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)

Long Evans Cinnamon (LEC) rats, showing spontaneous hereditary hepatitis and hepatic carcinoma, were found to possess autoimmune antibodies to liver microsomal proteins, particularly to proteins with the molecular weight of 56kD and 55kD. The antibodies occurred in association with acute lethal hepatitis in the LEC rats in our previous study. Two-dimensional immunoblot analysis of the antigenic proteins revealed that the 56kDa and 55kDa proteins showed 4.2 and 4.0 pI values and were estimated to be protein disulfide isomerase (PDI) and calreticulin, respectively, from NH2-terminal amino acid sequence analysis. These proteins were further identified by immunoblot analyses using purified proteins and specific antibodies. PDI was a major autoimmune antigenic protein.
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PMID:Identification of protein disulfide isomerase and calreticulin as autoimmune antigens in LEC strain of rats. 825 35

Plasma hyaluronan (HA) concentration and the rate of HA uptake by the isolated, perfused liver were measured in rats treated with saline, D-galactosamine (GaI-NH2, 50 mg/100 g body wt), gadolinium chloride (GdCl3) (0.5 mg/100 g body wt), and GdCl3 + GaI-NH2. GdCl3 was given 24 hr before GaI-NH2 or saline. Plasma L-alanine:2-oxoglutarate aminotransferase (EC 2.6.1.2), a marker for hepatocyte damage, was increased by 8 hr and remained elevated for 24 hr after GaI-NH2 injection. GdCl3 did not affect plasma enzyme levels when given alone or in association with, but prior to, GaI-NH2. Plasma HA levels were increased (200%) within 24 hr after GaI-NH2 administration. A plateau was reached at 8 hr, which was maintained for at least 24 hr. Although GdCl3 alone did not affect plasma HA levels, it slightly delayed the increase in HA concentration in GaI-NH2-treated rats. Livers, isolated 24 hr after GaI-NH2 treatment, exhibited a severe depression (approximately 67%) of HA uptake. GdCl3 did not prevent this suppression. The data presented indicate that: (1) one of the sinusoidal endothelial cell-dependent functions of the liver, i.e. removal of HA from the blood stream, is profoundly impaired during galactosamine-induced hepatitis, and (2) the adverse effect of GaI-NH2 on this sinusoidal endothelial cell function may not be dependent on CdCl3-suppressible Kupffer cell functions.
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PMID:Association of galactosamine-induced hepatitis in the rat with hyperhyaluronanaemia and decreased hyaluronan uptake by the isolated, perfused liver. 836 40

Clinical and laboratory evidence suggests that the fulminant liver failure sometimes associated with the inhalation anesthetic halothane may be an immune-mediated toxicity. Most importantly, the vast majority of patients with a clinical diagnosis of halothane hepatitis have serum antibodies, which react with one or more specific liver microsomal proteins that have been covalently altered by the trifluoroacetyl chloride metabolite of halothane. The serum antibodies are specific to halothane hepatitis patients and are not seen in sera of patients with other types of liver pathology. In this study, a 57-kD trifluoroacetylated liver microsomal neoantigen associated with halothane hepatitis and native 57-kD protein were purified from liver microsomes of halothane-treated and -untreated rats, respectively. When the purified trifluoroacetylated 57-kD and native 57-kD proteins were used as test antigens in an enzyme-linked immunosorbent assay, serum antibodies from halothane hepatitis patients (n = 40) reacted with both of these proteins to a significantly greater extent than did serum antibodies from control patients (n = 32). On the basis of its apparent monomeric molecular mass, isoelectric point and NH2-terminal amino acid and tryptic peptide sequences, the 57-kD protein has been identified as rat liver protein disulfide isomerase. Antibodies raised against rat liver protein disulfide isomerase also reacted with a protein of approximately 58-kD in human liver microsomes. The results of this investigation suggest that trifluoroacetylated protein disulfide isomerase is one of the immunogens associated with halothane hepatitis. In certain patients it might lead either to specific antibodies or, possibly, to specific T cells, which could be responsible for halothane hepatitis.
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PMID:Halothane hepatitis patients have serum antibodies that react with protein disulfide isomerase. 840 60

Three polymerase proteins of influenza type A virus interact with each other to form the active polymerase complex. Polymerase basic protein 1 (PB1) can interact with PB2 in the presence or absence of polymerase acidic protein. In this study, we investigated the domains of PB1 involved in complex formation with PB2 in vivo, using coexpression and coimmunoprecipitation of the PB1-PB2 complex with monospecific antibodies. Results show that PB1 possesses at least two regions which can interact independently and form stable complexes with PB2. Both of these regions are located at the NH2 terminus of PB1; the COOH-terminal half of PB1 is not involved in interacting with PB2. Deletion analysis further demonstrated that the interacting regions of PB1 encompass amino acids (aa) 48 to 145 and aa 251 to 321. Linker insertions throughout the PB1 sequences did not affect complex formation with PB2. Deletion and linker-insertion mutants of PB1 were tested for polymerase activity in vivo. For this analysis, we developed a simplified assay for viral polymerase activity that uses a reporter chloramphenicol acetyltransferase gene containing the 5' and 3' ends of influenza viral promoter and nontranslating regions (minus sense) of the NS gene joined to a hepatitis delta virus ribozyme at its 3' end. This assay demonstrated that all deletion mutants of PB1 exhibited either background or greatly reduced polymerase activity irrespective of the ability to interact with PB2 and that all linker-insertion mutants except one at the extreme COOH end (L-746) of PB1 were also negative for viral polymerase activity. These results show that compared with complex formation of PB1 with PB2, the polymerase activity of PB1 was extremely sensitive to structural perturbation.
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PMID:Influenza virus polymerase basic protein 1 interacts with influenza virus polymerase basic protein 2 at multiple sites. 879 8

Hepatitis delta antigens (HDAgs) are important for the replication and assembly of hepatitis delta virus (HDV). To understand the association between HDAgs and cellular proteins and the mechanism of viral multiplication, we have studied the interaction between HDAgs and nucleolin, a major nucleolar phosphoprotein. The interaction between HDAgs and nucleolin was first demonstrated by immunofluorescence staining studies. HDAgs and endogenous nucleolin were colocalized in the nucleoli of cultured cells transfected with plasmids encoding the small and large HDAg. Coimmunoprecipitation results indicated that the NH2-terminal domain of HDAg was essential for its binding to nucleolin. In vitro ligand binding assays revealed two nucleolin binding sites, NBS1 and NBS2. Each spanned amino acid residues 35-50 and 51-65, respectively, with a conserved core sequence K(K/R)XK. HDV replication was modulated by exogenous human nucleolin. In addition, a small HDAg mutant S-d65/75, which possesses both NBS1 and NBS2, was capable of transactivating HDV replication, whereas the small HDAg mutant S-d50/75, which retained NBS1 but not NBS2, was unable to support the replication of HDV. Thus, the nucleolin binding activity of HDAg is critical for its nucleolar targeting and is involved in the modulation of HDV replication.
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PMID:The nucleolin binding activity of hepatitis delta antigen is associated with nucleolus targeting. 951 70

Hepatitis C virus (HCV), discovered in 1989, is the major causative agent of parenteral non-A, non-B hepatitis worldwide. Following the development of a method of diagnosing HCV infection, it became apparent that HCV frequently causes chronic hepatitis. Persistent infection with HCV is implicated in liver cirrhosis and hepatocellular carcinoma. Current worldwide estimations suggest that more than 170 million people have been infected with HCV, an enveloped positive single-stranded RNA (9.6-kilobases) virus belonging to the Flaviviridae. The HCV genome shows remarkable sequence variation, especially in the hypervariable region 1 of the E2 protein-encoding region, and globally, HCV appears to be distributed with more than 30 genotypes. Complicated "quasispecies" and frequent mutations of viral genomes have also emerged. The HCV genome encodes a large polyprotein precursor of about 3,000 amino acid residues, and this precursor protein is cleaved by the host and viral proteinases to generate at least 10 proteins in the following order: NH2-core-envelope (E1)-E2-p7-nonstructural protein 2 (NS2)-NS3-NS4A-NS4B-NS5A-NS5B-COOH. These viral proteins not only function in viral replication but also affect a variety of cellular functions. Although several explanations have been proposed, the mechanisms of HCV infection and replication in targeted cells, the mechanism of persistent viral infection, and the pathogenesis of hepatic diseases (hepatitis or hepatocellular carcinoma) are all poorly understood. A major reason why these mechanisms remain unclear is the lack of a good experimental HCV replication system. Although several classical trials using cultured cells have been reported, several new, more promising experimental strategies (generations of infectious cDNA clone, replicon, animal models, etc.) are currently being designed and tested, in order to resolve these problems. In addition, new therapies for chronic hepatitis have also been developed. The enormous body of information collected thus far in the field of HCV research is summarized below, and an overview of the current status of HCV molecular virology of HCV is provided.
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PMID:Molecular virology of hepatitis C virus. 1143 27

AIM:To isolate mouse CCR5 cDNA (muCCR5) and study its expression in vivo.METHODS: Marathon PCR was used to isolate muCCR5 cDNA and two animal models were designed to investigate the gene expression in vivo, one was mouse fulminant hepatitis induced by Propionibacterium acnes (P.acnes) and the other was that with delayed type hypersensitivity reaction (DTH). A specific GST-NH2-terminus of muCCR5 fusion protein antibody F(ab')(2) was prepared and clarified. RT-PCR and immunohistochemical analysis were used to observe the expression level of CCR5 gene in mice.RESULTS: A positive reaction of mouse macrophage was found in DTH but not expressed in P.acnes induced fulminant hepatitis by RT-PCR and immunohistochemical analysis.CONCLUSION: This muCCR5 expression may be involved in an allergic processmediated by cellular immunity but not acute inflammatory reaction induced by P.acnes.
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PMID:CCR5 gene expression in fulminant hepatitis and DTH in mice. 1181 19

The relation between ammonia intoxication and liver disease is not clear. Ammonia appears to be relatively non-toxic to normal individuals, whereas some patients with liver disease appear to be exquisitely sensitive to dietary protein, ammonia-releasing substances, and ammonium salts. In an attempt to elucidate this relationship the intravenous LD(50) of ammonium chloride was determined in both normal mice and in those with liver disease produced by a variety of means. Parenchymal damage was created by acute and chronic carbon tetrachloride intoxication, a low-protein, lipotrope-deficient diet, and mouse hepatitis virus. Mice in which the portal vein had been partially ligated and those infected with Schistosoma mansoni developed portal-systemic collateral circulation. Groups of these mice were placed on high-protein diets and ammonia drinking water for periods as long as two months. A combination of both parenchymal damage and collateral circulation was induced in mice either by bile duct ligation or by a combination of schistosomiasis and acute carbon tetrachloride intoxication. When the above groups of mice with liver disease were compared with normal control mice in the same weight range, the LD(50) of ammonium chloride showed no striking change.
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PMID:Liver disease and ammonia intoxication. 1399 82

Hepatic encephalopathy is a complex neuropsychiatric syndrome, which derives from liver failure associated with severe liver damage such as fulminant hepatitis and liver cirrhosis, and vascular abnormalities associated with liver cirrhosis. Although the cause is explained by a multifactorial theory, the accumulation of ammonia has traditionally been considered to have an important role in the pathogenesis of hepatic encephalopathy. In addition, a number of other possible mechanisms have recently proposed, including production of false neurotransmitter, activation of central gamma-aminobutyric acid-benzodiazepine receptors by ligands of endogenous origin, altered cerebral metabolism. These pathogenetic mechanisms are not necessarily exclusive. The principle of treatment is to remove or correct aggravating factors and inhibit the transfer of toxic substances such as ammonia into the bloodstream by minimizing the interaction of intestinal bacteria and nitrogen substances. Most treatments of proved value are based on the ammonia hypothesis. Ammonia metabolism is regulated by numerous factors, among which zinc has long been indicated to be involved, and its clinical application has drawn attention recently.
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PMID:Ammonia metabolism and hepatic encephalopathy. 1560 43

Both forms of the hepatitis delta antigen (HDAg) encoded by hepatitis delta virus are active only as oligomers. Previous studies showed that quadrin, a synthetic 50-residue peptide containing residues 12-60 from the N-terminus of HDAg, interferes with HDAg oligomerization, forms an alpha-helical coiled coil in solution, and forms a novel square octamer in the crystal consisting of four antiparallel coiled-coil dimers joined at the corners by hydrophobic binding of oligomerization sites located at each end of the dimers. We designed and synthesized deltoid (CH3CO-[Cys23]HDAg-(12-27)-seryl-tRNA synthetae-(59-65)-[Cys42]HDAg-(34-60)-Tyr-NH2), a chimeric protein that structurally resembles one end of the quadrin dimer and contains a single oligomerization site. The 51-residue chain of deltoid contains a seven-residue alpha-hairpin loop in place of the remainder of the quadrin dimer plus Cys12 and Cys31 for forming an intrachain disulfide bridge. Reduced, unbridged deltoid (Tm=61 degrees C, DeltaG(H2O)=-1.7 kcal mol(-1)) was less stable to denaturation by heat or guanidine HCl than oxidized, intrachain disulfide-bridged deltoid (Tm>80 degrees C, DeltaG(H2O)=-2.6 kcal mol(-1)). Each form is an alpha-helical dimer that reversibly dissociates into two monomers (Kd=80 microM).
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PMID:Characterization of deltoid, a chimeric protein containing the oligomerization site of hepatitis delta antigen. 1754 9


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