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)

The recombinant plasmids containing the gene for hepatitis B viral core-antigen with the pre-core-sequence controlled by the early-late promoter of the 7.5' K protein gene were constructed. The recombinant strains of vaccinia virus were obtained on their basis (vHBe42-1 and vHBe42-3) selectively expressing HBeAg of hepatitis B virus. The kinetics of HBeAg synthesis was studied in infected cells as well as secretion of the protein into culturing medium. Three proteins were found by blotting technique in the cells infected by vHBe42-3 that react with the specific antiserum to HBeAg and have the mol. masses 25, 22 and 17 kD. The completely processed HBeAg 17 kD was found in the culturing medium. The rabbit serums from the animals immunized by recombinant vHBe42-3 contained antibodies to HBeAg but not to HBcAg. This makes it possible to study the structural and functional organization, immunological properties and role of this antigen in pathogenesis of hepatitis virus B and to construct the specific test systems for screening HBeAg and corresponding antibodies.
Mol Gen Mikrobiol Virusol 1991 Sep
PMID:[Synthesis of the E-antigen of the hepatitis B virus (HBeAg) in eukaryotic cells by a recombinant strain of the vaccinia virus]. 174 74

The nucleotide sequences of cDNAs (275 base-pairs) in the non-structural protein 5 regions of Japanese isolates of hepatitis C virus (HCV-J) from the plasma of 11 patients with non-A, non-B hepatitis and the livers of five patients with hepatocellular carcinoma were analyzed. Approximately 14 to 17% of nucleotide sequences of the HCV-Js examined differed from that of the original isolate in the United States (HCV-US). Furthermore, 2.5 to 11% sequence diversity was found among the HCV-Js. The nucleotide sequences of the HCV-Js showed characteristic common differences from that of HCV-US, although they also showed some random substitutions. Plural HCV-J genomes were found in two of the cDNAs derived from liver specimens, and a deletion of 102 nucleotides was found in the cDNA derived from one plasma specimen. These results suggest that HCV-J is a strain different from the HCV-US and that mutation of the viral genome occurs at as high a frequency as in that of the human immunodeficiency virus.
Mol Biol Med 1990 Dec
PMID:Sequence diversity of hepatitis C viral genomes. 196 17

Hepatitis B virus (HBV) DNA integrates into human hepatocyte DNA. We have gathered the available data on the structure of the integrants from human hepatocellular carcinomas, and classified them into those that seem to represent primary integrants and those that are the products of secondary rearrangements. By means of structural analyses of the possible primary integrants, we deduced that the replication intermediates of the viral genome are the preferred substrates for integration. The integrated HBV DNA and the target cellular DNA are invariably associated with deletions, possibly reflecting the substrate for, and the mechanism of, the integration reaction. The target cell DNA sequence, as well as the target site of integration in chromosomes, seems to be selected randomly, suggesting that HBV DNA integration should bring about random mutagenic effects. Several samples recovered from hepatocellular carcinomas show that the integrated HBV DNA can mediate secondary rearrangements of chromosomes, such as translocations, inversions, deletions and (possibly) amplifications. Thus, HBV DNA integration causes multiple mutagenic effects. We argue that during hepatitis infection, the tendency of rearrangement of hepatocyte chromosomes is combined with the forcible turnover of cells. This is a constantly operating system for the selection of cells that grow better than average cells, possibly involving important steps in multistaged hepatocarcinogeneses.
Mol Biol Med 1990 Jun
PMID:Integration of hepatitis B virus DNA and its implications for hepatocarcinogenesis. 217 Aug 10

The hydroxylamine and nitroso metabolites formed by N4-oxidation of sulfonamides are thought to be involved in the pathogenesis of idiosyncratic reactions to this class of drugs. Idiosyncratic reactions to sulfonamides are characterized by multisystemic toxicity, including hepatitis, nephritis, dermatitis, and blood dyscrasias (aplastic anemia, agranulocytosis). We have previously shown that cytochrome P-450 in the liver metabolizes sulfamethoxazole to its hydroxylamine metabolite. In this paper we report the N4-oxidation of sulfamethoxazole by activated monocytes and neutrophils (human and canine) to form sulfamethoxazole hydroxylamine and nitrosulfamethoxazole. The presumed nitroso intermediate was not detected. Purified myeloperoxidase and prostaglandin H synthase were also capable of mediating the oxidation of sulfamethoxazole. The present studies suggest that myeloperoxidase is responsible for the observed oxidation by phagocytic cells. Oxidation by neutrophils may play a role in agranulocytosis, and oxidation by monocytes may facilitate antigen presentation. Extrahepatic bioactivation of sulfonamides by peroxidases in phagocytic cells and other tissues may be important in determining the range of adverse reactions to sulfonamides that occur.
Mol Pharmacol 1990 Nov
PMID:Peroxidase-dependent oxidation of sulfonamides by monocytes and neutrophils from humans and dogs. 217 79

Homozygosity for alpha 1-antitrypsin deficiency, usually of the genotype PIZZ, is one of the more common single gene defects in infants of European origin, occurring in about 1 in 2000 to 1 in 7000 of the newborn population. About 17% of such infants present with neonatal hepatitis and a small number with intracranial haemorrhage thought to be caused by vitamin K deficiency associated with cholestasis. At least 3% of PIZZ infants will die of cirrhosis in later childhood unless successfully treated by liver transplant. The pathogenesis of the liver disease is not understood and this is unsatisfactory both for treatment and for genetic counselling. The locus coding for alpha 1-antitrypsin (alpha 1AT) is designated PI for proteinase inhibitor. Careful study of the genotypes at this locus in neonatal disease shows that the only certain association is with the homozygous PIZZ genotype. The mutation results in a normal rate of synthesis of a polypeptide that becomes entrapped in the endoplasmic reticulum of the hepatocyte. Some other factor (or factors), as yet unidentified, determines whether severe liver damage results. The low level of alpha 1AT in the plasma seems unlikely to be the primary cause of damage but may play a secondary role. There is some evidence that the other factor(s) may be familial since in one study, though not in all, a high correlation for severity of liver disease was found between PIZZ siblings. The heterogeneity of the clinical course does not result from heterogeneity of PIZ alleles and there is no evidence that it is determined by variation in other related genes on chromosome 14. Only two possible clues have emerged so far. There is some evidence of a protective effect of breast-feeding, and a recent study has found the HLA class II DR3 antigen to be more common than expected in children with alpha 1-antitrypsin deficiency and liver disease. Accumulation of alpha 1AT protein in the hepatocytes may predispose them to some unidentified alteration of the immune response. It is possible that lack of antiprotease activity in the plasma might exacerbate the original damage, so the possibility of useful therapy with alpha 1AT cannot be ruled out entirely. At present, there is no valid way of predicting the severity of disease in a PIZZ child; hence, it is common for parents of a severely affected child to wish to terminate any future PIZZ pregnancy. The most direct method to diagnose the PIZZ genotype of a chorion villus sample is by allele-specific hybridization or sequencing of amplified DNA.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Biol Med 1990 Apr
PMID:Genetics of alpha 1-antitrypsin deficiency in relation to neonatal liver disease. 218 61

In this investigation we have evaluated the feasibility of using the polymerase chain reaction (PCR) for hepatitis delta virus (HDV) RNA detection, cloning and sequencing. Total RNA from HDV-infected liver and serum samples was purified and Moloney murine leukaemia virus (M-MLV) reverse transcribed. HDV cDNA was then directly amplified with Taq polymerase using three pairs of specific primers. It was possible to amplify a region of about 1200 bp in three partially overlapping fragments including the whole HDAg-ORF. A DNA fragment of the expected size was repeatedly obtained from an initial sample of less than 0.1 pg of liver RNA and from 10 pl of infected serum. An amplified fragment of 359 bp obtained by PCR from an infected woodchucks' liver was sequenced. The sequence was 91.8% and 98.6% identical to previously published HDV sequences. In addition, amplified and 32P-radiolabelled HDV sequences were shown to hybridize specifically to HDV RNA extracted from HDV-infected liver and serum. In conclusion this technique promises to be of great value in the appraisal of HDV infection, rapid synthesis of HDV probes and analysis of the genetic variability of the virus.
Mol Cell Probes 1990 Feb
PMID:Amplification of hepatitis delta virus RNA sequences by polymerase chain reaction: a tool for viral detection and cloning. 231 96

Nuclear factor EF-C is present in extracts prepared from human HepG2 liver cells and from other, nonliver cell lines and binds to the hepatitis B virus and polyomavirus transcriptional enhancer regions in vitro. An inverted repeat (5'-GTTGCNNNGCAAC-3') is located within both binding regions. Diethyl pyrocarbonate interference binding assays and competition binding experiments using altered binding sites demonstrated that EF-C contacts symmetrical nucleotides within the inverted repeat. Mutations that changed the length of the spacer region between the arms of the inverted repeat were introduced in the hepatitis enhancer region. Introduction of 1 or 2 base pairs between the repeats did not affect EF-C binding, but deletion of 1 base pair or introduction of 3 to 9 base pairs reduced binding dramatically. Introduction of 10 base pairs restored partial EF-C binding ability. These and other results suggest that EF-C binding is stabilized by dimerization. In vivo assays for enhancer function using these mutants demonstrated that the EF-C binding site is a functional and important component of the hepatitis B virus enhancer region.
Mol Cell Biol 1989 Jul
PMID:Binding of nuclear factor EF-C to a functional domain of the hepatitis B virus enhancer region. 255 Jul 88

In order to characterize better the morphology and immune response in acute necrotizing HSV infection, murine HSV hepatitis was examined. BALB/c mice were inoculated intraperitoneally with 10(6) plaque-forming units (PFU) of HSV-1 (Lenette) and HSV-2 (D316). In both groups half the animals were pretreated with silica particles to block macrophage function. Up to 6 days after infection four mice from each group were sacrificed at daily intervals and the livers were examined by light and electron microscopy, immunohistology, in situ hybridization, combined immunohistology/in situ hybridization and titration of viral PFU. HSV-2 infected mice developed severe necrotizing hepatitis with persistence of HSV in the liver tissue until the end of the study. HSV-1 infected mice rapidly eliminated the virus and revealed only small necrotic foci. Early phase alterations and necrotic phase lesions were distinguished and characterized and morphologic evidence of a direct cytopathic effect of HSV was detected. A specific immune reaction in late stages appeared to be mediated by T4-positive T-lymphocytes. In situ hybridization and immunohistochemistry showed a close correlation with virus titration and were valuable in characterizing early phases and in the assessment of prognosis and differential diagnosis.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:HSV hepatitis in the mouse: a light and electron microscopic study with immunohistology and in situ hybridization. 256 83

We have developed a transgenic mouse strain, Z#2, which represents a model for alpha 1-protease inhibitor (alpha 1-antitrypsin: alpha 1-Pi)-associated liver disease (Dycaico et al., 1988). Fifteen percent of human infants with alpha 1-Pi disease develop non-viral hepatitis which is sometimes associated with growth retardation. Such hepatitis and growth retardation tend to occur in a subset of families with other alpha 1-Pi affected members who have had non-viral hepatitis. The Z#2 mouse strain exhibits non-viral hepatitis and growth retardation. This phenotype is more pronounced in transgenic offspring of crosses between Z#2 mice and DBA/2J inbred mice, and less pronounced in transgenic offspring of crosses between Z#2 and CBA/J inbred mice. Such phenotypic differences resemble the phenotypic differences seen in human families with alpha 1-Pi-associated liver disease.
Mol Biol Med 1989 Apr
PMID:Neonatal growth delay in alpha-1-antitrypsin disease. Influence of genetic background. 261 43

We have reported that a liver growth factor isolated from plasma of partially hepatectomized rats is an albumin-bilirubin complex. In this paper, we characterize the liver growth factor purified from subjects with hepatitis (h-LGF). This factor increases synthesis of DNA in a dose-dependent manner both in vivo in mouse hepatocytes, with a dose of maximal stimulation of 150 ng of h-LGF/mouse, and in vitro in rat liver cell culture, with maximal effect at 7.5 to 10 ng of h-LGF/ml. In vivo, h-LGF increases the mitotic index of mouse hepatocytes, its action being organ-specific, acting on liver, but not on spleen, kidney, lung or brain. In vitro, h-LGF stimulates the uptake of 22Na+ by hepatocytes. In addition, we carried out a study comparing it with human serum albumin in terms of absorbance, fluorescence, circular dichroism spectra, amino acid composition, tryptic maps and antigenic determinants (Ouchterlony immunodiffusion). All these tests suggested that human serum albumin is a constituent of h-LGF. Moreover, when albumin isolated from humans without hepatic pathology is incubated with bilirubin, the albumin-bilirubin complex formed mimics the activity of the human liver growth factor with respect to stimulation of DNA synthesis and the effects on the mitotic index of mouse hepatocytes in vivo. We propose that this human liver growth factor is an albumin-bilirubin complex.
Mol Biol Med 1989 Jun
PMID:Liver growth factor purified from human plasma is an albumin-bilirubin complex. 261 47


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