Search PubMed⌕ Search

Biomedical subjects

M J Silver

Publications and source records attributed to M J Silver.

At least 73 records · Page 4Linked to original sources
PubMed1979

19-Hydroxy-prostaglandin E and infertility in human males.

We measured the content of 19-hydroxy-prostaglandin E (19-OH-PGE) and prostaglandin E (PGE) in the semen of 10 infertile males by alkaline dehydration, thin layer chromatographic separation and ultraviolet spectrophotometry. 7 fertile males were also studied. In both groups the content of seminal 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) also was measured by thin layer chromatographic separation and highly specific radioimmunoassay. The amounts of 19-OH-PGE and PGE were significantly lower (p < .02, p < .05) in the infertile group than the fertile group. Differences in mean seminal 6-keto-F1 alpha were not significant. The uterine stimulatory actions of 19-OH-PGE demonstrable in the monkey may apply to fertility in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1979

Prostaglandins as inhibitors of human platelet aggregation.

The potencies of prostaglandins (PG) I2, PGD2 and PGE1 as inhibitors of human platelet aggregation induced by threshold concentrations of four aggregating agents were determined in platelet-rich plasma from normal individuals who had not ingested aspirin. The order of activity against ADP, adrenaline and collagen was always PGI2 greater than PGD2 greater than PGE1. However, PGD2 and PGE1 were almost equipotent with PGI2 when tested against arachidonic acid (AA). The threshold inhibitory effects of PGD2, PGE1 and PGI2 could be over come by increasing the concentrations of the aggregating agents AA, collagen or ADP. Adrenaline was found to be different from the other aggregating agents. It could overcome inhibition of platelet aggregation by PGD2 but could not overcome inhibition by PGI2 or PGE1. These facts support the hypothesis that platelet receptors for PGI2 and PGE1 are similar to each other and different from the receptor(s) for PGD2. PRP obtained from normal subjects after the ingestion of aspirin exhibited only one wave of aggregation in response to ADP, adrenaline or collagen, PGI2, PGD2 and PGE1 were all powerful inhibitors of this single wave of aggregation. The inhibitory activity of all three prostaglandins at threshold concentrations was overcome by increasing the concentration of ADP or collagen but not by increasing the concentration of adrenaline.

Adenosine Diphosphate↗
PubMed1979

Selective binding site for [3H]prostacyclin on platelets.

Prostacyclin (PGI(2)) is the most potent, naturally occurring inhibitor of platelet aggregation known. To determine whether PGI(2) is bound by platelets, high specific activity [9-(3)H]PGI(2) was synthesized by iodination and subsequent base treatment of the labeled precursor [9-(3)H]prostaglandin (PG)F(2alpha) methyl ester. Binding experiments were performed at room temperature with normal citrated human platelet-rich plasma that contained [(14)C]sucrose or [(14)C]PGF(1alpha) as an internal marker for the extracellular space. Binding of [(3)H]PGI(2) plateaued within 2 min and this bond radioactivity could be displaced rapidly by excess nonradioactive PGI(2). Scatchard analysis of concentration-dependent binding yielded a hyperbolic plot which appeared to be caused by the existence of two classes of binding sites. The higher affinity class has a dissociation constant of 12.1+/-2.7 nM and a capacity of 93 (+/-21)sites per platelet. The lower affinity class had a dissociation constant of 0.909+/-.236 muM and a capacity of 2,700+/-700 sites per platelet. The relative ability of PGI(2), PGE(1), PGE(2), and 6-keto-PGF(1alpha) to displace [(3)H]PGI(2) initially bound to the higher affinity class of sites were 100:5:<0.3: <0.3. These relative abilities parallel the relative potencies of these compounds as inhibitors of ADP-induced platelet aggregation in vitro. However PGD(2), which is more potent than PGE(1) as an inhibitor of aggregation, did not displace bound [(3)H]PGI(2). The higher affinity binding site for PGI(2) appears to be the specific receptor through which PGI(2) exerts its effect on platelets.

Binding Sites↗
PubMed1978

Prostacyclin: a potentially valuable agent for preserving myocardial tissue in acute myocardial ischemia.

Prostacyclin, a potent, naturally occurring prostaglandin exerts a variety of cardiovascular and cellular actions of potential value in acute myocardial ischemia. These properties include the reduction of systemic blood pressure without changing heart rate, the lowering of coronary vascular and total peripheral resistance, the inhibition of platelet aggregation and the concomitant formation of thromboxane B2, and the reduction of the release of lysosomal enzymes.

Animals↗
PubMed1978

Fatty acids and the initial events of endothelial damage seen by scanning and transmission electron microscopy.

A method was developed for observing changes in the endothelial cells in rabbit ear veins in vivo by scanning electron microscopy. Injection of fatty acids into the ear vein caused damage to the endothelium. The first signs of damage seen were marked bulges in the nuclei and loss of the rhomboidal shape of the endothelial cells. More severe damage included loss of nuclei, leaving holes in the cytoplasm. Some parts of the damaged endothelium showed complete separation of cells from each other and exposure of sub-endothelial tissue to which platelets with pseudopodia were adhering. Damage to the endothelium was produced by arachidonic, linoleic, gamma-linolenic, 8,11,14-eicosatrienoic, 5,8,11,14,-eicosatetraenoic or 15-hydroperoxy-5,8,11,13-eicosatetraenoic acids. The effect of arachidonic acid was not prevented by pre-treating the animals with aspirin. It appears that damage produced by the fatty acids is non-specific.

Animals↗
PubMed1978

Hereditary abnormality of platelet aggregation attributable to nucleotide storage pool deficiency.

An abnormality of platelet aggregation has been detected in six family members with mild bleeding tendencies. In citrated platelet-rich plasma, primary aggregation induced by ADP or epinephrine and agglutination in response to ristocetin were present but second wave aggregation and aggregation in response to collagen suspension were absent or greatly reduced. Sodium arachidonate-induced aggregation was normal although aggregation in response to prostaglandin G2 was reduced and depended entirely on the presence of plasma or ADP. Further tests indicated that the platelets produced prostaglandins but did not release ATP in response to thrombin or sodium arachidonate. Platelets from the patients were found to contain reduced amounts of ADP and 5-hydroxytryptamine and to be unable to retain radioactivity during prolonged incubation at 37 degree C with radiolabeled 5-hydroxytryptamine. Although electron microscopy revealed an absence of very dense bodies, the platelets appeared otherwise normal. The findings are discussed in relation to previous studies of nucleotide storage pool deficiency and the light they shed on platelet physiology in general.

Adenosine Diphosphate↗
PubMed1977

Selective release of archidonic acid from the phospholipids of human platelets in response to thrombin.

Arachidonic acid is unique amongst human platelet fatty acids in that it is the precursor of prostaglandins and thromboxanes. Since a number of these oxygenated products of arachidonic acid have potent effects on platelet function, an understanding of the metabolsim of their precursor is important. Human platelets have a mechanism for incorporating arachidonic acid from plasma into their phospholipids and, in response to thrombin, they reveal mechanisms for hydrolyzing this arachidonic acid from platelet phosphatidylcholine and phosphatidylinositol. This report deals with the specificity of these mechanisms. The present studies show that human platelets contain phospholipase A2 activities that preferentially release arachidonic acid. One of these activities specifically utilizes 1-acyl-2-arachidonyl-phosphatidyl-choline. Another utilizes platelet phosphatidylinositol and/or phosphatidylserine, both of which are highly enriched with arachidonic acid.

Arachidonic Acids↗
PubMed1976

Metabolism of [14C]arachidonic acid by human platelets.

A time dependent incorporation of [1-14C] arachidonic acid into platelet phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, and phosphatidylserine was observed in platelet-rich plasma. When platelets, so labelled, were washed and treated with thrombin, there was a major decrease in the radioactivity of phosphatidylcholine and phosphatidylinositol. This decrease was accounted for by the appearance of several previously identified (Hamberg and Samuelsson (1974) Proc. Natl. Acad. Sci. U.S. 71, 3400) 14C-labelled oxygenated products of arachidonic acid.

Arachidonic Acids↗
PubMed1976

Separation of prostaglandins E2 and F2alpha from their pulmonary metabolites by thin-layer chromatography.

A simple thin-layer chromatographic system has been developed separate PGE2 and PGF2alpha from 13, 14-dihydro-PGF2alpha, and other pulmonary metabolites of prostaglandins. The separation is achieved on Kieselgel-60 F-254 plates impregnated with both silver nitrate and boric acid. The system should be of use in the purification and tentative identification of primary prostaglandin.

Chromatography, Thin Layer↗
PubMed1976

Persistence of thromboxane A2-like material and platelet release-inducing activity in plasma.

During the incubation of arachidonic acid with platelet-rich plasma, a persistent activity appeared that caused the release of [14C]5-hydroxytryptamine from indomethacin-treated platelets. By the time-course of its appearance and disappearance, this release-inducing activity could be dissociated from prostaglandin endoperoxides and associated with thromboxane A2-like material. This material persists in plasma because of its continued production and increased stability.

Arachidonic Acids↗