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Biomedical subjects

A J Zuckerman

Publications and source records attributed to A J Zuckerman.

At least 19 recordsLinked to original sources
PubMed1992

Toga virus-like particles in acute liver failure attributed to sporadic non-A, non-B hepatitis and recurrence after liver transplantation.

Toga virus-like particles (typically 60-70 nm: enveloped with small surface spikes) were detected in the native hepatectomy specimens in 7 of 18 patients grafted for acute liver failure attributed to sporadic non-A, non-B hepatitis and in 2 patients grafted for fulminant hepatitis attributed to anti-epileptic drug hepatotoxicity. These particles were not detected in the hepatectomies from 12 other patients grafted for other causes of acute liver failure, 12 for various chronic liver diseases, and 2 histologically normal livers. Acute hepatic failure, characterized histologically by severe haemorrhagic necrosis, developed 7 days after grafting in 5 patients, all in the non-A, non-B group with toga virus-like particles in native liver. Similar virus-like particles were detected in all grafts and were in greater abundance than in the native livers. The agent may be novel because pre- and post-grafting sera were negative for antibodies against representative panels of arboviruses and in first and second generation antibody tests for hepatitis C virus.

Adolescent↗
PubMed1992

Improved diagnosis of chronic hepatitis C virus infection by detection of antibody to multiple epitopes: confirmation by antibody to synthetic oligopeptides.

Serum samples from 226 patients covering a wide spectrum of liver disease were tested for antibodies to hepatitis C virus (HCV) using both first and second generation enzyme linked immunosorbent assays. Selected sera were also tested by peptide immunoassays, by the four-antigen recombinant immunoblot assay (RIBA II), and for viral genome by the polymerase chain reaction. Antibody to c100-3 was detected in 61% of patients with chronic non-A, non-B (NANB) hepatitis and/or 46.5% with presumed NANB-related cirrhosis by the first generation test. These figures increased to 77% and 58% when antibodies to recombinant structural and non-structural HCV antigens were sought by the second generation assay. Supplemental testing against peptide Sp75 and Sp65/sp67 confirmed that reactivity of sera by second generation assays was due to antibodies to the additional structural and non-structural antigens. Samples negative by the first generation assay were not confirmed by the supplemental assay using peptides Sp75 and Sp65/Sp67. HCV RNA was detected in 60% of the anti-HCV positive sera tested, most of which were also RIBA II positive. Our findings confirm that the introduction of the structural and non-structural antigens, especially the putative nucleocapsid protein, improves sensitivity of detection of antibodies to HCV, and facilitates diagnosis in patients with "cryptogenic" chronic hepatitis.

Antigens, Viral↗
PubMed1992

Assessment of inactivation of hepatitis A vaccine by compound PCR.

Assuring the complete inactivation of hepatitis A virus (HAV) vaccine commonly requires prolonged tissue culture amplification, followed by detection of virus antigen in cell lysates. A reliable, but faster, alternative procedure is highly desirable since it will permit the prescreening of experimental batches of killed HAV, prior to tissue-culture amplification. We established experimental conditions for simultaneous, polymerase chain reaction (PCR)-based amplification of viral and cellular mRNA sequences from infected cell RNA (compound PCR). Under these conditions, the presence of virus-specific amplified sequences, as detected by Southern blot, allows the identification of incompletely inactivated vaccine batches with a threshold practically identical to that of the more time-consuming subculture and ELISA. Compound PCR is, by its nature flexible enough for adaption to different requirements and it should prove useful for rapid prescreening of vaccine batches and pilot studies for improvement of inactivation protocols.

Base Sequence↗
PubMed1991

Comparative evaluation of the immunogenicity of yeast-derived (recombinant) and plasma-derived hepatitis B vaccine in infants.

The immunogenicity of plasma-derived (HB Vax,MSD) and recombinant hepatitis B virus (Engerix B, SK&F) vaccines was evaluated in infants born to hepatitis B virus carrier mothers. The vaccination was carried out at 1 day, 1 month, and 6 months of age using 10 micrograms of the vaccine given intramuscularly. A total of 83/88 (94.3%) and 74/79 (93.6%) of the infants receiving the plasma-derived vaccine and yeast-derived vaccine showed antibody to hepatitis B surface antigen (anti-HBs). None of the maternal factors studied apart from the HBeAg positivity corellated with vaccine failure. The yeast-derived vaccine gives marginally lower antibody titre than the plasma-derived vaccine. The group-specific anti-"a" antibody was less than 10% of the total anti-HBsAg titre. It was observed that the vaccine alone without prior administration of hepatitis B immunoglobulin is effective in perinatal infection.

Biomarkers↗
PubMed1991

Independent emergence of a vaccine-induced escape mutant of hepatitis B virus.

We investigated the case of a child who was vaccinated at birth against hepatitis B and was also given hepatitis B immune globulin, but who nevertheless later became infected with the virus. Hepatitis B virus-specific deoxyribonucleic acid covering the region of the genome encoding the predominant a epitope of hepatitis B surface antigen was amplified using the polymerase chain reaction and the nucleotide sequence determined. We present evidence for the independent emergence of an escape mutant, similar to that previously identified in Italy, where a substitution of arginine for glycine has occurred in the second loop of the a epitope.

Amino Acid Sequence↗
PubMed1991

Characterization of a hepatitis A virus strain suitable for vaccine production.

A novel isolate of hepatitis A virus, obtained from a clinical sample, has been adapted to grow on cultured human diploid cells. Growth and purification parameters have been optimized to obtain conditions suitable for the development of an inactivated vaccine. The entire viral genome was molecularly cloned, and the gene encoding the VP3 capsid protein was expressed in Escherichia coli. The resulting recombinant VP3 was used to obtain rabbit antisera which recognize the denatured protein in purified virion preparations. Nucleotide sequencing data are presented and compared to known sequences of different strains.

Amino Acid Sequence↗
PubMed1990

Vaccine-induced escape mutant of hepatitis B virus.

In southern Italy, 44 contacts of hepatitis B virus carriers, including infants of carrier mothers, became HBsAg positive despite passive and active immunisation according to standard protocols. In 32 of these vaccinees infection was confirmed by the presence of additional markers of viral replication. In 1 infant, serious disease occurred. The virus from this patient is an escape mutant with a different sequence from that of the isolate from the mother. A point mutation from guanosine to adenosine at nucleotide position 587 resulted in an aminoacid substitution from glycine to arginine in the highly antigenic a determinant of HBsAg. This mutation is stable: it is present in an isolate from the child 5 years later. In some of these patients, including this child, the a determinant, to which a large part of the vaccine-induced immunity is directed, has been partly lost. Binding to HBsAg of a monoclonal antibody, previously mapped to the region of the mutation, was reduced in the child relative to that of the mother.

Biomarkers↗
PubMed1990

Diminished response to recombinant hepatitis B vaccine in homosexual men with HIV antibody: an indicator of poor prognosis.

Three doses of a recombinant DNA HBV vaccine (MSD) were given to healthy male homosexuals. Seventy-eight out of 104 (77.6%) participants had detectable antibody (anti-HBs) two months after the third dose. Seroconversion occurred in only 9 out of 27 subjects (33.3%) who were anti-HIV positive compared with 69 out of 77 (89.6%) who were negative (chi 2 = 30.8; P less than .001). Fifteen of the 18 anti-HIV positive who did not mount an antibody response to the hepatitis B vaccine (anti-HBs) later progressed to persistent generalised lymphadenopathy syndrome (5), AIDS-related complex (5), and AIDS (5). Only one of the nine anti-HIV positive anti-HBs responders developed PGL (chi 2 = 10.14; P less than .005). Our results show that anti-HIV positive homosexuals are poor responders to the recombinant hepatitis B vaccine and anti-HIV positive non-responders are more likely to develop clinically apparent HIV infection.

Follow-Up Studies↗
PubMed1990

Kinetics of antibody response to hepatitis B virus determinants and to recombinant vaccines in Italy.

The kinetics of antibody response to the group determinant a and subdeterminants d and y of hepatitis B virus were studied after infection and following immunisation with two recombinant DNA yeast-derived hepatitis B vaccines. The initial antibody response was to the subdeterminant epitopes, whereas anti-a antibody, which provides protection against different subtypes of the virus, was not detected for some weeks or months. The delay in the development of anti-a antibody after active immunisation raises important issues of early protection against infection.

Adolescent↗
PubMed1990

Other common types of viral hepatitis and exotic infections.

This chapter discusses two distinct sets of viruses which cause hepatitis. The first include common virus infections which cause mild hepatitis rarely in individuals with normal immunity but which may cause severe life-threatening hepatitis in the increasing number of patients with depressed cell mediated immune responses. The second comprise exotic virus infections which are prevalent in particular geographical areas and which frequently involve the liver with high mortality. For each of these viruses the epidemiology, clinical features, diagnosis and treatment are briefly reviewed.

Adenoviridae Infections↗