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Biomedical subjects

F Krempler

Publications and source records attributed to F Krempler.

At least 37 records · Page 2Linked to original sources
PubMed1995

A deletion polymorphism in the angiotensin converting enzyme gene is not associated with coronary heart disease in an Austrian population.

This study examined a possible relationship between genetic variation in the gene coding for the angiotensin converting enzyme (ACE) and increased risk for coronary heart disease (CHD) in an Austrian population. Polymerase chain reaction (PCR) was used to determine the genotypes for an insertion/deletion polymorphism in intron 16 of the ACE gene in 315 patients with CHD and in 149 normal controls. In the control group, the relative allele frequencies of the polymorphism were similar to those of previously published European studies. The genotype distribution among our patients was not significantly different from that among controls. We were not able to show a significant association of the DD genotype with coronary heart disease in subgroups containing patients considered at low coronary risk. There was no association of lipid parameters and ACE genotype. From these data we conclude that, in the Austrian population, the insertion/deletion polymorphism in the ACE gene cannot be used as a marker for coronary risk assessment.

Adult↗
PubMed1995

Postmenopausal hormone-replacement therapy and cardiovascular risk.

Case-control and cohort studies support the hypothesis that postmenopausal oestrogen-replacement therapy reduces the risk of atherosclerotic disease manifestations. The evidence for a cardioprotective effect of such a therapy is, however, incomplete because randomized prospective studies are missing. Because it may be almost impossible to conduct placebo-controlled trials in the future, other study designs will be needed to minimize selection bias. Further work is required to define the optimal dose and administration schedule of oestrogen and to determine whether addition of progestogens alters the beneficial effect of oestrogen on the cardiovascular system. Such studies may also provide mechanistic insight into the interaction between lipoprotein metabolism and haemostasis and its relation to the atherosclerotic disease process.

Cardiovascular Diseases↗
PubMed1988

Genetic variation in the apolipoprotein AI-CIII-AIV gene cluster and coronary heart disease.

Six RFLPs in the apolipoprotein (apo) AI-CIII-AIV gene region detected with the restriction enzymes XmnI, MspI, PstI, SstI and PvuII were used to study the role of genetic variation at this locus in the development of coronary heart disease and in the regulation of serum levels of various lipid and lipoprotein parameters in the Austrian population. 106 male patients with coronary heart disease and 118 matched controls were investigated. None of the alleles defined by these RFLPs was associated with increased coronary risk. In the patients, but not in the control group individuals with the genotype P1P2 for the PstI polymorphism in the 3' flanking region of the apo AI gene had significantly lower serum levels of high density lipoprotein (HDL)-cholesterol and apo AI levels than those with the genotype P1P1. The S2 allele of the SstI polymorphism at the 3' end of the apo CIII gene was significantly associated with elevated serum levels of triglycerides in the patient, but not in the control group. Controls with the genotype V2V2 for the PvuII(A) polymorphism at the 5' end of the apo CIII gene had significantly higher serum levels of apo B than those with V1V1 or V1V2. This association did not exist among the patients. These findings suggest that variation associated with some of these RFLPs is contributing to the determination of lipid levels in patients and controls, but that the RFLPs themselves cannot be used as markers for increased coronary risk in the Austrian population.

Adult↗
PubMed1988

Interaction of various lipoproteins from normal and dyslipoproteinemic plasma with mouse peritoneal macrophages.

In this study we tried to elucidate the atherogenicity of various plasma lipoproteins with respect to their capability of foam cell formation. Mouse peritoneal macrophages (MPM) were incubated with increasing amounts of lipoproteins and the incorporation of 14C oleate into the cholesteryl ester fraction was followed. The results may be summarized as follows: freshly isolated Lp(a) behaves very similar to normal LDL causing no or little increase in CE formation in MPM. Lp(a) treated with dextran sulfate as well as with antibodies to Apo-a, strongly interact with scavenger receptors causing massive accumulation of CE in MPM. The abnormal lipoproteins from patients suffering from liver disease, LP-X, HDL-E cause no increase in CE formation of MPM. They behave very similar to artificial PL/FC liposomes. If on the other hand these abnormal lipoproteins are mixed with Ac-LDL, a synergistic effect was observed causing an approx. 30 per cent increase in CE-formation as compared to Ac-LDL alone. This was caused by a net transfer of FC from abnormal lipoproteins to Ac-LDL alone. This was caused by a net transfer of FC from abnormal lipoproteins to Ac-LDL. It is concluded that the lipoproteins studied in this report by itself exert no atherogenic function in MPM. They may, however, aggravate the atherogenicity of other processes known to be involved in the development of vascular diseases.

Animals↗
PubMed1987

The existence of B/E and E receptors on Hep-G2 cells: a study using colloidal gold- and 125I-labeled lipoproteins.

The presence of specific receptors for apolipoprotein B (low-density lipoproteins) and apolipoprotein E (HDL-E) on Hep-G2 cells and human skin fibroblasts was studied by chemical methods and by electron microscopy using a differential gold labeling technique. Fibroblasts bound both types of lipoproteins to one and the same receptor (B/E receptor) as deduced from competition experiments with HDL-E and LDL. Labeled HDL-E, on the other hand, was only partially displaced by cold LDL but was completely displaced by unlabeled HDL-E. Scatchard analysis of lipoprotein binding to Hep-G2 cells revealed an approx 10 times higher binding affinity of apoE-containing lipoproteins as compared to apoB-containing ones. No differences between apoE- or apoB-containing lipoproteins with respect to the morphology of cell binding and intracellular processing were observed. The results are compatible with the concept that Hep-G2 cells possess two kinds of receptors, one specific for apoB- and apoE-containing lipoproteins (B/E receptor) and another specific for apoE only. From these studies we conclude that Hep-G2 cells may serve as a suitable model for studying the lipoprotein metabolism in the liver.

Apolipoproteins B↗
PubMed1987

Lipoprotein binding to cultured human hepatoma cells.

Binding of various 125I-lipoproteins to hepatic receptors was studied on cultured human hepatoma cells (Hep G2). Chylomicrons, isolated from a chylothorax, chylomicron remnants, hypertriglyceridemic very low-density lipoproteins, normotriglyceridemic very low-density lipoproteins (NTG-VLDL), their remnants, low-density lipoproteins (LDL), and HDL-E (an Apo E-rich high-density lipoprotein isolated from the plasma of a patient with primary biliary cirrhosis) were bound by high-affinity receptors. Chylomicron remnants and HDL-E were bound with the highest affinity. The results, obtained from competitive binding experiments, are consistent with the existence of two distinct receptors on Hep G2 cells: (a) a remnant receptor capable of high-affinity binding of triglyceride-rich lipoproteins and HDL-E, but not of Apo E free LDL, and (b) a LDL receptor capable of high-affinity binding of LDL, NTG-VLDL, and HDL-E. Specific binding of Apo E-free LDL was completely abolished in the presence of 3 mM EDTA, indicating that binding to the LDL receptor is calcium dependent. Specific binding of chylomicron remnants was not inhibited by the presence of even 10 mM EDTA. Preincubation of the Hep G2 cells in lipoprotein-containing medium resulted in complete suppression of LDL receptors but did not affect the remnant receptors. Hep G2 cells seem to be a suitable model for the study of hepatic receptors for lipoprotein in man.

Apolipoproteins E↗
PubMed1985

Altered metabolism of low density lipoprotein in humans after prolonged incubation in plasma.

Lecithin: cholesterol acyltransferase (LCAT) in combination with exchange and transfer proteins is known to alter the composition of all plasma lipoprotein fractions. Human plasma from healthy donors was incubated for 24 h at 37 degrees C in the absence and at 4 degrees C and at 37 degrees C in the presence of the LCAT inhibitors sodium iodoacetate (5 mmol/l), and the low density lipoprotein fractions (LDL) were isolated. LDL isolated from LCAT-active plasma (LDL-a) exhibited pronounced alterations in their surface material: the relative content of phospholipids and of free cholesterol was reduced and the content of tetramethylurea-soluble apolipoproteins was increased. LDL isolated from plasma incubated at 37 degrees C with or without sodium iodoacetate showed significantly increased triglyceride concentrations. The LDL fractions from LCAT-active and LCAT-inactive (LDL-i) incubates were iodinated with 125I and 131I respectively, and their metabolic behaviour was studied in humans. LDL-a was cleared from circulation at a slower rate as compared with LDL-i (t 1/2 = 3.17 +/- 0.47 vs 2.88 +/- 0.45 days). The apparent fractional catabolic rate of LDL-a, calculated according to a two-pool model, was reduced by 22.2 +/- 3.1%. Comparing LDL-a with LDL isolated from LCAT-inactive plasma which had been incubated at 37 degrees C, the changes in the metabolic variables were less pronounced. It is concluded that physiological alterations of the chemical compositions, caused by LCAT and exchange/transfer proteins, influence the metabolism of LDL.

Adult↗
PubMed1985

Demonstration of receptor binding of two apo-B containing lipoproteins by differential labelling with colloidal gold.

The interaction of two types of apo-B containing lipoproteins, human low density lipoprotein (LDL) and lipoprotein-a (Lp(a], with cultured human skin fibroblasts was studied by differential colloidal gold labelling in conjunction with thin sectioning and surface replication techniques. After separate exposure of the fibroblasts to either gold labelled LDL or Lp(a) for 15 to 30 min at 37 degrees C, labelled lipoproteins were predominantly found in coated pit areas. Excess of unlabelled LDL or Lp(a) completely displaced the gold labelled lipoproteins, indicating specific binding by the LDL-receptor. Simultaneous exposure of fibroblasts to LDL-16 nm gold and Lp(a)-40 nm gold conjugates revealed that both LDL and Lp(a) are bound in the same coated pit and internalized into the same endosome. In contrast to native lipoproteins, gold labelled acetylated lipoproteins were found diffusely distributed on membrane surface areas predominantly representing fibronectin-containing fibrils.

Apolipoproteins B↗
PubMed1984

[Metabolism and possible mechanisms of atherogenesis induced by lipoprotein (a)].

The mechanisms of atherogenesis are under intensive clinical and experimental investigation. It is commonly accepted that lipoproteins play a major role in atherogenesis. The results of several clinical studies suggest that lipoprotein (a) [Lp(a)] represents an independent risk factor for atherosclerosis. In order to obtain information on the physiological and pathological role of Lp(a), studies were undertaken to investigate the metabolism, removal sites, and possible atherogenic mechanisms of Lp(a). It was found that Lp(a) is not a metabolic product of other apoprotein B containing lipoproteins, but appears to be synthesized as a separate lipoprotein. The turnover parameters of Lp(a) resemble those of LDL. Binding studies of Lp(a) with cultured human fibroblasts demonstrated that Lp(a) is bound by the B-E receptor. After binding, Lp(a) is internalized and inhibits cellular cholesterol synthesis. In the presence of dextran sulfate or antibodies to the specific Lp(a) apoprotein or apoprotein B, Lp(a) is avidly taken up by macrophages. A similar mechanism might be responsible for the atherogenic effect of Lp(a).

Arteriosclerosis↗
PubMed1984

The interaction of human apoB-containing lipoproteins with mouse peritoneal macrophages: a comparison of Lp(a) with LDL.

Cholesteryl ester accumulation in macrophages and foam cell formation is believed to play an important role in atherogenesis. The effect of Lp(a) on the incorporation of [14C]oleate into cholesteryl esters was studied in mouse peritoneal macrophages. In view of the physico-chemical similarities between Lp(a) and LDL, the results were compared with those obtained with LDL. Native Lp(a) and LDL did not stimulate cholesteryl ester formation. Incubation of macrophages with Lp(a)- or LDL-dextran sulfate complexes caused a significant increase in cholesteryl ester formation. A similar effect was observed when Lp(a) or LDL were incubated with macrophages in the presence of antibodies directed against the specific Lp(a) apoprotein or against LpB. Treatment of Lp(a) with acetic anhydride or malondialdehyde (MDA) was followed by precipitation of most of the lipoprotein. Therefore, these modifications were not suitable to study the uptake of modified Lp(a) by macrophages. Studies with acetyl-LDL or MDA-treated LDL caused the well-known stimulation of [14C]oleate incorporation into cholesteryl esters. Thus, the modification of Lp(a) by sulfated polysaccharides or by treatment with antibodies yields similar cholesteryl ester deposition in mouse peritoneal macrophages as observed with modified LDL. This might be one mechanism by which Lp(a) exerts its atherogenicity.

Animals↗
PubMed1984

[A combination of methyldopa, hydrochlorothiazide and amiloride in the treatment of essential hypertension].

41 patients (35 males and 6 females) with moderate hypertension were treated with a combination of methyldopa/hydrochlorothiazide/amiloride (M/HCT/A). In a double blind study the blood-pressure-lowering effect of this combination was compared with the effect of M or HCT/A alone. After 8 weeks of treatment, the combination of M/HCT/A lowered the elevated blood pressure more efficiently than the two monotherapies . M counteracted the potassium-loosing effect of HCT/A, but did not prevent the elevation of serum urea, creatinine and uric acid which is observed under treatment with HCT/A.

Adult↗
PubMed1983

[Retrospective study of the evaluation of peptic ulcer recurrence after 4 weeks of pirenzepin (Gastrozepin) treatment].

In a recent study the effect of Pirencepine in the treatment of peptic gastric or duodenal ulcers was reported. Relapse rates were investigated one year after the end of these studies. The patients did not receive any treatment to prevent ulcer recurrence. It was found that 20% of the patients who have had ulcer healing after 4 weeks of Pirenzepine treatment, exhibited recurrent ulcers. The relapse rate was higher in these patients who had one or more ulcers prior to the Pirencepine studies. From the results of the present investigation it is concluded that Pirenzepine has a more beneficial effect in the treatment of peptic ulcers than placebo as observed in other studies.

Benzodiazepinones↗
PubMed1983

[The effect of an infusion of glucose-insulin-potassium and of heparin on the plasma free fatty acid levels and on blood glucose].

In the treatment of acute myocardial infarction infusion of glucose-insulin-potassium (GIP) and/or heparin are frequently administered. The effect of an infusion of GIP, heparin or GIP plus heparin on the concentration of plasma free fatty acids (FFA) and blood glucose was studied over a period of 90 min in 10 healthy volunteers. GIP caused a continuous decrease in the FFA level to 34% of the initial value. There was only a slight increase in blood glucose concentration. After the administration of heparin, a rapid increase was observed in the FFA level to nearly the double value of the initial concentration. Thereafter, the FFA level decreased in spite of continuous heparin infusion and after 90 min the FFA level was only 13% above the initial value. Heparin had no effect on the blood glucose concentration. The simultaneous administration of GIP plus heparin caused a rapid increase in FFA concentration, of the same magnitude as observed with heparin alone. Thereafter, the FFA level decreased slightly faster than with heparin alone. In some subjects, GIP plus heparin caused a substantially higher increase in blood glucose concentration than GIP alone. The possible implications of these metabolic effects on the course of acute myocardial infarction are discussed.

Adult↗
PubMed1983

[Effect of acute beta 1 and beta 1/beta 2 receptor blockade on carbohydrate and lipid metabolism during exertion].

The influence of acute beta 1-receptor blockade using 50 mg metoprolol or beta 1/beta 2-blockade using 40 mg propranolol resulted in an equipotent reduction of cardiac frequency and systolic blood pressure without influencing diastolic pressure in ten healthy probands. There was no reduction of maximal bicycle ergometric exercise by either beta-receptor blocking agent. Serum glucose levels did not change during metoprolol in comparison to pre-test values. In contrast, propranolol resulted in a significant decrease of glucose levels during maximal exercise and 5 minutes after end of exercise. Plasma lactate was moderately lowered by both beta-receptor blockers after 20 min constant exercising when compared to pre-medication. Both substances reduced the insulin level in a comparable way during the exercise test. Serum triglyceride concentrations did not alter significantly during exercise tests. Serum free fatty acid levels showed a decreasing tendency until maximal exercise; however, there was no significant difference between values obtained with metoprolol or propranolol and drug-free pre-test.

Adrenergic beta-Antagonists↗
PubMed1983

Studies on the role of specific cell surface receptors in the removal of lipoprotein (a) in man.

The binding of 125I-lipoprotein (a) [Lp(a)] to cell surface receptors was studied on cultured human fibroblasts. The results were compared with corresponding data obtained with 125I-low density lipoproteins (LDL). Equilibrium binding studies showed that Lp(a) is bound with high affinity by the cell surface receptors. The maximum binding capacity for Lp(a) was 37% lower than for LDL. For Lp(a) and LDL, the Scatchard plots displayed linearity, indicating a single category of binding sites. Half-maximal saturation occurred at a concentration of 9.52 +/- 1.04 nM for Lp(a) and 7.76 +/- 1.29 nM for LDL. Competition binding experiments revealed that Lp(a) and LDL are nearly equally potent in competing each other for the binding sites. Binding of Lp(a) and LDL were followed by suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Cyclohexanedione treatment of Lp(a) and LDL completely abolished receptor binding. Neither Lp(a) nor LDL were specifically bound by fibroblasts obtained from a patient with homozygous familial hypercholesterolemia (FH). The removal mechanisms for Lp(a) and LDL were further compared by in vivo studies. Radioiodinated Lp(a) and LDL were injected intravenously into 12 normolipemic individuals to measure kinetic parameters of these two lipoproteins simultaneously in each subject. Mean fractional catabolic rate (FCR) of Lp(a) was 0.260 +/- 0.060 and mean FCR of LDL was 0.377 +/- 0.077 (mean +/- SD). In each subject, FCR of Lp(a) was lower than the FCR of LDL; the mean difference was 31%. The absolute synthetic rate of Lp(a) was significantly lower than the corresponding value of LDL. In each individual, the percentage of total Lp(a) that was contained in the intravascular space was higher than the corresponding value of LDL; the mean difference was 19%. A highly significant positive correlation was found between FCR of LDL and FCR of Lp(a) (r = 0.853, P less than 0.01). No relationship was found between the serum concentration of LDL-apolipoprotein B and Lp(a). The serum level of Lp(a) was positively related to the absolute rate of Lp(a) synthesis (r = 0.979, P less than 0.01). The serum level of LDL-apolipoprotein B was inversely related to FCR of LDL (r = 0.613, P less than 0.05). In a patient with homozygous FH, FCR of LDL was 0.205 and FCR of Lp(a) was 0.210. The results of these studies show that Lp(a) is specifically bound with high affinity to the same receptors of human fibroblasts as LDL. The affinity and maximum binding capacity are slightly lower for Lp(a) than for LDL. The results of the turnover studies are consistent with the assumption that Lp(a) is removed from the plasma by similar mechanisms as LDL.

Adolescent↗
PubMed1983

[Wegener's granulomatosis as a rare cause for kidney failure].

Course and treatment of a case of Wegener's granulomatosis are reported. A 39-year-old man admitted to the hospital because of abnormal densities demonstrated by the X-ray examination of the chest. The patient developed a rapidly progressive renal failure with renal insufficiency. Diagnosis was obtained by biopsys from the upper respiratory tract and from the kidney. During hemodialysis and immunosuppressive therapy renal function improved and hemodialysis could be stopped. The patient was discharged from the hospital and kept on immunosuppressive therapy. The patient omitted the medication by himself and renal insufficiency reappeared. The disease was progressive and the patient died because of intestinal bleeding. Apart from the description of the symptoms of this rare disease, problems of diagnosis and treatment are discussed.

Acute Kidney Injury↗
PubMed1982

[Treatment of ulcers with pirenzepin. Results from clinic and practice].

In two studies the beneficial effect of Pirenzepine in the treatment of peptic duodenal and gastric ulcers was investigated in 1686 outpatients. Study 1 includes patients treated and controlled mainly in hospitals, in study 2 treatment and control was performed mainly by practitioners. After four weeks of treatment healing of duodenal ulcers was observed in 68% of the patients in study 1 and 66% in study 2. Healing of peptic gastric ulcers was observed in 62% of the patients in study 1 and 53% of the patients in study 2. Mild anticholinergic side effects were observed in approximately 10% of the patients. Healing rates under Pirenzepine are similar those reported for Cimetidin or Carbenoxolon. It is concluded that Pirenzepine has a beneficial effect in the treatment of peptic duodenal and gastric ulcer disease.

Adult↗