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Biomedical subjects

A J Zuckerman

Publications and source records attributed to A J Zuckerman.

At least 181 records · Page 10Linked to original sources
PubMed1981

Effects of amphotericin B on hepatitis B virus.

We investigated the effects of amphotericin B (AmB) on the ultrastructure and biochemistry of hepatitis B virus (HBV) and hepatitis B surface antigen (HBsAg) particles. These effects were compared with those reported for AmB and other polyene antibiotics on other lipid-enveloped viruses and artificial membranes. Treatment of HBV particles with concentrations of AmB ranging from 5 to 250 microgram/ml resulted in (i) an increase in HBV deoxyribonucleic acid polymerase activity as the concentration of Amb increased; (ii) changes in the electron microscopic appearance of HBV ranging from increased penetration of negative stain into the lipid envelope to disruption of the virus; and (iii) an increase in density form 1.165 to 1.225 g/ml. In addition, AmB treatment of HBsAg particles resulted in disruption into a nonparticulate HBsAg-reactive fraction and an HBsAg-AmB complex fraction with no HBsAg immunoreactivity.

Amphotericin B↗
PubMed1981

Nondetection of infectious hepatitis B virus in a human hepatoma cell line producing hepatitis B surface antigen.

The PLC/PRF/5 human hepatoma cell line producing hepatitis B surface antigen (HBsAg) was studied to determine whether infectious hepatitis B virus (HBV) was also being produced. 2 chimpanzees with no previous exposure to HBV and no serologic markers of past or active HBV infection were inoculated intravenously with 50 ml of either tissue culture supernatant fluid (357 ng/ml HBsAg) or a suspension of cells disrupted by repeated freeze-thaw cycles (57 ng/ml HBsAg). No evidence of HBV infection was detected in either chimpanzee during 6 months of evaluation. This study suggests that the expression of a portion of the HBV genome, when a portion or all of that genome has been incorporated into a host cell, can result in the production of HBsAg without infectious HBV. If it becomes possible to produce a similar expression of this portion of the genome by itself in nonmalignant cells, HBsAg without HBV may be produced in vitro for use in hepatitis B vaccines.

Animals↗
PubMed1981

Induction of cell-mediated immunity to HBsAg polypeptides.

Adult male guinea pigs were immunized with hepatitis B virus polypeptides prepared by Triton X-100 solubilization of purified 22-nm hepatitis B surface antigen (HBsAg) particles. A virus-specific subunit containing both the 28,000 molecular weight glycoprotein and the 23,000 molecular weight protein stimulated both cell-mediated and humoral immunity. A whole-blood-cell transformation assay additionally showed that the 64,000 molecular weight component of HBsAg, previously shown to contain host-specific antigens, also stimulated a cellular response to purified intact HBsAg particles, suggesting the additional presence of virus-specific material in this fraction. Immunization of animals with the 28,000--23,000 molecular weight polypeptides subsequently prepared in micelle form enhanced the demonstration of a cell-mediated reaction after only a single dose of immunogen. The results provide further evidence as to the suitability of HBsAg polypeptides prepared by Triton X-100 solubilization for hepatitis B prophylaxis.

Animals↗
PubMed1981

Ultrastructural changes in the liver in experimental non-A, non-B hepatitis.

Factor VIII, a blood-clotting derivative prepared from pooled human plasma, previously shown to cause a short-incubation-period non-A, non-B hepatitis in patients and in chimpanzees, was studied further to establish the nature of the pathological lesions associated with this infection. Percutaneous liver biopsy specimens were examined in detail. Cytoplasmic changes in the hepatocytes were observed on the 7th day after inoculation in one instance and after 13 days in the second, and persisted in the biopsy specimens for 13 weeks after infection. Abnormalities in hepatocyte nuclei, including aggregates of irregularly shaped particles 15-20 nm in size, were observed about 1 week after the onset of the cytoplasmic changes. The ultrastructural changes are described and their nature and significance discussed. Attention is drawn to somewhat similar cytoplasmic and nuclear changes occurring in other disease entities.

Animals↗
PubMed1980

Further evidence of cellular changes associated with non-A, non-B hepatitis.

Two distinct types of ultrastructural changes were found in the hepatocytes of chimpanzees infected with two forms of non-A, non-B hepatitis. In the type of infection that was of long incubation, there was a marked cytoplasmic derangement of the endoplasmic reticulum, with the formation of tubules, but no pathological changes in the nuclei. In the short-incubation type of non-A, non-B hepatitis, induced experimentally in a chimpanzee that had recovered from the long-incubation type of infection, nuclear alterations were found together with the presence of aggregates of particles measuring 15--27 nm in diameter. Cytoplasmic tubules were not seen in this type of non-A, non-B infection.

Animals↗
PubMed1980

Hepatitis B surface antigen production as a growth cycle-related terminal event in PLC/PRF/5 hepatoma cells.

The dynamics of hepatitis B surface antigen production of PLC/PRF/5 hepatoma cells were studied using a quantitative radioimmunoassay method. Maximum rates of antigen production were found in nutrient-depleted, non-dividing cultures and were temporally related to cytological changes preceding cell death. These results indicate that antigen production may be cell-cycle related and represent a terminal event.

Carcinoma, Hepatocellular↗
PubMed1980

Non-A/non-B hepatitis in experimentally infected chimpanzees: cross-challenge and electron microscopic studies.

Inoculation of eight chimpanzees with factor VIII, factor IX, or "H" strain plasma resulted in enzymatic and histopathologic evidence of non-A/non-B hepatitis in all eight animals. Challenge of two chimpanzees convalescent from factor VIII-induced disease with either factor IX or "H" strain plasma resulted in non-A/non-B hepatitis only in the animal inoculated with factor IX materials. Reciprocal cross-challenge of a chimpanzee convalescent from factor IX-induced disease with factor VIII also produced unequivocal enzymatic and histopathologic evidence of non-A/non-B hepatitis. Cross-challenge of a chimpanzee convalescent from "H" strain-induced non-A/non-B hepatitis with factor VII did not cause a second bout of non-A/non-B hepatitis. These findings suggest the factor VIII materials and "H" strain plasma used in these studies share a common etiologic agent (or agents), but that factor VIII and factor IX may contain two distinct agents. Electron microscopic (EM) examination of thin-sectioned, acute-phase liver biopsies from all but one of the chimpanzees receiving the primary inocula revealed the presence of abnormal hepatocyte cytoplasmic structures previously shown to be associated with non-A/non-B hepatitis. Crystalline structure containing 25 to 30 nm particles were visualized by EM in the cytoplasm of endothelial or Kupffer cells in acute-phase liver biopsies obtained from three chimpanzees inoculated with either factor VIII materials or "H" strain plasma.

Animals↗
PubMed1980

Establishment of a human hepatocellular carcinoma cell line releasing hepatitis B virus surface antigen.

A new hepatocellular carcinoma cell line, DELSH-5, derived from operative wedge biospy from a HBsAg sero- and tissue-positive patient, has been continuously propagated in vitro for nearly 22 months. The cells not only resemble hepatocytes on light and electron microscopic examination but also possess biosynthetic markers of the latter such as albumin and alpha-foetoprotein which were demonstrated in the supernatant medium as well as in the tumour cell cytoplasm. Karyology of cloned cells shows moderate aneuploidy, the major model chromosome number being 61. Though in the initial few passages HBsAg could not be detected, from the 13th passage onwards this viral component could be consistently demonstrated in small amounts in the concentrated supernatant medium by the macro- and micro-ELISA techniques. The immunohistochemical techniques as well as electron microscopy have failed to demonstrate any virus component inside the cell. The cell line reported here is the third of its kind which will act as a useful laboratory model to obtain pure HBsAg and to study the hepatitis-B-virus--liver-cell interaction with particular reference to the oncogenic potential of the virus.

Antigens, Neoplasm↗
PubMed1979

De novo acute infection and reactivation of hepatitis B virus in established cirrhosis.

Five patients with cirrhosis proved by biopsy had clinical, biochemical, and serological evidence of an acute hepatitis B infection. In two the illness was fulminant and led to death. Only one patient completely recovered. Serological markers for the hepatitis B virus were absent before the onset of the acute illness in four patients, which suggested that a de novo infection had been acquired as a result of recent transfusions of blood or blood products. The fifth patient, who had Goodpasture's syndrome, had antibody to the core of hepatitis B virus, indicating previous exposure to the virus; his acute hepatitis may have been related to immunosuppressive drug treatment, which may have reactivated a dormant virus infection. Thus an acute type B viral hepatitis due to either a de novo or a reactivated infection may be superimposed on cirrhosis.

Acute Disease↗