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Biomedical subjects

N R Shulman

Publications and source records attributed to N R Shulman.

At least 37 records · Page 2Linked to original sources
PubMed1980

Relative effects of aspirin on platelet aggregation and prostaglandin-mediated coronary vasodilatation in the dog.

Aspirin, as an inhibitor of platelet aggregation, may be of benefit in ischemic heart disease. However, aspirin blocks not only platelet aggregation but also synthesis of prostacyclin, a vasodilator and platelet deaggregator. The relative sensitivity of prostaglandin-mediated coronary vasodilatation and platelet aggregation to inhibition by aspirin remains uncertain. We therefore investigated the relative dose-response relationship of aspirin on arachidonic acid-induced increments in coronary blood flow and on ADP-induced aggregation of platelets. In 11 open-chest dogs, intracoronary arachidonic acid, 0.1-3.0 mg, produced dose-related increases in coronary blood flow that were inhibited progressively by i.v. aspirin over the dose range 0.3-3.0 mg/kg. Aspirin at 3 mg/kg almost completely obliterated the response to 3 mg of arachidonic acid. Similarly, aspirin doses of 0.3-3.0 mg/kg progressively raised the minimal concentration of ADP necessary for platelet aggregation. The threshold concentration of ADP that produced aggregation of platelets from 10 control dogs ranged from 2.3 x 10(-6) M to 1.2 x 10(-5) M. Aspirin at 3 mg/kg completely inhibited aggregation of platelets from 11 of 12 dogs, even with ADP at 2.3 x 10(-4) M concentration, the maximum tested. Aspirin at 0.1 mg/kg failed to inhibit either ADP-induced platelet aggregation or arachidonic acid-induced increments in coronary blood flow. Thus, the two test systems showed similar sensitivity to inhibition by aspirin with respect to threshold dose and maximal effect. These results show that very low doses of aspirin inhibit arachidonic acid-induced coronary vasodilatation and that aspirin at low doses does not appear to selectively inhibit platelet activity relative to coronary vasodilatation.

Adenosine Diphosphate↗
PubMed1977

[ABO compatibility and isoimmune neonatal thrombopenia].

25 families with serologically documented isoimmune neonatal thrombopenia were investigated for ABO-antigens of mother and child. In all cases mother and child were ABO-compatible. It is concluded that feto-maternal ABO-compatibility is a prerequisite for the development of isoimmune neonatal thrombopenia; hence, platelets must have ABO-antigens or be covered by soluble ABO-antigens.

ABO Blood-Group System↗
PubMed1977

Evidence for control of serotonin secretion from human platelets by hydroxyl ion transport and osmotic lysis.

Serotonin secretion from human platelets, stimulated either by thrombin or the calcium ionophore A23187, was found to be inhibited by anion transport blocking drugs such as 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), pyridoxal phosphate, probenecid, and suramin. These drugs have previously been shown to inhibit ATP-evoked release of epinephrine from isolated chromaffin granules by blocking chloride uptake and subsequent osmotic lysis. However, in contrast to granule release, platelet secretion was insensitive to chloride and, instead, was dependent on OH-. Platelet release was suppressed by low pH, and inhibition by the transport blocking drugs was competitive only with respect to OH-. Serotonin release from platelets was also suppressed by increasing extracellular osmotic strength, and the relationship between suppression and external osmotic strength was quantitatively similar to that observed in the case of chromaffin granules. We conclude that platelet exocytosis could occur when serotonergic granules are closely juxtaposed to the plasma membrane, thus exposing the granule anion transport site to the more alkaline medium. Secretion of serotonin could occur as a consequence of OH- transport and osmotic lysis of the granule-plasma membrane complex, analogous to the chemiosmotic mechanism of chloride-dependent epinephrine release from isolated chromaffin granules.

Anions↗
PubMed1977

Megakaryocyte maturation indicated by methanol inhibition of an acid phosphatase shared by magakaryocytes and platelets.

Optimal conditions necessary for the cytochemical demonstration of megakaryocyte (Mk) and platelet acid phosphatase (AP) were determined. Methanol, a constituent of fixatives commonly used in AP cytochemistry, was found to inhibit MkAP, and the degree of inhibition varied with Mk maturity. Immature Mk contained predominantly methanol-resistant AP, and mature Mk, predominantly methanol-sensitive AP. Platelets contained methanol-sensitive AP similar to mature Mk, suggesting that this enzyme provides an index of platelet formation by Mk. Soluble platelet AP showed three bands on polyacrylamide gel electrophoresis, visualized by the same reactions applied cytochemically. Two bands, accounting for 98% of the platelet AP activity, were slow moving and methanol sensitive; and one fast moving band accounting for 2% of activity was methanol resistant. Measurement of Mk and platelet AP isoenzymes may prove to have applications in evaluating Mk function.

Acid Phosphatase↗
PubMed1976

Platelet survival and morphology in homocystinuria due to cystathionine synthase deficiency.

In homocystinuria due to cystathionine synthase deficiency thromboembolism is a major cause of mortality and morbidity. Recent studies by others identified an abnormally shortened platelet survival and increased platelet vacuolization in patients with homocystinuria. When we studied six additional patients, however, we found the platelet survival to be within normal limits for each. The mean survival (+/-1 S.D.) was 9.75+/-0.94 days (normal, 9.27+/-1.06). In addition, platelets from five patients with homocystinuria and three obligate heterozygotes could not be distinguished from those of seven normal control subjects by electron microscopy. Specifically, no increased vacuolization was observed. Genetic heterogeneity, technical differences of differences in plasma homocystine concentrations could account for these descrepant results. The mechanism of thrombosis in homocystinuria remains an open question.

Adult↗
PubMed1975

Multiple neoplasms in two siblings with a variant form of Fanconi's anemia.

Two siblings with a variant form of Fanconi's anemia developed multiple neoplasms after prolonged survival and treatment with androgens. One of the siblings developed two separate oral squamous cell carcinomata, and the other developed acute leukemia and hepatoma. Androgens may have had a carcinogenic role in the appearance of the hepatic neoplasm. There is an increased incidence of neoplasm associated with Fanconi's anemia. This may be related to frequent spontaneous chromosomal abberations and/or to increased cellular susceptibility to viral transformation.

Acute Disease↗