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)

Eight patients with chronic hepatitis B infection (seven with chronic active hepatitis and one with chronic persistent hepatitis) were treated with daily intramuscular injections of human leucocyte interferon for periods of 5 to 8 weeks and in one case for 5 months. In one patient there was a marked fall in virus-associated DNA polymerase activity and in the number of DNA containing viral particles during each of two courses of interferon. Hepatitis Be antigen (HBeAg) also disappeared, the aspartate transaminase levels fell and liver histology improved. In the four other patients with detectable DNA polymerase activity there was an early fall but this was transient and in one of these patients there was a continuing rise in activity despite treatment. One other patient became HBeAg negative but hepatitis B surface antigen (HBsAg) titres were mostly unaffected by treatment. A marked decrease in T-lymphocyte mediated cytotoxicity towards HBsAg coated target cells was demonstrated and raises the possibility that an immunosuppressant action of interferon may offsets its direct anti-viral action but may also account for the improvement in liver function which occurred in some patients.
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PMID:Effects of human leucocyte interferon on hepatitis B virus replication and immune responses in patients with chronic hepatitis B infection. 50 26

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

We have studied antibodies (anti-pol antibody) against the polymerase gene product of hepatitis B virus by solid-phase enzyme immunoassay using synthetic peptides coded for by this gene. Sera from six patients with acute hepatitis B, 112 chronic hepatitis B virus carriers and six healthy individuals with naturally acquired immunity to hepatitis B virus were tested for anti-pol antibody. In acute hepatitis B virus infection, anti-pol antibody was detected in three of six patients. In chronic hepatitis B virus infection, anti-pol antibody was detected in 17 of 29 (59%), in 23 of 33 (70%) of cirrhotic patients and in 18 of 24 (75%) patients with cirrhosis complicated by hepatocellular carcinoma, compared with 4 of 19 (21%) asymptomatic carriers and 2 of 7 (29%) patients with chronic persistent hepatitis. Titers of anti-pol antibody were higher in cirrhotic patients with and without hepatocellular carcinoma than in patients with chronic active hepatitis. The presence of anti-pol antibody, however, had no relationship with hepatitis B virus-associated DNA polymerase activities and other viral replicative markers. As for sera from six healthy individuals with naturally acquired immunity to hepatitis B virus, two (33%) were positive for anti-pol antibody. These results indicate that the immune response toward the polymerase gene product is induced during acute and chronic hepatitis B virus infection. In chronic hepatitis B virus infection, anti-pol antibody may serve as a new marker indicative of a long period of hepatitis B virus-induced hepatitis.
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PMID:Detection of antibodies against the polymerase gene product in hepatitis B virus infection. 239 Oct 62

An uncontrolled pilot study of adenine arabinoside monophosphate intramuscularly (ARA-AMP) for 5 days at 10 mg/kg/day and 23 days at 5 mg/kg/day in divided doses, was conducted in 15 consecutive patients known to be HBeAg-positive for a minimum of 12 months. Two patients were lost to follow-up (1 having developed an hepatoma). Of the remaining 13, 11 remained HBeAg-positive at 1 year. During treatment, the median serum DNA polymerase (DNAp) activity fell from 592 cpm to 203 cpm/200 microliters. Of 12 patients initially positive for DNA polymerase, complete inhibition during treatment occurred in 6 and was permanent in 2, who developed anti-HBe. In the remaining 4 and in 6 further patients in whom inhibition was substantial but incomplete, DNAp activity rose to pretreatment levels within 1 month of completing treatment. All these patients remained DNAp + HBeAg-positive at one year. Serum HBV-DNA was measured in 7 patients, 6 who were initially DNAp-positive and 4 of whom had complete inhibition of DNAp during treatment. All 7 remained positive for HBV-DNA during treatment. Although side-effects were common there were no significant changes in biochemical or haematological parameters during or subsequent to therapy. Over the subsequent 48 months 2 more patients have developed an hepatoma and a further 5 have lost HBeAg; the 4 patients who remain alive and HBeAg-positive all had chronic persistent hepatitis initially.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effect of ARA-AMP on serum DNA polymerase activity and serum HBV-DNA in chronic hepatitis B virus infection. A possible reason for lack of efficacy. 243 80

Foscarnet (trisodium phosphonoformate) is a novel antiviral agent that inhibits viral-specific DNA polymerase. In the present study, eight males with chronic HBV carriage (HBeAg and HBV-DNA seropositivity greater than 12 months) showing chronic persistent hepatitis (CPH) or chronic active hepatitis (CAH) on liver biopsy received either a continuous infusion of foscarnet at 0.15 mg/kg/min for 7 days or 180 mg/kg/day divided into three daily boluses for 2 weeks. In all eight, HBV-DNA levels fell during therapy (median, 401 pg/40 microliters serum; range, 4-3, 100) vs. pretreatment levels (median, 533 pg/40 microliters; range, 30-4, 175), but in none was HBV-DNA undetectable at any stage. Within 1 month, the HBV-DNA had risen to pretreatment levels in all but one patient (with the lowest pretreatment level), who cleared HBeAg and developed anti-HBe within 3 months. Two further patients were anti-HBe positive at 6 months, but their pretreatment serum HBV-DNA levels were already low, suggesting a high probability of spontaneous seroconversion. Toxicity was not evident with the continuous infusion, but for those receiving IV bolus therapy, serum creatinine and phosphate levels rose in three of four patients, necessitating a 25% dose reduction. There was no difference in the effect on serum HBV-DNA between the two regimes. We conclude that foscarnet has only modest antiviral activity in chronic HBV carriers.
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PMID:Foscarnet therapy in chronic hepatitis B virus E antigen carriers. 253 40

DNA polymerase alpha (DNA-P alpha) in the nuclei of hepatocytes was visualized by the immunoperoxidase method to study the number of liver cells which were at the stage of G1, S, and G2 stage in the cell cycle. Seven liver specimens from patients with acute hepatitis (AH), 17 with chronic persistent hepatitis (CPH), 32 with chronic active hepatitis (CAH), 6 with liver cirrhosis (LC), 4 with hepatocellular carcinoma (HCC) and 4 with hospital controls were studied. The number of DNA-P alpha-positive hepatocytes in 1000 hepatocytes were as follows: 19.1 +/- 18.0 in AH, 8.8 +/- 6.1 in CPH, 27.3 +/- 23.8 in CAH, 21.8 +/- 14.3 in LC, 545.3 +/- 184.0 in HCC and 1.1 +/- 1.1 in hospital controls. The number of DNA-P alpha-positive hepatocytes in HCC were significantly increased compared with other liver diseases. Likewise, those in CAH and LC were higher than those in CPH and hospital controls. The liver cell necrosis was thought to be one of the secondary stimulators for cell division of hepatocytes.
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PMID:[A cell kinetic study of liver cells in various liver diseases by the detection of DNA polymerase alpha]. 268 24

To determine the antiviral effect of recombinant-interferon (rIFN)-alpha in hepatitis B virus (HBV) chronic infection, a controlled study was carried out. A total of 20 HBsAg chronic carriers (18 chronic active hepatitis and 2 chronic persistent hepatitis) were included. All of them had remained HBeAg, HBV-DNA and HBV-DNA polymerase (HBV-DNAp) positive at least six months before treatment. The patients were randomly assigned to two groups: control (n = 10), and treatment (n = 10). A dose of 5.5 megaunits of rIFN-alpha/m2 body surface was administered every day for 21 days (induction) and twice a week for six months thereafter (maintenance). No basal differences were observed between the two groups. No case of intolerable toxicity was observed. One treated patient died in a car crash in the second month. At the end of the first week of therapy, 7/10 (70%) of the treated patients became HBV-DNAp negative. However, in the fifth month only 2 patients remained HBV-DNAp negative and also became HBV-DNA and HBeAg negative. In contrast, no changes in viral markers among control cases were observed. In conclusion, rIFN-alpha has an antiviral effect on chronic HBV infection; however, the induction plus maintenance schedule is not useful to obtain a permanent effect.
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PMID:A controlled study of treatment with recombinant interferon alpha in chronic hepatitis B virus infection: induction and maintenance schedules. 350 Dec 74

Twenty patients with chronic active hepatitis and 12 patients with chronic persistent hepatitis associated with hepatitis B virus (HBV) infection were treated with human leukocyte interferon or adenine arabinoside alone or in combination. With interferon alone, four of 16 patients showed a permanent disappearance of HBV-associated DNA polymerase (DNAP) activity from serum. Of six patients treated with adenine arabinoside alone, only one patient became permanently DNAP-negative. With a regimen of multiple cycles of combined interferon and adenine arabinoside, seven of 16 male patients became permanently DNAP-negative. Of 69 patients who met the criteria for admission to the program, spontaneous decreases in DNAP activity without treatment were observed in only 9% during a mean observation period of 10 months. In general, patients with chronic active hepatitis, those who are female, and those with a history of recent steroid therapy responded to the antiviral agents significantly better than did the other patients.
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PMID:Antiviral treatment of chronic hepatitis B virus infection. I. Changes in viral markers with interferon combined with adenine arabinoside. 616 91

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

The entity of chronic hepatitis has long been an enigma, and its treatment confusing. Recent studies have indicated the importance of excluding causes such as drugs, Wilson's disease and alpha 1-antitrypsin deficiency. After excluding such causes, there are 3 major groups--'autoimmune', hepatitis B, and non-A, non-B (NANB) in all of which an immunological basis for pathogenesis exists. The autoimmune group has been subdivided into a milder type (chronic persistent hepatitis) and a more severe type (chronic active hepatitis) on histological grounds. Corticosteroids are indicated in chronic active hepatitis if cirrhosis or bridging necrosis is present. However, corticosteroids are contraindicated in disease due to the hepatitis B virus where chronic active hepatitis correlates with the presence of replicating virus (serum positive for e antigen, DNA polymerase and HBV-DNA), and in such cases antiviral agents and immunomodulation are being studied. Very little is known about NANB hepatitis in the absence of an assay and there may be more than a single agent. In hepatitis B, the development of serological markers, molecular probes (HBV-DNA), natural animal hepatitis with near-identical viruses, and delta antigen (a virus requiring co-infection with hepatitis B) have all extended our knowledge so dramatically that it is hoped that the enigma of chronic hepatitis will be solved when an assay for NANB hepatitis becomes available.
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PMID:Chronic hepatitis. Aetiology and current management. 673 69


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