Link between hepatoma and hepatitis B.
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Carcinoma, Hepatocellular↗
Biomedical subjects
M Omata
Publications and source records attributed to M Omata.
Comparison of serum hepatitis B surface antigen (HBsAg) and serum anticore with tissue HBsAg and hepatitis B core antigen (HBcAg).
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Autoimmune Diseases↗
Papular acrodermatitis of childhood and hepatitis B infection.
A case of papular acrodermatitis (PAC) associated with acute anicteric type B hepatitis occurred in a 2-year-old child. Immunocytochemical studies failed to detect the presence of viral antigens in the involved skin lesion. Current knowledge of the hepatitis B viral antigens and of their possible role in PAC is discussed.
Acrodermatitis↗
Transmission of duck hepatitis B virus from Chinese carrier ducks to Japanese ducklings: a study of viral DNA in serum and tissue.
Human hepatitis B-like viruses have been found in several animal species, including Chinese ducks. Sera from Chinese carrier ducks which were positive for duck hepatitis B virus (DHBV) were inoculated in 33 Japanese one-day-old ducklings. The same sera were inoculated in four 3-week-old ducklings, and three 3-month-old ducks. Ten uninoculated ducklings served as controls. Hepatitis B e-antigen positive human sera and DNA polymerase-positive woodchuck sera were also inoculated into ducklings. DHBV was demonstrated in serum of all ducklings inoculated at one day of age and persisted for more than 6 months in 17 of 20 ducks. In the three ducks in which viremia disappeared, viral DNA was found in liver tissue. Southern hybridization revealed only free viral DNA in infected ducks. Only 1 of 7 ducklings inoculated at 3 weeks or later developed persistent infection. No cross-infectivity by hepatitis B virus or by woodchuck hepatitis virus was demonstrated. By inoculating DHBV-positive sera into 1-day-old ducklings of a virus-free Japanese flock, we were able to transmit DHBV in all of them and established a chronic carrier state in all ducks which were inoculated at 1 day of age.
Alanine Transaminase↗
Liver orcein stain and viral DNA in duck hepatitis B virus infection in Chinese ducks and experimentally infected Japanese ducklings.
Liver sections were stained with orcein, and duck hepatitis B virus was identified in sera and livers by the hybridization technique in 106 ducks (44 Chinese ducks, 15 Japanese ducks and 47 Japanese ducklings). Orcein-positive hepatocytes were found in 18 of 38 (47%) duck hepatitis B virus DNA seropositive ducks, and only in 3 of 68 (4%) seronegative ducks. The three ducks were all from a heavily infected flock in southern China. Serial analyses of viral DNA by Southern blot and spot hybridizations in experimentally infected Japanese ducklings revealed a dissociation or a time gap between the amount of viral DNA in serum and the emergence of orcein positive hepatocytes. Orcein-positive hepatocytes were generally associated with prolonged presence of viral infection for at least 4 to 6 months. These findings support the clinical hypothesis that the presence of orcein-positive hepatocytes indicates persistent rather than acute infection. Since orcein-positive hepatocytes have been seen in infection with hepatitis B, woodchuck hepatitis, ground squirrel and duck hepatitis B viruses, accumulation of orcein-positive material in liver cells may be one of the common properties these viruses share. This stain may be utilized for screening new hepatitis B virus-like viruses.
Animals↗
Changes of hepatitis B virus DNA in liver and serum caused by recombinant leukocyte interferon treatment: analysis of intrahepatic replicative hepatitis B virus DNA.
Twenty patients with HBeAg-positive chronic liver disease were given large doses of recombinant leukocyte interferon for 4 weeks. Changes of hepatitis B virus DNA in livers and sera were analyzed by the molecular hybridization technique in paired biopsies obtained before and 2 weeks after treatment. Serum hepatitis B virus DNA was examined before, during and after the treatment until 4 weeks post-interferon. Analysis of hepatic hepatitis B virus DNA revealed species that appeared to represent various forms of replicative hepatitis B virus DNA, i.e., relaxed circular, linear, supercoiled and single-stranded hepatitis B virus DNA, respectively. No evidence of integration of hepatitis B virus DNA in genomic DNA was obtained. Of 15 cases which were positive for hepatic hepatitis B virus DNA before treatment and in which paired biopsies were obtained, hepatic hepatitis B virus DNA became negative in 4, decreased in 5 and unchanged in 6. Among several types of replicative viral DNA in liver tissue, supercoiled hepatitis B virus DNA tended to remain after other forms were reduced. A close correlation between hepatic and serum hepatitis B virus DNA was found in 37 liver biopsy samples and corresponding sera. These results indicate that interferon treatment reduces serum hepatitis B virus levels by inhibiting viral replication in the liver and that persistence or reappearance of hepatitis B virus in serum after interferon is associated with replication.
Adult↗
Analysis of DNA polymerase reaction products for detecting hepatitis B virus in serum--comparison with spot hybridization technique.
An assay for DNA polymerase reaction products using slab gel electrophoresis and autoradiography was compared with the spot hybridization technique for the detection of hepatitis B virus DNA in 317 blood samples. The former could identify the nature and size of DNA on electrophoresis, and reduce potentially false-positive results due to artifacts. Discordant results between the two methods occurred in 36 of 317 samples; 22 were positive by the spot technique alone, and 14 were positive by the analysis of DNA polymerase reaction products alone. However, the samples positive with the spot test alone showed weak radioactive signals on electrophoresis/autoradiography that were often interpreted as "inconclusive" by blind observations. Correlation of hepatitis B e antigen/antibody with hepatitis B virus DNA was studied in 91 patients with various chronic liver diseases. Discordant results, i.e., presence of the DNA in antibody positive sera, or its absence in the antigen positive sera, were obtained in 15 (19%) cases. Such patients tended to have advanced liver disease with fluctuating serum aminotransferase levels. Analysis of DNA polymerase reaction products by slab gel electrophoresis and autoradiography is not only sensitive, but is also as specific as the Southern blot technique in the detection of hepatitis B virus DNA in serum, and may prove useful in selected samples, especially where no cloned hepatitis B virus DNA is available, or in search of new hepatitis B virus-like viruses.
Adult↗
Effects of adenine arabinoside on serum and intrahepatic replicative forms of duck hepatitis B virus in chronic infection.
Adenine arabinoside is an antiviral agent which has been used in a number of clinical studies for the treatment of chronic infections with hepatitis B virus. In order to better understand its effects and mode of action, we treated ducks chronically infected with duck hepatitis B virus with a 2-week course and monitored the effects of the drug on viral replication by studying duck hepatitis B virus DNA in liver and serum using molecular biological techniques. We found the drug to be effective in ducks only at much higher doses than those used in humans. At high doses, adenine arabinoside had a dose-related inhibitory effect on viral replication during treatment, but there was a rapid return toward baseline values soon after the cessation of treatment. The supercoiled form of viral DNA was found to be most resistant to adenine arabinoside therapy, and the drug had a disproportionate inhibitory effect on viral plus (noncoding) strand synthesis. We conclude that adenine arabinoside likely exerts its effect in hepadna virus infections predominantly through inhibition of viral DNA polymerase. On the basis of our current study and previous trials in hepatitis B virus-infected patients, we predict that adenine arabinoside will not efficiently eliminate viral replication in chronic hepadna virus infection, when used as the sole therapeutic modality. Adenine arabinoside may have a role to play as an adjunct to immunomodulation or interferon therapy in chronic hepatitis B virus infection in man.
Animals↗
RNA transcripts of hepatitis B virus in hepatocellular carcinoma.
The states of hepatitis B virus DNA, RNA transcripts and antigens (HBsAg and HBcAg) were studied in the liver with hepatocellular carcinoma by blot hybridization and immunohistological methods. We used whole hepatitis B virus DNA and gene specific probes (S, C and X genes) for hybridization. Integrated viral DNA was found in all five tumors, but episomal DNA was not detected in the neoplastic tissue. In the nonneoplastic cirrhotic liver, episomal DNA was found in four cases and integrated viral DNA in four cases. A large amount of hepatitis B virus-specific RNA transcripts was demonstrated in nonneoplastic liver of all five cases. Two major transcripts, 2.4 and 3.4 kb in length, were identified. The former hybridized with the S gene probe and the latter with the C gene probe, suggesting that they were messenger RNAs for HBsAg and HBcAg, respectively. In contrast to nonneoplastic liver, RNA transcripts were found in the neoplastic portion in only two cases, small in quantity; they primarily hybridized with S and X, but not with C genes. Novel species of 4.0 and 3.9 kb transcripts were found in the neoplastic and the nonneoplastic portions, respectively, in one case. They may represent fusion transcripts of integrated viral DNA and cellular flanking sequences.
Adult↗
Role of insulin resistance in heart and skeletal muscle F-18 fluorodeoxyglucose uptake in patients with non-insulin-dependent diabetes mellitus.
BACKGROUND: Altered heart and skeletal glucose usage has been reported in patients with non-insulin-dependent diabetes mellitus (NIDDM). Although elevations in plasma free fatty acid (FFA) concentrations have been implicated in reduced myocardial 18fluorine-fluoro-2-deoxy-D-glucose uptake (MFU), the specific role of whole-body insulin resistance in MFU in patients with NIDDM compared with skeletal muscle metabolism remains controversial. PURPOSE: MFU and skeletal muscle 18fluorine-fluoro-2-deoxy-D-glucose uptake (SMFU) were compared with positron emission tomography and the whole-body glucose disposal rate (GDR) during hyperinsulinemic euglycemic clamping in 26 normotensive asymptomatic patients with NIDDM who were not taking medication. These factors were also compared in 12 age-matched control subjects to increase the knowledge of the influence of whole-body insulin resistance on MFU. In addition, independent factors for both SMFU and MFU were investigated. RESULTS: GDR in control subjects (10.0 +/- 2.97 mg/min per kilogram) was significantly higher than in patients with NIDDM (4.05 +/- 2.37 mg/min per kilogram, P < .01). SMFU in patients with NIDDM (0.826 +/- 0.604 mg/min per 100 g) was significantly lower than that in control subjects (1.86 +/- 1.06 mg/min per 100 g, P < .01). MFU in patients with NIDDM (5.35 +/- 2.10 mg/min per 100 g) was also significantly lower than that of control subjects (7.05 +/- 1.66 mg/min per 100 g, P = .0182). SMFU significantly correlated with GDR (r = .727, P < .01) and FFA (r = -.52, P < .01) in patients with NIDDM. MFU also correlated with GDR (r = .778, P < .01) and FFA (r = -.72, P < .01) in patients with NIDDM. Multivariate stepwise regression analysis showed that GDR (F = 36.8) was independently related to MFU (r = .85, P < .01) whereas FFA was not (F = 1.763), where F is the value for statistical analysis of multivariate stepwise regression analysis. CONCLUSION: Insulin resistance is the most essential factor for both heart and skeletal muscle FDG uptake in patients with NIDDM.
Adult↗
Amino acid residues of core region of hepatitis B virus. Asymptomatic carriers versus patients with liver disease.
Recent molecular biological studies have shown that mutations of hepatitis B virus (HBV) genes may have an important role in the pathogenesis of HBV-induced liver diseases. It has been suggested that the core antigen of HBV could be an immunologic target of cytotoxic T lymphocytes. In this study, nucleotide sequences encoding 183 amino acid residues of the core region of HBV were analysed in 4 asymptomatic healthy carriers and in 5 patients with chronic liver disease, in whom serum aminotransferase levels were fluctuating. A cluster of amino acid substitutions were found from codon 87 to 97 of the core region of HBV in all 5 patients with liver diseases. Such changes were not found in any of the asymptomatic carriers. These data suggest that the peptide sequence spanning 11 amino acid residues in this particular region may play an important role in the pathogenesis of B-viral liver disease, and could be an immunologic target of cytotoxic T lymphocytes.
Adult↗
Infection of human hepatocyte cell lines with hepatitis C virus in vitro.
Hepatocyte related cell lines, namely human embryonic hepatocyte cell line (WRL68) and hepatoblastoma cell line (Hep G2), were tested for their ability to support hepatitis C virus (HCV) replication in vitro. The replicative intermediate of the minus strand HCV RNA was newly transcribed from the inoculated virus, and was stable in WRL68 cells over a period of 62 days. HCV RNA detected in the culture medium at 62 days after infection suggested a long period of virus secretion from this cell line. In Hep G2, transcription of the minus strand HCV RNA was also detected until 39 days after infection, but transcription and secretion of viral progeny could not be demonstrated. Although HCV infection of WRL68 was not high, this cell line might prove to be a useful tool for studying HCV replication in vitro.
Base Sequence↗
Aflatoxin and p53 abnormality in duck hepatocellular carcinoma.
Recent studies have revealed that a point mutation at codon 249 in the p53 gene predominates in hepatocellular carcinoma (HCC) cases from Southern Africa and China, where infection with hepatitis B virus (HBV) and contamination of aflatoxin B1 in food are risk factors for HCC. This unique mutation from G to T at the third base in codon 249 observed in human HCC cases is suggested to be linked to aflatoxin exposure. Six ducks with HCC, five of which were fed a diet containing aflatoxin B1 for 1-2 years, were analysed for the presence of point mutations at this codon of the p53 gene by polymerase chain reaction and direct nucleotide sequencing. None of the six ducks with HCC showed the change at this codon regardless of duck hepatitis B virus infection. This suggests that aflatoxin B1 itself might not be involved in the unique mutation at codon 249 in hepatocarcinogenesis, or that other factors coincident with aflatoxin may be responsible for this unique mutation.
Aflatoxin B1↗
Histological analysis of the papilla after endoscopic papillary balloon dilation.
BACKGROUND/AIMS: Endoscopic papillary balloon dilation is an effective procedure in the management of bile duct stones and is believed to preserve the papillary function. The papillary architecture is also considered to be preserved. However, little is known about the effects of balloon dilation on papillary structure. The present study was conducted to elucidate these effects. METHODOLOGY: Since May 1994, endoscopic papillary balloon dilation was performed in 467 patients (407 patients for removal of bile duct stone, 57 for insertion of stent and 3 for baby cholangioscope). Of those, histological examinations were undertaken in 10 patients. The indications of endoscopic papillary balloon dilation were bile duct stone removal in 2 patients, stent insertion in 8. The specimens were obtained 2 to 63 weeks after endoscopic papillary balloon dilation during surgical operation in 6 patients and autopsy in 4 patients. Serial sections through the papilla were stained by hematoxylin and eosin and Masson's trichrome. The specimens were also obtained from 4 patients without biliary disease as control. RESULTS: No smooth muscle disruption nor architectural distortion was observed except for one patient who had mild disruption of smooth muscle caused by a biliary drainage tube. However, mild to moderate inflammation and fibrosis were seen in 9 patients and in 8, respectively. CONCLUSIONS: The papillary architecture is not affected by endoscopic papillary balloon dilation. This may imply that endoscopic papillary balloon dilation preserves papillary function.
Aged↗
Endoscopic submucosal dissection for gastric neoplasia: experience with the flex-knife.
Although the standard treatment for gastric neoplasia is still surgical resection, endoscopic resection has been accepted for some of these lesions in an early stage. Among several methods of endoscopic resection, endoscopic submucosal dissection has been developed to remove the lesions in an en bloc fashion regardless of size, shape, coexisting ulcer, and location. However, indication of endoscopic submucosal dissection is strictly confined by two aspects; those are the possibility of nodal metastases and technical difficulty. Nowadays, several knives for endoscopic submucosal dissection are available and each of them has some merits and demerits. We describe how to perform endoscopic submucosal dissection in the stomach by using the flex-knife, a new endoscopic device specifically designed for submucosal dissection, emphasizing its special features from our experience.
Endoscopy↗