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Biomedical subjects

I Gust

Publications and source records attributed to I Gust.

At least 19 recordsLinked to original sources
PubMed1991

A seroepidemiological study of hepatitis B amongst Fiji health care workers.

Hepatitis B immunization for health care workers is common policy in many countries where they constitute a particular at risk group. A seroepidemiological study of hepatitis B virus (HBV) in Fiji health care workers was conducted to determine whether this occupational group (or subgroups thereof) were at higher risk of infection than the general Fiji population. The purpose of this study was to ascertain whether health staff should be immunized, or whether it would be more productive to focus resources on neonatal immunization. Blood samples were obtained from 2,639 health workers and the sera analysed by radio-immunoassay for hepatitis B surface antigen (HBsAg), and hepatitis B surface antibody (anti-HBs). Prevalence rates of HBV markers of infection were compared with those observed in the general population, from a previous population-based cluster sample survey. Approximately 70% of the health care staff participated in the study. Prevalence of total HBV markers was 24%. The rate of HBsAg was 5%. Sex and ethnic group specific prevalence rates varied. Male subjects, Fijians and "other" Pacific Islanders all experienced higher rates of infection. Rural/urban and age related trends were also observed. Rates of infection in health staff were lower than those reported in the general population. Previous studies have indicated that most of the transmission of hepatitis B in hyperemdemic Pacific populations occurs at birth or within the next few years. There was no consistent pattern of hepatitis B infection in different occupational groups of health care workers. Certain relatively socially homogeneous subgroups of health workers were analysed separately, and among these health workers there was evidence for increased risk of infection due to exposure to blood or used hypodermic syringes, but not due to patient contact. Until health staff assume a higher risk of infection than the general Fijian population, efforts directed at community-wide control of hepatitis B continue to be the most appropriate use of resources.

Adolescent↗
PubMed1991

Functional studies of hepatitis delta antigen and delta virus RNA.

We have sequenced an HDV RNA from an acute delta hepatitis patient from the Nauru Islands. By comparison with other HDV sequences previously reported, we have identified three conserved regions: the first one is the sequence around the catalytic cleavage site for genomic-sense RNA; the second is the corresponding site for the antigenomic sense RNA; and the third is the sequence encoding the middle domain of the hepatitis delta antigen. We have shown that the middle domain of the delta antigen can bind specifically to the HDV RNA. This binding was demonstrated both in vitro and in the purified virion. It was suggested that this RNA-protein interaction is important for HDV RNA replication. We also suggest that the conserved sequences provide ideal primers for use in polymerase chain reaction (PCR) in clinical diagnosis of HDV infections. We recommend the use of nucleotides 870-900 and 690-720 (Makino et al., 1987a) as primers for routine screening.

Amino Acid Sequence↗
PubMed1990

Antiviral strategies in chronic hepatitis B virus infection: I. Establishment of an in vitro system using the duck hepatitis B virus model.

Primary duck hepatocyte (PDH) cultures were established from ducklings congenitally infected with the duck hepatitis B virus (DHBV), plated onto feeder cell layers of irradiated human embryonic lung fibroblasts, and observed for 2 to 3 weeks. This system permitted the survival of the PDH in a differentiated form free of fibroblastic overgrowth for at least 3 weeks. The hepatocytes were shown to contain all the replicative DNA intermediates found during DHBV replication as well as the DHBV structural proteins PRE-S1, PRE-S2, and S of duck hepatitis B surface antigen (DHBsAg). The pool of supercoiled (SC) DHBV DNA increased dramatically from days 10 to 14 postplating. This PDH-feeder cell layer cell culture model provides a convenient system to study the effects of conventional inhibitors of DHBV replication and compounds targeted at the supercoiled form of DHBV DNA. This approach should allow the evaluation of a variety of strategies for treating chronic carriers of hepadnaviruses.

Animals↗
PubMed1990

Antiviral strategies in chronic hepatitis B virus infection: II. Inhibition of duck hepatitis B virus in vitro using conventional antiviral agents and supercoiled-DNA active compounds.

Primary duck hepatocyte (PDH) cultures, congenitally infected with the duck hepatitis B virus (DHBV), were grown on feeder cell layers of irradiated human embryonic lung fibroblasts and then exposed to a number of compounds with recognized or potential antiviral activity. These compounds included conventional antiviral agents, reverse transcriptase inhibitors, compounds with activity to supercoiled-DNA, and DNA-binding agents. Twenty-three compounds were evaluated, and 13 were found to inhibit significantly viral DNA replication. Seven of these compounds (ellipticine, amsacrine, coumermycin A1, Adriamycin, mitozantrone, chloroquine, and neocarzinostatin) acted at the level of viral SC DNA and significantly inhibited production of duck hepatitis B surface antigen (DHBsAg). Conventional agents that inhibited DHBV DNA replication included ganciclovir, acyclovir, bromovinyldeoxyuridine, ribavirin, phosphonoformate, and dideoxyadenosine. Except for dideoxyadenosine, these inhibitors of viral DNA synthesis did not significantly inhibit DHBsAg production. Two additional compounds, novobiocin and nalidixic acid, altered the pattern of viral DNA replication, especially the generation and processing of viral SC DNA, and also inhibited the production of DHBsAg. Several compounds acting at the level of viral SC DNA have now been identified and may offer potential for the management of chronic hepatitis B virus infection.

Animals↗
PubMed1990

Effect of Phyllanthus amarus on duck hepatitis B virus replication in vivo.

Nine ducks congenitally infected with the duck hepatitis B virus (DHBV) were treated either orally (four ducks for 10 weeks) or intraperitoneally (five ducks for 12 weeks) with the Indian traditional herbal remedy Phyllanthus amarus. Compared to placebo-treated control ducks, these treatments did not result in a reduction of circulating viral DNA in the serum or in the level of viral DNA replication in the liver. In two of the five intraperitoneal-treated ducks, a reduction in the levels of duck hepatitis B surface antigenaemia (DHBsAg) was observed. The data strongly suggest that Phyllanthus amarus has no significant inhibitory effect on DHBV DNA replication and only a minor effect on DHBsAg production.

Animals↗
PubMed1990

Sequence conservation and divergence of hepatitis delta virus RNA.

The complete RNA sequence of the hepatitis delta virus (HDV) obtained from the Nauru Island in the Pacific was determined by cDNA cloning and amplification by polymerase chain reaction (PCR). The sequence showed 14-17% divergence from the two known HDV RNA sequences. There are three highly conserved domains: the region around the autocatalytic cleavage site of the genomic RNA (nucleotides 659 to 772), the region around the autocatalytic cleavage site of the antigenomic-sense RNA (nucleotides 847 to 966), and the region around the middle one-third domain of the open reading frame (ORF) encoding the hepatitis delta antigen on the antigenomic RNA (nucleotides 1267 to 1347). The two autocatalytic activities are required for the cleavage and ligation of HDV RNA during RNA replication. The third conserved domain codes for the RNA-binding domain of HDAg, which specifically interacts with HDV RNA. Three nucleotide changes within the genomic catalytic sequence are present but did not alter the catalytic cleavage activity of the HDV RNA. Microheterogeneity of the RNA sequences was also detected. One of these occurred within the coding region of the delta antigen, creating an amber termination codon in some of the RNA species. Thus, this HDV strain contains two different RNA species, one of which encodes a delta antigen of 214 amino acids and the other 195 amino acids. These two protein species were detected by immunoblotting of the patient's plasma. In contrast to other HDV strains, only three ORFs capable of encoding more than 100 amino acids each are present in this HDV RNA. We recommend that oligonucleotides complementary to the highly conserved sequences should be used as primers for PCR in clinical detection assays of hepatitis delta virus infection.

Adult↗
PubMed1990

Decreased in vitro susceptibility to zidovudine of HIV isolates obtained from patients with AIDS.

This study tested isolates of human immunodeficiency virus, obtained before and after zidovudine therapy from 10 patients, for susceptibility to the drug in vitro. The isolates collected after therapy were less susceptible to zidovudine as assessed by replication in MT-2 cells and production of reverse transcriptase activity by infected mononuclear leucocytes in the presence of the drug. Furthermore, pretherapy isolates were sensitive to a range of zidovudine concentrations when 100% inhibition was used as the end point. The loss of zidovudine susceptibility did not correlate with any clinical or virologic consequences in this small group of patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Factors affecting the prevalence of infection with hepatitis B virus among non-pregnant women in the Alexishafen area of Papua New Guinea.

The prevalence of hepatitis B viral markers was studied in 673 women of childbearing age in 17 villages (12 indigenous and five plantation villages) on the north coast of Papua New Guinea. Some 7.9% of women were HBsAg positive and 41.3% were positive for anti-HBs. There was significant variation in prevalence between villages, ranging from 0 to 13.9% for HBsAg and 26.0 to 71.0% for all markers. The 12 indigenous villages were classified into three groups according to language (Austronesian or non-Austronesian), location (inland or coastal), and marriage patterns. The prevalence of hepatitis B was significantly higher in Austronesian than in non-Austronesian villages (P less than 0.01), and it remained significant after controlling for age differences and for possible effects on prevalence caused by women marrying into the three village groups from other areas. Interactions between malaria and hepatitis B were also investigated. Non-Austronesian villages with the highest spleen rates had the lowest prevalence of hepatitis B infection, and there was no correlation with parasitaemia. These results may reflect a lower exposure of women to hepatitis B infection in non-Austronesian villages, or may indicate different genetic or immunological responses to infection between Austronesians and non-Austronesians.

Adolescent↗
PubMed1989

Hepatitis B infection in Vanuatu: age of acquisition of infection and possible routes of transmission.

Seroepidemiological studies of hepatitis B were carried out on diverse groups of children (477) and adults (629) from the Pacific Island country of Vanuatu. In children under 14 years, prevalences of HBsAg and of all markers were 6% and 53.3% respectively; in adults greater than or equal to 20 years the prevalences were 15% and 70%. Age specific prevalence of hepatitis B infection (all markers) was low in infancy (less than 1 year) but rose sharply afterwards, suggesting that the main mechanism of transmission was horizontal spread. This finding is consistent with other developing country studies from the Pacific Islands and elsewhere. In view of the main ages and mechanisms of transmission of hepatitis B in children in developing countries and the need for simple and inexpensive immunisation strategies in this context, it is recommended that mass vaccination of all infants with hepatitis B vaccine be undertaken in hyperendemic areas.

Adolescent↗