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Biomedical subjects

L Corash

Publications and source records attributed to L Corash.

100 records · Page 6Linked to original sources

Heterogeneity of human whole blood platelet subpopulations. II. Use of a subhuman primate model to analyze the relationship between density and platelet age.

A subhuman primate model was developed to ascertain whether or not platelet heterogeneity could be explained by aging in the peripheral circulation. Density-dependent platelet cohorts, postulated to represent cells of different ages, were isolated on isosmolar arabinogalactan gradients and labeled with radiochromium. Mean platelet lifespan was measured for the different density cohorts, and simultaneous sequential density distribution analysis was performed to follow changes in cell density during aging. The average mean lifespan of light platelets was 74.6 hr, compared to 313.6 hr for heavy platelets. After injection, labeled light platelets were recovered only in the gradient light region, in contrast to labeled heavy platelets, which were initially restricted to the dense region and progressively migrated to the light region during their lifespan. This study supports the hypothesis that platelet age in unstressed primates correlates with cell density and provides a rationale for the use of "age-dependent" markers to estimate platelet turnover rates.

Animals↗

Erythrocyte survival in Duchenne muscular dystrophy.

Hemolysis was investigated in seven patients with Duchenne dystrophy. No increase in red-cell turnover was detected by indirect measurement (hemoglobin, reticulocyte count, plasma hemoglobin, serum haptoglobin) or by turnover of 51Cr-labeled erythrocytes. Our findings fail to support the likelihood of a significant erythrocyte membrane defect.

Adolescent↗

Heterogeneity of human whole blood platelet subpopulations. I. Relationship between buoyant density, cell volume, and ultrastructure.

A quantitative high yield method utilizing isosmotic arabino-galactan (Stractan) solutions and isopycnic centrifugation was developed to isolate and to fractionate total human platelet populations into density-dependent subpopulations. Isolated platelets were free of factor VIII/von Willebrand factor and other plasma proteins. They responded to ADP, epinephrine, and collagen with a sensitivity equal to platelet-rich plasma platelets. The correlation of platelet density with volume and ultrastructure was examined for normal subjects. Recovery of total platelet populations averaged 92.76%+/-3.64% (SD). Normal individuals exhibited a narrow range of platelet buoyant density distribution. Computerized probability plot analysis of platelet volume distribution for 15 normal subjects' total platelet populations showed a mean volume of 5.17+/-0.46 cu mum (SD). Platelets with buoyant density less than or equal to 1.062 g/ml had a mean volume of 4.50+/-0.48 cu mum, while platelets with buoyant density greater than 1.071 g/ml, but less than or equal to 1.084 g/ml, had a mean volume of 5.32+/-0.63 cu mum (SD). The volume difference by paired t test was significant, p less than 0.001. Thin-section electron microscopy demonstrated a significant reduction of granule content in light platelets, as compared to heavy platelets, but an equal number of mitochondria for both groups. These differences of platelet volume and structure between light and heavy platelets suggested that aging may be a determinant of platelet heterogeneity.

Adult↗

The cell-free synthesis of the alpha subunit of human chorionic gonadotropin.

The synthesis of the alpha subunit of human chorionic gonadotropin (hCG) was demonstrated in a cell-free system composed of polysomes derived from first trimester placenta and cell sap prepared from ascites tumor cells. The in vitro synthesized proteins labeled with [35S]methionine were shown to have at least 4 tryptic peptides that co-migrated with the same peptides from authentic hCG. Sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed the synthesis of a discrete protein, migrating with an apparent molecular weight of about 17,000, which contained methionine-labeled tryptic peptides found in the alpha subunit. The level of radioactivity in these tryptic peptides was five times greater with polysomes from first trimester placentae than with those from term placentae. The efficiency of total protein synthesis in both cases was about the same. These data strongly suggest that the decrease in blood levels of hCG after the first trimester is caused by a selective decrease in the rate of synthesis of the hormone.

Amino Acids↗

Photochemical decontamination of blood components containing hepatitis B and non-A, non-B virus.

Diluted plasma samples containing 10(2), 10(3), 10(4), and 10(5) chimpanzee infectious doses (CID) of a human non-A, non-B hepatitis virus (NANBV) were treated with a combination of two psoralen compounds, 4'-aminomethyl-4,5',8-trimethylpsoralen and 4,5',8-trimethylpsoralen, and exposed to long wavelength ultraviolet. Each dilution was then transfused into one of four chimpanzees. In a second experiment, three samples containing 10(4.5) CID of hepatitis B virus (HBV) and two samples containing 10(4) CID of NANBV were treated with 8-methoxypsoralen (8-MOP) and ultraviolet irradiation. Two chimpanzees were each transfused with both a treated HBV and a treated NANBV sample. The third chimpanzee was inoculated with a treated HBV sample alone. In the six months after inoculation none of the animals showed biochemical or histological evidence of hepatitis. In experiments involving NANBV inocula, the susceptibility of the animals was confirmed by subsequent challenge with untreated NANBV. Factor VIII concentrate containing virus and photochemically treated as in the first experiment retained an average of 91% of its activity while that in the second experiment retained 94% of its activity.

Animals↗

Platelet function and survival in patients wit severe hypercholesterolemia.

Platelet aggregation and survival were measured in twelve subjects with severe hypercholesterolemia. There was a small increase in sensitivity to epinephrine and adenosine diphosphate among the most hypercholesterolemic patients, but this did not correlate with reduced platelet lifespan. Platelet survival was normal or only moderately reduced in the markedly hypercholesterolemic homozygous subjects. However, the incidence of reduced platelet survival was significantly increased (p less than 0.05) among the older patients with more extensive atherosclerotic vascular disease compared to the younger patients with limited vascular disease. Marked hypercholesterolemia in the absence of atherosclerosis does not appear to accelerate platelet destruction, although a modest increased aggregability is present.

Adolescent↗