Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A segment from the pre-s region of the woodchuck hepatitis virus (WHV) was inserted into an open reading frame vector allowing for the expression in Escherichia coli of viral determinants as part of a fusion protein. The bacterially synthesized fusion molecule contained eight amino acids from beta-galactosidase (beta-gal) at the N terminus, followed by 89 pre-s-encoded amino acids and 219 amino acids of chloramphenicol acetyltransferase (CAT) at the C terminus (beta-gal:pre-s:CAT). This tribrid protein was used to generate antiserum which had a significant titer to the viral portion of the fusion polypeptide. Anti-beta-gal:pre-s:CAT was used in Western blot analysis to identify viral proteins containing pre-s-encoded determinants. Antiserum to the tribrid molecule recognized four WHV polypeptides with molecular masses of 33, 36, 45, and 47 kilodaltons, each of which was also recognized by a monoclonal antibody to WHV surface antigen. Using the same anti-tribrid serum, we also identified analogous polypeptides from ground squirrel hepatitis virus. The antiserum was also used to immunoprecipitate virus particles containing endogenous DNA polymerase activity, indicating that pre-s determinants are found on the surface of mature virions. Based on previous computer studies and the location of pre-s-encoded molecules on the surface of virus particles, a role in hepadnavirus host cell entry is suggested for these polypeptides.
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PMID:Identification and localization of pre-s-encoded polypeptides from woodchuck and ground squirrel hepatitis viruses. 394 37

Hepatitis B immune globulin was given intramuscularly to 102 staff members of a dialysis unit within 48 h after the accidental needlestick exposure to blood containing hepatitis B surface antigen (HBsAg). Hepatitis B virus (HBV) infection developed in 11 of 56 persons (20%) who had been exposed to blood containing hepatitis B e antigen (HBeAg). Among 56 HBeAg-positive inocula, HBsAg-associated deoxyribonucleic acid polymerase activity in the 11 inocula that transmitted HBV infection was significantly higher than that in the remaining 45 inocula that did not (log counts per minute 3.27 +/- 0.57 vs. 2.09 +/- 1.19, p less than 0.001). These 11 HBeAg-positive inocula revealed higher hemagglutination titers of HBsAg (geometric mean 13.5 +/- 1.4 vs. 11.2 +/- 3.2, p less than 0.001). The receptor for polymerized human serum albumin was detected significantly more often in the inocula that transmitted HBV infection than those that did not (10/11 vs. 24/45, p less than 0.05). Based on the results obtained, the failure in protecting all of those exposed to HBeAg-positive blood would be attributable to a high concentration of HBV in some HBeAg-positive inocula and the inability of intramuscular injection to raise a protective level of antibody in the circulation immediately.
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PMID:Factors influencing postexposure immunoprophylaxis of hepatitis B virus infection with hepatitis B immune globulin. High deoxyribonucleic acid polymerase activity in the inocula of unsuccessful cases. 396 63

Three asymptomatic chronic carriers of hepatitis B surface antigen, who had normal serum aminotransferase levels and no detectable hepatitis B e antigen in serum, developed icteric, symptomatic acute hepatitis. Serologic evidence of acute infection with hepatitis A virus, delta hepatitis virus, cytomegalovirus, or Epstein-Barr virus was absent. However, hepatitis B virus DNA and DNA polymerase activity, which were not detectable before the exacerbation, appeared in the serum of all three patients during the acute illness, confirming the diagnosis of spontaneous reactivation of chronic type B hepatitis. Thus, acute exacerbations of chronic type B hepatitis may present as an acute hepatitis superimposed on the chronic carrier state.
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PMID:Reactivation of chronic type B hepatitis presenting as acute viral hepatitis. 399 87

Serum samples from 130 persons who were seropositive for hepatitis B surface antigen and who had various forms of accompanying liver disease were tested for immunoglobulin M (IgM) antibody to hepatitis B core antigen. In 99% of patients with hepatitis B antigen-positive chronic type B hepatitis, IgM antibody to hepatitis B core antigen was present. This antibody was not present in "healthy" hepatitis B surface antigen carriers and was detectable in only 30% of patients with delta hepatitis. Testing of serial sera from 38 patients with chronic type B hepatitis revealed that IgM antibody to hepatitis B core antigen persisted in patients who had evidence of persistent hepatitis B virus replication but ultimately disappeared in those patients who exhibited a sustained loss of serum markers of viral replication (hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase activity). These findings suggest that the presence of IgM antibody to hepatitis B core antigen in chronic hepatitis B surface antigen carriers indicates an active immune response to persistent viral replication.
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PMID:Immunoglobulin M antibody to hepatitis B core antigen in patients with chronic type B hepatitis. 400 16

Hepatitis B virus infections are common in the Eskimo (Inuit) populations of the world. In this study, serologic markers of hepatitis B infection were measured in 172 inhabitants (78%) of an isolated Canadian Inuit settlement. Evidence of hepatitis B infection was found in 22% of residents. The prevalence increased with age, being uncommon under the age of 20 (7%), yet present in the majority of inhabitants over the age of 40 (64%). Sera from four individuals (2.3%) were hepatitis B surface antigen- (HBsAg) positive. All four HBsAg carriers were negative for immunoglobulin M (IgM) antibody to hepatitis B core antigen (IgM anti-HBc), hepatitis B e antigen (HBeAg), and DNA polymerase, but positive for antibody to hepatitis B e antigen (anti-HBe). These data suggest that hepatitis B infection has become relatively uncommon in the inhabitants of this community born during the past 20-30 years. The apparent decline in prevalence did not appear to be related to recent demographic or socioeconomic changes in the area.
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PMID:The changing epidemiology of hepatitis B virus infection in the Canadian north. 401 49

Experiments were done to show that the human hepatitis B antigen (HBAg)-associated DNA polymerase is a component of Dane particles and their antigenically distinct cores prepared by Nonidet P-40 detergent treatment of Dane particles. Before detergent treatment, the DNA polymerase was precipitated by serum containing anti-HB surface antigen (anti-HB(s)) but not with serum containing anti-HB core antigen (anti-HB(c)). After detergent treatment, the enzyme was precipitated by anti-HB(c)- and not by anti-HB(s)-containing serum. Highly purified 16- to 25-nm HBAg particles blocked only the precipitation of DNA polymerase in untreated HBAg preparations. The 110S structure with which the DNA reaction product remains associated in Nonidet P-40-treated preparations was identified as Dane particle core by immunoprecipitation with serum containing anti-HB(c). The DNA polymerase and the radioactive DNA reaction product were used as markers for core in immunoprecipitation tests for anticore. In such assays, 8 of 11 human sera with anti-HB(s) activity and all of 10 sera from chronic HBAg carriers were found to contain anti-HB(c) activity.
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PMID:DNA polymerase in the core of the human hepatitis B virus candidate. 483 9

We have determined the complete nucleotide sequence of an infectious cloned genome of ground squirrel hepatitis virus (GSHV), a nonpathogenic member of the hepadnavirus group. The genome is 3,311 base pairs long and contains the major open reading frames described for the related human and woodchuck hepatitis B viruses (HBV and WHV, respectively). These reading frames include genes for the major structural proteins (the surface and core antigens), unassigned open reading frames (A and B), the longer of which is presumed to encode the viral DNA polymerase, and an open reading frame preceding and continuous with the surface antigen gene. The arrangement of these open reading frames is similar to that encountered in the genomes of HBV and WHV: all of the reading frames are encoded on the same strand, they are positioned in the same fashion with respect to each other, and a large portion (at least 51%) of the genome can be translated in two reading frames. Comparisons of the predicted translational products of the three mammalian hepadnaviruses reveal 78% amino acid homology between the proteins of GSHV and WHV and 43% homology between those of GSHV and HBV. In addition, a perfect direct repeat of 10 to 11 base pairs, separated by ca. 46 to 223 base pairs, is present in the three mammalian viruses and in duck hepatitis B virus; the position of the repeats near the 5' termini of the two strands of virion DNA suggests a role in viral replication.
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PMID:Nucleotide sequence of an infectious molecularly cloned genome of ground squirrel hepatitis virus. 608 50

Twenty patients with chronic type B hepatitis were entered into a randomized, controlled study of adenine arabinoside monophosphate. Before entry, all patients were documented to have stable levels of hepatitis B surface antigen, hepatitis B e antigen, serum hepatitis B virus deoxyribonucleic acid, and deoxyribonucleic acid polymerase activity. Ten patients received adenine arabinoside monophosphate and 10 received no treatment. The two groups were well matched with respect to age, sex, known duration of hepatitis B surface antigen, presence of symptoms, serum aminotransferase levels, and hepatic histopathology. During the 4 wk of therapy, serum levels of hepatitis B virus fell dramatically. However, serum hepatitis B virus-deoxynbonucleic acid or deoxyribonucleic acid polymerase activity, or both, remained detectable, and levels of hepatitis B virus invariably rose once therapy was stopped. From 2 to 9 mo after therapy, 4 of the 10 treated patients became hepatitis B e antigen or hepatitis B virus-deoxyribonucleic acid and deoxyribonucleic acid polymerase negative, or both, and the results of routine serum biochemical tests improved. However, 2 of these 4 patients later relapsed. In the control group, 2 patients became seronegative for hepatitis B virus-deoxyribonucleic acid and deoxyribonucleic acid polymerase and manifested improvement in serum biochemical results by 18-24 mo after randomization. Thus, long-term improvements in clinical and serologic features of disease occurred in 20% of both treated and control patients. Side effects of adenine arabinoside monophosphate therapy were common, and 3 patients developed a severe and prolonged neuropathic pain syndrome. These results suggest that a 4-wk course of adenine arabinoside monophosphate therapy does not induce an increased rate of long-term remissions in chronic type B hepatitis.
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PMID:Randomized controlled trial of adenine arabinoside monophosphate for chronic type B hepatitis. 619 51

DNA was isolated from the ayw subtype of hepatitis B virus (HBV) that had been incubated in vitro with all four deoxynucleoside triphosphates in order to complete the circular viral genome by means of the endogenous DNA polymerase. The purified viral DNA was cleaved with EcoRI restriction endonuclease, inserted into the EcoRI site of plasmid pBR322, and cloned in Escherichia coli chi 1776. DNA from a clone, pHBV-1, that contained a 3200-base-pair insert of HBV DNA was cleaved with EcoRI and incubated with phage T4 ligase under conditions favoring intramolecular ligation. HeLa cell cultures exposed to this DNA showed marked cytopathic changes, accompanied by production of hepatitis B core and surface antigens, 11-14 days after subculture. Electron microscopic examination of anti-hepatitis B surface antigen immunoprecipitates from culture media of these cells revealed both 42-nm particles with central cores and 20-nm round particles. Although neither intact circular nor EcoRI-cleaved linear pHBV-1 DNAs evoked these effects in HeLa cells, both cytopathic changes and intranuclear hepatitis B core antigen were detected in HeLa cells infected with Dane particles.
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PMID:Expression of cloned hepatitis B virus DNA in human cell cultures. 625 85

The livers of 33 captive woodchucks were examined histologically in 30 biopsy and 10 autopsy specimens and the findings were correlated with serum determinations for woodchuck hepatitis virus (WHV), surface antigen (WHsAg) and antibody (anti-WHs), and WHV DNA and DNA polymerase. The liver appeared normal in all 3 serum-negative animals, 7 of 16 with indeterminate WHV status, and 1 of 4 with anti-WHs, but not in 10 animals with WHsAg, WHV DNA, and DNA polymerase. Mild hepatic inflammation was found in 7 woodchucks with indeterminate status, 4 with anti-WHs, and 2 with each marker of WHV infection. Significant inflammation was found in 2 of indeterminate status and 4 with every marker, whereas more severe lesions (2 of chronic active type) occurred, almost always in autopsy specimens, in 8 animals with every marker. Eight of 10 animals with all markers had orcein-positive inclusions (Shikata's technique) and 6 had hepatocellular carcinoma associated with acute and chronic hepatic inflammation and, usually, neoplastic nodules in the noncarcinomatous parenchyma. Features distinguishing the woodchuck lesion from human hepatitis B disease were: association of carcinoma with acute hepatic inflammation (but not with cirrhosis) and DNA polymerase in the serum; transition to carcinoma from neoplastic nodules; conspicuous plasma-cellular reaction of hepatic inflammation, and hematopoietic cells in the tumor. Significant hepatic lesions in the woodchucks were regularly associated with serum WHsAg, WHV DNA, and DNA polymerase. In contrast to man, hepatocellular carcinoma in woodchucks was regularly associated with these markers of active viral replication. The nature of the orcein-positive inclusions requires elucidation, although they may assist in screening for similar viruses in other species. The woodchuck may help in the study of the relation between hepatocellular carcinoma and hepatitis B, including the possibility of cocarcinogenic factors.
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PMID:Woodchuck hepatitis and hepatocellular carcinoma: correlation of histologic with virologic observations. 626 81


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