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Biomedical subjects

M J Browne

Publications and source records attributed to M J Browne.

48 records · Page 3Linked to original sources

Comparative inhibition of influenza and parainfluenza virus replication by ribavirin in MDCK cells.

Actinomycin D inhibited the yield of influenza virus hemagglutinin from MDCK cells infected at high multiplicity, but had little effect on the yield of parainfluenza virus hemagglutinin. In similar hemagglutinin yield experiments, ribavirin was only slightly more active (threefold) against influenza virus than against parainfluenza virus replication. In plaque inhibition experiments, ribavirin depressed influenza virus plaque formation by 50% at a concentration of approximately 3 micrograms/ml, whereas the corresponding figure for parainfluenza viruses was threefold higher. The concentration of ribavirin demonstrating anti-influenza activity was indistinguishable for that inhibiting host cell growth. It is concluded that, unlike actinomycin D, ribavirin is unlikely to have a major effect on the provision of host cell 5-germinal methylated cap structures and the subsequent priming of influenza messenger ribonucleic acid synthesis.

Animals↗

Mechanism and specificity of action of ribavirin.

Ribavirin at a concentration of 30 mug/ml added immediately after infection completely inhibited influenza A/Port Chalmers/1/73 (H(3)N(2)) virus hemagglutinin production in infected MDCK cells. Under these conditions, host cell protein synthesis was inhibited by only 10 to 20%. Polyacrylamide gel electrophoresis of [(35)S]methionine-labeled material from virus-infected cultures confirmed that ribavirin inhibited viral but not host cell protein synthesis. In parallel experiments, actinomycin D also preferentially inhibited viral protein synthesis. The possibility that ribavirin inhibited viral protein synthesis as a result of general inhibition of ribonucleic acid synthesis was therefore examined. In uninfected cells, ribavirin at 30 mug/ml inhibited the incorporation of [(14)C]inosine or [(3)H]uridine into ribonucleic acid but stimulated the incorporation of [(3)H]guanosine. The effects noted are consistent with an inhibition of the host cell enzyme inosine 5'-monophosphate dehydrogenase. This suggestion is supported by the finding that addition of guanosine, but not inosine, to the culture medium substantially reversed the antiviral effect of ribavirin. There was no separation between the concentration of ribavirin causing inhibition of influenza A viral protein synthesis or inhibition of MDCK cell ribonucleic acid synthesis, suggesting that ribavirin is not specifically antiviral in this system but inhibits viral protein synthesis as a result of the general inhibition of ribonucleic acid synthesis.

Animals↗

The sequence specificity of vertebrate DNA methylation.

The relative quantity of 5-methyl cytosine in vertebrate nuclear DNA shows species and tissue variation. To determine whether this is due to the action of species or cell specific DNA methylases the sequence specificity of the 5-methyl cytosine distribution in the DNA of a range of cells has been partially characterised. The pattern of methylation was found to be remarkably constant and indicates stringent evolutionary conservation of the characteristics of vertebrate DNA methylation.

Animals↗

The sequence specificity of a mammalian DNA methylase.

The sequence specificity of an extensively purified DNA methylase preparation from Krebs II mouse ascites cells has been examined. The enzyme appears to be highly sequence dependent. Moreover the sequence distribution of cytosine residues that are methylated, bears a very close resemblance to the sequence distribution of 5'-methyl cytosine found in vivo in a wide range of vertebrate cells and is consistent with methylation of cytosines in the sequence R-Yn-C-R.

Animals↗

Maternal to fetal movement of creatinine as a measure of perfusion efficiency and diffusional transfer in the isolated human placental lobule.

A method employing the maternal to fetal transfer of the slowly diffusing molecule creatinine in the closed-circuit dual perfusion of a term human placental lobule is described. This molecule provides an alternative to the use of antipyrine and is a useful tool in determining the overlap of the two circulations and the available exchange area in this preparation.

Antipyrine↗

Asymmetric information and the demand for Medigap insurance.

The Medigap insurance market has been characterized as having considerable cross-policy variation in contract design and relatively high premiums vis-a-vis average risk exposure. One explanation for these characteristics is that adverse selection exists in the Medigap market. The purpose of this study is to investigate adverse selection effects among those purchasing Medigap insurance. Findings are consistent with the presence of adverse selection in the Medigap market and premium cross-subsidization from low- to high-risk insured individuals.

Health Expenditures↗