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Biomedical subjects

W Krone

Publications and source records attributed to W Krone.

At least 145 records · Page 8Linked to original sources
PubMed1987

Effects of calcium antagonists and adrenergic antihypertensive drugs on plasma lipids and cellular cholesterol metabolism.

Calcium antagonists and antihypertensive alpha-adrenergic and beta-adrenergic drugs may cause changes in plasma lipoprotein levels. Different mechanisms by which these antihypertensive agents effect cellular lipid metabolism have been proposed. The activity of lipoprotein lipase that determines the catabolism of very low density lipoproteins (VLDL) is decreased by the beta-blocker propranolol and increased by alpha 1-antagonists. The plasma cholesterol or low density lipoprotein (LDL) level is inversely associated with the number of LDL receptors. Catecholamines suppress the LDL receptor activity, thus leading to an increase in plasma cholesterol concentration. The calcium antagonist verapamil and the beta-blocker propranolol may increase LDL receptor activity either per se or by its antagonizing effect on the catecholamine action. The metabolism of high density lipoproteins (HDL) may be affected directly by catecholamines, which might increase HDL binding activity, thereby enhancing efflux of cholesterol from cells. Catecholamines inhibit cholesterol biosynthesis in extrahepatic cells. The effects are mediated by alpha 2- and beta 2-adrenergic receptors. Accordingly, the alpha 2-agonists clonidine and alpha-methyldopa mimicked and propranolol opposed the catecholamine action. In contrast, the alpha 1 antagonists indoramin, prazosin, and urapidil had no effect on cholesterol synthesis. The results provide evidence that calcium antagonists and various antihypertensive drugs, depending upon their action on beta- or alpha-adrenergic receptors, affect lipid metabolism differently. The metabolic effect may play a role in atherogenesis and may be of clinical importance when antihypertensive treatment is considered.

Adrenergic alpha-Antagonists↗
PubMed1986

Cell culture studies on neurofibromatosis (von Recklinghausen). V. Monosomy 22 and other chromosomal anomalies in cultures from peripheral neurofibromas.

Cell cultures grown from peripheral neurofibromas of three patients suffering from sporadic peripheral neurofibromatosis (NF) were analysed cytogenetically at early in vitro passages. The NF-cultures exhibited a 6.7-fold higher frequency of aneuploid mitoses, including pseudodiploids, than the control cultures derived from the skin of three healthy donors. The predominant numerical anomaly was monosomy 22. Several, as yet unidentified marker chromosomes occurred in the NF-cultures, which also showed a much higher level of unstable chromosomal anomalies. The role of monosomy 22 in tumorigenesis of meningiomas and neurofibromas is discussed.

Cells, Cultured↗
PubMed1986

Cell culture studies on neurofibromatosis (von Recklinghausen's disease). IV. Collagen synthesis.

Comparative measurements of collagen synthesis as a portion of total protein synthesis were performed with fragments of peripheral neurofibromas, of skin adjacent to the tumors, and of unaffected skin from patients with neurofibromatosis (NF). No significant difference was found among these various samples. Collagen synthesis was also measured in cell cultures derived from peripheral neurofibromas of eight NF patients and from skin of ten healthy donors. No differences observed in the following respective parameters: dependence on the concentration of fetal calf serum; dependence on cell population density; portion of synthesized collagens in the culture medium and the cell layer. The ratios of synthesized collagen types III to type I, determined in five pairs of NF and control strains, vary within the same range.

Cell Count↗
PubMed1985

The prostacyclin analogue iloprost and prostaglandin E1 suppress sterol synthesis in freshly isolated human mononuclear leukocytes.

The effects of the stable prostacyclin analogue iloprost, prostaglandin E1 and prostaglandin F2 alpha on sterol synthesis were investigated in freshly isolated human mononuclear leukocytes. Incubation of cells for 6 h in a medium containing lipid-depleted serum led to a 3-fold rise in the rate of sterol synthesis from [14C]acetate or tritiated water. Iloprost and prostaglandin E1 added in increasing concentrations at zero time resulted in an inhibition of the synthesis of sterols, the suppression being 50 and 55% at a concentration of 1 mumol/1, respectively. Both prostaglandins yielded a sigmoidal log dose-effect curve. In contrast, prostaglandin F2 alpha had no influence on sterol synthesis up to a concentration of 1 mumol/1. The action of the prostacyclin analogue and prostaglandin E1 on the relative rate of sterol synthesis was not immediate, since the prostaglandins had no effect when given at 6 h to the incubation medium, and the incorporation of [14C]acetate into sterols was measured thereafter. The results suggest that prostacyclin and prostaglandin E1 affect cholesterol synthesis and therefore may play a role in the regulation of cellular cholesterol homeostasis and in the development of atherosclerosis.

Alprostadil↗
PubMed1985

Cell-culture studies on neurofibromatosis (von Recklinghausen's disease). III. Experiments on X-ray sensitivity.

The X-ray sensitivity of strains of fibroblast-like cells derived from peripheral neurofibromas of ten patients with neurofibromatosis was compared with that of 12 strains of skin fibroblasts derived from healthy donors. Quantitative parameters of the dose-dependent reduction in colony-forming ability did not differ significantly between these two groups of strains. The cloning efficiencies of nonirradiated controls varied within the same range in strains derived from patients and from healthy donors.

Cell Survival↗
PubMed1984

Stimulation of beta 2-adrenergic receptors suppresses sterol synthesis in human mononuclear leukocytes.

The beta-adrenergic receptor mediating the inhibition of sterol synthesis by catecholamines in freshly isolated human mononuclear leukocytes was defined pharmacologically by using selective beta 1- and beta 2-agonists and -antagonists. Incubation of cells for 6 h in a medium containing lipid-depleted serum resulted in a 3-fold increase in the incorporation of [14C]acetate or tritiated water into sterols. The beta-agonist (-)-isoproterenol was approximately equipotent with (-)-epinephrine and (-)-norepinephrine in suppressing sterol synthesis, yielding a sigmoidal log-dose-effect curve. Accordingly, the effects of the catecholamines were reversed by the beta-antagonist (+/-)-propranolol. The beta 2-agonists terbutaline and salbutamol inhibited sterol synthesis by 42 and 26%, respectively, at a concentration of 0.1 mmol/l. Contrary to that, the beta 1-agonists prenalterol and dobutamine had no effect. In accordance with the influence of the agonists, the beta 2-antagonist butoxamine, but not the beta 1-antagonists atenolol, metoprolol and practolol, reversed the catecholamine action on sterol synthesis. The results provide evidence that catecholamines may regulate sterol synthesis by stimulating beta 2-adrenergic receptors.

Adrenergic beta-Agonists↗
PubMed1984

[Antihypertensive therapy and lipid metabolism].

Hypertension, hyperlipidaemia and cigarette smoking are major risk factors in coronary heart disease. Since many antihypertensive drugs alter plasma lipid levels it is a subject of current discussion that these agents may increase associated coronary risk and therefore offset the beneficial effects of lowering blood pressure. The purpose of this paper is to review clinical and experimental data in the literature on the influence of data in the literature on the influence of antihypertensive drugs on lipid metabolism. The thiazides hydrochlorothiazide and chlorthalidone cause an elevation of plasma triglycerides and very low density lipoprotein (VLDL) but have little effect on total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL). The unspecific beta-blockers, e.g. propranolol, do not affect total cholesterol and LDL but increase total triglycerides and VLDL and decrease HDL. The changes of plasma lipids and lipoproteins caused by cardio-selective beta-blockers, e.g. atenolol and metoprolol, and unspecific beta-blockers with intrinsic sympathomimetic activity (ISA), e.g. oxprenolol and pindolol, appear to be qualitatively similar but less pronounced. The alpha 1-blocker prazosin reduces total triglycerides and slightly lowers total cholesterol. The concentration of VLDL plus LDL decreases while HDL may increase. Only very few studies have been reported on the effects of other antihypertensive drugs, e.g. clonidine, hydralazine, on plasma lipids. Several experimental studies reveal that antihypertensive agents exert direct effects on triglyceride and cholesterol metabolism. Although the pathophysiological mechanisms and the significance of the alterations of lipid metabolism induced by antihypertensive drugs are not yet clear, the following guidelines for the clinical use of these agents are recommended: (1) before initiating drug treatment in hypertensive patients, blood lipid levels should be measured to exclude a preexisting hyperlipidaemia, (2) during long-term therapy with antihypertensive agents, lipoprotein fractions should be controlled in order to reconsider the therapeutic regime if major alterations of blood lipid levels are observed.

Adrenergic alpha-Antagonists↗
PubMed1984

Evidence for post-transcriptional regulation by insulin of 3-hydroxy-3-methylglutaryl coenzyme A reductase and sterol synthesis in human mononuclear leucocytes.

Incubation of freshly isolated human mononuclear leucocytes in lipid-depleted serum for 4 h resulted in a two-fold increase in 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity. Insulin, when added to the incubation medium at concentrations of 10 and 100 nmol/l at zero time, caused additional increases in the enzyme activity of 30% and 37%, respectively. The hormone action was not immediate because no effect was observed when insulin was added at 4 h and activity examined thereafter. Under these conditions sterol synthesis from 14C-acetate and tritiated water was strictly proportional to the activity of HMG-CoA reductase. Cycloheximide (20 micrograms/ml), a translational inhibitor of protein synthesis, prevented the insulin-mediated increase in the enzyme activity and the incorporation of 14C-acetate into sterols. Cordycepin (50 micrograms/ml) inhibited messenger RNA synthesis by greater than 50%, but had no inhibitory effect on the induction of HMG-CoA reductase and sterol synthesis. Low density lipoprotein (80 micrograms protein/ml) and complete serum blocked the induction of the enzyme and sterol synthesis from 14C-acetate caused by lipid-depleted serum. The insulin-effect, however, remained unchanged. The results suggest that insulin may regulate the de novo synthesis of HMG-CoA reductase and accordingly sterol synthesis at a post-transcriptional level.

Acetates↗
PubMed1983

Cell culture studies on neurofibromatosis (von Recklinghausen). II. Occurrence of glial cells in primary cultures of peripheral neurofibromas.

The occurrence of glial cells in primary cultures established from peripheral neurofibromas of 18 patients with neurofibromatosis (von Recklinghausen) is described. The spindle-shaped cells can be distinguished from fibroblasts on the basis of morphological and ultrastructural criteria. As demonstrated by immunocytochemical analysis, the spindle cells express S-100 protein. Neither glial fibrillar acidic protein nor myelin basic protein can be detected in these cells. In many respects the spindle cells resemble immature Schwann cells in culture.

Cells, Cultured↗