Infiltration and thrombosis in atherogenesis. A study using immunofluorescent techniques.
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Biomedical subjects
Publications and source records attributed to N Woolf.
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An inherited metabolic disorder in a strain of New Zealand White rabbits, characterized by marked hypercholesterolemia (394 +/- 100 mg/dl), with moderately elevated or normal triglyceride levels is described. Low density lipoprotein (LDL), intermediate density lipoprotein (IDL) and very low density lipoprotein (VLDL) cholesterol levels were increased. VLDL and IDL, and to a lesser extent LDL, had increased free cholesterol and esterified cholesterol content, and triglyceride content was reduced. Kinetic studies with 131I and 125I-labelled rabbit lipoproteins showed a marked increase in production rates of VLDL apo B and LDL apo B. LDL cholesterol levels were directly related to LDL apo B production rate (r = 0.938, p less than 0.001). Both in hypercholesterolemic and normal rabbits injected with labelled VLDL, the specific activity-time curves of VLDL apo B and LDL apo B did not intersect, indicating that LDL apo B was in part derived from sources other than VLDL. No defect was demonstrated in receptor-mediated catabolism of LDL by cultured skin fibroblasts from hyperlipidemic animals. The fractional catabolic rate of LDL apo B was subnormal, but increased when the expanded LDL apo B pool size was reduced by exchange transfusion; the low fractional catabolism may therefore be attributable, at least in part, to saturation of LDL receptors consequent upon the increased pool size of LDL. The hyperlipidemia in this strain of rabbits may be unique in that the underlying mechanism appears to be overproduction of VLDL and LDL.
A genetically determined hyperlipidemic strain of New Zealand White rabbit that has features in common with combined familial hyperlipidemia in humans has been identified. The morphologic findings in a few animals fed a normal chow diet are reported. These consisted of macroscopically visible aortic intimal elevations found in the greatest number in the descending thoracic aorta. The plaques showed the presence of a cell population consisting of modified smooth muscle cells and lipid-laden macrophages. The lesion bases were necrotic and acellular, and some showed the presence of dystrophic calcification. Scanning electron microscopy revealed numerous monocytes attached to the endothelium. Endothelial defects were common, and these were filled with swollen and "ruffled" macrophages. Transmission electron microscopy confirmed the presence of lipid-laden cells penetrating between adjacent endothelial cells. These findings resemble those reported in a number of different animal species after dietary induction of hyperlipidemia. This strain is a useful new model for the study of atherogenesis.
The blood vessels of the cochlea were studied from birth up to adult age in the gerbil. Even at birth the principal vascular arrangement could be identified in the external wall. However, the early circulatory mainstream appeared even more predominantly radial apico-basal over radiating arterioles-arteriovenous anastomoses-collecting venules than at later stages. At birth, only small sections of capillaries could be observed in the stria vascularis. Stria vascularis achieved its adult vascular appearance rapidly between 8-10 days after birth (DAB). The rapid development of stria vascularis immediately preceded the development of cochlear function and may have been related to the development of the ionic composition of endolymph. At birth the vessel of the basilar membrane showed many large vascular connections with the collecting venules in the scala tympani of the external wall but very few supplying and draining ramifications on the medial side of the vessel. This suggests that the vessel of the basilar membrane originates from the external wall vessels, not from the spiral lamina vessels as has previously been supposed. The peripheral vascular connections degenerated rapidly after birth. The vessel, being very large at birth, degenerated completely by 15 to 20 DAB, ultimately disappearing in the basal turn. The degeneration suggests that its major importance may be during embryonic stages, with great probability for the development of the organ of Corti.
Measurements of the urinary loss of adrenaline and noradrenaline and of cortisol in a competitor of the Paris-Colmar march permits to draw some conclusions concerning the hypothalamic condition of the said competitor during the race. It concerns a total stimulation, the determining factors of which, as seen from the differences between the various phases of competition, remain uncertain. The limitations which such an analysis is bound to have in the given circumstances are clearly shown.