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)

Four patients who had chronic liver disease and were positive for hepatitis B surface antigen (HBsAg) were treated with vidarabine, a synthetic purine nucleoside that inhibits DNA polymerase activity in vitro and in vivo. Before treatment all had raised serum DNA polymerase concentrations. Three also had hepatitis B e (HBe) and were shown by electron microscopy to have hepatitis B virus (Dane) particles in their serum. In all patients 10 days' treatment with vidarabine resulted in an immediate loss of DNA polymerase activity. In three patients the activity returned when treatment was stopped. In those three patients Dane particles and HBe antigen persisted during and after treatment; in the fourth patient, who remained negative for DNA polymerase, HBsAg titres fell. Although vidarabine inhibited virus replication, virus particles did not disappear from the blood in these patients, presumably because the particles were cleared only slowly. Similar results with interferon suggest that the virus disappears, and HBsAg titres fall, some weeks after the fall in DNA polymerase activity. Continued treatment may therefore have a sustained effect on viral replication. Whether vidarabine can permanently clear HBsAg and so arrest chronic liver disease remains to be seen, but at the very least it could reduce the spread of infection.
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PMID:HBsAg-positive chronic liver disease: inhibition of DNA polymerase activity by vidarabine. 69 57

Circulating complete and defective hepatitis B virus forms, as represented by full, DNA polymerase-positive and empty, DNA polymerase-negative Dane particles, respectively, were investigated in sera from patients with chronic hepatitis B virus infection and related to the presence of e antigen and antibody and to the histological findings on liver biopsy. Complete hepatitis B virus particles were detected in the serum of all patients postive for e antigen, their percentage ranging from 15 to 61% of the total Dane particle population. Although most of these cases had chronic persistent or chronic active hepatitis, complete viral particles were also found in serum of 3 healthy carriers of hepatitis B surface antigen who had e antigen. These results indicate that e antigen is a marker of active virus replication and support its association with infectivity. It is also associated with liver damage because production of complete virus is a feature of chronic hepatitis. In the presence of anti-e, detection of Dane particles in serum appeared to be related to the histological findings. Most of the healthy carriers had no Dane particles in serum, whereas 80% of the cases with chronic liver disease had circulating Dane particles. However, in contrast to the cases with e antigen, 98 to 100% of Dane particles in these cases appeared to be defective in nucleic acid material on electron microscopy after positive staining. All of the patients with chronic active hepatitis in this group had progressed to cirrhosis and it is possible that production of complete virus particles is reduced in the later stages of the illness.
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PMID:Full and empty Dane particles in chronic hepatitis B virus infection: relation to hepatitis B e antigen and presence of liver damage. 70 Mar 29

We analyzed the binding of 125I-labelled IFN-alpha to peripheral blood mononuclear cells in 19 healthy controls, 25 asymptomatic HBV carriers (AsC), and 69 patients with HBs antigen positive chronic liver disease (CLD). Histological examination showed that of the 69 patients with CLD, 14 had chronic persistent hepatitis (CPH), 46 had chronic active hepatitis (CAH), 9 had liver cirrhosis (LC). The mean number of IFN-alpha/beta receptor sites per cell totaled 1270 +/- 340 in the healthy controls, 1440 +/- 290 in AsC, and 1600 +/- 480 in CLD (with 1770 +/- 480 in CPH, 1580 +/- 490 in CAH, and 1420 +/- 410 in LC). HBV carriers had more IFN-alpha/beta receptor sites than the healthy controls (AsC: P less than 0.1, CLD: P less than 0.01). In CLD, patients with LC tended to have fewer IFN-alpha/beta receptor sites than those with CPH or CAH. The number of IFN-alpha/beta receptor sites in CLD was correlated with the HBe antigen titer (P less than 0.01), and activity of HBV-DNA polymerase (P less than 0.05). These results were suggested that IFN-alpha/beta receptor sites was higher at the HBV carrier state, and correlated with viral replication.
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PMID:[Interferon-alpha/beta receptors in patients with chronic HBV infection]. 214 66

Since 1965, when Blumberg discovered the Australia antigen, the hepatitis B surface antigen (HBsAg), the research on viral hepatitis has rapidly progressed. The identification of specific hepatitis B associated antigens and antibodies in blood, and liver tissue, together with the improvement of detection systems, have enhanced our knowledge about the mechanism of liver injury and the natural history of hepatitis B virus (HBV) infection. Now it has been recognized that HBV has no direct cytopathic effect on hepatocytes and that hepatocyte necrosis is associated with the virus induced immunological reaction of the host. From the reaction, there are two types of HBV infection, i.e., transient (acute) and persistent (chronic) infection. In addition to the conventional measurements, such as HBsAg, anti-HBs, anti-HBc, HBeAg, anti-HBe and anti-IgM HBc, recently pre S1, pre S2 antigen/antibody systems and polymerized human albumin receptor and antibody have been developed. The significance of the detection of these antigen/antibody systems was discussed. On the other hand, to determine the presence of HBV, the state of HBV replication or the infectivity directly, HBV associated DNA polymerase and HBVDNA should have been detected. (Very recently, the polymerase chain reaction method has been introduced to detect very small amounts of HBVDNA). In this presentation, the change of these viral markers in various cases was shown, and especially emphasized was anti-IgM HBc in acute hepatitis and HBeAg/Ab status in chronic liver disease. Lastly, the present state of Interferon therapy for type B chronic hepatitis was mentioned.
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PMID:[Diagnosis of type B hepatitis]. 219 6

To identify factors predicting response to antiviral therapy, we reviewed the clinical features of 38 male hepatitis B surface antigen (HBsAg) carriers who received adenine arabinoside or lymphoblastoid interferon. All patients were followed for one year or longer. Response was defined as loss of hepatitis B e antigen, hepatitis B virus DNA and DNA polymerase from the serum. Only 2 of 19 (11%) homosexual men responded, compared with 10 of 19 (53%) heterosexual men (P less than 0.02). Both responders in the homosexual group had received lymphoblastoid interferon. None of the 13 homosexual men, but 8 of 16 heterosexual men, responded to adenine arabinoside or its monophosphate (P less than 0.01). Responders to antiviral therapy had higher (P less than 0.05) serum levels of aspartate aminotransferase (median 115, range 51-344) than did non-responders (median 83, range 32-181). The decreased responsiveness of homosexual men to antiviral therapy may be a result of more severe immunologic abnormalities in homosexual than in heterosexual men with HBsAg-positive chronic liver disease.
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PMID:Diminished responsiveness of homosexual men to antiviral therapy for HBsAg-positive chronic liver disease. 241 58

We have analyzed the immunomodulatory effect of 5 and 2 MU of recombinant interferon-gamma (rIFN-gamma) administered to 8 carriers of HBsAg with histologically proven chronic active liver disease. After the rIFN-gamma administration, T8 lymphocyte subsets showed a significant decrease (basal vs. 4 weeks, p less than 0.05) and T4/T8 ratios were higher than the basal values in 6/8 patients. Serum levels of the HLA class I-associated beta 2-microglobulin increased significantly in all patients within the first week of treatment, both with the high (p less than 0.01) and the low (p less than 0.05) rIFN-gamma dose. Then, differences between the two doses reached statistical significance (p less than 0.03). Similar results (p less than 0.05) were obtained by measuring the 2',5'-oligoadenylate (2-5A) synthetase activity, co-occurring with the decreases in HBV-DNA polymerase and HBV-DNA, although no differences were found between the two doses. In addition, levels of 2-5A synthetase correlated significantly with those of beta 2-microglobulin (r = 0.743, p less than 0.01). On the other hand, after the rIFN-gamma administration, all the patients had liver membrane antibodies (LMA) in their serum (p less than 0.05); only two patients (who were anti-HD positive) showed LMA at the end of the follow-up. rIFN-gamma has both antiviral and immunomodulatory effects in HBeAg carriers with chronic liver disease.
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PMID:Elevation of 2',5'-oligoadenylate synthetase activity and HLA-I associated beta 2-microglobulin in response to recombinant interferon-gamma administration in chronic HBeAg-positive hepatitis. 314 6

To investigate the relationship between hepatitis B virus (HBV) replication and chronic liver disease, age-specific prevalences of HBeAg, anti-HBe, and HBV DNA polymerase (DNAP) activity were studied in 295 asymptomatic HBV carriers and 183 patients with B-type chronic liver diseases. DNAP activity decreased with age, and there was no difference in the overall prevalence of DNAP activity between the asymptomatic carriers (27.8%) and the chronic liver disease patients (27.3%). The prevalence of DNAP activity in the 40-and-over age group was significantly higher for the chronic liver disease patients (17.5%) than for the asymptomatic carriers (1.7%). The prevalence of HBeAg in the 40-and-over age group was also significantly higher for the chronic liver disease patients (33.8%) than for the asymptomatic carriers (2.6%). These data suggest that viral replication decreased with age and that viral replication occurring in older persons closely related to chronic liver disease.
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PMID:Hepatitis B virus DNA polymerase activity and hepatitis B e antigen (HBeAg)/anti-HBe status among type B chronic liver diseases. 338 75

The efficacy of adenine arabinoside (Ara-A) alone or in combination with prednisolone utilizing its withdrawal effect was studied in 43 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis. Ten patients were treated with 10 mg/kg body wt of Ara-A alone for 4-8 wk. In 9 cases, prednisolone (40 mg/day) was given at a constant dosage for 4 wk before Ara-A treatment. Fourteen patients received oral prednisolone alone for 4 wk, and 10 patients served as untreated controls. Six of 9 patients (67%) undergoing the combination therapy became seronegative for hepatitis B e antigen, whereas only 4 of 24 patients (17%) treated either with Ara-A alone or prednisolone alone lost the antigen. Two of the 10 untreated patients became seronegative for hepatitis B e antigen during the same follow-up period of 9 mo. This prospective controlled study suggests that the combination of immunomodulation by steroid withdrawal and subsequent Ara-A is more effective in the treatment of patients with chronic liver disease and active hepatitis B virus replication than treatment with Ara-A alone.
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PMID:Combination of short-term prednisolone and adenine arabinoside in the treatment of chronic hepatitis B. A controlled study. 400 15

The complete hepatitis B virus (Dane particle) contains a circular doublestranded DNA with single stranded regions and an endogenous DNA polymerase. The HBV associated DNA polymerase closes the single stranded regions of the HBV-DNA in the presence of triphosphatase and a detergent. The DNA polymerase reaction can be inhibition by antiviral substances that exhibit different mode of actions: intercalating agents, phosphonoformiate and the triphosphates of arabinofuranosyladenine and arabinofuranosylcytosine. The value of these in vitro test for the therapy of HBsAg positive chronic liver disease is limited by the fact that is remains so far unclear whether the HBV associated DNA polymerase is a virus- or a host-coded enzyme, and whether virus- or host-coded enzymes are involved in HBV-DNA synthesis in vivo.
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PMID:[Inhibition of hepatitis B virus associated DNA polymerase by antiviral agents: in vitro studies with clinical implications (author's transl)]. 645 51

Survival data from 379 patients with chronic hepatitis B were analyzed to determine life expectancy for the patient from the time of first contact. One hundred twenty-one patients had chronic persistent hepatitis, 128 had chronic active hepatitis, and 130 had chronic active hepatitis with cirrhosis. The frequency of symptoms (p less than 0.001), stigmata of chronic liver disease (p less than 0.001), and liver function test abnormalities (p less than 0.001) increased as the histologic features worsened, whereas the percentage of patients with circulating hepatitis B DNA polymerase declined (p less than 0.001). Women were uncommon in our series and had less severe disease than men (p less than 0.02). Fifty-one patients had died by the time of this analysis. The estimated 5-year survival rates were 97% for patients with chronic persistent hepatitis, 86% for those with chronic active hepatitis, and 55% for those with chronic active hepatitis with cirrhosis. The usual cause of death was liver failure and its sequelae. A multivariate analysis found age of 40 years or more, total bilirubin level of 1.5 mg/dL or more, ascites, and spider nevi to be factors that identified patients at a higher risk of death. The prognosis for patients with chronic hepatitis B is similar to that for patients with chronic hepatitis of other causes.
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PMID:Survival in chronic hepatitis B. An analysis of 379 patients. 648 92


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