911627901@GENIA Treebank@formal@@1@S@Lineage- and stage-specific expression of runt box polypeptides in primitive and definitive hematopoiesis.@@@@1@14@@oe@16-12-2010 911627902@GENIA Treebank@formal@@1@S@Translocations involving the human CBFA2 locus have been associated with leukemia.@@@@1@12@@oe@16-12-2010 911627903@GENIA Treebank@formal@@1@S@This gene, originally named AML1, is a human homologue of the Drosophila gene runt that controls early events in fly embryogenesis.@@@@1@24@@oe@16-12-2010 911627904@GENIA Treebank@formal@@1@S@To clarify the role of mammalian runt products in normal and leukemic hematopoiesis, we have studied their pattern of expression in mouse hematopoietic tissues in the adult and during ontogeny using an anti-runt box antiserum.@@@@1@37@@oe@16-12-2010 911627905@GENIA Treebank@formal@@1@S@In the adult bone marrow, we found expression of runt polypeptides in differentiating myeloid cells and in B lymphocytes.@@@@1@21@@oe@16-12-2010 911627906@GENIA Treebank@formal@@1@S@Within the erythroid lineage, runt expression is biphasic, clearly present in the erythroblasts of early blood islands and of the fetal liver, but absent in the adult.@@@@1@31@@oe@16-12-2010 911627907@GENIA Treebank@formal@@1@S@Biochemical analysis by Western blotting of fetal and adult hematopoietic populations shows several runt isoforms.@@@@1@16@@oe@16-12-2010 911627908@GENIA Treebank@formal@@1@S@At least one of them appears to be myeloid specific.@@@@1@11@@oe@16-12-2010 911902501@GENIA Treebank@formal@@1@S@Cell-to-cell contact activates the long terminal repeat of human immunodeficiency virus 1 through its kappaB motif.@@@@1@17@@oe@16-12-2010 911902502@GENIA Treebank@formal@@1@S@Cell-to-cell contact between peripheral blood lymphocytes and transfected human colonic carcinoma cell line HT29 activates transcription of the long terminal repeats (LTR) of human immunodeficiency virus.@@@@1@29@@oe@16-12-2010 911902503@GENIA Treebank@formal@@1@S@HIV-1 LTR transcription is controlled by a complex array of virus-encoded and cellular proteins.@@@@1@15@@oe@16-12-2010 911902504@GENIA Treebank@formal@@1@S@Using various constructs expressing a lacZ reporter gene under the control of the intact or three deleted forms of HIV-1 LTR, we obtained evidence that the kappaB regulatory elements located in the U3 region are involved in cell-to-cell activation of HIV-1 LTR.@@@@1@44@@oe@16-12-2010 911902505@GENIA Treebank@formal@@1@S@Cell-to-cell contact activates in vitro binding of the nuclear factor kappaB (NF-kappaB) p50/p65 heterodimer to an HIV-1 kappaB oligonucleotide.@@@@1@22@@oe@16-12-2010 911902506@GENIA Treebank@formal@@1@S@Cell-to-cell contact activation of NF-kappaB was only partially inhibited by 100 microM pyrrolidine dithiocarbamate and was not correlated with a significant decrease of cellular inhibitor kappaB alpha.@@@@1@28@@oe@16-12-2010 911902507@GENIA Treebank@formal@@1@S@NF-kappaB nuclear activation was not detectable before 1 h after cell contact and was dependent on protein synthesis.@@@@1@19@@oe@16-12-2010 911922801@GENIA Treebank@formal@@1@S@ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function.@@@@1@17@@oe@16-12-2010 911922802@GENIA Treebank@formal@@1@S@LEF-1 is a transcription factor that participates in the regulation of the T-cell receptor alpha (TCR alpha) enhancer by facilitating the assembly of multiple proteins into a higher order nucleoprotein complex.@@@@1@34@@oe@16-12-2010 911922803@GENIA Treebank@formal@@1@S@The function of LEF-1 is dependent, in part, on the HMG domain that induces a sharp bend in the DNA helix, and on an activation domain that stimulates transcription only in a specific context of other enhancer-binding proteins.@@@@1@42@@oe@16-12-2010 911922804@GENIA Treebank@formal@@1@S@With the aim of gaining insight into the function of context-dependent activation domains, we cloned ALY, a novel LEF-1-interacting protein.@@@@1@23@@oe@16-12-2010 911922805@GENIA Treebank@formal@@1@S@ALY is a ubiquitously expressed, nuclear protein that specifically associates with the activation domains of LEF-1 and AML-1 (CBF alpha2, PEBP2 alpha(B), which is another protein component of the TCR alpha enhancer complex.@@@@1@41@@oe@16-12-2010 911922806@GENIA Treebank@formal@@1@S@In addition, ALY can increase DNA binding by both LEF-1 and AML proteins.@@@@1@15@@oe@16-12-2010 911922807@GENIA Treebank@formal@@1@S@Overexpression of ALY stimulates the activity of the TCR alpha enhancer complex reconstituted in transfected nonlymphoid HeLa cells, whereas down-regulation of ALY by anti-sense oligonucleotides virtually eliminates TCR alpha enhancer activity in T cells.@@@@1@36@@oe@16-12-2010 911922808@GENIA Treebank@formal@@1@S@Similar to LEF-1, ALY can stimulate transcription in the context of the TCR alpha enhancer but apparently not when tethered to DNA through an heterologous DNA-binding domain.@@@@1@29@@oe@16-12-2010 911922809@GENIA Treebank@formal@@1@S@We propose that ALY mediates context-dependent transcriptional activation by facilitating the functional collaboration of multiple proteins in the TCR alpha enhancer complex.@@@@1@23@@oe@16-12-2010 911999901@GENIA Treebank@formal@@1@S@HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28.@@@@1@13@@oe@16-12-2010 911999902@GENIA Treebank@formal@@1@S@In this report, we demonstrate that the T cell tropic strain of HIV, LAI, does not replicate in naive CD4 T cells stimulated by cross-linking CD3 and CD28.@@@@1@32@@oe@16-12-2010 911999903@GENIA Treebank@formal@@1@S@In contrast, LAI replicates well in memory CD4 T cells stimulated in the same way.@@@@1@17@@oe@16-12-2010 911999904@GENIA Treebank@formal@@1@S@Unlike this physiologically relevant stimulation, PHA stimulates productive LAI replication in both naive and memory T cells.@@@@1@19@@oe@16-12-2010 911999905@GENIA Treebank@formal@@1@S@These studies were conducted with highly purified (FACS-isolated) subsets of CD4 T cells identified by expression of both CD45RA and CD62L.@@@@1@24@@oe@16-12-2010 911999906@GENIA Treebank@formal@@1@S@Remixing of purified T cells showed that naive T cells do not suppress LAI replication in memory T cells and that memory T cells do not restore LAI expression in naive T cells.@@@@1@34@@oe@16-12-2010 911999907@GENIA Treebank@formal@@1@S@The suppression of productive LAI replication in naive T cells is not due to differential expression of viral coreceptors, nor is it due to inhibition of activation of the important HIV transcription factors, nuclear factor-kappaB and activator protein-1.@@@@1@41@@oe@16-12-2010 911999908@GENIA Treebank@formal@@1@S@The inherent resistance of naive T cells to productive HIV infection, coupled with their proliferative advantage as demonstrated here, provides a sound basis for proposed clinical therapies using ex vivo expansion and reinfusion of CD4 T cells from HIV-infected adults.@@@@1@43@@oe@16-12-2010 912031001@GENIA Treebank@formal@@1@S@Nuclear factor-kappa B potently up-regulates the promoter activity of RANTES, a chemokine that blocks HIV infection.@@@@1@18@@oe@16-12-2010 912031002@GENIA Treebank@formal@@1@S@The complex network of cytokines that are involved in inflammatory and immunoregulatory responses plays a critical role in the pathogenesis of HIV infection.@@@@1@24@@oe@16-12-2010 912031003@GENIA Treebank@formal@@1@S@RANTES (regulated upon activation, normal T cell expressed and secreted) is a cytokine that belongs to the beta-chemokine family; it is chemoattractant for CD4+/CD45RO T cells, it is produced by various cell types including CD8+ and CD4+ T cells as well as monocytes/macrophages, and has recently been shown to suppress replication of macrophage-tropic strains of HIV in CD4+ T cells.@@@@1@67@@oe@16-12-2010 912031004@GENIA Treebank@formal@@1@S@To investigate the molecular mechanisms of RANTES expression, the RANTES promoter region was analyzed by transient expression and gel-mobility shift assays.@@@@1@23@@oe@16-12-2010 912031005@GENIA Treebank@formal@@1@S@We demonstrate that: 1) RANTES promoter activity is up-regulated by PMA plus ionomycin, coexpression of the p65 subunit of nuclear factor (NF)-kappa B, the proinflammatory cytokines TNF-alpha and IL-1 beta, and the CD28 costimulatory pathway; 2) the RANTES promoter region contains four NF-kappa B binding sites at positions -30, -44, -213, and -579 relative to the transcription start site; 3) one site (-213) is an NF-AT (nuclear factor of activated T cells) binding site that also has weak affinity to NF-kappa B, and the most distal site (-579) also serves as a CD28-responsive element; and 4) mutation on any of those NF-kappa B sites or coexpression of I kappa B alpha (cytoplasmic inhibitor of NF-kappa B) markedly reduced the promoter activity.@@@@1@148@@oe@16-12-2010 912031006@GENIA Treebank@formal@@1@S@Thus, NF-kappa B, a potent transcriptional activator of HIV expression, is also involved in the expression of RANTES, a chemokine that blocks infection by macrophage-tropic strains of HIV.@@@@1@33@@oe@16-12-2010 912038801@GENIA Treebank@formal@@1@S@Selective expression of an interleukin-12 receptor component by human T helper 1 cells.@@@@1@14@@oe@16-12-2010 912038802@GENIA Treebank@formal@@1@S@Interleukin-12 (IL-12), a heterodimeric cytokine produced by activated monocytes and dendritic cells, plays a crucial role in regulating interferon (IFN)-gamma production and in the generation of IFN-gamma-producing T helper 1 (Th1) cells.@@@@1@42@@oe@16-12-2010 912038803@GENIA Treebank@formal@@1@S@Here we show that the IL-12 receptor (IL-12R) beta 2 subunit, a recently cloned binding and signal transducing component of the IL-12R, is expressed on human Th1 but not Th2 clones and is induced during differentiation of human naive cells along the Th1 but not the Th2 pathway.@@@@1@53@@oe@16-12-2010 912038804@GENIA Treebank@formal@@1@S@IL-12 and type I but not type II interferons induce expression of the IL-12R beta 2 chain during in vitro T cell differentiation after antigen receptor triggering.@@@@1@28@@oe@16-12-2010 912038805@GENIA Treebank@formal@@1@S@The selective expression and regulation of the IL-12R beta 2 subunit may help to understand the basis of Th1/Th2 differentiation and may provide therapeutic options for altering the Th1/Th2 balance in several immuno-pathological conditions such as autoimmune diseases and allergies.@@@@1@41@@oe@16-12-2010 912145501@GENIA Treebank@formal@@1@S@Control of NFATx1 nuclear translocation by a calcineurin-regulated inhibitory domain.@@@@1@11@@oe@16-12-2010 912145502@GENIA Treebank@formal@@1@S@The nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of several cytokine genes.@@@@1@29@@oe@16-12-2010 912145503@GENIA Treebank@formal@@1@S@NFATx1, which is preferentially expressed in the thymus and peripheral blood leukocytes, is one of four members of the NFAT family of transcription factors.@@@@1@27@@oe@16-12-2010 912145504@GENIA Treebank@formal@@1@S@We have performed domain analysis of NFATx1 by examining the effects of deletion mutations.@@@@1@15@@oe@16-12-2010 912145505@GENIA Treebank@formal@@1@S@We found that NFATx1 DNA binding activity and interaction with AP-1 polypeptides were dependent on its central Rel similarity region and that transcriptional activation was reduced by deletions of either its N-terminal domain or its C-terminal domain, suggesting the presence of intrinsic transcriptional activation motifs in both regions.@@@@1@50@@oe@16-12-2010 912145506@GENIA Treebank@formal@@1@S@We also identified a potent inhibitory sequence within its N-terminal domain.@@@@1@12@@oe@16-12-2010 912145507@GENIA Treebank@formal@@1@S@We show that the inactivation of the inhibition was dependent on the activity of calcineurin, a calcium-calmodulin-dependent phosphatase.@@@@1@20@@oe@16-12-2010 912145508@GENIA Treebank@formal@@1@S@We also show that calcineurin associated with the N-terminal domain of NFATx1 at multiple docking sites and caused a reduction of size, indicative of dephosphorylation, in NFATx1.@@@@1@30@@oe@16-12-2010 912145509@GENIA Treebank@formal@@1@S@We have mapped the inhibitory activity to less than 60 residues, containing motifs that are conserved in all NFAT proteins.@@@@1@22@@oe@16-12-2010 912145510@GENIA Treebank@formal@@1@S@Finally, we demonstrate that deletion in NFATx1 of the mapped 60 residues leads to its nuclear translocation independent of calcium signaling.@@@@1@23@@oe@16-12-2010 912145511@GENIA Treebank@formal@@1@S@Our results support the model proposing that the N-terminal domain confers calcium-signaling dependence on NFATx1 transactivation activity by regulating its intracellular localization through a protein module that associates with calcineurin and is a target of its phosphatase activity.@@@@1@39@@oe@16-12-2010 912223301@GENIA Treebank@formal@@1@S@A PMLRARalpha transgene initiates murine acute promyelocytic leukemia.@@@@1@9@@oe@16-12-2010 912223302@GENIA Treebank@formal@@1@S@The malignant cells of acute promyelocytic leukemia (APL) contain a reciprocal chromosomal translocation that fuses the promyelocytic leukemia gene (PML) with the retinoic acid receptor alpha gene (RAR alpha).@@@@1@36@@oe@16-12-2010 912223303@GENIA Treebank@formal@@1@S@To test the hypothesis that the chimera PMLRAR alpha plays a role in leukemogenesis, we expressed a PMLRAR alpha cDNA in myeloid cells of transgenic mice.@@@@1@28@@oe@16-12-2010 912223304@GENIA Treebank@formal@@1@S@PMLRAR alpha transgenic mice exhibited impaired neutrophil maturation early in life, which progressed at a low frequency over the course of several months to overt APL.@@@@1@28@@oe@16-12-2010 912223305@GENIA Treebank@formal@@1@S@Both the preleukemic state and the leukemia could be transplanted to nontransgenic mice, and the transplanted preleukemia could progress to APL.@@@@1@23@@oe@16-12-2010 912223306@GENIA Treebank@formal@@1@S@The APL recapitulated features of the human disease, including a response to retinoic acid.@@@@1@16@@oe@16-12-2010 912223307@GENIA Treebank@formal@@1@S@Retinoic acid caused the leukemic cells to differentiate in vitro and in vivo, eliciting remissions of both the preleukemic state and APL in mice.@@@@1@26@@oe@16-12-2010 912223308@GENIA Treebank@formal@@1@S@Our results demonstrate that PMLRAR alpha impairs neutrophil differentiation and initiates the development of APL.@@@@1@16@@oe@16-12-2010 912223309@GENIA Treebank@formal@@1@S@The transgenic mice described here provide an apparently accurate model for human APL that includes clear evidence of tumor progression.@@@@1@21@@oe@16-12-2010 912223310@GENIA Treebank@formal@@1@S@The model should be useful for exploring the molecular pathogenesis of APL and the mechanisms of the therapeutic response to retinoic acid, as well as for preclinical studies of therapeutic regimens.@@@@1@33@@oe@16-12-2010 912224301@GENIA Treebank@formal@@1@S@Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3-mediated survival of pro-B lymphocytes.@@@@1@15@@oe@16-12-2010 912224302@GENIA Treebank@formal@@1@S@The E2A-HLF (hepatic leukemia factor) oncoprotein, generated in pro-B lymphocytes by fusion of the trans-activation domain of E2A to the basic region/leucine zipper (bZIP) domain of HLF, functions as an anti-apoptotic transcription factor in leukemic cell transformation.@@@@1@44@@oe@16-12-2010 912224303@GENIA Treebank@formal@@1@S@When introduced into interleukin 3 (IL-3)-dependent mouse pro-B lymphocytes, E2A-HLF prevents apoptosis induced by growth factor deprivation, suggesting that IL-3 mediates cell survival through activation of a transcription factor whose activity can be constitutively replaced by the chimeric oncoprotein.@@@@1@45@@oe@16-12-2010 912224304@GENIA Treebank@formal@@1@S@We considered four bZIP transcription factors as candidates for this putative IL-3-regulated factor, each of which binds avidly to the DNA consensus sequence recognized by E2A-HLF and is related to the Caenorhabditis elegans CES-2 (cell death specification protein) neuron-specific mediator of cell death.@@@@1@47@@oe@16-12-2010 912224305@GENIA Treebank@formal@@1@S@The expression and binding activity of the Nfil3 protein (also called E4bp4), but not of Hlf, Dbp, or Tef, was found to be regulated by IL-3 in mouse pro-B cell lines (Baf-3 and FL5.12).@@@@1@43@@oe@16-12-2010 912224306@GENIA Treebank@formal@@1@S@Northern blot analysis showed that Nfil3/E4bp4 is regulated as a "delayed-early" IL-3-responsive gene, requiring de novo protein synthesis.@@@@1@22@@oe@16-12-2010 912224307@GENIA Treebank@formal@@1@S@In the absence of IL-3, enforced expression of the human NFIL3/E4BP4 cDNA promoted the survival but not the growth of IL-3-dependent pro-B cells.@@@@1@25@@oe@16-12-2010 912224308@GENIA Treebank@formal@@1@S@Our results implicate NFIL3/E4BP4 (nuclear factor regulated by IL-3/adenovirus E4 promoter binding protein) in a distinct growth factor-regulated signaling pathway that is responsible for the survival of early B-cell progenitors, and whose alteration by E2A-HLF leads to childhood B lineage leukemia.@@@@1@45@@oe@16-12-2010 912225501@GENIA Treebank@formal@@1@S@Neuronal (type I) nitric oxide synthase regulates nuclear factor kappaB activity and immunologic (type II) nitric oxide synthase expression.@@@@1@24@@oe@16-12-2010 912225502@GENIA Treebank@formal@@1@S@Nitric oxide subserves diverse physiologic roles in the nervous system.@@@@1@11@@oe@16-12-2010 912225503@GENIA Treebank@formal@@1@S@NO is produced from at least three different NO synthase (NOS) isoforms: neuronal NOS (nNOS), endothelial NOS, and immunologic NOS (iNOS).@@@@1@31@@oe@16-12-2010 912225504@GENIA Treebank@formal@@1@S@We show that nNOS is the predominant isoform constitutively expressed in glia.@@@@1@13@@oe@16-12-2010 912225505@GENIA Treebank@formal@@1@S@NO derived from nNOS in glia inhibits the transcription factor nuclear factor kappaB (NF kappaB) as NOS inhibitors enhance basal NF kappaB activation.@@@@1@26@@oe@16-12-2010 912225506@GENIA Treebank@formal@@1@S@Pyrrolidine dithiocarbamate (PDTC) is an inhibitor of NF kappaB in most cells; however, we show that PDTC is also a potent scavenger of NO through formation of mononitrosyl iron complexes with PDTC.@@@@1@37@@oe@16-12-2010 912225507@GENIA Treebank@formal@@1@S@In Jurkat cells, a human T-cell lymphoma cell line, tumor necrosis factor-alpha (TNF-alpha) induces NF kappaB activation that is inhibited by PDTC.@@@@1@27@@oe@16-12-2010 912225508@GENIA Treebank@formal@@1@S@Contrary to the results in Jurkat cells, PDTC did not inhibit tumor necrosis factor-alpha-induced NF kappaB activation in astrocytes; instead PDTC itself induces NF kappaB activation in astrocytes, and this may be related to scavenging of endogenously produced NO by the PDTC iron complex.@@@@1@48@@oe@16-12-2010 912225509@GENIA Treebank@formal@@1@S@In astrocytes PDTC also dramatically induces the NF kappaB-dependent enzyme, iNOS, supporting the physiologic relevance of endogenous NO regulation of NF kappaB.@@@@1@26@@oe@16-12-2010 912225510@GENIA Treebank@formal@@1@S@NF kappaB activation in glia from mice lacking nNOS responds more rapidly to PDTC compared with astrocytes from wild-type mice.@@@@1@21@@oe@16-12-2010 912225511@GENIA Treebank@formal@@1@S@Our data suggest that nNOS in astrocytes regulates NF kappaB activity and iNOS expression, and indicate a novel regulatory role for nNOS in tonically suppressing central nervous system, NF kappaB-regulated genes.@@@@1@34@@oe@16-12-2010 912530801@GENIA Treebank@formal@@1@S@Induction of vascular cell adhesion molecule-1 by low-density lipoprotein.@@@@1@10@@oe@16-12-2010 912530802@GENIA Treebank@formal@@1@S@Low-density lipoprotein (LDL) is a well-established risk factor for atherosclerosis.@@@@1@13@@oe@16-12-2010 912530803@GENIA Treebank@formal@@1@S@When endothelial cells are incubated with this lipoprotein in pathophysiologic amounts, the cells are activated.@@@@1@17@@oe@16-12-2010 912530804@GENIA Treebank@formal@@1@S@Among the documented cellular responses to LDL is increased recruitment of monocytes, which are believed to play a major role in promoting intimal plaque formation.@@@@1@27@@oe@16-12-2010 912530805@GENIA Treebank@formal@@1@S@The findings presented here link an atheogenic lipoprotein, LDL, with the induction of an adhesion molecule important in atherogenesis@@@@1@21@@oe@16-12-2010 912530806@GENIA Treebank@formal@@1@S@Human LDL induces the vascular cell adhesion molecule-1 (VCAM-1) transcriptionally with an increase in mRNA levels through activation of the VCAM promoter.@@@@1@25@@oe@16-12-2010 912530807@GENIA Treebank@formal@@1@S@This effect is blocked by anti-VCAM antibodies.@@@@1@8@@oe@16-12-2010 912530808@GENIA Treebank@formal@@1@S@After a 2-day incubation in LDL, the binding of NF-kappa B, which is believed to be a key oxidative-stress sensor for VCAM regulation, remains at basal level.@@@@1@31@@oe@16-12-2010 912530809@GENIA Treebank@formal@@1@S@In contrast, the binding activities of AP-1 and GATA, on the other hand, are increased by LDL.@@@@1@21@@oe@16-12-2010 912530810@GENIA Treebank@formal@@1@S@Thus, a component of LDL-enhanced endothelial recruitment of monocytes is attributed to VCAM-1 expression, which appears to be mediated through AP-1 and GATA.@@@@1@26@@oe@16-12-2010 912530811@GENIA Treebank@formal@@1@S@These data identify LDL as a VCAM-inducer possibly distinct from cytokines and endotoxin.@@@@1@14@@oe@16-12-2010 912700501@GENIA Treebank@formal@@1@S@Activation of Ras and mitogen-activated protein kinase pathway by terminal complement complexes is G protein dependent.@@@@1@17@@oe@16-12-2010 912700502@GENIA Treebank@formal@@1@S@Assembly of terminal complement complexes (TCC) C5b-7, C5b-8, and C5b-9 on target cells during acute and chronic inflammation induces hydrolysis of plasma membrane phospholipids and heterotrimeric G protein activation.@@@@1@34@@oe@16-12-2010 912700503@GENIA Treebank@formal@@1@S@TCC also stimulate a variety of cellular activities, which include cytokine synthesis, proto-oncogene activation, and mitotic signaling.@@@@1@21@@oe@16-12-2010 912700504@GENIA Treebank@formal@@1@S@Now we report that sublytic TCC induced Ras, Raf-1, and extracellular signal-regulated kinase (ERK) 1 activation in JY25 B cell line.@@@@1@26@@oe@16-12-2010 912700505@GENIA Treebank@formal@@1@S@When cells were exposed to C5b-9, GTP-bound Ras in anti-C5b-9 immunoprecipitates was increased 3.2-fold at 2 min, while GTP-bound Ras in anti-Ras immunoprecipitates was increased 2-fold at 10 min.@@@@1@32@@oe@16-12-2010 912700506@GENIA Treebank@formal@@1@S@Both C5b-9 and C5b-7, but not C5b6, increased Raf-1 kinase activity maximum 3.3-fold at 2 min and 2.8-fold at 5 min, respectively.@@@@1@26@@oe@16-12-2010 912700507@GENIA Treebank@formal@@1@S@ERK1 activity was 2-fold increased by C5b-9 at 2 min and by C5b-7 at 10 min, over the C5b6 level.@@@@1@22@@oe@16-12-2010 912700508@GENIA Treebank@formal@@1@S@The role of mitogen-activated protein kinase (MAPK) pathway on TCC-inducible mitotic signaling was evaluated by assessing DNA synthesis and activator protein 1 (AP-1) DNA-binding activity.@@@@1@30@@oe@16-12-2010 912700509@GENIA Treebank@formal@@1@S@The MAPK/ERK-specific inhibitor PD 098,059 abolished the C5b-9-induced DNA synthesis.@@@@1@11@@oe@16-12-2010 912700510@GENIA Treebank@formal@@1@S@Involvement of G protein in the activation of MAPK pathway by TCC was indicated by inhibition of Raf-1 and ERK1 kinase activity, as well as the DNA synthesis by pretreatment of cells with pertussis toxin.@@@@1@37@@oe@16-12-2010 912700511@GENIA Treebank@formal@@1@S@Overexpression of beta-adrenergic receptor kinase 1 carboxyl-terminal peptide in JY25 cells also inhibited Raf-1 and ERK1 activity, indicating a direct involvement of G betagamma subunits in the signal transduction generated through activation of MAPK pathway by TCC assembly in the plasma membrane.@@@@1@44@@oe@16-12-2010 912872701@GENIA Treebank@formal@@1@S@Reconstitution of T cell antigen receptor-induced Erk2 kinase activation in Lck-negative JCaM1 cells by Syk.@@@@1@16@@oe@16-12-2010 912872702@GENIA Treebank@formal@@1@S@The two related protein-tyrosine kinases Syk and Zap are rapidly phosphorylated on tyrosine residues and enzymatically activated upon crosslinking of the T cell antigen receptor.@@@@1@26@@oe@16-12-2010 912872703@GENIA Treebank@formal@@1@S@We have previously reported that the activation of Syk is less dependent on the Src family kinase Lck than the activation of Zap.@@@@1@24@@oe@16-12-2010 912872704@GENIA Treebank@formal@@1@S@Here we report that overexpression of Syk in the Lck-negative JCaM1 cells enabled the T cell antigen receptor/CD3 complex to induce a normal activation of the mitogen-activated protein kinase (MAPK) pathway and expression of a nuclear factor of activated T cells reporter construct.@@@@1@46@@oe@16-12-2010 912872705@GENIA Treebank@formal@@1@S@In contrast, Zap and other protein-tyrosine kinases were unable to reconstitute these signaling pathways when expressed at the same levels.@@@@1@22@@oe@16-12-2010 912872706@GENIA Treebank@formal@@1@S@In parallel, Syk was phosphorylated on tyrosine, while Zap was not.@@@@1@14@@oe@16-12-2010 912872707@GENIA Treebank@formal@@1@S@The Syk-mediated T cell antigen receptor-induced MAPK activation was detectable within 1 min of receptor stimulation and peaked at 3-5 min.@@@@1@22@@oe@16-12-2010 912872708@GENIA Treebank@formal@@1@S@The capacity of Syk to reconstitute the MAPK response required the catalytic activity of Syk, an intact autophosphorylation site (Y518 and Y519), both Src homology 2 domains and it was blocked by the inhibitory N17-mutated dominant-negative Ras construct.@@@@1@43@@oe@16-12-2010 912872709@GENIA Treebank@formal@@1@S@A Y341-->F mutant of Syk, which is deficient in its interaction with phospholipase Cy1 and Vav, was less efficient than wild-type Syk.@@@@1@27@@oe@16-12-2010 912872710@GENIA Treebank@formal@@1@S@Our results suggest that Syk, in contrast to Zap, can transduce signals from the T cell antigen receptor independently of Lck.@@@@1@24@@oe@16-12-2010 912904201@GENIA Treebank@formal@@1@S@Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II.@@@@1@20@@oe@16-12-2010 912904202@GENIA Treebank@formal@@1@S@Clinical efficacy and pharmacokinetics in relapsed patients.@@@@1@8@@oe@16-12-2010 912904203@GENIA Treebank@formal@@1@S@The therapeutic effect of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) was evaluated among 15 APL patients at relapse after all-trans retinoic acid (ATRA) induced and chemotherapy maintained complete remission (CR).@@@@1@44@@oe@16-12-2010 912904204@GENIA Treebank@formal@@1@S@As2O3 was administered intravenously at the dose of 10 mg/d.@@@@1@11@@oe@16-12-2010 912904205@GENIA Treebank@formal@@1@S@Clinical CR was achieved in nine of 10 (90%) patients treated with As2O3 alone and in the remaining five patients treated by the combination of As2O3 and low-dose chemotherapeutic drugs or ATRA.@@@@1@36@@oe@16-12-2010 912904206@GENIA Treebank@formal@@1@S@During the treatment with As2O3, there was no bone marrow depression and only limited side effects were encountered.@@@@1@20@@oe@16-12-2010 912904207@GENIA Treebank@formal@@1@S@Pharmacokinetic studies, which were performed in eight patients, showed that after a peak level of 5.54 micromol/L to 7.30 micromol/L, plasma arsenic was rapidly eliminated, and the continuous administration of As2O3 did not alter its pharmacokinetic behaviors.@@@@1@42@@oe@16-12-2010 912904208@GENIA Treebank@formal@@1@S@In addition, increased amounts of arsenic appeared in the urine, with a daily excretion accounting for approximately 1% to 8% of the total daily dose administered.@@@@1@31@@oe@16-12-2010 912904209@GENIA Treebank@formal@@1@S@Arsenic contents in hair and nail were increased, and the peak content of arsenic could reach 2.5 to 2.7 microg/g tissue at CR.@@@@1@25@@oe@16-12-2010 912904210@GENIA Treebank@formal@@1@S@On the other hand, a decline of the arsenic content in hair and nail was observed after withdrawal of the drug.@@@@1@23@@oe@16-12-2010 912904211@GENIA Treebank@formal@@1@S@We conclude that As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy.@@@@1@22@@oe@16-12-2010 912905001@GENIA Treebank@formal@@1@S@Activation of the NF-kappaB pathway by inflammatory stimuli in human neutrophils.@@@@1@12@@oe@16-12-2010 912905002@GENIA Treebank@formal@@1@S@Activated neutrophils have the ability to upregulate the expression of many genes, in particular those encoding cytokines and chemokines, and to subsequently release the corresponding proteins.@@@@1@29@@oe@16-12-2010 912905003@GENIA Treebank@formal@@1@S@Although little is known to date concerning the regulation of gene transcription in neutrophils, it is noteworthy that many of these genes depend on the activation of transcription factors, such as NF-kappaB, for inducible expression.@@@@1@39@@oe@16-12-2010 912905004@GENIA Treebank@formal@@1@S@We therefore investigated whether NF-kappaB/Rel proteins are expressed in human neutrophils, as well as their fate on cell activation.@@@@1@21@@oe@16-12-2010 912905005@GENIA Treebank@formal@@1@S@We now report that dimers consisting of p50 NFkappaB1, p65 RelA, and/or c-Rel are present in neutrophils and that the greater part of these protein complexes is physically associated with cytoplasmic IkappaB-alpha in resting cells.@@@@1@38@@oe@16-12-2010 912905006@GENIA Treebank@formal@@1@S@Following neutrophil stimulation with proinflammatory agonists (such as lipopolysaccharide [LPS], tumor necrosis factor-alpha [TNF-alpha], and fMet-Leu-Phe) that induce the production of cytokines and chemokines in these cells, NF-kappaB/Rel proteins translocated to nuclear fractions, resulting in a transient induction of NF-kappaB DNA binding activity, as determined in gel mobility shift assays.@@@@1@62@@oe@16-12-2010 912905007@GENIA Treebank@formal@@1@S@The onset of both processes was found to be closely paralleled by, and dependent on, IkappaB-alpha degradation.@@@@1@20@@oe@16-12-2010 912905008@GENIA Treebank@formal@@1@S@Proinflammatory neutrophil stimuli also promoted the accumulation of IkappaB-alpha mRNA transcripts, resulting in the reexpression of the IkappaB-alpha protein.@@@@1@21@@oe@16-12-2010 912905009@GENIA Treebank@formal@@1@S@To our knowledge, this constitutes the first indication that NF-kappaB activation may underlie the action of proinflammatory stimuli towards human neutrophil gene expression and, as such, adds a new facet to our understanding of neutrophil biology.@@@@1@40@@oe@16-12-2010 912997901@GENIA Treebank@formal@@1@S@Preferential presentation of herpes simplex virus T-cell antigen by HLA DQA1*0501/DQB1*0201 in comparison to HLA DQA1*0201/DQB1*0201.@@@@1@17@@oe@16-12-2010 912997902@GENIA Treebank@formal@@1@S@The HLA DQA1 locus is polymorphic.@@@@1@7@@oe@16-12-2010 912997903@GENIA Treebank@formal@@1@S@Haplotypes containing HLA DQA1*0501, but not HLA DQA1*0201, together with HLA DQB1*0201 are associated with Grave's disease and celiac sprue.@@@@1@24@@oe@16-12-2010 912997904@GENIA Treebank@formal@@1@S@In this report, we demonstrate a functional correlate of DQA1 polymorphism.@@@@1@13@@oe@16-12-2010 912997905@GENIA Treebank@formal@@1@S@T cells infiltrating a herpes simplex virus (HSV) lesion from a HLA DQ 2,7 individual yielded a virus-specific CD4+ clone restricted by DQ2.@@@@1@26@@oe@16-12-2010 912997906@GENIA Treebank@formal@@1@S@Presentation of viral peptide and protein segregated with DQA1 allele, because cell lines bearing DQA1*0501/DQB1*0201 heterodimers presented antigen in proliferation and cytotoxicity assays much more efficiently than cell lines bearing DQA1*0201/DQB1*0201.@@@@1@33@@oe@16-12-2010 912997907@GENIA Treebank@formal@@1@S@Binding of viral peptide to cell lines bearing DQA1*0201, in comparison to DQA1*0501, was only moderately reduced and may not explain this effect.@@@@1@26@@oe@16-12-2010 912997908@GENIA Treebank@formal@@1@S@Truncation and substitution analyses of peptide binding and T-cell activation were performed to determine which viral peptide residues contacting TCR might therefore be presented in an altered conformation by DQA1*0201/DQB1*0201.@@@@1@31@@oe@16-12-2010 912997909@GENIA Treebank@formal@@1@S@Residues 432, 435, 437, 438, and 440 (position P1, P4, P6, P7, and P9) contributed to DQ2 binding, whereas residues 431, 433, 434, and 436 (positions P 1, P2, P3, and P5) contributed to TCR contact.@@@@1@56@@oe@16-12-2010 912997910@GENIA Treebank@formal@@1@S@Differential presentation of peptide by HLA DQ2 heterodimers varying at the DQA1 locus may have relevance to host defense and the pathogenesis of HLA DQ2-associated autoimmune diseases.@@@@1@28@@oe@16-12-2010 912999701@GENIA Treebank@formal@@1@S@Glucocorticoid-resistance in peripheral-blood lymphocytes does not correlate with number of affinity of glucocorticoid-receptors in chronic renal failure patients.@@@@1@19@@oe@16-12-2010 912999702@GENIA Treebank@formal@@1@S@Glucocorticoid (GC) resistance in patients with chronic renal failure (CRF) seriously impairs successive GC therapy after renal transplantation.@@@@1@23@@oe@16-12-2010 912999703@GENIA Treebank@formal@@1@S@We examined the relationship between GC-receptor (GC-R) parameters in peripheral-blood mononuclear cells (PBMC) and PBMC resistance to GC in 21 CRF patients and 18 healthy subjects.@@@@1@31@@oe@16-12-2010 912999704@GENIA Treebank@formal@@1@S@Each subject group was divided into two subgroups according to PBMC sensitivity to prednisolone in a mitogen assay procedure; i.e., sensitive (IC50 < 381 ng/mL) and resistant (IC50 > 381 ng/mL) groups.@@@@1@39@@oe@16-12-2010 912999705@GENIA Treebank@formal@@1@S@In healthy subjects, the mean GC-R Bmax and Kd in quiescent PBMC of the GC-sensitive group were 2.89 +/- 1.23 fmol/10(6) cells and 4.00 +/- 2.24 nM, respectively.@@@@1@31@@oe@16-12-2010 912999706@GENIA Treebank@formal@@1@S@The Bmax in these subjects significantly increased to 6.61 +/- 2.02 (257.7 +/- 107.8%) after 24 h stimulation with concanavalin A (p < 0.01), while the Kd change was not significant.@@@@1@38@@oe@16-12-2010 912999707@GENIA Treebank@formal@@1@S@The GC-R Bmax and Kd in quiescent PBMC of the GC-resistant group were 5.33 +/- 1.37 fmol/10(6) cells and 3.20 +/- 1.39 nM, respectively.@@@@1@26@@oe@16-12-2010 912999708@GENIA Treebank@formal@@1@S@Both of these parameters, however, did not change significantly after mitogen stimulation.@@@@1@15@@oe@16-12-2010 912999709@GENIA Treebank@formal@@1@S@There was a significant negative correlation between IC50S of prednisolone and increase-ratios (post/pre ratio) of Bmax after mitogen stimulation (p < 0.05).@@@@1@27@@oe@16-12-2010 912999710@GENIA Treebank@formal@@1@S@In CRF patients, Bmax and Kd in quiescent PBMC of the GC-sensitive group were 6.04 +/- 2.35 fmol/10(6) cells and 3.49 +/- 1.72 nM, respectively, while those in PBMC of the GC-resistant group were 5.13 +/- 2.31 fmol/10(6) cells and 4.04 +/- 1.62 nM, respectively.@@@@1@50@@oe@16-12-2010 912999711@GENIA Treebank@formal@@1@S@The Bmax and Kd were not significantly changed after mitogen stimulation in both subgroups of CRF.@@@@1@17@@oe@16-12-2010 912999712@GENIA Treebank@formal@@1@S@Moreover, in contrast to healthy subjects, there was no correlation between IC50 and GC-R parameters in CRF.@@@@1@20@@oe@16-12-2010 912999713@GENIA Treebank@formal@@1@S@We concluded that, in healthy subjects, decreased PBMC capacity to amplify GC-R numbers in response to mitogen is correlated with GC resistance, whereas in CRF patients the resistant mechanism is not correlated with GC-R parameters.@@@@1@39@@oe@16-12-2010 912999714@GENIA Treebank@formal@@1@S@An unknown event might be involved in GC-resistance of CRF.@@@@1@11@@oe@16-12-2010 913047701@GENIA Treebank@formal@@1@S@Regulation of human epsilon germline transcription: role of B-cell-specific activator protein.@@@@1@13@@oe@16-12-2010 913047702@GENIA Treebank@formal@@1@S@Germline transcripts initiate from promoters upstream of the immunoglobulin switch region, and are necessary to target the appropriate switch region for recombination and switching.@@@@1@26@@oe@16-12-2010 913047703@GENIA Treebank@formal@@1@S@Different cytokines activate transcription at the appropriate germline promoter.@@@@1@10@@oe@16-12-2010 913047704@GENIA Treebank@formal@@1@S@Because binding sites for B-cell-specific activator protein (BSAP) are located upstream of several switch regions in the immunoglobulin heavy chain gene cluster, BSAP might play a role in the regulation of germline transcription and isotype switching.@@@@1@40@@oe@16-12-2010 913047705@GENIA Treebank@formal@@1@S@We investigated whether BSAP plays a role in the transcriptional regulation of the epsilon germline promoter in human B cells.@@@@1@21@@oe@16-12-2010 913047706@GENIA Treebank@formal@@1@S@Our results showed that BSAP plays a role in both IL-4-dependent induction and CD40-mediated upregulation of human epsilon germline transcription.@@@@1@21@@oe@16-12-2010 913047707@GENIA Treebank@formal@@1@S@BSAP is unique among the transcription factors that regulate epsilon germline expression, because it is B cell specific, and is at the merging point of two signalling pathways that are critical for IgE switching.@@@@1@37@@oe@16-12-2010 913051201@GENIA Treebank@formal@@1@S@Retinoic acid-induced modulation of IL-2 mRNA production and IL-2 receptor expression on T cells.@@@@1@15@@oe@16-12-2010 913051202@GENIA Treebank@formal@@1@S@BACKGROUND: Retinoic acid (RA) has important immune-modulating effects on both T and B cell function.@@@@1@19@@oe@16-12-2010 913051203@GENIA Treebank@formal@@1@S@Our laboratory has shown that RA can enhance in vitro polyclonal B cell immunoglobulin (Ig) response.@@@@1@19@@oe@16-12-2010 913051204@GENIA Treebank@formal@@1@S@Investigating cytokines known to affect B cell differentiation, we have recently shown that IL-6 production is augmented by RA.@@@@1@21@@oe@16-12-2010 913051205@GENIA Treebank@formal@@1@S@In the present study we have examined the immune modulating effects of RA on IL-2 mRNA, another important cytokine for B cell immunoglobulin production, the expression of IL-2 receptors on T cells, and the RA nuclear receptors.@@@@1@41@@oe@16-12-2010 913051206@GENIA Treebank@formal@@1@S@METHODS: Purified T cells were obtained from adenoidal tissues, and incubated with RA (10(-7) M) or DMSO solvent/media control for 0, 6-8, and 24 h.@@@@1@32@@oe@16-12-2010 913051207@GENIA Treebank@formal@@1@S@Total mRNA was extracted from T cells, and using RT-PCR, changes in the production of IL-2 and RA receptors (RAR)-alpha,beta,gamma mRNA were determined.@@@@1@33@@oe@16-12-2010 913051208@GENIA Treebank@formal@@1@S@The effects of RA on IL-2-alpha receptor expression was determined by flow cytometry on T cells.@@@@1@17@@oe@16-12-2010 913051209@GENIA Treebank@formal@@1@S@CONCLUSION: These studies suggest that RA can augment IL-2 mRNA production by T cells with a possible paracrine effect on IL-2R-alpha expression.@@@@1@24@@oe@16-12-2010 913051210@GENIA Treebank@formal@@1@S@These changes appear to be mediated by RAR-alpha.@@@@1@9@@oe@16-12-2010 913051211@GENIA Treebank@formal@@1@S@Thus, IL-2 may be another important cytokine modulated by RA in the immune response.@@@@1@16@@oe@16-12-2010 913061501@GENIA Treebank@formal@@1@S@Significance of quantitative analysis of AML1/ETO transcripts in peripheral blood stem cells from t(8;21) acute myelogenous leukemia.@@@@1@18@@oe@16-12-2010 913061502@GENIA Treebank@formal@@1@S@Autologous peripheral blood stem cell transplantation (PBSCT) is replacing autologous bone marrow transplantation (BMT) in the treatment of leukemia.@@@@1@24@@oe@16-12-2010 913061503@GENIA Treebank@formal@@1@S@One of the potential advantages of autologous PBSCT is the possibility that peripheral blood stem cells (PBSC) are less likely to be contaminated by leukemic cells than bone marrow grafts.@@@@1@33@@oe@16-12-2010 913061504@GENIA Treebank@formal@@1@S@However, the major problem still remains the high incidence of leukemic relapse following autologous PBSCT, which may be caused by the reinfusion of PBSC contaminated by leukemic cells.@@@@1@31@@oe@16-12-2010 913061505@GENIA Treebank@formal@@1@S@Recently, we have developed a quantitative assay using competitive reverse transcriptase polymerase chain reaction that estimates the number of AML1/ETO transcripts in t(8;21) acute myelogenous leukemia (AML), in order to determine the degree of leukemic cell contamination in PBSC harvests, and to monitor minimal residual disease (MRD) quantitatively in patients with t(8;21) AML.@@@@1@61@@oe@16-12-2010 913061506@GENIA Treebank@formal@@1@S@Our data indicate that although PBSC harvests collected after consolidation chemotherapy are contaminated by leukemic cells, the degree of leukemic cell contamination decreases with repeated cycles of chemotherapy.@@@@1@30@@oe@16-12-2010 913061507@GENIA Treebank@formal@@1@S@Furthermore, the MRD in PBSC harvests is less than in the corresponding bone marrow obtained on the day of the PBSC collection.@@@@1@24@@oe@16-12-2010 913061508@GENIA Treebank@formal@@1@S@There appears to be no relationship between the number of AML1/ETO transcripts found in the infused PBSC harvests and the incidence of leukemic relapse following autologous PBSCT in our study.@@@@1@31@@oe@16-12-2010 913061509@GENIA Treebank@formal@@1@S@However, a substantial decrease of AML1/ETO transcripts was seen following autologous PBSCT.@@@@1@14@@oe@16-12-2010 913061510@GENIA Treebank@formal@@1@S@Thus, the quantitative analysis of AML1/ETO transcripts may be clinically useful in patients with t(8;21) AML.@@@@1@18@@oe@16-12-2010 913063201@GENIA Treebank@formal@@1@S@Itk, a T cell-specific tyrosine kinase, is required for CD2-mediated interleukin-2 promoter activation in the human T cell line Jurkat.@@@@1@23@@oe@16-12-2010 913063202@GENIA Treebank@formal@@1@S@We investigated the functional role of Itk, a member of the cytoplasmic tyrosine kinase Tec family, in T cell activation.@@@@1@23@@oe@16-12-2010 913063203@GENIA Treebank@formal@@1@S@Stimulation of either CD2 or T cell receptor (TCR)/CD3 on Tcells by monoclonal antibody-mediated cross-linking induced tyrosine phosphorylation of Itk, which was maximal as early as 1 min after stimulation.@@@@1@35@@oe@16-12-2010 913063204@GENIA Treebank@formal@@1@S@The tyrosine kinase activity in the anti-Itk immunoprecipitate was significantly activated upon these stimulations.@@@@1@15@@oe@16-12-2010 913063205@GENIA Treebank@formal@@1@S@Interleukin-2 (IL-2) promoter activity stimulated by cross-linking of CD2, TCR/CD3, and CD28 with antibodies was significantly reduced by transient expression of an Itk mutant lacking the kinase activity.@@@@1@33@@oe@16-12-2010 913063206@GENIA Treebank@formal@@1@S@The reduction paralleled a decrease in tyrosine phosphorylation of endogenous wild-type Itk.@@@@1@13@@oe@16-12-2010 913063207@GENIA Treebank@formal@@1@S@Stimulation of CD2 or TCR/CD3 induced activation of the nuclear factor of activated T cells (NFAT), the binding site of which is included in the IL-2 gene promoter.@@@@1@32@@oe@16-12-2010 913063208@GENIA Treebank@formal@@1@S@The activation of NFAT was also impaired by expression of the Itk mutant.@@@@1@14@@oe@16-12-2010 913063209@GENIA Treebank@formal@@1@S@These results demonstrate that Itk plays a role in IL-2 production, indicating a critical involvement of Itk in the initial stage of T cell activation by mediating signals from the TCR/CD3 complex, CD2, and CD28.@@@@1@39@@oe@16-12-2010 913068501@GENIA Treebank@formal@@1@S@DNA methylation changes in hematologic malignancies: biologic and clinical implications.@@@@1@12@@oe@16-12-2010 913068502@GENIA Treebank@formal@@1@S@DNA methylation changes are among the most common detectable abnormalities in human neoplasia.@@@@1@14@@oe@16-12-2010 913068503@GENIA Treebank@formal@@1@S@Hypermethylation within the promoters of selected genes appears to be especially common in all types of human hematopoietic neoplasms, and is usually associated with inactivation of the involved gene(s).@@@@1@34@@oe@16-12-2010 913068504@GENIA Treebank@formal@@1@S@Such hypermethylation-associated silencing of gene expression has been shown for several genes regulating the growth and differentiation of hematopoietic cells, including the estrogen receptor (ER) gene, P15, P16 and others.@@@@1@36@@oe@16-12-2010 913068505@GENIA Treebank@formal@@1@S@Hypermethylation within the promoters of some genes appear to be an early event in the pathogenesis of neoplasia (ER, P15), while other genes seem to become methylated during the progression of leukemias (HIC1, c-abl).@@@@1@42@@oe@16-12-2010 913068506@GENIA Treebank@formal@@1@S@The high prevalence of promoter methylation suggests that this molecular abnormality can be used to monitor disease activity during therapy.@@@@1@21@@oe@16-12-2010 913068507@GENIA Treebank@formal@@1@S@In addition, new technology allows the sensitive identification of gene hypermethylation in a background of normal cells, suggesting possible new strategies for the detection of minimal residual disease.@@@@1@31@@oe@16-12-2010 913068508@GENIA Treebank@formal@@1@S@Finally, reactivation of tumor-suppressor gene expression through pharmacologic inhibition of DNA methyltransferase and resultant DNA demethylation appears to be a promising new avenue of therapy in acute leukemia.@@@@1@30@@oe@16-12-2010 913341701@GENIA Treebank@formal@@1@S@Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells.@@@@1@18@@oe@16-12-2010 913341702@GENIA Treebank@formal@@1@S@CD40 is a receptor that is critical for the survival, growth, differentiation, and isotype switching of B lymphocytes.@@@@1@22@@oe@16-12-2010 913341703@GENIA Treebank@formal@@1@S@Although CD40 lacks intrinsic tyrosine kinase activity, its ligation induces protein tyrosine phosphorylation, which is necessary for several CD40-mediated events.@@@@1@23@@oe@16-12-2010 913341704@GENIA Treebank@formal@@1@S@We show that engagement of CD40 induces tyrosine phosphorylation and activation of Jak3 as well as of STAT3.@@@@1@19@@oe@16-12-2010 913341705@GENIA Treebank@formal@@1@S@Jak3 is constitutively associated with CD40, and this interaction requires a proline-rich sequence in the membrane-proximal region of CD40.@@@@1@21@@oe@16-12-2010 913341706@GENIA Treebank@formal@@1@S@Deletion of this sequence abolishes the capacity of CD40 to induce expression of CD23, ICAM-1, and lymphotoxin-alpha genes in B cells.@@@@1@24@@oe@16-12-2010 913341707@GENIA Treebank@formal@@1@S@These results indicate that signaling through Jak3 is activated by CD40 and plays an important role in CD40-mediated functions.@@@@1@20@@oe@16-12-2010 913555201@GENIA Treebank@formal@@1@S@The tumour associated cell surface antigen A6H is costimulatory for human CD4+ but not CD8+ T cells.@@@@1@18@@oe@16-12-2010 913555202@GENIA Treebank@formal@@1@S@The A6H monoclonal antibody (mAb) recognizes a 120,000-140,000 MW antigen that is expressed at similar densities on 85-90% of human CD4+ and CD8+ T cells and on renal cell carcinomas.@@@@1@34@@oe@16-12-2010 913555203@GENIA Treebank@formal@@1@S@The binding of the A6H mAb induced a costimulatory signal in anti-CD3 activated T cells.@@@@1@16@@oe@16-12-2010 913555204@GENIA Treebank@formal@@1@S@In the present report, we show that A6H costimulated cell proliferation and cytokine production in purified CD4+ T cells.@@@@1@21@@oe@16-12-2010 913555205@GENIA Treebank@formal@@1@S@Unexpectedly, the CD8+ T-cell subpopulation failed to respond.@@@@1@10@@oe@16-12-2010 913555206@GENIA Treebank@formal@@1@S@CD4+ T cells costimulated with the A6H mAb upregulated CD80, CD86, CD71, interleukin-2 (IL-2)R alpha, IL-2R beta and IL-2R gamma, while no corresponding up-regulation of these cell surface molecules was seen in CD8+ T cells.@@@@1@44@@oe@16-12-2010 913555207@GENIA Treebank@formal@@1@S@In order to investigate the nature of the A6H mAb costimulus at the transcriptional level we have examined induction of the transcription factors OCT-1, AP-1 and NF-kappa B which are known to be transcriptional regulators of several cytokine and cytokine receptor genes, including the IL-2 and IL-2R genes.@@@@1@51@@oe@16-12-2010 913555208@GENIA Treebank@formal@@1@S@Co-ligation of the A6H antigen and the CD3 complex induced expression of the transcription factor AP-1 in CD4+ T cells, whereas no increase in NF-kappa B and octamer-binding (Oct) proteins was seen compared to T cells stimulated with anti-CD3 alone.@@@@1@44@@oe@16-12-2010 913555209@GENIA Treebank@formal@@1@S@Furthermore, no induction of AP-1 was seen in A6H costimulated CD8+ T cells.@@@@1@15@@oe@16-12-2010 913555210@GENIA Treebank@formal@@1@S@These results suggests that both proximal steps in CD8+ T-cell activation as well as the later phases are unresponsive to A6H ligation.@@@@1@23@@oe@16-12-2010 913555211@GENIA Treebank@formal@@1@S@Molecular differences of the A6H molecule or distinct regulation of the A6H transduced AP-1 activation pathway may exist in CD4+ and CD8+ T cell subpopulations.@@@@1@26@@oe@16-12-2010 913608001@GENIA Treebank@formal@@1@S@Structure and function analysis of the human myeloid cell nuclear differentiation antigen promoter: evidence for the role of Sp1 and not of c-Myb or PU.1 in myelomonocytic lineage-specific expression.@@@@1@31@@oe@16-12-2010 913608002@GENIA Treebank@formal@@1@S@The human myeloid nuclear differentiation antigen (MNDA) is expressed specifically in maturing cells of the myelomonocytic lineage and in monocytes and granulocytes.@@@@1@25@@oe@16-12-2010 913608003@GENIA Treebank@formal@@1@S@Epitope enhancement was used to confirm the strict lineage- and stage-specific expression of MNDA in bone marrow as well as in other paraffin-embedded fixed tissues.@@@@1@26@@oe@16-12-2010 913608004@GENIA Treebank@formal@@1@S@A 1-kb region of the gene that includes 5' flanking sequence was reported earlier to contain functional promoter activity and was specifically demethylated in expressing cells in contrast to null cells.@@@@1@32@@oe@16-12-2010 913608005@GENIA Treebank@formal@@1@S@Further analysis has revealed that this 1-kb fragment promotes higher reporter gene activity in MNDA-expressing cells than non-expressing cells, indicating cell-specific differences in transactivation.@@@@1@26@@oe@16-12-2010 913608006@GENIA Treebank@formal@@1@S@This sequence contains consensus elements consistent with myeloid-specific gene expression, including a PU.1 consensus site near the major transcription start site and a cluster of c-Myb sites located several hundred bases upstream of this region.@@@@1@37@@oe@16-12-2010 913608007@GENIA Treebank@formal@@1@S@However, analysis of deletion mutants localized nearly all of the promoter activity to a short region (-73 to -16) that did not include the cluster of c-Myb sites.@@@@1@32@@oe@16-12-2010 913608008@GENIA Treebank@formal@@1@S@A 4-bp mutation of the core Sp1 consensus element (GC box) (-20) reduced overall promoter activity of the 1-kb fragment.@@@@1@25@@oe@16-12-2010 913608009@GENIA Treebank@formal@@1@S@Mutation of the PU.1 site did not significantly affect promoter activity.@@@@1@12@@oe@16-12-2010 913608010@GENIA Treebank@formal@@1@S@Only a small region (-35 to +22) including the Sp1 element and transcription start site, but not the PU.1 site was footprinted.@@@@1@26@@oe@16-12-2010 913608011@GENIA Treebank@formal@@1@S@The 4-bp mutation of the core Sp1 consensus element abolished footprinting at the site and an antibody super-shift reaction showed that Sp1 is one of the factors binding the consensus site.@@@@1@32@@oe@16-12-2010 913608012@GENIA Treebank@formal@@1@S@The Sp1 site also co-localizes with a DNase I hypersensitive site.@@@@1@12@@oe@16-12-2010 913608013@GENIA Treebank@formal@@1@S@The results indicate that DNA methylation, chromatin structure, and transactivation at an Sp1 site contribute to the highly restricted expression of this myelomonocytic lineage specific gene.@@@@1@29@@oe@16-12-2010 913698901@GENIA Treebank@formal@@1@S@Inhibitor (IK) of IFN-gamma induced HLA class II antigens expression also inhibits HLA class II constitutive expression in the human Raji B cell line.@@@@1@27@@oe@16-12-2010 913698902@GENIA Treebank@formal@@1@S@The expression of major histocompatibility complex (MHC) class II antigens is constitutive in professional antigen presenting cells (APCs) but can also be induced by interferon-gamma (IFN-gamma) on the majority of the non professional APCs (e.g. fibroblasts).@@@@1@45@@oe@16-12-2010 913698903@GENIA Treebank@formal@@1@S@We have recently characterised a new factor called IK which is an efficient inhibitor of IFN-gamma induction of MHC class II antigens expression.@@@@1@24@@oe@16-12-2010 913698904@GENIA Treebank@formal@@1@S@Here, we demonstrate a novel role for IK in MHC class II expression since over-expression of this protein by stable transfection into human B cells led to a total disappearance of constitutive MHC class II mRNA expression.@@@@1@39@@oe@16-12-2010 913698905@GENIA Treebank@formal@@1@S@The class II transactivator (CIITA) is necessary for both constitutive and IFN-gamma induced MHC class II expressions.@@@@1@20@@oe@16-12-2010 913698906@GENIA Treebank@formal@@1@S@Examination of CIITA mRNA in IK stably transfected clones revealed a marked reduction of CIITA mRNA transcription.@@@@1@18@@oe@16-12-2010 913698907@GENIA Treebank@formal@@1@S@Taken together these results demonstrate that the IK protein plays a key role in the constitutive expression of MHC class II antigens and that inhibition induced by IK is upstream of CIITA in this regulatory pathway.@@@@1@37@@oe@16-12-2010 913808801@GENIA Treebank@formal@@1@S@Effects of TPA, bryostatin 1, and retinoic acid on PO-B, AP-1, and AP-2 DNA binding during HL-60 differentiation.@@@@1@23@@oe@16-12-2010 913808802@GENIA Treebank@formal@@1@S@PO-B was originally characterized as a transcriptional regulatory factor of the pro-opiomelanocortin (POMC) gene; however, it has become increasingly clear that this protein may be active in tissues outside the pituitary, since it is present in diverse cell types, including differentiated HL-60 promyelocytic leukemia cells.@@@@1@52@@oe@16-12-2010 913808803@GENIA Treebank@formal@@1@S@We previously showed that PO-B DNA-binding is progressively induced during differentiation of promyelomonocytic leukemic HL-60 cells to the macrophage-like lineage (with phorbol esters).@@@@1@26@@oe@16-12-2010 913808804@GENIA Treebank@formal@@1@S@We now report that PO-B DNA-binding in HL-60 cells is similarly induced during differentiation to the granulocytic lineage (with either retinoic acid or dimethylsulfoxide).@@@@1@27@@oe@16-12-2010 913808805@GENIA Treebank@formal@@1@S@Either a genetic or pharmacologic blockade of HL-60 differentiation prohibited these inductive effects.@@@@1@14@@oe@16-12-2010 913808806@GENIA Treebank@formal@@1@S@These studies have prompted our interest in the dynamics of other transcription factor changes during HL-60 differentiation.@@@@1@18@@oe@16-12-2010 913808807@GENIA Treebank@formal@@1@S@Of these, we observed that another transcription factor (AP-1) is also robustly induced at the DNA-binding level during macrophage-like HL-60 differentiation, but not during granulocytic differentiation.@@@@1@31@@oe@16-12-2010 913808808@GENIA Treebank@formal@@1@S@Conversely, the DNA-binding of the transcription factor AP-2 was slightly reduced by TPA-induced HL-60 differentiation but unchanged during granulocyte differentiation.@@@@1@22@@oe@16-12-2010 913808809@GENIA Treebank@formal@@1@S@From these data, we conclude that the induction of PO-B DNA binding is a general marker of HL-60 myelomonocytic differentiation, but that qualitative aspects of the induction of additional distinct transcription factors, such as AP-1, may contribute to lineage-specific determinants of cell fate.@@@@1@48@@oe@16-12-2010 913908101@GENIA Treebank@formal@@1@S@Detection of adenovirus DNA in peripheral blood mononuclear cells by polymerase chain reaction assay.@@@@1@15@@oe@16-12-2010 913908102@GENIA Treebank@formal@@1@S@Adenovirus can establish persistent infections which may reactivate and cause disease in immunocompromised hosts.@@@@1@15@@oe@16-12-2010 913908103@GENIA Treebank@formal@@1@S@Lymphocytes have been postulated to serve as a site of adenoviral persistence based upon the ability to isolate adenovirus from tonsils and to detect adenovirus DNA by Southern blot hybridization in peripheral blood mononuclear cells (PBMC).@@@@1@39@@oe@16-12-2010 913908104@GENIA Treebank@formal@@1@S@To test this hypothesis, a more sensitive and specific polymerase chain reaction (PCR) assay was developed to detect adenovirus DNA.@@@@1@24@@oe@16-12-2010 913908105@GENIA Treebank@formal@@1@S@Two sets of nested primers were designed to conserved sequences in the adenovirus E1A and hexon genes.@@@@1@18@@oe@16-12-2010 913908106@GENIA Treebank@formal@@1@S@The E1A and hexon primers amplified DNA from representative adenoviral serotypes in all six adenoviral groups (A-F).@@@@1@20@@oe@16-12-2010 913908107@GENIA Treebank@formal@@1@S@Both primers detected a single copy of the adenovirus type 2 genome but were less sensitive for the group B type 35.@@@@1@23@@oe@16-12-2010 913908108@GENIA Treebank@formal@@1@S@None of 33 PBMC specimens from healthy adults and only one of 40 pediatric samples was positive (at a low level) for adenovirus DNA by nested PCR assay.@@@@1@31@@oe@16-12-2010 913908109@GENIA Treebank@formal@@1@S@In comparison, PBMC from two children with fatal adenoviral infection were both strongly positive for adenovirus DNA.@@@@1@19@@oe@16-12-2010 913908110@GENIA Treebank@formal@@1@S@It is concluded that, in contrast to a previous study, PBMC are not a common site of persistent group C adenoviral infection.@@@@1@25@@oe@16-12-2010 913908111@GENIA Treebank@formal@@1@S@In addition, assay of PBMC by the adenovirus-specific PCR may help detect early invasive disease and warrants further evaluation.@@@@1@21@@oe@16-12-2010 914213601@GENIA Treebank@formal@@1@S@Molecular actions of prolactin in the immune system.@@@@1@9@@oe@16-12-2010 914213602@GENIA Treebank@formal@@1@S@The immunoregulatory properties of prolactin, a pituitary peptide hormone, have received renewed attention.@@@@1@16@@oe@16-12-2010 914213603@GENIA Treebank@formal@@1@S@The prolactin receptor, a member of the hematopoietin/cytokine receptor superfamily, is ubiquitously expressed by cells in the immune system.@@@@1@22@@oe@16-12-2010 914213604@GENIA Treebank@formal@@1@S@Certain subpopulations of lymphocytes synthesize and secrete biologically active prolactin, which suggests that prolactin can act as an autocrine and/or paracrine factor to modulate the activities of cells of the immune system.@@@@1@34@@oe@16-12-2010 914213605@GENIA Treebank@formal@@1@S@This review focuses on the molecular actions of prolactin in the immune system.@@@@1@14@@oe@16-12-2010 914213606@GENIA Treebank@formal@@1@S@Emphasis is given to recent information about the molecular mechanisms of prolactin receptor signal transduction, and the signaling molecules and prolactin-inducible target genes that participate in these responses.@@@@1@30@@oe@16-12-2010 914213607@GENIA Treebank@formal@@1@S@In particular, the prolactin-inducible interferon regulatory factor-1 gene and its roles in mediating diverse immune responses.@@@@1@18@@oe@16-12-2010 914328401@GENIA Treebank@formal@@1@S@Spontaneous occurrence of early region 1A reiteration mutants of type 5 adenovirus in persistently infected human T-lymphocytes.@@@@1@18@@oe@16-12-2010 914328402@GENIA Treebank@formal@@1@S@Mutants of type 5 adenovirus (Ad5) with reiterated DNA sequences in the E1a region appeared in a human T-lymphocyte cell line, Molt-4, persistently infected with H5sub304, a deletion/substitution mutant that has a wild-type phenotype in viral replication.@@@@1@43@@oe@16-12-2010 914328403@GENIA Treebank@formal@@1@S@Endonuclease analyses and DNA sequencing revealed DNA reiteration in each mutant.@@@@1@12@@oe@16-12-2010 914328404@GENIA Treebank@formal@@1@S@In the four representative mutants investigated, the DNA reiterations all started within a six-base-pair consensus sequence, G(or C)CTGTG, located in the second exon of the E1a region (at nt 1333, 1367, or 1419).@@@@1@45@@oe@16-12-2010 914328405@GENIA Treebank@formal@@1@S@There was not any DNA homology between the breakpoints in the second exon and the inserting sequences (starting at nt 532, 710, or 792).@@@@1@29@@oe@16-12-2010 914328406@GENIA Treebank@formal@@1@S@Northern analyses suggested that the reiterated splicing sites of the representative mutants were all used in RNA splicing, and the closest donor and recipient joints were used most frequently.@@@@1@31@@oe@16-12-2010 914328407@GENIA Treebank@formal@@1@S@These observations imply that during persistent infection Ad5 underwent spontaneous mutations by sequence-specific breakage and nonhomologous end-end joining recombination events.@@@@1@21@@oe@16-12-2010 914328408@GENIA Treebank@formal@@1@S@These E1a reiteration mutants could be propagated in HeLa, A549, and KB cells; they were genetically stable; and they killed CREF cells at a strikingly high frequency.@@@@1@32@@oe@16-12-2010 914328409@GENIA Treebank@formal@@1@S@Preliminary observations tend to correlate this CREF cell killing with the accumulation of the early viral proteins and/or viral DNA in the infected cells.@@@@1@25@@oe@16-12-2010 914328410@GENIA Treebank@formal@@1@S@This degree of cell damage was not observed in Ad5wt or H5sub304 infection of CREF cells.@@@@1@17@@oe@16-12-2010 914328411@GENIA Treebank@formal@@1@S@The observed E1a reiterations provide a model to gain insight into understanding the evolutionary events of some, if not all, adenovirus types during many years of symbiotic, persistent relationship in human tonsils and adenoids and possibly other lymphoid organs.@@@@1@43@@oe@16-12-2010 914368501@GENIA Treebank@formal@@1@S@The role of the Ikaros gene in lymphocyte development and homeostasis.@@@@1@12@@oe@16-12-2010 914368502@GENIA Treebank@formal@@1@S@The Ikaros gene, which encodes a family of hemopoietic-specific zinc finger proteins, is described as a central regulator of lymphocyte differentiation.@@@@1@24@@oe@16-12-2010 914368503@GENIA Treebank@formal@@1@S@During fetal development, it is required at the earliest stage of T cell and B cell specification.@@@@1@19@@oe@16-12-2010 914368504@GENIA Treebank@formal@@1@S@In the adult, however, lymphoid lineages rely on Ikaros at distinct phases of their development.@@@@1@18@@oe@16-12-2010 914368505@GENIA Treebank@formal@@1@S@Its activity is essential for the generation of B cell but not of T cell precursors, although the differentiation of the latter is not normal.@@@@1@27@@oe@16-12-2010 914368506@GENIA Treebank@formal@@1@S@A significant increase in CD4 thymocytes and their immediate precursors is detected, and because these cells lack markers that correlate with positive selection, a deregulation in their maturation process is suggested.@@@@1@34@@oe@16-12-2010 914368507@GENIA Treebank@formal@@1@S@Furthermore, Ikaros-null thymocytes hyperproliferate in response to T cell receptor (TCR) signaling; within days after their appearance in the thymus, clonally expanding populations are detected.@@@@1@31@@oe@16-12-2010 914368508@GENIA Treebank@formal@@1@S@Deregulated TCR-mediated responses and the fast kinetics of tumor development in these mutant thymocytes implicate Ikaros as a central tumor suppressor gene for the T cell lineage.@@@@1@28@@oe@16-12-2010 914368509@GENIA Treebank@formal@@1@S@In addition, lack of natural killer cells and selective defects in gamma delta T cells and dendritic antigen-presenting cells point to Ikaros as an essential factor for the establishment of early branchpoints of the T cell pathway.@@@@1@39@@oe@16-12-2010 914368510@GENIA Treebank@formal@@1@S@The dominant interference activity of Ikaros isoforms unable to bind DNA and their effects in lymphocyte development suggest that Ikaros works in concert with other factors.@@@@1@27@@oe@16-12-2010 914368511@GENIA Treebank@formal@@1@S@The role of Aiolos, a lymphoid-restricted and structurally related gene, in lymphoid differentiation is discussed.@@@@1@18@@oe@16-12-2010 914368512@GENIA Treebank@formal@@1@S@A model is proposed that defines Ikaros as the backbone of a complex regulatory protein network that controls cell fate decisions and regulates homeostasis in the hemo-lymphoid system.@@@@1@29@@oe@16-12-2010 914368513@GENIA Treebank@formal@@1@S@Changes in this regulatory network may reflect differentiation and proliferation adjustments made in hemo-lymphoid progenitors and precursors as they give rise to the cells of our immune system.@@@@1@29@@oe@16-12-2010 914421801@GENIA Treebank@formal@@1@S@An enhancer-blocking element between alpha and delta gene segments within the human T cell receptor alpha/delta locus.@@@@1@18@@oe@16-12-2010 914421802@GENIA Treebank@formal@@1@S@T cell receptor (TCR) alpha and delta gene segments are organized within a single genetic locus but are differentially regulated during T cell development.@@@@1@27@@oe@16-12-2010 914421803@GENIA Treebank@formal@@1@S@An enhancer-blocking element (BEAD-1, for blocking element alpha/delta 1) was localized to a 2.0-kb region 3' of TCR delta gene segments and 5' of TCR alpha joining gene segments within this locus.@@@@1@36@@oe@16-12-2010 914421804@GENIA Treebank@formal@@1@S@BEAD-1 blocked the ability of the TCR delta enhancer (Edelta) to activate a promoter when located between the two in a chromatin-integrated construct.@@@@1@26@@oe@16-12-2010 914421805@GENIA Treebank@formal@@1@S@We propose that BEAD-1 functions as a boundary that separates the TCR alpha/delta locus into distinct regulatory domains controlled by Edelta and the TCR alpha enhancer, and that it prevents Edelta from opening the chromatin of the TCR alpha joining gene segments for VDJ recombination at an early stage of T cell development.@@@@1@55@@oe@16-12-2010 914423201@GENIA Treebank@formal@@1@S@Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice.@@@@1@10@@oe@16-12-2010 914423202@GENIA Treebank@formal@@1@S@Acute promyelocytic leukemia (APL) is associated with reciprocal chromosomal translocations involving the retinoic acid receptor alpha (RARalpha) locus on chromosome 17.@@@@1@26@@oe@16-12-2010 914423203@GENIA Treebank@formal@@1@S@In the majority of cases, RARalpha translocates and fuses with the promyelocytic leukemia (PML) gene located on chromosome 15.@@@@1@23@@oe@16-12-2010 914423204@GENIA Treebank@formal@@1@S@The resulting fusion genes encode the two structurally unique PML/RARalpha and RARalpha/PML fusion proteins as well as aberrant PML gene products, the respective pathogenetic roles of which have not been elucidated.@@@@1@33@@oe@16-12-2010 914423205@GENIA Treebank@formal@@1@S@We have generated transgenic mice in which the PML/RARalpha fusion protein is specifically expressed in the myeloid-promyelocytic lineage.@@@@1@19@@oe@16-12-2010 914423206@GENIA Treebank@formal@@1@S@During their first year of life, all the PML/RARalpha transgenic mice have an abnormal hematopoiesis that can best be described as a myeloproliferative disorder.@@@@1@26@@oe@16-12-2010 914423207@GENIA Treebank@formal@@1@S@Between 12 and 14 months of age, 10% of them develop a form of acute leukemia with a differentiation block at the promyelocytic stage that closely mimics human APL even in its response to retinoic acid.@@@@1@39@@oe@16-12-2010 914423208@GENIA Treebank@formal@@1@S@Our results are conclusive in vivo evidence that PML/RARalpha plays a crucial role in the pathogenesis of APL.@@@@1@19@@oe@16-12-2010 914433801@GENIA Treebank@formal@@1@S@Quantification of vitamin D receptor mRNA by competitive polymerase chain reaction in PBMC: lack of correspondence with common allelic variants.@@@@1@22@@oe@16-12-2010 914433802@GENIA Treebank@formal@@1@S@It has been recently claimed that polymorphism for the vitamin D receptor (VDR) influences several aspects of calcium and bone metabolism.@@@@1@24@@oe@16-12-2010 914433803@GENIA Treebank@formal@@1@S@To evaluate the physiologic plausibility of these claims, we compared the abundance of the VDR mRNA in peripheral blood mononuclear cells (PBMCs) between different VDR genotypes using a quantitative reverse transcribed polymerase chain reaction-based method.@@@@1@39@@oe@16-12-2010 914433804@GENIA Treebank@formal@@1@S@The method is based on the coamplification of VDR cDNA and an internal standard consisting of known concentrations of a human VDR CDNA mutated at a BglII restriction site; the interassay coefficient of variation is 11%.@@@@1@39@@oe@16-12-2010 914433805@GENIA Treebank@formal@@1@S@To validate the method, we made use of earlier receptor binding studies indicating that normal human monocytes and activated, but not resting, lymphocytes expressed the VDR.@@@@1@30@@oe@16-12-2010 914433806@GENIA Treebank@formal@@1@S@The concentration of the VDR mRNA was 10(-8) to 10(-7) g/g of total RNA in cell-sorted monocytes and in in vitro activated lymphocytes, but only 10(-12) g/g of total mRNA in resting lymphocytes, establishing that the VDR mRNA determined by our method in PBMCs is due to constitutive expression in monocytes.@@@@1@54@@oe@16-12-2010 914433807@GENIA Treebank@formal@@1@S@Following an initial genotype screening of 85 normal volunteers by polymerase chain reaction or restriction fragment length polymorphism analysis, 14 individuals with the Bb genotype, 12 with the bb genotype, and 12 with the BB genotype were selected.@@@@1@42@@oe@16-12-2010 914433808@GENIA Treebank@formal@@1@S@The concentration of the VDR mRNA, corrected for the number of monocytes, was similar among the three genotype groups, as were the other variables examined: serum calcitriol, serum osteocalcin, and vertebral and hip bone density.@@@@1@42@@oe@16-12-2010 914433809@GENIA Treebank@formal@@1@S@We conclude that VDR polymorphism does not affect the abundance of the VDR mRNA.@@@@1@15@@oe@16-12-2010 914447201@GENIA Treebank@formal@@1@S@Regulation of CD95 (Fas) ligand expression by TCR-mediated signaling events.@@@@1@13@@oe@16-12-2010 914447202@GENIA Treebank@formal@@1@S@Stimulation of mature peripheral T cells by TCR engagement results in activation of signals that drive induction of cytokine gene expression and clonal expansion.@@@@1@25@@oe@16-12-2010 914447203@GENIA Treebank@formal@@1@S@However, under some conditions, engagement of the TCR leads instead to apoptosis.@@@@1@15@@oe@16-12-2010 914447204@GENIA Treebank@formal@@1@S@Recent studies demonstrate that TCR-stimulated apoptosis requires expression of CD95 ligand on activated T cells followed by an interaction between CD95 ligand and the CD95 receptor also expressed on this population.@@@@1@32@@oe@16-12-2010 914447205@GENIA Treebank@formal@@1@S@The experiments reported in this study were designed to address the signaling events triggered by TCR engagement that are important for regulating CD95 ligand gene expression.@@@@1@27@@oe@16-12-2010 914447206@GENIA Treebank@formal@@1@S@To approach this, we generated a luciferase reporter construct containing elements of the CD95 ligand promoter.@@@@1@18@@oe@16-12-2010 914447207@GENIA Treebank@formal@@1@S@Using a previously described mutant of the Jurkat T cell line, we show that proximal signaling events dependent on the presence of the CD45 tyrosine phosphatase are required for TCR-stimulated CD95 ligand expression.@@@@1@35@@oe@16-12-2010 914447208@GENIA Treebank@formal@@1@S@Transient transfection studies demonstrate further that TCR-stimulated activation of the Ras signaling pathway is required for optimal activation of CD95 ligand.@@@@1@22@@oe@16-12-2010 914447209@GENIA Treebank@formal@@1@S@Next, in an effort to determine critical transcription factors that regulate CD95 ligand expression, we demonstrate a cyclosporin A-sensitive nuclear factor-AT response element in the promoter region of this gene that is critical for optimal CD95 ligand reporter activity in stimulated T cells.@@@@1@46@@oe@16-12-2010 914447210@GENIA Treebank@formal@@1@S@Together, these studies begin a dissection of the biochemical events that lead to expression of CD95 ligand, a required step for TCR-induced apoptosis.@@@@1@26@@oe@16-12-2010 914447901@GENIA Treebank@formal@@1@S@CD40 is a functional activation antigen and B7-independent T cell costimulatory molecule on normal human lung fibroblasts.@@@@1@18@@oe@16-12-2010 914447902@GENIA Treebank@formal@@1@S@CD40 is an important signaling and activation Ag found on certain bone marrow-derived cells.@@@@1@15@@oe@16-12-2010 914447903@GENIA Treebank@formal@@1@S@Recently, CD40 also has been shown to be expressed by mesenchymal cells, including human fibroblasts.@@@@1@18@@oe@16-12-2010 914447904@GENIA Treebank@formal@@1@S@Little is known about the role of CD40 in fibroblasts.@@@@1@11@@oe@16-12-2010 914447905@GENIA Treebank@formal@@1@S@The current study investigates the hypothesis that CD40 expressed on lung fibroblasts is an activation structure and mechanism for interaction with hemopoietic cells.@@@@1@24@@oe@16-12-2010 914447906@GENIA Treebank@formal@@1@S@Communication between resident tissue fibroblasts and T cells is necessary for normal wound healing, and can be pathologic, resulting in tissue fibrosis.@@@@1@25@@oe@16-12-2010 914447907@GENIA Treebank@formal@@1@S@Signaling through CD40 with soluble CD40 ligand stimulated fibroblast activation, as evidenced by mobilization of nuclear factor-kappaB and by induction of the proinflammatory and chemoattractant cytokines IL-6 and IL-8.@@@@1@31@@oe@16-12-2010 914447908@GENIA Treebank@formal@@1@S@IFN-gamma-primed lung fibroblasts costimulate T lymphocyte proliferation utilizing CD40, but not the well-studied costimulatory molecules B7-1 and B7-2.@@@@1@20@@oe@16-12-2010 914447909@GENIA Treebank@formal@@1@S@Data reported herein support the hypothesis that cognate interactions between tissue fibroblasts and infiltrating T lymphocytes, via the CD40/CD40L pathway, augment inflammation and may promote fibrogenesis by activating both cell types.@@@@1@34@@oe@16-12-2010 914449601@GENIA Treebank@formal@@1@S@HLA-DMA and HLA-DMB gene expression functions through the conserved S-X-Y region.@@@@1@12@@oe@16-12-2010 914449602@GENIA Treebank@formal@@1@S@The MHC class II homologous proteins HLA-DMA and HLA-DMB function in the loading of peptides onto class II molecules.@@@@1@20@@oe@16-12-2010 914449603@GENIA Treebank@formal@@1@S@Like the class II genes, the HLA-DM genes contain upstream regulatory sequences similar to the S-X-Y regulatory region as well as additional putative regulatory sites.@@@@1@27@@oe@16-12-2010 914449604@GENIA Treebank@formal@@1@S@To determine whether the DM genes are regulated in a similar manner as class II genes, a series of in vivo and in vitro analyses was performed.@@@@1@29@@oe@16-12-2010 914449605@GENIA Treebank@formal@@1@S@Deletion analysis showed that expression from the DM promoters is dependent on the conserved S-X-Y region.@@@@1@17@@oe@16-12-2010 914449606@GENIA Treebank@formal@@1@S@The class II-specific transcription factors RFX and CIITA are also required for expression, as cell lines deficient in these factors failed to allow transcription from the DM promoters.@@@@1@30@@oe@16-12-2010 914449607@GENIA Treebank@formal@@1@S@In addition, in vivo footprint analysis showed the putative X and Y boxes to be occupied by transcription factors in wild-type B cells, but not in RFX-deficient B cells.@@@@1@32@@oe@16-12-2010 914449608@GENIA Treebank@formal@@1@S@In astrocytes, IFN-gamma treatment induced increased occupancy of these sites.@@@@1@12@@oe@16-12-2010 914449609@GENIA Treebank@formal@@1@S@None of the other putative regulatory sites was occupied in vivo, indicating that they may not be functional.@@@@1@20@@oe@16-12-2010 914449610@GENIA Treebank@formal@@1@S@Finally, gel shift analysis showed synergistic complex formation between proteins that bind to the putative X boxes of the DM genes, as is found for the DRA gene.@@@@1@31@@oe@16-12-2010 914449611@GENIA Treebank@formal@@1@S@Therefore, the DM genes share a common mechanism of regulation with the class II genes.@@@@1@17@@oe@16-12-2010 914682401@GENIA Treebank@formal@@1@S@Plasma sialyltransferase levels in psychiatric disorders as a possible indicator of HPA axis function.@@@@1@15@@oe@16-12-2010 914682402@GENIA Treebank@formal@@1@S@A dysfunction in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis, possibly attributed to a change in glucocorticoid receptor (GR) functionality, has been implicated in depression.@@@@1@32@@oe@16-12-2010 914682403@GENIA Treebank@formal@@1@S@We have measured both lymphocyte GR receptor binding parameters and plasma sialyltransferase activity, as a biochemical marker of GR function, in two groups of patients suffering from depression or schizophrenia and in a group of age- and sex-matched controls.@@@@1@42@@oe@16-12-2010 914682404@GENIA Treebank@formal@@1@S@While there was a significant increase in plasma cortisol levels in the depressed group, there were no changes in the lymphocyte GR binding parameters (K(m) and Bmax).@@@@1@34@@oe@16-12-2010 914682405@GENIA Treebank@formal@@1@S@There was, however, a significant decrease in the plasma sialyltransferase: cortisol ratio in the depressed group suggesting an inability of the raised cortisol levels to induce enzyme expression and this ratio may provide a useful biochemical marker of cortisol receptor function.@@@@1@45@@oe@16-12-2010 914682406@GENIA Treebank@formal@@1@S@Although there was an increase in the plasma activity of the alpha 2,6 sialyltransferase isozyme in the schizophrenic group, no other changes were determined.@@@@1@26@@oe@16-12-2010 914682407@GENIA Treebank@formal@@1@S@Therefore, while the total plasma sialyltransferase:cortisol ratio reflects HPA axis function, alterations in specific isozyme activity may also be associated with other CNS disease states.@@@@1@30@@oe@16-12-2010 914990901@GENIA Treebank@formal@@1@S@Triggering of HLA-DR antigens differentially modulates tumor necrosis factor alpha release by B cells at distinct stage of maturation.@@@@1@20@@oe@16-12-2010 914990902@GENIA Treebank@formal@@1@S@Triggering of HLA class II antigens by the anti-HLA-DR monoclonal antibody (mAb) L243 significantly (P < 0.05) and differentially enhanced the release of tumor necrosis factor alpha (TNF-alpha) by the non-Hodgkin's lymphoma cells Ri-I, Ci-I, and Sc-I, which are at a distinct stage of B-cell differentiation, and by the more mature Burkitt lymphoma cell Raji; in contrast, it did not induce TNF-alpha release by the pre-B leukemia cells Nalm-6 and BV173.@@@@1@85@@oe@16-12-2010 914990903@GENIA Treebank@formal@@1@S@TNF-alpha release peaked at 24 h and decreased thereafter, and it was dose dependent and preceded by an increase of TNF-alpha mRNA detectable after 3 h of stimulation with mAb L243.@@@@1@33@@oe@16-12-2010 914990904@GENIA Treebank@formal@@1@S@Secreted TNF-alpha mediated the enhancement of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) binding activity; in fact, the triggering of HLA-DR antigens in the presence of antihuman TNF-alpha-neutralizing antibodies did not upregulate NF-kappa B and AP-1.@@@@1@46@@oe@16-12-2010 914990905@GENIA Treebank@formal@@1@S@In contrast, released TNF-alpha was not responsible for the homotypic aggregation of Ri-I, Ci-I, Sc-I, and Raji cells induced by mAb L243, and it did not affect the proliferation of B cells investigated.@@@@1@39@@oe@16-12-2010 914990906@GENIA Treebank@formal@@1@S@Altogether, our data demonstrate that: (a) the ability of B cells to release TNF-alpha after triggering of HLA-DR antigens depends on their stage of differentiation; (b) levels of released TNF-alpha seem to correlate with the stage of B-cell maturation but do not correlate with the amounts of cell surface HLA-DR antigens; (c) secreted TNF-alpha regulates the levels of expression of NF-kappa B and AP-1 by an autocrine loop; and (d) intracellular signals mediating TNF-alpha release by B cells are distinct from those regulating homotypic aggregation and proliferation.@@@@1@101@@oe@16-12-2010 915170801@GENIA Treebank@formal@@1@S@A new mouse gene, SRG3, related to the SWI3 of Saccharomyces cerevisiae, is required for apoptosis induced by glucocorticoids in a thymoma cell line.@@@@1@28@@oe@16-12-2010 915170802@GENIA Treebank@formal@@1@S@We isolated a new mouse gene that is highly expressed in thymocytes, testis, and brain.@@@@1@18@@oe@16-12-2010 915170803@GENIA Treebank@formal@@1@S@This gene, SRG3, showed a significant sequence homology to SWI3, a yeast transcriptional activator, and its human homolog BAF155.@@@@1@24@@oe@16-12-2010 915170804@GENIA Treebank@formal@@1@S@SRG3 encodes 1,100 amino acids and has 33-47% identity with SWI3 protein over three regions.@@@@1@17@@oe@16-12-2010 915170805@GENIA Treebank@formal@@1@S@The SRG3 protein contains an acidic NH2 terminus, a myb-like DNA binding domain, a leucine-zipper motif, and a proline- and glutamine-rich region at its COOH terminus.@@@@1@30@@oe@16-12-2010 915170806@GENIA Treebank@formal@@1@S@Rabbit antiserum raised against a COOH-terminal polypeptide of the SRG3 recognized a protein with an apparent molecular mass of 155 kD.@@@@1@22@@oe@16-12-2010 915170807@GENIA Treebank@formal@@1@S@The serum also detected a 170-kD protein that seems to be a mouse homologue of human BAF170.@@@@1@18@@oe@16-12-2010 915170808@GENIA Treebank@formal@@1@S@Immunoprecipitation of cell extract with the antiserum against the mouse SRG3 also brought down a 195-kD protein that could be recognized by an antiserum raised against human SWI2 protein.@@@@1@30@@oe@16-12-2010 915170809@GENIA Treebank@formal@@1@S@The results suggest that the SRG3 protein associates with a mouse SWI2.@@@@1@13@@oe@16-12-2010 915170810@GENIA Treebank@formal@@1@S@The SRG3 protein is expressed about three times higher in thymocytes than in peripheral lymphocytes.@@@@1@16@@oe@16-12-2010 915170811@GENIA Treebank@formal@@1@S@The expression of anti-sense RNA to SRG3 mRNA in a thymoma cell line, S49.1, reduced the expression level of the SRG3 protein, and decreased the apoptotic cell death induced by glucocorticoids.@@@@1@35@@oe@16-12-2010 915170812@GENIA Treebank@formal@@1@S@These results suggest that the SRG3 protein is involved in the glucocorticoid-induced apoptosis in the thymoma cell line.@@@@1@19@@oe@16-12-2010 915170813@GENIA Treebank@formal@@1@S@This implicates that the SRG3 may play an important regulatory role during T cell development in thymus.@@@@1@18@@oe@16-12-2010 915189801@GENIA Treebank@formal@@1@S@Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response.@@@@1@19@@oe@16-12-2010 915189802@GENIA Treebank@formal@@1@S@Epstein-Barr virus (EBV), a human gamma-herpesvirus, can establish both nonproductive (latent) and productive (lytic) infections.@@@@1@24@@oe@16-12-2010 915189803@GENIA Treebank@formal@@1@S@Although the CD8+ cytotoxic T lymphocyte (CTL) response to latently infected cells is well characterized, very little is known about T cell controls over lytic infection; this imbalance in our understanding belies the importance of virus-replicative lesions in several aspects of EBV disease pathogenesis.@@@@1@49@@oe@16-12-2010 915189804@GENIA Treebank@formal@@1@S@The present work shows that the primary CD8+ CTL response to EBV in infectious mononucleosis patients contains multiple lytic antigen-specific reactivities at levels at least as high as those seen against latent antigens; similar reactivities are also detectable in CTL memory.@@@@1@43@@oe@16-12-2010 915189805@GENIA Treebank@formal@@1@S@Clonal analysis revealed individual responses to the two immediate early proteins BZLF1 and BRLF1, and to three (BMLF1, BMRF1, and BALF2) of the six early proteins tested.@@@@1@33@@oe@16-12-2010 915189806@GENIA Treebank@formal@@1@S@In several cases, the peptide epitope and HLA-restricting determinant recognized by these CTLs has been defined, one unusual feature being the number of responses restricted through HLA-C alleles.@@@@1@31@@oe@16-12-2010 915189807@GENIA Treebank@formal@@1@S@The work strongly suggests that EBV-replicative lesions are subject to direct CTL control in vivo and that immediate early and early proteins are frequently the immunodominant targets.@@@@1@28@@oe@16-12-2010 915189808@GENIA Treebank@formal@@1@S@This contrasts with findings in alpha- and beta- herpesvirus systems (herpes simplex, cytomegalovirus) where viral interference with the antigen-processing pathway during lytic infection renders immediate early and early proteins much less immunogenic.@@@@1@35@@oe@16-12-2010 915189809@GENIA Treebank@formal@@1@S@The unique capacity of gamma-herpesvirus to amplify the viral load in vivo through a latent growth-transforming infection may have rendered these agents less dependent upon viral replication as a means of successfully colonizing their hosts.@@@@1@36@@oe@16-12-2010 915429801@GENIA Treebank@formal@@1@S@Cytomegalovirus immediate early genes upregulate interleukin-6 gene expression.@@@@1@9@@oe@16-12-2010 915429802@GENIA Treebank@formal@@1@S@BACKGROUND: The immediate early genes (IE) of human cytomegalovirus (CMV) can be expressed in monocytic cells and are known to regulate viral and cellular genes.@@@@1@31@@oe@16-12-2010 915429803@GENIA Treebank@formal@@1@S@Interleukin-6 (IL-6) plays a central role in numerous inflammatory and immune processes.@@@@1@15@@oe@16-12-2010 915429804@GENIA Treebank@formal@@1@S@Interleukin-6 levels are increased in lung transplant patients clinically diagnosed with CMV pneumonitis.@@@@1@14@@oe@16-12-2010 915429805@GENIA Treebank@formal@@1@S@The regulation of IL-6 is dependent on various stimuli that include lipopolysaccharide (LPS), viruses, and other cytokines.@@@@1@22@@oe@16-12-2010 915429806@GENIA Treebank@formal@@1@S@These studies examined the ability of CMV IE gene products to modulate IL-6 production.@@@@1@15@@oe@16-12-2010 915429807@GENIA Treebank@formal@@1@S@METHODS: THP-1 cells, a monocytic cell line, were transfected with the CMV IE genes.@@@@1@18@@oe@16-12-2010 915429808@GENIA Treebank@formal@@1@S@Interleukin-6 protein and IL-6 mRNA were measured in control and CMV immediate early transfected cells.@@@@1@16@@oe@16-12-2010 915429809@GENIA Treebank@formal@@1@S@Cotransfection of CMV IE genes and IL-6 chloramphenicol acetyl transferase (CAT) or IL-6 luciferase constructs were used to study IL-6 promoter activity.@@@@1@25@@oe@16-12-2010 915429810@GENIA Treebank@formal@@1@S@RESULTS: Interleukin-6 protein and mRNA production were significantly increased in cells transfected with the CMV IE genes and stimulated with LPS compared to LPS-stimulated control cells.@@@@1@28@@oe@16-12-2010 915429811@GENIA Treebank@formal@@1@S@Cytomegalovirus IE gene products significantly enhanced LPS stimulation of IL-6 promoter activity in both IL-6 CAT and IL-6 luciferase assays.@@@@1@21@@oe@16-12-2010 915429812@GENIA Treebank@formal@@1@S@A deletion construct that contains a NF-kappa B site but is missing the multiple response region demonstrated a continued increase in IL-6 luciferase activity in LPS-stimulated CMV transfected cells.@@@@1@30@@oe@16-12-2010 915429813@GENIA Treebank@formal@@1@S@CONCLUSION: Cytomegalovirus immediate early gene products significantly enhanced expression of IL-6 in LPS-stimulated cells.@@@@1@16@@oe@16-12-2010 915429814@GENIA Treebank@formal@@1@S@The increase in IL-6 luciferase activity occurs in the absence of the multiple response region, the area of the IL-6 promoter responsive to IL-1, TNF alpha, cyclic amp, and phorbol 12-myristate 13-acetate.@@@@1@37@@oe@16-12-2010 915429815@GENIA Treebank@formal@@1@S@The ability of CMV IE gene products to enhance IL-6 production may play an important role in immune inflammatory states associated with CMV infection.@@@@1@25@@oe@16-12-2010 915564001@GENIA Treebank@formal@@1@S@Involvement of Stat3 in interleukin-6-induced IgM production in a human B-cell line.@@@@1@13@@oe@16-12-2010 915564002@GENIA Treebank@formal@@1@S@Interleukin-6 (IL-6) is an important B-cell growth and differentiation factor.@@@@1@13@@oe@16-12-2010 915564003@GENIA Treebank@formal@@1@S@IL-6 treatment of the human lymphoblastoid cell line, SKW6.4, leads to increased IgM production.@@@@1@17@@oe@16-12-2010 915564004@GENIA Treebank@formal@@1@S@We have previously shown that IL-6 induces activation of JAK1 and JAK2 in human B cell lines.@@@@1@18@@oe@16-12-2010 915564005@GENIA Treebank@formal@@1@S@A chimeric IL-6 receptor, comprised of the intracellular tail of the IL-6 receptor subunit gp130 fused to the extracellular domain of the epidermal growth factor (EGF) receptor, was stably transfected into SKW6.4 cells.@@@@1@38@@oe@16-12-2010 915564006@GENIA Treebank@formal@@1@S@EGF treatment induced IgM production in cells transfected with an intact gp130 cytoplasmic tail, but not in untransfected cells or cells transfected with a cytoplasmic tail lacking all four signal transducers and activators of transcription (Stat) binding sites.@@@@1@42@@oe@16-12-2010 915564007@GENIA Treebank@formal@@1@S@Moreover, EGF treatment induced Stat3 phosphorylation in cells transfected with the intact chimeric EGF-gp130 receptor along with induction of DNA-mobility shift of a classical interferon-gamma-activated site.@@@@1@28@@oe@16-12-2010 915564008@GENIA Treebank@formal@@1@S@To define further the relation between Stat3 activation and enhanced IgM production, we determined the effect of chimeric gp130 on the transcriptional activation of a genetic element linked to immunoglobulin production, namely the immunoglobulin heavy chain enhancer (IgH-enhancer).@@@@1@43@@oe@16-12-2010 915564009@GENIA Treebank@formal@@1@S@Parental as well as transfected SKW6.4 cells were transiently transfected with an IgH-enhancer-luciferase construct.@@@@1@15@@oe@16-12-2010 915564010@GENIA Treebank@formal@@1@S@The transcriptional activity of the IgH-luciferase construct was induced upon ligation of the full-length chimeric receptor but not by truncated gp130 receptors.@@@@1@23@@oe@16-12-2010 915564011@GENIA Treebank@formal@@1@S@Moreover, the gp130-induced activity of this reporter gene was abrogated by Stat3EE, a mutant Stat3 incapable of binding DNA.@@@@1@22@@oe@16-12-2010 915564012@GENIA Treebank@formal@@1@S@These results indicate that IL-6-induced B-cell differentiation, as measured by IgM production, may be controlled by Stat3 proteins.@@@@1@21@@oe@16-12-2010 915565501@GENIA Treebank@formal@@1@S@Cellular redox status influences both cytotoxic and NF-kappa B activation in natural killer cells.@@@@1@15@@oe@16-12-2010 915565502@GENIA Treebank@formal@@1@S@The role of cellular redox status in both cytotoxic activity and NF-kappa B activation in natural killer (NK) cells was investigated.@@@@1@24@@oe@16-12-2010 915565503@GENIA Treebank@formal@@1@S@The results indicate that stimulation of NK cells, either freshly isolated from peripheral blood lymphocytes (PBL) or long-term cultured NK clones, with specific cell targets results in an increased binding activity of NF-kappa B and AP-1 transcription factors measured by gel retardation.@@@@1@47@@oe@16-12-2010 915565504@GENIA Treebank@formal@@1@S@Pretreatment of NK cells with the antioxidant pyrrolidine dithiocarbarmate (PDTC) leads to the inhibition of NF-kappa B activation but the AP-1 binding to DNA was superinduced.@@@@1@29@@oe@16-12-2010 915565505@GENIA Treebank@formal@@1@S@The inhibition of NF-kappa B by PDTC paralleled with an inhibition of spontaneous cytotoxicity mediated by NK cells.@@@@1@19@@oe@16-12-2010 915565506@GENIA Treebank@formal@@1@S@Moreover, the inhibitors of serine proteases, N-alpha-tosyl-L-lysine chloromethyl ketone and N-alpha-tosyl-L-phenylalanine chloromethyl ketone, also blocked the cytolytic activity of NK cells against the sensitive target K562.@@@@1@30@@oe@16-12-2010 915565507@GENIA Treebank@formal@@1@S@In contrast, NK activity was not affected by pretreatment of the effector cells with the proteasome inhibitor N-acetyl-leu-leu-norleucinal which selectively inhibits NF-kappa B activation.@@@@1@26@@oe@16-12-2010 915565508@GENIA Treebank@formal@@1@S@Altogether, these results support the hypothesis that the activation of NK cells involved transcriptional and post-transcriptional events, and that reactive intermediates may play an important role in the molecular processes related with the generation of a cytotoxic response by NK cells.@@@@1@44@@oe@16-12-2010 915916601@GENIA Treebank@formal@@1@S@Homodimerization of the human interleukin 4 receptor alpha chain induces Cepsilon germline transcripts in B cells in the absence of the interleukin 2 receptor gamma chain.@@@@1@27@@oe@16-12-2010 915916602@GENIA Treebank@formal@@1@S@The cytokines interleukin (IL)-4 and IL-13 play a critical role in inducing Cepsilon germline transcripts and IgE isotype switching in human B cells.@@@@1@27@@oe@16-12-2010 915916603@GENIA Treebank@formal@@1@S@The IL-4 receptor (IL-4R) in B cells is composed of two chains, the IL-4-binding IL-4Ralpha chain, which is shared with the IL-13R, and the IL-2Rgamma (gammac) chain, which is shared with IL-7R, IL-9R, and IL-15R.@@@@1@46@@oe@16-12-2010 915916604@GENIA Treebank@formal@@1@S@IL-4 induces Cepsilon germline transcripts and IgE isotype switching in B cells from patients with gammac chain deficiency.@@@@1@19@@oe@16-12-2010 915916605@GENIA Treebank@formal@@1@S@Induction of Cepsilon germline transcripts by IL-4 in B cells that lack the gammac chain may involve signaling via the IL-13R.@@@@1@22@@oe@16-12-2010 915916606@GENIA Treebank@formal@@1@S@Alternatively, the IL-4Ralpha chain may transduce intracellular signals that lead to Cepsilon gene transcription independently of its association with other chains.@@@@1@23@@oe@16-12-2010 915916607@GENIA Treebank@formal@@1@S@We show that ligand-induced homodimerization of chimeric surface receptors consisting of the extracellular and transmembrane domains of the erythropoietin receptor and of the intracellular domain of IL-4Ralpha induces Janus kinase 1 (Jak1) activation, STAT6 activation, and Cepsilon germline transcripts in human B cell line BJAB.@@@@1@50@@oe@16-12-2010 915916608@GENIA Treebank@formal@@1@S@Disruption of the Jak1-binding proline-rich Box1 region of IL-4Ralpha abolished signaling by this chimeric receptor.@@@@1@16@@oe@16-12-2010 915916609@GENIA Treebank@formal@@1@S@Furthermore, B cells transfected with a chimeric CD8alpha/IL-4Ralpha receptor, which is expressed on the cell surface as a homodimer, constitutively expressed Cepsilon germline transcripts.@@@@1@28@@oe@16-12-2010 915916610@GENIA Treebank@formal@@1@S@These results suggest that homodimerization of the IL-4Ralpha chain is sufficient to transduce Jak1-dependent intracellular signals that lead to IgE isotype switching.@@@@1@23@@oe@16-12-2010 916088701@GENIA Treebank@formal@@1@S@Characterization of peripheral blood T-lymphocytes transduced with HTLV-I Tax mutants with different trans-activating phenotypes.@@@@1@15@@oe@16-12-2010 916088702@GENIA Treebank@formal@@1@S@Tax1, a transcriptional trans-activator of the Human T-cell leukemia virus type I (HTLV-I), induces the expression of many cellular genes through interaction with at least three distinct cellular transcription factors; CREB/ATF, NF-kappaB, and SRF.@@@@1@42@@oe@16-12-2010 916088703@GENIA Treebank@formal@@1@S@This Tax1-induced activation of cellular genes is considered to be a critical event in T-cell transformation by HTLV-I.@@@@1@19@@oe@16-12-2010 916088704@GENIA Treebank@formal@@1@S@To elucidate the role of each Tax1-inducible transcriptional pathway in T-cell transformation, we introduced Tax1 mutants with different trans-activating phenotypes into peripheral blood lymphocytes (PBL) by retroviral vectors.@@@@1@32@@oe@16-12-2010 916088705@GENIA Treebank@formal@@1@S@Analysis of these PBLs revealed that activation of the NF-kappaB pathway is sufficient to promote the growth response to IL-2.@@@@1@21@@oe@16-12-2010 916088706@GENIA Treebank@formal@@1@S@However, for the clonal expansion of CD4+ T-cells, which is a characteristic result of HTLV-I infection, activation of the CREB/ATF and SRF pathways is also required.@@@@1@30@@oe@16-12-2010 916209101@GENIA Treebank@formal@@1@S@Involvement of phosphatidylinositol 3-kinase in NFAT activation in T cells.@@@@1@11@@oe@16-12-2010 916209102@GENIA Treebank@formal@@1@S@Phosphatidylinositol 3-kinase (PI3-K) has been implicated in the regulation of cell proliferation in many cell types.@@@@1@19@@oe@16-12-2010 916209103@GENIA Treebank@formal@@1@S@We have previously shown that in T cells the PI3-K inhibitor, wortmannin, interferes with activation of the mitogen-activated kinase, Erk2, after T cell receptor (TcR) stimulation.@@@@1@33@@oe@16-12-2010 916209104@GENIA Treebank@formal@@1@S@To further explore the involvement of PI3-K in T cell activation, we created a set of potentially dominant negative PI3-K constructs comprising individual or tandem domains of the regulatory p85 subunit and tested their effect on downstream signaling events like Erk2 activation and transcription from an NFAT (nuclear factor of activated T cells) element taken from the interleukin-2 promoter.@@@@1@63@@oe@16-12-2010 916209105@GENIA Treebank@formal@@1@S@Following TcR stimulation, activation of Erk2 was only inhibited by a previously described truncated form of p85 that cannot bind the catalytic subunit, but not by other constructs of p85.@@@@1@34@@oe@16-12-2010 916209106@GENIA Treebank@formal@@1@S@In contrast, several mutant p85 alleles had dramatic effects on NFAT activation.@@@@1@14@@oe@16-12-2010 916209107@GENIA Treebank@formal@@1@S@Most interestingly, the N-terminal SH2 domain had an inhibitory effect, whereas a mutant p85 containing only the two SH2 domains enhanced basal NFAT activity in a Ras-dependent manner.@@@@1@31@@oe@16-12-2010 916209108@GENIA Treebank@formal@@1@S@Ionomycin induced synergistic activation of NFAT in cells expressing p85 mutants that contained the C-terminal SH2 domain.@@@@1@18@@oe@16-12-2010 916209109@GENIA Treebank@formal@@1@S@Analysis of phosphotyrosine-containing proteins bound to truncated p85 constructs revealed cooperative binding of the two SH2 domains but no apparent differences between the N- and C- terminal SH2 domains.@@@@1@29@@oe@16-12-2010 916209110@GENIA Treebank@formal@@1@S@Wortmannin did not interfere with NFAT activation, although it inhibited PI3-K and Erk2 activation in the same experiment.@@@@1@20@@oe@16-12-2010 916209111@GENIA Treebank@formal@@1@S@These results suggest that PI3-K is involved in NFAT activation through a complex adaptor function of its regulatory subunit and that its lipid kinase activity is dispensable for this effect.@@@@1@31@@oe@16-12-2010 916484101@GENIA Treebank@formal@@1@S@Involvement of the N-terminal region of the human mineralocorticoid receptor hormone-binding domain in agonist and antagonist binding as revealed by a new monoclonal antibody.@@@@1@25@@oe@16-12-2010 916484102@GENIA Treebank@formal@@1@S@To gain a better understanding of the mechanism of binding to the human mineralocorticoid receptor (hMR), we developed a new monoclonal antibody (mAb) raised against the hormone-binding domain (HBD).@@@@1@37@@oe@16-12-2010 916484103@GENIA Treebank@formal@@1@S@For this purpose, mice were immunized with a fusion protein including the sequence Thr729-Lys984 of hMR.@@@@1@18@@oe@16-12-2010 916484104@GENIA Treebank@formal@@1@S@After ELISA screening, mAb 18C7 was selected for its specificity towards the HBD.@@@@1@15@@oe@16-12-2010 916484105@GENIA Treebank@formal@@1@S@This antibody recognized both the denatured and native MR forms, as well as the hetero-oligomeric MR form and the transformed MR state.@@@@1@24@@oe@16-12-2010 916484106@GENIA Treebank@formal@@1@S@By using several HBD subfragments, the mAb 18C7 epitope was located in the N-terminal region of the HBD from Thr729 to Leu765.@@@@1@24@@oe@16-12-2010 916484107@GENIA Treebank@formal@@1@S@We then studied the effect of the antibody on aldosterone and progesterone binding to the hMR.@@@@1@17@@oe@16-12-2010 916484108@GENIA Treebank@formal@@1@S@When 18C7 was incubated with liganded MR, it was able to partly displace (20%) the hormone from its binding site.@@@@1@25@@oe@16-12-2010 916484109@GENIA Treebank@formal@@1@S@When 18C7 was incubated with MR before aldosterone or progesterone, the antibody inhibited 75-80% of the binding.@@@@1@20@@oe@16-12-2010 916484110@GENIA Treebank@formal@@1@S@The effect of 18C7 on the binding was similar with both hormones.@@@@1@13@@oe@16-12-2010 916484111@GENIA Treebank@formal@@1@S@A sucrose gradient analysis indicated the simultaneous presence of two kinds of receptor complexes: the steroid-MR complex and the antibody-MR complex.@@@@1@23@@oe@16-12-2010 916484112@GENIA Treebank@formal@@1@S@After its associated proteins, especially the heat-shock protein hsp90, had been cross-linked with the hMR by dimethylpimelimidate, 18C7 was still able to react with the receptor.@@@@1@30@@oe@16-12-2010 916484113@GENIA Treebank@formal@@1@S@Our results indicated that the epitope recognized by 18C7 was directly implicated in hormone binding.@@@@1@16@@oe@16-12-2010 916484114@GENIA Treebank@formal@@1@S@The lack of steroid binding of HBD mutants with the Thr729-Leu765 sequence deleted [Jalaguier, Mesnier, Leger and Auzou (1996) J.Steroid Biochem.Mol.Biol.57, 43-50] supports this hypothesis.@@@@1@33@@oe@16-12-2010 916484115@GENIA Treebank@formal@@1@S@Because of the similar behaviours of aldosterone and progesterone, we conclude that the N-terminal Thr729-Leu765 region of the HBD is similarly involved in the binding of both hormones.@@@@1@30@@oe@16-12-2010 916491901@GENIA Treebank@formal@@1@S@Abnormal T lymphocyte development induced by targeted overexpression of IkappaB alpha.@@@@1@12@@oe@16-12-2010 916491902@GENIA Treebank@formal@@1@S@A role in thymic maturation for factors of the NF-kappaB family has long been suspected, but not yet proven.@@@@1@21@@oe@16-12-2010 916491903@GENIA Treebank@formal@@1@S@Transgenic mice with a lymphocyte-specific defect in NF-kappaB activation were produced by targeted expression of human IkappaB alpha.@@@@1@19@@oe@16-12-2010 916491904@GENIA Treebank@formal@@1@S@The thymic cellularity of these mice was significantly decreased.@@@@1@10@@oe@16-12-2010 916491905@GENIA Treebank@formal@@1@S@The proportion of mature, TCRhigh thymocytes of the alphabeta lineage was reduced, and the remaining TCRhigh population contained an unusually high proportion of double-positive cells.@@@@1@28@@oe@16-12-2010 916491906@GENIA Treebank@formal@@1@S@This defect in maturation resulted in a transgene dose-dependent reduction in peripheral T lymphocytes, with the CD8 lineage being more severely affected.@@@@1@24@@oe@16-12-2010 916491907@GENIA Treebank@formal@@1@S@These data provide direct evidence for the involvement of NF-kappaB/Rel family proteins in late stages of T lymphocyte development, coincident with positive and negative selection.@@@@1@27@@oe@16-12-2010 916494801@GENIA Treebank@formal@@1@S@Sequential development of structural and functional alterations in T cells from tumor-bearing mice.@@@@1@14@@oe@16-12-2010 916494802@GENIA Treebank@formal@@1@S@The TCR alpha beta or -gamma delta chains bind the peptide ligand, whereas the associated CD3 delta epsilon gamma and TCR zeta subunits couple the TCR to intracellular signal transduction components.@@@@1@33@@oe@16-12-2010 916494803@GENIA Treebank@formal@@1@S@Recently, several groups have described marked alterations in signal transduction elements in T cells from cancer patients or in mice bearing tumor for a few weeks (>26 days).@@@@1@33@@oe@16-12-2010 916494804@GENIA Treebank@formal@@1@S@The sequence in which these alterations develop is unknown.@@@@1@10@@oe@16-12-2010 916494805@GENIA Treebank@formal@@1@S@The aim of this study was to explore the kinetics of the development of alterations in signal transduction molecules (TCR zeta chain, NF kappaB family proteins, and tyrosine kinase p56(lck)) in mice bearing MC38 colon adenocarcinoma.@@@@1@44@@oe@16-12-2010 916494806@GENIA Treebank@formal@@1@S@The results demonstrate that alterations in NF kappaB family proteins, specifically the failure of p65 translocation to the nucleus, occur earlier and more frequently than the decrease in zeta-chain.@@@@1@32@@oe@16-12-2010 916494807@GENIA Treebank@formal@@1@S@These defects are paralleled by an impaired ability to produce Th1 cytokines (IL-2 and IFN-gamma).@@@@1@18@@oe@16-12-2010 916494808@GENIA Treebank@formal@@1@S@These initial changes are followed by the eventual loss of TCR zeta chain and p56(lck) and a marked decrease in cytotoxic function.@@@@1@26@@oe@16-12-2010 916494809@GENIA Treebank@formal@@1@S@An increased rate of lysosomal degradation is one of the mechanisms responsible for the loss of zeta-chain.@@@@1@18@@oe@16-12-2010 916641801@GENIA Treebank@formal@@1@S@An isotype-specific activator of major histocompatibility complex (MHC) class II genes that is independent of class II transactivator.@@@@1@21@@oe@16-12-2010 916641802@GENIA Treebank@formal@@1@S@Patients with one type of major histocompatibility complex class II combined immunodeficiency have mutations in a gene termed class II transactivator (CIITA), which coordinately controls the transcription of the three major human class II genes, HLA-DR, -DQ, and -DP.@@@@1@46@@oe@16-12-2010 916641803@GENIA Treebank@formal@@1@S@However, the experimentally derived B-lymphoblastoid cell line, clone 13, expresses high levels of HLADQ in the absence of HLA-DR and HLA-DP, despite its mapping by complementation analysis to this group.@@@@1@35@@oe@16-12-2010 916641804@GENIA Treebank@formal@@1@S@It was possible that one of the clone 13 CIITA alleles bore a mutation that allowed HLA-DQ, but not HLA-DR or -DP transcription.@@@@1@25@@oe@16-12-2010 916641805@GENIA Treebank@formal@@1@S@Alternatively, another factor, distinct from CIITA, might control HLA-DQ expression.@@@@1@14@@oe@16-12-2010 916641806@GENIA Treebank@formal@@1@S@We report here that ectopic expression of CIITA cDNAs derived by reverse transcriptase polymerase chain reaction from clone 13 do not restore expression of HLA-DQ in another CIITA-deficient cell line, RJ2.2.5.@@@@1@33@@oe@16-12-2010 916641807@GENIA Treebank@formal@@1@S@In addition, no CIITA protein is detectable in clone 13 nuclear extracts.@@@@1@14@@oe@16-12-2010 916641808@GENIA Treebank@formal@@1@S@In contrast, somatic cell fusion between clone 13 and RJ2.2.5 restored expression of the HLA-DQ haplotype encoded by the RJ2.2.5 DQB gene.@@@@1@24@@oe@16-12-2010 916641809@GENIA Treebank@formal@@1@S@Taken together, these data demonstrate the existence of an HLA-DQ isotype-specific trans-acting factor, which functions independently of CIITA.@@@@1@21@@oe@16-12-2010 916685701@GENIA Treebank@formal@@1@S@Characterization of interleukin-10 receptor expression on B-cell chronic lymphocytic leukemia cells.@@@@1@12@@oe@16-12-2010 916685702@GENIA Treebank@formal@@1@S@B-cell chronic lymphocytic leukemia (B-CLL) cells accumulate in vivo in the G0/G1 phase of the cell cycle, suggesting that their malignant expansion is due, at least in part, to a delay in cell death.@@@@1@40@@oe@16-12-2010 916685703@GENIA Treebank@formal@@1@S@However, the cellular or molecular factors responsible for a delay in B-CLL cell death are unknown.@@@@1@18@@oe@16-12-2010 916685704@GENIA Treebank@formal@@1@S@B-CLL cells do express receptors for interferon-alpha (IFN-alpha) and IFN-gamma, and activation of both has been shown to promote B-CLL survival in vitro by preventing apoptosis.@@@@1@30@@oe@16-12-2010 916685705@GENIA Treebank@formal@@1@S@The interleukin-10 (IL-10) receptor is another member of the IFN receptor family, but its ligand, IL-10, has been reported to induce apoptosis in B-CLL cells.@@@@1@31@@oe@16-12-2010 916685706@GENIA Treebank@formal@@1@S@In the current study, we undertook a biochemical analysis of IL-10 receptor expression on freshly isolated B-CLL cells and characterized the functional responsiveness of IL-10 binding to its constitutively expressed receptor.@@@@1@33@@oe@16-12-2010 916685707@GENIA Treebank@formal@@1@S@We show that B-CLL cells bind IL-10 with significant specificity and express between 47 and 127 IL-10 receptor sites per cell, with a dissociation constant in the range of 168 to 426 x 10(-12) mol/L.@@@@1@37@@oe@16-12-2010 916685708@GENIA Treebank@formal@@1@S@Ligand binding and activation of the IL-10 receptor expressed on B-CLL cells results in the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 proteins.@@@@1@31@@oe@16-12-2010 916685709@GENIA Treebank@formal@@1@S@This pattern of STAT protein phosphorylation is identical to IL-10 receptor activation on normal cells and similar to IFN-alpha (STAT1 and STAT3) and IFN-gamma (STAT1) receptor activation in CLL.@@@@1@34@@oe@16-12-2010 916685710@GENIA Treebank@formal@@1@S@Further, in consecutive samples of fresh blood obtained from patients with B-CLL cells, the addition of IL-10 inhibited B-CLL proliferation, enhanced B-CLL differentiation, but did not induce apoptosis.@@@@1@33@@oe@16-12-2010 916685711@GENIA Treebank@formal@@1@S@Indeed, IL-10, like IFN-gamma, was able to significantly reduce the amount of B-CLL cell death caused by hydrocortisone-induced apoptosis.@@@@1@23@@oe@16-12-2010 916685712@GENIA Treebank@formal@@1@S@We conclude that cytokines, which signal through the interferon family of receptors, have comparable functional effects on B-CLL cells.@@@@1@22@@oe@16-12-2010 916881501@GENIA Treebank@formal@@1@S@Uncoupling of cell cycle arrest from the expression of monocytic differentiation markers in HL60 cell variants.@@@@1@17@@oe@16-12-2010 916881502@GENIA Treebank@formal@@1@S@Differentiation generally leads to cell cycle arrest.@@@@1@8@@oe@16-12-2010 916881503@GENIA Treebank@formal@@1@S@Human leukemia HL60 cells respond to the presence of 1,25-dihydroxyvitamin D3 (1,25D3) by expressing a number of markers of the monocyte/macrophage phenotype and become arrested predominantly in the G1 phase of the cell cycle.@@@@1@37@@oe@16-12-2010 916881504@GENIA Treebank@formal@@1@S@We have recently reported a series (A) of 1,25D3-resistant variants of HL60 cells which proliferate in the presence of 1,25D3 and do not express differentiation markers (Exp. Cell Res. 224, 312, 1996).@@@@1@39@@oe@16-12-2010 916881505@GENIA Treebank@formal@@1@S@We now describe another series (B) of such variants, which differ from A series cells grown in similar concentrations of 1,25D3 in that they express the CD14 antigen and nonspecific esterase, characteristic of the monocyte, while continuing to proliferate and they develop hypotetraploid DNA (4C) content at higher concentrations of ambient 1,25D3 than the A series cells.@@@@1@65@@oe@16-12-2010 916881506@GENIA Treebank@formal@@1@S@Cells in the B series with 4C DNA content (100B and 200B) also differed from the A series 4C cells by the absence of DNA binding by the full-length Sp1 transcription factor.@@@@1@35@@oe@16-12-2010 916881507@GENIA Treebank@formal@@1@S@However, B series cells resembled the A series cells in exhibiting faster growth rates than the parental HL60 cells and showed high levels of vitamin D receptor and retinoid receptor X proteins.@@@@1@34@@oe@16-12-2010 916881508@GENIA Treebank@formal@@1@S@These results show that the initial steps in the 1,25D3 signaling pathway are intact in B series resistant cells and lead to the appearance of early markers of monocytic differentiation.@@@@1@31@@oe@16-12-2010 916881509@GENIA Treebank@formal@@1@S@However, the progression to subsequent events which comprise terminal differentiation and cell cycle arrest is halted during the adaptation to the presence of 1,25D3 in these cells.@@@@1@29@@oe@16-12-2010 916881510@GENIA Treebank@formal@@1@S@Thus, the availability of these variant cells should provide a system for studying the link between differentiation and cell cycle arrest.@@@@1@23@@oe@16-12-2010 917040101@GENIA Treebank@formal@@1@S@Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets.@@@@1@12@@oe@16-12-2010 917040102@GENIA Treebank@formal@@1@S@BACKGROUND: Activated platelets tether and activate myeloid leukocytes.@@@@1@10@@oe@16-12-2010 917040103@GENIA Treebank@formal@@1@S@To investigate the potential relevance of this mechanism in acute myocardial infarction (AMI), we examined cytokine induction by leukocyte-platelet adhesion and the occurrence of leukocyte-platelet conjugates in patients with AMI.@@@@1@34@@oe@16-12-2010 917040104@GENIA Treebank@formal@@1@S@METHODS AND RESULTS: We obtained peripheral venous blood samples in 20 patients with AMI before and daily for 5 days after direct percutaneous transluminal coronary angioplasty (PTCA) and in 20 patients undergoing elective PTCA.@@@@1@38@@oe@16-12-2010 917040105@GENIA Treebank@formal@@1@S@Throughout the study period, CD41 immunofluorescence of leukocytes (flow cytometry) revealed increased leukocyte-platelet adhesion in patients with AMI compared with control patients (mean +/- SE of fluorescence [channels] before PTCA: 77 +/- 16 versus 35 +/- 9; P = .003).@@@@1@50@@oe@16-12-2010 917040106@GENIA Treebank@formal@@1@S@In vitro, thrombin-stimulated fixed platelets bound to neutrophils and monocytes.@@@@1@12@@oe@16-12-2010 917040107@GENIA Treebank@formal@@1@S@Within 2 hours, this resulted in increased mRNA for interleukin (IL),1 beta, IL-8, and monocyte chemoattractant protein (MCP)-1 in unfractionated leukocytes.@@@@1@32@@oe@16-12-2010 917040108@GENIA Treebank@formal@@1@S@After 4 hours, IL-1 beta and IL-8 concentration of the cell-free supernatant had increased by 268 +/- 36% and 210 +/- 7%, respectively, and cellular MCP-1 content had increased by 170 +/- 8%.@@@@1@40@@oe@16-12-2010 917040109@GENIA Treebank@formal@@1@S@Addition of activated platelets to adherent monocytes had a similar effect and was associated with nuclear factor-kappa B activation.@@@@1@20@@oe@16-12-2010 917040110@GENIA Treebank@formal@@1@S@Inhibition of binding by anti-P selectin antibodies reduced the effect of activated platelets on cytokine production.@@@@1@17@@oe@16-12-2010 917040111@GENIA Treebank@formal@@1@S@CONCLUSIONS: In patients with AMI, leukocyte-platelet adhesion is increased.@@@@1@12@@oe@16-12-2010 917040112@GENIA Treebank@formal@@1@S@Binding of activated platelets induces IL-1 beta, IL-8, and MCP-1 in leukocytes.@@@@1@15@@oe@16-12-2010 917040113@GENIA Treebank@formal@@1@S@Our findings suggest that leukocyte-platelet adhesion contributes to the regulation of inflammatory responses in AMI.@@@@1@16@@oe@16-12-2010 917110801@GENIA Treebank@formal@@1@S@The class II trans-activator CIITA interacts with the TBP-associated factor TAFII32.@@@@1@12@@oe@16-12-2010 917110802@GENIA Treebank@formal@@1@S@The class II trans- activator (CIITA) is the main transcriptional co-activator for the expression of MHC class II proteins.@@@@1@21@@oe@16-12-2010 917110803@GENIA Treebank@formal@@1@S@Its N-terminal 125 amino acids function as an independent transcriptional activation domain.@@@@1@13@@oe@16-12-2010 917110804@GENIA Treebank@formal@@1@S@Analyses of the primary amino acid sequence of the activation domain predict the presence of three alpha-helices, each with a high proportion of acidic residues.@@@@1@27@@oe@16-12-2010 917110805@GENIA Treebank@formal@@1@S@Using site-directed mutagenesis, we found that two of these predicted alpha-helices are required for full transcriptional activation by CIITA.@@@@1@21@@oe@16-12-2010 917110806@GENIA Treebank@formal@@1@S@Moreover, a CIITA protein in which both functional alpha-helices have been deleted displays a dominant negative phenotype.@@@@1@19@@oe@16-12-2010 917110807@GENIA Treebank@formal@@1@S@This activation domain of CIITA interacts with the 32 kDa subunit of the general transcription complex TFIID, TAFII32.@@@@1@20@@oe@16-12-2010 917110808@GENIA Treebank@formal@@1@S@Decreased transcriptional activation by N-terminal deletions of CIITA is correlated directly with their reduced binding to TAFII32.@@@@1@18@@oe@16-12-2010 917110809@GENIA Treebank@formal@@1@S@We conclude that interactions between TAFII32 and CIITA are responsible for activation of class II genes.@@@@1@17@@oe@16-12-2010 917123601@GENIA Treebank@formal@@1@S@Defective survival and activation of thymocytes in transgenic mice expressing a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV.@@@@1@20@@oe@16-12-2010 917123602@GENIA Treebank@formal@@1@S@We have generated transgenic mice that express a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) specifically in thymic T cells.@@@@1@25@@oe@16-12-2010 917123603@GENIA Treebank@formal@@1@S@The presence of this protein results in a markedly reduced thymic cellularity, although the distribution of the remaining cells is normal based on evaluation of the CD4 and CD8 cell surface antigens that are used to gauge T cell development.@@@@1@42@@oe@16-12-2010 917123604@GENIA Treebank@formal@@1@S@Isolated thymic T cells from the transgenic mice also show a dramatically decreased survival rate when evaluated in culture under conditions that do not favor activation.@@@@1@27@@oe@16-12-2010 917123605@GENIA Treebank@formal@@1@S@When challenged with an activating stimulus such as alpha-CD3 or a combination of phorbol ester plus ionophore, the cells are severely compromised in their ability to produce the cytokine interleukin-2 (IL-2).@@@@1@35@@oe@16-12-2010 917123606@GENIA Treebank@formal@@1@S@Reduction of IL-2 production is secondary to the inability to phosphorylate the cAMP response element binding protein, CREB, and induce expression of the immediate early genes such as Fos B that are required to transactivate the IL-2 promoter.@@@@1@41@@oe@16-12-2010 917123607@GENIA Treebank@formal@@1@S@Because transgene expression was regulated by the proximal promoter of the murine lck gene and this promoter is inactivated in T cells that exit the thymus, the mutant hCaMKIV is not present in peripheral T cells.@@@@1@38@@oe@16-12-2010 917123608@GENIA Treebank@formal@@1@S@Consequently, T lymphocytes present in the spleen can be activated normally in response to either stimulus mentioned above, demonstrating that the effects of the inactive CaMKIV on activation are reversible.@@@@1@33@@oe@16-12-2010 917123609@GENIA Treebank@formal@@1@S@Our results suggest that CaMKIV may represent a physiologically relevant CREB kinase in T cells and that the enzyme is also required to ensure normal expansion of T cells in the thymus.@@@@1@33@@oe@16-12-2010 917123610@GENIA Treebank@formal@@1@S@Whereas the pathway responsible for this latter role is yet to be elucidated, it is unlikely to include CREB phosphorylation.@@@@1@22@@oe@16-12-2010 917459801@GENIA Treebank@formal@@1@S@Constitutive and inducible protein/DNA interactions of the interferon-gamma promoter in vivo in [corrected] CD45RA and CD45R0 T helper subsets [published erratum appears in Eur J Immunol 1997 Jul;27(7):1830]@@@@1@39@@oe@16-12-2010 917459802@GENIA Treebank@formal@@1@S@Interferon-gamma (IFN-gamma) is a key cytokine of T lymphocytes with major regulatory functions in the immune system.@@@@1@20@@oe@16-12-2010 917459803@GENIA Treebank@formal@@1@S@To determine and compare protein/DNA interactions at the native IFN-gamma locus in T cells, we analyzed the human IFN-gamma promoter by ligation-mediated polymerase chain reaction (LM-PCR) techniques.@@@@1@31@@oe@16-12-2010 917459804@GENIA Treebank@formal@@1@S@Accordingly, Jurkat T cells and primary CD45RA and CD45R0 CD4+ T cell subsets isolated from peripheral blood using immunomagnetic beads were cultured and analyzed by LM-PCR.@@@@1@28@@oe@16-12-2010 917459805@GENIA Treebank@formal@@1@S@Constitutive and inducible protein/DNA interactions of the IFN-gamma promoter in vivo were detected in all T cells tested.@@@@1@19@@oe@16-12-2010 917459806@GENIA Treebank@formal@@1@S@Interestingly, an inducible footprint between -183 and -196 was consistently observed in Jurkat T cells and CD45RA and CD45R0 T helper subsets upon stimulation with phorbol 12-myristate 13-acetate+phytohemagglutinin (PMA+PHA) that was highly sensitive to treatment with corticosteroids.@@@@1@41@@oe@16-12-2010 917459807@GENIA Treebank@formal@@1@S@This novel target site, denoted the C-site, was shown by several criteria, including cell distribution studies, stimulation experiments, supershift assays, and cross-competition electrophoretic mobility shift assays to bind the transcription factor AP-1.@@@@1@39@@oe@16-12-2010 917459808@GENIA Treebank@formal@@1@S@Mutation of the C-site that prevented AP-1 binding to this site was sufficient strikingly to reduce inducible promoter activity in primary CD45R0 T cells.@@@@1@25@@oe@16-12-2010 917459809@GENIA Treebank@formal@@1@S@In summary, the data demonstrate that IFN-gamma gene transcription in primary T cells is regulated in vivo at the level of constitutive and inducible protein/DNA interactions.@@@@1@28@@oe@16-12-2010 917459810@GENIA Treebank@formal@@1@S@We propose a model where basal transcription is maintained by binding of various transcription factors to the IFN-gamma promoter, whereas PMA+PHA-inducible IFN-gamma transcription in CD45R0 T cells is associated with binding of AP-1 to the C-site.@@@@1@38@@oe@16-12-2010 917583501@GENIA Treebank@formal@@1@S@Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation.@@@@1@18@@oe@16-12-2010 917583502@GENIA Treebank@formal@@1@S@Tip of herpesvirus saimiri associates with Lck and down-regulates Lck-mediated activation.@@@@1@12@@oe@16-12-2010 917583503@GENIA Treebank@formal@@1@S@We identified a novel cellular Tip-associated protein (Tap) by a yeast two-hybrid screen.@@@@1@16@@oe@16-12-2010 917583504@GENIA Treebank@formal@@1@S@Tap associated with Tip following transient expression in COS-1 cells and stable expression in human Jurkat-T cells.@@@@1@18@@oe@16-12-2010 917583505@GENIA Treebank@formal@@1@S@Expression of Tip and Tap in Jurkat-T cells induced dramatic cell aggregation.@@@@1@13@@oe@16-12-2010 917583506@GENIA Treebank@formal@@1@S@Aggregation was likely caused by the up-regulated surface expression of adhesion molecules including integrin alpha, L-selectin, ICAM-3, and H-CAM.@@@@1@23@@oe@16-12-2010 917583507@GENIA Treebank@formal@@1@S@Furthermore, NF-kappaB transcriptional factor of aggregated cells had approximately 40-fold higher activity than that of parental cells.@@@@1@19@@oe@16-12-2010 917583508@GENIA Treebank@formal@@1@S@Thus, Tap is likely to be an important cellular mediator of Tip function in T cell transformation by herpesvirus saimiri.@@@@1@22@@oe@16-12-2010 917721601@GENIA Treebank@formal@@1@S@Transactivation by CIITA, the type II bare lymphocyte syndrome-associated factor, requires participation of multiple regions of the TATA box binding protein.@@@@1@24@@oe@16-12-2010 917721602@GENIA Treebank@formal@@1@S@CIITA is a positive regulator of class II major histocompatibility complex gene transcription that has been found to be defective in one of the five complementation groups of class II major histocompatibility complex-negative cell lines.@@@@1@36@@oe@16-12-2010 917721603@GENIA Treebank@formal@@1@S@Its N-terminal region is capable of activating transcription from a reporter gene when fused to a DNA binding domain.@@@@1@20@@oe@16-12-2010 917721604@GENIA Treebank@formal@@1@S@We have investigated the mechanism of transactivation mediated by the CIITA activation domain by studying its role in the process of transcription initiation and elongation.@@@@1@26@@oe@16-12-2010 917721605@GENIA Treebank@formal@@1@S@Specifically the altered specificity TBP (TATA box binding protein) assay has been used to analyze the response of the CIITA activation domain to mutations in TBP known to disrupt its interaction with its associated general factors.@@@@1@39@@oe@16-12-2010 917721606@GENIA Treebank@formal@@1@S@Transactivation by CIITA was extremely sensitive to a mutation in TBP that in yeast is known to abolish VP16-mediated transcription but leaves basal transcription unaffected.@@@@1@26@@oe@16-12-2010 917721607@GENIA Treebank@formal@@1@S@A TBP mutant defective in interaction with TBP-associated factor TAFII250 also failed to mediate transactivation through the CIITA activation domain.@@@@1@21@@oe@16-12-2010 917721608@GENIA Treebank@formal@@1@S@Certain interactions between TBP and general factors that are specifically required for acidic activation domains were also required for CIITA-mediated transactivation to reach its full potential.@@@@1@27@@oe@16-12-2010 917721609@GENIA Treebank@formal@@1@S@Finally, like VP16, CIITA was able to stimulate elongation of transcription.@@@@1@14@@oe@16-12-2010 917721610@GENIA Treebank@formal@@1@S@Overall the mechanism of transactivation by the human B-cell-specific CIITA is very similar to that mediated by the herpes virus transactivator VP16 in the ways that have been tested.@@@@1@30@@oe@16-12-2010 917721701@GENIA Treebank@formal@@1@S@Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5.@@@@1@15@@oe@16-12-2010 917721702@GENIA Treebank@formal@@1@S@Two of the genes defective in the five complementation groups identified in the class II-negative bare lymphocyte syndrome or corresponding laboratory mutants have been cloned.@@@@1@26@@oe@16-12-2010 917721703@GENIA Treebank@formal@@1@S@One gene encodes a protein, RFX5, that is a member of the RFX family of DNA binding proteins.@@@@1@21@@oe@16-12-2010 917721704@GENIA Treebank@formal@@1@S@The other, CIITA, encodes a large protein with a defined acidic transcriptional activation domain; this protein does not interact with DNA.@@@@1@25@@oe@16-12-2010 917721705@GENIA Treebank@formal@@1@S@Expression plasmids encoding regions of RFX5 fused to the GAL4 DNA binding domain activated transcription from a reporter construct containing GAL4 sites in a cotransfection assay in the Raji human B cell line.@@@@1@34@@oe@16-12-2010 917721706@GENIA Treebank@formal@@1@S@However, these plasmids produced transcriptional activity in HeLa cells only in conjunction with interferon gamma stimulation, a condition in which expression of both CIITA and class II major histocompatibility complex surface proteins are induced.@@@@1@36@@oe@16-12-2010 917721707@GENIA Treebank@formal@@1@S@Furthermore, these plasmids were not active in RJ2.2.5, an in vitro mutagenized derivative of Raji in which both copies of CIITA are defective.@@@@1@26@@oe@16-12-2010 917721708@GENIA Treebank@formal@@1@S@Transcriptional activation by the RFX5 fusion protein could be restored in RJ2.2.5 by cotransfection with a CIITA expression plasmid.@@@@1@20@@oe@16-12-2010 917721709@GENIA Treebank@formal@@1@S@Finally, a direct interaction between RFX5 and CIITA was detected with the yeast two-hybrid and far-Western blot assays.@@@@1@20@@oe@16-12-2010 917721710@GENIA Treebank@formal@@1@S@Thus, RFX5 can activate transcription only in cooperation with CIITA.@@@@1@12@@oe@16-12-2010 917721711@GENIA Treebank@formal@@1@S@RFX5 and CIITA associate to form a complex capable of activating transcription from class II major histocompatibility complex promoters.@@@@1@20@@oe@16-12-2010 917721712@GENIA Treebank@formal@@1@S@In this complex, promoter specificity is determined by the DNA binding domain of RFX5 and the general transcription apparatus is recruited by the acidic activation domain of CIITA.@@@@1@30@@oe@16-12-2010 917724001@GENIA Treebank@formal@@1@S@CCAAT/enhancer binding protein epsilon is preferentially up-regulated during granulocytic differentiation and its functional versatility is determined by alternative use of promoters and differential splicing.@@@@1@25@@oe@16-12-2010 917724002@GENIA Treebank@formal@@1@S@CCAAT/enhancer binding protein (C/EBP) epsilon is a recently cloned member of the C/EBP family of transcription factors and is expressed exclusively in cells of hematopoietic origin.@@@@1@29@@oe@16-12-2010 917724003@GENIA Treebank@formal@@1@S@The human C/EBPepsilon gene is transcribed by two alternative promoters, Palpha and Pbeta.@@@@1@15@@oe@16-12-2010 917724004@GENIA Treebank@formal@@1@S@A combination of differential splicing and alternative use of promoters generates four mRNA isoforms, of 2.6 kb and 1.3-1.5 kb in size.@@@@1@24@@oe@16-12-2010 917724005@GENIA Treebank@formal@@1@S@These transcripts can encode three proteins of calculated molecular mass 32.2 kDa, 27.8 kDa, and 14.3 kDa.@@@@1@20@@oe@16-12-2010 917724006@GENIA Treebank@formal@@1@S@Accordingly, Western blots with antibodies specific for the DNA-binding domain, that is common to all forms, identify multiple proteins.@@@@1@23@@oe@16-12-2010 917724007@GENIA Treebank@formal@@1@S@C/EBPepsilon mRNA was greatly induced during in vitro granulocytic differentiation of human primary CD34(+) cells.@@@@1@16@@oe@16-12-2010 917724008@GENIA Treebank@formal@@1@S@Retinoic acid treatment of HL60 promyelocytic leukemia cells for 24 hr induced C/EBPepsilon mRNA levels by 4-fold, while prolonged treatment gradually reduced mRNA expression to pretreatment levels.@@@@1@29@@oe@16-12-2010 917724009@GENIA Treebank@formal@@1@S@Transient transfection experiments with expression vectors for two of the isoforms demonstrated that the 32.2-kDa protein is an activator of transcription of granulocyte colony-stimulating factor receptor promoter, while the 14.3-kDa protein is not.@@@@1@35@@oe@16-12-2010 917724010@GENIA Treebank@formal@@1@S@Thus, C/EBPepsilon is regulated in a complex fashion and may play a role in the regulation of genes involved in myeloid differentiation.@@@@1@24@@oe@16-12-2010 917810701@GENIA Treebank@formal@@1@S@Reactive oxygen species and antioxidants in inflammatory diseases.@@@@1@9@@oe@16-12-2010 917810702@GENIA Treebank@formal@@1@S@This paper aims to review the role of free radical-induced tissue damage and antioxidant defence mechanisms in inflammatory diseases that involve pathogenic processes similar to the periodontal diseases.@@@@1@29@@oe@16-12-2010 917810703@GENIA Treebank@formal@@1@S@There is a clearly defined and substantial role for free radicals or reactive oxygen species (ROS) in periodontitis, but little research has been performed in this area.@@@@1@31@@oe@16-12-2010 917810704@GENIA Treebank@formal@@1@S@This paper reviews the considerable data available relating ROS activity and antioxidant defence to inflammatory diseases and attempts to draw parallels with periodontitis, in an effort to stimulate more periodontal research in this important area.@@@@1@37@@oe@16-12-2010 917810705@GENIA Treebank@formal@@1@S@The recent discovery of the transcription factor nuclear factor kappa B (NF-kappa B) is reviewed and several potential pathways for cytokine-induced periodontal tissue damage, mediated by NF-kappa B1 are discussed.@@@@1@34@@oe@16-12-2010 917810706@GENIA Treebank@formal@@1@S@Emphasis is placed on cytokines that have been studied in periodontitis, principally TNF-alpha, IL-1, IL-6, IL-8 and beta-interferon.@@@@1@23@@oe@16-12-2010 917810707@GENIA Treebank@formal@@1@S@The link between cellular production of such important mediators of inflammation and the antioxidant (AO) thiols, cysteine and reduced glutathione (GSH), is discussed and it is hypothesised that NF-kappa B antagonists may offer important therapeutic benefits.@@@@1@43@@oe@16-12-2010 918026601@GENIA Treebank@formal@@1@S@Transcriptional activity and constitutive nuclear localization of the ETS protein Elf-1.@@@@1@12@@oe@16-12-2010 918026602@GENIA Treebank@formal@@1@S@Elf-1 is a lymphoid-specific transcription factor that belongs to the ETS protein family.@@@@1@14@@oe@16-12-2010 918026603@GENIA Treebank@formal@@1@S@It can bind to DNA target sequences within a variety of cytokine genes.@@@@1@14@@oe@16-12-2010 918026604@GENIA Treebank@formal@@1@S@We demonstrate that Elf-1 is constitutively localized in the nucleus which is dependent on the presence of amino acids 86-265.@@@@1@21@@oe@16-12-2010 918026605@GENIA Treebank@formal@@1@S@Analysis of Gal4-Elf-1 fusion proteins revealed that the N-terminal 86 amino acids of Elf-1 contain a transcriptional activation domain, the activity of which is attenuated by an internal repression domain.@@@@1@32@@oe@16-12-2010 918026606@GENIA Treebank@formal@@1@S@Furthermore, Elf-1 interacts specifically with the E74 target sequence and can stimulate transcription driven by the E74 site independent of mitogenic signaling.@@@@1@24@@oe@16-12-2010 918026607@GENIA Treebank@formal@@1@S@Thus, Elf-1 is able to stimulate gene transcription which may be required for the development and activity of lymphocytes.@@@@1@21@@oe@16-12-2010 918255601@GENIA Treebank@formal@@1@S@Overexpression of HSF2-beta inhibits hemin-induced heat shock gene expression and erythroid differentiation in K562 cells.@@@@1@16@@oe@16-12-2010 918255602@GENIA Treebank@formal@@1@S@Acquisition of heat shock factor 2 (HSF2) DNA binding activity is accompanied by induced transcription of heat shock genes in hemin-treated K562 cells undergoing erythroid differentiation.@@@@1@29@@oe@16-12-2010 918255603@GENIA Treebank@formal@@1@S@Previous studies revealed that HSF2 consists of two alternatively spliced isoforms, HSF2-alpha and HSF2-beta, whose relative abundance is developmentally regulated and varies between different tissues.@@@@1@28@@oe@16-12-2010 918255604@GENIA Treebank@formal@@1@S@To investigate whether the molar ratio of HSF2-alpha and HSF2-beta isoforms is crucial for the activation of HSF2 and whether the HSF2 isoforms play functionally distinct roles during the hemin-mediated erythroid differentiation, we generated cell clones expressing different levels of HSF2-alpha and HSF2-beta.@@@@1@45@@oe@16-12-2010 918255605@GENIA Treebank@formal@@1@S@We show that in parental K562 cells, the HSF2-alpha isoform is predominantly expressed and HSF2 can be activated upon hemin treatment.@@@@1@23@@oe@16-12-2010 918255606@GENIA Treebank@formal@@1@S@In contrast, when HSF2-beta is expressed at levels exceeding those of endogenous HSF2-alpha, the hemin-induced DNA binding activity and transcription of heat shock genes are repressed, whereas overexpression of HSF2-alpha results in an enhanced hemin response.@@@@1@40@@oe@16-12-2010 918255607@GENIA Treebank@formal@@1@S@Furthermore, the hemin-induced accumulation of globin, known as a marker of erythroid differentiation, is decreased in cells overexpressing HSF2-beta.@@@@1@23@@oe@16-12-2010 918255608@GENIA Treebank@formal@@1@S@We suggest that HSF2-beta acts as a negative regulator of HSF2 activity during hemin-mediated erythroid differentiation of K562 cells.@@@@1@20@@oe@16-12-2010 918550601@GENIA Treebank@formal@@1@S@Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras.@@@@1@11@@oe@16-12-2010 918550602@GENIA Treebank@formal@@1@S@Giant cell arteritis (GCA) is a vasculitic syndrome that preferentially affects medium and large-sized arteries.@@@@1@18@@oe@16-12-2010 918550603@GENIA Treebank@formal@@1@S@Glucocorticoid therapy resolves clinical symptoms within hours to days, but therapy has to be continued over several years to prevent disease relapses.@@@@1@24@@oe@16-12-2010 918550604@GENIA Treebank@formal@@1@S@It is not known whether and how glucocorticoids affect the function of the inflammatory infiltrate or why the disease persists subclinically despite chronic treatment.@@@@1@25@@oe@16-12-2010 918550605@GENIA Treebank@formal@@1@S@GCA is self-sustained in temporal arteries engrafted into SCID mice, providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo.@@@@1@31@@oe@16-12-2010 918550606@GENIA Treebank@formal@@1@S@Administration of dexamethasone to temporal artery-SCID chimeras for 1 wk induced a partial suppression of T cell and macrophage function as indicated by the reduced tissue concentrations of IL-2, IL-1beta, and IL-6 mRNA, and by the diminished expression of inducible NO synthase.@@@@1@46@@oe@16-12-2010 918550607@GENIA Treebank@formal@@1@S@In contrast, synthesis of IFN-gamma mRNA was only slightly decreased, and expression of TGF-beta1 was unaffected.@@@@1@19@@oe@16-12-2010 918550608@GENIA Treebank@formal@@1@S@These findings correlated with activation of the IkappaBalpha gene and blockade of the nuclear translocation of NFkappaB in the xenotransplanted tissue.@@@@1@22@@oe@16-12-2010 918550609@GENIA Treebank@formal@@1@S@Dose-response experiments suggested that steroid doses currently used in clinical medicine are suboptimal in repressing NFkappaB-mediated cytokine production in the inflammatory lesions.@@@@1@23@@oe@16-12-2010 918550610@GENIA Treebank@formal@@1@S@Chronic steroid therapy was able to deplete the T cell products IL-2 and IFN-gamma, whereas the activation of tissue-infiltrating macrophages was only partially affected.@@@@1@26@@oe@16-12-2010 918550611@GENIA Treebank@formal@@1@S@IL-1beta transcription was abrogated; in contrast, TGF-beta1 mRNA synthesis was steroid resistant.@@@@1@15@@oe@16-12-2010 918550612@GENIA Treebank@formal@@1@S@The persistence of TGF-beta1-transcribing macrophages, despite paralysis of T cell function, may provide an explanation for the chronicity of the disease, and may identify a novel therapeutic target in this inflammatory vasculopathy.@@@@1@36@@oe@16-12-2010 918726401@GENIA Treebank@formal@@1@S@Histamine modulates the expression of c-fos through cyclic AMP production via the H2 receptor in the human promonocytic cell line U937.@@@@1@22@@oe@16-12-2010 918726402@GENIA Treebank@formal@@1@S@We examined the effects of histamine and its agonists on the expression of the c-fos and c-myc proto-oncogenes at the transcriptional and translational levels in the human promonocytic U937 cell line.@@@@1@32@@oe@16-12-2010 918726403@GENIA Treebank@formal@@1@S@Histamine transiently increased cAMP and c-fos expression through H2 receptors.@@@@1@11@@oe@16-12-2010 918726404@GENIA Treebank@formal@@1@S@Dibutyryl cAMP also increased c-fos mRNA and protein, and levels remained elevated even after 12 hr of treatment.@@@@1@20@@oe@16-12-2010 918726405@GENIA Treebank@formal@@1@S@Dose-dependence studies using histamine and dimaprit showed that the EC50 values for cAMP production and c-fos increase were similar, suggesting that cAMP might be involved in c-fos induction via H2 receptors.@@@@1@33@@oe@16-12-2010 918726406@GENIA Treebank@formal@@1@S@Furthermore, studies carried out using H7, a protein kinase A/protein kinase C inhibitor, blocked c-fos induction, whereas no effect was observed with bisindolylmaleimide, a specific protein kinase C inhibitor.@@@@1@35@@oe@16-12-2010 918726407@GENIA Treebank@formal@@1@S@No modification of c-myc expression could be detected on treatment with histamine or its analogues.@@@@1@16@@oe@16-12-2010 918726408@GENIA Treebank@formal@@1@S@Nevertheless, dibutyryl cAMP induced a down-regulation of the levels of this proto-oncogene.@@@@1@14@@oe@16-12-2010 918726409@GENIA Treebank@formal@@1@S@In addition, dibutyryl cAMP inhibited cell growth in a dose-dependent manner, whereas histamine failed to affect proliferation and differentiation of U937 cells.@@@@1@25@@oe@16-12-2010 918726410@GENIA Treebank@formal@@1@S@Cells pretreated with dimaprit showed a decrease in the cAMP response to subsequent addition of H2 agonists, whereas the cAMP response to prostaglandin E2 remained unaltered.@@@@1@28@@oe@16-12-2010 918726411@GENIA Treebank@formal@@1@S@This homologous mechanism of H2 receptor desensitization was time dependent.@@@@1@11@@oe@16-12-2010 918726412@GENIA Treebank@formal@@1@S@These results indicate that histamine activates several mechanisms involved in the induction of differentiation, such as cAMP and c-fos production, but fails to promote differentiation of U937 cells, apparently due to the rapid desensitization of H2 receptors.@@@@1@41@@oe@16-12-2010 918865101@GENIA Treebank@formal@@1@S@Human cytomegalovirus induces interleukin-8 production by a human monocytic cell line, THP-1, through acting concurrently on AP-1- and NF-kappaB-binding sites of the interleukin-8 gene.@@@@1@27@@oe@16-12-2010 918865102@GENIA Treebank@formal@@1@S@Cytomegalovirus (CMV) infection induced interleukin-8 (IL-8) gene transcription in a human monocytic cell line, THP-1 cells, leading to IL-8 secretion.@@@@1@27@@oe@16-12-2010 918865103@GENIA Treebank@formal@@1@S@The functional analysis of the IL-8 gene revealed that both AP-1- and NF-kappaB factor-binding elements were involved in conferring the responsiveness to CMV.@@@@1@24@@oe@16-12-2010 918865104@GENIA Treebank@formal@@1@S@Moreover, electrophoretic mobility shift assays demonstrated that CMV induced the formation of NF-kappaB and AP-1 complexes.@@@@1@18@@oe@16-12-2010 918865105@GENIA Treebank@formal@@1@S@These results suggest that CMV activates these transcriptional factors, resulting in IL-8 gene expression.@@@@1@16@@oe@16-12-2010 918884201@GENIA Treebank@formal@@1@S@Concomitant downregulation of IgH 3' enhancer activity and c-myc expression in a plasmacytoma x fibroblast environment: implications for dysregulation of translocated c-myc.@@@@1@24@@oe@16-12-2010 918884202@GENIA Treebank@formal@@1@S@Regulation of immunoglobulin heavy chain (IgH) gene expression is controlled by a B cell-specific promoter, intronic enhancer and additional B cell-specific enhancer elements identified recently in the 3' end of the IgH locus.@@@@1@37@@oe@16-12-2010 918884203@GENIA Treebank@formal@@1@S@One of the latter elements, the IgH 3' enhancer, is of particular interest: (1) it is B cell-specific and active only in late B cell development; (2) in rodent plasmacytomas and in some human Burkitt's lymphomas it is part of a locus control region (LCR) that is involved in deregulation of the c-myc oncogene as a result of translocation into the IgH locus; and (3) it has been implicated in the mechanisms that control Ig gene class switch recombination.@@@@1@94@@oe@16-12-2010 918884204@GENIA Treebank@formal@@1@S@We have used a somatic cell hybridization approach to genetically analyse regulation of the activity of the IgH 3' enhancer.@@@@1@21@@oe@16-12-2010 918884205@GENIA Treebank@formal@@1@S@When mouse MPC11 plasmacytoma cells, in which the IgH 3' enhancer is active, are fused with fibroblasts, Ig expression is extinguished at the level of transcription.@@@@1@30@@oe@16-12-2010 918884206@GENIA Treebank@formal@@1@S@Here we show that in a MPC11 plasmacytoma x fibroblast environment, the IgH 3' enhancer is transcriptionally inactive.@@@@1@20@@oe@16-12-2010 918884207@GENIA Treebank@formal@@1@S@Furthermore, we demonstrate that binding of several B cell-specific transcription factors, essential for IgH 3' enhancer activity, is lacking, which may explain 3' enhancer inactivity, although the binding of repressors cannot be excluded.@@@@1@40@@oe@16-12-2010 918884208@GENIA Treebank@formal@@1@S@Moreover, the high expression level of c-myc, characteristic of the parental MPC11 cells carrying the t(12;15) translocation, is down-regulated in the hybrids to that in unfused fibroblasts.@@@@1@31@@oe@16-12-2010 918884209@GENIA Treebank@formal@@1@S@Therefore, inactivation of the IgH 3' enhancer is a multifactorial process affecting several transcription factors that control the cell-specific and developmental activity of the enhancer.@@@@1@27@@oe@16-12-2010 918977001@GENIA Treebank@formal@@1@S@Construction and biological characterization of an interleukin-12 fusion protein (Flexi-12): delivery to acute myeloid leukemic blasts using adeno-associated virus.@@@@1@23@@oe@16-12-2010 918977002@GENIA Treebank@formal@@1@S@Interleukin-12 (IL-12) is a cytokine that exhibits pleiotropic effects on lymphocytes and natural killer cells and has been shown to have promise for the immunotherapy of cancer.@@@@1@30@@oe@16-12-2010 918977003@GENIA Treebank@formal@@1@S@The combination of the immune costimulatory molecule B7.1 and IL-12 has been shown to be synergistic for T cell activation.@@@@1@21@@oe@16-12-2010 918977004@GENIA Treebank@formal@@1@S@By transfecting tumor cells with both IL-12 and B7.1 cDNAs, it may be possible to use these modified targets as vaccines.@@@@1@23@@oe@16-12-2010 918977005@GENIA Treebank@formal@@1@S@A major obstacle in designing a vector to deliver these genes results from the structure of IL-12.@@@@1@18@@oe@16-12-2010 918977006@GENIA Treebank@formal@@1@S@Functional IL-12 is a heterodimer composed of two distinct subunits that are encoded by separate genes on different chromosomes.@@@@1@20@@oe@16-12-2010 918977007@GENIA Treebank@formal@@1@S@Production of functional IL-12 requires the coordinated expression of both genes.@@@@1@12@@oe@16-12-2010 918977008@GENIA Treebank@formal@@1@S@This presents several problems in vectors, particularly those in which additional genes, either a co-stimulatory gene or a selectable marker, are inserted.@@@@1@26@@oe@16-12-2010 918977009@GENIA Treebank@formal@@1@S@Therefore, we have constructed a single cDNA that encodes a single-chain protein, called Flexi-12, which retains all of the biological characteristics of recombinant IL-12 (rIL-12).@@@@1@31@@oe@16-12-2010 918977010@GENIA Treebank@formal@@1@S@The monomeric polypeptide Flexi-12 is able to induce the proliferation of phytohemagglutinin (PHA) blasts, induce PHA blasts to secrete interferon-gamma (IFN-gamma) and additionally, by preincubation, enhance the killing of K562 targets by PBLs.@@@@1@41@@oe@16-12-2010 918977011@GENIA Treebank@formal@@1@S@These phenomena are in a dose-dependent manner comparable to that seen with rIL-12.@@@@1@14@@oe@16-12-2010 918977012@GENIA Treebank@formal@@1@S@We have also shown that tyrosine phosphorylation of the STAT 4 transcription factor, which has been shown to be unique to the IL-12 signaling pathway, occurs with Flexi-12 at levels similar to those seen with rIL-12.@@@@1@39@@oe@16-12-2010 918977013@GENIA Treebank@formal@@1@S@We have packaged Flexi-12 into a recombinant adeno-associated virus (AAV) and used this vector to infect acute myeloid leukemic (AML) blasts.@@@@1@26@@oe@16-12-2010 918977014@GENIA Treebank@formal@@1@S@Infected AML blasts produced between 2 and 6 ng of IL-12/10(6) cells per ml per 48 hr.@@@@1@21@@oe@16-12-2010 918977015@GENIA Treebank@formal@@1@S@These studies also confirm that AAV is an efficient delivery vehicle for cytokines to leukemic cells.@@@@1@17@@oe@16-12-2010 918977016@GENIA Treebank@formal@@1@S@Direct analysis of these modified cells acting as tumor vaccines is underway.@@@@1@13@@oe@16-12-2010 919090101@GENIA Treebank@formal@@1@S@ETS1, NFkappaB and AP1 synergistically transactivate the human GM-CSF promoter.@@@@1@12@@oe@16-12-2010 919090102@GENIA Treebank@formal@@1@S@Activation of helper T cells results in coordinate expression of a number of cytokines involved in differentiation, proliferation and activation of the haematopoietic system.@@@@1@26@@oe@16-12-2010 919090103@GENIA Treebank@formal@@1@S@Granulocyte-macrophage colony stimulating factor (GM-CSF) is one such cytokine, whose increased expression results mostly from increases in transcription.@@@@1@22@@oe@16-12-2010 919090104@GENIA Treebank@formal@@1@S@Cis-acting elements with NFkappaB, AP1 and ETS-like binding motifs have been identified in the promoter region of the GM-CSF gene, and are important or essential for transcriptional activity following T cell activation.@@@@1@35@@oe@16-12-2010 919090105@GENIA Treebank@formal@@1@S@ETS1 is a transcription factor of the ETS family that is expressed in T cells.@@@@1@16@@oe@16-12-2010 919090106@GENIA Treebank@formal@@1@S@We have previously shown that ETS1 can transactivate GM-CSF in Jurkat T cells, but only after the cells have been stimulated by treatment with PMA and ionomycin, agents that mimic T cell activation.@@@@1@36@@oe@16-12-2010 919090107@GENIA Treebank@formal@@1@S@Thus we proposed that ETS1, which is expressed constitutively in Jurkat cells, may act in concert with PMA/ionomycin inducible factors.@@@@1@23@@oe@16-12-2010 919090108@GENIA Treebank@formal@@1@S@Here we show that ETS1 can transactivate a GM-CSF reporter construct in unstimulated Jurkat cells, providing that either NFkappaB or AP1 transcription factors are supplied by co-transfection.@@@@1@29@@oe@16-12-2010 919090109@GENIA Treebank@formal@@1@S@We confirm that binding of endogenous NFkappaB and AP1 is induced following PMA/ionomycin treatment of T cells.@@@@1@18@@oe@16-12-2010 919090110@GENIA Treebank@formal@@1@S@Transactivation by ETS1, NFkappaB and AP1 is synergistic, and mutation of the individual binding sites reveals that the transcriptional activities of these factors are interdependent.@@@@1@28@@oe@16-12-2010 919090111@GENIA Treebank@formal@@1@S@Our results suggest that constitutive ETS1, and inducible NFkappaB and AP1, cooperate as part of a higher order transcriptional complex in activated T cells.@@@@1@27@@oe@16-12-2010 919093801@GENIA Treebank@formal@@1@S@The IL-4 receptor alpha-chain cytoplasmic domain is sufficient for activation of JAK-1 and STAT6 and the induction of IL-4-specific gene expression.@@@@1@22@@oe@16-12-2010 919093802@GENIA Treebank@formal@@1@S@The common gamma-chain (gamma(c)) is a functional component of the IL-4R, yet cells lacking gamma(c) are able to respond to IL-4.@@@@1@25@@oe@16-12-2010 919093803@GENIA Treebank@formal@@1@S@This has led to the suggestion that a surrogate gamma'-chain, which can interact with the IL-4R alpha chain to mediate signaling, is expressed on cells lacking gamma(c).@@@@1@30@@oe@16-12-2010 919093804@GENIA Treebank@formal@@1@S@An alternative possibility is that in the absence of gamma(c), the IL-4R alpha chain is able to transduce signals by homodimerization.@@@@1@23@@oe@16-12-2010 919093805@GENIA Treebank@formal@@1@S@To test this latter possibility, a chimeric receptor containing the extracellular domain of c-kit (the stem cell factor (SCF) receptor) and the cytoplasmic and transmembrane domains of the IL-4R alpha chain was generated.@@@@1@39@@oe@16-12-2010 919093806@GENIA Treebank@formal@@1@S@Treatment of cells expressing the chimeric receptor kit/IL-4R alpha with SCF induces activation of the IL-4R alpha-associated kinase JAK-1 and the transcription factor STAT6.@@@@1@25@@oe@16-12-2010 919093807@GENIA Treebank@formal@@1@S@However, tyrosine phosphorylation of JAK-3, which associates with gamma(c), is not induced by SCF in these cells.@@@@1@21@@oe@16-12-2010 919093808@GENIA Treebank@formal@@1@S@SCF-mediated ligation of kit/IL-4R alpha is sufficient to elicit IL-4-specific gene expression, including up-regulation of CD23 and synthesis of germ-line epsilon transcripts.@@@@1@24@@oe@16-12-2010 919093809@GENIA Treebank@formal@@1@S@In the T cell line CTLL2, ligation of kit/IL-4R alpha induces cellular proliferation.@@@@1@15@@oe@16-12-2010 919093810@GENIA Treebank@formal@@1@S@Finally, in JAK-1-deficient HeLa cells, STAT6 activation by IL-4 is completely abolished.@@@@1@15@@oe@16-12-2010 919093811@GENIA Treebank@formal@@1@S@Together, these data demonstrate that the IL-4R alpha cytoplasmic domain is sufficient to activate JAK-1 and STAT6 and to induce expression of IL-4 target genes, thus identifying a mechanism by which IL-4 signaling can proceed in the absence of JAK-3 and gamma(c).@@@@1@45@@oe@16-12-2010 919105701@GENIA Treebank@formal@@1@S@Relief of cyclin A gene transcriptional inhibition during activation of human primary T lymphocytes via CD2 and CD28 adhesion molecules.@@@@1@21@@oe@16-12-2010 919105702@GENIA Treebank@formal@@1@S@Cyclin A transcription is cell cycle regulated and induced by cell proliferative signals.@@@@1@14@@oe@16-12-2010 919105703@GENIA Treebank@formal@@1@S@To understand the mechanisms underlined in this regulation in normal human cells, we have analysed in vivo protein-DNA interactions at the Cyclin A locus in primary T lymphocytes.@@@@1@30@@oe@16-12-2010 919105704@GENIA Treebank@formal@@1@S@Stimulation of purified T lymphocytes by a combination of monoclonal antibodies directed at CD2 and CD28 adhesion molecules gives rise to a long lasting proliferation in the absence of accessory cells.@@@@1@32@@oe@16-12-2010 919105705@GENIA Treebank@formal@@1@S@Cyclin A was observed after 4 days of costimulation with anti CD2 + CD28 whereas stimulation by anti CD2 or anti CD28 alone was not effective.@@@@1@27@@oe@16-12-2010 919105706@GENIA Treebank@formal@@1@S@In vivo genomic DMS footprinting revealed upstream of the major transcription initiation sites, the presence of at least three protein binding sites, two of which were constitutively occupied.@@@@1@31@@oe@16-12-2010 919105707@GENIA Treebank@formal@@1@S@They bind in vitro respectively ATF-1 and NF-Y proteins.@@@@1@10@@oe@16-12-2010 919105708@GENIA Treebank@formal@@1@S@The third site was occupied in quiescent cells or in cells stimulated by anti CD2 or anti CD28 alone.@@@@1@20@@oe@16-12-2010 919105709@GENIA Treebank@formal@@1@S@The mitogenic combination of anti CD2 + anti CD28 released the footprint as cells were committed to proliferation.@@@@1@19@@oe@16-12-2010 919105710@GENIA Treebank@formal@@1@S@Consistent with theses results, nuclear extracts prepared from quiescent cells formed a specific complex with this element, whereas extracts prepared from cells treated with anti CD2 + anti CD28 failed to do so after cells entered a proliferative state.@@@@1@42@@oe@16-12-2010 919276101@GENIA Treebank@formal@@1@S@Thrombin generation by apoptotic vascular smooth muscle cells.@@@@1@9@@oe@16-12-2010 919276102@GENIA Treebank@formal@@1@S@Thrombin activation requires assembly of a prothrombinase complex of activated coagulation factors on an anionic phospholipid surface, classically provided by activated platelets.@@@@1@24@@oe@16-12-2010 919276103@GENIA Treebank@formal@@1@S@We have previously shown that anionic phosphatidylserine is exposed by rat vascular smooth muscle cells (VSMCs) undergoing apoptosis after serum withdrawal.@@@@1@24@@oe@16-12-2010 919276104@GENIA Treebank@formal@@1@S@In this study, using a chromogenic assay, we have shown thrombin generation by apoptotic VSMCs expressing c-myc (VSMC-myc) with an area under the thrombin-generation curve (AUC) of 305 +/- 17 nmol x min/L and a peak thrombin (PT) of 154 +/- 9 nmol/L.@@@@1@52@@oe@16-12-2010 919276105@GENIA Treebank@formal@@1@S@The thrombin-generating potential of the apoptotic VSMC-myc cells was greater than that of unactivated platelets (P = .003 for AUC; P = .0002 for PT) and similar to calcium-ionophore activated platelets (AUC of 332 +/- 15 nmol x min/L, P = .3; PT of 172 +/- 8 nmol/L, P = .2).@@@@1@60@@oe@16-12-2010 919276106@GENIA Treebank@formal@@1@S@Thrombin activation was also seen with apoptotic human VSMCs (AUC of 211 +/- 8 nmol x min/L; PT of 103 +/- 4 nmol/L) and was inhibited by annexin V (P < .0001 for AUC and PT).@@@@1@42@@oe@16-12-2010 919276107@GENIA Treebank@formal@@1@S@VSMC-myc cells maintained in serum generated less thrombin than after serum withdrawal (P = .0002 for AUC and PT).@@@@1@22@@oe@16-12-2010 919276108@GENIA Treebank@formal@@1@S@VSMCs derived from human coronary atherosclerotic plaques that apoptose even in serum also generated thrombin (AUC of 260 +/- 2 nmol x min/L; PT of 128 +/- 4 nmol/L).@@@@1@33@@oe@16-12-2010 919276109@GENIA Treebank@formal@@1@S@We conclude that apoptotic VSMCs possess a significant thrombin-generating capacity secondary to phosphatidylserine exposure.@@@@1@15@@oe@16-12-2010 919276110@GENIA Treebank@formal@@1@S@Apoptotic cells within atherosclerotic plaques may allow local thrombin activation, thereby contributing to disease progression.@@@@1@17@@oe@16-12-2010 919276901@GENIA Treebank@formal@@1@S@Molecular cloning and characterization of a cDNA, CHEMR1, encoding a chemokine receptor with a homology to the human C-C chemokine receptor, CCR-4.@@@@1@26@@oe@16-12-2010 919276902@GENIA Treebank@formal@@1@S@Chemokines refer to a rapidly expanding family of small cytokines whose primary function is recruitment of leukocytes to inflammatory sites.@@@@1@21@@oe@16-12-2010 919276903@GENIA Treebank@formal@@1@S@These are known to bind to seven-transmembrane-domain containing receptors.@@@@1@10@@oe@16-12-2010 919276904@GENIA Treebank@formal@@1@S@A cDNA clone, CHEMR1, resembling the typical G protein-coupled receptor, was isolated from a mouse cytotoxic T-lymphocyte (CTL) library.@@@@1@25@@oe@16-12-2010 919276905@GENIA Treebank@formal@@1@S@Northern blot analysis in mouse cell lines suggests that its expression is found in a variety of cells, including T cells, B cells, and macrophages.@@@@1@29@@oe@16-12-2010 919276906@GENIA Treebank@formal@@1@S@The CHEMR1 gene Scya3r2 is a single-copy gene whose open reading frame may be in a single exon and maps to the distal region of mouse Chr 9 where the mouse macrophage inflammatory protein-1alpha (MIP-1alpha) receptor gene Scya3r and two related C-C chemokine receptor-like genes reside.@@@@1@49@@oe@16-12-2010 919276907@GENIA Treebank@formal@@1@S@Amino acid sequence comparison shows that CHEMR1 is 84% identical to human CCR-4, indicating that CHEMR1 is likely to be a mouse CCR-4.@@@@1@26@@oe@16-12-2010 919276908@GENIA Treebank@formal@@1@S@Binding assays using 125I-labeled C-C chemokines in mammalian cells indicated that CHEMR1 did not bind MIP-1alpha, RANTES, or MIP-1beta, whereas CCR-1 binds MIP-1alpha and RANTES.@@@@1@29@@oe@16-12-2010 919276909@GENIA Treebank@formal@@1@S@Our result is different from the reported properties of human CCR-4.@@@@1@12@@oe@16-12-2010 919276910@GENIA Treebank@formal@@1@S@This suggests that CHEMR1 may be a receptor for unidentified C-C chemokine or a low-affinity receptor for MIP-1alpha.@@@@1@19@@oe@16-12-2010 919277001@GENIA Treebank@formal@@1@S@Interleukin-10 inhibits interferon-gamma-induced intercellular adhesion molecule-1 gene transcription in human monocytes.@@@@1@12@@oe@16-12-2010 919277002@GENIA Treebank@formal@@1@S@Interleukin-10 (IL-10) is a potent monocyte regulatory cytokine that inhibits gene expression of proinflammatory mediators.@@@@1@18@@oe@16-12-2010 919277003@GENIA Treebank@formal@@1@S@In this study, we investigated the mechanism by which IL-10 downregulates expression of intercellular adhesion molecule-1 (ICAM-1) on the cell surface of normal human monocytes activated with interferon-gamma (IFN-gamma).@@@@1@35@@oe@16-12-2010 919277004@GENIA Treebank@formal@@1@S@IL-10 inhibition of IFN-gamma-induced ICAM-1 expression was apparent as early as 3 hours and was blocked by an anti-IL-10 antibody but not by an isotype-matched control antibody.@@@@1@28@@oe@16-12-2010 919277005@GENIA Treebank@formal@@1@S@Northern blot analysis showed that IL-10 reduced the accumulation of ICAM-1 mRNA in IFN-gamma-stimulated monocytes.@@@@1@16@@oe@16-12-2010 919277006@GENIA Treebank@formal@@1@S@IL-10 inhibition of ICAM-1 steady-state mRNA was detected at 3 hours and remained at 24 hours.@@@@1@17@@oe@16-12-2010 919277007@GENIA Treebank@formal@@1@S@Nuclear run-on transcription assays showed that IL-10 inhibited the rate of IFN-gamma-induced transcription of the ICAM-1 gene, and mRNA stability studies showed that IL-10 did not alter the half-life of IFN-gamma-induced ICAM-1 message.@@@@1@35@@oe@16-12-2010 919277008@GENIA Treebank@formal@@1@S@Thus, IL-10 inhibits IFN-gamma-induced ICAM-1 expression in monocytes primarily at the level of gene transcription.@@@@1@17@@oe@16-12-2010 919277009@GENIA Treebank@formal@@1@S@Activation of IFN-gamma-responsive genes requires tyrosine phosphorylation of the transcriptional factor STAT-1alpha (signal transducer and activator of transcription-1alpha).@@@@1@21@@oe@16-12-2010 919277010@GENIA Treebank@formal@@1@S@However, IL-10 did not affect IFN-gamma-induced tyrosine phosphorylation of STAT-1alpha or alter STAT-1alpha binding to the IFN-gamma response element (IRE) in the ICAM-1 promoter.@@@@1@28@@oe@16-12-2010 919277011@GENIA Treebank@formal@@1@S@Instead, IL-10 prevented IFN-gamma-induced binding activity at the NF-kappaB site of the tumor necrosis factor alpha (TNF-alpha)-responsive NF-kappaB/C-EBP composite element in the ICAM-1 promoter.@@@@1@29@@oe@16-12-2010 919277012@GENIA Treebank@formal@@1@S@These data indicate that IL-10 inhibits IFN-gamma-induced transcription of the ICAM-1 gene by a regulatory mechanism that may involve NF-kappaB.@@@@1@21@@oe@16-12-2010 919512701@GENIA Treebank@formal@@1@S@Biphasic control of NF-kappa B activation induced by the triggering of HLA-DR antigens expressed on B cells.@@@@1@18@@oe@16-12-2010 919512702@GENIA Treebank@formal@@1@S@The regulation of NF-kappa B activation following the triggering of HLA-DR antigens by mAb L243 has been studied at various times in Raji cells.@@@@1@25@@oe@16-12-2010 919512703@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift assays demonstrated a strong increase of NF-kappa B DNA binding after triggering of HLA-DR antigens.@@@@1@19@@oe@16-12-2010 919512704@GENIA Treebank@formal@@1@S@Using TNF-alpha-activity neutralizing antibodies, the authors demonstrated that the upregulation of NF-kappa B was found to depend, at later time point, on an autocrine effect of TNF-alpha secreted following triggering of HLA-DR antigens.@@@@1@37@@oe@16-12-2010 919512705@GENIA Treebank@formal@@1@S@In contrast, it was found to be TNF-alpha independent in the early time point.@@@@1@16@@oe@16-12-2010 919512706@GENIA Treebank@formal@@1@S@Moreover, the upregulation of NF-kappa B binding activity is regulated by the triggering of selected epitopes of HLA-DR antigens.@@@@1@21@@oe@16-12-2010 919512707@GENIA Treebank@formal@@1@S@In fact, mAb L243 but not the staphylococcal superantigens, staphylococcal exotoxin toxic shock syndrome toxin-I or staphylococcal enterotoxin B, regulate the NF-kappa B binding activity.@@@@1@29@@oe@16-12-2010 919930001@GENIA Treebank@formal@@1@S@Comparison of the transactivation domains of Stat5 and Stat6 in lymphoid cells and mammary epithelial cells.@@@@1@17@@oe@16-12-2010 919930002@GENIA Treebank@formal@@1@S@Stat (signal transducers and activators of transcription) and Jak (Janus kinases) proteins are central components in the signal transduction events in hematopoietic and epithelial cells.@@@@1@30@@oe@16-12-2010 919930003@GENIA Treebank@formal@@1@S@They are rapidly activated by various cytokines, hormones, and growth factors.@@@@1@14@@oe@16-12-2010 919930004@GENIA Treebank@formal@@1@S@Upon ligand binding and cytokine receptor dimerization, Stat proteins are phosphorylated on tyrosine residues by Jak kinases.@@@@1@19@@oe@16-12-2010 919930005@GENIA Treebank@formal@@1@S@Activated Stat proteins form homo- or heterodimers, translocate to the nucleus, and induce transcription from responsive genes.@@@@1@20@@oe@16-12-2010 919930006@GENIA Treebank@formal@@1@S@Stat5 and Stat6 are transcription factors active in mammary epithelial cells and immune cells.@@@@1@15@@oe@16-12-2010 919930007@GENIA Treebank@formal@@1@S@Prolactin activates Stat5, and interleukin-4 (IL-4) activates Stat6.@@@@1@12@@oe@16-12-2010 919930008@GENIA Treebank@formal@@1@S@Both cytokines are able to stimulate cell proliferation, differentiation, and survival.@@@@1@14@@oe@16-12-2010 919930009@GENIA Treebank@formal@@1@S@We investigated the transactivation potential of Stat6 and found that it is not restricted to lymphocytes.@@@@1@17@@oe@16-12-2010 919930010@GENIA Treebank@formal@@1@S@IL-4-dependent activation of Stat6 was also observed in HC11 mammary epithelial cells.@@@@1@13@@oe@16-12-2010 919930011@GENIA Treebank@formal@@1@S@In these cells, Stat6 activation led to the induction of the beta-casein gene promoter.@@@@1@16@@oe@16-12-2010 919930012@GENIA Treebank@formal@@1@S@The induction of this promoter was confirmed in COS7 cells.@@@@1@11@@oe@16-12-2010 919930013@GENIA Treebank@formal@@1@S@The glucocorticoid receptor was able to further enhance IL-4-induced gene transcription through the action of Stat6.@@@@1@17@@oe@16-12-2010 919930014@GENIA Treebank@formal@@1@S@Deletion analysis of the carboxyl-terminal region of Stat6 and recombination of this region with a heterologous DNA binding domain allowed the delimitation and characterization of the transactivation domain of Stat6.@@@@1@31@@oe@16-12-2010 919930015@GENIA Treebank@formal@@1@S@The potencies of the transactivation domains of Stat5, Stat6, and viral protein VP16 were compared.@@@@1@18@@oe@16-12-2010 919930016@GENIA Treebank@formal@@1@S@Stat6 had a transactivation domain which was about 10-fold stronger than that of Stat5.@@@@1@15@@oe@16-12-2010 919930017@GENIA Treebank@formal@@1@S@In pre-B cells (Ba/F3), the transactivation domain of Stat6 was IL-4 regulated, independently from its DNA binding function.@@@@1@23@@oe@16-12-2010 919930501@GENIA Treebank@formal@@1@S@The immediate-early gene product Egr-1 regulates the human interleukin-2 receptor beta-chain promoter through noncanonical Egr and Sp1 binding sites.@@@@1@20@@oe@16-12-2010 919930502@GENIA Treebank@formal@@1@S@The interleukin-2 IL-2 receptor beta-chain (IL-2Rbeta) is an essential component of the receptors for IL-2 and IL-15.@@@@1@20@@oe@16-12-2010 919930503@GENIA Treebank@formal@@1@S@Although IL-2Rbeta is constitutively expressed by lymphocytes, its expression can be further induced by a number of stimuli, including phorbol 12-myristate 13-acetate (PMA).@@@@1@28@@oe@16-12-2010 919930504@GENIA Treebank@formal@@1@S@We have now characterized factors that bind to an enhancer region located between nucleotides -170 and -139 of the human IL-2Rbeta promoter.@@@@1@23@@oe@16-12-2010 919930505@GENIA Treebank@formal@@1@S@Both Sp1 and Sp3 bound to the 5' portion of this region, whereas a PMA-inducible factor (PIF) mainly bound to its 3' portion and bound to the Sp binding motifs as well.@@@@1@36@@oe@16-12-2010 919930506@GENIA Treebank@formal@@1@S@In Jurkat T cells, induction of PIF DNA binding activity was rapidly induced, required de novo protein synthesis, and was sustained at a high level for at least 23 h.@@@@1@34@@oe@16-12-2010 919930507@GENIA Treebank@formal@@1@S@Interestingly, PIF was constitutively activated in human T-cell leukemia virus type 1-transformed MT-2 cells.@@@@1@16@@oe@16-12-2010 919930508@GENIA Treebank@formal@@1@S@In this paper, we demonstrate that PIF is Egr-1 based on its recognition by anti-Egr-1 antisera in gel mobility shift assays, even though the IL-2Rbeta DNA binding motif differed substantially from the canonical Egr-1 binding site.@@@@1@39@@oe@16-12-2010 919930509@GENIA Treebank@formal@@1@S@In addition, Egr-1 bound to the Sp binding site.@@@@1@11@@oe@16-12-2010 919930510@GENIA Treebank@formal@@1@S@In Jurkat cells, both sites were required for maximal IL-2Rbeta promoter activity, and in HeLaS3 cells, transfection of Egr-1 could drive activity of a reporter construct containing both sites.@@@@1@33@@oe@16-12-2010 919930511@GENIA Treebank@formal@@1@S@Moreover, Sp1 and Egr-1 could form a complex with kinetics that correlated with the production of Egr-1 in Jurkat cells upon PMA stimulation.@@@@1@25@@oe@16-12-2010 919930512@GENIA Treebank@formal@@1@S@Thus, Sp1 and Egr-1 physically and functionally cooperate to mediate maximal IL-2Rbeta promoter activity.@@@@1@16@@oe@16-12-2010 919946401@GENIA Treebank@formal@@1@S@Anti-Ehrlichia chaffeensis antibody complexed with E. chaffeensis induces potent proinflammatory cytokine mRNA expression in human monocytes through sustained reduction of IkappaB-alpha and activation of NF-kappaB.@@@@1@26@@oe@16-12-2010 919946402@GENIA Treebank@formal@@1@S@Ehrlichia chaffeensis is an obligatory intracellular bacterium that infects monocytes and macrophages and is the etiologic agent of human ehrlichiosis in the United States.@@@@1@25@@oe@16-12-2010 919946403@GENIA Treebank@formal@@1@S@Our previous studies showed that the exposure of human monocytes to E. chaffeensis induces the expression of interleukin-1beta (IL-1beta), IL-8, and IL-10 genes in vitro but not the expression of tumor necrosis factor alpha (TNF-alpha) and IL-6 mRNAs.@@@@1@45@@oe@16-12-2010 919946404@GENIA Treebank@formal@@1@S@In this study, the effect of anti-E. chaffeensis antibody complexed with E. chaffeensis on the expression of major proinflammatory cytokines in human monocytes was examined.@@@@1@27@@oe@16-12-2010 919946405@GENIA Treebank@formal@@1@S@Human monocytic cell line THP-1 was treated with E. chaffeensis which had been preincubated with human anti-E. chaffeensis serum for 2 h, and the levels of cytokine mRNAs were evaluated by competitive reverse transcription-PCR.@@@@1@36@@oe@16-12-2010 919946406@GENIA Treebank@formal@@1@S@Anti-E. chaffeensis antibody complexed with E. chaffeensis significantly enhanced mRNA expression of IL-1beta in THP-1 cells.@@@@1@17@@oe@16-12-2010 919946407@GENIA Treebank@formal@@1@S@The expression of TNF-alpha and IL-6 mRNAs was also induced.@@@@1@11@@oe@16-12-2010 919946408@GENIA Treebank@formal@@1@S@The levels of secreted IL-1beta, TNF-alpha, and IL-6 during 24 h of stimulation were comparable to those induced by Escherichia coli lipopolysaccharide at 1 microg/ml.@@@@1@28@@oe@16-12-2010 919946409@GENIA Treebank@formal@@1@S@Fab fragment of anti-E. chaffeensis immunoglobulin G complexed with E. chaffeensis did not induce any of these three cytokines, indicating that ehrlichial binding is required for IL-1beta mRNA expression and that binding of the immune complex to the Fc gamma receptor is required for TNF-alpha and IL-6 mRNA expression and enhanced IL-1beta mRNA expression.@@@@1@56@@oe@16-12-2010 919946410@GENIA Treebank@formal@@1@S@Furthermore, prolonged degradation of IkappaB-alpha and activation of NF-kappaB were demonstrated in THP-1 cells exposed to anti-E. chaffeensis serum and E. chaffeensis.@@@@1@24@@oe@16-12-2010 919946411@GENIA Treebank@formal@@1@S@This result implies that development of anti-E. chaffeensis antibody in patients can result in the production of major proinflammatory cytokines, which may play an important role in the pathophysiology of ehrlichiosis and immune responses to it.@@@@1@38@@oe@16-12-2010 919989801@GENIA Treebank@formal@@1@S@S-allyl cysteine inhibits activation of nuclear factor kappa B in human T cells.@@@@1@14@@oe@16-12-2010 919989802@GENIA Treebank@formal@@1@S@Reactive oxygen species are involved in signal transduction pathways leading to nuclear factor kappa B (NF-kappa B) activation which has been implicated in the regulation of gene transcription.@@@@1@31@@oe@16-12-2010 919989803@GENIA Treebank@formal@@1@S@We recently reported that a garlic compound, S-allyl cysteine (SAC), protects bovine pulmonary artery endothelial cells from oxidant injury induced by hydrogen peroxide (H2O2).@@@@1@31@@oe@16-12-2010 919989804@GENIA Treebank@formal@@1@S@In this study we determined the effects of SAC on NF-kappa B activation in human T lymphocytes (Jurkat cells) induced by tumor necrosis factor alpha (TNF- alpha) and H2O2.@@@@1@33@@oe@16-12-2010 919989805@GENIA Treebank@formal@@1@S@Activated NF-kappa B in nuclear extracts was measured by an electrophoretic mobility shift assay using 32P-labeled probe.@@@@1@18@@oe@16-12-2010 919989806@GENIA Treebank@formal@@1@S@SAC consistently exhibited a dose-dependent inhibition of NF-kappa B activation induced by both TNF-alpha and H2O2.@@@@1@17@@oe@16-12-2010 919989807@GENIA Treebank@formal@@1@S@Supershift with specific antibodies to NF-kappa B subunits confirmed that the inducible retarded bands observed in the EMSA and p65-p50 heterodimer of the NF-kappa B/Rel protein.@@@@1@27@@oe@16-12-2010 919989808@GENIA Treebank@formal@@1@S@Our data suggest that SAC may act via antioxidant mechanisms to block NF-kappa B activation in Jurkat cells.@@@@1@19@@oe@16-12-2010 920124201@GENIA Treebank@formal@@1@S@Effect of adenovirus 2 on cellular gene activation in blood-derived monocytes and macrophages.@@@@1@14@@oe@16-12-2010 920124202@GENIA Treebank@formal@@1@S@We have investigated the effect of adenovirus 2 (Ad2) infection on human monocytes and monocyte-derived macrophages with regard to expression of TNF-alpha and IL-1 beta.@@@@1@28@@oe@16-12-2010 920124203@GENIA Treebank@formal@@1@S@In monocytes, the virus was bound to the surface without being internalized.@@@@1@14@@oe@16-12-2010 920124204@GENIA Treebank@formal@@1@S@On the other hand, Ad2 was internalized by macrophages.@@@@1@11@@oe@16-12-2010 920124205@GENIA Treebank@formal@@1@S@No virus replication and no transcription of the Ad2 early genes was observed in either of the cells.@@@@1@19@@oe@16-12-2010 920124206@GENIA Treebank@formal@@1@S@Ad2 infection induced transient increase in the mRNA levels for TNF-alpha and IL-1 beta in both monocytes and in macrophages, although the kinetics of the transcription was slightly different.@@@@1@31@@oe@16-12-2010 920124207@GENIA Treebank@formal@@1@S@The production of both cytokines, measured by ELISA tests, was enhanced in monocytes.@@@@1@16@@oe@16-12-2010 920124208@GENIA Treebank@formal@@1@S@In macrophages, a slight enhancement of TNF-alpha production was seen, whereas IL-1 beta was not detected.@@@@1@19@@oe@16-12-2010 920124209@GENIA Treebank@formal@@1@S@The data indicate that cellular genes might be activated by Ad2 virus infection in nonpermissive cells where no viral gene products could be detected.@@@@1@25@@oe@16-12-2010 920509801@GENIA Treebank@formal@@1@S@Chimeric oncoprotein E2a-Pbx1 induces apoptosis of hematopoietic cells by a p53-independent mechanism that is suppressed by Bcl-2.@@@@1@18@@oe@16-12-2010 920509802@GENIA Treebank@formal@@1@S@The chimeric oncoprotein E2a-Pbx1 results from fusion of the E2A and PBX1 genes following t(1;19) chromosomal translocations in B cell precursor acute leukemias.@@@@1@24@@oe@16-12-2010 920509803@GENIA Treebank@formal@@1@S@Experimentally B cell progenitors do not tolerate constitutive expression of E2a-Pbx1 which contrasts with transformation of several other cell types following its stable expression both in vitro and in vivo.@@@@1@31@@oe@16-12-2010 920509804@GENIA Treebank@formal@@1@S@To further investigate the effects of E2a-Pbx1 on the B cell progenitors, we conditionally expressed E2a-Pbx1 under control of a metal response element in hematopoietic precursor cell lines in vitro.@@@@1@32@@oe@16-12-2010 920509805@GENIA Treebank@formal@@1@S@Inducible expression of E2a-Pbx1 resulted in cell death with the morphologic and molecular features of apoptosis.@@@@1@17@@oe@16-12-2010 920509806@GENIA Treebank@formal@@1@S@A structure-function analysis demonstrated that induction of apoptosis was not a dominant-negative effect of the E2a moiety but, rather, required the DNA-binding homeodomain of Pbx1.@@@@1@28@@oe@16-12-2010 920509807@GENIA Treebank@formal@@1@S@E2a-Pbx1-induced apoptosis proceeded through a BCL2-responsive checkpoint eventuating in PARP inactivation but did require p53.@@@@1@16@@oe@16-12-2010 920509808@GENIA Treebank@formal@@1@S@Constitutive expression of E2a-Pbx1 did not induce apoptosis or continued cycling of Rat-1 fibroblasts in low serum conditions.@@@@1@19@@oe@16-12-2010 920509809@GENIA Treebank@formal@@1@S@These studies demonstrate that E2a-Pbx1 initiates programmed cell death of hematopoietic precursers by a mechanism that requires its chimeric transcriptional properties, but, unlike other nuclear oncoproteins, is independent of p53.@@@@1@34@@oe@16-12-2010 920926801@GENIA Treebank@formal@@1@S@Activation of nuclear factor-kappa B by beta-amyloid peptides and interferon-gamma in murine microglia.@@@@1@14@@oe@16-12-2010 920926802@GENIA Treebank@formal@@1@S@An increasing body of evidence suggests that amyloid-beta (A beta) peptides and microglia are crucially involved in the pathogenesis of Alzheimer's disease.@@@@1@26@@oe@16-12-2010 920926803@GENIA Treebank@formal@@1@S@In an effort to further elucidate the biological effects of A beta towards microglia, we investigated the ability of A beta peptides to activate nuclear factor (NF)-kappa B in the N9 murine microglial cell line.@@@@1@40@@oe@16-12-2010 920926804@GENIA Treebank@formal@@1@S@Co-stimulation of microglia with suboptimal concentrations of A beta(25-35) and 100 U/ml IFN gamma resulted in the detection of a specific NF-kappa B DNA-binding activity in nuclear extracts, as determined in gel mobility shift assays.@@@@1@40@@oe@16-12-2010 920926805@GENIA Treebank@formal@@1@S@This response required at least 120 min to be evident and supershift experiments revealed that the NF-kappa B complex contains both RelA and p50.@@@@1@25@@oe@16-12-2010 920926806@GENIA Treebank@formal@@1@S@Accordingly, immunoblot experiments showed that amongst NF-kappa B/Rel proteins, RelA and p50 are mobilized to the nucleus following microglial cell stimulation with A beta(25-35) plus IFN gamma.@@@@1@33@@oe@16-12-2010 920926807@GENIA Treebank@formal@@1@S@Higher concentrations of A beta(25-35) were effective by themselves in inducing NF-kappa B activation, both in the N9 microglial cell line and in rat primary microglia, as well as in human monocytes.@@@@1@38@@oe@16-12-2010 920926808@GENIA Treebank@formal@@1@S@For purposes of comparison, microglia were also stimulated with bacterial LPS, a known NF-kappa B inducer.@@@@1@19@@oe@16-12-2010 920926809@GENIA Treebank@formal@@1@S@As expected, LPS strongly induced the formation of two NF-kappa B DNA-binding activities, one of which was identified as RelA/p50.@@@@1@23@@oe@16-12-2010 920926810@GENIA Treebank@formal@@1@S@The LPS response was also more rapid, as it was already evident by 40 min and remained sustained for up to 3 h.@@@@1@25@@oe@16-12-2010 920926811@GENIA Treebank@formal@@1@S@Collectively, these findings indicate that NF-kappa B activation might constitute one of the mechanisms underlying the inducible expression of kappa B-dependent genes in microglia stimulated by A beta peptides and IFN gamma, or by LPS.@@@@1@38@@oe@16-12-2010 920928101@GENIA Treebank@formal@@1@S@Sp family members preferentially interact with the promoter proximal repeat within the HTLV-I enhancer.@@@@1@15@@oe@16-12-2010 920928102@GENIA Treebank@formal@@1@S@Human T cell lymphotropic virus type I (HTLV-I) encodes the transactivator protein, Tax, which facilitates viral transcription from three 21 bp repeated elements within the U3 region of the long terminal repeat (LTR).@@@@1@40@@oe@16-12-2010 920928103@GENIA Treebank@formal@@1@S@Examination of the basal factors interacting with the 21 bp repeat elements through electrophoretic mobility shift (EMS) analyses has demonstrated the formation of DNA-protein complexes common to each of the 21 bp repeats (C1-C3) as well as three DNA-protein complexes specific to the promoter proximal (pp) repeat (U1 (U1A/U1B) and U2; 1-4).@@@@1@64@@oe@16-12-2010 920928104@GENIA Treebank@formal@@1@S@These studies have indicated that the individual repeats are not identical with respect to the cellular factors with which they interact.@@@@1@22@@oe@16-12-2010 920928105@GENIA Treebank@formal@@1@S@EMS analyses utilizing a series of mutated pp repeat elements demonstrate that the nucleotide sequence requirements for U1 (U1A/U1B) and U2 formation are separable from those required for C1-C3 formation.@@@@1@33@@oe@16-12-2010 920928106@GENIA Treebank@formal@@1@S@Competition EMS analyses utilizing Sp1 and CREB binding site oligonucleotides demonstrate that Sp family members are critical components of U1 (U1A/U1B) and U2 and that ATF/CREB family members are critical components of C1-C3.@@@@1@36@@oe@16-12-2010 920928107@GENIA Treebank@formal@@1@S@EMS supershift analyses have demonstrated that Sp1 is involved in U1A formation while Sp3 is involved in U1B and U2 formation.@@@@1@22@@oe@16-12-2010 920928108@GENIA Treebank@formal@@1@S@EMS analyses performed with nuclear extracts from Tax-expressing Jurkat cells and HTLV-I-transformed peripheral blood mononuclear cells demonstrate that Tax prevents the formation of U1 (U1A/U1B) and U2 DNA-protein complexes.@@@@1@32@@oe@16-12-2010 920928109@GENIA Treebank@formal@@1@S@Therefore, Tax appears to inhibit the interaction of Sp family members with the pp repeat.@@@@1@17@@oe@16-12-2010 920928110@GENIA Treebank@formal@@1@S@Based on these observations, it is possible that the interaction of Sp and ATF/CREB family members with the pp repeat during basal and Tax-mediated transcription may play a critical role in viral gene expression during the initial stages of virus infection or during activation of a latent infection.@@@@1@50@@oe@16-12-2010 920928401@GENIA Treebank@formal@@1@S@AP-1 derived from mature monocytes and astrocytes preferentially interacts with the HTLV-I promoter central 21 bp repeat.@@@@1@18@@oe@16-12-2010 920928402@GENIA Treebank@formal@@1@S@Characterization of the cellular transcription factors interacting with the human T cell lymphotropic virus type I (HTLV-I) long terminal repeat (LTR) is essential to dissecting the mechanisms involved in viral transcription that may be pertinent to the oncogenic and neuropathogenic processes associated with HTLV-I infection in both the immune and nervous systems.@@@@1@57@@oe@16-12-2010 920928403@GENIA Treebank@formal@@1@S@Electrophoretic mobility shift (EMS) analyses utilizing oligonucleotides homologous to each of the 21 bp repeat elements reacted with nuclear extracts derived from cell lines of lymphocytic, monocytic, neuronal, and glial cell origin have demonstrated differential binding of cellular factors to the three 21 bp repeats (1-4).@@@@1@54@@oe@16-12-2010 920928404@GENIA Treebank@formal@@1@S@ATF/CREB and Sp family members interacted with the 21 bp repeats to form DNA-protein complexes common to all cell types examined.@@@@1@22@@oe@16-12-2010 920928405@GENIA Treebank@formal@@1@S@However, a unique DNA-protein complex was detected when the promoter central 21 bp repeat was reacted with nuclear extracts derived from either the U-373 MG glioblastoma cell line or the THP-1 mature monocytic cell line.@@@@1@37@@oe@16-12-2010 920928406@GENIA Treebank@formal@@1@S@Based on nucleotide sequence requirements and immunoreactivity, we demonstrate that this DNA-protein complex is comprised of the AP-1 components, Fos and Jun.@@@@1@25@@oe@16-12-2010 920937201@GENIA Treebank@formal@@1@S@An acute myeloid leukemia gene, AML1, regulates transcriptional activation and hemopoietic myeloid cell differentiation antagonistically by two alternative spliced forms.@@@@1@23@@oe@16-12-2010 920937202@GENIA Treebank@formal@@1@S@The AML1 gene on chromosome 21 is disrupted in the (8;21)(q22;q22) and (3;21)(q26;q22) translocations associated with myelogenous leukemias and encodes a DNA-binding protein.@@@@1@24@@oe@16-12-2010 920937203@GENIA Treebank@formal@@1@S@From AML1 gene, two representative forms of proteins, AML1a and AML1b, are produced by an alternative splicing.@@@@1@21@@oe@16-12-2010 920937204@GENIA Treebank@formal@@1@S@Both forms have DNA-binding domain, but AML1a lacks a putative transcriptional activation domain which AML1b has.@@@@1@18@@oe@16-12-2010 920937205@GENIA Treebank@formal@@1@S@Here we demonstrate that AML1a, which solely has no effects as a transcriptional regulator, dominantly suppresses transcriptional activation by AML1b, and that AML1a exhibits the higher affinity for DNA-binding than AML1b.@@@@1@35@@oe@16-12-2010 920937206@GENIA Treebank@formal@@1@S@Furthermore a dominant negative form of AML1, AML1a, totally suppressed granulocytic differentiation otherwise induced by granulocyte colony-stimulating factor when AML1a was overexpressed in 32Dc13 murine myeloid cells.@@@@1@30@@oe@16-12-2010 920937207@GENIA Treebank@formal@@1@S@Such differentiation block by AML1a was canceled by the concomitant overexpression of AML1b.@@@@1@14@@oe@16-12-2010 920937208@GENIA Treebank@formal@@1@S@These data strongly suggest that a transcriptionally active form of AML1 is essential for the myeloid cell differentiation.@@@@1@19@@oe@16-12-2010 920937209@GENIA Treebank@formal@@1@S@In addition, we observed an altered expression level of AML1 along with the myeloid differentiation in several hemopoietic cell lines.@@@@1@22@@oe@16-12-2010 920937210@GENIA Treebank@formal@@1@S@In these cases, at least, the AML1 expression level is a potential regulator for myeloid cell differentiation.@@@@1@20@@oe@16-12-2010 920943801@GENIA Treebank@formal@@1@S@Of the GATA-binding proteins, only GATA-4 selectively regulates the human IL-5 gene promoter in IL-5 producing cells which express multiple GATA-binding proteins.@@@@1@24@@oe@16-12-2010 920943802@GENIA Treebank@formal@@1@S@Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B cell growth and eosinophilic differentiation of the progenitor cells.@@@@1@24@@oe@16-12-2010 920943803@GENIA Treebank@formal@@1@S@Using ATL-16T cells which express IL-5 mRNA, we have identified a region, within the human IL-5 gene promoter, that regulates IL-5 gene transcription.@@@@1@27@@oe@16-12-2010 920943804@GENIA Treebank@formal@@1@S@This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of these family members.@@@@1@25@@oe@16-12-2010 920943805@GENIA Treebank@formal@@1@S@In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region.@@@@1@32@@oe@16-12-2010 920943806@GENIA Treebank@formal@@1@S@By promoter deletion and mutation analyses, we established this region as a positive regulatory element.@@@@1@17@@oe@16-12-2010 920943807@GENIA Treebank@formal@@1@S@Cotransfection experiments revealed that both hGATA-4 and PMA/A23187 stimulation are necessary for the IL-5 promoter activation.@@@@1@17@@oe@16-12-2010 920943808@GENIA Treebank@formal@@1@S@The requirement of another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated.@@@@1@22@@oe@16-12-2010 920943809@GENIA Treebank@formal@@1@S@ATL-16T cells express mRNA of three GATA-binding proteins, hGATA-2, hGATA-3 and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/ A) motif.@@@@1@30@@oe@16-12-2010 920943810@GENIA Treebank@formal@@1@S@However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms specific DNA-protein complex with the -70 GATA site.@@@@1@27@@oe@16-12-2010 920943811@GENIA Treebank@formal@@1@S@The electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity to the -70 GATA site among the three GATA-binding proteins.@@@@1@32@@oe@16-12-2010 920943812@GENIA Treebank@formal@@1@S@When the transactivation ability was compared among the three, GATA-4 showed the highest activity.@@@@1@16@@oe@16-12-2010 920943813@GENIA Treebank@formal@@1@S@These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed.@@@@1@29@@oe@16-12-2010 921037201@GENIA Treebank@formal@@1@S@Cytokines: shared receptors, distinct functions.@@@@1@8@@oe@16-12-2010 921037202@GENIA Treebank@formal@@1@S@That the signal transduction pathways used by the cytokines IL-2 and IL-15 are identical would suggest that these cytokines have redundant roles in lymphoid development; instead, IL-2 is the guardian of thymus-derived T-cell homeostasis, while interleukin-15 promotes extrathymic development of T and NK cells.@@@@1@48@@oe@16-12-2010 921184701@GENIA Treebank@formal@@1@S@Inducible expression and phosphorylation of coactivator BOB.1/OBF.1 in T cells [see comments]@@@@1@14@@oe@16-12-2010 921184702@GENIA Treebank@formal@@1@S@BOB.1/OBF.1 is a transcriptional coactivator that is constitutively expressed in B cells and interacts with the Oct1 and Oct2 transcription factors.@@@@1@22@@oe@16-12-2010 921184703@GENIA Treebank@formal@@1@S@Upon activation of Jurkat T cells and primary murine thymocytes with phorbol esters and ionomycin, BOB.1/OBF.1 expression and transactivation function were induced.@@@@1@24@@oe@16-12-2010 921184704@GENIA Treebank@formal@@1@S@BOB.1/OBF.1 was phosphorylated at Ser184 both in vivo and in vitro, and this modification was required for inducible activation.@@@@1@21@@oe@16-12-2010 921184705@GENIA Treebank@formal@@1@S@Mutation of Ser184 also diminished transactivation function in B cells, suggesting that the activating phosphorylation that is inducible in T cells is constitutively present in B cells.@@@@1@29@@oe@16-12-2010 921184706@GENIA Treebank@formal@@1@S@Thus, BOB.1/OBF.1 is a transcriptional coactivator that is critically regulated by posttranslational modifications to mediate cell type-specific gene expression.@@@@1@21@@oe@16-12-2010 921188901@GENIA Treebank@formal@@1@S@The cytoplasmic domain of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit is essential for both GM-CSF-mediated growth and differentiation.@@@@1@22@@oe@16-12-2010 921188902@GENIA Treebank@formal@@1@S@Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates differentiation, survival, and proliferation of colony-forming unit-granulocyte-macrophage progenitor cells.@@@@1@19@@oe@16-12-2010 921188903@GENIA Treebank@formal@@1@S@The biologic actions of GM-CSF are mediated by binding to a specific receptor consisting of two chains designated as alpha and beta subunits.@@@@1@24@@oe@16-12-2010 921188904@GENIA Treebank@formal@@1@S@We have demonstrated that the murine FDC-P1-derived cell line WT-19 transfected with the human GM-CSF receptor alpha and beta subunits (GM-CSFRalpha and beta) can be induced to differentiate by the addition of human GM-CSF (hGM-CSF).@@@@1@40@@oe@16-12-2010 921188905@GENIA Treebank@formal@@1@S@By expressing a series of GM-CSFRalpha mutants in WT19 cells, we have determined the amino acid domains of the GM-CSFRalpha cytoplasmic domain that regulate cell differentiation, proliferation, and survival.@@@@1@33@@oe@16-12-2010 921188906@GENIA Treebank@formal@@1@S@We found that the membrane proximal proline-rich domain and adjacent 16 residues are essential for both hGM-CSF-dependent cell proliferation and differentiation.@@@@1@22@@oe@16-12-2010 921188907@GENIA Treebank@formal@@1@S@In contrast, the C-terminal region of the GM-CSFRalpha cytoplasmic domain was not necessary for cell differentiation mediated by hGM-CSF, but the removal of this region severely impaired the ability of hGM-CSF to support cell survival.@@@@1@38@@oe@16-12-2010 921188908@GENIA Treebank@formal@@1@S@While the activation of JAK2, Shc, Erk, and STAT5 proteins correlated with hGM-CSF-mediated cell growth, cellular differentiation occurred in the absence of activation of these signal transduction pathways.@@@@1@33@@oe@16-12-2010 921193301@GENIA Treebank@formal@@1@S@Lipopolysaccharide induction of the tumor necrosis factor-alpha promoter in human monocytic cells.@@@@1@13@@oe@16-12-2010 921193302@GENIA Treebank@formal@@1@S@Regulation by Egr-1, c-Jun, and NF-kappaB transcription factors.@@@@1@11@@oe@16-12-2010 921193303@GENIA Treebank@formal@@1@S@Biosynthesis of tumor necrosis factor-alpha (TNF-alpha) is predominantly by cells of the monocytic lineage.@@@@1@17@@oe@16-12-2010 921193304@GENIA Treebank@formal@@1@S@This study examined the role of various cis-acting regulatory elements in the lipopolysaccharide (LPS) induction of the human TNF-alpha promoter in cells of monocytic lineage.@@@@1@28@@oe@16-12-2010 921193305@GENIA Treebank@formal@@1@S@Functional analysis of monocytic THP-1 cells transfected with plasmids containing various lengths of TNF-alpha promoter localized enhancer elements in a region (-182 to -37 base pairs (bp)) that were required for optimal transcription of the TNF-alpha gene in response to LPS.@@@@1@46@@oe@16-12-2010 921193306@GENIA Treebank@formal@@1@S@Two regions were identified: region I (-182 to -162 bp) contained an overlapping Sp1/Egr-1 site, and region II (-119 to -88) contained CRE and NF-kappaB (designated kappaB3) sites.@@@@1@37@@oe@16-12-2010 921193307@GENIA Treebank@formal@@1@S@In unstimulated THP-1, CRE-binding protein and, to a lesser extent, c-Jun complexes were found to bind to the CRE site.@@@@1@24@@oe@16-12-2010 921193308@GENIA Treebank@formal@@1@S@LPS stimulation increased the binding of c-Jun-containing complexes.@@@@1@9@@oe@16-12-2010 921193309@GENIA Treebank@formal@@1@S@In addition, LPS stimulation induced the binding of cognate nuclear factors to the Egr-1 and kappaB3 sites, which were identified as Egr-1 and p50/p65, respectively.@@@@1@29@@oe@16-12-2010 921193310@GENIA Treebank@formal@@1@S@The CRE and kappaB3 sites in region II together conferred strong LPS responsiveness to a heterologous promoter, whereas individually they failed to provide transcriptional activation.@@@@1@27@@oe@16-12-2010 921193311@GENIA Treebank@formal@@1@S@Furthermore, increasing the spacing between the CRE and the kappaB3 sites completely abolished LPS induction, suggesting a cooperative interaction between c-Jun complexes and p50/p65.@@@@1@27@@oe@16-12-2010 921193312@GENIA Treebank@formal@@1@S@These studies indicate that maximal LPS induction of the TNF-alpha promoter is mediated by concerted participation of at least two separate cis-acting regulatory elements.@@@@1@25@@oe@16-12-2010 921205301@GENIA Treebank@formal@@1@S@Increased expression of Gs(alpha) enhances activation of the adenylyl cyclase signal transduction cascade.@@@@1@14@@oe@16-12-2010 921205302@GENIA Treebank@formal@@1@S@Expression of the stimulatory G protein, G(S)alpha, can vary over a 3-fold range in human tissues and in rodent central nervous system.@@@@1@25@@oe@16-12-2010 921205303@GENIA Treebank@formal@@1@S@In fact, the offspring of alcoholics have higher levels of G(S)alpha expression in certain tissues compared with the offspring of nonalcoholics.@@@@1@23@@oe@16-12-2010 921205304@GENIA Treebank@formal@@1@S@The aim of this research was to test the hypothesis that a causal relationship exists between the level of expression of G(S)alpha and induction of the adenylyl cyclase (AC) cascade.@@@@1@33@@oe@16-12-2010 921205305@GENIA Treebank@formal@@1@S@The methodology employed transient transfection of HEK 293 cells with a cDNA for the 52-kDa form of G(S)alpha under regulation by inducible metallothionein promoters.@@@@1@25@@oe@16-12-2010 921205306@GENIA Treebank@formal@@1@S@Transfectants were exposed to varying concentrations (0-125 microM) of zinc sulfate that produced a 3-fold range of membrane G(S)alpha expression.@@@@1@23@@oe@16-12-2010 921205307@GENIA Treebank@formal@@1@S@The range of G(S)alpha expression produced was found to mimic a physiologically relevant spectrum of G(S)alpha expression in membranes derived from human tissues and rat brain.@@@@1@27@@oe@16-12-2010 921205308@GENIA Treebank@formal@@1@S@It was observed that induction of G(S)alpha expression increased constitutive as well as stimulated cAMP accumulation.@@@@1@17@@oe@16-12-2010 921205309@GENIA Treebank@formal@@1@S@Moreover, induction of G(S)alpha expression increased events distal to the accumulation of cAMP including the phosphorylation of the transcription factor, cAMP response element binding protein and transcriptional activation of cAMP-dependent reporter genes.@@@@1@35@@oe@16-12-2010 921205310@GENIA Treebank@formal@@1@S@In summary, these studies show that the amount of G(S)alpha expression has a marked impact on the level of activity of the AC cascade from the membrane through to the nucleus.@@@@1@33@@oe@16-12-2010 921205311@GENIA Treebank@formal@@1@S@It is hypothesized that individuals who differ in G(S)alpha expression may also differ in the expression of certain cAMP-dependent genes.@@@@1@21@@oe@16-12-2010 921529801@GENIA Treebank@formal@@1@S@gamma-Interferon-induced resistance to 1,25-(OH)2 D3 in human monocytes and macrophages: a mechanism for the hypercalcemia of various granulomatoses.@@@@1@20@@oe@16-12-2010 921529802@GENIA Treebank@formal@@1@S@The hypercalcemia of various granulomatoses is caused by endogenous 1,25-dihydroxyvitamin D [1,25-(OH)2D3] overproduction by disease-activated macrophages.@@@@1@19@@oe@16-12-2010 921529803@GENIA Treebank@formal@@1@S@The inability of 1,25(OH)2D3 to suppress its synthesis in macrophages contrasts with the tight control of its production in macrophage precursors, peripheral blood monocytes (PBM).@@@@1@29@@oe@16-12-2010 921529804@GENIA Treebank@formal@@1@S@We examined whether 1,25(OH)2D3 resistance develops as PBM differentiate to macrophages or with macrophage activation.@@@@1@16@@oe@16-12-2010 921529805@GENIA Treebank@formal@@1@S@Normal human pulmonary alveolar macrophages (PAM) are less sensitive to 1,25(OH)2D3 than PBM, despite similar vitamin D receptor content; however, both PBM and PAM respond to exogenous 1,25-(OH)2D3 by inhibiting 1,25(OH)2D3 synthesis and inducing 1,25(OH)2D3 degradation through enhancement of 24-hydroxylase mRNA levels and activity.@@@@1@50@@oe@16-12-2010 921529806@GENIA Treebank@formal@@1@S@The human monocytic cell line THP-1 mimics PAM in 1,25(OH)2D3 synthesis and sensitivity to exogenous 1,25(OH)2D3.@@@@1@17@@oe@16-12-2010 921529807@GENIA Treebank@formal@@1@S@We utilized THP-1 cells to examine the response to 1,25(OH)2D3 with macrophage activation.@@@@1@14@@oe@16-12-2010 921529808@GENIA Treebank@formal@@1@S@Activation of THP-1 cells with gamma-interferon (gamma-IFN) enhances 1,25(OH)2D3 synthesis 30-fold, blocks 1,25-(OH)2D3 suppression of its synthesis, and reduces by 42.2% 1,25-(OH)2D3 induction of its degradation.@@@@1@32@@oe@16-12-2010 921529809@GENIA Treebank@formal@@1@S@The antagonistic effects of gamma-IFN are not merely restricted to enzymatic activities.@@@@1@13@@oe@16-12-2010 921529810@GENIA Treebank@formal@@1@S@In THP-1 cells and in normal PBM, gamma-IFN inhibits 1,25-(OH)2D3 induction of 24-hydroxylase mRNA levels without reducing mRNA stability, suggesting gamma-IFN inhibition of 1,25(OH)2D3 transactivating function.@@@@1@29@@oe@16-12-2010 921529811@GENIA Treebank@formal@@1@S@These results explain 1,25(OH)2D3 overproduction in granulomatoses and demonstrate potent inhibition by gamma-IFN of 1,25(OH)2D3 action in immune cells.@@@@1@20@@oe@16-12-2010 921574801@GENIA Treebank@formal@@1@S@Expression of transcription factors during sodium phenylacetate induced erythroid differentiation in K562 cells.@@@@1@14@@oe@16-12-2010 921574802@GENIA Treebank@formal@@1@S@During 15 days of treatment of K562 cells with sodium phenylacetate, we observed an increase in the cellular hemoglobin concentration with a similar increase in the expression of gamma-globin mRNA.@@@@1@32@@oe@16-12-2010 921574803@GENIA Treebank@formal@@1@S@Morphological studies demonstrated characteristic features of erythroid differentiation and maturation.@@@@1@11@@oe@16-12-2010 921574804@GENIA Treebank@formal@@1@S@At the same time there was no change in the level of expression of the cell surface antigenes CD33, CD34, CD45, CD71 and glycophorin A.@@@@1@29@@oe@16-12-2010 921574805@GENIA Treebank@formal@@1@S@Likewise, the level of expression of the erythroid transcription factors GATA-1, GATA-2, NF-E2, SCL and RBTN2, all expressed in untreated K562 cells, did not increase during sodium phenylacetate induced erythroid differentiation.@@@@1@38@@oe@16-12-2010 921574806@GENIA Treebank@formal@@1@S@The expression of the nuclear factors Evi-1 and c-myb, known to inhibit erythroid differentiation, did not decrease.@@@@1@20@@oe@16-12-2010 921574807@GENIA Treebank@formal@@1@S@We conclude that sodium phenylacetate treatment of K562 cells increases gamma-globin mRNA and induces cell maturation as judged by morphology without affecting the expression of the erythroid transcription factors, some of which are known to be involved in the regulation of beta-like globin genes.@@@@1@46@@oe@16-12-2010 921729001@GENIA Treebank@formal@@1@S@Glucocorticoid receptors in human peripheral blood mononuclear cells in relation to age and to sport activity.@@@@1@17@@oe@16-12-2010 921729002@GENIA Treebank@formal@@1@S@Glucocorticoid receptors (GR) are ubiquitous molecules and are present also in the hippocampus and in several other nervous and immune tissues.@@@@1@24@@oe@16-12-2010 921729003@GENIA Treebank@formal@@1@S@Peripheral blood mononuclear cells (PBMCs) are a good model for studies of GR in humans.@@@@1@18@@oe@16-12-2010 921729004@GENIA Treebank@formal@@1@S@Glucocorticoids are important for maintaining cellular and humoral homeostasis and are key mediators of neuroendocrine-immune regulatory interactions.@@@@1@18@@oe@16-12-2010 921729005@GENIA Treebank@formal@@1@S@The increase of cortisol is immunosuppressive and reduces GR concentration both in nervous and immune systems.@@@@1@17@@oe@16-12-2010 921729006@GENIA Treebank@formal@@1@S@Variation of glucocorticoids in healthy aged subjects and athletes has been shown.@@@@1@13@@oe@16-12-2010 921729007@GENIA Treebank@formal@@1@S@Prompted by these results, we have investigated in man a possible relationship between GR binding capacity in the PBMCs and age, in relation also to plasma testosterone and cortisol.@@@@1@32@@oe@16-12-2010 921729008@GENIA Treebank@formal@@1@S@The same parameters have been examined in a group of soccer players for comparison with the sedentary group.@@@@1@19@@oe@16-12-2010 921729009@GENIA Treebank@formal@@1@S@GR binding capacity was higher in younger subjects than in older ones, and lower in the group of athletes than in the younger and older sedentary subjects.@@@@1@29@@oe@16-12-2010 921729010@GENIA Treebank@formal@@1@S@In the sedentary group a negative correlation was present between GR binding capacity and age.@@@@1@16@@oe@16-12-2010 921729011@GENIA Treebank@formal@@1@S@Plasma cortisol was higher and testosterone lower in the athletes; they were negatively correlated in athletes and positively correlated in the sedentary subjects.@@@@1@25@@oe@16-12-2010 921729012@GENIA Treebank@formal@@1@S@The results for athletes agree with their lower anabolic/catabolic balance.@@@@1@11@@oe@16-12-2010 921729013@GENIA Treebank@formal@@1@S@The mechanism of reduced GR levels in relation to age and sport activity could involve a loss or an involution of receptor synthesis.@@@@1@24@@oe@16-12-2010 921729014@GENIA Treebank@formal@@1@S@However other possibilities, such as altered distribution of lymphocyte subpopulations with different receptor concentrations and with different cytokine production, cannot be excluded.@@@@1@26@@oe@16-12-2010 921729015@GENIA Treebank@formal@@1@S@Several neuroendocrine-immune interactions could be responsible for reduced GR levels with age and sport activity in man.@@@@1@18@@oe@16-12-2010 921853401@GENIA Treebank@formal@@1@S@Role of the X2 box in activated transcription from the DRA promoter in B cells.@@@@1@16@@oe@16-12-2010 921853402@GENIA Treebank@formal@@1@S@We investigated the function of the evolutionary conserved X2 box in the promoter of the HLA-DRA gene from the human major histocompatibility complex (MHC) in resting and activated B cells.@@@@1@33@@oe@16-12-2010 921853403@GENIA Treebank@formal@@1@S@NF-X2, which contains members of the AP-1/ATF/CREB families of transcription factors, interacts with the X2 box (5'-TGCGTCA-3') from positions -97 to -91 in the DRA promoter.@@@@1@31@@oe@16-12-2010 921853404@GENIA Treebank@formal@@1@S@In resting Raji cells, little to no binding to the X2 box was observed.@@@@1@16@@oe@16-12-2010 921853405@GENIA Treebank@formal@@1@S@In sharp contrast, in B cells treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), strong interactions between the X2 box and NF-X2 containing c-Fos were observed.@@@@1@30@@oe@16-12-2010 921853406@GENIA Treebank@formal@@1@S@As determined by transient expression and RNA analyses, the activation of protein kinase C (PKC) also increased rates of transcription from the wild-type DRA promoter but not from a DRA promoter bearing clustered point mutations in the X2 box.@@@@1@43@@oe@16-12-2010 921853407@GENIA Treebank@formal@@1@S@Since the co-expression with a dominant negative c-Fos abolished the responsiveness to TPA, we conclude that activated transcription of the DRA gene depends on interactions between the X2 box and NF-X2, which contains c-Fos.@@@@1@37@@oe@16-12-2010 921859701@GENIA Treebank@formal@@1@S@Interferons up-regulate STAT1, STAT2, and IRF family transcription factor gene expression in human peripheral blood mononuclear cells and macrophages.@@@@1@22@@oe@16-12-2010 921859702@GENIA Treebank@formal@@1@S@IFN signaling is mediated by binding of IFNs to their receptors and subsequent activation of Janus tyrosine kinase (JAK)-STAT signaling pathway.@@@@1@25@@oe@16-12-2010 921859703@GENIA Treebank@formal@@1@S@Stimulation of cells with IFN-alpha leads to the assembly of IFN-stimulated gene factor 3 transcription factor complex formed by STAT1, STAT2, and p48 protein.@@@@1@27@@oe@16-12-2010 921859704@GENIA Treebank@formal@@1@S@IFN-gamma signaling is mediated by homodimeric STAT1 protein.@@@@1@9@@oe@16-12-2010 921859705@GENIA Treebank@formal@@1@S@Although these signaling molecules are expressed constitutively, there is also evidence of transcriptional regulation by IFNs.@@@@1@18@@oe@16-12-2010 921859706@GENIA Treebank@formal@@1@S@We have characterized the expression of STAT and IFN regulatory factor (IRF) family transcription factors in primary human blood mononuclear cells and macrophages in response to IFN-alpha and IFN-gamma stimulation.@@@@1@33@@oe@16-12-2010 921859707@GENIA Treebank@formal@@1@S@We show that IFN-alpha and IFN-gamma rapidly and efficiently enhanced STAT1, STAT2, p48, and IRF-1 gene expression.@@@@1@21@@oe@16-12-2010 921859708@GENIA Treebank@formal@@1@S@IFN-gamma induced IRF-1 gene expression more strongly than IFN-alpha.@@@@1@10@@oe@16-12-2010 921859709@GENIA Treebank@formal@@1@S@Stimulation experiments in the presence of protein synthesis inhibitor, cycloheximide, suggested that these genes were activated directly by IFNs.@@@@1@22@@oe@16-12-2010 921859710@GENIA Treebank@formal@@1@S@IRF-2 gene was apparently only weakly responsive to IFNs in these cells.@@@@1@13@@oe@16-12-2010 921859711@GENIA Treebank@formal@@1@S@When macrophages were pretreated with low doses of IFN-gamma and then stimulated with IFN-alpha, clearly enhanced formation of specific transcription factor complexes was detected.@@@@1@26@@oe@16-12-2010 921859712@GENIA Treebank@formal@@1@S@This suggests that higher intracellular levels of STAT1, STAT2, and p48 protein may result in enhanced signal transduction for cytokines utilizing these transcription factors.@@@@1@27@@oe@16-12-2010 921884301@GENIA Treebank@formal@@1@S@Rescue by cytokines of apoptotic cell death induced by IL-2 deprivation of human antigen-specific T cell clones.@@@@1@18@@oe@16-12-2010 921884302@GENIA Treebank@formal@@1@S@The control of cell survival and cell death is of central importance in tissues with high cell turnover such as the lymphoid system.@@@@1@24@@oe@16-12-2010 921884303@GENIA Treebank@formal@@1@S@We have examined the effect of cytokines on IL-2 deprivation-induced apoptosis of human antigen-specific T helper clones with different cytokine production profiles.@@@@1@23@@oe@16-12-2010 921884304@GENIA Treebank@formal@@1@S@We found that IL-2, interferon-alpha (IFN-alpha), and IFN-beta inhibited IL-2 deprivation apoptosis in Th0, Th1, and Th2 clones.@@@@1@25@@oe@16-12-2010 921884305@GENIA Treebank@formal@@1@S@We also found that IL-2 protects T cell clones from IL-2 deprivation apoptosis accompanying active proliferation and enhanced expression of P53, Rb and Bcl-xL proteins.@@@@1@27@@oe@16-12-2010 921884306@GENIA Treebank@formal@@1@S@In contrast, IFN-alpha/beta rescued T cell clones from apoptosis without active proliferation, and expression of apoptosis-associated proteins tested so far was unaffected.@@@@1@25@@oe@16-12-2010 921884307@GENIA Treebank@formal@@1@S@This may be due to the fact that T cells treated with IL-2 contained those located in S + G2/M phases of the cell cycle, whereas the vast majority of T cells treated with IFN-alpha/beta were located in G0/G1 phase.@@@@1@42@@oe@16-12-2010 921884308@GENIA Treebank@formal@@1@S@IFN-alpha/beta specifically induced tyrosine phosphorylation and translocation into nucleus of signal transducers and activators of transcription (STAT) 2 protein in the T cell clones.@@@@1@27@@oe@16-12-2010 921884309@GENIA Treebank@formal@@1@S@In addition, over-expression of STAT2 by transfection of the cDNA prevented apoptosis of the T cell clones.@@@@1@19@@oe@16-12-2010 921884310@GENIA Treebank@formal@@1@S@Our present study shows that IFN-alpha and -beta mediate anti-apoptotic effect through other pathways than that of IL-2 in growth factor deprivation apoptosis.@@@@1@24@@oe@16-12-2010 921905801@GENIA Treebank@formal@@1@S@Association between expression of intercellular adhesion molecule-1 and integration of human T-cell-leukemia virus type 1 in adult T-cell leukemia cells.@@@@1@21@@oe@16-12-2010 921905802@GENIA Treebank@formal@@1@S@It is known that the expression levels of intercellular adhesion molecule-1 (ICAM-1) in adult T cell leukemia(ATL) cells are high, whereas those in T-lymphoid cells are not.@@@@1@34@@oe@16-12-2010 921905803@GENIA Treebank@formal@@1@S@In order to investigate the factors that influence the induction of ICAM-1 molecules, Northern blot analysis to measure the expression level of ICAM-1 mRNAs and Southern blot hybridization to analyze the integration of human T-cell-leukemia virus type 1 (HTLV-1) provirus were done.@@@@1@46@@oe@16-12-2010 921905804@GENIA Treebank@formal@@1@S@The levels of ICAM-1 mRNA expression of ATL cells were generally higher than those of T-lymphoid cells.@@@@1@18@@oe@16-12-2010 921905805@GENIA Treebank@formal@@1@S@However, ILT-mat cells and ATL16T(-) cells, although they were ATL cells, showed rather low surface ICAM-1 expression and ICAM-1 mRNA expression.@@@@1@25@@oe@16-12-2010 921905806@GENIA Treebank@formal@@1@S@Southern blot hybridization showed that only two and four bands were found in ILT-mat and ATL16T(-) cells, respectively, whereas > 10 bands were detected in other ATL cells.@@@@1@31@@oe@16-12-2010 921905807@GENIA Treebank@formal@@1@S@These results suggest that monoclonal integration of HTLV-1 provirus to the genome of T cell, especially the number of integration sites, is one of the factors for induction of ICAM-1 molecules.@@@@1@34@@oe@16-12-2010 922350601@GENIA Treebank@formal@@1@S@Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity.@@@@1@21@@oe@16-12-2010 922350602@GENIA Treebank@formal@@1@S@When transcriptionally active, the human immunodeficiency virus (HIV) promoter contains a nucleosome-free region encompassing both the promoter/enhancer region and a large region (255 nucleotides [nt]) downstream of the transcription start site.@@@@1@39@@oe@16-12-2010 922350603@GENIA Treebank@formal@@1@S@We have previously identified new binding sites for transcription factors downstream of the transcription start site (nt 465 to 720): three AP-1 sites (I, II, and III), an AP3-like motif (AP3-L), a downstream binding factor (DBF) site, and juxtaposed Sp1 sites.@@@@1@56@@oe@16-12-2010 922350604@GENIA Treebank@formal@@1@S@Here, we show that the DBF site is an interferon-responsive factor (IRF) binding site and that the AP3-L motif binds the T-cell-specific factor NF-AT.@@@@1@28@@oe@16-12-2010 922350605@GENIA Treebank@formal@@1@S@Mutations that abolish the binding of each factor to its cognate site are introduced in an infectious HIV-1 molecular clone to study their effect on HIV-1 transcription and replication.@@@@1@30@@oe@16-12-2010 922350606@GENIA Treebank@formal@@1@S@Individual mutation of the DBF or AP3-L site as well as the double mutation AP-1(III)/AP3-L did not affect HIV-1 replication compared to that of the wild-type virus.@@@@1@28@@oe@16-12-2010 922350607@GENIA Treebank@formal@@1@S@In contrast, proviruses carrying mutations in the Sp1 sites were totally defective in terms of replication.@@@@1@18@@oe@16-12-2010 922350608@GENIA Treebank@formal@@1@S@Virus production occurred with slightly delayed kinetics for viruses containing combined mutations in the AP-1(III), AP3-L, and DBF sites and in the AP3-L and DBF-sites, whereas viruses mutated in the AP-1(I,II,III) and AP3-L sites and in the AP-1(I,II,III), AP3-L, and DBF sites exhibited a severely defective replicative phenotype.@@@@1@54@@oe@16-12-2010 922350609@GENIA Treebank@formal@@1@S@No RNA-packaging defect could be measured for any of the mutant viruses as determined by quantification of their HIV genomic RNA.@@@@1@22@@oe@16-12-2010 922350610@GENIA Treebank@formal@@1@S@Measurement of the transcriptional activity of the HIV-1 promoter after transient transfection of the HIV-1 provirus DNA or of long terminal repeat-luciferase constructs showed a positive correlation between the transcriptional and the replication defects for most mutants.@@@@1@38@@oe@16-12-2010 922420301@GENIA Treebank@formal@@1@S@The role of nuclear factor-kappa B in cytokine gene regulation.@@@@1@11@@oe@16-12-2010 922420302@GENIA Treebank@formal@@1@S@Transcription factors are DNA-binding proteins that regulate gene expression.@@@@1@10@@oe@16-12-2010 922420303@GENIA Treebank@formal@@1@S@Nuclear factor-kappa B (NF-kappa B) is a critical transcription factor for maximal expression of many cytokines that are involved in the pathogenesis of inflammatory diseases, such as adult respiratory distress syndrome (ARDS) and sepsis syndrome.@@@@1@41@@oe@16-12-2010 922420304@GENIA Treebank@formal@@1@S@Activation and regulation of NF-kappa B are tightly controlled by a group of inhibitory proteins (I kappa B) that sequester NF-kappa B in the cytoplasm of immune/inflammatory effector cells.@@@@1@32@@oe@16-12-2010 922420305@GENIA Treebank@formal@@1@S@NF-kappa B activation involves signaled phosphorylation, ubiquitination, and proteolysis of I kappa B.@@@@1@16@@oe@16-12-2010 922420306@GENIA Treebank@formal@@1@S@Liberated NF-kappa B migrates to the nucleus, where it binds to specific promoter sites and activates gene transcription.@@@@1@20@@oe@16-12-2010 922420307@GENIA Treebank@formal@@1@S@The activation of NF-kappa B initiates both extracellular and intracellular regulatory events that result in autoregulation of the inflammatory cascade through modulation of NF-kappa B activation.@@@@1@27@@oe@16-12-2010 922420308@GENIA Treebank@formal@@1@S@Recently, activation of NF-kappa B has been linked to ARDS and has been shown to be a critical proximal step in the initiation of neutrophilic inflammation in animal models.@@@@1@31@@oe@16-12-2010 922420309@GENIA Treebank@formal@@1@S@Activation of NF-kappa B can be inhibited in vivo by treatment with antioxidants, corticosteroids, and the induction of endotoxin tolerance.@@@@1@23@@oe@16-12-2010 922420310@GENIA Treebank@formal@@1@S@Identification of more specific and efficacious inhibitors of NF-kappa B activation might prove beneficial for the treatment of cytokine-mediated inflammatory diseases.@@@@1@22@@oe@16-12-2010 922462501@GENIA Treebank@formal@@1@S@Role of ascorbate in the activation of NF-kappaB by tumour necrosis factor-alpha in T-cells.@@@@1@15@@oe@16-12-2010 922462502@GENIA Treebank@formal@@1@S@The first product of ascorbate oxidation, the ascorbate free radical (AFR), acts in biological systems mainly as an oxidant, and through its role in the plasma membrane redox system exerts different effects on the cell.@@@@1@41@@oe@16-12-2010 922462503@GENIA Treebank@formal@@1@S@We have investigated the role of ascorbate, AFR and dehydroascorbate (DHA) in the activation of the NF-kappaB transcription factor in Jurkat T-cells stimulated by tumour necrosis factor-alpha (TNF-alpha).@@@@1@34@@oe@16-12-2010 922462504@GENIA Treebank@formal@@1@S@Here we show, by electrophoretic mobility shift assays, that ascorbate increases the binding of NF-kappaB to DNA in TNF-alpha-stimulated Jurkat cells.@@@@1@24@@oe@16-12-2010 922462505@GENIA Treebank@formal@@1@S@The ability of ascorbate to enhance cytoplasmic inhibitory IkBalpha protein degradation correlates completely with its capacity to induce NF-kappaB binding to DNA and to potentiate NF-kappaB-mediated transactivation of the HIV-1 long terminal repeat promoter in TNF-alpha-stimulated Jurkat cells but not in cells stimulated with PMA plus ionomycin.@@@@1@48@@oe@16-12-2010 922462506@GENIA Treebank@formal@@1@S@AFR behaves like ascorbate, while DHA and ascorbate phosphate do not affect TNF-alpha-mediated NF-kappaB activation.@@@@1@17@@oe@16-12-2010 922462507@GENIA Treebank@formal@@1@S@These results provide new evidence for a possible relationship between the activation of the electron-transport system at the plasma membrane by ascorbate or its free radical and redox-dependent gene transcription in T-cells.@@@@1@33@@oe@16-12-2010 923166401@GENIA Treebank@formal@@1@S@Pancreatic islet expression studies and polymorphic DNA markers in the genes encoding hepatocyte nuclear factor-3alpha, -3beta, -3gamma, -4gamma, and -6.@@@@1@25@@oe@16-12-2010 923166402@GENIA Treebank@formal@@1@S@The genes encoding the functionally related hepatocyte nuclear factors HNF-1alpha and HNF-4alpha play a critical role in normal pancreatic beta-cell function.@@@@1@22@@oe@16-12-2010 923166403@GENIA Treebank@formal@@1@S@Mutations in these liver-enriched transcription factors result in two forms of early-onset type 2 diabetes (maturity-onset diabetes of the young [MODY]), MODY3 and MODY1, which are characterized by impaired glucose-stimulated insulin secretion, early disease onset, and autosomal dominant inheritance.@@@@1@48@@oe@16-12-2010 923166404@GENIA Treebank@formal@@1@S@The transcriptional hierarchy of HNFs suggests that other proteins of the regulatory cascade might be responsible for other forms of MODY and/or late-onset type 2 diabetes.@@@@1@27@@oe@16-12-2010 923166405@GENIA Treebank@formal@@1@S@In this study, we show that HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 are expressed in pancreatic beta-cells.@@@@1@23@@oe@16-12-2010 923166406@GENIA Treebank@formal@@1@S@We report the identification and characterization of simple tandem repeat DNA polymorphisms in the genes encoding HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 and the mapping of HNF-6 to chromosome bands 15q21.1-21.2 by fluorescence in situ hybridization.@@@@1@41@@oe@16-12-2010 923166407@GENIA Treebank@formal@@1@S@These markers will be useful to study the role of genetic variation in these genes in the pathogenesis of type 2 diabetes.@@@@1@23@@oe@16-12-2010 923362301@GENIA Treebank@formal@@1@S@RP1, a new member of the adenomatous polyposis coli-binding EB1-like gene family, is differentially expressed in activated T cells.@@@@1@22@@oe@16-12-2010 923362302@GENIA Treebank@formal@@1@S@Cross-linking of the CD3 and CD28 molecules on T lymphocytes represents one of the most effective signals for T lymphocyte activation and triggering of their cytotoxic effector function.@@@@1@29@@oe@16-12-2010 923362303@GENIA Treebank@formal@@1@S@To identify genes that are expressed in T cells after stimulation, mRNA from T lymphocytes that had been activated by the simultaneous stimulation of the CD3 and CD28 trigger molecules was transcribed for a differential mRNA display analysis into cDNA and was compared with cDNA from CD28- or CD3-activated or resting lymphocytes.@@@@1@54@@oe@16-12-2010 923362304@GENIA Treebank@formal@@1@S@Differential expression was confirmed subsequently by Northern blot analysis.@@@@1@10@@oe@16-12-2010 923362305@GENIA Treebank@formal@@1@S@One of the cDNA fragments expressed specifically in CD3- and CD28-activated T cells was designated RP1.@@@@1@17@@oe@16-12-2010 923362306@GENIA Treebank@formal@@1@S@The predictive protein-coding region of RP1 had a significant homology to members of the recently found adenomatous polyposis coli (APC) protein-binding EB1 gene family, which codes for yet unknown protein(s).@@@@1@37@@oe@16-12-2010 923362307@GENIA Treebank@formal@@1@S@Bacterially expressed RP1 protein revealed specific binding to wild-type but not to mutated APC protein.@@@@1@16@@oe@16-12-2010 923362308@GENIA Treebank@formal@@1@S@The rapid up-regulation of RP1 mRNA in properly activated T cells suggests that this gene might belong to the immediate/early gene family, which controls the signal transduction cascade downstream of the TCR.@@@@1@34@@oe@16-12-2010 923362309@GENIA Treebank@formal@@1@S@As the expression level of the RP1 gene in activated T cells and a spectrum of tumor-derived cell lines correlates with the proliferative status of the cells, members of the EB1-like gene family may not only be involved in the tumorigenesis of colorectal cancers but may also play a role in the proliferative control of normal cells.@@@@1@59@@oe@16-12-2010