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A J Zuckerman

Publications and source records attributed to A J Zuckerman.

At least 37 records · Page 2Linked to original sources
PubMed1995

Precore and core mutations in HBV from individuals in India with chronic infection.

Ten hepatitis B surface antigen seropositive carriers (5 asymptomatic and 5 with chronic liver disease) were tested for HBeAg/anti-HBe and for HBV-DNA using the polymerase chain reaction. Five were DNA-positive, 2 with HBeAg and 3 with anti-HBe. Nucleotide sequences were determined for these 5 cases. Hepatitis B virus DNA from one cirrhotic carrier with anti-HBe had a mutation in the precore region (nucleotide position 1862) which may affect signal peptide cleavage and HBeAg synthesis. In the other 2 anti-HBe- and DNA-positive cases, a cirrhotic carrier and an asymptomatic case, there was a mutation at nucleotide position 1896 leading to a termination codon in the precore region. In all 5 patients, except for one or two missense mutations, there was no significant variation in the core region.

Amino Acid Sequence↗
PubMed1995

Occupational exposure to hepatitis B virus and human immunodeficiency virus: a comparative risk analysis.

Health care workers have expressed concern regarding the risk of infection from patients with AIDS. Much less attention is given to the possibility of exposure to patients infected with the hepatitis B virus. This article reviews the data on the probability of exposure to HIV or hepatitis B and subsequent seroconversion, as well as the mortality and morbidity rates associated with both viruses. A decision-analytic analysis of the occupational risk for HIV and hepatitis B is also presented. This model indicates that quality-adjusted loss in life expectancy is greater after percutaneous exposure to a patient who is seropositive for the hepatitis B e antigen than after exposure to a patient with symptomatic HIV infection.

Blood-Borne Pathogens↗
PubMed1995

Molecular epidemiology of hepatitis B virus vaccine variants in Singapore.

Perinatal infection with variants of hepatitis B virus occurs despite combined immunoprophylaxis with hepatitis B immunoglobulin and currently licensed plasma-derived and recombinant yeast hepatitis B vaccines. Several variants have been detected during a large study of infants born to carrier mothers in Singapore. The most frequent variant was a virus in which a single amino acid substitution Gly to Arg occurred at amino acid position 145 of the outer protein coat of the virus. Similar mutations have been described in Italy, Japan, the USA and a number of other countries. The emergence of antibody escape mutants is a cause for concern for the detection of virus and possibly for future immunization programmes.

Amino Acids↗
PubMed1995

Diversity of genotypes of hepatitis C virus in southern India.

A second generation assay for antibody to hepatitis C virus (anti-HCV) was used to screen 78 southern Indian individuals with a high risk of infection. RT-PCR targeted at the 5' end untranslated region (5'UTR) of the HCV genome was used to evaluate evidence of viraemia in 32 anti-HCV positive sera. The PCR products amplified from the 5'UTR of the HCV genome from 24 patients were sequenced, revealing the existence of two distinct groups of sequences: 21 corresponded to HCV type 1 while the other three sequences had 95% to 99% identity to HCV type 3. Two of these three isolates had more than 90% nucleotide identity in the NS5 region to established 3b sequences whereas the other had less than 74% nucleotide identity to any of the published genotype 3 (3a, 3b, 3c, 3d, 3e and 3f) sequences. However, a search of the EMBL nucleotide database revealed 91% identity to the unpublished sequence of an isolate of HCV from Indonesia. We provide evidence that these two isolates may represent a novel subtype within genotype 3. Our data also suggest that HCV genotype 1 predominates over HCV genotype 3 in southern India.

Base Sequence↗
PubMed1995

[Expression of 12 antibody escape mutants of hepatitis B virus surface antigen gene in mammalian cell by using an Epstein-Barr based vector].

A 900bp DNA fragment of hepatitis B virus surface antigen gene by digesting BamHI and HpaI sites on the open reading frame of HBV DNA on plasmid pEcob6 containing double copes of HBV DNA was cloned into SmaI site on the phagmide vector pBluescribt SK +. From this recombinant vector, 12 hepatitis B virus surface antigen gene mutants were obtained by oligonucleotide-mediated site directed mutagenesis. The expression vector-pMEP4HBS mutants are constructed by sub-cloning all of these mutant fragments of hepatitis B virus surface antigen gene on pBluescritSK+HBSM into BsmHI and KpnI sites on an Epstein-Barr virus based on eukaryotic expression vector-pMEp4. The vector pMEp4HBSMs were transfected to human hepatocellular carcinoma cell line-HepG2 by calcium phosphate mediated transfection, and resistant cell clones were obtained 3 weeks after selecting by hygromycine B. The results of detection of HBsAg excreted by resistant cell clones with monoclonal antibody to HBsAg showed that all antibody escape mutants of HBsAg except mutant 145R, a substitution of arginine for glycine at amino acid 145 position in HBsAg, were positive.

Carcinoma, Hepatocellular↗
PubMed1995

Prospects for hepatitis C vaccine.

The genetic and serological heterogeneity of hepatitis C virus and reinfections will make the development of a broad spectrum effective hepatitis C vaccine difficult. Important steps are identification of neutralising antibodies; reproducible techniques for tissue culture of HCV; the application of methods used for the development of vaccines against flaviviruses and pestiviruses, and the application of gene transfer techniques.

Animals↗
PubMed1994

Southern hybridisation analysis of HBV DNA in peripheral blood leucocytes and of different cell types: changes during the natural history and with interferon-alpha therapy in patients with hepatitis B virus infection.

Hepatitis B virus (HBV) DNA was evaluated in peripheral blood mononuclear cells (PBMC) from 50 individuals utilising Southern hybridisation analysis. HBV DNA sequences were detected in PBMC from 16/29 (55 percent) of chronic hepatitis B virus (HBV) carriers with serum HBeAg and HBV DNA, compared with 1/8 (13%) of carriers with anti-HBe and HBV DNA negative (P = NS). Two of 7 patients with previous HBV infection and chronic liver disease had detectable HBV DNA in PBMC. Of the 19 patients with HBV DNA in PBMC, 18 had high molecular weight species. In addition, five of these had free, monomeric HBV DNA and six patients had low molecular weight bands. For nine of the above patients, total peripheral blood leucocytes were separated into PBMC and polymorphonuclear cells. Four had HBV DNA in PBMC only, two only in polymorphonuclear cells and three in both types of cell. Eleven patients with chronic HBV infection were studied at monthly intervals for 6 months. Six were untreated and five received IFN-alpha. Three patients who responded to IFN-alpha had HBV DNA present in PBMC before therapy, and two became negative. Two of 3 untreated patients had intermittent HBV DNA in PBMC and the other remained persistently negative. Of the patients positive on more than one occasion, the pattern of HBV DNA was similar. Peripheral blood leucocytes often contain multimers of free HBV DNA, more commonly in patients with serum HBeAg and HBV DNA and may occur even in the absence of serum HBsAg. These findings have implications for recurrence of disease after hepatic transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗
PubMed1994

Review: protective efficacy of hepatitis B vaccines in neonates.

A literature search was carried out to investigate the factors that influence the protective efficacy (PE) of hepatitis B vaccines when given to neonates of hepatitis B surface antigen and e antigen positive mothers. Hepatitis B vaccines with either high or low antigen doses are very effective in preventing chronic hepatitis B infection in neonates at risk, but there is evidence that with lower dosages simultaneous use of hepatitis B immune globulin (HBIG) administration is more important than with higher dosages to elicit good protection (PE > or = 90%). There is also a tendency for lower dosages to confer high PE less consistently, with noticeably greater numbers of chronic surface antigen carriers in neonates who received a complete vaccination course. Furthermore vaccination courses with higher vaccine dosages give high PEs, without concomitant HBIG administration at birth, provided that the first vaccine dose is given at birth and that the second dose follows within 2 months.

Dose-Response Relationship, Immunologic↗
PubMed1994

Diagnosis of hepatitis C virus-associated chronic liver disease in India: comparison of HCV antibody assay with a polymerase chain reaction for the 5' noncoding region.

The relative value of an anti-hepatitis C virus (HCV) serological assay and reverse transcriptase-nested polymerase chain reaction assays (RT-PCR) were investigated for the constant 5' putative noncoding region of HCV for the diagnosis of HCV-associated chronic liver diseases in India. One hundred fifteen patients with biopsy proven chronic active hepatitis and 140 cases of cirrhosis of the liver were investigated for anti-HCV antibody using a second generation commercial enzyme-linked immunosorbent assay (ELISA). A proportion of these patients: 42 with chronic hepatitis and 27 with cirrhosis of the liver were analysed further for HCV RNA in the serum using RT-nested PCR assay. Thirty-three (12.9%) of the 255 patients were positive for anti-HCV antibody and 23 of 69 (33.3%) patients were positive for HCV RNA in serum. Fifteen of the 33 (45.5%) anti-HCV positive patients had HCV RNA in the serum. Eight of 36 (22.2%) HCV seronegative patients tested were found with HCV RNA. This indicates that the diagnosis of HCV infection is not possible if it is based solely on the available serodiagnostic tests. Inclusion of both assays improved the diagnostic efficiency, 18.8% (13/69) were negative for all virological markers associated with HBV and HCV infection. Since a majority of the chronic liver disease patients (143/255 [56%]) were seronegative for either HBV or HCV infection, it is significant that HCV RNA was detected in 38% (8/21) of a randomly selected group from these patients. The antibody assay and PCR were compared using interclass correlation (kappa statistics).(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

A long-term follow-up of hepatitis B vaccination in patients with congenital clotting disorders.

All patients with congenital clotting disorders attending our centre routinely receive hepatitis B vaccination. We have assessed retrospectively the vaccine responses in 167 such individuals, with a follow-up period of up to 7.5 years. The initial postvaccine anti-HBs response was lower in older patients (p = 0.001), those infected with human immunodeficiency virus (HIV) (p = 0.05), and those who received intradermal rather than subcutaneous administration of vaccine (p = 0.08). It was estimated that the median time for anti-HBs levels to fall to 100 IU l-1 was between 36 and 42 months, with a shorter period for older or HIV-infected patients. Although the persistence of protective antibody levels can be predicted to some extent from the absolute levels of initial postvaccine anti-HBs, the wide variation in antibody decline between individuals precludes recommendation of the timing of vaccine booster doses solely based on this value.

Adolescent↗
PubMed1994

Analysis of integrated hepatitis B virus DNA and flanking cellular sequences in the hepatocellular carcinoma cell line HCC36.

A hepatocellular carcinoma cell line, HCC36, was established from an adult HBV carrier in Taiwan. From Southern blot analysis, there were at least four sites of integration of HBV DNA, and no viral replicative intermediates were detected. A genomic library was constructed from HCC36 DNA, and two phage clones, designated lambda 36A and lambda 36B, were shown to contain HBV DNA and flanking cellular sequences. In lambda 36A, HBV DNA sequences were quite conserved, and 7.4% base variation was detected. The viral sequences in lambda 36A and lambda 36B differed in only four bases, in addition to the microdeletion and -insertion observed in lambda 36B. The flanking cellular sequences identified in lambda 36A were human Alu sequences and in lambda 36B satellite sequences.

Base Sequence↗
PubMed1993

Preparation and immunogenicity of an inactivated hepatitis A vaccine.

A hepatitis A vaccine was prepared by formaldehyde inactivation of purified hepatitis A virus (HAV) LSH/S strain grown on human diploid MRC-5 cells. The vaccine was devoid of residual infectivity in vitro and failed to induce in marmoset monkeys any pathological features or variations of haematological and clinical chemistry values. Infectious HAV particles were not detected in faeces and sera of the vaccinated primates by ELISA or after passages in MRC-5 cells. The immunogenicity of the vaccine was evaluated by injecting guinea-pigs with 0.8, 0.2 or 0.05 micrograms of HAV antigen adsorbed onto 0.5 and 1 mg of Al (OH)3 or 0.3 mg of AlPO4. The antibody response, measured by a competitive radioimmunoassay, was dose- and adjuvant-dependent. One injection of 0.2 micrograms of AlPO4-adsorbed HAV antigen induced seroconversion in 100% of animals and high levels of specific and neutralizing serum antibodies. A further increase of antibody titres was observed after the second and third inoculations. These results show that this vaccine formulation is safe and immunogenic in animal models, and suggest that it should be evaluated further by human clinical studies.

Adjuvants, Immunologic↗
PubMed1993

Treatment of chronic viral hepatitis.

A substantial number of anti-viral compounds have been evaluated for the treatment of patients with chronic viral hepatitis. A few of these compounds have now achieved clinical applicability. alpha-Interferon is the most widely studied and remains the main treatment for chronic hepatitis B and C. Unfortunately in both these conditions only a minority of patients respond to interferon therapy, although the response can be complete in some patients. Some parameters have been identified which assist in the selection of patients for treatment. Several other cytokines, including thymosin, have been evaluated for the treatment of chronic hepatitis B. There are a number of promising new nucleosides which may inhibit hepatitis B virus and their action is being studied. Relapse rates are unknown however with these compounds. Ribavirin, a guanosine analogue, is also efficacious in treating a proportion of patients with chronic hepatitis C and the drug may be useful in treating patients with cirrhosis or patients who have an auto-immune diathesis.

Acute Disease↗
PubMed1993

Viral hepatitis.

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Genome, Viral↗
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↗