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Biomedical subjects

D Crook

Publications and source records attributed to D Crook.

115 records · Page 7Linked to original sources
PubMed1975

Prostaglandin synthetase activity from human rheumatoid synovial tissue and its inhibition by non-steroidal anti-inflammatory drugs.

1. Prostaglandin synthetase activity was found in a microsomal fraction from human rheumatoid synovia. 2. The microsomes produced PGE2 and a small amount of PGF2 when incubated with arachidonic acid. 3. The pH optimum of the enzyme from this source was similar to that found with microsomal preparations from rabbit renal medullae and bovine seminal vesicles. 4. The enzyme was inhibited in vitro by the non-steroidal anti-inflammatory drugs flurbiprofen, indomethacin and aspirin in the same rank order of potency as prostaglandin synthetase from other tissues.

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PubMedDate not supplied

Direct evidence that reverse cholesterol transport is mediated by high-density lipoprotein in rabbit.

Mammalian cells obtain cholesterol for membrane synthesis mostly via the receptor-mediated endocytosis of low-density lipoprotein (LDL). Macrophages and vascular endothelium additionally have receptors that recognize certain modified forms of LDL (for example, acetyl-LDL). The process by which cholesterol returns from peripheral cells to hepatocytes (reverse cholesterol transport) has not been established; although tissue culture studies have favoured high-density lipoprotein (HDL) as the principal vehicle, the in vivo evidence for this is meagre. When cholesterol-loaded macrophages are incubated in medium containing plasma, cholesterol moves from the cells to HDL and is then esterified by lecithin/cholesterol acyltransferase. The accumulation of cholesteryl esters in the particles increases their size and decreases their density; enrichment with apoprotein E (apo E) also occurs, producing a decrease in electrophoretic mobility. We now report that similar changes occur in the circulating HDL of rabbits, when their peripheral tissues are loaded with cholesterol by intravenous (i.v.) injection of acetylated or native human LDL. This result suggests that HDL is involved in reverse cholesterol transport in vivo.

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PubMedDate not supplied

Isolation and characterization of several plasma apolipoproteins of common marmoset monkey.

To explore the potential of the common marmoset monkey (Callithrix jacchus) as a model for human plasma lipoprotein metabolism, several marmoset apolipoproteins were isolated and characterized in this study. Based on several properties, including molecular weight, amino acid composition, and sequence, the marmoset apolipoproteins are strikingly similar to human apolipoprotein (apo) A-I, A-II, C-III, and A-IV. The first 54 residues of marmoset apo A-I showed 87% sequence identity with the corresponding region of human apo A-I. Amino-terminal sequence analysis of a minor basic apo A-I isoform revealed that it contained an amino-terminal hexapeptide extension (Arg-His-Phe-Gln-Gln-) identical to that found in human proapo A-I. Like apo A-II in most nonhuman primates, marmoset apo-A-II differed from human apo A-II in that it did not contain cysteine and therefore existed as a monomer. The complete amino acid sequence of marmoset apo A-II was deduced. The protein contains 77 amino acids, as does human apo A-II, and showed an 82% identity with its human equivalent. In both species, apo C-III and E had similar amino-terminal sequences and amino acid compositions. Like human apo E, marmoset apo E contained minor sialylated isoforms. However, unlike human apo C-III, no sialyated isoforms of marmoset apo C-III were observed. In addition, the marmoset possessed an apolipoprotein whose molecular weight and amino acid composition were similar to those of human apo A-IV. The close structural similarities between corresponding marmoset and human apolipoproteins indicate that the marmoset monkey will be useful as a model for human lipoprotein metabolism.

Amino Acid Sequence↗
PubMedDate not supplied

Isolation and characterization of plasma lipoproteins of common marmoset monkey. Comparison of effects of control and atherogenic diets.

This study examines the potential of the common marmoset monkey (Callithrix jacchus) to serve as a model for human lipoprotein metabolism and atherosclerosis. The lipoproteins of animals fed a low-fat, low-cholesterol diet and a high-fat (12% wt/wt lard), high-cholesterol (0.34% wt/wt) diet were characterized by the combination of sequential ultracentrifugation and Pevikon block electrophoresis. Based on chemical and physical properties, equivalents of human very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL), including and HDL-with apolipoprotein E subclass, were demonstrated. In control animals, whose plasma cholesterol concentration was 140.1 +/- 20.2 mg/dl (means +/- SD), approximately 40% of the plasma cholesterol was transported by LDL as compared with approximately 70% in humans. The cholesterol-fed marmosets segregated into two groups: hypo- and hyper-responders. The hyper-responders had plasma cholesterol levels of 450 to 970 mg/ml. The hypercholesterolemia was associated with elevated concentrations of VLDL, intermediate density lipoproteins, and LDL; in addition, these lipoproteins were enriched in cholesteryl esters relative to lipoproteins isolated from control animals. The HDL (d greater than 1.09 g/ml) levels did not change in response to cholesterol feeding, although the HDL-with apolipoprotein E found in the d = 1.02 to 1.09 g/ml fraction increased approximately fivefold. Based on immunological characteristics and sialic acid content, the common marmoset appeared to lack a lipoprotein(a) equivalent. The results of a short-term feeding study (11 months) suggest that this monkey was susceptible to the development of diet-induced atherosclerosis. The hyper-responsive animals developed foam cell lesions and moderately proliferative intimal lesions, predominantly within the thoracic aorta. In summary, the results of our studies indicate that the common marmoset monkey potentially is a useful model for the study of both lipoprotein metabolism and diet-induced atherosclerosis.

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