Search PubMed⌕ Search

Biomedical subjects

R Poledne

Publications and source records attributed to R Poledne.

At least 19 recordsLinked to original sources
PubMed1999

[Frequency of occurrence of apolipoprotein E isoforms in patients with various types of hyperlipoproteinemias].

BACKGROUND: Apolipoprotein E is a polymorphic protein playing a crucial role in the metabolism of plasma lipoproteins. Three alleles referred to as epsilon 2, epsilon 3 and epsilon 4 code for three common isoforms of apoE. The most frequent allele in the population at large is epsilon 3 allele. epsilon 2 and epsilon 4 alleles are connected with lipoprotein disorders as well as with other diseases. The aim of our study was to establish frequencies of apoE coding alleles in patients with different types of hyperlipidaemia (HLP) and to reveal differences in their distribution in comparison with the general population. METHODS AND RESULTS: Therefore apoE genotype was assayed in 752 patients with primary HLP and 291 subjects randomly selected from the general Czech population. Allele frequencies were determined separately in a group of patients with familial hypercholesterolaemia (FH), polygenic hypercholesterolaemia (PHC), familial combined hyperlipidaemia (FCH) and in patients with type III. hyperlipidaemia (III). In patients with HLP a significantly higher frequency of epsilon 4 allele than in control subjects was found. In the group of FH patients frequency of the epsilon 2 allele was higher than in control subjects. In patients with PHC a significantly higher frequency of the epsilon 4 allele and lower frequency of the epsilon 2 allele were observed. In the group of FCH patients distribution of epsilon alleles did not differ from the control group. Frequency of the epsilon 2 allele in patients with type III. hyperlipidaemia was significantly higher than in controls. CONCLUSIONS: We conclude that there exist significant differences in frequencies of apoE coding alleles between patients with primary hyperlipidaemia and a randomly selected population sample. The revealed differences in allelic distribution suggest that the impact of apoE polymorphism is not uniform in all types of hyperlipidaemia.

Alleles↗
PubMed1999

C(-260)-->T polymorphism in the promoter of the CD14 monocyte receptor gene as a risk factor for myocardial infarction.

BACKGROUND: The CD14 receptor of monocytes is an important mediator for the activation of monocytes/macrophages by endotoxins from the envelope of Gram-negative bacteria (lipopolysaccharides). We identified a polymorphism in the CD14 receptor and examined whether this genetic marker influenced the expression of the CD14 receptor on monocytes and affected the predisposition to myocardial infarction. METHODS AND RESULTS: We identified a C(-260)-->T nucleotide change, creating a HaeIII polymorphism in the promoter of the CD14 gene. The polymorphism was determined in 178 male patients <65 years old (cases; average age, 55.9+/-6.3 years) at the time of their first myocardial infarction and in 135 representative selected male control subjects (controls; average age, 55.2+/-11.5 years). The frequency of the T allele (absence of the cutting site) was 0.49 in cases and 0.35 in controls (P=0.0005; OR, 1.781; 95% CI, 1.286 to 2.465). Subsequently, we measured the expression of monocyte CD14 by flow cytometry in 18 volunteers with different CD14 genotypes. A significantly higher density of the CD14 receptor was shown in the T/T homozygotes than in the others (P=0.0028). CONCLUSIONS: A higher frequency of allele T(-260) in the promoter of the CD14 receptor gene was found in myocardial infarction survivors than in controls. At the same time, this variation was associated with a higher density of CD14 receptors in healthy volunteers. Therefore, we can conclude that in addition to the well-established risk factors, a genetically determined reaction of monocytes/macrophages to infectious stimuli could play an important role in the process of atherosclerosis.

Aged↗
PubMed1999

[Age and changes in dietary habits affect hyperlipoproteinemia after kidney transplantation].

BACKGROUND: Atherosclerosis of the blood vessels is the most frequent cause of morbidity and mortality of patients after transplantation of the kidneys with a long-term function of the graft. It is assumed that the most significant risk factor for its development is secondary hyperlipoproteinaemia (HLP). In the development of HLP a number of factors may participate (chronic renal insufficiency, proteinuria, immunosuppressive treatment, diet, increment of body weight, age, genetic factors). The objective of the investigation was to follow changes of the lipid spectrum after renal transplantation and evaluate the impact of different factors which participate in these changes. METHODS AND RESULTS: The authors investigated in a retrospective metabolic study for a period of 18 months a total of 348 patients after the first cadaverous kidney transplantation. They compared the findings in 34 patients (group I) who had throughout the investigation period a total cholesterol of < or = 5.2 and triacylglycerols < or = 2.3 and group II (314 patients) who had elevated values of these factors. The mean values of different parameters differed highly significantly (group I vs. group II): cholesterol 4.6 +/- 0.4 vs 6.8 +/- 1.5 (p < 0.001), triacylglycerols 1.8 +/- 0.8 vs 3.6 +/- 1.6 (p < 0.001), LDL-cholesterol 2.6 +/- 0.6 vs 4.0 +/- 1.1 (p < 0.001), (all in mmol/l) and HDL/total cholesterol 0.28 +/- 0.07 vs 0.20 +/- 0.09 (p < 0.01). The authors did not detect a difference in the incidence of isoforms of apo E. There were no differences in the mean cyclosporin A levels: 394 +/- 114 vs. 489 +/- 202 (ng/ml) and renal function CCr 1.0 +/- 0.6 vs 0.9 +/- 0.3 (ml/s). In group I there was a significantly higher intake of energy 150 +/- 20 vs. 125 +/- 25 (kJ), of fat 1.6 +/- 0.3 vs. 1.0 +/- 0.2 (g/kg) and disaccharides (by 50%). With this corresponded also a significantly higher increment of BMI 27.4 +/- 4.6 vs. 23.8 +/- 3.3 (p < 0.01). Patients in group II were also significantly older (44.5 +/- 14.1 vs 49.4 +/- 12.5, p < 0.01). CONCLUSIONS: It is assumed that one of the main causes of the development of HLP after transplantation are poor dietary habits of the patients associated with an excessive intake of energy, fats and disaccharides and an increase of body weight. The patient's age is significantly higher. Standard lower doses of immunosuppressive drugs have obviously only a supportive effect.

Adult↗
PubMed1999

Does angiotensin-converting enzyme polymorphism influence the clinical manifestation and progression of heart failure in patients with dilated cardiomyopathy?

To evaluate the role of angiotensin-converting enzyme (ACE) polymorphism on the development of end-stage dilated cardiomyopathy, the ACE gene polymorphism of 90 patients after heart transplantation because of this disease was compared with the population sample. No difference in gene frequencies was found, but when compared with the population sample there were fewer ID heterozygotes detected; no significant influence of ACE polymorphism on the course of the disease before transplantation was found.

Adult↗
PubMed1999

European Lipoprotein Club: report of the 21st Annual Conference, Tutzing, September 28-October 1, 1998.

Molecular biology and genetics were the hallmarks of the conference. Attendees from 20 European countries participated in lively discussions with international speakers. The opening round table session entitled 'Genetic approach to complex diseases' was chaired by Harald Funke. Steve Humphries (London) presented association studies and Harald Funke (Munster) presented multiparameter analyses, as models of genetic epidemiological approaches to atherosclerosis. Gerd Utermann (Innsbruck) showed, through sib pair linkage analysis, how apo (a) gene polymorphism determines plasma levels of Lp(a). Klaus Lindpainter (Basel) described novel genetic strategies heading for a more targeted medicine, through the identification of genetic mechanisms of disease and therapeutic responses. Session I, chaired by Richard James (Geneva) and Guido Franceschini (Milano), on 'Basic mechanisms of action of drugs' highlighted molecular and cellular actions by which present (fibrates, statins) or future (ACAT or MTP inhibitors) drugs or hormones may modulate lipoprotein metabolism. Marten Hofker (Leiden) and Philippa Talmud (London) chaired Session II on 'Regulation of gene expression', which reported cellular regulations by nuclear receptors (PPARs), or the regulation of lipid trafficking by membrane receptors (SR-BI, Megalin, Apo-E receptor, scavenger receptors) or by intracellular (IFN gamma signalling pathways) or extracellular proteins (lipases). Beyond gene expression, Session III, 1st part, entitled 'Lipoprotein modifying enzymes' was chaired by Katriina Aalto-Setälä (Tampere). Roles of lipases (HL, LPL) and transfer proteins (CETP, PLTP), as well as structures of lipid binding molecules (LCAT, apolipoproteins), were further explored. The 'Gene interactions' session chaired by Rudolph Poledne (Prague), and 'Novelties' chaired by Hans Dieplinger (Innsbruck), reported elegant models of cross-bred, tissue specific knock-out or YAC-transgenic mice for lipoprotein metabolism, and descriptions of gene interactions in polygenic disorders or new loci for familial lipid disorders (familial combined hyperlipidemia, metabolic syndrome and Tangier disease) in humans.

Animals↗
PubMed1999

(TTA)n repeat polymorphism in the HMG-CoA reductase gene and cholesterolaemia.

BACKGROUND: Hypercholesterolaemia is one of the main risk factors of atherosclerosis. Both environmental and genetic factors have been implicated in the development of hypercholesterolaemia. The enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase plays an important role in cholesterol synthesis. Thus we supposed that polymorphisms in this gene could influence cholesterolaemia. PATIENTS AND METHODS: Using PCR, we measured the (TTA)n repeat polymorphism near the Alu sequence of the gene for HMG-CoA reductase in two groups of children selected from opposite ends of the cholesterolaemia distribution curve obtained from measuring cholesterolaemia in 2000 children. Eighty-two children in high- and eighty-six children in low-cholesterolaemic groups participated on the study. RESULTS: A significant difference was found in the frequencies of the genotypes of the 10+ add alleles (43.9% in high-cholesterolaemic children vs 24.4% in low-cholesterolaemic children p < 0.025). No differences were demonstrated in the frequencies of other genotypes (allele 10+ even and without allele 10). No associations between lipid parameters and genotypes or genotype subgroups within the group of high- and low-cholesterolaemic children were found. CONCLUSION: The (TTA)n repeat polymorphism in the gene for HMG-CoA reductase could be another genetic marker that plays a role in the genetic determination of cholesterolaemia.

Child↗
PubMed1999

Intima-media thickness of carotid arteries in borderline hypertensives.

The purpose of this study was to assess the effect of the main risk factors for cardiovascular disease on the process of subclinical atherosclerosis in originally borderline hypertensives. The relation of far wall common carotid artery intima-media thickness (IMT CCA) measured by B-mode ultrasound to smoking, body mass index (BMI), blood pressure, lipids, and angiotensin-converting enzyme (ACE) gene polymorphism was analyzed. In 48 subjects examined (mean age, 61.9 +/- 2.54 years), median IMT CCA was 0.708 mm. Statistically significant differences in BMI (26.5 vs. 29.2 kg/m2, p < 0.025) and HDL-cholesterol level (1.42 vs. 1.1 mmol/l, p < 0.025) between the first and third tertile of IMT CCA were found. No differences were observed between "controls" and "cases" in blood pressure, total cholesterol, and triacylglycerols. No significant differences in IMT CCA were found between smokers and nonsmokers and among different alleles of the ACE gene. These data reflect the importance of HDL-cholesterol and BMI on the process of atherosclerosis within an otherwise homogeneous group of patients.

Adult↗
PubMed1998

A genetic and correlation analysis of liver cholesterol concentration in rat recombinant inbred strains fed a high cholesterol diet.

Liver cholesterol concentration in rats fed a high cholesterol diet, is under genetic control which is supported by significant differences observed among inbred strains. For instance, the Brown Norway (BN-Lx/Cub) rat developed a twofold higher liver cholesterol concentration than the spontaneously hypertensive rat (SHR/Ola). In the current study, we used 30 recombinant inbred (RI) strains, derived from BN-Lx and SHR progenitors, to locate quantitative trait loci (QTL) that are responsible for differences in liver cholesterol concentrations between the BN-Lx and SHR strains. The heritability of liver cholesterol was estimated to be 0.55 and a significant association was detected between concentration of liver cholesterol and the D10Cebrp1016s2 marker on chromosome 10 (lod score = 3.3); this putative QTL was responsible for nearly 64% of additive genetic variability and thus represents a major genetic determinant of liver cholesterol concentration. Liver cholesterol concentrations significantly correlated with intermediate density lipoprotein (IDL) cholesterol levels.

Animals↗
PubMed1998

European Lipoprotein Club: report of the 20th annual conference, Tutzing, 8-11 September 1997.

The year 1997 celebrated the 20th anniversary of the European Lipoprotein Club. Sessions explored topics in the line of classical concepts and forthcoming advances in the field of basic and clinical research on lipoproteins. Participants from 18 European countries attended the conference. Recent Developments in Lipoprotein Research, were reviewed by Thomas Olivecrona (Umea, Sweden), who gave a perspective on lipolysis; and Gerd Assmann (Münster, Germany), who overviewed epidemiological data of the PROCAM study and focused on the biochemical and genetic components of reverse cholesterol transport. Session I, chaired by Katriina Aalto Setälä (Tampere, Finland) and Marten Hofker (Leiden, Netherlands) was dedicated to 'Lipoprotein receptors (old and new)'. Various structural and functional aspects were reported for the newcomers in the ever enriching LDL receptor gene family (VLDLR, LR7/8B, LR11, Megalin, RAP-related proteins). However, a decade of identification of LDL receptors gene defects reveals now that phenocopies of familial hypercholesterolemia may be linked to a third, yet unknown locus. Identification of pathways which clear HDL is underway. Session II, chaired by David Bowyer (Cambridge, United Kingdom) and Richard W James (Geneva, Switzerland), was entitled 'Significance of lipoprotein heterogeneity (metabolic and pathological aspects)'. Factors involved in lipoprotein modification (dense LDL, oxidation), transient production (post prandial, VLDL synthesis) or degradation (complement activation) and controversial hypotheses on their links with atherosclerosis were discussed. Session III on 'Novel methodologies for lipoprotein research' was chaired by Rudolph Poledne (Prague, Czech Republic) and Armin Steinmetz (Marburg, Germany). Simple technologies for routine assessment of lipoprotein metabolism, as well as the most sophisticated ones, to study lipid and free radical exchanges between particles, were presented.

Electrophoresis, Capillary↗
PubMed1998

Apolipoprotein E genotypes in offspring with a positive and negative family history of premature myocardial infarction.

Apolipoprotein E (apo-E) allele and genotype frequencies were evaluated in offspring with positive (MI-offspring) and negative (control-offspring) parental history of myocardial infarction (MI). The apo-E allele frequencies in MI- and control-offspring were as follows: epsilon2: 9.04 and 2.08% (p < 0.02), epsilon3: 84.04 and 87.5%, epsilon4: 6.91 and 10.41%, respectively. The frequencies of the E2-genotypes were significantly lower in offspring of controls (4.2%, 17.0%, respectively, p < 0.03). The epsilon2-allele is associated with raised plasma triglyceride concentrations in subjects on a diet high in saturated fat. We therefore hypothesize that offspring carrying an epsilon2-allele are predisposed to develop disturbance of plasma triglyceride metabolism when exposed to a traditional Slovak high-fat diet and/or weight gain, resulting in altered lipid levels and increased predisposition to atherosclerosis.

Adolescent↗
PubMed1998

Fasting plasma insulin levels in an unselected Prague suburban population.

OBJECTIVE: The aim of the study was to determine the levels of fasting plasma insulin in an unselected population of a Prague suburban community and correlate the levels of insulin with other metabolic and anthropometric parameters which could be directly or indirectly associated with insulin levels. RESEARCH DESIGN AND METHODS: A total of 835 adult inhabitants, the Prague suburban community, were examined. Mean age of examined people was 44.9 +/- 16.9 years, the group included 370 men and 465 women, 189 of the latter were in the menopause. The parameters examined included the fasting plasma levels of insulin, glycaemia, total cholesterol, HDL cholesterol and triacylglycerols; LDL cholesterol and, using the basic anthropometric data, the body mass index (BMI) and the waist/hip ratio (WHR) were calculated. RESULTS: The levels of all parameters were divided in ten-year groups of men and women. The average levels of fasting plasma insulin in all ten-year groups of men and women were normal. We found in the men small but constant rise of fasting insulinaemia in the decades. This was not observed in women, where the insulin levels were similar up to the time after menopause, then the level of average plasma insulin rose significantly. We found the positive correlation of plasma insulin levels with triacylglycerol levels (p < or = 0.001), BMI (p < or = 0.001) and WHR (p < or = 0.001) and a negative correlation with plasma HDL cholesterol (p < or = 0.001) in the whole group of probands. No significant correlation was demonstrated between fasting insulinaemia and total or LDL cholesterol. When dividing the group by age and sex, the strongest positive correlations were seen between insulin and triacylglycerols, glycaemia, BMI, and WHR, and negative correlations between insulin and HDL cholesterol. CONCLUSION: Fasting plasma insulin levels in an unselected population were within the normal range, but follow a continuous and steady upward course in men while did not change until after the menopause when they bounce in women; compared to insulin levels in younger women, insulinaemia does not increase up to 55 years of age. The strongest positive correlations were demonstrated between plasma insulin and triacylglycerols, and between insulin and BMI and WHR in men and postmenopausal but not premenopausal women whereas a negative correlation was observed between fasting plasma insulin and HDL cholesterol.

Adolescent↗
PubMed1998

Lack of an association between apolipoprotein B XbaI polymorphism and blood lipid parameters in childhood.

The frequencies of the alleles of XbaI polymorphism in the apolipoprotein B gene were determined in two groups of children, 82 with high (HCG) and 86 with low (LCG) cholesterol levels. A slightly higher incidence of the X2X2 genotype in HCG was found, but the differences were not statistically significant. No relations were found between the XbaI polymorphic site and the levels of serum lipids and lipoproteins. Common XbaI polymorphism in the apolipoprotein B gene does not determine significantly the plasma cholesterol levels in childhood.

Alleles↗
PubMed1998

Imprinting of high sensitivity to a high-cholesterol diet by nutrition in early life.

Imprinting of an increased sensitivity to a high-fat, high cholesterol (HFHC) diet by dietary manipulation in early life was studied in two strains of rat, i.e. in Prague hereditary hypercholesterolaemic rats (PHHC) and Wistar rats, from which the PHHC strain was obtained by selection and inbreeding. Whereas no effect of early life nutrition on cholesterolaemia induced by HFHC diet was found in control Wistar rats, significant imprinting of increased sensitivity to the same diet was demonstrated in PHHC rats. This imprinting increased the concentration of apoB-containing lipoprotein and liver cholesterol concentration in animals fed HFHC diet for a period of two months after weaning. No effect of this imprinting on endogenous cholesterol synthesis could be demonstrated. It is concluded that imprinting of increased sensitivity to HFHC diet by dietary manipulation in early life is not a general phenomenon but depends on underlying genetic predisposition(s).

Animals↗
PubMed1998

Indicators of risk of ischaemic heart disease in patients with acute myocardial infarction under 65 years and their relatives.

The incidence of risk factors for atherosclerosis was investigated in a group of 846 patients under 65 years of age, hospitalized with acute myocardial infarction (AIM) in coronary hospital units in 21 districts of the Czech Republic in 1996. The group of patients comprises 649 men and 197 women. The incidence of risk factors in patients was compared with the incidence of risk factors in the population of the Czech Republic: the mean values of the investigated indicators are in patients with AIM higher in both sexes (total serum cholesterol, triacylglycerols, BMI, WHR). As to anamnestic data, in the majority low or irregular physical activity predominates, a high percentage of patients reported that they "do not restrict" or "rather do not restrict" their total food intake nor the intake of animal fats. Among the patients 52.6% males and 42.1% females were smokers. The results indicate that patients with AIM have a higher incidence of risk factors for atherosclerosis, a higher percentage of patients have cumulated risks and a higher percentage of patients has a higher risk score than the general population. The incidence of AIM is markedly higher in subjects with lower education.

Adult↗
PubMed1998

[Hyperlipidemia after kidney transplantation and its control by individualized therapy: evaluation of the first years' trial].

Secondary hyperlipidaemia (HLP) is one of the most serious metabolic complications in patients after transplantations of the kidney. In its development a number of factors may participate, the most important ones being immunosuppressive drugs (cyclosporin A and prednisone) and the patients dietary habits. In a prospective metabolic trial a group of 248 patients after transplantation of the kidney with a long-term stable function of the graft were followed up for 12 months. Group I (128 patients) was systematically followed up in the Institute of Clinical and Experimental Medicine and the patients were treated by individualized dietetic and pharmacological intervention. Group II (120 patients) were out-patients who were treated according to current procedures in other departments than the Institute of Clinical and Experimental Medicine. The cholesterol and LDL-cholesterol increased significantly in both groups starting with the 3rd month of the follow-up. A subsequent decline was observed in group I from the 9th month onward, while in group II both values rose steadily. The triacylglycerol level rose in both groups during the 6th month, there were however great interindividual differences. There was a significant rise of the HDL-cholesterol. The Lp(a) level changed also significantly--its values--after an initial drop during the 3rd month--rose significantly in group II.

Adult↗
PubMed1997

[Decrease in cardiovascular disease mortality in the Czech Republic from 1984 to 1993 and its possible causes].

BACKGROUND: The objective of the investigation was to evaluate the ten-year development of the cardiovascular mortality rate in two population groups in the age bracket from 25 to 64 years, i.e. in subjects living in six districts which participated in the international WHO project MONICA and in the population of the whole Czech Republic. METHODS AND RESULTS: Data on the mortality rate in 1984-1993 for the age group from 25-64 years were provided by the Institute of Health Information and Statistics, information on the prevalence of risk factors was obtained in three cross-sectional studies implemented in six districts as part of the MONICA project in 1985, 1988 and 1992. In the mortality rate per 100,000 population in the six districts the following changes were revealed (in parentheses the values for 1984 and 1993 are given): men - a statistically significant declining trend in the from all caused mortality (849.3-742.5; p < 0.001) and cardiovascular mortality (367.2-280.4; p < 0.001) and cerebrovascular mortality (69.7-44.8; p < 0.001). In the mortality from ischaemic heart disease (215.7-170.6; ns) a declining trend was not recorded. In women aged 25-64 years in the six districts there was a statistically significant decline of the mortality from all caused (359.5-322.1; p < 0.001), the cardiovascular mortality (115.6-100.6; p < 0.001) and cerebrovascular mortality (31.1-23.6; p < 0.001). The mortality from ischaemic heart disease did not change (49.2-48.8; ns). In the population of the Czech Republic in men the following were detected: a drop of the from all caused mortality (907.1-784.8; P < 0.001), the cardiovascular mortality (383.5-308.4; p < 0.001) and cerebrovascular mortality (76.5-55.3; p < 0.001). Also in women of the Czech Republic a decline of the mortality from all caused was recorded (390.1-328.5; p < 0.001), the cardiovascular mortality (135.3-103.8; p < 0.001), ischaemic heart disease (58.0-48.6; p < 0.001) and cerebrovascular mortality (43.5-27.4; p < 0.001). In 1990 an increased cardiovascular mortality was recorded in men different from the trend during 1984-1993, statistically significant in the Czech Republic (p < 0.05) and in the six districts (p < 0.05). The reasons of this trend are not clear. The role of health services in the mortality drop is not clear, although available data indicate their improvement. Favourable changes were found in risk factors: during the period from 1985-1992 the prevalence of hypercholesterolaemia declined significantly in men and women, the prevalence of hypertension in women and the prevalence of smoking in men declined in the six districts. From nationwide data ensues that after 1989 significant changes occurred in the diet of the Czech population. The meat consumption declined by 1993 by 13%, the milk and dairy product consumption by 26.8% the butter consumption by 43.6% the consumption of vegetable fats increased by 16%, of vegetables by 8%, tropical fruit by 43.2%. These changes probably had an impact on the cholesterol level and BMI of the Czech population. CONCLUSIONS: In the declining cardiovascular mortality trend during 1984-1993 the following may have participated: improved medical care, dietary changes, improvement of the risk profile and other, in particular socioeconomic factors. With regard to the close temporal association of the investigated changes it may be assumed that this development is at least partly associated with changes of the political and economic position in the Czech Republic after 1989.

Adult↗