937895301@GENIA Treebank@formal@@1@S@Nuclear localization of RelB is associated with effective antigen-presenting cell function.@@@@1@12@@oe@16-12-2010 937895302@GENIA Treebank@formal@@1@S@Dendritic cells (DC) are potent APCs that enter resting tissues as precursors and, after Ag exposure, differentiate and migrate to draining lymph nodes.@@@@1@28@@oe@16-12-2010 937895303@GENIA Treebank@formal@@1@S@The phenotype of RelB knockout mice implicates this member of the NF kappa B/Rel family in DC differentiation.@@@@1@19@@oe@16-12-2010 937895304@GENIA Treebank@formal@@1@S@To further elucidate the role of RelB in DC differentiation, mRNA, intracellular protein expression, and DNA binding activity of RelB were examined in immature and differentiated human DC, as well as other PB mononuclear cell populations.@@@@1@41@@oe@16-12-2010 937895305@GENIA Treebank@formal@@1@S@RelB protein and mRNA were detected constitutively in lymphocytes and in activated monocytes, differentiated DC, and monocyte-derived DC.@@@@1@21@@oe@16-12-2010 937895306@GENIA Treebank@formal@@1@S@Immunohistochemical staining demonstrated RelB within the differentiated lymph node interdigitating DC and follicular DC, but not undifferentiated DC in normal skin.@@@@1@23@@oe@16-12-2010 937895307@GENIA Treebank@formal@@1@S@Active nuclear RelB was detected by supershift assay only in differentiated DC derived from either PB precursors or monocytes and in activated B cells.@@@@1@25@@oe@16-12-2010 937895308@GENIA Treebank@formal@@1@S@These RelB+ APC were potent stimulators of the MLR.@@@@1@10@@oe@16-12-2010 937895309@GENIA Treebank@formal@@1@S@The data indicate that RelB expression is regulated both transcriptionally and post-translationally in myeloid cells.@@@@1@16@@oe@16-12-2010 937895310@GENIA Treebank@formal@@1@S@Within the nucleus, RelB may specifically transactivate genes that are critical for APC function.@@@@1@16@@oe@16-12-2010 937900201@GENIA Treebank@formal@@1@S@Regulation of nuclear factor-kappa B and its inhibitor I kappa B-alpha/MAD-3 in monocytes by Mycobacterium tuberculosis and during human tuberculosis.@@@@1@21@@oe@16-12-2010 937900202@GENIA Treebank@formal@@1@S@Blood monocytes from patients with active tuberculosis are activated in vivo, as evidenced by an increase in the stimulated release of proinflammatory cytokines, such as TNF-alpha, and the spontaneous expression of IL-2R.@@@@1@36@@oe@16-12-2010 937900203@GENIA Treebank@formal@@1@S@Further, monocytes from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro.@@@@1@18@@oe@16-12-2010 937900204@GENIA Treebank@formal@@1@S@Mycobacterium tuberculosis and its components are strong signals to activate monocytes to production of cytokines.@@@@1@16@@oe@16-12-2010 937900205@GENIA Treebank@formal@@1@S@In this study we examined the basis of activation of monocytes during active tuberculosis and by M. tuberculosis.@@@@1@19@@oe@16-12-2010 937900206@GENIA Treebank@formal@@1@S@We found a constitutive degradation of I kappa B-alpha, the major cytoplasmic inhibitor of nuclear factor kappa B (NF-kappa B), in freshly isolated PBMC and monocytes from patients with tuberculosis.@@@@1@35@@oe@16-12-2010 937900207@GENIA Treebank@formal@@1@S@In contrast, I kappa B-alpha levels in PBMC and monocytes from healthy subjects or from patients with nontuberculous pulmonary conditions were intact.@@@@1@24@@oe@16-12-2010 937900208@GENIA Treebank@formal@@1@S@Further, by electrophoretic mobility shift assay, NF-kappa B was activated in monocytes from tuberculous patients.@@@@1@18@@oe@16-12-2010 937900209@GENIA Treebank@formal@@1@S@The expression of I kappa B-alpha gene, which is responsive to activation by NF-kappa B, was up-regulated in PBMC and monocytes from patients, but not in mononuclear cells from healthy subjects or those with nontuberculous lung diseases.@@@@1@41@@oe@16-12-2010 937900210@GENIA Treebank@formal@@1@S@By contrast, the expression of other adherence-associated early genes, such as IL-8 and IL-1 beta, was not up-regulated in PBMC of tuberculous patients.@@@@1@27@@oe@16-12-2010 937900211@GENIA Treebank@formal@@1@S@Further, M. tuberculosis and its tuberculin, purified protein derivative, induced the degradation of I kappa B-alpha and the expression of I kappa B-alpha mRNA, and purified protein derivative induced the activation of NF-kappa B in monocytes.@@@@1@41@@oe@16-12-2010 938382801@GENIA Treebank@formal@@1@S@Pathogenesis.@@@@1@2@@oe@16-12-2010 938382802@GENIA Treebank@formal@@1@S@There are many hypotheses concerning the pathogenesis of endometriosis, though no single theory can explain all cases.@@@@1@19@@oe@16-12-2010 938382803@GENIA Treebank@formal@@1@S@It is likely that several mechanisms are involved.@@@@1@9@@oe@16-12-2010 938382804@GENIA Treebank@formal@@1@S@Early studies concentrated on the histogenesis of the endometriotic lesion.@@@@1@11@@oe@16-12-2010 938382805@GENIA Treebank@formal@@1@S@Recent evidence has implicated components of the immune system in the pathogenesis of endometriosis.@@@@1@15@@oe@16-12-2010 938382806@GENIA Treebank@formal@@1@S@This review considers the evidence for different theories of the histogenesis of endometriosis and discusses possible immune factors that may be involved in the pathophysiology of the disease.@@@@1@29@@oe@16-12-2010 938466101@GENIA Treebank@formal@@1@S@Expression of c-fos correlates with IFN-alpha responsiveness in Philadelphia chromosome positive chronic myelogenous leukemia.@@@@1@15@@oe@16-12-2010 938466102@GENIA Treebank@formal@@1@S@This study evaluates (i) constitutive levels of oncogene and p53 transcripts in chronic phase CML patients and (ii) their modulations subsequent to in vivo therapy with rIFN-alpha 2c.@@@@1@33@@oe@16-12-2010 938466103@GENIA Treebank@formal@@1@S@Peripheral blood mononuclear cells (pbmc) and bone marrow cells of 26 patients were examined for c-fos, c-myc, p53 and the hybrid bcr/abl mRNA levels.@@@@1@29@@oe@16-12-2010 938466104@GENIA Treebank@formal@@1@S@Results indicated that (i) constitutive c-fos transcript levels are significantly higher in patients subsequently responding to IFN-alpha therapy (p < 0.01) and positively correlated with the proportion of lymphocytes (r = 0.6895, p < 0.01) and negatively with the proportion of immature cells (r = -0.568, p < 0.01) contained in the pbmc preparations tested, (ii) constitutive mRNA levels of the hybrid bcr/abl, c-myc and p53 are positively correlated with each other, but failed to relate to disease parameters, and (iii) acute and chronic in vivo exposure to IFN-alpha is accompanied by upregulation of c-fos and downregulation of c-myc mRNA levels in responder patients.@@@@1@123@@oe@16-12-2010 938762301@GENIA Treebank@formal@@1@S@[The value of the clinical test of glucocorticoid receptors of peripheral blood leukocytes in patients with chronic pulmonary heart disease]@@@@1@22@@oe@16-12-2010 938762302@GENIA Treebank@formal@@1@S@In order to inquire into the functional state of adrenal cortex in patients with pulmonary heart disease, the number of glucocorticoid receptors(GCR) of peripheral blood leukocytes in patients with chronic pulmonary heart disease was determined with radioligand-binding assay and the corresponding plasma cortisol levels were assessed with radioimmune assays.@@@@1@54@@oe@16-12-2010 938762303@GENIA Treebank@formal@@1@S@The results showed that the number of GCR in the patients was significantly reduced (P < 0.01) and it was increased when their health state was improved.@@@@1@30@@oe@16-12-2010 938762304@GENIA Treebank@formal@@1@S@However, it was still lower than that in healthy subjects (P < 0.01).@@@@1@17@@oe@16-12-2010 938762305@GENIA Treebank@formal@@1@S@The number of GCR in the patients was greatly increased when these patients were treated with oxygen (P < 0.01).@@@@1@23@@oe@16-12-2010 938762306@GENIA Treebank@formal@@1@S@No difference in plasma cortisol was found between the patients and the healthy subjects (P > 0.05).@@@@1@20@@oe@16-12-2010 938762307@GENIA Treebank@formal@@1@S@These results indicate that the function of adrenal cortex may be improved by the compensation mechanism of the patients, but the lower GCR number was the result of lacking of oxygen in the patients.@@@@1@36@@oe@16-12-2010 938762308@GENIA Treebank@formal@@1@S@The number of GCR may be improved by inhalation of oxygen.@@@@1@12@@oe@16-12-2010 938762309@GENIA Treebank@formal@@1@S@Therefore oxygen therapy is helpful in raising the activity of glucocorticoid receptors and controlling the development of the disease.@@@@1@20@@oe@16-12-2010 938847501@GENIA Treebank@formal@@1@S@Molecular cloning and functional characterization of murine cDNA encoding transcription factor NFATc.@@@@1@13@@oe@16-12-2010 938847502@GENIA Treebank@formal@@1@S@Transcription factors of the NFAT (nuclear factor of activated T cells) family play important roles in immune and inflammatory responses by regulating the expression of genes encoding cytokines and immunoregulatory proteins.@@@@1@34@@oe@16-12-2010 938847503@GENIA Treebank@formal@@1@S@Here we describe cloning and characterization of full-length cDNA encoding murine (m) NFATc which predicts that the protein has all the conserved structural motifs of NFAT family members, including the rel homology domain, the NFAT homology domain and the nuclear translocation signals.@@@@1@47@@oe@16-12-2010 938847504@GENIA Treebank@formal@@1@S@mNFATc complexed with AP-1 bound specifically to the murine IL-2 NFAT recognition sequence and activated transcription from the co-transfected IL-2 promoter in COS-7 cells.@@@@1@25@@oe@16-12-2010 938847505@GENIA Treebank@formal@@1@S@Northern blot analysis showed that the cDNA probe hybridized with a 4.5 kb transcript which is highly inducible in murine T cells.@@@@1@23@@oe@16-12-2010 938847506@GENIA Treebank@formal@@1@S@By Northern and in situ hybridization, mNFATc transcript was detected from the early stage of development.@@@@1@18@@oe@16-12-2010 938847507@GENIA Treebank@formal@@1@S@In the mouse embryo, mNFATc transcript was strongly expressed in thymus, lung and submandibular gland and weakly in skeletal muscle and heart suggesting that mNFATc may have a role both in embryogenesis and in mature T cells.@@@@1@40@@oe@16-12-2010 939069101@GENIA Treebank@formal@@1@S@Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F.@@@@1@13@@oe@16-12-2010 939069102@GENIA Treebank@formal@@1@S@Cell cycle progression initiated by interleukin-2 (IL-2) in T cells is critical for lymphoproliferation and an immune response.@@@@1@21@@oe@16-12-2010 939069103@GENIA Treebank@formal@@1@S@Phosphatidyl inositol 3-kinase (PI3K) is activated by IL-2.@@@@1@11@@oe@16-12-2010 939069104@GENIA Treebank@formal@@1@S@However, nuclear targets for PI3K are not known.@@@@1@10@@oe@16-12-2010 939069105@GENIA Treebank@formal@@1@S@Here we identify the cell cycle regulator E2F as an IL-2 target in T lymphocytes and PI3K as the critical signaling pathway.@@@@1@23@@oe@16-12-2010 939069106@GENIA Treebank@formal@@1@S@We eliminate both Stat5 and Raf/MEK pathways from E2F regulation.@@@@1@11@@oe@16-12-2010 939069107@GENIA Treebank@formal@@1@S@Protein kinase B (PKB) is activated by IL-2 via PI3K.@@@@1@13@@oe@16-12-2010 939069108@GENIA Treebank@formal@@1@S@The expression of an active PKB is sufficient to induce E2F activity.@@@@1@13@@oe@16-12-2010 939069109@GENIA Treebank@formal@@1@S@Inhibition of PI3K inhibits phosphorylation of Rb, induction of cyclin D3, and degradation of p27kip1.@@@@1@18@@oe@16-12-2010 939069110@GENIA Treebank@formal@@1@S@These results establish a crucial PI3K/PKB-mediated link between the IL-2 teceptor and the cell cycle machinery.@@@@1@17@@oe@16-12-2010 939483201@GENIA Treebank@formal@@1@S@Thiol modulation inhibits the interleukin (IL)-1-mediated activation of an IL-1 receptor-associated protein kinase and NF-kappa B.@@@@1@20@@oe@16-12-2010 939483202@GENIA Treebank@formal@@1@S@The interleukin-1 receptor type I (IL-1RI) is associated with other proteins thus forming a complex system by which IL-1 exerts its various signals.@@@@1@26@@oe@16-12-2010 939483203@GENIA Treebank@formal@@1@S@The initiating event is still uncertain, but activation of a recently described receptor-associated protein kinase is one of the earliest events detectable (Martin et al., Eur.J.Immunol.1994.24: 1566).@@@@1@33@@oe@16-12-2010 939483204@GENIA Treebank@formal@@1@S@IL-1 signaling is commonly accompanied by oxidative processes and is thought to be subject to redox regulation.@@@@1@18@@oe@16-12-2010 939483205@GENIA Treebank@formal@@1@S@We therefore investigated whether the activation of the IL-1RI-associated protein kinase could be a target for redox regulation and whether an altered activity of the kinase could influence IL-1-mediated NF-kappa B activation.@@@@1@33@@oe@16-12-2010 939483206@GENIA Treebank@formal@@1@S@A murine T cell line, EL4, was stimulated with IL-1 with and without pretreatment with different compounds known to influence the cellular redox status.@@@@1@27@@oe@16-12-2010 939483207@GENIA Treebank@formal@@1@S@Thiol modifying agents like diamide, menadione, pyrrolidine dithiocarbamate (PDTC), diethyl dithiocarbamate or phenylarsine oxide inhibited the IL-1-induced activation of the IL-1RI-associated protein kinase.@@@@1@29@@oe@16-12-2010 939483208@GENIA Treebank@formal@@1@S@N-Acetylcysteine, alpha,alpha'-dipyridyl, aminotriazole or nitrofurantoin did not show any effect.@@@@1@13@@oe@16-12-2010 939483209@GENIA Treebank@formal@@1@S@The inhibition by PDTC was reversible unless glutathione synthesis was blocked by buthionine sulfoximine.@@@@1@15@@oe@16-12-2010 939483210@GENIA Treebank@formal@@1@S@The described conditions which inhibited or prevented the activation of the IL-1RI-associated kinase similarly impaired the activation of NF-kappa B in EL4 cells.@@@@1@24@@oe@16-12-2010 939483211@GENIA Treebank@formal@@1@S@From these observations we conclude that free thiols in the IL-1RI complex are essential for the activation of the IL-1RI-associated protein kinase and that this process is mandatory for IL-1 signaling leading to NF-kappa B activation.@@@@1@37@@oe@16-12-2010 939808701@GENIA Treebank@formal@@1@S@Differanisole A, a novel antitumor antibiotic, enhances growth inhibition and differentiation of human myeloid leukemia cells induced by 9-cis retinoic acid.@@@@1@24@@oe@16-12-2010 939808702@GENIA Treebank@formal@@1@S@Differanisole A, 3,5-dichloro-2-hydroxy-4-methoxy-6-n-propylbenzoic acid, inhibited growth of human myeloid leukemia cells.@@@@1@14@@oe@16-12-2010 939808703@GENIA Treebank@formal@@1@S@The compound induced G1 arrest and granulocytic differentiation of HL-60 cells, although the differentiation-inducing effect was modest.@@@@1@19@@oe@16-12-2010 939808704@GENIA Treebank@formal@@1@S@Differanisole A and 9-cis retinoic acid (9cisRA) synergistically inhibited the growth and induced functional and morphologic differentiation of HL-60 and NB4 cells, whereas the combined treatment with differanisole A and all-trans retinoic acid or 1alpha,25-dihydroxyvitamin D3 was less effective.@@@@1@43@@oe@16-12-2010 939808705@GENIA Treebank@formal@@1@S@Similar results were obtained in primary culture of leukemia cells from a patient with acute promyelocytic leukemia.@@@@1@18@@oe@16-12-2010 939808706@GENIA Treebank@formal@@1@S@The synergistic effect on growth inhibition and induction of differentiation required simultaneous treatment with differanisole A and 9cisRA.@@@@1@19@@oe@16-12-2010 939808707@GENIA Treebank@formal@@1@S@Differanisole A and an RXR-specific ligand (Ro47-5944) cooperatively inhibited the cell growth, while the combined effect of differanisole A and an RAR-specific ligand Am80 was just additive.@@@@1@31@@oe@16-12-2010 939808708@GENIA Treebank@formal@@1@S@Differanisole A in combination with 9cisRA may have implications for therapy of acute promyelocytic leukemia patients.@@@@1@17@@oe@16-12-2010 939816301@GENIA Treebank@formal@@1@S@ATF1 and CREB trans-activate a cell cycle regulated histone H4 gene at a distal nuclear matrix associated promoter element.@@@@1@20@@oe@16-12-2010 939816302@GENIA Treebank@formal@@1@S@Proteins of the ATF/CREB class of transcription factors stimulate gene expression of several cell growth-related genes through protein kinase A-related cAMP response elements.@@@@1@24@@oe@16-12-2010 939816303@GENIA Treebank@formal@@1@S@The promoter activity of cell cycle regulated histone H4 genes is regulated by at least four principal cis-acting elements which mediate G1/S phase control and/or enhancement of transcription during the cell cycle.@@@@1@33@@oe@16-12-2010 939816304@GENIA Treebank@formal@@1@S@Using protein-DNA interaction assays we show that the H4 promoter contains two ATF/CREB recognition motifs which interact with CREB, ATF1, and ATF2 but not with ATF4/CREB2.@@@@1@29@@oe@16-12-2010 939816305@GENIA Treebank@formal@@1@S@One ATF/CRE motif is located in the distal promoter at the nuclear matrix-associated Site IV, and the second motif is present in the proximal promoter at Site I.@@@@1@30@@oe@16-12-2010 939816306@GENIA Treebank@formal@@1@S@Both ATF/CRE motifs overlap binding sequences for the multifunctional YY1 transcription factor, which has previously been shown to be nuclear matrix associated.@@@@1@24@@oe@16-12-2010 939816307@GENIA Treebank@formal@@1@S@Subnuclear fractionation reveals that there are two ATF1 isoforms which appear to differ with respect to DNA binding activity and partition selectively between nuclear matrix and nonmatrix compartments, consistent with the role of the nuclear matrix in regulating gene expression.@@@@1@42@@oe@16-12-2010 939816308@GENIA Treebank@formal@@1@S@Site-directed mutational studies demonstrate that Site I and Site IV together support ATF1- and CREB-induced trans-activation of the H4 promoter.@@@@1@21@@oe@16-12-2010 939816309@GENIA Treebank@formal@@1@S@Thus, our data establish that ATF/CREB factors functionally modulate histone H4 gene transcription at distal and proximal promoter elements.@@@@1@21@@oe@16-12-2010 939840401@GENIA Treebank@formal@@1@S@IL-2 and IL-7 induce heterodimerization of STAT5 isoforms in human peripheral blood T lymphoblasts.@@@@1@15@@oe@16-12-2010 939840402@GENIA Treebank@formal@@1@S@Despite differences in T cell responses induced by interleukin (IL)-2 and IL-7, both cytokines modulate T cell functions by activation of signal transducers and activators of transcription (STAT) proteins.@@@@1@36@@oe@16-12-2010 939840403@GENIA Treebank@formal@@1@S@We examined the contribution of the two isoforms of STAT5, STAT5A and STAT5B, to IL-2- and IL-7-induced activation of human peripheral blood T lymphoblasts.@@@@1@27@@oe@16-12-2010 939840404@GENIA Treebank@formal@@1@S@Both cytokines induced assembly of STAT5A and STAT5B containing complexes capable of binding to the interferon-gamma activation sequence (GAS), and these complexes rapidly translocated (within 1 min) into the nucleus of IL-2- or IL-7-treated cells.@@@@1@41@@oe@16-12-2010 939840405@GENIA Treebank@formal@@1@S@The kinetics of this translocation were delayed in IL-7-treated as compared to IL-2-treated cells.@@@@1@15@@oe@16-12-2010 939840406@GENIA Treebank@formal@@1@S@IL-2 and IL-7 were equivalent in their ability to induce tyrosine phosphorylation of STAT5A and STAT5B and to facilitate binding of these STATs to an immobilized GAS element.@@@@1@29@@oe@16-12-2010 939840407@GENIA Treebank@formal@@1@S@Both IL-2 and IL-7 induced substantial amounts of STAT5A/STAT5B heterodimerization.@@@@1@11@@oe@16-12-2010 939840408@GENIA Treebank@formal@@1@S@Moreover, we observed constitutive association of STAT3 with each STAT5 isomer.@@@@1@13@@oe@16-12-2010 939840409@GENIA Treebank@formal@@1@S@These data suggest that IL-2 and IL-7 induce assembly of STAT heterodimers in a similar manner and that subsequent cellular responses may be driven by induction of similar sets of genes.@@@@1@32@@oe@16-12-2010 939996101@GENIA Treebank@formal@@1@S@B lymphocytes from patients with chronic lymphocytic leukemia contain signal transducer and activator of transcription (STAT) 1 and STAT3 constitutively phosphorylated on serine residues.@@@@1@27@@oe@16-12-2010 939996102@GENIA Treebank@formal@@1@S@To explore the pathogenesis of chronic lymphocytic leukemia (CLL), we examined whether phosphorylation of one or more signal transducer and activator of transcription (STAT) factors was abnormal in cells from CLL patients.@@@@1@38@@oe@16-12-2010 939996103@GENIA Treebank@formal@@1@S@No constitutive tyrosine phosphorylation was detected on any STAT in CLL cells.@@@@1@13@@oe@16-12-2010 939996104@GENIA Treebank@formal@@1@S@To assess the phosphorylation of serine residues of STAT1 and STAT3 in CLL cells, we raised antibodies that specifically recognize the form of STAT1 phosphorylated on ser-727 and the form of STAT3 phosphorylated on ser-727.@@@@1@37@@oe@16-12-2010 939996105@GENIA Treebank@formal@@1@S@We found that in 100% of patients with CLL (n = 32), STAT1 and STAT3 were constitutively phosphorylated on serine.@@@@1@25@@oe@16-12-2010 939996106@GENIA Treebank@formal@@1@S@This was in contrast to normal peripheral blood B lymphocytes or CD5+) B cells isolated from tonsils, in which this phosphorylation was absent.@@@@1@25@@oe@16-12-2010 939996107@GENIA Treebank@formal@@1@S@Serine phosphorylation of STAT1 and STAT3 was seen occasionally in other leukemias, but it was a universal finding only in CLL.@@@@1@23@@oe@16-12-2010 939996108@GENIA Treebank@formal@@1@S@The serine phosphorylation of these STATs was a continuous process, as incubation of CLL cells with the kinase inhibitor H7 led to the dephosphorylation of these serine residues.@@@@1@30@@oe@16-12-2010 939996109@GENIA Treebank@formal@@1@S@The STAT serine kinase in CLL cells has not been identified, and appears to be neither mitogen-activated protein kinase nor pp70(s6k).@@@@1@23@@oe@16-12-2010 939996110@GENIA Treebank@formal@@1@S@In summary, the constitutive serine phosphorylation of STAT1 and STAT3 is present in all CLL samples tested to date, although the physiologic significance of this modification remains to be determined.@@@@1@33@@oe@16-12-2010 940037201@GENIA Treebank@formal@@1@S@Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells.@@@@1@11@@oe@16-12-2010 940037202@GENIA Treebank@formal@@1@S@The objectives of this study were to (1) determine the time course of neutrophil adhesion to monolayers of human umbilical vein endothelial cells (HUVECs) that were exposed to 60 minutes of anoxia followed by 30 to 600 minutes of reoxygenation and (2) define the mechanisms responsible for both the early (minutes) and late (hours) hyperadhesivity of postanoxic HUVECs to human neutrophils.@@@@1@72@@oe@16-12-2010 940037203@GENIA Treebank@formal@@1@S@The results clearly demonstrate that anoxia/reoxygenation (A/R) leads to a biphasic increase in neutrophil adhesion to HUVECs, with peak responses occurring at 30 minutes (phase 1) and 240 minutes (phase 2) after reoxygenation.@@@@1@41@@oe@16-12-2010 940037204@GENIA Treebank@formal@@1@S@Oxypurinol and catalase inhibited phase-1 adhesion, suggesting a role for xanthine oxidase and H2O2.@@@@1@16@@oe@16-12-2010 940037205@GENIA Treebank@formal@@1@S@In comparison, platelet activating factor (PAF) contributed to both phases of neutrophil adhesion.@@@@1@17@@oe@16-12-2010 940037206@GENIA Treebank@formal@@1@S@Anti-intercellular adhesion molecule-1 (ICAM-1) and anti-P-selectin antibodies (monoclonal antibodies [mAbs]) attenuated phase-1 neutrophil adhesion, consistent with roles for constitutively expressed ICAM-1 and enhanced surface expression of preformed P-selectin.@@@@1@36@@oe@16-12-2010 940037207@GENIA Treebank@formal@@1@S@Phase-2 neutrophil adhesion was attenuated by an anti-E-selectin mAb, indicating a dominant role of this adhesion molecule in the late phase response.@@@@1@24@@oe@16-12-2010 940037208@GENIA Treebank@formal@@1@S@Pretreatment with actinomycin D and cycloheximide or with competing ds-oligonucleotides containing the nuclear factor-kappa B or activator protein-1 cognate DNA sequences significantly attenuated phase-2 response, suggesting a role for de novo macromolecule synthesis.@@@@1@35@@oe@16-12-2010 940037209@GENIA Treebank@formal@@1@S@Surface expression of ICAM-1, P-selectin, and E-selectin on HUVECs correlated with the phase-1 and -2 neutrophil adhesion responses.@@@@1@21@@oe@16-12-2010 940037210@GENIA Treebank@formal@@1@S@Collectively, these findings indicate that A/R elicits a two-phase neutrophil-endothelial cell adhesion response that involves transcription-independent and transcription-dependent surface expression of different endothelial cell adhesion molecules.@@@@1@28@@oe@16-12-2010 940684801@GENIA Treebank@formal@@1@S@C/EBP activates the human corticotropin-releasing hormone gene promoter.@@@@1@9@@oe@16-12-2010 940684802@GENIA Treebank@formal@@1@S@The purpose of these studies was to identify whether transcription factors, associated with cytokine signalling, affected promoter activity of the corticotropin releasing hormone (CRH) gene.@@@@1@30@@oe@16-12-2010 940684803@GENIA Treebank@formal@@1@S@Fragments of a 3.6 kb sequence of the human CRH gene promoter were amplified by PCR and ligated upstream of a CAT reporter.@@@@1@24@@oe@16-12-2010 940684804@GENIA Treebank@formal@@1@S@These constructs were transfected into a variety of cell lines, either alone or together, with transcription factor expression vectors.@@@@1@22@@oe@16-12-2010 940684805@GENIA Treebank@formal@@1@S@Basal activity of a 3070 bp CRH promoter fragment was only seen in neuronal and lymphoblastoid cell lines.@@@@1@19@@oe@16-12-2010 940684806@GENIA Treebank@formal@@1@S@Promoter activity was increased by the transcription factors C/EBPbeta (NF-IL6) and more strongly, by C/EBPdelta (NF-IL6beta).@@@@1@22@@oe@16-12-2010 940684807@GENIA Treebank@formal@@1@S@Increased CRH promoter activity following phorbol ester treatment was inhibited by a dominant negative NF-IL6 mutant, showing that the effects of phorbol ester were principally mediated by C/EBP.@@@@1@30@@oe@16-12-2010 940684808@GENIA Treebank@formal@@1@S@Moreover, the inverse changes in the expression of CRH in the hypothalamus and spleens of arthritic rats were paralleled by similar inverse changes in NF-IL6beta expression in these organs.@@@@1@31@@oe@16-12-2010 940684809@GENIA Treebank@formal@@1@S@These data show that some transcription factors associated with cytokine signalling can also activate the CRH promoter.@@@@1@18@@oe@16-12-2010 941399901@GENIA Treebank@formal@@1@S@A novel form of the myeloid-specific zinc finger protein (MZF-2).@@@@1@13@@oe@16-12-2010 941399902@GENIA Treebank@formal@@1@S@BACKGROUND: Myeloid cell development is controlled by tissue-specific transcription factors.@@@@1@12@@oe@16-12-2010 941399903@GENIA Treebank@formal@@1@S@Human myeloid zinc finger protein (MZF-1) is a putative transcription factor containing 13 zinc fingers, and has been suggested that it regulates the development of neutrophilic granulocytes.@@@@1@31@@oe@16-12-2010 941399904@GENIA Treebank@formal@@1@S@RESULTS: Here, we have isolated the murine and human cDNAs which encode a novel form of MZF protein (MZF-2).@@@@1@24@@oe@16-12-2010 941399905@GENIA Treebank@formal@@1@S@Murine and human MZF-2 proteins consisted of 814 and 775 amino acids, respectively, and have identity of 75.3% between them.@@@@1@24@@oe@16-12-2010 941399906@GENIA Treebank@formal@@1@S@The C-terminal half of human MZF-2, carrying the zinc finger domains, was completely identical with that of human MZF-1, whereas the N-terminal half of MZF-2 was different from the corresponding region of human MZF-1, and was coded by distinct exons.@@@@1@45@@oe@16-12-2010 941399907@GENIA Treebank@formal@@1@S@MZF-2 mRNA was expressed in myeloid cells, particularly in the cells committed to the neutrophilic lineage, and down-regulated by G-CSF.@@@@1@23@@oe@16-12-2010 941399908@GENIA Treebank@formal@@1@S@CONCLUSIONS: MZF-1 and MZF-2 mRNAs seem to be produced by the alternative use of two different transcription initiation sites.@@@@1@21@@oe@16-12-2010 941399909@GENIA Treebank@formal@@1@S@The distinct N-terminal half of MZF-2 carries two characteristic domains, a leucine-rich domain called LeR and an acidic domain, which suggests a unique function of MZF-2 in neutrophil development.@@@@1@32@@oe@16-12-2010 941412901@GENIA Treebank@formal@@1@S@c-Rel and p65 subunits bind to an upstream NF-kappaB site in human granulocyte macrophage-colony stimulating factor promoter involved in phorbol ester response in 5637 cells.@@@@1@26@@oe@16-12-2010 941412902@GENIA Treebank@formal@@1@S@To further clarify the complex transcriptional regulation of the human GM-CSF gene, which was extensively investigated in activated T cells, we have studied the role of an upstream NF-kappaB like site in the 5637 non-lymphoid cell line, which derives from a bladder carcinoma and constitutively produces GM-CSF.@@@@1@51@@oe@16-12-2010 941412903@GENIA Treebank@formal@@1@S@This sequence, named the A element, has an active role on GM-CSF transcription and is responsive to the tumor promoter PMA in transient transfection experiments.@@@@1@28@@oe@16-12-2010 941412904@GENIA Treebank@formal@@1@S@We describe here a heterodimeric binding complex of NF-kappaB subunits (c-Rel and p65) which is identical to the one obtained using the HIV-LTR-kappaB site as recognition sequence and different from the one (c-Rel and p50) observed with nuclear extracts from Mo T-lymphoid HTLV-II infected cells.@@@@1@50@@oe@16-12-2010 941563901@GENIA Treebank@formal@@1@S@T cell reactivity to Sjogren's syndrome related antigen La(SSB).@@@@1@14@@oe@16-12-2010 941563902@GENIA Treebank@formal@@1@S@OBJECTIVE.@@@@1@2@@oe@16-12-2010 941563903@GENIA Treebank@formal@@1@S@Many patients with primary Sjogren's syndrome (SS) make high titer IgG autoantibodies to the La(SSB) antigen, suggesting antigen specific T cell-B cell interactions.@@@@1@31@@oe@16-12-2010 941563904@GENIA Treebank@formal@@1@S@T cell responses to some nuclear antigens, particularly U1RNP, have been detected in patients with systemic lupus erythematosus (SLE) and in healthy subjects.@@@@1@28@@oe@16-12-2010 941563905@GENIA Treebank@formal@@1@S@We investigated T cell reactivity to the autoantigen SSB in patients with SS and healthy controls.@@@@1@17@@oe@16-12-2010 941563906@GENIA Treebank@formal@@1@S@METHODS.@@@@1@2@@oe@16-12-2010 941563907@GENIA Treebank@formal@@1@S@Using the [3H]thymidine proliferation assay, we determined reactivity to purified recombinant SSB (rSSB) in 20 patients with SS and 19 controls.@@@@1@25@@oe@16-12-2010 941563908@GENIA Treebank@formal@@1@S@Specificity was determined using tetanus toxoid, endotoxin, and 3 other autoantigens (PBC.M2, Sc170, and GAD).@@@@1@22@@oe@16-12-2010 941563909@GENIA Treebank@formal@@1@S@Precursor frequency was calculated by limiting dilution analysis.@@@@1@9@@oe@16-12-2010 941563910@GENIA Treebank@formal@@1@S@HLA Class II dependency was investigated using anti-Class II monoclonal antibodies.@@@@1@12@@oe@16-12-2010 941563911@GENIA Treebank@formal@@1@S@HLA-DR typing was by polymerase chain reaction and sequence specific oligonucleotide typing.@@@@1@13@@oe@16-12-2010 941563912@GENIA Treebank@formal@@1@S@RESULTS.@@@@1@2@@oe@16-12-2010 941563913@GENIA Treebank@formal@@1@S@Six of 20 patients with SS and 10/19 controls proliferated to La(rSSB).@@@@1@16@@oe@16-12-2010 941563914@GENIA Treebank@formal@@1@S@Precursor frequency of anti-SSB T cells was 1:77,040 and 1:115,000 in 2 healthy subjects and 1:230,250 and 1:103,034 in two patients with SS.@@@@1@24@@oe@16-12-2010 941563915@GENIA Treebank@formal@@1@S@Anti-HLA-DR abrogated proliferation to SSB and tetanus toxoid.@@@@1@9@@oe@16-12-2010 941563916@GENIA Treebank@formal@@1@S@Thirteen of 15 patients with SS and 4/17 controls were HLA-DR3 positive, with no apparent association of HLA-DR3 with SSB reactivity in controls.@@@@1@25@@oe@16-12-2010 941563917@GENIA Treebank@formal@@1@S@CONCLUSION.@@@@1@2@@oe@16-12-2010 941563918@GENIA Treebank@formal@@1@S@Anti-La(SSB) specific T cells occur in a significant proportion of controls and in some patients with SS.@@@@1@18@@oe@16-12-2010 941563919@GENIA Treebank@formal@@1@S@The function of SSB T cells in controls remains to be defined.@@@@1@13@@oe@16-12-2010 941563920@GENIA Treebank@formal@@1@S@They may represent immunoregulatory cells, and further analysis of these cells, and a comparison to those found in patients with SS, may elucidate normal immunoregulation and the derangements that lead to Sjogren's syndrome.@@@@1@38@@oe@16-12-2010 941688701@GENIA Treebank@formal@@1@S@Cyclosporin A inhibits monocyte tissue factor activation in cardiac transplant recipients.@@@@1@12@@oe@16-12-2010 941688702@GENIA Treebank@formal@@1@S@BACKGROUND: Fibrin deposition and thrombosis have been implicated in both allograft rejection and vasculopathy after cardiac transplantation.@@@@1@19@@oe@16-12-2010 941688703@GENIA Treebank@formal@@1@S@Because monocytes play a pivotal role in the pathophysiology of intravascular coagulation activation through their ability to synthesize tissue factor (TF), we asked (1) whether monocyte TF activation occurs in cardiac transplant recipients and (2) whether monocyte TF expression is affected by treatment with cyclosporin A (CsA).@@@@1@57@@oe@16-12-2010 941688704@GENIA Treebank@formal@@1@S@METHODS AND RESULTS: We measured levels of TF activity in peripheral blood mononuclear cells and highly purified monocytes/macrophages from 10 consecutive cardiac transplant recipients and 10 healthy control subjects.@@@@1@31@@oe@16-12-2010 941688705@GENIA Treebank@formal@@1@S@TF activity generated by both unstimulated and endotoxin-stimulated cells was significantly higher in transplant recipients than in control subjects (P<.05).@@@@1@25@@oe@16-12-2010 941688706@GENIA Treebank@formal@@1@S@Increased monocyte TF expression in transplant recipients was shown to be adversely affected by treatment with CsA: TF induction was markedly reduced by CsA serum concentrations reaching peak CsA drug levels.@@@@1@33@@oe@16-12-2010 941688707@GENIA Treebank@formal@@1@S@Inhibition of TF induction in the presence of high CsA blood concentrations was also observed when stimulation of cells was performed with interferon-gamma or interleukin-1beta.@@@@1@26@@oe@16-12-2010 941688708@GENIA Treebank@formal@@1@S@As shown by reverse transcription-polymerase chain reaction and electrophoretic mobility shift assay, respectively, treatment with CsA leads to decreased TF mRNA expression and reduced activation of the NF-kappaB transcription factor, which is known to contribute to the induction of the TF promotor in human monocytes.@@@@1@49@@oe@16-12-2010 941688709@GENIA Treebank@formal@@1@S@CONCLUSIONS: This study demonstrates that TF activation, occurring in mononuclear cells of cardiac transplant recipients, is inhibited by treatment with CsA.@@@@1@25@@oe@16-12-2010 941688710@GENIA Treebank@formal@@1@S@Inhibition of monocyte TF induction by CsA may contribute to its successful use in cardiac transplant medicine and might be useful in managing further settings of vascular pathology also known to involve TF expression and NF-kappaB activation.@@@@1@38@@oe@16-12-2010 941813501@GENIA Treebank@formal@@1@S@Selection of a diverse TCR repertoire in response to an Epstein-Barr virus-encoded transactivator protein BZLF1 by CD8+ cytotoxic T lymphocytes during primary and persistent infection.@@@@1@26@@oe@16-12-2010 941813502@GENIA Treebank@formal@@1@S@We investigated the CD8+ cytotoxic T lymphocyte (CTL) repertoire to an HLA B8-restricted peptide, RAKFKQLLQ, located in the Epstein-Barr virus (EBV) immediate-early protein, BZLF1.@@@@1@32@@oe@16-12-2010 941813503@GENIA Treebank@formal@@1@S@Repertoire selection was monitored by determining the TCR beta chain sequences of RAKFKQLLQ-specific CTL established from primary infected and healthy virus carriers.@@@@1@23@@oe@16-12-2010 941813504@GENIA Treebank@formal@@1@S@PCR analysis of spontaneous EBV-transformed lymphoblastoid cell lines (LCL) from three individuals with primary infection showed that two were infected with type A and one with type B EBV.@@@@1@32@@oe@16-12-2010 941813505@GENIA Treebank@formal@@1@S@Polyclonal and clonal CTL that were generated by stimulating peripheral blood mononuclear cells with an HLA B8+ homozygous LCL lysed T cell blasts pulsed with the peptide, RAKFKQLLQ; lysis of certain HLA B8+ LCL targets was associated with the abundance of BZLF1 transcripts.@@@@1@46@@oe@16-12-2010 941813506@GENIA Treebank@formal@@1@S@TCR beta analysis showed that while there was loop length restriction in the putative peptide contact site of all responding beta chains, diverse and unique (non-recurrent) TCR beta clonotypes were selected in individuals during primary infection and continued to emerge after long-term virus exposure.@@@@1@48@@oe@16-12-2010 941813507@GENIA Treebank@formal@@1@S@TCR-contact site heterogeneity was excluded as the selective force in diversity generation since the epitope-encoded sequences were found to be identical within endogenous virus isolates.@@@@1@26@@oe@16-12-2010 941813508@GENIA Treebank@formal@@1@S@In this first study of TCR repertoire selection for an EBV lytic antigen, a BZLF1-reactive component of diverse clonotypes was identified in primary type A or type B EBV infection which was sustained in the EBV-specific memory response throughout life-long infection.@@@@1@43@@oe@16-12-2010 941813509@GENIA Treebank@formal@@1@S@This diversity selection is likely to play a critical role in maintaining a balanced viral load throughout EBV persistence.@@@@1@20@@oe@16-12-2010 941943001@GENIA Treebank@formal@@1@S@Agonistic activity of a CD40-specific single-chain Fv constructed from the variable regions of mAb G28-5.@@@@1@16@@oe@16-12-2010 941943002@GENIA Treebank@formal@@1@S@A single-chain Fv (sFv) was expressed from the variable regions of the CD40-specific mAb G28-5.@@@@1@18@@oe@16-12-2010 941943003@GENIA Treebank@formal@@1@S@The molecule bound CD40 with a high affinity (2.2 nM) and was a monomer in solution.@@@@1@19@@oe@16-12-2010 941943004@GENIA Treebank@formal@@1@S@Surprisingly, G28-5 sFv was a potent CD40 agonist that rapidly crosslinked CD40 on the cell surface but did not crosslink CD40-Ig in solution.@@@@1@25@@oe@16-12-2010 941943005@GENIA Treebank@formal@@1@S@G28-5 sFv was a more potent agonist than G28-5 IgG and was able to stimulate CD40 responses by B cells and monocytes.@@@@1@23@@oe@16-12-2010 941943006@GENIA Treebank@formal@@1@S@G28-5 IgG partially blocked, whereas G28-5 sFv augmented CD40 responses during stimulation with natural ligand (gp39-CD8 fusion protein).@@@@1@22@@oe@16-12-2010 941943007@GENIA Treebank@formal@@1@S@These results indicate that the functional activity of ligands built from the binding site of G28-5 is highly dependent upon the size and physical properties of the molecule both in solution and on the cell surfaces.@@@@1@37@@oe@16-12-2010 942753301@GENIA Treebank@formal@@1@S@Competent transcription initiation by RNA polymerase II in cell-free extracts from xeroderma pigmentosum groups B and D in an optimized RNA transcription assay.@@@@1@24@@oe@16-12-2010 942753302@GENIA Treebank@formal@@1@S@The human autosomal recessive disease, xeroderma pigmentosum (XP), can result from mutations in any one of seven genes, designated XPA through XPG.@@@@1@28@@oe@16-12-2010 942753303@GENIA Treebank@formal@@1@S@Of these, the XPB and XPD genes encode proteins that are subunits of a general transcription factor, TFIIH, involved in both nucleotide excision repair (NER) and initiation of mRNA transcription by RNA polymerase II.@@@@1@40@@oe@16-12-2010 942753304@GENIA Treebank@formal@@1@S@In humans, mutation of the XPB or XPD gene impairs NER, resulting in hyper-sensitivity to sunlight and greatly increased skin tumor formation.@@@@1@25@@oe@16-12-2010 942753305@GENIA Treebank@formal@@1@S@However, no transcription deficiency has been demonstrated in either XP-B or XP-D.@@@@1@14@@oe@16-12-2010 942753306@GENIA Treebank@formal@@1@S@We have employed an optimized cell-free RNA transcription assay to analyze transcription activity of XP-B and XP-D.@@@@1@18@@oe@16-12-2010 942753307@GENIA Treebank@formal@@1@S@Although the growth rate was normal, the XP-B and XP-D cells contained reduced amounts of TFIIH.@@@@1@18@@oe@16-12-2010 942753308@GENIA Treebank@formal@@1@S@Extracts prepared from XP-B and XP-D lymphoblastoid cells exhibited similar transcription activity from the adenovirus major late promoter when compared to that in extracts from normal cells.@@@@1@28@@oe@16-12-2010 942753309@GENIA Treebank@formal@@1@S@Thus, we conclude that the XP-B and XP-D lymphoblastoid cells do not have impaired RNA transcription activity.@@@@1@19@@oe@16-12-2010 942753310@GENIA Treebank@formal@@1@S@We consider the possible consequences of the reduced cellular content of TFIIH for the clinical symptoms in XP-B or XP-D patients, and discuss a 'conditional phenotype' that may involve an impairment of cellular function only under certain growth conditions.@@@@1@43@@oe@16-12-2010 942879301@GENIA Treebank@formal@@1@S@Cyclosporin A inhibits early mRNA expression of G0/G1 switch gene 2 (G0S2) in cultured human blood mononuclear cells.@@@@1@21@@oe@16-12-2010 942879302@GENIA Treebank@formal@@1@S@Cyclosporin A (CsA) may achieve its immunosuppressive effects by inhibiting the calcium- and calmodulin-dependent phosphatase calcineurin which is required for activation of target genes by members of the NFAT (nuclear factor of activated T cells) transcription factor family.@@@@1@43@@oe@16-12-2010 942879303@GENIA Treebank@formal@@1@S@Among these target genes is the gene encoding interleukin-2 (IL2), a cytokine facilitating progression through the G1 phase of the cell cycle.@@@@1@26@@oe@16-12-2010 942879304@GENIA Treebank@formal@@1@S@However, IL2 does not reverse CsA inhibition, suggesting that at least one other NFAT-sensitive gene may be involved.@@@@1@21@@oe@16-12-2010 942879305@GENIA Treebank@formal@@1@S@The human G0/G1 switch gene, G0S2, has potential NFAT-binding sites in the 5' flank and encodes a small basic potential phosphoprotein of unknown function.@@@@1@27@@oe@16-12-2010 942879306@GENIA Treebank@formal@@1@S@Using a sensitive, reverse transcription-polymerase chain reaction (RT-PCR) assay, G0S2 mRNA levels were assayed in cultured blood mononuclear cells.@@@@1@24@@oe@16-12-2010 942879307@GENIA Treebank@formal@@1@S@Freshly isolated cells contain high levels of G0S2 mRNA which rapidly decline.@@@@1@13@@oe@16-12-2010 942879308@GENIA Treebank@formal@@1@S@This "spontaneous stimulation" is also noted with some other G0S genes and has been attributed to some aspect of the isolation procedure.@@@@1@25@@oe@16-12-2010 942879309@GENIA Treebank@formal@@1@S@In cells that have been preincubated to lower mRNA levels, there is a transient increase in G0S2 mRNA, peaking between 1-2 h, in response to Concanavalin-A (ConA), or to the combination of phorbol ester (TPA), and the calcium ionophore, ionomycin.@@@@1@51@@oe@16-12-2010 942879310@GENIA Treebank@formal@@1@S@Both these responses are inhibited by CsA.@@@@1@8@@oe@16-12-2010 942879311@GENIA Treebank@formal@@1@S@Our results suggest that G0S2 expression is required to commit cells to enter the G1 phase of the cell cycle, and that, while not excluding other possible targets, early inhibition of G0S2 expression by CsA may be important in achieving immunosuppression.@@@@1@45@@oe@16-12-2010 942879312@GENIA Treebank@formal@@1@S@G0S2 may be of value as a reporter gene for analyzing the mechanism of action of CsA and its influence on the positive and negative selection of lymphocytes in response to self and not-self antigens.@@@@1@36@@oe@16-12-2010 942879601@GENIA Treebank@formal@@1@S@Estrogen receptor diminishes DNA-binding activities of chicken GATA-1 and CACCC-binding proteins.@@@@1@12@@oe@16-12-2010 942879602@GENIA Treebank@formal@@1@S@The estrogen receptor (ER) repressed erythroid differentiation and erythroid-specific gene expression.@@@@1@14@@oe@16-12-2010 942879603@GENIA Treebank@formal@@1@S@In this study, we investigated the effect of ER alpha (referred to throughout as ER) on DNA-binding activities of transcription factors involved in regulating the expression of erythroid-specific genes, and, in particular, the histone H5 gene.@@@@1@43@@oe@16-12-2010 942879604@GENIA Treebank@formal@@1@S@Using electrophoretic mobility shift assays, we found that in the presence of rabbit reticulocyte lysate, human ER reduced the binding activities of chicken immature erythrocyte nuclear extracted proteins to GATA and CACCC sites in the H5 promoter and enhancer.@@@@1@42@@oe@16-12-2010 942879605@GENIA Treebank@formal@@1@S@In contrast, the binding activities of NF1 and Sp1 were not affected by ER.@@@@1@16@@oe@16-12-2010 942879606@GENIA Treebank@formal@@1@S@Binding of ER to an estrogen response element was enhanced by addition of rabbit reticulocyte lysate.@@@@1@17@@oe@16-12-2010 942879607@GENIA Treebank@formal@@1@S@This lysate was also necessary for ER to diminish the DNA-binding activity of GATA-1.@@@@1@15@@oe@16-12-2010 942879608@GENIA Treebank@formal@@1@S@These results suggest that additional factor(s) are necessary for full ER function.@@@@1@16@@oe@16-12-2010 942879609@GENIA Treebank@formal@@1@S@Both GATA-1 and CACCC-binding proteins are critical for the developmentally regulated expression of erythroid-specific genes.@@@@1@16@@oe@16-12-2010 942879610@GENIA Treebank@formal@@1@S@We hypothesize that interference in DNA-binding activities of GATA-1 and CACCC-binding proteins is the mechanism by which the ER inhibits regulation of these genes.@@@@1@25@@oe@16-12-2010 942892101@GENIA Treebank@formal@@1@S@HLA binding characteristics and generation of cytotoxic lymphocytes against peptides derived from oncogenic proteins.@@@@1@15@@oe@16-12-2010 942892102@GENIA Treebank@formal@@1@S@AIMS AND BACKGROUND: Structurally altered proteins (derived from chromosomal translocations or gene mutations) can be considered tumor specific antigens and represent an attractive target for a T-cell mediated response.@@@@1@33@@oe@16-12-2010 942892103@GENIA Treebank@formal@@1@S@T lymphocytes recognize antigens in the form of peptides bound to HLA-molecules.@@@@1@13@@oe@16-12-2010 942892104@GENIA Treebank@formal@@1@S@MATERIALS AND METHODS: Peptides derived from oncogenic proteins were screened for the presence of HLA binding motifs; actual binding were evaluated by HLA stabilization experiments using transfectants and specific anti-HLA antibodies.@@@@1@34@@oe@16-12-2010 942892105@GENIA Treebank@formal@@1@S@Specific lymphocytes were induced by in vitro peptide sensitization and screened by thymidine uptake or cellular cytotoxic assays.@@@@1@19@@oe@16-12-2010 942892106@GENIA Treebank@formal@@1@S@RESULTS: We identified peptides derived from EWS/FLI-1 fusion protein and from mutated K-RAS protein (encompassing respectively the fusion point and the mutation at position 12) that showed binding motif for HLA-Cw*0702 and HLA-A3 respectively.@@@@1@38@@oe@16-12-2010 942892107@GENIA Treebank@formal@@1@S@The actual binding of these peptides was analysed in a stabilization assay.@@@@1@13@@oe@16-12-2010 942892108@GENIA Treebank@formal@@1@S@We detected binding for the EWS/FLI-1 peptide and for 5 RAS peptides (1 wild type and 4 mutated).@@@@1@21@@oe@16-12-2010 942892109@GENIA Treebank@formal@@1@S@The effect of temperature, beta 2-microglobulin (beta 2-m) and fetal calf serum (FCS) on the binding and the stability of the HLA/peptide complex was studied.@@@@1@31@@oe@16-12-2010 942892110@GENIA Treebank@formal@@1@S@A low temperature (26 degrees C) increased the binding both in HLA-A3 and HLA-Cw*0702, while FCS reduced it.@@@@1@22@@oe@16-12-2010 942892111@GENIA Treebank@formal@@1@S@beta 2-m increased the binding to the HLA-A3 molecule but did not influence the binding to the HLA-Cw*0702.@@@@1@19@@oe@16-12-2010 942892112@GENIA Treebank@formal@@1@S@The stability of already formed complexed was somewhat different in the HLA-A3 and HLA-Cw*0702 system: both were more stable at 26 degrees C than at 37 degrees C but while the beta 2-m and FCS did not influence the stability of the HLA-A3/peptide complex, they seemed to cause opposite effects in the HLA-Cw*0702 system (beta 2-m stabilized and FCS destabilized the complex).@@@@1@67@@oe@16-12-2010 942892113@GENIA Treebank@formal@@1@S@Finally, we were able to generate a specific CD8+ CTL line against a K-RAS mutated peptide.@@@@1@18@@oe@16-12-2010 942892114@GENIA Treebank@formal@@1@S@CONCLUSIONS: Although binding motifs and actual HLA binding can be detected in several cases, the generation of a cellular response is infrequent, confirming that HLA binding is necessary but not sufficient to obtain an in vitro response.@@@@1@41@@oe@16-12-2010 942892115@GENIA Treebank@formal@@1@S@Further optimization of culture conditions, type of Antigen Presenting Cells (APC), peptides, use of stabilizers like beta 2-m are still needed.@@@@1@27@@oe@16-12-2010 942899201@GENIA Treebank@formal@@1@S@Constitutive expression c-fos, c-jun, and NF kappa B mRNA is in nucleated fetal blood cells and up-regulation of c-fos and c-jun with anti-CD3 stimulation.@@@@1@27@@oe@16-12-2010 942899202@GENIA Treebank@formal@@1@S@Fetal and neonatal lymphocytes are relatively resistant to activation and cytokine production when stimulated either via their T-cell antigen receptors or lectins.@@@@1@23@@oe@16-12-2010 942899203@GENIA Treebank@formal@@1@S@The molecular mechanism(s) responsible for this phenomenon have not been clearly elucidated.@@@@1@16@@oe@16-12-2010 942899204@GENIA Treebank@formal@@1@S@We have hypothesized that such defects in fetal/neonatal T-cell activation may be due to lack of expression of the transcriptional regulatory elements required for T-cell activation.@@@@1@27@@oe@16-12-2010 942899205@GENIA Treebank@formal@@1@S@We used reverse transcriptase-polymerase chain reaction to examine both fetal and term neonatal cord bloods for mRNA expression of three transcription factors implicated in T-cell activation: c-jun, c-fos, and NF kappa B (p50 subunit).@@@@1@40@@oe@16-12-2010 942899206@GENIA Treebank@formal@@1@S@We demonstrate that mRNAs for all three of these regulatory factors are expressed in fetal blood cells by the 27th week of gestation and in term cord bloods.@@@@1@29@@oe@16-12-2010 942899207@GENIA Treebank@formal@@1@S@Activation of term infant cord blood mononuclear cells with anti-CD3 monoclonal antibodies resulted in up-regulation of both c-jun and c-fos mRNAs within 15 min of stimulation.@@@@1@27@@oe@16-12-2010 942899208@GENIA Treebank@formal@@1@S@However, secretion of IL-2 by anti-CD3-stimulated cord blood mononuclear cells was still blunted compared with control cells from adults.@@@@1@21@@oe@16-12-2010 942899209@GENIA Treebank@formal@@1@S@We conclude that fetal nucleated blood cells constitutively express important genes for cytokine regulation and are able to increase intracellular accumulation of the mRNAs for these factors in response to anti-CD3 stimulation.@@@@1@33@@oe@16-12-2010 942899210@GENIA Treebank@formal@@1@S@Thus, qualitative differences in the capacity to regulate these factors could not be shown in fetal blood cells.@@@@1@20@@oe@16-12-2010 942899211@GENIA Treebank@formal@@1@S@Quantitative experiments comparing binding of these transcription factors to the IL-2 promoter are currently under investigation.@@@@1@17@@oe@16-12-2010 943849501@GENIA Treebank@formal@@1@S@Replication of human immunodeficiency virus-1 in primary human T cells is dependent on the autocrine secretion of tumor necrosis factor through the control of nuclear factor-kappa B activation.@@@@1@29@@oe@16-12-2010 943849502@GENIA Treebank@formal@@1@S@Tumor necrosis factor (TNF)-alpha controls T-cell activation and is a major inducer of human immunodeficiency virus (HIV)-1 replication in chronically infected cells.@@@@1@29@@oe@16-12-2010 943849503@GENIA Treebank@formal@@1@S@Therefore, we have investigated its role in primary cultures of HIV-infected human T lymphocytes by using neutralizing anti-TNF-alpha antibodies or TNF-alpha.@@@@1@23@@oe@16-12-2010 943849504@GENIA Treebank@formal@@1@S@Primary resting T lymphocytes produced TNF-alpha and supported HIV replication after T-cell receptor activation.@@@@1@15@@oe@16-12-2010 943849505@GENIA Treebank@formal@@1@S@Addition of neutralizing anti-TNF-alpha antibodies drastically reduced p24 antigen release and prevented CD4+ cell depletion associated with infection.@@@@1@19@@oe@16-12-2010 943849506@GENIA Treebank@formal@@1@S@Anti-TNF-alpha also prevented nuclear factor-kappa B (NF-kappa B) activation, and a good correlation between this inhibition and inhibition of HIV replication was observed.@@@@1@27@@oe@16-12-2010 943849507@GENIA Treebank@formal@@1@S@Moreover, supplementing the cultures with high doses of IL-2 reverted anti-TNF-alpha inhibition of cell proliferation but did not affect the inhibition of HIV p24 antigen release or NF-kappa B activation in the same cultures.@@@@1@36@@oe@16-12-2010 943849508@GENIA Treebank@formal@@1@S@Moreover, anti-TNF-alpha inhibited HIV-1 long terminal repeat (LTR)-driven transcription of a reporter gene in primary T cells in response to activation, either in the presence or the absence of HIV-1 Tat.@@@@1@37@@oe@16-12-2010 943849509@GENIA Treebank@formal@@1@S@Our results support an important role for autocrine TNF-alpha secretion in controlling HIV replication in primary T cells because of its ability to maintain NF-kappa B elevated in the nucleus of T cells.@@@@1@34@@oe@16-12-2010 944054201@GENIA Treebank@formal@@1@S@A thiol antioxidant regulates IgE isotype switching by inhibiting activation of nuclear factor-kappaB.@@@@1@14@@oe@16-12-2010 944054202@GENIA Treebank@formal@@1@S@The binding site for nuclear factor-kappaB (NF-kappaB) is present at the promoter region of the germline Cepsilon gene, but there is little information on whether this factor is involved in regulating IgE synthesis by human B cells.@@@@1@41@@oe@16-12-2010 944054203@GENIA Treebank@formal@@1@S@Accordingly, we studied the role of NF-kappaB in germline Cepsilon transcription by using two human Burkitt's lymphoma B cell lines, DND39 and DG75.@@@@1@27@@oe@16-12-2010 944054204@GENIA Treebank@formal@@1@S@In both cell lines, n-acetyl-L-cysteine (NAC), a potent thiol antioxidant, inhibited the triggering of the nuclear expression of NF-kappaB by IL-4 and by anti-CD40 monoclonal antibody.@@@@1@32@@oe@16-12-2010 944054205@GENIA Treebank@formal@@1@S@Although IL-4 activated signal transducers and activators of transcription (STAT) 6 in addition to NF-kappaB, NAC treatment or the transfection of decoy oligodeoxynucleotides for NF-kappaB or STAT6 only partly blocked IL-4-induced germline Cepsilon transcription.@@@@1@38@@oe@16-12-2010 944054206@GENIA Treebank@formal@@1@S@However, these two decoy oligodeoxynucleotides together almost completely abrogated IL-4-induced germline Cepsilon transcription.@@@@1@15@@oe@16-12-2010 944054207@GENIA Treebank@formal@@1@S@Of note, CD40-mediated enhancement of IL-4-driven germline Cepsilon transcription was markedly decreased by NAC or by a decoy oligodeoxynucleotide for NF-kappaB.@@@@1@23@@oe@16-12-2010 944054208@GENIA Treebank@formal@@1@S@The effect of NAC was also examined on deletional switch recombination underlying the isotype switch to IgE.@@@@1@18@@oe@16-12-2010 944054209@GENIA Treebank@formal@@1@S@NAC inhibited the generation of Smu/Sepsilon switch fragments in normal human B cells costimulated with IL-4 and anti-CD40 monoclonal antibody.@@@@1@21@@oe@16-12-2010 944054210@GENIA Treebank@formal@@1@S@It also abolished IL-4-induced upregulation of CD40 but promoted upregulation of CD23.@@@@1@13@@oe@16-12-2010 944054211@GENIA Treebank@formal@@1@S@These results suggest that coordination of NF-kappaB and STAT6 may be required for induction of germline Cepsilon transcription by IL-4, and that CD40-mediated NF-kappaB activation may be important in regulating both enhancement of germline Cepsilon transcription and class switching to IgE.@@@@1@43@@oe@16-12-2010 944054601@GENIA Treebank@formal@@1@S@Cellular and molecular mechanisms of IL-5 synthesis in atopic diseases: a study with allergen-specific human helper T cells.@@@@1@20@@oe@16-12-2010 944054602@GENIA Treebank@formal@@1@S@BACKGROUND: Cytokines produced by helper T cells are intimately involved in chronic allergic diseases associated with eosinophilic inflammation.@@@@1@20@@oe@16-12-2010 944054603@GENIA Treebank@formal@@1@S@OBJECTIVE: We investigated the production of IL-5, a potent growth factor and chemotactic factor for eosinophils, by CD4+ T lymphocytes in patients with asthma.@@@@1@28@@oe@16-12-2010 944054604@GENIA Treebank@formal@@1@S@METHODS: Allergen-specific T cell clones and T cell hybridomas were established from the peripheral blood lymphocytes of patients with asthma, and the responses to various stimuli were determined.@@@@1@31@@oe@16-12-2010 944054605@GENIA Treebank@formal@@1@S@RESULTS: After nonspecific stimulation, IL-5 production by CD4+ T cells from both atopic and nonatopic subjects with asthma was significantly enhanced compared with that by cells from healthy controls.@@@@1@32@@oe@16-12-2010 944054606@GENIA Treebank@formal@@1@S@Peripheral blood mononuclear cells from atopic asthma patients both proliferated and produced IL-5 after incubation with mite allergen, suggesting that mite-specific helper T cells were involved in the eosinophilic inflammation of atopic asthma.@@@@1@35@@oe@16-12-2010 944054607@GENIA Treebank@formal@@1@S@A human IL-5 promoter/enhancer luciferase gene construct transfected into IL-5-producing T cell clones was clearly transcribed after stimulation, indicating that the 515 base pair IL-5 gene segment upstream of the coding region was sufficient to respond to activating signals in human helper T cells.@@@@1@46@@oe@16-12-2010 944054608@GENIA Treebank@formal@@1@S@The same gene segment was not transcribed in IL-5-nonproducing T cell clones, suggesting that human T cell IL-5 synthesis is regulated at the transcriptional level.@@@@1@27@@oe@16-12-2010 944054609@GENIA Treebank@formal@@1@S@Experiments with T cell hybridomas confirmed these findings and suggested that a unique transcription factor may be essential for human IL-5 gene transcription.@@@@1@24@@oe@16-12-2010 944054610@GENIA Treebank@formal@@1@S@CONCLUSION: Enhanced IL-5 production by helper T cells seems to cause the eosinophilic inflammation of both atopic and nonatopic asthma.@@@@1@22@@oe@16-12-2010 944054611@GENIA Treebank@formal@@1@S@Elucidation of IL-5-specific regulatory mechanisms may facilitate the development of novel treatments for allergic diseases associated with eosinophilic inflammation.@@@@1@20@@oe@16-12-2010 944237301@GENIA Treebank@formal@@1@S@Regulation of NF-kappa B activity by I kappa B alpha and I kappa B beta stability.@@@@1@17@@oe@16-12-2010 944237302@GENIA Treebank@formal@@1@S@Transcription factor NF-kappa B must be released from cytoplasmic inhibitory molecules (I kappa Bs) in order to move to the nucleus and to activate its target genes.@@@@1@30@@oe@16-12-2010 944237303@GENIA Treebank@formal@@1@S@Little is known about the mechanisms regulating the maintenance of constitutive nuclear NF-kappa B in some cell-types and of sustained nuclear NF-kappa B activity after stimulation.@@@@1@27@@oe@16-12-2010 944237304@GENIA Treebank@formal@@1@S@Increased turnover has been implicated in the regulation of constitutive NF-kappa B activity in mature B cells.@@@@1@18@@oe@16-12-2010 944237305@GENIA Treebank@formal@@1@S@We therefore compared the turnover of I kappa B alpha and I kappa B beta in mature B cells and HeLa cells.@@@@1@23@@oe@16-12-2010 944237306@GENIA Treebank@formal@@1@S@Both proteins display a high turnover in B cells although I kappa B beta is considerably more stable than I kappa B alpha.@@@@1@24@@oe@16-12-2010 944237307@GENIA Treebank@formal@@1@S@The half-life of both inhibitors is increased in HeLa cells.@@@@1@11@@oe@16-12-2010 944237308@GENIA Treebank@formal@@1@S@In contrast, all other NF-kappa B/I kappa B molecules tested are relatively stable in both cell-types.@@@@1@18@@oe@16-12-2010 944237309@GENIA Treebank@formal@@1@S@The elevated turnover of endogenous I kappa B alpha in Namalwa cells is inhibited by a proteasome inhibitor and thus seems to be driven by the same degradation machinery as the slower turnover in non-B cells.@@@@1@37@@oe@16-12-2010 944237310@GENIA Treebank@formal@@1@S@Furthermore, we investigated the processes involved in persistent activation of NF-kappa B.@@@@1@14@@oe@16-12-2010 944237311@GENIA Treebank@formal@@1@S@TNF-alpha signaling leads to a rapid depletion of cellular I kappa B beta pools.@@@@1@15@@oe@16-12-2010 944237312@GENIA Treebank@formal@@1@S@I kappa B alpha is efficiently resynthesized whereas I kappa B beta levels stay low for a prolonged time.@@@@1@20@@oe@16-12-2010 944237313@GENIA Treebank@formal@@1@S@NF-kappa B binding activity can be detected for several hours after stimulation.@@@@1@13@@oe@16-12-2010 944237314@GENIA Treebank@formal@@1@S@We found that removal of the TNF-alpha containing medium causes a rapid decrease in nuclear NF-kappa B.@@@@1@18@@oe@16-12-2010 944237315@GENIA Treebank@formal@@1@S@A phosphoform of newly synthesized I kappa B alpha is visible when degradation by the proteasome is inhibited and new I kappa B alpha displays the same properties regarding phosphorylation and degradation in response to a second inducer.@@@@1@39@@oe@16-12-2010 944237316@GENIA Treebank@formal@@1@S@There is no significant difference in the turnover of pre- and post-inductive I kappa B alpha.@@@@1@17@@oe@16-12-2010 944237317@GENIA Treebank@formal@@1@S@These observations suggest that resynthesis of I kappa B alpha and removal of the stimulus are obligatory steps for the inactivation of nuclear NF kappa B.@@@@1@27@@oe@16-12-2010 944237401@GENIA Treebank@formal@@1@S@Control of NF-kappa B activity by the I kappa B beta inhibitor.@@@@1@13@@oe@16-12-2010 944237402@GENIA Treebank@formal@@1@S@The transcription factor NF-kappa B is maintained in an inactive cytoplasmic state by I kappa B inhibitors.@@@@1@18@@oe@16-12-2010 944237403@GENIA Treebank@formal@@1@S@In mammalian cells, I kappa B alpha and I kappa B beta proteins have been purified and shown to be the inhibitors of NF-kappa B through their association with the p65 or c-Rel subunits.@@@@1@36@@oe@16-12-2010 944237404@GENIA Treebank@formal@@1@S@In addition, we have isolated a third NF-kappa B inhibitor, I kappa B epsilon (1).@@@@1@20@@oe@16-12-2010 944237405@GENIA Treebank@formal@@1@S@Upon treatment with a large variety of inducers, I kappa B alpha, I kappa B beta are proteolytically degraded, resulting in NF-kappa B translocation into the nucleus.@@@@1@31@@oe@16-12-2010 944237406@GENIA Treebank@formal@@1@S@Here we show that in E29.1 T cell hybridoma I kappa B alpha and I kappa B beta are equally associated with p65 and that I kappa B beta is degraded in response to TNF alpha in contrast to what has been originally published.@@@@1@45@@oe@16-12-2010 944237407@GENIA Treebank@formal@@1@S@Our data also suggest that, unlike I kappa B alpha, I kappa B beta is constitutively phosphorylated and resynthesized as a hypophosphorylated form.@@@@1@26@@oe@16-12-2010 944237408@GENIA Treebank@formal@@1@S@The absence of slow migrating forms of I kappa B beta following stimulation suggests that the phosphorylation does not necessarily constitute the signal-induced event which targets the molecule for proteolysis.@@@@1@31@@oe@16-12-2010 944237701@GENIA Treebank@formal@@1@S@NF-kappa B/Rel family members regulating the ICAM-1 promoter in monocytic THP-1 cells.@@@@1@13@@oe@16-12-2010 944237702@GENIA Treebank@formal@@1@S@A kappa B-site was identified in the promoter of the intercellular adhesion molecule-1 (ICAM-1) gene, which is involved in regulation of ICAM-1 expression by tumor necrosis factor alpha (TNF-alpha) and glucocorticoids.@@@@1@37@@oe@16-12-2010 944237703@GENIA Treebank@formal@@1@S@We now report on the transcription factors which bind and transactivate this enhancer sequence.@@@@1@15@@oe@16-12-2010 944237704@GENIA Treebank@formal@@1@S@In vitro, the ICAM-1 kappa B site appeared to bind RelA and c-Rel homodimers as well as heterodimers with NF-kappa B1, but weakly NF-kappa B1 homodimers.@@@@1@29@@oe@16-12-2010 944237705@GENIA Treebank@formal@@1@S@In addition, both RelA and c-Rel, but not NF-kappa B1, were shown to transactivate an ICAM-1 kappa B-reporter construct.@@@@1@23@@oe@16-12-2010 944237706@GENIA Treebank@formal@@1@S@In monocytic THP-1 cells TNF-alpha induced two nuclear complexes which in vitro bound to the ICAM-1 kappa B site.@@@@1@20@@oe@16-12-2010 944237707@GENIA Treebank@formal@@1@S@Using antibodies in an electrophoretic mobility supershift assay, one of these complexes was shown to contain NF-kappa B1 and RelA, and to bind with higher affinity to the consensus kappa B site in the HIV long terminal repeat.@@@@1@41@@oe@16-12-2010 944237708@GENIA Treebank@formal@@1@S@The second complex contained RelA, and exhibited higher affinity towards the ICAM-1 kappa B than to the HIV kappa B site.@@@@1@23@@oe@16-12-2010 944237709@GENIA Treebank@formal@@1@S@The glucocorticoid receptor was shown to repress activity of both the RelA homodimer and the NF-kappa B1/RelA heterodimer.@@@@1@19@@oe@16-12-2010 944237710@GENIA Treebank@formal@@1@S@We argue that in vivo RelA homodimers are likely to play a dominant role in TNF-alpha-induced ICAM-1 transcription in monocytic cells.@@@@1@22@@oe@16-12-2010 944238001@GENIA Treebank@formal@@1@S@LPS tolerance in monocytes/macrophages: three 3' cytosins are required in the DNA binding motif for detection of upregulated NF-kappa B p50 homodimers.@@@@1@24@@oe@16-12-2010 944238002@GENIA Treebank@formal@@1@S@When monocytes are stimulated with LPS (lipopolysaccharide) repeatedly then the initially high expression of the TNF (tumor necrosis factor) gene is only very low, i.e. the cells are tolerant to LPS.@@@@1@37@@oe@16-12-2010 944238003@GENIA Treebank@formal@@1@S@Tolerant cells still express the CD14 receptor and they can still be activated to mobilize NF-kappa B into nucleus.@@@@1@20@@oe@16-12-2010 944238004@GENIA Treebank@formal@@1@S@Analysis of the binding proteins employing the -605 motif of the human TNF promoter (GGGGCTGTCCC) revealed that in tolerant cells of the human monocytic cell line Mono Mac 6 there is a predominance of p50p50 of NF-kappa B.@@@@1@41@@oe@16-12-2010 944238005@GENIA Treebank@formal@@1@S@We now show that a mutant motif that exchanges the terminal 3' C for a G fails to bind the p50 homodimer that is upregulated in LPS toler ant human Mono Mac 6 cells.@@@@1@35@@oe@16-12-2010 944238006@GENIA Treebank@formal@@1@S@The same is true for nuclear extracts taken from the murine P388D1 macrophage cell line when tested with the -516 motif of the murine TNF promoter (GGGGGCTTTCCC).@@@@1@30@@oe@16-12-2010 944238007@GENIA Treebank@formal@@1@S@Here the wild type motif gives efficient binding of p50p50 that again is upregulated in tolerant cells whereas a mutant with a 3' G shows hardly any binding of p50p50.@@@@1@31@@oe@16-12-2010 944238008@GENIA Treebank@formal@@1@S@Conversely, the murine kappa light chain enhancer motif (GGGGACTTTCCG) does not efficiently bind the nuclear p50p50 from tolerant murine P388 macrophages.@@@@1@25@@oe@16-12-2010 944238009@GENIA Treebank@formal@@1@S@Binding is, however, readily detected when the 3' G is replaced by a C.@@@@1@17@@oe@16-12-2010 944238010@GENIA Treebank@formal@@1@S@These data show that the detection of upregulated p50 homodimers in LPS tolerant cells is dependent on subtle differences in the sequence of the DNA binding motif.@@@@1@28@@oe@16-12-2010 944238701@GENIA Treebank@formal@@1@S@The winged-helix transcription factor Trident is expressed in actively dividing lymphocytes.@@@@1@12@@oe@16-12-2010 944238702@GENIA Treebank@formal@@1@S@We recently identified the winged-helix transcription factor Trident and described its expression pattern in synchronized fibroblasts.@@@@1@17@@oe@16-12-2010 944238703@GENIA Treebank@formal@@1@S@We have now studied Trident expression in cell lines, differentiating thymocytes and in lymphocytes derived from peripheral blood.@@@@1@20@@oe@16-12-2010 944238704@GENIA Treebank@formal@@1@S@During T cell differentiation, expression peaked in the actively dividing immature single positive cells.@@@@1@16@@oe@16-12-2010 944238705@GENIA Treebank@formal@@1@S@In peripheral blood lymphocytes, expression of Trident mRNA was absent, but could be induced upon stimulation with mitogens in vitro.@@@@1@23@@oe@16-12-2010 944238706@GENIA Treebank@formal@@1@S@These observations imply a function for Trident in dividing lymphocytes.@@@@1@11@@oe@16-12-2010 944238801@GENIA Treebank@formal@@1@S@Inefficient termination of antigen responses in NF-ATp-deficient mice.@@@@1@9@@oe@16-12-2010 944238802@GENIA Treebank@formal@@1@S@In order to elucidate the role of NF-ATp, one of the most prominent members of family of NF-AT transcription factors in peripheral T lymphocytes, in T cell activation and differentiation we created NF-ATp-deficient mice by gene targeting.@@@@1@40@@oe@16-12-2010 944238803@GENIA Treebank@formal@@1@S@Such NF-ATp-/- mice are born and appear to develop a normal immune system.@@@@1@14@@oe@16-12-2010 944238804@GENIA Treebank@formal@@1@S@Apart from clear-cut defects in the synthesis of mRNAs for Th2-type lymphokines, such as IL-4, IL-5, IL-10 and IL-13, in primary and secondary stimulations of spleen cells in vitro, of a distinct impaired deletion of V beta 11+/CD4+ T lymphocytes from these mice was detected after superantigen injection.@@@@1@54@@oe@16-12-2010 944238805@GENIA Treebank@formal@@1@S@Moreover, NF-ATp-/- mice older than 6 weeks show an 2-5 fold increase in number of lymphocytes.@@@@1@18@@oe@16-12-2010 944238806@GENIA Treebank@formal@@1@S@This is correlated with an increased expression of activation markers CD44 and CD69 and decreased expression of CD62.@@@@1@19@@oe@16-12-2010 944239301@GENIA Treebank@formal@@1@S@Identification of target genes of the lymphoid-specific transcription factor Oct2.@@@@1@11@@oe@16-12-2010 944239302@GENIA Treebank@formal@@1@S@The Oct2 transcription factor is expressed predominantly in B lymphocytes and plays an essential role during the terminal phase of B cell differentiation.@@@@1@24@@oe@16-12-2010 944239303@GENIA Treebank@formal@@1@S@The regulatory regions of several genes specifically expressed in B cells contain functional binding sites for Oct2.@@@@1@18@@oe@16-12-2010 944239304@GENIA Treebank@formal@@1@S@Nevertheless, none of the genes originally thought to be regulated by Oct2 were affected in their expression in Oct2-deficient B cells.@@@@1@23@@oe@16-12-2010 944239305@GENIA Treebank@formal@@1@S@In an attempt to find such elusive Oct2 target genes and to understand the molecular function of Oct2 in B cell development, we isolated cDNAs for Oct2 target genes.@@@@1@31@@oe@16-12-2010 944239306@GENIA Treebank@formal@@1@S@So far, we have identified five potential targets for Oct2: the membrane glycoprotein CD36, the cysteine-rich secreted protein 3 (CRISP-3), a mouse homolog of the human monocyte/neutrophil elastase inhibitor (mEI) and two unknown cDNA sequences Nov1 and Nov2.@@@@1@47@@oe@16-12-2010 944239307@GENIA Treebank@formal@@1@S@These target genes show quite distinct expression patterns demonstrating that transcription factors in addition to Oct2 are involved in their regulation.@@@@1@22@@oe@16-12-2010 944239308@GENIA Treebank@formal@@1@S@Whereas CD36 and mEI were expressed in all hematopoetic cell lines containing Oct2,. CRISP-3 is pre-B cell-specific, Nov1 is plasma B cell-specific and Nov2 is B cell-specifically expressed.@@@@1@32@@oe@16-12-2010 944239501@GENIA Treebank@formal@@1@S@Temporal control of IgH gene expression in developing B cells by the 3' locus control region.@@@@1@17@@oe@16-12-2010 944239502@GENIA Treebank@formal@@1@S@The suggested roles of the downstream 3' regions acting as a Locus Control Region (LCR), have allowed comparisons to be made between the regulation of the IgH locus with other model systems whose gene expression is governed by LCR activity.@@@@1@44@@oe@16-12-2010 944239503@GENIA Treebank@formal@@1@S@Here we summarize the importance of the IgH 3'LCR and its putative functional role in IgH gene expression and compare it with the 5'LCR regulatory region of the human beta-globin locus.@@@@1@32@@oe@16-12-2010 944240001@GENIA Treebank@formal@@1@S@Expression of transcription factor genes after influenza A virus infection.@@@@1@11@@oe@16-12-2010 944240002@GENIA Treebank@formal@@1@S@Infection of human monocytes with influenza A virus induces a broad range of proinflammatory cytokines and mononuclear cell attracting chemokines before the infected cells undergo apoptosis.@@@@1@27@@oe@16-12-2010 944240003@GENIA Treebank@formal@@1@S@The underlying mechanisms by which the corresponding genes are transcriptionally initiated after virus infection are still poorly understood.@@@@1@19@@oe@16-12-2010 944240004@GENIA Treebank@formal@@1@S@Activation of NF-kappa B seems to play an important role in the regulation of many proinflammatory cytokine genes, but cannot be the only mechanism, since several cytokine genes lack respective binding sites in their promoter regions.@@@@1@40@@oe@16-12-2010 944240005@GENIA Treebank@formal@@1@S@Therefore, we additionally investigated other transcription factors of possible importance such as CREB, CTF, OTF-1, and OTF-2.@@@@1@22@@oe@16-12-2010 944240006@GENIA Treebank@formal@@1@S@To explore long-term regulatory mechanisms, we investigated the induction of transcription factors on the gene expression level which may be important to substitute for metabolized transcription factor proteins after their activation.@@@@1@33@@oe@16-12-2010 944240007@GENIA Treebank@formal@@1@S@We identified a cell-type-specific differential response: CREB, CTF, OTF-1, OFT-2, and NF-kappa B genes were strongly induced 1 to 4 hours after influenza A virus infection in the monocytic cell line Mono Mac 6, while in freshly prepared human monocytes no significant changes were detected.@@@@1@52@@oe@16-12-2010 944240008@GENIA Treebank@formal@@1@S@In infected monocytes, which die by apoptosis, the expression of CREB, CTF, and OTF-2 was rather suppressed 8 hours after infection.@@@@1@26@@oe@16-12-2010 944240009@GENIA Treebank@formal@@1@S@In conclusion, the long-term regulation of transcription factor gene expression in non-proliferating cells seems to be of minor importance after influenza infection since in apoptosisprone cells an immediate availability of transcription factor proteins is required.@@@@1@37@@oe@16-12-2010 944632201@GENIA Treebank@formal@@1@S@[Molecular-biologic aspects of interaction between nervous and immune systems]@@@@1@11@@oe@16-12-2010 944632202@GENIA Treebank@formal@@1@S@The problem of the neuro-immuno interactions on the level of the protein trans-factors, stimulating interleukin-2 (IL-2) gene expression was discussed.@@@@1@24@@oe@16-12-2010 944632203@GENIA Treebank@formal@@1@S@The physico-chemical and functional parameters of the low molecular nuclear proteins (SP and BP- 14, 18, 19 kDs) isolated from splenic and brain cells of immunized rats were studied.@@@@1@33@@oe@16-12-2010 944632204@GENIA Treebank@formal@@1@S@The binding of these proteins to the regulatory region of IL-2 gene in vitro and stimulation of the IL-2mRNA synthesis in splenic T-lymphocytes culture in normal conditions were shown.@@@@1@31@@oe@16-12-2010 944632205@GENIA Treebank@formal@@1@S@The protective effect of SP and BP on the IL-2mRNA synthesis in stressful conditions and by the T-cells treatment with the CsA was demonstrated.@@@@1@25@@oe@16-12-2010 946483601@GENIA Treebank@formal@@1@S@Induction of interleukin-12 p40 transcript by CD40 ligation via activation of nuclear factor-kappaB.@@@@1@14@@oe@16-12-2010 946483602@GENIA Treebank@formal@@1@S@Interleukin-12 is produced in response to infection with bacteria or parasites or to bacterial constituents such as LPS in monocytes/macrophages and dendritic cells, and also generated by the interaction between activated T cells and antigen-presenting cells via CD40-CD40 ligand (CD40L).@@@@1@44@@oe@16-12-2010 946483603@GENIA Treebank@formal@@1@S@So far, transcriptional analyses of p40 have been carried out only using bacterial constituents such as LPS as stimuli.@@@@1@21@@oe@16-12-2010 946483604@GENIA Treebank@formal@@1@S@In the present study, we have characterized the transcriptional induction of p40 by CD40 ligation in a human B lymphoblastoid cell line, Daudi, and a human acute monocytic leukemia cell line, THP-1.@@@@1@37@@oe@16-12-2010 946483605@GENIA Treebank@formal@@1@S@These cells, stimulated by an agonistic monoclonal antibody against CD40 or by transfection with a CD40L expression vector, secreted p40 and showed enhanced p40 mRNA expression.@@@@1@29@@oe@16-12-2010 946483606@GENIA Treebank@formal@@1@S@Sequence analysis of the p40 promoter region identified two potential nuclear factor (NF)-kappaB binding sites conserved between mouse and human.@@@@1@24@@oe@16-12-2010 946483607@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assay revealed that the potential NF-kappaB binding sequence which is located around 120 bp upstream of the transcription initiation site in murine and human p40 genes formed an NF-kappaB complex with nuclear extract from Daudi cells stimulated by CD40 ligation.@@@@1@44@@oe@16-12-2010 946483608@GENIA Treebank@formal@@1@S@Moreover, transfection of Daudi cells with the polymerized NF-kappaB binding sequence ligated to a thymidine kinase/chloramphenicol acetyltransferase (CAT) reporter plasmid greatly induced CAT activity, but transfection with the polymerized mutated NF-kappaB binding sequence did not.@@@@1@40@@oe@16-12-2010 946483609@GENIA Treebank@formal@@1@S@These results suggest that the NF-kappaB binding site located around 120 bp upstream of the transcription initiation site in murine and human p40 promoter regions could be important for the p40 induction by CD40 ligation via activation of NF-kappaB.@@@@1@40@@oe@16-12-2010 946737601@GENIA Treebank@formal@@1@S@Inhibition of nuclear factor kappa B subunit p65 mRNA accumulation in lipopolysaccharide-stimulated human monocytic cells treated with sodium salicylate.@@@@1@20@@oe@16-12-2010 946737602@GENIA Treebank@formal@@1@S@Lipopolysaccharide is one of the most potent trigger substances for monocytes and macrophages causing secretion of inflammatory mediators such as tumor necrosis factor and interleukin-1.@@@@1@26@@oe@16-12-2010 946737603@GENIA Treebank@formal@@1@S@The nature of the nuclear factors involved in regulation of these cytokine genes is still unknown.@@@@1@17@@oe@16-12-2010 946737604@GENIA Treebank@formal@@1@S@Nuclear factor kappa B (NF-kappa B; heterodimer of p50 and p65) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with lipopolysaccharide.@@@@1@36@@oe@16-12-2010 946737605@GENIA Treebank@formal@@1@S@Nonsteroidal anti-inflammatory drugs such as salicylates have been used to treat symptoms of inflammation, and a new mechanism of drug action was suggested recently.@@@@1@26@@oe@16-12-2010 946737606@GENIA Treebank@formal@@1@S@Salicylates have been shown to inhibit lipopolysaccharide-induced gene transcription via inhibition of NF-kappa B activation by preventing the degradation of NF-kappa B inhibitor "I kappa B", blocking the translocation of NF-kappa B into the nuclear compartment.@@@@1@40@@oe@16-12-2010 946737607@GENIA Treebank@formal@@1@S@However, the nature of the subunit involved in this mechanism has not been defined.@@@@1@16@@oe@16-12-2010 946737608@GENIA Treebank@formal@@1@S@To examine the mechanisms by which salicylates affect cytokine gene transcription, the amount of active and inactive NF-kappa B and NF-kappa B mRNA, in Porphyromonas gingivalis lipopolysaccharide-stimulated human monocytic cells was assessed.@@@@1@35@@oe@16-12-2010 946737609@GENIA Treebank@formal@@1@S@High doses of sodium salicylate suppressed NF-kappa B p65 mRNA accumulation, resulting in suppression of total NF-kappa B, p50 on tissue oligonucleotide had no effects on lipopolysaccharide-induced NF-kappa B activation.@@@@1@33@@oe@16-12-2010 946737610@GENIA Treebank@formal@@1@S@The data demonstrate that the p65 subunit of NF-kappa B is inhibited by salicylate treatment and highlight the role of salicylate in the control of gene expression of inflammatory mediators.@@@@1@31@@oe@16-12-2010 947531501@GENIA Treebank@formal@@1@S@Glucocorticoid receptors in cord blood lymphocytes of healthy neonates and of preterms suffering from respiratory distress syndrome.@@@@1@18@@oe@16-12-2010 947531502@GENIA Treebank@formal@@1@S@We measured the number of glucocorticoid receptors (GR) in cord blood lymphocytes and the binding affinity (Kd) in 15 term and in 20 preterm babies.@@@@1@30@@oe@16-12-2010 947531503@GENIA Treebank@formal@@1@S@Thirteen preterms of the latter group received prenatal steroid treatment.@@@@1@11@@oe@16-12-2010 947531504@GENIA Treebank@formal@@1@S@Seven preterms developed neonatal respiratory distress syndrome (NRDS).@@@@1@11@@oe@16-12-2010 947531505@GENIA Treebank@formal@@1@S@The number of GR and the Kd were similar in the term and preterm (with and without NRDS) babies.@@@@1@22@@oe@16-12-2010 947531506@GENIA Treebank@formal@@1@S@The maximum (3H)-thymidine incorporation into DNA of cord blood lymphocytes from all preterms, with or without NRDS was suppressed when compared to that from term babies or adults.@@@@1@30@@oe@16-12-2010 947531507@GENIA Treebank@formal@@1@S@This could partly be explained by the antenatal steroid treatment.@@@@1@11@@oe@16-12-2010 947531508@GENIA Treebank@formal@@1@S@Sensitivity (ID50) of the lymphocytes for the inhibitory effect of dexamethasone was the same in all groups.@@@@1@20@@oe@16-12-2010 947531509@GENIA Treebank@formal@@1@S@In this study on the number and function of GR in lymphocytes, we were unable to find a relation between the functionality of the GR and the development of NRDS.@@@@1@32@@oe@16-12-2010 947962801@GENIA Treebank@formal@@1@S@Oxidants, transcription factors, and intestinal inflammation.@@@@1@9@@oe@16-12-2010 947962802@GENIA Treebank@formal@@1@S@It is now well appreciated that chronic gut inflammation is characterized by enhanced production of reactive metabolites of oxygen and nitrogen.@@@@1@22@@oe@16-12-2010 947962803@GENIA Treebank@formal@@1@S@Some of these oxidants are known to modulate the expression of a variety of genes that are involved in the immune and inflammatory responses.@@@@1@25@@oe@16-12-2010 947962804@GENIA Treebank@formal@@1@S@For example, certain oxidants are known to activate the nuclear transcription factor kappa B, which regulates the expression of a variety of different adhesion molecules, cytokines, and enzymes.@@@@1@33@@oe@16-12-2010 947962805@GENIA Treebank@formal@@1@S@Oxidants are also known to activate another transcription factor, activator protein-1.@@@@1@13@@oe@16-12-2010 947962806@GENIA Treebank@formal@@1@S@This transcription factor is composed of products from the fos and jun proto-oncogene family and is believed to be important in regulating cell growth and proliferation.@@@@1@27@@oe@16-12-2010 947962807@GENIA Treebank@formal@@1@S@Finally, oxidants are believed to promote intestinal epithelial cell apoptosis, and the B-cell lymphoma/leukemia-2 gene product is believed to inhibit this phenomenon in an antioxidant-dependent manner.@@@@1@29@@oe@16-12-2010 947962808@GENIA Treebank@formal@@1@S@Taken together, these observations suggest that nontoxic concentrations of reactive metabolites of oxygen and nitrogen play an important role in regulating the expression of genes involved in the inflammatory response and in modulating apoptosis.@@@@1@36@@oe@16-12-2010 948370501@GENIA Treebank@formal@@1@S@Glucocorticoid receptors, fibromyalgia and low back pain.@@@@1@9@@oe@16-12-2010 948370502@GENIA Treebank@formal@@1@S@Recently, fibromyalgia (FMS) was shown to be a disorder associated with an altered functioning of the stress response system.@@@@1@23@@oe@16-12-2010 948370503@GENIA Treebank@formal@@1@S@FMS patients display a hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin-induced hypoglycemia.@@@@1@25@@oe@16-12-2010 948370504@GENIA Treebank@formal@@1@S@We suggested that negative feedback of cortisol could be deranged.@@@@1@11@@oe@16-12-2010 948370505@GENIA Treebank@formal@@1@S@Therefore we investigated the properties and function of the glucocorticoid receptors (GR) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain (LBP a localized pain condition).@@@@1@41@@oe@16-12-2010 948370506@GENIA Treebank@formal@@1@S@Forty primary FMS patients (F:M = 36:4), 28 LBP patients (25:3) and 14 (12:2) healthy, sedentary control persons were recruited for the study.@@@@1@40@@oe@16-12-2010 948370507@GENIA Treebank@formal@@1@S@Urinary free cortisol excretion in FMS and LBP patients was lower compared to controls.@@@@1@15@@oe@16-12-2010 948370508@GENIA Treebank@formal@@1@S@Only FMS patients displayed lower CBG and basal serum cortisol concentrations when compared to controls.@@@@1@16@@oe@16-12-2010 948370509@GENIA Treebank@formal@@1@S@However, plasma free cortisol concentrations were similar in the three groups.@@@@1@13@@oe@16-12-2010 948370510@GENIA Treebank@formal@@1@S@There was no difference in the number of GR per cell among the three groups (FMS: 6498 +/- 252, LBP: 6625 +/- 284, controls: 6576 +/- 304), but the dissociation constant (Kd) of the FMS (14.5 +/- 0.9 nmol/l) and LBP (14.7 +/- 1.3 nmol/l) subjects was significantly higher than that of the controls (10.9 +/- 0.8 nmol/l) (p < .05).@@@@1@80@@oe@16-12-2010 948370511@GENIA Treebank@formal@@1@S@The maximal stimulation of the lymphocytes, as measured by the maximal thymidine incorporation (in the absence of cortisol) in the FMS group was approximately 1.5 times higher (p < .05) than in the control or LBP group.@@@@1@43@@oe@16-12-2010 948370512@GENIA Treebank@formal@@1@S@The ED50 (the cortisol concentration giving 50% inhibition of the thymidine incorporation), however, was identical in all three groups.@@@@1@25@@oe@16-12-2010 948370513@GENIA Treebank@formal@@1@S@We conclude that FMS patients have a mild hypocortisolemia, increased cortisol feedback resistance in combination probably with a reduced CRH synthesis or release in the hypothalamus.@@@@1@28@@oe@16-12-2010 948370514@GENIA Treebank@formal@@1@S@The role of the GR and mineralocorticoid receptor (MR) in the CRH regulation in the FMS patients remains to be solved.@@@@1@24@@oe@16-12-2010 948804901@GENIA Treebank@formal@@1@S@Cytokine rescue from glucocorticoid induced apoptosis in T cells is mediated through inhibition of IkappaBalpha.@@@@1@16@@oe@16-12-2010 948804902@GENIA Treebank@formal@@1@S@We previously reported that dexamethasone (DEX), a synthetic glucocorticoid, causes apoptosis in mature Th cell lines, and that this induction of cell death is prevented by specific cytokines, namely, by IL-2 in Th1 cells and by IL-4 in Th2 cells.@@@@1@48@@oe@16-12-2010 948804903@GENIA Treebank@formal@@1@S@We now show that this differential rescue by specific cytokines in Th cells correlates with the level of IkappaBalpha that is regulated by DEX and cytokines.@@@@1@27@@oe@16-12-2010 948804904@GENIA Treebank@formal@@1@S@In both cell types the cellular levels of IkappaBalpha mRNA and protein were evaluated by DEX treatment.@@@@1@18@@oe@16-12-2010 948804905@GENIA Treebank@formal@@1@S@Interestingly, the DEX-mediated IkappaBalpha induction was completely inhibited by IL-2, but not IL-4, in Th1 cells, while the reverse profile was seen in Th2 cells.@@@@1@30@@oe@16-12-2010 948804906@GENIA Treebank@formal@@1@S@In both cell types, the cytokine that inhibits the induction of IkappaBalpha by DEX, also rescues these cells from DEX-induced apoptosis, although the rescue cytokine is different in Th1 and Th2 cells.@@@@1@36@@oe@16-12-2010 948804907@GENIA Treebank@formal@@1@S@Our results imply that T cells need to maintain a certain level of NF-kappaB transcriptional activity in order to survive; up- or down-regulation of nuclear NF kappaB through modulation of IkappaBalpha expression by cytokines or DEX may lead to cell survival or cell death, respectively.@@@@1@48@@oe@16-12-2010 949297701@GENIA Treebank@formal@@1@S@Genes that regulate interleukin-4 expression in T cells.@@@@1@9@@oe@16-12-2010 949297702@GENIA Treebank@formal@@1@S@Interleukin-4 is an immunomodulatory cytokine which plays a central role in the regulation of allergic and atopic immune responses.@@@@1@20@@oe@16-12-2010 949297703@GENIA Treebank@formal@@1@S@Significant progress has been made in gaining a detailed understanding of the transcriptional regulation of the interleukin-4 gene.@@@@1@19@@oe@16-12-2010 949297704@GENIA Treebank@formal@@1@S@The recent identification and characterization of several key transcription factors has helped to elucidate the molecular mechanisms of T helper cell cytokine gene expression.@@@@1@25@@oe@16-12-2010 949749301@GENIA Treebank@formal@@1@S@Endothelial production of MCP-1: modulation by heparin and consequences for mononuclear cell activation.@@@@1@15@@oe@16-12-2010 949749302@GENIA Treebank@formal@@1@S@Heparin is a polyanionic glycosaminoglycan (GAG) that can bind with high affinity to a range of cytokines including interferon-gamma (IFN-gamma) and members of the chemokine superfamily.@@@@1@31@@oe@16-12-2010 949749303@GENIA Treebank@formal@@1@S@This GAG also possesses immunomodulatory activity in vivo and can antagonize the capacity of IFN-gamma to induce class II MHC antigen expression, and to up-regulate intercellular adhesion molecule-1, by cultured endothelial cells.@@@@1@35@@oe@16-12-2010 949749304@GENIA Treebank@formal@@1@S@Previous studies have shown that binding to cell-surface heparan sulphate is essential for optimal activity of IFN-gamma and that free heparin competitively inhibits this sequestration process.@@@@1@27@@oe@16-12-2010 949749305@GENIA Treebank@formal@@1@S@The present study was performed to increase our understanding of the immunosuppressive activity of heparin by investigation of potential antagonism of the production and function of monocyte chemotactic peptide-1 (MCP-1), a chemokine important for mononuclear leucocyte recruitment across vascular endothelium.@@@@1@44@@oe@16-12-2010 949749306@GENIA Treebank@formal@@1@S@It was found that mixture of heparin with IFN-gamma inhibited up-regulation of the signal transducer and activator of transcription protein, STAT-1 produced normally by treatment of endothelial cells with IFN-gamma.@@@@1@32@@oe@16-12-2010 949749307@GENIA Treebank@formal@@1@S@An inhibition of MCP-1 production was observed that was specifically caused by mixture of IFN-gamma with heparin-like, and therefore cytokine-binding, GAGs.@@@@1@24@@oe@16-12-2010 949749308@GENIA Treebank@formal@@1@S@It was also shown that mixture of heparin-like GAGs with MCP-1 inhibited the rapid tyrosine phosphorylation of phosphatidylinositol 3-kinase which is normally produced by treatment of mononuclear leucocytes with this chemokine.@@@@1@32@@oe@16-12-2010 949749309@GENIA Treebank@formal@@1@S@Blockade of this intracellular signalling event was associated with a reduction in the normal transendothelial migration response towards MCP-1.@@@@1@20@@oe@16-12-2010 949749310@GENIA Treebank@formal@@1@S@Results from this study indicate that soluble, heparin-like GAGs can block IFN-gamma-dependent up-regulation of MCP-1 production by cultured endothelial cells, and can also antagonize the leucocyte-activating and migration-promoting properties of pre-existing MCP-1.@@@@1@35@@oe@16-12-2010 949749311@GENIA Treebank@formal@@1@S@These activities may contribute to the immunomodulatory properties of heparin.@@@@1@11@@oe@16-12-2010 950773401@GENIA Treebank@formal@@1@S@Xenogeneic human serum promotes leukocyte adhesion to porcine endothelium under flow conditions, possibly through the activation of the transcription factor NF-kappa B.@@@@1@24@@oe@16-12-2010 950773402@GENIA Treebank@formal@@1@S@Endothelial cell activation and leukocyte infiltration are a consistent feature of discordant xenograft rejection.@@@@1@15@@oe@16-12-2010 950773403@GENIA Treebank@formal@@1@S@Here we evaluated whether xenogeneic serum, as a source of xenoreactive natural antibodies and complement, induced endothelial cell activation with consequent leukocyte adhesion under flow conditions.@@@@1@29@@oe@16-12-2010 950773404@GENIA Treebank@formal@@1@S@Porcine aortic endothelial cells (PAEC) were incubated for 1 hr 30 min or 5 hr with 10% homologous porcine serum (control) or 10% xenogeneic human serum and then perfused with total human leukocytes in a parallel plate flow chamber under laminar flow (1.5 dynes/cm2).@@@@1@53@@oe@16-12-2010 950773405@GENIA Treebank@formal@@1@S@Adherent cells were counted by digital image analysis.@@@@1@9@@oe@16-12-2010 950773406@GENIA Treebank@formal@@1@S@Xenogeneic human serum significantly (P < 0.01) increased the number of adherent leukocytes as compared with porcine serum.@@@@1@21@@oe@16-12-2010 950773407@GENIA Treebank@formal@@1@S@A similar adhesive response was elicited by TNF alpha (100 U/ml), one of the most potent inducers of endothelial cell adhesive properties, here used as positive control.@@@@1@32@@oe@16-12-2010 950773408@GENIA Treebank@formal@@1@S@In order to elucidate possible mechanisms underlying endothelial cell activation by xenogeneic serum, we focussed on transcription factor NF-kappa B, a central regulator for the induction of different genes, including adhesive molecules and chemoattractants.@@@@1@38@@oe@16-12-2010 950773409@GENIA Treebank@formal@@1@S@By confocal fluorescence microscopy, we observed a positive staining for NF-kappa B (p65 subunit) in the nuclei of PAEC exposed for 1 hr 30 min to human serum, which indicated NF-kappa B activation in this setting.@@@@1@41@@oe@16-12-2010 950773410@GENIA Treebank@formal@@1@S@At variance, in PAEC incubated with the homologous serum, NF-kappa B was strictly localized in the cell cytoplasm.@@@@1@21@@oe@16-12-2010 950773411@GENIA Treebank@formal@@1@S@Treatment of PAEC exposed to xenogeneic serum with the NF-kappa B inhibitors pyrrolidinedithiocarbamate (PDTC, 25 microM) and tosyl-phechloromethylketone (TPCK, 25 microM) significantly (P < 0.01) reduced leukocyte adhesion in respect to PAEC treated with human serum alone.@@@@1@46@@oe@16-12-2010 950773412@GENIA Treebank@formal@@1@S@Findings that xenogeneic serum promotes leukocyte-endothelium interaction possibly through NF-kappa B activation might be relevant for designing future therapeutic strategies aimed at prolonging xenograft survival.@@@@1@26@@oe@16-12-2010 951006401@GENIA Treebank@formal@@1@S@Regulation of the human interleukin-2 gene by the alpha and beta isoforms of the glucocorticoid receptor.@@@@1@17@@oe@16-12-2010 951006402@GENIA Treebank@formal@@1@S@The immunosuppressive effects of glucocorticoids are largely due to transcriptional inhibition of immunologically relevant genes, such as the interleukin-2 (IL-2) gene.@@@@1@25@@oe@16-12-2010 951006403@GENIA Treebank@formal@@1@S@These effects are mediated by the intracellular glucocorticoid receptor (GR).@@@@1@13@@oe@16-12-2010 951006404@GENIA Treebank@formal@@1@S@In humans, alternative splicing of the GR precursor mRNA gives rise to two receptor isoforms, termed GRalpha and GRbeta.@@@@1@22@@oe@16-12-2010 951006405@GENIA Treebank@formal@@1@S@We previously demonstrated that GRbeta could antagonize GRalpha-mediated transactivation of a glucocorticoid-responsive element (GRE)-driven reporter gene in COS-7 cells.@@@@1@24@@oe@16-12-2010 951006406@GENIA Treebank@formal@@1@S@The present study was designed to analyze the roles of the two GR isoforms on glucocorticoid-mediated transrepression of the IL-2 gene.@@@@1@22@@oe@16-12-2010 951006407@GENIA Treebank@formal@@1@S@Using a recently developed transfection technique, we demonstrate that in primary human lymphocytes, stimulation of a 548 bp IL-2 promoter-luciferase reporter construct by phorbol ester and calcium ionophore is reversed by dexamethasone to a similar extent as in Jurkat T lymphoma cells transfected with a GRalpha expression vector.@@@@1@51@@oe@16-12-2010 951006408@GENIA Treebank@formal@@1@S@Transfection of a GRbeta expression vector alone did not result in IL-2 promoter repression in response to glucocorticoids.@@@@1@19@@oe@16-12-2010 951006409@GENIA Treebank@formal@@1@S@Furthermore, GRbeta did not antagonize the repressive effects of GRalpha on IL-2 promoter activity.@@@@1@16@@oe@16-12-2010 951006410@GENIA Treebank@formal@@1@S@Surprisingly, overexpression of GRbeta in Jurkat cells did not cause significant inhibition of GRalpha-induced transactivation of a GRE-dependent luciferase reporter gene either.@@@@1@24@@oe@16-12-2010 951006411@GENIA Treebank@formal@@1@S@We conclude that the transrepressive effect of glucocorticoids on IL-2 gene transcription is exclusively mediated by GRalpha.@@@@1@18@@oe@16-12-2010 951006412@GENIA Treebank@formal@@1@S@GRbeta can neither antagonize GRalpha-mediated transactivation nor transrepression in Jurkat cells, indicating a cell type-specific pattern of GRbeta-mediated antiglucocorticoid activity.@@@@1@22@@oe@16-12-2010 954848301@GENIA Treebank@formal@@1@S@Delta-opioid receptors expressed by Jurkat T cells enhance IL-2 secretion by increasing AP-1 complexes and activity of the NF-AT/AP-1-binding promoter element.@@@@1@22@@oe@16-12-2010 954848302@GENIA Treebank@formal@@1@S@Recent molecular evidence points to transient and/or stage-specific expression of delta- and kappa-opioid receptors by thymic and peripheral T lymphocytes.@@@@1@21@@oe@16-12-2010 954848303@GENIA Treebank@formal@@1@S@Since medical treatments or stress commonly increase opioid levels, it is important to understand the mechanisms by which opioids affect T lymphocyte functions.@@@@1@25@@oe@16-12-2010 954848304@GENIA Treebank@formal@@1@S@We therefore created and studied a T cell line expressing the cloned delta-opioid receptor (DOR1).@@@@1@18@@oe@16-12-2010 954848305@GENIA Treebank@formal@@1@S@DOR1 ligation by a specific DOR1 agonist, deltorphin, augmented IL-2 secretion by synergizing with signals from TCR-CD3 and CD28.@@@@1@22@@oe@16-12-2010 954848306@GENIA Treebank@formal@@1@S@Reporter gene constructs were used to map this effect of deltorphin to the AP-1- and NF-AT/AP-1-binding sites of the IL-2 promoter.@@@@1@22@@oe@16-12-2010 954848307@GENIA Treebank@formal@@1@S@Although DOR1 signaling increased [Ca2+]i, deltorphin enhanced transcriptional activity of the NF-AT/AP-1-binding site via a mechanism independent of calcineurin and distinct from the effects of elevated [Ca2+]i.@@@@1@29@@oe@16-12-2010 954848308@GENIA Treebank@formal@@1@S@Deltorphin also increased accumulation of AP-1 transcription factor complexes, suggesting that DOR1 augments IL-2 secretion by increasing the AP-1 component of the NF-AT/AP-1 transcription factor.@@@@1@27@@oe@16-12-2010 954848309@GENIA Treebank@formal@@1@S@These results advance the molecular understanding of opioid effects on lymphocytes, and in addition, demonstrate regulation of IL-2 synthesis and secretion by the novel mechanism of receptor-mediated AP-1 induction.@@@@1@32@@oe@16-12-2010 954848501@GENIA Treebank@formal@@1@S@Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of NF-kappaB-mediated transcription.@@@@1@15@@oe@16-12-2010 954848502@GENIA Treebank@formal@@1@S@The NF-kappaB family of transcription factors regulates the inducible expression of a variety of genes.@@@@1@16@@oe@16-12-2010 954848503@GENIA Treebank@formal@@1@S@Recently, we showed that elevation of intracellular cyclic AMP inhibits NF-kappaB-mediated transcription in human monocytes and endothelial cells without preventing nuclear translocation of NF-kappaB complexes.@@@@1@27@@oe@16-12-2010 954848504@GENIA Treebank@formal@@1@S@The present study examined the molecular mechanism of this inhibition.@@@@1@11@@oe@16-12-2010 954848505@GENIA Treebank@formal@@1@S@We hypothesized that activation of the protein kinase A signaling pathway may inhibit NF-kappaB-mediated transcription by phosphorylating proteins, such as cAMP response element-binding protein (CREB), which compete for limiting amounts of the coactivator CBP.@@@@1@39@@oe@16-12-2010 954848506@GENIA Treebank@formal@@1@S@Here, we show that the amino-terminal region (amino acids 1-450) of CBP specifically interacts with the carboxyl-terminal region (amino acids 286-551) of NF-kappaB p65 (RelA) both in vitro and in vivo.@@@@1@39@@oe@16-12-2010 954848507@GENIA Treebank@formal@@1@S@Functional studies using human endothelial cells demonstrated that overexpression of CBP rescued cAMP inhibition of NF-kappaB-mediated transcription and transcription mediated by a chimeric protein, GAL4-p65(286-551), which contained the GAL4 DNA binding domain fused to the carboxyl-terminal region of p65 (amino acids 286-551).@@@@1@50@@oe@16-12-2010 954848508@GENIA Treebank@formal@@1@S@In contrast, overexpression of CREB inhibited GAL4-p65(286-551)-mediated transcription.@@@@1@10@@oe@16-12-2010 954848509@GENIA Treebank@formal@@1@S@These results suggest that activation of the protein kinase A pathway inhibits NF-kappaB transcription by phosphorylating CREB, which competes with p65 for limiting amounts of CBP.@@@@1@28@@oe@16-12-2010 954849001@GENIA Treebank@formal@@1@S@Differential induction of DNA-binding activities following CD19 cross-linking in human B lineage cells.@@@@1@14@@oe@16-12-2010 954849002@GENIA Treebank@formal@@1@S@The B cell-specific cell surface molecule CD19 is expressed at all stages of B cell development, including normal plasma cells, and mediates signal transduction via interaction with cytoplasmic effector proteins.@@@@1@33@@oe@16-12-2010 954849003@GENIA Treebank@formal@@1@S@Cross-linking CD19 on early human B lineage cells induces the formation of a CD19/Vav/phosphatidylinositol-3 kinase complex, tyrosine phosphorylation of CD19 and Vav, and activation of the Ras pathway.@@@@1@31@@oe@16-12-2010 954849004@GENIA Treebank@formal@@1@S@To further explore the ramifications of CD19 signaling, the current study examined whether phosphorylation of Elk-1, activation of activator protein-1 (AP-1), or activation of nuclear factor-kappaB (NF-kappaB) transcription factors occurred following CD19 cross-linking.@@@@1@41@@oe@16-12-2010 954849005@GENIA Treebank@formal@@1@S@The cells used were the BLIN-1 pre-B cell line expressing low levels of cell surface mu heavy chain associated with surrogate light chain and the 1E8 immature B cell line expressing cell surface mu/kappa.@@@@1@35@@oe@16-12-2010 954849006@GENIA Treebank@formal@@1@S@Lysates from CD19 cross-linked 1E8 cells induced robust phosphorylation of an Elk-1 fusion protein in vitro, whereas no phosphorylation of Elk-1 fusion protein occurred using lysates from CD19 cross-linked BLIN-1 cells.@@@@1@33@@oe@16-12-2010 954849007@GENIA Treebank@formal@@1@S@An electrophoretic mobility shift assay employing AP-1 and NF-kappaB consensus oligonucleotides was used to demonstrate that AP-1 -binding activity increased, while constitutive NF-kappaB-binding activity was not enhanced, following 2 h of CD19 cross-linking in 1E8 cells.@@@@1@38@@oe@16-12-2010 954849008@GENIA Treebank@formal@@1@S@Supershift experiments revealed that JunD and c-Fos proteins mediated anti-CD19 induced AP-1-binding activity in 1E8 cells.@@@@1@17@@oe@16-12-2010 954849009@GENIA Treebank@formal@@1@S@In contrast, CD19 cross-linking in BLIN-1 cells resulted in the induction of NF-kappaB, but had no apparent effect on AP-1-binding activity.@@@@1@24@@oe@16-12-2010 954849010@GENIA Treebank@formal@@1@S@These data suggest that CD19-mediated signal transduction activates different transcription factors at juxtaposed stages of B cell development that may culminate in the activation or suppression of distinct sets of genes.@@@@1@32@@oe@16-12-2010 955038501@GENIA Treebank@formal@@1@S@Pharmacological control of antigen responsiveness in genetically modified T lymphocytes.@@@@1@11@@oe@16-12-2010 955038502@GENIA Treebank@formal@@1@S@A chimeric TCR gene, comprising an anti-hapten single-chain Ab variable fragment fused to the transmembrane and cytoplasmic regions of the human TCR zeta-chain, was used to determine whether the tetracycline-regulatable system could be used to regulate gene expression in T cells.@@@@1@44@@oe@16-12-2010 955038503@GENIA Treebank@formal@@1@S@Jurkat T cells were stably transfected with a single vector encoding the tetracycline trans-activator protein, controlled by a constitutive promoter, and the chimeric TCR, under the control of a trans-activator protein-responsive promoter.@@@@1@36@@oe@16-12-2010 955038504@GENIA Treebank@formal@@1@S@In the absence of tetracyclines, the transfected T cells were shown to express the chimeric receptor on the cell surface and could be activated by its cognate Ag, leading to the secretion of IL-2.@@@@1@37@@oe@16-12-2010 955038505@GENIA Treebank@formal@@1@S@When the cells were exposed to increasing concentrations of tetracyclines, surface expression of the chimeric receptor was suppressed in a dose-dependent manner, and this suppression was sufficient to result in complete loss of responsiveness to the targeted Ag.@@@@1@41@@oe@16-12-2010 955038506@GENIA Treebank@formal@@1@S@Prolonged suppression of trans-gene expression for up to 7 days was observed after doxycycline was removed from the cultures, but eventual recovery of surface expression was complete, and the absolute time to recovery was directly proportional to the initial concentration of the drug.@@@@1@46@@oe@16-12-2010 955038507@GENIA Treebank@formal@@1@S@Pharmacologic control of trans-gene expression in gene-modified T cells will not only facilitate new approaches to the study of different aspects of T cell biology, but will also provide the basis for new gene therapy strategies.@@@@1@38@@oe@16-12-2010 955042601@GENIA Treebank@formal@@1@S@IFN-gamma and IL-10 inhibit induction of IL-1 receptor type I and type II gene expression by IL-4 and IL-13 in human monocytes.@@@@1@23@@oe@16-12-2010 955042602@GENIA Treebank@formal@@1@S@The Th2-type cytokines IL-4 and IL-13 induce expression of a distinct subset of genes in human monocytes.@@@@1@18@@oe@16-12-2010 955042603@GENIA Treebank@formal@@1@S@These include Fc epsilonRII (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R).@@@@1@29@@oe@16-12-2010 955042604@GENIA Treebank@formal@@1@S@IFN-gamma has been shown to inhibit induction of CD23 and 15-lipoxygenase in monocytes; however, the effects of IFN-gamma on type I and type II IL-1R gene expression have not been defined.@@@@1@34@@oe@16-12-2010 955042605@GENIA Treebank@formal@@1@S@We examined the effects of IFN-gamma on both basal and IL-4/IL-13-induced IL-1R gene expression in primary monocytes.@@@@1@18@@oe@16-12-2010 955042606@GENIA Treebank@formal@@1@S@IL-4 and IL-13 induced dose- and time-dependent increases in IL-1RI and IL-1RII mRNA levels.@@@@1@15@@oe@16-12-2010 955042607@GENIA Treebank@formal@@1@S@IFN-gamma decreased basal expression as well as the induction of these genes by IL-4 and IL-13.@@@@1@17@@oe@16-12-2010 955042608@GENIA Treebank@formal@@1@S@Inhibition of IL-1RI and IL-1RII mRNA levels by IFN-gamma was transcriptionally mediated, and correlated directly with decreased production of soluble IL-1RII.@@@@1@23@@oe@16-12-2010 955042609@GENIA Treebank@formal@@1@S@Furthermore, the ability to suppress IL-1RI and IL-1RII mRNA levels was not unique to IFN-gamma because IL-10 also inhibited expression of these genes in IL-4/IL-13-stimulated monocytes.@@@@1@28@@oe@16-12-2010 955042610@GENIA Treebank@formal@@1@S@Inhibition of IL-1R gene expression by IFN-gamma and IL-10 was not due to down-regulation of surface IL-4R because pretreatment with these cytokines did not decrease the number of IL-4 binding sites per cell.@@@@1@34@@oe@16-12-2010 955042611@GENIA Treebank@formal@@1@S@However, suppression of IL-1R gene expression by IFN-gamma and IL-10 was associated with decreased tyrosine phosphorylation and nuclear translocation of the IL-4/IL-13-inducible transcription factor, Stat6, suggesting a potential mechanism by which IFN-gamma and IL-10 may mediate their suppressive effects.@@@@1@43@@oe@16-12-2010 955042612@GENIA Treebank@formal@@1@S@These findings demonstrate that certain cytokines, including IFN-gamma and IL-10, antagonize the ability of IL-4 and IL-13 to induce increased expression of the IL-1RI and IL-1RII genes in monocytes.@@@@1@32@@oe@16-12-2010 957051201@GENIA Treebank@formal@@1@S@Human immunodeficiency virus type 1 long terminal repeat quasispecies differ in basal transcription and nuclear factor recruitment in human glial cells and lymphocytes.@@@@1@24@@oe@16-12-2010 957051202@GENIA Treebank@formal@@1@S@The generation of genomic diversity during the course of infection has the potential to affect all aspects of HIV-1 replication, including expression of the proviral genome.@@@@1@28@@oe@16-12-2010 957051203@GENIA Treebank@formal@@1@S@To gain a better understanding of the impact of long terminal repeat (LTR) sequence diversity on LTR-directed gene expression in cells of the central nervous system (CNS) and immune system, we amplified and cloned LTRs from proviral DNA in HIV-1-infected peripheral blood.@@@@1@48@@oe@16-12-2010 957051204@GENIA Treebank@formal@@1@S@Sequence analysis of nineteen LTRs cloned from 2 adult and 3 pediatric patients revealed an average of 33 nucleotide changes (with respect to the sequence of the LAI LTR) within the 455-bp U3 region.@@@@1@37@@oe@16-12-2010 957051205@GENIA Treebank@formal@@1@S@Transient expression analyses in cells of neuroglial and lymphocytic origin demonstrated that some of these LTRs had activities which varied significantly from the LAI LTR in U-373 MG cells (an astrocytoma cell line) as well as in Jurkat cells (a CD4-positive lymphocyte cell line).@@@@1@50@@oe@16-12-2010 957051206@GENIA Treebank@formal@@1@S@While LTRs which demonstrated the highest activities in U-373 MG cells also yielded high activities in Jurkat cells, the LTRs were generally more active in Jurkat cells when compared to the LAI LTR.@@@@1@35@@oe@16-12-2010 957051207@GENIA Treebank@formal@@1@S@Differences in LTR sequence also resulted in differences in transcription factor recruitment to cis-acting sites within the U3 region of the LTR, as demonstrated by electrophoretic mobility shift assays.@@@@1@31@@oe@16-12-2010 957051208@GENIA Treebank@formal@@1@S@In particular, naturally occurring sequence variation impacted transcription factor binding to an activating transcription factor/cAMP response element binding (ATF/CREB) binding site (located between the LEF-1 and distal NF-kappaB transcription factor binding sites) that we identified in previous studies of the HIV-1 LTR.@@@@1@48@@oe@16-12-2010 957051209@GENIA Treebank@formal@@1@S@These findings suggest that LTR sequence changes can significantly affect basal LTR function and transcription factor recruitment, which may, in turn, alter the course of viral replication in cells of CNS and immune system origin.@@@@1@39@@oe@16-12-2010 957299001@GENIA Treebank@formal@@1@S@Activation of Stat-3 is involved in the induction of apoptosis after ligation of major histocompatibility complex class I molecules on human Jurkat T cells.@@@@1@25@@oe@16-12-2010 957299002@GENIA Treebank@formal@@1@S@Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators of transcription (Stat) after ligation of major histocompatibility complex class I (MHC-I) was explored in Jurkat T cells.@@@@1@36@@oe@16-12-2010 957299003@GENIA Treebank@formal@@1@S@Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3.@@@@1@18@@oe@16-12-2010 957299004@GENIA Treebank@formal@@1@S@In addition, the transcription factor Stat-3 was tyrosine phosphorylated in the cytoplasm and subsequently translocated to the cell nucleus.@@@@1@21@@oe@16-12-2010 957299005@GENIA Treebank@formal@@1@S@Data obtained by electrophoretic mobility shift assay suggested that the activated Stat-3 protein associates with the human serum-inducible element (hSIE) DNA-probe derived from the interferon-gamma activated site (GAS) in the c-fos promoter, a common DNA sequence for Stat protein binding.@@@@1@46@@oe@16-12-2010 957299006@GENIA Treebank@formal@@1@S@An association between hSIE and Stat-3 after MHC-I ligation was directly demonstrated by precipitating Stat-3 from nuclear extracts with biotinylated hSIE probe and avidin-coupled agarose.@@@@1@26@@oe@16-12-2010 957299007@GENIA Treebank@formal@@1@S@To investigate the function of the activated Stat-3, Jurkat T cells were transiently transfected with a Stat-3 isoform lacking the transactivating domain.@@@@1@24@@oe@16-12-2010 957299008@GENIA Treebank@formal@@1@S@This dominant-negative acting Stat-3 isoform significantly inhibited apoptosis induced by ligation of MHC-I.@@@@1@14@@oe@16-12-2010 957299009@GENIA Treebank@formal@@1@S@In conclusion, our data suggest the involvement of the Jak/Stat signal pathway in MHC-I-induced signal transduction in T cells.@@@@1@21@@oe@16-12-2010 961615901@GENIA Treebank@formal@@1@S@Inhibition of nuclear factor kappaB activation attenuates apoptosis resistance in lymphoid cells.@@@@1@13@@oe@16-12-2010 961615902@GENIA Treebank@formal@@1@S@Death-inducing ligands (DILs) such as tumor necrosis factor alpha (TNFalpha) or the cytotoxic drug doxorubicin have been shown to activate a nuclear factor kappaB (NFkappaB)-dependent program that may rescue cells from apoptosis induction.@@@@1@41@@oe@16-12-2010 961615903@GENIA Treebank@formal@@1@S@We demonstrate here that TRAIL (TNF-related apoptosis-inducing ligand), a recently identified DIL, also activates NFkappaB in lymphoid cell lines in a kinetic similar to TNFalpha.@@@@1@30@@oe@16-12-2010 961615904@GENIA Treebank@formal@@1@S@NFkappaB activity is independent from FADD, caspases, and apoptosis induction.@@@@1@13@@oe@16-12-2010 961615905@GENIA Treebank@formal@@1@S@To study the influence of NFkappaB activity on apoptosis mediated by TRAIL, CD95, TNFalpha, or doxorubicin, NFkappaB activation was inhibited using the proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal or transient overexpression of mutant IkappaBalpha.@@@@1@36@@oe@16-12-2010 961615906@GENIA Treebank@formal@@1@S@Sensitivity for induction of apoptosis was markedly increased by these treatments in apoptosis sensitive cell lines.@@@@1@17@@oe@16-12-2010 961615907@GENIA Treebank@formal@@1@S@Moreover, both in cell lines and in primary leukemia cells that are resistant towards induction of apoptosis by DILs and doxorubicin, antagonization of NFkappaB activity partially restored apoptosis sensitivity.@@@@1@32@@oe@16-12-2010 961615908@GENIA Treebank@formal@@1@S@These data suggest that inhibition of NFkappaB activation may provide a molecular approach to increase apoptosis sensitivity in anticancer treatment.@@@@1@21@@oe@16-12-2010 961616301@GENIA Treebank@formal@@1@S@MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11): both rearrangements are associated with a poor prognosis.@@@@1@27@@oe@16-12-2010 961616302@GENIA Treebank@formal@@1@S@The translocation t(10;11)(p13;q14) has been observed in acute lymphoblastic leukemia (ALL) as well as acute myeloid leukemia (AML).@@@@1@23@@oe@16-12-2010 961616303@GENIA Treebank@formal@@1@S@A recent study showed a MLL/AF10 fusion in all cases of AML with t(10;11) and various breakpoints on chromosome 11 ranging from q13 to q23.@@@@1@26@@oe@16-12-2010 961616304@GENIA Treebank@formal@@1@S@We recently cloned CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene), the fusion partner of AF10 at 11q14 in the monocytic cell line U937.@@@@1@27@@oe@16-12-2010 961616305@GENIA Treebank@formal@@1@S@To further define the role of these genes in acute leukemias, 10 cases (9 AML and 1 ALL) with cytogenetically proven t(10;11)(p12-14;q13-21) and well-characterized morphology, immunophenotype, and clinical course were analyzed.@@@@1@37@@oe@16-12-2010 961616306@GENIA Treebank@formal@@1@S@Interphase fluorescence in situ hybridization (FISH) was performed with 2 YACs flanking the CALM region, a YAC contig of the MLL region, and a YAC spanning the AF10 breakpoint.@@@@1@34@@oe@16-12-2010 961616307@GENIA Treebank@formal@@1@S@Rearrangement of at least one of these genes was detected in all cases with balanced t(10;11).@@@@1@17@@oe@16-12-2010 961616308@GENIA Treebank@formal@@1@S@In 4 cases, including 3 AML with immature morphology (1 AML-M0 and 2 AML-M1) and 1 ALL, the signals of the CALM YACS were separated in interphase cells, indicating a translocation breakpoint within the CALM region.@@@@1@42@@oe@16-12-2010 961616309@GENIA Treebank@formal@@1@S@MLL was rearranged in 3 AML with myelomonocytic differentiation (2 AML-M2 and 1 AML-M5), including 1 secondary AML.@@@@1@22@@oe@16-12-2010 961616310@GENIA Treebank@formal@@1@S@In all 3 cases, a characteristic immunophenotype was identified (CD4+, CD13-, CD33+, CD65s+).@@@@1@20@@oe@16-12-2010 961616311@GENIA Treebank@formal@@1@S@AF-10 was involved in 5 of 6 evaluable cases, including 1 case without detectable CALM or MLL rearrangement.@@@@1@20@@oe@16-12-2010 961616312@GENIA Treebank@formal@@1@S@In 2 complex translocations, none of the three genes was rearranged.@@@@1@13@@oe@16-12-2010 961616313@GENIA Treebank@formal@@1@S@All cases had a remarkably poor prognosis, with a mean survival of 9.6 +/- 6.6 months.@@@@1@18@@oe@16-12-2010 961616314@GENIA Treebank@formal@@1@S@For the 7 AML cases that were uniformly treated according to the AMLCG86/92 protocols, disease-free and overall survival was significantly worse than for the overall study group (P = .03 and P = .01, respectively).@@@@1@40@@oe@16-12-2010 961616315@GENIA Treebank@formal@@1@S@We conclude that the t(10;11)(p13;q14) indicates CALM and MLL rearrangements in morphologically distinct subsets of acute leukemia and may be associated with a poor prognosis.@@@@1@26@@oe@16-12-2010 961875801@GENIA Treebank@formal@@1@S@HMG box containing transcription factors in lymphocyte differentiation.@@@@1@9@@oe@16-12-2010 961875802@GENIA Treebank@formal@@1@S@The identification of the mammalian sex-determining gene Sry has led to the discovery of a large family of related ('HMG box') transcription factors that control developmental events in yeast, C. elegans, Drosophila and vertebrates.@@@@1@41@@oe@16-12-2010 961875803@GENIA Treebank@formal@@1@S@In lymphocyte differentiation, several HMG box proteins play a decisive role.@@@@1@13@@oe@16-12-2010 961875804@GENIA Treebank@formal@@1@S@Sox-4 is important for very early B-cell differentiation, while TCF-1/LEF-1 play a crucial role in early thymocyte development.@@@@1@20@@oe@16-12-2010 961875805@GENIA Treebank@formal@@1@S@TCF/LEF proteins have recently been found to constitute a downstream component of the Wingless/Wnt signal transduction pathway.@@@@1@18@@oe@16-12-2010 961875806@GENIA Treebank@formal@@1@S@In flies, this pathway controls segment polarity; in Xenopus it controls the definition of the body axis.@@@@1@20@@oe@16-12-2010 961875807@GENIA Treebank@formal@@1@S@Deregulation of the pathway occurs in several human tumors.@@@@1@10@@oe@16-12-2010 961875808@GENIA Treebank@formal@@1@S@These insights in the molecular events that are involved in TCF/LEF function in these organisms may eventually lead to the understanding of the function of these HMG box proteins in lymphoid development.@@@@1@33@@oe@16-12-2010 961875901@GENIA Treebank@formal@@1@S@Loss- and gain-of-function mutations reveal an important role of BSAP (Pax-5) at the start and end of B cell differentiation.@@@@1@23@@oe@16-12-2010 961875902@GENIA Treebank@formal@@1@S@Pax-5 codes for the transcription factor BSAP which is expressed throughout B cell development except in terminally differentiated plasma cells.@@@@1@21@@oe@16-12-2010 961875903@GENIA Treebank@formal@@1@S@Gene targeting experiments in the mouse revealed a differential dependency of fetal and adult B-lymphopoiesis on this transcription factor.@@@@1@20@@oe@16-12-2010 961875904@GENIA Treebank@formal@@1@S@BSAP is required for B-lineage commitment in the fetal liver and for progression beyond an early pro-B cell stage in adult bone marrow.@@@@1@24@@oe@16-12-2010 961875905@GENIA Treebank@formal@@1@S@The characterization of Pax-5-deficient pro-B cells demonstrated an important role of BSAP in the regulation of the CD19, mb-1 (Ig alpha) and N-myc genes as well as in the developmental pathway controlling VH-to-DHJH recombination at the immunoglobulin heavy-chain (IgH) locus.@@@@1@46@@oe@16-12-2010 961875906@GENIA Treebank@formal@@1@S@The human PAX-5 gene was recently shown to participate together with the IgH locus in the chromosomal translocation t(9;14)(p13;q32).@@@@1@20@@oe@16-12-2010 961875907@GENIA Treebank@formal@@1@S@This translocation is characteristic of a small subset of non-Hodgkin lymphomas exhibiting plasmacytoid differentiation.@@@@1@15@@oe@16-12-2010 961875908@GENIA Treebank@formal@@1@S@The translocated PAX-5 gene is deregulated by the insertion of IgH regulatory elements into its 5' region, which may contribute to tumorigenesis by interfering with the shut-down of PAX-5 transcription and thus with the completion of plasma cell differentiation.@@@@1@41@@oe@16-12-2010 961876001@GENIA Treebank@formal@@1@S@The role of E-proteins in B- and T-lymphocyte development.@@@@1@10@@oe@16-12-2010 961876002@GENIA Treebank@formal@@1@S@Department of lymphocytes from hematopoietic stem cells is controlled, in part, by the activity of transcriptional regulatory proteins.@@@@1@21@@oe@16-12-2010 961876003@GENIA Treebank@formal@@1@S@In particular, one class of helix-loop-helix proteins, termed E-proteins, have been implicated in the regulation of gene expression during B-cell development.@@@@1@25@@oe@16-12-2010 961876004@GENIA Treebank@formal@@1@S@Recent analysis of gene-targeted mice has allowed a direct assessment of the functional roles of several E-protein family members in hematopoiesis.@@@@1@22@@oe@16-12-2010 961876005@GENIA Treebank@formal@@1@S@In this review we describe the defects in B- and T- lymphocyte development in mice carrying targeted mutations in the E-protein genes and discuss our current understanding of the role of these proteins in lymphoid development.@@@@1@36@@oe@16-12-2010 961991801@GENIA Treebank@formal@@1@S@IL-2-induced growth of CD8+ T cell prolymphocytic leukemia cells mediated by NF-kappaB induction and IL-2 receptor alpha expression.@@@@1@19@@oe@16-12-2010 961991802@GENIA Treebank@formal@@1@S@The binding of interleukin-2 (IL-2) to its receptor on normal T cells induces nuclear expression of nuclear factor kappaB (NF-kappaB), activation of the IL-2 receptor (IL-2R) alpha chain gene, and cell proliferation.@@@@1@41@@oe@16-12-2010 961991803@GENIA Treebank@formal@@1@S@In the present study, the role of IL-2R signaling in the growth of CD8+ T cell prolymphocytic leukemia (T-PLL) cells has been investigated.@@@@1@27@@oe@16-12-2010 961991804@GENIA Treebank@formal@@1@S@Flow cytometry revealed that primary leukemia cells from a patient with CD8+ T-PLL expressed IL-2Ralpha and beta chains, and the cells showed a proliferative response and an increase in IL-2Ralpha expression on culture with exogeneous IL-2.@@@@1@38@@oe@16-12-2010 961991805@GENIA Treebank@formal@@1@S@Northern blot analysis failed to detect IL-2 mRNA, suggesting that IL-2 may act in a paracrine manner in vivo.@@@@1@21@@oe@16-12-2010 961991806@GENIA Treebank@formal@@1@S@Electrophoretic mobility-shift assays revealed that recombinant IL-2 increased NF-kappaB binding activity in nuclear extracts of the leukemia cells, and Northern blot analysis showed that IL-2 increased the abundance of mRNAs encoding the NF-kappaB components c-Rel and KBF1 in these cells.@@@@1@42@@oe@16-12-2010 961991807@GENIA Treebank@formal@@1@S@IL-2 binding analysis demonstrated that IL-2 markedly increased the number of low affinity IL-2Rs on the leukemia cells, without an effect on the number of high-affinity IL-2Rs.@@@@1@29@@oe@16-12-2010 961991808@GENIA Treebank@formal@@1@S@These results show that IL-2 is capable of inducing the nuclear expression of NF-kappaB in primary CD8+ T-PLL cells, and that this effect is mediated, at least in part, at a pretranslational level.@@@@1@37@@oe@16-12-2010 962577001@GENIA Treebank@formal@@1@S@The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6).@@@@1@26@@oe@16-12-2010 962577002@GENIA Treebank@formal@@1@S@The human homologue of Drosophila Toll (hToll) is a recently cloned receptor of the interleukin 1 receptor (IL-1R) superfamily, and has been implicated in the activation of adaptive immunity.@@@@1@35@@oe@16-12-2010 962577003@GENIA Treebank@formal@@1@S@Signaling by hToll is shown to occur through sequential recruitment of the adapter molecule MyD88 and the IL-1R-associated kinase.@@@@1@20@@oe@16-12-2010 962577004@GENIA Treebank@formal@@1@S@Tumor necrosis factor receptor-activated factor 6 (TRAF6) and the nuclear factor kappaB (NF-kappaB)-inducing kinase (NIK) are both involved in subsequent steps of NF-kappaB activation.@@@@1@32@@oe@16-12-2010 962577005@GENIA Treebank@formal@@1@S@Conversely, a dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways.@@@@1@30@@oe@16-12-2010 963276401@GENIA Treebank@formal@@1@S@Coactivation by OCA-B: definition of critical regions and synergism with general cofactors.@@@@1@14@@oe@16-12-2010 963276402@GENIA Treebank@formal@@1@S@Molecular dissection of the B-cell-specific transcription coactivator OCA-B has revealed distinct regions important, respectively, for recruitment to immunoglobulin promoters through interaction with octamer-bound Oct-1 and for subsequent coactivator function.@@@@1@32@@oe@16-12-2010 963276403@GENIA Treebank@formal@@1@S@Further analysis of general coactivator requirements showed that selective removal of PC4 from the essential USA fraction severely impairs Oct-1 and OCA-B function in a cell-free system reconstituted with partially purified factors.@@@@1@33@@oe@16-12-2010 963276404@GENIA Treebank@formal@@1@S@Full activity can be restored by the combined action of recombinant PC4 and the PC4-depleted USA fraction, thus suggesting a joint requirement for PC4 and another, USA-derived component(s) for optimal function of Oct-1/OCA-B in the reconstituted system.@@@@1@43@@oe@16-12-2010 963276405@GENIA Treebank@formal@@1@S@Indeed, USA-derived PC2 was found to act synergistically with PC4 in reproducing the function of intact USA in the assay system.@@@@1@23@@oe@16-12-2010 963276406@GENIA Treebank@formal@@1@S@Consistent with the requirement for PC4 in the reconstituted system, OCA-B was found to interact directly with PC4.@@@@1@20@@oe@16-12-2010 963276407@GENIA Treebank@formal@@1@S@Surprisingly, however, removal of PC4 from the unfractionated nuclear extract has no detrimental effect on OCA-B/Oct-1-dependent transcription.@@@@1@20@@oe@16-12-2010 963276408@GENIA Treebank@formal@@1@S@These results lead to a general model for the synergistic function of activation domains in Oct-1 and OCA-B (mediated by the combined action of the multiple USA components) and, further, suggest a functional redundancy in general coactivators.@@@@1@42@@oe@16-12-2010 963382601@GENIA Treebank@formal@@1@S@Limited proteolysis for assaying ligand binding affinities of nuclear receptors.@@@@1@11@@oe@16-12-2010 963382602@GENIA Treebank@formal@@1@S@The binding of natural or synthetic ligands to nuclear receptors is the triggering event leading to gene transcription activation or repression.@@@@1@22@@oe@16-12-2010 963382603@GENIA Treebank@formal@@1@S@Ligand binding to the ligand binding domain of these receptors induces conformational changes that are evidenced by an increased resistance of this domain to proteases.@@@@1@26@@oe@16-12-2010 963382604@GENIA Treebank@formal@@1@S@In vitro labeled receptors were incubated with various synthetic or natural agonists or antagonists and submitted to trypsin digestion.@@@@1@20@@oe@16-12-2010 963382605@GENIA Treebank@formal@@1@S@Proteolysis products were separated by SDS-PAGE and quantified.@@@@1@9@@oe@16-12-2010 963382606@GENIA Treebank@formal@@1@S@The amount of trypsin-resistant fragments was proportional to receptor occupancy by the ligand, and allowed the determination of dissociation constants (kDa).@@@@1@25@@oe@16-12-2010 963382607@GENIA Treebank@formal@@1@S@Using the wild-type or mutated human retinoic acid receptor alpha as a model, kDa values determined by classical competition binding assays using tritiated ligands are in agreement with those measured by the proteolytic assay.@@@@1@36@@oe@16-12-2010 963382608@GENIA Treebank@formal@@1@S@This method was successfully extended to human retinoic X receptor alpha, glucocorticoid receptor, and progesterone receptor, thus providing a basis for a new, faster assay to determine simultaneously the affinity and conformation of receptors when bound to a given ligand.@@@@1@45@@oe@16-12-2010 963407501@GENIA Treebank@formal@@1@S@Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB-dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells.@@@@1@21@@oe@16-12-2010 963407502@GENIA Treebank@formal@@1@S@Tuberculosis has emerged as an epidemic, extended by the large number of individuals infected with human immunodeficiency virus type 1 (HIV-1).@@@@1@25@@oe@16-12-2010 963407503@GENIA Treebank@formal@@1@S@The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan (ManLAM) of Mycobacterium tuberculosis (M. tuberculosis) could activate transcription of HIV-1 in T cells with the use of an in vitro cell culture system.@@@@1@46@@oe@16-12-2010 963407504@GENIA Treebank@formal@@1@S@These experiments are of prime importance considering that CD4-expressing T lymphocytes represent the major virus reservoir in the peripheral blood of infected individuals.@@@@1@24@@oe@16-12-2010 963407505@GENIA Treebank@formal@@1@S@Using the 1G5 cell line harbouring the luciferase reporter gene under the control of the HIV-1 LTR, it was first found that culture protein filtrates (CFP) from M. tuberculosis or purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike similarly prepared CFP extracts devoid of ManLAM.@@@@1@50@@oe@16-12-2010 963407506@GENIA Treebank@formal@@1@S@The implication of protein tyrosine kinase(s), protein kinase A and/or protein kinase C was highlighted by the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7.@@@@1@37@@oe@16-12-2010 963407507@GENIA Treebank@formal@@1@S@It was also determined, using electrophoresis mobility shift assays, that M. tuberculosis ManLAM led to the nuclear translocation of the transcription factor NF-kappaB.@@@@1@26@@oe@16-12-2010 963407508@GENIA Treebank@formal@@1@S@M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type, but not the kappaB-mutated, HIV-1 LTR region.@@@@1@28@@oe@16-12-2010 963407509@GENIA Treebank@formal@@1@S@Finally, the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of endogenous TNF-alpha.@@@@1@24@@oe@16-12-2010 963407510@GENIA Treebank@formal@@1@S@The results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells and could thus have the potential to influence the pathogenesis of HIV-1 infection.@@@@1@27@@oe@16-12-2010 963752901@GENIA Treebank@formal@@1@S@IL-4-dependent regulation of TGF-alpha and TGF-beta1 expression in human eosinophils.@@@@1@11@@oe@16-12-2010 963752902@GENIA Treebank@formal@@1@S@TGFs play important roles in wound healing and carcinogenesis.@@@@1@10@@oe@16-12-2010 963752903@GENIA Treebank@formal@@1@S@We have previously demonstrated that eosinophils infiltrating into different pathologic processes elaborate TGF-alpha and TGF-beta1.@@@@1@16@@oe@16-12-2010 963752904@GENIA Treebank@formal@@1@S@Eosinophils infiltrating hamster cutaneous wounds were found to express TGFs sequentially.@@@@1@12@@oe@16-12-2010 963752905@GENIA Treebank@formal@@1@S@In this study, we examined the biologic mediators that may regulate the expression of TGF-alpha and -beta1 by eosinophils.@@@@1@21@@oe@16-12-2010 963752906@GENIA Treebank@formal@@1@S@Eosinophils were isolated from the peripheral blood of healthy donors and cultured in the absence or presence of IL-3, IL-4, and IL-5.@@@@1@25@@oe@16-12-2010 963752907@GENIA Treebank@formal@@1@S@Cells were analyzed by in situ hybridization and immunohistochemistry.@@@@1@10@@oe@16-12-2010 963752908@GENIA Treebank@formal@@1@S@Supernatants from these cultures were assayed for secreted TGF-alpha and TGF-beta1 using TGF-specific ELISAs.@@@@1@15@@oe@16-12-2010 963752909@GENIA Treebank@formal@@1@S@IL-3, IL-4, and IL-5 independently up-regulated TGF-beta1 mRNA and product expression by eosinophils in all donors.@@@@1@19@@oe@16-12-2010 963752910@GENIA Treebank@formal@@1@S@Interestingly, TGF-alpha production by eosinophils was up-regulated by IL-3 and IL-5 but was down-regulated by IL-4.@@@@1@18@@oe@16-12-2010 963752911@GENIA Treebank@formal@@1@S@Consistent with the ability of IL-4 to regulate eosinophil responses, IL-4 signaling molecules are present in human eosinophils.@@@@1@20@@oe@16-12-2010 963752912@GENIA Treebank@formal@@1@S@The observation that IL-4 can differentially regulate the expression of TGF-alpha and TGF-beta1 suggests that IL-4 may serve as a physiologic molecular switch of TGF expression by the infiltrating eosinophils in wound healing and carcinogenesis.@@@@1@36@@oe@16-12-2010 964356901@GENIA Treebank@formal@@1@S@Minimal residual disease in acute myelogenous leukemia with PML/RAR alpha or AML1/ETO mRNA and phenotypic analysis of possible T and natural killer cells in bone marrow.@@@@1@27@@oe@16-12-2010 964356902@GENIA Treebank@formal@@1@S@Here we studied minimal residual disease (MRD) of patients with acute myeloid leukemia (AML) who have PML/RAR alpha or AML1/ETO as well as the phenotypic analysis of lymphocyte subsets involved in antitumor immunity.@@@@1@38@@oe@16-12-2010 964356903@GENIA Treebank@formal@@1@S@Eight patients in long-term (LT; 3 to 15 years) and 15 patients in short-term (ST; up to 3 years) remission were studied.@@@@1@29@@oe@16-12-2010 964356904@GENIA Treebank@formal@@1@S@Using the reverse transcription-polymerase chain reaction (RT) assay, the limit of detection was 10(-5) to 10(-6) for PML/RAR alpha transcript and 10(-4) to 10(-5) for the AML1/ETO transcript.@@@@1@32@@oe@16-12-2010 964356905@GENIA Treebank@formal@@1@S@Simultaneously, T lymphocyte subsets and NK cells from the peripheral blood (PB) and bone marrow (BM) were investigated by flow cytometric analysis.@@@@1@28@@oe@16-12-2010 964356906@GENIA Treebank@formal@@1@S@Four of the eight patients in LT and 7 of the 15 patients in ST remission were MRD-positive.@@@@1@19@@oe@16-12-2010 964356907@GENIA Treebank@formal@@1@S@Although all MRD-positive patients in LT remission are still until now event-free, 3 of the 7 MRD-positive (MRD+) patients in ST remission soon relapsed.@@@@1@28@@oe@16-12-2010 964356908@GENIA Treebank@formal@@1@S@The total populations of CD4+, CD8+ and CD56+ [possible T-cell and natural killer (T/NK) populations] in the BM of ST patients and MRD+/LT patients were significantly (p < .01) low.@@@@1@38@@oe@16-12-2010 964356909@GENIA Treebank@formal@@1@S@The CD8+ CD28+ population showed the same tendency (p < .01-.02).@@@@1@14@@oe@16-12-2010 964356910@GENIA Treebank@formal@@1@S@The T/NK subsets in the BM of MRD-negative (MRD-) LT (MRD-/LT) patients showed similar numbers of cells as normal volunteers.@@@@1@25@@oe@16-12-2010 964356911@GENIA Treebank@formal@@1@S@Basically, the total percentage of the CD4+, CD8+ and CD56+ cell populations in the BM was increased and in the following order: MRD-/LT patients, normal volunteers, MRD+/LT patients and MRD+ or -/ST patients.@@@@1@39@@oe@16-12-2010 964356912@GENIA Treebank@formal@@1@S@The percentages of the T/NK-cell subsets in the PB were not significantly different among these groups.@@@@1@17@@oe@16-12-2010 964356913@GENIA Treebank@formal@@1@S@Thus, the difference of the possible T/NK-cell phenotype in the BM may strongly influence clinical and molecular remission.@@@@1@20@@oe@16-12-2010 964356914@GENIA Treebank@formal@@1@S@These results still remain to be confirmed by further studies of the functional anti-tumor immunity of T/NK cells of AML in remission.@@@@1@23@@oe@16-12-2010 964722701@GENIA Treebank@formal@@1@S@Differential regulation of the Janus kinase-STAT pathway and biologic function of IL-13 in primary human NK and T cells: a comparative study with IL-4.@@@@1@26@@oe@16-12-2010 964722702@GENIA Treebank@formal@@1@S@IL-13, a cytokine similar to IL-4, is a regulator of human B cell and monocyte functions.@@@@1@19@@oe@16-12-2010 964722703@GENIA Treebank@formal@@1@S@Biologic effects of IL-13 on primary human NK and T cells have not been well defined.@@@@1@17@@oe@16-12-2010 964722704@GENIA Treebank@formal@@1@S@We demonstrate that, in primary NK cells, IL-13, but not IL-4, may induce low levels of IFN-gamma secretion.@@@@1@23@@oe@16-12-2010 964722705@GENIA Treebank@formal@@1@S@When NK cells were costimulated with IL-13 and IL-2, IL-13 generally resulted in two types of reactivity: IL-13 synergized with IL-2 to stimulate IFN-gamma production or it modestly inhibited IL-2-mediated IFN-gamma production.@@@@1@35@@oe@16-12-2010 964722706@GENIA Treebank@formal@@1@S@In both types of donors, the effect of IL-13 on IL-2-induced IFN-gamma production was in marked contrast to the strong inhibition seen with IL-4 in NK cells.@@@@1@29@@oe@16-12-2010 964722707@GENIA Treebank@formal@@1@S@Additionally, IL-13 suppresses IL-2-induced NK cytolytic and proliferative activities although less efficiently than IL-4.@@@@1@16@@oe@16-12-2010 964722708@GENIA Treebank@formal@@1@S@In T cells, IL-13 inhibits anti-CD3 mAb/IL-2- or PHA-mediated IFN-gamma production and enhances cytolytic potential.@@@@1@17@@oe@16-12-2010 964722709@GENIA Treebank@formal@@1@S@Furthermore, we demonstrate that IL-13, like IL-4, induces distinct STAT6-DNA binding complexes and tyrosine phosphorylation of STAT6 and Janus kinase 3 (JAK3) in NK and T cells.@@@@1@33@@oe@16-12-2010 964722710@GENIA Treebank@formal@@1@S@We observed that Abs directed against unique domains of STAT6 have differential effects on complexes in T cells but not in NK cells, suggesting different STAT6 isoforms.@@@@1@29@@oe@16-12-2010 964722711@GENIA Treebank@formal@@1@S@These findings show that IL-13 and IL-4 have the ability to regulate NK and T cell activation and that IL-13 is a potent regulator of STAT6 and JAK3 in these cell types.@@@@1@34@@oe@16-12-2010 964918601@GENIA Treebank@formal@@1@S@Oxidative stress suppresses transcription factor activities in stimulated lymphocytes.@@@@1@10@@oe@16-12-2010 964918602@GENIA Treebank@formal@@1@S@Effects of oxidative stress on stimulation-dependent signal transduction, leading to IL-2 expression, were studied.@@@@1@17@@oe@16-12-2010 964918603@GENIA Treebank@formal@@1@S@Purified quiescent human blood T lymphocytes were subjected to: (i) acute exposure to hydrogen peroxide; (ii) chronic exposure to hydrogen peroxide; and (iii) acute exposure to ionizing radiation.@@@@1@38@@oe@16-12-2010 964918604@GENIA Treebank@formal@@1@S@The cells were then stimulated for 6 h.@@@@1@9@@oe@16-12-2010 964918605@GENIA Treebank@formal@@1@S@DNA-binding activities (determined by the electrophoretic mobility shift assay) of three transcription factors: NFkappaB, AP-1 and NFAT, were abolished in the lymphocytes by all three modes of oxidative stress.@@@@1@35@@oe@16-12-2010 964918606@GENIA Treebank@formal@@1@S@The lymphocytes exhibited lipid peroxidation only upon exposure to the lowest level of hydrogen peroxide used (20 microM).@@@@1@21@@oe@16-12-2010 964918607@GENIA Treebank@formal@@1@S@All three modes of oxidative stress induced catalase activity in the lymphocytes.@@@@1@13@@oe@16-12-2010 964918608@GENIA Treebank@formal@@1@S@The only exception was hydrogen peroxide at 20 microM, which did not induce catalase activity.@@@@1@17@@oe@16-12-2010 964918609@GENIA Treebank@formal@@1@S@We conclude that: (i) suppression of specific transcription factor functions can potentially serve as a marker of exposure to oxidative stress and its effects on human lymphocytes; (ii) lipid peroxidation is only detectable in human lymphocytes upon exposure to weak oxidative stress which does not induce catalase activity; (iii) therefore, transcription factor DNA-binding activities are more sensitive to oxidative stress than lipid peroxidation.@@@@1@74@@oe@16-12-2010 964934101@GENIA Treebank@formal@@1@S@Ro 09-2210 exhibits potent anti-proliferative effects on activated T cells by selectively blocking MKK activity.@@@@1@16@@oe@16-12-2010 964934102@GENIA Treebank@formal@@1@S@By using high throughput screening of microbial broths, we have identified a compound, designated Ro 09-2210, which is able to block anti-CD3 induced peripheral blood T cell activation with an IC50 = 40 nM.@@@@1@38@@oe@16-12-2010 964934103@GENIA Treebank@formal@@1@S@Ro 09-2210 was also able to block antigen-induced IL-2 secretion with an IC50 = 30 nM, but was considerably less potent at blocking Ca2+ flux stimulated by anti-CD3 treatment.@@@@1@31@@oe@16-12-2010 964934104@GENIA Treebank@formal@@1@S@To determine the mechanism of action of Ro 09-2210, we set up a transient expression system in Jurkat T cells using a variety of reporter gene constructs and showed effective inhibition of phorbol ester/ionomycin-induced NF-AT activation and anti-CD3 induced NF-AT with IC50 = 7.7 and 10 nM, respectively.@@@@1@51@@oe@16-12-2010 964934105@GENIA Treebank@formal@@1@S@Ro 09-2210 was also able to inhibit phorbol ester/ionomycin-induced activation of AP1 with IC50 = <10 nM.@@@@1@19@@oe@16-12-2010 964934106@GENIA Treebank@formal@@1@S@We further showed that Ro 09-2210 was unable to inhibit c-jun induced expression of AP1-dependent reporter constructs (IC50 > 500 nM), but was able to potently inhibit ras-induced AP1 activation (IC50 = 20 nM).@@@@1@40@@oe@16-12-2010 964934107@GENIA Treebank@formal@@1@S@This suggested that Ro 09-2210 was inhibiting an activator of AP-1 which was upstream of c-jun and downstream of ras signaling.@@@@1@22@@oe@16-12-2010 964934108@GENIA Treebank@formal@@1@S@To investigate further, we then purified a number of different kinases, including PKC, PhK, ZAP-70, ERK, and MEK 1 (a MKK), and showed that Ro 09-2210 was a selective inhibitor of MEK1 in vitro (IC50 = 59 nM).@@@@1@50@@oe@16-12-2010 965772001@GENIA Treebank@formal@@1@S@A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor [see commetns]@@@@1@12@@oe@16-12-2010 965772002@GENIA Treebank@formal@@1@S@A nonpeptidyl small molecule SB 247464, capable of activating granulocyte-colony-stimulating factor (G-CSF) signal transduction pathways, was identified in a high-throughput assay in cultured cells.@@@@1@29@@oe@16-12-2010 965772003@GENIA Treebank@formal@@1@S@Like G-CSF, SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated primary murine bone marrow cells to form granulocytic colonies in vitro.@@@@1@26@@oe@16-12-2010 965772004@GENIA Treebank@formal@@1@S@It also elevated peripheral blood neutrophil counts in mice.@@@@1@10@@oe@16-12-2010 965772005@GENIA Treebank@formal@@1@S@The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464, suggesting that the compound acts by oligomerizing receptor chains.@@@@1@27@@oe@16-12-2010 965772006@GENIA Treebank@formal@@1@S@The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand.@@@@1@20@@oe@16-12-2010 965774201@GENIA Treebank@formal@@1@S@Role of GATA-1 in proliferation and differentiation of definitive erythroid and megakaryocytic cells in vivo.@@@@1@16@@oe@16-12-2010 965774202@GENIA Treebank@formal@@1@S@To elucidate the contributions of GATA-1 to definitive hematopoiesis in vivo, we have examined adult mice that were rendered genetically defective in GATA-1 synthesis (Takahashi et al, J Biol Chem 272:12611, 1997).@@@@1@40@@oe@16-12-2010 965774203@GENIA Treebank@formal@@1@S@Because the GATA-1 gene is located on the X chromosome, which is randomly inactivated in every cell, heterozygous females can bear either an active wild-type or mutant (referred to as GATA-1.05) GATA-1 allele, consequently leading to variable anemic severity.@@@@1@45@@oe@16-12-2010 965774204@GENIA Treebank@formal@@1@S@These heterozygous mutant mice usually developed normally, but they began to die after 5 months.@@@@1@17@@oe@16-12-2010 965774205@GENIA Treebank@formal@@1@S@These affected animals displayed marked splenomegaly, anemia, and thrombocytopenia.@@@@1@12@@oe@16-12-2010 965774206@GENIA Treebank@formal@@1@S@Proerythroblasts and megakaryocytes massively accumulated in the spleens of the heterozygotes, and we showed that the neomycin resistance gene (which is the positive selection marker in ES cells) was expressed profusely in the abnormally abundant cells generated in the GATA-1.05 mutant females.@@@@1@46@@oe@16-12-2010 965774207@GENIA Treebank@formal@@1@S@We also observed hematopoiesis outside of the bone marrow in the affected mutant mice.@@@@1@15@@oe@16-12-2010 965774208@GENIA Treebank@formal@@1@S@These data suggest that a small number of GATA-1.05 mutant hematopoietic progenitor cells begin to proliferate vigorously during early adulthood, but because the cells are unable to terminally differentiate, this leads to progenitor proliferation in the spleen and consequently death.@@@@1@43@@oe@16-12-2010 965774209@GENIA Treebank@formal@@1@S@Thus, GATA-1 plays important in vivo roles for directing definitive hematopoietic progenitors to differentiate along both the erythroid and megakaryocytic pathways.@@@@1@23@@oe@16-12-2010 965774210@GENIA Treebank@formal@@1@S@The GATA-1 heterozygous mutant mouse shows a phenotype that is analogous to human myelodysplastic syndrome and thus may serve as a useful model for this disorder.@@@@1@27@@oe@16-12-2010 965774301@GENIA Treebank@formal@@1@S@Erythropoietin induces tyrosine phosphorylation of Jak2, STAT5A, and STAT5B in primary cultured human erythroid precursors.@@@@1@18@@oe@16-12-2010 965774302@GENIA Treebank@formal@@1@S@We examined signaling by erythropoietin in highly purified human colony forming unit-erythroid cells, generated in vitro from CD34(+) cells.@@@@1@21@@oe@16-12-2010 965774303@GENIA Treebank@formal@@1@S@We found that erythropoietin induces tyrosine phosphorylation of Jak2, STAT5A, and STAT5B.@@@@1@15@@oe@16-12-2010 965774304@GENIA Treebank@formal@@1@S@Tyrosine phosphorylation of Jak2 reaches a peak around 10 minutes after stimulation and is maximum at 5 U/mL of erythropoietin.@@@@1@21@@oe@16-12-2010 965774305@GENIA Treebank@formal@@1@S@Tyrosine phosphorylation of STAT5 is accompanied by the translocation of activated STAT5 to the nucleus as shown by electrophoretic mobility shift assay (EMSA) using 32Pi-labeled STAT5 binding site in the beta-casein promoter.@@@@1@35@@oe@16-12-2010 965774306@GENIA Treebank@formal@@1@S@Tyrosine phosphorylation STAT1 or STAT3 was not detected in human erythroid precursors after stimulation with erythropoietin.@@@@1@17@@oe@16-12-2010 965774307@GENIA Treebank@formal@@1@S@Crkl, an SH2/SH3 adapter protein, becomes coimmunoprecipitated specifically with STAT5 from erythropoietin-stimulated erythroid cells; although it was shown to become associated with c-Cbl in the studies using cell lines.@@@@1@33@@oe@16-12-2010 965774308@GENIA Treebank@formal@@1@S@Thus, human erythroid precursors can be expanded in vitro in sufficient numbers and purity to allow its usage in signal transduction studies.@@@@1@24@@oe@16-12-2010 965774309@GENIA Treebank@formal@@1@S@This report sets a basis for further studies on signaling in primary cultured human erythroid precursors, which in turn contribute to our better understanding in the differentiation processes of erythrocytes and their precursors.@@@@1@35@@oe@16-12-2010 965774501@GENIA Treebank@formal@@1@S@A novel function of Stat1 and Stat3 proteins in erythropoietin-induced erythroid differentiation of a human leukemia cell line.@@@@1@19@@oe@16-12-2010 965774502@GENIA Treebank@formal@@1@S@We recently determined that erythropoietin (EPO) activates 3 members of the signal transducer and activator of transcription (STAT) family, Stat1alpha, Stat3, and Stat5, in the human EPO-dependent cell lines, UT-7 and UT-7/EPO (Kirito et al, J Biol Chem 272:16507, 1997).@@@@1@56@@oe@16-12-2010 965774503@GENIA Treebank@formal@@1@S@In addition, we have shown that Stat1alpha, but not Stat3, is involved in EPO-induced cellular proliferation.@@@@1@20@@oe@16-12-2010 965774504@GENIA Treebank@formal@@1@S@In this study, we examined the roles of Stat1alpha and Stat3 in EPO-induced erythroid differentiation.@@@@1@17@@oe@16-12-2010 965774505@GENIA Treebank@formal@@1@S@UT-7/GM was used as a model system, because this cell line can differentiate into erythroid-lineage cells with EPO treatment (Komatsu et al, Blood 89:4021, 1997).@@@@1@33@@oe@16-12-2010 965774506@GENIA Treebank@formal@@1@S@We found that EPO did not activate Stat1alpha or Stat3 in UT-7/GM cells.@@@@1@14@@oe@16-12-2010 965774507@GENIA Treebank@formal@@1@S@Transfection experiments showed that both Stat1alpha and Stat3 inhibited the induction by EPO of gamma-globin and erythroid-specific 5-aminolevulinate synthetase transcripts, resulting in a reduction of the percentage of hemoglobin-positive cells.@@@@1@32@@oe@16-12-2010 965774508@GENIA Treebank@formal@@1@S@Dominant negative forms of Stat1alpha or Stat3 promoted the EPO-induced erythroid differentiation of UT-7/GM cells, even in the presence of granulocyte-macrophage colony-stimulating factor, although this cytokine never induced erythroid differentiation of the parent UT-7/GM cells with or without EPO.@@@@1@42@@oe@16-12-2010 965774509@GENIA Treebank@formal@@1@S@A cell cycle analysis showed that the constitutive activation of Stat1alpha, but not Stat3, shortened the period of G0/G1 prolongation caused by EPO stimulation.@@@@1@27@@oe@16-12-2010 965774510@GENIA Treebank@formal@@1@S@Taken together, our data suggest that Stat1alpha and Stat3 act as negative regulators in EPO-induced erythroid differentiation.@@@@1@19@@oe@16-12-2010 965774511@GENIA Treebank@formal@@1@S@Specifically, Stat1alpha may activate a cell cycle-associated gene(s), leading to the entry of cells into the cell cycle.@@@@1@24@@oe@16-12-2010 966093801@GENIA Treebank@formal@@1@S@DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-kappa B and AP-1.@@@@1@23@@oe@16-12-2010 966093802@GENIA Treebank@formal@@1@S@Apoptosis induced by DNA damage and other stresses can proceed via expression of Fas ligand (FasL) and ligation of its receptor, Fas (CD95).@@@@1@29@@oe@16-12-2010 966093803@GENIA Treebank@formal@@1@S@We report that activation of the two transcription factors NF-kappa B and AP-1 is crucially involved in FasL expression induced by etoposide, teniposide, and UV irradiation.@@@@1@29@@oe@16-12-2010 966093804@GENIA Treebank@formal@@1@S@A nondegradable mutant of I kappa B blocked both FasL expression and apoptosis induced by DNA damage but not Fas ligation.@@@@1@22@@oe@16-12-2010 966093805@GENIA Treebank@formal@@1@S@These stimuli also induced the stress-activated kinase pathway (SAPK/JNK), which was required for the maximal induction of apoptosis.@@@@1@22@@oe@16-12-2010 966093806@GENIA Treebank@formal@@1@S@A 1.2 kb FasL promoter responded to DNA damage, as well as coexpression with p65 Rel or Fos/Jun.@@@@1@20@@oe@16-12-2010 966093807@GENIA Treebank@formal@@1@S@Mutations in the relevant NF-kappa B and AP-1 binding sites eliminated these responses.@@@@1@14@@oe@16-12-2010 966093808@GENIA Treebank@formal@@1@S@Thus, activation of NF-kappa B and AP-1 contributes to stress-induced apoptosis via the expression of FasL.@@@@1@18@@oe@16-12-2010 966346701@GENIA Treebank@formal@@1@S@Thrombopoietin supports in vitro erythroid differentiation via its specific receptor c-Mpl in a human leukemia cell line.@@@@1@18@@oe@16-12-2010 966346702@GENIA Treebank@formal@@1@S@Thrombopoietin (TPO) acts on megakaryopoiesis and erythropoiesis in vitro and in vivo.@@@@1@15@@oe@16-12-2010 966346703@GENIA Treebank@formal@@1@S@We isolated a novel subline, UT-7/GMT, from the human leukemia cell line UT-7/GM (N. Komatsu, et al., Blood, 89: 4021-4033, 1997).@@@@1@31@@oe@16-12-2010 966346704@GENIA Treebank@formal@@1@S@A small population of UT-7/GM cells positively stained for hemoglobin (Hb) after a 7-day exposure to TPO.@@@@1@20@@oe@16-12-2010 966346705@GENIA Treebank@formal@@1@S@More than 50% of TPO-treated UT-7/GMT cells positively stained for Hb.@@@@1@13@@oe@16-12-2010 966346706@GENIA Treebank@formal@@1@S@Using UT-7/GMT cells, we examined how TPO promotes hemoglobinization.@@@@1@11@@oe@16-12-2010 966346707@GENIA Treebank@formal@@1@S@TPO induced tyrosine phosphorylation of the TPO receptor but not the erythropoietin (EPO) receptor.@@@@1@17@@oe@16-12-2010 966346708@GENIA Treebank@formal@@1@S@There was no competition between TPO and EPO for binding to EPO receptor.@@@@1@14@@oe@16-12-2010 966346709@GENIA Treebank@formal@@1@S@These findings suggest that TPO has a direct effect on hemoglobinization via a specific receptor on UT-7/GMT cells.@@@@1@19@@oe@16-12-2010 966346710@GENIA Treebank@formal@@1@S@Isoelectric focusing demonstrated that TPO induced fetal and adult Hb synthesis, whereas EPO induced embryonic, fetal, and adult Hb synthesis.@@@@1@24@@oe@16-12-2010 966346711@GENIA Treebank@formal@@1@S@Thus, our data suggest that TPO has a distinct action on erythropoiesis.@@@@1@14@@oe@16-12-2010 966546001@GENIA Treebank@formal@@1@S@Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator-activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro.@@@@1@30@@oe@16-12-2010 966546002@GENIA Treebank@formal@@1@S@Mononuclear phagocytes play an important role in atherosclerosis and its sequela plaque rupture in part by their secretion of matrix metalloproteinases (MMPs), including MMP-9.@@@@1@28@@oe@16-12-2010 966546003@GENIA Treebank@formal@@1@S@Peroxisomal proliferator-activated receptor gamma (PPARgamma), a transcription factor in the nuclear receptor superfamily, regulates gene expression in response to various activators, including 15-deoxy-delta12,14-prostaglandin J2 and the antidiabetic agent troglitazone.@@@@1@35@@oe@16-12-2010 966546004@GENIA Treebank@formal@@1@S@The role of PPARgamma in human atherosclerosis is unexplored.@@@@1@10@@oe@16-12-2010 966546005@GENIA Treebank@formal@@1@S@We report here that monocytes/macrophages in human atherosclerotic lesions (n = 12) express immunostainable PPARgamma.@@@@1@18@@oe@16-12-2010 966546006@GENIA Treebank@formal@@1@S@Normal artery specimens (n = 6) reveal minimal immunoreactive PPARgamma.@@@@1@13@@oe@16-12-2010 966546007@GENIA Treebank@formal@@1@S@Human monocytes and monocyte-derived macrophages cultured for 6 days in 5% human serum expressed PPARgamma mRNA and protein by reverse transcription-polymerase chain reaction and Western blotting, respectively.@@@@1@30@@oe@16-12-2010 966546008@GENIA Treebank@formal@@1@S@In addition, PPARgamma mRNA expression in U937 cells increased during phorbol 12-myristate 13 acetate-induced differentiation.@@@@1@17@@oe@16-12-2010 966546009@GENIA Treebank@formal@@1@S@Stimulation of PPARgamma with troglitazone or 15-deoxy-delta12,14-prostaglandin J2 in human monocyte-derived macrophages inhibited MMP-9 gelatinolytic activity in a concentration-dependent fashion as revealed by zymography.@@@@1@25@@oe@16-12-2010 966546010@GENIA Treebank@formal@@1@S@This inhibition correlates with decreased MMP-9 secretion as determined by Western blotting.@@@@1@13@@oe@16-12-2010 966546011@GENIA Treebank@formal@@1@S@Thus, PPARgamma is present in macrophages in human atherosclerotic lesions and may regulate expression and activity of MMP-9, an enzyme implicated in plaque rupture.@@@@1@27@@oe@16-12-2010 966546012@GENIA Treebank@formal@@1@S@PPARgamma is likely to be an important regulator of monocyte/macrophage function with relevance for human atherosclerotic disease.@@@@1@18@@oe@16-12-2010 966588401@GENIA Treebank@formal@@1@S@Uncoupling of nonreceptor tyrosine kinases from PLC-gamma1 in an SLP-76-deficient T cell.@@@@1@13@@oe@16-12-2010 966588402@GENIA Treebank@formal@@1@S@Activation of nonreceptor protein tyrosine kinases (PTKs) is essential for T cell receptor (TCR) responsiveness; however, the function of individual PTK substrates is often uncertain.@@@@1@32@@oe@16-12-2010 966588403@GENIA Treebank@formal@@1@S@A mutant T cell line was isolated that lacked expression of SLP-76 (SH2 domain-containing leukocyte protein of 76 kilodaltons), a hematopoietically expressed adaptor protein and PTK substrate.@@@@1@31@@oe@16-12-2010 966588404@GENIA Treebank@formal@@1@S@SLP-76 was not required for TCR-induced tyrosine phosphorylation of most proteins, but was required for optimal tyrosine phosphorylation and activation of phospholipase C-gamma1 (PLC-gamma1), as well as Ras pathway activation.@@@@1@35@@oe@16-12-2010 966588405@GENIA Treebank@formal@@1@S@TCR-inducible gene expression was dependent on SLP-76.@@@@1@8@@oe@16-12-2010 966588406@GENIA Treebank@formal@@1@S@Thus, coupling of TCR-regulated PTKs to downstream signaling pathways requires SLP-76.@@@@1@13@@oe@16-12-2010 967676101@GENIA Treebank@formal@@1@S@Peripheral blood T cells and monocytes and B cell lines derived from patients with lupus express estrogen receptor transcripts similar to those of normal cells.@@@@1@26@@oe@16-12-2010 967676102@GENIA Treebank@formal@@1@S@OBJECTIVE: To identify and characterize estrogen receptor (ER) transcripts expressed in immune cells of patients with systemic lupus erythematosus (SLE) and healthy donors.@@@@1@29@@oe@16-12-2010 967676103@GENIA Treebank@formal@@1@S@METHODS: Peripheral blood monocytes and T cells were prepared from patients with SLE (n = 6) and healthy donors (n = 8).@@@@1@28@@oe@16-12-2010 967676104@GENIA Treebank@formal@@1@S@T cells were separated into CD4 and CD8.@@@@1@9@@oe@16-12-2010 967676105@GENIA Treebank@formal@@1@S@Some monocytes and T cells were stimulated with estradiol, PMA, and ionomycin.@@@@1@15@@oe@16-12-2010 967676106@GENIA Treebank@formal@@1@S@Epstein-Barr virus-transformed B cell lines (n = 7) and B cell hybridomas (n = 2) established from patients with SLE and a healthy individual were used as a B cell source.@@@@1@36@@oe@16-12-2010 967676107@GENIA Treebank@formal@@1@S@These cells were examined for ER mRNA by reverse transcription nested polymerase chain reaction.@@@@1@15@@oe@16-12-2010 967676108@GENIA Treebank@formal@@1@S@Amplified cDNA were sequenced by standard methods.@@@@1@8@@oe@16-12-2010 967676109@GENIA Treebank@formal@@1@S@RESULTS: In all cells tested, ER mRNA was expressed without prior in vitro stimulation.@@@@1@17@@oe@16-12-2010 967676110@GENIA Treebank@formal@@1@S@Partial sequences from exons 1-8 were nearly identical to the published sequence of the human ER mRNA.@@@@1@18@@oe@16-12-2010 967676111@GENIA Treebank@formal@@1@S@There were no notable differences in the ER transcripts between patients and healthy controls.@@@@1@15@@oe@16-12-2010 967676112@GENIA Treebank@formal@@1@S@Variant receptor transcripts lacking exon 5 or exon 7, which encodes the hormone binding domain, were identified in the majority of the cells.@@@@1@26@@oe@16-12-2010 967676113@GENIA Treebank@formal@@1@S@Precise deletion of the exons suggests that they are alternatively spliced transcripts.@@@@1@13@@oe@16-12-2010 967676114@GENIA Treebank@formal@@1@S@Whether the detected transcripts are translated into functional receptor proteins remains to be determined.@@@@1@15@@oe@16-12-2010 967676115@GENIA Treebank@formal@@1@S@In vitro stimulation did not affect ER mRNA expression.@@@@1@10@@oe@16-12-2010 967676116@GENIA Treebank@formal@@1@S@The presence of variants did not correlate with disease activity or medication.@@@@1@13@@oe@16-12-2010 967676117@GENIA Treebank@formal@@1@S@CONCLUSION: Monocytes, T cells, and B cells in patients express transcripts of the normal wild type ER and the hormone binding domain variants in vivo.@@@@1@29@@oe@16-12-2010 967871801@GENIA Treebank@formal@@1@S@A novel retinoic acid receptor (RAR)-selective antagonist inhibits differentiation and apoptosis of HL-60 cells: implications of RARalpha-mediated signals in myeloid leukemic cells.@@@@1@27@@oe@16-12-2010 967871802@GENIA Treebank@formal@@1@S@Retinoic acid (RA) induces HL-60 cells to differentiate terminally into mature granulocytes, which subsequently die by apoptosis.@@@@1@21@@oe@16-12-2010 967871803@GENIA Treebank@formal@@1@S@The biological effects of RA are mediated by two distinct families of transcription factors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs).@@@@1@29@@oe@16-12-2010 967871804@GENIA Treebank@formal@@1@S@RARs and RXRs form heterodimers and regulate retinoid-mediated gene expression.@@@@1@11@@oe@16-12-2010 967871805@GENIA Treebank@formal@@1@S@We have recently developed a novel RAR-selective antagonist (ER27191) which prevents RAR activation by retinoids.@@@@1@18@@oe@16-12-2010 967871806@GENIA Treebank@formal@@1@S@Using this RAR-selective antagonist, and RXR and RAR agonist, we demonstrate the RAR-mediated signaling pathway is important for differentiation and apoptosis of myeloid leukemic cells.@@@@1@28@@oe@16-12-2010 967871807@GENIA Treebank@formal@@1@S@Simple activation of RXRs is not sufficient to induce apoptosis of the cells.@@@@1@14@@oe@16-12-2010 967871808@GENIA Treebank@formal@@1@S@Interestingly, the combination of the RAR-selective antagonist and 9-cis RA resulted in partial differentiation and apoptosis of HL-60 and NB4 cells, whereas the RAR antagonist completely blocked all-trans RA-induced differentiation and apoptosis of the cells.@@@@1@38@@oe@16-12-2010 967871809@GENIA Treebank@formal@@1@S@Additional experiments showed that levels of BCL-2 protein decreased during differentiation of myeloid leukemic cells.@@@@1@16@@oe@16-12-2010 967871810@GENIA Treebank@formal@@1@S@Furthermore, HL-60 cells transduced with a bcl-2 expression vector showed the same differentiation response to retinoids as did parental HL-60 cells even though apoptosis was inhibited in these bcl-2-transduced cells, suggesting that differentiation and apoptosis are regulated independently in myeloid leukemic cells.@@@@1@45@@oe@16-12-2010 967982901@GENIA Treebank@formal@@1@S@Suppression of human anti-porcine T-cell immune responses by major histocompatibility complex class II transactivator constructs lacking the amino terminal domain.@@@@1@21@@oe@16-12-2010 967982902@GENIA Treebank@formal@@1@S@BACKGROUND: The class II transactivator (CIITA) is a bi- or multifunctional domain protein that acts as a transcriptional activator and plays a critical role in the expression of MHC class II genes.@@@@1@36@@oe@16-12-2010 967982903@GENIA Treebank@formal@@1@S@We have previously demonstrated that a mutated form of the human CIITA gene, coding for a protein lacking the amino terminal 151 amino acids, acts as a potent dominant-negative suppressor of HLA class II expression.@@@@1@38@@oe@16-12-2010 967982904@GENIA Treebank@formal@@1@S@Porcine MHC class II antigens are potent stimulators of direct T-cell recognition by human CD4+ T cells and are, therefore, likely to play an important role in the rejection responses to transgenic pig donors in clinical xenotransplantation.@@@@1@40@@oe@16-12-2010 967982905@GENIA Treebank@formal@@1@S@We were, therefore, interested in examining mutated CIITA constructs for their effect on porcine MHC class II expression.@@@@1@21@@oe@16-12-2010 967982906@GENIA Treebank@formal@@1@S@METHODS: Stable transfectants of the porcine vascular endothelial cell line PIEC with mutated CIITA constructs were tested for SLA-DR and SLA-DQ induction by recombinant porcine interferon-gamma.@@@@1@28@@oe@16-12-2010 967982907@GENIA Treebank@formal@@1@S@Transient transfectants of the porcine B-cell line L23 with the mutated CIITA constructs were tested for the suppression of constitutive SLA-DR and SLA-DQ expression.@@@@1@25@@oe@16-12-2010 967982908@GENIA Treebank@formal@@1@S@T-cell proliferation studies were performed using highly purified human CD4+ T cells.@@@@1@13@@oe@16-12-2010 967982909@GENIA Treebank@formal@@1@S@RESULTS: In preliminary studies, we demonstrated that transfection of the PIEC line with full-length human CIITA constructs resulted in strong expression of SLA-DR and SLA-DQ antigens, thus establishing the cross-species effectiveness of human CIITA in the pig.@@@@1@41@@oe@16-12-2010 967982910@GENIA Treebank@formal@@1@S@The mutated human CIITA constructs were, therefore, tested in the pig.@@@@1@14@@oe@16-12-2010 967982911@GENIA Treebank@formal@@1@S@PIEC clones stably transfected with one of these constructs showed up to 99% suppression of SLA-DR and SLA-DQ antigen induction and marked suppression of SLA-DRA mRNA induction.@@@@1@29@@oe@16-12-2010 967982912@GENIA Treebank@formal@@1@S@Moreover, transient transfection of the porcine B-cell line L23 showed up to 90% suppression of constitutive SLA-DR and SLA-DQ antigen expression in 5-8 days.@@@@1@27@@oe@16-12-2010 967982913@GENIA Treebank@formal@@1@S@In functional studies, interferon-gamma-stimulated PIEC clones transfected with this mutated CIITA construct failed to stimulate purified human CD4+ T lymphocytes.@@@@1@22@@oe@16-12-2010 967982914@GENIA Treebank@formal@@1@S@CONCLUSION: Mutated human CIITA constructs are potent suppressors of porcine MHC class II expression.@@@@1@16@@oe@16-12-2010 968018101@GENIA Treebank@formal@@1@S@Redox signals and NF-kappaB activation in T cells.@@@@1@9@@oe@16-12-2010 968018102@GENIA Treebank@formal@@1@S@Accumulating data from a number of laboratories have recently indicated that the response of transcription factor NF-kappaB to alterations in the redox homeostasis of cells may play an important role in modulating immune function.@@@@1@35@@oe@16-12-2010 968018103@GENIA Treebank@formal@@1@S@The activation of NF-kappaB has been recognized to regulate a number of genes necessary for normal T cell responses including IL-2, IL-6, IL-8, and several T cell surface receptors.@@@@1@33@@oe@16-12-2010 968018104@GENIA Treebank@formal@@1@S@Diminished NF-kappaB activity has been shown to occur in T cells with aging, suggesting that impaired activation of NF-kappaB might occur during cellular senescence.@@@@1@26@@oe@16-12-2010 968018105@GENIA Treebank@formal@@1@S@In addition, aberrancies in NF-kappaB activity have been implicated in the immunopathogenesis of diseases involving immune or inflammatory processes such as atherosclerosis and HIV-1 infection.@@@@1@27@@oe@16-12-2010 968018106@GENIA Treebank@formal@@1@S@The role of H2O2 and other reactive oxygen species (ROS) as an integratory secondary messenger for divergent T cell signals has been complicated by the fact that various T cell lines and peripheral blood T cells differ markedly in the levels of NF-kappaB activation induced by oxidant stress.@@@@1@51@@oe@16-12-2010 968018107@GENIA Treebank@formal@@1@S@Additionally, proposed pathways of NF-kappaB activation have been based on indirect evidence provided by experiments which used antioxidants to inhibit active NF-kappaB formation.@@@@1@25@@oe@16-12-2010 968018108@GENIA Treebank@formal@@1@S@Further, complete activation of T cells requires at least two signals, one that stimulates an increase in intracellular calcium and one that stimulates enzymatic processes including kinases.@@@@1@30@@oe@16-12-2010 968018109@GENIA Treebank@formal@@1@S@Similarly, substantial evidence indicates that full activation of NF-kappaB requires dual signals.@@@@1@14@@oe@16-12-2010 968018110@GENIA Treebank@formal@@1@S@The ability of H2O2 or other ROS to induce T cell signals and functional responses by these two mechanisms is reviewed and the specific response of NF-kappaB to redox changes in T cells is examined.@@@@1@36@@oe@16-12-2010 968018111@GENIA Treebank@formal@@1@S@Data are also presented to suggest that the redox regulation in NF-kappaB activation may be relevant to immune-related diseases and to aging.@@@@1@23@@oe@16-12-2010 968661201@GENIA Treebank@formal@@1@S@Fibrinogen activates NF-kappa B transcription factors in mononuclear phagocytes.@@@@1@10@@oe@16-12-2010 968661202@GENIA Treebank@formal@@1@S@Adhesion to extracellular matrices is known to modulate leukocyte activation, although the mechanisms are not fully understood.@@@@1@19@@oe@16-12-2010 968661203@GENIA Treebank@formal@@1@S@Mononuclear phagocytes are exposed to fibrinous provisional matrix throughout migration into inflammatory foci, so this study was undertaken to determine whether fibrinogen triggers activation of NF-kappa B transcription factors.@@@@1@31@@oe@16-12-2010 968661204@GENIA Treebank@formal@@1@S@U937 cells differentiated with PMA in nonadherent culture were shown to express two fibrinogen-binding integrins, predominately CD11b/CD18, and to a lesser extent, CD11c/CD18.@@@@1@27@@oe@16-12-2010 968661205@GENIA Treebank@formal@@1@S@Cells stimulated with fibrinogen (10-100 microg/ml)/Mn2+ (50 microM) for 2 h were examined by electrophoretic mobility shift assay.@@@@1@24@@oe@16-12-2010 968661206@GENIA Treebank@formal@@1@S@NF-kappa B activation, minimal in unstimulated cells, was substantially up-regulated by fibrinogen.@@@@1@15@@oe@16-12-2010 968661207@GENIA Treebank@formal@@1@S@Fibrinogen also caused activation of AP-1, but not SP1 or cAMP response element-binding protein (CREB) factors.@@@@1@20@@oe@16-12-2010 968661208@GENIA Treebank@formal@@1@S@Blocking mAbs against CD18 and CD11b abrogated fibrinogen-induced NF-kappa B activation.@@@@1@12@@oe@16-12-2010 968661209@GENIA Treebank@formal@@1@S@To determine the effects on transcriptional regulation, U937 cells were transfected with a plasmid containing the HIV-1 enhancer (bearing two NF-kappa B sites) coupled to a chloramphenicol acetyltransferase (CAT) reporter.@@@@1@36@@oe@16-12-2010 968661210@GENIA Treebank@formal@@1@S@Cells were subsequently stimulated with 1) PMA for 24 h, inducing CAT activity by 2.6-fold, 2) fibrinogen/Mn2+ for 2 h, inducing CAT activity by 3.2-fold, or 3) costimulation with fibrinogen and PMA, inducing 5.7-fold the CAT activity induced by PMA alone.@@@@1@50@@oe@16-12-2010 968661211@GENIA Treebank@formal@@1@S@We conclude that contact with fibrinogen-derived proteins may contribute to mononuclear phagocyte activation by signaling through CD11b/CD18, resulting in selective activation of transcriptional regulatory factors, including NF-kappa B.@@@@1@31@@oe@16-12-2010 968738501@GENIA Treebank@formal@@1@S@Ciprofloxacin induces an immunomodulatory stress response in human T lymphocytes.@@@@1@11@@oe@16-12-2010 968738502@GENIA Treebank@formal@@1@S@Exposure of cells to adverse environmental conditions invokes a genetically programmed series of events resulting in the induction of specific genes.@@@@1@22@@oe@16-12-2010 968738503@GENIA Treebank@formal@@1@S@The fluoroquinolone antibiotic ciprofloxacin has recently been reported to upregulate interleukin-2 (IL-2) gene induction.@@@@1@17@@oe@16-12-2010 968738504@GENIA Treebank@formal@@1@S@In the present investigation, the effect of ciprofloxacin at supratherapeutic concentrations on immediate-early (<2 h) gene expression in primary human peripheral blood lymphocytes was studied with Northern blots.@@@@1@33@@oe@16-12-2010 968738505@GENIA Treebank@formal@@1@S@In addition, transcriptional activity of IL-2 and metallothionein enhancer and promoter regions and transcription factors AP-1, NF-kappaB, and NF-AT were analyzed by chloramphenicol acetyltransferase (CAT) and electrophoretic mobility shift assays, respectively.@@@@1@38@@oe@16-12-2010 968738506@GENIA Treebank@formal@@1@S@The concentration of c-fos, c-jun, c-myc, junB, and fra-1 mRNAs was increased in activated peripheral blood lymphocytes incubated with ciprofloxacin compared to that in untreated controls.@@@@1@31@@oe@16-12-2010 968738507@GENIA Treebank@formal@@1@S@Ciprofloxacin increased CAT activity in stimulated lymphocytes transfected with plasmids containing either the IL-2 or metallothionein enhancer.@@@@1@18@@oe@16-12-2010 968738508@GENIA Treebank@formal@@1@S@Furthermore, among the transcription factors tested, AP-1 activity was increased in stimulated purified T helper lymphocytes incubated with ciprofloxacin compared to drug-free controls.@@@@1@26@@oe@16-12-2010 968738509@GENIA Treebank@formal@@1@S@Taken together, ciprofloxacin increased the levels of immediate-early transcripts, enhanced IL-2 and metallothionein promoter induction, and upregulated AP-1 concentrations in primary lymphocytes, reflecting a program commonly observed in mammalian stress responses.@@@@1@36@@oe@16-12-2010 969045501@GENIA Treebank@formal@@1@S@Ex vivo activation of tumor-draining lymph node T cells reverses defects in signal transduction molecules.@@@@1@16@@oe@16-12-2010 969045502@GENIA Treebank@formal@@1@S@The adoptive transfer of tumor-draining lymph node (LN) T cells activated ex vivo with anti-CD3 and interleukin 2 (IL-2) mediates the regression of the poorly immunogenic murine melanoma D5.@@@@1@34@@oe@16-12-2010 969045503@GENIA Treebank@formal@@1@S@The efficacy of the activated LN cells is augmented when the sensitizing tumor is a genetically modified variant (designated D5G6) that secretes granulocyte/macrophage-colony-stimulating factor.@@@@1@27@@oe@16-12-2010 969045504@GENIA Treebank@formal@@1@S@In contrast to anti-CD3/IL-2-activated LN cells, adoptive transfer of freshly isolated tumor-draining LN T cells has no therapeutic activity.@@@@1@21@@oe@16-12-2010 969045505@GENIA Treebank@formal@@1@S@To determine whether the acquisition of antitumor function during ex vivo activation is associated with modifications in signal transduction capacity, the protein tyrosine kinases p56lck and p59fyn and proteins of the NF-kappaB family were analyzed in tumor-draining LN T cells.@@@@1@42@@oe@16-12-2010 969045506@GENIA Treebank@formal@@1@S@The levels of p56lck and p59fyn were lower in tumor-draining than in normal LN T cells and production of tyrosine-phosphorylated substrates was markedly depressed following anti-CD3 stimulation.@@@@1@28@@oe@16-12-2010 969045507@GENIA Treebank@formal@@1@S@After 5-day anti-CD3/IL-2 activation, levels of p56lck and p59fyn and protein tyrosine kinase activity increased.@@@@1@17@@oe@16-12-2010 969045508@GENIA Treebank@formal@@1@S@Interestingly, the levels of p56lck, p59fyn, and tyrosine kinase activity were higher in activated T cells derived from LN that drained D5G6 than they were in those from D5 tumors.@@@@1@34@@oe@16-12-2010 969045509@GENIA Treebank@formal@@1@S@In contrast, the cytoplasmic levels of c-Rel and Rel A were normal in freshly isolated tumor-draining LN, as was nuclear kappaB DNA-binding activity induced by anti-CD3 mAb or phorbol myristate acetate.@@@@1@34@@oe@16-12-2010 969045510@GENIA Treebank@formal@@1@S@Stimulation of activated LN cells with D5 tumor cells induced the nuclear translocation of NF-kappaB.@@@@1@16@@oe@16-12-2010 969045511@GENIA Treebank@formal@@1@S@These findings indicate that the recovery of proteins mediating signal transduction through the T cell receptor/CD3 complex in LN T cells activated ex vivo was associated with the acquisition of antitumor function.@@@@1@33@@oe@16-12-2010 969091701@GENIA Treebank@formal@@1@S@Expression of gamma-IFN responsive genes in scavenger receptor over-expressing monocytes is associated with xanthomatosis.@@@@1@15@@oe@16-12-2010 969091702@GENIA Treebank@formal@@1@S@We have recently described an inherited over-expression of the macrophage scavenger receptor (SR) in blood monocytes from members of a kindred, only two of whom displayed extensive xanthomatosis.@@@@1@32@@oe@16-12-2010 969091703@GENIA Treebank@formal@@1@S@Using mRNA differential display we demonstrated abnormally high expression of the signal transducer and activator of transcription (STAT1alpha) in monocytes from the proband II-2.@@@@1@27@@oe@16-12-2010 969091704@GENIA Treebank@formal@@1@S@Expression of gamma-interferon inducible protein 10 (IP-10), a STAT1alpha-responsive gene and mediator of inflammatory response, was also abnormally expressed in the monocytes from II-2.@@@@1@29@@oe@16-12-2010 969091705@GENIA Treebank@formal@@1@S@Over-expression of both genes was restricted to monocytes from II-2 and was not observed in monocytes from the clinically unaffected family members, unlike that of SR.@@@@1@28@@oe@16-12-2010 969091706@GENIA Treebank@formal@@1@S@Gel retardation assays with THP-1 cell extracts identified gamma-IFN inducible DNA binding activity to three potential STATI DNA binding elements in the human IP-10 promoter region from nucleotides - 245 to - 188.@@@@1@32@@oe@16-12-2010 969091707@GENIA Treebank@formal@@1@S@Taken together these results suggest that gamma-interferon mediated cell activation is responsible for STAT1alpha-induced transcription of the IP-10 gene in THP-1 macrophages as well as in monocytes from II-2.@@@@1@30@@oe@16-12-2010 969091708@GENIA Treebank@formal@@1@S@Analysis of monocytes from familial hypercholesterolemic (FH) subjects, who frequently develop xanthomatosis, revealed a significant number of subjects with elevated STAT1alpha and IP-10 expression.@@@@1@29@@oe@16-12-2010 969091709@GENIA Treebank@formal@@1@S@Our data suggest that the inflammatory effects of gamma-IFN signaling could play a role in foam cell formation and xanthomatosis.@@@@1@21@@oe@16-12-2010 969684401@GENIA Treebank@formal@@1@S@Recognition of herpes simplex virus type 2 tegument proteins by CD4 T cells infiltrating human genital herpes lesions.@@@@1@19@@oe@16-12-2010 969684402@GENIA Treebank@formal@@1@S@The local cellular immune response to herpes simplex virus (HSV) is important in the control of recurrent HSV infection.@@@@1@22@@oe@16-12-2010 969684403@GENIA Treebank@formal@@1@S@The antiviral functions of infiltrating CD4-bearing T cells may include cytotoxicity, inhibition of viral growth, lymphokine secretion, and support of humoral and CD8 responses.@@@@1@28@@oe@16-12-2010 969684404@GENIA Treebank@formal@@1@S@The antigens recognized by many HSV-specific CD4 T cells localizing to genital HSV-2 lesions are unknown.@@@@1@17@@oe@16-12-2010 969684405@GENIA Treebank@formal@@1@S@T cells recognizing antigens encoded within map units 0.67 to 0.73 of HSV DNA are frequently recovered from herpetic lesions.@@@@1@21@@oe@16-12-2010 969684406@GENIA Treebank@formal@@1@S@Expression cloning with this region of DNA now shows that tegument protein VP22 and the viral dUTPase, encoded by genes UL49 and UL50, respectively, are T-cell antigens.@@@@1@31@@oe@16-12-2010 969684407@GENIA Treebank@formal@@1@S@Separate epitopes in VP22 were defined for T-cell clones from each of three patients.@@@@1@15@@oe@16-12-2010 969684408@GENIA Treebank@formal@@1@S@Reactivity with the tegument protein encoded by UL21 was identified for an additional patient.@@@@1@15@@oe@16-12-2010 969684409@GENIA Treebank@formal@@1@S@Three new epitopes were identified in VP16, a tegument protein associated with VP22.@@@@1@15@@oe@16-12-2010 969684410@GENIA Treebank@formal@@1@S@Some tegument-specific CD4 T-cell clones exhibited cytotoxic activity against HSV-infected cells.@@@@1@12@@oe@16-12-2010 969684411@GENIA Treebank@formal@@1@S@These results suggest that herpes simplex tegument proteins are processed for antigen presentation in vivo and are possible candidate compounds for herpes simplex vaccines.@@@@1@25@@oe@16-12-2010 969784401@GENIA Treebank@formal@@1@S@Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.@@@@1@15@@oe@16-12-2010 969784402@GENIA Treebank@formal@@1@S@MyD88, originally isolated as a myeloid differentiation primary response gene, is shown to act as an adaptor in interleukin-1 (IL-1) signaling by interacting with both the IL-1 receptor complex and IL-1 receptor-associated kinase (IRAK).@@@@1@41@@oe@16-12-2010 969784403@GENIA Treebank@formal@@1@S@Mice generated by gene targeting to lack MyD88 have defects in T cell proliferation as well as induction of acute phase proteins and cytokines in response to IL-1.@@@@1@29@@oe@16-12-2010 969784404@GENIA Treebank@formal@@1@S@Increases in interferon-gamma production and natural killer cell activity in response to IL-18 are abrogated.@@@@1@16@@oe@16-12-2010 969784405@GENIA Treebank@formal@@1@S@In vivo Th1 response is also impaired.@@@@1@8@@oe@16-12-2010 969784406@GENIA Treebank@formal@@1@S@Furthermore, IL-18-induced activation of NF-kappaB and c-Jun N-terminal kinase (JNK) is blocked in MyD88-/- Th1-developing cells.@@@@1@20@@oe@16-12-2010 969784407@GENIA Treebank@formal@@1@S@Taken together, these results demonstrate that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor.@@@@1@28@@oe@16-12-2010 970005301@GENIA Treebank@formal@@1@S@Human 15-lipoxygenase gene promoter: analysis and identification of DNA binding sites for IL-13-induced regulatory factors in monocytes.@@@@1@19@@oe@16-12-2010 970005302@GENIA Treebank@formal@@1@S@In order to study the transcriptional control of 15-LO expression, we have cloned and sequenced the human 15-LO promoter region.@@@@1@22@@oe@16-12-2010 970005303@GENIA Treebank@formal@@1@S@The 15-LO promoter is associated with a CpG island at the 5'-end of the gene, and sequence analysis reveals putative Sp1 and Ap2 binding site/s and absence of TATA or CAAT motifs.@@@@1@34@@oe@16-12-2010 970005304@GENIA Treebank@formal@@1@S@Transcription is initiated at one major site.@@@@1@8@@oe@16-12-2010 970005305@GENIA Treebank@formal@@1@S@Using deletion constructs, we have defined an active promoter region of 1056 bp.@@@@1@15@@oe@16-12-2010 970005306@GENIA Treebank@formal@@1@S@Gel-shift assays revealed that transcriptional factor(s) induced only in response to IL-13 treatment of human peripheral blood monocytes bind to the 15-LO promoter DNA.@@@@1@28@@oe@16-12-2010 970005307@GENIA Treebank@formal@@1@S@Two regions, DP1 (-140 to -92 bp) and DP2 (-353 to -304 bp) of the promoter were essential for transcription in HeLa cells and human peripheral monocytes.@@@@1@33@@oe@16-12-2010 970005308@GENIA Treebank@formal@@1@S@Hela nuclear extracts contained a specific nuclear factor(s) binding to 15-LO promoter DNA which are distinct from those derived from IL-13-treated human peripheral monocyte nuclear extracts.@@@@1@30@@oe@16-12-2010 970005309@GENIA Treebank@formal@@1@S@In addition, fluorescent in situ hybridization (FISH) results refined the previous localization of 15-LO to human chromosome 17p13.3.@@@@1@22@@oe@16-12-2010 970010101@GENIA Treebank@formal@@1@S@Changes in PKC isoforms in human alveolar macrophages compared with blood monocytes.@@@@1@13@@oe@16-12-2010 970010102@GENIA Treebank@formal@@1@S@Alveolar macrophages play an important role in host defense and in other types of inflammatory processes in the lung.@@@@1@20@@oe@16-12-2010 970010103@GENIA Treebank@formal@@1@S@These cells exhibit many alterations in function compared with their precursor cells, blood monocytes.@@@@1@16@@oe@16-12-2010 970010104@GENIA Treebank@formal@@1@S@To evaluate a potential mechanism for these differences in function, we evaluated expression of protein kinase C (PKC) isoforms.@@@@1@23@@oe@16-12-2010 970010105@GENIA Treebank@formal@@1@S@We found an increase in Ca2+-dependent PKC isoforms in monocytes compared with alveolar macrophages.@@@@1@15@@oe@16-12-2010 970010106@GENIA Treebank@formal@@1@S@We also found differential expression of the Ca2+-independent isoforms in alveolar macrophages compared with monocytes.@@@@1@16@@oe@16-12-2010 970010107@GENIA Treebank@formal@@1@S@One consequence of the activation of PKC can be increased expression of mitogen-activated protein (MAP) kinase pathways.@@@@1@20@@oe@16-12-2010 970010108@GENIA Treebank@formal@@1@S@Therefore, we also evaluated activation of the MAP kinase extracellular signal-regulated kinase (ERK) 2 by the phorbol ester phorbol 12-myristate 13-acetate (PMA).@@@@1@28@@oe@16-12-2010 970010109@GENIA Treebank@formal@@1@S@PMA activated ERK2 kinase in both alveolar macrophages and monocytes; however, monocytes consistently showed a significantly greater activation of ERK2 kinase by PMA compared with alveolar macrophages.@@@@1@30@@oe@16-12-2010 970010110@GENIA Treebank@formal@@1@S@Another known consequence of the activation of PKC and subsequent activation of ERK kinase is activation of the transcription factor activator protein-1 (AP-1).@@@@1@26@@oe@16-12-2010 970010111@GENIA Treebank@formal@@1@S@We evaluated the activation of AP-1 by PMA in both monocytes and macrophages.@@@@1@14@@oe@16-12-2010 970010112@GENIA Treebank@formal@@1@S@We found very little detectable activation of AP-1, as assessed in a gel shift assay, in alveolar macrophages, whereas monocytes showed a substantial activation of AP-1 by PMA.@@@@1@32@@oe@16-12-2010 970010113@GENIA Treebank@formal@@1@S@These studies show that the differential expression of PKC isoforms in alveolar macrophages and blood monocytes is associated with important functional alterations in the cells.@@@@1@26@@oe@16-12-2010 970756501@GENIA Treebank@formal@@1@S@Acetylation and modulation of erythroid Kruppel-like factor (EKLF) activity by interaction with histone acetyltransferases.@@@@1@17@@oe@16-12-2010 970756502@GENIA Treebank@formal@@1@S@Erythroid Kruppel-like factor (EKLF) is a red cell-specific transcriptional activator that is crucial for consolidating the switch to high levels of adult beta-globin expression during erythroid ontogeny.@@@@1@30@@oe@16-12-2010 970756503@GENIA Treebank@formal@@1@S@EKLF is required for integrity of the chromatin structure at the beta-like globin locus, and it interacts with a positive-acting factor in vivo.@@@@1@25@@oe@16-12-2010 970756504@GENIA Treebank@formal@@1@S@We find that EKLF is an acetylated transcription factor, and that it interacts in vivo with CBP, p300, and P/CAF.@@@@1@24@@oe@16-12-2010 970756505@GENIA Treebank@formal@@1@S@However, its interactions with these histone acetyltransferases are not equivalent, as CBP and p300, but not P/CAF, utilize EKLF as a substrate for in vitro acetylation within its trans-activation region.@@@@1@35@@oe@16-12-2010 970756506@GENIA Treebank@formal@@1@S@The functional effects of these interactions are that CBP and p300, but not P/CAF, enhance EKLF's transcriptional activation of the beta-globin promoter in erythroid cells.@@@@1@29@@oe@16-12-2010 970756507@GENIA Treebank@formal@@1@S@These results establish EKLF as a tissue-specific transcription factor that undergoes post-translational acetylation and suggest a mechanism by which EKLF is able to alter chromatin structure and induce beta-globin expression within the beta-like globin cluster.@@@@1@36@@oe@16-12-2010 970760801@GENIA Treebank@formal@@1@S@Epstein-Barr virus-transforming protein latent infection membrane protein 1 activates transcription factor NF-kappaB through a pathway that includes the NF-kappaB-inducing kinase and the IkappaB kinases IKKalpha and IKKbeta.@@@@1@28@@oe@16-12-2010 970760802@GENIA Treebank@formal@@1@S@The Epstein-Barr virus oncoprotein latent infection membrane protein 1 (LMP1) is a constitutively aggregated pseudo-tumor necrosis factor receptor (TNFR) that activates transcription factor NF-kappaB through two sites in its C-terminal cytoplasmic domain.@@@@1@37@@oe@16-12-2010 970760803@GENIA Treebank@formal@@1@S@One site is similar to activated TNFRII in associating with TNFR-associated factors TRAF1 and TRAF2, and the second site is similar to TNFRI in associating with the TNFRI death domain interacting protein TRADD.@@@@1@35@@oe@16-12-2010 970760804@GENIA Treebank@formal@@1@S@TNFRI has been recently shown to activate NF-kappaB through association with TRADD, RIP, and TRAF2; activation of the NF-kappaB-inducing kinase (NIK); activation of the IkappaB alpha kinases (IKKalpha and IKKbeta); and phosphorylation of IkappaB alpha.@@@@1@45@@oe@16-12-2010 970760805@GENIA Treebank@formal@@1@S@IkappaB alpha phosphorylation on Ser-32 and Ser-36 is followed by its degradation and NF-kappaB activation.@@@@1@16@@oe@16-12-2010 970760806@GENIA Treebank@formal@@1@S@In this report, we show that NF-kappaB activation by LMP1 or by each of its effector sites is mediated by a pathway that includes NIK, IKKalpha, and IKKbeta.@@@@1@32@@oe@16-12-2010 970760807@GENIA Treebank@formal@@1@S@Dominant negative mutants of NIK, IKKalpha, or IKKbeta substantially inhibited NF-kappaB activation by LMP1 or by each of its effector sites.@@@@1@24@@oe@16-12-2010 971014901@GENIA Treebank@formal@@1@S@Dimethyldithiocarbamate inhibits in vitro activation of primary human CD4+ T lymphocytes.@@@@1@12@@oe@16-12-2010 971014902@GENIA Treebank@formal@@1@S@Dithiocarbamates (DTC), a diverse group of industrial and therapeutic chemicals, have been reported to inhibit, enhance or have no effect on the immune system.@@@@1@30@@oe@16-12-2010 971014903@GENIA Treebank@formal@@1@S@These apparent inconsistencies reflect the complexity of the DTCs biological activities and are probably due in part to differences in dose, route of exposure, animal species used and/or specific compound tested.@@@@1@34@@oe@16-12-2010 971014904@GENIA Treebank@formal@@1@S@The studies described herein were undertaken to investigate the immunotoxicity of one member of this family, dimethyldithiocarbamate (DMDTC).@@@@1@22@@oe@16-12-2010 971014905@GENIA Treebank@formal@@1@S@We demonstrate that 0.1-0.5 microM DMDTC inhibits TNF-alpha-induced activation of NF-kappaB in primary human CD4+ T cells.@@@@1@18@@oe@16-12-2010 971014906@GENIA Treebank@formal@@1@S@This inhibition is not accompanied by a loss in viability, and DMDTC-treated T cells retain other active signaling pathways throughout the exposure duration.@@@@1@25@@oe@16-12-2010 971014907@GENIA Treebank@formal@@1@S@The inhibition of NF-kappaB is apparently permanent as DMDTC-treated T cells did not regain normal TNF-alpha activation, even after 72 h in culture.@@@@1@25@@oe@16-12-2010 971014908@GENIA Treebank@formal@@1@S@DMDTC does not appear to alter NF-kappaB directly as pre-incubation of nuclear extracts with DMDTC does not diminish binding activity of this protein.@@@@1@24@@oe@16-12-2010 971014909@GENIA Treebank@formal@@1@S@We further demonstrate that 0.1-0.5 microM DMDTC inhibits intracellular IL-2 production and decreases surface expression of CD25 (the alpha subunit of the IL-2 receptor) in T cells stimulated with phorbol ester.@@@@1@34@@oe@16-12-2010 971014910@GENIA Treebank@formal@@1@S@These data demonstrate that DMDTC is a potent immunosuppressive compound in vitro.@@@@1@13@@oe@16-12-2010 971021501@GENIA Treebank@formal@@1@S@A regulatory element in the CD95 (APO-1/Fas) ligand promoter is essential for responsiveness to TCR-mediated activation.@@@@1@19@@oe@16-12-2010 971021502@GENIA Treebank@formal@@1@S@Expression of the CD95 (APO-1/Fas) ligand (CD95L) in activated T cells is a major cause of T cell activation-induced apoptosis.@@@@1@25@@oe@16-12-2010 971021503@GENIA Treebank@formal@@1@S@To study the molecular mechanisms of transcriptional control of CD95L expression in T cells, we investigated the human CD95L promoter in Jurkat T cells.@@@@1@26@@oe@16-12-2010 971021504@GENIA Treebank@formal@@1@S@Deletion studies revealed that the CD95L proximal promoter sequence from -220 to the transcription start site is essential for T cell stimulation-induced expression of CD95L.@@@@1@26@@oe@16-12-2010 971021505@GENIA Treebank@formal@@1@S@In this study, we discovered a novel regulatory element located at -120 of the CD95L promoter which contains DNA binding sites for SP-1 and a yet unknown inducible factor.@@@@1@31@@oe@16-12-2010 971021506@GENIA Treebank@formal@@1@S@Mutation analysis demonstrated that binding of the inducible factor to the -120 region is crucial for the biological function of the CD95L promoter upon T cell stimulation.@@@@1@28@@oe@16-12-2010 971021507@GENIA Treebank@formal@@1@S@The DNA sequence at -120 also contains two DNA motifs homologous to the binding site for NF-AT.@@@@1@18@@oe@16-12-2010 971021508@GENIA Treebank@formal@@1@S@NF-AT does not directly bind to this element.@@@@1@9@@oe@16-12-2010 971021509@GENIA Treebank@formal@@1@S@However, cotransfection studies with an NF-AT expression vector showed that NF-AT may confer a strong inducible activity to the CD95L promoter at this regulatory region.@@@@1@27@@oe@16-12-2010 971021510@GENIA Treebank@formal@@1@S@Our data also show that the immunosuppressive agent cyclosporin A down-regulates CD95L transcription by inhibiting the function of this positive regulatory element.@@@@1@23@@oe@16-12-2010 971044801@GENIA Treebank@formal@@1@S@Highly polarized HLA class II antigen processing and presentation by human intestinal epithelial cells.@@@@1@15@@oe@16-12-2010 971044802@GENIA Treebank@formal@@1@S@The high concentration of foreign antigen in the lumen of the gastrointestinal tract is separated from the underlying lymphocytes by a single cell layer of polarized epithelium.@@@@1@28@@oe@16-12-2010 971044803@GENIA Treebank@formal@@1@S@Intestinal epithelial cells can express HLA class II antigens and may function as antigen-presenting cells to CD4(+) T cells within the intestinal mucosa.@@@@1@24@@oe@16-12-2010 971044804@GENIA Treebank@formal@@1@S@Using tetanus toxoid specific and HLA-DR-restricted T lymphocytes, we show that polarized intestinal epithelial cells directed to express HLA-DR molecules are able to initiate class II processing only after internalization of antigen from their apical surface.@@@@1@38@@oe@16-12-2010 971044805@GENIA Treebank@formal@@1@S@Coexpression of the class II transactivator CIITA in these cells, which stimulates highly efficient class II processing without the characteristic decline in barrier function seen in polarized monolayers treated with the proinflammatory cytokine gamma-IFN, facilitates antigen processing from the basolateral surface.@@@@1@44@@oe@16-12-2010 971044806@GENIA Treebank@formal@@1@S@In both cases, peptide presentation to T cells via class II molecules was restricted to the basolateral surface.@@@@1@20@@oe@16-12-2010 971044807@GENIA Treebank@formal@@1@S@These data indicate a highly polarized functional architecture for antigen processing and presentation by intestinal epithelial cells, and suggest that the functional outcome of antigen processing by the intestinal epithelium is both dependent on the cellular surface at which the foreign antigen is internalized and by the underlying degree of mucosal inflammation.@@@@1@54@@oe@16-12-2010 971058201@GENIA Treebank@formal@@1@S@The small GTP-binding protein Rho potentiates AP-1 transcription in T cells.@@@@1@12@@oe@16-12-2010 971058202@GENIA Treebank@formal@@1@S@The Rho family of small GTP-binding proteins is involved in the regulation of cytoskeletal structure, gene transcription, specific cell fate development, and transformation.@@@@1@27@@oe@16-12-2010 971058203@GENIA Treebank@formal@@1@S@We demonstrate in this report that overexpression of an activated form of Rho enhances AP-1 activity in Jurkat T cells in the presence of phorbol myristate acetate (PMA), but activated Rho (V14Rho) has little or no effect on NFAT, Oct-1, and NF-kappaB enhancer element activities under similar conditions.@@@@1@56@@oe@16-12-2010 971058204@GENIA Treebank@formal@@1@S@Overexpression of a V14Rho construct incapable of membrane localization (CAAX deleted) abolishes PMA-induced AP-1 transcriptional activation.@@@@1@19@@oe@16-12-2010 971058205@GENIA Treebank@formal@@1@S@The effect of Rho on AP-1 is independent of the mitogen-activated protein kinase pathway, as a dominant-negative MEK and a MEK inhibitor (PD98059) did not affect Rho-induced AP-1 activity.@@@@1@33@@oe@16-12-2010 971058206@GENIA Treebank@formal@@1@S@V14Rho binds strongly to protein kinase Calpha (PKCalpha) in vivo; however, deletion of the CAAX site on V14Rho severely diminished this association.@@@@1@27@@oe@16-12-2010 971058207@GENIA Treebank@formal@@1@S@Evidence for a role for PKCalpha as an effector of Rho was obtained by the observation that coexpression of the N-terminal domain of PKCalpha blocked the effects of activated Rho plus PMA on AP-1 transcriptional activity.@@@@1@37@@oe@16-12-2010 971058208@GENIA Treebank@formal@@1@S@These data suggest that Rho potentiates AP-1 transcription during T-cell activation.@@@@1@12@@oe@16-12-2010 971060001@GENIA Treebank@formal@@1@S@Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha (IKKalpha) and IKKbeta cellular kinases.@@@@1@25@@oe@16-12-2010 971060002@GENIA Treebank@formal@@1@S@Tax corresponds to a 40-kDa transforming protein from the pathogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) that activates nuclear expression of the NF-kappaB/Rel family of transcription factors by an unknown mechanism.@@@@1@36@@oe@16-12-2010 971060003@GENIA Treebank@formal@@1@S@Tax expression promotes N-terminal phosphorylation and degradation of IkappaB alpha, a principal cytoplasmic inhibitor of NF-kappaB.@@@@1@18@@oe@16-12-2010 971060004@GENIA Treebank@formal@@1@S@Our studies now demonstrate that HTLV-1 Tax activates the recently identified cellular kinases IkappaB kinase alpha (IKKalpha) and IKKbeta, which normally phosphorylate IkappaB alpha on both of its N-terminal regulatory serines in response to tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) stimulation.@@@@1@51@@oe@16-12-2010 971060005@GENIA Treebank@formal@@1@S@In contrast, a mutant of Tax termed M22, which does not induce NF-kappaB, fails to activate either IKKalpha or IKKbeta.@@@@1@24@@oe@16-12-2010 971060006@GENIA Treebank@formal@@1@S@Furthermore, endogenous IKK enzymatic activity was significantly elevated in HTLV-1-infected and Tax-expressing T-cell lines.@@@@1@16@@oe@16-12-2010 971060007@GENIA Treebank@formal@@1@S@Transfection of kinase-deficient mutants of IKKalpha and IKKbeta into either human Jurkat T or 293 cells also inhibits NF-kappaB-dependent reporter gene expression induced by Tax.@@@@1@26@@oe@16-12-2010 971060008@GENIA Treebank@formal@@1@S@Similarly, a kinase-deficient mutant of NIK (NF-kappaB-inducing kinase), which represents an upstream kinase in the TNF-alpha and IL-1 signaling pathways leading to IKKalpha and IKKbeta activation, blocks Tax induction of NF-kappaB.@@@@1@37@@oe@16-12-2010 971060009@GENIA Treebank@formal@@1@S@However, plasma membrane-proximal elements in these proinflammatory cytokine pathways are apparently not involved since dominant negative mutants of the TRAF2 and TRAF6 adaptors, which effectively block signaling through the cytoplasmic tails of the TNF-alpha and IL-1 receptors, respectively, do not inhibit Tax induction of NF-kappaB.@@@@1@50@@oe@16-12-2010 971060010@GENIA Treebank@formal@@1@S@Together, these studies demonstrate that HTLV-1 Tax exploits a distal part of the proinflammatory cytokine signaling cascade leading to induction of NF-kappaB.@@@@1@24@@oe@16-12-2010 971060011@GENIA Treebank@formal@@1@S@The pathological alteration of this cytokine pathway leading to NF-kappaB activation by Tax may play a central role in HTLV-1-mediated transformation of human T cells, clinically manifested as the adult T-cell leukemia.@@@@1@34@@oe@16-12-2010 971201901@GENIA Treebank@formal@@1@S@Class II transactivator-independent endothelial cell MHC class II gene activation induced by lymphocyte adhesion.@@@@1@15@@oe@16-12-2010 971201902@GENIA Treebank@formal@@1@S@NK cells induce MHC class II molecules on the surface of allogeneic endothelial cells in an adhesion-dependent, IFN-gamma-independent manner.@@@@1@21@@oe@16-12-2010 971201903@GENIA Treebank@formal@@1@S@Here, we demonstrate that NK cells induce HLA-DR on the surface of a mutant cell line that is defective in IFN-gamma-induced MHC class II expression.@@@@1@27@@oe@16-12-2010 971201904@GENIA Treebank@formal@@1@S@RNA analysis in these cells and in a cell line that is defective in class II transactivator (CIITA) demonstrates that NK cell-induced HLA-DR alpha mRNA expression is also CIITA-independent.@@@@1@32@@oe@16-12-2010 971201905@GENIA Treebank@formal@@1@S@The Janus kinase-1-deficient cell line U4A expresses HLA-DR alpha mRNA in response to NK cell activation, and HLA-DR alpha promoter constructs transfected into these cells are induced by NK cells but not IFN-gamma.@@@@1@35@@oe@16-12-2010 971201906@GENIA Treebank@formal@@1@S@These data indicate that the IFN-gamma-independent component of the target cell HLA-DR expression induced by lymphocyte adhesion uses a signaling pathway that is distinct from the IFN-gamma-dependent mechanism and also suggest that CIITA is not required.@@@@1@37@@oe@16-12-2010 971202601@GENIA Treebank@formal@@1@S@A CD28-associated signaling pathway leading to cytokine gene transcription and T cell proliferation without TCR engagement.@@@@1@17@@oe@16-12-2010 971202602@GENIA Treebank@formal@@1@S@Stimulation of resting human T cells with the CD28-specific mAb BW 828 induces proliferation and cytokine synthesis without further requirement for TCR coengagement.@@@@1@24@@oe@16-12-2010 971202603@GENIA Treebank@formal@@1@S@This observation prompted us to postulate that signal 2 (costimulatory signal) alone without signal 1 (TCR signal) can activate T cells.@@@@1@26@@oe@16-12-2010 971202604@GENIA Treebank@formal@@1@S@To test whether this putative function of CD28 is mediated via a particular signaling pathway, we compared early signaling events initiated in resting T cells by the stimulatory mAb BW 828 with signals triggered by the nonstimulating CD28 mAb 9.3.@@@@1@42@@oe@16-12-2010 971202605@GENIA Treebank@formal@@1@S@Stimulation of T cells with BW 828 induced an increase in intracellular Ca2+, but did not lead to detectable activation of the protein kinases p56(lck) and c-Raf-1.@@@@1@29@@oe@16-12-2010 971202606@GENIA Treebank@formal@@1@S@This pathway resulted in the induction of the transcription factors NF-kappa B, NF-AT, and proteins binding to the CD28 response element of the IL-2 promoter.@@@@1@28@@oe@16-12-2010 971202607@GENIA Treebank@formal@@1@S@On the other hand, stimulation of T cells with mAb 9.3 increased the level of intracellular Ca2+ and triggered the activation of p56(lck) and c-Raf-1, but was unable to induce the binding of transcription factors to the IL-2 promoter.@@@@1@42@@oe@16-12-2010 971202608@GENIA Treebank@formal@@1@S@In contrast to the differential signaling of BW 828 and 9.3 in resting T cells, the two mAbs exhibited a similar pattern of early signaling events in activated T cells and Jurkat cells (p56(lck) activation, association of phosphatidylinositol 3-kinase with CD28), indicating that the signaling capacity of CD28 changes with activation.@@@@1@57@@oe@16-12-2010 971202609@GENIA Treebank@formal@@1@S@These data support the view that stimulation through CD28 can induce some effector functions in T cells and suggest that this capacity is associated with a particular pattern of early signaling events.@@@@1@33@@oe@16-12-2010 971204701@GENIA Treebank@formal@@1@S@Cyclosporin A-resistant transactivation of the IL-2 promoter requires activity of okadaic acid-sensitive serine/threonine phosphatases.@@@@1@15@@oe@16-12-2010 971204702@GENIA Treebank@formal@@1@S@Expression of the IL-2 gene requires activation of T cells through stimulation of the TCR and costimulation through accessory receptors.@@@@1@21@@oe@16-12-2010 971204703@GENIA Treebank@formal@@1@S@We have found recently that okadaic acid-sensitive Ser/Thr phosphatases are involved in a cyclosporin A-insensitive pathway that selectively transmits costimulatory signals.@@@@1@22@@oe@16-12-2010 971204704@GENIA Treebank@formal@@1@S@In this study, we analyzed whether activities of these phosphatases are necessary for the expression of the IL-2 gene.@@@@1@21@@oe@16-12-2010 971204705@GENIA Treebank@formal@@1@S@In both activated peripheral blood T lymphocytes and activated tumorigenic T cell lines, IL-2 gene expression was blocked at the transcriptional level by okadaic acid.@@@@1@27@@oe@16-12-2010 971204706@GENIA Treebank@formal@@1@S@The transcription factors active at the IL-2 promoter were differentially influenced: upon down-modulation of okadaic acid-sensitive phosphatases, transactivation by octamer, NF-kappa B, and NF of activated T cells proteins was abrogated, while transactivation by AP-1 proteins was even enhanced.@@@@1@45@@oe@16-12-2010 971206801@GENIA Treebank@formal@@1@S@Inducible nitric oxide: an autoregulatory feedback inhibitor of vascular inflammation.@@@@1@12@@oe@16-12-2010 971206802@GENIA Treebank@formal@@1@S@Inducible nitric oxide (iNO) is produced at sites of vascular inflammation by resident and nonresident vascular wall cells, but its role in the inflammatory process is not known.@@@@1@32@@oe@16-12-2010 971206803@GENIA Treebank@formal@@1@S@In this study, we show that a novel function of iNO is to terminate inflammatory processes.@@@@1@18@@oe@16-12-2010 971206804@GENIA Treebank@formal@@1@S@We find that iNO produced by murine macrophage-like cells, RAW264.7, can inhibit cytokine-induced endothelial cell activation in a separated and mixed endothelial-RAW264.7 coculture system.@@@@1@27@@oe@16-12-2010 971206805@GENIA Treebank@formal@@1@S@Both iNO production and endothelial VCAM-1 expression were induced simultaneously with bacterial LPS and murine-specific IFN-gamma.@@@@1@17@@oe@16-12-2010 971206806@GENIA Treebank@formal@@1@S@Inhibition of iNO synthase (iNOS) activity with N omega-monomethyl-L-arginine in endothelial-RAW264.7 cocultures, stimulated with murine-specific IFN-gamma and LPS, decreased iNO production by 86%, augmented VCAM-1 and iNOS expression in endothelial and RAW264.7 cells, respectively, and increased monocyte adhesion to the endothelial cell surface.@@@@1@52@@oe@16-12-2010 971206807@GENIA Treebank@formal@@1@S@Transient transfection studies using various VCAM-1 promoter constructs demonstrated that inhibitory effects of iNO on VCAM-1 gene transcription were mediated, in part, by inhibitory effects of iNO on kappa B cis-acting elements.@@@@1@35@@oe@16-12-2010 971206808@GENIA Treebank@formal@@1@S@Immunofluorescence studies using an Ab to the RelA (p65) subunit of nuclear factor-kappa B revealed that iNO inhibited the activation of nuclear factor-kappa B.@@@@1@27@@oe@16-12-2010 971206809@GENIA Treebank@formal@@1@S@These studies indicate that iNO attenuates iNOS expression in macrophages and inhibits monocyte adhesion to endothelial cells, and suggest that endogenously derived iNO may be an important autoregulatory inhibitor of vascular inflammation.@@@@1@34@@oe@16-12-2010 971270301@GENIA Treebank@formal@@1@S@The peroxisome proliferator-activated receptor alpha (PPARalpha) ligand WY 14,643 does not interfere with leukotriene B4 induced adhesion of neutrophils to endothelial cells.@@@@1@25@@oe@16-12-2010 971270302@GENIA Treebank@formal@@1@S@Peroxisome proliferator-activated receptors (PPAR) control discrete genes involved in fatty acid and lipid metabolism.@@@@1@17@@oe@16-12-2010 971270303@GENIA Treebank@formal@@1@S@Recently, it was suggested that activation of the alpha isoform of PPAR by the potent proinflammatory mediator leukotriene B4 (LTB4) enhanced degradation of this eicosanoid, offersuggesting a new aspect of down-regulation of inflammation.@@@@1@38@@oe@16-12-2010 971270304@GENIA Treebank@formal@@1@S@Here, we studied whether PPARalpha activation (by means of the selective agonist WY 14,643) of endothelial cells, pivotal in the regulation of inflammatory responses, interfered with LTB4 induced adhesion of PMN neutrophil granulocytes in vitro.@@@@1@41@@oe@16-12-2010 971270305@GENIA Treebank@formal@@1@S@When endothelial cells were treated with WY 14,643 prior to activation with LTB4 (or fMLP, IL-1beta or TNFalpha, as controls) we could not document any effect on the number of adhering PMN or duration of the response.@@@@1@42@@oe@16-12-2010 971270306@GENIA Treebank@formal@@1@S@Thus, this study provides no evidence indicating a regulatory function of PPARalpha in LTB4 induced adhesive interactions between endothelial cells and neutrophils.@@@@1@24@@oe@16-12-2010 971272101@GENIA Treebank@formal@@1@S@Stimulation of B and T cells activates expression of transcription and differentiation factors.@@@@1@14@@oe@16-12-2010 971272102@GENIA Treebank@formal@@1@S@During B and T cell differentiation and proliferation many genes are induced or repressed while certain genes are constitutively expressed.@@@@1@21@@oe@16-12-2010 971272103@GENIA Treebank@formal@@1@S@To investigate processes related to B and T cell activation, the gene expression of stimulated and nonstimulated Ramos and Jurkat cells was studied using cDNA microarray technology.@@@@1@29@@oe@16-12-2010 971272104@GENIA Treebank@formal@@1@S@Simultaneous analysis of close to 600 genes indicated highest increase in the expression of certain transcription, differentiation and proliferation factors.@@@@1@22@@oe@16-12-2010 971272105@GENIA Treebank@formal@@1@S@Many of these genes have not previously been shown to funcion in the stimulated lymphocytes.@@@@1@16@@oe@16-12-2010 971272106@GENIA Treebank@formal@@1@S@Also genes encoding proteins involved in DNA replication, binding, transcription and translation were induced.@@@@1@17@@oe@16-12-2010 971272107@GENIA Treebank@formal@@1@S@Large part of the activated genes were under very stringent regulation being expressed only after stimulation.@@@@1@17@@oe@16-12-2010 971272108@GENIA Treebank@formal@@1@S@The mechanism and function of the expressed genes during lymphocyte differentiation and in disorders is discussed.@@@@1@17@@oe@16-12-2010 971526501@GENIA Treebank@formal@@1@S@Characterization of cytokine differential induction of STAT complexes in primary human T and NK cells.@@@@1@16@@oe@16-12-2010 971526502@GENIA Treebank@formal@@1@S@Cytokines, IL-2, IL-4, IL-6, IL-7, IL-12, and IL-15 are key regulators of human peripheral blood T and NK cell activation and differentiation but the precise mechanisms that give rise to their differential activities within these cells are not clear.@@@@1@46@@oe@16-12-2010 971526503@GENIA Treebank@formal@@1@S@Recent studies reveal that a family of transcription factors, signal transducers and activators of transcription (STATs) directly mediate many cytokine signals.@@@@1@25@@oe@16-12-2010 971526504@GENIA Treebank@formal@@1@S@We analyzed the activation of STATs in primary human T and NK cells by a variety of specific cytokines.@@@@1@20@@oe@16-12-2010 971526505@GENIA Treebank@formal@@1@S@We demonstrate that IL-12 induces STAT4 only in freshly isolated primary NK cells, but not in primary T cells, consistent with the lack of the IL-12 receptor in resting T cells.@@@@1@34@@oe@16-12-2010 971526506@GENIA Treebank@formal@@1@S@In contrast, IL-4 induces different C epsilon GAS DNA-protein binding complexes in both T and NK cells.@@@@1@19@@oe@16-12-2010 971526507@GENIA Treebank@formal@@1@S@Moreover, IL-4 costimulation with IL-2 or IL-12 does not alter their own preferential GAS-like DNA binding patterns when C epsilon-, Fc gamma RI-, and SIE GAS motif containing oligonucleotide probes are compared, suggesting that induction of GAS-like DNA-protein binding complexes by IL-2, IL-4, and IL-12 is highly selective and represents one important factor in determining specific gene activation.@@@@1@65@@oe@16-12-2010 971526508@GENIA Treebank@formal@@1@S@In addition, IL-6 and IL-2 synergistically induce homo- and heterodimerized STAT1 alpha and STAT3 in both NK and T cells, consistent with their reported synergism in modulating perforin gene expression.@@@@1@33@@oe@16-12-2010 971526509@GENIA Treebank@formal@@1@S@We further demonstrated that IL-2, -7, and -15 induce multiple STAT proteins, including STAT5a, STAT5b, STAT1 alpha, STAT3, and another unidentified Fc gamma RI GAS DNA-binding protein.@@@@1@35@@oe@16-12-2010 971526510@GENIA Treebank@formal@@1@S@Finally, we observed that activated STAT5a and STAT5b proteins form distinct Fc gamma RI GAS binding patterns in T and NK cells, suggesting that they might have different roles in gene regulation.@@@@1@35@@oe@16-12-2010 971526511@GENIA Treebank@formal@@1@S@Our data provide evidence that the differential responses in gene expression and cell activation seen in primary NK and T cells on direct stimulation with different cytokines may be a direct result of distinct activation of STAT transcription factors.@@@@1@40@@oe@16-12-2010 971583801@GENIA Treebank@formal@@1@S@Inhibition of HIV-1 replication by combination of a novel inhibitor of TNF-alpha with AZT.@@@@1@15@@oe@16-12-2010 971583802@GENIA Treebank@formal@@1@S@The small molecule S9a was derived from an established tumor necrosis factor-alpha (TNF-alpha) inhibitor (Canventol) by replacement of the isopropylidine group with a phenyl ring.@@@@1@30@@oe@16-12-2010 971583803@GENIA Treebank@formal@@1@S@S9a at 10 to 100 nM inhibited HIV production as potently as 3'-azido-3'-deoxythymidine (AZT), an inhibitor of viral reverse transcriptase.@@@@1@24@@oe@16-12-2010 971583804@GENIA Treebank@formal@@1@S@Furthermore, S9a and AZT in combination, at noncytoxic concentrations strongly inhibited HIV-1 replication that was more than additive and substantially prolonged the appearance of virus both in acutely infected CD4+ lymphocytes (SupT) in culture and in peripheral blood mononuclear cells (PBMCs) infected with a primary HIV-1 isolate.@@@@1@54@@oe@16-12-2010 971583805@GENIA Treebank@formal@@1@S@S9a inhibited TNF-alpha promoter-driven reporter gene activity.@@@@1@8@@oe@16-12-2010 971583806@GENIA Treebank@formal@@1@S@It was proposed that the mechanism of antiviral action of S9a was on the host cell, by blocking TNF-alpha transcription via a Tat-induced tar-independent loop, which decreases downstream NF-kappaB activation of HIV-1 long terminal repeat (LTR).@@@@1@41@@oe@16-12-2010 971583807@GENIA Treebank@formal@@1@S@S9a was superior to the first generation compound Canventol, which was superior to the natural compound sarcophytol A, demonstrating that further structure-based enhancement of potency of these compounds is feasible.@@@@1@33@@oe@16-12-2010 971583808@GENIA Treebank@formal@@1@S@This study suggests a therapeutic approach against AIDS by application of two drugs, one against a cellular and the other a viral target, which may provide an approach to the problem of frequent emergence of resistant variants to combinations of drugs that target only HIV genes.@@@@1@49@@oe@16-12-2010 971596601@GENIA Treebank@formal@@1@S@Specific glucocorticoid binding at different levels of human motor activity.@@@@1@11@@oe@16-12-2010 971596602@GENIA Treebank@formal@@1@S@We studied the number of glucocorticoid receptors and dissociation constant in isolated human lymphocytes as well as blood concentrations of hormones produced by the hypothalamic-hypophyseal-adrenocortical system in three experimental series: at normal (17 subjects), decreased (10 subjects, a 360-d head-down bed rest) and increased (8 subjects, physical exercise on bicycle ergometer) levels of motor activity.@@@@1@66@@oe@16-12-2010 971596603@GENIA Treebank@formal@@1@S@In the first series we found that the number of glucocorticoid receptors and dissociation constant did not depend on the season, on the age of subjects nor on cortisol concentrations in blood.@@@@1@34@@oe@16-12-2010 971596604@GENIA Treebank@formal@@1@S@In the second series we observed the following: at the end of the first month of bed rest the number of glucocorticoid receptors and receptor affinity significantly increased; at the beginning of the third month of bed rest specific glucocorticoid binding significantly decreased and circadian rhythms of adrenocorticotropin and cortisol in blood varied markedly; at the end of the sixth month of bed rest the number of glucocorticoid receptors returned to prebed rest levels and dissociation constant decreased.@@@@1@82@@oe@16-12-2010 971596605@GENIA Treebank@formal@@1@S@In the third series physical exercises that induced an activation of the hypothalamic-hypophyseal-adrenocortical system (maximal physical exercises and prolonged submaximal exercises at 70% of maximal oxygen uptake) led to a significant increase in the number of glucocorticoid receptors without changes of dissociation constant.@@@@1@47@@oe@16-12-2010 971596606@GENIA Treebank@formal@@1@S@These results indicate that both a decrease and an increase of human motor activity resulted in significant changes of specific glucocorticoid binding which were not influenced by changes of circulating hormone concentrations in blood but by some other factors affected by physical activity.@@@@1@44@@oe@16-12-2010 971660001@GENIA Treebank@formal@@1@S@Retinoic acid inhibits CD40 + interleukin-4-mediated IgE production in vitro.@@@@1@11@@oe@16-12-2010 971660002@GENIA Treebank@formal@@1@S@To elucidate the role of retinoic acid (RA) in anti-CD40 + interleukin-4 (IL-4)-mediated B-cell activation, the effect of 10(-12) to 10(-6) mol/L RA was studied in anti-CD40 (1 microgram/mL) + IL-4 (5 ng/mL)-mediated proliferation and Ig synthesis by human peripheral blood mononuclear cells (PBMC) and B cells in healthy donors.@@@@1@64@@oe@16-12-2010 971660003@GENIA Treebank@formal@@1@S@Anti-CD40 + IL-4-mediated proliferation of PBMC and B cells was inhibited by RA in a dose-dependent manner, with maximal inhibition of 62% +/- 5% in PBMC and 55% +/- 4.4% in B cells by all-trans RA, and 58% +/- 6.7% and 51% +/- 4.7%, respectively by 13-cis RA.@@@@1@60@@oe@16-12-2010 971660004@GENIA Treebank@formal@@1@S@IgE synthesis was even more markedly inhibited by RA starting at concentrations of >10(-14) mol/L for B cells and >10(-10) mol/L for PBMC.@@@@1@26@@oe@16-12-2010 971660005@GENIA Treebank@formal@@1@S@Maximal inhibition of IgE production for B cells was at 10(-8) mol/L for all-trans RA (94% +/- 1.8%) and 96% +/- 3.2% for 13-cis RA.@@@@1@32@@oe@16-12-2010 971660006@GENIA Treebank@formal@@1@S@Low concentrations of RA inhibiting IgE synthesis (10(-10) mol/L) affected neither B-cell proliferation nor the production of IgA, IgG, and IgM.@@@@1@26@@oe@16-12-2010 971660007@GENIA Treebank@formal@@1@S@Elucidation of the mechanism involved in this inhibition of IgE production shows that epsilon germline transcription is decreased by RA, whereas production of interferon-gamma (IFN-gamma) was not enhanced in the presence of RA.@@@@1@37@@oe@16-12-2010 971660008@GENIA Treebank@formal@@1@S@To differentiate whether the RA effect was mediated by RA receptors alpha, beta, and gamma, the expression of the retinoic acid receptors (RAR) was examined by reverse transcriptase-polymerase chain reaction (RT-PCR).@@@@1@39@@oe@16-12-2010 971660009@GENIA Treebank@formal@@1@S@The data show that unstimulated human peripheral B cells express mRNA of the RA receptor alpha, beta, and gamma.@@@@1@22@@oe@16-12-2010 971660010@GENIA Treebank@formal@@1@S@Using retinoids with different receptor binding specificity (CD336, CD437, CD2019, CD367), dose-dependent inhibition of IgE synthesis was shown by all four derivates, but was most marked by an RA binding the alpha receptor with high specificity.@@@@1@44@@oe@16-12-2010 971660011@GENIA Treebank@formal@@1@S@Taken together, this study shows that RA inhibits IgE production of anti-CD40 + IL-4-stimulated B cells in vitro.@@@@1@20@@oe@16-12-2010 971660012@GENIA Treebank@formal@@1@S@Copyright 1998 by The American Society of Hematology.@@@@1@9@@oe@16-12-2010