Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human PBMC from HIV-1-infected individuals produced ex vivo in response to vesicular stomatitis virus only low amounts of IFN-alpha. This impairment was significant as early as Walter Reed (WR) stage 2; at WR stage 4-5, the production was almost zero. At WR stage 2 of infection, IFN-alpha mRNA was exclusively found in association with polyribosomes, indicating that IFN-alpha gene was transcriptionally inactive under the experimental conditions used. A similar decrease of the level of transcripts as a function of the progression of the disease was also observed for the IFN-gamma mRNA. In contrast, TNF-alpha production was strongly enhanced in PBMC from HIV-1-infected individuals after stimulation with LPS compared to the TNF-alpha production of activated PBMC from healthy donors. Almost parallel with the increase of the level of the transcript for TNF-alpha, the level of TNF-beta increases as well. Data are presented which show that the increased TNF-alpha production is due to a longer half-life of TNF-alpha transcripts in PBMC from infected individuals. These results let us suggest that the up-regulation of TNF-alpha gene expression in PBMC from HIV-infected individuals is controlled predominantly on the posttranscriptional level, whereas transcriptional events regulate the level of IFN-alpha transcripts. This assumption is supported by run-on experiments which revealed that the extent of transcription of TNF-alpha gene is almost identical in nuclei from stimulated PBMC of noninfected and HIV-infected donors, whereas the transcription of IFN-alpha gene is strongly suppressed in nuclei from HIV-infected individuals at WR stages 3 and 6.
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PMID:Differential gene expression of IFN-alpha and tumor necrosis factor-alpha in peripheral blood mononuclear cells from patients with AIDS related complex and AIDS. 229 23

We have evaluated the efficacy of mitogen (LPS/DxSO4)-activated B cells (B lymphoblasts) to function as antigen-presenting cells (APC) for vesicular stomatitis virus (VSV). Our studies revealed that B lymphoblasts induced potent cytotoxic thymus (T)-derived lymphocyte (CTL) activity in VSV-immune splenic T cells depleted of adherent accessory cells. Dose-response curves indicated that B lymphoblasts were approximately 15-20 times more efficient APC than spleen cells for CTL induction against VSV. There was little evidence of reprocessing of viral antigens by the responder population because only CTL activity restricted to the parental haplotype of the B lymphoblast was generated following stimulation of VSV-immune F1 T cells. B lymphoblasts activated VSV-specific memory CTL which expressed the Lyt-1-23+, AsGM1+ phenotype without activating natural killer and/or lymphokine-activated killer cells. The ability of B lymphoblasts to function as efficient APC was not related to enhanced viral replication in these cells because potent VSV-specific proliferative and class I-restricted CTL responses were induced by B lymphoblasts infected with VSV rendered noninfectious by exposure to ultraviolet (uv) light. This indicates that activated B cells can efficiently process and present input virion protein. Purified splenic B cells that were not activated by mitogen stimulation did not function as APC for VSV even at high multiplicities of infection. The failure of B cells to function as APC for VSV was related to inefficient uptake of VSV and their inability to provide accessory cell signals required for T-cell proliferation; both these functions developed following mitogen stimulation. These data suggest that activated B cells may function as a potent APC population for virus independent of the specificity of their immunoglobulin antigen receptor.
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PMID:Antigen-presenting B cells: efficient uptake and presentation by activated B cells for induction of cytotoxic T lymphocytes against vesicular stomatitis virus. 283 71

A cytotoxic factor was induced by the injection of LPS into the peritoneal fluids of mice which had been previously primed with a streptococcal antitumor preparation, OK-432. No cytotoxic effect on L-929 cells was observed in the peritoneal fluids of mice singly treated with OK-432 or LPS. Various mouse and human tumor cell lines were effectively killed by this peritoneal cytotoxic factor, though normal cell lines were insensitive, which indicates that this factor is not species-specific. The highest level of cytotoxic activity was obtained when LPS was given to mice 5 days after the injection of OK-432. The optimal time for collection of peritoneal fluids for the cytotoxic factor was 2h following the LPS injection. Interferon activity was found to be negative by the plaque reduction test using L-929 cells with vesicular stomatitis virus.
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PMID:[Production of a cytotoxic factor in mouse peritoneal fluid by OK-432, a streptococcal preparation]. 370 50

A cytotoxic factor was induced by the injection of LPS into the peritoneal fluids of mice which had been previously primed with a streptococcal antitumor preparation, OK-432. No cytotoxic effect on L-929 cells was observed in the peritoneal fluids of mice singly treated with OK-432 or LPS. Various mouse and human tumor cell lines were effectively killed by this peritoneal cytotoxic factor, though normal cell lines were insensitive, which indicates that this factor is not species-specific. The highest level of cytotoxic activity was obtained when LPS was given to mice 5 days after the injection of OK-432. The optimal time for collection of peritoneal fluids for the cytotoxic factor was 2 h following the LPS injection. Interferon activity was found to be negative by the plaque reduction test using L-929 cells with vesicular stomatitis virus. These results suggest that this cytotoxic factor is similar to the tumor necrosis factor (TNF) in the mouse serum.
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PMID:Production of cytotoxic factor into mouse peritoneal fluid by OK-432, a streptococcal preparation. 408 64

Small resting B cells do not support a productive vesicular stomatitis virus (VSV) infection, but are induced by B cell activators to become fully permissive for VSV replication. Nonpermissive B cell populations restrict VSV expression at multiple points: transcript levels, translation, and maturation. Unstimulated resting G0 B cells can be infected by VSV and support the synthesis of all VSV mRNAs. Steady-state levels of viral transcripts are selectively enhanced by T cell-derived cytokines to an extent comparable with that seen for cytokine-regulated cellular mRNAs. However, viral proteins are not detected in immunoprecipitates from unstimulated or cytokine-stimulated B cells despite the fact that viral mRNAs are associated with polysomes and can be translated in vitro. This translational block is released by stimulation of infected B cells with mitogenic anti-lg or LPS, or non-mitogenic PMA. VSV virion maturation is also regulated by activation signals, because neither anti-lg nor PMA-stimulated B cells produce high levels of infectious VSV particles. Because anti-lg stimulation supports viral genome replication, maturational arrest is apparently at virus assembly or release. PMA and ionomycin induces changes beyond those seen with anti-lg, because these B cells produce PFUs at levels comparable with those seen with LPS-activated B cells and VSV-permissive cell lines. Activation-dependent regulation of virus expression provides a new paradigm for assessing activator-induced events in B cell differentiation not revealed by previous assessments of proliferation of Ab synthesis.
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PMID:Progression of a vesicular stomatitis virus infection in primary lymphocytes is restricted at multiple levels during B cell activation. 765 Mar 83

To characterize the effect of 60Co gamma radiation on cell-cell and pathogen-cell interactions, the adherence of undifferentiated HL-60 cells to HUVEC monolayers was tested in the absence and presence of LPS or influenza virus type A. Basal HL-60 cell adherence to uninfected HUVEC monolayers (3.0 +/- 1.6%, n = 30) was not altered when HUVECs were exposed to 1- to 10-Gy gamma irradiation 4 to 72 h before the adhesion assay. LPS treatment of HUVEC monolayers (0.5 microgram/ml, 4 h) produced a 6.9-fold increase in adherence that was not altered by previous irradiation. However, when HUVEC monolayers were subjected to 1-10 Gy 41 h before influenza virus infection (10(6) pfu/ml) for 7 h, virus-induced adherence was enhanced in a dose-dependent manner. Increased virus hemagglutinin (HA) protein expression mediated the radiation-induced adherence for the following reasons: 1) HA Ag increases paralleled increases in leukocyte adherence. 2) Northern blot analysis demonstrated a time-dependent increase in mRNA HA levels. 3) Anti-HA blocked HL-60 cell adherence to irradiated and virus-infected HUVEC monolayers. These changes were associated with an increased virus titer yield and virus-induced HUVEC killing. In contrast, cytotoxicity produced by vesicular stomatitis virus, which unlike influenza virus replicates cytoplasmically, was not altered by radiation in HUVECs. In related studies, the canine kidney epithelial (MDCK) cell line showed a similar increased influenza virus production after gamma radiation, indicating that the radiation-induced increase in production of influenza virus is not cell-specific and probably involves a nuclear mechanism.
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PMID:Ionizing radiation increases endothelial and epithelial cell production of influenza virus and leukocyte adherence. 796 77

Human monocytes and murine macrophages were found to be susceptible to influenza A virus infection. We could show that virus was absorbed and de novo virus protein synthesis was initiated, but actual virus replication was extremely low; 24-36 h after infection, monocytes and macrophages died of apoptosis. Before cell death, an influenza A virus infection induced strong mRNA accumulation of cytokines: tumour necrosis factor-alpha (TNF alpha), interleukin-1 (IL1) and IL6. However, the translation into bioactive cytokine protein was rather low, and high cytokine production was only found when a secondary signal such as LPS was added. Influenza A virus infection of mononuclear phagocytes displayed a characteristic feature at the level of cytokine gene transcription which was not found with other viruses such as vesicular stomatitis virus: in addition to the regular 1.7-kb TNF alpha mRNA, a high molecular weight (hmw) TNF alpha mRNA of 2.4 kb was detected. This hmw TNF alpha mRNA did not contain intron or intergenic region elements, was polyadenylated and carried the regular 5' and 3' untranslated regions. The generation of hmw TNF alpha mRNA required exposure to fully infectious influenza A virus, since virus inactivation at 56 degrees C induced only regular and not hmw TNF alpha mRNA. Whether this unique hmw TNF alpha mRNA represents a virus-induced abnormality or only a superinduction of an otherwise minor TNF alpha transcript, and whether this mRNA species codes for a biologically active product, remain to be further studied.
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PMID:Infection of macrophages by influenza A virus: characteristics of tumour necrosis factor-alpha (TNF alpha) gene expression. 890 31

We previously reported that resting mouse peritoneal macrophages (PM) constitutively express low levels of IFN-gamma, whose production is consistently enhanced by exogenous IFN-gamma. In this study, we investigated the effects of IL-12 on the replication of vesicular stomatitis virus and on IFN-gamma gene expression in mouse PM. The addition of IL-12 to freshly explanted PM resulted in the persistence of an antiviral state to vesicular stomatitis virus, while control PM progressively became permissive for virus replication after 3 to 4 days in culture. The IL-12-induced antiviral state was inhibited by Abs to IFN-gamma, suggesting that endogenous IFN-gamma was largely responsible for this antiviral response. Moreover, IL-12 induced a consistent secretion of IFN-gamma, especially in cultured PM. The IL-1 2-induced antiviral state and IFN-gamma production were observed using PM from various strains of mice, including LPS-defective C3H/HeJ, NK-deficient bg/bg, DBA/2, Swiss (CD1), and Swiss nude mice treated or not with anti-asialo GM1 Abs. A 4-h treatment with IL-12 was sufficient to induce a marked accumulation of IFN-gamma mRNA, which was greater in cultured PM than in freshly harvested cells. Lastly, immunofluorescence studies in IL-12-stimulated macrophages clearly showed an enhancement of immunoreactive IFN-gamma compared with basal levels in cells exhibiting a macrophage (i.e., F4/80-positive) phenotype. Together, these findings demonstrate that IL-12 can directly stimulate mouse PM to produce IFN-gamma. We suggest that IL-12-induced IFN-gamma production by macrophages can play some role in the generation of the antiviral and immunoregulatory effects of IL-12.
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PMID:IL-12 induces IFN-gamma expression and secretion in mouse peritoneal macrophages. 931 48

The GTPase superfamily includes a diversity of molecules whose functions are regulated through the binding and hydrolysis of GTP. This superfamily can be segregated into families of functionally related molecules that typically share amino acid sequence similarity within and around the nucleotide-binding domains. A new family of putative GTPases, including IRG-47, LRG-47, IGTP, and TGTP/Mg21, has recently emerged that share significant sequence identity (25-40%). Expression of these molecules has been shown to be selectively induced by IFN-gamma and in some cases by IFN-alpha beta or bacterial LPS. This induction pattern implicates these putative GTPases as part of the innate defense of cells to infection, but their role in such defense has not yet been defined. We have previously described the cloning of TGTP and now confirm its intrinsic activity as a GTPase. We found that TGTP is strongly induced by endogenous IFN-alpha beta produced in response to standard lipofection of plasmid DNA or polyinosinic polycytidylic acid. The ability of endogenously produced IFN-alpha beta to efficiently induce expression of TGTP under these conditions suggested that TGTP might participate in defense against viral infection. This proposal was borne out when TGTP-transfected L cells displayed relative resistance to plaque formation by vesicular stomatitis virus but not herpes simplex virus. This observation places TGTP among a small family of innate antiviral agents and has implications for the functions of other members of this family of GTPases.
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PMID:Specific antiviral activity demonstrated by TGTP, a member of a new family of interferon-induced GTPases. 972 30

The proto-oncogene product Vav is required for receptor clustering, proliferation, and differentiation of T cells, and Vav was identified as a substrate in the TCR and B cell receptor signaling pathway. The role of Vav in B cell responses to Ag challenge in vivo is not known. In this study, we show that Vav regulates B cell proliferation following in vitro activation of Ag receptors, but Vav has no apparent role in CD40-, IL-4-, or LPS-induced B cell activation. Increased degrees of Ag receptor cross-linking can partially reverse the proliferative defect in the anti-IgM response of vav-/- B cells. In vivo, vav-/- mice mounted protective antiviral IgM and IgG responses to infections with vesicular stomatitis virus and recombinant vaccinia virus expressing the vesicular stomatitis virus glycoprotein, which harbor repetitive surface epitopes that directly cross-link the Ag receptor and activate B cells in the absence of T cell help. vav-/- B cells also responded normally to the polyvalent, repetitive hapten Ag trinitrophenyl (TNP)-Ficoll that effectively cross-links B cell receptors. However, vav-/- mice failed to mount immune responses to the nonrepetitive, T cell-dependent hapten Ag (4-hydroxy-5-iodo-3-nitrophenyl)acetyl (NIP)-OVA. These results provide the first genetic evidence on the role of the guanine exchange factor Vav in immune responses to viral infections and antigenic challenge in vivo, and suggest that Vav adjusts the threshold for Ag receptor-mediated B cell activation depending on the nature of the Ag.
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PMID:The guanine-nucleotide exchange factor Vav is a crucial regulator of B cell receptor activation and B cell responses to nonrepetitive antigens. 1038 9


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