Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
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The morphological, chemical and physical properties of HBAg suggest that the 42 nm component of the antigen, the Dane particle, represents the agent of viral hepatitis B. Its core contains a circular, double stranded DNA, a DNA polymerase and carried HBc-Ag. HBc-Ag is localized on the 21 nm particle, the tubular structures and the surface of the Dane particles. At least 8 different subdeterminants of HBs-Ag could be distinguished by means of specific animal anti-sera. HBs-Ag activity was demonstrated in almost all body fluids and excreta. The results of combined histologic, fluorescent and electronmicroscopic studies suggest ath HBc-Ag is localized in the liver cell nucleus and that HBs-Ag is found in the cysterna of the smooth endoplasmatic reticulum of the hepatocytes. The demonstration of HBs-Ag and the specific DNA polymerase in the serum indicate a hepatitis b virus infection with persistent reproduction of the agent, while demonstration of anti-HBs indicates that the infection has been overcome. The clinical importance importance of anti-HBc is controversial.
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PMID:[Nature, character, occurrence, and demonstration of hepatitis B antigens (author's transl)]. 5 90

The e determinant of hepatitis B surface antigen (HBS Ag) was found in 23 of 42 patients with chronic hepatitis B virus (HBV) infection. Presence of e antigen was associated with increases in DNA polymerase activity and in the number of circulating Dane particles. In the group with detectable e antigen, the average DNA polymerase activity was 367+/-78 counts per minute (cpm; mean+/-standard error [SE]), and the average number of Dane particles counted in electron micrographs was 4.4% of the total HBS Ag. In contrast, e antigen-negative patients had an average DNA polymerase activity of 40+/-6.9 cpm (P less than 0.1) and an average Dane particle count equal to 0.6% of the HBS Ag. The e antigen was detected in 68% of patients who were HBS Ag carriers or had persistent viral hepatitis and 40% of those with chronic active type B hepatitis. Thus, the presence of e antigen correlated with both the chronicity and presence of infectious HBV. However, it did not correlate with the type or severity of liver disease after HBV infection, since e antigen was present in both chronic benign and chronic aggressive hepatitis B infections.
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PMID:Correlation of e antigen, DNA polymerase activity, and Dane particles in chronic benign and chronic active type B hepatitis infections. 6 88

Resulting directly from the discovery of virus-related antigens, rapid progress has marked the last decade of viral hepatitis research. The hepatitis B virion has been tentatively identified as a DNA virus with an endogenous DNA polymerase, and new serological markers for type B hepatitis have been discovered. Hepatitis A antigen has been identified on a virus-like particle thought to be the hepatitis A virion. Progressively more sophisticated assays for hepatitis antigens and antibodies have been applied to the study of viral hepatitis epidemiology and biochemical-biophysical characterization of the agents. Most recently, knowledge learned from such studies has been exploited to develop a prototype non-infectious but immunogenic hepatitis B vaccine using hepatitis B surface antigen (HBsAg) purified in large quantities from chronic HBsAg carriers. Especially exciting is the prospect, suggested by serological studies of viral hepatitis, that hepatitis viruses besides hepatitis A and B viruses will be identified.
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PMID:Recent advances in the identification of hepatitis viruses. 19 74

Studies conducted in 1970 and 1971 with heat-inactivated MS-2 serum revealed that this active immunizing procedure was associated with a protective effect, a more attenuated hepatitis B infection and a decreased hepatitis B carrier rate. More recent studies have revealed striking differences in the response of unimmunized and immunized persons following a parenteral exposure to the MS-2 strain of hepatitis B virus. Serial tests for the detection of hepatitis B surface antigen (HBsAg), DNA polymerase activity, serum transaminase (SGOT), antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) revealed the following findings. In serosusceptible unimmunized persons HBsAg was detectable about 4 weeks after exposure, DNA polymerase activity at about 6 weeks, abnormal SGOT levels at about 8 weeks, anti-HBc at about 8-10 weeks, and anti-HBs usually after 20 weeks. In successfully immunized persons HBsAg, DNA polymerase activity, abnormal SGOT levels, and anti-HBc were not detectable, evidence of a booster response of pre-existing or non-detectable anti-HBs was observed one to two weeks after exposure. Studies by various investigators have revealed that anti-HBs is associated with protection and resistance to reinfection. In contrast, anti-HBc is not protective and does not correlate positively with either resistance to infection or recovery from infection. The availability of sophisticated biophysical and biochemical techniques has enabled several investigators to prepare candidate inactivated hepatitis B vaccines from purified preparations of HBsAg. The successful propagation of hapatitis B virus infection to susceptible chimpanzees has provided an excellent animal model for the evaluation of hepatitis B vaccines. At the present time various investigators are studying the immunogenic and protective effect of the vaccine in these animals. Prospects for the development of a vaccine for the prevention of viral hepatitis type B are encouraging. It is extraordinary that this objective will be achieved in spite of the failure to isolate the etiologic agent in tissue culture.
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PMID:Viral hepatitis type B: propects for active immunization. 120 71

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 analyze the process of liver regeneration and the initiation of hepatocellular carcinoma (HCC), we studied histochemically the morphologic features of proliferating parenchymal cells stained for DNA polymerase alpha (DPA), in 31 patients with various diseases, by use of a monoclonal antibody against DPA. In specimens from patients with acute viral hepatitis with confluent necrosis, most stained hepatocytes were small, with basophilic cytoplasm, and were located next to the necrotic areas. Under electron microscopy, stained granules were seen in the nucleus. Most stained hepatocytes had immature organelles. In specimens from patients with cirrhosis of the liver, the number of stained hepatocytes greatly differed in different pseudolobules. In specimens from patients with adenomatous hyperplasia, stained hepatocytes, mostly small and basophilic, were found diffusely; electron microscopy showed slightly indented nuclei with a few organelles and less condensed chromatin than normal. In specimens from patients with HCC, most stained cancer cells were small and basophilic; electron microscopy showed indented nuclei with a few organelles and less than normal condensed chromatin. Staining showed that during regeneration, immature hepatocytes reentered the cell cycle and repaired a large necrotic area. It was conceivable that in the initiation of HCC, some small hepatocytes with indented nuclei and less condensed chromatin might become HCC cells.
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PMID:Identification and fine structure of proliferating hepatocytes in malignant and nonmalignant liver diseases by use of a monoclonal antibody against DNA polymerase alpha. 221 Jul 24

During a prospective study of acute symptomatic viral hepatitis, started in 1978, 664 consecutive adult patients, including 223 drug abusers, fulfilled the diagnostic criteria (anti-HBc IgM positivity) for acute type B hepatitis. In order to evaluate the outcome of the disease, 443 patients were followed for up to 12 months after the onset. 2.4% of the infections became chronic; the rate did not significantly differ between drug addicts and non-drug abusers, suggesting that chronic hepatitis is a rare complication of acute symptomatic hepatitis type B. Ongoing liver damage after clearance of HBsAg from serum was observed in drug abusers only (14% of the cases). Clinical, biochemical and virological features of the acute phase in patients with ongoing infection were compared with those of uncomplicated cases. Anicteric hepatitis and lower transaminase values were significantly (p less than 0.05) associated to a chronic evolution of the disease, as well as a higher prevalence of HBV-DNA, DNA polymerase and HBcAg positivity in serum. Testing HBV-DNA and DNA polymerase early in the course of the infection appeared to be of high predictive value for the subsequent outcome of the illness.
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PMID:Chronic evolution of acute hepatitis type B: prevalence and predictive markers. 371 May 94

Interferon treatment (3.0 x 10(6) units of human leucocyte interferon) was initiated in a 64-year-old woman with acute hepatitis B infection showing a prolonged course. A decline in serum bilirubin, HBsAg and DNA polymerase activity started during the 10-day period of interferon treatment, and 4 weeks after start of treatment the liver function tests were quite normal. It is possible that the interferon treatment had a beneficial influence on the clinical course of the illness and may be worth trying also in acute fulminant cases of viral hepatitis.
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PMID:Interferon treatment in acute hepatitis B infection with prolonged course. 615 76

Two human hypatitis viruses have been identified and characterized, but one or more additional agents exist. Hepatitis B virus (HBV) is a complex 42-nm predominantly double-stranded DNA virus with distinct surface and core antigens and an endogenous DNA polymerase. Hepatitis A virus (HAV) is a 27-nm RNA virus with enterovirus-like properties. Progressively more sensitive and specific immunologic assays have been applied to the study of viral hepatitis and are available for routine diagnostic purposes. As a result we recognize distinct serologic response patterns to infection, new antigenic markers, biochemical-biophysical characteristics of the viruses, and their epidemiologic features. Recombinant DNA technology has permitted the cloning of HBV genetic material and gene products in E. coli, but the virus has not been cultivated in vitro. In contrast, successful in vitro cultivation of HAV has finally been accomplished. Application of sensitive serologic tests for HAV and HBV has revealed that "non-A, non-B" agents account for a substantial proportion of transfusion-associated hepatitis as well as hepatitis occurring in the absence of percutaneous exposure. These agents have been transmitted to chimpanzees, and several putative virus antigen-antibody systems have been described; however, a specific association between these virus antigens and non-A, non-B hepatitis has not been established.
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PMID:Hepatitis viruses: characterization and diagnostic techniques. 624 88

Sera from 71 patients with acute liver injury have been tested for antibodies to hepatocyte membrane lipoprotein complex (LSP) using a sensitive radioimmunoassay. Two main patterns of anti-LSP response were seen. In the first, seen in patients with type A and B viral hepatitis, anti-LSP antibodies were detectable at presentation, with the highest titres two to 10 days before the peak in serum aminotransferases and, in the hepatitis B patients, when viral DNA polymerase concentrations were still high, indicating active viral replication. These findings are consistent with the anti-LSP response being consequent on an interaction between T cells and neoantigens on the liver cell surface. A similar pattern was found in halothane hepatitis where immune responses to a halothane-altered liver membrane antigen are present early in the course of the disease. In the second type of response, exemplified by cases with paracetamol-induced hepatic necrosis, anti-LSP was only occasionally detectable at presentation, although present in very low titre later in the clinical course. This may be due to the release of altered antigen at the time of hepatocellular injury. The same pattern was found in a selected group of patients with uncomplicated acute alcoholic hepatitis, suggesting that in both these groups of patients the liver damage may have been due to a direct toxic effect on liver cells.
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PMID:Anti-LSP antibodies in acute liver disease. 708 6


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