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)

Hepatitis B viral particles (HB-VP) were purified from sera of chronic hepatitis B surface antigen (HBsAg) positive carriers by consecutive isopycnic and rate-zonal sedimentation in sucrose gradients. Their immunological properties [HBsAg, hepatitis B core antigen (HBcAg) and hepatitis B e-antigen (HBeAg) activities] were examined by a radioimmunoassay based upon the classical "sandwich principle". A double antibody specificity radioimmunoassay (DAS-RIA) was then developed to determine whether envelope proteins (HBsAg) with binding activity for polymerized human serum albumin (pHSA-BA) were associated with core-specific antigenicities (HBc/HBeAg). An e-antigen activity cosedimenting with intact HB-VP (negative for HBcAg reactivity) was detected in association with HBsAg and receptors for pHSA. The presence of HBcAg-specific determinant(s) on HBeAg molecules was also indicated by DAS-RIA. So, we postulated that such hepatitis B virion (HBV) specific molecules are involved in immune complexes with anti-HBc as antibodies in sera of patients with chronic HBV infection. To define the significance of these molecular forms in HB-VP morphogenesis, we studied the effects of a mild treatment with a chaotropic salt, NaSCN, on HB-VP-rich fractions (DNA polymerase positive). A small mol. wt HBeAg derived from HB-VP by dissociating treatment was detected. We found that core-specific determinants (HBe/HBcAg) were bound to large surface proteins (HBsAg) with pHSA-BA and therefore probably contained the pre-S sequence. The selective release from HB-VP of such molecular forms, which could be a product of the major S-region transcript, suggests that they may be components of complete virions.
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PMID:Demonstration of a firm association between hepatitis B surface antigen proteins bearing polymerized human albumin binding sites and core-specific determinants in serum hepatitis B viral particles. 241 11

The effects of suramin, an antiparasitic agent, upon in vitro hepatitis B surface antigen production by the human hepatoma cell line PLC/PRF/5 and hepatitis B virus associated DNA polymerase activity in the serum of a chronically infected patient were examined. Treatment with suramin resulted in decreases in hepatitis B surface antigen production and hepatitis B-virus associated DNA polymerase activity. The decrease in hepatitis B surface antigen production was paralleled by a general decrease in hepatoma cell viability and cellular protein synthesis. Although the inhibitory effects of suramin for hepatitis B virus appear to be nonspecific as demonstrated in these two in vitro systems, the recently announced trial of suramin for the treatment of the acquired immunodeficiency syndrome should afford an unusual opportunity to evaluate the effectiveness of suramin in the treatment of chronic hepatitis B virus infection.
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PMID:Effects of suramin on in vitro HBsAg production by PLC/PRF/5 cells and hepatitis B virus DNA polymerase activity. 242 68

We measured 2',5'-oligoadenylate synthetase activities in serum and peripheral blood mononuclear cells from 10 patients with chronic hepatitis B who were being treated with interferon so as to determine whether 2',5'-oligoadenylate synthetase activity in serum reflected 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells, and whether it could be used to monitor interferon treatment. Pretreatment values of 2',5'-oligoadenylate synthetase activity in patients' serum and peripheral blood mononuclear cells were not statistically different from values from control subjects. When interferon was administered, serum levels of 2',5'-oligoadenylate synthetase began to rise within 3 hr, reached peak values at 12 hr and then declined. The levels of 2',5'-oligoadenylate synthetase activity both in serum and peripheral blood mononuclear cells increased substantially during interferon treatment, ranging 2- to 50-fold greater than initial levels. The levels of 2',5'-oligoadenylate synthetase in serum correlated closely with levels in peripheral blood mononuclear cells. In addition, when the levels of 2',5'-oligoadenylate synthetase rose during interferon administration, serum hepatitis B virus DNA polymerase values fell, and, in some cases, DNA polymerase rose again when 2',5'-oligoadenylate synthetase fell after discontinuation of interferon. These findings suggest that 2',5'-oligoadenylate synthetase activity in serum accurately reflects the antiviral effect of interferon and could be used to monitor interferon treatment.
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PMID:Serum 2',5'-oligoadenylate synthetase activity during interferon treatment of chronic hepatitis B. 245 34

The binding of polyalbumin to hepatitis B virus (HBV)-associated envelope epitopes has been studied by means of a radioimmunoprecipitation technique. HBV particles were purified from the sera of chronic hepatitis B surface antigen (HBsAg) carriers and labelled through the endogenous HBV-DNA polymerase reaction. Human albumin, polymerized through glutaraldehyde cross-linking, was able to precipitate (100%) labelled HBV at concentrations of 31.2 and 62.5 micrograms/ml, in contrast to monomeric albumin (HSA). This event was further confirmed by immune electron microscopy. The addition of anti-HSA to the mixture HBV plus polyalbumin gave a 100% precipitation in a wide dilution range (15.6-500 micrograms/ml). The binding of polyalbumin (31.2 micrograms/ml) to virions was strongly inhibited (up to 98%) when preincubating with antibody to a glycosylation-dependent preS2 epitope on HBV. The same was accounted (up to 99%) for polyvalent IgG anti-HBs. However, antibodies to the group 'a' and subtype 'd' determinants, as well as anti-preS1 region antibodies, inhibited weakly polyalbumin binding to HBV. The binding site of the inhibitory antibody overlaps probably with neutralizing epitopes. Our findings support the hypothesis that albumin binding plays an important role in the viral life cycle.
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PMID:Inhibition of albumin binding to hepatitis B virions by monoclonal antibody to the preS2 domain of the viral envelope. 245 8

Two years or more after 35 patients (29 men and six women) with chronic hepatitis B were treated by interferon, we studied relationships of age, ALT activity, activity of serum DNA polymerase associated with the hepatitis B virus, serum levels of hepatitis B e antigen and activity of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells when treatment started in comparison with treatment results. Seventeen patients were given human lymphoblastoid interferon-alpha; the other 18 patients were given interferon-beta. We measured the activity of 2',5'-oligoadenylate synthetase in these mononuclear cells and found the rate of increase in vivo and in vitro; the correlation between the two was r = 0.68. This enzyme activity in the patients who became negative for DNA polymerase after interferon treatment increased more both in vivo and in vitro than in patients who did not became negative. Also, both the in vivo and in vitro activity increased more in patients who became negative for the e antigen after interferon therapy than in those who remained positive. In the first group, interferon was considered to be effective; in the second, ineffective. Of the patients who became negative, some developed e antibodies and some did not; the increase in this enzyme activity in the two groups was not significantly different. The increase in the activity of 2',5'-oligoadenylate synthetase activity could be used to predict the results of interferon treatment and is an index that can be used before treatment to predict the response.
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PMID:Relationship of the effects of interferon on chronic hepatitis B and the induction of 2',5'-oligoadenylate synthetase. 247 40

The effect of 2',3'-dideoxycytidine, a potent antiviral agent, which, following anabolic phosphorylation, inhibits the reverse transcriptase of the human immunodeficiency virus in vitro, was assessed in 16 Pekin ducks chronically infected with the duck hepatitis B virus. Nine ducks were given 11 mg/m2 of dideoxycytidine intravenously every 6 h, and 7 ducks received no treatment. Serum duck hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase activity decreased in every duck treated with dideoxycytidine. The mean inhibition of deoxyribonucleic acid polymerase and duck hepatitis B virus deoxyribonucleic acid on the third day of treatment measured 64% (p less than 0.01) and 73% (p less than 0.01), respectively. The inhibition of deoxyribonucleic acid polymerase persisted after treatment was stopped, and 4 ducks continued to show greater than 50% inhibition 12 days after stopping treatment. Duck hepatitis B virus deoxyribonucleic acid, which was measured in total cellular deoxyribonucleic acid extracted from liver biopsy specimens obtained before and on the last day of treatment with dideoxycytidine, showed an average inhibition of 96% in 3 ducks treated with dideoxycytidine, but showed no decrease in the remaining 5 ducks. Thus, dideoxycytidine has potent antiviral activity against duck hepatitis B virus and warrants further evaluation as an antiviral agent in the treatment of chronic hepatitis B virus infection in humans.
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PMID:Inhibition of duck hepatitis B virus replication by 2',3'-dideoxycytidine. A potent inhibitor of reverse transcriptase. 247 99

In ten carriers positive for chronic hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and DNA polymerase, the authors investigated the efficacy of the combination therapy consisting of glycyrrhizin withdrawal and human fibroblast interferon (locally produced). Glycyrrhizin was given for four weeks and was stopped without tapering off the dose. Human fibroblast interferon was given continuously. Thirty-six weeks after the end of this treatment, three of the ten patients were HBeAg negative but not anti-HBe positive, and in one of these three DNA polymerase became undetectable. Another patient showed a loss of DNA polymerase with HBeAg. Transaminase levels decreased in nine of the patients. Glycyrrhizin appeared to act as an antiviral agent in four patients and had a corticoid-like effect in three. DNA polymerase decreased remarkably after interferon administration, and serum transaminase levels increased. No side effects were reported in patients receiving glycyrrhizin. In contrast, almost all patients receiving human fibroblast interferon had influenza-like symptoms, which, although initially severe, decreased with subsequent injections of interferon. Thus this combination therapy seems safe and effective.
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PMID:Combination therapy of glycyrrhizin withdrawal and human fibroblast interferon for chronic hepatitis B. 249 83

Ten patients with chronic type B hepatitis were treated with three courses of adenine arabinoside monosphosphate (Ara-AMP). The drug was given intramuscularly at a dosage of 10 mg/kg/day in ten-day courses during each of three sequential months. The patients were all men, aged 31-61 years, who were known to have had chronic hepatitis for one to four years. Each of the ten-day courses of Ara-AMP was accompanied by a marked inhibition in the serum levels of hepatitis B virus (HBV) DNA and DNA polymerase activity. However, HBV-DNA remained detectable in every patient during treatment and invariably rebounded to pretreatment levels soon after each course was stopped. One patient developed severe, and two patients developed mild neuromuscular side effects. During a 12-18-month follow-up period, only one of the ten patients has had a sustained clinical, serum biochemical, and serological remission. In this patient, serum HBeAg, HBV-DNA, and DNA polymerase became undetectable three months after the final course of treatment; serum aminotransferase levels subsequently fell into the normal range; and a follow-up liver biopsy showed a diminution in the chronic inflammatory cell activity and a disappearance of intrahepatic hepatitis B core antigen reactivity. Thus, multiple ten-day courses of Ara-AMP do not induce a high rate of remissions in this disease and are associated with appreciable neuromuscular toxicity. Ara-AMP is a potent inhibitor of serum levels of hepatitis B virus, but Ara-AMP therapy has not been shown to have long-term beneficial effects in chronic type B hepatitis.
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PMID:Treatment of chronic type B hepatitis with multiple ten-day courses of adenine arabinoside monophosphate. 257 92

Thirty-five patients with active chronic hepatitis B (ACH-B) were evaluated. They were in stable replicative phase (HBeAg +; DNA polymerase and ALT stable in two determinations at least one month apart) and had not been infected by delta virus or HIV-1. Thirty-four patients were heterosexual and no patient was a drug abuser except one. The 23 initial cases were followed up for 15 months without therapy. The subsequent 12 cases were treated with maximal doses of 2.5 megaunits/m2 of lymphoblastoid alpha interferon (IFN-L) daily for two weeks and three times a week during 10 more weeks. While in the controls only two cases (8.69%) lost the DNA-polymerase activity and HBeAg, 5 treated patients (41.66%; p less than 0.05) developed seroconversion to nonreplicative phase. No patient from the control series lost the HBsAg; however, this happened in 2 treated patients (16.66%). These results show that IFN-L is effective in heterosexual patients with ACH-B in replicative phase without delta virus or HIV-I co-infection.
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PMID:[Treatment of chronic hepatitis B with lymphoblastoid alpha interferon]. 261 34

The detection of HBV-DNA in serum by molecular hybridization is the most sensitive and specific marker or replication and infectivity of hepatitis B virus and currently is proposed as a routine diagnostic technique in the follow-up of HBV-related diseases. Comparing different techniques already described, we found that direct spotting of serum samples on nitrocellulose membranes under vacuum filtration, followed by denaturing and neutralizing washes is more practical, simple, sensible and reproducible. DNA polymerase assay using phosphonoformic acid as specific viral inhibitor has shown 86.8% of concordance with HBV-DNA detection, and so, it is an useful alternative in the follow-up of hepatitis B chronic patients. We found 19.2% HBeAg positive samples with no other markers of viral replication and no anti-HBe positive sample had detectable HBV-DNA. Discordance between the 2 systems have been extensively described, and we confirm this for the first time in our country. Molecular biological techniques are essential to determine the replication status of chronic hepatitis B patients.
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PMID:Comparison of serum hepatitis B virus replication markers in patients with chronic hepatitis B: studies on HBeAg/anti-HBe system, viral DNA polymerase and HBV-DNA. 262 62


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