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Biomedical subjects

A J Zuckerman

Publications and source records attributed to A J Zuckerman.

At least 127 records · Page 7Linked to original sources
PubMed1985

Imported epidemic non-A, non-B hepatitis in Qatar.

During one year, 198 patients were admitted to the Hamad General Hospital, Qatar, with acute viral hepatitis. Sera from 126 of these were tested for HBsAg, IgM anti-HBc, IgG anti-HAV, IgM anti-HAV, and delta antibody in those positive for HBsAg. Only 6% of the patients were Qatari nationals and the remainder were immigrants. Of the 126 patients tested, 7 had acute hepatitis A, 29 had acute hepatitis B (none were positive for delta antibody), and the remaining 91 were regarded as having had acute non-A, non-B hepatitis. Of this latter group, 75% were Indian immigrants of whom 59% presented within six weeks of arrival in Qatar and only 2 patients presented later than eight weeks. These patients were thought to have contracted the infection in transit camps in India before immigration to Qatar.

Adolescent↗
PubMed1985

Experimental in ovo transmission of duck hepatitis B virus.

Inoculation of fertile Pekin duck eggs with diluted serum containing DHBV into eggs incubated for 24 h and into the extra-embryonic cavities of 14-day-old embryos resulted in a high proportion of viraemic ducklings irrespective of the route of inoculation. Long-term observation of som of the ducks established that the viraemia induced experimentally is long-lasting and has persisted for periods up to 16 mth post-hatch. Separation of DHBV from the plasma of carrier ducks by rate zonal centrifugation was examined by DNA polymerase (DNAP) activity. Particles in the fraction with peak DNAP activity had a buoyant density of 1.16 g X cm-3 in sucrose and an estimated sedimentation coefficient, S20.w of 77. DHBV particles, the morphology of which could be resolved under the electron microscope, consisted of a coat (about 10 nm in thickness) surrounding a core with a diameter measuring 40 nm but not 27 nm as previously reported. Spike-like projections were found on the surface of the core as described previously by W.S. Mason, G. Seal and J. Summers, 1980, J. Virol. 36, 829-836.

Animals↗
PubMed1985

Subunit, recombinant and synthetic hepatitis B vaccines.

Hepatitis B surface antigen in the form of 22 nm spherical particles (and tubular forms) is excess virus coat protein. Guidelines for the preparation of the 22 nm spherical particles (and their separated polypeptides) derived from the plasma of asymptomatic human carriers, were suggested by the WHO Expert Committee on Viral Hepatitis in 1977, and the proposed requirements for the 22 nm hepatitis B particle vaccine were published by the WHO Expert Committee on Biological Standardisation in 1981 and revised in 1983. Such preparations have been tested for safety and protective efficacy and many clinical trials with the plasma-derived vaccine have demonstrated the immunogenicity, high protective efficacy and safety of the currently licensed preparations. Polypeptide vaccines, derived from the surface antigen from any source, have several advantages which include precise biochemical characterisation, exclusion of genetic material of viral origin, exclusion of host or donor-derived substances and enhanced potency. A polypeptide vaccine in micellar form has been developed in London. The applications of recombinant DNA technology permit the isolation, purification and selective amplification of almost any individual segment of DNA from practically any organism in convenient biological systems such as bacteria, yeast, or any other cell including mammalian cells. Considerable progress has been made with vaccines prepared from antigen expressed in yeast (Saccharomyces cerevisiae). Cloning of the DNA of hepatitis B virus has resulted in sequencing of nucleotides and mapping of the amino acids of antigens. Information obtained from the sequencing of the 226 amino acids of hepatitis B surface antigen has led to the development of chemically synthesised peptides corresponding to amino acid sequences predicted from the nucleotide map. Several such synthetic peptides, when linked to potent adjuvants elicit antibodies in experimental animals which react with the surface antigen. The potential of pure chemically synthetic vaccines against hepatitis B, and other infectious agents, is under intensive investigation since such vaccines should be chemically well-defined, uniform, safe and cheap to produce. Studies have been carried out recently using a chemically synthetic peptide in a linear and in a cyclical form corresponding to the amino acids sequence 139-147 of the major polypeptide I of hepatitis B surface antigen. The synthetic antigens and the native polypeptide complex p23-gp28 purified from hepatitis B surface antigen in plasma were used for the measurement of affinity of the antibody to the surface antigen (anti-HBs) in human sera.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1985

Subunit, recombinant and synthetic hepatitis B vaccines.

The failure to propagate hepatitis B virus in vitro has prevented the development of vaccines from virus grown in cell cultures. Alternative approaches including the use of surface antigen purified from plasma, subunit polypeptide vaccines, vaccines produced by recombinant DNA technology, expression by a recombinant vaccinia virus and the chemical synthesis of small peptides representing specific regions of surface antigens are reviewed in this article.

Amino Acid Sequence↗
PubMed1984

Determination of the affinity of antibodies to hepatitis B surface antigen in human sera.

The measurement of the affinity of anti-HBs antibody in human sera using 3 HBsAg-related antigens is described. The antigens used were (i) a synthetic linear peptide corresponding to amino acids 139-147 of the major polypeptide of HBsAg, (ii) a cyclical form of this same peptide and (iii) a polypeptide complex of a 28,000 MW glycoprotein and a 23,000 MW protein from purified HBsAg. The method was established with a pooled human anti-HBs immunoglobulin preparation and a monoclonal anti-HBs antibody reactive to the 'a' determinant of HBsAg. The results indicate that both these antibody preparations effectively bind the 3 antigens with affinity values of between 2 X 10(6) to 9 X 10(7) litres/mole. However, the affinity of both antibody preparations for the cyclical form of the peptide was higher than for the linear form. The level of antibody (expressed as Abt, molar antigen binding sites) in the pooled human immunoglobulin for each of the 3 antigens was similar. Measurements of anti-HBs antibodies in the sera of recovered acute hepatitis B patients and from HBsAg negative chronic liver disease patients showed that the cyclical form of the antigen was bound with a higher affinity than the linear form. Affinity values of antibody in the sera of the latter group of patients was significantly lower (3 X 10(5) to 2.7 X 10(6) litres/mole) than those observed in sera from other individuals. The implication of these results in determining the importance of the measurement of affinity in the assessment of the efficacy of vaccines is discussed.

Amino Acid Sequence↗
PubMed1984

Affinity of antibody responses in man to hepatitis B vaccine determined with synthetic peptides.

The affinity and level of antibody to hepatitis B surface antigen (anti-HBs) in recipients of a plasma-derived hepatitis B vaccine were determined with three different antigens. The first two antigens were prepared by chemical synthesis, to represent linear or cyclical forms of aminoacid sequences 139 to 147 of the major hepatitis B surface antigen (HBsAg) polypeptide. The binding of antibodies to these synthetic peptides was compared with that to a third antigen, prepared by solubilisation of the naturally occurring HBsAg, the basic component of the currently licensed hepatitis B vaccine in the United Kingdom. Antibody levels, expressed as total antibody combining sites (Abt) in fixed volumes of immune sera, increased throughout the course of immunisation and correlated with the development of antibody as measured by a commercially available radioimmunoassay. Abt values were similar for both forms of the synthetic peptide, although higher affinity values were found with the cyclical structure, which illustrates the importance of protein conformation in antibody responses to HBsAg. Antibody affinity for the three antigens increased progressively throughout the immunisation schedule but the pattern of affinity maturation varied according to the peptide used as an antigen probe and between subjects. Most subjects showed a significant rise in antibody affinity after the third (booster) dose of vaccine given at six months. The use of synthetic peptides allowed a quantitative and qualitative assessment of antibody responses to hepatitis B vaccine and confirmed that selected peptides corresponding to relevant HBsAg epitopes may be useful as alternative hepatitis B vaccines.

Antibody Affinity↗
PubMed1984

Intracytoplasmic inclusions in human hepatocytes in non-A, non-B hepatitis: an ultrastructural study.

An ultrastructural study was carried out on 114 liver biopsies obtained for diagnostic purposes from patients with various pathological disorders of the liver including hepatitis B-related liver disease, non-A, non-B hepatitis, alcoholic liver disease, fatty change, and cryptogenic cirrhosis. The opportunity was taken to evaluate the significance of intracytoplasmic crystalline structures found in the hepatocytes of nine patients with a variety of liver disorders. The cytoplasmic inclusions varied in size up to 2 microns in length and shape and were not limited by membranes. The presence of these inclusions cannot, however, be correlated either specifically with non-A, non-B hepatitis or with other known nonviral liver disease. The functional, physiological, and pathological significance of the crystalline structures remain to be elucidated.

Adult↗