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Biomedical subjects

A J Zuckerman

Publications and source records attributed to A J Zuckerman.

At least 325 records · Page 18Linked to original sources

Acute hepatitis A infection in hepatitis B chimpanzee carriers.

Two hepatitis B virus carrier chimpanzees which were superinfected with hepatitis A virus developed acute hepatitis followed by the production of antibodies to hepatitis A virus. The Southern blot technique employed to monitor liver hepatitis B virus DNA revealed that the amount of viral DNA in both animals was significantly reduced during the acute phase of hepatitis A infection. The levels of plasma hepatitis B DNA polymerase activity were also reduced in one chimpanzee. The high titers of HBsAg in the circulation remained unchanged throughout the study, and antibodies to the surface antigen and to e antigen were not detected. The morphological lesions in the liver were severe in one chimpanzee from whom one specimen showed both periportal focal necrosis and zonal parenchymal necrosis.

Animals↗

Maternal transmission of duck hepatitis B virus in pedigree Pekin ducks.

A 14-month old female Pekin duck experimentally infected as an embryo with duck hepatitis B virus via the amniotic route has been a chronic carrier of duck hepatitis B virus with very high (P/N) values of DNA polymerase activity since hatching. All the progeny were, on evaluation for congenital infection, found to be duck hepatitis B virus positive by endogenous DNA polymerase reaction and electron microscopy. These offspring remained persistently viremic throughout the study. Maternal transmission therefore bred true to a total of 49 offspring--24 ducklings (less than 24 hr old) and 25 ducks--studied. Six of these 25 ducks matched for age and sex and bled weekly for 6 weeks exhibited fluctuating plasma levels of DNA polymerase activity. Higher DNA polymerase activity was detected in newly hatched ducklings than in older viremic ducks. This observation was corroborated with the results of electron microscopic examination of thin sections of liver. Duck hepatitis B virus particles, located within vesicles of rough endoplasmic reticulum in the cytoplasm of hepatocytes, were more abundant, and therefore more readily observed, in ducklings than in older ducks.

Animals↗

Detection of hepatitis B virus DNA in hepatocellular carcinoma: analysis by hybridization with subgenomic DNA fragments.

We have previously reported an analysis of DNA extracted from 31 primary liver tumors where, in 25 cases, we found chromosomal integration of hepatitis B virus DNA sequences. We describe here an investigation of the extent of the viral genome at each integration site in 15 of the hepatitis B virus DNA-positive tumors using subgenomic fragments of the viral genome as probes. Probes were roughly equivalent to the pre-S region, the surface antigen gene, the region containing the enhancer, the x gene and the core antigen gene. We found the core antigen gene to be that most underrepresented in the tumors and speculate that, since cells which express core antigen in the infected liver may be targeted for lysis by the immune system, modifications of the integrated viral DNA which prevent core antigen expression may be selected. Conversely, the region of the genome present in the greatest number of integrations was the surface antigen gene and, because it is known that the major surface antigen promoter is active in the integrated state, we find promoter insertion an attractive hypothesis to explain oncogenesis by hepatitis B virus.

Antigens, Surface↗

Detection of hepatitis B virus DNA in hepatocellular carcinoma: methylation of integrated viral DNA.

In order to determine whether integrated hepatitis B virus DNA sequences in primary liver tumours are methylated we have analysed tumour DNA digested with either MspI or HpaII restriction endonuclease by Southern hybridization. Our results demonstrate methylation in 11 of 17 tumour DNA samples. Where possible, we have examined the tumour tissues for expression of HBsAg and HBcAg using the indirect immunoperoxidase technique. One tumour was positive for both HBsAg and HBcAg and a second was positive for HBsAg alone. Both of these tumours were in the group in which methylation of integrated HBV DNA sequences could not be detected. We postulate that methylation of integrated HBV DNA sequences may influence HBV gene expression in hepatocellular carcinoma.

Carcinoma, Hepatocellular↗