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Biomedical subjects

J T Smith

Publications and source records attributed to J T Smith.

At least 163 records · Page 9Linked to original sources

The effect of a plasmid on growth and survival of E. coli.

We studied the growth characteristics of a pair of Escherichia coli strains, isogenic apart from the possession of a nonconjugative plasmid. There was no difference between the two strains when they were grown separately. In mixed culture, a second slow phase of growth that normally occurred following the end of rapid exponential growth, was absent from the plasmid-carrying strain. This resulted in a considerable decrease in the proportion of the cells that carried the plasmid after overnight incubation. The effect of different conditions of growth is reported. The plasmid-carrying strain survived extended incubation (150 days at 37 degrees C) as well as did the plasmid free strain separately. In a mixture, the proportion of plasmid-carrying cells declined rapidly, and none was detected after 100 days.

Cell Division↗

Types of beta-lactamase determined by plasmids in gram-negative bacteria.

Two species of beta-lactamase determined by plasmids in enteric bacteria that show some resemblance to TEM enzymes are described. Both are distinct from all other plasmid-mediated beta-lactamases and differ from the TEM beta-lactamases in ability to hydrolyze some substrates, in isoelectric point, in immunological specificity, and in susceptibility to inhibition. One of the enzyme species, mediated by plasmid p453, has been briefly described previously. We have discovered that this beta-lactamase, designated SHV-1, is unique in its response to inhibition by the sulfhydryl group reagent p-chloromercuribenzoate, because the hydrolysis of cephaloridine but not that of benzylpenicillin is affected. This enzyme is found in a variety of plasmid types which were transferred from several bacterial species collected from a wide geographic range. The other enzyme species is novel; only a single plasmid determining this kind of beta-lactamase (designated HMS-1) has been detected.

Cephalosporins↗

Teaching "street law" to the criminally insane.

A course in "Street Law" was taught to forensic patients by law students, following a format used by Georgetown University Law Center. Although the course has been taught to high school students and inmates of correctional facilities, this was the first time it has been extended to mental patients found not guilty of crimes by reason of insanity. An outstanding feature of the course was marked enthusiasm shown by patients who, through long institutionalization, had become apathetic, indifferent, and despairing. Their readiness and ability to learn brought to mind a couple of old sayings often heard around mental hospitals, "I may be crazy but I'm not stupid," and "Sometimes you can't tell the patients from the staff." The staff of at least one ward has picked up "teaching and learning to use as a central theme in treatment of patients, not abandoning traditional methods, but shifting the emphasis from therapy to teaching as a way of getting the patient's interest in his own rehabilitation. Judges, reviewing cases for release, have looked quizzical when the patients' active participation in a "law course" has been used as evidence of satisfactory progress.

Criminal Law↗

R-factor mediated dihydrofolate reductases which confer trimethoprim resistance.

Six different R-factors conferring trimethoprim resistance had been isolated from a variety of sources. The trimethoprim-resistant dihydrofolate reductases (EC 1.5.1.3) from strains containing these R-factors were purified by ammonium sulphate precipitation and DEAE-cellulose ion-exchange chromatography. The enzymes showed no significant differences in molecular weight, pH profile, substrate profile, heat sensitivity, inhibition profile and Michaelis-Menten kinetics. There was, however, considerable variation in the specific activity of these enzymes in the same bacterial host. When two Escherichia coli trimethoprimsensitive dihydrofolate reductases were examined as controls, considerable differences between their properties and those of the enzymes mediated by R-factors were detected. The data suggest that one trimethoprim resistance gene could be spreading through the bacterial population, possibly situated on a transposon.

Escherichia coli↗

R-factor mediated trimethoprim resistance: result of two three-month clinical surveys.

All urinary tract isolates were monitored in the Whittington Hospital, London for trimethoprim resistance over a three-month period in 1975; this survey was repeated 18 months later in 1977. In the later survey the incidence of trimethoprim resistance had increased significantly, and the proportion of strains carrying R-factors conferring trimethoprim resistance had nearly doubled. The pattern of resistances associated with R-factor trimethoprim resistance also changed betweeen these two surveys.

Bacteria↗

Curing of an R factor from Escherichia coli by hydroxyurea and cytosine arabinoside.

Hydroxyurea (HU) and cytosine arabinoside (Ara-C) eliminate R factor R46 from Escherichia coli strain J5-3. The highest frequency of elimination for both drugs occurred at concentrations and times that produced the lowest survivor levels. 5% of cells were antibiotic-sensitive after 5 h incubation in 5 mg/ml Ara-C, whilst 6 and 7% of the survivors had lost the R factor after 8 and 24 h incubation, respectively in 20 mg/ml HU. The number of survivors began to increase after 5 h incubation in Ara-C, probably due to the inactivation of the drug in the phosphate-buffered medium. All four antibiotic resistances (ampicillin, streptomycin, sulphonamide and tetracycline) mediated by R46 were lost simultaneously and elimination of the whole plasmid was confirmed by conjugation experiments in which the 'cured' cells was shown to be as efficient recipients of R46 as the control R- strain in crosses with E. coli strain J6-2 (R46). No covalently closed circular plasmid DNA was demonstrable in cured cell lines. R+ and R- strains had similar sensitivities to HU but J5-3 R+ was much more sensitive to Ara-C than the isogenic R- strain. It may be concluded that HU eliminates R46 actively whereas although Ara-C may produce some active elimination it acts mainly by selection of R- cells present in the culture.

Culture Media↗