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)

Fas is a cell-surface protein mediating apoptosis. Fas ligand is a type II membrane protein and induces apoptosis by binding to Fas. Fas ligand is expressed in activated T cells, and works as an effector of cytotoxic lymphocytes. Molecular and genetic analysis of Fas and Fas ligand indicated that mouse lymphoproliferation mutation (lpr) and generalized lymphoproliferative disease (gld) are mutations of Fas and Fas ligand respectively. The lpr of gld mice develop lymphadenopathy, and suffer from autoimmune disease. Based on these phenotypes and other studies, it was concluded that the Fas system is involved in the apoptotic process during T-cell development, specifically peripheral clonal deletion or activation-induced suicide of mature T cells. In addition to the activated lymphocytes, Fas is expressed in the liver, heart and lung. Administration of agonistic anti-Fas antibody into mice induced apoptosis in the liver and quickly killed the mice, causing liver damage. These findings suggest that the Fas system plays a role not only in the physiological process of lymphocyte development, but also in the cytotoxic T-lymphocyte-mediated disease such as fulminant hepatitis.
Prog Mol Subcell Biol 1996
PMID:Apoptosis mediated by the Fas system. 882 94

A novel calcium-binding protein regucalcin has been shown to be specifically expressed in the liver of various specifies including human. Regucalcin concentration in the serum of patients with chronic liver injury was estimated by enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG. Serum samples were obtained from 42 persons who were diagnosed as liver disorder. Serum regucalcin concentration in all patients was in the range of 3.7-69.6 ng/ml, although regucalcin was not entirely seen in the serum of normal subjects (10 persons) without hepatitis. Meanwhile, in 18 patients with liver injury, serum glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) activities were normal value (less than 40 I.U./I). Serum GOT and GPT activities from 24 patients showed a comparatively higher level (50-234 I.U./I). The present results demonstrate the potential sensitivity of regucalcin as a marker of chronic liver injury.
Mol Cell Biochem 1997 Feb
PMID:Potential sensitivity of hepatic specific protein regucalcin as a marker of chronic liver injury. 905 96

Double-stranded (ds) RNA-specific adenosine deaminase converts adenosine residues into inosines in dsRNA and edits transcripts of certain cellular and viral genes such as glutamate receptor (GluR) subunits and hepatitis delta antigen. The first member of this type of deaminase, DRADA1, has been recently cloned based on the amino acid sequence information derived from biochemically purified proteins. Our search for DRADA1-like genes through expressed sequence tag databases led to the cloning of the second member of this class of enzyme, DRADA2, which has a high degree of sequence homology to DRADA1 yet exhibits a distinctive RNA editing site selectivity. There are four differentially spliced isoforms of human DRADA2. These different isoforms of recombinant DRADA2 proteins, including one which is a human homolog of the recently reported rat RED1, were analyzed in vitro for their GluR B subunit (GluR-B) RNA editing site selectivity. As originally reported for rat RED1, the DRADA2a and -2b isoforms edit GluR-B RNA efficiently at the so-called Q/R site, whereas DRADA1 barely edits this site. In contrast, the R/G site of GluR-B RNA was edited efficiently by the DRADA2a and -2b isoforms as well as DRADA1. Isoforms DRADA2c and -2d, which have a distinctive truncated shorter C-terminal structure, displayed weak adenosine-to-inosine conversion activity but no editing activity tested at three known sites of GluR-B RNA. The possible role of these DRADA2c and -2d isoforms in the regulatory mechanism of RNA editing is discussed.
Mol Cell Biol 1997 May
PMID:Editing of glutamate receptor B subunit ion channel RNAs by four alternatively spliced DRADA2 double-stranded RNA adenosine deaminases. 911 10

Cytochromes P450 and UDP-Glucuronosyltransferases (UGT) are targets of microsomal autoantibodies in liver and kidney (LKM). LKM autoantibodies are observed in autoimmune hepatitis, in some patients with viral hepatitis, drug-induced hepatitis and autoimmune hepatitis as disease component of the autoimmune polyglandular syndrome type 1 (APS-1). In autoimmune hepatitis LKM antibodies are markers of autoimmune hepatitis type 2. The major target of LKM-1 antibodies is cytochrome P450 2D6; a second less frequent target was the described UGTs of family 1. In autoimmune hepatitis LKM-1 autoantibodies are usually directed against small linear epitopes. LKM autoantibodies are also associated with infection with hepatitis viruses C and D. In hepatitis C about 1-2% of patients develop LKM-1 autoantibodies. About 60% of these autoantibodies are conformation dependent. The presence of LKM autoantibodies in hepatitis C may be associated with an increased risk in interferon treatment. LKM-3 autoantibodies are found in about 8% of patients with hepatitis D and are directed against conformational epitopes. Patients treated with certain drugs may develop drug induced hepatitis. In hepatitis induced by tienilic acid, tienilic acid is activated by and covalently bound to cytochrome P450 2C9. Activation of the immune system results in the formation of autoantibodies against cytochrome P450 2C9 (LKM-2) and infiltration of the liver with immune cells. A similar mechanism has been described for dihydralazine induced hepatitis, where autoantibodies are directed against P450 1A2 (LM). Autoantibodies directed against cytochrome P450 1A2 also are found in patients suffering from hepatitis as a disease component of APS-1.
Mol Biol Rep 1996
PMID:Cytochrome P450 enzymes and UDP-glucuronosyltransferases as hepatocellular autoantigens. 911 34

Varkud Satellite (VS) RNA contains a small self-cleaving RNA motif that is distinct in its sequence and secondary structure from the hammerhead, hairpin, and hepatitis delta virus ribozymes, which are found in other natural RNAs. We have used a base specific chemical damage selection (modification interference) assay to identify functionally important nucleotides and structural elements in VS RNA. Many modified bases interfered with self-cleavage and most of these clustered at helix junctions, certain internal loops, and in a long-range pseudoknot; these correspond to previously determined sites of magnesium-dependent protection from chemical modification. The clustering suggests that these bases are important not only for a large number of individual interactions, but because they form a smaller number of structural elements that are important for activity. Modification of bases in other single-stranded regions, which did not exhibit magnesium-dependent protection, generally did not interfere with activity, suggesting that some of these regions might be dispensable for function. Surprisingly, we found a separate cluster of bases whose modification significantly enhanced cleavage. These bases appear to form a structural element that naturally attenuates the self-cleavage reaction. In natural VS RNA this attenuator structure may affect the cleavage/ligation equilibrium by inhibiting circle re-opening, thereby helping to maintain the RNA in a circular form, which is the predominant form of VS RNA in vivo. Taken together, the results of the damage selection experiments localize the catalytic core of VS RNA to a small subset of the previously determined minimal contiguous sequence.
J Mol Biol 1997 Apr 11
PMID:Identification of functional domains in the self-cleaving Neurospora VS ribozyme using damage selection. 913 15

To confirm whether or not cytosolic NADPH-UQ reductase is involved in the recycling of cellular ubiquinol (UQH2) consumed during lipid peroxidation, the effect of a UQ-10 supplement on the NADPH-UQ reductase and cellular defense against oxidative damage in rat livers was investigated. Supplements of UQ-10 for 14 days enhanced the levels of UQH2-10 and NADPH-UQ reductase in rat livers without any appreciable changes in other antioxidant contents and related enzyme activities. However, the injection of carbon tetrachloride (CCl4) into the rats induced lipid peroxidation and decreased the cellular UQH2-10 contents (and increased equivalent amounts of UQ-10), as well as decreasing the ascorbic acid, reduced glutathione (GSH) and alpha-tocopherol contents of the rat livers. Administration of the UQ-10 supplement prior to the CCl4 treatment spared alpha-tocopherol (but not GSH or ascorbic acid), inhibited lipid peroxidation, and thus improved CCl4-induced hepatitis. These findings support the notion that NADPH-UQ reductase in cytosol is the enzyme responsible for the regeneration of UQH2 from UQ formed by lipid peroxidation in cells.
Mol Aspects Med 1997
PMID:Cytosolic NADPH-UQ reductase-linked recycling of cellular ubiquinol: its protective effect against carbon tetrachloride hepatotoxicity in rat. 926 8

Oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance in favor of the former and has been suggested to be a relevant factor in aging as well as in different pathological conditions, such as heart attack, diabetes, and cancer. Ubiquinol is very sensitive against oxygen radicals and gives ubiquinone as an oxidation product. Therefore, the ratio of ubiquinol to ubiquinone should be a good marker of oxidative stress because of its definition. A method for the simultaneous detection of ubiquinol-10 and ubiquinone-10 in human plasma is described. Heparinized human plasma was mixed with 5 volumes of methanol and 10 volumes of hexane. After vigorous shaking and centrifugation, the hexane phase (5 microliters) was injected immediately and directly on to reverse-phase HPLC equipped with an on-line reduction column and an electrochemical detector in order to avoid the oxidation of ubiquinol to ubiquinone. It was found that the ratio of ubiquinol-10 to ubiquinone-10 was about 95/5 in human plasma from healthy donors. A significant increase in the oxidized form (ubiquinone-10) content was observed in plasmas of patients with hepatitis, cirrhosis, and hepatoma when compared with normal subjects, suggesting increased oxidative stress in these patients.
Mol Aspects Med 1997
PMID:Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. 926 9

Genome RNA of hepatitis Delta virus (HDV) was isolated from the blood sera of 4 independently infected patients. The genome fragment of 901-1265 was obtained for each isolate by the RT-PCR. The resultant sequences showed that all isolates belonged to HDV genotype I. Russian isolates were shown to be closely related to an Italian one (98.1-97.5% and 97.1-95.1% identity for the nucleic acid and amino acid levels, respectively); they may represent an extra subtype within genotype I. No appreciable differences between the Russian strains were found, which fact may reflect a possible homogeneity of HDV population in North-Western Russia.
Mol Gen Mikrobiol Virusol 1997
PMID:[Determination of nucleotide sequences of Russian isolates of delta hepatitis virus]. 929 10

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.
J Mol Med (Berl) 1997 Sep
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), a major etiologic agent of transfusion associated hepatitis, is a positive, single-stranded RNA virus and is also known to be implicated in liver cirrhosis and hepatocellular carcinoma. Nonstructural protein 5A (NS5A) of HCV contains acidic and proline-rich amino acids in its carboxy-terminal half. These structural features resemble eukaryotic transcription activators. In this report, we show that NS5A functions as a potent transcriptional activator when fused to the yeast (Saccharomyces cerevisiae) GAL4 DNA-binding domain (1-147). The potential transcriptional activator maps to the C-terminal half of NS5A in the yeast cell. Therefore, our data provides the first evidence that NS5A may modulate host cell function at the transcriptional level.
Mol Cells 1997 Oct 31
PMID:Hepatitis C virus nonstructural protein 5A contains potential transcriptional activator domains. 938 55


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