Search PubMed⌕ Search

Biomedical subjects

A J Zuckerman

Publications and source records attributed to A J Zuckerman.

At least 163 records · Page 9Linked to original sources

Preparation of hepatitis B polypeptide micelles from human carrier plasma.

Water-soluble protein micelles consisting of the 28,000 (gp28) and 23,00 (p23) molecular weight polypeptide complex of hepatitis B surface antigen can be readily prepared from human plasma containing the surface antigen and other markers of infection with hepatitis B virus. The antigenic activity of the polypeptides was preserved throughout the process of solubilisation and reassociation into micelles. Such preparations are therefore eminently suitable as "second generation" hepatitis B vaccines.

Carrier State↗

Application of electron microscopy to the study of structural changes in the liver in non-A, non-B hepatitis.

Ultrastructural studies employing techniques such as alternative electron metal stain, high-angle tilting and high-voltage electron microscopy were carried out on liver biopsies obtained from chimpanzees infected with non-A, non-B hepatitis. Typical derangement of the endoplasmic reticulum leading to the formation of tubular structures in hepatocytes was observed. The use of potassium permanganate as an alternative stain revealed two features which have not been previously described. The first of these shows the wall of the tubular structures to be composed of a well-defined fibrillar-like meshwork with a periodicity of approximately 15 nm. The second feature is the demonstration of clusters of fibrin-like inclusions consisting of striated fibrils in the neighborhood of the tubular structures. The presence of intracytoplasmic fibrin may indicate non-specific morphological evidence of cell injury. Crystalline structures containing arrays of particles with an average size of 24 nm were also observed in the endoplasmic reticulum of endothelial cells of the hepatic sinusoids. Morphological differences between the crystalline lattice and the reticular arrangement, demonstrated with the use of high-angle tilting of the specimen in the electron microscopy suggest that the arrays may not be viral particules but a reflection of pathological response of the host cell.

Animals↗

A study of ultrastructural alterations in experimental non-A, non-B hepatitis by electron-beam analysis.

An electron-beam X-ray microanalysis was carried out on sections of liver biopsy specimens obtained from chimpanzees infected with non-A, non-B hepatitis. The microanalysis was concentrated over areas where typical derangement of the endoplasmic reticulum, with the formation of tubular forms possessing walls with electron-dense central membrane, was visualized. These tubular structures are regarded as the most notable pathological alteration in affected hepatocytes. However, the electron-probe microanalysis showed no deviation of the energy spectrum when compared with the background or control analysis.

Animals↗

Non-A, non-B hepatitis in West London.

Acute and convalescent sera from 368 patients drawn from a 3-year survey of viral hepatitis in West London were tested for radioimmunoassay for evidence of recent infection with hepatitis A or B and, if neither was found, antibody to Epstein-Barr (EB) virus and cytomegalovirus. In 215 patients (58%) there was evidence of hepatitis A, in 98 (27%) hepatitis B, and in 5 both A and B. 2 patients with evidence of recent EB virus infection were excluded, leaving 48 (13%) attributed to non-A, non-B hepatitis. This illness was milder than hepatitis B as judged by duration of jaundice and peak serum bilirubin alanine-aminotransferase levels. The ratio of men to women was 1.4 to 1, but there was an excess of women in their twenties, most of whom were single. Only one had received blood, and none was a drug addict.

Adult↗

Hepatitis B polypeptide vaccine preparation in micelle form.

The immunoprophylaxis of hepatitis B is hampered by the lack of a technique for growing hepatitis B virus (HBV) in tissue culture. Plasma from persistently infected individuals, one source of viral antigen, contains characteristic 22-nm spherical particles which share a common antigen (the hepatitis B surface antigen or HBsAg) with the outer envelope of the 42-nm double-shelled DNA virus. Highly purified inactivated 22-nm particles have been shown to be safe and to confer protective immunity against HBV in a recent large-scale clinical trial. We have already described the extraction from the particles of a complex of two proteins which are antigenic determinants of HBV--the polypeptide with molecular weight (MW) between 22,000 and 24,000 (called p23) and the glycosylated polypeptide (called gp28) with MW in the range 26,000--29,000 which is thought to be the glycosylated form of p23. We now report the preparation from this complex of water-soluble protein micelles which may be a suitable basis for a second-generation hepatitis B vaccine.

Animals↗

Specificity of an immunoprecipitin test for non-A non-B hepatitis.

An immunodiffusion system detecting an antigen showing immunological identity with international laboratory reference sera was developed by use of acute-phase and recovery sera from patients with transmission-proven non-A, non-B acute hepatitis. In other liver diseases the antigen was also present in a high proportion of patients and there were similar findings in conditions with high levels of circulating immune complexes in the serum. Fractionation of antigen-containing sera by column chromatography, polyethylene glycol treatment, and reduction and alkylation also suggested that immune complexes may be responsible for antigenic activity. The precipitation lines did not develop in the presence of 10 mmol/l EDTA or at a pH less than 8.0 and the reactant in "antibody" containing sera was shown not to be an immunoglobulin. Although the transmission of non-A, non-B hepatitis by blood and blood products shows that viral antigens are likely to be present in the circulation, this study shows that immune reactions apparently closely associated with the infection may be detecting immune complexes rather than specific viral components and emphasises the need for careful evaluation of the specificity of other reported serological tests for non-A, non-B hepatitis.

Acute Disease↗

Detection of HBsAg in a clone derived from the PLC/PRF/5 human hepatoma cell line.

A total of 28 clones were established from the PLC/PRF/5 hepatoma cell line by a plating procedure. All clones were found to secrete HBsAg into the supernatant culture fluids. Of these, one clone (No. 23) free of detectable mycoplasma contamination and showing smooth epithelial morphology was selected for further study. Maximum accumulation of HBsAg occurred 9 days after sub-culture and intracellular antigen was detected by indirect immunofluorescence both in the cytoplasm and at the plasma membrane. Granules and perinuclear staining reactions were also observed in clone 23 cells and these findings are compared to the previously published properties of the parental PLC/PRF/5 cell line.

Carcinoma, Hepatocellular↗

The use of markers in immune electron microscopy.

Immune electron microscopy (IEM) cannot be used successfully for structures that do not have recognisable morphology. However, at least some of these structures or components are related antigenically to recognisable antigens or viruses. We have therefore mixed unknown antigens with known markers and looked for the presence of mixed aggregates. The present study examined a low molecular weight subunit of rotavirus and a micellar form of hepatitis B surface antigen. In both cases mixed immune aggregates were found showing that the unknown components had antigens in common with the established virus or antigen.

Antigen-Antibody Complex↗