PubMed Health⌕ Search

Biomedical subjects

M J Fowler

Publications and source records attributed to M J Fowler.

31 records · Page 2Linked to original sources

Failure to detect nucleic acid homology between some non-A, non-B viruses and hepatitis B virus DNA.

Some studies suggest that there is antigenic and nucleic acid homology of one type of non-A, non-B hepatitis virus with hepatitis B viral (HBV) proteins and DNA. Using molecular hybridization under high and low stringency conditions with high specific activity 32P-HBV DNA as a probe, serum and liver samples from patients and nonhuman primates infected with non-A, non-B hepatitis were examined. Our results provide no evidence of significant homology between the DNA extracted from serum and liver of patients and nonhuman primates infected with one type of non-A, non-B hepatitis and HBV DNA.

Animals↗

Acyclovir in hepatitis B antigen-positive chronic liver disease: inhibition of viral replication and transient renal impairment with iv bolus administration.

Six patients with hepatitis B virus (HBV) related chronic liver disease were treated with acyclovir, 5-15 mg/kg 8 hourly, given as an iv bolus or iv infusion over 1 h for up to 7 days. Two patients treated with 10 and 15 mg/kg 8 hourly showed a decrease in HBV-DNA polymerase and HBV-DNA when mean trough acyclovir plasma concentrations of 5.0 +/- 0.6 and 13.2 +/- 3.0 microM were attained. Inhibition of viral replication was not seen in patients treated with lower doses. Transient renal impairment was seen in two patients who received high dosage by the iv bolus mode of administration. This complication may be prevented by a high oral fluid intake or iv infusion of the drug over 1 h. Further study with acyclovir 15 mg/kg 8-hourly given as an iv infusion for longer periods is warranted.

Acyclovir↗

Defective hepatitis B virus DNA molecules detected in a stable integration pattern in a hepatoma cell line, and in induced tumours and derived cell lines.

Hepatitis B virus (HBV) DNA was found to be integrated into seven sites in the DNA of the PLC/PRF/5 hepatoma cell line as determined by digestion with the restriction endonuclease HindIII which does not cut through the viral genome. The integration pattern was stable in the cell line, in tumours induced in athymic mice by this line and in cell lines derived from such tumours. Syntheses of hepatitis B surface antigen and alphafoetoprotein were maintained in the induced tumours and derived cell lines. A defective HBV DNA molecule (approx. 2.8 kilobase pairs) appears to be integrated in a head-to-tail tandem arrangement and it is proposed that such defective molecules may be involved in the process of neoplastic transformation by HBV.

Animals↗

Relationship between HBV-specific DNA polymerase and HBe antigen/antibody system in chronic HBV infection: factors determining selection of patients and outcome of antiviral therapy.

The sera of 23% of HBe antigen positive patients with chronic hepatitis are HBV-DNA polymerase negative. These patients are probably undergoing spontaneous seroconversion from a state of high to low viral replication and do not require antiviral therapy. In chronic HBV infection rapid changes in viral replication as a result of antiviral therapy are reflected by changes in HBV-DNA and HBV-DNA polymerase but not by changes in HBe antigen concentrations. Disappearance of HBe antigen from serum may be delayed for 180 days after permanent inhibition of HBV replication with adenine arabinoside or its monophosphate derivative.

DNA-Directed DNA Polymerase↗

Analysis of hepatitis virus DNA in the liver and serum of HBe antigen positive chimpanzee carriers.

Hepatitis B viral DNA present in the liver of HBe antigen positive chimpanzee carriers is in the form of viral molecules (3.2 Kb) and no integration into host DNA was observed. The 3.2 Kb form was not detected in the serum. Other discrete HBV DNA species with faster mobilities than the major 3.2 Kb were consistently detected both in the liver and in the serum and their possible significance is discussed.

Animals↗

The detection of HBV-DNA in serum by molecular hybridisation: a more sensitive method for the detection of complete HBV particles.

Existing methods for detecting complete virus particles in the serum of patients with chronic HBV infection are either insensitive or indirect. A method is described in which Dane particle-associated DNA is extracted from a small volume of serum and detected by molecular hybridization using 32P-labeled cloned HBV-DNA or HBV-DNA extracted from the serum of an immunosuppressed patient, followed by autoradiography and densitometry. There was a positive correlation between the amount of HBV-DNA detected using HBV particle-derived and cloned HBV-DNA probes. The amount of HBV-DNA detected in serum samples showed a positive correlation with the HBV-DNA polymerase. The method was more sensitive than the DNA polymerase and HBeAg assays in detecting complete virus particles. It may be useful in determining the level of infectivity in patients and in monitoring response to antiviral therapy.

Cloning, Molecular↗

Successful treatment of HBs and HBeAg positive chronic liver disease: prolonged inhibition of viral replication by highly soluble adenine arabinoside 5'-monophosphate (ARA-AMP).

In eight HBs and HBe antigen positive patients with chronic active liver disease, adenine arabinoside 5'-monophosphate (ARA-AMP) given, intravenously or intramuscularly, six or 12 hours, produced inhibition of viral replication. In five patients given a short course of therapy with 10 or 15 mg/kg/day this effect was transient and in two thrombocytopenia occurred. In three further consecutive cases given a longer course with 5 mg/kg/day after five days of the high dose, thrombocytopenia was not seen and inhibition of viral replication for up to 13 months occurred. These patients lost HBV-DNA polymerase activity, serum viral DNA and HBeAg, developed anti-HBe, and HBsAg concentrations decreased. A course of twice daily intramuscular ARA-AMP given for three to five weeks as an outpatient may be expected to produce a long-term reduction in infectivity.

Adult↗

Sleep and memory.

Two experiments demonstrated that memory over an interval with relatively high amounts of rapid eye movement (REM) sleep was inferior to memory over an interval with relatively high amounts of stage 4 sleep. The results suggest that, at least for humans, REM sleep does not facilitate memory consolidation and that stage 4 sleep may be beneficial to memory.

Adult↗

Natural history of chronic hepatitis B virus infection in Taiwan: studies of hepatitis B virus DNA in serum.

Hepatitis B virus DNA (HBV DNA) in serum was measured by a Spot hybridization technique in a consecutive series of 79 cases with chronic HBV infection from Taiwan. HBV DNA was found in 96.3% (52/54) of HBeAg-positive, 66% (2/3) with neither HBeAg or anti-HBe and in 63.6% (14/22) of anti-HBe positive patients. The levels of HBV DNA in the HBe-Ag-positive patients were significantly higher than in the anti-HBe positive patients (median, 944 vs. 58 pg per ml, p less than 0.001). The mean ages increased from 28.7 years for the cases with high levels of HBV DNA, to 34.7 years for those with low levels (p less than 0.01) and to 41.0 years in those without HBV DNA in serum (p less than 0.05 when compared with those with low level of HBV DNA). Ninety per cent of patients (27/30) with high levels of HBV DNA showed only minor hepatic inflammatory activity, as did 91% (10/11) of those without HBV DNA. In contrast, histologic signs of chronic active hepatitis or chronic lobular hepatitis were demonstrated in 76% of cases (29/38) with low levels of HBV DNA. These data are consistent with the hypothesis that liver damage occurs during the period of clearance of hepatocytes supporting HBV replication, and are inconsistent with the view that HBV may be directly cytopathic. Thus, the natural history of chronic HBV infection may be divided into three phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗