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)

Three patients with submassive hepatic necrosis developed acute liver failure during the severe reactivation of chronic hepatitis B. The activity of hepatitis B virus (HBV) DNA polymerase increased in all three patients immediately before the onset of hepatic failure. Liver biopsy specimens obtained before and after the episode of submassive hepatic necrosis showed progression to advanced liver cirrhosis. The nucleotide sequences of the precore and core regions of HBV-DNA were investigated in two of the three patients and in another two patients with piecemeal and bridging necrosis. The nucleotide and amino acid sequences of the HBV-DNA core region changed after reactivation in the the two patients with submassive hepatic necrosis, while the sequences in the other two patients with piecemeal necrosis remained unchanged before and after reactivation. These results suggest that the antigenicity of the HBV-DNA core region may have been changed before and after severe reactivation. Due to mutation at the core region, a different type of epitope would be expressed on the hepatocytes after submassive hepatic necrosis, which would not be a target for the cytotoxic T cell. This was evident by the continuation of the normal serum GPT for 5 and 9 years, respectively.
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PMID:Mutation of the core region of HBV-DNA and submassive hepatic necrosis in patients with anti-HBe-positive chronic hepatitis B. 139 28

In a 47-year-old male patient a tonsillar swelling was pointed out in May, 1991. Lymph node biopsy revealed that he had malignant lymphoma (diffuse large cell type). He had no hepatic dysfunction on admission, but because of positive hepatitis B (HB) antigen and negative HB antibody, he was diagnosed as an asymptomatic HB carrier. The staging examination showed that he had stage IIA lymphoma. Treatment with the COP-BLAM regimen was initiated on June 8. But the level of serum GOT and GPT increased to 286 IU/l and 392 IU/l, respectively. Serum DNA polymerase also increased to 9492 cpm. Interferon-alpha (3 x 10(6) units daily) was administered intramuscularly from June 8. Serum DNA polymerase decreased to zero on September 2, and his HBe antibody became positive indicating seroconversion. COP-BLAM chemotherapy without prednisolone was initiated from September 9 and complete remission was achieved. He was discharged from our hospital on September 25. It has been frequently reported that asymptomatic HB antigen carriers developed fulminant hepatitis during the course of chemotherapy. Our case suggests that it is necessary to continue chemotherapy in order to attain seroconversion by early use of interferon-alpha, when lymphoma patients display aggravated hepatic dysfunction and increased DNA polymerase levels.
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PMID:[Successful interferon-alpha treatment of hepatitis B developing during chemotherapy of malignant lymphoma]. 143 50

The future of patients with chronic hepatitis (HC) due to B virus depends above all on the tendency of the interaction between viral activity and immune response. Viral activity (replication) (RV) can be expressed in these patients by two variants: a) "complete" or "early", associated with the presence in serum of HBsAg, HBeAg, and significant DNA polymerase activity, and b) "incomplete" or "late", in which anti-HBe is found in serum and there are scant or no histopathologic changes ("healthy carriers" in some cases). In prolonged infections viral replication declines gradually, although viral capsid protein continues to be synthesized and DNA-HBV is integrated into the genome. Viral replication per se does not condition the histologic damage (DH) expressive of liver cirrhosis with HBV (HCB). Other publications take a different view of this problem. The increase in viral replication often is proportional to a rise in serum GPT (an expression of histologic damage), but viral replication is not always associated with a progressive disease course. The immune defense leads to cytolysis and subsequent elimination of the HB virus. Some patients with high HBsAg levels have little active forms of liver cirrhosis; the DNA-HBV integrated would be capable of producing HBsAg but not HBcAg. It is precisely this that induces the response of cytotoxic T lymphocytes at the level of the hepatocyte surface. The presence in serum of anti-HBe IgM would be related to the expression of HBcAg on the hepatocyte membrane and/or the liberation of HBcAg particles by lysed hepatocytes. The relationship between the degree of histologic damage and serum aminotransferase levels is better established.
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PMID:[Viral replication, histologic damage and enzymatic activity in chronic hepatopathies caused by B virus]. 266 54

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

In 21 patients from the out-patient clinic of the Internal Medicine Department of our hospital with chronic hepatitis (HC) due to B virus (HBV) and anti-HBC (IgG) serology but not HBsAg, a study was made of the possible correlation between viral replication levels (RV) --as expressed by DNA polymerase values (DNAp)-- and, respectively, histologic changes and serum enzyme movements (GPT, GOT). Our study parted from the diverse criteria cited in the literature concerning the role assigned to viral replication per se and/or immune response per se in the genesis of histologic damage (DH). All patients exhibited signs of moderate clinical and enzymatic activity. The levels of viral replication in the group studies were significant (compared to a control group), which supports the thesis that a certain degree of viral replication, although very attenuated, persists in these patients and is the basis of the continued histological damage that eventually leads to liver cirrhosis (CH) and its derivatives, often with little clinical translation. As regards histologic damage, the correlation with DNAp is reciprocal and of moderate significance, supporting the criterion that the multiform expression of histologic damage in liver cirrhosis due to HBV (HCB) (cellular necrosis, intracellular degenerative phenomena, inflammatory cellular infiltrate, fibrosis) is, at the very least, unproportional to the degree of viral replication and can even be reciprocal. Only the severity of the overall hepatic process remains a function of immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Viral replication, histologic damage and enzymatic activity in chronic hepatopathies caused by B virus. Analysis of 21 patients]. 276 33

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

Twelve hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA polymerase (HBV-DNAp) and hepatitis B virus DNA (HBV-DNA) positive patients with chronic active hepatitis (CAH) were treated with doses of either 20 X 10(6) IU/m2 or 10 X 10(6) IU/m2 body surface of recombinant interferon (rIFN)-alpha-2A, I.M., twice a week, during a period of 6 months. No appreciable differences with respect to clinical history, liver function tests and markers of HBV replication between the two groups were apparent at the time of entry into the trial. At the third month of treatment HBV-DNAp became negative in 10 out of 12 patients (83%). After a 15-month follow-up, HBV-DNAp, HBV-DNA and HBeAg were negative in 7 out of 12 patients (38%) (responders). Furthermore, at 24 months, 2 non-responder patients became HBV-DNA and HBV-DNAp negative and one responder lost serum HBsAg. In addition, HBsAg concentration, GPT level and histological Knodell's index decreased significantly in the responder patients, while no changes were observed in non-responders. Five out of six patients who received a low rIFN dose responded to the treatment, and only 2 out of 6 with a higher dose. No unacceptable toxicity was noted in any of the 12 patients. All of them completed the course of treatment. The results suggest that long-term rIFN-alpha-2A therapy has an antiviral effect in CAH due to HBV infection and is well tolerated.
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PMID:Prolonged (6 months) treatment of chronic hepatitis B virus infection with recombinant leukocyte A interferon. 343 94

Intensive multidrug chemotherapy with concomitant IFN was performed in three hepatitis B virus (HBV) carriers with malignant lymphomas. All of the patients were HBsAg+, HBsAb-, HBcAb+, HBeAg- and HBeAb+ (mutant strain+). HBV-DNA polymerase (DNA-P) was normal at the beginning of chemotherapy, and complete response was achieved with CO-BLAM chemotherapy (without PDN) in all cases. In case 1, a slight elevation of DNA-P and normal GOT and GPT was observed after IFN-alpha was started during the third course. IFN-alpha was administered twice a week. In case 2, elevation of DNA-P and normal GOT and GTP were noted at the end of the 5th course, then daily IFN-alpha was started. In case 3, daily IFN-alpha was started during the 3rd course because of elevation of DNA-P. It was possible to prevent severe liver damage by administering IFN immediately after the elevation of DNA-P, since DNA-P elevation is noted before GOT and GPT elevation. The detection of the HBV mutant strain could be helpful in the treatment of HBsAg+ and HBeAb+ patients. In all of three patients, DNA-P, serum GOT and GPT normalized quickly after the administration of IFN-alpha. Severe hepatitis did not develop.
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PMID:[Chemotherapy with concomitant IFN treatment in three HBV carriers (mutant strain) with malignant lymphoma]. 756 13