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Biomedical subjects

L Harker

Publications and source records attributed to L Harker.

23 records · Page 2Linked to original sources
PubMed1976

Hyperlipidemia and atherosclerosis.

These studies provide new insight into the complex mechanisms wherby hyperlipidemia causes progressive atherosclerosis. It has been shown that physical injury to the endothelial lining of arteries sets off a process which probably is an attempt at healing the injury but which can lead to atherosclerosis. It has also been found that chemical agents such as homocystine can produce a similar series of events leading to atherosclerosis. These events include focal loss of endothelium, exposure of subendothelial connective tissue, and adherence of platelets followed by release of factors that stimulate intimal smooth muscle proliferation. The present studies indicate that the effects of chronic hyperlipidemia are complex in that the condition results not only in the deposition of lipids in the atheromatous lesions but that it may produce the primary endothelial injury that initiates the process of atherosclerosis as well.

Animals↗
PubMed1976

Renal microangiopathy of the hemolytic-uremic syndrome in childhood.

18 children with clinical and laboratory findings characteristic of the hemolytic uremic syndrome were retrospectively studied. Thrombocytopenia due to platelet destruction was accompanied by only minimal changes in fibrinogen turnover and fibrinolytic degradation products. The most consistent pathologic feature was severe renal endothelial cell injury, which was postulated to produce both platelet and red cell destruction. Despite initially severe renal damage, 90% of the patients ultimately recovered normal renal function if adequately supported during the acute phase of the disease.

Adolescent↗
PubMed1974

A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro.

Dialyzed serum from clotted monkey blood ("blood serum") promotes the proliferation of monkey arterial smooth muscle cells in culture, but dialyzed serum prepared from recalcified platelet-poor plasma ("plasma serum") is much less effective. Addition of platelets and calcium to platelet-poor plasma increases the activity of plasma serum to the same level achieved with blood serum. Furthermore, addition to plasma serum of a platelet-free supernatant prepared by exposing purified platelets to thrombin also stimulates the proliferation of smooth muscle cells. Thus, much of the growth-promoting activity of dialyzed serum is directly or indirectly derived from platelets. This finding has important implications for the response of arteries to localized injury and provides a key to further understanding of the role of factors derived from blood serum in promoting cell proliferation in vitro.

Animals↗
PubMedDate not supplied

Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation.

Morphologic studies resulting from events that occur during the development of the lesions of atherosclerosis were studied in chronic, diet-induced hypercholesterolemia in a series of nonhuman primates. Within 12 days of hypercholesterolemia in Macaca nemestrina, monocytes became adherent to the surface of the endothelium. These monocytes appeared to migrate subendothelially, accumulate lipid, and become lipid-laden macrophages (foam cells). Within a month, a "serofibrinous insudate" formed together with variable numbers of subendothelial lipid-laden macrophages. By the second month, foam cells increased in number, often in multilayers, to form a fatty streak. Concomitantly, the luminal surface of the arteries became increasingly irregular due to the subendothelial accumulation of foam cells. Numerous monocytes continued to attach to the endothelial surface over the fatty streaks, and many of them appeared to enter the intima and participate in the growth of the fatty streaks. Lipid-laden smooth muscle cells appeared in small numbers and formed two to four layers between the macrophages and the internal elastic lamella at 2 to 3 months. During the third month of hypercholesterolemia, endothelial cell continuity over the lipid-laden macrophages became interrupted, exposing the underlying foam cells to circulating blood. Foam cells were then readily observed in whole blood smears, suggesting that many of the lipid-laden macrophages leave the intima and enter the circulation. After 4 months, significant endothelial denudation was found in the iliac artery and many exposed macrophages were covered by adherent platelets in the form of a mural thrombus. Thus, the early components of atherosclerosis induced by chronic hypercholesterolemia centered around the monocyte-macrophage and its interaction with endothelium in the induction of the fatty streak. Subsequent changes that lead to macrophage-smooth muscle interactions, platelet-macrophage interactions, and platelet-endothelial interactions appeared to set the stage for the development of more advanced proliferative lesions.

Animals↗