Search PubMed⌕ Search

Biomedical subjects

H L Ullman

Publications and source records attributed to H L Ullman.

25 records · Page 2Linked to original sources

Effects of acetyl glyceryl ether phosphorylcholine on human platelet function in vitro.

AGEPC (PAF), at 1.9 x 10(-8) M or higher, induced concentration-dependent aggregation and release in human platelet-rich plasma. Comparative studies with arachidonate, collagen, ionophore, and ADP suggested that AGEPC was a strong stimulus for platelet aggregation and probably a moderate agonist for release, as well as a relatively weak inducer of TXA2 production. The initial phase of AGEPC-induced aggregation was independent of ADP release and TXA2 formation, since it was not inhibited by ASA, apyrase, or CP/CPK. Whereas irreversible aggregation always required ADP release, TXA2 formation was not essential in each instance. Thus, in several experiments, full aggregation responses took place in AGEPC-stimulated platelets that had been pretreated with ASA. AGEPC-induced release of 5-HT, beta -thromboglobulin and PF-4 occurred in parallel and were inhibited by both apyrase and ASA. Washed human platelets did not respond to exogenous AGEPC in the absence of ADP and did not appear to generate significant quantities of AGEPC upon stimulation with thrombin or ionophore.

Adenosine Diphosphate↗

Superoxide production and reducing activity in human platelets.

Human platelets contain the cuprozinc (cytoplasmic) and manganese (mitochondrial) forms of superoxide dismutase. Nevertheless, superoxide radicals were detectable in the surrounding medium of metabolically viable platelet suspensions by using two assay systems: cytochrome c and nitroblue tetrazolium. The quantity of superoxide generated by platelets (5 X 10(5) superoxide radicals/platelet per 10 min) was constant and did not increase after aggregation by agents such as collagen and thrombin. The superoxide-generating system was present in the supernate of both aggregated and resting platelets and therefore was not platelet-bound. Platelet superoxide production was unaffected by prior ingestion of aspirin, indicating that the prostaglandin and thromboxane pathways were not involved. Both resting and aggregated platelets exhibited a reductive capacity toward cytochrome c and nitroblue tetrazolium which was unrelated to superoxide production. Furthermore, the aggregation process always resulted in a marked increase in this reduction. The nonsuperoxide reduction associated with aggregation was found to be membrane bound and to decrease with an apparent first order reaction rate (k1 = 0.067 min-1). In addition, accumulative, time-dependent nonsuperoxide-related cytochrome c reduction was also detected. Since there is no superoxide dismutase in plasma, the presence of superoxide radicals in the surrounding medium of platelets may have in vitro significance for platelet and leukocyte concentration and storage and in vivo significance for hemostasis, coagulation, and thrombosis. The nonsuperoxide-related reducing activities may represent a biochemical basis for platelet-blood vessel interactions, with particular reference to blood vessel integrity.

Aspirin↗

Studies on human platelet gangliosides.

Gangliosides, glycosphingolipids which contain sialic acid, were studied in human platelets. They represented 0.5% of the platelet lipids and accounted for 6% of the total neuraminic acid content of platelets. Three major ganglioside fractions were identified and characterized. Ganglioside I was hematoside (G(6)) and comprised 92% of the platelet gangliosides. It contained glucose, galactose, and sialic acid in molar ratios of 1:1:1 and no hexosamine. The major fatty acid was behenate (22:0). Ganglioside I was also identified in isolated platelet granules and membranes. Ganglioside II (5%) contained glucose, galactose, sialic acid, and hexosamines (molar ratios 1:2:1:1). The hexosamines were glucosamine (72%) and galactosamine (28%). It was therefore designated as ganglioside lacto-N-neotetraose. Ganglioside III (2%) contained disialosyllactosyl ceramide (G(3A)) as well as two other gangliosides which could not be precisely characterized. Gangliosides I, II, and III were susceptible to the action of Clostridium perfringens neuraminidase as evidenced by full recovery of sialic acid in its free form after incubation. Neutral platelet glycolipids were qualitatively examined by thin-layer chromatography. The major component was lactosyl ceramide. Interactions of gangliosides I and III and serotonin-(14)C were examined in an equilibrium dialysis system at 4 degrees C. The gangliosides bound serotonin-(14)C in relatively small quantities, whereas control lipids were negative. The binding was essentially unchanged by reverse dialysis, ultracentrifugation and subsequent thin-layer chromatography. The results are comparable to the previously observed nonmetabolic interactions between whole platelets and serotonin in the cold. It is suggested that the orientation and specific distribution of platelet membrane glycolipids may be important determinants of the unique surface properties of platelets.

Blood Platelets↗

Lipid composition of subcellular particles of human blood platelets.

Human platelets can be fractionated into three main subcellular components: granules, membranes, and a soluble fraction. In this study we determined the phospholipid and neutral lipid content of the granules and membranes. Quantitative relationships between lipids and protein were examined. The fatty acid and aldehyde composition of individual phospholipids and neutral lipids was also determined. Whole platelets had a lower lipid to protein ratio than did the subcellular particles, but the basic lipid composition of the granules, membranes, and platelets was similar. The phospholipid composition of platelets and subcellular fractions was found to differ only in that granules had a lower percentage of lecithin. Each of the phospholipid classes displayed a distinctive fatty acid pattern which was the same in all fractions and in whole platelets. The major neutral lipid was free cholesterol. Cholesteryl esters, triglycerides, and free fatty acids were minor components. The molar ratio of cholesterol to phospholipid in the platelet membranes was lower than that of brain myelin and erythrocyte ghosts. Some differences in fatty acid composition of the neutral lipids of platelet fractions were found. A special lipid composition or constituent that would correlate with platelet function has not been found.

Aldehydes↗