Biomedical subjects
G Schettler
Publications and source records attributed to G Schettler.
A new role for nicotine: selective inhibition of thromboxane formation by direct interaction with thromboxane synthase in human promyelocytic leukaemia cells differentiating into macrophages.
Thromboxane, one of the major oxygenated arachidonic acid metabolites of human macrophages, is the most potent vasoconstricting and proaggregatory molecule known. In addition, thromboxane has been shown to be related to host defence mechanisms. We studied the effects of nicotine and its major metabolites on thromboxane formation using cultured macrophage-like cells (HL-60), microsomal assays and purified thromboxane synthase. In intact cells, nicotine, cotinine and methylnicotine at submicromolar concentrations inhibited the rate of conversion of both arachidonic acid and the unstable endoperoxide prostaglandin H2 into thromboxane but not into other eicosanoids. This indicates that nicotine selectively inhibits thromboxane synthase at concentrations that are readily observed in the circulation of smokers. Microsomal assays revealed that nicotine decreased the maximal velocity of thromboxane synthase without affecting the apparent affinity of the enzyme for its substrate. In contrast, no effect of nicotine on kinetic parameters of prostaglandin H synthase or prostacyclin synthase could be observed. Difference spectra, using purified thromboxane synthase, revealed that nicotine directly interacts with the enzyme, presumably by binding the nitrogen of the nicotine ring structure to the iron of the cytochrome P-450 component of thromboxane synthase.
Observations on leukocytes from patients with severe familial hypercholesterolemia.
Differences in light scatter and fluorescence emission of blood leukocytes from patients with familial hypercholesterolemia (FH) and normal patients incubated with oil red O and r(NBD-Cl)-acetyl-LDL were observed by flow-through cytofluorometry and used to distinguish a subclass of leukocytes. The appearance of this subpopulation of leukocytes in FH apparently correlated with the excessive hypercholesterolemia. In addition, microscopic evaluation of blood smears suggested the formation of small cytoplasmic vacuoles in a population of FH monocytic cells. While these are preliminary observations on a small number of patients, they warrant further study. However, the use of lipophilic dyes and fluorescent acetyl-LDL in combination with flow cytometry may be another useful means for evaluation of FH.
Plasmalipoproteins and atherosclerosis.
The author describes and classifies the different types of lipo-proteins and their connection with the various types of hyperlipoproteinemias and he discusses their possible role in producing atherosclerosis.
[Strategy for the prevention of ischemic heart disease. Directives from the European Society of Atherosclerosis].
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Advances in lipoprotein research. Biochemical and clinical aspects.
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[Secondary prevention of coronary heart disease. Recommendations of the Workshop of the International Society and Federation of Cardiology on the Secondary Prevention of Coronary Heart Disease. Titisee (German Federal Republic), 21-14 October 1983].
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