Search PubMed⌕ Search

Biomedical subjects

R W Alexander

Publications and source records attributed to R W Alexander.

At least 253 records · Page 14Linked to original sources

Angiotensin II stimulation of prostaglandin production in cultured human vascular endothelium.

Immunoreactive material resembling prostaglandin E accumulates in the medium of cultured human umbilical vein endothelial cells. Prodcution is inhibited by indomethacin and stimulated by angiotensin II. Prostaglandin secretion by endothelium may be important in platelet-dependent thrombotic phenomena, and in local control of vascular permeability and tone in vivo.

Angiotensin II↗

Identification of cardiac beta-adrenergic receptors by (minus) [3H]alprenolol binding.

(Minus) [3-H] alprenolol, a potent beta-adrenergic antagonist, was used to identify binding sites in a fraction of canine cyocardium. Beta adrenergic agonists and antagonists compete for these binding sites in a manner which directly parallels their known affinity for the cardiac beta-adrenergic receptor. Thus, binding was highly stereo-specific, with the (minus) isomers of beta-adrenergic agonists or antagonists being at least two orders of magnitude more potent than were the (plus) isomers in competing for these sites. The order of potency for inhibition of binding by beta-adrenergic agonists was (minus) isoproterenol greater than (minus) epinephrine greater than (minus) norepinephrine. The dissociation constant (KD) of (minus) alprenolol for the beta-adrenergic receptors was 7-11 nM as determined independently by direct binding studies or by inhibition of isoproterenol-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. The beta-adrenergic antagonist (minus) propranolol also had high affinity for the binding sites (KD equals 12 nM). The physiologically inactive catechol-containing compounds pyrocatechol and (plus or minus) dihydroxymandelic acid, as well as the metabolite (plus or minus) normetanephrine, and the alpha-adrenergic antagonist phentolamine did not compete for the binding sites at a concentration of 160 muM. Binding was rapid (t1/2 less than 30 sec) and was rapidly reversible (t1/2 less than 15 sec). The binding sites were saturable and bound 0.35 pmol of (minus) [3-H] alprenolol per mg of membrane protein. These characteristics suggest that these binding sites represent the cardiac beta-adrenergic receptors.

Adenylyl Cyclases↗

Regulation of postocclusive hyperemia by endogenously synthesized prostaglandins in the dog heart.

Experiments were performed to evaluate the role of prostaglandin synthesis in the regulation of coronary blood flow in dog hearts. The left main coronary artery was cannulated and flow measured both in otherwise intact animals and in canine heart-lung preparations. Prostaglandin E was measured by radioimmunoassay. Reactive hyperemia (flow after occlusion release) was induced by coronary occlusion for 10, 15, and 20 s and was 39 plus or minus 13 (mean plus or minus SEM), 66 plus or minus 21, and 82 plus or minus 24 ml, respectively. Indomethacin, an inhibitor of prostaglandin synthetase, reduced reactive hyperemia at 10, 15, and 20 s to 15 plus or minus 5, 33 plus or minus 11, and 47 plus or minus 17 ml, respectively (P smaller than 0.05). Meclofenamate, a different prostaglandin synthetase inhibitor, gave similar results. In a second group of five dogs, prostaglandin production of the heart was examined in response to 20-s occlusions. There was a significant increase in prostaglandin production from a basal level of 18.6 plus or minus 4.9 mg/min to 35.3 plus or minus 5.8 ng/min after occlusion of the coronary artery for 20 s (P smaller than 0.05). After indomethacin, this increase in prostaglandin production was not observed and reactive hyperemia was significantly reduced. Thus, prostaglandin synthesis appears to be important to modulating canine coronary blood flow in response to brief periods of coronary occlusion.

Adenosine↗

Postauricular approach for surgery of the temporomandibular articulation.

The adaptation of a postauricular approach for surgical exposure of the temporomandibular articulation is presented. The ease, safety, and predictability of extensive exposure have led us to use this approach exclusively for surgical intervention in this region. It has been effectively used in cases of trauma, pathologic conditions, and reconstruction involving the TMJ. In addition to the cases reported in this series, the procedure may be adapted to oblique subcondylar oestotomies and to the treatment of a variety of regional neoplastic processes and other forms of TMJ dysfunctions that may be encountered.

Humans↗

The validity of preemployment medical evaluations.

A protocol is described to determine whether a medical preemployment evaluation can be predictive for attendance or work performance. In addition, the dollar benefit and the cost of such a program is assessed. The present analysis is based on 4,936 men and women, who were processed as prospective hires into non-hazardous job assignments. A medical preemployment evaluation was performed on all applicants, identifying factors which could influence attendance or work performance. Sixty-nine per cent of the examined applicants were hired. During the employment process, all applicants were randomly assigned to a control or trial group. Those in the trial group were hired by the employment office without knowledge of the results of the medical preemployment evaluation, whereas these results were fully disclosed for applicants in the control group. Three months after hire, supervisors answered a detailed questionnaire relating to absence and work performance for each hire. No differences were identified between control and trial groups for overall job performance, appropriateness of the job match and work force losses. A small but significant difference, on the other hand, was identified for sickness absence in the trial group between medical evaluation category A (normal risk) and category R (increased risk identified). Omission of a preemployment medical evaluation, as simulated by the trial group, increased the absence cost for the company by $2.30 per year for each new hire. Compared to a $17.50 cost per preemployment health evaluation, the average length of service of new hires would have to exceed 7.6 years to realize a dollar benefit from the medical examination. Examinations performed on applicants who were never hired further increases the cost of a medical preemployment examination program.

Absenteeism↗

Effects of dietary sodium and of acute saline infusion on the interrelationship between dopamine excretion and adrenergic activity in man.

The effects of dietary sodium and of saline infusion on urinary dopamine and norepinephrine and on the relationship of these catecholamines to adrenergic activity were determined. In seven normal subjects on a 9-meq sodium intake, urinary dopamine and norepinephrine were 136+/-18 (SE) and 37.4+/-5.3 mug/day, respectively. When sodium intake was increased to 209 or 259 meq/day, urinary dopamine increased to 195+/-20 mug/day (P<0.01) whereas urinary norepinephrine decreased to 21.1+/-3.0 mug/day (P<0.01). Infusion of saline in seven subjects increased sodium excretion and urinary dopamine (from 2.18+/-0.22 to 2.79+/-0.19 mug/20 min, P<0.01), but decreased plasma dopamine-beta-hydroxylase by 33% and urinary norepinephrine insignificantly. The clearance of inulin and p-aminohippurate did not change significantly and filtration fraction was the same. The data indicate that an increase in dietary sodium or infusion of saline results in an apparent decrease in adrenergic activity and an increase in urinary dopamine. Dopamine excretion would thus appear to relate inversely to adrenergic activity and to parallel sodium excretion. These findings suggest a possible role for dopamine and norepinephrine in the regulation of renal sodium excretion.

Adult↗