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Biomedical subjects

L Sweetman

Publications and source records attributed to L Sweetman.

At least 163 records · Page 9Linked to original sources

Determination of plaque inhibitory activity of adenine arabinoside (9-beta-D-arabinofuranosyladenine) for herpesviruses using an adenosine deaminase inhibitor.

The in vitro susceptibility of type 1 and type 2 strains of Herpesvirus hominis to 9-beta-d-arabinofuranosyladenine (adenine arabinoside, ara-A) was measured in a system where deamination was inhibited. Under these conditions, it was possible to measure the activity of low concentrations of ara-A. It was determined that plaque inhibitory concentration for type 1 viruses was less than 3 mug/ml for all strains tested. The plaque inhibitory concentration for 7 of 10 type 2 strains was also less than 3 mug/ml. The method used identified and controlled the interaction between antiviral agent (ara-A) and the indicator system, human skin fibroblastic cells. Otherwise, metabolism of ara-A resulted in rapid enzymatic degradation and loss of antiviral activity.

Adenosine Deaminase Inhibitors↗

Effect of adenosine deaminase upon the antiviral activity in vitro of adenine arabinoside for vaccinia virus.

This study determined that the effect of 9-beta-d-arabinofuranosyl-adenine (adenine arabinoside, Ara-A) upon vaccinia virus plaque development in the stable monkey kidney line, LLC-MK(2), was increased approximately 40-fold when an inhibitor of adenosine deaminase (ADA) was added to the tissue culture media along with infective inocula. The concentration of Ara-A required to completely suppress plaque development (total plaque inhibitory concentration(100); TPIC(100)) was greater than 10 mug/ml. However, when ADA activity was inhibited, the TPIC(100) was 0.5 mug/ml or less. Chromatographic assay of arabinosylpurines in the media provided evidence that adenine arabinoside was rapidly deaminated to 9-beta-d-arabinofuranosylhypoxanthine by the cellular monolayers, in the absence of animal serum, and that the rate of deamination, at 5 mug/ml, by the cells was equal to the rate of diffusion of Ara-A across the cellular membrane. The half-life of Ara-A in the media, starting with 5 mug/ml, was 2 to 3 h and shorter at lower concentrations. The study demonstrates the profound effect that an indicator system, acting as an intact biological unit, can have upon a potential antiviral compound.

Adenosine Deaminase↗

Chemical analysis of succinylacetone and 4-hydroxyphenyllactate in amniotic fluid using selective ion monitoring.

A method for the measurement of the concentration of succinylacetone and 4-hydroxyphenyllactic acid in amniotic fluid was developed for the prenatal diagnosis of hereditary tyrosinemia. Succinylacetone was converted to 5-methyl-3-isoxazolepropionic acid and isolated with 4-hydroxyphenyllactic acid by liquid partition chromatography and the trimethylsilyl derivatives quantified by ammonia chemical ionization selected ion monitoring gas chromatography-mass spectrometry with 2-hydroxy-n-caproic acid as the internal standard. The concentration of 4-hydroxyphenyllactic acid in normal amniotic fluid was 1.97 +/- 0.75 (S.D.) mumol/l while succinylacetone was undetectable. A pregnancy at risk for tyrosinemia type II was monitored. The concentration of 4-hydroxyphenyllactic acid was within the normal range and a healthy child was born.

Amino Acid Metabolism, Inborn Errors↗