Biomedical subjects

G R Thompson

Publications and source records attributed to G R Thompson.

At least 145 records · Page 8Linked to original sources

PubMed1984

Effects of starvation and plasma exchange on lecithin: cholesterol acyltransferase activity and cholesterol efflux in cholesterol-fed pigs.

The effects of starvation and of plasma exchange with a cholesterol-free substitute on efflux of tissue cholesterol and on lecithin: cholesterol acyltransferase (LCAT) activity in plasma and peripheral lymph were investigated in two pigs fed a cholesterol diet for 3-4 months. The pigs were labelled with i.v. [14C]cholesterol before plasma exchange or starvation. The cholesterol diet increased plasma total cholesterol concentration and LCAT activity in plasma and lymph, but had little effect on the rate of esterification of cholesterol in plasma or lymph. During cholesterol feeding, and when the animals were fed a normal diet, cholesterol esterification rates in plasma and lymph were much lower than the maximum rates achieved when LCAT was saturated with substrate, suggesting that LCAT in normal pig plasma and lymph is not saturated with substrate. Plasma exchange, carried out when the specific activity of tissue cholesterol exceeded that of plasma cholesterol, was followed by a brief rise in the specific activity of plasma cholesterol to a maximum value between the specific activities of muscle and adipose-tissue cholesterol, reflecting the transfer of radioactive cholesterol from tissue to plasma. During the rise in plasma total cholesterol specific activity there were no differences between the specific activities of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol in plasma or lymph. Starvation had no effect on the plasma-cholesterol specific-activity curve. From about day 14 after labelling, cholesterol-specific activity decreased in the order: tissues greater than lymph greater than plasma. This suggests that the transfer of cholesterol from tissues to plasma was mediated by lipoproteins in the interstitial fluid.

Animals↗

PubMed1984

Effects of short term beta adrenoreceptor blockade on serum lipids and lipoproteins in patients with hypertension or coronary artery disease.

The effects of beta adrenoceptor blockade with propranolol or pindolol on serum total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and its subfractions HDL2 and HDL3, serum triglyceride, and Intralipid clearance were studied in 17 normolipidaemic, non-diabetic patients with hypertension or angina pectoris. Both pindolol and propranolol had similar effects on fasting serum total and lipoprotein cholesterol concentrations. HDL2 cholesterol concentrations were reduced by 9 +/- 29% and HDL3 cholesterol increased by 11 +/- 16%, but there were no significant changes in total or LDL cholesterol in the combined groups after six weeks' treatment. After 12 weeks' treatment total cholesterol concentrations were reduced by 7 +/- 10% mainly owing to a reduction in the LDL fraction of 9 +/- 15%. Concentrations of HDL2 remained low, 8% less than control values. Serum triglyceride concentrations were increased by both drugs at six weeks but had returned to base values in the pindolol group by the twelfth week. Pindolol, but not propranolol, enhanced the rate of clearance of intravenous Intralipid.

Adult↗

PubMed1984

Circulating human C-reactive protein binds very low density lipoproteins.

Native human CRP in solution formed complexes with the abnormal lipoprotein beta-VLDL in serum of patients with type III hyperlipoproteinaemia. CRP also formed complexes in sera from individuals with type IV and type V hyperlipoproteinaemia. The binding was calcium-dependent and inhibitable by free phosphoryl choline. No complexes were demonstrable in sera containing high LDL levels from cases of type IIa hyperlipoproteinaemia. Addition of isolated beta-VLDL, but not of isolated LDL, to acute phase normolipoproteinaemic serum caused the appearance of soluble CRP-lipoprotein complexes. In contrast, addition of an excess of isolated normal VLDL to acute phase serum or to isolated CRP was followed by agglutination (creaming) of the lipoprotein particles. Rabbit CRP, on the other hand, formed soluble complexes both with normal human apoB containing lipoproteins and with the abnormal beta-VLDL. Human CRP complexed with rabbit beta-VLDL but not with normal rabbit serum lipoproteins. These interactions may be important for the role of CRP in health and disease.

Animals↗

PubMed1983

Collagen content of atherosclerotic arteries is higher in smokers than in non-smokers.

The biochemical composition of coronary endarterectomy and aortic samples obtained during 52 coronary artery bypass graft operations was analysed. The content of cholesterol or collagen relative to protein in the aorta or endarterectomy specimens did not correlate with serum total cholesterol, triglyceride, or high-density-lipoprotein cholesterol, nor were there any significant differences between samples from normotensive and hypertensive patients. However, smokers had a significantly higher content of collagen in coronary endarterectomy specimens and the aorta and a higher content of cholesterol in the aorta than non-smokers.

Aorta↗

PubMed1983

Cinnamic aldehyde: a survey of consumer patch-test sensitization.

The potential for cinnamic aldehyde, an important fragrance and flavour ingredient, to induce or to elicit delayed contact hypersensitivity reactions in man was evaluated by analysing patch-test data. Results of studies involving a total of 4117 patch tests on various consumer products and fragrance blends containing cinnamic aldehyde and on the material itself were collected from fragrance and formulator companies. The data indicate that cinnamic aldehyde contained in consumer products and fragrance blends at concentrations up to 6 X 10(-1)%, and patch-tested at concentrations up to 8 X 10(-3)%, has no detectable potential to induce hypersensitivity. Cinnamic aldehyde when tested alone induced a dose-related hypersensitivity response. According to published reports, cinnamic aldehyde elicited positive delayed hypersensitivity responses in dermatitic patients. However, results of the current survey show that when cinnamic aldehyde was tested alone or as part of a mixture in subjects in the general population, no pre-existing hypersensitivity reactions to the fragrance material were observed in any of the 4117 patch tests which constituted the survey. Cinnamic aldehyde at the concentrations contained in consumer products and fragrances, has a very low potential to induce hypersensitivity ('induced' reactions) or to elicit sensitization reactions ('elicited' reactions) in the general population.

Acrolein↗

PubMed1983

Eugenol and clove leaf oil: a survey of consumer patch-test sensitization.

The potential of eugenol and of clove leaf oil, which contains a high concentration of eugenol, to induce delayed skin hypersensitivity or to elicit reactions due to pre-existing skin sensitization in man was evaluated by analysing patch-test data. Results from a total of 11,632 patch tests on eugenol itself, on various consumer products containing eugenol and/or clove leaf oil, and on fragrance blends containing eugenol and/or clove leaf oil were collected from fragrance and formulation companies. One instance of induced hypersensitivity and one instance of pre-existing sensitization were observed at eugenol patch-test concentrations of 5 X 10(-2) and 9 X 10(-2)% respectively. In both cases, subsequent patch testing showed skin responses to mixtures of eugenol and isoeugenol, but no further attempt was made to define the causative agent. The survey indicates that, at the concentrations present in consumer products, eugenol alone or as part of clove leaf oil has a very low potential either to elicit pre-existing sensitization ('elicited' reactions) or to induce hypersensitivity ('induced' reactions).

Dermatitis, Contact↗

PubMed1983

Isoeugenol: a survey of consumer patch-test sensitization.

The potential of isoeugenol, an important fragrance and flavour ingredient, to induce delayed contact hypersensitivity or to elicit pre-existing sensitization reactions in man was evaluated by analysing patch-test data from dermatitic and non-dermatitic subjects. Results from a total of 6512 patch tests (involving approximately 5850 subjects) on isoeugenol alone and on various consumer products and fragrance blends containing isoeugenol, were collected from fragrance and formulator companies. Hypersensitivity induced by isoeugenol was concentration dependent. All but two of the reactions occurring in this survey were at exposure concentrations greater than or equal to 0.8% isoeugenol. No induced reactions occurred in the 1004 patch tests reported at isoeugenol concentrations between 0.03 and 0.5%. One induced reaction in 32 patch tests was attributable to isoeugenol at a concentration of 0.02% while another induced reaction in 23 patch tests conducted at the same concentration was resolved to an isoeugenol-eugenol mixture. One elicited reaction at an isoeugenol concentration of 0.04% occurred in the 6512 patch tests reported in this survey. This single elicitation was resolved to an isoeugenol-eugenol mixture, but the specific causative agent was not identified. The results of this survey indicate that isoeugenol has a very low potential for either eliciting pre-existing sensitization reactions ('elicited' reactions) or inducing hypersensitivity ('induced' reactions) in subjects exposed to consumer products containing this ingredient.

Dermatitis, Contact↗

PubMed1983

Benzyl salicylate: a survey of consumer patch-test sensitization.

The potential of benzyl salicylate, an important fragrance and flavour ingredient, to induce hypersensitivity or to elicit reactions to pre-existing hypersensitivity in the general population was evaluated by analysing patch-test data. Results obtained from fragrance and formulator companies for a total of 10,538 patch tests on benzyl salicylate alone, on a variety of household and personal care consumer products and on fragrance blends containing benzyl salicylate were analysed as part of this survey. No induced or elicited responses directly attributable to benzyl salicylate were observed in the 35 patch tests on benzyl salicylate alone, or in the 10,503 patch tests on consumer products or fragrance blends containing benzyl salicylate. The highest concentration of benzyl salicylate tested in the consumer-product tests was 2 X 10(-1)%, and benzyl salicylate alone was tested at 10% in ethanol. This study indicates that benzyl salicylate has a very low potential to induce hypersensitivity ('induced' reactions) or to elicit reactions presumably attributable to pre-existing sensitization ('elicited' reactions) and thus supports the safe use of benzyl salicylate in consumer products and fragrance blends.

Dermatitis, Contact↗

PubMed1983

Normal adrenocortical response to adrenocorticotrophic hormone in patients with homozygous familial hypercholesterolaemia.

1. Plasma cortisol concentration was measured in three subjects with homozygous familial hypercholesterolaemia immediately before, and 30 and 60 min after, an intramuscular injection of adrenocorticotrophic hormone. The baseline values and the values at 30 and 60 min were within the normal range. 2. We conclude that in the presence of a genetic deficiency of low-density lipoprotein receptors, the human adrenal cortex can respond to a single injection of adrenocorticotrophic hormone with a normal increase in corticosteroid production.

Adolescent↗

PubMed1983

Composition and distribution of low density lipoprotein fractions in hyperapobetalipoproteinemia, normolipidemia, and familial hypercholesterolemia.

Hyperapobetalipoproteinemia is defined as the combination of a normal low density lipoprotein (LDL) cholesterol in the face of an increased LDL apolipoprotein B (apoB) protein. To examine the physical basis for the apparent disproportion between LDL cholesterol and apoB characteristic of this syndrome, we used density gradient ultracentrifugation to isolate LDL fractions from 10 normal subjects, from 20 patients with hyperapobetalipoproteinemia (10 normotriglyceridemic and 10 hypertriglyceridemic), and from 7 patients with familial hypercholesterolemia. In familial hypercholesterolemia, more LDL was in fraction 1--"light" LDL--and this LDL was relatively enriched in cholesterol and poor in protein. By contrast, it was fraction 2--"heavy" LDL--that differed in hyperapobetalipoproteinemia, being denser, depleted of cholesterol (particularly cholesteryl ester), and relatively enriched in apoB. These findings were more pronounced in the hypertriglyceridemic patients than in the normotriglyceridemic patients with hyperapobetalipoproteinemia. Thus this study confirms that considerable heterogeneity exists between LDL subfractions within individuals but, in addition, indicates there are also marked--and apparently characteristic--differences in LDL composition amongst normal subjects and patients with hyperapobetalipoproteinemia or familial hypercholesterolemia.

Apolipoproteins↗

PubMed1983

Cross sectional echocardiographic assessment of the aortic root and coronary ostial stenosis in familial hypercholesterolaemia.

Aortic root abnormalities (atherosclerotic thickening and obstruction) seen at necropsy may readily be detected by aortography in familial hypercholesterolaemia. We studied 35 patients with familial types IIa and IIb hyperlipoproteinaemia including three homozygotes and 32 heterozygotes. Two homozygotes showed abnormal bright echoes (atheroma) encircling the proximal aortic root, which interfered with full excursion of the aortic cusps. One homozygote showed the typical echocardiographic features of supravalvular aortic stenosis at the superior border of the sinus of Valsava with normal aortic cusps. Cardiac catheterisation showed valvular gradients of 15 and 80 mm Hg in two homozygotes and a supravalvular gradient of 40 mm Hg in the third. Left coronary artery ostial stenosis was identified by echocardiography in all three homozygotes. Echocardiographic measurements of the aortic root in the 32 heterozygotes were similar to the control group, but 10 patients showed abnormal bright echoes within the aortic cusps and four had supravalvular changes similar to, but less severe than, the homozygotes. In one severely heterozygote supravalvular atheroma prevented full aortic cusp excursion, and this finding was confirmed during coronary artery bypass surgery.

Adolescent↗

PubMed1983

Effect of partial ileal bypass on the gut hormone responses to food in man.

The integrated response of the regulatory peptides of the gastrointestinal tract to a test meal was studied in six hypercholesterolaemic patients who had undergone partial ileal bypass (PIB) and compared with responses in ten age- and sex-matched controls. Plasma motilin was found to rise significantly whereas plasma pancreatic polypeptide release was impaired after PIB. Plasma cholecystokinin rose promptly in both controls and the partial ileal bypass patients, and the latter group showed marked further rises, at 60 and 120 minutes after the meal, which were significantly higher than controls. Basal and postprandial plasma gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, insulin and pancreatic glucagon were similar in the two groups.

Adult↗

PubMed1982

Receptor-mediated low-density lipoprotein catabolism.

Low-density lipoprotein (LDL) receptors are demonstrable in cultured fibroblasts from normal subjects but are decreased or absent in cells from patients with heterozygous or homozygous familial hypercholesterolaemia. In vivo receptor-mediated LDL catabolism, determined as the difference between the turnover rates of 125I-LDL and 131I-LDL coupled with cyclohexanedione, is responsible for approximately one-third of the total catabolism of LDL in normal subjects, but less than one-fifth in heterozygotes and is totally absent in homozygotes. Receptor-mediated catabolism can be stimulated in normal subjects and in heterozygotes by measures that promote bile acid synthesis, namely, administration of anion-exchange resins or creating a partial ileal bypass. Studies in dogs have shown that such measures stimulate the high-affinity binding of LDL by liver cell membranes. Taken together, these observations suggest the existence of LDL receptors in human liver, the function of which is to maintain cholesterol homeostasis within the hepatocyte during periods of increased demand. Partial or complete absence of such hepatic receptors may play a major role in the pathogenesis of familial hypercholesterolaemia.

Cholestyramine Resin↗

PubMed1982

The effect of partial ileal bypass on receptor-mediated uptake and catabolism of low density lipoprotein in the rhesus monkey.

The fractional rates of catabolism (FCR) of 125I-labelled low-density lipoprotein (LDL) and 131I-labelled LDL coupled with 1,2-cyclohexanedione (LDL-CHD) were determined before and 6 weeks after partial ileal bypass in three Rhesus monkeys. Receptor-mediated catabolism, determined as the difference between the FCRs of 125I-LDL and 131I-LDL-CHD, increased significantly after partial ileal bypass. Analysis of tissue distribution of radioactivity in one monkey, killed at the conclusion of a third turnover study 6 months after partial ileal bypass, suggested that the liver was the main tissue site of accumulation of LDL, and that uptake had occurred mainly via a receptor-mediated mechanism. It is concluded that partial ileal bypass stimulates receptor-mediated LDL catabolism in the Rhesus monkey as in man, and that this increase is probably mediated via hepatic LDL receptors.

Animals↗

PubMed1982

X-linked spondyloepiphyseal dysplasia tarda: mucopolysaccharide excretion studies.

Sex linked spondyloepiphyseal dysplasia tarda is described in a family with four affected members. The characteristic features of short trunk, hip disease, and flattening of the vertebrae with a posterior "hump" were present. Urinary mucopolysaccharides were characterized both quantitatively and qualitatively and were within normal values.

Adult↗

PubMed1982

Gold toxicity presenting as peripheral neuropathy.

A patient with rheumatoid arthritis developed gold induced peripheral neuropathy after 255 mgs of aurothioglucose. This neuropathy is characterized by weakness and numbness of the hands and feet in association with hyperalgesia of the palmar surface of the hands. The absence of vasculitis permits differentiation of gold neuropathy from the neuritis associated with rheumatoid arthritis or systemic lupus erythematosus. Treatment consists in cessation of gold and possibly the use of dimercaprol; recovery is slow but generally complete.

Adult↗

PubMed1982

The metabolism of very low density and intermediate density lipoproteins in patients with familial hypercholesterolaemia.

The metabolism of apolipoprotein B (apoB) in very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) was studied in normal subjects and in patients with familial hypercholesterolaemia (FH) after an intravenous injection of autologous VLDL labelled with 125I. There were no significant differences in half life, pool size and turnover rate (mg/kg/h) of VLDL-apoB between the normal subjects, the FH heterozygotes and the FH homozygotes. IDL-apoB metabolism in the FH patients differed significantly from that in the normal subjects. In the FH patients, the rise to the maximum of the specific activity curve was slower, the half life of the descending limb of the specific-activity curve was longer, the fractional rate of turnover was lower and the plasma concentration was higher than in the normals. The effect of cholestyramine on IDL-apoB metabolism in the normal subjects did not differ from that in the FH heterozygotes and homozygotes, though cholestyramine is known to stimulate hepatic uptake of low density lipoprotein (LDL) by the LDL receptor. It is suggested that in normal human subjects the LDL receptor makes some contribution to the hepatic uptake of IDL-apoB derived from VLDL, but that IDL uptake is mediated partly by a separate receptor that recognizes apolipoprotein E but not apoB.

Adolescent↗

PubMed1982

Difference in saturable binding of low density lipoprotein to liver membranes from normocholesterolemic subjects and patients with heterozygous familial hypercholesterolemia.

To investigate the possible role of the low density lipoprotein (LDL) receptor in the catabolism of LDL by the human liver, the binding of 125I-labeled LDL to membrane fractions prepared from human liver biopsies was determined. Biopsy samples taken for routine histology were obtained from seven patients with heterozygous familial hypercholesterolemia, one with non-familial hypercholesterolemia, and seven normocholesterolemic subjects. LDL was bound by the membranes from normal subjects in a saturable manner that was inhibited by 56% in the presence of excess LDL. Binding of LDL was also inhibited by modification of the lipoproteins with 1,2-cyclohexanedione. The amount of 125I-labeled LDL bound to membranes from familial hypercholesterolemic livers that could be displaced with excess LDL was significantly less than that bound by normocholesterolemic membranes. These observations suggest that LDL receptors are expressed in normal human liver and are defective in the livers of familial hypercholesterolemic patients.

Cell Membrane↗