PubMed Health⌕ Search

Biomedical subjects

C J Packard

Publications and source records attributed to C J Packard.

At least 163 records · Page 9Linked to original sources
PubMed1987

Lipid transport through the plasma: the metabolic basis of hyperlipidaemia.

Plasma lipid abnormalities derive their importance from their association with coronary artery disease. Elevated cholesterol levels accentuate risk, and clinical trials have shown that reductions lead to a decline in coronary events. The major plasma lipids, cholesterol and triglyceride, circulate in association with specific proteins as lipid-protein or lipoprotein complexes. The proteins direct and regulate the metabolism of these complexes by interacting with tissue enzymes and receptors. The metabolic fate of circulating triglyceride is governed by the activity of the enzyme lipoprotein lipase, situated in adipose tissue and skeletal muscle. Cellular demand for cholesterol, on the other hand, is met by activation of a specific receptor which mediates the delivery of sterol-rich lipoproteins to lysosomal degradation in liver and peripheral tissues. In order to prevent excess cholesterol accumulation at the periphery, there is a system of reverse cholesterol transport which involves assimilation and trapping of the sterol in the plasma lipoproteins through the action of the enzyme lecithin:cholesterol acyltransferase. Thereafter, the cholesterol is delivered to the liver, the only organ capable of excreting it in significant amounts. Disturbances in these processes may produce gross changes in the plasma lipid profile, clearly recognizable as hyperlipidaemia. However, it is becoming increasingly clear that a number of inherited traits can subtly perturb the lipoprotein spectrum and increase coronary risk even in subjects whose plasma lipoprotein profile would be considered normal.

Apolipoproteins↗
PubMed1986

The effect of sotalol on plasma lipoproteins and apolipoproteins.

Plasma lipoproteins were estimated in ten hypertensive subjects (mean age 51 +/- 11.2 yr), before, 6 wk and 6 mth following treatment with Sotalol 320 mg/day. Heart rate fell sequentially throughout the study (p less than 0.01) and although there was a sequential fall in mean blood pressure this did not reach statistical significance. There was a significant increase in plasma triglyceride concentration from a basal value of 1.87 +/- 1.064 to 2.50 +/- 0.877 mmol/l (p less than 0.005) at 6 mth. No significant change was found in very low density, low density and high density lipoprotein cholesterol or apolipoprotein concentrations (Apo A-I, Apo A-II, Apo B). We conclude that Sotalol exerts a similar influence on plasma lipoproteins as other non-cardioselective beta-adrenoceptor blockers without intrinsic sympathomimetic activity and its use does not constitute an increased risk of developing atherosclerosis, when compared with other beta-blockers.

Adult↗
PubMed1986

Prevention of cardiovascular disease in general practice: a proposed model.

A screening model based in general practice for the detection of subjects at risk of premature cardiovascular disease is described. Opportunistic screening is performed by a trained nurse who also gives initial advice on management. Immediate feedback to patients is possible since a rapid dry chemistry technique is used to measure blood cholesterol concentrations. The collation and analysis of data are achieved using a microcomputer. A central deidentified database is incorporated to allow epidemiological studies and intervention strategy evaluations to be made. Nineteen health centres have evaluated the model, and 40,000 subjects have been screened: 10% had diastolic blood pressures of over 95 mm Hg and 15% had a blood cholesterol concentration over 7 mmol/l (270 mg/100 ml) and 2% over 9 mmol/l (347 mg/100 ml). The initial data suggest that the model is acceptable to both health centre personnel and the general public and that the offer of screening is taken up by all elements of the target population.

Adult↗
PubMed1986

Receptor-independent low-density lipoprotein catabolism.

Cultured cells, animal models, and man all possess mechanisms for LDL degradation that do not require the agency of the high-affinity receptor. In healthy individuals their functional significance can be determined using LDL which has been modified by specific chemical reactions designed to inhibit it receptor binding. Although the precise nature of the pathways has not been defined, there is evidence to implicate the monocyte-macrophage system in the process.

Animals↗
PubMed1986

Lipoprotein receptors and atherosclerosis.

Mammalian cholesterol metabolism is governed by two key features of the steroid nucleus: it is poorly soluble in plasma and it cannot be degraded in animal tissues. Cells which require the lipid import it through their cytoplasmic membranes in the form of solubilized lipid-protein complexes, and a similar export mechanism is essential in order to maintain cellular homoeostasis. The translocation is mediated by high affinity receptors which, under normal circumstances, operate in close synchrony. Changes in the nature of the lipoprotein ligand or of the cell itself may disturb this balance and lead to the pathological sterol accumulation which characterizes atherosclerotic lesions. All body tissues engage in this traffic in cholesterol but the liver is the single most important organ since it has the capacity both to synthesize large quantities of the lipid and to excrete it from the body via a variety of receptors designed to maintain peripheral sterol levels within safe limits.

Arteriosclerosis↗
PubMed1986

Effects of bezafibrate on apolipoprotein B metabolism in type III hyperlipoproteinemic subjects.

This study was designed to investigate the response of Type III hyperlipoproteinemic subjects to bezafibrate therapy. The metabolism of apolipoprotein B was examined in four lipoprotein subclasses of Sf 60-400 (large very low density lipoprotein (VLDL)), Sf 20-60 (small VLDL), Sf 12-20 (intermediate density lipoprotein (IDL)), and Sf 0-12 (low density lipoprotein (LDL)) before and during bezafibrate therapy. Treatment reduced the plasma concentration of VLDL and raised high density lipoprotein (HDL) cholesterol. There was no net change in LDL cholesterol or its associated apolipoprotein B. The decrease in plasma VLDL derived mainly from an inhibition of synthesis of both large and small subfractions which reduced the number of particles in the circulation without normalizing their lipid composition. Catabolism of the larger VLDL also increased, presumably as a result of lipoprotein lipase activation. Although the plasma concentration of LDL was unchanged, both its synthesis and catabolism were perturbed. Its fractional catabolic rate fell by 50%, but the impact that this would have had on its steady state level in the circulation was apparently blunted by a decrease in its synthesis from Sf 12-20 IDL. In the control phase of the study, most IDL apolipoprotein B was converted to LDL. Bezafibrate therapy channelled this material towards direct catabolism.

Adult↗
PubMed1986

The pathogenesis of hyperlipoproteinaemia.

The hyperlipoproteinaemias are among the most commonly encountered metabolic derangements seen in clinical practice, and are important because of their frequent association with atherosclerotic vascular disease. Although their underlying biochemical defects are not yet completely elucidated, sufficient comprehension of normal lipoprotein metabolism has now been acquired to permit us to ascribe mechanisms to these clinical conditions as we know them. This article briefly summarises the plasma lipoprotein transport system and classifies the major primary lipoprotein disorders according to current understanding of the pathological changes responsible for their presentation.

Humans↗
PubMed1985

The pathophysiology of cholesterol metabolism in man.

The concentration of low density lipoprotein in human plasma depends on the balance between its rates of synthesis and catabolism. Although both processes appear to be independently regulated they occur side by side in the liver and may be linked via the activity of the high affinity low density lipoprotein receptor on hepatocyte membranes. Dietary changes such as cholesterol feeding or variation in fat content can promote synthesis of the lipoprotein without changing catabolism while other interventions (e.g. sequestrant resin therapy) have the opposite effect. These different responses may be explained on the basis of compartmentalisation of regulatory sterol pools in the liver cell.

Apolipoproteins A↗