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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

EDRF coordinates the behaviour of vascular resistance vessels.

Constriction of vascular smooth muscle in response to the stimulus of raised intravascular pressure--the myogenic response--represents a positive feedback mechanism which, if unopposed, could theoretically lead to instability in the intact circulation. Dilation in response to increased intraluminal flow would provide an opposing feedback mechanism which could confer overall stability. Flow-dependent dilation in conduit vessels is mediated by endothelium-derived relaxing factor (EDRF), but the relationship between flow and EDRF activity has not been studied in resistance vessels in situ. We here demonstrate that EDRF can coordinate the aggregate hydrodynamic properties of an intact network. Under control conditions, EDRF maintains a fourth-power relationship between diameter and flow so that the pressure gradient in each vessel asymptotically approaches a constant value at high flow rates. Basal EDRF release may also maintain a similar spatial distribution of flow at different flow rates, even under conditions of moderate pharmacological constriction.

Animals↗

PubMedDate not supplied

The influence of subconjunctival depot corticosteroid on choroidal detachment following retinal detachment surgery.

This study indicates that primary retinal detachment surgery on patients aged 55 or over is complicated by uveitis and choroidal detachment at approximate rates of 24% and 44%, respectively. These complications did not influence the anatomic cure rate or recovery of visual acuity. Although only 89 patients were recruited, the technique of random selection equally distributed the parameters studied and provided results of high reliability. The internal controls of the protocol prevented the examiners from being aware of whether the drug or placebo had been administered. We were concerned that the corticosteroid injection might have been producing the apparent increase in infection rate of 7.7% and the study was temporarily discontinued. Because statistical analysis showed there was no significant difference in infection rate between the treatment and control groups, the project could have been continued again.

Aged↗

PubMedDate not supplied

Ocular complication in HIV infected individuals.

The incidence of acquired immunodeficiency syndrome is growing within all levels of Alaskan society. All physicians will be touched in some manner by this epidemic and there is a growing need for a thorough understanding of all aspects of the human immunodeficiency virus and acquired immunodeficiency syndrome. Visual complications associated with this disease are devastating, common, and in many cases treatable. The following discussion is an overview, in outline form, of the ocular complications associated with the human immunodeficiency virus and acquired immunodeficiency syndrome.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Comparative preclinical toxicology and pharmacology of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) in vitro and in rodents and primates.

4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) is being evaluated for its anticancer activities. Acute, subacute and chronic oral, dermal, opthalmic and dermal LD50 and acceptance studies in adult mice, rats, rabbits and monkeys demonstrated some vomiting at 5 g/kg doses in monkeys but otherwise no unacceptable toxicities. In vitro, T.I. for A-007 were calculated using murine bone marrow GM-CFC and human cancer cell lines. A relative oral bioavailability factor of 2% was calculated for rats and monkeys for plasma A-007. Non-compartmental pharmacokinetic analysis suggests enterohepatic circulation. Plasma A-007 could not be detected after applying a 0.25% gel topically. Generally, A-007 is well tolerated.

Administration, Oral↗