regulatory mechanisms.@@@@1@36@@oe@16-12-2010 985221112@GENIA Treebank@formal@@1@S@Disturbance of both the immune surveillance as well as viral gene regulation may result in EBV-associated disease.@@@@1@18@@oe@16-12-2010 985231001@GENIA Treebank@formal@@1@S@Human immunodeficiency virus type-1 transcription: role of the 5'-untranslated leader region (review).@@@@1@16@@oe@16-12-2010 985231002@GENIA Treebank@formal@@1@S@Human immunodeficiency virus type-1 (HIV-1) transcription is dependent on the interaction of host-cell transcription factors with cis-regulatory DNA elements within the viral long terminal repeat (LTR).@@@@1@31@@oe@16-12-2010 985231003@GENIA Treebank@formal@@1@S@Much attention has focused on the series of sequence elements upstream of the transcriptional initiation site in the U3 region of the LTR including the Sp1 and NF-kappaB binding sites.@@@@1@31@@oe@16-12-2010 985231004@GENIA Treebank@formal@@1@S@Recent studies, however, demonstrate that the transcribed 5'-untranslated leader region (5'-UTR) also contains important transcriptional elements.@@@@1@21@@oe@16-12-2010 985231005@GENIA Treebank@formal@@1@S@These regulatory elements situated downstream of transcription interact with constitutive and inducible transcription factors, mediate transmission of cellular activation signals, and are important for efficient HIV-1 transcription and replication.@@@@1@32@@oe@16-12-2010 985231006@GENIA Treebank@formal@@1@S@The 5'-UTR contains binding sites for the transcription factors AP-1, NF-kappaB, NF-AT, IRF, and Sp1.@@@@1@20@@oe@16-12-2010 985231007@GENIA Treebank@formal@@1@S@Mutations in these binding sites can interfere with the viral response to cell activation signals, decrease LTR transcription, and inhibit viral replication.@@@@1@25@@oe@16-12-2010 985231008@GENIA Treebank@formal@@1@S@The 5'-UTR also interacts with a specific nucleosome that is rapidly displaced during transcriptional activation of the latent provirus.@@@@1@20@@oe@16-12-2010 985231009@GENIA Treebank@formal@@1@S@We propose that the inducible transcription factor binding sites in the 5'-UTR comprise a downstream enhancer domain that can function independent of, or in concert with, the LTR promoter to rapidly increase latent proviral transcription in response to cell activation signals.@@@@1@44@@oe@16-12-2010 985231010@GENIA Treebank@formal@@1@S@In this review, we describe the host-cell transcription factors that interact with the 5'-UTR and discuss their role in the transcriptional regulation of HIV-1 gene expression.@@@@1@28@@oe@16-12-2010 985295801@GENIA Treebank@formal@@1@S@Molecular cloning of FKHRL1P2, a member of the developmentally regulated fork head domain transcription factor family.@@@@1@18@@oe@16-12-2010 985295802@GENIA Treebank@formal@@1@S@Here we report the expression of a fork head domain protein in human T helper cells.@@@@1@17@@oe@16-12-2010 985295803@GENIA Treebank@formal@@1@S@We cloned and characterized a fork head cDNA from human T helper cell mRNA using differential display RT-PCR.@@@@1@19@@oe@16-12-2010 985295804@GENIA Treebank@formal@@1@S@The cDNA contains a 546-nucleotide (nt) open reading frame (ORF) that codes for the carboxyl-terminal 180 amino acids (aa) of the recently identified fkhrl1 gene.@@@@1@32@@oe@16-12-2010 985295805@GENIA Treebank@formal@@1@S@This ORF does not contain the characteristic DNA-binding domain found in members of the forkhead protein family.@@@@1@18@@oe@16-12-2010 985295806@GENIA Treebank@formal@@1@S@In-vitro transcription/translation of this cDNA expressed a protein of approximately 20 kDa.@@@@1@13@@oe@16-12-2010 985295807@GENIA Treebank@formal@@1@S@We have generated antibodies that specifically immunoprecipitated the in-vitro-translated 20-kDa protein.@@@@1@12@@oe@16-12-2010 985295808@GENIA Treebank@formal@@1@S@This antibody also recognizes in human T lymphocytes a 70-kDa protein corresponding in size to that predicted for the fkhrl1 gene product.@@@@1@23@@oe@16-12-2010 985295809@GENIA Treebank@formal@@1@S@The mRNA levels for fkhrl1 is elevated in T helper-induced lymphocytes in comparison to PHA-stimulated T lymphocytes.@@@@1@18@@oe@16-12-2010 985295810@GENIA Treebank@formal@@1@S@Further characterization of FKHRL1 and its related family members should shed light on the transcriptional mechanisms of this fork head gene subfamily and their role in T helper cell differentiation and regulation of cell growth.@@@@1@36@@oe@16-12-2010 985297101@GENIA Treebank@formal@@1@S@Isolation and utilization of human dendritic cells from peripheral blood to assay an in vitro primary immune response to varicella-zoster virus peptides.@@@@1@23@@oe@16-12-2010 985297102@GENIA Treebank@formal@@1@S@A human dendritic cell-based assay used to monitor a T cell proliferation response to viral peptides in vitro is described.@@@@1@21@@oe@16-12-2010 985297103@GENIA Treebank@formal@@1@S@Dendritic cells and autologous CD4+ T cells were isolated from peripheral blood by a series of density-gradient centrifugations or magnetic bead separations (or both).@@@@1@27@@oe@16-12-2010 985297104@GENIA Treebank@formal@@1@S@Peptides corresponding to residues of the immediate early protein, IE62, of varicella-zoster virus (VZV) were used as stimulating antigens, and persons with no history of varicella and no humoral or cellular immunity to VZV served as naive donors for the assays.@@@@1@47@@oe@16-12-2010 985297105@GENIA Treebank@formal@@1@S@Three VZV-susceptible donors were tested, and all demonstrated an in vitro response to multiple VZV peptides.@@@@1@18@@oe@16-12-2010 985297106@GENIA Treebank@formal@@1@S@This assay has potential as a screen to establish the immunogenicity of viral antigens in vitro using T cells from naive donors.@@@@1@23@@oe@16-12-2010 985468001@GENIA Treebank@formal@@1@S@The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity.@@@@1@16@@oe@16-12-2010 985468002@GENIA Treebank@formal@@1@S@Glucocorticoid receptors (GR) and 3-O-methyl-D glucose (3-O-MG) transport were determined in mononuclear leukocytes (MNL) from 11 abdominal obese subjects, 10 pituitary-dependent Cushing's syndrome (Cushing's disease) and 10 healthy controls.@@@@1@41@@oe@16-12-2010 985468003@GENIA Treebank@formal@@1@S@Using a whole-cell competitive binding assay and 3H-dexamethasone as tracer, MNL of abdominal obese subjects were found to have 4855 +/- 1389 sites/cell which was significantly lower (p < 0.05) than controls (6234 +/- 1568 sites/cell), although no significant difference was found in the mean serum cortisol level.@@@@1@55@@oe@16-12-2010 985468004@GENIA Treebank@formal@@1@S@Their mean Kd (affinity) was also significantly lower than that found in the healthy controls (obese Kd:2.92 +/- 0.84 nmol/l, control Kd: 4.55 +/- 0.67 nM, p < 0.05).@@@@1@39@@oe@16-12-2010 985468005@GENIA Treebank@formal@@1@S@On the other hand, the receptor characteristics in Cushing's disease patients were within the normal range.@@@@1@19@@oe@16-12-2010 985468006@GENIA Treebank@formal@@1@S@At the same time, 3-O-MG transport was determined in the same subjects.@@@@1@14@@oe@16-12-2010 985468007@GENIA Treebank@formal@@1@S@In Cushing's disease, 3-O-MG transport was within the normal range, whereas in abdominal obesity this value was significantly lower than the healthy controls (abdominal obese: 31.90 +/- 8.20; control: 46.26 +/- 12.91 fmol/10(6) cell, min, p < 0.05).@@@@1@49@@oe@16-12-2010 985468008@GENIA Treebank@formal@@1@S@We also found a positive correlation between 3-O-MG transport and GR binding capacity in abdominal subjects (r = 0.89, p < 0.001), however we did not find such a correlation in Cushing's disease (r = 0.60, p > 0.05).@@@@1@48@@oe@16-12-2010 985468009@GENIA Treebank@formal@@1@S@These results indicated that, in abdominal obesity, the GR binding capacity in MNL is influenced by the changes in glucose transport.@@@@1@24@@oe@16-12-2010 985707401@GENIA Treebank@formal@@1@S@Down-regulation of human granzyme B expression by glucocorticoids.@@@@1@9@@oe@16-12-2010 985707402@GENIA Treebank@formal@@1@S@Dexamethasone inhibits binding to the Ikaros and AP-1 regulatory elements of the granzyme B promoter.@@@@1@16@@oe@16-12-2010 985707403@GENIA Treebank@formal@@1@S@The serine protease granzyme B is an essential component of the granule exocytosis pathway, a major apoptotic mechanism used by cytotoxic T lymphocytes and natural killer cells to induce target cell apoptosis.@@@@1@34@@oe@16-12-2010 985707404@GENIA Treebank@formal@@1@S@Granzyme B gene transcription is induced in activated lymphocytes upon antigenic stimulation, and several regulatory regions including CBF, AP-1, and Ikaros binding sites have been shown to be essential in the control of granzyme B promoter activation.@@@@1@41@@oe@16-12-2010 985707405@GENIA Treebank@formal@@1@S@Dexamethasone, a glucocorticoid that is widely used as an immunomodulatory and anti-inflammatory agent, inhibits granzyme B mRNA transcript in phytohemagglutinin-activated peripheral blood mononuclear cells.@@@@1@27@@oe@16-12-2010 985707406@GENIA Treebank@formal@@1@S@Transfection of a reporter construct containing the -148 to +60 region of the human granzyme B promoter demonstrated that this region was the target for dexamethasone repression.@@@@1@28@@oe@16-12-2010 985707407@GENIA Treebank@formal@@1@S@Mutation of Ikaros or AP-1 binding sites in the context of the granzyme B promoter demonstrated that both sites participate in dexamethasone-mediated inhibition of the granzyme B promoter activity.@@@@1@30@@oe@16-12-2010 985707408@GENIA Treebank@formal@@1@S@Electromobility shift assay revealed that dexamethasone abolished the binding of nuclear transcription factors to the Ikaros binding site and reduced AP-1 binding activity.@@@@1@24@@oe@16-12-2010 985707409@GENIA Treebank@formal@@1@S@These results indicate that dexamethasone is able to abrogate the transcriptional activity of the human granzyme B gene promoter by inhibiting the binding of nuclear factors at the AP-1 and Ikaros sites.@@@@1@33@@oe@16-12-2010 985824101@GENIA Treebank@formal@@1@S@Activation of the human delta-globin gene promoter in primary adult erythroid cells.@@@@1@13@@oe@16-12-2010 985824102@GENIA Treebank@formal@@1@S@Restoration of the CCAAT box or insertion of an erythroid Kruppel-like factor (EKLF) binding site in the delta promoter activates its expression in several erythroid cell lines.@@@@1@30@@oe@16-12-2010 985824103@GENIA Treebank@formal@@1@S@We extended these studies using a novel primary human adult erythroid cell (hAEC) system to investigate these effects at the late erythroblast stage.@@@@1@26@@oe@16-12-2010 985824104@GENIA Treebank@formal@@1@S@Restoration of the CCAAT box at -70 bp, or insertion of an EKLF binding site at -85 bp or -95 bp in the promoter significantly increased delta globin gene expression in hAEC.@@@@1@34@@oe@16-12-2010 985824105@GENIA Treebank@formal@@1@S@Our results demonstrate that the altered CCAAT box (CCAAC) and the lack of an EKLF binding site in delta-globin contribute to its low level of expression in the hAEC model as well.@@@@1@35@@oe@16-12-2010 985856301@GENIA Treebank@formal@@1@S@The B29 (immunoglobulin beta-chain) gene is a genetic target for early B-cell factor.@@@@1@16@@oe@16-12-2010 985856302@GENIA Treebank@formal@@1@S@Early B-cell factor (EBF) is a transcription factor suggested as essential for early B-lymphocyte development by findings in mice where the coding gene has been inactivated by homologous disruption.@@@@1@32@@oe@16-12-2010 985856303@GENIA Treebank@formal@@1@S@This makes the identification of genetic targets for this transcription factor pertinent for the understanding of early B-cell development.@@@@1@20@@oe@16-12-2010 985856304@GENIA Treebank@formal@@1@S@The lack of B29 transcripts, coding for the beta subunit of the B-cell receptor complex, in pro-B cells from EBF-deficient mice suggested that B29 might be a genetic target for EBF.@@@@1@34@@oe@16-12-2010 985856305@GENIA Treebank@formal@@1@S@We here present data suggesting that EBF interacts with three independent sites within the mouse B29 promoter.@@@@1@18@@oe@16-12-2010 985856306@GENIA Treebank@formal@@1@S@Furthermore, ectopic expression of EBF in HeLa cells activated a B29 promoter-controlled reporter construct 13-fold and induced a low level of expression from the endogenous B29 gene.@@@@1@29@@oe@16-12-2010 985856307@GENIA Treebank@formal@@1@S@Finally, mutations in the EBF binding sites diminished B29 promoter activity in pre-B cells while the same mutations did not have as striking an effect on the promoter function in B-cell lines of later differentiation stages.@@@@1@38@@oe@16-12-2010 985856308@GENIA Treebank@formal@@1@S@These data suggest that the B29 gene is a genetic target for EBF in early B-cell development.@@@@1@18@@oe@16-12-2010 985861801@GENIA Treebank@formal@@1@S@Interactions between the class II transactivator and CREB binding protein increase transcription of major histocompatibility complex class II genes.@@@@1@20@@oe@16-12-2010 985861802@GENIA Treebank@formal@@1@S@Class II major histocompatibility (class II) genes are regulated in a B-cell-specific and gamma interferon-inducible fashion.@@@@1@19@@oe@16-12-2010 985861803@GENIA Treebank@formal@@1@S@The master switch for the expression of these genes is the class II transactivator (CIITA).@@@@1@18@@oe@16-12-2010 985861804@GENIA Treebank@formal@@1@S@In this report, we demonstrate that one of the functions of CIITA is to recruit the CREB binding protein (CBP) to class II promoters.@@@@1@28@@oe@16-12-2010 985861805@GENIA Treebank@formal@@1@S@Not only functional but also specific binding interactions between CIITA and CBP were demonstrated.@@@@1@15@@oe@16-12-2010 985861806@GENIA Treebank@formal@@1@S@Moreover, a dominant negative form of CBP decreased the activity of class II promoters and levels of class II determinants on the surface of cells.@@@@1@27@@oe@16-12-2010 985861807@GENIA Treebank@formal@@1@S@Finally, the inhibition of class II gene expression by the glucocorticoid hormone could be attributed to the squelching of CBP by the glucocorticoid receptor.@@@@1@26@@oe@16-12-2010 985861808@GENIA Treebank@formal@@1@S@We conclude that CBP, a histone acetyltransferase, plays an important role in the transcription of class II genes.@@@@1@21@@oe@16-12-2010 985861901@GENIA Treebank@formal@@1@S@Interdomain B in ZAP-70 regulates but is not required for ZAP-70 signaling function in lymphocytes.@@@@1@16@@oe@16-12-2010 985861902@GENIA Treebank@formal@@1@S@The protein tyrosine kinase ZAP-70 plays an important role in T-cell activation and development.@@@@1@15@@oe@16-12-2010 985861903@GENIA Treebank@formal@@1@S@After T-cell receptor stimulation, ZAP-70 associates with the receptor and is phosphorylated on many tyrosines, including Y292, Y315, and Y319 within interdomain B.@@@@1@28@@oe@16-12-2010 985861904@GENIA Treebank@formal@@1@S@Previously, we demonstrated that Y292 negatively regulates ZAP-70 function and that Y315 positively regulates ZAP-70 function by interacting with Vav.@@@@1@22@@oe@16-12-2010 985861905@GENIA Treebank@formal@@1@S@Recent studies have suggested that Y319 also positively regulate ZAP-70 function.@@@@1@12@@oe@16-12-2010 985861906@GENIA Treebank@formal@@1@S@Paradoxically, removal of interdomain B (to create the construct designated Delta), containing the Y292, Y315, and Y319 sites, did not eliminate the ability of ZAP-70 to induce multiple gene reporters in Syk-deficient DT-40 B cells and ZAP-70/Syk-deficient Jurkat cells.@@@@1@47@@oe@16-12-2010 985861907@GENIA Treebank@formal@@1@S@Here we show that Delta still utilizes the same pathways as wild-type ZAP-70 to mediate NF-AT induction.@@@@1@18@@oe@16-12-2010 985861908@GENIA Treebank@formal@@1@S@This is manifested by the ability of Delta to restore induction of calcium fluxes and mitogen-activated protein kinase activation and by the ability of dominant negative Ras and FK506 to block the induction of NF-AT activity mediated by Delta.@@@@1@40@@oe@16-12-2010 985861909@GENIA Treebank@formal@@1@S@Biochemically we show that the stimulated tyrosine phosphorylation of Vav, Shc, and ZAP-70 itself is diminished, whereas that of Slp-76 is increased in cells reconstituted with Delta.@@@@1@31@@oe@16-12-2010 985861910@GENIA Treebank@formal@@1@S@Deletion of interdomain B did not affect the ability of ZAP-70 to bind to the receptor.@@@@1@17@@oe@16-12-2010 985861911@GENIA Treebank@formal@@1@S@The in vitro kinase activity of ZAP-70 lacking interdomain B was markedly reduced, but the kinase activity was still required for the protein's in vivo activity.@@@@1@29@@oe@16-12-2010 985861912@GENIA Treebank@formal@@1@S@Based on these data, we concluded that interdomain B regulates but is not required for ZAP-70 signaling function leading to cellular responses.@@@@1@24@@oe@16-12-2010 985888001@GENIA Treebank@formal@@1@S@In situ RT-PCR detection of Epstein-Barr virus immediate-early transcripts in CD4+ and CD8+ T lymphocytes.@@@@1@16@@oe@16-12-2010 985888002@GENIA Treebank@formal@@1@S@AIDS-related Epstein-Barr virus (EBV)-associated T cell lymphomas are emerging as a new, distinct histopathological entity.@@@@1@20@@oe@16-12-2010 985888003@GENIA Treebank@formal@@1@S@The pathway whereby EBV infects T cells as well as the initial EBV transcriptional program in T cells has not been established.@@@@1@23@@oe@16-12-2010 985888004@GENIA Treebank@formal@@1@S@In order to shed light on the early events of the EBV infection of T cells, we have used in situ reverse transcription based polymerase chain reaction (RT-PCR) to study the initial EBV transcriptional program in homogeneous CD4+ and CD8+ lymphocytes.@@@@1@45@@oe@16-12-2010 985888005@GENIA Treebank@formal@@1@S@Following EBV infection, Epstein-Barr nuclear antigen (EBNA) expression could be detected in T rosetting CD4+ and CD8+ T lymphocytes.@@@@1@23@@oe@16-12-2010 985888006@GENIA Treebank@formal@@1@S@Only a few cells showed viral capsid antigen (VCA).@@@@1@12@@oe@16-12-2010 985888007@GENIA Treebank@formal@@1@S@EBV immediate-early gene transcripts (BZLF1, BRLF1, and BMLF1) encoded in the BamHI Z, R, and M fragments could be detected by in situ RT-PCR in the EBV producer cell line B95.8.@@@@1@38@@oe@16-12-2010 985888008@GENIA Treebank@formal@@1@S@Both BZLF1 and BRLF1 immediate-early transcripts, but not BMLF1 transcript, could be detected in individual CD4+ and CD8+ T cells infected with EBV.@@@@1@26@@oe@16-12-2010 985888009@GENIA Treebank@formal@@1@S@Demonstration of EBV mRNA transcripts encoding immediate-early transcriptional transactivators in EBV-infected T cells provides the first evidence for a possible mechanism whereby EBV could contribute to T cell proliferation and EBV-associated T cell malignancies.@@@@1@35@@oe@16-12-2010 986013701@GENIA Treebank@formal@@1@S@Enhanced differentiation of HL-60 leukemia cells to macrophages induced by ciprofibrate.@@@@1@12@@oe@16-12-2010 986013702@GENIA Treebank@formal@@1@S@Ciprofibrate, an hypolipidaemic peroxisome proliferator, induced differentiation of HL-60 cells.@@@@1@13@@oe@16-12-2010 986013703@GENIA Treebank@formal@@1@S@The effect was greatly potentiated by phorbol 12-myristate 13-acetate at a concentration where neither phorbol ester nor ciprofibrate alone had any effect on these cells.@@@@1@26@@oe@16-12-2010 986013704@GENIA Treebank@formal@@1@S@As occurs for HL-60 cell differentiation induced by high phorbol ester concentration, the ciprofibrate-induced phorbol ester-dependent differentiation of HL-60 cells proceeded through the monocytic/macrophage pathway and induced the phosphorylation of proteins with similar molecular weights suggesting that increased protein kinase C activity may be involved in the effect.@@@@1@50@@oe@16-12-2010 986013705@GENIA Treebank@formal@@1@S@The peroxisome proliferator-activated receptor (PPARalpha) transcription factor is expressed in HL-60 cells, but no changes were observed in its expression upon HL-60 cell differentiation.@@@@1@28@@oe@16-12-2010 986266601@GENIA Treebank@formal@@1@S@Nuclear factor of activated T cells and AP-1 are insufficient for IL-2 promoter activation: requirement for CD28 up-regulation of RE/AP.@@@@1@22@@oe@16-12-2010 986266602@GENIA Treebank@formal@@1@S@IL-2 gene transcription in T cells requires both TCR and costimulatory signals.@@@@1@13@@oe@16-12-2010 986266603@GENIA Treebank@formal@@1@S@IL-2 promoter activation in Jurkat T cells stimulated with superantigen presented by Raji B cells requires CD28 activation.@@@@1@19@@oe@16-12-2010 986266604@GENIA Treebank@formal@@1@S@The addition of rCTLA4Ig, which blocks CD28 binding to its ligand, to the cultures decreased IL-2 promoter activation by >80%.@@@@1@25@@oe@16-12-2010 986266605@GENIA Treebank@formal@@1@S@Interestingly, CTLA4Ig did not significantly inhibit the activation of either NF of activated T cells (NFAT) or AP-1 reporters.@@@@1@23@@oe@16-12-2010 986266606@GENIA Treebank@formal@@1@S@Therefore, activation of NFAT and AP-1 is insufficient for IL-2 promoter activation.@@@@1@14@@oe@16-12-2010 986266607@GENIA Treebank@formal@@1@S@In contrast, an RE/AP reporter was blocked by CTLA4Ig by >90%.@@@@1@15@@oe@16-12-2010 986266608@GENIA Treebank@formal@@1@S@Thus, the requirement for CD28 in IL-2 promoter activation appears to be due to RE/AP and not the NFAT or AP-1 sites.@@@@1@24@@oe@16-12-2010 986266609@GENIA Treebank@formal@@1@S@In addition, these data suggest that transcriptional activation of RE/AP is not mediated by NFAT, because activation of a NFAT reporter is not affected by the addition of CTLA4Ig.@@@@1@32@@oe@16-12-2010 986267301@GENIA Treebank@formal@@1@S@CD27/CD70 interaction augments IgE secretion by promoting the differentiation of memory B cells into plasma cells.@@@@1@17@@oe@16-12-2010 986267302@GENIA Treebank@formal@@1@S@The induction of IgE switching in B cells requires several signals given by cytokines and cell contact-delivered signals.@@@@1@19@@oe@16-12-2010 986267303@GENIA Treebank@formal@@1@S@Here, we investigated the role of CD27/CD70 interaction in B cell IgE synthesis.@@@@1@15@@oe@16-12-2010 986267304@GENIA Treebank@formal@@1@S@The addition of CD27 ligand (CD70) transfectants to B cell cultures increased the IgE synthesis synergistically in the presence of IL-4 plus anti-CD40 mAb (anti-CD40).@@@@1@30@@oe@16-12-2010 986267305@GENIA Treebank@formal@@1@S@The effect of CD70 transfectants was dose dependent and was completely blocked by anti-CD70 mAb.@@@@1@16@@oe@16-12-2010 986267306@GENIA Treebank@formal@@1@S@CD27+ B cells had the ability to produce IgE, which was increased by contact with CD70 transfectants, whereas CD27- B cells did not produce IgE.@@@@1@28@@oe@16-12-2010 986267307@GENIA Treebank@formal@@1@S@CD27/CD70 interaction enhanced B cell proliferation in the presence of IL-4 or IL-4 plus anti-CD40.@@@@1@16@@oe@16-12-2010 986267308@GENIA Treebank@formal@@1@S@The augmentation of B cell proliferation by CD70 transfectants was apparent in CD27+ B cells, but was mild in CD27- B cells.@@@@1@24@@oe@16-12-2010 986267309@GENIA Treebank@formal@@1@S@The helper activity for IgE synthesis by the CD27/CD70 interaction did not contribute to the enhancement of germline epsilon transcripts.@@@@1@21@@oe@16-12-2010 986267310@GENIA Treebank@formal@@1@S@Flow cytometric and morphological analyses demonstrated that the addition of CD70 transfectants to B cell cultures remarkably promoted differentiation into plasma cells in the presence of IL-4 and CD40 signaling.@@@@1@31@@oe@16-12-2010 986267311@GENIA Treebank@formal@@1@S@Finally, CD27 cross-linking resulted in the up-regulation of positive regulatory domain I-binding factor-1.@@@@1@15@@oe@16-12-2010 986267312@GENIA Treebank@formal@@1@S@Taken together, our findings indicate that signaling via CD27 on B cells induces IgE synthesis, in cooperation with IL-4 and CD40 signaling, by promoting the generation of plasma cells through up-regulation of positive regulatory domain I-binding factor-1.@@@@1@41@@oe@16-12-2010 986268301@GENIA Treebank@formal@@1@S@The role of Stat4 in species-specific regulation of Th cell development by type I IFNs.@@@@1@16@@oe@16-12-2010 986268302@GENIA Treebank@formal@@1@S@Type I IFNs (IFN-alpha/beta), in addition to IL-12, have been shown to play an important role in the differentiation of human, but not mouse, Th cells.@@@@1@33@@oe@16-12-2010 986268303@GENIA Treebank@formal@@1@S@We show here that IFN-alpha/beta act directly on human T cells to drive Th1 development, bypassing the need for IL-12-induced signaling, whereas IFN-alpha cannot substitute IL-12 for mouse Th1 development.@@@@1@34@@oe@16-12-2010 986268304@GENIA Treebank@formal@@1@S@The molecular basis for this species specificity is that IFN-alpha/beta activate Stat4 in differentiating human, but not mouse, Th cells.@@@@1@23@@oe@16-12-2010 986268305@GENIA Treebank@formal@@1@S@Unlike IL-12, which acts only on Th1 cells, IFN-alpha/beta can activate Stat4 not only in human Th1, but also in Th2 cells.@@@@1@26@@oe@16-12-2010 986268306@GENIA Treebank@formal@@1@S@However, restimulation of human Th2 lines and clones in the presence of IFN-alpha does not induce the production of IFN-gamma.@@@@1@22@@oe@16-12-2010 986268307@GENIA Treebank@formal@@1@S@These results suggest that activation of Stat4, which is necessary for the differentiation of naive T cells into polarized Th1 cells, is not sufficient to induce phenotype reversal of human Th2 cells.@@@@1@35@@oe@16-12-2010 986350101@GENIA Treebank@formal@@1@S@Phenylarsine oxide inhibits ex vivo HIV-1 expression.@@@@1@8@@oe@16-12-2010 986350102@GENIA Treebank@formal@@1@S@Phenylarsine oxide (PAO), which is described as an inhibitor of tyrosine phosphatase activity, inhibits H2O2 release from human peripheral blood mononuclear cells (PBMCs) as measured by electrochemistry.@@@@1@34@@oe@16-12-2010 986350103@GENIA Treebank@formal@@1@S@Since human immunodeficiency virus type 1 (HIV-1) replication is known to be favored under oxidative stress conditions, ex vivo experiments using uninfected PBMCs, primary monocytes or a latently infected promonocytic U1 cell line show that HIV-1 replication and reactivation, monitored by p24 antigen measurement, are inhibited by PAO in a time- and concentration-dependent manner.@@@@1@61@@oe@16-12-2010 986350104@GENIA Treebank@formal@@1@S@These observations can be linked with the inhibition of NF-kappa B activation when uninfected monocytes are induced by either tumor necrosis factor alpha (TNF-alpha) phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS).@@@@1@38@@oe@16-12-2010 986416301@GENIA Treebank@formal@@1@S@Mechanism of interleukin-10 inhibition of T-helper cell activation by superantigen at the level of the cell cycle.@@@@1@18@@oe@16-12-2010 986416302@GENIA Treebank@formal@@1@S@We have analyzed the effects of interleukin-10 (IL-10) on the entry of quiescent CD4(+) T cells into the cell cycle upon stimulation with the superantigen staphylococcal enterotoxin B (SEB).@@@@1@34@@oe@16-12-2010 986416303@GENIA Treebank@formal@@1@S@IL-10 arrested cells at G0/G1.@@@@1@6@@oe@16-12-2010 986416304@GENIA Treebank@formal@@1@S@IL-10 treatment prevented the downregulation of p27(Kip1), an inhibitory protein that controls progression out of the G0 phase of the cell cycle.@@@@1@24@@oe@16-12-2010 986416305@GENIA Treebank@formal@@1@S@IL-10 also prevented the upregulation of the G1 cyclins D2 and D3, proteins necessary for entry and progression through the G1 phase of the cell cycle.@@@@1@28@@oe@16-12-2010 986416306@GENIA Treebank@formal@@1@S@Associated with the inhibition of the cell cycle, IL-10 suppressed SEB induction of interleukin-2 (IL-2).@@@@1@19@@oe@16-12-2010 986416307@GENIA Treebank@formal@@1@S@Addition of exogenous IL-2 to IL-10-treated cells significantly reversed the antiproliferative effects of IL-10.@@@@1@15@@oe@16-12-2010 986416308@GENIA Treebank@formal@@1@S@Moreover, IL-10 effects on the early G1 proteins p27(Kip1) and cyclin D2 were similarly reversed by exogenous IL-2.@@@@1@20@@oe@16-12-2010 986416309@GENIA Treebank@formal@@1@S@Although this reversal by IL-2 was pronounced, it was not complete, suggesting that IL-10 may have some effects not directly related to the suppression of IL-2 production.@@@@1@30@@oe@16-12-2010 986416310@GENIA Treebank@formal@@1@S@Cell separation experiments suggest that IL-10 can effect purified CD4(+) T cells directly, providing functional evidence for the presence of IL-10 receptors on CD4(+) T cells.@@@@1@28@@oe@16-12-2010 986416311@GENIA Treebank@formal@@1@S@IL-10 also inhibited expression of IL-2 transcriptional regulators c-fos and c-jun, which also inhibit other cell functions.@@@@1@19@@oe@16-12-2010 986416312@GENIA Treebank@formal@@1@S@Our studies show that the mechanism of IL-10 regulation of quiescent CD4(+) T-cell activation is mainly by blocking induction of IL-2 that is critical to downregulation of p27(Kip1) and upregulation of D cyclins in T-cell activation and entry into the cell cycle.@@@@1@43@@oe@16-12-2010 986725501@GENIA Treebank@formal@@1@S@Effect of environmental estrogens on IL-1beta promoter activity in a macrophage cell line.@@@@1@14@@oe@16-12-2010 986725502@GENIA Treebank@formal@@1@S@Environmental estrogens or estrogen disrupters have recently received a great deal of attention because of their potential health impact on reproductive tissues.@@@@1@23@@oe@16-12-2010 986725503@GENIA Treebank@formal@@1@S@Few, if any, studies have been made on the impact of these compounds on the immune system.@@@@1@20@@oe@16-12-2010 986725504@GENIA Treebank@formal@@1@S@We sought to determine the activities of various environmental estrogens on the modulation of the interleukin-1beta (IL-1beta) gene in a model monocytic cell line, hER + IL-1beta-CAT+.@@@@1@29@@oe@16-12-2010 986725505@GENIA Treebank@formal@@1@S@This cell line stably transfected with the human estrogen receptor, and an IL-1beta promoter construct fused to the CAT reporter gene allows us to monitor the effect of estrogenic compounds on IL-1beta promoter activity.@@@@1@36@@oe@16-12-2010 986725506@GENIA Treebank@formal@@1@S@17beta-estradiol (E2) markedly enhanced lipopolysaccharide- (LPS) induced IL-1beta promoter-driven CAT activity in a dose-dependent manner.@@@@1@20@@oe@16-12-2010 986725507@GENIA Treebank@formal@@1@S@The mycotoxins alpha-zearalenol and zearalenone both exhibited full agonist activity, but at lower potencies, with EC50 values of 1.8 and 54 nM, respectively, compared with E2 at 0.5 nM.@@@@1@34@@oe@16-12-2010 986725508@GENIA Treebank@formal@@1@S@In addition, genistein was a very low-potency agonist, having an EC50 of 1.5 microM.@@@@1@17@@oe@16-12-2010 986725509@GENIA Treebank@formal@@1@S@Similar to the E2 response, the slope factors for alpha-zearalenol, zearalenone, and genistein were close to 3.0, suggesting positive cooperativity in the estrogenic response.@@@@1@29@@oe@16-12-2010 986725510@GENIA Treebank@formal@@1@S@The activity of the mycotoxins appeared to be mediated through the estrogen receptor, since both the antiestrogens H1285 and ICI 182,780 effectively inhibited their agonist activity in a dose-dependent manner.@@@@1@34@@oe@16-12-2010 986725511@GENIA Treebank@formal@@1@S@Representative environmental estrogenic compounds both from plant and industrial sources were also tested.@@@@1@14@@oe@16-12-2010 986725512@GENIA Treebank@formal@@1@S@Unlike the mycoestrogens, none of the compounds, with the exception of genistein, synergized with LPS to enhance IL-1beta promoter activity.@@@@1@24@@oe@16-12-2010 986725513@GENIA Treebank@formal@@1@S@When tested for antiestrogenic activity, the industrial compound 4-octylphenol was able to antagonize the response to E2; however, the response was three orders of magnitude less potent than H 1285.@@@@1@34@@oe@16-12-2010 986725514@GENIA Treebank@formal@@1@S@Naringenin, a plant flavonoid, showed little or no ability to antagonize the response to E2.@@@@1@18@@oe@16-12-2010 986725515@GENIA Treebank@formal@@1@S@Overall, the results show that some environmental estrogens that display agonist activity in reproductive tissue also have an effect on IL-1 gene expression in hemopoietic-derived tissue.@@@@1@28@@oe@16-12-2010 987058101@GENIA Treebank@formal@@1@S@The position of the ZEBRA activation domain does not influence its biological activity.@@@@1@14@@oe@16-12-2010 987058102@GENIA Treebank@formal@@1@S@Epstein-Barr virus (EBV) is a human herpesvirus which latently infects B lymphocytes.@@@@1@15@@oe@16-12-2010 987058103@GENIA Treebank@formal@@1@S@EBV encodes a unique transcriptional activator, known as ZEBRA, which can disrupt viral latency in B cells and induce lytic viral replication.@@@@1@25@@oe@16-12-2010 987058104@GENIA Treebank@formal@@1@S@Furthermore, ZEBRA has been shown to bind at the EBV origin of lytic replication, and is necessary for viral DNA replication to occur.@@@@1@26@@oe@16-12-2010 987058105@GENIA Treebank@formal@@1@S@Previously we demonstrated that heterologous activation domains can fully substitute for the ZEBRA activation domain.@@@@1@16@@oe@16-12-2010 987058106@GENIA Treebank@formal@@1@S@Here we extend those results by showing that the position of the ZEBRA activation domain or a heterologous replacement domain does not influence its ability to function in the disruption of EBV latency.@@@@1@34@@oe@16-12-2010 987058107@GENIA Treebank@formal@@1@S@In this study three novel clones were constructed in which the ZEBRA activation region was repositioned to the carboxy terminus of the protein.@@@@1@24@@oe@16-12-2010 987058108@GENIA Treebank@formal@@1@S@These mutants were used to demonstrate that the ability of ZEBRA's wild type domain to function in the complex biological process of virus activation is not compromised by altering its position within the protein.@@@@1@36@@oe@16-12-2010 987267601@GENIA Treebank@formal@@1@S@Interleukin-10 stabilizes inhibitory kappaB-alpha in human monocytes.@@@@1@8@@oe@16-12-2010 987267602@GENIA Treebank@formal@@1@S@Interleukin-10 (IL-10) protects animals from lethal endotoxemia.@@@@1@10@@oe@16-12-2010 987267603@GENIA Treebank@formal@@1@S@This beneficial effect is mediated, in part, by inhibition of inflammatory cytokine production, including tumor necrosis factor-alpha (TNF-alpha).@@@@1@24@@oe@16-12-2010 987267604@GENIA Treebank@formal@@1@S@Evidence suggests that IL-10 may inhibit activation of the transcription factor nuclear factor-kappaB (NF-kappaB) through an unknown mechanism.@@@@1@21@@oe@16-12-2010 987267605@GENIA Treebank@formal@@1@S@NF-kappaB activation in response to inflammatory signals is dependent upon degradation of its associated inhibitory peptide, inhibitory kappaB-alpha (IkappaB-alpha).@@@@1@23@@oe@16-12-2010 987267606@GENIA Treebank@formal@@1@S@We hypothesized that IL-10 prevents human monocyte NF-kappaB activation and resultant TNF-alpha production by stabilization of IkappaB-alpha.@@@@1@18@@oe@16-12-2010 987267607@GENIA Treebank@formal@@1@S@The purpose of this study was to determine the effect of IL-10 on lipopolysaccharide (LPS)-induced human monocyte TNF-alpha production, NF-kappaB activation, and IkappaB-alpha degradation.@@@@1@30@@oe@16-12-2010 987267608@GENIA Treebank@formal@@1@S@Monocytes were isolated from human donors.@@@@1@7@@oe@16-12-2010 987267609@GENIA Treebank@formal@@1@S@Cells were stimulated with endotoxin (LPS, 100 ng/mL) with and without human IL-10 (10 ng/mL).@@@@1@21@@oe@16-12-2010 987267610@GENIA Treebank@formal@@1@S@Following stimulation, TNF-alpha was measured in cell supernatants by ELISA, NF-kappaB activity by electrophoretic mobility shift assay, and IkappaB-alpha levels by Western blot.@@@@1@27@@oe@16-12-2010 987267611@GENIA Treebank@formal@@1@S@We observed that after LPS stimulation of human monocytes, TNF-alpha increased to 798+/-67 pg/mL (p < .001 versus control).@@@@1@23@@oe@16-12-2010 987267612@GENIA Treebank@formal@@1@S@IL-10 attenuated LPS-stimulated TNF-alpha production (297+/-54; p < .001 versus LPS alone).@@@@1@16@@oe@16-12-2010 987267613@GENIA Treebank@formal@@1@S@After LPS stimulation in human monocytes, IkappaB-alpha protein levels decreased, and NF-kappaB DNA binding increased.@@@@1@18@@oe@16-12-2010 987267614@GENIA Treebank@formal@@1@S@IL-10 pretreatment prevented LPS-induced decreases in IkappaB-alpha protein levels and attenuated NF-kappaB DNA binding.@@@@1@15@@oe@16-12-2010 987267615@GENIA Treebank@formal@@1@S@IL-10 appears to prevent activation of NF-kappaB by preserving IkappaB-alpha protein levels, leading to a reduction in TNF-alpha release.@@@@1@21@@oe@16-12-2010 987293701@GENIA Treebank@formal@@1@S@Functional testosterone receptors in plasma membranes of T cells.@@@@1@10@@oe@16-12-2010 987293702@GENIA Treebank@formal@@1@S@T cells are considered to be unresponsive to testosterone due to the absence of androgen receptors (AR).@@@@1@20@@oe@16-12-2010 987293703@GENIA Treebank@formal@@1@S@Here, we demonstrate the testosterone responsiveness of murine splenic T cells in vitro as well as the presence of unconventional cell surface receptors for testosterone and classical intracellular AR.@@@@1@31@@oe@16-12-2010 987293704@GENIA Treebank@formal@@1@S@Binding sites for testosterone on the surface of both CD4(+) and CD8(+) subsets of T cells are directly revealed with the impeded ligand testosterone-BSA-FITC by confocal laser scanning microscopy (CLSM) and flow cytometry, respectively.@@@@1@38@@oe@16-12-2010 987293705@GENIA Treebank@formal@@1@S@Binding of the plasma membrane impermeable testosterone-BSA conjugate induces a rapid rise (<5 s) in [Ca2+]i of Fura-2-loaded T cells.@@@@1@24@@oe@16-12-2010 987293706@GENIA Treebank@formal@@1@S@This rise reflects influx of extracellular Ca2+ through non-voltage-gated and Ni2+-blockable Ca2+ channels of the plasma membrane.@@@@1@18@@oe@16-12-2010 987293707@GENIA Treebank@formal@@1@S@The testosterone-BSA-induced Ca2+ import is not affected by cyproterone, a blocker of the AR.@@@@1@16@@oe@16-12-2010 987293708@GENIA Treebank@formal@@1@S@In addition, AR are not detectable on the surface of intact T cells when using anti-AR antibodies directed against the amino and carboxy terminus of the AR, although T cells contain AR, as revealed by reverse transcription-polymerase chain reactions and Western blotting.@@@@1@46@@oe@16-12-2010 987293709@GENIA Treebank@formal@@1@S@AR can be visualized with the anti-AR antibodies in the cytoplasm of permeabilized T cells by using CLSM, though AR are not detectable in cytosol fractions when using the charcoal binding assay with 3H-R1881 as ligand.@@@@1@38@@oe@16-12-2010 987293710@GENIA Treebank@formal@@1@S@Cytoplasmic AR do not translocate to the nucleus of T cells in the presence of testosterone, in contrast to cytoplasmic AR in human cancer LNCaP cells.@@@@1@28@@oe@16-12-2010 987293711@GENIA Treebank@formal@@1@S@These findings suggest that the classical AR present in splenic T cells are not active in the genomic pathway.@@@@1@20@@oe@16-12-2010 987293712@GENIA Treebank@formal@@1@S@By contrast, the cell surface receptors for testosterone are in a functionally active state, enabling T cells a nongenomic response to testosterone.@@@@1@25@@oe@16-12-2010 987304101@GENIA Treebank@formal@@1@S@Regulation of fas-ligand expression during activation-induced cell death in T lymphocytes via nuclear factor kappaB.@@@@1@16@@oe@16-12-2010 987304102@GENIA Treebank@formal@@1@S@T cell receptor engagement activates transcription factors important for cytokine gene regulation.@@@@1@13@@oe@16-12-2010 987304103@GENIA Treebank@formal@@1@S@Additionally, this signaling pathway also leads to activation-induced apoptosis in T lymphocytes that is dependent on FasL transcription and expression.@@@@1@22@@oe@16-12-2010 987304104@GENIA Treebank@formal@@1@S@Here we demonstrate that nuclear factor kappaB (NF-kappaB), which is involved in the transcriptional regulation of many cytokine genes expressed in activated lymphocytes, also plays a role in T cell activation-induced FasL expression.@@@@1@38@@oe@16-12-2010 987304105@GENIA Treebank@formal@@1@S@Inhibition of NF-kappaB activity in a T cell hybridoma leads to decreased FasL expression and apoptosis upon T cell receptor stimulation.@@@@1@22@@oe@16-12-2010 987304106@GENIA Treebank@formal@@1@S@We identified the NF-kappaB site in the FasL promoter that contributes to such regulation.@@@@1@15@@oe@16-12-2010 987304107@GENIA Treebank@formal@@1@S@Co-expression of p65 (Rel A) with the FasL promoter enhanced its activity, and co-expression of IkappaB dramatically inhibited the inducible promoter activity.@@@@1@26@@oe@16-12-2010 987304108@GENIA Treebank@formal@@1@S@In contrast, the transcription factor AP-1 is not required for activation-induced FasL promoter activity.@@@@1@16@@oe@16-12-2010 987304109@GENIA Treebank@formal@@1@S@These results define a role for NF-kappaB in mediating FasL expression during T cell activation.@@@@1@16@@oe@16-12-2010 987451501@GENIA Treebank@formal@@1@S@X-rays-induced secretion of cellular factor(s) that enhance(s) HIV-1 promoter transcription in various non-irradiated transfected cell lines.@@@@1@23@@oe@16-12-2010 987451502@GENIA Treebank@formal@@1@S@Various cellular stress agents like ionizing radiation exposure could activate human immunodeficiency virus type 1 (HIV- 1) replication or reporter gene expression.@@@@1@24@@oe@16-12-2010 987451503@GENIA Treebank@formal@@1@S@In addition, extracellular factor(s) released by X-ray-treated human colonic carcinoma cell line (HT29) might activate the long terminal repeat (LTR) of HIV-1 in non-irradiated HT29 cells.@@@@1@35@@oe@16-12-2010 987451504@GENIA Treebank@formal@@1@S@In the present report we show that in various transiently or stably transfected cell lines, X-ray irradiation up-regulates HIV-1 LTR transcription through the kappaB regulatory elements.@@@@1@28@@oe@16-12-2010 987451505@GENIA Treebank@formal@@1@S@A factor(s), which is processed by and acts upon a variety of cell types, was detected by addition to non-irradiated cells of either X-ray-treated cells or a conditioned medium taken from irradiated cultures.@@@@1@39@@oe@16-12-2010 987451506@GENIA Treebank@formal@@1@S@The magnitude of responsiveness is cell type dependent.@@@@1@9@@oe@16-12-2010 987451507@GENIA Treebank@formal@@1@S@In addition, X-ray activation of HIV-1 LTR in transiently or stably transfected cell lines is inhibited by a potent antioxidant drug, pyrrolidine dithiocarbamate and by another drug, known for its role in the trapping of growth factors, suramin.@@@@1@43@@oe@16-12-2010 987451508@GENIA Treebank@formal@@1@S@The importance of these observations in the pathophysiology of patients with AIDS-related cancers treated by radiotherapy remains to be established.@@@@1@21@@oe@16-12-2010 987532501@GENIA Treebank@formal@@1@S@Characterisation of regulatory sequences at the Epstein-Barr virus BamHI W promoter.@@@@1@12@@oe@16-12-2010 987532502@GENIA Treebank@formal@@1@S@Epstein-Barr virus, a human gammaherpesvirus, possesses a unique set of latent genes whose constitutive expression in B cells leads to cell growth transformation.@@@@1@26@@oe@16-12-2010 987532503@GENIA Treebank@formal@@1@S@The initiation of this growth transforming infection depends on a viral promoter in BamHI W (Wp) whose regulation is poorly understood.@@@@1@24@@oe@16-12-2010 987532504@GENIA Treebank@formal@@1@S@Using Wp reporter constructs in in vitro transfection assays, we found that Wp was 11- to 190-fold more active in B cell than in non-B cell lines and that three regions of the promoter (termed UAS1, UAS2, and UAS3) contributed to transcriptional activation.@@@@1@49@@oe@16-12-2010 987532505@GENIA Treebank@formal@@1@S@The upstream regions UAS3 (-1168 to -440) and UAS2 (-352 to -264) both functioned in a cell lineage-independent manner and were together responsible for the bulk of Wp activity in non-B cells; mutational analysis indicated the importance of a YY1 binding site in UAS2 in that context.@@@@1@53@@oe@16-12-2010 987532506@GENIA Treebank@formal@@1@S@By contrast, UAS1 (-140 to -87) was B cell specific and was the key determinant of the promoter's increased activity in B cell lines.@@@@1@29@@oe@16-12-2010 987532507@GENIA Treebank@formal@@1@S@Mutational analysis of UAS1 sequences combined with in vitro bandshift assays revealed the presence of three binding sites for cellular factors in this region.@@@@1@25@@oe@16-12-2010 987532508@GENIA Treebank@formal@@1@S@When mutations that abolished factor binding in bandshift assays were introduced into a Wp reporter construct, the loss of any one of the three UAS1 binding sites was sufficient to reduce promoter activity by 10- to 30-fold in B cells.@@@@1@42@@oe@16-12-2010 987532509@GENIA Treebank@formal@@1@S@From sequence analysis, two of these appear to be novel transcription factor binding sites, whereas the third was identified as a cyclic AMP response element (CRE).@@@@1@31@@oe@16-12-2010 987532510@GENIA Treebank@formal@@1@S@Our data indicate that this CRE interacts with CREB and ATF1 proteins present in B cell nuclear extracts and that this interaction is important for Wp activity.@@@@1@28@@oe@16-12-2010 987553701@GENIA Treebank@formal@@1@S@Transcription factor binding to the core promoter of the human monoamine oxidase B gene in the cerebral cortex and in blood cells.@@@@1@23@@oe@16-12-2010 987553702@GENIA Treebank@formal@@1@S@Many studies show that monoamine oxidase B in blood cells is a biological marker for personality characteristics such as sensation seeking.@@@@1@22@@oe@16-12-2010 987553703@GENIA Treebank@formal@@1@S@The mechanism underlying this association is so far not explored.@@@@1@11@@oe@16-12-2010 987553704@GENIA Treebank@formal@@1@S@In the present study we have performed electrophoretic mobility-shift assays to investigate the pattern of protein binding to a 150 bp fragment of the proximal 5'-flanking region of the human monoamine oxidase B gene.@@@@1@35@@oe@16-12-2010 987553705@GENIA Treebank@formal@@1@S@We compared the pattern using nuclear extracts from human brain and lymphocytes.@@@@1@13@@oe@16-12-2010 987553706@GENIA Treebank@formal@@1@S@Interestingly, a correlation was observed between monoamine oxidase B enzyme activity in blood cells (platelets) and the binding pattern of two uncharacterized transcription factors.@@@@1@28@@oe@16-12-2010 987553707@GENIA Treebank@formal@@1@S@These data are well in line with the long-standing notion that interindividual differences in platelet monoamine oxidase may represent differences in expression of the enzyme rather than genotypic variation.@@@@1@30@@oe@16-12-2010 987860801@GENIA Treebank@formal@@1@S@Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein.@@@@1@25@@oe@16-12-2010 987860802@GENIA Treebank@formal@@1@S@Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), or human herpesvirus 8, is a lymphotropic virus strongly linked to several AIDS-related neoplasms.@@@@1@28@@oe@16-12-2010 987860803@GENIA Treebank@formal@@1@S@The primary reservoir of infection consists of latently infected B lymphocytes and possibly other mononuclear cells.@@@@1@17@@oe@16-12-2010 987860804@GENIA Treebank@formal@@1@S@Viral reactivation from latency and spread from this lymphoid reservoir is presumably required for development of nonlymphoid tumors like KS.@@@@1@21@@oe@16-12-2010 987860805@GENIA Treebank@formal@@1@S@Here we show that deregulated expression of a single viral gene, ORF 50, which encodes a transactivator able to selectively upregulate delayed-early viral genes, suffices to disrupt latency and induce the lytic gene cascade in latently infected B cells.@@@@1@43@@oe@16-12-2010 987860806@GENIA Treebank@formal@@1@S@The identification of this gene opens the way to studies of the physiologic mechanisms controlling reactvation of KSHV from latency.@@@@1@21@@oe@16-12-2010 987860807@GENIA Treebank@formal@@1@S@Copyright 1998 Academic Press.@@@@1@5@@oe@16-12-2010 987862101@GENIA Treebank@formal@@1@S@Regulation of interleukin-1beta transcription by Epstein-Barr virus involves a number of latent proteins via their interaction with RBP.@@@@1@19@@oe@16-12-2010 987862102@GENIA Treebank@formal@@1@S@Epstein-Barr virus (EBV) infects B cells, resulting in the outgrowth of immortalised lymphoblastoid cell lines (LCLs).@@@@1@22@@oe@16-12-2010 987862103@GENIA Treebank@formal@@1@S@Here, we demonstrate through the use of intracellular staining that interleukin-1beta (IL-1beta) is expressed in LCLs and investigate the influence of the individual latent proteins on the expression of IL-1beta.@@@@1@34@@oe@16-12-2010 987862104@GENIA Treebank@formal@@1@S@Using RT-PCR, IL-1beta was shown to be up-regulated in EBV-transformed LCLs as well as in group III Burkitt's lymphoma (BL) cell lines, compared with group I BL cell lines.@@@@1@35@@oe@16-12-2010 987862105@GENIA Treebank@formal@@1@S@The up-regulation of IL-1beta message could be mediated by the latent membrane protein-1, EBV nuclear proteins 2, 3, 4, and 6 genes.@@@@1@27@@oe@16-12-2010 987862106@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assays (EMSAs) demonstrated that the -300 region of the IL-1beta promoter, which contains a nuclear factor-kappaB (NF-kappaB) binding site, contained a functional RBP binding site.@@@@1@35@@oe@16-12-2010 987862107@GENIA Treebank@formal@@1@S@Binding of RBP to this site could be inhibited by addition of EBV nuclear proteins 3 and 6, suggesting that these proteins displace RBP from its recognition sequence, removing transcriptional repression and allowing gene transcription to occur.@@@@1@40@@oe@16-12-2010 987862108@GENIA Treebank@formal@@1@S@In group I BL cells, containing low levels of NF-kappaB, only RBP binding was observed in EMSAs, whereas NF-kappaB binding could be demonstrated in EBV-transformed B cell lines containing high levels of activated NF-kappaB.@@@@1@38@@oe@16-12-2010 987862109@GENIA Treebank@formal@@1@S@In addition, the expression of latent membrane protein-1 led to activation of NF-kappaB that was capable of binding the IL-1beta promoter.@@@@1@23@@oe@16-12-2010 987862110@GENIA Treebank@formal@@1@S@The study demonstrates that EBV can up-regulate IL-1beta expression, possibly by using RBP, NF-kappaB, or both.@@@@1@20@@oe@16-12-2010 987862111@GENIA Treebank@formal@@1@S@Copyright 1998 Academic Press.@@@@1@5@@oe@16-12-2010 988024001@GENIA Treebank@formal@@1@S@X chromosome inactivation patterns in normal females.@@@@1@8@@oe@16-12-2010 988024002@GENIA Treebank@formal@@1@S@Since one of the two X chromosomes is randomly inactivated at an early stage of female embryonic development, X-linked markers have been used to study the origin and development of various neoplastic disorders in affected heterozygous women; clonality assays have provided a useful tool to the understanding of the mechanisms underlying the development of neoplasia.@@@@1@58@@oe@16-12-2010 988024003@GENIA Treebank@formal@@1@S@Recently, a technique of clonal analysis has been devised that takes advantage of a highly polymorphic short tandem repeat within the X-linked human androgen receptor (AR) gene, resulting in a heterozygosity rate approaching 90%.@@@@1@40@@oe@16-12-2010 988024004@GENIA Treebank@formal@@1@S@The rapid expansion of the number of women now suitable for X inactivation analysis has however given rise to new controversies, one of the more troublesome being the possibility of a modification of the pattern of X- chromosome inactivation pattern in blood cells of elderly women.@@@@1@47@@oe@16-12-2010 988024005@GENIA Treebank@formal@@1@S@In the present study we analyze with the AR assay a group of 166 healthy females aged between 8 and 94 years, with no history of genetic or neoplastic familial disorders.@@@@1@33@@oe@16-12-2010 988024006@GENIA Treebank@formal@@1@S@We failed to find any correlation between age and X- chromosome inactivation pattern (r = 0.17), even subdividing the subjects in different age groups according to the criteria used by other researchers, and therefore reaffirm that, when tested for with well-standardized and accurate criteria, extremely unbalanced inactivation of the X chromosome is a truly uncommon phenomenon in normal women.@@@@1@65@@oe@16-12-2010 988024007@GENIA Treebank@formal@@1@S@Copyright 1998 Academic Press.@@@@1@5@@oe@16-12-2010 988055501@GENIA Treebank@formal@@1@S@Characterization of the human elk-1 promoter.@@@@1@7@@oe@16-12-2010 988055502@GENIA Treebank@formal@@1@S@Potential role of a downstream intronic sequence for elk-1 gene expression in monocytes.@@@@1@14@@oe@16-12-2010 988055503@GENIA Treebank@formal@@1@S@To characterize the human elk-1 promoter, we mapped the transcriptional start site and isolated elk-1-specific genomic phage clones that contained extensive upstream and downstream sequences.@@@@1@27@@oe@16-12-2010 988055504@GENIA Treebank@formal@@1@S@A TATA-like motif was identified immediately upstream of the transcriptional start site.@@@@1@13@@oe@16-12-2010 988055505@GENIA Treebank@formal@@1@S@Functional analyses of DNA fragments containing the TATA element and the identification of a DNase I-hypersensitive chromatin site (HS 1) in close proximity to the TATA box suggest that the identified TATA motif is important for elk-1 transcription in vivo.@@@@1@43@@oe@16-12-2010 988055506@GENIA Treebank@formal@@1@S@Sequences upstream and downstream from the TATA box were found to contribute to elk-1 promoter activity.@@@@1@17@@oe@16-12-2010 988055507@GENIA Treebank@formal@@1@S@A second hypersensitive site (HS 2) was identified within the first intron in pre-monocytic cells, which express Elk-1 only when differentiating to monocytes.@@@@1@27@@oe@16-12-2010 988055508@GENIA Treebank@formal@@1@S@In a variety of other cell types, which display a constitutive Elk-1 expression, HS 2 did not exist, suggesting that inducibility of elk-1 expression is associated with the presence of HS 2.@@@@1@36@@oe@16-12-2010 988055509@GENIA Treebank@formal@@1@S@Egr-1 and the serum response factor were found to interact specifically with the intronic sequence at +265 and +448, respectively.@@@@1@22@@oe@16-12-2010 988055510@GENIA Treebank@formal@@1@S@Because Egr-1 mRNA and protein levels were observed to increase significantly before induction of elk-1 expression, we propose that Egr-1 is important for the regulation of elk-1 transcription in differentiating monocytes.@@@@1@33@@oe@16-12-2010 988197701@GENIA Treebank@formal@@1@S@Direct suppression of Stat1 function during adenoviral infection.@@@@1@9@@oe@16-12-2010 988197702@GENIA Treebank@formal@@1@S@The action of adenoviral E1A oncoprotein on host immune-response genes has been attributed to interaction with p300/CBP-type transcriptional coactivators in competition with endogenous transcription factors such as signal transducer and activator of transcription (STAT) proteins.@@@@1@38@@oe@16-12-2010 988197703@GENIA Treebank@formal@@1@S@However, we show that mutant forms of E1A that no longer bind p300/CBP can still interact directly with Stat1 (via E1A N-terminal and Stat1 C-terminal residues) and block IFNgamma-driven, Stat1-dependent gene activation and consequent function during early-phase infection in the natural host cell.@@@@1@48@@oe@16-12-2010 988197704@GENIA Treebank@formal@@1@S@The results provide a distinct and more specific mechanism for E1A-mediated immune suppression and an alternative model of IFNgamma-driven enhanceosome formation that may allow for other adaptors (in addition to p300/CBP) to link Stat1 to the basal transcription complex.@@@@1@42@@oe@16-12-2010 988233101@GENIA Treebank@formal@@1@S@Human T-cell leukemia virus type 1 tax protein abrogates interleukin-2 dependence in a mouse T-cell line.@@@@1@17@@oe@16-12-2010 988233102@GENIA Treebank@formal@@1@S@Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia.@@@@1@18@@oe@16-12-2010 988233103@GENIA Treebank@formal@@1@S@Tax, the viral protein, is thought to be crucial in the development of the disease, since it transforms healthy T cells in vitro and induces tumors in transgenic animals.@@@@1@33@@oe@16-12-2010 988233104@GENIA Treebank@formal@@1@S@We examined the effect of Tax activity on the growth of the interleukin-2 (IL-2)-dependent T-cell line CTLL-2.@@@@1@21@@oe@16-12-2010 988233105@GENIA Treebank@formal@@1@S@Stable expression of Tax in CTLL-2 transformed cell growth from being IL-2 dependent to IL-2 independent.@@@@1@17@@oe@16-12-2010 988233106@GENIA Treebank@formal@@1@S@Tax stimulated transcription through NF-kappaB and the cyclic AMP-responsive element-like sequence in the HTLV-1 promoter.@@@@1@16@@oe@16-12-2010 988233107@GENIA Treebank@formal@@1@S@The finding of Tax mutants segregating these two pathways suggested that the NF-kappaB pathway was essential for IL-2-independent growth of CTLL-2 cells while the CRE pathway was unnecessary.@@@@1@29@@oe@16-12-2010 988233108@GENIA Treebank@formal@@1@S@However, both pathways were necessary for another transformation-related activity (colony formation in soft agar) of CTLL-2/Tax.@@@@1@20@@oe@16-12-2010 988233109@GENIA Treebank@formal@@1@S@Our results show that Tax has at least two distinct activities on T cells, and suggest that Tax plays a crucial role in IL-2-independent T-cell transformation induced by HTLV-1, in addition to its well-known IL-2-dependent cell transformation.@@@@1@40@@oe@16-12-2010 988262401@GENIA Treebank@formal@@1@S@Mildly oxidized low-density lipoproteins decrease early production of interleukin 2 and nuclear factor kappaB binding to DNA in activated T-lymphocytes.@@@@1@21@@oe@16-12-2010 988262402@GENIA Treebank@formal@@1@S@Activated T-lymphocytes are found early in atherosclerosis lesions, but little is known about their role.@@@@1@17@@oe@16-12-2010 988262403@GENIA Treebank@formal@@1@S@Oxidized low-density lipoproteins (oxLDLs) are considered to be involved in the pathogenesis of the lesions, and we have previously demonstrated that oxLDLs inhibit not only interleukin (IL)-2-receptor expression on the surface of in vitro-activated T-lymphocytes but also their proliferation.@@@@1@46@@oe@16-12-2010 988262404@GENIA Treebank@formal@@1@S@We have now investigated the effect of oxLDLs on blast differentiation, on IL-2 synthesis and on the activation of the nuclear factor kappaB (NF-kappaB) system in activated lymphocytes.@@@@1@32@@oe@16-12-2010 988262405@GENIA Treebank@formal@@1@S@Mildly oxLDLs (50 and 100 microgram/ml) decreased the number of lymphoblasts and the level of IL-2 concentration in the culture supernatants after activation of lymphocytes by phytohaemagglutinin and PMA+ionomycin.@@@@1@32@@oe@16-12-2010 988262406@GENIA Treebank@formal@@1@S@The inhibition of IL-2 production was observed in the CD3(+) T-lymphocyte cytoplasm as early as 4 h after activation by PMA+ionomycin.@@@@1@22@@oe@16-12-2010 988262407@GENIA Treebank@formal@@1@S@The study of NF-kappaB showed that oxLDLs led to a decrease of activation-induced p65/p50 NF-kappaB heterodimer binding to DNA, whereas the presence of the constitutive nuclear form of p50 dimer was unchanged.@@@@1@34@@oe@16-12-2010 988262408@GENIA Treebank@formal@@1@S@This was correlated with an unchanged level of the active form of the cytosolic inhibitor protein IkappaB-alpha.@@@@1@18@@oe@16-12-2010 988262409@GENIA Treebank@formal@@1@S@Taken together, these observations suggest that the immunosuppressive effect of oxLDLs might operate via a dysregulation of the T-lymphocyte activation mechanisms.@@@@1@23@@oe@16-12-2010 988380301@GENIA Treebank@formal@@1@S@Binding of HMG-I(Y) elicits structural changes in a silencer of the human beta-globin gene.@@@@1@15@@oe@16-12-2010 988380302@GENIA Treebank@formal@@1@S@Proteins involved in repression of the human beta-globin gene may be useful in the treatment of sickle cell anemia, in conjunction with therapy to reactivate fetal globin genes.@@@@1@30@@oe@16-12-2010 988380303@GENIA Treebank@formal@@1@S@If there is a reciprocal elevation of gamma-globin expression upon repression, this approach could be useful in additional hemoglobinopathies.@@@@1@21@@oe@16-12-2010 988380304@GENIA Treebank@formal@@1@S@We previously showed that repression of the beta-globin gene appears to be mediated through two DNA sequences, silencers I and II, and identified a protein termed BP1 which binds to both silencer sequences.@@@@1@36@@oe@16-12-2010 988380305@GENIA Treebank@formal@@1@S@In this study, we cloned two cDNAs encoding proteins which bind to an oligonucleotide in silencer I containing a BP1 binding site.@@@@1@24@@oe@16-12-2010 988380306@GENIA Treebank@formal@@1@S@These cDNAs correspond to HMG-I and HMG-Y, isoforms regarded as architectural proteins.@@@@1@14@@oe@16-12-2010 988380307@GENIA Treebank@formal@@1@S@We demonstrate that binding of HMG-I(Y) to this oligonucleotide causes bending/flexure of the DNA.@@@@1@15@@oe@16-12-2010 988380308@GENIA Treebank@formal@@1@S@HMG-I(Y) also binds to a second oligonucleotide containing a BP1 binding site located in a negative control region upstream of the delta-globin gene, suggesting a role for HMG-I(Y) in repression of adult globin genes.@@@@1@36@@oe@16-12-2010 988380309@GENIA Treebank@formal@@1@S@Expression studies revealed that HMG-I(Y) is ubiquitously expressed in human tissues that do not express beta-globin, being present in 48 of 50 tissues and six hematopoietic cell lines examined.@@@@1@31@@oe@16-12-2010 988380310@GENIA Treebank@formal@@1@S@Furthermore, HMG-I(Y) expression is down-regulated during differentiation of primary erythroid cells.@@@@1@13@@oe@16-12-2010 988380311@GENIA Treebank@formal@@1@S@We present a model in which HMG-I(Y) alters DNA conformation to allow binding of repressor proteins, and in which the relative amount of HMG-I(Y) helps to determine the repressive state of the beta-globin gene.@@@@1@36@@oe@16-12-2010 988396601@GENIA Treebank@formal@@1@S@Induction of the pro-myelocytic leukaemia gene by type I and type II interferons.@@@@1@14@@oe@16-12-2010 988396602@GENIA Treebank@formal@@1@S@The physiological role of the pro-myelocytic leukaemia (PML) gene product is poorly defined.@@@@1@16@@oe@16-12-2010 988396603@GENIA Treebank@formal@@1@S@Among other functions, PML is involved in haematopoietic differentiation and in control of cell growth and tumorigenesis.@@@@1@19@@oe@16-12-2010 988396604@GENIA Treebank@formal@@1@S@We investigated the regulation of human PML expression by interferons (IFNs) and IL-1 in various human haematopoietic lines (U937, THP1, HL60, NB4), in human diploid fibroblasts and in human peripheral blood leukocytes.@@@@1@41@@oe@16-12-2010 988396605@GENIA Treebank@formal@@1@S@Cytokine-induced modulation of PML expression was assessed by Northern blot analyses, flow cytometry studies and in situ immunolabelling.@@@@1@20@@oe@16-12-2010 988396606@GENIA Treebank@formal@@1@S@Our data show that IFNs and IL-1 upregulate PML transcript and protein expression in a time and dose-dependent manner.@@@@1@20@@oe@16-12-2010 988396607@GENIA Treebank@formal@@1@S@In situ immunolabelling revealed that upregulation of protein expression by IFN-alpha is a consequence of a marked increase in both the number and the intensity of the staining of so-called PML nuclear bodies.@@@@1@34@@oe@16-12-2010 988396608@GENIA Treebank@formal@@1@S@Our data suggest that stimulation of PML expression by interferons and IL-1 may account for upregulation of PML proteins observed in inflammatory tissues and in proliferative states.@@@@1@28@@oe@16-12-2010 988521301@GENIA Treebank@formal@@1@S@The activity of the CCAAT-box binding factor NF-Y is modulated through the regulated expression of its A subunit during monocyte to macrophage differentiation: regulation of tissue-specific genes through a ubiquitous transcription factor.@@@@1@34@@oe@16-12-2010 988521302@GENIA Treebank@formal@@1@S@In this study, we analyzed the regulation of NF-Y expression during human monocyte to macrophage maturation.@@@@1@18@@oe@16-12-2010 988521303@GENIA Treebank@formal@@1@S@NF-Y is a ubiquitous and evolutionarily conserved transcription factor that binds specifically to the CCAAT motif present in the 5' promoter region of a wide variety of genes.@@@@1@29@@oe@16-12-2010 988521304@GENIA Treebank@formal@@1@S@We show here that in circulating monocytes, NF-Y binding activity is not detected on the CCAAT motif present in the promoters of genes such as major histocompatibility complex (MHC) class II, gp91-phox, mig, and fibronectin, whereas during macrophage differentiation, a progressive increase in NF-Y binding activity is observed on these promoters.@@@@1@60@@oe@16-12-2010 988521305@GENIA Treebank@formal@@1@S@Analysis of NF-Y subunit expression indicates that the absence of NF-Y activity in circulating monocytes is caused by a lack of the A subunit.@@@@1@25@@oe@16-12-2010 988521306@GENIA Treebank@formal@@1@S@Furthermore, addition of the recombinant NF-YA subunit restores NF-Y binding.@@@@1@12@@oe@16-12-2010 988521307@GENIA Treebank@formal@@1@S@We show that the lack of NF-YA protein is due to posttranscriptional regulation and not to a specific proteolytic activity.@@@@1@21@@oe@16-12-2010 988521308@GENIA Treebank@formal@@1@S@In fact, NF-YA mRNA is present at the same level at all days of monocyte cultivation, whereas the protein is absent in freshly isolated monocytes but is progressively synthesized during the maturation process.@@@@1@36@@oe@16-12-2010 988521309@GENIA Treebank@formal@@1@S@We thus conclude that the NF-YA subunit plays a relevant role in activating transcription of genes highly expressed in mature monocytes.@@@@1@22@@oe@16-12-2010 988521310@GENIA Treebank@formal@@1@S@In line with this conclusion, we show that the cut/CDP protein, a transcriptional repressor that inhibits gpc91-phox gene expression by preventing NF-Y binding to the CAAT box, is absent in monocytes.@@@@1@35@@oe@16-12-2010 988591701@GENIA Treebank@formal@@1@S@Mice lacking the transcription factor CIITA--a second look.@@@@1@11@@oe@16-12-2010 988591702@GENIA Treebank@formal@@1@S@We have generated a second line of mice lacking a transcription factor thought to be a critical regulator of MHC class II gene expression, CIITA (for class II transactivator).@@@@1@33@@oe@16-12-2010 988591703@GENIA Treebank@formal@@1@S@Our and the previously published lines differ in the deletion that was engineered and by the fact that we removed the neomycin-resistance promoter and structural gene via the cre-loxP recombination system.@@@@1@32@@oe@16-12-2010 988591704@GENIA Treebank@formal@@1@S@Characterization of our line led to two new findings.@@@@1@10@@oe@16-12-2010 988591705@GENIA Treebank@formal@@1@S@First, a substantial number of cells can express class II molecules in the absence of CIITA, albeit at 5-fold reduced levels, most notably dendritic cells in s.c. lymph nodes; therefore, the CIITA gene cannot be an absolute 'master gene' controlling the expression of class II molecules, as had been thought.@@@@1@60@@oe@16-12-2010 988591706@GENIA Treebank@formal@@1@S@Second, in contrast to recent results on human cell lines, CIITA is not critically involved in the IFN-gamma-induced up-regulation of MHC class I genes.@@@@1@27@@oe@16-12-2010 988641901@GENIA Treebank@formal@@1@S@Regulation of IL-6 synthesis in human peripheral blood mononuclear cells by C3a and C3a(desArg).@@@@1@15@@oe@16-12-2010 988641902@GENIA Treebank@formal@@1@S@The anaphylatoxin C3a has been reported to have immunomodulatory effects on a number of different cell types.@@@@1@18@@oe@16-12-2010 988641903@GENIA Treebank@formal@@1@S@In this study we investigated the effects of C3a and C3a(desArg) on gene expression and protein secretion of IL-6 in human PBMCs, either alone or in combination with LPS or IL-1beta.@@@@1@33@@oe@16-12-2010 988641904@GENIA Treebank@formal@@1@S@C3a or C3a(desArg) alone exhibited no effect on the expression or secretion of IL-6.@@@@1@15@@oe@16-12-2010 988641905@GENIA Treebank@formal@@1@S@However, when PBMC were stimulated with LPS or IL-1beta, both C3a and C3a(desArg) were found to enhance IL-6 release by PBMC in a dose-dependent manner.@@@@1@28@@oe@16-12-2010 988641906@GENIA Treebank@formal@@1@S@Since C3a has been shown to induce PGE2 production by monocytes, and PGE2 has been shown to influence cytokine production, we investigated the potential role of PGE2 in C3a-mediated enhancement of LPS- and IL-1beta-induced IL-6 production.@@@@1@39@@oe@16-12-2010 988641907@GENIA Treebank@formal@@1@S@Indomethacin blocked PGE2 release, but had no influence on the observed effects of C3a, suggesting that the effects of C3a on IL-6 production are independent of PGE2 formation by monocytes.@@@@1@33@@oe@16-12-2010 988641908@GENIA Treebank@formal@@1@S@Northern blot analysis showed that C3a as well as C3a(desArg) enhanced LPS-induced mRNA levels for IL-6.@@@@1@17@@oe@16-12-2010 988641909@GENIA Treebank@formal@@1@S@Pretreatment of PBMCs with pertussis toxin blocked the functions of C3a and C3a(desArg), indicating that the actions of these two molecules are mediated by a G protein-coupled pathway.@@@@1@30@@oe@16-12-2010 988641910@GENIA Treebank@formal@@1@S@Furthermore, we investigated the effects of C3a and C3a(desArg) on induction of NF-kappaB and activating protein-1 binding.@@@@1@19@@oe@16-12-2010 988641911@GENIA Treebank@formal@@1@S@Both molecules enhanced LPS-induced NF-kappaB and activating protein-1 binding activity.@@@@1@11@@oe@16-12-2010 988641912@GENIA Treebank@formal@@1@S@These results demonstrate the capacity of intact C3a and its circulating des-Arg form to exert immunmodulatory effects in vitro.@@@@1@20@@oe@16-12-2010 988643301@GENIA Treebank@formal@@1@S@Comparison of primary sensitization of naive human T cells to varicella-zoster virus peptides by dendritic cells in vitro with responses elicited in vivo by varicella vaccination.@@@@1@27@@oe@16-12-2010 988643302@GENIA Treebank@formal@@1@S@Dendritic cells (DC) are potent APC during primary and secondary immune responses.@@@@1@15@@oe@16-12-2010 988643303@GENIA Treebank@formal@@1@S@The first objective of this study was to determine whether human DC mediate in vitro sensitization of naive CD4+ T cells to epitopes of the immediate early 62 (IE62) protein of varicella zoster virus (VZV).@@@@1@40@@oe@16-12-2010 988643304@GENIA Treebank@formal@@1@S@The induction of CD4+ T cell proliferative responses to eight synthetic peptides representing amino acid sequences of the VZV IE62 protein was assessed using T cells and DC from VZV-susceptible donors.@@@@1@32@@oe@16-12-2010 988643305@GENIA Treebank@formal@@1@S@The second objective was to compare in vitro responses of naive T cells with responses to VZV peptides induced in vivo after immunization with varicella vaccine.@@@@1@27@@oe@16-12-2010 988643306@GENIA Treebank@formal@@1@S@T cell proliferation was induced by three peptides, P1, P4, and P7, in 71-100% of the donors tested before and after vaccination using DC as APC.@@@@1@32@@oe@16-12-2010 988643307@GENIA Treebank@formal@@1@S@Monocytes were effective APC for VZV peptides only after immunization.@@@@1@11@@oe@16-12-2010 988643308@GENIA Treebank@formal@@1@S@Two peptides, P2 and P8, induced naive T cell proliferation less effectively and were also less immunogenic for T cells from vaccinated or naturally immune donors.@@@@1@29@@oe@16-12-2010 988643309@GENIA Treebank@formal@@1@S@T cell recognition of specific peptides was concordant between naive, DC-mediated responses, and postvaccine responses using monocytes as APC in 69% of comparisons (p = 0.05; chi2); the predictive value of a positive response to an IE62 peptide before immunization for T cell sensitization in vivo was 82%.@@@@1@57@@oe@16-12-2010 988643310@GENIA Treebank@formal@@1@S@These observations indicate that primary T cell responses detected in vitro using DC as APC may be useful to characterize the potential immunogenicity of viral protein epitopes in vivo.@@@@1@30@@oe@16-12-2010 988705001@GENIA Treebank@formal@@1@S@Differential monocyte adhesion and adhesion molecule expression in venous and arterial endothelial cells.@@@@1@14@@oe@16-12-2010 988705002@GENIA Treebank@formal@@1@S@We compared U-937 cell adhesion and adhesion molecule expression in human umbilical venous (HUVECs) and arterial (HUAECs) endothelial cells exposed to tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide (LPS).@@@@1@40@@oe@16-12-2010 988705003@GENIA Treebank@formal@@1@S@TNF and LPS stimulated vascular cell adhesion molecule (VCAM)-1 surface expression and adhesion of U-937 monocyte-like cells to HUVECs but not to HUAECs.@@@@1@27@@oe@16-12-2010 988705004@GENIA Treebank@formal@@1@S@Antibody studies demonstrated that in HUVECs at least 75% of the adhesion response is VCAM-1 mediated.@@@@1@18@@oe@16-12-2010 988705005@GENIA Treebank@formal@@1@S@Interleukin-1 stimulated U-937 cell adhesion to and VCAM-1 surface expression in both HUVECs and HUAECs.@@@@1@16@@oe@16-12-2010 988705006@GENIA Treebank@formal@@1@S@Pyrrolidinedithiocarbamate and the proteasome inhibitor MG-132 blocked TNF- and LPS-stimulated U-937 cell adhesion to HUVECs.@@@@1@16@@oe@16-12-2010 988705007@GENIA Treebank@formal@@1@S@These agents also significantly decreased TNF- and LPS-stimulated increases in HUVEC surface VCAM-1.@@@@1@14@@oe@16-12-2010 988705008@GENIA Treebank@formal@@1@S@TNF increased VCAM-1 protein and mRNA in HUVECs that was blocked by pyrrolidinedithiocarbamate.@@@@1@14@@oe@16-12-2010 988705009@GENIA Treebank@formal@@1@S@However, neither TNF or LPS stimulated VCAM-1 expression in HUAECs.@@@@1@12@@oe@16-12-2010 988705010@GENIA Treebank@formal@@1@S@TNF stimulated expression of both intercellular adhesion molecule-1 and E-selectin in HUVECs, but in HUAECs, only intercellular adhesion molecule-1 was increased.@@@@1@24@@oe@16-12-2010 988705011@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assays demonstrated no difference in the pattern of TNF-stimulated nuclear factor-kappaB activation between HUVECs and HUAECs.@@@@1@20@@oe@16-12-2010 988705012@GENIA Treebank@formal@@1@S@These studies demonstrate a novel and striking insensitivity of arterial endothelium to the effects of TNF and LPS and indicate a dissociation between the ability of HUAECs to upregulate nuclear factor-kappaB and VCAM-1.@@@@1@34@@oe@16-12-2010 988886501@GENIA Treebank@formal@@1@S@Tissue factor expression of human monocytes is suppressed by lysophosphatidylcholine.@@@@1@11@@oe@16-12-2010 988886502@GENIA Treebank@formal@@1@S@The expression of tissue factor (TF), the principal initiator of coagulation, is increased during inflammation and atherosclerosis.@@@@1@22@@oe@16-12-2010 988886503@GENIA Treebank@formal@@1@S@Both conditions are promoted by lysophosphatidylcholine (lysoPC).@@@@1@10@@oe@16-12-2010 988886504@GENIA Treebank@formal@@1@S@We observed in the present study that lysoPC (1 to 10 micromol/L) dose-dependently reduced TF activity in human monocytes, as elicited by lipopolysaccharide (LPS).@@@@1@30@@oe@16-12-2010 988886505@GENIA Treebank@formal@@1@S@Lysophosphatidylethanolamine (lysoPE) and other lysophospholipids did not affect LPS-induced TF activity of human monocytes.@@@@1@17@@oe@16-12-2010 988886506@GENIA Treebank@formal@@1@S@TF antigen expression as elicited by LPS was also lowered by lysoPC.@@@@1@13@@oe@16-12-2010 988886507@GENIA Treebank@formal@@1@S@Phospholipid analyses indicated a selective increase in the lysoPC content of the monocytes after preincubation with the lysophospholipid.@@@@1@19@@oe@16-12-2010 988886508@GENIA Treebank@formal@@1@S@LysoPC inhibited the TF activity of Mono Mac-6 cells to a similar extent as in the monocytes.@@@@1@18@@oe@16-12-2010 988886509@GENIA Treebank@formal@@1@S@LPS binding to plasma membrane receptors and internalization of LPS into monocytes were not affected by lysoPC.@@@@1@18@@oe@16-12-2010 988886510@GENIA Treebank@formal@@1@S@In contrast, LPS-mediated nuclear binding of nuclear factor-kappaB/Rel to a TF-specific kappaB site was inhibited by lysoPC.@@@@1@19@@oe@16-12-2010 988886511@GENIA Treebank@formal@@1@S@Induction of TF mRNA expression by LPS tended to be partially reduced by the lysophospholipid.@@@@1@16@@oe@16-12-2010 988886512@GENIA Treebank@formal@@1@S@Preincubation with lysoPC increased monocytic cAMP levels.@@@@1@8@@oe@16-12-2010 988886513@GENIA Treebank@formal@@1@S@Inhibition of adenylyl cyclase by pretreatment with 2'-deoxy-3'-adenosine monophosphate partially reversed the inhibition of TF activity promoted by lysoPC.@@@@1@20@@oe@16-12-2010 988886514@GENIA Treebank@formal@@1@S@In conclusion, lysoPC markedly decreases LPS-mediated TF expression of human monocytes, the effect probably being mediated by both transcriptional and posttranscriptional mechanisms.@@@@1@25@@oe@16-12-2010 988886515@GENIA Treebank@formal@@1@S@LysoPC may thus attenuate activation of coagulation during inflammation and atherosclerosis.@@@@1@12@@oe@16-12-2010 988919701@GENIA Treebank@formal@@1@S@Intranuclear targeted delivery of functional NF-kappaB by 70 kDa heat shock protein.@@@@1@13@@oe@16-12-2010 988919702@GENIA Treebank@formal@@1@S@The 70 kDa heat shock protein (Hsp70) is a highly conserved, ubiquitous protein involved in chaperoning proteins to various cellular organelles.@@@@1@25@@oe@16-12-2010 988919703@GENIA Treebank@formal@@1@S@Here we show that when added exogenously to cells, Hsp70 is readily imported into both cytoplasmic and nuclear compartments in a cell-type-specific fashion.@@@@1@25@@oe@16-12-2010 988919704@GENIA Treebank@formal@@1@S@We exploited this ability of Hsp70 to deliver NF-kappaB, a key transcriptional regulator of inflammatory responses.@@@@1@18@@oe@16-12-2010 988919705@GENIA Treebank@formal@@1@S@We demonstrate that a fusion protein composed of a C-terminal Hsp70 peptide and the p50 subunit of NF-kappaB was directed into the nucleus of cells, could bind DNA specifically, and activated Igkappa expression and TNFalpha production.@@@@1@39@@oe@16-12-2010 988919706@GENIA Treebank@formal@@1@S@We therefore propose that Hsp70 can be used as a vehicle for intracytoplasmic and intranuclear delivery of proteins or DNA to modulate gene expression and thereby control immune responses.@@@@1@30@@oe@16-12-2010 988919801@GENIA Treebank@formal@@1@S@Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation.@@@@1@15@@oe@16-12-2010 988919802@GENIA Treebank@formal@@1@S@The molecular basis for restricted cytokine expression by T helper 1 (Th1) and T helper 2 (Th2) cells is unclear.@@@@1@25@@oe@16-12-2010 988919803@GENIA Treebank@formal@@1@S@Previous studies found that P1, an element of the interleukin 4 (IL-4) promoter that binds AP-1, is important for Th2-restricted IL-4 expression.@@@@1@27@@oe@16-12-2010 988919804@GENIA Treebank@formal@@1@S@Here we show that JunB, but not the other Jun family members, was selectively induced in Th2 cells and not in Th1 cells during differentiation.@@@@1@28@@oe@16-12-2010 988919805@GENIA Treebank@formal@@1@S@JunB has previously been considered to be a negative regulator of transcription.@@@@1@13@@oe@16-12-2010 988919806@GENIA Treebank@formal@@1@S@However, we show that JunB binds directly to the P1 site and synergizes with c-Maf to activate an IL-4 luciferase reporter gene.@@@@1@24@@oe@16-12-2010 988919807@GENIA Treebank@formal@@1@S@JunB-control of IL-4 expression is mediated by the phosphorylation of JunB at Thr102 and -104 by JNK MAP kinase.@@@@1@20@@oe@16-12-2010 988919808@GENIA Treebank@formal@@1@S@The synergy between c-Maf and JunB can be attributed to cooperative DNA binding, which is facilitated by JunB phosphorylation.@@@@1@21@@oe@16-12-2010 988919809@GENIA Treebank@formal@@1@S@In transgenic mice, elevated JunB levels caused increased expression of several Th2 cytokines in developing Th1 cells.@@@@1@19@@oe@16-12-2010 988919810@GENIA Treebank@formal@@1@S@JunB also upregulated IL-4 expression in response to immunization.@@@@1@10@@oe@16-12-2010 988919811@GENIA Treebank@formal@@1@S@Thus, the early increase of JunB protein in Th2 cells can provide the specificity for c-Maf in IL-4 expression during T cell development and directs thereby Th2 differentiation.@@@@1@30@@oe@16-12-2010 989304301@GENIA Treebank@formal@@1@S@CD2 signalling induces phosphorylation of CREB in primary lymphocytes.@@@@1@10@@oe@16-12-2010 989304302@GENIA Treebank@formal@@1@S@Promoter sequences responsive to cyclic AMP (cAMP) are found in a number of cellular genes, and bind transcription factors of the cAMP response element binding protein (CREB)/activating transcription factor-1 (ATF-1) family.@@@@1@41@@oe@16-12-2010 989304303@GENIA Treebank@formal@@1@S@We have used a human T-lymphotropic virus type 1 (HTLV-1) model of cAMP response element (CRE) transcription to investigate the influence of lymphocyte activation on transcription from homologous regions in the viral promoter.@@@@1@38@@oe@16-12-2010 989304304@GENIA Treebank@formal@@1@S@We previously demonstrated increased HTLV-1 transcription following CD2 but not CD3 receptor cross-linking.@@@@1@14@@oe@16-12-2010 989304305@GENIA Treebank@formal@@1@S@We hypothesized that this increased viral transcription was mediated, in part, through the phosphorylation of CREB.@@@@1@19@@oe@16-12-2010 989304306@GENIA Treebank@formal@@1@S@Therefore, we investigated CD2 and CD3 receptor-mediated signalling in primary human peripheral blood mononuclear cells (PBMC).@@@@1@20@@oe@16-12-2010 989304307@GENIA Treebank@formal@@1@S@CD2, but not CD3, cross-linking increased cAMP detected by competitive enzyme-linked immunosorbent assay (ELISA) approximately fourfold.@@@@1@21@@oe@16-12-2010 989304308@GENIA Treebank@formal@@1@S@CD2 cross-linking concurrently increased phosphorylation of CREB detected by immunoblot assay eightfold.@@@@1@13@@oe@16-12-2010 989304309@GENIA Treebank@formal@@1@S@Consistent with post-translational regulation, no change in total level of CREB protein was observed.@@@@1@16@@oe@16-12-2010 989304310@GENIA Treebank@formal@@1@S@Phosphorylation of CREB occurred through a herbimycin A and Rp-cAMP- sensitive pathway, suggesting phosphorylation required antecedent activation of both protein tyrosine kinases (PTK) and protein kinase A (PKA).@@@@1@33@@oe@16-12-2010 989304311@GENIA Treebank@formal@@1@S@Both CD2 and CD3 cross-linking increased binding of nuclear proteins to a radiolabelled CRE oligonucleotide probe in electrophoretic mobility shift assays suggesting that lymphocyte activation enhances binding independently of phosphorylation of CREB at serine 133.@@@@1@36@@oe@16-12-2010 989304312@GENIA Treebank@formal@@1@S@These data indicate specific modulation of the CREB/ATF-1 family of transcription factors by the CD2 signalling pathway and suggest CD2 receptor modulation of CRE-mediated transcription following ligand engagement (e.g. cell-to-cell contact).@@@@1@34@@oe@16-12-2010 991577901@GENIA Treebank@formal@@1@S@Anoxia/reoxygenation-induced tolerance with respect to polymorphonuclear leukocyte adhesion to cultured endothelial cells.@@@@1@13@@oe@16-12-2010 991577902@GENIA Treebank@formal@@1@S@A nuclear factor-kappaB-mediated phenomenon.@@@@1@5@@oe@16-12-2010 991577903@GENIA Treebank@formal@@1@S@Exposing human umbilical vein endothelial cells (HUVECs) to anoxia/reoxygenation (A/R) results in an increase in polymorphonuclear leukocyte (PMN) adhesion to HUVECs.@@@@1@28@@oe@16-12-2010 991577904@GENIA Treebank@formal@@1@S@This A/R-induced hyperadhesion is completely prevented by a previous (24 hours earlier) exposure of HUVECs to A/R.@@@@1@20@@oe@16-12-2010 991577905@GENIA Treebank@formal@@1@S@This phenomenon has been termed "A/R tolerance."@@@@1@10@@oe@16-12-2010 991577906@GENIA Treebank@formal@@1@S@Exposing HUVECs to A/R induces an increase in nuclear factor kappaB (NF-kappaB) in HUVEC nuclei within 4 hours.@@@@1@21@@oe@16-12-2010 991577907@GENIA Treebank@formal@@1@S@Interfering with either NF-kappaB activation (proteasome inhibitor) or translocation (double-stranded oligonucleotides containing NF-kappaB binding sequence) prevents the development of A/R tolerance (ie, the increase in A/R-induced PMN adhesion to HUVECs is the same after the first and second A/R challenges).@@@@1@48@@oe@16-12-2010 991577908@GENIA Treebank@formal@@1@S@NO production by HUVECs is increased after the second A/R challenge, but not after the first A/R challenge.@@@@1@20@@oe@16-12-2010 991577909@GENIA Treebank@formal@@1@S@Inhibition of NO synthase (NOS) during the second A/R challenge prevents the development of A/R tolerance with respect to PMN adhesion.@@@@1@24@@oe@16-12-2010 991577910@GENIA Treebank@formal@@1@S@However, while HUVECs contained endothelial NOS protein, no inducible NOS was detected in either tolerant or nontolerant cells.@@@@1@21@@oe@16-12-2010 991577911@GENIA Treebank@formal@@1@S@Further studies indicated that inhibition of GTP-cyclohydrolase I (an enzyme involved in de novo synthesis of an important cofactor for NOS activity, tetrahydrobiopterin) prevented the generation of NO in A/R-tolerant cells.@@@@1@35@@oe@16-12-2010 991577912@GENIA Treebank@formal@@1@S@Extracellular generation of NO (NO donor) did not effect the hyperadhesion response induced by the initial A/R challenge.@@@@1@21@@oe@16-12-2010 991577913@GENIA Treebank@formal@@1@S@A/R also induced an oxidant stress in naive HUVECs, but not in A/R-tolerant HUVECs.@@@@1@16@@oe@16-12-2010 991577914@GENIA Treebank@formal@@1@S@Inhibition of NOS during the second A/R insult results in the generation of an oxidant stress similar to that observed after the first A/R challenge.@@@@1@26@@oe@16-12-2010 991577915@GENIA Treebank@formal@@1@S@Taken together, the findings of the present study are consistent with a role for NF-kappaB in the development of A/R tolerance (with respect to PMN adhesion), perhaps by transcriptional regulation of GTP-cyclohydrolase.@@@@1@37@@oe@16-12-2010 991577916@GENIA Treebank@formal@@1@S@The increased NO production during the second A/R insult reduces PMN adhesion most likely by reducing the intracellular oxidant stress induced by A/R.@@@@1@24@@oe@16-12-2010 991585001@GENIA Treebank@formal@@1@S@CD80 and CD86 are not equivalent in their ability to induce the tyrosine phosphorylation of CD28.@@@@1@17@@oe@16-12-2010 991585002@GENIA Treebank@formal@@1@S@Ligation of either CD80 (B7-1) or CD86 (B7-2), two principal ligands for CD28, is thought to skew the immune response toward Th1 or Th2 differentiation.@@@@1@32@@oe@16-12-2010 991585003@GENIA Treebank@formal@@1@S@We have examined early signal transduction pathways recruited following T cell stimulation with either CD80 or CD86.@@@@1@18@@oe@16-12-2010 991585004@GENIA Treebank@formal@@1@S@Purified human peripheral T cells or Jurkat T cells were stimulated with Chinese hamster ovary (CHO) cells expressing either human CD80 (CHO-CD80) or human CD86 (CHO-CD86) or with anti-CD28 monoclonal antibody (mAb).@@@@1@41@@oe@16-12-2010 991585005@GENIA Treebank@formal@@1@S@In the presence of phorbol 12-myristate 13-acetate, both CHO-CD80 and CHO-CD86, like anti-CD28 mAb, were capable of stimulating cytokine production from both human peripheral T cells and Jurkat T cells.@@@@1@34@@oe@16-12-2010 991585006@GENIA Treebank@formal@@1@S@Both CHO-CD80 and CHO-CD86, in the presence of anti-CD3 mAb, costimulated NFAT-dependent transcriptional activation.@@@@1@17@@oe@16-12-2010 991585007@GENIA Treebank@formal@@1@S@Several intracellular signaling proteins, such as CBL and VAV, were phosphorylated on tyrosine in response to CD80, CD86, and anti-CD28 mAb.@@@@1@26@@oe@16-12-2010 991585008@GENIA Treebank@formal@@1@S@Surprisingly, although stimulation of Jurkat T cells with either CHO-CD80 or anti-CD28 mAb resulted in robust tyrosine phosphorylation of CD28 itself, ligation with CHO-CD86 was unable to induce detectable CD28 tyrosyl phosphorylation over a range of stimulation conditions.@@@@1@41@@oe@16-12-2010 991585009@GENIA Treebank@formal@@1@S@In addition, the association of phosphoinositide 3-kinase with CD28 and enhanced tyrosine phosphorylation of phospholipase Cgamma were seen after anti-CD28 mAb and CHO-CD80 stimulation but to a much lesser extent after CHO-CD86 stimulation.@@@@1@35@@oe@16-12-2010 991585010@GENIA Treebank@formal@@1@S@Thus, ligation of CD28 with either CD80 or CD86 leads to shared early signal transduction events such as the tyrosine phosphorylation of CBL and VAV, to NFAT-mediated transcriptional activation, and to the costimulation of interleukin-2 and granulocyte-macrophage colony-stimulating factor production.@@@@1@44@@oe@16-12-2010 991585011@GENIA Treebank@formal@@1@S@However, CD80 and CD86 also induce distinct signal transduction pathways including the tyrosine phosphorylation of CD28 and phospholipase Cgamma1 and the SH2-dependent association of phosphoinositide 3-kinase with CD28.@@@@1@30@@oe@16-12-2010 991585012@GENIA Treebank@formal@@1@S@These quantitative, if not qualitative, differences between signaling initiated by these two ligands for CD28 may contribute to functional differences (e.g. Th1 or Th2 differentiation) in T cell responses.@@@@1@34@@oe@16-12-2010 991586301@GENIA Treebank@formal@@1@S@Role of Egr-2 in up-regulation of Fas ligand in normal T cells and aberrant double-negative lpr and gld T cells.@@@@1@21@@oe@16-12-2010 991586302@GENIA Treebank@formal@@1@S@We previously identified a Fas ligand regulatory element (FLRE) in the Fas ligand (fasL) promoter that binds Egr family proteins and demonstrated that Egr-3 (PILOT) but not Egr-1 (NGFI-A, Krox-24, Tis-8, and Zif-268) induces transcription of fasL.@@@@1@49@@oe@16-12-2010 991586303@GENIA Treebank@formal@@1@S@The aberrant CD4(-)CD8(-) T cells from lpr/lpr and gld/gld mice, which have mutations in the genes encoding Fas and FasL, respectively, have an activated phenotype and constitutively express high levels of fasL mRNA, prompting us to ask what role if any the FLRE and Egr family proteins have in this aberrant expression of fasL.@@@@1@60@@oe@16-12-2010 991586304@GENIA Treebank@formal@@1@S@Unstimulated MRL-lpr/lpr and C3H-gld/gld CD4(-)CD8(-) T cells constitutively contained high levels of two proteins that bound to the FLRE.@@@@1@21@@oe@16-12-2010 991586305@GENIA Treebank@formal@@1@S@Supershift analysis revealed these proteins to be Egr-1 and Egr-2 (Krox-20); Egr-3 was not detected.@@@@1@19@@oe@16-12-2010 991586306@GENIA Treebank@formal@@1@S@Activation of normal lymph node cells resulted in increased expression of Egr-1, -2, and -3.@@@@1@18@@oe@16-12-2010 991586307@GENIA Treebank@formal@@1@S@As with egr-3, expression of egr-2 was blocked by cyclosporin A.@@@@1@13@@oe@16-12-2010 991586308@GENIA Treebank@formal@@1@S@Although overexpressed Egr-1 was ineffective, overexpressed Egr-2 was as potent as Egr-3 in inducing fasL promoter-dependent reporter constructs in T cell hybridomas and HeLa cells, and both up-regulated endogenous fasL mRNA in HeLa cells.@@@@1@37@@oe@16-12-2010 991586309@GENIA Treebank@formal@@1@S@FasL-dependent reporter constructs in MRL-lpr/lpr and C3H-gld/gld CD4(-)CD8(-) T cells were constitutively active, and this activity was largely prevented by mutation of the critical Egr family binding element.@@@@1@31@@oe@16-12-2010 991586310@GENIA Treebank@formal@@1@S@Thus, Egr-2, in addition to Egr-3, regulates FasL expression in activated normal T cells, and Egr-2 is likely to play a direct role in aberrant fasL up-regulation in lpr/lpr and gld/gld CD4(-)CD8(-) T cells.@@@@1@40@@oe@16-12-2010 991607801@GENIA Treebank@formal@@1@S@Involvement of mitogen-activated protein kinase pathways in interleukin-8 production by human monocytes and polymorphonuclear cells stimulated with lipopolysaccharide or Mycoplasma fermentans membrane lipoproteins.@@@@1@24@@oe@16-12-2010 991607802@GENIA Treebank@formal@@1@S@Interleukin-8 (IL-8) is a chemokine that belongs to the alpha-chemokine or CXC subfamily and is produced by a wide variety of human cells, including monocytes and polymorphonuclear cells (PMN).@@@@1@35@@oe@16-12-2010 991607803@GENIA Treebank@formal@@1@S@IL-8 is secreted in response to inflammatory stimuli, notably bacterial products such as lipopolysaccharide (LPS), but little is known about the mechanisms by which these agents mediate IL-8 induction.@@@@1@34@@oe@16-12-2010 991607804@GENIA Treebank@formal@@1@S@In this report, we show that Mycoplasma fermentans lipid-associated membrane proteins (LAMPf) induce the production of high levels of IL-8 by THP-1 (human monocyte) cells and PMN at the same extent as LPS.@@@@1@39@@oe@16-12-2010 991607805@GENIA Treebank@formal@@1@S@It was previously demonstrated that stimulation of monocytic cells with either LPS or LAMPf led to a series of common downstream signaling events, including the activation of protein tyrosine kinase and of mitogen-activated protein kinase cascades.@@@@1@38@@oe@16-12-2010 991607806@GENIA Treebank@formal@@1@S@By using PD-98059 and SB203580, two potent and selective inhibitors of MEK1 (a kinase upstream of ERK1/2) and p38, respectively, we have demonstrated that both ERK1/2 and p38 cascades play a key role in the production of IL-8 by monocytes and PMN stimulated with bacterial fractions.@@@@1@52@@oe@16-12-2010 991667901@GENIA Treebank@formal@@1@S@Protective effects of notch-1 on TCR-induced apoptosis.@@@@1@8@@oe@16-12-2010 991667902@GENIA Treebank@formal@@1@S@The Notch receptor protein was originally identified in Drosophila and is known to mediate cell to cell communication and influence cell fate decisions.@@@@1@24@@oe@16-12-2010 991667903@GENIA Treebank@formal@@1@S@Members of this family have been isolated from invertebrates as well as vertebrates.@@@@1@14@@oe@16-12-2010 991667904@GENIA Treebank@formal@@1@S@We isolated mouse Notch-1 in a yeast two-hybrid screen with Nur77, which is a protein that has been shown previously to be required for apoptosis in T cell lines.@@@@1@31@@oe@16-12-2010 991667905@GENIA Treebank@formal@@1@S@The data presented below indicate that Notch-1 expression provides significant protection to T cell lines from TCR-mediated apoptosis.@@@@1@19@@oe@16-12-2010 991667906@GENIA Treebank@formal@@1@S@These data demonstrate a new antiapoptotic role for Notch-1, providing evidence that, in addition to regulating cell fate decisions, Notch-1 can play a critical role in controlling levels of cell death in T cells.@@@@1@38@@oe@16-12-2010 991670901@GENIA Treebank@formal@@1@S@T cell priming enhances IL-4 gene expression by increasing nuclear factor of activated T cells.@@@@1@16@@oe@16-12-2010 991670902@GENIA Treebank@formal@@1@S@The repetitive activation of T cells (priming) enhances the expression of many cytokines, such as IL-4, but not others, such as IL-2.@@@@1@28@@oe@16-12-2010 991670903@GENIA Treebank@formal@@1@S@Molecular mechanisms underlying selective expression of cytokines by T cells remain poorly understood.@@@@1@14@@oe@16-12-2010 991670904@GENIA Treebank@formal@@1@S@Here we show that priming of CD4 T cells selectively enhances IL-4 expression relative to IL-2 expression by a transcriptional mechanism involving nuclear factor of activated T cells (NFAT) proteins.@@@@1@33@@oe@16-12-2010 991670905@GENIA Treebank@formal@@1@S@As detected by in vivo footprinting, priming markedly increases the activation-dependent engagement of the P0 and P1 NFAT-binding elements of the IL-4 promoter.@@@@1@25@@oe@16-12-2010 991670906@GENIA Treebank@formal@@1@S@Moreover, each proximal P element is essential for optimal IL-4 promoter activity.@@@@1@14@@oe@16-12-2010 991670907@GENIA Treebank@formal@@1@S@Activated primed CD4 T cells contain more NFAT1 and support greater NFAT-directed transcription than unprimed CD4 T cells, while activator protein 1 binding and activator protein 1-mediated transcription by both cell types is similar.@@@@1@36@@oe@16-12-2010 991670908@GENIA Treebank@formal@@1@S@Increased expression of wild-type NFAT1 substantially increases IL-4 promoter activity in unprimed CD4 T cells, suggesting NFAT1 may be limiting for IL-4 gene expression in this cell type.@@@@1@30@@oe@16-12-2010 991670909@GENIA Treebank@formal@@1@S@Furthermore, a truncated form of NFAT1 acts as a dominant-negative, reducing IL-4 promoter activity in primed CD4 T cells and confirming the importance of endogenous NFAT to increased IL-4 gene expression by effector T cells.@@@@1@38@@oe@16-12-2010 991670910@GENIA Treebank@formal@@1@S@NFAT1 appears to be the major NFAT family member responsible for the initial increased expression of IL-4 by primed CD4 T cells.@@@@1@23@@oe@16-12-2010 991882401@GENIA Treebank@formal@@1@S@Requirement of GATA-1 and p45 NF-E2 expression in butyric acid-induced erythroid differentiation.@@@@1@13@@oe@16-12-2010 991882402@GENIA Treebank@formal@@1@S@Butyric acid (BA) is known to induce overexpression of fetal hemoglobin and then erythroid differentiation.@@@@1@18@@oe@16-12-2010 991882403@GENIA Treebank@formal@@1@S@Therefore, BA is currently under clinical investigation as a potential therapy for the treatment of sickle cell disease and cancer.@@@@1@22@@oe@16-12-2010 991882404@GENIA Treebank@formal@@1@S@Nevertheless, the molecular mechanisms involved in BA-induced differentiation remain largely unknown.@@@@1@13@@oe@16-12-2010 991882405@GENIA Treebank@formal@@1@S@Previous reports have shown that BA-induced overexpression of erythroid genes occurred at the transcriptional level, suggesting the involvement of erythroid transcription factors.@@@@1@24@@oe@16-12-2010 991882406@GENIA Treebank@formal@@1@S@Here, we intend to demonstrate the requirement of GATA-1 and NF-E2 transcription factors in the BA-induced erythroid differentiation of human leukemic K562 cells.@@@@1@25@@oe@16-12-2010 991882407@GENIA Treebank@formal@@1@S@Time-course experiments showed that nuclear levels of GATA-1 and p45 NF-E2 proteins increased during BA treatment.@@@@1@17@@oe@16-12-2010 991882408@GENIA Treebank@formal@@1@S@Moreover, antisense oligodeoxynucleotides targeting either GATA-1 or p45 NF-E2 proteins inhibited both protein expression and BA-induced differentiation.@@@@1@19@@oe@16-12-2010 991882409@GENIA Treebank@formal@@1@S@In contrast, BA-induced cell growth inhibition was not affected.@@@@1@11@@oe@16-12-2010 991882410@GENIA Treebank@formal@@1@S@These results provide the first direct evidence for the requirement of GATA-1 and NF-E2 in BA-induced differentiation process.@@@@1@19@@oe@16-12-2010 991953601@GENIA Treebank@formal@@1@S@Inhibition of NF-kappa B activation in vitro and in vivo: role of 26S proteasome.@@@@1@16@@oe@16-12-2010 991953602@GENIA Treebank@formal@@1@S@It is becoming increasingly apparent that NF-kappa B plays a critical role in regulating the inflammatory response.@@@@1@18@@oe@16-12-2010 991953603@GENIA Treebank@formal@@1@S@Data obtained from studies in our laboratories demonstrate that the proteasome plays an important role in the inflammatory cascade by regulating the activation of NF-kappa B.@@@@1@27@@oe@16-12-2010 991953604@GENIA Treebank@formal@@1@S@Indeed, the availability of selective and orally active proteasome inhibitors should prove useful in delineating the roles of the proteasome and NF-kappa B in other pathophysiological conditions such as cancer and heart disease.@@@@1@35@@oe@16-12-2010 992077801@GENIA Treebank@formal@@1@S@Imbalanced expression of the glucocorticoid receptor isoforms in cultured lymphocytes from a patient with systemic glucocorticoid resistance and chronic lymphocytic leukemia.@@@@1@22@@oe@16-12-2010 992077802@GENIA Treebank@formal@@1@S@The human glucocorticoid receptor (GR) is expressed as two alternatively spliced isoforms, GRalpha and GRbeta.@@@@1@19@@oe@16-12-2010 992077803@GENIA Treebank@formal@@1@S@Whereas GRalpha is a hormone-activated transcription factor, GRbeta does not bind glucocorticoids (GCs), is transcriptionally inactive, and is a potential inhibitor of activated GRalpha.@@@@1@30@@oe@16-12-2010 992077804@GENIA Treebank@formal@@1@S@Differential expression of GR isoforms may play a role in generalized or tissue-specific GC resistance.@@@@1@16@@oe@16-12-2010 992077805@GENIA Treebank@formal@@1@S@GCs induce apoptosis in neoplastic lymphoid cells; and, defective apoptosis is implicated in the genesis of chronic lymphocytic leukemia (CLL).@@@@1@25@@oe@16-12-2010 992077806@GENIA Treebank@formal@@1@S@We studied a patient with generalized GC resistance and CLL.@@@@1@11@@oe@16-12-2010 992077807@GENIA Treebank@formal@@1@S@GR number in the patient's transformed lymphocytes was approximately one half that of control cells with a approximately 10-fold reduction in binding affinity for dexamethasone.@@@@1@27@@oe@16-12-2010 992077808@GENIA Treebank@formal@@1@S@In vitro apoptosis induction in CLL cells was delayed in response to GCs, but not to other apoptosis inducers.@@@@1@21@@oe@16-12-2010 992077809@GENIA Treebank@formal@@1@S@Sequencing of the GR cDNA and gene including the 2.3-kb coding region, the intron/exon junctions, the known 5'-regulatory region, and approximately 300 bp of the 3'-region revealed no alterations.@@@@1@33@@oe@16-12-2010 992077810@GENIA Treebank@formal@@1@S@Western blot with an N-terminal antibody showed normal levels of immunoreactive GR, but quantitative analysis with isoform-specific C-terminal antibodies revealed a markedly reduced GRalpha expression, and high GRbeta expression.@@@@1@32@@oe@16-12-2010 992077811@GENIA Treebank@formal@@1@S@These findings indicate that imbalanced expression of the GR isoforms may be a mechanism of GC resistance, and may have implications for tumorigenesis by enhancing cell survival.@@@@1@29@@oe@16-12-2010 992077812@GENIA Treebank@formal@@1@S@Copyright 1999 Academic Press.@@@@1@5@@oe@16-12-2010 992298501@GENIA Treebank@formal@@1@S@1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with renal insufficiency.@@@@1@14@@oe@16-12-2010 992298502@GENIA Treebank@formal@@1@S@A reduced expression of the vitamin D receptor (VDR) in parathyroid glands of uremic animals and humans has been observed.@@@@1@23@@oe@16-12-2010 992298503@GENIA Treebank@formal@@1@S@Similar results have been obtained by our own group in peripheral blood mononuclear cells (PBMC) from patients with secondary hyperparathyroidism to chronic renal failure.@@@@1@27@@oe@16-12-2010 992298504@GENIA Treebank@formal@@1@S@However, the reasons for these changes are not clear.@@@@1@11@@oe@16-12-2010 992298505@GENIA Treebank@formal@@1@S@In the present study, we have investigated the specific uptake of [3H]1,25(OH)2D3 by PBMC of 11 women with advanced chronic renal failure (A-CRF), 6 women with mild-moderate renal insufficiency (M-CRF), and 23 healthy women.@@@@1@42@@oe@16-12-2010 992298506@GENIA Treebank@formal@@1@S@The mean dissociation constant (KD) was similar in both groups of patients and in healthy women (A-CRF: 0.7 +/- 0.5 x 10(-10) M; M-CRF: 1.1 +/- 0.9 x 10(-10) M; controls: 1.0 +/- 0.6 x 10(-10) M).@@@@1@47@@oe@16-12-2010 992298507@GENIA Treebank@formal@@1@S@However, VDR concentration was significantly decreased in A-CRF (0.8 +/- 0.5 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in controls, p < 0.001), whereas no changes were seen in M-CRF (1.7 +/- 0.7 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in controls).@@@@1@52@@oe@16-12-2010 992298508@GENIA Treebank@formal@@1@S@No correlation was seen between VDR and serum calcitriol or PTH levels, when considering both groups of patients together or separately.@@@@1@23@@oe@16-12-2010 992298509@GENIA Treebank@formal@@1@S@Conversely, a significant negative correlation was found between VDR and serum creatinine values when A-CRF and M-CRF were considered altogether (r = -0.63; p < 0.01).@@@@1@31@@oe@16-12-2010 992298510@GENIA Treebank@formal@@1@S@Treatment with two different schedules of oral calcitriol (five patients with 0.5 microgram/day for 1 month and four patients with 2 micrograms/day for 7 days) did not change VDR concentrations.@@@@1@33@@oe@16-12-2010 992298511@GENIA Treebank@formal@@1@S@We conclude that the low levels of serum 1,25(OH)2D3 of uremia are not responsible for the decrease in VDR concentration found in these patients.@@@@1@25@@oe@16-12-2010 992344701@GENIA Treebank@formal@@1@S@A novel growth-factor-dependent myeloid cell line derived from mouse bone marrow cells contains progenitors endowed with high proliferative potential.@@@@1@20@@oe@16-12-2010 992344702@GENIA Treebank@formal@@1@S@Constitutive expression of human colony-stimulating factor-1 receptor (CSF-1R) confers long-lasting CSF-1-dependent proliferation to mouse myeloid cell lines.@@@@1@20@@oe@16-12-2010 992344703@GENIA Treebank@formal@@1@S@We developed mice transgenic for human CSF-1R because mouse CSF-1 cannot activate human CSF-1R.@@@@1@16@@oe@16-12-2010 992344704@GENIA Treebank@formal@@1@S@Then bone marrow cells from transgenic mice were plated onto MS-5 stromal cells expressing the membrane form of human CSF-1 (2M-1 cells) in order to combine the hematopoietic supporting properties of stromal cells and the proliferative effects of CSF-1.@@@@1@42@@oe@16-12-2010 992344705@GENIA Treebank@formal@@1@S@Thus, we were able to derive a hematopoietic cell line, called 47.10, that grew indefinitely under these conditions, whereas no cell line could be developed from nontransgenic mice.@@@@1@33@@oe@16-12-2010 992344706@GENIA Treebank@formal@@1@S@Proliferation of 47.10 cells is severely affected by neutralizing anti-CSF-1R monoclonal antibodies.@@@@1@13@@oe@16-12-2010 992344707@GENIA Treebank@formal@@1@S@Morphologic and cytofluorometry analysis established that most 47.10 cells are immature myelomonocytic cells.@@@@1@14@@oe@16-12-2010 992344708@GENIA Treebank@formal@@1@S@Consistent with this phenotype, the myeloid transcription factor PU.1, but not the erythroid transcription factor GATA-1, is expressed in 47.10 cells.@@@@1@25@@oe@16-12-2010 992344709@GENIA Treebank@formal@@1@S@A few 47.10 cells (3-5%) do not express lineage specific markers; they differentiate spontaneously to lineage-positive cells after replating on 2M-1 cells.@@@@1@27@@oe@16-12-2010 992344710@GENIA Treebank@formal@@1@S@In agar cultures, 47.10 cells form 7- and 14-day colonies in response to a cocktail of granulocyte/macrophage colony-stimulating factor (2.5 ng/mL), interleukin-3 (1 ng/mL), and mouse CSF-1 (10 ng/mL).@@@@1@39@@oe@16-12-2010 992344711@GENIA Treebank@formal@@1@S@Under these conditions, about 0.5% of 47.10 cells formed large 14-day colonies (>1 mm) composed of mature monocytes and granulocytes, reflecting the presence of progenitors endowed with high proliferative potential (HPP-47.10 cells).@@@@1@41@@oe@16-12-2010 992344712@GENIA Treebank@formal@@1@S@In conclusion, we have characterized a novel continuous myeloid cell line presenting a hierarchical structure similar to that of the bone marrow progenitor cell compartment.@@@@1@27@@oe@16-12-2010 992593001@GENIA Treebank@formal@@1@S@Transcription factor effects on chromosome constitution of cell hybrids.@@@@1@10@@oe@16-12-2010 992593002@GENIA Treebank@formal@@1@S@When immunoglobulin (Ig)-secreting plasmacytomas are fused to a T-cell lymphoma, Ig gene expression ceases in greater than 95% of the resulting hybrids.@@@@1@28@@oe@16-12-2010 992593003@GENIA Treebank@formal@@1@S@In the rare hybrids that continue to express Ig, all other tested B lymphocyte-specific genes also remain active.@@@@1@20@@oe@16-12-2010 992593004@GENIA Treebank@formal@@1@S@The low frequency with which these Ig-expressing hybrids are recovered, along with the fact that cell fusions can lead to chromosome loss, led us to propose that this rare phenotype was due to loss of a T-cell-derived chromosome encoding a factor or factors with gene silencing activity.@@@@1@50@@oe@16-12-2010 992593005@GENIA Treebank@formal@@1@S@To identify the relevant chromosome, we have used a polymerase chain reaction (PCR)-assisted method of chromosome mapping to analyze both Ig-silenced (common) and Ig-expressing (rare) hybrids.@@@@1@35@@oe@16-12-2010 992593006@GENIA Treebank@formal@@1@S@Although no single chromosome was found to correlate with Ig gene silencing, we discovered that the two types of hybrids had undergone distinct patterns of chromosome loss.@@@@1@29@@oe@16-12-2010 992593007@GENIA Treebank@formal@@1@S@Moreover, we found that ectopic expression of a B-cell-specific transcription factor (Oct-2) dramatically altered both the phenotype and chromosome constitution of hybrids arising in these cell fusions.@@@@1@31@@oe@16-12-2010 992872301@GENIA Treebank@formal@@1@S@Comparison of HTLV-I basal transcription and expression of CREB/ATF-1/CREM family members in peripheral blood mononuclear cells and Jurkat T cells.@@@@1@21@@oe@16-12-2010 992872302@GENIA Treebank@formal@@1@S@HTLV-I is the etiologic agent of adult T-cell leukemia/lymphoma and is associated with tropical spastic paraparesis/HTLV-I-associated myelopathy.@@@@1@18@@oe@16-12-2010 992872303@GENIA Treebank@formal@@1@S@Following integration into the host cell genome, HTLV-I replication is regulated by both host and viral mechanisms that control transcription.@@@@1@22@@oe@16-12-2010 992872304@GENIA Treebank@formal@@1@S@Low levels of viral transcription (basal transcription) occur before expression of the virally encoded Tax protein (Tax-mediated transcription).@@@@1@23@@oe@16-12-2010 992872305@GENIA Treebank@formal@@1@S@Members of the cyclic adenosine monophosphate (cAMP) response element binding (CREB)/activating transcription factor 1 (ATF-1) family of transcription factors bind three 21-bp repeats (Tax-responsive element-1, or TRE-1) within the viral promoter and are important for basal and Tax-mediated transcription.@@@@1@50@@oe@16-12-2010 992872306@GENIA Treebank@formal@@1@S@Using mitogen stimulated and quiescent peripheral blood mononuclear cells (PBMC) and Jurkat cells, we compared differences in basal transcription and amounts and binding of transcription factors with TRE-1.@@@@1@32@@oe@16-12-2010 992872307@GENIA Treebank@formal@@1@S@We demonstrate that amounts of transcriptionally active phosphorylated CREB protein (P-CREB) differ between activated PBMC and Jurkat cells.@@@@1@21@@oe@16-12-2010 992872308@GENIA Treebank@formal@@1@S@Following stimulation, P-CREB levels remain elevated in PBMC for up to 24 hours whereas CREB is dephosphorylated in Jurkat cells within 4 hours following stimulation.@@@@1@27@@oe@16-12-2010 992872309@GENIA Treebank@formal@@1@S@The differences in P-CREB levels between PBMC and Jurkat cells were directly correlated with basal transcription of HTLV-I in the two cell types.@@@@1@24@@oe@16-12-2010 992872310@GENIA Treebank@formal@@1@S@Using electrophoretic mobility shift assays, we determined that the pattern of band migration differed between the two cell types.@@@@1@21@@oe@16-12-2010 992872311@GENIA Treebank@formal@@1@S@These data demonstrate that PBMC differentially regulate basal HTLV-I transcription compared with Jurkat T cells, and this differential regulation is due, in part to differential phosphorylation and binding of CREB/ATF-1 to TRE-1 in the HTLV-I promoter.@@@@1@39@@oe@16-12-2010 992872312@GENIA Treebank@formal@@1@S@We demonstrate the utility of using primary lymphocyte models to study HTLV-I transcription in the context of cell signaling and suggest that activated PBMC maintain elevated levels of P-CREB, which promote basal HTLV-I transcription and enhance viral persistence in vivo.@@@@1@42@@oe@16-12-2010 992911101@GENIA Treebank@formal@@1@S@Heterogeneity of clonal development in chronic myeloproliferative disorders.@@@@1@9@@oe@16-12-2010 992911102@GENIA Treebank@formal@@1@S@Recent reports have suggested a previously unexpected variability in the expression of the dominant neoplastic clone in myeloproliferative disorders (MPD).@@@@1@23@@oe@16-12-2010 992911103@GENIA Treebank@formal@@1@S@We evaluated 49 female patients with MPD and informative at the X-linked androgen receptor (AR) locus to establish the X chromosome inactivation pattern of hemopoietic cells.@@@@1@29@@oe@16-12-2010 992911104@GENIA Treebank@formal@@1@S@Whereas in chronic myelogenous leukemia (CML) the granulocytes (PMN) were uniformly of monoclonal origin, a striking heterogeneity of clonal development was found in PMN from patients with other MPD, with up to 50% of them expressing a polyclonal pattern of X inactivation.@@@@1@50@@oe@16-12-2010 993363201@GENIA Treebank@formal@@1@S@NF-kappaB activation is a critical regulator of human granulocyte apoptosis in vitro.@@@@1@13@@oe@16-12-2010 993363202@GENIA Treebank@formal@@1@S@During beneficial inflammation, potentially tissue-damaging granulocytes undergo apoptosis before being cleared by phagocytes in a non-phlogistic manner.@@@@1@19@@oe@16-12-2010 993363203@GENIA Treebank@formal@@1@S@Here we show that the rate of constitutive apoptosis in human neutrophils and eosinophils is greatly accelerated in both a rapid and concentration-dependent manner by the fungal metabolite gliotoxin, but not by its inactive analog methylthiogliotoxin.@@@@1@38@@oe@16-12-2010 993363204@GENIA Treebank@formal@@1@S@This induction of apoptosis was abolished by the caspase inhibitor zVAD-fmk, correlated with the inhibition of nuclear factor-kappa B (NF-kappaB), and was mimicked by a cell permeable inhibitory peptide of NF-kappaB, SN-50; other NF-kappaB inhibitors, curcumin and pyrrolidine dithiocarbamate; and the proteasome inhibitor, MG-132.@@@@1@54@@oe@16-12-2010 993363205@GENIA Treebank@formal@@1@S@Gliotoxin also augmented dramatically the early (2-6 h) pro-apoptotic effects of tumor necrosis factor-alpha (TNF-alpha) in neutrophils and unmasked the ability of TNF-alpha to induce eosinophil apoptosis.@@@@1@32@@oe@16-12-2010 993363206@GENIA Treebank@formal@@1@S@In neutrophils, TNF-alpha caused a gliotoxin-inhibitable activation of an inducible form of NF-kappaB, a response that may underlie the ability of TNF-alpha to delay apoptosis at later times (12-24 h) and limit its early killing effect.@@@@1@41@@oe@16-12-2010 993363207@GENIA Treebank@formal@@1@S@Furthermore, cycloheximide displayed a similar capacity to enhance TNF-alpha induced neutrophil apoptosis even at time points when cycloheximide alone had no pro-apoptotic effect, suggesting that NF-kappaB may regulate the production of protein(s) which protect neutrophils from the cytotoxic effects of TNF-alpha.@@@@1@47@@oe@16-12-2010 993363208@GENIA Treebank@formal@@1@S@These data shed light on the biochemical and molecular mechanisms regulating human granulocyte apoptosis and, in particular, indicate that the transcription factor NF-kappaB plays a crucial role in regulating the physiological cell death pathway in granulocytes.@@@@1@39@@oe@16-12-2010 994917801@GENIA Treebank@formal@@1@S@Both Stat3-activation and Stat3-independent BCL2 downregulation are important for interleukin-6-induced apoptosis of 1A9-M cells.@@@@1@15@@oe@16-12-2010 994917802@GENIA Treebank@formal@@1@S@A unique subclone of a bone marrow-derived stromal cell line, BMS2.4, produces soluble factors that inhibit proliferation of several types of hematopoietic cell lines.@@@@1@27@@oe@16-12-2010 994917803@GENIA Treebank@formal@@1@S@An understanding of these molecules may be informative about negative regulatory circuits that can potentially limit blood cell formation.@@@@1@20@@oe@16-12-2010 994917804@GENIA Treebank@formal@@1@S@We used expression cloning to identify interleukin-6 (IL-6) as one factor that suppressed growth of a pre-B-cell variant line, 1A9-M.@@@@1@24@@oe@16-12-2010 994917805@GENIA Treebank@formal@@1@S@Moreover, IL-6 induced macrophage-differentiation and apoptosis of 1A9-M cells.@@@@1@11@@oe@16-12-2010 994917806@GENIA Treebank@formal@@1@S@During this process, IL-6 downregulated expression of BCL2 in 1A9-M cells and stimulated BCL-XL expression, but had no effect on p53, Bax, or Bak gene expression.@@@@1@31@@oe@16-12-2010 994917807@GENIA Treebank@formal@@1@S@Mechanisms for transduction of IL-6-induced signals were then evaluated in IL-6-stimulated 1A9-M cells.@@@@1@14@@oe@16-12-2010 994917808@GENIA Treebank@formal@@1@S@Whereas the signal transducer and activator of transcription 3 (Stat3) was phosphorylated and activated, there was no effect on either Stat1 or Stat5.@@@@1@27@@oe@16-12-2010 994917809@GENIA Treebank@formal@@1@S@The importance of BCL2 and Stat3 on IL-6-induced macrophage-differentiation and apoptosis was studied with 1A9-M cells expressing human BCL2 or a dominant-negative form of Stat3, respectively.@@@@1@28@@oe@16-12-2010 994917810@GENIA Treebank@formal@@1@S@IL-6-induced apoptosis, but not macrophage-differentiation, was blocked by continuously expressed BCL2.@@@@1@14@@oe@16-12-2010 994917811@GENIA Treebank@formal@@1@S@A dominant-negative form of Stat3 inhibited both macrophage-differentiation and apoptosis induced by IL-6.@@@@1@14@@oe@16-12-2010 994917812@GENIA Treebank@formal@@1@S@However, diminished Stat3 activity did not prevent IL-6-induced downregulation of the BCL2 gene.@@@@1@15@@oe@16-12-2010 994917813@GENIA Treebank@formal@@1@S@Therefore, activation of Stat3 is essential for IL-6-induced macrophage-differentiation and programmed cell death in this model.@@@@1@18@@oe@16-12-2010 994917814@GENIA Treebank@formal@@1@S@Whereas overexpression of BCL2 abrogates the apoptotic response, Stat3-independent signals appear to downregulate expression of the BCL2 gene.@@@@1@20@@oe@16-12-2010 994928501@GENIA Treebank@formal@@1@S@Granulosa cell tumor of the ovary.@@@@1@7@@oe@16-12-2010 994928502@GENIA Treebank@formal@@1@S@Immunohistochemical evidence of low proliferative activity and virtual absence of mutation of the p53 tumor-suppressor gene.@@@@1@17@@oe@16-12-2010 994928503@GENIA Treebank@formal@@1@S@BACKGROUND AND METHODS: Because the use of immunohistochemistry in the diagnosis of granulosa cell tumor (GCT) has not been fully explored, routinely processed (formalin-fixed, paraffin-embedded) tissue from 11 GCT, adult type, was investigated immunohistochemically (ABC method) with a broad spectrum of antibodies against various markers, including p53 and Ki-67.@@@@1@62@@oe@16-12-2010 994928504@GENIA Treebank@formal@@1@S@All of the tumors exhibited typical morphology, were limited to the ovary (stage I), and 7 cases followed a benign clinical course.@@@@1@27@@oe@16-12-2010 994928505@GENIA Treebank@formal@@1@S@RESULTS: All the tumors exhibited strong expression of vimentin, but most other antigens (including smooth muscle actin) were expressed infrequently by a minority of tumor cells or not at all.@@@@1@35@@oe@16-12-2010 994928506@GENIA Treebank@formal@@1@S@Tumor cells in 9 GCT expressed inhibin A.@@@@1@9@@oe@16-12-2010 994928507@GENIA Treebank@formal@@1@S@All the tumors exhibited very low proliferative activity, fewer than 10% of the tumor cell nuclei being stained by the antibody MIB-1 (Ki-67 antigen).@@@@1@29@@oe@16-12-2010 994928508@GENIA Treebank@formal@@1@S@The antibody D07 revealed marked overexpression of p53 protein in only one tumor.@@@@1@14@@oe@16-12-2010 994928509@GENIA Treebank@formal@@1@S@Clinical outcome was not found to be related to immunophenotypic differences.@@@@1@12@@oe@16-12-2010 994928510@GENIA Treebank@formal@@1@S@CONCLUSIONS: The diagnosis of GCT should be based primarily on the typical morphology revealed by conventional stains, but additional immunohistochemical staining with a small panel of selected antibodies (for example, against keratin, vimentin, and inhibin A) may be helpful in a few cases.@@@@1@51@@oe@16-12-2010 994928511@GENIA Treebank@formal@@1@S@The very low proliferative activity and the lack of overexpression of p53 protein are consistent with the benign clinical behavior of the majority of GCT.@@@@1@26@@oe@16-12-2010 995237201@GENIA Treebank@formal@@1@S@Lactobacilli and vaginal host defense: activation of the human immunodeficiency virus type 1 long terminal repeat, cytokine production, and NF-kappaB.@@@@1@24@@oe@16-12-2010 995237202@GENIA Treebank@formal@@1@S@Lactobacilli, a component of the normal vaginal flora, can activate the human immunodeficiency virus (HIV)-1 long terminal repeat (LTR) in the Jurkat T lymphocyte and THP-1 macrophage cell lines.@@@@1@37@@oe@16-12-2010 995237203@GENIA Treebank@formal@@1@S@Activation of the LTR in Jurkat cells was strongly enhanced by vanadate and inhibited by catalase, implicating H2O2.@@@@1@20@@oe@16-12-2010 995237204@GENIA Treebank@formal@@1@S@In contrast, activation in THP-1 cells occurred in the absence of vanadate and was unaffected by catalase.@@@@1@19@@oe@16-12-2010 995237205@GENIA Treebank@formal@@1@S@The active material partitioned into the phenol layer on hot aqueous phenol extraction.@@@@1@14@@oe@16-12-2010 995237206@GENIA Treebank@formal@@1@S@Lactobacilli also increased tumor necrosis factor-alphaand interleukin-1betaproduction and activated NF-kappaB in THP-1 cells and increased tumor necrosis factor-alphaproduction by human monocytes.@@@@1@25@@oe@16-12-2010 995237207@GENIA Treebank@formal@@1@S@Human vaginal fluid specimens had comparable properties, which correlated with their bacterial content.@@@@1@15@@oe@16-12-2010 995237208@GENIA Treebank@formal@@1@S@These findings suggest the presence in vaginal fluid of agent(s) derived from indigenous bacteria that can activate the HIV-1 LTR, cytokine production, and NF-kappaB in cells of macrophage lineage, with possible influence on vaginal physiology and host defense.@@@@1@45@@oe@16-12-2010 995238601@GENIA Treebank@formal@@1@S@Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene.@@@@1@18@@oe@16-12-2010 995238602@GENIA Treebank@formal@@1@S@The active metabolite of vitamin D, 1,25 dihydroxyvitamin D3, is an important immunoregulatory hormone [1].@@@@1@20@@oe@16-12-2010 995238603@GENIA Treebank@formal@@1@S@Its effects are exerted by interaction with the vitamin D receptor, which is present on human monocytes and activated T and B lymphocytes.@@@@1@25@@oe@16-12-2010 995238604@GENIA Treebank@formal@@1@S@Variation in the vitamin D receptor gene was typed in 2015 subjects from large case-control studies of three major infectious diseases: tuberculosis, malaria, and hepatitis B virus.@@@@1@31@@oe@16-12-2010 995238605@GENIA Treebank@formal@@1@S@Homozygotes for a polymorphism at codon 352 (genotype tt) were significantly underrepresented among those with tuberculosis (chi2=6.22, 1 df, P=.01) and persistent hepatitis B infection (chi2=6.25, 1 df, P=.01) but not in subjects with clinical malaria compared with the other genotypes.@@@@1@60@@oe@16-12-2010 995238606@GENIA Treebank@formal@@1@S@Therefore, this genetic variant, which predisposes to low bone mineral density in many populations, may confer resistance to certain infectious diseases.@@@@1@25@@oe@16-12-2010 997178801@GENIA Treebank@formal@@1@S@High-level replication of human immunodeficiency virus in thymocytes requires NF-kappaB activation through interaction with thymic epithelial cells.@@@@1@18@@oe@16-12-2010 997178802@GENIA Treebank@formal@@1@S@We have previously demonstrated that interaction of infected thymocytes with autologous thymic epithelial cells (TEC) is a prerequisite for a high level of human immunodeficiency virus type 1 (HIV-1) replication in thymocytes (M.Rothe, L.Chene, M.Nugeyre, F.Barre-Sinoussi, and N.Israel, J.Virol.72:5852-5861, 1998).@@@@1@55@@oe@16-12-2010 997178803@GENIA Treebank@formal@@1@S@We report here that this activation of HIV replication takes place at the transcriptional level through activation of the Rel/NF-kappaB transcription factors.@@@@1@23@@oe@16-12-2010 997178804@GENIA Treebank@formal@@1@S@We first demonstrate that an HIV-1 provirus (SF-2 strain) very effectively replicates in thymocytes cocultured with TEC whereas this provirus, with kappaB sites deleted, fails to replicate.@@@@1@32@@oe@16-12-2010 997178805@GENIA Treebank@formal@@1@S@We provide evidence that several NF-kappaB complexes are constitutively found in the nuclei of thymocytes either freshly isolated from the thymus or maintained in coculture with autologous or heterologous TEC.@@@@1@31@@oe@16-12-2010 997178806@GENIA Treebank@formal@@1@S@The prevalent complex is the heterodimer p50-p65.@@@@1@8@@oe@16-12-2010 997178807@GENIA Treebank@formal@@1@S@NF-kappaB activity is tightly correlated with the transcriptional activity of a long terminal repeat (LTR) of HIV-1 transfected in thymocytes.@@@@1@23@@oe@16-12-2010 997178808@GENIA Treebank@formal@@1@S@The cotransfection of this LTR with a mutated IkappaBalpha molecule formally demonstrates that LTR transactivation is regulated by members of the Rel/NF-kappaB family in thymocytes.@@@@1@26@@oe@16-12-2010 997178809@GENIA Treebank@formal@@1@S@We also showed that tumor necrosis factor (TNF) and to a lesser extent interleukin-1 (IL-1), secreted within the coculture, induce NF-kappaB activity and a correlative LTR transactivation.@@@@1@34@@oe@16-12-2010 997178810@GENIA Treebank@formal@@1@S@However IL-7, a crucial factor for thymopoiesis that is secreted mainly by TEC, is a necessary cofactor for NF-kappaB activation elicited by TNF or IL-1.@@@@1@28@@oe@16-12-2010 997178811@GENIA Treebank@formal@@1@S@Together, these data indicate that NF-kappaB activation, required for a high level of HIV replication in thymocytes, is regulated in a specific manner in the thymic microenvironment which provides the necessary cytokines: TNF, IL-1, and IL-7.@@@@1@43@@oe@16-12-2010 997337301@GENIA Treebank@formal@@1@S@Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis.@@@@1@18@@oe@16-12-2010 997337302@GENIA Treebank@formal@@1@S@Two variants of the IL-4R alpha-chain (IL-4Ralpha) gene have been recently identified in association with different atopic disorders.@@@@1@21@@oe@16-12-2010 997337303@GENIA Treebank@formal@@1@S@To clarify the etiological relationship between the two variants, we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551.@@@@1@37@@oe@16-12-2010 997337304@GENIA Treebank@formal@@1@S@The substitution of Ile for Val augmented STAT6 activation, proliferation, and transcription activity of the Iepsilon promoter by IL-4, whereas that of Arg for Gln did not change these IL-4 signals.@@@@1@35@@oe@16-12-2010 997337305@GENIA Treebank@formal@@1@S@Arg551 was not associated with atopic asthma in the Japanese population.@@@@1@12@@oe@16-12-2010 997337306@GENIA Treebank@formal@@1@S@CD23 expression and IgE synthesis by IL-4 were augmented in Ile50-bearing PBMC, compared with those bearing Val50.@@@@1@19@@oe@16-12-2010 997337307@GENIA Treebank@formal@@1@S@Taken together, substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript, whereas the substitution of Ile50 contributes to enhancement of IgE synthesis.@@@@1@31@@oe@16-12-2010 997340201@GENIA Treebank@formal@@1@S@Evidence for repression of IL-2 gene activation in anergic T cells.@@@@1@12@@oe@16-12-2010 997340202@GENIA Treebank@formal@@1@S@The induction of clonal anergy in a T cell inhibits IL-2 secretion because of the development of a proximal signal transduction defect.@@@@1@23@@oe@16-12-2010 997340203@GENIA Treebank@formal@@1@S@Fusion of anergic murine T cells to human Jurkat T leukemia cells and formation of heterokaryons failed to result in a complementation of this signaling defect and restoration of murine IL-2 mRNA inducibility.@@@@1@34@@oe@16-12-2010 997340204@GENIA Treebank@formal@@1@S@Instead, signal transduction to the human IL-2 gene became disrupted.@@@@1@12@@oe@16-12-2010 997340205@GENIA Treebank@formal@@1@S@Heterokaryons formed by the fusion of anergic murine T cells to normal murine T cells also failed to accumulate intracellular IL-2 protein in response to stimulation either with the combination of CD3 and CD28 mAbs or with ionomycin plus a protein kinase C-activating phorbol ester.@@@@1@46@@oe@16-12-2010 997340206@GENIA Treebank@formal@@1@S@The results argue against a loss-of-function signaling defect as the sole basis for clonal anergy induction and document the presence of a dominant-acting repressor molecule that inhibits signal transduction to the IL-2 gene within viable anergic T cells.@@@@1@39@@oe@16-12-2010 997346901@GENIA Treebank@formal@@1@S@Fas ligand induction in human NK cells is regulated by redox through a calcineurin-nuclear factors of activated T cell-dependent pathway.@@@@1@21@@oe@16-12-2010 997346902@GENIA Treebank@formal@@1@S@Fas ligand (FasL) on cytotoxic lymphocytes is important for mediating apoptosis of activated lymphocytes and other target cells.@@@@1@21@@oe@16-12-2010 997346903@GENIA Treebank@formal@@1@S@We have reported that NK cell functions, such as proliferation, cell death, and killing activity, are subject to regulation by cellular redox status.@@@@1@28@@oe@16-12-2010 997346904@GENIA Treebank@formal@@1@S@Here, we report that expression of FasL protein and mRNA in activated NK cells is also regulated by redox.@@@@1@21@@oe@16-12-2010 997346905@GENIA Treebank@formal@@1@S@Ligation of CD16 on IL-2-preactivated NK cells resulted in reduction of intracellular peroxide level as well as induction of FasL expression.@@@@1@22@@oe@16-12-2010 997346906@GENIA Treebank@formal@@1@S@This CD16-induced FasL expression was suppressed by oxidative stress, including thiol deprivation or treatment with hydrogen peroxide (H2O2).@@@@1@22@@oe@16-12-2010 997346907@GENIA Treebank@formal@@1@S@Addition of thiol-reducing compounds, such as L-cystine, 2-ME, or N-acetyl cysteine, restored FasL expression.@@@@1@19@@oe@16-12-2010 997346908@GENIA Treebank@formal@@1@S@These data suggest that CD16 stimulation requires cellular reducing status for FasL induction in NK cells.@@@@1@17@@oe@16-12-2010 997346909@GENIA Treebank@formal@@1@S@Because FasL gene activation following CD16 cross-linking is regulated by the NF of activated T cells (NFAT), we examined the effect of oxidative stresses on NFAT activation.@@@@1@31@@oe@16-12-2010 997346910@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assays revealed that both thiol insufficiency and H2O2 treatment suppressed DNA-binding activity of NFAT and that addition of thiol-reducing compounds reversed or even enhanced it.@@@@1@29@@oe@16-12-2010 997346911@GENIA Treebank@formal@@1@S@Furthermore, these oxidative stresses inhibited activity of calcineurin, a serine/threonine phosphatase that regulates NFAT activation.@@@@1@18@@oe@16-12-2010 997346912@GENIA Treebank@formal@@1@S@These results suggest that suppression of calcineurin and NFAT activation is a mechanism by which oxidative stress inhibits FasL induction in activated NK cells and further support the hypothesis that thiol-reducing compounds might be required for maintenance of optimal NK functions under physiologic oxidative conditions.@@@@1@46@@oe@16-12-2010 997352001@GENIA Treebank@formal@@1@S@Cross-linking of CD44 on rheumatoid synovial cells up-regulates VCAM-1.@@@@1@10@@oe@16-12-2010 997352002@GENIA Treebank@formal@@1@S@CD44 is a ubiquitous molecule also known as hyaluronic acid or homing receptor.@@@@1@14@@oe@16-12-2010 997352003@GENIA Treebank@formal@@1@S@However, the cellular functions and its role in inflammation, for example, rheumatoid synovitis, are currently unknown.@@@@1@21@@oe@16-12-2010 997352004@GENIA Treebank@formal@@1@S@In this study, we propose a novel function for CD44.@@@@1@12@@oe@16-12-2010 997352005@GENIA Treebank@formal@@1@S@Using synovial cells from rheumatoid arthritis (RA) patients, we demonstrated that CD44 cross-linking and binding to hyaluronan augmented VCAM-1 expression and subsequently VCAM-1-mediated cell adhesion.@@@@1@29@@oe@16-12-2010 997352006@GENIA Treebank@formal@@1@S@Briefly, we found that 1) rheumatoid synovial cells highly expressed CD44; 2) cross-linking of CD44 markedly but transiently augmented VCAM-1 expression and its mRNA transcription much more than did IL-1beta and TNF-alpha; 3) hyaluronan, especially when fragmented, also up-regulated VCAM-1; 4) CD44 activated the transcription factor AP-1; and 5) the integrin-dependent adhesive function of RA synovial cells to T cells was also amplified by CD44 cross-linking.@@@@1@79@@oe@16-12-2010 997352007@GENIA Treebank@formal@@1@S@These results indicate that the adhesion of RA synovial cells to matrices such as hyaluronic acid through CD44 could up-regulate VCAM-1 expression and VCAM-1-mediated adhesion to T cells, which might in turn cause activation of T cells and synovial cells in RA synovitis.@@@@1@45@@oe@16-12-2010 997352008@GENIA Treebank@formal@@1@S@We therefore propose that such cross-talking among distinct adhesion molecules may be involved in the pathogenesis of inflammation, including RA synovitis.@@@@1@23@@oe@16-12-2010 997440101@GENIA Treebank@formal@@1@S@Oleic acid inhibits endothelial activation : A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet.@@@@1@20@@oe@16-12-2010 997440102@GENIA Treebank@formal@@1@S@Because oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet, we investigated whether this fatty acid can modulate endothelial activation, ie, the concerted expression of gene products involved in leukocyte recruitment and early atherogenesis.@@@@1@42@@oe@16-12-2010 997440103@GENIA Treebank@formal@@1@S@We incubated sodium oleate with human umbilical vein endothelial cells for 0 to 72 hours, followed by coincubation of oleate with human recombinant tumor necrosis factor, interleukin (IL)-1alpha, IL-1beta, IL-4, Escherichia coli lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate for a further 6 to 24 hours.@@@@1@57@@oe@16-12-2010 997440104@GENIA Treebank@formal@@1@S@The endothelial expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 was monitored by cell surface enzyme immunoassays or flow cytometry, and steady-state levels of VCAM-1 mRNA were assessed by Northern blot analysis.@@@@1@42@@oe@16-12-2010 997440105@GENIA Treebank@formal@@1@S@At 10 to 100 micromol/L for >24 hours, oleate inhibited the expression of all adhesion molecules tested.@@@@1@20@@oe@16-12-2010 997440106@GENIA Treebank@formal@@1@S@After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 microg/mL LPS, VCAM-1 expression was reduced by >40% compared with control.@@@@1@30@@oe@16-12-2010 997440107@GENIA Treebank@formal@@1@S@Adhesion of monocytoid U937 cells to LPS-treated endothelial cells was reduced concomitantly.@@@@1@13@@oe@16-12-2010 997440108@GENIA Treebank@formal@@1@S@Oleate also produced a quantitatively similar reduction of VCAM-1 mRNA levels on Northern blot analysis and inhibited nuclear factor-kappaB activation on electrophoretic mobility shift assays.@@@@1@26@@oe@16-12-2010 997440109@GENIA Treebank@formal@@1@S@Incubation of endothelial cells with oleate for 72 hours decreased the relative proportions of saturated (palmitic and stearic) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids.@@@@1@46@@oe@16-12-2010 997440110@GENIA Treebank@formal@@1@S@Although less potent than polyunsaturated fatty acids in inhibiting endothelial activation, oleic acid may contribute to the prevention of atherogenesis through selective displacement of saturated fatty acids in cell membrane phospholipids and a consequent modulation of gene expression for molecules involved in monocyte recruitment.@@@@1@46@@oe@16-12-2010 998950301@GENIA Treebank@formal@@1@S@Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling.@@@@1@14@@oe@16-12-2010 998950302@GENIA Treebank@formal@@1@S@Using the coiled-coil region of Stat5b as the bait in a yeast two-hybrid screen, we identified the association of Nmi, a protein of unknown function previously reported as an N-Myc interactor.@@@@1@34@@oe@16-12-2010 998950303@GENIA Treebank@formal@@1@S@We further show that Nmi interacts with all STATs except Stat2.@@@@1@12@@oe@16-12-2010 998950304@GENIA Treebank@formal@@1@S@We evaluated two cytokine systems, IL-2 and IFNgamma, and demonstrate that Nmi augments STAT-mediated transcription in response to these cytokines.@@@@1@23@@oe@16-12-2010 998950305@GENIA Treebank@formal@@1@S@Interestingly, Nmi lacks an intrinsic transcriptional activation domain; instead, Nmi enhances the association of CBP/p300 coactivator proteins with Stat1 and Stat5, and together with CBP/p300 can augment IL-2- and IFNgamma-dependent transcription.@@@@1@36@@oe@16-12-2010 998950306@GENIA Treebank@formal@@1@S@Therefore, our data not only reveal that Nmi can potentiate STAT-dependent transcription, but also suggest that it can augment coactivator protein recruitment to at least some members of a group of sequence-specific transcription factors.@@@@1@37@@oe@16-12-2010 999006001@GENIA Treebank@formal@@1@S@GA-binding protein factors, in concert with the coactivator CREB binding protein/p300, control the induction of the interleukin 16 promoter in T lymphocytes.@@@@1@25@@oe@16-12-2010 999006002@GENIA Treebank@formal@@1@S@Interleukin 16 (IL-16) is a chemotactic cytokine that binds to the CD4 receptor and affects the activation of T cells and replication of HIV.@@@@1@27@@oe@16-12-2010 999006003@GENIA Treebank@formal@@1@S@It is expressed as a large 67-kDa precursor protein (pro-IL-16) in lymphocytes, macrophages, and mast cells, as well as in airway epithelial cells from asthmatics after challenge with allergen.@@@@1@35@@oe@16-12-2010 999006004@GENIA Treebank@formal@@1@S@This pro-IL-16 is subsequently processed to the mature cytokine of 13 kDa.@@@@1@13@@oe@16-12-2010 999006005@GENIA Treebank@formal@@1@S@To study the expression of IL-16 at the transcriptional level, we cloned the human chromosomal IL-16 gene and analyzed its promoter.@@@@1@23@@oe@16-12-2010 999006006@GENIA Treebank@formal@@1@S@The human IL-16 gene consists of seven exons and six introns.@@@@1@12@@oe@16-12-2010 999006007@GENIA Treebank@formal@@1@S@The 5' sequences up to nucleotide -120 of the human and murine IL-16 genes share >84% sequence homology and harbor promoter elements for constitutive and inducible transcription in T cells.@@@@1@33@@oe@16-12-2010 999006008@GENIA Treebank@formal@@1@S@Although both promoters lack any TATA box, they contain two CAAT box-like motifs and three binding sites of GA-binding protein (GABP) transcription factors.@@@@1@27@@oe@16-12-2010 999006009@GENIA Treebank@formal@@1@S@Two of these motifs are part of a highly conserved and inducible dyad symmetry element shown previously to control a remote IL-2 enhancer and the CD18 promoter.@@@@1@28@@oe@16-12-2010 999006010@GENIA Treebank@formal@@1@S@In concert with the coactivator CREB binding protein/p300, which interacts with GABPalpha, the binding of GABPalpha and -beta to the dyad symmetry element controls the induction of IL-16 promoter in T cells.@@@@1@35@@oe@16-12-2010 999006011@GENIA Treebank@formal@@1@S@Supplementing the data on the processing of pro-IL-16, our results indicate the complexity of IL-16 expression, which is tightly controlled at the transcriptional and posttranslational levels in T lymphocytes.@@@@1@32@@oe@16-12-2010 1002243501@GENIA Treebank@formal@@1@S@Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the immunophilin FKBP51.@@@@1@15@@oe@16-12-2010 1002243502@GENIA Treebank@formal@@1@S@Squirrel monkeys are neotropical primates that have high circulating cortisol to compensate for expression of glucocorticoid receptors (GRs) with reduced affinity.@@@@1@24@@oe@16-12-2010 1002243503@GENIA Treebank@formal@@1@S@The low binding affinity of squirrel monkey GR does not result from substitutions in the receptor, because squirrel monkey GR expressed in vitro exhibits high affinity.@@@@1@28@@oe@16-12-2010 1002243504@GENIA Treebank@formal@@1@S@Rather, squirrel monkeys express a soluble factor that, in mixing studies of cytosol from squirrel monkey lymphocytes (SML) and mouse L929 cells, reduced GR binding affinity by 11-fold.@@@@1@34@@oe@16-12-2010 1002243505@GENIA Treebank@formal@@1@S@In an effort to identify this factor, the cellular levels of components of the GR heterocomplex in SML and human lymphocytes (HL) were compared.@@@@1@28@@oe@16-12-2010 1002243506@GENIA Treebank@formal@@1@S@The immunophilin FKBP51 was 13-fold higher in SML than in HL cytosol; FKBP52 in SML was 42% of that in HL cytosol.@@@@1@25@@oe@16-12-2010 1002243507@GENIA Treebank@formal@@1@S@A role for changes in immunophilins, causing glucocorticoid resistance in neotropical primates, is supported by the following: the changes in FKBP51 and FKBP52 were observed in cells from other neotropical primates with glucocorticoid resistance; the elevated level of FKBP51 was reflected in an abundance of FKBP51 in heat shock protein 90 complexes in SML; when cytosols of SML and L929 cells were mixed, the decrease in GR binding was associated with incorporation of FKBP51 into GR heterocomplexes; the effect of SML cytosol on GR binding was reproduced with cytosol from COS cells expressing squirrel monkey FKBP51; and both the effect of SML cytosol on GR binding and the incorporation of FKBP51 into GR heterocomplexes were blocked by FK506.@@@@1@127@@oe@16-12-2010 1002243508@GENIA Treebank@formal@@1@S@Regulation of GR binding by FKBP51 represents a previously unrecognized mechanism for regulating glucocorticoid sensitivity.@@@@1@16@@oe@16-12-2010 1002288201@GENIA Treebank@formal@@1@S@Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity.@@@@1@14@@oe@16-12-2010 1002288202@GENIA Treebank@formal@@1@S@We previously reported that the role of reactive oxygen intermediates (ROIs) in NF-kappaB activation by proinflammatory cytokines was cell specific.@@@@1@23@@oe@16-12-2010 1002288203@GENIA Treebank@formal@@1@S@However, the sources for ROIs in various cell types are yet to be determined and might include 5-lipoxygenase (5-LOX) and NADPH oxidase.@@@@1@26@@oe@16-12-2010 1002288204@GENIA Treebank@formal@@1@S@5-LOX and 5-LOX activating protein (FLAP) are coexpressed in lymphoid cells but not in monocytic or epithelial cells.@@@@1@21@@oe@16-12-2010 1002288205@GENIA Treebank@formal@@1@S@Stimulation of lymphoid cells with interleukin-1beta (IL-1beta) led to ROI production and NF-kappaB activation, which could both be blocked by antioxidants or FLAP inhibitors, confirming that 5-LOX was the source of ROIs and was required for NF-kappaB activation in these cells.@@@@1@46@@oe@16-12-2010 1002288206@GENIA Treebank@formal@@1@S@IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappaB induction was not influenced by 5-LOX inhibitors.@@@@1@20@@oe@16-12-2010 1002288207@GENIA Treebank@formal@@1@S@However, reintroduction of a functional 5-LOX system in these cells allowed ROI production and 5-LOX-dependent NF-kappaB activation.@@@@1@19@@oe@16-12-2010 1002288208@GENIA Treebank@formal@@1@S@In monocytic cells, IL-1beta treatment led to a production of ROIs which is independent of the 5-LOX enzyme but requires the NADPH oxidase activity.@@@@1@26@@oe@16-12-2010 1002288209@GENIA Treebank@formal@@1@S@This pathway involves the Rac1 and Cdc42 GTPases, two enzymes which are not required for NF-kappaB activation by IL-1beta in epithelial cells.@@@@1@24@@oe@16-12-2010 1002288210@GENIA Treebank@formal@@1@S@In conclusion, three different cell-specific pathways lead to NF-kappaB activation by IL-1beta: a pathway dependent on ROI production by 5-LOX in lymphoid cells, an ROI- and 5-LOX-independent pathway in epithelial cells, and a pathway requiring ROI production by NADPH oxidase in monocytic cells.@@@@1@48@@oe@16-12-2010 1002289701@GENIA Treebank@formal@@1@S@Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment.@@@@1@13@@oe@16-12-2010 1002289702@GENIA Treebank@formal@@1@S@Fas (CD95) and Fas ligand (CD95L) are an interacting receptor-ligand pair required for immune homeostasis.@@@@1@20@@oe@16-12-2010 1002289703@GENIA Treebank@formal@@1@S@Lymphocyte activation results in the upregulation of Fas expression and the acquisition of sensitivity to FasL-mediated apoptosis.@@@@1@18@@oe@16-12-2010 1002289704@GENIA Treebank@formal@@1@S@Although Fas upregulation is central to the preservation of immunologic tolerance, little is known about the molecular machinery underlying this process.@@@@1@23@@oe@16-12-2010 1002289705@GENIA Treebank@formal@@1@S@To investigate the events involved in activation-induced Fas upregulation, we have examined mRNA accumulation, fas promoter activity, and protein expression in the Jurkat T-cell line treated with phorbol myristate acetate and ionomycin (P/I), pharmacological mimics of T-cell receptor activation.@@@@1@46@@oe@16-12-2010 1002289706@GENIA Treebank@formal@@1@S@Although resting Jurkat cells express Fas, Fas mRNA was induced approximately 10-fold in 2 h upon P/I stimulation.@@@@1@20@@oe@16-12-2010 1002289707@GENIA Treebank@formal@@1@S@Using sequential deletion mutants of the human fas promoter in transient transfection assays, we identified a 47-bp sequence (positions -306 to -260 relative to the ATG) required for activation-driven fas upregulation.@@@@1@35@@oe@16-12-2010 1002289708@GENIA Treebank@formal@@1@S@Sequence analysis revealed the presence of a previously unrecognized composite binding site for both the Sp1 and NF-kappaB transcription factors at positions -295 to -286.@@@@1@26@@oe@16-12-2010 1002289709@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assay (EMSA) and supershift analyses of this region documented constitutive binding of Sp1 in unactivated nuclear extracts and inducible binding of p50-p65 NF-kappaB heterodimers after P/I activation.@@@@1@33@@oe@16-12-2010 1002289710@GENIA Treebank@formal@@1@S@Sp1 and NF-kappaB transcription factor binding was shown to be mutually exclusive by EMSA displacement studies with purified recombinant Sp1 and recombinant p50.@@@@1@24@@oe@16-12-2010 1002289711@GENIA Treebank@formal@@1@S@The functional contribution of the kappaB-Sp1 composite site in P/I-inducible fas promoter activation was verified by using kappaB-Sp1 concatamers (-295 to -286) in a thymidine kinase promoter-driven reporter construct and native promoter constructs in Jurkat cells overexpressing IkappaB-alpha.@@@@1@41@@oe@16-12-2010 1002289712@GENIA Treebank@formal@@1@S@Site-directed mutagenesis of the critical guanine nucleotides in the kappaB-Sp1 element documented the essential role of this site in activation-dependent fas promoter induction.@@@@1@24@@oe@16-12-2010 1002377401@GENIA Treebank@formal@@1@S@RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes.@@@@1@17@@oe@16-12-2010 1002377402@GENIA Treebank@formal@@1@S@RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) is a chemoattractant cytokine (chemokine) important in the generation of inflammatory infiltrate and human immunodeficiency virus entry into immune cells.@@@@1@36@@oe@16-12-2010 1002377403@GENIA Treebank@formal@@1@S@RANTES is expressed late (3-5 days) after activation in T lymphocytes.@@@@1@14@@oe@16-12-2010 1002377404@GENIA Treebank@formal@@1@S@Using expression cloning, we identified the first "late" T lymphocyte associated transcription factor and named it "RANTES Factor of Late Activated T Lymphocytes-1" (RFLAT-1).@@@@1@32@@oe@16-12-2010 1002377405@GENIA Treebank@formal@@1@S@RFLAT-1 is a novel, phosphorylated, zinc finger transcription factor that is expressed in T cells 3 days after activation, coincident with RANTES expression.@@@@1@27@@oe@16-12-2010 1002377406@GENIA Treebank@formal@@1@S@While Rel proteins play the dominant role in RANTES gene expression in fibroblasts, RFLAT-1 is a strong transactivator for RANTES in T cells.@@@@1@25@@oe@16-12-2010 1002461801@GENIA Treebank@formal@@1@S@Daidzein and genistein glucuronides in vitro are weakly estrogenic and activate human natural killer cells at nutritionally relevant concentrations.@@@@1@20@@oe@16-12-2010 1002461802@GENIA Treebank@formal@@1@S@Daidzein and genistein glucuronides (DG and GG), major isoflavone metabolites, may be partly responsible for biological effects of isoflavones, such as estrogen receptor binding and natural killer cell (NK) activation or inhibition.@@@@1@40@@oe@16-12-2010 1002461803@GENIA Treebank@formal@@1@S@DG and GG were synthesized using 3-methylcholanthrene-induced rat liver microsomes.@@@@1@11@@oe@16-12-2010 1002461804@GENIA Treebank@formal@@1@S@The Km and Vmax for daidzein and genistein were 9.0 and 7.7 micromol/L, and 0.7 and 1.6 micromol/(mg protein. min), respectively.@@@@1@27@@oe@16-12-2010 1002461805@GENIA Treebank@formal@@1@S@The absence of ultraviolet absorbance maxima shifts in the presence of sodium acetate confirmed that the synthesized products were 7-O-glucuronides.@@@@1@21@@oe@16-12-2010 1002461806@GENIA Treebank@formal@@1@S@DG and GG were further purified by a Sephadex LH-20 column.@@@@1@12@@oe@16-12-2010 1002461807@GENIA Treebank@formal@@1@S@DG and GG competed with the binding of 17beta-(3H) estradiol to estrogen receptors of B6D2F1 mouse uterine cytosol.@@@@1@19@@oe@16-12-2010 1002461808@GENIA Treebank@formal@@1@S@The concentrations required for 50% displacement of 17beta-(3H) estradiol (CB50) were: 17beta-estradiol, 1.34 nmol/L; diethylstilbestrol, 1.46 nmol/L; daidzein, 1.6 micromol/L; DG, 14.7 micromol/L; genistein, 0.154 micromol/L; GG, 7.27 micromol/L.@@@@1@45@@oe@16-12-2010 1002461809@GENIA Treebank@formal@@1@S@In human peripheral blood NK cells, genistein at <0.5 micromol/L and DG and GG at 0.1-10 micromol/L enhanced NK cell-mediated K562 cancer cell killing significantly (P < 0.05).@@@@1@33@@oe@16-12-2010 1002461810@GENIA Treebank@formal@@1@S@At > 0.5 micromol/L, genistein inhibited NK cytotoxicity significantly (P < 0.05).@@@@1@16@@oe@16-12-2010 1002461811@GENIA Treebank@formal@@1@S@The glucuronides only inhibited NK cytotoxicity at 50 micromol/L.@@@@1@10@@oe@16-12-2010 1002461812@GENIA Treebank@formal@@1@S@Isoflavones, and especially the isoflavone glucuronides, enhanced activation of NK cells by interleukin-2 (IL-2), additively.@@@@1@21@@oe@16-12-2010 1002461813@GENIA Treebank@formal@@1@S@At physiological concentrations, DG and GG were weakly estrogenic, and they activated human NK cells in nutritionally relevant concentrations in vitro, probably at a site different from IL-2 action.@@@@1@33@@oe@16-12-2010 1002566801@GENIA Treebank@formal@@1@S@Osteoclast markers accumulate on cells developing from human peripheral blood mononuclear precursors.@@@@1@13@@oe@16-12-2010 1002566802@GENIA Treebank@formal@@1@S@Recent studies show that human osteoclasts develop in vitro from hematopoietic cells; however, special cultures conditions and/or cytokine mobilized peripheral blood are apparently required.@@@@1@27@@oe@16-12-2010 1002566803@GENIA Treebank@formal@@1@S@Here, we report that cells expressing osteoclast markers differentiate from precursors present in nonmobilized peripheral blood mononuclear cells (PBMC), without the addition of stromal cells, growth factors, cytokines or steroids; and characterize their phenotype.@@@@1@42@@oe@16-12-2010 1002566804@GENIA Treebank@formal@@1@S@Three days after establishing high-density PBMC cultures (1.5 x 10(6) cells/cm2), in serum-containing medium, small adherent colonies of tartrate resistant acid phosphatase positive (TRAP+) cells emerge, amidst massive monocyte cell death.@@@@1@39@@oe@16-12-2010 1002566805@GENIA Treebank@formal@@1@S@These adherent cells have an eccentrically placed, round nucleus, and express low levels of TRAP and sodium fluoride-resistant- alpha-naphthyl-acetate-esterase (NaF-R-NSE).@@@@1@24@@oe@16-12-2010 1002566806@GENIA Treebank@formal@@1@S@Over the next week, this cell population accumulates phenotypic markers of osteoclasts (vitronectin receptor [VR], calcitonin receptor, TRAP, cathepsin K protein, and mRNA) with increased nuclearity, covering the entire surface by 15 days.@@@@1@44@@oe@16-12-2010 1002566807@GENIA Treebank@formal@@1@S@When cultured on bone, VR+, TRAP+ cells of low multinuclearity appear and cover up to 50% of the surface.@@@@1@23@@oe@16-12-2010 1002566808@GENIA Treebank@formal@@1@S@Resorption lacunae can be observed by day 22.@@@@1@9@@oe@16-12-2010 1002566809@GENIA Treebank@formal@@1@S@Although these pits are not nearly as numerous as the cells of preosteoclast phenotype, they do represent the activity of a subset of osteoclast-like cells that has achieved osteoclastic maturity under these culture conditions.@@@@1@36@@oe@16-12-2010 1002566810@GENIA Treebank@formal@@1@S@Transcripts for osteoprotegerin ligand (OPGL), an osteoclast differentiation factor (also known as RANKL and TRANCE) are expressed, likely by adherent cells.@@@@1@28@@oe@16-12-2010 1002566811@GENIA Treebank@formal@@1@S@Thus, an adherent population of cells, with preosteoclast/osteoclast phenotypic properties, arises selectively under simple culture conditions from normal PBMC.@@@@1@23@@oe@16-12-2010 1002566812@GENIA Treebank@formal@@1@S@Further characterization of these cells should identify factors involved in the growth, terminal differentiation and activation of osteoclasts.@@@@1@20@@oe@16-12-2010 1002762301@GENIA Treebank@formal@@1@S@Phenotypic and functional studies of leukocytes in human endometrium and endometriosis.@@@@1@12@@oe@16-12-2010 1002762302@GENIA Treebank@formal@@1@S@The aetiology of endometriosis, a common and disabling disorder, is presently unknown, although immune dysfunction could allow ectopic endometrial fragments to survive outside the uterine cavity.@@@@1@30@@oe@16-12-2010 1002762303@GENIA Treebank@formal@@1@S@These studies investigate the relationship between leukocyte populations, steroid hormone receptor expression, proliferative activity, bcl-2 expression and apoptosis in eutopic and ectopic endometrium from women with endometriosis or adenomyosis at different phases of the menstrual cycle.@@@@1@40@@oe@16-12-2010 1002762304@GENIA Treebank@formal@@1@S@Significantly increased oestrogen receptor expression, bcl-2 expression and numbers of CD8+ leukocytes were found in ectopic compared with eutopic endometrium in endometriosis, and CD56+ endometrial granulated lymphocytes (eGLs) were significantly reduced in ectopic endometrium.@@@@1@39@@oe@16-12-2010 1002762305@GENIA Treebank@formal@@1@S@Apoptotic cells were rarely found in control and subject endometria.@@@@1@11@@oe@16-12-2010 1002762306@GENIA Treebank@formal@@1@S@In contrast with endometriosis, adenomyotic lesions showed identical steroid hormone receptor expression, proliferative activity, bcl-2 expression and leukocyte subpopulations to eutopic endometrium, indicating different aetiologies for these disorders.@@@@1@33@@oe@16-12-2010 1002762307@GENIA Treebank@formal@@1@S@The unusual CD56+ CD16- eGLs present in large numbers in late secretory phase eutopic endometrium were highly purified (>98%) by immunomagnetic separation.@@@@1@27@@oe@16-12-2010 1002762308@GENIA Treebank@formal@@1@S@Except for a negligible cytotoxic activity of eGLs from early proliferative samples, cytotoxic activity of eGLs from non-pregnant endometrium during the menstrual cycle was comparable with those in peripheral blood, predominantly CD56+ CD16+ natural killer cells.@@@@1@39@@oe@16-12-2010 1002762309@GENIA Treebank@formal@@1@S@eGLs from non-pregnant endometrium and early pregnancy showed a variable proliferative response to 5 and 100 U/ml interleukin-2 over 48-h and 120-h time courses.@@@@1@25@@oe@16-12-2010 1002762310@GENIA Treebank@formal@@1@S@eGLs are evidently functionally important in the eutopic endometrium.@@@@1@10@@oe@16-12-2010 1002762311@GENIA Treebank@formal@@1@S@Their absence in endometriotic lesions together with increased CD+8 T-cell numbers and increased oestrogen receptor and bcl-2 expression may have significant effects on the development and progression of endometriosis.@@@@1@30@@oe@16-12-2010 1002957101@GENIA Treebank@formal@@1@S@Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1.@@@@1@18@@oe@16-12-2010 1002957102@GENIA Treebank@formal@@1@S@Interleukin-10 (IL-10) helps maintain polarized T-helper cells in a T-helper lymphocyte 2 (Th2) phenotype.@@@@1@19@@oe@16-12-2010 1002957103@GENIA Treebank@formal@@1@S@Part of this process involves the prevention of the development of Th1 cells, which are a primary source of interferon gamma (IFNgamma), a potent activator of monocytes and an inhibitor of Th2 proliferation.@@@@1@38@@oe@16-12-2010 1002957104@GENIA Treebank@formal@@1@S@Because monocytes and macrophages are important mediators of Th1-type responses, such as delayed-type hypersensitivity, we sought to determine if IL-10 could directly mediate inhibition of IFNgamma- and IFNalpha-induced gene expression in these cells.@@@@1@36@@oe@16-12-2010 1002957105@GENIA Treebank@formal@@1@S@Highly purified monocytes were incubated with IL-10 for 60 to 90 minutes before the addition of IFNgamma or IFNalpha.@@@@1@20@@oe@16-12-2010 1002957106@GENIA Treebank@formal@@1@S@IL-10 preincubation resulted in the inhibition of gene expression for several IFN-induced genes, such as IP-10, ISG54, and intercellular adhesion molecule-1.@@@@1@25@@oe@16-12-2010 1002957107@GENIA Treebank@formal@@1@S@The reduction in gene expression resulted from the ability of IL-10 to suppress IFN-induced assembly of signal transducer and activator of transcription (STAT) factors to specific promoter motifs on IFNalpha- and IFNgamma-inducible genes.@@@@1@36@@oe@16-12-2010 1002957108@GENIA Treebank@formal@@1@S@This was accomplished by preventing the IFN-induced tyrosine phosphorylation of STAT1, a component of both IFNalpha- and IFNgamma-induced DNA binding complexes.@@@@1@23@@oe@16-12-2010 1002957109@GENIA Treebank@formal@@1@S@Therefore, IL-10 can directly inhibit STAT-dependent early response gene expression induced by both IFNalpha and IFNgamma in monocytes by suppressing the tyrosine phosphorylation of STAT1.@@@@1@27@@oe@16-12-2010 1002957110@GENIA Treebank@formal@@1@S@This may occur through the ability of IL-10 to induce expression of the gene, suppressor of cytokine signaling 3 (SOCS3).@@@@1@24@@oe@16-12-2010 1002958901@GENIA Treebank@formal@@1@S@The Megakaryocyte/Platelet-specific enhancer of the alpha2beta1 integrin gene: two tandem AP1 sites and the mitogen-activated protein kinase signaling cascade.@@@@1@21@@oe@16-12-2010 1002958902@GENIA Treebank@formal@@1@S@The alpha2beta1 integrin, a collagen receptor on platelets and megakaryocytes, is required for normal platelet function.@@@@1@19@@oe@16-12-2010 1002958903@GENIA Treebank@formal@@1@S@Transcriptional regulation of the alpha2 integrin gene in cells undergoing megakaryocytic differentiation requires a core promoter between bp -30 and -92, a silencer between bp -92 and -351, and megakaryocytic enhancers in the distal 5' flank.@@@@1@39@@oe@16-12-2010 1002958904@GENIA Treebank@formal@@1@S@We have now identified a 229-bp region of the distal 5' flank of the alpha2 integrin gene required for high-level enhancer activity in cells with megakaryocytic features.@@@@1@28@@oe@16-12-2010 1002958905@GENIA Treebank@formal@@1@S@Two tandem AP1 binding sites with dyad symmetry are required for enhancer activity and for DNA-protein complex formation with members of the c-fos/c-jun family.@@@@1@25@@oe@16-12-2010 1002958906@GENIA Treebank@formal@@1@S@The requirement for AP1 activation suggested a role for the mitogen-activated protein kinase (MAPK) signaling pathway in regulating alpha2 integrin gene expression.@@@@1@25@@oe@16-12-2010 1002958907@GENIA Treebank@formal@@1@S@Inhibition of the MAP kinase cascade with PD98059, a specific inhibitor of MAPK kinase 1, prevented the expression of the alpha2 integrin subunit in cells induced to become megakaryocytic.@@@@1@32@@oe@16-12-2010 1002958908@GENIA Treebank@formal@@1@S@We provide a model of megakaryocytic differentiation in which expression of the alpha2 integrin gene requires signaling via the MAP kinase pathway to activate two tandem AP1 binding sites in the alpha2 integrin enhancer.@@@@1@35@@oe@16-12-2010 1002959401@GENIA Treebank@formal@@1@S@Clonality of isolated eosinophils in the hypereosinophilic syndrome.@@@@1@9@@oe@16-12-2010 1002959402@GENIA Treebank@formal@@1@S@The idiopathic hypereosinophilic syndrome (IHES) is a rare disorder characterized by unexplained, persistent eosinophilia associated with multiple organ dysfunction due to eosinophilic tissue infiltration.@@@@1@28@@oe@16-12-2010 1002959403@GENIA Treebank@formal@@1@S@In the absence of karyotypic abnormalities, there is no specific test to detect clonal eosinophilia in IHES.@@@@1@19@@oe@16-12-2010 1002959404@GENIA Treebank@formal@@1@S@Analysis of X-chromosome inactivation patterns can be used to determine whether proliferative disorders are clonal in origin.@@@@1@18@@oe@16-12-2010 1002959405@GENIA Treebank@formal@@1@S@Methylation of HpaII and Hha I sites near the polymorphic trinucleotide repeat of the human androgen receptor gene (HUMARA) has been shown to correlate with X-inactivation.@@@@1@29@@oe@16-12-2010 1002959406@GENIA Treebank@formal@@1@S@In this study, we have used the polymerase chain reaction (PCR) with nested primers to analyze X-inactivation patterns of the HUMARA loci in purified eosinophils from female patients with eosinophilia.@@@@1@34@@oe@16-12-2010 1002959407@GENIA Treebank@formal@@1@S@Peripheral blood eosinophils were isolated by their autofluoresence using flow cytometric sorting.@@@@1@13@@oe@16-12-2010 1002959408@GENIA Treebank@formal@@1@S@Eosinophils purified from a female patient presenting with IHES were found to show a clonal pattern of X-inactivation.@@@@1@19@@oe@16-12-2010 1002959409@GENIA Treebank@formal@@1@S@Eosinophil-depleted leukocytes from this patient were polyclonal by HUMARA analysis, thus excluding skewedness of random X-inactivation.@@@@1@18@@oe@16-12-2010 1002959410@GENIA Treebank@formal@@1@S@After corticosteroid suppression of her blood eosinophilia, a clonal population of eosinophils could no longer be detected in purified eosinophils.@@@@1@22@@oe@16-12-2010 1002959411@GENIA Treebank@formal@@1@S@In contrast, eosinophils purified from a patient with Churg-Strauss syndrome and from six patients with reactive eosinophilias attributed to allergy, parasitic infection, or drug reaction showed a polyclonal pattern of X-inactivation by HUMARA analysis.@@@@1@38@@oe@16-12-2010 1002959412@GENIA Treebank@formal@@1@S@The finding of clonal eosinophilia in a patient presenting with IHES indicates that such patients may have, in reality, a low-grade clonal disorder that can be distinguished from reactive eosinophilias by HUMARA analysis.@@@@1@36@@oe@16-12-2010 1002959413@GENIA Treebank@formal@@1@S@Further, the method described can be used to monitor disease progression.@@@@1@13@@oe@16-12-2010 1003713801@GENIA Treebank@formal@@1@S@Differential expression and phosphorylation of CTCF, a c-myc transcriptional regulator, during differentiation of human myeloid cells.@@@@1@19@@oe@16-12-2010 1003713802@GENIA Treebank@formal@@1@S@CTCF is a transcriptional repressor of the c-myc gene.@@@@1@10@@oe@16-12-2010 1003713803@GENIA Treebank@formal@@1@S@Although CTCF has been characterized in some detail, there is very little information about the regulation of CTCF activity.@@@@1@21@@oe@16-12-2010 1003713804@GENIA Treebank@formal@@1@S@Therefore we investigated CTCF expression and phosphorylation during induced differentiation of human myeloid leukemia cells.@@@@1@16@@oe@16-12-2010 1003713805@GENIA Treebank@formal@@1@S@We found that: (i) both CTCF mRNA and protein are down-regulated during terminal differentiation in most cell lines tested; (ii) CTCF down-regulation is retarded and less pronounced than that of c-myc; (iii) CTCF protein is differentially phosphorylated and the phosphorylation profiles depend on the differentiation pathway.@@@@1@56@@oe@16-12-2010 1003713806@GENIA Treebank@formal@@1@S@We concluded that CTCF expression and activity is controlled at transcriptional and post-transcriptional levels.@@@@1@15@@oe@16-12-2010 1003775101@GENIA Treebank@formal@@1@S@T-cell expression of the human GATA-3 gene is regulated by a non-lineage-specific silencer.@@@@1@14@@oe@16-12-2010 1003775102@GENIA Treebank@formal@@1@S@The GATA-3 transcription factor is required for development of the T-cell lineage and Th2 cytokine gene expression in CD4 T-cells.@@@@1@21@@oe@16-12-2010 1003775103@GENIA Treebank@formal@@1@S@We have mapped the DNase-I-hypersensitive (HS) regions of the human GATA-3 gene in T-cells and non-T-cells and studied their transcriptional activities.@@@@1@24@@oe@16-12-2010 1003775104@GENIA Treebank@formal@@1@S@HS I-III, located 5' from the transcriptional initiation site, were found in hematopoietic and non-hematopoietic cells, whereas HS IV-VII, located 3' from the transcriptional start site, were exclusively observed in T-cells.@@@@1@37@@oe@16-12-2010 1003775105@GENIA Treebank@formal@@1@S@Among these hypersensitive sites, two transcriptional control elements were found, one in the first intron of the GATA-3 gene and the other between 8.3 and 5.9 kilobases 5' from the GATA-3 transcriptional initiation site.@@@@1@37@@oe@16-12-2010 1003775106@GENIA Treebank@formal@@1@S@The first intron acted as a strong transcriptional activator in a position-dependent manner and with no cell-type specificity.@@@@1@19@@oe@16-12-2010 1003775107@GENIA Treebank@formal@@1@S@The upstream regulatory element could confer T-cell specificity to the GATA-3 promoter activity, and analysis of this region revealed a 707-base pair silencer that drastically inhibited GATA-3 promoter activity in non-T-cells.@@@@1@33@@oe@16-12-2010 1003775108@GENIA Treebank@formal@@1@S@Two CAGGTG E-boxes, located at the 5'- and 3'-ends of the silencer, were necessary for this silencer activity.@@@@1@21@@oe@16-12-2010 1003775109@GENIA Treebank@formal@@1@S@The 3'-CAGGTG E-box could bind USF proteins, the ubiquitous repressor ZEB, or the basic helix-loop-helix proteins E2A and HEB, and we showed that a competition between ZEB and E2A/HEB proteins is involved in the silencer activity.@@@@1@40@@oe@16-12-2010 1004904801@GENIA Treebank@formal@@1@S@Clonality analysis of refractory anemia with ring sideroblasts: simultaneous study of clonality and cytochemistry of bone marrow progenitors.@@@@1@20@@oe@16-12-2010 1004904802@GENIA Treebank@formal@@1@S@X chromosome inactivation and polymorphism of the human androgen receptor (HUMARA) gene has been applied for analyzing the clonality of blood cells.@@@@1@25@@oe@16-12-2010 1004904803@GENIA Treebank@formal@@1@S@In the present study, the clonal relationship was investigated between peripheral blood polymorphonuclear cells (PMNCs) and marrow progenitor cells and the origin of ringed sideroblasts in patients with refractory anemia with ring sideroblasts (RARS) by polymerase chain reaction (PCR) of HUMARA gene.@@@@1@50@@oe@16-12-2010 1004904804@GENIA Treebank@formal@@1@S@The X-inactivation patterns of circulating PMNCs and T lymphocytes as well as individual granulocyte colonies grown in vitro from bone marrow cells were analyzed.@@@@1@25@@oe@16-12-2010 1004904805@GENIA Treebank@formal@@1@S@The development of ringed sideroblasts in erythroid colonies by iron staining and their X-inactivation pattern were also examined.@@@@1@19@@oe@16-12-2010 1004904806@GENIA Treebank@formal@@1@S@All three RARS patients showed monoclonal PMNCs.@@@@1@8@@oe@16-12-2010 1004904807@GENIA Treebank@formal@@1@S@In granulocyte colonies, however, two different X-inactivation patterns were observed in all patients, indicating that non-clonal progenitor cells remained in the bone marrow.@@@@1@27@@oe@16-12-2010 1004904808@GENIA Treebank@formal@@1@S@All erythroid colonies consisted of ringed sideroblasts exclusively showed one pattern dominant in those of PMNCs.@@@@1@17@@oe@16-12-2010 1004904809@GENIA Treebank@formal@@1@S@Our findings suggest that non-clonal progenitor cells persist in some RARS cases, that erythroid progenitors show mosaicism, and that ringed sideroblasts may be derived from an abnormal clone involved in the pathogenesis of this disease.@@@@1@38@@oe@16-12-2010 1005087701@GENIA Treebank@formal@@1@S@Binding of c-Rel to STAT5 target sequences in HTLV-I-transformed T cells.@@@@1@12@@oe@16-12-2010 1005087702@GENIA Treebank@formal@@1@S@The type I human T-cell leukemia virus (HTLV-I) induces abnormal growth and subsequent transformation of T cells, which is associated with the development of an acute T-cell malignancy termed adult T-cell leukemia.@@@@1@36@@oe@16-12-2010 1005087703@GENIA Treebank@formal@@1@S@A characteristic of HTLV-I-transformed T cells is the constitutive nuclear expression of NF-kappaB/Rel family of transcription factors, which appears to be essential for the growth of these transformed cells.@@@@1@31@@oe@16-12-2010 1005087704@GENIA Treebank@formal@@1@S@Although NF-kappaB/Rel factors are known to induce the expression of T-cell growth factor interleukin (IL)-2, it is unclear how they participate in the IL-2-independent growth of HTLV-I-transformed cells.@@@@1@33@@oe@16-12-2010 1005087705@GENIA Treebank@formal@@1@S@In this study, we show that certain NF-kappaB/Rel members, predominantly c-Rel, interact with enhancer sequences for STAT5, a key transcription factor mediating IL-2-induced T-cell proliferation.@@@@1@30@@oe@16-12-2010 1005087706@GENIA Treebank@formal@@1@S@Reporter gene assays reveal that the binding of c-Rel to the STAT5 site present in the Fc gammaR1 gene leads to potent transactivation of this enhancer.@@@@1@27@@oe@16-12-2010 1005087707@GENIA Treebank@formal@@1@S@Binding of c-Rel to the Fc gammaR1 STAT site also occurs in human peripheral blood T cells immortalized with HTLV-I in vitro and is correlated with enhanced levels of proliferation of these cells.@@@@1@34@@oe@16-12-2010 1005087708@GENIA Treebank@formal@@1@S@These results raise the possibility that NF-kappaB/Rel may participate in the growth control of HTLV-I-transformed T cells by regulating genes driven by both kappaB and certain STAT enhancers.@@@@1@29@@oe@16-12-2010 1005163201@GENIA Treebank@formal@@1@S@Crossreactive recognition of viral, self, and bacterial peptide ligands by human class I-restricted cytotoxic T lymphocyte clonotypes: implications for molecular mimicry in autoimmune disease.@@@@1@28@@oe@16-12-2010 1005163202@GENIA Treebank@formal@@1@S@The immunodominant, CD8(+) cytotoxic T lymphocyte (CTL) response to the HLA-B8-restricted peptide, RAKFKQLL, located in the Epstein-Barr virus immediate-early antigen, BZLF1, is characterized by a diverse T cell receptor (TCR) repertoire.@@@@1@41@@oe@16-12-2010 1005163203@GENIA Treebank@formal@@1@S@Here, we show that this diversity can be partitioned on the basis of crossreactive cytotoxicity patterns involving the recognition of a self peptide-RSKFRQIV-located in a serine/threonine kinase and a bacterial peptide-RRKYKQII-located in Staphylococcus aureus replication initiation protein.@@@@1@47@@oe@16-12-2010 1005163204@GENIA Treebank@formal@@1@S@Thus CTL clones that recognized the viral, self, and bacterial peptides expressed a highly restricted alphabeta TCR phenotype.@@@@1@21@@oe@16-12-2010 1005163205@GENIA Treebank@formal@@1@S@The CTL clones that recognized viral and self peptides were more oligoclonal, whereas clones that strictly recognized the viral peptide displayed a diverse TCR profile.@@@@1@27@@oe@16-12-2010 1005163206@GENIA Treebank@formal@@1@S@Interestingly, the self and bacterial peptides equally were substantially less effective than the cognate viral peptide in sensitizing target cell lysis, and also resulted only in a weak reactivation of memory CTLs in limiting dilution assays, whereas the cognate peptide was highly immunogenic.@@@@1@47@@oe@16-12-2010 1005163207@GENIA Treebank@formal@@1@S@The described crossreactions show that human antiviral, CD8(+) CTL responses can be shaped by peptide ligands derived from autoantigens and environmental bacterial antigens, thereby providing a firm structural basis for molecular mimicry involving class I-restricted CTLs in the pathogenesis of autoimmune disease.@@@@1@45@@oe@16-12-2010 1006406401@GENIA Treebank@formal@@1@S@AML and Ets proteins regulate the I alpha1 germ-line promoter.@@@@1@11@@oe@16-12-2010 1006406402@GENIA Treebank@formal@@1@S@The immunoglobulin heavy chain (IgH) class switch recombination of B lymphocytes preferentially targets unrearranged IgH genes that have already been rendered transcriptionally active.@@@@1@26@@oe@16-12-2010 1006406403@GENIA Treebank@formal@@1@S@Transcription of the germ-line IgH genes is controlled by intervening (I) regions upstream of their switch regions.@@@@1@20@@oe@16-12-2010 1006406404@GENIA Treebank@formal@@1@S@The I alpha1 promoter activates transcription of the human germ-line C alpha1 gene for IgA1 and mediates the transforming growth factor (TGF)-beta1 responsiveness of this locus.@@@@1@30@@oe@16-12-2010 1006406405@GENIA Treebank@formal@@1@S@Here we show that the I alpha1 promoter contains several binding sites for the AML/PEBP2/CBF family of transcription factors and that AML and Ets proteins are major regulators of the basal and TGF-beta-inducible promoter activity.@@@@1@36@@oe@16-12-2010 1006406406@GENIA Treebank@formal@@1@S@Our data constitute a starting point for studies to elucidate the molecular mechanism by which TGF-beta regulates IgA production.@@@@1@20@@oe@16-12-2010 1006410301@GENIA Treebank@formal@@1@S@Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kappaB.@@@@1@21@@oe@16-12-2010 1006410302@GENIA Treebank@formal@@1@S@Increased oxidative stress and subsequent activation of the transcription factor NF-kappaB has been linked to the development of late diabetic complications.@@@@1@22@@oe@16-12-2010 1006410303@GENIA Treebank@formal@@1@S@To determine whether oxidative stress dependent NF-kappaB activation is evident in patients with diabetic nephropathy we used an Electrophoretic Mobility Shift Assay based semiquantitative detection system which enabled us to determine NF-kappaB activation in ex vivo isolated peripheral blood mononuclear cells.@@@@1@42@@oe@16-12-2010 1006410304@GENIA Treebank@formal@@1@S@We examined 33 patients with diabetes mellitus (Type I and Type II).@@@@1@15@@oe@16-12-2010 1006410305@GENIA Treebank@formal@@1@S@Patients with diabetic nephropathy showed higher NF-kappaB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kappaBp65 than patients without renal complications.@@@@1@27@@oe@16-12-2010 1006410306@GENIA Treebank@formal@@1@S@NF-kappaB binding activity correlated with the degree of albuminuria (r = 0.316) and with thrombomodulin plasma concentrations (r = 0.33), indicative for albuminuria associated endothelial dysfunction.@@@@1@32@@oe@16-12-2010 1006410307@GENIA Treebank@formal@@1@S@In a 3 day intervention study in which 600 mg of the antioxidant thioctic acid (alpha-lipoic acid) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48% and NF-kappaB binding activity in ex vivo isolated peripheral blood mononuclear cells by 38%.@@@@1@55@@oe@16-12-2010 1006410308@GENIA Treebank@formal@@1@S@In conclusion, activation of the transcription factor NF-kappaB in ex vivo isolated peripheral blood mononuclear cells of patients with diabetes mellitus correlates with the degree of diabetic nephropathy.@@@@1@30@@oe@16-12-2010 1006410309@GENIA Treebank@formal@@1@S@NF-kappaB activation is at least in part dependent on oxidative stress since thioctic acid (alpha-lipoic acid) reduced NF-kappaB binding activity.@@@@1@23@@oe@16-12-2010 1006858801@GENIA Treebank@formal@@1@S@Activation of human immunodeficiency virus type 1 expression by Gardnerella vaginalis.@@@@1@12@@oe@16-12-2010 1006858802@GENIA Treebank@formal@@1@S@Bacterial vaginosis (BV) is associated with an increased rate of sexual transmission of human immunodeficiency virus (HIV) type 1, and Gardnerella vaginalis is frequently isolated from the genital tracts of women with BV.@@@@1@39@@oe@16-12-2010 1006858803@GENIA Treebank@formal@@1@S@G. vaginalis lysates were found to significantly stimulate HIV expression in monocytoid cells.@@@@1@14@@oe@16-12-2010 1006858804@GENIA Treebank@formal@@1@S@Stimulation was significantly higher when lysates were heated at 100 degrees C for 5 min but was reduced by treatment with lysozyme or protease.@@@@1@25@@oe@16-12-2010 1006858805@GENIA Treebank@formal@@1@S@G. vaginalis lysates also activated HIV expression in certain T cell lines.@@@@1@13@@oe@16-12-2010 1006858806@GENIA Treebank@formal@@1@S@G. vaginalis lysates activated HIV long-terminal repeat transcription in HIV-infected cells and increased NF-kappaB binding activity, indicating an effect by G. vaginalis on HIV transcription.@@@@1@27@@oe@16-12-2010 1006858807@GENIA Treebank@formal@@1@S@The activation of HIV production by G. vaginalis suggests that genital tract infection with G. vaginalis increases the risk of HIV transmission by increasing HIV expression in the genital tract.@@@@1@31@@oe@16-12-2010 1006858808@GENIA Treebank@formal@@1@S@This may explain, at least in part, the increased rate of HIV transmission in women with BV.@@@@1@20@@oe@16-12-2010 1006867101@GENIA Treebank@formal@@1@S@Interferon-alpha activates multiple STAT proteins and upregulates proliferation-associated IL-2Ralpha, c-myc, and pim-1 genes in human T cells.@@@@1@20@@oe@16-12-2010 1006867102@GENIA Treebank@formal@@1@S@Interferon-alpha (IFN-alpha) is a pleiotropic cytokine that has antiviral, antiproliferative, and immunoregulatory functions.@@@@1@18@@oe@16-12-2010 1006867103@GENIA Treebank@formal@@1@S@There is increasing evidence that IFN-alpha has an important role in T-cell biology.@@@@1@14@@oe@16-12-2010 1006867104@GENIA Treebank@formal@@1@S@We have analyzed the expression of IL-2Ralpha, c-myc, and pim-1 genes in anti-CD3-activated human T lymphocytes.@@@@1@19@@oe@16-12-2010 1006867105@GENIA Treebank@formal@@1@S@The induction of these genes is associated with interleukin-2 (IL-2)-induced T-cell proliferation.@@@@1@16@@oe@16-12-2010 1006867106@GENIA Treebank@formal@@1@S@Treatment of T lymphocytes with IFN-alpha, IL-2, IL-12, and IL-15 upregulated IL-2Ralpha, c-myc, and pim-1 gene expression.@@@@1@23@@oe@16-12-2010 1006867107@GENIA Treebank@formal@@1@S@IFN-alpha also sensitized T cells to IL-2-induced proliferation, further suggesting that IFN-alpha may be involved in the regulation of T-cell mitogenesis.@@@@1@23@@oe@16-12-2010 1006867108@GENIA Treebank@formal@@1@S@When we analyzed the nature of STAT proteins capable of binding to IL-2Ralpha, pim-1, and IRF-1 GAS elements after cytokine stimulation, we observed IFN-alpha-induced binding of STAT1, STAT3, and STAT4, but not STAT5 to all of these elements.@@@@1@45@@oe@16-12-2010 1006867109@GENIA Treebank@formal@@1@S@Yet, IFN-alpha was able to activate binding of STAT5 to the high-affinity IFP53 GAS site.@@@@1@17@@oe@16-12-2010 1006867110@GENIA Treebank@formal@@1@S@IFN-alpha enhanced tyrosine phosphorylation of STAT1, STAT3, STAT4, STAT5a, and STAT5b.@@@@1@16@@oe@16-12-2010 1006867111@GENIA Treebank@formal@@1@S@IL-12 induced STAT4 and IL-2 and IL-15 induced STAT5 binding to the GAS elements.@@@@1@15@@oe@16-12-2010 1006867112@GENIA Treebank@formal@@1@S@Taken together, our results suggest that IFN-alpha, IL-2, IL-12, and IL-15 have overlapping activities on human T cells.@@@@1@23@@oe@16-12-2010 1006867113@GENIA Treebank@formal@@1@S@These findings thus emphasize the importance of IFN-alpha as a T-cell regulatory cytokine.@@@@1@14@@oe@16-12-2010 1006941201@GENIA Treebank@formal@@1@S@Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-alpha-induced HIV-1 replication in latently infected OM10.1 and Ach2 cells.@@@@1@17@@oe@16-12-2010 1006941202@GENIA Treebank@formal@@1@S@NF-kappaB is a potent cellular activator of HIV-1 gene expression.@@@@1@11@@oe@16-12-2010 1006941203@GENIA Treebank@formal@@1@S@Down-regulation of NF-kappaB activation is known to inhibit HIV replication from the latently infected cells.@@@@1@16@@oe@16-12-2010 1006941204@GENIA Treebank@formal@@1@S@Gold compounds have been effectively used for many decades in the treatment of rheumatoid arthritis.@@@@1@16@@oe@16-12-2010 1006941205@GENIA Treebank@formal@@1@S@We previously reported that gold compounds, especially aurothioglucose (AuTG) containing monovalent gold ion, inhibited the DNA-binding of NF-kappaB in vitro.@@@@1@25@@oe@16-12-2010 1006941206@GENIA Treebank@formal@@1@S@In this report we have examined the efficacy of the gold compound AuTG as an inhibitor of HIV replication in latently infected OM10.1 and Ach2 cells.@@@@1@27@@oe@16-12-2010 1006941207@GENIA Treebank@formal@@1@S@Tumor necrosis factor (TNF)-alpha-induced HIV-1 replication in OM10.1 or Ach2 cells was significantly inhibited by non-cytotoxic doses of AuTG (>10 microM in OM10.1 cells and >25 F.M in Ach2 cells), while 25 microM of the counter-anion thioglucose (TG) or gold compound containing divalent gold ion, HAuCl3, had no effect.@@@@1@62@@oe@16-12-2010 1006941208@GENIA Treebank@formal@@1@S@The effect of AuTG on NF-kappaB-dependent gene expression was confirmed by a transient CAT assay.@@@@1@16@@oe@16-12-2010 1006941209@GENIA Treebank@formal@@1@S@Specific staining as well as electron microscopic examinations revealed the accumulation of metal gold in the cells, supporting our previous hypothesis that gold ions could block NF-kappaB-DNA binding by a redox mechanism.@@@@1@34@@oe@16-12-2010 1006941210@GENIA Treebank@formal@@1@S@These observations indicate that the monovalent gold compound AuTG is a potentially useful drug for the treatment of patients infected with HIV.@@@@1@23@@oe@16-12-2010 1006942801@GENIA Treebank@formal@@1@S@Evidence for suppressed activity of the transcription factor NFAT1 at its proximal binding element P0 in the IL-4 promoter associated with enhanced IL-4 gene transcription in T cells of atopic patients.@@@@1@32@@oe@16-12-2010 1006942802@GENIA Treebank@formal@@1@S@Allergen-specific T cells in atopic patients are polarized IL-4-producing Th2 cells, promoting IgE synthesis by B cells.@@@@1@19@@oe@16-12-2010 1006942803@GENIA Treebank@formal@@1@S@The molecular basis for increased IL-4 gene expression in atopy is not fully understood.@@@@1@15@@oe@16-12-2010 1006942804@GENIA Treebank@formal@@1@S@IL-4 gene regulation in general involves the nuclear factor of activated T cells (NFAT) family of transcription factors, of which NFAT1 and NFAT2 are most prominent in peripheral T cells.@@@@1@34@@oe@16-12-2010 1006942805@GENIA Treebank@formal@@1@S@Recently, a unique inhibitory role of NFAT1 in IL-4 gene control was shown in the mouse.@@@@1@18@@oe@16-12-2010 1006942806@GENIA Treebank@formal@@1@S@In a series of electrophoretic mobility shift assays with protein extracts of highly polarized Th2 clones from atopics and Th1 clones from controls we compared DNA-binding activities at the two NFAT-binding elements P0 and P1 of the crucial proximal human IL-4 promoter.@@@@1@43@@oe@16-12-2010 1006942807@GENIA Treebank@formal@@1@S@At the most proximal P0 site, NFAT-containing complexes devoid of NFAT2 were readily inducible in the Th1 clones, but hardly or not in the Th2 clones.@@@@1@29@@oe@16-12-2010 1006942808@GENIA Treebank@formal@@1@S@In contrast, both in Th1 and Th2 clones NFAT-containing complexes were strongly inducible at the P1 site, consisting of NFAT2 and a P0-compatible NFAT activity, without apparent differences between Th1 and Th2 clones.@@@@1@37@@oe@16-12-2010 1006942809@GENIA Treebank@formal@@1@S@Like in Th2 clones, suppressed NFAT-P0 complex formation was observed also at the polyclonal level in peripheral blood mononuclear cells (PBMC) of three of five severe atopic dermatitis patients with strongly elevated serum IgE levels, but not in control PBMC.@@@@1@45@@oe@16-12-2010 1006942810@GENIA Treebank@formal@@1@S@These findings suggest that high-level IL-4 production in atopic Th2 cells is associated with selective reduction of suppressive NFAT1 activity at the IL-4 P0 element and that some patients with this multifactorial disease may have a putative systemic disorder at this level.@@@@1@43@@oe@16-12-2010