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)

A recombinant polypeptide corresponding to a virus-specific cDNA clone (c100-3) serves as the antigen for a hepatitis C virus (HCV) antibody assay. Previous investigations have shown an 80% prevalence of HCV antibodies in sera of patients suffering from post-transfusional chronic hepatitis non-A, non-B, but positive results were also obtained for 30 to 70% of sera from patients with chronic hepatitis B or autoimmune hepatitis. In this study we show that HCV antibodies are secreted by peripheral blood lymphocytes (PBL) in vitro. PBL from 12/35 patients with chronic non-A, non-B hepatitis and 1/6 patients with chronic active hepatitis B spontaneously secreted HCV antibodies in cell culture supernatants. The results were confirmed by neutralisation assay and ELISAs using recombinant and synthetic polypeptides derived from the c100-3 antigen and from the HCV core antigen. Two patients suffering from non-A, non-B hepatitis were negative for HCV antibodies in serum, but their PBL produced HCV c100-3 antibodies in vitro. PBL from patients suffering from autoimmune chronic hepatitis, primary biliary cirrhosis, toxic-liver injury and healthy blood donors did not produce antibodies to HCV c100 antigen irrespective of HCV antibody test results in their sera. Polyclonal B cell activation or mitogenic stimulation of T helper cells led to increased immunoglobulin synthesis by PBL in vitro, but did not lead to enhancement of specific HCV antibody production. In addition, HCV antibody production was not induced by these stimulation procedures in control lymphocytes. This spontaneous HCV antibody production in vitro suggests persistent antigenic stimulation of the B cells in vivo.
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PMID:Hepatitis C virus antibody secretion in vitro by peripheral blood lymphocytes. 131 Jul 3

The prevalence of hepatitis C virus (HCV) infection in 182 prospectively followed adult patients (110 males, 72 females) with acute non-A, non-B hepatitis and its correlation with progression to chronic hepatitis were studied. These patients were followed for a mean of 24.7 +/- 13.1 (range, 6-57) months. By using a specific enzyme immunoassay for the detection of antibodies against C100-3 polypeptide of HCV, 96 (52.7%) were found antibody positive. HCV was implicated in 64/89 (71.9%) of the cases with classical parenteral exposure but only in 18/64 (28.1%) of the community-acquired cases. Progression to chronic hepatitis was observed more frequently in antibody-positive than in antibody-negative cases (60/96 or 62.5% vs. 27/86 or 31.4%, P = 0.00002). Progression was also observed more often in males than in females (66/112 or 58.9% vs. 21/70 or 30.0% P = 0.0001), both in the antibody positive (48/68 or 70.6% vs. 12/28 or 42.9%, P = 0.01) and in the antibody negative (18/44 or 40.9% vs. 9/42 or 21.4%, P = 0.043) cases. These data indicate that (a) acute hepatitis due to HCV is characterized by a high rate of chronicity, especially in males, and (b) a non-A, non-B, non-C agent or a different strain of HCV may be responsible for the majority of the community-acquired cases of non-A, non-B hepatitis in Greece.
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PMID:Role of hepatitis C virus in acute non-A, non-B hepatitis in Greece: a 5-year prospective study. 131 Dec 75

The concentration of copper in the livers of Long-Evans rats with cinnamon-like coat color (LEC), in which hepatitis and then hepatomas develop spontaneously, was recently found to be abnormally high. Therefore, we examined the copper concentrations in the livers of LEC F1 backcrosses (LEC F1 x LEC) to determine the linkage of copper accumulation with development of hepatitis. Consistent with a previously reported ratio of rats with hepatitis to rats without hepatitis of about 1:1, hepatitis developed in 14 of 30 F1 backcrosses. The copper concentrations in the livers of all LEC F1 backcrosses with hepatitis were abnormally high and comparable to those of LEC rats. In contrast, the concentrations in all backcrosses without hepatitis were similar to those in normal Long-Evans with agouti coat color or Brown-Norway rats. Copper accumulation was shown to be closely linked with the development of hepatitis in LEC rats and appeared to be a possible cause of hepatitis. The concentrations of copper in the livers of Fischer 344 rats after carbon tetrachloride treatment were in the range for normal liver, indicating that a high copper concentration in the liver is specific to LEC rats and not a specific characteristic of hepatitis. Furthermore, we found that the size and level of ceruloplasmin mRNA in the livers of LEC rats were the same as those in LEA rats and that the size and level of ceruloplasmin polypeptide in their livers and plasma were almost the same as those in LEA rats. Therefore, these results suggest that the copper accumulation is not due to alteration of expression or to gross alteration of the ceruloplasmin gene.
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PMID:Genetic linkage between copper accumulation and hepatitis/hepatoma development in LEC rats. 131 58

We report the cloning and sequencing of the putative structural region of the hepatitis C virus (HCV) genome (2229 nucleotides) from an isolate derived from a British case of chronic sporadic non-A, non-B hepatitis. The overall sequence shows a higher similarity with one type of HCV, HCV1 (92%), than with HCV2 (80%), is very highly conserved at the 5' end (99%) preceding the long open reading frame, is well conserved also in the putative core region (90 to 97%), but shows marked variation in the putative envelope region, particularly in the envelope 2/non-structural 1 region (70%). The putative core gene was cloned in pJ3 omega under the early simian virus 40 promoter and expressed in human hepatoma cells. A predominantly cytoplasmic 22K polypeptide was expressed which was antigenically reactive with serum from chronically infected HCV patients.
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PMID:Cloning and sequencing of the structural region and expression of putative core gene of hepatitis C virus from a British case of chronic sporadic hepatitis. 131 44

Hepatitis C Virus, major causative agent of parenterally transmitted non-A non-B hepatitis was identified by Choo et al. in 1988 using molecular biology technologies. This virus contains a positive stranded RNA genome, it has been shown to have a small diameter. These structure and properties suggest that HCV shares many features in common with Pestiviruses and Flaviviruses. After many years of research, two major objectives were reached: -the identification of viral genome and the main purified viral polypeptide derived from recombinant yeast. Major information were recently appearing about the nucleotide sequences of different isolates coming from US, Europe and Japan; -the preparation of specific tool (ELISA anti-HCV) for detection of circulating HCV antibodies.
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PMID:[Hepatitis C virus]. 132 90

In 1974, Prince et al. reported the existence of posttransfusion hepatitis with a long incubation period which was not related to hepatitis B virus (HBV). These cases were named "non-A, non-B" (NANB) hepatitis. The genome of NANB hepatitis virus was discovered recently using a recombinant complementary DNA (cDNA) approach. It was termed the hepatitis C virus (HCV), and a specific diagnostic tool for the circulating HCV antibody (anti-HCV) was developed using a purified viral polypeptide derived from recombinant yeast expressing a small part of the HCV genome. HCV is believed to be the main cause of blood-borne non-A, non-B hepatitis worldwide, which frequently evolves to chronic hepatitis and cirrhosis, and which may also be involved in the development of hepatocellular carcinoma. HCV is classified as part of the flaviviridae family and contains a positive-stranded RNA molecule by approximately 10 kb nucleotides. The HCV genome encodes a large polyprotein precursor, which is processed in structural nucleocapsid and envelope proteins and in non-structural proteins (NS1-NS5). Nucleotide sequence comparisons of distinct HCV isolates have shown a significant genetic variability between the different HCV strains. At present the diagnosis of HCV infection depends on various anti-HCV tests including second generation HCV Ab. Antigenic markers for HCV are being developed but the concentrations of HCV antigens in serum are at the lower limit of detectability by existing immunoassay technology. A polymerase chain reaction has been used to detect HCV RNA in the serum and liver. Serum HCV RNA disappears from serum after effective IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fundamental studies of hepatitis C virus: a review]. 133 74

An enzyme-linked immunosorbent assay (ELISA) was developed by using a synthetic polypeptide (SP) whose sequence was derived from the structural region of hepatitis C virus (HCV). Results of several coded panels of sera obtained from volunteer blood donors and patients with apparent non-A, non-B hepatitis and/or hepatitis B virus used in this ELISA were compared with those of a commercially available first-generation C-100 ELISA (using nonstructural HCV antigens), an experimental second-generation C-200/C-22 ELISA (using both structural and nonstructural HCV antigens), and recombinant immunoblot assays RIBA-I and RIBA-II. In the majority of cases, the results obtained with the HCV-SP ELISA correlated well with those obtained by RIBA-II and C-200/C-22 ELISA. In contrast, many samples that were repeatedly reactive in the C-100 ELISA results were nonreactive with RIBA and HCV-SP ELISA. In addition, HCV-SP detected HCV-specific antibody that appeared within a month of infection and coincided with the earliest increase in alanine aminotransferase. In summary, we have developed an ELISA based on a structural HCV synthetic polypeptide, HCV-SP, that has high specificity and sensitivity and is capable of detecting specific antibodies in the acute phase of HCV infection.
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PMID:Detection of acute hepatitis C virus infection by ELISA using a synthetic peptide comprising a structural epitope. 137 3

The recombinant hepatitis delta virus antigen was obtained as a chimaeric protein fused to the C-terminus of the phage MS2 RNA polymerase. Following induction of the temperature-sensitive promoter, two major polypeptides of about 34 kDa and 29 kDa, and two minor peptides about 21 kDa and 18 kDa, were obtained on PAGE. The 34-kDa protein was identified as the expected recombinant protein by confirming 82% of the primary structure using fast-atom-bombardment mass spectrometry. The most represented degradation product, i.e. the 29-kDa polypeptide, was also characterized by means of mass spectrometry and found to be produced by cleavage between amino acids 261 and 265. The presence of two main protein bands, with a similar difference in size, is also a typical feature of delta antigens, both extracted and recombinant, and it is considered to be derived either from heterogeneity of viral sequences, which can encode hepatitis delta antigen proteins of 195 and 214 amino acids, or from proteolysis of a single precursor. Since the data were obtained with a single viral sequence coding for 195 amino acids fused to 106 residues from MS2 polymerase, there is direct evidence that intrinsic structural properties of the protein sequence are able to cause a specific proteolysis resulting in the presence of two major forms, of which the smaller is 35-40 amino acids at the C-terminus. The recombinant protein can be used as an antigenic substitute of viral antigens both for immunoassays and for the preparation of anti-(hepatitis delta virus) antisera.
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PMID:Characterization by mass spectrometry of a recombinant hepatitis delta virus antigen and its proteolytic products. 154 Dec 67

Polymerase chain reaction was used to investigate RNA splicing in liver of woodchucks infected with woodchuck hepatitis virus (WHV). Two spliced species were detected, and the splice junctions were sequenced. The larger spliced RNA has an intron of 1300 nucleotides, and the smaller spliced sequence shows an additional downstream intron of 1104 nucleotides. We did not detect singly spliced sequences from which the smaller intron alone was removed. Control experiments showed that spliced sequences are present in both RNA and DNA in infected liver, showing that the viral reverse transcriptase can use spliced RNA as template. Spliced sequences were detected also in virion DNA prepared from serum. The upstream intron produces a reading frame that fuses the core to the polymerase polypeptide, while the downstream intron causes an inframe deletion in the polymerase open reading frame. Whereas the splicing patterns in WHV are superficially similar to those reported recently in hepatitis B virus, we detected no obvious homology in the coding capacity of spliced RNAs from these two viruses.
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PMID:Spliced RNA of woodchuck hepatitis virus. 160 14

Hepatocarcinogenesis in woodchucks that are persistently infected with woodchuck hepatitis virus (WHV) follows a progressive course characterized by foci of altered hepatocytes, benign neoplastic nodules and finally hepatocellular carcinoma (HCC). In situ hybridization studies have demonstrated that insulin-like growth factor II (IGF-II) is expressed in most HCCs in woodchucks but that the patterns of expression are variable from tumor to tumor. In some cases, expression of IGF-II is high throughout the tumor, and in others expression is limited to the growing edge of the tumor. IGF-II expression is also activated in focal groups of cells in neoplastic nodules. The major IGF-II mRNA in nodules and HCCs is a 3.4 kb transcript corresponding to one of two IGF-II RNAs in fetal woodchuck liver. A single 15 kDa IGF-II polypeptide accumulates in the perinuclear cytoplasm of hepatocytes in fetal woodchuck liver, neoplastic nodules and HCCs. Thus IGF-II expression in woodchuck liver is reactivated in lesions which are believed to be the precursors of HCC and continues to be expressed as HCCs develop.
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PMID:Analysis of insulin-like growth factor II (IGF-II) expression in neoplastic nodules and hepatocellular carcinomas of woodchucks utilizing in situ hybridization and immunocytochemistry. 165 28


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