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S R Slater

Publications and source records attributed to S R Slater.

7 recordsLinked to original sources
PubMed2004

Genetic and phenotypic analysis of biofilm phenotypic variation in multiple Staphylococcus epidermidis isolates.

Production of biofilm in Staphylococcus epidermidis is mediated through enzymes produced by the four-gene operon ica and is subject to phenotypic variation. The purpose of these experiments was to investigate the regulation of ica and icaR transcription in phenotypic variants produced by multiple unrelated isolates of S. epidermidis. Ten isolates were chosen for the study, four of which contained IS256. IS256 mediates a reversible inactivation of ica in approximately 30 % of phenotypic variants. All ten strains produced at least two types of phenotypic variant (intermediate and smooth) in which biofilm formation was significantly impaired. Reversion studies indicated that all phenotypic variants were stable after overnight growth, but began to revert to other phenotypic forms after 5 days of incubation at 37 degrees C. ica transcriptional analysis was performed on phenotypic variants from three IS256-negative isolates; 1457, SE5 and 14765. This analysis demonstrated that ica transcription was significantly reduced in the majority of phenotypic variants, although two variants from SE5 and 1457 produced wild-type quantities of ica transcript. Analysis of seven additional phenotypic variants from SE5 revealed that ica expression was only reduced in three. Expression of icaR transcript was unaffected in all smooth phenotypic variants. Mutations within ica were identified in two SE5 variants with wild-type levels of ica transcription. It is concluded that mutation and transcriptional regulation of ica are the primary mechanisms that govern phenotypic variation of biofilm formation within IS256-negative S. epidermidis.

Bacterial Proteins↗
PubMed1992

Reproduction toxicity studies with pamidronate.

Peroral Segment I, II and III reproduction toxicity studies in rats and peroral Segment II studies in rabbits were conducted with pamidronate (disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate, CGP 23339 A, CAS 57248-88-1). In addition, intravenous Segment II studies were carried out in rats and rabbits. Only about 2% of a peroral dose of pamidronate is absorbed from the gastro-intestinal tract. However, with both modes of administration, it was evident that after equivalent dosing peroral and parenteral studies yielded similar results. The most relevant consistent findings in the rat were failure of the dams to complete and/or survive a protracted parturition and a reduced number of viable pups. There was evidence that the distressed state of the dams shortly before parturition was associated with acutely reduced serum calcium concentrations. In both species, at daily doses about ten times higher than the recommended human therapeutic dose, maternal toxicity, embryolethality or severe general underdevelopment and a marked skeletal retardation of the fetuses were observed. There was no evidence that pamidronate has a teratogenic potential, nor did it affect reproductive performance. Nevertheless, in view of the effects of pamidronate on parturition and the fact that it crosses the placenta and binds to fetal bone, use of the drug in pregnancy should be avoided unless there is a life-saving medical need.

Administration, Oral↗
PubMed1992

Metabolic studies in kidney stone disease.

Patients with kidney stones (n = 59) and healthy controls (n = 31) collected a 24-hour urine sample and later underwent a 6-hour 'fast and load' test in which an oral calcium load was taken after 2 hours. In the 24-hour urine sample, mean calcium excretion was higher in patients than controls, while mean urate, oxalate and citrate levels were similar. The patients had higher levels of fasting plasma calcium, serum calcitriol and fasting urinary calcium, and lower levels of plasma phosphate than did the controls. Following the calcium load, plasma and urinary calcium increased similarly in both groups. Serum parathyroid hormone (PTH) levels were similar in both groups and decreased similarly following the calcium load. Multiple linear regression, relating the presence or absence of stone formation to all variables, found the only variables significantly related to stone formation to be plasma levels of calcium (p less than 0.001) and phosphate (p = 0.001) and fasting urinary urea (p less than 0.001), and 24-hour urinary calcium excretion (p less than 0.05). Urinary oxalate and citrate were not related to stone formation. The data do not support the hypothesis that primary stimulation by calcitriol produces a normal fasting plasma calcium level, with an exaggerated increase after an oral calcium load. The findings instead suggest an abnormality of parathyroid cell 'set point', such that PTH secretion continues until the plasma calcium level is a little higher and the phosphate a little lower than in controls.

Adult↗
PubMedDate not supplied

Estrogen-receptor binding and biologic activity of tamoxifen and its metabolites.

In female patients treated with tamoxifen (T), the major metabolite of T in serum is N-desmethyltamoxifen (N-d-Me T). The serum concentration of d-Me T may equal or exceed that of T, and 4-hydroxytamoxifen (4-OH T) is present in much lower concentration (< 10% that of T). The biologic properties and estrogen-receptor binding affinity of T and its desmethyl and 4-hydroxy metabolites have been compared. In competition studies with the rat uterus estrogen receptor at 0 degrees C and 25 degrees C, the relative affinities of T and d-Me T were similar, and their apparent affinity decreased when the incubation temperature was increased (38.2, 21.0 and 1.8, 1.1, respectively at 0 degrees C and 25 degrees C; 17 beta-estradiol = 100). In contrast, 4-OH T was a more potent inhibitor of estradiol binding (110 and 188 at 0 degrees C and 25 degrees C and its apparent affinity increased, rather than decreased, when the incubation temperature was raised from 0 degrees C to 25 degrees C. These differences in receptor binding were not reflected in biologic activity; all three compounds were potent antiestrogens of approximately equal activity in the rat. In patients, the pharmacologic effect of T may be due, in part, to d-Me T, but it is unlikely that 4-OH T plays a major role because of its relatively low serum concentration. The antiestrogenic potencies of T, d-Me T, and 4-OH T are similar, so the extent of metabolism in individual patients is unlikely to influence clinical response to tamoxifen therapy.

Animals↗