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Biomedical subjects

A J Zuckerman

Publications and source records attributed to A J Zuckerman.

At least 217 records · Page 12Linked to original sources

Effect of ethanol during hepatitis B virus infection in chimpanzees.

To determine whether the use of ethyl alcohol (ethanol, C2H5OH) may increase the liver damage caused by hepatitis B virus infection, ethanol was infused into four chimpanzees on one or two occasions during the course of natural or experimentally induced hepatitis B virus infections. A fifth chimpanzee, without active hepatitis B virus infection, served as a control. Moderate elevations of serum aspartate or alanine aminotransferases occurred in four of the five chimpanzees, including the control chimpanzee, in direct association with ethanol infusion; pre-existing enzyme elevations persisted in a fifth chimpanzee. No alteration occurred in the titers of hepatitis B surface antigen or of antibody to hepatitis B core antigen in three of the four infected chimpanzees. There was no significant alteration in the course of hepatitis B virus infection by ethanol infusion in these chimpanzees.

Acute Disease↗

Developments in viral hepatitis.

Viral hepatitis is a major public health problem occurring endemically in all parts of the world. The general term viral hepatitis refers to infections caused by hepatitis virus type A, type B and a more recently identified infection referred to as "non-A: non-B" hepatitis. These clinically and pathologically similar forms of hepatitis have been studied intensively following the discovery of a specific antigen, Australia antigen, one of the markers of infection with hepatitis B virus.

Animals↗

Biological activity of hepatitis B antigens in cell culture.

Direct interference by purified hepatitis B surface antigen or virus particles was not demonstrated in tissue culture. Significant levels of interferon were not induced. The surface antigen did not block the adsorption of other viruses.

Adsorption↗

The labelling of galactose residues in hepatitis B surface antigen glycoprotein.

The 20 to 25 nm particles of hepatitis B surface antigen were purified from the serum of a carrier chimpanzee. Five major polypeptide species were revealed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Treatment of the particles with neuraminidase (EC 3.2.1.18) and galactose oxidase (EC 1.1.3.9) followed by reduction with tritiated sodium borohydride labelled galactose residues in a single glycoprotein with an apparent mol. wt. of 28 000. The glycoprotein was not labelled when neuraminidase treatment was omitted, indicating that the galactose residues are in subterminal positions in the oligosaccharide chains. There was no significant incorporation of radiolabel into lipid. The serological activity of the antigen, as measured by a competitive double-antibody radioimmunoprecipitation assay, was not altered by the labelling procedure nor by exposure to neuraminidase alone.

Animals↗

Viral antigens and antibodies in hepatitis B infection.

Hepatitis B virus antigens and antibodies were detected in the sera of acute and persistently infected patients. Evidence of active virus replication was confined to immediately before or during the initial detection of hepatitis B surface antigen during acute hepatitis B. Hepatitis B core antibody appeared during the period of antigenaemia and preceded recovery. Hepatitis B e antigen was dound in a proportion of sera which contained significant levels of virus particles. In contrast, all sera containing hepatitis B virus particles from persistently infected patients treated by maintenance haemodialysis also contained the e antigen. Among a group of 50 persistent carriers of hepatitis B virus, significant levels of virus production occurred in the presence of antibody to e antigen. In addition, evidence of exposure to hepatitis B virus was found among 3% of blood donors in whose sera the surface antigen was not detected by radioimmunoassay. The significance of these findings is discussed in relation to the aetiology of hepatitis type B.

Antibodies, Viral↗

A three-year survey of viral hepatitis in West London.

During a total population survey of viral hepatitis in the London Boroughs of Hounslow, Richmond and Ealing, 784 patients were seen in three years from 1 March 1972 to 28 February 1975. A diagnosis of viral hepatitis was accepted in 489. The annual incidence was 24 per 100 000. 455 of the patients were tested for the hepatitis B surface antigen (HBsAg) by a radioimmunoassay technique and 93 (20%) of these were positive. The majority of the patients with type B hepatitis were in their third or fourth decades. None was under the age of 16. The male to female ratio among patients with hepatitis B was 2 to 1 in those under the age of 30 and 5 to 1 in those aged 30 and over. The seasonal distribution of viral hepatitis showed a peak in the spring, solely from an increased incidence of non-B hepatitis, and a second, smaller peak in the autumn. There was no appreciable clustering of patients except for one local outbreak in a housing estate during the first year affecting mainly children going to the same primary school, and their parents. Patients with hepatitis B had a longer pre-icteric illness (p less than 0.05), greater duration of jaundice (p less than 0.001) and higher peak levels of serum bilirubin (p less than 0.0005) and serum alanine amino transferase (A1T) (p less than 0.03) than patients with non-B hepatitis. The finding of the surface antigen was also associated with a higher frequency of skin rash (p less than 0.0005) and a greater duration of arthralgia (p less than 0.03). Among the HBsAg negative patients the incidence of arthralgia increased with age (p less than 0.0005). Abdominal pain (p less than 0.005) and vomiting (p less than 0.005) were more common in the young. The injection experience of patients with hepatitis B showed a high proportion of 'non-therapeutic' exposure such as drug addiction. Significantly more HBsAg positive men were single than in the local community (p less than 0.001) or among the HBsAg negative men (p less than 0.01). There was no significant difference between the proportions of single women among the antigen positive and negative patients. Many of the HBsAg positive single men were either known to be or strongly suspected of being homosexual. The ad subtype of the HBsAg was found more often in males (p less than 0.01), particularly over the age of 30. All eight drug addicts tested for subtype were ay, as were two non-addicted female consorts. The association between addiction and ay subtype was highly significant in the males (p less than 0.001). The ad subtype was found in all 11 of the admitted homosexual HBsAg positive men and in all but one of the 17 strongly suspected of being homosexual.

Adolescent↗

The three type of human viral hepatitis.

Infections with hepatitis A and B viruses are common in all parts of the world and constitute a major public health problem. The identification of specific antigenic markers of these viruses has led to the development of sensitive laboratory tests. These, in turn, have resulted in a better understanding of the epidemiology, pathogenesis, immunology, and the nature of these common infections. In the case of hepatitis type B, laboratory tests revealed a persistent carrier state of the surface antigen in some 120-175 million people and established the significance of hepatitis B virus in the pathogenesis of serious chronic liver disease, including a strong association with primary hepatocellular carcinoma in tropical and some subtropical regions. In addition, the specific diagnosis of hepatitis types A and B has revealed a previously unrecognized form of hepatitis which is clearly unrelated to either type. This new form of infection of the liver is now the most common type of hepatitis after the transfusion of blood and blood products in some areas of the world and it also appears to be an important cause of sporadic hepatitis, particularly among adults.

Animals↗

Long-term cultivation of functionally-active human foetal hepatocytes.

Livers from human foetuses obtained from terminations of pregnancy by suction were used to establish long-term cultures of hepatocytes. Functional activities of the hepatocellular population in these cultures were monitored by immunoperoxidase staining during and up to the 90 days' life of the cultures. Intracellular localization of albumin and alpha-foetoprotien in cultures of the same age and from the same specimen indicate that syntheses of these two markers in foetal hepatocytes occur simultaneously. No qualitative differences were observed in the biosynthetic capacity of the cells maintained in tissue culture medium with and without serum. Fibroblast-like cells seen in the almost homogeneous population of hepatocytes did not stain for albumin and alpha-foetoprotein.

Albumins↗

Seroepidemiological investigation of patients and family contacts in an epidemic of hepatitis A.

Serial blood and faecal samples were collected from patients and family contacts during an outbreak of hepatitis A in a village and tested by a solid-phase competitive type radioimmunoassay for hepatitis A antigen and hepatitis A antibody. The amount and duration of excretion of hepatitis A antigen was correlated with the severity of the illness. In 2 severe clinical cases, hepatitis A antigen was demonstrated in faecal extracts 11 days before the onset of jaundice and continuing for 10 days thereafter, with maximum shedding during the late incubation period. Faecal antigen was demonstrated in low concentrations for only 2 days in a patient with mild disease and in a person with subclinical infection. There was an inverse correlation between the incidence of infection and prevalence of hepatitis A antibody and age. Of 24 infections, 19 (79%) occurred in persons in the age group 0 to 20 years, a group in which only 6% of individuals had pre-existing antibody. Hepatitis A antibody was present in the serum of 3 persons in low titres of 1:20 to 1:40 on the day jaundice developed. The antibody titres increased very rapidly during the following 2 weeks of illness and slowly during the following months, reaching titres of 1:900 to 1:3500. In a separate study, a mean antibody titre of 1:591 was found in 13 patients, 12 years after clinical hepatitis A with jaundice.

Adolescent↗

Immunotherapy of viral infections with transfer factor.

It has been reported that dialysable leucocyte extract preparations, thought to contain transfer factor, may be used therapeutically for the treatment of a variety of immunodeficiency syndromes. Clinical and laboratory studies have suggested that such preparations, in addition to transferring specific cellular immunity may also contain non-specific adjuvant activities. Attempts at immunotherapy of viral infections are described against a background of current research on the biological and biochemical properties of leucocyte dialysates.

Adult↗

Core antigen and circulating anti-core antibody in hepatitis B infection.

Core antigen was obtained from the sera of persistent chronic carriers of hepatitis B virus by centrifugation and treatment with Nonidet P40 and 2-mercaptoethanol. The separated core antigen was radiolabelled and identified as a nucleoprotein structure of buoyant density 1.36 g/cm3 and possessing an isoelectric point of 4.4. This material was employed in a radioimmunoassay procedure of high sensitivity for the detection of core antibody. In a series of sera from patients with acute type B hepatitis, core antibody was demonstrated 2 to 3 weeks after the onset of jaundice during the period of surface antigenaemia. The presence of core antibody may therefore provide an accurate serological marker for the detection of active or recent virus replication in future epidemiological studies of hepatitis B infection.

Animals↗

The distribution and significance of hepatitis B surface antigen in a rural population in Kenya.

A rural population in Kenya was studied and a prevalence of HBsAg of 5-0% and an antibody prevalence of 50% in HBsAg in negative subjects has been found; 1-2% of the negative subjects converted to positive over a six-month period. A group of HBsAg positive subjects was compared with a matched group of HBsAg negative controls clinically in liver function tests and past medical history. No statistically significant differences were found between the two groups and neither group had experienced in the past significantly more skin scarification, injections or illness with jaundice. Both ad and ay subtypes occurred in the population. This is an unexpected and important finding, which gives scope for further detailed epidemiological studies in this population.

Adolescent↗

Immune responses to the hepatitis B surface antigen and liver-specific lipoprotein in acute type B hepatitis.

A serial prospective study of cellular immunity to HBsAg and liver-specific membrane lipoprotein was undertaken in 21 adults with acute hepatitis type B. Cellular immunity to HBsAg as determined by leucocyte migration inhibition with partially purified HBsAg as antigen was detected in all the patients during the recovery phase of the illness and was already detectable at the time of admission in 13 (62%) of the cases. In five of the remaining eight the titre of HBsAg in the serum at this time was high and in the whole series there was an inverse correlation between the degree of migration inhibition on admission and the peak HBsAg titre suggesting that antigen or possibly antigen/antibody complexes might be interfering with the demonstration of cellular immunity in vitro. Using a combination of minimum migration index recorded during the recovery period peak HBsAg titre, it was possible to compute the peak aspartate aminotransferase level with reasonable accuracy, a finding consistent with the hypothesis that the severity of the illness is related to both the number of infected hepatocytes and the vigour of the immune response to HBsAg. Evidence of an immune response to the liver-specific hepatocyte membrane lipoprotein was present in 50% of the patients tested at the time of admission, but was transient, having disappeared in every case by four weeks. The minimum migration index recorded with HBsAg as antigen was significantly lower in those with detectable sensitisation to the lipoprotein and it is possible that this autoimmune reaction is also generated by the interaction of T cells with viral antigenic determinants on the liver cell surface.

Acute Disease↗

Correlations between the detection of e antigen or antibody and electron microscopic pattern of hepatitis B surface antigen (HBsAg) associated particles in the serum of HBsAg carriers.

The distribution of HBsAg associated particles, especially the presence of Dane particles, was studied by electron microscopy in coded sera of 68 chronic HBsAg carriers. Results were correlated with the detection of eAg or Ab and clinical diagnosis. Sera from haemodialysis and chronic hepatitis patients showed a high prevalence of e antigenaemia (9/13, 69-2% and 8/19, 42-1%) and Dane particles (11 and 16 respectively, 84%). By contrast, out of 36 chronic asymptomatic carriers of HBsAg, 28 (77-7%) were positive for e antibody but only 1 (2-7%) had eAg. Dane particles were found in 13/36 (36-1%). A statistically significant correlation was observed between the detection of eAg and the presence of Dane particles (94-4%) in the serum. However, Dane particles were still observed in 10/28 (35-7%) of anti-e positive sera. The data suggest that eAg may be linked to complete HB virions.

Antibodies↗