971664801@GENIA Treebank@formal@@1@S@CIITA B-cell-specific promoter suppression in MHC class II-silenced cell hybrids.@@@@1@11@@oe@16-12-2010 971664802@GENIA Treebank@formal@@1@S@In this study, various sets of somatic cell hybrids, generated by the fusion of epithelial cell lines with B-lymphoblastoid cell lines, were analyzed for the expression of major histocompatibility complex (MHC) class II antigens.@@@@1@40@@oe@16-12-2010 971664803@GENIA Treebank@formal@@1@S@We first demonstrate, in human and mouse intraspecies hybrids, the coordinate suppression of MHC class II, Ii (invariant chain) and HLA-DM gene transcription, and the release of the silencing by the addition of interferon gamma.@@@@1@42@@oe@16-12-2010 971664804@GENIA Treebank@formal@@1@S@Using interspecies hybrids, the segregation of human chromosomes allowed us to establish that MHC class II extinction is linked to the presence in the hybrids of the chromosomes from the epithelial fusion partner.@@@@1@35@@oe@16-12-2010 971664805@GENIA Treebank@formal@@1@S@Moreover, our data provide evidence that the expression pattern of MHC class II mRNA is correlated with that of the class II transactivator (CIITA), suggesting that CIITA is the actual target of the silencing.@@@@1@39@@oe@16-12-2010 971664806@GENIA Treebank@formal@@1@S@To gain further insight into the suppression phenomenon we performed luciferase assays which show that silencing affects the activity of the B-cell-specific promoter of CIITA.@@@@1@26@@oe@16-12-2010 971664807@GENIA Treebank@formal@@1@S@These results therefore demonstrate that the MHC class II gene silencing in somatic cell hybrids is due to an active suppression of one of the promoters of the CIITA gene, mediated by the epithelial cell fusion partner.@@@@1@39@@oe@16-12-2010 971767401@GENIA Treebank@formal@@1@S@The transcription factors c-myb and C/EBP alpha regulate the monocytic/myeloic gene MRP14.@@@@1@13@@oe@16-12-2010 971767402@GENIA Treebank@formal@@1@S@The entry of microorganisms into the body induces inflammatory processes.@@@@1@11@@oe@16-12-2010 971767403@GENIA Treebank@formal@@1@S@During this process a sequence of cellular, humoral, non-specific and specific actions are evoked to combat the infection.@@@@1@21@@oe@16-12-2010 971767404@GENIA Treebank@formal@@1@S@Macrophages and granulocytes, which are developed from a common progenitor cell, are the cellular components of the specific and non-specific immunoreaction.@@@@1@24@@oe@16-12-2010 971767405@GENIA Treebank@formal@@1@S@MRP14 (Macrophage migration inhibitory related protein) and MRP8, two S-100 proteins contained in high concentrations in these cells are obviously essential for adhesion and migration of monocytes and granulocytes.@@@@1@33@@oe@16-12-2010 971767406@GENIA Treebank@formal@@1@S@To investigate the transcriptional regulation of these genes we cotransfected constructs expressing CAT under control of the MRP14 promoter and expression constructs of C/EBP alpha and v-myb, two transcription factors involved in myeloid/monocytic differentiation.@@@@1@36@@oe@16-12-2010 971767407@GENIA Treebank@formal@@1@S@Transfection with C/EBP alpha revealed a massive enhancement of the MRP14 promoter in both, HL 60 cells (granulocytic differentiated) and L132 fibroblasts.@@@@1@26@@oe@16-12-2010 971767408@GENIA Treebank@formal@@1@S@In contrast, v-myb reduces MRP14 promoter activity.@@@@1@9@@oe@16-12-2010 971767409@GENIA Treebank@formal@@1@S@Northern blot analysis of L132 cells transfected with the C/EBP alpha expression vector demonstrate that C/EBP alpha is sufficient to enhance MRP14 expression in the context of the whole genome.@@@@1@31@@oe@16-12-2010 972064801@GENIA Treebank@formal@@1@S@Nuclear factor-kappaB induction in CD45RO+ and CD45RA+ T cell subsets during aging.@@@@1@13@@oe@16-12-2010 972064802@GENIA Treebank@formal@@1@S@An increase in the ratio of memory to naive T cells has been postulated to underlie immune hyporesponsiveness accompanying aging.@@@@1@21@@oe@16-12-2010 972064803@GENIA Treebank@formal@@1@S@Our analyses of the induction of nuclear factor-kappaB (NFkappaB) in activated memory (CD45RO+) and naive (CD45RA+) T cell subsets from young and elderly donors has demonstrated that, regardless of donor age, memory T cells are not significantly altered in their responsiveness to TNF-alpha-mediated induction of NFkappaB.@@@@1@55@@oe@16-12-2010 972064804@GENIA Treebank@formal@@1@S@Although treatment with TNF-alpha induced nuclear localization of NFkappaB in both memory and naive T cell subsets, irrespective of the age of the donor, the levels of induced NFkappaB were significantly lower in both subsets of T cells obtained from the elderly, when compared to those in young.@@@@1@52@@oe@16-12-2010 972064805@GENIA Treebank@formal@@1@S@Examination of IkappaB alpha regulation revealed that TNF-alpha-mediated degradation of IkappaB alpha in both memory and naive T cells from the elderly was severely impaired, thus contributing to the lowered induction of the observed NFkappaB.@@@@1@37@@oe@16-12-2010 972064806@GENIA Treebank@formal@@1@S@In addition, this age-related decrease in induction of nuclear NFkappaB correlated with decrease in intracellular IL-2 receptor expression and anti-CD3-induced proliferation of both memory and naive T cells subsets.@@@@1@31@@oe@16-12-2010 972064807@GENIA Treebank@formal@@1@S@Taken together, our results suggest that the age-related hyporesponsiveness cannot be attributed to a skewing of the T cell population towards a memory phenotype in the elderly.@@@@1@30@@oe@16-12-2010 972260001@GENIA Treebank@formal@@1@S@Activation of E2F-mediated transcription by human T-cell leukemia virus type I Tax protein in a p16(INK4A)-negative T-cell line.@@@@1@23@@oe@16-12-2010 972260002@GENIA Treebank@formal@@1@S@The human T-cell leukemia virus type I (HTLV-I) is a causative agent of adult T-cell leukemia.@@@@1@19@@oe@16-12-2010 972260003@GENIA Treebank@formal@@1@S@Although the exact mechanism by which HTLV-I contributes to leukemogenesis is still unclear, the Tax protein is thought to play a major role in this process.@@@@1@28@@oe@16-12-2010 972260004@GENIA Treebank@formal@@1@S@This 40-kDa polypeptide is able to interact with the tumor suppressor p16(INK4A).@@@@1@16@@oe@16-12-2010 972260005@GENIA Treebank@formal@@1@S@Consequently, Tax can activate the signaling pathway that lead to the release of E2F that in turn induces expression of factors required for cell cycle progression.@@@@1@28@@oe@16-12-2010 972260006@GENIA Treebank@formal@@1@S@In this paper, we demonstrate that Tax can also activate E2F-mediated transcription independently of p16(INK4A).@@@@1@20@@oe@16-12-2010 972260007@GENIA Treebank@formal@@1@S@Indeed, when Tax is coexpressed with the E2F-1 transcription factor in CEM T-cells, which lack expression of p16(INK4A), it strongly potentiates the E2F-dependent activation of a reporter construct driven by a promoter containing E2F binding sites.@@@@1@43@@oe@16-12-2010 972260008@GENIA Treebank@formal@@1@S@This stimulation is abrogated by mutations affecting the E2F-binding sites.@@@@1@11@@oe@16-12-2010 972260009@GENIA Treebank@formal@@1@S@In addition, Tax also stimulates the transcription of the E2F-1 gene itself.@@@@1@14@@oe@16-12-2010 972260010@GENIA Treebank@formal@@1@S@Using Tax mutants that fail to activate either ATF- or NF-kappaB-dependent promoters and different 5' truncation mutants of the E2F-1 promoter, we show that the Tax-dependent transcriptional control of the E2F1 gene involves, at least in part, the ATF binding site located in the E2F-1 promoter.@@@@1@50@@oe@16-12-2010 972263101@GENIA Treebank@formal@@1@S@The MHC class II transactivator (CIITA) requires conserved leucine charged domains for interactions with the conserved W box promoter element.@@@@1@23@@oe@16-12-2010 972263102@GENIA Treebank@formal@@1@S@The class II transactivator CIITA is required for transcriptional activation of the major histocompatibility complex (MHC) class II genes.@@@@1@22@@oe@16-12-2010 972263103@GENIA Treebank@formal@@1@S@Aside from an N-terminal acidic transcriptional activation domain, little is known about how this factor functions.@@@@1@18@@oe@16-12-2010 972263104@GENIA Treebank@formal@@1@S@Extensive mutagenesis of CIITA was undertaken to identify structural motifs required for function.@@@@1@14@@oe@16-12-2010 972263105@GENIA Treebank@formal@@1@S@The ability of mutants to activate a reporter gene under the control of MHC class II conserved W-X-Y or X-Y regulatory elements was determined.@@@@1@25@@oe@16-12-2010 972263106@GENIA Treebank@formal@@1@S@Two mutants displayed differential activity between the two promoters, activating transcription with the W-X-Y but not the X-Y elements.@@@@1@21@@oe@16-12-2010 972263107@GENIA Treebank@formal@@1@S@All mutants were tested for their ability to interfere with wild-type CIITA activity.@@@@1@14@@oe@16-12-2010 972263108@GENIA Treebank@formal@@1@S@Five CIITA mutant constructions were able to down-regulate wild-type CIITA activity.@@@@1@12@@oe@16-12-2010 972263109@GENIA Treebank@formal@@1@S@Three of these mutants contained targeted disruptions of potential functional motifs: the acidic activation domain, a putative GTP-binding motif and two leucine charged domains (LCD motifs).@@@@1@31@@oe@16-12-2010 972263110@GENIA Treebank@formal@@1@S@The other two contained mutations in regions that do not have homology to described proteins.@@@@1@16@@oe@16-12-2010 972263111@GENIA Treebank@formal@@1@S@The characterization of CIITA mutants that are able to discriminate between promoters with or without the W box strongly suggests that CIITA requires such interactions for function.@@@@1@28@@oe@16-12-2010 972263112@GENIA Treebank@formal@@1@S@The identification of LCD motifs required for CIITA function brings to light a previously undefined role of these motifs in CIITA function.@@@@1@23@@oe@16-12-2010 972343001@GENIA Treebank@formal@@1@S@Calcineurin and the biological effect of cyclosporine and tacrolimus.@@@@1@10@@oe@16-12-2010 972343002@GENIA Treebank@formal@@1@S@The mechanism of the immunosuppressive effect of CyA and FK 506 can be monitored in vivo in humans.@@@@1@19@@oe@16-12-2010 972343003@GENIA Treebank@formal@@1@S@The picture emerging is of a close relationship between drug concentrations and CN inhibition.@@@@1@15@@oe@16-12-2010 972343004@GENIA Treebank@formal@@1@S@But many puzzles of the drugs remain.@@@@1@8@@oe@16-12-2010 972343005@GENIA Treebank@formal@@1@S@What is the role of CyA in the activation of transforming growth factor-beta (TGF-beta), particularly in relationship to nephrotoxicity and fibrogenesis?@@@@1@25@@oe@16-12-2010 972343006@GENIA Treebank@formal@@1@S@How important are the anti-inflammatory (non T) effects of CyA, and which cells do they operate in?@@@@1@21@@oe@16-12-2010 972343007@GENIA Treebank@formal@@1@S@Are there effects of CyA and FK 506 all attributable to CN inhibition, and how much of them are mediated through the NFATC family of transcription factors?@@@@1@29@@oe@16-12-2010 972343008@GENIA Treebank@formal@@1@S@Finally, it would be useful to know what the inhibitory effects of CyA are on tolerance and negative regulatory events.@@@@1@22@@oe@16-12-2010 972388901@GENIA Treebank@formal@@1@S@Regulation of the vitellogenin gene B1 promoter after transfer into hepatocytes in primary cultures.@@@@1@15@@oe@16-12-2010 972388902@GENIA Treebank@formal@@1@S@The estrogen-dependent and tissue-specific regulation of the Xenopus laevis vitellogenin gene B1 promoter has been studied by lipid-mediated DNA transfer into Xenopus hepatocytes in primary culture.@@@@1@27@@oe@16-12-2010 972388903@GENIA Treebank@formal@@1@S@Hepatocytes achieve an efficient hormonal control of this promoter through a functional interaction between the estrogen responsive elements and a promoter proximal region upstream of the TATA box, which is characterized by a high density of binding sites for the transcription factors CTF/NF-1, C/EBP and HNF3.@@@@1@49@@oe@16-12-2010 972388904@GENIA Treebank@formal@@1@S@DNA accessibility to restriction enzymes within the chromosomal copy of the vitellogenin gene B1 promoter shows that the estrogen responsive unit and the promoter proximal region are sensitive to digestion in uninduced and estrogen-induced hepatocytes but not in erythrocyte nuclei.@@@@1@41@@oe@16-12-2010 972388905@GENIA Treebank@formal@@1@S@Together, these findings support the notion that chromatin configuration as well as the interplay of promoter elements mediate proper hormone-dependent and tissue-specific expression of the B1 vitellogenin gene.@@@@1@30@@oe@16-12-2010 972403401@GENIA Treebank@formal@@1@S@Glucocorticoid-induced apoptosis and regulation of NF-kappaB activity in human leukemic T cells.@@@@1@13@@oe@16-12-2010 972403402@GENIA Treebank@formal@@1@S@Glucocorticoid-induced apoptosis was investigated in glucocorticoid-sensitive 6TG1.1 and resistant ICR27TK.3 human leukemic T cells.@@@@1@15@@oe@16-12-2010 972403403@GENIA Treebank@formal@@1@S@Following glucocorticoid treatment of 6TG1.1 cells, chromatin fragmentation was observed after a delay of 24 h.@@@@1@18@@oe@16-12-2010 972403404@GENIA Treebank@formal@@1@S@Fragmentation was not observed in ICR27TK.3 cells containing mutant glucocorticoid receptors (L753F) that are activation-deficient but retain the ability to repress AP-1 activity.@@@@1@26@@oe@16-12-2010 972403405@GENIA Treebank@formal@@1@S@Nor was fragmentation observed after treatment with RU38486, indicating that repression of AP-1 activity is not involved.@@@@1@19@@oe@16-12-2010 972403406@GENIA Treebank@formal@@1@S@As described in other systems, fragmentation required ongoing protein synthesis.@@@@1@12@@oe@16-12-2010 972403407@GENIA Treebank@formal@@1@S@However, inhibition of protein synthesis with cycloheximide anytime during the first 18 h of steroid treatment was as effective in blocking chromatin fragmentation as inhibition for the entire period, suggesting that synthesis of a component with a rapid turnover rate is required.@@@@1@45@@oe@16-12-2010 972403408@GENIA Treebank@formal@@1@S@Dexamethasone treatment completely blocked 12-O-tetradecanoylphorbol 13-acetate induction of nuclear factor-kappaB (NF-kappaB) activity and elicited an increase in the amount of immunoreactive IkappaB alpha in sensitive 6TG1.1 cells but not in resistant ICR27TK.3 cells.@@@@1@36@@oe@16-12-2010 972403409@GENIA Treebank@formal@@1@S@In addition, mild detergent treatment of cell extracts indicated that a substantial amount of cytoplasmic NF-kappaB is complexed with IkappaB alpha or some other inhibitory factor.@@@@1@28@@oe@16-12-2010 972403410@GENIA Treebank@formal@@1@S@These results suggest that induction of a labile inhibitory factor such as IkappaB alpha may contribute to glucocorticoid-induced apoptosis.@@@@1@20@@oe@16-12-2010 972408801@GENIA Treebank@formal@@1@S@Peripheral T lymphocytes from women with breast cancer exhibit abnormal protein expression of several signaling molecules.@@@@1@17@@oe@16-12-2010 972408802@GENIA Treebank@formal@@1@S@We examined signaling molecules of peripheral blood T lymphocytes obtained from women with breast cancer.@@@@1@16@@oe@16-12-2010 972408803@GENIA Treebank@formal@@1@S@In 6 of 14 patients, T lymphocytes displayed an impaired ability to translocate NFeB p65 (Rel-A) following activation by anti-CD3 and IL-2.@@@@1@26@@oe@16-12-2010 972408804@GENIA Treebank@formal@@1@S@This observation was made despite normal cytoplasmic levels of the Rel-A protein.@@@@1@13@@oe@16-12-2010 972408805@GENIA Treebank@formal@@1@S@We also detected abnormally low levels of the signaling molecules T-cell receptor (TCR)-zeta, ZAP-70 and p56lck in 4 of 14 breast cancer patients, i.e., defects in T-cell signaling molecules.@@@@1@36@@oe@16-12-2010 972408806@GENIA Treebank@formal@@1@S@T lymphocytes from 6 of the 14 patients also exhibited an increased expression of the dual specificity phosphatase, map kinase phosphatase-1 (MKP-1).@@@@1@26@@oe@16-12-2010 972408807@GENIA Treebank@formal@@1@S@MKP-1 inactivates MAP kinase and therefore may interfere with the activation of c-jun and c-fos.@@@@1@16@@oe@16-12-2010 972408808@GENIA Treebank@formal@@1@S@Abnormalities of I or more signaling molecules were found in 9 of 14 patients; however, only 3 patients had T cells that exhibited all 5 defects.@@@@1@29@@oe@16-12-2010 972408809@GENIA Treebank@formal@@1@S@Our data have implications for the detection of potentially dysfunctional T cells in patients with cancer.@@@@1@17@@oe@16-12-2010 972408810@GENIA Treebank@formal@@1@S@For example, the analysis of only 1 signaling molecule may allow patients with significant defects in T-cell signaling to go unnoticed.@@@@1@23@@oe@16-12-2010 972408811@GENIA Treebank@formal@@1@S@Finally, despite impaired Rel-A translocation, T cells were capable of transcribing IL-2.@@@@1@15@@oe@16-12-2010 972408812@GENIA Treebank@formal@@1@S@Impairments in the translocation of Rel-B and c-Rel further suggest that the NFKB family members Rel-A, Rel-B and c-Rel are not required for the transcription of IL-2 in the peripheral T lymphocytes of patients with breast cancer.@@@@1@39@@oe@16-12-2010 972521201@GENIA Treebank@formal@@1@S@Protein kinase C regulates Fas (CD95/APO-1) expression.@@@@1@10@@oe@16-12-2010 972521202@GENIA Treebank@formal@@1@S@Fas (CD95/APO-1) is a transmembrane protein of the TNF/neuron growth factor receptor family.@@@@1@16@@oe@16-12-2010 972521203@GENIA Treebank@formal@@1@S@Ligation of Fas by specific Abs or Fas ligand (FasL/CD95 ligand) induces rapid apoptotic cell death in a variety of cell types.@@@@1@25@@oe@16-12-2010 972521204@GENIA Treebank@formal@@1@S@Despite progress in understanding the death signals transduced from Fas, very little is known with regard to the mechanisms by which Fas expression is regulated.@@@@1@27@@oe@16-12-2010 972521205@GENIA Treebank@formal@@1@S@Using our previously established murine T cell hybridoma model A1.1, we show that specific protein kinase C (PKC) inhibitors could block activation-induced Fas expression and apoptosis.@@@@1@30@@oe@16-12-2010 972521206@GENIA Treebank@formal@@1@S@The activation of PKC with PMA or 1-oleoyl-2-acetyl-sn-glycerol could mimic the TCR signal by inducing the expression of Fas but not FasL.@@@@1@23@@oe@16-12-2010 972521207@GENIA Treebank@formal@@1@S@PKC-dependent Fas expression was also observed in several murine and human tumor cell lines.@@@@1@15@@oe@16-12-2010 972521208@GENIA Treebank@formal@@1@S@Since the inhibition of Ca2+ redistribution by an inhibitor of intracellular Ca2+ mobilization, 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride, inhibited TCR-induced FasL but not Fas, the expression of Fas appears to be independent of Ca2+ mobilization.@@@@1@36@@oe@16-12-2010 972521209@GENIA Treebank@formal@@1@S@Significantly, expression of the newly identified Fas-regulatory gene, TDAG51, was found to be dependent upon the activity of PKC.@@@@1@23@@oe@16-12-2010 972521210@GENIA Treebank@formal@@1@S@PKC activation only induced Fas expression in cells expressing wild-type TDAG51.@@@@1@12@@oe@16-12-2010 972521211@GENIA Treebank@formal@@1@S@Thus, Fas expression is likely mediated by PKC through TDAG51.@@@@1@12@@oe@16-12-2010 972522001@GENIA Treebank@formal@@1@S@Transcription of a minimal promoter from the NF-IL6 gene is regulated by CREB/ATF and SP1 proteins in U937 promonocytic cells.@@@@1@21@@oe@16-12-2010 972522002@GENIA Treebank@formal@@1@S@NF-IL6 is an important transcriptional regulator of genes induced in activated monocytes/macrophages, and NF-IL6 is the only CCAAT/enhancer-binding protein (C/EBP) family member whose steady-state mRNA levels increase upon activation of monocytes (1).@@@@1@38@@oe@16-12-2010 972522003@GENIA Treebank@formal@@1@S@We show that increased transcription of the NF-IL6 gene is responsible, at least in part, for induction of NF-IL6 mRNA following activation of U937 promonocytic cells.@@@@1@29@@oe@16-12-2010 972522004@GENIA Treebank@formal@@1@S@We have identified a 104-bp minimal promoter region of the NF-IL6 gene that is sufficient for basal and activation-dependent induction of transcription in U937 cells.@@@@1@26@@oe@16-12-2010 972522005@GENIA Treebank@formal@@1@S@This region contains binding sites for the cAMP response element-binding protein/activation transcription factor (CREB/ATF) and Sp1 families of transcription factors.@@@@1@23@@oe@16-12-2010 972522006@GENIA Treebank@formal@@1@S@Each site is functionally important and contributes independently to transcription of the NF-IL6 gene in U937 cells.@@@@1@18@@oe@16-12-2010 972697001@GENIA Treebank@formal@@1@S@p130, p107, and pRb are differentially regulated in proliferating cells and during cell cycle arrest by alpha-interferon.@@@@1@20@@oe@16-12-2010 972697002@GENIA Treebank@formal@@1@S@We have determined how the phosphorylation of the retinoblastoma family (pRb, p107, and p130) is governed in individual cell cycle phases of Daudi B-cells during cell cycle exit triggered by alpha-interferon (alpha-IFN).@@@@1@39@@oe@16-12-2010 972697003@GENIA Treebank@formal@@1@S@alpha-IFN causes dephosphorylation of pRb and loss of p130 phosphorylated Form 3.@@@@1@13@@oe@16-12-2010 972697004@GENIA Treebank@formal@@1@S@However, the change in p130 phosphorylation in response to alpha-IFN occurs before dephosphorylation of pRb is complete because loss of p130 Form 3 occurs throughout the cell cycle prior to complete arrest in G1, whereas pRb is dephosphorylated only in G1.@@@@1@44@@oe@16-12-2010 972697005@GENIA Treebank@formal@@1@S@In contrast, p107 is dephosphorylated and is then depleted from cells as they exit the cell cycle.@@@@1@19@@oe@16-12-2010 972697006@GENIA Treebank@formal@@1@S@p130, predominantly in Form 1, and hypophosphorylated pRb bind an E2F DNA binding site; p130 complexes E2F-4, whereas pRb binds both E2F-4 and E2F-1.@@@@1@29@@oe@16-12-2010 972697007@GENIA Treebank@formal@@1@S@The phosphorylated forms of E2F-4 that bind to the E2F DNA site are different from hyperphosphorylated E2F-4, which predominates in primary hemopoietic cells in G0.@@@@1@27@@oe@16-12-2010 972697008@GENIA Treebank@formal@@1@S@We conclude that although cell cycle arrest induced by alpha-IFN may be mediated in part by formation of a complex containing p130 and E2F-4, alpha-IFN does not induce hyperphosphorylation of E2F-4, which characterizes primary hemopoietic cells in G0.@@@@1@41@@oe@16-12-2010 972700001@GENIA Treebank@formal@@1@S@Two-site interaction of nuclear factor of activated T cells with activated calcineurin.@@@@1@13@@oe@16-12-2010 972700002@GENIA Treebank@formal@@1@S@Transcription factors belonging to the nuclear factor of activated T cells (NFAT) family regulate the expression of cytokine genes and other inducible genes during the immune response.@@@@1@30@@oe@16-12-2010 972700003@GENIA Treebank@formal@@1@S@The functions of NFAT proteins are directly controlled by the calcium- and calmodulin- dependent phosphatase calcineurin.@@@@1@16@@oe@16-12-2010 972700004@GENIA Treebank@formal@@1@S@Here we show that the binding of calcineurin to NFAT is substantially increased when calcineurin is activated with calmodulin and calcium.@@@@1@22@@oe@16-12-2010 972700005@GENIA Treebank@formal@@1@S@FK506.FKBP12 drug-immunophilin complexes inhibited the interaction of NFAT with activated calcineurin much more effectively than they inhibited the interaction with inactive calcineurin, suggesting that part of the interaction with activated calcineurin involved the enzyme active site.@@@@1@38@@oe@16-12-2010 972700006@GENIA Treebank@formal@@1@S@We have previously shown that NFAT is targeted to inactive calcineurin at a region distinct from the calcineurin active site (Aramburu, J., Garcia-Cozar, F. J., Raghavan, A., Okamura, H., Rao, A., and Hogan, P. G. (1998) Mol. Cell 1, 627-637); this region is also involved in NFAT binding to activated calcineurin, since binding is inhibited by an NFAT peptide spanning the calcineurin docking site on NFAT.@@@@1@85@@oe@16-12-2010 972700007@GENIA Treebank@formal@@1@S@The interacting surfaces are located on the catalytic domain of the calcineurin A chain and on an 86-amino acid fragment of the NFAT regulatory domain.@@@@1@26@@oe@16-12-2010 972700008@GENIA Treebank@formal@@1@S@NFAT binding to the calcineurin catalytic domain was inhibited by the calcineurin autoinhibitory domain and the RII substrate peptide, which bind in the calcineurin active site, as well as by the NFAT docking site peptide, which binds to a region of calcineurin distinct from the active site.@@@@1@51@@oe@16-12-2010 972700009@GENIA Treebank@formal@@1@S@We propose that, in resting cells, NFAT is targeted to a region of the calcineurin catalytic domain that does not overlap the calcineurin active site.@@@@1@28@@oe@16-12-2010 972700010@GENIA Treebank@formal@@1@S@Upon cell activation, displacement of the autoinhibitory domain by calmodulin binding allows NFAT to bind additionally to the calcineurin active site, thus positioning NFAT for immediate dephosphorylation at functional phosphoserine residues.@@@@1@34@@oe@16-12-2010 972704901@GENIA Treebank@formal@@1@S@A p56lck-independent pathway of CD2 signaling involves Jun kinase.@@@@1@10@@oe@16-12-2010 972704902@GENIA Treebank@formal@@1@S@The p56 Src family non-receptor tyrosine kinase has been shown to be critical for T lymphocyte differentiation and activation.@@@@1@20@@oe@16-12-2010 972704903@GENIA Treebank@formal@@1@S@Hence in the absence of p56, T cell receptor triggered activation does not occur.@@@@1@16@@oe@16-12-2010 972704904@GENIA Treebank@formal@@1@S@We now provide evidence for a CD2-based signaling pathway which, in contrast to that of the T cell receptor, is independent of p56.@@@@1@26@@oe@16-12-2010 972704905@GENIA Treebank@formal@@1@S@CD2-mediated interleukin-2 production occurs via activation of Jun kinase in cell lines lacking p56.@@@@1@15@@oe@16-12-2010 972704906@GENIA Treebank@formal@@1@S@Jun kinase then facilitates the binding of c-Jun/c-Fos heterodimers to the AP-1 consensus site and the subsequent transcriptional activity of the interleukin-2 promoter.@@@@1@24@@oe@16-12-2010 972704907@GENIA Treebank@formal@@1@S@These data elucidate differences between TCR and CD2 signaling pathways in the same T cells.@@@@1@16@@oe@16-12-2010 972805701@GENIA Treebank@formal@@1@S@Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury.@@@@1@14@@oe@16-12-2010 972805702@GENIA Treebank@formal@@1@S@Hemorrhagic shock (HS) initiates an inflammatory cascade that includes the production of cytokines and recruitment of neutrophils (PMN) and may progress to organ failure, inducing acute respiratory distress syndrome (ARDS).@@@@1@38@@oe@16-12-2010 972805703@GENIA Treebank@formal@@1@S@To examine the hypothesis that interleukin-6 (IL-6) contributes to PMN infiltration and lung damage in HS, we examined the lungs of rats subjected to unresuscitated and resuscitated HS for the production of IL-6 and activation of Stat3.@@@@1@41@@oe@16-12-2010 972805704@GENIA Treebank@formal@@1@S@Using semiquantitative RT-PCR, we found a striking increase in IL-6 mRNA levels only in resuscitated HS, with peak levels observed 1 h after initiation of resuscitation.@@@@1@29@@oe@16-12-2010 972805705@GENIA Treebank@formal@@1@S@Increased IL-6 protein expression was localized to bronchial and alveolar cells.@@@@1@12@@oe@16-12-2010 972805706@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assay of protein extracts from shock lungs exhibited an increase in Stat3 activation with kinetics similar to IL-6 mRNA.@@@@1@23@@oe@16-12-2010 972805707@GENIA Treebank@formal@@1@S@In situ DNA binding assay determined Stat3 activation predominantly within alveoli.@@@@1@12@@oe@16-12-2010 972805708@GENIA Treebank@formal@@1@S@Intratracheal instillation of IL-6 alone into normal rats resulted in PMN infiltration into lung interstitium and alveoli, marked elevation of bronchoalveolar lavage cellularity, and increased wet-to-dry ratio.@@@@1@30@@oe@16-12-2010 972805709@GENIA Treebank@formal@@1@S@These findings indicate that IL-6 production and Stat3 activation occur early in HS and may contribute to PMN-mediated lung injury, including ARDS after HS.@@@@1@26@@oe@16-12-2010 972904501@GENIA Treebank@formal@@1@S@CD30 is a CD40-inducible molecule that negatively regulates CD40-mediated immunoglobulin class switching in non-antigen-selected human B cells.@@@@1@18@@oe@16-12-2010 972904502@GENIA Treebank@formal@@1@S@We used our monoclonal model of germinal center maturation, CL-01 B cells, to investigate the role of CD30 in human B cell differentiation.@@@@1@26@@oe@16-12-2010 972904503@GENIA Treebank@formal@@1@S@CL-01 cells are IgM+ IgD+ CD30+ and switch to IgG, IgA, and IgE when exposed to CD40L and IL-4.@@@@1@22@@oe@16-12-2010 972904504@GENIA Treebank@formal@@1@S@Switching is hampered by CD30 coengagement, possibly through interference with the CD40-mediated NF-kappaB-dependent transcriptional activation of downstream C(H) genes.@@@@1@21@@oe@16-12-2010 972904505@GENIA Treebank@formal@@1@S@The physiological relevance of this phenomenon is emphasized by similar CD30-mediated effects in naive B cells.@@@@1@17@@oe@16-12-2010 972904506@GENIA Treebank@formal@@1@S@Expression of CD30 by these cells is induced by CD40L but is inhibited by B cell receptor coengagement and/or exposure to IL-6 and IL-12.@@@@1@25@@oe@16-12-2010 972904507@GENIA Treebank@formal@@1@S@Our data suggest that CD30 critically regulates the CD40-mediated differentiation of non-antigen-selected human B cells.@@@@1@16@@oe@16-12-2010 973095701@GENIA Treebank@formal@@1@S@Induction of Mn SOD in human monocytes without inflammatory cytokine production by a mutant endotoxin.@@@@1@16@@oe@16-12-2010 973095702@GENIA Treebank@formal@@1@S@Endotoxin selectively induces monocyte Mn superoxide dismutase (SOD) without affecting levels of Cu,Zn SOD, catalase, or glutathione peroxidase.@@@@1@25@@oe@16-12-2010 973095703@GENIA Treebank@formal@@1@S@However, little is known about the structure-activity relationship and the mechanism by which endotoxin induces Mn SOD.@@@@1@19@@oe@16-12-2010 973095704@GENIA Treebank@formal@@1@S@In this study we demonstrated that a mutant Escherichia coli endotoxin lacking myristoyl fatty acid at the 3' R-3-hydroxymyristate position of the lipid A moiety retained its full capacity to coagulate Limulus amoebocyte lysate compared with the wild-type E. coli endotoxin and markedly stimulated the activation of human monocyte nuclear factor-kappaB and the induction of Mn SOD mRNA and enzyme activity.@@@@1@62@@oe@16-12-2010 973095705@GENIA Treebank@formal@@1@S@However, in contrast to the wild-type endotoxin, it failed to induce significant production of tumor necrosis factor-alpha and macrophage inflammatory protein-1alpha by monocytes and did not induce the phosphorylation and nuclear translocation of mitogen-activated protein kinase.@@@@1@39@@oe@16-12-2010 973095706@GENIA Treebank@formal@@1@S@These results suggest that 1) lipid A myristoyl fatty acid, although it is important for the induction of inflammatory cytokine production by human monocytes, is not necessary for the induction of Mn SOD, 2) endotoxin-mediated induction of Mn SOD and inflammatory cytokines are regulated, at least in part, through different signal transduction pathways, and 3) failure of the mutant endotoxin to induce tumor necrosis factor-alpha production is, at least in part, due to its inability to activate mitogen-activated protein kinase.@@@@1@92@@oe@16-12-2010 973120801@GENIA Treebank@formal@@1@S@An allosteric drug, o,o'-bismyristoyl thiamine disulfide, suppresses HIV-1 replication through prevention of nuclear translocation of both HIV-1 Tat and NF-kappa B.@@@@1@24@@oe@16-12-2010 973120802@GENIA Treebank@formal@@1@S@The efficacy of o,o'-bismyristoyl thiamine disulfide (BMT) was examined in detail against HIV-1 laboratory isolates (HTLV-IIIB, JRFL, and MN), primary isolates (KMT and KMO), and simian immunodeficiency virus (SIVmac251) in vitro.@@@@1@46@@oe@16-12-2010 973120803@GENIA Treebank@formal@@1@S@BMT inhibited the replication of HIV-1 in both laboratory and primary isolates in vitro.@@@@1@15@@oe@16-12-2010 973120804@GENIA Treebank@formal@@1@S@In addition, BMT exhibited antiviral activity against SIVmac251.@@@@1@10@@oe@16-12-2010 973120805@GENIA Treebank@formal@@1@S@Minimizing energy studies of BMT structure reveal that a trans-disulfide of thiamine (holo drug) disulfide (TDS, protodrug) is allosterically transited to the reactive twisted disulfide of BMT (allo drug) by o,o'-bismyristoyl esterification of TDS.@@@@1@44@@oe@16-12-2010 973120806@GENIA Treebank@formal@@1@S@BMT inhibits nuclear translocation of both HIV-1 transactivator (TAT) and the cellular transcriptional nuclear factor-KB (NF-kappa B), resulting in the suppression of HIV-1 replication.@@@@1@30@@oe@16-12-2010 973169701@GENIA Treebank@formal@@1@S@Retinoid X receptor and c-cerbA/thyroid hormone receptor regulate erythroid cell growth and differentiation.@@@@1@14@@oe@16-12-2010 973169702@GENIA Treebank@formal@@1@S@Nuclear receptors are important regulators of erythroid cell development.@@@@1@10@@oe@16-12-2010 973169703@GENIA Treebank@formal@@1@S@Here we investigated the impact of retinoid X receptor (RXR), retinoic acid receptor (RAR), and of the c-erbA/thyroid hormone (T3) receptor (c-erbA/TR) on growth and differentiation of erythroid cells using an in vitro culture system of stem cell factor-dependent erythroid progenitors.@@@@1@52@@oe@16-12-2010 973169704@GENIA Treebank@formal@@1@S@RXR, RAR, and c-erbA/TR-specific ligands were found to induce erythroid-specific gene expression and to accelerate erythroid differentiation in culture, with T3 being most effective.@@@@1@28@@oe@16-12-2010 973169705@GENIA Treebank@formal@@1@S@Furthermore, while ligand-activated c-erbA/TR accelerated differentiation, unliganded c-erbA/TR effectively blocked differentiation and supported sustained progenitor growth in culture.@@@@1@21@@oe@16-12-2010 973169706@GENIA Treebank@formal@@1@S@Thus, c-erbA/TR appears to act as a binary switch affecting erythroid cell fate: unliganded c-erbA/TR supports growth while ligand-activated c-erbA/TR induces differentiation.@@@@1@25@@oe@16-12-2010 973169707@GENIA Treebank@formal@@1@S@Additionally, to determine the impact of RXR for erythroid cell development, dominant interfering mutant RXRs, lacking the transcriptional activator functions AF-1 and AF-2, or AF-2 only, or the entire DNA-binding domain, were introduced into erythroid progenitor cells via recombinant retrovirus vectors and analyzed for RXR-specific effects.@@@@1@53@@oe@16-12-2010 973169708@GENIA Treebank@formal@@1@S@It was found that expression of wild-type RXR and of the RXR mutants devoid of AF-1 and/or AF-2 supported a transient outgrowth of erythroid cells.@@@@1@26@@oe@16-12-2010 973169709@GENIA Treebank@formal@@1@S@In marked contrast, expression of the dominant interfering deltaDNA-binding domain RXR, containing a deletion of the entire DNA-binding domain, was incompatible with erythroid cell growth in vitro, suggesting a pivotal role of RXR for erythroid cell development.@@@@1@42@@oe@16-12-2010 973371601@GENIA Treebank@formal@@1@S@Phosphatidylinositides bind to plasma membrane CD14 and can prevent monocyte activation by bacterial lipopolysaccharide.@@@@1@15@@oe@16-12-2010 973371602@GENIA Treebank@formal@@1@S@Although bacterial lipopolysaccharides (LPS) and several other microbial agonists can bind to mCD14 (membrane CD14), a cell-surface receptor found principally on monocytes and neutrophils, host-derived mCD14 ligands are poorly defined.@@@@1@37@@oe@16-12-2010 973371603@GENIA Treebank@formal@@1@S@We report here that phosphatidylinositol (PtdIns), phosphatidylinositol-4-phosphate, and other phosphatidylinositides can bind to mCD14.@@@@1@19@@oe@16-12-2010 973371604@GENIA Treebank@formal@@1@S@Phosphatidylserine (PS), another anionic glycerophospholipid, binds to mCD14 with lower apparent affinity than does PtdIns.@@@@1@20@@oe@16-12-2010 973371605@GENIA Treebank@formal@@1@S@LPS-binding protein, a lipid transfer protein found in serum, facilitates both PS- and PtdIns-mCD14 binding.@@@@1@18@@oe@16-12-2010 973371606@GENIA Treebank@formal@@1@S@PtdIns binding to mCD14 can be blocked by anti-CD14 monoclonal antibodies that inhibit LPS-mCD14 binding, and PtdIns can inhibit both LPS-mCD14 binding and LPS-induced responses in monocytes.@@@@1@29@@oe@16-12-2010 973371607@GENIA Treebank@formal@@1@S@Serum-equilibrated PtdIns also binds to mCD14-expressing cells, raising the possibility that endogenous PtdIns may modulate cellular responses to LPS and other mCD14 ligands in vivo.@@@@1@27@@oe@16-12-2010 973383601@GENIA Treebank@formal@@1@S@The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes.@@@@1@17@@oe@16-12-2010 973383602@GENIA Treebank@formal@@1@S@The transition of Epstein-Barr virus (EBV) from latency into the lytic cycle is associated with the expression of two immediate-early viral genes, BZLF1 and BRLF1.@@@@1@29@@oe@16-12-2010 973383603@GENIA Treebank@formal@@1@S@Overexpression of ZEBRA, the product of BZLF1, is sufficient to disrupt latency in B lymphocytes and epithelial cells by stimulating expression of lytic cycle genes, including BRLF1.@@@@1@31@@oe@16-12-2010 973383604@GENIA Treebank@formal@@1@S@The BRLF1 product Rta functions as a transcriptional activator in both B lymphocytes and epithelial cells.@@@@1@17@@oe@16-12-2010 973383605@GENIA Treebank@formal@@1@S@However, Rta has recently been reported to disrupt latency in an epithelial specific manner (S. Zalani, E. Holley-Guthrie, and S. Kenney, Proc. Natl. Acad. Sci. USA 93:9194-9199, 1996).@@@@1@38@@oe@16-12-2010 973383606@GENIA Treebank@formal@@1@S@Here we demonstrate that expression of Rta is also sufficient for disruption of latency in a permissive B-cell line.@@@@1@20@@oe@16-12-2010 973383607@GENIA Treebank@formal@@1@S@In HH514-16 cells, transfection of Rta leads to synthesis of ZEBRA, viral DNA replication, and late gene expression.@@@@1@22@@oe@16-12-2010 973383608@GENIA Treebank@formal@@1@S@However, Rta by itself is less potent than ZEBRA in the ability to activate most early and late lytic cycle genes.@@@@1@23@@oe@16-12-2010 973383609@GENIA Treebank@formal@@1@S@In light of previous work implicating ZEBRA in the activation of Rta, we suggest a cooperative model for EBV entry into the lytic cycle.@@@@1@26@@oe@16-12-2010 973383610@GENIA Treebank@formal@@1@S@Expression of either BZLF1 or BRLF1 triggers expression of the other immediate-early factor, and together these activators act individually or in synergy on downstream targets to activate the viral lytic cycle.@@@@1@33@@oe@16-12-2010 973384601@GENIA Treebank@formal@@1@S@Molecular and cellular analysis of human immunodeficiency virus-induced apoptosis in lymphoblastoid T-cell-line-expressing wild-type and mutated CD4 receptors.@@@@1@18@@oe@16-12-2010 973384602@GENIA Treebank@formal@@1@S@We have previously shown that the presence of the CD4 cytoplasmic tail is critical for human immunodeficiency virus (HIV)-induced apoptosis (J.Corbeil, M.Tremblay, and D.D.Richman, J.Exp.Med.183:39-48, 1996).@@@@1@38@@oe@16-12-2010 973384603@GENIA Treebank@formal@@1@S@We have pursued our investigation of the role of the CD4 transduction pathway in HIV-induced apoptosis.@@@@1@17@@oe@16-12-2010 973384604@GENIA Treebank@formal@@1@S@To do this, wild-type and mutant forms of the CD4 cytoplasmic tail were stably expressed in the lymphoblastoid T-cell line A2.01.@@@@1@23@@oe@16-12-2010 973384605@GENIA Treebank@formal@@1@S@Apoptosis was prevented when CD4 truncated at residue 402 was expressed; however, cells expressing mutated receptors that do not associate with p56(lck) (mutated at the dicysteine motif and truncated at residue 418) but which conserved proximal domains of the cytoplasmic tail underwent apoptosis like wild- type CD4.@@@@1@51@@oe@16-12-2010 973384606@GENIA Treebank@formal@@1@S@The differences between wild-type and mutated receptors in the induction of apoptosis were not related to levels of p56(lck) or NF- kappaB activation.@@@@1@23@@oe@16-12-2010 973384607@GENIA Treebank@formal@@1@S@Initial signaling through the CD4 receptor played a major role in the sensitization of HIV-infected T cells to undergo apoptosis.@@@@1@21@@oe@16-12-2010 973384608@GENIA Treebank@formal@@1@S@Incubation of HIV-infected cells with monoclonal antibody (MAb) 13B8-2, which binds to CD4 in a region critical for dimerization of the receptor, prevented apoptosis without inhibiting HIV replication.@@@@1@33@@oe@16-12-2010 973384609@GENIA Treebank@formal@@1@S@Moreover, the apoptotic process was not related to Fas-Fas ligand interaction; however, an antagonistic anti-Fas MAb (ZB-4) enhanced apoptosis in HIV-infected cells without inducing apoptosis in uninfected cells.@@@@1@34@@oe@16-12-2010 973384610@GENIA Treebank@formal@@1@S@These observations demonstrate that CD4 signaling mediates HIV-induced apoptosis by a mechanism independent of Fas-Fas ligand interaction, does not require p56(lck) signaling, and may involve a critical region for CD4 dimerization.@@@@1@34@@oe@16-12-2010 973466101@GENIA Treebank@formal@@1@S@Establishment and characterization of EBV-positive and EBV-negative primary effusion lymphoma cell lines harbouring human herpesvirus type-8.@@@@1@17@@oe@16-12-2010 973466102@GENIA Treebank@formal@@1@S@In this study we report on the establishment and characterization of two novel lymphoma cell lines (CRO-AP/3 and CRO-AP/5) which carry infection by human herpesvirus type-8 (HHV-8) and have derived from AIDS-related primary effusion lymphoma (PEL).@@@@1@43@@oe@16-12-2010 973466103@GENIA Treebank@formal@@1@S@These two cell lines are representative of different virologic subtypes of PEL, i.e. HHV-8+/EBV- PEL in the case of CRO-AP/3 and HHV-8+/EBV+ PEL in the case of CRO-AP/5.@@@@1@30@@oe@16-12-2010 973466104@GENIA Treebank@formal@@1@S@Consistent with the diagnosis of PEL, both CRO-AP/3 and CRO-AP/5 expressed indeterminate (i.e. non-B, non-T) phenotypes although immunogenotypic studies documented their B-cell origin.@@@@1@28@@oe@16-12-2010 973466105@GENIA Treebank@formal@@1@S@Both cell lines are devoid of genetic lesions of c-MYC, BCL-2 and p53 as well as gross rearrangements of BCL-6.@@@@1@22@@oe@16-12-2010 973466106@GENIA Treebank@formal@@1@S@Detailed histogenetic characterization of these novel PEL cell lines suggests that PEL may derive from a post-germinal centre B cell which has undergone pre-terminal differentiation.@@@@1@26@@oe@16-12-2010 973466107@GENIA Treebank@formal@@1@S@The CRO-AP/3 and CRO-AP/5 cell lines may provide a valuable model for clarifying the pathogenesis of PEL.@@@@1@18@@oe@16-12-2010 973466108@GENIA Treebank@formal@@1@S@In particular, these cell lines may help understand the relative contribution of HHV-8 and EBV to PEL growth and development and may facilitate the identification of recurrent cytogenetic abnormalities highlighting putative novel cancer related loci relevant to PEL.@@@@1@40@@oe@16-12-2010 973634001@GENIA Treebank@formal@@1@S@Interferon-gamma-induced factor binding to the interleukin-4-responsive element of CD23b promoter in human tonsillar mononuclear cells: role in transient up-regulation of the interleukin-4-induced CD23b mRNA.@@@@1@26@@oe@16-12-2010 973634002@GENIA Treebank@formal@@1@S@Stimulation of human tonsillar mononuclear cells with interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) rapidly induced the activation of distinct nuclear factors with different mobilities, both of which bind the IL-4 response element (IL-4RE) of CD23b promoter as examined by electrophoretic mobility shift assays (EMSA).@@@@1@53@@oe@16-12-2010 973634003@GENIA Treebank@formal@@1@S@Co-treatment of IL-4 and IFN-gamma induced, in addition to the two distinct complexes, a new complex with an intermediate mobility.@@@@1@23@@oe@16-12-2010 973634004@GENIA Treebank@formal@@1@S@The IL-4-induced complex reacted with anti-STAT (signal transducers and activators of transcription) 6, resulting in a supershift whereas the formation of the IFN-gamma-induced complex was inhibited by anti-STAT 1.@@@@1@33@@oe@16-12-2010 973634005@GENIA Treebank@formal@@1@S@The intermediate complex appeared to react with both anti-STAT 6 and anti-STAT 1.@@@@1@14@@oe@16-12-2010 973634006@GENIA Treebank@formal@@1@S@Although IFN-gamma alone did not induce CD23 mRNA transcription, Northern blot analysis revealed a transient up-regulation of the IL-4-induced CD23 mRNA by IFN-gamma within 2 h of IFN-gamma treatment in these tonsillar cells.@@@@1@35@@oe@16-12-2010 973634007@GENIA Treebank@formal@@1@S@The results suggest that the IL-4RE of the IL-4-inducible gene can accommodate both IL-4- and IFN-gamma-activated factors, such as STAT 6 and STAT 1, either in homodimeric or heterodimeric forms and the binding of these different proteins to the respective promoter may play a potential regulatory role in the IL-4-inducible gene expression.@@@@1@55@@oe@16-12-2010 973769301@GENIA Treebank@formal@@1@S@Models of lineage switching in hematopoietic development: a new myeloid-committed eosinophil cell line (YJ) demonstrates trilineage potential.@@@@1@21@@oe@16-12-2010 973769302@GENIA Treebank@formal@@1@S@A new human leukemia cell line with an eosinophilic phenotype, designated YJ, was established from the peripheral blood cells of a patient with chronic myelomonocytic leukemia (CMMoL) with eosinophilia.@@@@1@34@@oe@16-12-2010 973769303@GENIA Treebank@formal@@1@S@When cultured in RPMI 1640 medium containing 10% fetal bovine serum, most YJ cells were myeloblastoid with a small number of the cells having eosinophilic granules.@@@@1@29@@oe@16-12-2010 973769304@GENIA Treebank@formal@@1@S@Cell surface markers in the YJ cells were positive for CD33 and were negative for CD34, CD16 and CD23.@@@@1@21@@oe@16-12-2010 973769305@GENIA Treebank@formal@@1@S@The eosinophilic characteristics of YJ cells were confirmed by histochemical staining with Fast-Green/Neutral-Red and by the expression of mRNAs for eosinophil-associated granule proteins, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO), and major basic protein (MBP), and for the Charcot-Leyden crystal (CLC) protein.@@@@1@61@@oe@16-12-2010 973769306@GENIA Treebank@formal@@1@S@The YJ cells could be induced towards monocytic differentiation by stimulation with phorbol 12-myristate 13-acetate (PMA).@@@@1@19@@oe@16-12-2010 973769307@GENIA Treebank@formal@@1@S@The monocytic characteristics of YJ cells treated with PMA were confirmed by morphological analysis with alpha-naphthyl butyrate esterase staining, by CD14 expression, and by increased expression of Egr-1 mRNA.@@@@1@32@@oe@16-12-2010 973769308@GENIA Treebank@formal@@1@S@Furthermore, YJ cells could be differentiated towards the neutrophil lineage by stimulation with all-trans retinoic acid (RA).@@@@1@21@@oe@16-12-2010 973769309@GENIA Treebank@formal@@1@S@YJ cells treated in vitro with 2 microM RA differentiated into metamyelocytes and band neutrophils, and increased the number of nitroblue tetrazolium (NBT)-positive cells and increased gp91phox mRNA expression.@@@@1@34@@oe@16-12-2010 973769310@GENIA Treebank@formal@@1@S@Thus, the YJ cell line exhibited eosinophilic characteristics, but was able to differentiate to the monocytic or neutrophilic lineages in response to PMA or RA, respectively.@@@@1@30@@oe@16-12-2010 973769311@GENIA Treebank@formal@@1@S@The expression of genes for transcription factors involved in myeloid differentiation was evaluated by Northern blot analysis.@@@@1@18@@oe@16-12-2010 973769312@GENIA Treebank@formal@@1@S@Increased expression of Egr-1 was observed with macrophage differentiation.@@@@1@10@@oe@16-12-2010 973769313@GENIA Treebank@formal@@1@S@In contrast, increased expressions of C/EBPbeta and MZF-1 mRNA occurred with neutrophilic differentiation.@@@@1@15@@oe@16-12-2010 973769314@GENIA Treebank@formal@@1@S@The YJ cell line should be useful for elucidating the molecular mechanisms governing lineage switching from the eosinophil to monocytic or neutrophil lineages.@@@@1@24@@oe@16-12-2010 974133701@GENIA Treebank@formal@@1@S@Low CD3+CD28-induced interleukin-2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells.@@@@1@16@@oe@16-12-2010 974133702@GENIA Treebank@formal@@1@S@The capacity of neonatal T cells to secrete interleukin-2 (IL-2) has been reported to be variable.@@@@1@19@@oe@16-12-2010 974133703@GENIA Treebank@formal@@1@S@We analysed IL-2 production in purified neonatal and adult T cells using polyclonal activator phorbol ester + calcium ionophore (PDBu + iono) or receptor-mediated anti-CD3/anti-CD3+ anti-CD28 stimulation.@@@@1@30@@oe@16-12-2010 974133704@GENIA Treebank@formal@@1@S@PDBu + iono induced equally high IL-2 levels in both groups and, when stimulated with plate-bound anti-CD3 monoclonal antibody (mAb), the IL-2 secretion by neonatal cells was undetectable and adult cells produced low amounts of IL-2 (mean 331 +/- 86 pg/ml).@@@@1@48@@oe@16-12-2010 974133705@GENIA Treebank@formal@@1@S@The addition of anti-CD28 mAb to anti-CD3-stimulated cells markedly increased IL-2 production in both cell types, but levels of IL-2 in neonatal T cells remained clearly lower than those of adult T cells (respective mean values: 385 +/- 109 pg/ml and 4494 +/- 1199 pg/ml).@@@@1@50@@oe@16-12-2010 974133706@GENIA Treebank@formal@@1@S@As NF-kappa B is a critical transcription factor in the control of IL-2 expression, we next analysed its nuclear translocation in neonatal and adult T cells using the electrophoretic mobility shift assay and, because induction of reactive oxygen intermediates (ROI) is required for the activation of NF-kappa B, we also analysed levels of intracellular ROI in these cells using the ROI-reactive fluorochrome DCFH-DA and flow cytometry.@@@@1@72@@oe@16-12-2010 974133707@GENIA Treebank@formal@@1@S@In neonatal T cells NF-kappa B activation and ROI formation after anti-CD3 stimulation were low compared with adult T cells and, although addition of anti-CD28 mAb increased induction of NF-kappa B and ROI formation, levels similar to those of adults were not achieved.@@@@1@46@@oe@16-12-2010 974133708@GENIA Treebank@formal@@1@S@After PDBu + iono stimulation, the cells showed similar ROI formation and IL-2 secretion.@@@@1@16@@oe@16-12-2010 974133709@GENIA Treebank@formal@@1@S@Our results suggest that reduced IL-2 production by neonatal T cells is specific for anti-CD3 and anti-CD3+ anti-CD28-mediated stimulation and that these activators cannot effectively activate the ROI-NF-kappa B signalling pathway in neonatal T cells.@@@@1@37@@oe@16-12-2010 974212001@GENIA Treebank@formal@@1@S@The AD1 and AD2 transactivation domains of E2A are essential for the antiapoptotic activity of the chimeric oncoprotein E2A-HLF.@@@@1@20@@oe@16-12-2010 974212002@GENIA Treebank@formal@@1@S@The chimeric oncoprotein E2A-HLF, generated by the t(17;19) chromosomal translocation in pro-B-cell acute lymphoblastic leukemia, incorporates the transactivation domains of E2A and the basic leucine zipper (bZIP) DNA-binding and protein dimerization domain of HLF (hepatic leukemic factor).@@@@1@44@@oe@16-12-2010 974212003@GENIA Treebank@formal@@1@S@The ability of E2A-HLF to prolong the survival of interleukin-3 (IL-3)-dependent murine pro-B cells after IL-3 withdrawal suggests that it disrupts signaling pathways normally responsible for cell suicide, allowing the cells to accumulate as transformed lymphoblasts.@@@@1@41@@oe@16-12-2010 974212004@GENIA Treebank@formal@@1@S@To determine the structural motifs that contribute to this antiapoptotic effect, we constructed a panel of E2A-HLF mutants and programmed their expression in IL-3-dependent murine pro-B cells (FL5.12 line), using a zinc-inducible vector.@@@@1@38@@oe@16-12-2010 974212005@GENIA Treebank@formal@@1@S@Neither the E12 nor the E47 product of the E2A gene nor the wild-type HLF protein was able to protect the cells from apoptosis induced by IL-3 deprivation.@@@@1@29@@oe@16-12-2010 974212006@GENIA Treebank@formal@@1@S@Surprisingly, different combinations of disabling mutations within the HLF bZIP domain had little effect on the antiapoptotic property of the chimeric protein, so long as the amino-terminal portion of E2A remained intact.@@@@1@35@@oe@16-12-2010 974212007@GENIA Treebank@formal@@1@S@In the context of a bZIP domain defective in DNA binding, mutants retaining either of the two transactivation domains of E2A were able to extend cell survival after growth factor deprivation.@@@@1@33@@oe@16-12-2010 974212008@GENIA Treebank@formal@@1@S@Thus, the block of apoptosis imposed by E2A-HLF in pro-B lymphocytes depends critically on the transactivating regions of E2A.@@@@1@21@@oe@16-12-2010 974212009@GENIA Treebank@formal@@1@S@Since neither DNA binding nor protein dimerization through the bZIP domain of HLF is required for this effect, we propose mechanisms whereby protein-protein interactions with the amino-terminal region of E2A allow the chimera to act as a transcriptional cofactor to alter the expression of genes regulating the apoptotic machinery in pro-B cells.@@@@1@54@@oe@16-12-2010 974337001@GENIA Treebank@formal@@1@S@Human T cell leukemia virus-I (HTLV-I) Tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state.@@@@1@21@@oe@16-12-2010 974337002@GENIA Treebank@formal@@1@S@We have shown that an estradiol-dependent activation of human T cell leukemia virus-I Tax leads to the inhibition of cell proliferation and to the induction of apoptosis.@@@@1@28@@oe@16-12-2010 974337003@GENIA Treebank@formal@@1@S@The present study demonstrates that a hormone-dependent activation of Tax promotes an enhanced prooxidant state in stably transfected Jurkat cells as measured by changes in the intracellular levels of glutathione and H2O2; these changes are followed by apoptotic cell death.@@@@1@42@@oe@16-12-2010 974337004@GENIA Treebank@formal@@1@S@Additional stimulation of the CD3/TCR pathway enhances the oxidative and apoptotic effects.@@@@1@13@@oe@16-12-2010 974337005@GENIA Treebank@formal@@1@S@Both Tax-mediated apoptosis and oxidative stress can be potently suppressed by antioxidants, as is seen with the administration of recombinant thioredoxin (adult T cell leukemia-derived factor) or pyrrolidine dithiocarbamate.@@@@1@33@@oe@16-12-2010 974337006@GENIA Treebank@formal@@1@S@Hormone-induced Tax activation induces a long-lasting activation of NF-kappaB, which is a major target of reactive oxygen intermediates.@@@@1@20@@oe@16-12-2010 974337007@GENIA Treebank@formal@@1@S@The long-term exposure of Jurkat cells to hormone eventually results in a selection of cell clones that have lost Tax activity.@@@@1@22@@oe@16-12-2010 974337008@GENIA Treebank@formal@@1@S@A subsequent transfection of these apparently "nonresponsive" clones allows the recovery of Tax responses in these cells.@@@@1@20@@oe@16-12-2010 974337009@GENIA Treebank@formal@@1@S@Our observations indicate that changes in the intracellular redox status may be a determining factor in Tax-mediated DNA damage, apoptosis, and selection against the long-term expression of Tax function.@@@@1@32@@oe@16-12-2010 974350601@GENIA Treebank@formal@@1@S@Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells [see comments]@@@@1@21@@oe@16-12-2010 974350602@GENIA Treebank@formal@@1@S@BACKGROUND: Platelet/endothelium interaction plays an important role in the pathophysiology of inflammation and atherosclerosis.@@@@1@16@@oe@16-12-2010 974350603@GENIA Treebank@formal@@1@S@The role of platelets for monocyte chemotactic protein-1 (MCP-1) secretion and surface expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells has been assessed.@@@@1@29@@oe@16-12-2010 974350604@GENIA Treebank@formal@@1@S@METHODS AND RESULTS: Monolayers of human umbilical vein endothelial cells were incubated with nonstimulated or ADP-activated platelets for 6 hours, and secretion of MCP-1 and surface expression of ICAM-1 were determined by ELISA and flow cytometry, respectively.@@@@1@41@@oe@16-12-2010 974350605@GENIA Treebank@formal@@1@S@In the presence of ADP-activated platelets, both MCP-1 secretion and ICAM-1 surface expression were significantly increased compared with nonstimulated platelets (P<0.02).@@@@1@27@@oe@16-12-2010 974350606@GENIA Treebank@formal@@1@S@Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) determined by electrophoretic mobility shift assay and kappaB-dependent transcriptional activity was enhanced in the presence of activated platelets.@@@@1@29@@oe@16-12-2010 974350607@GENIA Treebank@formal@@1@S@In addition, ADP-activated platelets induced MCP-1 and ICAM-1 promoter-dependent transcription.@@@@1@12@@oe@16-12-2010 974350608@GENIA Treebank@formal@@1@S@Liposomal transfection of a double-stranded kappaB phosphorothioate oligonucleotide, but not of the mutated form, inhibited MCP-1 secretion and surface expression of ICAM-1 on activated endothelium (P<0.05).@@@@1@33@@oe@16-12-2010 974350609@GENIA Treebank@formal@@1@S@CONCLUSIONS: The present study indicates that activated platelets modulate chemotactic (MCP-1) and adhesive (ICAM-1) properties of endothelial cells via an NF-kappaB-dependent mechanism.@@@@1@28@@oe@16-12-2010 974350610@GENIA Treebank@formal@@1@S@Platelet-induced activation of the NF-kappaB system might contribute to early inflammatory events in atherogenesis.@@@@1@15@@oe@16-12-2010 974353501@GENIA Treebank@formal@@1@S@Upregulation of interleukin 6 and granulocyte colony-stimulating factor receptors by transcription factor CCAAT enhancer binding protein alpha (C/EBP alpha) is critical for granulopoiesis.@@@@1@26@@oe@16-12-2010 974353502@GENIA Treebank@formal@@1@S@Cytokines stimulate granulopoiesis through signaling via receptors whose expression is controlled by lineage-specific transcription factors.@@@@1@16@@oe@16-12-2010 974353503@GENIA Treebank@formal@@1@S@Previously, we demonstrated that granulocyte colony-stimulating factor (G-CSF) receptor mRNA was undetectable and granulocyte maturation blocked in CCAAT enhancer binding protein alpha (C/EBPalpha)-deficient mice.@@@@1@31@@oe@16-12-2010 974353504@GENIA Treebank@formal@@1@S@This phenotype is distinct from that of G-CSF receptor-/- mice, suggesting that other genes are likely to be adversely affected by loss of C/EBPalpha.@@@@1@26@@oe@16-12-2010 974353505@GENIA Treebank@formal@@1@S@Here we demonstrate loss of interleukin 6 (IL-6) receptor and IL-6-responsive colony-forming units (CFU-IL6) in C/EBPalpha-/- mice.@@@@1@22@@oe@16-12-2010 974353506@GENIA Treebank@formal@@1@S@The observed failure of granulopoiesis could be rescued by the addition of soluble IL-6 receptor and IL-6 or by retroviral transduction of G-CSF receptors, demonstrating that loss of both of these receptors contributes to the absolute block in granulocyte maturation observed in C/EBPalpha-deficient hematopoietic cells.@@@@1@47@@oe@16-12-2010 974353507@GENIA Treebank@formal@@1@S@The results of these and other studies suggest that additional C/EBPalpha target genes, possibly other cytokine receptors, are also important for the block in granulocyte differentiation observed in vivo in C/EBPalpha-deficient mice.@@@@1@35@@oe@16-12-2010 974486301@GENIA Treebank@formal@@1@S@Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the beta-globin locus control region in vivo.@@@@1@23@@oe@16-12-2010 974486302@GENIA Treebank@formal@@1@S@The locus control region of the beta-globin cluster contains five DNase I hypersensitive sites (5'HS1-5) required for locus activation.@@@@1@22@@oe@16-12-2010 974486303@GENIA Treebank@formal@@1@S@5'HS3 contains six G-rich motifs that are essential for its activity.@@@@1@12@@oe@16-12-2010 974486304@GENIA Treebank@formal@@1@S@Members of a protein family, characterized by three zinc fingers highly homologous to those found in transcription factor Sp1, interact with these motifs.@@@@1@26@@oe@16-12-2010 974486305@GENIA Treebank@formal@@1@S@Because point mutagenesis cannot distinguish between family members, it is not known which protein activates 5'HS3.@@@@1@19@@oe@16-12-2010 974486306@GENIA Treebank@formal@@1@S@We show that the function of such closely related proteins can be distinguished in vivo by matching point mutations in 5'HS3 with amino acid changes in the zinc fingers of Sp1 and EKLF.@@@@1@34@@oe@16-12-2010 974486307@GENIA Treebank@formal@@1@S@Testing their activity in transgenic mice shows that EKLF is a direct activator of 5'HS3.@@@@1@16@@oe@16-12-2010 974675801@GENIA Treebank@formal@@1@S@Expression status of BCL-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin's disease.@@@@1@15@@oe@16-12-2010 974675802@GENIA Treebank@formal@@1@S@The tumor cells in most cases of Hodgkin's disease (HD) have been recently recognized to originate from the B-cell lineage, but their precise differentiation stage is not fully clarified.@@@@1@34@@oe@16-12-2010 974675803@GENIA Treebank@formal@@1@S@Recently, we have reported that the histogenesis of B-cell lymphomas may be assessed by monitoring the expression pattern of BCL-6, a transcription factor expressed in germinal center (GC) B cells, and CD138/syndecan-1 (syn-1), a proteoglycan associated with post-GC, terminal B-cell differentiation.@@@@1@51@@oe@16-12-2010 974675804@GENIA Treebank@formal@@1@S@In this study, we have applied these two markers to the study of HD histogenesis.@@@@1@17@@oe@16-12-2010 974675805@GENIA Treebank@formal@@1@S@We have found that in nodular lymphocyte predominance HD (NLPHD) tumor cells consistently display the BCL-6(+)/syn-1(-) phenotype, indicating their derivation from GC B cells.@@@@1@28@@oe@16-12-2010 974675806@GENIA Treebank@formal@@1@S@Conversely, classic HD (CHD) is heterogeneous because the tumor cells of a fraction of CHD display the BCL-6(-)/syn-1(+) phenotype of post-GC B-cells, whereas another fraction of CHD is constituted by a mixture of tumor cells reflecting the GC (BCL-6(+)/syn-1(-)) or post-GC (BCL-6(-)/syn-1(+)) phenotypes.@@@@1@52@@oe@16-12-2010 974675807@GENIA Treebank@formal@@1@S@BCL-6(-)/syn-1(+) tumor cells of CHD are mostly found surrounded by T cells expressing CD40L, consistent with the observation that CD40 signaling downregulates BCL-6 expression.@@@@1@26@@oe@16-12-2010 974675808@GENIA Treebank@formal@@1@S@These data indicate that tumor cells of NLPHD uniformly display a GC B-cell phenotype, whereas the phenotype of tumor cells of CHD appears to be modulated by the surrounding cellular background, particularly CD40L+ reactive T cells.@@@@1@39@@oe@16-12-2010 974676001@GENIA Treebank@formal@@1@S@A novel mutation in the coding sequence of the FY*B allele of the Duffy chemokine receptor gene is associated with an altered erythrocyte phenotype.@@@@1@25@@oe@16-12-2010 974676002@GENIA Treebank@formal@@1@S@The Duffy blood group system is of clinical and biological significance.@@@@1@12@@oe@16-12-2010 974676003@GENIA Treebank@formal@@1@S@Antibodies to Duffy antigens are responsible for some cases of transfusion incompatibility and newborn hemolytic disease.@@@@1@17@@oe@16-12-2010 974676004@GENIA Treebank@formal@@1@S@The Duffy protein is a receptor for the Plasmodium vivax erythrocyte-binding protein and is also a receptor for various chemokines (thus renamed Duffy Antigen Receptor for Chemokines [DARC]).@@@@1@33@@oe@16-12-2010 974676005@GENIA Treebank@formal@@1@S@The two Duffy polymorphic antigens, Fya and Fyb (coded by the FY*A and FY*B alleles), are present on erythrocyte membranes.@@@@1@25@@oe@16-12-2010 974676006@GENIA Treebank@formal@@1@S@The Fy(a-b-) phenotype is the predominant one in populations of black people and also occurs in other populations, including some non-Ashkenazi Jewish groups.@@@@1@25@@oe@16-12-2010 974676007@GENIA Treebank@formal@@1@S@The Fy(a-b-) phenotype has been associated with a mutation in the FY*B promoter at the GATA box that abolishes the expression of erythrocyte Duffy protein.@@@@1@26@@oe@16-12-2010 974676008@GENIA Treebank@formal@@1@S@We describe here a novel mutation, present in the FY*B coding sequence (271C --> T), that is associated with some Fy(b-) phenotypes among non-Ashkenazi Jews and among Brazilian blacks.@@@@1@34@@oe@16-12-2010 974676009@GENIA Treebank@formal@@1@S@The mutation is present in Fy(b-) individuals, who have wild-type FY*B GATA and carry the previously described 304G --> A substitution.@@@@1@23@@oe@16-12-2010 974676010@GENIA Treebank@formal@@1@S@The 271C --> T and 304G --> A can be identified by restriction enzyme-generated restriction fragment length polymorphisms.@@@@1@19@@oe@16-12-2010 974676011@GENIA Treebank@formal@@1@S@The 271C --> T substitution represents a considerable change in chemical nature (Arg91 --> Cys), one which may affect the antigenic determinants of DARC, and thus be of clinical significance.@@@@1@35@@oe@16-12-2010 974676012@GENIA Treebank@formal@@1@S@The mutation may have implications for some physiological roles of DARC and be of interest in malaria research and in studies of population genetics.@@@@1@25@@oe@16-12-2010 974679101@GENIA Treebank@formal@@1@S@Interleukin-4 and -13 induce upregulation of the murine macrophage 12/15-lipoxygenase activity: evidence for the involvement of transcription factor STAT6.@@@@1@21@@oe@16-12-2010 974679102@GENIA Treebank@formal@@1@S@When human monocytes or alveolar macrophages are cultured in the presence of interleukin (IL)-4 or IL-13, the expression of the reticulocyte-type 15-lipoxygenase is induced.@@@@1@29@@oe@16-12-2010 974679103@GENIA Treebank@formal@@1@S@In mice a 15-lipoxygenase is not expressed, but a leukocyte-type 12-lipoxygenase is present in peritoneal macrophages.@@@@1@18@@oe@16-12-2010 974679104@GENIA Treebank@formal@@1@S@To investigate whether both lipoxygenase isoforms exhibit a similar regulatory response toward cytokine stimulation, we studied the regulation of the leukocyte-type 12-lipoxygenase of murine peritoneal macrophages by interleukins and found that the activity of this enzyme is upregulated in a dose-dependent manner when the cells were cultured in the presence of the IL-4 or IL-13 but not by IL-10.@@@@1@61@@oe@16-12-2010 974679105@GENIA Treebank@formal@@1@S@When peripheral murine monocytes that do not express the lipoxygenase were treated with IL-4 expression of 12/15-lipoxygenase mRNA was induced, suggesting pretranslational control mechanisms.@@@@1@26@@oe@16-12-2010 974679106@GENIA Treebank@formal@@1@S@In contrast, no upregulation of the lipoxygenase activity was observed when the macrophages were prepared from homozygous STAT6-deficient mice.@@@@1@21@@oe@16-12-2010 974679107@GENIA Treebank@formal@@1@S@Peritoneal macrophages of transgenic mice that systemically overexpress IL-4 exhibited a threefold to fourfold higher 12-lipoxygenase activity than cells prepared from control animals.@@@@1@24@@oe@16-12-2010 974679108@GENIA Treebank@formal@@1@S@A similar upregulation of 12-lipoxygenase activity was detected in heart, spleen, and lung of the transgenic animals.@@@@1@20@@oe@16-12-2010 974679109@GENIA Treebank@formal@@1@S@Moreover, a strong induction of the enzyme was observed in red cells during experimental anemia in mice.@@@@1@19@@oe@16-12-2010 974679110@GENIA Treebank@formal@@1@S@The data presented here indicate that (1) the 12-lipoxygenase activity of murine macrophages is upregulated in vitro and in vivo by IL-4 and/or IL-13, (2) this upregulation requires expression of the transcription factor STAT6, and (3) the constitutive expression of the enzyme appears to be STAT6 independent.@@@@1@56@@oe@16-12-2010 974679111@GENIA Treebank@formal@@1@S@The cytokine-dependent upregulation of the murine macrophage 12-lipoxygenase and its induction during experimental anemia suggests its close relatedness with the human reticulocyte-type 15-lipoxygenase despite their differences in the positional specificity of arachidonic acid oxygenation.@@@@1@35@@oe@16-12-2010 974772001@GENIA Treebank@formal@@1@S@NF-kappaB only partially mediates Epstein-Barr virus latent membrane protein 1 activation of B cells.@@@@1@15@@oe@16-12-2010 974772002@GENIA Treebank@formal@@1@S@The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is required for EBV-induced immortalization of human B cells and causes tumorigenic transformation of cell lines.@@@@1@31@@oe@16-12-2010 974772003@GENIA Treebank@formal@@1@S@LMP1 expression induces phenotypic changes resembling B cell activation, such as cell size increase and up-regulation of cell surface activation markers.@@@@1@23@@oe@16-12-2010 974772004@GENIA Treebank@formal@@1@S@LMP1 contains two domains that activate the transcription factor NF-kappaB, one through interactions with TRAF proteins and the other with the TRADD protein.@@@@1@25@@oe@16-12-2010 974772005@GENIA Treebank@formal@@1@S@The purpose of the present study was to investigate the importance of NF-kappaB induction in the up-regulation of the B cell activation markers ICAM-1 and CD71 by LMP1.@@@@1@29@@oe@16-12-2010 974772006@GENIA Treebank@formal@@1@S@This study shows that expression of LMP1 activates transcription from p50/p65- and c-Rel- responsive promoters, and that this activity can be completely inhibited by expression of a dominant inhibitory IkappaB mutant.@@@@1@32@@oe@16-12-2010 974772007@GENIA Treebank@formal@@1@S@ICAM-1 and CD71 are nevertheless up-regulated by LMP1 in primary B cells and cell lines expressing the dominant IkappaB.@@@@1@20@@oe@16-12-2010 974772008@GENIA Treebank@formal@@1@S@Furthermore, LMP1-induced cell size increase of primary B cells was unaffected by IkappaB expression.@@@@1@16@@oe@16-12-2010 974772009@GENIA Treebank@formal@@1@S@It was concluded that even when LMP1 is unable to activate NF-kappaB, it is still capable of inducing certain characteristics of activated B cells, strongly suggesting that LMP1 can also activate cells independently of NF-kappaB.@@@@1@38@@oe@16-12-2010 974832301@GENIA Treebank@formal@@1@S@Activation of distinct transcription factors in neutrophils by bacterial LPS, interferon-gamma, and GM-CSF and the necessity to overcome the action of endogenous proteases.@@@@1@26@@oe@16-12-2010 974832302@GENIA Treebank@formal@@1@S@Human neutrophils can be induced to actively transcribe a number of early-response genes, in particular those encoding cytokines, chemokines, and the high-affinity surface receptor for IgG, FcgammaRI.@@@@1@32@@oe@16-12-2010 974832303@GENIA Treebank@formal@@1@S@Although little is known to date about the regulation of gene transcription in neutrophils, several indications point to a role for distinct transcription factors, such as members of the NF-kappaB and STAT families.@@@@1@36@@oe@16-12-2010 974832304@GENIA Treebank@formal@@1@S@In this study, we investigated whether these transcription factors become activated under stimulatory conditions which are known to induce gene transcription in neutrophils.@@@@1@25@@oe@16-12-2010 974832305@GENIA Treebank@formal@@1@S@Unexpectedly, we found that conventional procedures employed to prepare cellular extracts cause the release of proteolytic activities that are normally stored in intracellular granules, resulting in the degradation of various NF-kappaB/Rel and STAT proteins.@@@@1@37@@oe@16-12-2010 974832306@GENIA Treebank@formal@@1@S@To circumvent this problem, we developed an alternative procedure which allowed us to show that in neutrophils, LPS and TNFalpha induce a NF-kappaB DNA-binding activity which essentially consists of p50/RelA dimers, and that IFNgamma promotes the binding of STAT1 homodimers to the IFNgamma response region of the FcgammaRI promoter.@@@@1@53@@oe@16-12-2010 974832307@GENIA Treebank@formal@@1@S@Moreover, we report that neutrophil stimulation with GM-CSF results in the formation of a STAT5-containing DNA-binding activity.@@@@1@19@@oe@16-12-2010 974832308@GENIA Treebank@formal@@1@S@Collectively, the current findings open new perspectives about mechanisms that are likely to regulate gene transcription in neutrophils.@@@@1@20@@oe@16-12-2010 974832309@GENIA Treebank@formal@@1@S@In addition, the procedure described herein could prove useful in other cell types that express high levels of endogenous proteases.@@@@1@22@@oe@16-12-2010 975174801@GENIA Treebank@formal@@1@S@BCL-6 mutations in normal germinal center B cells: evidence of somatic hypermutation acting outside Ig loci.@@@@1@18@@oe@16-12-2010 975174802@GENIA Treebank@formal@@1@S@The molecular mechanism involved in the process of antigen-driven somatic hypermutation of Ig genes is unknown, but it is commonly believed that this mechanism is restricted to the Ig loci.@@@@1@32@@oe@16-12-2010 975174803@GENIA Treebank@formal@@1@S@B cell lymphomas commonly display multiple somatic mutations clustering in the 5'-regulatory region of BCL-6, a proto-oncogene encoding for a POZ/Zinc finger transcriptional repressor expressed in germinal center (GC) B cells and required for GC formation.@@@@1@40@@oe@16-12-2010 975174804@GENIA Treebank@formal@@1@S@To determine whether BCL-6 mutations represent a tumor-associated phenomenon or reflect a physiologic mechanism, we screened single human tonsillar GC B cells for mutations occurring in the BCL-6 5'-noncoding region and in the Ig variable heavy chain sequences.@@@@1@40@@oe@16-12-2010 975174805@GENIA Treebank@formal@@1@S@Thirty percent of GC B cells, but not naive B cells, displayed mutations in the 742 bp region analyzed within the first intron of BCL-6 (overall frequency: 5 x 10(-4)/bp).@@@@1@36@@oe@16-12-2010 975174806@GENIA Treebank@formal@@1@S@Accordingly, an expanded survey in lymphoid malignancies showed that BCL-6 mutations are restricted to B cell tumors displaying GC or post-GC phenotype and carrying mutated Ig variable heavy chain sequences.@@@@1@32@@oe@16-12-2010 975174807@GENIA Treebank@formal@@1@S@These results indicate that the somatic hypermutation mechanism active in GC B cells physiologically targets non-Ig sequences.@@@@1@18@@oe@16-12-2010 975175601@GENIA Treebank@formal@@1@S@The PEBP2betaMYH11 fusion created by Inv(16)(p13;q22) in myeloid leukemia impairs neutrophil maturation and contributes to granulocytic dysplasia.@@@@1@18@@oe@16-12-2010 975175602@GENIA Treebank@formal@@1@S@Chromosomal translocations involving the genes encoding the alpha and beta subunits of the Pebp2/Cbf transcription factor have been associated with human acute myeloid leukemia and the preleukemic condition, myelodysplasia.@@@@1@31@@oe@16-12-2010 975175603@GENIA Treebank@formal@@1@S@Inv(16)(p13;q22) fuses the gene encoding the beta subunit of Pebp2 to the MYH11 gene encoding a smooth muscle myosin heavy chain (Smmhc).@@@@1@25@@oe@16-12-2010 975175604@GENIA Treebank@formal@@1@S@To examine the effect of the inv(16)(p13;q22) on myelopoiesis, we used the hMRP8 promoter element to generate transgenic mice expressing the Pebp2beta Smmhc chimeric fusion protein in myeloid cells.@@@@1@31@@oe@16-12-2010 975175605@GENIA Treebank@formal@@1@S@Neutrophil maturation was impaired in PEBP2betaMYH11 transgenic mice.@@@@1@9@@oe@16-12-2010 975175606@GENIA Treebank@formal@@1@S@Although the transgenic mice had normal numbers of circulating neutrophils, their bone marrow contained increased numbers of immature neutrophilic cells, which exhibited abnormal characteristics.@@@@1@27@@oe@16-12-2010 975175607@GENIA Treebank@formal@@1@S@In addition, PEBP2betaMYH11 inhibited neutrophilic differentiation in colonies derived from hematopoietic progenitors.@@@@1@14@@oe@16-12-2010 975175608@GENIA Treebank@formal@@1@S@Coexpression of both PEBP2betaMYH11 and activated NRAS induced a more severe phenotype characterized by abnormal nuclear morphology indicative of granulocytic dysplasia.@@@@1@22@@oe@16-12-2010 975175609@GENIA Treebank@formal@@1@S@These results show that PEBP2betaMYH11 can impair neutrophil development and provide evidence that alterations of Pebp2 can contribute to the genesis of myelodysplasia.@@@@1@24@@oe@16-12-2010 975641701@GENIA Treebank@formal@@1@S@Transcription factor activation in lymphokine activated killer cells and lymphocytes from patients receiving IL-2 immunotherapy.@@@@1@16@@oe@16-12-2010 975641702@GENIA Treebank@formal@@1@S@Administration of the cytokine interleukin-2 (IL-2) can result in therapeutic benefits for individuals with renal cell carcinoma and melanoma.@@@@1@22@@oe@16-12-2010 975641703@GENIA Treebank@formal@@1@S@Here we report an analysis of the transcription factor families AP-1, Sp1, NF-kappaB, and signal transducers and activators of transcription (STAT) in cancer patients' lymphocytes before and after IL-2 immunotherapy, as assessed by a gel-shift assay.@@@@1@44@@oe@16-12-2010 975641704@GENIA Treebank@formal@@1@S@An in vitro surrogate of IL-2 immunotherapy is the incubation of fresh peripheral blood mononuclear cells (PBMC) from healthy individuals in IL-2 for several days, resulting in the production of lymphokine-activated killer (LAK) activity in these cultures.@@@@1@43@@oe@16-12-2010 975641705@GENIA Treebank@formal@@1@S@One purpose of this study was to describe the profile of transcription factor activation in these different populations, and assess whether the patterns observed correlated with functional differences in these cells.@@@@1@33@@oe@16-12-2010 975641706@GENIA Treebank@formal@@1@S@Prior to in vivo IL-2 administration, the typical binding pattern of transcription factors in PBMC from patients resembled that seen in fresh PBMC from healthy individuals.@@@@1@28@@oe@16-12-2010 975641707@GENIA Treebank@formal@@1@S@Over a 3-week course of IL-2 therapy, in most patients the binding patterns of AP-1 , Sp1, and NF-kappaB proteins changed to resemble those seen in PBMC activated by IL-2 in vitro.@@@@1@35@@oe@16-12-2010 975641708@GENIA Treebank@formal@@1@S@However, the cells obtained from IL-2-treated patients did not have low-level constitutive expression of STAT binding factors as did LAK cells.@@@@1@23@@oe@16-12-2010 975641709@GENIA Treebank@formal@@1@S@When these patient cells were further stimulated by IL-2 in vitro, additional differences in STAT induction patterns were noted.@@@@1@21@@oe@16-12-2010 975641710@GENIA Treebank@formal@@1@S@These data provide further information on the molecular events occurring in immune cells generated through in vivo and in vitro administration of IL-2, and further document that there is not a precise congruence between PBMC activated in vivo and in vitro by IL-2.@@@@1@45@@oe@16-12-2010 975664301@GENIA Treebank@formal@@1@S@Induction of T cell anergy by high concentrations of immunodominant native peptide is accompanied by IL-10 production and a block in JNK activity.@@@@1@24@@oe@16-12-2010 975664302@GENIA Treebank@formal@@1@S@The ability to induce anergy in antigen-specific T cells has potential therapeutic value for altering pathologic immune responses.@@@@1@19@@oe@16-12-2010 975664303@GENIA Treebank@formal@@1@S@This study was undertaken to further analyze changes in cytokine production and intracellular signaling during anergy induction using high concentrations of native peptide ligand of tetanus toxoid (TT)- and myelin basic protein (MBP)-specific human T cell lines.@@@@1@44@@oe@16-12-2010 975664304@GENIA Treebank@formal@@1@S@The TT-selected T cell line could be rendered unresponsive to its dominant epitope in a dose-dependent manner (IC50 = 0.03 microg/ml).@@@@1@24@@oe@16-12-2010 975664305@GENIA Treebank@formal@@1@S@The TT-selected line, as well as three T cell clones established from this line, continued to produce IFN-gamma and significantly increased IL-4 and IL-10 production when anergy was induced with high concentrations of the immunodominant epitope.@@@@1@39@@oe@16-12-2010 975664306@GENIA Treebank@formal@@1@S@JNK enzymatic activity was blocked in anergized T cells.@@@@1@10@@oe@16-12-2010 975664307@GENIA Treebank@formal@@1@S@The MBP-selected line could likewise be rendered unresponsive by incubation with supraoptimal concentrations of immunodominant peptide and anergy induction was accompanied by IL-10 release.@@@@1@25@@oe@16-12-2010 975664308@GENIA Treebank@formal@@1@S@Both T cell lines could be anergized by the autopresentation of native peptide since anergy was induced in cultures lacking fresh antigen-presenting cells.@@@@1@24@@oe@16-12-2010 975664309@GENIA Treebank@formal@@1@S@This study shows that the mitogen-activated protein kinase cascade is blocked when anergy is induced to high concentrations of soluble peptide.@@@@1@22@@oe@16-12-2010 975664310@GENIA Treebank@formal@@1@S@Copyright 1998 Academic Press.@@@@1@5@@oe@16-12-2010 975986401@GENIA Treebank@formal@@1@S@Carboxyl-terminal 15-amino acid sequence of NFATx1 is possibly created by tissue-specific splicing and is essential for transactivation activity in T cells.@@@@1@22@@oe@16-12-2010 975986402@GENIA Treebank@formal@@1@S@NFAT regulates transcription of a number of cytokine and other immunoregulatory genes.@@@@1@13@@oe@16-12-2010 975986403@GENIA Treebank@formal@@1@S@We have isolated NFATx, which is one of four members of the NFAT family of transcription factors and is preferentially expressed in the thymus and peripheral blood leukocytes, and an isoform of NFATx, NFATx1.@@@@1@38@@oe@16-12-2010 975986404@GENIA Treebank@formal@@1@S@Here we provide evidence showing that 15 amino acids in the carboxyl-terminal end of NFATx1 are required for its maximum transactivation activity in Jurkat T cells.@@@@1@27@@oe@16-12-2010 975986405@GENIA Treebank@formal@@1@S@A fusion between these 15 amino acids and the GAL4 DNA binding domain was capable of transactivating reporters driven by the GAL4 DNA binding site.@@@@1@26@@oe@16-12-2010 975986406@GENIA Treebank@formal@@1@S@Interestingly, this 15-amino acid transactivation sequence is well conserved in NFAT family proteins, although the sequences contiguous to the carboxyl-terminal regions of the NFAT family are much less conserved.@@@@1@32@@oe@16-12-2010 975986407@GENIA Treebank@formal@@1@S@We also report three additional isoforms of NFATx, designated NFATx2, NFATx3, and NFATx4.@@@@1@17@@oe@16-12-2010 975986408@GENIA Treebank@formal@@1@S@This transactivation sequence is altered by tissue-specific alternative splicing in newly isolated NFATx isoforms, resulting in lower transactivation activity in Jurkat T cells.@@@@1@25@@oe@16-12-2010 975986409@GENIA Treebank@formal@@1@S@NFATx1 is expressed predominantly in the thymus and peripheral blood leukocyte, while the skeletal muscle expressed primarily NFATx2.@@@@1@20@@oe@16-12-2010 975986410@GENIA Treebank@formal@@1@S@In Jurkat cells, transcription from the NFAT site of the IL-2 promoter is activated strongly by NFATx1 but only weakly by NFATx2.@@@@1@24@@oe@16-12-2010 975986411@GENIA Treebank@formal@@1@S@These data demonstrate that the 15-amino acid sequence of NFATx1 is a major transactivation sequence required for induction of genes by NFATx1 in T cells and possibly regulates NFAT activity through tissue-specific alternative splicing.@@@@1@35@@oe@16-12-2010 976361301@GENIA Treebank@formal@@1@S@A critical role of the p75 tumor necrosis factor receptor (p75TNF-R) in organ inflammation independent of TNF, lymphotoxin alpha, or the p55TNF-R.@@@@1@27@@oe@16-12-2010 976361302@GENIA Treebank@formal@@1@S@Despite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor (p75TNF-R) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis, inflammatory liver disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of this receptor remains poorly defined in vivo.@@@@1@54@@oe@16-12-2010 976361303@GENIA Treebank@formal@@1@S@We show here that at levels relevant to human disease, production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas, liver, kidney, and lung, and characterized by constitutively increased NF-kappaB activity in the peripheral blood mononuclear cell compartment.@@@@1@52@@oe@16-12-2010 976361304@GENIA Treebank@formal@@1@S@This process is shown to evolve independently of the presence of TNF, lymphotoxin alpha, or the p55TNF-R, although coexpression of a human TNF transgene accelerated pathology.@@@@1@30@@oe@16-12-2010 976361305@GENIA Treebank@formal@@1@S@These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies.@@@@1@33@@oe@16-12-2010 976361601@GENIA Treebank@formal@@1@S@The interleukin 2 receptor alpha chain/CD25 promoter is a target for nuclear factor of activated T cells.@@@@1@18@@oe@16-12-2010 976361602@GENIA Treebank@formal@@1@S@The expression of the murine interleukin (IL)-2 receptor alpha chain/CD25 is strongly induced at the transcriptional level after T cell activation.@@@@1@25@@oe@16-12-2010 976361603@GENIA Treebank@formal@@1@S@We show here that nuclear factor of activated T cell (NF-AT) factors are involved in the control of CD25 promoter induction in T cells.@@@@1@27@@oe@16-12-2010 976361604@GENIA Treebank@formal@@1@S@NF-ATp and NF-ATc bind to two sites around positions -585 and -650 located upstream of the proximal CD25 promoter.@@@@1@20@@oe@16-12-2010 976361605@GENIA Treebank@formal@@1@S@Immediately 3' from these NF-AT motifs, nonconsensus sites are located for the binding of AP-1-like factors.@@@@1@18@@oe@16-12-2010 976361606@GENIA Treebank@formal@@1@S@Mutations of sites that suppress NF-AT binding impair the induction and strong NF-ATp-mediated transactivation of the CD25 promoter in T cells.@@@@1@22@@oe@16-12-2010 976361607@GENIA Treebank@formal@@1@S@In T lymphocytes from NF-ATp-deficient mice, the expression of CD25 is severely impaired, leading to a delayed IL-2 receptor expression after T cell receptor (TCR)/CD3 stimulation.@@@@1@32@@oe@16-12-2010 976361608@GENIA Treebank@formal@@1@S@Our data indicate an important role for NF-AT in the faithful expression of high affinity IL-2 receptors and a close link between the TCR-mediated induction of IL-2 and IL-2 receptor alpha chain promoters, both of which are regulated by NF-AT factors.@@@@1@43@@oe@16-12-2010 976366101@GENIA Treebank@formal@@1@S@Position effect of translocations involving the inactive X chromosome: physical linkage to XIC/XIST does not lead to long-range de novo inactivation in human differentiated cells.@@@@1@27@@oe@16-12-2010 976366102@GENIA Treebank@formal@@1@S@Given the reported long-range cis-inactivating effect of the XIST gene in early embryonic development and the lack of requirement of X-chromosome-specific elements for propagating the inactive state, there exists the possibility of cis inactivation of autosomal material after de novo translocation to an inactive X chromosome (Xi) in differentiated cells.@@@@1@54@@oe@16-12-2010 976366103@GENIA Treebank@formal@@1@S@We have analyzed de novo radiation-induced translocations between the Xi and autosomes to study the maintenance and spreading of X-chromosome inactivation (X inactivation) in relation to the position of the X-inactivation center (XIC)/XIST in differentiated cells.@@@@1@42@@oe@16-12-2010 976366104@GENIA Treebank@formal@@1@S@Autosome/Xi translocations were detected by fluorescence in situ hybridization (FISH).@@@@1@13@@oe@16-12-2010 976366105@GENIA Treebank@formal@@1@S@The activation status of the chromosomes involved in the translocation was determined by simultaneous immunocytogenetic studies using antibodies against either BrdU incorporated at late S phase or acetylated histone H4.@@@@1@31@@oe@16-12-2010 976366106@GENIA Treebank@formal@@1@S@The position of XIC/XIST in the reciprocal products of the translocation was determined by XIST-specific FISH and computer enhancement.@@@@1@20@@oe@16-12-2010 976366107@GENIA Treebank@formal@@1@S@In other experiments, the Xq13 region carrying XIC/XIST was localized by computer enhancement of the DAPI banding pattern.@@@@1@20@@oe@16-12-2010 976366108@GENIA Treebank@formal@@1@S@Our study in differentiated cells provides a visual demonstration that physical separation from XIC/XIST does not result in reactivation of inactive X-chromosome material and that X inactivation is not spread to the translocated autosomes irrespective of the position of XIC/XIST.@@@@1@41@@oe@16-12-2010 976366109@GENIA Treebank@formal@@1@S@This observation suggests that physical linkage to XIC/XIST does not lead to de novo inactivation of autosomal material.@@@@1@19@@oe@16-12-2010 976490701@GENIA Treebank@formal@@1@S@Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid, cepharanthine, in chronically infected monocytic cells.@@@@1@20@@oe@16-12-2010 976490702@GENIA Treebank@formal@@1@S@Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have antiinflammatory, antiallergic, and immunomodulatory activities in vivo.@@@@1@26@@oe@16-12-2010 976490703@GENIA Treebank@formal@@1@S@As several inflammatory cytokines and oxidative stresses are involved in the pathogenesis of HIV-1 infection, we investigated the inhibitory effects of cepharanthine on tumor necrosis factor alpha (TNF-alpha)- and phorbol 12-myristate 13-acetate (PMA)-induced HIV-1 replication in chronically infected cell lines.@@@@1@48@@oe@16-12-2010 976490704@GENIA Treebank@formal@@1@S@Two chronically HIV-1-infected cell lines, U1 (monocytic) and ACH-2 (T lymphocytic), were stimulated with TNF-alpha or PMA and cultured in the presence of various concentrations of the compound.@@@@1@35@@oe@16-12-2010 976490705@GENIA Treebank@formal@@1@S@HIV-1 replication was determined by p24 antigen level.@@@@1@9@@oe@16-12-2010 976490706@GENIA Treebank@formal@@1@S@The inhibitory effects of cepharanthine on HIV-1 long terminal repeat (LTR)-driven gene expression and nuclear factor kappaB (NF-kappaB) activation were also examined.@@@@1@28@@oe@16-12-2010 976490707@GENIA Treebank@formal@@1@S@Cepharanthine dose dependently inhibited HIV-1 replication in TNF-alpha- and PMA-stimulated U1 cells but not in ACH-2 cells.@@@@1@18@@oe@16-12-2010 976490708@GENIA Treebank@formal@@1@S@Its 50% effective and cytotoxic concentrations were 0.016 and 2.2 microg/ml in PMA-stimulated U1 cells, respectively.@@@@1@19@@oe@16-12-2010 976490709@GENIA Treebank@formal@@1@S@Cepharanthine was found to suppress HIV-1 LTR-driven gene expression through the inhibition of NF-kappaB activation.@@@@1@16@@oe@16-12-2010 976490710@GENIA Treebank@formal@@1@S@These results indicate that cepharanthine is a highly potent inhibitor of HIV-1 replication in a chronically infected monocytic cell line.@@@@1@21@@oe@16-12-2010 976490711@GENIA Treebank@formal@@1@S@Since biscoclaurine alkaloids, containing cepharanthine as a major component, are widely used for the treatment of patients with various inflammatory diseases in Japan, cepharanthine should be further pursued for its chemotherapeutic potential in HIV-1-infected patients.@@@@1@39@@oe@16-12-2010 976525601@GENIA Treebank@formal@@1@S@Prostaglandin E2 Up-regulates HIV-1 long terminal repeat-driven gene activity in T cells via NF-kappaB-dependent and -independent signaling pathways.@@@@1@19@@oe@16-12-2010 976525602@GENIA Treebank@formal@@1@S@Replication of human immunodeficiency virus type-1 (HIV-1) is highly dependent on the state of activation of the infected cells and is modulated by interactions between viral and host cellular factors.@@@@1@33@@oe@16-12-2010 976525603@GENIA Treebank@formal@@1@S@Prostaglandin E2 (PGE2), a pleiotropic immunomodulatory molecule, is observed at elevated levels during HIV-1 infection as well as during the course of other pathogenic infections.@@@@1@30@@oe@16-12-2010 976525604@GENIA Treebank@formal@@1@S@In 1G5, a Jurkat-derived T cell line stably transfected with a luciferase gene driven by HIV-1 long terminal repeat (LTR), we found that PGE2 markedly enhanced HIV-1 LTR-mediated reporter gene activity.@@@@1@36@@oe@16-12-2010 976525605@GENIA Treebank@formal@@1@S@Experiments have been conducted to identify second messengers involved in this PGE2-dependent up-regulating effect on the regulatory element of HIV-1.@@@@1@21@@oe@16-12-2010 976525606@GENIA Treebank@formal@@1@S@In this study, we present evidence indicating that signal transduction pathways induced by PGE2 necessitate the participation of cyclic AMP, protein kinase A, and Ca2+.@@@@1@29@@oe@16-12-2010 976525607@GENIA Treebank@formal@@1@S@Experiments conducted with different HIV-1 LTR-based vectors suggested that PGE2-mediated activation effect on HIV-1 transcription was transduced via both NF-kappaB-dependent and -independent signaling pathways.@@@@1@25@@oe@16-12-2010 976525608@GENIA Treebank@formal@@1@S@The involvement of NF-kappaB in the PGE2-dependent activating effect on HIV-1 transcription was further confirmed using a kappaB-regulated luciferase encoding vector and by electrophoretic mobility shift assays.@@@@1@28@@oe@16-12-2010 976525609@GENIA Treebank@formal@@1@S@Results from Northern blot and flow cytometric analyses, as well as the use of a selective antagonist indicated that PGE2 modulation of HIV-1 LTR-driven reporter gene activity in studied T lymphoid cells is transduced via the EP4 receptor subtype.@@@@1@41@@oe@16-12-2010 976525610@GENIA Treebank@formal@@1@S@These results suggest that secretion of PGE2 by macrophages in response to infection or inflammatory activators could induce signaling events resulting in activation of proviral DNA present into T cells latently infected with HIV-1.@@@@1@35@@oe@16-12-2010 976529501@GENIA Treebank@formal@@1@S@Fcgamma receptor-mediated mitogen-activated protein kinase activation in monocytes is independent of Ras.@@@@1@13@@oe@16-12-2010 976529502@GENIA Treebank@formal@@1@S@Receptors for the Fc portion of immunoglobulin molecules (FcR) present on leukocyte cell membranes mediate a large number of cellular responses that are very important in host defense, including phagocytosis, cell cytotoxicity, production and secretion of inflammatory mediators, and modulation of the immune response.@@@@1@51@@oe@16-12-2010 976529503@GENIA Treebank@formal@@1@S@Cross-linking of FcR with immune complexes leads, first to activation of protein-tyrosine kinases.@@@@1@15@@oe@16-12-2010 976529504@GENIA Treebank@formal@@1@S@The molecular events that follow and that transduce signals from these receptors to the nucleus are still poorly defined.@@@@1@20@@oe@16-12-2010 976529505@GENIA Treebank@formal@@1@S@We have investigated the signal transduction pathway from Fc receptors that leads to gene activation and production of cytokines in monocytes.@@@@1@22@@oe@16-12-2010 976529506@GENIA Treebank@formal@@1@S@Cross-linking of FcR, on the THP-1 monocytic cell line, by immune complexes resulted in both activation of the transcription factor NF-kappaB and interleukin 1 production.@@@@1@28@@oe@16-12-2010 976529507@GENIA Treebank@formal@@1@S@These responses were completely blocked by tyrosine kinase inhibitors.@@@@1@10@@oe@16-12-2010 976529508@GENIA Treebank@formal@@1@S@In contrast, expression of dominant negative mutants of Ras and Raf-1, in these cells, did not have any effect on FcR-mediated nuclear factor activation, suggesting that the mitogen-activated protein kinase (MAPK) signaling pathway was not used by these receptors.@@@@1@46@@oe@16-12-2010 976529509@GENIA Treebank@formal@@1@S@However, MAPK activation was easily detected by in vitro kinase assays, after FcR cross-linking with immune complexes.@@@@1@20@@oe@16-12-2010 976529510@GENIA Treebank@formal@@1@S@Using the specific MAPK/extracellular signal-regulated kinase kinase (MAPK kinase) inhibitor PD98059, we found that MAPK activation is necessary for FcR-dependent activation of the nuclear factor NF-kappaB.@@@@1@30@@oe@16-12-2010 976529511@GENIA Treebank@formal@@1@S@These results strongly suggest that the signaling pathway from Fc receptors leading to expression of different genes important to leukocyte biology, initiates with tyrosine kinases and requires MAPK activation; but in contrast to other tyrosine kinase receptors, FcR-mediated MAPK activation does not involve Ras and Raf.@@@@1@50@@oe@16-12-2010 976542401@GENIA Treebank@formal@@1@S@CD4 promoter transactivation by human herpesvirus 6.@@@@1@8@@oe@16-12-2010 976542402@GENIA Treebank@formal@@1@S@The observation that human herpesvirus 6 (HHV-6) can induce CD4 gene transcription and expression in CD4(-) cells was reported several years ago (P.Lusso, A.De Maria, M.Malnati, F.Lori, S.E.DeRocco, M. Baseler, and R.C.Gallo, Nature 349:533-535, 1991) and subsequently confirmed (P.Lusso, M.S.Malnati, A.Garzino-Demo, R.W.Crowley, E. O.Long, and R.C.Gallo, Nature 362:458-462, 1993; G.Furlini, M. Vignoli, E.Ramazzotti, M.C.Re, G.Visani, and M.LaPlaca, Blood 87:4737-4745, 1996).@@@@1@96@@oe@16-12-2010 976542403@GENIA Treebank@formal@@1@S@Our objective was to identify the mechanisms underlying such phenomena.@@@@1@11@@oe@16-12-2010 976542404@GENIA Treebank@formal@@1@S@Using reporter gene constructs driven by the CD4 promoter, we report that HHV-6 can efficiently transactivate such genetic elements.@@@@1@21@@oe@16-12-2010 976542405@GENIA Treebank@formal@@1@S@Activation of the CD4 promoter occurs in the presence of the viral DNA polymerase inhibitor phosphonoformic acid, which limits expression to the immediate-early and early classes of viral genes.@@@@1@31@@oe@16-12-2010 976542406@GENIA Treebank@formal@@1@S@Using deletion mutants and specific CD4 promoter mutants, we identified an ATF/CRE binding site located at nucleotides -67 to -60 upstream of the CD4 gene transcription start site that is important for HHV-6 transactivation.@@@@1@36@@oe@16-12-2010 976542407@GENIA Treebank@formal@@1@S@The ATF/CRE site is also essential for CD4 promoter activation by forskolin, an activator of adenylate cyclase.@@@@1@19@@oe@16-12-2010 976542408@GENIA Treebank@formal@@1@S@Using electrophoretic mobility shift assays and specific antibodies, we showed that CREB-1 binds specifically to the -79 to -52 region of the CD4 promoter.@@@@1@26@@oe@16-12-2010 976542409@GENIA Treebank@formal@@1@S@Last, we have identified two open reading frames (ORFs) of HHV-6, U86 and U89 from the immediate-early locus A, that can transactivate the CD4 promoter in HeLa cells.@@@@1@34@@oe@16-12-2010 976542410@GENIA Treebank@formal@@1@S@However, transactivation of the CD4 promoter by ORFs U86 and U89 is independent of the CRE element, suggesting that additional HHV-6 ORFs are likely to contribute to CD4 gene activation.@@@@1@33@@oe@16-12-2010 976542411@GENIA Treebank@formal@@1@S@Taken together, our results will help to understand the complex interactions occurring between HHV-6 and the CD4 promoter and provide additional information regarding the class of transcription factors involved in the control of CD4 gene expression.@@@@1@38@@oe@16-12-2010 976665301@GENIA Treebank@formal@@1@S@Tumor suppressor proteins as regulators of cell differentiation.@@@@1@9@@oe@16-12-2010 976665302@GENIA Treebank@formal@@1@S@The products of the tumor suppressor genes are considered to function as specific inhibitors of tumor cell growth.@@@@1@19@@oe@16-12-2010 976665303@GENIA Treebank@formal@@1@S@In this communication, we present evidence to show that these proteins inhibit tumor cell proliferation by participating in the activation of tumor cell differentiation.@@@@1@26@@oe@16-12-2010 976665304@GENIA Treebank@formal@@1@S@The ML-1 human myeloblastic leukemia cells used in this study proliferate when treated with insulin-like growth factor I and transferrin but differentiate to monocytes when exposed to tumor necrosis factor alpha or transforming growth factor beta1, or to macrophage-like cells when treated with both these cytokines.@@@@1@48@@oe@16-12-2010 976665305@GENIA Treebank@formal@@1@S@Initiation of proliferation but not of differentiation was followed by a 20- to 25-fold increase in the nuclear level of the DNA polymerase-associated processivity factor PCNA and of the proliferation-specific transcription factor E2F1.@@@@1@34@@oe@16-12-2010 976665306@GENIA Treebank@formal@@1@S@In contrast, induction of differentiation but not of proliferation was followed by a 25- to 30-fold increase in the nuclear level of the tumor suppressor proteins p53 (wild type), pRb, and p130/Rb2 and of the p53-dependent cyclin kinase inhibitor p21/Cip1.@@@@1@46@@oe@16-12-2010 976665307@GENIA Treebank@formal@@1@S@p53 and p21/Cip1, respectively, inhibit the expression and activation of PCNA, whereas p130 and pRb, respectively, inhibit the expression and activation of E2F1.@@@@1@29@@oe@16-12-2010 976665308@GENIA Treebank@formal@@1@S@As a result, G1-S-associated DNA and mRNA synthesis is inhibited, growth uncoupled from differentiation, and maturation enabled to proceed.@@@@1@23@@oe@16-12-2010 976665309@GENIA Treebank@formal@@1@S@Where this function of the tumor suppressor proteins is impaired, the capacity for differentiation is lost, which leads to the sustained proliferation that is characteristic of the cancer cell.@@@@1@32@@oe@16-12-2010 976716501@GENIA Treebank@formal@@1@S@musculin: a murine basic helix-loop-helix transcription factor gene expressed in embryonic skeletal muscle.@@@@1@15@@oe@16-12-2010 976716502@GENIA Treebank@formal@@1@S@We describe the embryonic expression of musculin, a new murine member of the bHLH family of transcription factors.@@@@1@20@@oe@16-12-2010 976716503@GENIA Treebank@formal@@1@S@Musculin protein is closely related to human ABF-1, which is expressed in activated B cells, and to epicardin/capsulin/Pod-1, which is expressed in branchial myoblasts, visceral and urogenital mesoderm and epicardium.@@@@1@35@@oe@16-12-2010 976716504@GENIA Treebank@formal@@1@S@In situ hybridisation revealed musculin expression in embryos was largely restricted to the embryonic skeletal muscle lineage.@@@@1@18@@oe@16-12-2010 976716505@GENIA Treebank@formal@@1@S@While all skeletal muscles expressed the gene, only a subset of myocytes within each muscle were positive, indicating molecular heterogeneity within fetal muscle.@@@@1@26@@oe@16-12-2010 976716506@GENIA Treebank@formal@@1@S@Copyright 1998 Elsevier Science Ireland Ltd.@@@@1@7@@oe@16-12-2010 976716507@GENIA Treebank@formal@@1@S@All Rights Reserved.@@@@1@4@@oe@16-12-2010 976859401@GENIA Treebank@formal@@1@S@Analysis of cytokine signaling in patients with extrinsic asthma and hyperimmunoglobulin E.@@@@1@13@@oe@16-12-2010 976859402@GENIA Treebank@formal@@1@S@BACKGROUND: Recent data suggest that the regulation of class switching to IgE by cytokines is mediated by STAT transcription factors.@@@@1@22@@oe@16-12-2010 976859403@GENIA Treebank@formal@@1@S@The induction of IgE by IL-4 and IL-13 occurs through the activation of the intracellular signal-transducing protein Stat6, whereas the inhibition of IgE class switching by interferon-y (IFN-gamma) occurs through the activation of Statl.@@@@1@38@@oe@16-12-2010 976859404@GENIA Treebank@formal@@1@S@OBJECTIVE: We hypothesized that in extrinsic asthma or in cases of markedly elevated IgE (ie, hyperimmunoglobulin E [HIE]) increased levels of IgE may be associated with alterations in the cytokine levels or the activation of Stat6.@@@@1@43@@oe@16-12-2010 976859405@GENIA Treebank@formal@@1@S@METHODS: PBMCs and sera from 8 patients with extrinsic asthma (mean IgE, 285+/-100 IU/mL), 3 patients with HIE (mean IgE, 7050+/-1122 IU/mL), and 14 nonatopic control subjects (mean IgE, 112+/-28 IU/mL) were analyzed.@@@@1@46@@oe@16-12-2010 976859406@GENIA Treebank@formal@@1@S@RESULTS: The mean IL-4 level detected by ELISA was much greater in patients with HIE than control subjects (88.6+/-11.5 pg/mL vs 11.5+/-7.1 pg/mL, P = .005), and increased IL-4 levels among patients with both asthma and HIE correlated with the increased IgE levels.@@@@1@49@@oe@16-12-2010 976859407@GENIA Treebank@formal@@1@S@In contrast, IL-13 levels were not elevated.@@@@1@9@@oe@16-12-2010 976859408@GENIA Treebank@formal@@1@S@Levels of Stat6 protein present in PBMCs did not differ in the patients and control subjects.@@@@1@17@@oe@16-12-2010 976859409@GENIA Treebank@formal@@1@S@Examination of Stat6 DNA-binding activity demonstrated no activation of IL-4 signaling in patients with either HIE or acute asthma.@@@@1@20@@oe@16-12-2010 976859410@GENIA Treebank@formal@@1@S@Interestingly, evidence for the presence of B cells that have already switched to IgE was seen in PBMCs of several patients with asthma or HIE.@@@@1@27@@oe@16-12-2010 976859411@GENIA Treebank@formal@@1@S@CONCLUSION: These results indicate that (1) IgE production in asthma and HIE usually is associated with elevated levels of IL-4, but not IL-13, in the peripheral blood; (2) the increased sera IL-4 levels in asthma and HIE are not sufficient to induce Stat6 activation in PBMCs; and (3) evidence of switch recombination to epsilon may be detected in isolated cases of elevated IgE.@@@@1@75@@oe@16-12-2010 976859412@GENIA Treebank@formal@@1@S@This implies that high levels of IgE in these patients either results from B cells that have already undergone class switching, from Ig class switching that is localized to target tissues, or both.@@@@1@36@@oe@16-12-2010 978014301@GENIA Treebank@formal@@1@S@Cross-priming of CTL responses in vivo does not require antigenic peptides in the endoplasmic reticulum of immunizing cells.@@@@1@19@@oe@16-12-2010 978014302@GENIA Treebank@formal@@1@S@It has been proposed that the cross-priming of CTL responses in vivo involves the transfer to host APCs of heat shock protein glycoprotein 96-chaperoned antigenic peptides released from the endoplasmic reticulum (ER) of dying or infected cells.@@@@1@40@@oe@16-12-2010 978014303@GENIA Treebank@formal@@1@S@We have tested this possibility directly using TAP-deficient cell lines lacking antigenic ER peptides derived from two model Ags, the human adenovirus type 5 early regions E1A and E1B.@@@@1@31@@oe@16-12-2010 978014304@GENIA Treebank@formal@@1@S@Although both proteins were well expressed, the cells were not recognized by E1A- or E1B-specific CTLs unless the relevant epitope was either provided exogenously as a synthetic peptide or targeted to the ER in a TAP-independent fashion.@@@@1@39@@oe@16-12-2010 978014305@GENIA Treebank@formal@@1@S@Despite the absence of these ER peptides, the TAP1-/- cells were able to efficiently cross-prime E1A- and E1B-specific CTLs following immunization of syngeneic mice.@@@@1@26@@oe@16-12-2010 978014306@GENIA Treebank@formal@@1@S@These results indicate that, although purified peptide/glycoprotein 96 complexes are potent immunogens, the mechanism of CTL cross-priming in vivo does not depend upon antigenic peptides in the ER of immunizing cells.@@@@1@34@@oe@16-12-2010 978014501@GENIA Treebank@formal@@1@S@Differential responsiveness of the IL-5 and IL-4 genes to transcription factor GATA-3.@@@@1@13@@oe@16-12-2010 978014502@GENIA Treebank@formal@@1@S@The cytokines IL-4 and IL-5 are often coordinately produced by Th2 cells as in asthma.@@@@1@16@@oe@16-12-2010 978014503@GENIA Treebank@formal@@1@S@However, it is unclear whether similar molecular mechanisms underlie transcription of the two genes.@@@@1@16@@oe@16-12-2010 978014504@GENIA Treebank@formal@@1@S@We have previously shown that the transcription factor GATA-3 is expressed in Th2 but not Th1 cells and is crucial for activation of the IL-5 promoter by different stimuli.@@@@1@30@@oe@16-12-2010 978014505@GENIA Treebank@formal@@1@S@In a different study, GATA-3 was shown to be sufficient for the expression of IL-4 and other Th2 cytokine genes.@@@@1@22@@oe@16-12-2010 978014506@GENIA Treebank@formal@@1@S@Here, we show that ectopic expression of GATA-3 is sufficient to drive IL-5 but not IL-4 gene expression.@@@@1@20@@oe@16-12-2010 978014507@GENIA Treebank@formal@@1@S@Also, in Th2 cells, antisense GATA-3 RNA inhibits IL-5 but not IL-4 promoter activation.@@@@1@17@@oe@16-12-2010 978014508@GENIA Treebank@formal@@1@S@The induction of IL-5 gene expression by GATA-3 involves high affinity binding of GATA-3 to an inverted GATA repeat in the IL-5 promoter.@@@@1@24@@oe@16-12-2010 978014601@GENIA Treebank@formal@@1@S@GATA-3-dependent enhancer activity in IL-4 gene regulation.@@@@1@8@@oe@16-12-2010 978014602@GENIA Treebank@formal@@1@S@Previously, we analyzed the proximal IL-4 promoter in directing Th2-specific activity.@@@@1@13@@oe@16-12-2010 978014603@GENIA Treebank@formal@@1@S@An 800-base pair proximal promoter conferred some Th2-selective expression in transgenic mice.@@@@1@13@@oe@16-12-2010 978014604@GENIA Treebank@formal@@1@S@However, this region directed extremely low reporter mRNA levels relative to endogenous IL-4 mRNA, suggesting that full gene activity requires additional enhancer elements.@@@@1@26@@oe@16-12-2010 978014605@GENIA Treebank@formal@@1@S@Here, we analyzed large genomic IL-4 regions for enhancer activity and interaction with transcription factors.@@@@1@17@@oe@16-12-2010 978014606@GENIA Treebank@formal@@1@S@The proximal IL-4 promoter is only moderately augmented by GATA-3, but certain genomic regions significantly enhanced GATA-3 promoter transactivation.@@@@1@21@@oe@16-12-2010 978014607@GENIA Treebank@formal@@1@S@Some enhancing regions contained consensus, GATA sites that bound Th2-specific complexes.@@@@1@13@@oe@16-12-2010 978014608@GENIA Treebank@formal@@1@S@However, retroviral transduction of GATA-3 into developing T cells induced IL-5 to full Th2 levels, but only partially restored IL-4 production.@@@@1@24@@oe@16-12-2010 978014609@GENIA Treebank@formal@@1@S@Thus, we propose that GATA-3 is permissive, but not sufficient, for full IL-4 enhancement and may act through GATA elements surrounding the IL-13/IL-4 gene locus.@@@@1@29@@oe@16-12-2010 978371201@GENIA Treebank@formal@@1@S@Seminoma in a postmenopausal woman with a Y;15 translocation in peripheral blood lymphocytes and a t(Y;15)/45,X Turner mosaic pattern in skin fibroblasts.@@@@1@23@@oe@16-12-2010 978371202@GENIA Treebank@formal@@1@S@We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses.@@@@1@20@@oe@16-12-2010 978371203@GENIA Treebank@formal@@1@S@The patient was a phenotypic female with late onset menarche (18 years of age), who was amenorrhoeic for the first year, followed by menses of one to three days' slight flow with dysmenorrhoea, but an otherwise normal menstrual history.@@@@1@46@@oe@16-12-2010 978371204@GENIA Treebank@formal@@1@S@A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass.@@@@1@24@@oe@16-12-2010 978371205@GENIA Treebank@formal@@1@S@Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46,X,-Y,t(Y;15)(q12;p13).@@@@1@12@@oe@16-12-2010 978371206@GENIA Treebank@formal@@1@S@Cytogenetic examination of the patient's younger brother, who had fathered three healthy children, showed an identical karyotype.@@@@1@21@@oe@16-12-2010 978371207@GENIA Treebank@formal@@1@S@Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in skin samples from the patient's elbow and genital regions, although there were no clinical stigmata of Turner syndrome.@@@@1@29@@oe@16-12-2010 978371208@GENIA Treebank@formal@@1@S@An androgen receptor binding assay of cultured genital skin fibroblasts was negative.@@@@1@13@@oe@16-12-2010 978371209@GENIA Treebank@formal@@1@S@Molecular analysis using Southern blot hybridisation, PCR, and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences, including the SRY (sex determining region of the Y chromosome) gene sequence.@@@@1@48@@oe@16-12-2010 978371210@GENIA Treebank@formal@@1@S@These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female, although we cannot exclude abnormalities of other genes related to sex differentiation.@@@@1@37@@oe@16-12-2010 978390901@GENIA Treebank@formal@@1@S@Differential RNA display identifies novel genes associated with decreased vitamin D receptor expression.@@@@1@14@@oe@16-12-2010 978390902@GENIA Treebank@formal@@1@S@To characterize further the function of the intracellular vitamin D receptor (VDR), we have developed stable transfectant variants of a vitamin D-responsive cell line (U937) which express either decreased or increased numbers of VDR.@@@@1@40@@oe@16-12-2010 978390903@GENIA Treebank@formal@@1@S@In this study we have analyzed changes in gene expression associated with this variable VDR expression.@@@@1@17@@oe@16-12-2010 978390904@GENIA Treebank@formal@@1@S@Initial experiments indicated that a 50% decrease in VDR levels was associated with a 2-fold increase in cell proliferation and a similar rise in c-myc mRNA expression.@@@@1@29@@oe@16-12-2010 978390905@GENIA Treebank@formal@@1@S@Further studies were carried out using differential RNA display (DD).@@@@1@13@@oe@16-12-2010 978390906@GENIA Treebank@formal@@1@S@Sequence analysis of DD products revealed two cDNAs with identity to known gene products: the catalytic sub-unit of DNA-protein kinase (DNA-PK(CS)), and the peroxisomal enzyme 17beta-hydroxysteroid dehydrogenase type IV (17beta-HSD IV).@@@@1@38@@oe@16-12-2010 978390907@GENIA Treebank@formal@@1@S@Northern analysis confirmed that expression of both mRNAs was reduced in cells with decreased numbers of VDR.@@@@1@18@@oe@16-12-2010 978390908@GENIA Treebank@formal@@1@S@Down-regulation of 17beta-HSD IV mRNA expression was associated with enhanced estradiol inactivation by U937 cells, suggesting a link between estrogenic pathways and cell proliferation.@@@@1@26@@oe@16-12-2010 978390909@GENIA Treebank@formal@@1@S@Further Northern analyses indicated that there was no significant change in 17beta-HSD IV or DNA-PK(CS) mRNA levels following treatment with 1,25(OH)2D3, although expression of both genes varied with changes in cell proliferation.@@@@1@34@@oe@16-12-2010 978390910@GENIA Treebank@formal@@1@S@These data suggest that, in addition to its established role as a hormone-dependent trans-activator, VDR may influence gene expression by ligand-independent mechanisms.@@@@1@25@@oe@16-12-2010 978466701@GENIA Treebank@formal@@1@S@c-fos and c-jun mRNA expression in activated cord and adult lymphocytes: an analysis by Northern hybridization.@@@@1@18@@oe@16-12-2010 978466702@GENIA Treebank@formal@@1@S@BACKGROUND AND OBJECTIVES: To further analyze the neonatal immune response to an antigenic challenge such as blood transfusion, c-fos and c-jun mRNA expression were analyzed in twelve in-vitro-stimulated normal cord blood and ten in-vitro-stimulated normal adult peripheral blood lymphocyte samples.@@@@1@43@@oe@16-12-2010 978466703@GENIA Treebank@formal@@1@S@MATERIALS AND METHODS: Lymphocyte samples were stimulated by either the mitogen phytohemagglutinin (PHA) or the monoclonal antibody alphaCD3.@@@@1@22@@oe@16-12-2010 978466704@GENIA Treebank@formal@@1@S@Proliferation rate and Northern blot hybridization were employed.@@@@1@9@@oe@16-12-2010 978466705@GENIA Treebank@formal@@1@S@RESULTS: Cord lymphocytes revealed a greater proliferation rate with PHA and alphaCD3 than adult lymphocytes (p = 0.0081 and 0.0023, respectively).@@@@1@26@@oe@16-12-2010 978466706@GENIA Treebank@formal@@1@S@In addition, Northern blot analysis of cord and adult samples revealed similar maximal increases in c-fos (99+/-15 and 126+/-11%, p = 0.0126) and c-jun (123+/-9 and 185+/-38%, p = 0.0291) mRNA expression, respectively, as early as 15 min post-alphaCD3 stimulation.@@@@1@52@@oe@16-12-2010 978466707@GENIA Treebank@formal@@1@S@Adult lymphocytes showed an equivalent increase in mRNA expression of c-fos and c-jun (140+/-25 and 155+/-31%) at 30 min post-PHA stimulation, while cord lymphocyte maximum c-fos and c-jun expression (82+/-6 and 142+/-12%) occurred at 15 min post-PHA stimulation (c-fos, p = 0.0354; c-jun, p = 0.0112).@@@@1@59@@oe@16-12-2010 978466708@GENIA Treebank@formal@@1@S@CONCLUSION: Although cord lymphocyte proliferation rates were significantly greater than those of adult lymphocytes following stimulation, lymphocyte activation, as analyzed by c-fos and c-jun mRNA expression, appears similar in both cord and adult samples.@@@@1@39@@oe@16-12-2010 978466709@GENIA Treebank@formal@@1@S@We conclude that cord lymphocyte activation exhibits an adult-type profile.@@@@1@11@@oe@16-12-2010 978688301@GENIA Treebank@formal@@1@S@Downstream activation of a TATA-less promoter by Oct-2, Bob1, and NF-kappaB directs expression of the homing receptor BLR1 to mature B cells.@@@@1@25@@oe@16-12-2010 978688302@GENIA Treebank@formal@@1@S@The chemokine receptor, BLR1, is a major regulator of the microenvironmental homing of B cells in lymphoid organs.@@@@1@21@@oe@16-12-2010 978688303@GENIA Treebank@formal@@1@S@In vitro studies identify three essential elements of the TATA-less blr1 core promoter that confer cell type- and differentiation-specific expression in the B cells of both humans and mice, a functional promoter region (-36 with respect to the transcription start site), a NF-kappaB motif (+44), and a noncanonical octamer motif (+157).@@@@1@61@@oe@16-12-2010 978688304@GENIA Treebank@formal@@1@S@The importance of these sites was confirmed by in vivo studies in gene-targeted mice deficient of either Oct-2, Bob1, or both NF-kappaB subunits p50 and p52.@@@@1@29@@oe@16-12-2010 978688305@GENIA Treebank@formal@@1@S@In all of these animals, the expression of BLR1 was reduced or absent.@@@@1@15@@oe@16-12-2010 978688306@GENIA Treebank@formal@@1@S@In mice deficient only of p52/NF-kappaB, BLR1 expression was unaffected.@@@@1@12@@oe@16-12-2010 978688307@GENIA Treebank@formal@@1@S@Thus our data demonstrate that BLR1 is a target gene for Oct-2, Bob1, and members of the NF-kappaB/Rel family and provides a link to the impaired B cell functions in mice deficient for these factors.@@@@1@38@@oe@16-12-2010 978718501@GENIA Treebank@formal@@1@S@Differential regulation of coproporphyrinogen oxidase gene between erythroid and nonerythroid cells.@@@@1@12@@oe@16-12-2010 978718502@GENIA Treebank@formal@@1@S@Coproporphyrinogen oxidase (CPO) catalyzes the sixth step of the heme biosynthetic pathway.@@@@1@15@@oe@16-12-2010 978718503@GENIA Treebank@formal@@1@S@To assess the tissue-specific regulation of the CPO gene promoter, mouse genomic DNA clones for CPO were isolated.@@@@1@20@@oe@16-12-2010 978718504@GENIA Treebank@formal@@1@S@Structural analysis demonstrated that the mouse CPO gene spans approximately 11 kb and consists of seven exons, just like its human counterpart.@@@@1@24@@oe@16-12-2010 978718505@GENIA Treebank@formal@@1@S@Functional analysis of the promoter by transient transfection assays indicated that synergistic action between an SP-1-like element at -21/-12, a GATA site at -59/-54, and a novel regulatory element, CPRE (-GGACTACAG-) at -49/-41, is essential for the promoter activity in murine erythroleukemia (MEL) cells.@@@@1@53@@oe@16-12-2010 978718506@GENIA Treebank@formal@@1@S@In nonerythroid NIH3T3 cells, however, the GATA site is not required.@@@@1@14@@oe@16-12-2010 978718507@GENIA Treebank@formal@@1@S@Gel mobility shift assays demonstrated that specific DNA-protein complexes can be formed with each element, and that there are cell-specific differences in factors, which bind to the SP-1-like element between MEL and NIH3T3 cells.@@@@1@37@@oe@16-12-2010 978718508@GENIA Treebank@formal@@1@S@These results provide evidence for differential regulation of the promoter function of CPO gene between erythroid and nonerythroid cells.@@@@1@20@@oe@16-12-2010 978718509@GENIA Treebank@formal@@1@S@Copyright 1998 by The American Society of Hematology@@@@1@8@@oe@16-12-2010 978901001@GENIA Treebank@formal@@1@S@Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands [see comments]@@@@1@17@@oe@16-12-2010 978901002@GENIA Treebank@formal@@1@S@Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes.@@@@1@17@@oe@16-12-2010 978901003@GENIA Treebank@formal@@1@S@Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis.@@@@1@15@@oe@16-12-2010 978901004@GENIA Treebank@formal@@1@S@Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-1, lymphoid-enhancer binding factor 1, and TATA-box binding protein.@@@@1@30@@oe@16-12-2010 978901005@GENIA Treebank@formal@@1@S@These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays.@@@@1@19@@oe@16-12-2010 978901006@GENIA Treebank@formal@@1@S@When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity.@@@@1@27@@oe@16-12-2010 978901007@GENIA Treebank@formal@@1@S@The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication.@@@@1@38@@oe@16-12-2010 979154101@GENIA Treebank@formal@@1@S@The role of caspases in T cell development and the control of immune responses.@@@@1@15@@oe@16-12-2010 979154102@GENIA Treebank@formal@@1@S@Apoptosis is responsible for the removal of potentially autoreactive or useless T cells during thymic selection and activated T cells in the periphery.@@@@1@24@@oe@16-12-2010 979154103@GENIA Treebank@formal@@1@S@Specific families of receptors, kinases, transcription factors, and cysteine proteases, termed caspases, are involved in the apoptotic cascade leading to proteolysis of specific substrates and to morphological changes associated with programmed cell death.@@@@1@39@@oe@16-12-2010 979154104@GENIA Treebank@formal@@1@S@Although common members of the apoptotic cascade are shared between different cell types, it appears that cell-specific factors can influence the response to a given apoptotic stimuli.@@@@1@29@@oe@16-12-2010 979154105@GENIA Treebank@formal@@1@S@Characterization and understanding of the basic mechanisms involved in the different pathways protecting or leading to cell death may provide novel ways to control inappropriate apoptosis involved in several diseases.@@@@1@31@@oe@16-12-2010 979214201@GENIA Treebank@formal@@1@S@Interleukin 1beta mediates the modulatory effects of monocytes on LNCaP human prostate cancer cells.@@@@1@15@@oe@16-12-2010 979214202@GENIA Treebank@formal@@1@S@Proliferative and secretory responses in androgen-sensitive prostate cancer LNCaP cells are regulated by steroid and peptide hormones and by differentiation-promoting substances.@@@@1@22@@oe@16-12-2010 979214203@GENIA Treebank@formal@@1@S@In the present study, we evaluated whether peripheral blood monocytes that exhibit anti-tumour activity in haematopoietic and solid tumours influence growth and secretion in the LNCaP cell line.@@@@1@30@@oe@16-12-2010 979214204@GENIA Treebank@formal@@1@S@For this purpose, LNCaP cells were incubated with monocyte-conditioned medium (MCM), and proliferation as well as expression of androgen receptor (AR) and secretion of prostate-specific antigen (PSA) were assessed.@@@@1@38@@oe@16-12-2010 979214205@GENIA Treebank@formal@@1@S@Conditioned medium from monocytes reduced proliferation in a dose-dependent manner.@@@@1@11@@oe@16-12-2010 979214206@GENIA Treebank@formal@@1@S@Incubation with 40% MCM caused a 50% reduction in cell proliferation.@@@@1@14@@oe@16-12-2010 979214207@GENIA Treebank@formal@@1@S@AR protein decreased by 70% and PSA levels in supernatants from LNCaP cells were reduced by approximately 80% following treatment with MCM.@@@@1@25@@oe@16-12-2010 979214208@GENIA Treebank@formal@@1@S@We focused on the contribution of two major products of activated monocytes, prostaglandin E2 and interleukin 1beta (IL-1beta), to the MCM modulatory action.@@@@1@28@@oe@16-12-2010 979214209@GENIA Treebank@formal@@1@S@LNCaP cells treated with prostaglandin E2 showed neither a reduction in proliferation nor a down-regulation of AR and PSA levels.@@@@1@21@@oe@16-12-2010 979214210@GENIA Treebank@formal@@1@S@The effects of MCM on cellular proliferation, AR protein and PSA secretion were abolished by pretreatment of MCM with a neutralizing anti-IL-1beta antibody.@@@@1@25@@oe@16-12-2010 979214211@GENIA Treebank@formal@@1@S@In addition, recombinant IL-1beta was able to replace MCM for the inhibition of proliferation and down-regulation of AR and PSA proteins.@@@@1@23@@oe@16-12-2010 979214212@GENIA Treebank@formal@@1@S@LNCaP cells were shown to express the IL-1beta receptor type 1, which transduces IL-1beta signal.@@@@1@17@@oe@16-12-2010 979214213@GENIA Treebank@formal@@1@S@Our findings reveal that monocyte-derived IL-1beta inhibits the proliferation of androgen-responsive prostate tumour cells and reduces AR and PSA levels.@@@@1@21@@oe@16-12-2010 979229401@GENIA Treebank@formal@@1@S@Identification of transcription factors expressed during ATRA-induced neutrophil differentiation of HL60 cells.@@@@1@13@@oe@16-12-2010 979229402@GENIA Treebank@formal@@1@S@A recent clinical therapeutic initiative has been the use of chemical agents which induce the leukaemic cells to overcome their block in differentiation.@@@@1@24@@oe@16-12-2010 979229403@GENIA Treebank@formal@@1@S@In order to understand this block the cascade of molecular events needs to be characterized.@@@@1@16@@oe@16-12-2010 979229404@GENIA Treebank@formal@@1@S@Haemopoietic differentiation is ultimately controlled at the level of gene transcription which is mediated by an array of transcription factors.@@@@1@21@@oe@16-12-2010 979229405@GENIA Treebank@formal@@1@S@Many transcription factors contain similar structural protein sequences, and we have used an RT-PCR-based approach to isolate sequences, from transcription factor gene families which share similar domains.@@@@1@30@@oe@16-12-2010 979229406@GENIA Treebank@formal@@1@S@Degenerate primers corresponding to the TFIIIA zinc-finger consensus amino acid sequences and to the POU-homeodomain and POU-specific domain were used to amplify genes on the basis that they contained similarities in structural motifs shared within these families of transcription factors.@@@@1@41@@oe@16-12-2010 979229407@GENIA Treebank@formal@@1@S@A serum-independent HL60 cell line was induced towards the neutrophil lineage by treatment with all-trans retinoic acid (ATRA) for 24 h.@@@@1@24@@oe@16-12-2010 979229408@GENIA Treebank@formal@@1@S@CD38+ cells committed towards this lineage were enriched and a population of these cells treated with dihydroxyvitamin D3 to induce neutrophil maturation.@@@@1@23@@oe@16-12-2010 979229409@GENIA Treebank@formal@@1@S@RNA extracted from uninduced, ATRA-induced CD38+ cells, and vitamin D3 treated maturing cell cultures were amplified using the degenerate primers.@@@@1@23@@oe@16-12-2010 979229410@GENIA Treebank@formal@@1@S@PCR fragments were cloned, sequenced, clustered into homologous groups, and the group sequences searched on the GenBank database.@@@@1@22@@oe@16-12-2010 979229411@GENIA Treebank@formal@@1@S@The Oct 1 transcription factor, and a very close homologue, KIAA0144, was identified using the POU family primers.@@@@1@22@@oe@16-12-2010 979229412@GENIA Treebank@formal@@1@S@The zinc-finger primers identified three zinc-finger genes.@@@@1@8@@oe@16-12-2010 979229413@GENIA Treebank@formal@@1@S@The pattern of gene expression was suggested from the number of clones in each group at neutrophil commitment and maturation.@@@@1@21@@oe@16-12-2010 979229414@GENIA Treebank@formal@@1@S@The differential expression of the genes in the zinc finger and POU families will lead to a better understanding of the cascade of gene expression which occurs following ATRA-induced differentiation.@@@@1@31@@oe@16-12-2010 979423801@GENIA Treebank@formal@@1@S@Relationship between IkappaBalpha constitutive expression, TNFalpha synthesis, and apoptosis in EBV-infected lymphoblastoid cells.@@@@1@16@@oe@16-12-2010 979423802@GENIA Treebank@formal@@1@S@In order to understand the role of NF-kappaB in EBV transformation we have established stably transfected IkappaBalpha into lymphoblastoid cells.@@@@1@21@@oe@16-12-2010 979423803@GENIA Treebank@formal@@1@S@Two clones were obtained in which the loss of NF-kappaB binding activity correlated with the constitutive expression of the transgenic IkappaBalpha.@@@@1@22@@oe@16-12-2010 979423804@GENIA Treebank@formal@@1@S@Protein latency expression was determined by immunocytochemistry.@@@@1@8@@oe@16-12-2010 979423805@GENIA Treebank@formal@@1@S@Expression of surface markers, intracytoplasmic content of cytokines cell cycle analysis after BrdU incorporation and DNA staining with propidium iodide were studied by flow cytometry.@@@@1@27@@oe@16-12-2010 979423806@GENIA Treebank@formal@@1@S@Percentage of apoptotic cells was determined by in-situ labelling of DNA strand breaks.@@@@1@14@@oe@16-12-2010 979423807@GENIA Treebank@formal@@1@S@No significative changes in EBV latency nor in cell surface marker expression was found.@@@@1@15@@oe@16-12-2010 979423808@GENIA Treebank@formal@@1@S@In contrast, intracytoplasmic TNFalpha levels were strongly reduced in transfected clones.@@@@1@13@@oe@16-12-2010 979423809@GENIA Treebank@formal@@1@S@Furthermore, 30% of IkappaBalpha transfected cells were apoptotic after 8 h of TNFalpha treatment.@@@@1@17@@oe@16-12-2010 979423810@GENIA Treebank@formal@@1@S@This correlated with a strong reduction of BrdU incorporation after 24 h of TNFalpha treatment.@@@@1@16@@oe@16-12-2010 979423811@GENIA Treebank@formal@@1@S@No effect was seen with non transfected cells or with cells transfected with a control plasmid.@@@@1@17@@oe@16-12-2010 979423812@GENIA Treebank@formal@@1@S@Our results suggest that the TNFalpha gene could be one of the targets of NF-kappaB in EBV infected cells and that NF-kappaB protects EBV-infected cells from apoptosis induced by TNFalpha, which may favour the proliferative effect of this cytokine.@@@@1@41@@oe@16-12-2010 979424101@GENIA Treebank@formal@@1@S@Signalling into the T-cell nucleus: NFAT regulation.@@@@1@9@@oe@16-12-2010 979424102@GENIA Treebank@formal@@1@S@The nuclear factor of activated T cells (NFAT) plays an important role in T-cell biology.@@@@1@18@@oe@16-12-2010 979424103@GENIA Treebank@formal@@1@S@Activation of T cells results in the rapid calcineurin-dependent translocation of NFAT transcription factors from the cytoplasm to the nucleus.@@@@1@21@@oe@16-12-2010 979424104@GENIA Treebank@formal@@1@S@This translocation process coupled to the subsequent active maintenance of NFAT in the nucleus compartment is critical for the induction of expression of several genes encoding cytokines and membrane proteins that modulate immune responses.@@@@1@35@@oe@16-12-2010 979424105@GENIA Treebank@formal@@1@S@The molecular cloning of the NFAT family of transcription factors has facilitated rapid progress in the understanding of the signalling mechanisms that control the activity of NFAT.@@@@1@28@@oe@16-12-2010 979437501@GENIA Treebank@formal@@1@S@Uncoupling activation-dependent HS1 phosphorylation from nuclear factor of activated T cells transcriptional activation in Jurkat T cells: differential signaling through CD3 and the costimulatory receptors CD2 and CD28.@@@@1@30@@oe@16-12-2010 979437502@GENIA Treebank@formal@@1@S@CD3, CD2, and CD28 are functionally distinct receptors on T lymphocytes.@@@@1@14@@oe@16-12-2010 979437503@GENIA Treebank@formal@@1@S@Engagement of any of these receptors induces the rapid tyrosine phosphorylation of a shared group of intracellular signaling proteins, including Vav, Cbl, p85 phosphoinositide 3-kinase, and the Src family kinases Lck and Fyn.@@@@1@38@@oe@16-12-2010 979437504@GENIA Treebank@formal@@1@S@Ligation of CD3 also induces the tyrosine phosphorylation of HS1, a 75-kDa hematopoietic cell-specific intracellular signaling protein of unknown function.@@@@1@22@@oe@16-12-2010 979437505@GENIA Treebank@formal@@1@S@We have examined changes in HS1 phosphorylation after differential stimulation of CD3, CD2, and CD28 to elucidate its role in T cells and to further delineate the signaling pathways recruited by these receptors.@@@@1@36@@oe@16-12-2010 979437506@GENIA Treebank@formal@@1@S@Unlike ligation of CD3, stimulation with anti-CD28 mAb or CHO cells expressing the CD28 ligands CD80 or CD86 did not lead to tyrosine phosphorylation of HS1 in Jurkat T cells.@@@@1@32@@oe@16-12-2010 979437507@GENIA Treebank@formal@@1@S@Additionally, no tyrosine phosphorylation of HS1 was induced by mitogenic pairs of anti-CD2 mAbs capable of activating the transcription factor NFAT (nuclear factor of activated T cells).@@@@1@31@@oe@16-12-2010 979437508@GENIA Treebank@formal@@1@S@Costimulation through CD28 and/or CD2 did not modulate the CD3-dependent phosphorylation of HS1.@@@@1@14@@oe@16-12-2010 979437509@GENIA Treebank@formal@@1@S@In vivo studies indicated that CD3-induced HSI phosphorylation was dependent upon both the Src family tyrosine kinase Lck and the tyrosine phosphatase CD45, did not require MEK1 kinase activity, and was regulated by protein kinase C activation.@@@@1@40@@oe@16-12-2010 979437510@GENIA Treebank@formal@@1@S@Thus, although CD3, CD28, and CD2 activate many of the same signaling molecules, they differed in their capacity to induce the tyrosine phosphorylation of HSI.@@@@1@30@@oe@16-12-2010 979437511@GENIA Treebank@formal@@1@S@Furthermore, activation-dependent tyrosine phosphorylation of HS1 was not required for NFAT transcriptional activation.@@@@1@15@@oe@16-12-2010 979438601@GENIA Treebank@formal@@1@S@A mouse carrying genetic defect in the choice between T and B lymphocytes.@@@@1@14@@oe@16-12-2010 979438602@GENIA Treebank@formal@@1@S@Transgenic mice with human CD3epsilon gene have been shown to exhibit early arrest of T cell development in the thymus.@@@@1@21@@oe@16-12-2010 979438603@GENIA Treebank@formal@@1@S@The present study shows that, instead of T cells, B cells are generated in the thymus of a line, tg epsilon26, of the human CD3epsilon transgenic mice.@@@@1@32@@oe@16-12-2010 979438604@GENIA Treebank@formal@@1@S@The accumulation of mature B cells in the thymus was found only in tg epsilon26 mice, not in other human CD3epsilon transgenic mouse lines or other T cell-deficient mice, including CD3-epsilon knockout mice and TCR-beta/TCR-delta double knockout mice.@@@@1@41@@oe@16-12-2010 979438605@GENIA Treebank@formal@@1@S@Hanging drop-mediated transfer into 2-deoxyguanosine-treated thymus lobes showed that lymphoid progenitor cells rather than thymus stromal cells were responsible for abnormal B cell development in tg epsilon26 thymus, and that tg epsilon26 fetal liver cells were destined to become B cells in normal thymus even in the presence of normal progenitor cells undergoing T cell development.@@@@1@58@@oe@16-12-2010 979438606@GENIA Treebank@formal@@1@S@These results indicate that lymphoid progenitor cells in tg epsilon26 mice are genetically defective in thymic choice between T cells and B cells, generating B cells even in normal thymus environment.@@@@1@33@@oe@16-12-2010 979438607@GENIA Treebank@formal@@1@S@Interestingly, tg epsilon26 thymocytes expressed GATA-3 and TCF-1, but not LEF-1 and PEBP-2alpha, among T cell-specific transcription factors that are involved in early T cell development, indicating that GATA-3 and TCF-1 expressed during thymocyte development do not necessarily determine the cell fate into T cell lineage.@@@@1@51@@oe@16-12-2010 979438608@GENIA Treebank@formal@@1@S@Thus, tg epsilon26 mice provide a novel mouse model in that lineage choice between T and B lymphocytes is genetically defective.@@@@1@23@@oe@16-12-2010 979438901@GENIA Treebank@formal@@1@S@IL-7 reconstitutes multiple aspects of v-Abl-mediated signaling.@@@@1@8@@oe@16-12-2010 979438902@GENIA Treebank@formal@@1@S@The mechanism by which early lymphoid cells are selectively transformed by v-Abl is currently unknown.@@@@1@16@@oe@16-12-2010 979438903@GENIA Treebank@formal@@1@S@Previous studies have shown constitutive activation of IL-4 and IL-7 signaling pathways, as measured by activation of Janus protein kinase (JAK)1, JAK3, STAT5, and STAT6, in pre-B cells transformed by v-Abl.@@@@1@40@@oe@16-12-2010 979438904@GENIA Treebank@formal@@1@S@To determine whether activation of these cytokine signaling pathways by v-Abl is important in the cellular events induced by the Abelson murine leukemia virus, the effects of IL-4 and IL-7 on pre-B cells transformed with a temperature-sensitive v-Abl mutant were examined.@@@@1@43@@oe@16-12-2010 979438905@GENIA Treebank@formal@@1@S@Whereas IL-4 had little or no effect, IL-7 delayed both the apoptosis and cell cycle arrest that occur upon v-Abl kinase inactivation.@@@@1@24@@oe@16-12-2010 979438906@GENIA Treebank@formal@@1@S@IL-7 also delayed the decreases in the levels of c-Myc, Bcl-2, and Bcl-xL that occur upon loss of v-Abl kinase activity.@@@@1@24@@oe@16-12-2010 979438907@GENIA Treebank@formal@@1@S@IL-7 did not maintain v-Abl-mediated differentiation arrest of the pre-B cells, as activation of NF-kappaB and RAG gene transcription was unaffected by IL-7.@@@@1@25@@oe@16-12-2010 979438908@GENIA Treebank@formal@@1@S@These results identify a potential role for IL-7 signaling pathways in transformation by v-Abl while demonstrating that a combination of IL-4 and IL-7 signaling cannot substitute for an active v-Abl kinase in transformed pre-B cells.@@@@1@37@@oe@16-12-2010 979441401@GENIA Treebank@formal@@1@S@The role of protein kinase C signaling in activated DRA transcription.@@@@1@12@@oe@16-12-2010 979441402@GENIA Treebank@formal@@1@S@Expression of human MHC HLA-DRA class II gene can be up-regulated in B cells by Ig cross-linking as well as by phorbol esters such as 12-O-tetradecanoyl phorbol 13-acetate (TPA).@@@@1@32@@oe@16-12-2010 979441403@GENIA Treebank@formal@@1@S@Induced DRA expression involves activation of restricted protein kinase C (PKC) isoforms, resulting in activated activator protein-1-dependent transcription.@@@@1@22@@oe@16-12-2010 979441404@GENIA Treebank@formal@@1@S@In this report expression profiles and activation of PKC were analyzed in human Raji B lymphoblastoid cells.@@@@1@18@@oe@16-12-2010 979441405@GENIA Treebank@formal@@1@S@Transient transfection analysis with target plasmids containing either DRA promoter (wild-type or mutated) or TPA response elements demonstrated that pretreatment with the selective PKC inhibitor GF 109203X repressed TPA-mediated activation.@@@@1@33@@oe@16-12-2010 979441406@GENIA Treebank@formal@@1@S@Western analysis performed on cellular fractions of resting cells and of TPA-activated cells revealed abundant expression of classical PKC-alpha (cPKC-alpha), cPKC-betaII, and atypical PKC-zeta isoforms and identified a sustained translocation of cPKC-alpha and cPKC-betaII from the cytosolic compartment to membranes.@@@@1@45@@oe@16-12-2010 979441407@GENIA Treebank@formal@@1@S@As expected, the distribution of atypical PKC-zeta was unaffected by TPA treatment and displayed an even distribution between cytosol and membranes.@@@@1@23@@oe@16-12-2010 979441408@GENIA Treebank@formal@@1@S@This finding was confirmed by immunofluorescence microscopy.@@@@1@8@@oe@16-12-2010 979441409@GENIA Treebank@formal@@1@S@The TPA-mediated translocation of cPKC-alpha and cPKC-betaII was not influenced by pretreatment with GF 109203X.@@@@1@16@@oe@16-12-2010 979441410@GENIA Treebank@formal@@1@S@Finally, functional activation and translocation of PKC were investigated with a selective in vitro kinase assay.@@@@1@18@@oe@16-12-2010 979441411@GENIA Treebank@formal@@1@S@Together, these results show that activated HLA-DRA expression in response to TPA treatment is strictly dependent on PKC activation acting on the X2 box of the DRA promoter and that selective inhibition of PKC enzymatic activity does not influence subcellular localization of expressed PKC isoenzymes.@@@@1@47@@oe@16-12-2010 979441412@GENIA Treebank@formal@@1@S@Thus, the translocation event per se occurs independently of PKC activation in these cells.@@@@1@16@@oe@16-12-2010 979442201@GENIA Treebank@formal@@1@S@Attenuation of HLA-DR expression by mononuclear phagocytes infected with Mycobacterium tuberculosis is related to intracellular sequestration of immature class II heterodimers.@@@@1@22@@oe@16-12-2010 979442202@GENIA Treebank@formal@@1@S@MHC class II expression was examined in macrophages infected with Mycobacterium tuberculosis.@@@@1@13@@oe@16-12-2010 979442203@GENIA Treebank@formal@@1@S@IFN-gamma increased the surface expression of class II molecules in THP-1 cells and this was markedly reduced in cells infected with M. tuberculosis.@@@@1@24@@oe@16-12-2010 979442204@GENIA Treebank@formal@@1@S@Despite this effect, steady state levels of HLA-DRalpha, HLA-DRbeta, and invariant (Ii) chains were equivalent in control and infected cells.@@@@1@26@@oe@16-12-2010 979442205@GENIA Treebank@formal@@1@S@Metabolic labeling combined with pulse-chase experiments and biochemical analysis showed that the majority of class II molecules in infected cells became resistant to endoglycosidase H, consistent with normal Golgi processing.@@@@1@32@@oe@16-12-2010 979442206@GENIA Treebank@formal@@1@S@However, results of intracellular staining and dual color confocal microscopy revealed a significant defect in transport of newly synthesized class II molecules through the endocytic compartment.@@@@1@28@@oe@16-12-2010 979442207@GENIA Treebank@formal@@1@S@Thus, compared with findings in control cells, class II molecules in infected cells colocalized to a minimal extent with a lysosomal-associated membrane protein-1+ endosomal compartment.@@@@1@28@@oe@16-12-2010 979442208@GENIA Treebank@formal@@1@S@In addition, in contrast to control cells, class II molecules in infected cells failed to colocalize with endocytosed BSA under conditions where this marker is known to label late endosomes, lysosomes, and the MHC class II compartment.@@@@1@42@@oe@16-12-2010 979442209@GENIA Treebank@formal@@1@S@Consistent with defective transport along the endocytic pathway, the maturation of SDS-stable class II alphabeta dimers--dependent upon removal of Ii chain and peptide loading of class II dimers in the MHC class II compartment--was markedly impaired in M. tuberculosis-infected cells.@@@@1@46@@oe@16-12-2010 979442210@GENIA Treebank@formal@@1@S@These findings indicate that defective transport and processing of class II molecules through the endosomal/lysosomal system is responsible for diminished cell surface expression of MHC class II molecules in cells infected with M. tuberculosis.@@@@1@35@@oe@16-12-2010 979481501@GENIA Treebank@formal@@1@S@The nuclear receptor PPARgamma - bigger than fat.@@@@1@9@@oe@16-12-2010 979481502@GENIA Treebank@formal@@1@S@Work reported over the past year has provided insights into the mechanisms whereby ligand activation of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) regulates systemic glucose and lipid homeostasis.@@@@1@33@@oe@16-12-2010 979481503@GENIA Treebank@formal@@1@S@PPARgamma has also been implicated recently in the biology of monocytes and in cell-cycle regulation and cancer.@@@@1@18@@oe@16-12-2010 979481504@GENIA Treebank@formal@@1@S@Polyunsaturated fatty acids and eicosanoids bind and activate PPARgamma, suggesting that these lipids may serve as hormonal regulators of a variety of biological processes.@@@@1@26@@oe@16-12-2010 979670201@GENIA Treebank@formal@@1@S@p21ras initiates Rac-1 but not phosphatidyl inositol 3 kinase/PKB, mediated signaling pathways in T lymphocytes.@@@@1@17@@oe@16-12-2010 979670202@GENIA Treebank@formal@@1@S@p21ras is activated by the T cell antigen receptor (TCR) and then co-ordinates important signaling pathways for T lymphocyte activation.@@@@1@23@@oe@16-12-2010 979670203@GENIA Treebank@formal@@1@S@Effector pathways for this guanine nucleotide binding protein in T cells are mediated by the serine/threonine kinase Raf-1 and the Ras-related GTPase Rac-1.@@@@1@24@@oe@16-12-2010 979670204@GENIA Treebank@formal@@1@S@In fibroblasts, an important effector for the Ras oncogene is Phosphatidylinositol 3-kinase (PtdIns 3-kinase).@@@@1@18@@oe@16-12-2010 979670205@GENIA Treebank@formal@@1@S@Activation of this lipid kinase is able to induce critical Rac-1 signaling pathways and can couple p21ras to cell survival mechanisms via the serine/threonine kinase Akt/PKB.@@@@1@27@@oe@16-12-2010 979670206@GENIA Treebank@formal@@1@S@The role of PtdIns 3-kinase in Ras signaling in T cells has not been explored.@@@@1@16@@oe@16-12-2010 979670207@GENIA Treebank@formal@@1@S@In the present study, we examined the ability of PtdIns 3-kinase to initiate the Rac-1 signaling pathways important for T cell activation.@@@@1@24@@oe@16-12-2010 979670208@GENIA Treebank@formal@@1@S@We also examined the possibility that Akt/PKB is regulated by Ras signaling pathways in T lymphocytes.@@@@1@17@@oe@16-12-2010 979670209@GENIA Treebank@formal@@1@S@The results show that Ras can initiate a Rac-1 mediated pathway that regulates the transcriptional function of AP-1 complexes.@@@@1@20@@oe@16-12-2010 979670210@GENIA Treebank@formal@@1@S@PtdIns 3-kinase signals cannot mimic p21ras and induce the Rac mediated responses of AP-1 transcriptional activation.@@@@1@18@@oe@16-12-2010 979670211@GENIA Treebank@formal@@1@S@Moreover, neither TCR or Ras activation of AP-1 is dependent on PtdIns 3-kinase.@@@@1@15@@oe@16-12-2010 979670212@GENIA Treebank@formal@@1@S@PKB is activated in response to triggering of the T cell antigen receptor; PtdIns 3-kinase activity is both required and sufficient for this TCR response.@@@@1@27@@oe@16-12-2010 979670213@GENIA Treebank@formal@@1@S@In contrast, p21ras signals are unable to induce Akt/PKB activity in T cell nor is Ras function required for Akt/PKB activation in response to the TCR.@@@@1@28@@oe@16-12-2010 979670214@GENIA Treebank@formal@@1@S@The present data thus highlight that PtdIns 3-kinase and Akt/PKB are not universal Ras effector molecules.@@@@1@17@@oe@16-12-2010 979670215@GENIA Treebank@formal@@1@S@Ras can initiate Rac-1 regulated signaling pathways in the context of T cell antigen receptor function independently of PtdIns 3-kinase activity.@@@@1@22@@oe@16-12-2010 979696301@GENIA Treebank@formal@@1@S@Signal transduction abnormalities in T lymphocytes from patients with advanced renal carcinoma: clinical relevance and effects of cytokine therapy.@@@@1@21@@oe@16-12-2010 979696302@GENIA Treebank@formal@@1@S@Studies have demonstrated abnormalities of the CD3/T-cell antigen receptor (TCR) and pathways of signal transduction in T lymphocytes from animals and patients with advanced malignancy.@@@@1@28@@oe@16-12-2010 979696303@GENIA Treebank@formal@@1@S@Diminished expression of TCRzeta and p56(lck) that are associated with the TCR and reduced nuclear localization of RelA containing nuclear factor kappaB (NFkappaB) complexes have been noted.@@@@1@30@@oe@16-12-2010 979696304@GENIA Treebank@formal@@1@S@These defects have been described in T cells from patients with malignant melanoma, renal cell carcinoma (RCC), ovarian cancer, and colorectal cancer.@@@@1@28@@oe@16-12-2010 979696305@GENIA Treebank@formal@@1@S@Preliminary observations also indicate possible correlation with clinical variables such as stage in selected instances.@@@@1@16@@oe@16-12-2010 979696306@GENIA Treebank@formal@@1@S@To further characterize altered expression of TCRzeta, p56(lck), and impaired activation of NFkappaB, T lymphocytes were obtained from 65 patients with RCC, the majority of whom were receiving combination cytokine therapy [interleukin (IL)-2, IFN alpha-containing regimens] and 37 control individuals.@@@@1@51@@oe@16-12-2010 979696307@GENIA Treebank@formal@@1@S@In 29 of these patients, levels of TCRzeta and p56(lck) were determined by Western blots of T-cell lysates and semiquantitated using densitometry.@@@@1@24@@oe@16-12-2010 979696308@GENIA Treebank@formal@@1@S@Relative levels were then correlated with a series of clinical variables including response to therapy, performance status, survival, disease sites, age, and others.@@@@1@29@@oe@16-12-2010 979696309@GENIA Treebank@formal@@1@S@In another group of 28 patients (three individuals from the first group), the frequency of abnormal NFkappaB activation was studied using electrophoretic mobility shift assays after activation of T cells with phorbol myristate acetate/ionomycin or anti-CD3 monoclonal antibody.@@@@1@42@@oe@16-12-2010 979696310@GENIA Treebank@formal@@1@S@Changes in these signaling molecules during cytokine treatment were also investigated.@@@@1@12@@oe@16-12-2010 979696311@GENIA Treebank@formal@@1@S@TCRzeta and p56(lck) were detected in the peripheral blood T cells in 27 of 29 patients, and overall, reduced levels were noted visually in 12 of 29 (41%) and 13 of 29 (45%) individuals, respectively.@@@@1@45@@oe@16-12-2010 979696312@GENIA Treebank@formal@@1@S@When levels were semiquantitated using densitometry, significant decreases of TCRzeta (P = 0.029) and p56(lck) (P = 0.029) but not CD3epsilon (P = 0.131), compared with control levels, were found.@@@@1@40@@oe@16-12-2010 979696313@GENIA Treebank@formal@@1@S@In patients treated with IL-2/IFN alpha-based therapy, relative levels of TCRzeta increased significantly (P = 0.002) on day 15 of cycle one compared with the baseline.@@@@1@30@@oe@16-12-2010 979696314@GENIA Treebank@formal@@1@S@Correlations of TCRzeta or p56(lck) levels with response or disease variables, except for lower TCRzeta levels (P < 0.001) in the presence of bone metastases, were not found.@@@@1@33@@oe@16-12-2010 979696315@GENIA Treebank@formal@@1@S@Abnormal NFkappaB activation after stimulation with phorbol myristate acetate/ionomycin and/or anti-CD3 monoclonal antibody was found in 59% of patients (17 of 28) and was not accounted for by the advanced age of the study cohort.@@@@1@39@@oe@16-12-2010 979696316@GENIA Treebank@formal@@1@S@Activation of NFkappaB in peripheral blood T cells was inducible during cytokine therapy in four of six individuals who displayed impaired NFkappaB activity prior to therapy.@@@@1@27@@oe@16-12-2010 979696317@GENIA Treebank@formal@@1@S@Moreover, impaired activation of NFkappaB does not appear linked to a reduction of TCRzeta expression, because in five patients, normal TCRzeta levels were present although kappaB binding was not inducible.@@@@1@34@@oe@16-12-2010 979696318@GENIA Treebank@formal@@1@S@In the majority of patients with advanced RCC, peripheral blood T cells express TCRzeta and p56(lck), and in a subset, reduced levels of these TCRzeta associated molecules are seen that may increase during cytokine-based therapy.@@@@1@39@@oe@16-12-2010 979696319@GENIA Treebank@formal@@1@S@Abnormal activation of NFkappaB is also present in >50% of patients and may also revert to normal during IL-2/IFN alpha-based treatment.@@@@1@24@@oe@16-12-2010 979696320@GENIA Treebank@formal@@1@S@This alteration in NFkappaB activation occurred in the presence of normal expression of TCRzeta-associated signaling elements.@@@@1@17@@oe@16-12-2010 979696321@GENIA Treebank@formal@@1@S@The clinical significance of these findings remains unclear.@@@@1@9@@oe@16-12-2010 979979801@GENIA Treebank@formal@@1@S@Transcriptional regulation of lysosomal acid lipase in differentiating monocytes is mediated by transcription factors Sp1 and AP-2.@@@@1@18@@oe@16-12-2010 979979802@GENIA Treebank@formal@@1@S@Human lysosomal acid lipase (LAL) is a hydrolase required for the cleavage of cholesteryl esters and triglycerides derived from plasma lipoproteins.@@@@1@24@@oe@16-12-2010 979979803@GENIA Treebank@formal@@1@S@It is shown here that during monocyte to macrophage differentiation, the expression of LAL-mRNA is induced.@@@@1@18@@oe@16-12-2010 979979804@GENIA Treebank@formal@@1@S@This induction is dependent on protein kinase C activity and protein synthesis.@@@@1@13@@oe@16-12-2010 979979805@GENIA Treebank@formal@@1@S@The cell type-specific increase in LAL expression is further investigated in the THP-1 cell line with respect to transcriptional regulation.@@@@1@21@@oe@16-12-2010 979979806@GENIA Treebank@formal@@1@S@The human monocytic leukemia cell line THP-1 differentiates into macrophage-like cells when treated with phorbol esters.@@@@1@17@@oe@16-12-2010 979979807@GENIA Treebank@formal@@1@S@In order to determine the cis-acting elements necessary for both basal and phorbol 12-myristate-13 acetate (PMA)-enhanced promoter activity, we performed deletion analysis and reporter gene assays.@@@@1@31@@oe@16-12-2010 979979808@GENIA Treebank@formal@@1@S@A PMA responsive element has been identified between -182 bp and -107 bp upstream of the major transcription start site.@@@@1@21@@oe@16-12-2010 979979809@GENIA Treebank@formal@@1@S@Gel mobility shift assays demonstrated that binding of Sp1 and AP-2 to the LAL promoter is increased by PMA in THP-1 cells.@@@@1@23@@oe@16-12-2010 979979810@GENIA Treebank@formal@@1@S@Co-transfections with expression plasmids for Sp1 and AP-2 further emphasized the important role of these transcription factors in both basal and PMA-enhanced LAL expression.@@@@1@25@@oe@16-12-2010 979979811@GENIA Treebank@formal@@1@S@Our data suggest that differentiation dependent increase of lysosomal acid lipase (LAL) expression in THP-1 cells is mediated by a concerted action of Sp1 and AP-2.@@@@1@29@@oe@16-12-2010 980047501@GENIA Treebank@formal@@1@S@[Molecular mechanism of cytokine gene expression in Th1 and Th2]@@@@1@12@@oe@16-12-2010 980047502@GENIA Treebank@formal@@1@S@Upon activation by antigens, helper T cells differentiate into one of several subsets, characterized by their distinct cytokine-production patterns.@@@@1@22@@oe@16-12-2010 980047503@GENIA Treebank@formal@@1@S@Among these subsets, Th1 cells are known to activate cellular immunity resulting in inflammatory response, whereas Th2 cells induce humoral and allergic responses and suppress inflammation.@@@@1@29@@oe@16-12-2010 980047504@GENIA Treebank@formal@@1@S@Th1 and Th2 effector functions and their development are attributable to their distinct cytokine expression patterns.@@@@1@17@@oe@16-12-2010 980047505@GENIA Treebank@formal@@1@S@Recent reports have demonstrated that differential expression of cell surface molecules, such as adhesion molecule and chemokine receptor, is involved in their recruitment into target tissues.@@@@1@29@@oe@16-12-2010 980047506@GENIA Treebank@formal@@1@S@It is, therefore, suggested that clarification of the mechanisms of differential gene expression in Th1/Th2 should lead to rational strategies for manipulating pathological immune responses.@@@@1@28@@oe@16-12-2010 980047507@GENIA Treebank@formal@@1@S@Activation of helper T cells mediated by the T cell receptor induces a series of biochemical events.@@@@1@18@@oe@16-12-2010 980047508@GENIA Treebank@formal@@1@S@Among them, both the activation of PKC/Ras- and CaM/CN-mediated pathways play a central role in the signal transduction of cytokine gene expression.@@@@1@24@@oe@16-12-2010 980047509@GENIA Treebank@formal@@1@S@Closer examination using non-transformed murine Th1 and Th2 clones suggested that a balance between the activities of the two signaling pathways contributes to cytokine gene expression.@@@@1@27@@oe@16-12-2010 980047510@GENIA Treebank@formal@@1@S@We propose that one of the targets of PGE2, whose effect distinguishes Th1 from Th2, resides in the downstream PKC/Ras-mediated pathway.@@@@1@24@@oe@16-12-2010 980115501@GENIA Treebank@formal@@1@S@GATA-3 represses gp91phox gene expression in eosinophil-committed HL-60-C15 cells.@@@@1@10@@oe@16-12-2010 980115502@GENIA Treebank@formal@@1@S@To study the regulatory mechanism of gp91phox gene expression in eosinophils, we transiently transfected eosinophil-committed HL-60-C15 cells with gp91phox promoter constructs, and identified a negative element from bp -267 to -246 of the gp91phox gene, the deletion of which caused an 83% increase in promoter activity.@@@@1@51@@oe@16-12-2010 980115503@GENIA Treebank@formal@@1@S@Electrophoresis mobility shift assays demonstrated GATA-3 binds to the GATA consensus site from bp -256 to -250.@@@@1@18@@oe@16-12-2010 980115504@GENIA Treebank@formal@@1@S@An 81% increment in promoter activity was obtained when a mutation was introduced in the GATA-3 binding site of the bp -267 to +12 construct, which is comparable to that of the bp -245 to +12 construct.@@@@1@40@@oe@16-12-2010 980115505@GENIA Treebank@formal@@1@S@We therefore conclude that GATA-3 specifically binding to the GATA site negatively regulates the expression of the gene in HL-60-C15 cells.@@@@1@22@@oe@16-12-2010 980297101@GENIA Treebank@formal@@1@S@A nongenomic mechanism for progesterone-mediated immunosuppression: inhibition of K+ channels, Ca2+ signaling, and gene expression in T lymphocytes.@@@@1@22@@oe@16-12-2010 980297102@GENIA Treebank@formal@@1@S@The mechanism by which progesterone causes localized suppression of the immune response during pregnancy has remained elusive.@@@@1@18@@oe@16-12-2010 980297103@GENIA Treebank@formal@@1@S@Using human T lymphocytes and T cell lines, we show that progesterone, at concentrations found in the placenta, rapidly and reversibly blocks voltage-gated and calcium-activated K+ channels (KV and KCa, respectively), resulting in depolarization of the membrane potential.@@@@1@46@@oe@16-12-2010 980297104@GENIA Treebank@formal@@1@S@As a result, Ca2+ signaling and nuclear factor of activated T cells (NF-AT)-driven gene expression are inhibited.@@@@1@22@@oe@16-12-2010 980297105@GENIA Treebank@formal@@1@S@Progesterone acts distally to the initial steps of T cell receptor (TCR)-mediated signal transduction, since it blocks sustained Ca2+ signals after thapsigargin stimulation, as well as oscillatory Ca2+ signals, but not the Ca2+ transient after TCR stimulation.@@@@1@44@@oe@16-12-2010 980297106@GENIA Treebank@formal@@1@S@K+ channel blockade by progesterone is specific; other steroid hormones had little or no effect, although the progesterone antagonist RU 486 also blocked KV and KCa channels.@@@@1@30@@oe@16-12-2010 980297107@GENIA Treebank@formal@@1@S@Progesterone effectively blocked a broad spectrum of K+ channels, reducing both Kv1.3 and charybdotoxin-resistant components of KV current and KCa current in T cells, as well as blocking several cloned KV channels expressed in cell lines.@@@@1@39@@oe@16-12-2010 980297108@GENIA Treebank@formal@@1@S@Progesterone had little or no effect on a cloned voltage-gated Na+ channel, an inward rectifier K+ channel, or on lymphocyte Ca2+ and Cl- channels.@@@@1@27@@oe@16-12-2010 980297109@GENIA Treebank@formal@@1@S@We propose that direct inhibition of K+ channels in T cells by progesterone contributes to progesterone-induced immunosuppression.@@@@1@18@@oe@16-12-2010 980480601@GENIA Treebank@formal@@1@S@Role of IKK1 and IKK2 in lipopolysaccharide signaling in human monocytic cells.@@@@1@13@@oe@16-12-2010 980480602@GENIA Treebank@formal@@1@S@Mononuclear phagocytes play a major role in immune and inflammatory responses.@@@@1@12@@oe@16-12-2010 980480603@GENIA Treebank@formal@@1@S@Bacterial lipopolysaccharide (LPS) induces monocytes to express a variety of genes by activating the NF-kappaB/Rel transcription factor family.@@@@1@21@@oe@16-12-2010 980480604@GENIA Treebank@formal@@1@S@Recently, we have reported that the tumor necrosis factor and interleukin 1 signaling pathways activate two kinases, IKK1 and IKK2.@@@@1@23@@oe@16-12-2010 980480605@GENIA Treebank@formal@@1@S@Phosphorylation of the IkappaB cytoplasmic inhibitors, IkappaBalpha, IkappaBbeta, and IkappaBepsilon, by these kinases triggers proteolytic degradation and the release of NF-kappaB/Rel proteins into the nucleus.@@@@1@30@@oe@16-12-2010 980480606@GENIA Treebank@formal@@1@S@At present, the role of the IKKs in LPS signaling has not been investigated.@@@@1@16@@oe@16-12-2010 980480607@GENIA Treebank@formal@@1@S@Here, we report that LPS induces IKK activity in human monocytes and THP-1 monocytic cells.@@@@1@17@@oe@16-12-2010 980480608@GENIA Treebank@formal@@1@S@The kinetics of activation of kinase activity in monocytic cells are relatively slow with maximal activity observed at 60 min, which coincides with the degradation of IkappaBs and the nuclear translocation of NF-kappaB.@@@@1@35@@oe@16-12-2010 980480609@GENIA Treebank@formal@@1@S@In transfection experiments, overexpression of wild type IKK1, a dominant negative mutant IKK1 (K44M), or wild type IKK2 did not affect LPS-induced kappaB-dependent transcription in monocytic cells.@@@@1@33@@oe@16-12-2010 980480610@GENIA Treebank@formal@@1@S@In contrast, a dominant negative mutant of IKK2 inhibited LPS induction of kappaB-dependent transcription in a dose-dependent manner.@@@@1@20@@oe@16-12-2010 980480611@GENIA Treebank@formal@@1@S@These results indicate that LPS induction of kappaB-dependent gene expression in human monocytic cells requires activation of IKK2.@@@@1@19@@oe@16-12-2010 980817801@GENIA Treebank@formal@@1@S@Effects of overexpression of IL-1 receptor-associated kinase on NFkappaB activation, IL-2 production and stress-activated protein kinases in the murine T cell line EL4.@@@@1@25@@oe@16-12-2010 980817802@GENIA Treebank@formal@@1@S@The association and activation of the IL-1 receptor-associated protein kinase (IRAK) to the IL-1 receptor complex is one of the earliest events detectable in IL-1 signal transduction.@@@@1@30@@oe@16-12-2010 980817803@GENIA Treebank@formal@@1@S@We generated permanent clones of the murine T cell line EL4 6.1 overexpressing human (h)IRAK to evaluate the role of this kinase in IL-1 signaling.@@@@1@29@@oe@16-12-2010 980817804@GENIA Treebank@formal@@1@S@Overexpression of hIRAK enhanced IL-1-stimulated activation of the transcription factor NFkappaB, whereas a truncated form (N-IRAK) specifically inhibited IL-1-dependent NFkappaB activity.@@@@1@25@@oe@16-12-2010 980817805@GENIA Treebank@formal@@1@S@In clones stably overexpressing hIRAK a weak constitutive activation of NFkappaB correlated with a low basal IL-2 production which was enhanced in an IL-1-dependent manner.@@@@1@26@@oe@16-12-2010 980817806@GENIA Treebank@formal@@1@S@Compared to the parental cell line the dose-response curve of IL-1-induced IL-2 production was shifted in both potency and efficacy.@@@@1@21@@oe@16-12-2010 980817807@GENIA Treebank@formal@@1@S@These results demonstrate that IRAK directly triggers NFkappaB-mediated gene expression in EL4 cells.@@@@1@14@@oe@16-12-2010 980817808@GENIA Treebank@formal@@1@S@Qualitatively different effects were observed for the IL-1-induced activation of stress-activated protein (SAP) kinases: permanent overexpression of IRAK did not affect the dose dependence but prolonged the kinetics of IL-1-induced activation of SAP kinases, suggesting that this signaling branch may be regulated by distinct mechanisms.@@@@1@50@@oe@16-12-2010 980818901@GENIA Treebank@formal@@1@S@Decreased IL-12 production and Th1 cell development by acetyl salicylic acid-mediated inhibition of NF-kappaB.@@@@1@15@@oe@16-12-2010 980818902@GENIA Treebank@formal@@1@S@IL-12 is a 75-kDa heterodimeric cytokine composed of two covalently linked p35 and p40 chains.@@@@1@16@@oe@16-12-2010 980818903@GENIA Treebank@formal@@1@S@This pro-inflammatory cytokine plays a prominent role in the development of Th1 cell-mediated immune responses.@@@@1@16@@oe@16-12-2010 980818904@GENIA Treebank@formal@@1@S@Th1 cell-mediated immune responses have been implicated in the pathogenesis of chronic inflammatory autoimmune diseases.@@@@1@16@@oe@16-12-2010 980818905@GENIA Treebank@formal@@1@S@Thus, IL-12 appears to be a critical factor in the generation and maintenance of chronic inflammatory conditions.@@@@1@19@@oe@16-12-2010 980818906@GENIA Treebank@formal@@1@S@In this study, we investigated the effects of a commonly prescribed anti-inflammatory drug, acetyl salicylic acid (ASA), on IL-12 production and Th1 cell development.@@@@1@30@@oe@16-12-2010 980818907@GENIA Treebank@formal@@1@S@ASA was found to inhibit secretion of the IL-12 heterodimer as well as p40 monomer by human monocytic cells.@@@@1@20@@oe@16-12-2010 980818908@GENIA Treebank@formal@@1@S@This was associated with the down-regulation of IL-12p40 mRNA expression.@@@@1@11@@oe@16-12-2010 980818909@GENIA Treebank@formal@@1@S@Analysis of the regulation of the p40 gene promoter revealed that ASA inhibited NF-kappaB activation and binding to the p40-kappaB site in the p40 promoter, leading to transcriptional repression of the p40 gene.@@@@1@35@@oe@16-12-2010 980818910@GENIA Treebank@formal@@1@S@Addition of ASA to an in vitro T helper cell differentiation system, at concentrations compatible with plasma levels reached during anti-inflammatory therapy, resulted in reduced development of Th1 cells.@@@@1@32@@oe@16-12-2010 980818911@GENIA Treebank@formal@@1@S@These results suggest that the inhibition of NF-kappaB activation by ASA leads to down-regulation of IL-12 production and inhibition of Th1 cell development.@@@@1@24@@oe@16-12-2010 980832001@GENIA Treebank@formal@@1@S@YM268 increases the glucose uptake, cell differentiation, and mRNA expression of glucose transporter in 3T3-L1 adipocytes.@@@@1@19@@oe@16-12-2010 980832002@GENIA Treebank@formal@@1@S@The purpose of this study was to examine the effects of bis[4-[2,4-dioxo-5-thiazolidinyl)methyl]phenyl]methane (YM-268), a thiazolidinedione derivative, on glucose uptake, adipocyte differentiation through peroxisome proliferator-activated receptor gamma(PPARgamma), and phosphatidylinositol 3-kinase (PI 3-kinase) activity in cultured cells.@@@@1@48@@oe@16-12-2010 980832003@GENIA Treebank@formal@@1@S@YM268 and pioglitazone dose-dependently increased the 2-deoxyglucose uptake in 3T3-L1 cells.@@@@1@12@@oe@16-12-2010 980832004@GENIA Treebank@formal@@1@S@YM268 facilitated the insulin-stimulated triglyceride accumulation in 3T3-L1 adipocytes and increased the mRNA expression of fatty acid-binding protein.@@@@1@19@@oe@16-12-2010 980832005@GENIA Treebank@formal@@1@S@YM268, with and without insulin, increased the mRNA expression of glucose transporter isoforms such as GLUT1 and GLUT4, indicating enhancement of adipocyte differentiation.@@@@1@27@@oe@16-12-2010 980832006@GENIA Treebank@formal@@1@S@Additionally, YM268 and pioglitazone showed activity of the PPARgamma ligand, a member of the nuclear receptor superfamily responsible for adipogenesis.@@@@1@23@@oe@16-12-2010 980832007@GENIA Treebank@formal@@1@S@To examine the possible involvement of the increased activity of PI 3-kinase in YM268-stimulated glucose uptake, the enzyme activity was estimated by measuring the phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) concentration in human monocytic cells.@@@@1@35@@oe@16-12-2010 980832008@GENIA Treebank@formal@@1@S@Insulin dose-dependently increased the PI-3,4,5-P3 production but YM268 had no significant effect on the insulin-dependent and -independent PI 3-kinase activation.@@@@1@21@@oe@16-12-2010 980832009@GENIA Treebank@formal@@1@S@These results indicate that the mechanism by which YM268 increased glucose uptake, may be accounted for in part by the enhancement of GLUT1 and GLUT4 expression through PPARgamma activation.@@@@1@31@@oe@16-12-2010 980842101@GENIA Treebank@formal@@1@S@Detection of oestrogen receptor variants in endometrium, myometrium, leiomyoma and peripheral blood mononuclear cells: comparison to variants present in breast cancer.@@@@1@25@@oe@16-12-2010 980842102@GENIA Treebank@formal@@1@S@Oestradiol has mitogenic and regulatory effects on various organs and cells, mediated mainly by its nuclear receptor (ER).@@@@1@22@@oe@16-12-2010 980842103@GENIA Treebank@formal@@1@S@The presence of aberrant ER forms in Oestrogen-dependent tumours has been discussed in correlation with tumour progression.@@@@1@18@@oe@16-12-2010 980842104@GENIA Treebank@formal@@1@S@ER variants, generated by alternative splicing, have been detected in human breast cancer, but also in normal mammary glands, therefore their role in tumorigenesis has been questioned.@@@@1@32@@oe@16-12-2010 980842105@GENIA Treebank@formal@@1@S@We have investigated, by the use of the reverse transcription polymerase chain reaction amplification technique, the possible existence of ER variants in other normal oestrogen target organs and cells, such as uterus (myometrium and endometrium), in peripheral blood mononuclear cells and in a benign uterus tumour (leiomyoma).@@@@1@56@@oe@16-12-2010 980842106@GENIA Treebank@formal@@1@S@We have detected variant ER in these samples and have compared the variant profile to that observed in breast cancer.@@@@1@21@@oe@16-12-2010 980842107@GENIA Treebank@formal@@1@S@All tissues and cells studied expressed both wild-type ER and variant species.@@@@1@13@@oe@16-12-2010 980842108@GENIA Treebank@formal@@1@S@Variant forms encompassed ER with deletions of exons 2, 5 and 7.@@@@1@14@@oe@16-12-2010 980842109@GENIA Treebank@formal@@1@S@Variants with exon 5 deleted were detected only in peripheral blood mononuclear cells and in breast cancer.@@@@1@18@@oe@16-12-2010 980842110@GENIA Treebank@formal@@1@S@Variants with exons 2 and 7 deleted were present in all specimens tested.@@@@1@14@@oe@16-12-2010 980842111@GENIA Treebank@formal@@1@S@These results corroborate previous findings that the presence of ER variants is not a characteristic of breast cancer.@@@@1@19@@oe@16-12-2010 980842112@GENIA Treebank@formal@@1@S@The physiological significance and possible clinical relevance of the variant ER forms remain to be elucidated.@@@@1@17@@oe@16-12-2010 980858601@GENIA Treebank@formal@@1@S@Interaction of sickle erythrocytes with endothelial cells in the presence of endothelial cell conditioned medium induces oxidant stress leading to transendothelial migration of monocytes.@@@@1@25@@oe@16-12-2010 980858602@GENIA Treebank@formal@@1@S@The abnormal adherence of sickle red blood cells (SS RBC) to endothelial cells has been thought to contribute to vascular occlusion, a major cause of morbidity in sickle cell disease (SCD).@@@@1@37@@oe@16-12-2010 980858603@GENIA Treebank@formal@@1@S@We determined whether the interaction of SS RBC with cultured endothelial cells induced cellular oxidant stress that would culminate in expression of cell adhesion molecules (CAMs) involved in the adhesion and diapedesis of monocytes and the adherence of SS reticulocytes.@@@@1@43@@oe@16-12-2010 980858604@GENIA Treebank@formal@@1@S@We showed that the interaction of SS RBC at 2% concentration in the presence of multimers of von Willebrand factor (vWf), derived from endothelial cell-derived conditioned medium (E-CM) with cultured human umbilical vein endothelial cells (HUVEC), resulted in a fivefold increased formation of thiobarbituric acid-reactive substances (TBARS) and activation of the transcription factor NF-kB, both indicators of cellular oxidant stress.@@@@1@73@@oe@16-12-2010 980858605@GENIA Treebank@formal@@1@S@Normal RBC show none of these phenomena.@@@@1@8@@oe@16-12-2010 980858606@GENIA Treebank@formal@@1@S@The oxidant stress-induced signaling resulted in an increased surface expression of a subset of CAMs, ICAM-1, E-selectin, and VCAM-1 in HUVEC.@@@@1@25@@oe@16-12-2010 980858607@GENIA Treebank@formal@@1@S@The addition of oxygen radical scavenger enzymes (catalase, superoxide dismutase) and antioxidant (probucol) inhibited these events.@@@@1@22@@oe@16-12-2010 980858608@GENIA Treebank@formal@@1@S@Additionally, preincubation of HUVEC with a synthetic peptide Arg-Gly-Asp (RGD) that prevents vWf-mediated adhesion of SS RBC reduced the surface expression of VCAM-1 and NF-kB activation.@@@@1@30@@oe@16-12-2010 980858609@GENIA Treebank@formal@@1@S@Furthermore, SS RBC-induced oxidant stress resulted in a twofold increase in the transendothelial migration of both monocyte-like HL-60 cells and human peripheral blood monocytes, and approximately a sixfold increase in platelet-endothelial cell adhesion molecule-1 (PECAM-1) phosphorylation, each of which was blocked by protein kinase C inhibitor and antioxidants.@@@@1@54@@oe@16-12-2010 980858610@GENIA Treebank@formal@@1@S@These results suggest that the adherence/contact of SS RBC to endothelial cells in large vessel can generate enhanced oxidant stress leading to increased adhesion and diapedesis of monocytes, as well as heightened adherence of SS reticulocytes, indicating that injury/activation of endothelium can contribute to vaso-occlusion in SCD.@@@@1@50@@oe@16-12-2010 981152501@GENIA Treebank@formal@@1@S@Interleukin 2 and 15 activate Stat3alpha in human T lymphocytes.@@@@1@11@@oe@16-12-2010 981152502@GENIA Treebank@formal@@1@S@Signal transducer and activator of transcription 3 (Stat3) has recently been shown to exist in two alternatively spliced isoforms, a short form, Stat3beta, and a longer form, Stat3alpha, displaying differences in transcriptional activity.@@@@1@41@@oe@16-12-2010 981152503@GENIA Treebank@formal@@1@S@It is unknown which Stat3 isoform(s) is activated in response to interleukin (IL)-2 and IL-15.@@@@1@22@@oe@16-12-2010 981152504@GENIA Treebank@formal@@1@S@Here, cytokine-induced activation of Stat3 in previously activated CD4(+) human T cells was examined using Stat3 antibodies directed against different regions of Stat3.@@@@1@25@@oe@16-12-2010 981152505@GENIA Treebank@formal@@1@S@As determined by tyrosine phosphorylation, nuclear translocation and binding to an hSIE-oligonucleotide probe, IL-2 and IL-15 activated the slowly migrating isoform, Stat3alpha.@@@@1@26@@oe@16-12-2010 981152506@GENIA Treebank@formal@@1@S@In contrast, minimal or no activation of Stat3beta was observed, suggesting that IL-2 and IL-15 predominantly activate Stat3alpha in human CD4(+) T cells.@@@@1@26@@oe@16-12-2010 981152507@GENIA Treebank@formal@@1@S@In this way, diversity in the expression and activation of Stat3 proteins may provide additional means of regulating cytokine-induced T cell responses.@@@@1@24@@oe@16-12-2010 981152508@GENIA Treebank@formal@@1@S@Copyright 1998 Academic Press.@@@@1@5@@oe@16-12-2010 981196601@GENIA Treebank@formal@@1@S@Promoter sequence, exon:intron structure, and synteny of genetic location show that a chicken cytokine with T-cell proliferative activity is IL2 and not IL15.@@@@1@26@@oe@16-12-2010 981196602@GENIA Treebank@formal@@1@S@The gene encoding a chicken cytokine with T-cell proliferative activity was cloned, sequenced, and mapped.@@@@1@18@@oe@16-12-2010 981196603@GENIA Treebank@formal@@1@S@The results show that this cytokine is chicken IL2 and not IL15.@@@@1@13@@oe@16-12-2010 981196604@GENIA Treebank@formal@@1@S@The exon:intron structure of chicken IL2 corresponds almost exactly to those of mammalian IL2s with the exceptions of exon 2 and introns 2 and 3 which are shorter.@@@@1@29@@oe@16-12-2010 981196605@GENIA Treebank@formal@@1@S@Chicken IL2 contains five repeats of the "instability" motif ATTTA in the 3'untranslated region in exon 4.@@@@1@21@@oe@16-12-2010 981196606@GENIA Treebank@formal@@1@S@It is a single-copy gene, with neither structural (amino acid) nor promoter sequence polymorphisms identified.@@@@1@19@@oe@16-12-2010 981196607@GENIA Treebank@formal@@1@S@Analysis of the predicted amino acid sequence suggests that overall protein structure is conserved, but the receptor binding sites are not.@@@@1@23@@oe@16-12-2010 981196608@GENIA Treebank@formal@@1@S@A number of potential regulatory sequences similar to those found in mammals have been identified in the promoter.@@@@1@19@@oe@16-12-2010 981196609@GENIA Treebank@formal@@1@S@These include (5'-3') a composite NF-AT/ "AP-1" element, a CD28 response element, an AP-1 element, an NF-AT element, and the AP-1 part of an AP-1/octamer composite element.@@@@1@36@@oe@16-12-2010 981196610@GENIA Treebank@formal@@1@S@The mammalian NF-kappaB and octamer binding sites seem to be absent, although there are alternative potential NF-kappaB and octamer-binding elements in the chicken IL2 promoter, in close proximity to their mammalian homologues.@@@@1@35@@oe@16-12-2010 981196611@GENIA Treebank@formal@@1@S@Sequence comparisons also predict other potential transcription factor binding sites as yet undescribed in mammalian IL2 promoters.@@@@1@18@@oe@16-12-2010 981196612@GENIA Treebank@formal@@1@S@A Taq I polymorphism was identified which enabled chicken IL2 to be mapped to chromosome 4, linked to ANX5, with synteny with mouse chromosome 3 and human chromosome 4.@@@@1@32@@oe@16-12-2010 981196613@GENIA Treebank@formal@@1@S@This is the first non-mammalian cytokine gene to be mapped.@@@@1@11@@oe@16-12-2010 981317801@GENIA Treebank@formal@@1@S@Tobacco smoke induces coordinate activation of HSF and inhibition of NFkappaB in human monocytes: effects on TNFalpha release.@@@@1@20@@oe@16-12-2010 981317802@GENIA Treebank@formal@@1@S@Tobacco smoke (TS) exposure is a major risk factor for human disease, and macrophages of healthy smokers have a depressed capacity to release cytokines, including tumor necrosis factor (TNF)alpha.@@@@1@37@@oe@16-12-2010 981317803@GENIA Treebank@formal@@1@S@TS induces the synthesis of heat shock (HS)/stress proteins (HSP), and, in particular, of Hsp70.@@@@1@24@@oe@16-12-2010 981317804@GENIA Treebank@formal@@1@S@We determined whether Hsp70 induction by TS was mediated by the activation of the HS transcription factor, HSF.@@@@1@20@@oe@16-12-2010 981317805@GENIA Treebank@formal@@1@S@HSF activation has been shown to inhibit NFkappaB.@@@@1@9@@oe@16-12-2010 981317806@GENIA Treebank@formal@@1@S@Thus, we also determined the effects of TS on NFkappaB.@@@@1@12@@oe@16-12-2010 981317807@GENIA Treebank@formal@@1@S@U937 cells and human peripheral blood monocytes were exposed to TS, binding activities of the respective transcription factors were analyzed, and Hsp70 expression and TNFalpha release were determined in parallel.@@@@1@33@@oe@16-12-2010 981317808@GENIA Treebank@formal@@1@S@TS activated HSF, which was associated with Hsp70 overexpression and inhibition of NFkappaB binding activity and TNFalpha release.@@@@1@20@@oe@16-12-2010 981317809@GENIA Treebank@formal@@1@S@The altered cytokine profile observed in smokers may relate to an HSF/Hsp70-mediated inhibition of NFkappaB activity.@@@@1@17@@oe@16-12-2010 981317810@GENIA Treebank@formal@@1@S@Copyright 1998 Academic Press.@@@@1@5@@oe@16-12-2010 981525801@GENIA Treebank@formal@@1@S@In vivo function of an interleukin 2 receptor beta chain (IL-2Rbeta)/IL-4Ralpha cytokine receptor chimera potentiates allergic airway disease.@@@@1@23@@oe@16-12-2010 981525802@GENIA Treebank@formal@@1@S@Strength of T cell receptor (TCR) signaling, coreceptors, costimulation, antigen-presenting cell type, and cytokines all play crucial roles in determining the efficiency with which type 2 T lymphocytes (Th2, Tc2) develop from uncommitted precursors.@@@@1@44@@oe@16-12-2010 981525803@GENIA Treebank@formal@@1@S@To investigate in vivo regulatory mechanisms that control the population of type 2 T cells and disease susceptibility, we have created lines of transgenic mice in which expression of a chimeric cytokine receptor (the mouse interleukin 2 receptor beta chain [IL-2Rbeta] extracellular domain fused to the cytoplasmic tail of IL-4Ralpha) is targeted to the T lymphoid lineage using the proximal lck promoter.@@@@1@68@@oe@16-12-2010 981525804@GENIA Treebank@formal@@1@S@This chimera transduced IL-4-specific signals in response to IL-2 binding and dramatically enhanced type 2 responses (IL-4, IL-5, and immunoglobulin E production) upon in vitro TCR stimulation or in vivo antigen challenge.@@@@1@37@@oe@16-12-2010 981525805@GENIA Treebank@formal@@1@S@Thus, type 2 effector function was augmented by IL-4 signals transduced through a chimeric receptor expressed in a T cell-specific manner.@@@@1@23@@oe@16-12-2010 981525806@GENIA Treebank@formal@@1@S@This influence was sufficient for establishment of antigen-induced allergic airway hyperresponsiveness on a disease-resistant background(C57BL/6).@@@@1@19@@oe@16-12-2010 981562801@GENIA Treebank@formal@@1@S@Immunohistochemical study of c-fos-positive lymphocytes infiltrated into human squamous cell carcinomas of the head and neck during radiation therapy and its clinical significance.@@@@1@24@@oe@16-12-2010 981562802@GENIA Treebank@formal@@1@S@C-fos has been reported to be one of the immediate early genes in signal transduction systems after many kinds of stresses, including ionizing radiation.@@@@1@26@@oe@16-12-2010 981562803@GENIA Treebank@formal@@1@S@Changes in c-fos expression induced by radiation therapy in tumor tissues have not yet been reported.@@@@1@17@@oe@16-12-2010 981562804@GENIA Treebank@formal@@1@S@In this study, we have attempted to determine whether c-fos expression is induced by radiotherapy in human squamous cell carcinomas of the head and neck and to establish a possible correlation between c-fos expression and the therapeutic effects of radiation therapy.@@@@1@43@@oe@16-12-2010 981562805@GENIA Treebank@formal@@1@S@Twenty-seven patients with tumors of the oral cavity, oropharynx, and maxillary sinus were examined, all of which were confirmed as squamous cell carcinomas.@@@@1@27@@oe@16-12-2010 981562806@GENIA Treebank@formal@@1@S@After obtaining the patients' informed consent, biopsies were performed before treatment and at doses of 4, 10, and 20 Gy of radiotherapy, and the specimens were preserved in liquid nitrogen for further examination.@@@@1@39@@oe@16-12-2010 981562807@GENIA Treebank@formal@@1@S@Serial sectioning of 6 micrometer was performed using a cryostat, and samples were immunohistochemically stained using the streptoavidin-biotin peroxidase method and a monoclonal antibody against c-fos.@@@@1@28@@oe@16-12-2010 981562808@GENIA Treebank@formal@@1@S@Three of the 27 patients with squamous cell carcinoma showed slight expression of c-fos in their tumor cells before and/or at 4 or 10 Gy of radiotherapy.@@@@1@28@@oe@16-12-2010 981562809@GENIA Treebank@formal@@1@S@The tumors showed high radiosensitivity.@@@@1@6@@oe@16-12-2010 981562810@GENIA Treebank@formal@@1@S@Concerning tumor-infiltrating lymphocytes, the rate of moderate or remarkable grades of c-fos-positive lymphocytes before radiotherapy and at radiation doses of 4, 10, and 20 Gy was 8.0, 29.2, 4.8, and 0%, respectively.@@@@1@41@@oe@16-12-2010 981562811@GENIA Treebank@formal@@1@S@The relationship between the immunohistochemical findings and the antitumor effect at a radiation dose of 20 Gy was examined on the corresponding H&E-stained sections.@@@@1@27@@oe@16-12-2010 981562812@GENIA Treebank@formal@@1@S@In patients whose infiltration of c-fos-positive lymphocytes into tumor tissues were moderate or remarkable at 4 Gy of radiotherapy, the tumors responded significantly well to radiation therapy (P < 0.025, chi2 test), and the patients took a significantly favorable clinical course (P < 0.05, chi2 test).@@@@1@55@@oe@16-12-2010 981562813@GENIA Treebank@formal@@1@S@In a sample from one of the patients, c-fos-positive lymphocytes were identified as CD4 positive and CD8 negative.@@@@1@20@@oe@16-12-2010 981562814@GENIA Treebank@formal@@1@S@Therefore, the high radiosensitivity of squamous cell carcinomas in our samples could be explained by an overexpression of c-fos in the tumor-infiltrating lymphocytes induced by small doses of radiation therapy, and these activated lymphocytes exerted a cytotoxic effect against the cancer cells.@@@@1@45@@oe@16-12-2010 981620801@GENIA Treebank@formal@@1@S@Lack of T-cell-mediated recognition of the fusion region of the pml/RAR-alpha hybrid protein by lymphocytes of acute promyelocytic leukemia patients.@@@@1@21@@oe@16-12-2010 981620802@GENIA Treebank@formal@@1@S@In previous studies, it was shown that the fusion region of the pml/RAR-alpha protein, expressed by acute promyelocytic leukemia (APL) cells, can be specifically recognized in vitro by donor (D. E.) CD4 T cells in a HLA class II DR11-restricted fashion.@@@@1@49@@oe@16-12-2010 981620803@GENIA Treebank@formal@@1@S@We present here the results on the recognition of several pml/RAR-alpha peptides by APL patients expressing HLA DR11.@@@@1@19@@oe@16-12-2010 981620804@GENIA Treebank@formal@@1@S@The in vitro immunization of peripheral blood lymphocytes from four patients in remission (S. R., F. R., M. M., P. G.) with BCR1/25, a 25-mer pml/RAR-alpha, did not elicit either a polyclonal or a clonal immune response specific to the peptide.@@@@1@46@@oe@16-12-2010 981620805@GENIA Treebank@formal@@1@S@We then generated new donor anti-pml/RAR-alpha CD4(+) T-cell clones.@@@@1@10@@oe@16-12-2010 981620806@GENIA Treebank@formal@@1@S@These clones were tested for their recognition of BCR1/25.@@@@1@10@@oe@16-12-2010 981620807@GENIA Treebank@formal@@1@S@One clone (C3/5, CD3(+), CD4(+), CD8(-)) was selected for further analysis.@@@@1@17@@oe@16-12-2010 981620808@GENIA Treebank@formal@@1@S@Clone C3/5 showed specific proliferation, cytotoxicity, and cytokine (tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor) production when challenged with autologous lymphoblastic cell lines pulsed with peptide BCR1/25.@@@@1@33@@oe@16-12-2010 981620809@GENIA Treebank@formal@@1@S@C3/5 cells developed specific proliferation and cytotoxicity when challenged with peptide-pulsed lymphoblastic cell lines and peripheral blood lymphocytes from the four DR11(+) APL patients.@@@@1@25@@oe@16-12-2010 981620810@GENIA Treebank@formal@@1@S@APL blasts, available only from patients F. R. and P. G., were not lysed by C3/5 and were unable to present peptide BCR1/25.@@@@1@24@@oe@16-12-2010 981620811@GENIA Treebank@formal@@1@S@Incubation of APL cells with IFN-gamma failed to induce HLA class II molecules and recognition by the C3/5 clone.@@@@1@20@@oe@16-12-2010 981620812@GENIA Treebank@formal@@1@S@Since APL cells do not express HLA class II molecules, we tested in two donors (D. E. and C. H. R.) and in patients S.R.and P.G.whether the use of 9-mer peptides (BCR1/9) would generate a CD8/HLA class I-restricted response.@@@@1@44@@oe@16-12-2010 981620813@GENIA Treebank@formal@@1@S@No peptide-specific T-cell line or clone could be generated from both donors and patients.@@@@1@15@@oe@16-12-2010 981620814@GENIA Treebank@formal@@1@S@These findings are discussed in relation to possible therapeutic approaches to the immunotherapy of APL.@@@@1@16@@oe@16-12-2010 981760301@GENIA Treebank@formal@@1@S@Transcriptional regulation of the beta-casein gene by cytokines: cross-talk between STAT5 and other signaling molecules.@@@@1@17@@oe@16-12-2010 981760302@GENIA Treebank@formal@@1@S@The beta-casein promoter has been widely used to monitor the activation of STAT (signal transducer and activator of transcription)5 since STAT5 was originally found as a mediator of PRL-inducible beta-casein expression.@@@@1@35@@oe@16-12-2010 981760303@GENIA Treebank@formal@@1@S@However, not only is expression of the beta-casein gene regulated by STAT5 but it is also affected by other molecules such as glucocorticoid and Ras.@@@@1@27@@oe@16-12-2010 981760304@GENIA Treebank@formal@@1@S@In this report, we describe the transcriptional regulation of the beta-casein gene by cytokines in T cells.@@@@1@19@@oe@16-12-2010 981760305@GENIA Treebank@formal@@1@S@We have found that the beta-casein gene is expressed in a cytotoxic T cell line, CTLL-2, in response to interleukin-2 (IL-2), which activates STAT5.@@@@1@30@@oe@16-12-2010 981760306@GENIA Treebank@formal@@1@S@While IL-4 does not activate STAT5, it induces expression of STAT5-regulated genes in CTLL-2, i.e. beta-casein, a cytokine-inducible SH2-containing protein (CIS), and oncostatin M (OSM), suggesting that STAT6 activated by IL-4 substitutes for the function of STAT5 in T cells.@@@@1@50@@oe@16-12-2010 981760307@GENIA Treebank@formal@@1@S@IL-2-induced beta-casein expression was enhanced by dexamethasone, and this synergistic effect of Dexamethasone requires the sequence between -155 and -193 in the beta-casein promoter.@@@@1@26@@oe@16-12-2010 981760308@GENIA Treebank@formal@@1@S@Coincidentally, a deletion of this region enhanced the IL-2-induced expression of beta-casein.@@@@1@14@@oe@16-12-2010 981760309@GENIA Treebank@formal@@1@S@Expression of an active form of Ras, Ras(G12V), suppressed the IL-2-induced beta-casein and OSM gene expression, and the negative effect of Ras is mediated by the region between -105 and -193 in the beta-casein promoter.@@@@1@39@@oe@16-12-2010 981760310@GENIA Treebank@formal@@1@S@In apparent contradiction, expression of a dominant negative form of Ras, RasN17, also inhibited IL-2-induced activation of the promoter containing the minimal beta-casein STAT5 element as well as the promoters of CIS and OSM.@@@@1@38@@oe@16-12-2010 981760311@GENIA Treebank@formal@@1@S@In addition, Ras(G12V) complemented signaling by an erythropoietin receptor mutant defective in Ras activation and augmented the activation of the beta-casein promoter by the mutant erythropoietin receptor signaling, suggesting a possible role of Ras in Stat5-mediated gene expression.@@@@1@41@@oe@16-12-2010 981760312@GENIA Treebank@formal@@1@S@These results collectively reveal a complex interaction of STAT5 with other signaling pathways and illustrate that regulation of gene expression requires integration of opposing signals.@@@@1@26@@oe@16-12-2010 981915101@GENIA Treebank@formal@@1@S@Transcription factor NF-kappaB regulation of renal fibrosis during ureteral obstruction.@@@@1@11@@oe@16-12-2010 981915102@GENIA Treebank@formal@@1@S@Irrespective of the etiology, many kidney diseases result in inflammation and fibrosis of the tubulointerstitium, with the subsequent loss of renal function.@@@@1@25@@oe@16-12-2010 981915103@GENIA Treebank@formal@@1@S@To initiate any disease process or for any disease process to progress, there must be changes in the transcription of genes within the affected tissue.@@@@1@27@@oe@16-12-2010 981915104@GENIA Treebank@formal@@1@S@The nuclear factor-kappa B (NF-kappaB) family of transcription factors regulates genes involved in inflammation, cell proliferation, and cell differentiation.@@@@1@24@@oe@16-12-2010 981915105@GENIA Treebank@formal@@1@S@This review discusses the NF-kappaB transcription factor family in general and the association of NF-kappaB activation with cellular/molecular events of renal inflammation and fibrosis.@@@@1@25@@oe@16-12-2010 981938201@GENIA Treebank@formal@@1@S@TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3.@@@@1@22@@oe@16-12-2010 981938202@GENIA Treebank@formal@@1@S@Previously, we have shown that TAL1 and the LIM-only protein gene (LMO) are regularly coactivated in T-cell acute lymphoblastic leukemia (T-ALL).@@@@1@27@@oe@16-12-2010 981938203@GENIA Treebank@formal@@1@S@This observation is likely to relate to the findings that TAL1 and LMO are highly synergistic in T-cell tumorigenesis in double-transgenic mice.@@@@1@23@@oe@16-12-2010 981938204@GENIA Treebank@formal@@1@S@To understand the molecular mechanisms of functional synergy between TAL1 and LMO in tumorigenesis and transcriptional regulation, we tried to identify downstream target genes regulated by TAL1 and LMO by a subtractive PCR method.@@@@1@36@@oe@16-12-2010 981938205@GENIA Treebank@formal@@1@S@One of the isolated genes, that for retinaldehyde dehydrogenase 2 (RALDH2), was regularly expressed in most of the T-ALL cell lines that coexpressed TAL1 and LMO.@@@@1@31@@oe@16-12-2010 981938206@GENIA Treebank@formal@@1@S@Exogenously transfected TAL1 and LMO, but not either alone, induced RALDH2 expression in a T-ALL cell line, HPB-ALL, not expressing endogeneous TAL1 or LMO.@@@@1@29@@oe@16-12-2010 981938207@GENIA Treebank@formal@@1@S@The RALDH2 transcripts in T-ALL were, however, mostly initiated within the second intron.@@@@1@16@@oe@16-12-2010 981938208@GENIA Treebank@formal@@1@S@Promoter analysis revealed that a GATA site in a cryptic promoter in the second intron was essential and sufficient for the TAL1- and LMO-dependent transcriptional activation, and GATA3 binds to this site.@@@@1@34@@oe@16-12-2010 981938209@GENIA Treebank@formal@@1@S@In addition, forced expression of GATA3 potentiated the induction of RALDH2 by TAL1 and LMO, and these three factors formed a complex in vivo.@@@@1@27@@oe@16-12-2010 981938210@GENIA Treebank@formal@@1@S@Furthermore, a TAL1 mutant not binding to DNA also activated the transcription of RALDH2 in the presence of LMO and GATA3.@@@@1@23@@oe@16-12-2010 981938211@GENIA Treebank@formal@@1@S@Collectively, we have identified the RALDH2 gene as a first example of direct transcriptional target genes regulated by TAL1 and LMO in T-ALL.@@@@1@25@@oe@16-12-2010 981938212@GENIA Treebank@formal@@1@S@In this case, TAL1 and LMO act as cofactors for GATA3 to activate the transcription of RALDH2.@@@@1@19@@oe@16-12-2010 981939001@GENIA Treebank@formal@@1@S@The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development.@@@@1@21@@oe@16-12-2010 981939002@GENIA Treebank@formal@@1@S@Hox11 is a homeobox gene essential for spleen formation in mice, since atrophy of the anlage of a developing spleen occurs in early embryonic development in Hox11 null mice.@@@@1@31@@oe@16-12-2010 981939003@GENIA Treebank@formal@@1@S@HOX11 is also expressed in a subset of T-cell acute leukemias after specific chromosomal translocations.@@@@1@16@@oe@16-12-2010 981939004@GENIA Treebank@formal@@1@S@Since the protein has a homeodomain and can activate transcription, it probably exerts at least some of its effects in vivo by regulation of target genes.@@@@1@28@@oe@16-12-2010 981939005@GENIA Treebank@formal@@1@S@Representational difference analysis has been used to isolate cDNA clones corresponding to mRNA species activated following stable expression of HOX11 in NIH 3T3 cells.@@@@1@25@@oe@16-12-2010 981939006@GENIA Treebank@formal@@1@S@The gene encoding the retinoic acid-synthesizing enzyme aldehyde dehydrogenase 1 (Aldh1), initially called Hdg-1, was found to be ectopically activated by HOX11 in this system.@@@@1@30@@oe@16-12-2010 981939007@GENIA Treebank@formal@@1@S@Study of Aldh1 gene expression during spleen development showed that the presence of Aldh1 mRNA inversely correlated with Hox11.@@@@1@20@@oe@16-12-2010 981939008@GENIA Treebank@formal@@1@S@Hox11 null mouse embryos have elevated Aldh1 mRNA in spleen primordia prior to atrophy, while Aldh1 seems to be repressed by Hox11 during organogenesis of the spleens of wild-type mice.@@@@1@32@@oe@16-12-2010 981939009@GENIA Treebank@formal@@1@S@This result suggests that expression of Aldh1 protein is negatively regulated by Hox11 and that abnormal expression of Aldh1 in Hox11 null mice may cause loss of splenic precursor cells by aberrant retinoic acid metabolism.@@@@1@36@@oe@16-12-2010 982377401@GENIA Treebank@formal@@1@S@Granulocyte colony-stimulating factor activates a 72-kDa isoform of STAT3 in human neutrophils.@@@@1@13@@oe@16-12-2010 982377402@GENIA Treebank@formal@@1@S@Granulocyte colony-stimulating factor (G-CSF) signaling involves activation of STATs, proteins that serve the dual function of signal transduction and activation of transcription.@@@@1@26@@oe@16-12-2010 982377403@GENIA Treebank@formal@@1@S@We previously demonstrated that G-CSF activated a distinct Stat3-like protein in immature and mature normal myeloid cells, StatG.@@@@1@20@@oe@16-12-2010 982377404@GENIA Treebank@formal@@1@S@StatG in normal immature human myeloid cells, i.e. adult CD34+ bone marrow cells, was composed of Stat3beta.@@@@1@20@@oe@16-12-2010 982377405@GENIA Treebank@formal@@1@S@This investigation was undertaken to determine the composition of StatG in mature normal human myeloid cells, i.e. polymorphonuclear neutrophilic granulocytes (PMN).@@@@1@25@@oe@16-12-2010 982377406@GENIA Treebank@formal@@1@S@These studies revealed that the major protein in extracts of PMN activated by G-CSF to bind the high-affinity serum-inducible element (hSIE) is a 72-kDa protein that cross-reacts with Stat3 monoclonal antibody, which we have designated Stat3gamma.@@@@1@40@@oe@16-12-2010 982377407@GENIA Treebank@formal@@1@S@Stat3gamma is derived from Stat3alpha by limited proteolysis and lacks the carboxyl-terminal portion of Stat3alpha.@@@@1@16@@oe@16-12-2010 982377408@GENIA Treebank@formal@@1@S@Because this region of Stat3alpha is involved in transcriptional activation, our findings suggest the possibility that Stat3gamma may be transcriptionally inactive and may compete with Stat3alpha for Stat3 binding sites in these terminally differentiated myeloid cells.@@@@1@38@@oe@16-12-2010 982448501@GENIA Treebank@formal@@1@S@Differential effects of protein kinase C inhibitors on fibronectin-induced interleukin-beta gene transcription, protein synthesis and secretion in human monocytic cells.@@@@1@22@@oe@16-12-2010 982448502@GENIA Treebank@formal@@1@S@Human monocytic cells express interleukin-1beta (IL-1beta) when stimulated with the extracellular matrix glycoprotein, fibronectin (FN).@@@@1@21@@oe@16-12-2010 982448503@GENIA Treebank@formal@@1@S@Protein kinase C (PKC) activation is considered important for this process; however, the metabolic steps at which PKC acts upon to mediate the FN-induced IL-1beta response remain unclear.@@@@1@33@@oe@16-12-2010 982448504@GENIA Treebank@formal@@1@S@We performed an analysis of the mechanisms by which two PKC inhibitors, Calphostin C and Staurosporine, prevent the FN-induced IL-1beta response.@@@@1@24@@oe@16-12-2010 982448505@GENIA Treebank@formal@@1@S@Both inhibitors blocked the secretion of IL-1beta protein into the media of peripheral blood mononuclear cells exposed to FN.@@@@1@20@@oe@16-12-2010 982448506@GENIA Treebank@formal@@1@S@Immunoprecipitation analysis revealed that under these circumstances, Calphostin C inhibited the production of IL-1beta protein, whereas Staurosporine allowed protein production, but inhibited its secretion.@@@@1@28@@oe@16-12-2010 982448507@GENIA Treebank@formal@@1@S@To determine the mechanisms responsible for these differences, we turned to human U937 promonocytic cells.@@@@1@17@@oe@16-12-2010 982448508@GENIA Treebank@formal@@1@S@U937 cells transfected with the human full-length IL-1beta promoter connected to a luciferase reporter gene were submitted to transcription assays, Northern blotting, and DNA electrophoresis mobility gel shift assays.@@@@1@32@@oe@16-12-2010 982448509@GENIA Treebank@formal@@1@S@These studies revealed that Calphostin C inhibited the nuclear translocation of the transcription factor activator protein-1 (AP-1) which is considered necessary for FN induction of IL-1beta gene transcription, and prevented the transcription of the IL-1beta gene.@@@@1@40@@oe@16-12-2010 982448510@GENIA Treebank@formal@@1@S@In contrast, Staurosporine alone induced AP-1 translocation and stimulation of the gene.@@@@1@14@@oe@16-12-2010 982448511@GENIA Treebank@formal@@1@S@Overall, our data indicate that Calphostin C prevents the transcription of the IL-1beta gene thereby inhibiting protein synthesis.@@@@1@20@@oe@16-12-2010 982448512@GENIA Treebank@formal@@1@S@Based on the high specificity of this compound for PKC, we conclude that PKC is necessary for FN-induced IL-1beta protein production.@@@@1@23@@oe@16-12-2010 982448513@GENIA Treebank@formal@@1@S@In contrast, Staurosporine prevented secretion of IL-1beta by unknown mechanisms.@@@@1@12@@oe@16-12-2010 982582001@GENIA Treebank@formal@@1@S@Membrane-associated lymphotoxin on natural killer cells activates endothelial cells via an NF-kappaB-dependent pathway.@@@@1@14@@oe@16-12-2010 982582002@GENIA Treebank@formal@@1@S@BACKGROUND: Inhibition of complement in small animal models of xenotransplantation has demonstrated graft infiltration with natural killer (NK) cells and monocytes associated with endothelial cell (EC) activation.@@@@1@33@@oe@16-12-2010 982582003@GENIA Treebank@formal@@1@S@We have previously demonstrated that human NK cells activate porcine EC in vitro, which results in adhesion molecule expression and cytokine secretion.@@@@1@24@@oe@16-12-2010 982582004@GENIA Treebank@formal@@1@S@In this study, we used the NK cell line NK92 to define the molecular and cellular basis of NK cell-mediated EC activation.@@@@1@24@@oe@16-12-2010 982582005@GENIA Treebank@formal@@1@S@METHODS: EC were transfected with either reporter constructs containing the luciferase gene driven either by E-selectin or interleukin (IL)-8 promoters or a synthetic NF-kappaB-dependent promoter.@@@@1@30@@oe@16-12-2010 982582006@GENIA Treebank@formal@@1@S@In addition, a dominant-negative mutant tumor necrosis factor receptor I (TNFRI) expression vector was co-transfected in inhibition studies.@@@@1@22@@oe@16-12-2010 982582007@GENIA Treebank@formal@@1@S@Forty-eight hours after transfection, EC were stimulated with NK cells or NK cell membrane extracts for 7 hr and activation was measured by a luciferase assay.@@@@1@28@@oe@16-12-2010 982582008@GENIA Treebank@formal@@1@S@RESULTS: Co-culture of NK cells with transfected EC enhanced E-selectin, IL-8, and NF-kappaB-dependent promoter activity.@@@@1@19@@oe@16-12-2010 982582009@GENIA Treebank@formal@@1@S@NK cell membrane extracts retained the capacity to activate EC and induced nuclear translocation of NF-kappaB (p50 and p65).@@@@1@22@@oe@16-12-2010 982582010@GENIA Treebank@formal@@1@S@Western blotting of NK cell and membrane extracts detected the presence of Lymphotoxin-alpha (LTalpha) but not tumor necrosis factor-alpha.@@@@1@22@@oe@16-12-2010 982582011@GENIA Treebank@formal@@1@S@Furthermore, LTalpha was secreted in NK:EC co-cultures.@@@@1@9@@oe@16-12-2010 982582012@GENIA Treebank@formal@@1@S@Co-transfection with dominant-negative mutant TNFRI inhibited EC activation by NK cell membrane extracts and by NK cells by 80% and 47%, respectively.@@@@1@26@@oe@16-12-2010 982582013@GENIA Treebank@formal@@1@S@The same pattern of inhibition was observed using anti-human LT sera.@@@@1@12@@oe@16-12-2010 982582014@GENIA Treebank@formal@@1@S@CONCLUSIONS: Human NK cell membrane-bound LT signals across species via TNFRI, leading to NF-kappaB nuclear translocation and transcription of E-selectin and IL-8, which results in EC activation.@@@@1@31@@oe@16-12-2010 982582015@GENIA Treebank@formal@@1@S@The discrepancy in the degree of inhibition by membrane extracts and NK cells with mutant TNFRI suggests that additional pathways are utilized by NK cells to activate EC.@@@@1@29@@oe@16-12-2010 982602801@GENIA Treebank@formal@@1@S@Triptolide induces apoptotic death of T lymphocyte.@@@@1@8@@oe@16-12-2010 982602802@GENIA Treebank@formal@@1@S@Extract of Tripterygium wilfordii Hook. f (TWHf) has immunosuppressive activity and has been used as anti-inflammatory agent in traditional Chinese medicine for centuries.@@@@1@26@@oe@16-12-2010 982602803@GENIA Treebank@formal@@1@S@Recent studies have demonstrated that triptolide is the major active component in the extract that inhibits antigen or mitogen-induced T cell proliferation.@@@@1@23@@oe@16-12-2010 982602804@GENIA Treebank@formal@@1@S@In attempting to investigate its effect on activation of T lymphocytes, we found triptolide induces apoptotic death of T cell hybridomas and peripheral T cells but not that of thymocytes.@@@@1@32@@oe@16-12-2010 982602805@GENIA Treebank@formal@@1@S@The triptolide-induced apoptosis is accompanied by increase of DEVD-cleavable caspases activity and degradation of caspase substrate poly (ADP-ribose) polymerase (PARP).@@@@1@25@@oe@16-12-2010 982602806@GENIA Treebank@formal@@1@S@A specific inhibitor of caspases, zVAD-FMK, prevents triptolide-induced PARP degradation and DNA fragmentation but not growth arrest.@@@@1@20@@oe@16-12-2010 982602807@GENIA Treebank@formal@@1@S@Furthermore, enforced expression of Bcl-2 inhibited triptolide-induced degradation of PARP and apoptosis.@@@@1@14@@oe@16-12-2010 982602808@GENIA Treebank@formal@@1@S@These results indicate that triptolide induces T cell apoptosis through activating caspases, and suggest the growth arrest and apoptotic effect of triptolide may contribute to the immunosuppressive activity of TWHf extract.@@@@1@33@@oe@16-12-2010 982653901@GENIA Treebank@formal@@1@S@Spi-1/PU.1 proto-oncogene induces opposite effects on monocytic and erythroid differentiation of K562 cells.@@@@1@14@@oe@16-12-2010 982653902@GENIA Treebank@formal@@1@S@Spi-1/PU.1 is a hematopoietic transcription factor of the Ets family.@@@@1@11@@oe@16-12-2010 982653903@GENIA Treebank@formal@@1@S@To analyze the effects of ectopic expression of spi-1 on the proliferation/differentiation of human myeloid leukemia cells, K562 cells were stably transfected with a spi-1 expression vector.@@@@1@29@@oe@16-12-2010 982653904@GENIA Treebank@formal@@1@S@The transfected cell lines expressed elevated levels of spi-1 mRNA and protein and high Spi-1-DNA binding activity.@@@@1@18@@oe@16-12-2010 982653905@GENIA Treebank@formal@@1@S@The spi-1 transfected cells showed reduced growth rates and reduced clonogenic cell growth.@@@@1@14@@oe@16-12-2010 982653906@GENIA Treebank@formal@@1@S@When the erythroid and monocytic differentiation markers were analyzed, spi-1 overexpression resulted in opposite effects: erythroid differentiation was significantly inhibited in spi-1 transfectants, while spi-1 overexpression increased the monocytic differentiation of cells.@@@@1@36@@oe@16-12-2010 982653907@GENIA Treebank@formal@@1@S@These results indicate a differential role of Spi-1 on the differentiation of human myeloid leukemia cells.@@@@1@17@@oe@16-12-2010 982653908@GENIA Treebank@formal@@1@S@Copyright 1998 Academic Press.@@@@1@5@@oe@16-12-2010 982812101@GENIA Treebank@formal@@1@S@The human gene encoding the lectin-type oxidized LDL receptor (OLR1) is a novel member of the natural killer gene complex with a unique expression profile.@@@@1@28@@oe@16-12-2010 982812102@GENIA Treebank@formal@@1@S@LOX-1 is an endothelial receptor for oxidized low-density lipoprotein that plays essential roles in atherogenesis.@@@@1@16@@oe@16-12-2010 982812103@GENIA Treebank@formal@@1@S@LOX-1 has the highest homology with C-type lectin receptors expressed on natural killer cells.@@@@1@15@@oe@16-12-2010 982812104@GENIA Treebank@formal@@1@S@In the present study, we cloned and characterized the human LOX-1 gene (HGMW-approved symbol OLR1).@@@@1@19@@oe@16-12-2010 982812105@GENIA Treebank@formal@@1@S@The gene structure of LOX-1 resembles that of the natural killer cell receptors.@@@@1@14@@oe@16-12-2010 982812106@GENIA Treebank@formal@@1@S@Fluorescence in situ hybridization and analyses of a yeast artificial chromosome contig revealed that the human LOX-1 gene is located in the natural killer gene complex on chromosome 12p12-p13, where the genes of the natural killer cell receptors cluster.@@@@1@41@@oe@16-12-2010 982812107@GENIA Treebank@formal@@1@S@In contrast, the expression pattern of LOX-1 is different from that of the natural killer cell receptors; LOX-1 is expressed in vascular-rich organs, but not in lymphocytes.@@@@1@31@@oe@16-12-2010 982812108@GENIA Treebank@formal@@1@S@A 1753-bp fragment of the 5' flanking region of the LOX-1 gene had a functional promoter activity.@@@@1@18@@oe@16-12-2010 982812109@GENIA Treebank@formal@@1@S@This region contains binding sites for several transcription factors, including the STAT family and NF-IL6, and the expression of LOX-1 was upregulated by several cytokines.@@@@1@28@@oe@16-12-2010 982812110@GENIA Treebank@formal@@1@S@These results demonstrate that the human LOX-1 gene is a new member of the natural killer gene complex with a unique expression profile.@@@@1@24@@oe@16-12-2010 982812111@GENIA Treebank@formal@@1@S@Copyright 1998 Academic Press.@@@@1@5@@oe@16-12-2010 982813001@GENIA Treebank@formal@@1@S@Cloning of ARE-containing genes by AU-motif-directed display.@@@@1@8@@oe@16-12-2010 982813002@GENIA Treebank@formal@@1@S@A procedure suitable for cloning labile mRNAs that contain AU motifs is presented (AU-DD).@@@@1@17@@oe@16-12-2010 982813003@GENIA Treebank@formal@@1@S@These motifs are regulatory sequences within the so-called AU-rich elements (AREs) often found in 3' untranslated regions of genes such as cytokines, proto-oncogenes, and transcription factors.@@@@1@31@@oe@16-12-2010 982813004@GENIA Treebank@formal@@1@S@AU-DD is an AU-motif-directed differential display that permits the identification of ARE-containing genes differentially expressed after cell activation.@@@@1@19@@oe@16-12-2010 982813005@GENIA Treebank@formal@@1@S@It has been applied to peripheral blood monocytes and a T cell clone to isolate 59 cDNA fragments associated to activation.@@@@1@22@@oe@16-12-2010 982813006@GENIA Treebank@formal@@1@S@Fourteen percent of isolated fragments belong to already known genes that certainly are cytokines and transduction/transcription factors.@@@@1@18@@oe@16-12-2010 982813007@GENIA Treebank@formal@@1@S@The remaining 86% correspond to unknown genes of which 92% have been confirmed to be differentially expressed.@@@@1@20@@oe@16-12-2010 982813008@GENIA Treebank@formal@@1@S@These data demonstrate the efficiency of the system and support the notion that numerous genes falling into those categories remain unidentified and that they can be cloned by this method.@@@@1@31@@oe@16-12-2010 982813009@GENIA Treebank@formal@@1@S@Copyright 1998 Academic Press.@@@@1@5@@oe@16-12-2010 983117001@GENIA Treebank@formal@@1@S@Thrombopoietin and its receptor.@@@@1@5@@oe@16-12-2010 983117002@GENIA Treebank@formal@@1@S@Thrombopoietin (TPO), the primary physiological regulator of platelet production, was initially thought to be a lineage-specific factor acting predominantly on megakaryocytopoiesis.@@@@1@26@@oe@16-12-2010 983117003@GENIA Treebank@formal@@1@S@Detailed studies establish that this cytokine mediates biological effects on a broad spectrum of hematopoietic progenitor cells, including stem cells.@@@@1@22@@oe@16-12-2010 983117004@GENIA Treebank@formal@@1@S@TPO is a hormone constitutively produced mainly by the liver and kidney.@@@@1@13@@oe@16-12-2010 983117005@GENIA Treebank@formal@@1@S@Plasma TPO levels are regulated by the platelet and megakaryocyte mass through Mpl receptor binding, internalization and degradation.@@@@1@20@@oe@16-12-2010 983117006@GENIA Treebank@formal@@1@S@The Mpl receptor is a member of the hematopoietin receptor superfamily lacking intrinsic kinase activity.@@@@1@16@@oe@16-12-2010 983117007@GENIA Treebank@formal@@1@S@Upon ligand-induced Mpl homodimerization, the major signaling events for proliferation are mediated through the JAK2/STAT5 pathway, while differentiation might occur through a prolonged activation of the MAPK pathway.@@@@1@31@@oe@16-12-2010 983117008@GENIA Treebank@formal@@1@S@Preclinical and clinical studies demonstrate the potential use of TPO in a variety of contexts, but it is too early to evaluate its benefit in reducing platelet transfusion.@@@@1@30@@oe@16-12-2010 983186501@GENIA Treebank@formal@@1@S@Differential activation of functionally distinct STAT5 proteins by IL-5 and GM-CSF during eosinophil and neutrophil differentiation from human CD34+ hematopoietic stem cells.@@@@1@23@@oe@16-12-2010 983186502@GENIA Treebank@formal@@1@S@Interleukin-5 (IL-5) and granulocyte macrophage-colony stimulating factor (GM-CSF) are important cytokines for the proliferation, differentiation, and activation of myeloid lineages.@@@@1@27@@oe@16-12-2010 983186503@GENIA Treebank@formal@@1@S@The JAK/STAT pathway is one of the signaling pathways implicated in mediating biological responses induced by these cytokines.@@@@1@19@@oe@16-12-2010 983186504@GENIA Treebank@formal@@1@S@Previous studies have demonstrated that these cytokines predominantly activate an 80 kDa STAT5 isoform in mature granulocytes.@@@@1@18@@oe@16-12-2010 983186505@GENIA Treebank@formal@@1@S@To better understand the role of STAT proteins during growth and differentiation of granulocytes, we evaluated differentiation of human CD34+ hematopoietic stem cells ex vivo toward eosinophils and neutrophils.@@@@1@31@@oe@16-12-2010 983186506@GENIA Treebank@formal@@1@S@Bandshift experiments showed that in an early stage of both differentiation pathways (14 days), the 94 kDa STAT5B protein was activated by both IL-5 (eosinophil lineage) and GM-CSF (neutrophil lineage).@@@@1@38@@oe@16-12-2010 983186507@GENIA Treebank@formal@@1@S@However, during maturation of both lineages (days 21 and 28), increased expression of a functionally distinct 80 kDa STAT5 isoform was observed, resulting in heterodimer DNA-binding complexes containing both the 94 and 80 kDa STAT5 proteins.@@@@1@42@@oe@16-12-2010 983186508@GENIA Treebank@formal@@1@S@The finding that functionally distinct isoforms of STAT5 are activated during the early and late differentiation stages of granulocytes suggests that they might be involved in regulating different biological functions in these cells.@@@@1@34@@oe@16-12-2010 983405501@GENIA Treebank@formal@@1@S@BASH, a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius.@@@@1@17@@oe@16-12-2010 983405502@GENIA Treebank@formal@@1@S@The bursa of Fabricius is a gut-associated lymphoid organ that is essential for the generation of a diversified B cell repertoire in the chicken.@@@@1@25@@oe@16-12-2010 983405503@GENIA Treebank@formal@@1@S@We describe here a novel gene preferentially expressed in bursal B cells.@@@@1@13@@oe@16-12-2010 983405504@GENIA Treebank@formal@@1@S@The gene encodes an 85-kDa protein, designated BASH (B cell adaptor containing SH2 domain), that contains N-terminal acidic domains with SH2 domain-binding phosphotyrosine-based motifs, a proline-rich domain, and a C-terminal SH2 domain.@@@@1@39@@oe@16-12-2010 983405505@GENIA Treebank@formal@@1@S@BASH shows a substantial sequence similarity to SLP-76, an adaptor protein functioning in TCR-signal transduction.@@@@1@17@@oe@16-12-2010 983405506@GENIA Treebank@formal@@1@S@BASH becomes tyrosine-phosphorylated with the B cell Ag receptor (BCR) cross-link or by coexpression with Syk and Lyn and associates with signaling molecules including Syk and a putative chicken Shc homologue.@@@@1@34@@oe@16-12-2010 983405507@GENIA Treebank@formal@@1@S@Overexpression of BASH results in suppression of the NF-AT activation induced by BCR-cross-linking.@@@@1@14@@oe@16-12-2010 983405508@GENIA Treebank@formal@@1@S@These findings suggest that BASH is involved in BCR-mediated signal transduction and could play a critical role in B cell development in the bursa.@@@@1@25@@oe@16-12-2010 983408101@GENIA Treebank@formal@@1@S@Signaling pathways mediated by the TNF- and cytokine-receptor families target a common cis-element of the IFN regulatory factor 1 promoter.@@@@1@21@@oe@16-12-2010 983408102@GENIA Treebank@formal@@1@S@CD40 activation of B cells is strongly influenced by the presence of cytokines.@@@@1@14@@oe@16-12-2010 983408103@GENIA Treebank@formal@@1@S@However, the molecular basis for the interplay between these distinct stimuli is not clearly delineated.@@@@1@17@@oe@16-12-2010 983408104@GENIA Treebank@formal@@1@S@IFN regulatory factor 1 (IRF-1) is a transcription factor activated by either CD40 or cytokines.@@@@1@18@@oe@16-12-2010 983408105@GENIA Treebank@formal@@1@S@We have found that these different sets of signals target a common cis-acting element in the promoter of this gene, the IRF-1 gamma-activated site (GAS).@@@@1@29@@oe@16-12-2010 983408106@GENIA Treebank@formal@@1@S@Targeting of the IRF-1 GAS is not confined to activation via CD40 but extends to other stimuli that mimic the CD40 signaling cascade, like TNF-alpha and EBV.@@@@1@29@@oe@16-12-2010 983408107@GENIA Treebank@formal@@1@S@In contrast to induction of STATs by cytokines, the IRF-1 GAS-binding complex activated by CD40, TNF-alpha, or EBV contains Rel proteins, specifically p50 and p65.@@@@1@30@@oe@16-12-2010 983408108@GENIA Treebank@formal@@1@S@In this system, simultaneous exposure to CD40L together with either IL-4 or IFN-gamma does not lead to the activation of novel Rel/STAT complexes.@@@@1@25@@oe@16-12-2010 983408109@GENIA Treebank@formal@@1@S@Given the importance of IRF-1 in a variety of biologic functions from proliferation to apoptosis, our findings support the notion that modulation of IRF-1 levels may be a critical control point in B cell activation.@@@@1@37@@oe@16-12-2010 983409201@GENIA Treebank@formal@@1@S@Regulation of NF-kappa B, AP-1, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50.@@@@1@31@@oe@16-12-2010 983409202@GENIA Treebank@formal@@1@S@Activation of T lymphocytes by Ags or cytokines results in translocation of the transcription factors NF-kappa B, AP-1, NFAT, and STAT from the cytoplasm into the nucleus.@@@@1@31@@oe@16-12-2010 983409203@GENIA Treebank@formal@@1@S@The first step in the nuclear import process is recognition of a nuclear localization sequence (NLS) within the karyophilic protein by a cytoplasmic receptor such as the importin (karyopherin)-alpha subunit.@@@@1@36@@oe@16-12-2010 983409204@GENIA Treebank@formal@@1@S@The NLSs of NF-kappa B, AP-1, and NFAT differ and the NLS of STAT1 has not yet been identified.@@@@1@22@@oe@16-12-2010 983409205@GENIA Treebank@formal@@1@S@Herein we demonstrate that the inducible nuclear import of NF-kappa B, AP-1, NFAT, and STAT1 in Jurkat T lymphocytes is significantly inhibited by a cell-permeable peptide carrying the NLS of the NF-kappa B p50 subunit.@@@@1@39@@oe@16-12-2010 983409206@GENIA Treebank@formal@@1@S@NLS peptide-mediated disruption of the nuclear import of these transcription factors results in inhibition of I kappa B alpha and IL-2 gene expression, processes dependent on NF-kappa B or the combination of NF-kappa B, AP-1, and NFAT.@@@@1@41@@oe@16-12-2010 983409207@GENIA Treebank@formal@@1@S@Further, we show that inhibitory NLS peptide interacts in vitro with a cytoplasmic NLS receptor complex comprised of the Rch1/importin (karyopherin)-beta heterodimer expressed in Jurkat T cells.@@@@1@32@@oe@16-12-2010 983409208@GENIA Treebank@formal@@1@S@Taken together, these data indicate that the inducible nuclear import of NF-kappa B, AP-1, NFAT, and STAT1 in Jurkat T cells can be regulated by NLS peptide delivered noninvasively to the cytoplasm of Jurkat T cells to target members of the importin (karyopherin)-alpha beta NLS receptor complex.@@@@1@55@@oe@16-12-2010 983427201@GENIA Treebank@formal@@1@S@Epithelial cell-initiated inflammation plays a crucial role in early tissue damage in amebic infection of human intestine.@@@@1@18@@oe@16-12-2010 983427202@GENIA Treebank@formal@@1@S@BACKGROUND & AIMS: Entamoeba histolytica infection of the intestine can induce severe gut inflammation.@@@@1@16@@oe@16-12-2010 983427203@GENIA Treebank@formal@@1@S@The aims of this study were to assess the role of the host inflammatory response in the tissue damage observed with amebiasis and the role of the intestinal epithelial cell in initiating that response.@@@@1@35@@oe@16-12-2010 983427204@GENIA Treebank@formal@@1@S@METHODS: E. histolytica infection was established in human intestinal xenografts in severe combined immunodeficient (SCID-HU-INT) mice.@@@@1@20@@oe@16-12-2010 983427205@GENIA Treebank@formal@@1@S@Human intestinal epithelial cell inflammatory responses to amebic infection were inhibited by the intraluminal administration of an antisense oligonucleotide to the human p65 subunit of nuclear factor kappaB, and the role of neutrophils in tissue damage observed with amebiasis was studied by depleting neutrophils from SCID-HU-INT mice.@@@@1@49@@oe@16-12-2010 983427206@GENIA Treebank@formal@@1@S@RESULTS: Administration of the antisense oligonucleotide blocked the production of human interleukin 1beta and interleukin 8 by intestinal epithelial cells and inhibited neutrophil influx into the E. histolytica-infected intestinal xenografts.@@@@1@32@@oe@16-12-2010 983427207@GENIA Treebank@formal@@1@S@Inhibition of the gut inflammatory response by the antisense oligonucleotide or the depletion of neutrophils from SCID-HU- INT mice blocked the increase in intestinal permeability observed with amebic infection.@@@@1@29@@oe@16-12-2010 983427208@GENIA Treebank@formal@@1@S@CONCLUSIONS: Intestinal epithelial cells initiate an inflammatory response with resulting neutrophil-mediated tissue damage in response to E. histolytica infection; this inflammatory cascade can be blocked by inhibiting the transcription of genes regulated by nuclear factor kappaB.@@@@1@39@@oe@16-12-2010 983562601@GENIA Treebank@formal@@1@S@In vitro suppression of programmed cell death of B cells by tissue inhibitor of metalloproteinases-1.@@@@1@16@@oe@16-12-2010 983562602@GENIA Treebank@formal@@1@S@Cellular pathways for induction of programmed cell death (PCD) have been identified, but little is known about specific extracellular matrix processes that may affect apoptosis along those pathways.@@@@1@32@@oe@16-12-2010 983562603@GENIA Treebank@formal@@1@S@In this study, a series of Burkitt's lymphoma (BL) cell lines were assayed for their expression of tissue inhibitor of metalloproteinases (TIMP)-1.@@@@1@30@@oe@16-12-2010 983562604@GENIA Treebank@formal@@1@S@Results indicate that TIMP-1-positive BL lines show resistance to cold-shock-induced apoptosis.@@@@1@12@@oe@16-12-2010 983562605@GENIA Treebank@formal@@1@S@Furthermore, recombinant TIMP-1, but not TIMP-2 or a synthetic metalloproteinase inhibitor (BB-94), confers resistance to apoptosis induced by both CD95-dependent and -independent (cold shock, serum deprivation, and gamma-radiation) pathways in TIMP-1-negative BL lines.@@@@1@43@@oe@16-12-2010 983562606@GENIA Treebank@formal@@1@S@TIMP-1 suppression of PCD is not due to metalloproteinase inhibition, as reduction and alkylation of the TIMP-1 did not abolish this activity.@@@@1@24@@oe@16-12-2010 983562607@GENIA Treebank@formal@@1@S@Retroviral induction of TIMP-1 not only resulted in cell survival but also in continued DNA synthesis for up to 5 d in the absence of serum, while controls underwent apoptosis.@@@@1@32@@oe@16-12-2010 983562608@GENIA Treebank@formal@@1@S@This resistance to apoptosis is reversed by anti-TIMP-1 antibodies, demonstrating that secreted TIMP-1 is active in blocking apoptosis.@@@@1@20@@oe@16-12-2010 983562609@GENIA Treebank@formal@@1@S@Furthermore, TIMP-1 upregulation induced expression of Bcl-XL but not Bcl-2 as well as decreased NF-kappaB activity as compared with controls.@@@@1@22@@oe@16-12-2010 983562610@GENIA Treebank@formal@@1@S@These results demonstrate that TIMP-1 suppresses apoptosis in B cells and suggests a novel activity for TIMP-1 in tissue homeostasis.@@@@1@21@@oe@16-12-2010