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)

The intrahepatic distribution of hepatitis B core antigen (HBcAg) was studied in 14 HBeAg-positive patients with chronic active hepatitis B who were treated with interferon. Patients received 5 to 6 million units daily of human lymphoblastoid interferon or human diploid fibroblast interferon for 28 days. Intrahepatic HBcAg was detected by the indirect immunoperoxidase technique. Before interferon therapy, the intrahepatic HBcAg was detected almost equally in both the nucleus and cytoplasm. The expression of nuclear HBcAg decreased significantly (p less than 0.001) after interferon therapy, irrespective of the outcome for DNA polymerase and/or HBeAg/anti-HBe status. The expression of cytoplasmic HBcAg decreased significantly (p less than 0.05) only in the patients who lost DNA polymerase after treatment, whereas it increased in patients with DNA polymerase and/or HBeAg in the serum. These findings suggested that a shift of intrahepatic HBcAg from the nucleus to the cytoplasm occurred in HBeAg-positive patients with chronic active hepatitis B receiving interferon therapy.
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PMID:Changes of intrahepatic localization of hepatitis B core antigen in HBeAg positive patients with chronic active hepatitis B treated with interferon. 219 93

Sera from four patients with acute hepatitis B and 87 patients with chronic hepatitis B were examined quantitatively for pre-S1 and pre-S2 antigens by solid-phase enzyme immunoassays. Pre-S1 and pre-S2 antigens were detected in HBsAg-positive sera irrespective of the presence of viral replicative markers, and their titers correlated with those of HBsAg (r = 0.74, p less than 0.01; r = 0.74, p less than 0.01, respectively). Sera positive for HBeAg showed higher titers of pre-S1 (p less than 0.01) and pre-S2 (p less than 0.01) antigens than sera negative for HBeAg. The titers of pre-S1 and pre-S2 antigens also correlated with the levels of HBV-associated DNA polymerase activity (r = 0.51, p less than 0.01; r = 0.59, p less than 0.01, respectively) and HBV-DNA (r = 0.50, p less than 0.01; r = 0.46, p less than 0.01, respectively). However, the ratios between the titers of pre-S antigens and HBsAg had no significant relationships with those viral replicative markers. These findings suggest that the expression of pre-S antigens is intimately related to the expression of HBsAg and that they are not useful as markers of viral replication. The ratios between the titers of pre-S antigens and HBsAg tended to be high in patients with chronic active hepatitis and high aminotransferase levels. This finding may have been due to the hepatic release of pre-S antigens, over-production of which may have some relationship to liver injury.
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PMID:Quantitative analysis of pre-S1 and pre-S2 in relation to HBsAg expression. 229 69

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

Eleven patients with hepatitis B e antigen (HBeAg)-positive chronic active hepatitis B were treated with an 8-wk course of prednisone followed by 28 days of adenine arabinoside 5'-monophosphate. Five individuals had a complete response (loss of HBeAg and DNA polymerase) whereas 3 had a partial response (sustained loss of DNA polymerase but persistence of HBeAg). At the present time 27 +/- 3 mo has elapsed since the completion of therapy, and 4 of 5 complete responders remain negative for replicative markers while the fifth person exhibited transient reactivation of infection. Elevated DNA polymerase has reappeared in two of the three partial responders, in one 22 mo after completion of therapy. These encouraging results have led to a randomized, controlled trial using short-term prednisone followed by recombinant alpha-interferon.
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PMID:The use of corticosteroids in conjunction with antiviral therapy in chronic hepatitis B with ongoing viral replication. 243 77

Twenty patients with HBe antigen positive, chronic active hepatitis receiving interferon-beta (HuIFN-beta) for 4 weeks were studied. Within the follow-up period (12.3 +/- 2.0 months; mean +/- SD), nine patients were seroconverted to anti-HBe positive and/or HBe antigen negative. In vitro synthesis of interleukin-1 (IL-1), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were determined from supernatants of peripheral blood mononuclear cells (PBMCs) cultured in the presence of lipopolysaccharide or concanavalin-A. PBMCs from patients before IFN-beta treatment secreted markedly reduced levels of IL-1 (p less than 0.01) and IFN-gamma (p less than 0.01) as compared with healthy controls. However, IFN-gamma synthesis in the patients was significantly increased (p less than 0.05) along with the IFN-beta treatment. IL-2 synthesis was similar in chronic active hepatitis B patients before and during IFN-beta treatment when compared to normal controls, but after the therapy, the elevation of IL-2 synthesis was observed in accordance with the elevation of serum AST in two cases. Nine patients who seroconverted to anti-HBe positive and/or HBe antigen negative showed the significantly lower levels of DNA polymerase before IFN-beta treatment than non-responder group. There were no other differences in sex, age, serum AST, histologic activities and cytokine production in vitro between two groups. These results indicate the presence of immunologic deficiencies in patients with HBe antigen positive chronic active hepatitis and give the rationales for the use of interferon treatment on immunologic basis.
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PMID:[In vitro cytokine production in patients with HBe antigen positive chronic active hepatitis receiving interferon-beta]. 250 83

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

We investigated the expression of Pre-S2 antigen (Ag) and antibody (Ab) in sera quantitatively using ELISA. Four patients with acute hepatitis B and 87 chronic HBV carriers were included in this study. We also investigated the expression of Pre-S2Ag in the liver tissues obtained from 26 chronic HBV carriers by direct fluorescent antibody method. There was a significant correlation between Pre-S2Ag titers and HBsAg titers in sera. Pre-S2Ag titers were higher in sera positive for HBeAg, HBV-related DNA polymerase or HBV-DNA than in sera negative for those markers. The ratio of Pre-S2Ag titers to HBsAg titers, however, was constant irrespective of virus replicative markers. Pre-S2Ag in the liver had almost same intracellular localization with HBsAg in the liver. It was suggested that Pre-S2Ag was expressed with an intimate relation to the expression of HBsAg and was not useful as a virus replicative marker. Pre-S2Ag titers/HBsAg titers tended to be high in patients with chronic active hepatitis and high serum GPT levels compared to patients with chronic inactive hepatitis. This may be explained by the release of Pre-S2Ag in the liver. In addition, all patients positive for Pre-S2Ag on the membrane of hepatocytes had chronic active hepatitis. The overproduction of Pre-S2-containing surface proteins in the liver may have some implication related to cell injury via the immune response to Pre-S2Ag etc. Pre-S2Ab was detected only in few cases of chronic HBV infected patients. The lack of immune response to Pre-S2 region may play a role in the persistence of HBV infection.
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PMID:[Expression of Pre-S2 antigen and antibody in patients with hepatitis B virus infection]. 268 90

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

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by the presence of hepatitis Be antigen (HBeAg), increased DNA polymerase (DNAp) and positive hepatitis B virus DNA (HBV-DNA) for more than 6 months, were entered into a prospective trial of recombinant human interferon therapy. Ten patients had chronic persistent or chronic lobular hepatitis, 8 chronic active hepatitis and 3 postnecrotic cirrhosis. All cases were treated with 5 x 10(6) units of recombinant interferon alfa-2B given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNAp levels, which reached normal values in 10 patients (48%). Viral replication was controlled over a 10-month follow-up period in 7 out of 21 patients (33%). Of these 7, five patients became HBeAg negative and HBeAb positive. HBsAg disappeared in one patient. The only serious adverse effect was thrombocytopenia in one patient in whom rapid recovery occurred when interferon was withdrawn. Treatment was also terminated in a second patient because of local reactions at the injection sites occurring after 10 weeks of therapy. Our data indicate that relatively small doses of recombinant alfa-2B interferon given during a 12-week period induce a significant reduction in viral replication and might approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.
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PMID:Prospective trial of recombinant leucocyte interferon in chronic hepatitis B: a 10-month follow-up study. 268 91

We investigated the expression of Pre-S1 antigen and Pre-S1 antibody using a synthetic peptide and the monoclonal antibody against it. Four patients with acute hepatitis B and 87 chronic HBsAg carriers were included in this study. There was a significant correlation between Pre-S1 antigen titers and HBsAg titers. Pre-S1 antigen showed higher titers in patients with active viral replication, positive for HBeAg, HBV-DNA or HBV-related DNA polymerase. The ratio of Pre-S1 antigen titers to HBsAg titers, however, had no significant relationship with those replicative markers. It was suggested that Pre-S1 antigen was expressed with an intimate relation to the expression of HBsAg and was not so useful as a new replicative marker. Pre-S1Ag titers/HBsAg titers tended to be high in patients with chronic active hepatitis and high serum GPT levels. This may be due to the release of overproduced intracellular Pre-S1 antigen. Pre-S1 antibody was detected only in few cases of chronic HBsAg carriers. This result shows that the immune tolerance to Pre-S1 region may play a role in the persistence of HBV infection.
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PMID:[Expression of pre-S1 antigen and pre-S1 antibody in sera obtained from HBV infected patients]. 279 57


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