Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
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The close association between hepatitis B antigen (HBAg) and the infectious agent of hepatitis B is clear. Many investigations have shown HBAg to be a useful tool for epidemiological studies of hepatitis B. The relation between HBAg and the postulated hepatitis B virus (HBV) is as yet not clear. In light of recent results a possible candidate could be the so-called Dane particle, which has HBAg reactivity on the surface, but possesses an antigenically distinct core. The core has been shown to have associated DNA polymerase activity. The particles which carry HBAg reactivity have surfaces which are antigenically complex. One common specificity a and 2 pairs of mutually exclusive determinants have been recognized namely d and y and w and r but further possible specificities are under investigation. Four different phenotypes have been described, adw, adr, ayw and ayr. Present evidence indicates that adw, adr and ayw are the phenotypic expression of 3 different transmissible strains of HBV. Studies on the epidemiology of these subtypes have shown 3 different geographic patterns. In the USA and Northern Europe both Dw (adw) and YW (ayw) are common, but in the Eastern Mediterranean and Middle East Yw is practically the only type found. In the Far East DR (adr) is the dominating subtype. Investigations have been done to determine whether there are any clinical differences in hepatitis caused by the different tubtypes. No certain differences have been shown.
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PMID:Some epidemiological and clinical aspects of hepatitis B antigen and its subtypes. 5 89

The morphological, chemical and physical properties of HBAg suggest that the 42 nm component of the antigen, the Dane particle, represents the agent of viral hepatitis B. Its core contains a circular, double stranded DNA, a DNA polymerase and carried HBc-Ag. HBc-Ag is localized on the 21 nm particle, the tubular structures and the surface of the Dane particles. At least 8 different subdeterminants of HBs-Ag could be distinguished by means of specific animal anti-sera. HBs-Ag activity was demonstrated in almost all body fluids and excreta. The results of combined histologic, fluorescent and electronmicroscopic studies suggest ath HBc-Ag is localized in the liver cell nucleus and that HBs-Ag is found in the cysterna of the smooth endoplasmatic reticulum of the hepatocytes. The demonstration of HBs-Ag and the specific DNA polymerase in the serum indicate a hepatitis b virus infection with persistent reproduction of the agent, while demonstration of anti-HBs indicates that the infection has been overcome. The clinical importance importance of anti-HBc is controversial.
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PMID:[Nature, character, occurrence, and demonstration of hepatitis B antigens (author's transl)]. 5 90

Phosphonoacetate is a highly specific inhibitor of herpes simplex virus-induced DNA polymerase. Sensitivity of herpesvirus type 1 or type 2 induced DNA polymerase to the drug was similar. However, DNA polymerases from other sources such as the host cells (Wi-38), Micrococcus luteus, and hepatitis B virus were highly resistant. In addition, Escherichia coli RNA polymerase and reverse transcriptase of Rous sarcoma virus were also insensitive to the drug. Enzyme kinetic studies showed that inhibition was noncompetitive with respect to deoxyribonucleotide triphosphates. The Ki value was about 0.45 muM. The apparent Km values for dTTP, dATP, dCTP, and dGTP were 0.71, 0.75, 0.42, and 0.39 muM, respectively. The base composition of template has no profound effect on the extent of inhibition. The drug caused uncompetititve inhibition with respect to template which indicated that phosphonoacetate did not bind directly to template DNA. Results are presented which suggest that phosphonoacetate did not affect the formation of the enzyme-DNA complex but probably inhibited the elongation step of DNA polymerase reaction.
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PMID:Mode of inhibition of herpes simplex virus DNA polymerase by phosphonoacetate. 5 71

A study of the e determinant of hepatitis B surface antigen in an area of hepatitis B hyperendemicity revealed that the presence of e antigen or of antibody to e in the sera of individuals was specifically related to evidence of past or present infection with hepatitis B virus. Among asymptomatic long-term carriers of hepatitis B surface antigen, presence of the e antigen was associated with elevated levels of aspartate and alanine aminotransferases in serum; this observation suggested that the e antigen might be a marker for persisting hepatic dysfunction. Higher levels of DNA polymerase found in carriers of the surface antigen with e antigen suggested that these individuals might have a higher level of circulating Dane particles and thus, perhaps, a higher level of hepatitis B virus infectivity.
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PMID:Relation of e antigen to hepatitis B virus infection in an area of hyperendemicity. 5 11

The e determinant of hepatitis B surface antigen (HBS Ag) was found in 23 of 42 patients with chronic hepatitis B virus (HBV) infection. Presence of e antigen was associated with increases in DNA polymerase activity and in the number of circulating Dane particles. In the group with detectable e antigen, the average DNA polymerase activity was 367+/-78 counts per minute (cpm; mean+/-standard error [SE]), and the average number of Dane particles counted in electron micrographs was 4.4% of the total HBS Ag. In contrast, e antigen-negative patients had an average DNA polymerase activity of 40+/-6.9 cpm (P less than 0.1) and an average Dane particle count equal to 0.6% of the HBS Ag. The e antigen was detected in 68% of patients who were HBS Ag carriers or had persistent viral hepatitis and 40% of those with chronic active type B hepatitis. Thus, the presence of e antigen correlated with both the chronicity and presence of infectious HBV. However, it did not correlate with the type or severity of liver disease after HBV infection, since e antigen was present in both chronic benign and chronic aggressive hepatitis B infections.
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PMID:Correlation of e antigen, DNA polymerase activity, and Dane particles in chronic benign and chronic active type B hepatitis infections. 6 88

The circular DNA of hepatitis B Dane particles, which serves as the primer/template for an endogenous DNA polymerase, was analyzed by electrophoresis before and after a polymerase reaction and after digestion by restriction endonuclease or single-strand-specific endonuclease S1. The unreacted molecules extracted from the particles were electrophoretically heterogeneous, and treatment with S1 nuclease produced double-stranded linear DNA ranging in length from 1,700 to 2,800 base pairs (bp). After an endogenous DNA polymerase reaction, two discrete species of DNA molecules were found: a circular form and a linear form 3,200 bp long. The reaction resulted in a population of molecules with an elongated and more homogeneous double-stranded region. These results suggest that the circular molecules in Dane particles have single-stranded regions of varying lengths that are made double stranded during the DNA polymerase reaction. The endogenous DNA polymerase was found to initiate apparently at random in a region spanning more than a third of the molecule. Analysis of restriction endonuclease cleavage fragments of the fully elongated DNA revealed that although the molecules were of a uniform length, they were somewhat heterogeneous in sequence. The sum of the sizes of the 10 major endonuclease Hae III-generated fragments, detected by ethidium bromide, was 3,880 bp. Two additional fragments (B and G) detected by autoradiography after an endogenous DNA polymerase reaction with (32)P-labeled deoxynucleoside triphosphates made the total 4,910 bp.
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PMID:Structure of hepatitis B Dane particle DNA and nature of the endogenous DNA polymerase reaction. 6 27

It is well known that primary hepatocellular carcinoma could be derived from chronic hepatitis and liver cirrhosis in epidemiologic studies. However, it is still not clear what kinds of hepatocyte are premalignant cells. Recently we have focused on liver cell dysplasia as a possible premalignant cell, and showed localization of alpha-fetoprotein in the cytoplasma of these cells. Although the dysplastic cells were often seen in the liver of chronic active hepatitis, hepatitis B virus associated DNA polymerase activity was also significantly high in the sera from the patients with chronic active hepatitis. In this paper, we discuss the possible role of hepatitis B virus through hepatocarcinogenesis in human.
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PMID:Early lesions and development of primary hepatocellular carcinoma in man--association with hepatitis B viral infection. 7 Mar 87

A study was undertaken to assess the state of hepatitis B virus infection in a group of asymptomatic hepatitis B surface antigen (HBsAg) carriers. This study confirmed that the presence of hepatitis B e antigen (HBeAg) in serum was closely associated with serum HBsAg-specific deoxyribonucleic acid polymerase activity, hepatitis B core antigen (HBcAg) in serum and liver cell nuclei, and a histological picture of chronic hepatitis. No HBsAg-specific deoxyribonucleic acid polymerase activity or HBcAg was detected in highly concentrated anti-HBe-positive sera. In addition, liver biopsy specimens from carriers with anti-HBe were negative for HbcAg by immunofluorescence, and the liver histology was either normal or revealed only fatty changes. These data indicate that the anti-HBe-positive sera contained either no Dane particles or, if present, at least a 500-fold-lower concentration of Dane particles than that found in HBeAg-positive sera.
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PMID:Expression of hepatitis B virus-specific markers in asymptomatic hepatitis B surface antigen carriers. 7 Dec 67

Twelve infants, born to mothers with hepatitis B virus infection, were inoculated within 7 days of birth with immune serum globulin containing antibody to hepatitis B surface antigen (HBsAg) titers of 1:32 to 1:64 as measured by passive hemagglutination. Six of nine infants (66.7%) born to HBsAg-positive carrier mothers became HBsAg-positive within 3 mo of age. In addition, two of three treated infants born to mothers with acute hepatitis B during the delivery period also developed HBsAg. The hepatitis e antigen was detected in four of five carrier mothers and in two mothers with acute hepatitis, whose infants subsequently became HBsAg positive. In addition, hepatitis B-specific DNA polymerase activity was detected in the seven HBsAg-positive mothers who transmitted the virus to their infants. All eight infants have remained persistently HBsAg positive. Thus, the immune serum globulin containing low-titer antibody to HBsAg is not protective when given to infants born to HBsAg carrier mothers or to mothers with acute hepatitis B during the delivery period.
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PMID:Failure of immune serum globulin to prevent hepatitis B virus infection in infants born to HBsAg-positive mothers. 8 62

Partially purified hepatitis B e antigen (HBeAG) was prepared by ultracentrifugation, ammonium sulfate precipitation, and molecular sieve chromatography of sera obtained from asymptomatic carriers of hepatitis B surface antigen. The antigenic specificity of the HBeAG preparations was investigated further with affinity chromatography. The results indicated that HBeAG is distinct and separable from DNA polymerase activity. Columns coupled with either goat IgG prepared from antiserum to human IgG or antibody to HBeAg bound all detectable HBeAg and bound 31% and 100% of the IgG, respectively, from a partially purified HBeAg preparation. Rate zonal sucrose sedimentation and molecular sieve and ion-exchange chromatography indicated a variability in molecular weight and charge; this finding suggested a heterogenous population of immunoreactivities containing HBeAg. Our preliminary results suggest the existence of an HBeAg-IgG complex.
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PMID:A partial characterization of hepatitis B e antigen. 8 89


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