Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently developed a new colorimetric method, DNA enzyme immunoassay (DEIA), for detecting specific hybrids of complementary nucleic acids. This technology is based on an antibody that selectively recognizes double, but not single-stranded DNA. The molecule does not react with a specific probe immobilized on microwells through an avidin-biotin bridge, nor with non-specific amplified sequences, since they are removed by washing. The antibody reveals the hybridization event, independently of the DNA sequences and, for this reason, the method is broadly applicable and extremely versatile. Although we chose a format based on the immobilization of the probe through an avidin-biotin interaction, DEIA assay can also be applied to other analytical schemes that do not require any modification of the probe. Most importantly, the test has an ELISA format and is rapid and convenient for processing large numbers of samples. This technology has been applied, in our laboratory, to different areas, including virology, genetic and basic immunology. The DEIA assay has been successfully used to detect the presence of hepatitis B (HBV), hepatitis C (HCV) and hepatitis delta virus (HDV) sequences in serum of patients, to discriminate different HLA alleles, to identify mutations in the Cystic Fibrosis gene, and to investigate the role of the T cell receptor in some immunological diseases. The results obtained in all our experiments demonstrated that the advantages offered by the assay do not penalize its analytical performance as compared to conventional Southern blot.
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PMID:Non-radioisotopic methods for DNA probes. 133 35

The portal tract mononuclear cell infiltrate has been characterised in 28 liver biopsy samples showing features of chronic aggressive hepatitis from 12 patients with autoimmune chronic active hepatitis, 12 with primary sclerosing cholangitis, and four with other chronic liver diseases (two with alpha 1-antitrypsin deficiency, one with Wilson's disease, and one with chronic hepatitis B infection). In all patients liver disease had started in childhood. The mononuclear cell infiltrate was investigated by a two step immunoperoxidase technique using monoclonal antibodies to: total, alpha/beta T cell receptor positive, helper/inducer, suppressor/cytotoxic T lymphocytes; B lymphocytes; killer/natural killer cells; monocyte/macrophages; and to the activation markers HLA-DR antigens, interleukin 2 receptor (IL-2R), transferrin receptor, and 4F2Ag. In all samples the infiltrate consisted of mainly alpha/beta T cell receptor T lymphocytes. Although T helper/inducer cells predominated in patients with autoimmune chronic active hepatitis, T suppressor/cytotoxic lymphocytes were preponderant in patients with primary sclerosing cholangitis and the other chronic liver diseases. Killer/natural killer cells accounted for up to 25% of the mononuclear cell infiltrate in patients with autoimmune chronic active hepatitis, being rare or absent in the other diseases. Monocytes/macrophages were always found, but they were more numerous in primary sclerosing cholangitis than in the other chronic liver diseases. B lymphocytes were rare or absent in all subjects. Activated mononuclear cells were present in all subjects, but although in patients with autoimmune chronic active hepatitis and primary sclerosing cholangitis most cells of the infiltrate expressed HLA-DR antigens and up to 75% IL-2R, in other forms of chronic liver diseases HLA-DR positive cells were less common and IL-2R positive cells ere rare or absent. These results show that the cells responsible for the histological characteristics of chronic aggressive hepatitis vary in their functional phenotype and state of activation according to the type of underlying liver disorder, confirming the involvement of different pathogenetic mechanisms.
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PMID:Immunohistochemical features of the portal tract mononuclear cell infiltrate in chronic aggressive hepatitis. 148 23

The pathogenetic mechanism leading to liver tissue injury in hepatitis caused by hepatitis A virus is unclear. We have randomly established T cell clones from liver biopsies from 4 patients with hepatitis A. A total of 578 clones was phenotypically analyzed. Whereas during the acute phase of disease CD8+ clones dominated over CD4+ clones, from a biopsy taken late after onset of clinical syndromes more CD4+ than CD8+ clones were obtained. Interestingly, in a patient with a second exacerbation of the disease, more than 20% of all clones had the CD3+ WT31- CD4- CD8- gamma delta TCR+ phenotype. Variable IFN-gamma production was observed with all types of T cell clones. All CD8+ clones had cytotoxic activity, and approximately 60% of all CD8+ clones showed specific cytotoxicity against autologous fibroblasts infected with hepatitis A virus but not with herpes simplex, adeno- or enteroviruses. These results show that the liver injury in hepatitis A is not caused by a viral cytopathogenic effect but is due to an immunopathological reaction of sensitized cytotoxic T lymphocytes against infected hepatocytes. In addition, these studies show an enrichment of CD4-8- alpha beta T cell receptor negative T lymphocytes at the site of an inflammation and suggest a role of these cells in an antiviral reaction.
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PMID:Demonstration of virus-specific cytotoxic T lymphocytes in liver tissue in hepatitis A--a model for immunopathological reactions. 193 98

Cytokines released by infiltrating T cells may contribute to the hepatic injury in chronic hepatitis. Therefore, we characterized peripheral blood- and liver-infiltrating T cells from patients with chronic hepatitis of different etiology and determined the T cell phenotypes and the cytokine release. Liver tissue and peripheral blood-derived T cells from patients with autoimmune hepatitis and primary biliary cirrhosis predominantly expressed CD4-molecules and the alpha- and beta-chains of the T cell receptor (TCR). In chronic viral hepatitis B and C, liver- and blood-derived T cells were preferentially CD8+ T cells expressing the alpha beta TCR. Mitogenic stimulation with irradiated Daudi lymphoma cells and phytohemagglutinin led to a strong release of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) by T cells in patients with chronic hepatitis and in healthy controls. T cells from patients with primary biliary cirrhosis and some patients with autoimmune hepatitis showed a significantly higher secretion of interleukin-4 (IL-4) and interleukin-10 (IL-10) than T cells from patients with chronic viral hepatitis or healthy controls. Histologic inflammatory activity did not correlate with the amount of cytokines released after mitogenic activation. In conclusion, liver tissue and peripheral blood T cells of patients with autoimmune hepatitis and primary biliary cirrhosis were dominated by CD4+ TCR alpha beta+ T helper/inducer cells, whereas in chronic viral hepatitis an enrichment of CD8+ TCR alpha beta + cytotoxic/suppressor T cells was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T lymphocytes from patients with chronic hepatitis of different etiology. 807 96

After intraperitoneal infection with mouse hepatitis virus, strain JHM (JHMV), JHMV replicated in the spleen of C57BL/6 mice for a few days but cleared within a week. The acute viral clearance coincided with moderate expansion of CD8+T cells and modest expansion of CD4+T cells, and was impaired moderately in mice depleted of CD8+T cells and completely in mice depleted of both CD4+ and CD8+T cell subsets. Flow cytometric analysis showed that expression of cell surface markers on the spleen T cells changed during JHMV infection. CD8+T cells expressing increased amounts of CD11a, CD43, CD44 and CD49d, and those expressing decreased levels of T cell receptor alpha beta, CD8, CD45RB and L-selectin were expanded in the spleen after JHMV infection. However, they did not express CD11b, CD25 or NK1.1. They used highly heterogenous V beta chains for their T cell receptors. In addition to CD11ahighCD8+T cells, CD11ahighCD4+T cells were detected transiently after JHMV infection. The virus-specific cytotoxic T lymphocyte (CTL) activity was observed in both CD4+ and CD8+ spleen T cells from mice 7 days post-infection. The present study shows the dynamics of CD8+ and CD4+T cells in the spleen during JHMV infection in mice and suggests that CD11ahighT cells may be involved in JHMV clearance in vivo because their appearance was temporally correlated with T cell-mediated viral clearance in vivo and antiviral CTL activity in vitro.
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PMID:Characterization of T cells expanded in vivo during primary mouse hepatitis virus infection in mice. 874 3

Analysis of the variable chains (V alpha/V beta) of the specific T cell receptor (TCR) of organ-infiltrating T cells may provide further insights into the pathogenesis of many infectious diseases, malignancies, and autoimmune disorders. To determine the TCR V beta repertoire of these small T cell populations antigen-independent in vitro expansion is necessary but may select for certain T cell subpopulations. In this study various antigen independent T cell activation protocols were used to stimulate peripheral blood mononuclear cells (PBMC) of six healthy blood donors, and TCR V beta molecules were analyzed by flow cytometry and semiquantitative reverse-transcriptase polymerase chain reaction. In addition, the analysis of in vitro expanded liver-infiltrating T cells and autologous peripheral blood T cells derived from five patients with autoimmune hepatitis but none of six controls revealed a selective overexpression of single TCR V beta molecules in the liver tissue. In contrast to freshly isolated PBMC, no preferential expansion of single TCR V beta families was observed using phytohemagglutinin, anti-CD3 antibodies, or oxidative stress for antigen-independent T cell activation. In conclusion, antigen-independent T cell activation offers the chance to analyze small populations of organ-infiltrating T cells without skewing the TCR V beta repertoire.
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PMID:Antigen-independent in vitro expansion of T cells does not affect the T cell receptor V beta repertoire. 935 7

Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the major causative agents of chronic liver disease. However, the mechanisms responsible for liver cell injury remain to be clarified. Playing crucial roles in the clearance of viral infection are cytotoxic T lymphocytes. Recently, it has been demonstrated that perforin- and Fas-based mechanisms account for all T cell-mediated cytotoxicity. Therefore, we examined the correlation between liver cell damage and the Fas system in the liver of patients with chronic hepatitis C. Fas is a cell surface protein that mediates apoptosis with treatment of the Fas ligand or the anti-Fas antibody. To investigate the role of Fas in type C hepatitis, we examined the correlation between liver cell damage and Fas expression. Fas expression was found mainly in the cytoplasm of hepatocytes and these positive cells were found particularly among infiltrating lymphocytes. A high prevalence of Fas expression was shown in liver tissue with more severe inflammation. The Fas system-mediated death signal requires the interaction of Fas ligand with Fas on target cells. We isolated a 1.9 kb cDNA clone for the human Fas ligand and examined the expression of the Fas ligand in liver-infiltrating mononuclear cells obtained from patients with chronic hepatitis C. The open reading frame encodes 281 amino acids. Next, we examined the expression of the Fas ligand in liver-infiltrating mononuclear cells obtained from patients with chronic hepatitis C. The amplified products (231 bp) derived from Fas ligand transcripts were detected in liver-infiltrating mononuclear cells, whereas no signal was observed in liver tissues. In HCV infection, Fas expression in hepatocytes is up-regulated in accordance with the severity of liver inflammation. When HCV-specific T cells migrate into hepatocytes and recognize the viral antigen via the T cell receptor, they become activated and express Fas ligand that can transduce the apoptotic death signal to Fas-bearing hepatocytes. Thus, the Fas system plays an important role in liver cell injury by HCV infection.
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PMID:Fas system and apoptosis in viral hepatitis. 940 41

A case of pure non-epidermotropic cutaneous lymphoma in a human immunodeficiency virus-infected patient is reported following a viral opportunistic infection [cytomegalovirus (CMV) hepatitis]. The lymphoid infiltrate was Epstein-Barr virus and CMV negative with a CD30-positive T-cell phenotype. Molecular analysis demonstrated T cell receptor gene rearrangement, but a non-aggressive disease course was noted supporting a cautious therapeutic approach in this case.
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PMID:Cutaneous non-epidermotropic lymphoma associated with human immunodeficiency virus infection. 960 50

Despite a large number of T cells infiltrating into the liver of patients with autoimmune hepatitis (AIH), little is known about their roles or target antigens. To investigate the roles of these T cells in the pathogenesis of AIH, we have studied the clonality of alphabeta T cell populations in liver tissue by size spectratyping the complementarity-determining region (CDR)3 size lengths of T cell receptor (TCR) Vbeta-chain transcripts. Analysis of nine AIH patients who had the HLA DR4 haplotype showed clonal expansion in all samples. More than two T cell clones expanded in most patients. Although the expression of the TCR Vbeta genes was different among the nine patients, clonal expansion of T cells expressing either TCR Vbeta2, 3, 4, 16, or 22 was observed in two patients or more. TCR Vbeta4 clones expanded in 5 cases. Cloning and sequencing of TCR Vbeta CDR3 from PCR products revealed no whole CDR3-shared clones among different patients. In conclusion, several T cell clonotypes first recognize target antigens, then expand and accumulate in the liver of AIH patients. These suggest heterogeneity of autoantigens and the complexity of AIH immunopathogenesis in individual patients.
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PMID:T cell repertoire in the liver of patients with autoimmune hepatitis. 1052 87

Demyelination in multiple sclerosis and in animal models is associated with infiltrating CD8+ and CD4+ T cells. Although oligodendrocytes and axons are damaged in these diseases, the roles T cells play in the demyelination process are not completely understood. Antigen-specific CD8+ T cell lysis of target cells is dependent on interactions between the T cell receptor and major histocompatibility complex (MHC) class I-peptide complexes on the target cell. In the normal central nervous system, expression of MHC molecules is very low but often increases during inflammation. We set out to precisely define which central nervous system cells express MHC molecules in vivo during infection with a strain of murine hepatitis virus that causes a chronic, inflammatory demyelinating disease. Using double immunofluorescence labeling, we show that during acute infection with murine hepatitis virus, MHC class I is expressed in vivo by oligodendrocytes, neurons, microglia, and endothelia, and MHC class II is expressed only by microglia. These data indicate that oligodendrocytes and neurons have the potential to present antigen to T cells and thus be damaged by direct antigen-specific interactions with CD8+ T lymphocytes.
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PMID:In vivo expression of major histocompatibility complex molecules on oligodendrocytes and neurons during viral infection. 1158 48


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