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J L Beaumont

Publications and source records attributed to J L Beaumont.

At least 91 records · Page 5Linked to original sources

Inhibition of lipoprotein lipase activity by a monoclonal immunoglobulin in autoimmune hyperlipidemia.

Autoimmune hyperlipidemia (AIH) may be induced a variety of antibodies which inhibit different stages of the lipolytic process by which the lipid load is removed from the circulating lipoproteins. In a patient having a monoclonal gammopathy and a nephrotic syndrome with a glomerulonephritis and a marked hypertriglyceridemia, it was found previously that the monoclonal IgG gamma Lac. reacted with human VLDL as well as with human serum albumin. Here it is demonstrated that the purified IgG gamma inhibits the lipolysis of triglyceride substrates by reacting with a substance (Lac. S) necessary for lipoprotein lipase activity. The interaction of IgG lambda Lac. with serum or HDL-activated triglyceride substrates inhibits the lipolytic activity of human and rat plasma post heparin and also adipose tissue lipases. It slightly inhibits the activity of swine pancreatic lipases. The Lac S. which reacts with IgG Lac. is associated to whole and delipidated VLDL and HDL and not to LDL or purified APo-A. It may be an Apo-C or a non-peptidic co-factor of the lipases which remains bound to the apoprotein core after delipidation. Its lack of species specificity and its presence as traces in HSA preparations favors the latter hypothesis. The Lac. substances is different from the Pg and As substances which were found to react with IgA anti-Pg and IgG anti-As antibodies in previously reported antilipoprotein AIH.

Adult↗

Effects of edible oils on blood and arterial lipids in rats after one year's balanced normolipidic diet.

Male Sprague-Dawley rats were fed during one year with diets containing 12% of one of the following fats: butter, sunflower oil, rapeseed oil, soybean oil, hydrogenated soybean oil, palm oil, canbra oil and arachid oil. Total serum cholesterol was lower in the arachid, suflower and butter groups and higher in the palm and hydrogenated soybean groups (p less than 0.01); serum cholesterol esters were lower in the arachid, sunflower and soybean groups, but higher in the palm and hydrogenated soybean groups ( p less than 0.01). Serum triglycerides were lower in the sunflower and arachid groups and higher in the butter and palm groups (p less than 0.01). There was a positive, significant correlation between serum cholesterol and phospholipids in the various groups. In aortas, free cholesterol levels were the same in different groups, but cholesterol ester levels increased in the following order: canbra, butter, arachid, palm, sunflower, rapeseed, hydrogenated soybean and soybean red groups (p less than 0.01). There was a significant correlation between aorta cholesterol esters and the ratio 18:0 + 18:1 of the dietary fat (r = 0.69; p less than 0.001).

Animals↗

[Immunochemical study of the lipoprotein substance Pg (author's transl)].

Site Pg is an antigenic determinant which is present on the surface of serum lipoproteins and reacts with an antilpoprotein myelomatous immunoglobulin, the IgA, Ger. Firstly site Pg is extracted from LDL with the major part of lipids, by an ether-methanol mixture at 6 p. 100. Then the organic substrate obtained is evaporated under vacuum and dissolved in saline before being submitted to an extraction by ehter only. Under these conditions, site Pg remains in the aqueous phase. A polyacrylamide gel filtration on Biogel P2 allows then to separate the substance which reacts with IgA Ger. anti-Pg, from the aqueous phase. The identification of site Pg allowed us to recognize the presence of galactose, phosphorus and choline, and to evaluate its molecular weight of about 330. The reactivity of site Pg with IgA anti-Pg was measured by inhibition of passive hemagglutination and fluorescence quenching. The association constant of site Pg with the whole IgA Ger. or with its Fab fragment could thus be calculated (1.6 10(5) M-1 with the whole IgA; 2.3 10(5) M-1 with the Fab fragment). We showed also that if phosphorylcholine plays an immunodominant role, the presence of sugar seems necessary, since the association constant of the whole IgA Ger. with site Pg is higher than that of IgA Ger. with phosphorylcholine alone.

Binding Sites, Antibody↗

[Antiheparin immunoglobulin in malignant lymphoma with hypertriglyceridemia, in the hamster].

A massive hypertriglyceridemia associated with low post heparin lipolytic activity, was demonstrated during the growth of a transplanted lymphoma in Hamsters. An immunoglobulin, with high anti-heparin activity, was extracted from the tumor. It could inhibit both the anti-thrombin and prolipase activity of heparin. The role of this anti-heparin immunoglobulin in triglyceride metabolism allows us to consider the hypertriglyceridemia of lymphoma-bearing Hamsters as one of the two previously described types of auto-immune hyperlipidemia.

Animals↗

[Association of monoclonal gammopathy with chronic glomerulonephritis and autoimmune hyperlipemia. Course of disease during therapy].

A case of benign monoclonal gammapathy associated with an auto-immune hyperlipidaemia and a chronic glomerulopathy is reported. Extraction of the monoclonal immunoglobulin made it possible to demonstrate its anti-lipoprotein antibody activity. Parallel changes in serum lipid levels and monoclonal immunoglobulin levels under the influence of melphalan confirmed the direction relationship between the lipid and protein disorders. The pathogenesis of the glomerulopathy and of the massive and prolonged activation of the classical complement pathway is more difficult to affirm. It is nevertheless possible that the renal involvement is due to an auto-immune complex disease.

Adult↗

Ischaemic disease in men and women with familial hypercholesterolaemia and xanthomatosis. A comparative study of genetic and environmental factors in 274 heterozygous cases.

The incidence of ischaemic diseases in familial hypercholesterolaemia and xanthomatosis (familial Type II) was studied in a group of 158 men and 116 women. (1) Men and women did not differ with regard to the inherited metabolic disease. Levels of serum cholesterol, the marker of the genetic defect, were not statistically different, and cholesterol deposition in tissues, visualized by skin tendon xanthomas, was not sex related. (2) Men and women were different with regard to ischaemic diseases. The incidence was much lower in women, and the mean age of onset 9 years later. Moreover, there was a sex difference in the nature of the ischaemic disease, with a high male predominance of myocardial infarction. (3) Since the major risk factor hypercholesterolaemia could not explain such a difference, the role of other risk factors was investigated. It was shown that the incidence of ischaemic diseases was increased in women by cigarette smoking and hypertension, and that the difference in age of onset between males and females was no longer seen in smoking women. It is suggested that the genetic factor is responsible for the atherosclerotic lesion in both sexes and that other factors playing a role in ischaemic complications including tobacco and hypertension may explain the difference between men and women.

Adult↗

A new serum lipoprotein associated erythrocyte antigen which reacts with a monoclonal IgM. The stored human red blood cell SHRBC antigen.

A monoclonal IgM (IgM) was found to react with stored human red blood cells (SHRBC) and human low density lipoprotein (LDL). IgM Re Fab fragment was reactive. SHRBC antigen was present, in a hidden state, in all fresh human ABO erythrocytes studies; it was not present in fresh or stored animal RBC. Cross reactivity of SHRBC and LDL antigens against IgM Re and IgM Re Fab was demonstrated. In contrast with SHRBC antigen, LDL antigen has no species specificity and was also found in rabbit and rat LDL. Furthermore, cross-reacting soluble inhibitors were also found in human saliva, and in a small molecule fraction issued from human and rabbit serum. The IgM Re also reacted with human and animal glomerular membrane. These findings are suggestive of two closely related but not identical antigens: a human specific SHRBC antigen and a LDL-associated, SHRBC-like antigen, which is a secreted, non-human specific substance. The former is part of the human RBC structure, the latter is a soluble molecule which may be found in saliva and in serum where it may be free or bound to LDL; it also binds to glomerular membranes.

Aged↗

Circulating lipophages and aortic foam cells in experimental atherosclerosis of rabbits under altered reticuloendothelial activity.

Administration of Freund's adjuvant to cholesterol-fed rabbits inhibited the induction of atheroma in the aorta of rabbits when compared with cholesterol-fed indiaink-treated animals and cholesterol-fed saline-treated controls. Simultanously the blockade of the reticuloendothelial system by india ink caused a greater degree of atheromatous lesions in these rabbits. Smears of peripheral blood studied by light microscopy revealed the presence of circulating lipophages which were morphologically similar to the aortic foam cells isolated from the same animal. Isolation of mononuclear lipid-containing foam cells from aortic intima and the presence of a morphologically similar type of cell in circulating blood indicate that the blood might be the most likely source of intimal foam cells.

Animals↗

[Oral vitamin A tolerance tests in hypertriglyceridemia (author's transl)].

HVA tolerance tests were performed to study the post-absorptive lipemia of 32 patients with hypertriglyceridemia. Among them 10 had a normal test and 22 a pathological test. This difference shows the existence of an exogenous factor in the second group of hypertriglyceridemias, which is poorly related to the typing of the WHO classification, but much more to the value of the cholesterol/triglycerides ratio of each patient. The separation of these two groups is of great interest for their therapeutical management, the hypertriglyceridemias with exogenous factor being more sensitive to diet than the others.

Administration, Oral↗

Oral contraceptive, pulmonary artery thrombosis and anti-ethinyl-oestradiol monoclonal IgG.

Pulmonary artery thrombosis and an anti-ethinyl-oestradiol monoclonal IgGlambda were found to be associated in a 36-year-old woman (Mrs MAI.) who took an oral contraceptive containing 50 mug ethinyl-oestradiol and 500 mug nor-ethisterone daily. After appropriate purification including methods by which the IgG was separated of bound circulating hormones, its binding activity was demonstrated by several methods: passive haemagglutination of oestradiol-benzoate sensitized red blood cells; gel filtration on Sephadex G-25; ultracentrifugation and equilibrium dialysis. IgGlambda MAI bound ethinyl oestradiol (Ka=2-7 X 10(1) M-1) and also 17-beta-oestradiol, with a lower affinity (Ka=0-4 X 10(7) M-1). The valency for these two hormones was near 2. Ethinyl-oestradiol bound to the IgG was displaced by ethinyl-oestradiol itself and in decreasing order of potency by 17-beta-oestradiol, progesterone, oestriol, and testosterone. Oestrone and hydrocortisone had no effect. Although the localization of the binding sites of this IgGlambda was not studied, it is likely that they were the antibody sites of the molecule and, according to immunochemical criteria, it may be classified as a monoclonal anti-ethinyl-oestradiol antibody. It is felt that its association with the pulmonary thrombosis and the oral contraceptive may be significant. This supports the hypothesis of an immunological mechanism for the unexplained thrombotic risk of oral contraceptives.

Adult↗