UMLS:C0019163 - FACTA Search

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Query: UMLS:C0019163 (hepatitis B)
38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a study of low dose interferon alfa-2b in 587 patients expected to show a good response to treatment, 76-87% patients in different countries had alanine amino-transferase activities returned to normal after four months' treatment, 49-72% were negative for hepatitis B virus (HBV)-DNA, 51-66% were negative for hepatitis B e antigen (HBeAg), and 44-62% were anti-HBe positive. These effects were maintained after nine to 12 months' follow up. Side effects were mild, but led to discontinuation of treatment in 12 patients.
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PMID:Low dose interferon alfa-2b for chronic hepatitis B in Asian countries. 831

A unique hepatitis B virus (HBV) variant has been identified in a gibbon (Hylobates lar) which could be passed to a chimpanzee by experimental inoculation. This HBV variant had been shown to have no reactivity to a monoclonal anti-preS2 antibody (preS2 mAb 116-34) differentiating it from all human HBV specimens tested. This gibbon sera also was not recognized by an anti-preS1 mAb which binds the preS1 hepatocyte receptor region, amino acids 27-35. In this paper, we report the DNA sequence of the gibbon HBV PreS gene. The lack of preS2 mAb (116-34) binding can be explained by a unique nucleotide substitution of A for C in the second codon of the preS2 region leading to the replacement of glutamine with lysine. Two other unique changes were observed at the seventh and 24th amino acid positions in the preS2 gene leading to a substitution of a valine for threonine and alanine, respectively. Unlike all human derived HBV sequences in the preS1 region, the gibbon HBV had a glutamic acid instead of an aspartic acid at amino acid residue 27. Another unique substitution was a leucine for alanine at preS1 position 33. These amino acid changes in the gibbon HBV may explain its unique preS mAb reactivity.
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PMID:Unique preS sequence in a gibbon-derived hepatitis B virus variant. 836 98

A G:C-->T:A mutational hotspot at codon 249 of the p53 tumor suppressor gene has previously been identified in hepatocellular carcinoma (HCC) of patients from Qidong, China and southern Africa in which aflatoxin B1 (AFB1) and hepatitis B virus (HBV) are known synergistic risk factors. We have examined p53 mutation patterns of HCC from geographic areas in which the risk factors vary. Nine HCC lines and four hepatoblastoma lines (HB) were examined for p53 gene mutations and the relationship with HBV infection. Five of the nine HCC lines had homozygous mutation or deletion randomly distributed in exons 6-8, whereas none of the four HB cell lines had p53 mutations. One of the four HB lines (HepG2) had an N-ras mutation at codon 61 position 2. The p53 point mutations in the three HCC cell lines from Japan resulted in the amino acid changes of cysteine for tyrosine in cell line HuH 7 at codon 220 (A:T-->G:C), alanine for glycine in cell line HLF at codon 244 (G:C-->C:G), and serine for arginine in cell line HLE at codon 249 (G:C-->C:G). In addition, the deletion of 18 base pairs from codon 264 position 3 to codon 270 position 1 has resulted in the deletion of Leu-Gly-Arg-Asn-Ser-Phe from the amino acids sequences 256-270 in the Japanese cell line HuH 4. The cell line PLC/PRF/5 that showed p53 mutation at codon 249 (G:C-->T:A) with substitution of serine for arginine was derived from a South African patient. Our results indicate that whereas the p53 gene is not mutated in the HB cell lines, the HCC cell lines frequently contain an abnormal p53 gene. In addition, p53 point mutations were not detected in the four Japanese HCC cell lines that were positive for genomic integration of HBV X-gene and surface antigen gene. The three Japanese HCC cell lines with p53 mutations did not contain HBV sequences, indicating that hepatocarcinogenesis associated with p53 mutation does not require the genomic integration of HBV sequences.
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PMID:p53 gene mutation and integrated hepatitis B viral DNA sequences in human liver cancer cell lines. 838 56

We conducted a prospective, descriptive cohort study of all 217 cases of acute viral hepatitis (AVH) seen in adults during 1992 at the sole hospitals with infectious disease departments in the second and third largest cities in the Kingdom of Saudi Arabia. In addition, we undertook a nested case-control study. Our goals were (1) to determine the causes, demographics, risk factors, and clinical characteristics of AVH in the Kingdom; (2) to evaluate the reliability of diagnostic tests for acute hepatitis C and E; and (3) to assess the relative importance, characteristics, and risk factors of a sixth hepatitis agent, non-A-E. All cases and controls completed a questionnaire. Cases provided blood samples for studies of serum bilirubin, alanine and aspartate aminotransferases, and antibody to hepatitis viruses as well as genome detection studies. The results of serological and molecular tests were used to categorize each case as hepatitis A, B, C, D, E, or non-A-E. Historical, clinical, and laboratory determinants were statistically analyzed by comparisons between groups with different types of AVH and controls. Analysis of risk factors suggested that hepatitis C and D were parenterally transmitted, while hepatitis A, E, and non-A-E were not; the route of transmission of hepatitis B was unclear. Hepatitis E was strongly associated with living or traveling on the Indian subcontinent. The clinical disease caused by all six agents was indistinguishable. The putative sixth agent caused 13% of cases. The second-generation tests for antibody to HCV and HEV were relatively reliable for the diagnosis of AVH.
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PMID:Acute viral hepatitis in Saudi Arabia: seroepidemiological analysis, risk factors, clinical manifestations, and evidence for a sixth hepatitis agent. 852 54

This study was performed in patients with hepatitis C virus (HCV) who were treated with hemodialysis to determine the relationships among alanine amino-transferase (ALT) levels, immunoglobulin (Ig) G anti-HCV, IgM anti-HCV core, and HCV RNA. Of 107 patients on hemodialysis, 27 had positive IgG anti-HCV. Eight of the patients who had HCV were evaluated every 8 months during a period of 2 years, using the following selection criteria: positive IgG against c-22, c33-c, 5-1-1, and c100-3 viral peptides; absence of infection by hepatitis A virus, hepatitis B virus, cytomegalo-virus, Epstein-Barr virus, herpes simplex virus, and human immunodeficiency virus, as well as absence of hepatotoxic drugs or cholelithiasis. We considered elevated ALT values as those more than 150% of the upper limit of normal. Three of the patients had persistent elevation of ALT levels, two had alternating elevation of ALT levels, and three had normal ALT levels in all blood samples. Of the 24 blood samples, 11 had elevation of ALT (45.8%) levels that showed positive IgM anti-HCV, but only 7 of these 11 had positive HCV RNA (63.6%). None of the 13 blood samples without elevation of ALT had positive IgM anti-HCV, but 5 had positive HCV RNA (38.5%). We found an excellent correlation between IgM anti-HCV and ALT levels (r = 0.81). There was no statistically significant difference between the mean ALT values on the 12 blood samples that had positive HCV RNA and the mean ALT values of the negative HCV RNA samples (53.5 +/- 28.0 IU/l vs. 37.4 +/- 17.5 IU/l, respectively). IgM anti-HCV is related to the elevation of ALT levels and can be used as a serologic marker to indicate the presence of active HCV induced liver damage. Serum ALT levels do not correlate with the detection of viral genome in sera. IgG anti-HCV is not necessarily associated with HCV RNA or IgM anti-HCV. The absence of IgM and HCV RNA in patients with IgG anti-HCV and normal ALT levels does not necessarily suggest the absence of active HCV infection.
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PMID:Hepatitis C virus RNA in patients with anti-HCV on hemodialysis. Relationship to transaminase levels. 855 56

The large surface protein (L) of the enveloped hepatitis B virus (HBV) is myristylated at glycine 2. To investigate whether this fatty acid moiety is required for HBV infectivity we made use of a point mutant in which the myristyl acceptor was mutated to a nonfunctional alanine. The mutant virus and a wild-type control were expressed in a human hepatoma cell line by transfection of genomic DNA constructs. Comparable amounts of virions were secreted by both strains as measured by the endogenous polymerase activity of immunoprecipitated virions. The presentation of an N-terminal epitope of L on the virion surface was not influenced by the mutation. To test the infectivity of this mutant virus primary human hepatocytes were incubated with the media of transfected cells. The covalently circular closed HBV DNA molecules generated after infection were discriminated from the open circular DNA genomes of inoculated virions by a sensitive PCR-based technique. The experiments demonstrated that the wild type was infectious but not the myristate negative mutant. This reflects the phenotype of an homologous duck hepatitis B virus mutant although the N-terminal L protein domains of this virus and of HBV show no primary sequence homology.
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PMID:Myristylation of the large surface protein is required for hepatitis B virus in vitro infectivity. 861 Apr 67

The a determinant of hepatitis B surface antigen (HBsAg) is the most critical determinant for both diagnosis and immunoprophylaxis of the hepatitis B virus. We have used synthetic peptides and an anti-a mAb to identify a peptide sequence corresponding to amino acid residues 117 to 128 of HBsAg as an antigenic epitope contributing to the a determinant. Compared to the native protein HBsAg, the cyclic form of the peptide (aa 117-128) is only 20-fold less effective, whereas the linear form of the peptide is 160-fold less effective in the inhibition of mAb binding to HBsAg. Based on these results, we have postulated a previously unidentified disulfide bond between residue Cysl21 and Cysl24. Individual substitution of amino acids in the peptide (aa 117-128) with alanine identified three residues Cys121, Thr123, and Cys124 as the most critical residues for mAb recognition. Substitution of alanine for any one of the three residues caused a substantial loss in binding free energy (greater than 4.5 kcal/mol). Sequence analysis indicated that the C(K/R)TC motif is highly conserved among 100 subtypes and mutants of HBsAg isolates. Collectively, these results show that the cyclic C(K/R)TC motif is an essential part of the a determinant of HBsAg. Synthetic peptides containing the C(K/R)TC motif are potentially useful as alternative hepatitis B vaccines and as diagnostic reagents for the detection of the hepatitis B virus.
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PMID:Identification and characterization of a C(K/R)TC motif as a common epitope present in all subtypes of hepatitis B surface antigen. 861 60

Genetic heterogeneity of the hepatitis B virus (HBV) has been shown to influence the serological pattern and clinical picture in HBV infection. Thailand has a high transmission rate of HBV, but the molecular epidemiology of HBV strains circulating in this region was hitherto unknown. In this study, the HBV strains from 34 Thai HBsAg-positive patients were investigated. In a proportion of these samples, an antigenically important region of the S gene (n = 18), and the pre-S2 and precore genes (n = 15) were sequenced after PCR amplification. Four strains had in-frame deletions of an upstream region of the pre-S2 gene, with all deletions ending at the same nucleotide. In one of three anti-HBe positive strains without a translational stop at codon 28 of the precore gene, there was a one nucleotide insertion in the precore gene. This insertion would cause a frame shift and result in a nonsense protein being expressed, thus providing one explanation for the lack of HBeAg in this patient. Several rare or unique amino acid changes in the region between residues 120 and 161 of the S protein were found. Glycine 145 was changed to alanine in one strain, and this position showed an apparent mixture of glycine and arginine in another. In total, 10 strains displayed unexpected changes that were not related to the normal variability between subtypes or genetic subgroups. It is concluded that there is considerable heterogeneity in HBV strains in Thailand and that this could have clinical and epidemiological importance in a region with high HBV transmission rates.
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PMID:Hepatitis B virus strains in Thailand: genomic variants in chronic carriers. 863 19

P18(IIIB) is a highly immunogenic peptide from the V3 loop of the HIV-1 gp160 envelope protein that is presented promiscuously by multiple class I MHC molecules. Understanding the molecular basis for promiscuous presentation may have many practical applications. As the highly prevalent HLA-A2.1 class I molecule is known to present P18(IIIB) for recognition by cytotoxic T lymphocytes (CTL) found in peripheral blood mononuclear cells of HIV+ donors, a P18(IIIB)-specific CTL line was generated from and HLA-A2(+), HIV- donor in order to define the molecular basis for, and ultimately improve upon the binding of, this peptide to HLA-A2.1. The minimal epitope recognized by the line was a decamer, I10, with the sequence RGPGRAFVTI. Interestingly, this decamer is identical to the minimal epitope from P18(IIIB) seen by murine CTL restricted by H-2Dd. A panel of Ala-substituted peptides was employed in MHC-binding and T cell response studies to identify MHC- and TCR-binding residues. Notably, many of the agretopic and epitopic residues identified were identical to those involved in the corresponding interactions of I10 with the H-2Dd MHC molecule and murine I10-specific CTL. The I10 peptide does not contain the described HLA-A2.1 binding motif. Instead a Pro at P3, a Phe at P7 and an Ile at P10 are utilized for MHC binding. Agretopic residue similarities with the hepatitis B nucleocapsid decamer suggest that these residues may comprise an alternative motif of anchors utilized by decamers for binding to HLA-A2.1.
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PMID:Molecular analysis of presentation by HLA-A2.1 of a promiscuously binding V3 loop peptide from the HIV-envelope protein to human cytotoxic T lymphocytes. 867 51

Hepatitis delta virus (HDV) contains two virus-specific delta antigens (HDAgs), large and small forms, which are identical in sequence except that the large one contains 19 extra amino acids at the C terminus. HDAgs are nuclear phosphoproteins with distinct biological functions; the small form activates HDV RNA replication, whereas the large form suppresses this process but is required for viral particle assembly. In this study, we have characterized the phosphorylative property of HDAg in a human hepatoma cell line (HuH-7) and examined the role of phosphorylation in HDAg function. As demonstrated by in vivo labeling and kinase inhibitor experiments, the phosphorylation levels of both HDAgs were diminished by the inhibitor of casein kinase II (CKII). Nevertheless, phosphorylation of only the small form could be markedly reduced by the protein kinase C (PKC) inhibitor, suggesting different phosphorylation properties between the two HDAgs. When these two kinase inhibitors were added separately to the transient-expression system, HDV RNA replication was profoundly suppressed. In contrast, the inhibitors did not affect the assembly of empty HDAg particle from HDAgs and hepatitis B virus surface antigen. To further examine the role of phosphorylation in HDAg function, two conservative CKII recognition sites at Ser-2 and Ser-123 of both HDAgs and one potential PKC recognition site at Ser-210 of the large HDAg were altered to alanine by site-directed mutagenesis. Transfection experiments indicated that mutation at Ser-2, but not Ser-123, significantly impaired the activity of the small HDAg in assisting HDV RNA replication. This property is in accordance with our observation that Ser-2, not Ser-123, was the predominant CKII phosphorylation site in the small HDAg. Our studies also excluded the possibility that the phosphorylation of Ser-2, Ser-123, or Ser-210, had roles in the trans-suppression activity of the large HDAg, in the assembly of empty virus-like HDAg particle, and in the nuclear transport of HDAgs. In conclusion, our results indicate that both CKII and PKC positively modulate HDV RNA replication but not the assembly of empty HDAg particle. The role of CKII in HDV replication may at least in part be accounted for by the phosphorylation of Ser-2 in the small HDAg. The effect of PKC on HDV RNA replication is, however, not to mediate the phosphorylation of the conservative Ser-210 in the large HDAg but rather to act on as-yet-unidentified Ser or Thr residues in the small HDAg or cellular factors. These findings provide the first insight into the roles of phosphorylation of the two HDAgs in the HDV replication cycle.
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PMID:Casein kinase II and protein kinase C modulate hepatitis delta virus RNA replication but not empty viral particle assembly. 870 45

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