[Atheromatous lesions. Description of lesions and pathogenic mechanisms].
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Biomedical subjects
Publications and source records attributed to J L Beaumont.
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In this method, under certain experimental conditions, the use of calibrated glass beads permitted the separation of lg with antilipoprotein antibody activity (HLAA). The sera are first precipitated on ammorium sulphate at 25 per cent, 30 per cent and 40 per cent saturation. The precipitates are then submitted to short ultracentrifugation and the product of ultra-entrifugation is fractionnated on a glass bead column, balanced then eluted with an acetate veronal buffer at pH 9. The eluted fraction in peak 1 contains antibodies (IgG or IgA) and albumin. Passive hemagglutination with red cells covered with beta and alpha-lipoproteins, through chromium chloride, together with inhibition of the reaction show that the activity of these Ig antibodies is directed against lipoprotein antigens.
LDL interact with fibroblasts through specific membrane sites. This reaction is the first step of a mechanism which leads to the regulation of intracellular cholesterol synthesis. When LDL form a complex with an IgA from a myeloma serum with mixed hyperlipidemia and xanthomatosis, they no longer function as a regulator, and the result is excess production of free intracellular cholesterol. No excess cholesterol production is observed when myeloma IgA is replaced by control IgG and IgA.
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Human LDL were bound and internalized by cultured human fibroblasts. When an antilipoprotein IgA kappa from a case of myeloma with hyperlipidemia and xanthomatosis was introduced into the system, LDL uptake dropped by 50% but LDL binding to fibroblasts was unchanged. In the same system, IgG and IgA controls were inactive.
In a five-day clinical test, the dietary effects of canbra oil and butter on normal human subjects were studied with special reference to lipid metabolism, clotting times and platelet functions. There was no difference between the canbra oil and butter diets as regard triglyceridemia or clotting times, but cholesterolemia and in vitro platelet aggregation by ADP dropped significantly in subjects fed the canbra oil diet. The platelet count did not change significantly. A possible explanation of these results might to be the difference in the fatty acid composition of canbra oil and butter.
During the five last years, we observed under the microscope all the hyperlipidemic sera received in our laboratory, to search a lipid particle agglutination. We have retained 24 sera with obvious agglutination (9 types V, 9 types IV and 6 types IIb), the lipidemia of which was compared, type to type, to 56 control sera (16 types V, 16 types IV and 24 types IIb), in which no agglutination has been found. We observed significant differences in the means of cholesterol (CT) triglycerids (TG), vitamin A (VA) and CT/TG, VA/TG and VA/CT ratios, comparing agglutinated and control sera. These differences suggest that the agglutination phenomenon is in relation with the nature of the lipid particles present in the hyperlipidemic sera, which could be "chylomicron remnants" in type V hyperlipidemias, and other forms of "remnants" in type IV and IIb hyperlipidemias. These "remnants" could result from a blockade of lipolysis. This blockade of lipolysis in the agglutinated sera might be related to what is known about the authentificated autoimmune hyperlipidemia (AIH). Thus we can suppose that hyperlipidemias with obvious serum lipid particle agglutination are autoimmune hyperlipidemias.
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If the method using Hyland LAS-RTM kit reagent recommended by the manufactorer yielded excellent results to measure immunoglobulins free in serum, the same is not true when one quantitates immunoglobulins bound with antigens, especially with lipidic antigens. Since the specificity of Hyland antisera is not the cause of this difference, we have studied therefore the effect of the diluting buffer on the antisera, on the blank, and its consequences on the assay. The abnormalities encountered in the results were due to precipitation of lipoproteins and immune complexes by the diluting buffer yielded in the kit. We avoided entirely these errors by preparing a blank, not in NaCl 0.15 M, but in the kit reagent used to dilute the antisera.
The monoclonal anti-ethinyl-estradiol antibody previously found in the serum of a woman on oral contraceptives, was precipitated by 25% saturated ammonium sulfate à 22 degrees C. This simple test has been used to investigate the possible relationship between abnormally precipitating gamma-globulins (GAP) and the vascular risk of the pill. Four groups of women were studied: --50 women who had never used the pill; --100 women on oral contraceptives; --30 women who had stopped the pill; --17 women had experienced venous or arterial thrombosis during oral contraception. The results obtained indicate: 1) that a GAP increase is nearly always associated with the thrombotic events (90% of the cases in group 4); 2) that the presence of GAP is seen only in part of the women population on oral contraceptives representing approximately 30% of the total population investigated as indicated by a bimodal distribution. 3) that the GAP remain increased for months and even years after the pill was discontineud. The significance of this test is discussed. It is proposed that the presence of GAP in the serum appears to be related to the presence of ethinyl-estradiol binding antibodies. This hypothesis is verified by experiments in progress.
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