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Biomedical subjects

N H Fidge

Publications and source records attributed to N H Fidge.

68 records · Page 4Linked to original sources
PubMed1969

Vitamin A and carotenoids. The enzymic conversion of beta-carotene into retinal in hog intestinal mucosa.

The conversion of beta-carotene into retinal was studied in vitro with enzyme preparations from homogenates of hog intestinal mucosa. The hog mucosal enzyme was purified about 27-fold by precipitation with ammonium sulphate, chromatography on DEAE-Sephadex and gel filtration on Sephadex G-200. The reaction displayed a narrow optimum pH range (approx. 7.8-8.2). The enzyme was stimulated strongly by the addition of thiols, and was inhibited by thiol inhibitors and by the chelating agents alphaalpha'-bipyridyl and o-phenanthroline. The reaction required the addition of an appropriate detergent (or bile salt); maximal activity was obtained by addition of an appropriate combination of detergents and lipid (specifically Tween 40, sodium glycocholate and sphingomyelin). The reaction displayed Michaelis kinetics with K(m)1.3x10(-6)m and V(max.)1.1nmole of retinal formed/hr. (for 0.7mg. of enzyme protein). The properties of the hog enzyme are similar to those previously reported for a less purified rat enzyme preparation.

Animals↗
PubMed1969

The metabolism of chylomicron cholesteryl ester in rat liver. A combined radioautographic-electron microscopic and biochemical study.

Chylomicrons containing labeled cholesterol, mainly (70%) present as cholesteryl ester, were injected intravenously into intact rats, and samples of liver were obtained 27-210 min later. Most (58-75%) of the injected label was recovered in the liver after 27-75 min. Hepatic uptake occurred without hydrolysis of the labeled cholesteryl ester. In separate experiments, in vitro perfusion of livers of similarly treated rats for 30-35 min washed out only 3-9% of the labeled sterol. Samples of liver and small intestine were prepared for electron microscopy with Aquon as the dehydrating agent. Good retention (70% or more) of labeled cholesterol and satisfactory preservation of ultrastructure were obtained. After 30 min, the radioautographic reaction was localized mainly over the region of the cell boundary of the parenchymal liver cells, with fewer grains being present over intracellular organelles. At later time intervals, when considerable hydrolysis of the labeled cholesteryl ester had occurred, the radioautographic reaction was more evenly distributed. Phagocytosed labeled lipid was seen in Kupffer cells after the larger lipid load; phagocytosis by parenchymal cells was not seen. In other experiments, cholesteryl ester hydrolase activity was found in all subcellular fractions, the microsome and plasma membrane fractions showing the highest activity per mg protein. The mechanism of cholesteryl ester transport into the liver cell may involve: (1) hydrolysis at the cell surface; or (2) slow entry of intact molecules followed by intracellular hydrolysis of the ester bond.

Animals↗
PubMed1968

Pathways of absorption of retinal and retinoic acid in the rat.

The chemical and anatomical pathways of absorption of dietary retinal, retinoic acid, and retinol were examined in rats containing lymph, bile, and duodenal cannulae. The experiments were designed to maintain physiological conditions to the greatest possible extent. In each rat an uninterrupted flow of bile into the duodenum was maintained by connecting the duodenal cannula to the bile duct of a second rat. Labeled vitamin A compounds were introduced into the duodenum in very small amounts (7-14 micrograms) in the form of a bile-lipid mixture resembling normal intestinal contents. Under these conditions, most (70-80%) of the radioactivity recovered after the feeding of labeled retinol or retinal was found in the lymph, predominantly in saturated retinyl esters. In contrast, 92-95% of the radioactivity recovered after the feeding of labeled retinoic acid was found in the bile, and was contained in a mixture of polar metabolites, most of them more polar than free retinoic acid. Two-thirds of the small amount of radioactivity found in lymph after retinoic acid-(14)C feeding was in the form of free retinoic acid. The results indicate that under normal conditions the major pathway of retinal absorption involves its reduction to retinol, which is then esterified and transported via the lymphatics in a manner similar to that of dietary retinol. A small proportion of retinal is apparently normally oxidized, and is then transported via the portal vein and excreted in the bile in a manner similar to that of dietary retinoic acid. The relative importance, in quantitative terms, of these two pathways of retinal metabolism can vary, depending on the status of the animal.

Animals↗
PubMed1966

Effect of cholesterol in suspension on the incorporation of phosphate into phospholipid by macrophages in vitro.

Macrophages obtained from the peritoneal cavity of rabbits were incubated with phosphate-(32)P in order to investigate the synthesis of phospholipid by these cells. After 6 hr of incubation 0.25% of the phosphate added to the medium had been incorporated into phospholipid by the macrophages, mainly into lecithin and sphingomyelin, but partly also into phosphatidyl ethanolamine and inositol phosphatide. The addition of cholesterol to the macrophage suspensions increased the rate of incorporation by 20% with 1 mg of cholesterol added, and 44% with 2.5 mg added. The increase was similar for all the phospholipid fractions, and was not accompanied by any increase in oxygen uptake by the cells. The addition of carbon particles (as a specific check for phagocytic effects) had only a small effect on the rate of incorporation. The data provide support for the concept that cholesterol stimulates phospholipid synthesis by similar cells in the arterial wall during atherogenesis.

Animals↗
PubMedDate not supplied

Homozygous familial hypercholesterolemia occurring with apoprotein E3 deficiency. Report of two cases.

This is the first report of homozygous familial hypercholesterolemia (FH) occurring together with dysbetalipoproteinemia. The former was demonstrated by deficiency of specific receptors for apoprotein B of low density lipoproteins and the latter by isoelectric focusing of the E isoapoproteins and the presence of a broad-beta band on electrophoresis. Two young boys of Lebanese extraction had extensive tuberous and tendinous xanthomata, serum cholesterol concentrations of 29.9 and 28.4 mmol/liter, respectively, and mildly raised serum triglycerides due to an accumulation of lipoprotein remnant particles. Homozygosity for FH was demonstrated in both boys by the deficiency of specific binding of low density lipoprotein to cultured skin fibroblasts (less than 15% and less than 10% of normal, respectively). The E apoprotein phenotypes showed E3/E2 in one boy and E2/E2 in the other. The treatment of both boys with cholestyramine and probucol reduced the serum cholesterol concentration to between 15 and 18 mmol/liter and dramatically lessened the severity of xanthomatosis.

Apolipoprotein E3↗