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Biomedical subjects

C R Minick

Publications and source records attributed to C R Minick.

At least 37 records · Page 2Linked to original sources
PubMed1979

Atheroarteriosclerosis induced by infection with a herpesvirus.

Atheroarteriosclerosis closely resembling that in humans was induced in normocholesterolemic and hypercholesterolemic chickens by infection with Marek's disease herpesvirus (MDV). Four comparably sized groups of chickens were used. Each group was initially fed a diet relatively poor in cholesterol. Group I and II were inoculated intratracheally at 2 days of age with MDV. At 15 weeks, one group of virus-infected chickens (Group II) and one group of uninfected controls (Group IV) were fed a 2% cholesterol supplement for an additional 15 weeks. Group I, infected, and III, uninfected, were continued on a cholesterol-poor diet. All groups were killed at 30 weeks. Striking grossly visible atherosclerotic lesions were seen in large coronary arteries, aortas, and major aortic branches of both Groups I and II but not in those of Groups III and IV. Microscopically, arterial changes in infected animals were characterized by occlusive fibromuscular intimal thickening, which formed fibrous caps overlying areas of atheromatous change. This change closely resembled chronic atherosclerosis in humans. These results may be important to our understanding of human arteriosclerosis, since there is widespread and persistent infection of human populations with as many as five herpesviruses.

Animals↗
PubMed1979

Role of endothelium and hypercholesterolemia in intimal thickening and lipid accumulation.

In experiments reported here we tested the hypothesis that persistent absence of endothelium favors intimal thickening, lipid accumulation, and atherosclerosis. Rabbit aortas were de-endothelialized with a balloon catheter at Day 0. Initially, all rabbits were fed a diet low in lipid. Some rabbits (Group I) were continued on a diet low in lipid for 8 to 20 weeks after de-endothelialization. Beginning 4 to 9 weeks after de-endothelialization, other rabbits were fed semisynthetic lipid-rich diets (Group II) or cholesterol-supplemented diets (Groups III) for 4 to 20 weeks. Lipid accumulation in all groups was significantly greater in the re-endothelialized intima than in adjacent intima lacking an endothelial lining. In aortas of Groups I, II, and III the degree of intimal thickening was significantly greater in re-endothelialized areas than in adjacent areas lacking endothelium. Intimal thickness was enhanced in re-endothelialized areas of hypercholesterolemic rabbits of Group III compared with normocholesterolemic rabbits of Group I but not in areas lacking endothelium. Thus, results of these experiments do not support the hypothesis that the absence of endothelium particularly favors intimal thickening and intimal lipid accumulation. Results indicate that intima covered by regenerated endothelium is significantly thicker and more likely to accumulate lipid.

Animals↗
PubMed1978

Virus-induced atherosclerosis.

Of four groups of chickens, two (groups I and II) were infected with MDV and two were not (groups III and IV). Groups I and III were fed diets low in lipid, and groups II and IV were fed cholesterol-supplemented diets. Striking grossly visible atherosclerotic lesions were seen in large coronary arteries, aortas, and major aortic branches of infected normocholesterolemic and hypercholesterolemic chickens (groups I and II). In contrast, grossly visible atherosclerotic lesions were not seen in uninfected normocholesterolemic chickens (group III), nor in uninfected hypercholesterolemic chickens (group IV). Microscopically, arterial changes in the infected animals were characterized by occlusive fibromuscular intimal thickening which formed fibrous caps overlying areas of atheromatous change. This change closely resembled chronic atherosclerosis in man. These results may have important bearing on our understanding of the etiology and pathogenesis of human arteriosclerosis since there is widespread and persistent infection of human populations with up to five different herpes-viruses.

Animals↗
PubMed1978

Morphologic examination of a prototype liver assist device composed of cultured cells and artificial capillaries.

Cultures of the minimal deviation rat hepatoma cell line H4-11-E derived from the Reuber hepatoma were grown on bundles of artificial capillaries. Sections of those cells grown in circumfusion culture on acrylic copolymer and polysulfone capillaries were prepared. Light, transmission and scanning electron micrographs disclosed variations in cell viability in different parts of the bundle, variations in capillary wall structure affecting the proximity of cells to capillary lumen, and intraluminal sediment deposits derived from pump tubes used for circulating the culture medium. These sediments, by obstructing capillaries, inhibited cell growth and caused focal necrosis of cells. The importance of monitoring the morphology of cell cultures grown on bundles of artificial capillaries which are to be used as artificial organs is emphasized.

Animals↗
PubMed1977

Effect of regenerated endothelium on lipid accumulation in the arterial wall.

We tested the hypothesis that loss of endothelium results in increased transport of lipoprotein into the arterial wall, favors accumulation of lipid, and thus predisposes to atherosclerosis. In rabbits initially fed a diet low in lipid, the aortas were de-endothlialized with an intraarterial balloon catheter; 28 days later, the animals were divided into two groups. Group I animals were continued on a diet low in lipid and sacrificed at 8, 11, 13, and 15 weeks after de-endothelialization. Group II animals were fed the same diet supplemented with 0.5% cholesterol and sacrificed at comparable intervals. Aortas of group I animals revealed proliferative fibromuscular intimal thickening in both de-endothelialized and re-endothelialized areas, with little or no fatty change in the intima. In contrast, aortas of group II animals revealed slight to marked fatty change in the intima, characterized by accumulation of oil red O-positive material with anisotropic lipid inclusions. The greatest quantity of lipid was present in intimal thickening beneath regenerated endothelium, and not in adjacent intimal thickening lacking an endothelial lining. These results do not support the hypothesis that the absence of endothelium favors accumulation of lipid and predisposes to atherosclerosis. The experiments indicate that lipid accumulates preferentially in areas of intimal thickening covered by regenerated endothelium.

Animals↗
PubMed1977

Studies on the pathogenesis of atheroarteriosclerosis induced in rabbit cardiac allografts by the synergy of graft rejection and hypercholesterolemia.

Heterotopic cardiac allografts were placed in the necks of 48 rabbits. In rabbits that were not immunosuppressed, allografts beat as long as 12 days, while in immunosuppressed rabbits allografts beat as long as 101 days. Coronary arterial lesions in donor hearts of rabbits fed a lipid-poor diet were found in arteries of all sizes and were mainly proliferative without fatty change. In cholesterol-fed rabbits, arterial lesions were similarly distributed, but the majority of lesions in longer surviving transplants were fatty-proliferative and some bore close resemblance to chronic human coronary atheroselerosis. In contrast to findings in cardiac homotransplants, only occasional predominantly fatty lesions were induced in small intramyocardial arteries of cholesterol-fed recipients. By electron microscopy, early arterial lesions in allografts were characterized by platelet aggregates in widened junctions between endothelial cells, sloughing of endothelium without intimal thickening but with adherence of platelets to the denuded arterial wall, and platelets deep within essentially normal media. Platelets were also seen adhering to the lining cells overlying the thickened intima of more advanced arterial lesions. Results indicate that immunologic arterial injury due to allograft rejection acting in synergy with hypercholesterolemia resulting from a dietary supplement of cholesterol can lead to rapidly developing atherosclerosis. Observations of early and evolving lesions indicate that endothelial injury and platelet interaction with the arterial wall are early and continuing events and may be of primary importance in the pathogenesis of experimental graft-induced atheroarteriosclerosis. In man, similar mechanisms may be involved in the pathogenesis of graft-induced athererosclerosis and in other instances of atherosclerosis. (Am J Pathol 87:415-442, 1977).

Animals↗
PubMed1976

Synthesis of basement membrane collagen by cultured human endothelial cells.

Studies were performed to determine if cultured human endothelial cells synthesized basement membrane collagen. In culture, endothelial cells were attached to grossly visible membranous structures which on light microscopy were composed of ribbons of dense, amorphous material. On transmission electron microscopy, these membranous structures consisted of amorphous basement membrane, and material morphologically similar to microfibrils and elastic fibers. By immunofluorescence microscopy, these membranous structures stained brightly with antisera to human glomerular basement membrane. Cultured endothelial cells incorporated [3H]proline into protein; 18% of the incorporated [3H]proline was solubilized by purified collagenase. When endothelial cells were cultured with [14C]proline, 7.1% of the incorporated counts were present as [14C]hydroxyproline. Cultured endothelial cells were labeled with [3H]glycine and [3H]proline and digested with pepsin. The resulting fractions on analysis by SDS-polyacrylamide gel electrophoresis contained two radioactive protein peaks of mol wt 94,200 and 120,500. Both these peaks disappeared after digestion with purified collagenase. The peak of mol wt 120,500 corresponds to that of alpha1 (IV) collagen; the peak of the mol wt 94,200 probably corresponds to that of alpha1 (III) collagen. Thus, cultured human endothelial cells synthesize material which is morphologically and immunologically like amorphous basement membrane and biochemically like basement membrane collagen. Cultured endothelial cells probably also synthesize material which is morphologically similar to microfibrils and elastic fibers.

Basement Membrane↗
PubMed1973

Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria.

Endothelial cells were isolated from freshly obtained human umbilical cords by collagenase digestion of the interior of the umbilical vein. The cells were grown in tissue culture as a homogeneous population for periods up to 5 mo and some lines were subcultured for 10 serial passages. During the logarithmic phase of cell growth, cell-doubling time was 92 h. Light, phase contrast, and scanning electron microscopy demonstrated that cultured human endothelial cells grew as monolayers of closely opposed, polygonal large cells whereas both cultured human fibroblasts and human smooth muscle cells grew as overlapping layers of parallel arrays of slender, spindle-shaped cells. By transmission electron microscopy, cultured endothelial cells were seen to contain cytoplasmic inclusions (Weibel-Palade bodies) characteristic of in situ endothelial cells. These inclusions were also found in endothelial cells lining umbilical veins but were not seen in smooth muscle cells or fibroblasts in culture or in situ. Cultured endothelial cells contained abundant quantities of smooth muscle actomyosin. Cultured endothelial cells also contained ABH antigens appropriate to the tissue donor's blood type; these antigens were not detectable on cultured smooth muscle cells or fibroblasts. These studies demonstrate that it is possible to culture morphologically and immunologically identifiable human endothelial cells for periods up to 5 mo.

ABO Blood-Group System↗
PubMed1973

Experimental induction of atheroarteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. II. Effect of repeatedly injected foreign protein in rabbits fed a lipid-rich, cholesterol-poor diet.

Rabbits fed a lipid-rich, cholesterol-poor diet and given concomitant injections of foreign protein, over a period as long as 17 months, developed in their coronary arteries both a) proliferative fibromuscular intimal thickening closely resembling the diffuse intimal thickening that commonly occurs in coronary arteries of man, and b) fatty-proliferative fibromuscular intimal thickening that closely resembles coronary atherosclerosis in man. In contrast, rabbits of another group that were concurrently fed the same diet for as long as 22 months without injections of foreign protein developed changes in arteries of their hearts that resemble neither coronary atherosclerosis nor diffuse intimal thickening in man. Fatty-proliferative changes in aortas of the first group of rabbits are strikingly greater and more closely resemble human aortic atherosclerosis than those in the latter group. In the course of the experiments, the average serum cholesterol was not significantly different in the two groups of rabbits. It was approximately 200 to 250 mg%, which is the average serum cholesterol in adult humans in the United States. These experiments support the hypothesis that the synergy of arterial injury, in particular immunologic injury, and a diet rich in lipid can lead to atherosclerosis in man.

Animals↗
PubMed1973

Experimental induction of atheroarteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. 3. The role of earlier acquired fibromuscular intimal thickening in the pathogenesis of later developing atherosclerosis.

Clinicopathologic evidence suggests that diffuse intimal thickening, a type of arteriosclerosis without manifest lipid deposit, may predispose to later developing atherosclerosis in man. This hypothesis was tested in the following experiments. Injury to coronary arteries of rabbits was induced by immunologic means, and arterial lesions were allowed to heal for many weeks. One group of animals was then sacrificed, and in their coronary arteries were found numerous fibromuscular intimal lesions closely resembling diffuse intimal thickening in man. The remaining rabbits were fed a cholesterol-supplemented diet for 80 days and then sacrificed. Fibromuscular intimal lesions of coronary arteries were found in these rabbits also. However, approximately two-thirds of these lesions were found to contain lipid, and many closely resembled coronary atherosclerosis in man. Further analysis of the data indicates that the atherosclerotic lesions in the rabbits evolved from immunologically induced fibromuscular intimal lesions which later and preferentially accumulated lipid in the presence of hypercholesterolemia. Results of these experiments suggest that in man fibromuscular intimal lesions, and in particular diffuse intimal thickening, acquired earlier in life can later accumulate lipid preferentially and thus redispose to atherosclerosis.

Animals↗