Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two patients with two and three types respectively of ground-glass hepatocyte inclusions are described. Both were hepatitis B surface antigen (HBsAG) positive and received cyanamide for alcohol aversion therapy. In addition, one of them had taken benzodiazepines and barbiturates. In one patient, cyanamide and HBsAg inclusions co-existed in the same hepatocytes.
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PMID:Co-existence of hepatocyte ground-glass inclusions from several causes. 215 37

In a retrospective review of 2400 consecutive liver biopsy specimens, 60 cases with ground-glass hepatocytes were identified, 41 specimens gave a positive reaction to orcein stain and 19 a negative staining. These 19 specimens were obtained from chronic alcoholics who had been admitted to a detoxication program that used aversive drugs and who were hepatitis B surface antigen negative. The use of cyanamide (Colme), an inhibitor of aldehyde dehydrogenase could be documented in 11 instances. In addition to ground-glass hepatocytes, which were periodic acid-Schiff positive and had a periportal or paraseptal distribution, these liver specimens showed a variety of hepatic lesions: cirrhosis in five cases, portal and periportal inflammation in six, triaditis in five, portal fibrosis in two, and minimal changes in one. Patients with shorter courses of cyanamide were those who had less severe histologic lesions. In three patients who had a liver biopsy carried out before the cyanamide treatment ground-glass hepatocytes were not found. These data indicate that ground-glass hepatocytes that stain with periodic acid-Schiff may develop after cyanamide treatment. They are associated with structural hepatic damage of varied severity in patients submitted to a long-term treatment.
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PMID:Hepatic disease associated with ground-glass inclusions in hepatocytes after cyanamide therapy. 302 Oct 86

Low levels of hepatitis B virus (HBV) replication and serum Dane particles have been commonly observed in chimpanzee chronic HBV carriers. To evaluate the possibility of extrahepatic sites of replication, DNA from various organs of a chimpanzee HBV carrier were evaluated by Southern blot analysis. With cloned, repurified HBV DNA of 3.2 kilobases (Kb) as a hybridization probe under stringent conditions, analysis of liver DNA revealed a diffuse hybridization pattern below 3.2 Kb and full-length double-stranded HBV genomes at 3.2 and 1.8 Kb, the latter representing the supercoiled (CCC) form found in the nucleus. No HBV DNA was found in pancreas, muscle, renal, or adrenal gland. Analysis of splenic DNA revealed diffuse hybridization below 3.2 Kb within the cytoplasmic subcellular fraction, and full-length HBV genomic forms in the nuclear fraction of splenic tissue. Use of (-) and (+) strand-specific HBV DNA and RNA probes demonstrated asymmetric viral replication within the spleen cytoplasm as previously demonstrated in liver. Northern blot analysis of total RNA from chimpanzee spleen and liver revealed HBV RNA sequences in both of these tissues, suggesting active viral gene expression and/or replication in chimpanzee spleen as well as in liver. Elucidation of the splenic cell type supporting viral propagation may serve as a basis for development of a tissue culture system to study molecular events of HBV replication.
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PMID:Splenic replication of hepatitis B virus in the chimpanzee chronic carrier. 358 88

Hepadnaviruses contain a relaxed circular DNA genome (RC-DNA) with discontinuities in both strands. Upon infectious entry into a host cell, this genome is converted into a covalently closed superhelical form (CCC-DNA), which later serves as the template for transcription. Here we examined whether the viral polymerase activity is required for this repair reaction. Primary hepatocytes prepared from embryonated duck eggs were infected with the duck hepatitis B virus. Conversion of the RC-DNA into the CCC-DNA was then analyzed by a newly developed polymerase chain reaction technique. This method allows the efficient discrimination between the two DNA forms and is sensitive enough to monitor repair of the infecting viral DNA in the absence of replication and amplification. Thus, we were able to monitor this process in the presence of a potent inhibitor of the viral polymerase, the nucleoside analog 2',3'-dideoxyguanosine. The data show that inhibition of the viral polymerase activity has no influence on genome repair, suggesting that this enzymatic function is not required for conversion of the RC-DNA into the CCC-DNA. Consequently, antiviral drugs blocking the polymerase activity cannot prevent the infectious entry of the virus into a host cell.
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PMID:Analysis of the earliest steps of hepadnavirus replication: genome repair after infectious entry into hepatocytes does not depend on viral polymerase activity. 833 30

The emergence of HBe-minus hepatitis B virus (HBV) mutants, usually through a UAG nonsense mutation at codon 28 of the precore region, helps the virus to survive the anti-HBe immune response of the host. Host and viral factors that predispose to the emergence of such mutants are not well characterized. The fact that the precore region forms a hairpin structure essential for the packaging of viral pregenomic RNA may explain the extremely high prevalence of the UAG mutation at codon 28. It converts a wobble U-G pair in the packaging signal between nucleotide 3 of codon 15 (CCU) and nucleotide 2 of codon 28 (UGG) into a U-A pair. Since genotype A of HBV has a CCC sequence at codon 15, the UAG mutation would, instead, disrupt a C-G pair present in the wild-type virus. This alteration was shown by transfection experiments to greatly compromise the packaging of pregenomic RNA. The implication of this finding was elucidated by molecular epidemiological studies. Genotype A was found to be the most prevalent genotype in the wild-type virus populations in France but was found in only 1 of the 46 isolates of HBe-minus mutants found there. These mutants were contributed chiefly by genotype D, the second most prevalent genotype in France, which is characterized by a CCU sequence at codon 15. The role of the single nucleotide at codon 15 was confirmed by the finding of the single genotype A isolate in which both wild-type and mutant viruses were present. Interestingly, nearly all of the mutants had a codon 15 sequence of CCU instead of the CCC present in the wild-type viruses. Our results suggest that genotype A of HBV rarely circulates as HBe-minus mutants, probably because of a requirement for a simultaneous sequence change at codon 15. These data, together with the virtual absence of genotype A in the Chinese samples examined, may provide some insights into the uneven prevalence of HBe-minus mutants in the world.
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PMID:Hepatitis B virus genotype A rarely circulates as an HBe-minus mutant: possible contribution of a single nucleotide in the precore region. 835 Apr 3

Aberrations of the p53 and Rb tumour suppressor genes were examined in 12 human hepatocellular carcinoma (HCC)-derived cell lines from different geographic areas and 9 local HCCs by restriction fragment length polymorphisms (RFLP), polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and DNA sequencing. The relationships between genetic changes and hepatitis B virus (HBV) DNA integration in samples were compared. None of the cell lines and tumours showed structural changes in the Rb gene, while 6 cell lines and 2 tumours had mutation or deletion in exons 5 to 8 of p53. Mutations include an AGG --> AGT (Arg --> Ser) transversion at codon 249 in PLC/PRF/5 and Mahlavu, an AAT --> AAA (Asn --> Cys) transversion at codon 200 in TONG/HCC, an AAG --> GAG (Lys --> Glu) transition at codon 139 in HCC-T, a CAT --> CGT (His --> Arg) transition at codon 214 in SC4, and a CCC --> CTC (Pro --> Leu) transition at codon 250 in SC8. In Huh4, an 18-bp deletion from codon 264 to 270 resulted in loss of Leu-Gly-Arg-Asn-Ser-Phe from the amino acid sequences 265 to 270, whereas Hep3B had a 7-kb deletion after exon 7 of p53. Our data indicate that whereas Rb may not have pleiotropic effects on HCC, p53 aberrations are frequently involved in hepatocarcinogenesis. Further, HBV infection appears to be unrelated to the micro-genetic changes of p53. The G to T codon-249-mutation is consistent with HCCs arising from areas at high risk for both aflatoxin B1 (AFB1) exposure and HBV infection.
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PMID:Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma. 877 41

A method based on the polymerase chain reaction (PCR) for evidencing repair of the hepatitis B virus (HBV) genome is described. Hepadnaviruses have a partially double-stranded relaxed circular genome (RC-DNA) which is converted into a covalently closed circular DNA (CCC-DNA) after entry of the virus into a target cell. Our aim was to set up a technique enabling us to determine whether possible in vitro replication of the virus in non-hepatic cells is initiated by formation of CCC-DNA. The relevant part of the strategy used for this PCR consisted of priming the HBV-DNA template with the same forward primer and with a reverse primer located either downstream or upstream from the minus strand gap. The CCC-DNA form was found, as expected, in cells in which the virus was known to be actively replicating; although most sera contained only the RC-DNA form, it was also possible to evidence the CCC form. Such PCR amplification led to detection of 50-500 copies of the viral DNA. The method described should be useful in studying the biological fate of HBV in non-hepatic cells (considered as non-permissive for virus replication), and in exploring the clinical significance of the presence of CCC-DNA in sera.
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PMID:Polymerase chain reaction to monitor repair of the HBV genome, the first step in viral replication. 888 36

Our purpose was to ascertain if mutations of the precore region of the hepatitis B virus genome, in particular the 1896 stop codon mutation, are responsible for the 95% hepatitis B e antigen (HBeAg)-negativity rate in southern African black adult carriers. Hepatitis B virus (HBV) DNA was extracted from the serum of 57 asymptomatic carriers (42 HBeAg-negative; 15 HBeAg-positive), the precore region was amplified using the polymerase chain reaction (PCR), and sequenced. Six carriers (14.6%) had mutations known to prevent HBeAg synthesis: 4 involved the precore initiation codon (1814), and one created a stop codon at 1874. The 1896 mutation occurred alone in one carrier only (2.4%). The infrequency of the 1896 mutation can be explained by the high prevalence (70%) of the adw subtype in the carriers studied. Inter alia, adw differs from ayw in that codon 15 is comprised of CCC instead of CCT. The presence of C instead of T in position 1858 precludes the G-to-A mutation at 1896 because the coexistence of these two mutations would destabilize the stem-loop structure of the RNA encapsidation signal, a finding confirmed by our observation that the CCC polymorphism and the 1896 mutation were mutually exclusive. Ten HBeAg-negative carriers (24%) had a missense mutation at position 1862 in the bulge of the RNA encapsidation signal, which may possibly affect HBeAg expression by interfering with either priming of reverse transcription or signal peptide cleavage. We conclude that the 1896 stop codon mutation accounts for a minority only of HBeAg-negative black carriers. A missense mutation in the bulge of the encapsidation signal may contribute to HBeAg negativity.
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PMID:Nucleic acid sequence analysis of the precore region of hepatitis B virus from sera of southern African black adult carriers of the virus. 898 97

A novel L-nucleoside analog of deoxycytidine, 2',3'-dideoxy-2', 3'-didehydro-beta-L-5-fluorocytidine (beta-L-Fd4C), was recently shown to strongly inhibit hepatitis B virus (HBV) replication in the 2.2.15 cell line. Therefore, its antiviral activity was evaluated in the duck HBV (DHBV) infection model. Using a cell-free system for the expression of the DHBV polymerase, beta-L-Fd4C-TP exhibited a concentration-dependent inhibition of dCTP incorporation into viral minus-strand DNA with a 50% inhibitory concentration of 0.2 microM which was lower than that of other tested deoxycytidine analogs, i.e. , lamivudine-TP, ddC-TP, and beta-L-FddC-TP. Further analysis showed that beta-L-Fd4C-TP is likely to be a competitive inhibitor of dCTP incorporation and to cause premature DNA chain termination. In primary duck hepatocyte cultures infected in vitro, beta-L-Fd4C administration exhibited a long-lasting inhibitory effect on viral DNA synthesis but could not clear viral covalently closed circular DNA (CCC DNA). Results of short-term antiviral treatment in experimentally infected ducklings showed that beta-L-Fd4C exhibited the most potent antiviral effect, followed by beta-L-FddC, lamivudine, and ddC. Longer administration of beta-L-Fd4C induced a sustained suppression of viremia (>95% of controls) and of viral DNA synthesis within the liver. However, the persistence of trace amounts of viral CCC DNA detected only by PCR was associated with a recurrence of viral replication after drug withdrawal. In parallel, beta-L-Fd4C treatment suppressed viral antigen expression within the liver and decreased intrahepatic inflammation and was not associated with any sign of toxicity. Our data, therefore, demonstrate that in the duck model of HBV infection, beta-L-Fd4C is a potent inhibitor of DHBV reverse transcriptase activity in vitro and suppresses viral replication in the liver in vivo.
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PMID:Characterization of the antiviral effect of 2',3'-dideoxy-2', 3'-didehydro-beta-L-5-fluorocytidine in the duck hepatitis B virus infection model. 1060 31

Hepatitis B virus (HBV) with T-1856 of the precore region is always associated with C-1858 (i.e., TCC at nucleotides 1856 to 1858), and it is reported only in genotype C HBV isolates. We aimed to investigate the phylogenetic, virological, and clinical characteristics of HBV isolates bearing TCC at nucleotides 1856 to 1858. We have previously reported on the presence of two major subgroups in genotype C HBV, namely, HBV genotype Cs (Southeast Asia) and HBV genotype Ce (Far East). We have designed a novel 5' nuclease technology based on the nucleotide polymorphism (C or A) at nucleotide 2733 to differentiate the two genotype C HBV subgroups. The mutations at the basal core promoter and precore regions were analyzed by direct sequencing. Among 214 genotype C HBV-infected patients, 31% had TCC, 37% had CCC, 3% had CTC, and 29% had CCT at nucleotides 1856 to 1858. All except one HBV strain with TCC at nucleotides 1856 to 1858 belonged to subgroup Cs, which has been reported only in Hong Kong; Guangzhou, China; and Vietnam. HBV with TCC at nucleotides 1856 to 1858 was associated with the G1898A mutation (64%). Patients infected with HBV harboring TCC had more liver cirrhosis than those infected with HBV harboring CCC (18% versus 5%; P = 0.008), and more of the patients infected with HBV harboring TCC were positive for HBeAg (58% versus 36%; P = 0.01) and had higher median alanine aminotransferase levels (65 IU/liter versus 49 IU/liter; P = 0.006); but similar proportions of patients infected with HBV harboring TCC and those infected with HBV harboring CCT had liver cirrhosis (18% versus 13%; P = 0.43). In summary, we report that HBV with TCC at nucleotides 1856 to 1858 of the precore region might represent a specific HBV strain associated with more aggressive liver disease than other genotype C HBV strains.
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PMID:Phylogenetic, virological, and clinical characteristics of genotype C hepatitis B virus with TCC at codon 15 of the precore region. 1651 39


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