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Biomedical subjects

S Greer

Publications and source records attributed to S Greer.

At least 109 records · Page 6Linked to original sources
PubMed1976

Enzymatic basis for the selective inhibition of varicella-zoster virus by 5-halogenated analogues of deoxycytidine.

5-Bromodeoxycytidine (BrdC) and 5-iododeoxycytidine, at a concentration of 100 mug/ml, effectively inhibit the replication of varicella-zoster (VZ) virus in tissue culture. No toxicity could be demonstrated in uninfected cells under the same conditions. Studies on the enzymatic basis for this selective inhibition were undertaken. Infection of human embryonic lung cell monolayers with VZ virus-infected cells results in the induction of thymidine (dT), deoxycytidine (dC), and BrdC kinase activities (which are increased 10-, 40-, and 60-fold, respectively) and in a 70-fold stimulation in the incorporation of 3H nucleotide (5-bromodeoxyuridylate) derived from BrdC into DNA. The thermal stability of the VZ virus-induced activities differs significantly from the activities induced by herpes simplex virus type 1 and herpes simplex virus type 2 and those present in uninfected human embryonic lung cells. The VZ virus-induced dT, dC, and BrdC kinase are similarly affected by temperature and cofractionate upon Sephadex gel filtration, findings consistent with the hypothesis that these activities are the function of a single enzyme: a pyrimidine deoxyribonucleoside kinase. The molecular weight, calculated on the basis of the elution pattern on Sephadex G-150, is 70,000. Kinetic studies, demonstrating that dT and dC competively inhibit the phosphorylation of BrdC, are consistent with the phosphorylation of these substrates at a common active site. Kinetic parameters include: KidT = 0.6 MUM; KidC = 60 muM; KmBrdC = 8.5 muM. In contrast to its relatively high affinity for the VZ virus-induced kinase, BrdC is a relatively poor substrate for the host kinases. Therefore, the basis for the selective inhibition of VZ virus by 5-halogenated analogues of dC is reflected in the induction of a pyrimidine deoxyribonucleoside kinase with a high affinity for BrdC.

Bromodeoxycytidine↗
PubMed1973

Threonine synthetase-catalyzed conversion of phosphohomoserine to alpha-ketobutyrate in Bacillus subtilis.

An enzyme activity of Bacillus subtilis has been found that catalyzes the dephosphorylation and deamination of phosphohomoserine to alpha-ketobutyrate, resulting in a bypass of threonine in isoleucine biosynthesis. In crude extracts of a strain deficient in the biosynthetic isoleucine-inhibitable threonine dehydratase, phosphohomoserine was converted to alpha-ketobutyrate. Phosphohomoserine conversion to alpha-ketobutyrate was shown not to involve a threonine intermediate. Single mutational events affecting threonine synthetase also affected the phosphohomoserine-deaminating activity, suggesting that the deamination of phosphohomoserine was catalyzed by the threonine synthetase enzyme. It was demonstrated in vivo, in a strain deficient in the biosynthetic threonine dehydratase, that isoleucine was synthesized from homoserine without intermediate formation of threonine.

Aminohydrolases↗
PubMed1971

Effect of psychiatric intervention in attempted suicide: a controlled study.

All patients presenting at the casualty department of King's College Hospital during the first six months of 1968 with deliberate self-poisoning or self-injury were followed up. Of 211 patients 204 (97%) were traced after a mean interval of 18 months (range one to two years). Despite official hospital policy, 22% had not been seen by a psychiatrist before discharge; these 44 untreated patients were compared with the remaining 160 who had received either brief (one or two interviews) or more prolonged psychiatric and social help.Subsequent suicidal attempts occurred significantly more often among untreated than among treated patients, prolonged treatment being associated with the best prognosis. The same trend was observed in respect of actual suicide, though the numbers were small and differences did not reach statistical significance. These findings held good when the untreated and treated groups were controlled for other variables which were found to be correlated with outcome. These results indicate that psychiatric intervention is associated with a significant reduction in subsequent suicidal behaviour.

Adjustment Disorders↗
PubMed1971

Suppression by derepression in threonine dehydratase-deficient mutants of Bacillus subtilis.

Partial suppressors of isoleucine-requiring mutants (Ile(-)), deficient in threonine dehydratase (TD), were studied. The suppression enables these auxotrophs to grow on the precursors homoserine or threonine as well as isoleucine. There are two genetically distinct classes of these suppressors: sprB, linked to threonine mutational sites, and sprA which is not linked to the Ile or Thr genetic region. SprA leads to the appearance of a low level of TD activity (2 to 4% of wild type) compared to <0.2% in Ile(-) mutants. This new TD activity is not activated by glutathione or adenosine monophosphate. Unlike the major TD, it is insensitive to inhibition by isoleucine and it is not coordinately controlled with dihydroxy acid dehydratase. Another class of auxotrophs, containing no suppressor mutation, can grow on isoleucine and homoserine or threonine because they possess structural gene mutations located near the terminus of the TD gene that result in partial impairment of TD. This TD activity (2% of wild type) is end product inhibited by isoleucine to a lesser extent than wild type TD. In this and a following paper, evidence is presented that sprA acts by derepressing a minor TD activity encoded within the threonine synthetic region. The major TD gene is separated from the region encoding the enzymes of threonine biosynthesis by 73% of the chromosome. Like the major TD, the minor TD catalyzes the first reaction in the conversion of threonine to isoleucine and is therefore closely related biochemically and genetically to the enzymes of the threonine synthetic region.

Adenine Nucleotides↗