Biomedical subjects
A J Zuckerman
Publications and source records attributed to A J Zuckerman.
Hepatitis B virus infection in two Gambian villages.
The prevalence of hepatitis B virus infection was markedly different in two neighbouring Gambian villages. 62% of children in Manduar aged 2-4 years were infected whereas in Keneba, the other village, only 27% of this age-group were infected. However, in both villages few infants were infected--none under 6 months of age and only 2 of 58 between the ages of 6 and 12 months. Carriage of hepatitis B surface antigen (HBsAg) was high, reaching a peak of 36% in the 5-9 age-group in Manduar and 17.6% in the 2-4 age-group in Keneba. 86% of all the children under the age of five who were HBsAg-positive also carried hepatitis B e antigen (HBeAg). This proportion fell to 17.6% for children aged 10-14 years and to 12.9% for mothers. Infection clustered in families, transmission from sib to sib being of major importance. The chances of a child being an HBsAg carrier were approximately 42% if an elder sib carried the antigen, 27% if either mother or father was a carrier, and 15% if neither mother or father was a carrier. There were 4 HBeAg-positive mothers who were highly infectious, since 10 of 11 of their children became HBsAg carriers. Carriage of surface antigen lasted many years; 63% of those carrying the antigen in 1972 were still positive in late 1980. 4 cases of primary hepatocellular carcinoma out of 672 adults have been diagnosed in the past five years. All 4 were in HBsAg carriers.
Non-A, non-B hepatitis in persistent carriers of hepatitis B virus.
There are reports in the literature that infection with hepatitis A virus in hepatitis B carriers can result in resolution of the carrier state. In an attempt to induce clearance of the carrier state of hepatitis B virus in two persistently infected chimpanzees, the chimpanzees were infused with documented non-A, non-B infectious material. Biochemical and histopathological evidence of hepatitis was accompanied by the unique abnormalities of endoplasmic reticulum associated with non-A, non-B hepatitis in the chimpanzees. Elevation of alanine aminotransferase was accompanied by fourfold reduction in one chimpanzee and sixfold reduction in the other in the plasma levels of HBV-associated DNA polymerase activity and simultaneously by twofold reduction in the concentration of hepatitis B surface antigen in both chimpanzees. A mediator may account for these changes in markers of hepatitis B virus infection, and this mechanism may also explain the occurrence of spontaneous regression in some persistently infected carriers. The significance of transient red cell anaemia in non-A, non-B hepatitis, which was observed in one of the chimpanzees, is yet to be established.
Failure to detect nucleic acid homology between some non-A, non-B viruses and hepatitis B virus DNA.
Some studies suggest that there is antigenic and nucleic acid homology of one type of non-A, non-B hepatitis virus with hepatitis B viral (HBV) proteins and DNA. Using molecular hybridization under high and low stringency conditions with high specific activity 32P-HBV DNA as a probe, serum and liver samples from patients and nonhuman primates infected with non-A, non-B hepatitis were examined. Our results provide no evidence of significant homology between the DNA extracted from serum and liver of patients and nonhuman primates infected with one type of non-A, non-B hepatitis and HBV DNA.
Cell-mediated immunity: correlation of mixed-leucocyte-macrophage migration inhibition with delayed-type hypersensitivity after immunization and donor-specific transfer of cell migration inhibition by dialyzable leucocyte extract.
Active and adoptive sensitization of rhesus monkeys (Macacca mulatta) as well as the development of a novel sensitive in vitro cell migration inhibition assay for cell-mediated immunity (CMI) in this species are described. First, the correlation of mixed leucocyte-macrophage migration tests (LMMI) with the whole blood lymphocyte transformation (LT) and the delayed hypersensitivity skin test (DH) in immunized animals are shown. Second, these tests are used to demonstrate adoptive transfer of specific/nonspecific cellular immunity (CMI) with dialyzable leucocyte extract (DLE) from immunized donor to unimmunized recipient monkeys. Seventeen animals were immunized with keyhole limpet haemocyanin (KLH) or hepatitis B surface antigen (HBsAg) in Freund's complete adjuvant (FCA) or with FCA alone. Acquisition of antigen-specific cell-mediated immunity was detected by all three tests within 5 weeks of immunization. Positive LMMI responses were associated with positive DH and LT. However, there was no correlation between the magnitude or time of development of the three responses. Therefore, the LMMI test, like the LT test, is an in vitro parameter of DH, but reflects the activity of different subpopulations of lymphocytes and is regulated by different mechanisms. In addition, 12 naive animals received DLE. Within 3 weeks, transfer of sensitivity was detected towards antigens to which the recipients had previously not been reactive but the donors had been. An enhancement of transformation response to phytohaemagglutinin was also seen. Thus, rhesus DLE contains both donor-specific transfer factor-like and nonspecific adjuvant-like activities. In DLE recipients, unlike immunized animals, LMMI responses were dissociated from DH or LT responses in that positive LMMI was mostly seen with negative DH or LT to antigens. Therefore, LMMI emerged as the most sensitive assay for detecting adoptive transfer of CMI by DLE in vivo, supporting the view that different mechanisms regulate LMMI, LT, and DH.
A new method for detecting hepatitis B surface antigen in liver by silver staining.
Staining of tubular and circular structures within the cisternae of the endoplasmic reticulum of the cytoplasm of liver cells infected with hepatitis B virus was enhanced by the use of 1% aqueous silver proteinate.
Assay of HBV DNA in the plasma of HBV-carrier chimpanzees superinfected with non-A, non-B hepatitis.
A dot hybridisation technique was used to monitor the levels of hepatitis B virus (HBV) DNA in the plasma of two HBV-carrier chimpanzees which had been inocula ed with documented infectious non-A, non-B hepatitis agents. A marked decrease in the quantity of HBV DNA in the plasma during the acute phase of the non-A, non-B hepatitis was observed in both carriers. The possible role of interferon or a similar antiviral agent in modulation of the HBV-carrier state is discussed. Hybridisation may become, in due course, the method of choice for examining blood samples for infectious hepatitis B virus.
The association of hepatitis B with primary hepatocellular carcinoma.
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Replication of influenza A and B viruses in human diploid cells.
Under optimal conditions, of high multiplicities of infection and with trypsin included in the medium throughout the incubation period, high yields of infectious influenza A and B viruses (10(6 . 5) p.f.u./ml) and of antigenically active haemagglutinin (HA)(1 microgram/HA/10(6) cells) were produced in human diploid MRC-5 cells. Budding virus particles were seen as spherical or short rod-like protrusions on the surface of the infected cells, and also on cell filopodia. Virus-induced cytoplasmic and nuclear inclusions were present in infected cells. This virus-human cell system may be suitable for studies of influenza virus persistence and for production of immunologically active HA antigen.
The association of hepatitis B virus with primary hepatocellular carcinoma.
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Aspects of the ecology of viral hepatitis.
Human viral hepatitis, a major public health problem throughout the world, is caused by several different viruses. Hepatitis A virus is a member of the enterovirus genus. Hepatitis B is as yet an unclassified DNA virus. A number of unidentified viruses cause at least two different types of non-A, non-B hepatitis. The delta agent, which has been described more recently, is a transmissible agent which is dependent for its replication on a helper function provided by hepatitis B virus. Aspects of the ecology of viral hepatitis are described.
Fluorescein fluorescence photography for the evaluation of burn injury.
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Priorities for immunisation against hepatitis B.
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Developing synthetic vaccines.
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Examination of crystalline arrays in non-A, non-B hepatitis.
Individual patients within crystalline arrays found in the endothelial cells of hepatic sinusoids in experimental non-A, non-B hepatitis were examined by the Markham rotation technique. The particles appeared to possess an outer structure with 16-18 divisions. The presence of the crystalline structures is probably a reflection of host cell response to infection.
Analysis of hepatitis virus DNA in the liver and serum of HBe antigen positive chimpanzee carriers.
Hepatitis B viral DNA present in the liver of HBe antigen positive chimpanzee carriers is in the form of viral molecules (3.2 Kb) and no integration into host DNA was observed. The 3.2 Kb form was not detected in the serum. Other discrete HBV DNA species with faster mobilities than the major 3.2 Kb were consistently detected both in the liver and in the serum and their possible significance is discussed.
Non-A, non-B hepatitis: a case report.
Ultrastructural changes in a liver biopsy obtained for diagnostic purposes from a patient with suspected non-A, non-B hepatitis were consistent with hepatitis and included dilatation and disaggregation of the endoplasmic reticulum, hepatocyte disarray, and variations in mitochondrial size. In addition, some foci of hepatocytes showed atypical cytoplasmic changes including intranuclear cytoplasmic pseudo-inclusions, consisting basically of invaginations of the cytoplasmic mass into the nucleus, glycogen deposits in the same nuclei, and frequently accumulations of fat droplets. The mitochondria were generally pleomorphic, and occasionally the mitochondrial cristae were arranged longitudinally. Dilatation, hypertrophy, and distortion of the Golgi complexes were found in affected hepatocytes. Similar ultrastructural changes have previously been reported in human hepatocellular carcinoma as well as in carcinomas of other tissues.
Immunogenicity in chimpanzees of experimental hepatitis B vaccines prepared from intact hepatitis B virus, purified polypeptides, or polypeptide micelles.
The immunogenicity of three experimental hepatitis B vaccines was evaluated in chimpanzees. Although no antibody to hepatitis B surface antigen (anti-HBs) was detected in two chimpanzees that received an aqueous polypeptide vaccine subcutaneously, a strong anti-HBs response was observed two and ten weeks, respectively, following challenge with hepatitis B virus. Inoculation of two additional chimpanzees with a micellar preparation of these polypeptides by the intravenous route resulted in anti-HBs production in one of the chimpanzees. Two chimpanzees inoculated subcutaneously with an aqueous vaccine of formalin-inactivated intact hepatitis B virus developed anti-HBs in low titers, but the development of antibody to the hepatitis B core antigen following challenge inoculations suggested that subclinical HBV infections may have occurred despite prior vaccination.