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Biomedical subjects

R L Smith

Publications and source records attributed to R L Smith.

At least 505 records · Page 28Linked to original sources
PubMed1981

Prolactin and impotence in diabetes mellitus.

A study was undertake to determine whether impotence in some diabetic patients might be due to a coincidental prolactinoma and therefore be potentially treatable. Of 83 consecutive men attending a diabetic clinic, three were found to have persistent mile to moderate hyperprolactinaemia. None of the three was impotent or taking any drug know to be associated with elevated serum prolactin, and anterior pituitary responses and pituitary fossa tomograms did not reveal any abnormality. The mean serum prolactin concentration of the 37 insulin-treated men was not significantly different from that of the 46 men on diet with or without anti-diabetic tablets, nor was there any significant difference between the mean serum prolactin concentrations of the 19 impotent men and of the 64 non-impotent men.

Adolescent↗
PubMed1980

A study of the vanadate-trapped state of the (Na,K)-ATPase. Evidence against interacting nucleotide site models.

The state of the Na+- and K+-stimulated adenosine triphosphatase ((Na,K)-ATPase) which binds vanadate was investigated by taking advantage of the slow rate of vanadate release (koff = 0.32/h at 25 degrees C and 0.045/h at 4 degrees C). Vanadate release from the enzyme could be accelerated approximately 2-fold by addition of K+ and 50-fold by addition of Na+. The K+ effect saturated hyperbolically with a K1/2 of 0.5 mM, while the Na+ effect had a sigmoidal activation curve and K1/2 of 250 mM. These results indicate that either Na+ or K+ can equilibrate with the vanadate-"trapped" enzyme prior to vanadate release. In the presence of vanadate, a saturable Mn2+ binding site could be detected with a dissociation constant of 120 nM. When 54Mn2+ was added during incubation of the enzyme with vanadate, 1 mol of 54Mn2+ could be trapped/mol of vanadate trapped and the two metals dissociated in parallel. This result indicates a single divalent cation site is involved in stabilizing vanadate (and probably phosphate) binding. Addition of 1 to 4 mM of ATP to the vanadate-trapped enzyme had no affect on the rate of vanadate release. Also, the high affinity ATP site could not be detected in equilibrium-binding studies with the vanadate-trapped enzyme. Since kinetic experiments indicate that vanadate binding is competitive with the low affinity ATP site (Cantley, L. C., Jr., Cantley, L. G., and Josephson, L. (1978) J. Biol. Chem. 253, 7361--7368) and the high affinity ATP site is absent on vanadate-trapped enzyme, it appears unlikely that ATP can occupy either a high or low affinity site on the vanadate-trapped enzyme. We show that nonlinear Lineweaver-Burk plots for ATP hydrolysis can be explained by a single hydrolysis site which exhibits a low affinity for ATP prior to the rate-limiting E2 to E1 conformational change, but a high affinity for ATP following the conformational change.

Animals↗
PubMed1980

Toxicological implications of polymorphic drug metabolism.

The occurrence of genetic polymorphisms of drug metabolism means that populations contain subgroups (phenotypes) that differ sharply in their abilities to effect a number of metabolic reactions. Because of this, major interphenotype differences occur in responsiveness to drugs and toxic substances. The well established genetic polymorphisms of acetylation and hydrolysis illustrate the important association that exists between phenotype and propensity to develop toxic and exaggerated responses to some substances. Recently, for metabolic oxidation, a new genetic polymorphism of drug metabolism has been described and it promises to provide a better understanding of inter-individual variability in the metabolic handling of, and responsiveness to, drugs and toxic substances. The following effects of the polymorphism are described here: (a) its influence in determining variable presystemic metabolism and hence systemic drug availability; (b) its role in determining alternative toxic pathways of metabolism in individuals who have a genetically determined impairment of oxidative capacity and (c) its influence on the development of agranulocytosis associated with metiamide administration.

Alleles↗
PubMed1980

Response modulation of auditory-nerve fibers by AM stimuli: effects of average intensity.

Auditory-nerve responses were obtained for characteristic frequency tones which were amplitude modulated by sinusoids. Response modulation (RM) was determined from folded histograms which were synchronized to the modulating wave form. As the average intensity increased from threshold, RM increased to a maximum and then decreased, and the shape of the RM function resembled that described previously for incremental responses. However, unlike the latter, the RM function could not be predicted directly from the steady-state rate-intensity function. In general, the maximum RM occurred at a higher intensity than predicted, and RM occurred over a wider range of average intensities than predicted. The results are interpreted as reflecting a dynamic response characteristic with an operating range that exceeds that determined from the steady-state rate-intensity function.

Acoustic Stimulation↗
PubMed1980

2-(Aminomethyl)phenols, a new class of saluretic agents. 1. Effects of nuclear substitution.

A series of 2-(aminomethyl)phenols was synthesized and tested in rats and dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration. The most active compounds belong to a subseries of 4-alkyl-6-halo derivatives of which 2, 2-(aminomethyl)-4-(1,1-dimethylethyl)-6-iodophenol, is the most active. Compound 2 also possesses significant antihypertensive activity, an adjunctive pharmacological parameter which distinguishes 2 from the other compounds prepared in this series. In addition, 2 displays both topical saluretic and antiinflammatory activities.

Administration, Oral↗
PubMed1980

Clinical pharmacokinetics of fazadinium.

Fazadinium was administered as an intravenous bolus of 0.5 or 1 mg/kg to nine patients during neurolept-anaesthesia. Continuous recording of neuromuscular activity and serial collection of blood samples for drug assay allowed the relationship between neuromuscular blockade and plasma fazadinium concentration to be studied. Pharmacokinetic analysis demonstrated high plasma clearances (221 and 185 ml/min), and short terminal half-lives, (30 and 50 min), for the two doses of the drug. Mean plasma concentrations at 10 and 50% recovery were 1.42 and 0.88 micrograms/ml respectively, demonstrating that the potency of fazadinium is approximately half that of tubocurarine and one eighth that of pancuronium. In addition, the relationship between plasma concentration and depression of neuromuscular activity during spontaneous recovery from the relaxant is described.

Adult↗