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M Novak

Publications and source records attributed to M Novak.

At least 19 recordsLinked to original sources
PubMed2006

Practical way to assess metabolic syndrome using a continuous score obtained from principal components analysis.

AIMS/HYPOTHESIS: We devised a practical continuous score to assess the metabolic syndrome, and assessed whether this syndrome score predicts incident diabetes and cardiovascular disease. SUBJECTS AND METHODS: Among 5,024 participants of the Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) cohort, we defined a metabolic syndrome score by the first principal component (PC1), using only the correlations between continuous metabolic syndrome measures (glucose, waist circumference, triglycerides, and systolic blood pressure). This metabolic syndrome score was highly correlated with a similar score also including insulin and HDL cholesterol (r ( s )=0.94). Over 9 years of follow-up, incident diabetes and cardiovascular disease (CVD) were predicted by logistic regression using the simpler metabolic syndrome score. RESULTS: The means of the metabolic syndrome measures differed between men and women. Nevertheless, as the degree of variance explained and the PC1 coefficients were remarkably similar, we used a common metabolic syndrome score. The metabolic syndrome score explained 50% of the variance of the metabolic syndrome measures, and waist circumference had the highest correlation (0.59) with this score. Each standard deviation increase in the metabolic syndrome score was associated with a markedly increased age-adjusted risk of developing diabetes (odds ratios: men 3.4 [95% CI 2.6-4.4]; women 5.1 [3.6-7.2]) and with increased incident CVD of 1.7 (1.4-2.1) in men and 1.7 (1.0-2.7) in women. CONCLUSIONS/INTERPRETATION: Our results, which should be confirmed in other populations, suggest that it is possible to evaluate the risk of the metabolic syndrome in a pragmatic fashion with a continuous score, obtained from principal components analysis of the basic, continuous syndrome measures.

Adult↗
PubMed2006

A life-course approach in explaining social inequity in obesity among young adult men and women.

OBJECTIVE: To examine the cumulative influence of adverse behavioural, social, and psychosocial circumstances from adolescence to young adulthood in explaining social differences in overweight and obesity at age 30 years and if explanations differ by gender. DESIGN: A 14-year longitudinal study with 96.4% response rate. SUBJECT: Data from 547 men and 497 women from a town in north Sweden who were baseline examined at age 16 years and prospectively followed up to age 30 years. MEASUREMENTS: Overweight and obesity were ascertained at ages 16 and 30 years. Occupation and education were used to measure socioeconomic status. The explanatory measurements were: age at menarche, smoking, physical activity, alcohol consumption, TV viewing, home and school environment, social support, social network, and work environment. RESULTS: No gender or social difference in overweight was observed at age 16 years. At age 30 years, significantly more men than women (odds ratio (OR) = 2.81, 95% confidence interval (CI) 2.14-3.68) were overweight or obese. Educational level was associated with overweight at age 30 years, but not occupational class. Both men (OR = 1.55, 95% CI 1.10-2.19) and women (OR = 1.78, 95% CI 1.16-2.73) with low education (< or =11 years) were at risk of overweight. The factors that explained the educational gradient in overweight among men were low parental support in education during adolescence, and physical inactivity, alcohol consumption, and nonparticipation in any association during young adulthood. The educational gradient in overweight in women was explained mostly by adolescence factors, which include early age at menarche, physical inactivity, parental divorce, not being popular in school, and low school control. Restricted financial resource during young adulthood was an additional explanatory factor for women. All these factors were significantly more common among men and women with low education than with high education. CONCLUSION: Social inequities in overweight reflect the cumulative influence of multiple adverse circumstances experienced from adolescence to young adulthood. Underlying pathways to social inequity in overweight differ between men and women. Policy implications to reduce social inequity in overweight include reduction of social differences in health behaviours and social circumstances that take place at different life stages, particularly psychosocial circumstances during adolescence.

Adolescent↗
PubMed2006

Rupture of abdominal aortic aneurysm--factors of mortality.

PURPOSE: The purpose of this study was to evaluate the main factors of the 30-day mortality rate in patients operated on for rupture of abdominal aortic aneurysm (RAAA). PATIENTS AND METHOD: Univariate and multivariate analysis of various factors associated with RAAA was performed in the group of 182 patients operated on for RAAA between 1/1/1992 to 1/9/2005. RESULTS: The 30-day mortality rate was 33.5%. The main mortality factors were: misdiagnosis, cardiopulmocerebral resuscitation (CPCR) on admission, configuration of RAAA(p<0.001), number of blood transfusions, hypotension on admission (p<0.0001) and duration of operation, type of reconstruction and hypertension in history (p<0.01). Important factors (p<0.05) of postoperative mortality included also low haemoglobin level on admission, abdominal aortic aneurysm (AAA) diameter and ischaemic heart disease in history. The probability of patient's death is the highest (p<0.003), if factors like CPCR, number of blood transfusions and aneurysm diameter are combined (multivariate analysis, stepwise method). CONCLUSION: The early detection and surgical or endovascular elective treatment of AAA, regular dispensarization of patients with small AAA, especially hypertonics, correct diagnosis of RAAA without time delay, are the best tools for patients survival. The patient's survival increases with trained prehospital resuscitation system and experienced team of vascular surgeons and anestesiologists in centres (Tab. 3, Ref. 20).

Aged↗
PubMed2004

The screening for X-linked Emery-Dreifuss muscular dystrophy amongst young patients with idiopathic heart conduction system disease treated by a pacemaker implant.

The X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) is a hereditary muscle disorder associated with cardiac involvement. Sinus node dysfunction and atrioventricular conduction defects, typical of X-EDMD, occur in both males and females and may result in sudden cardiac death unless treated by permanent pacing. The objective of the study was to determine the frequency and relevance of X-EDMD in heart conduction system disease in young individuals treated with a pacemaker implant. The medical history of 3450 paced individuals in the region of South Moravia, Czech republic, was reviewed. Thirty-five patients, 20 males and 15 females, with idiopathic heart conduction disease of onset before age 40 were identified and screened for X-EDMD. Within these 35 individuals, only one male was found to carry a mutation in X-EDMD gene. We conclude that the clinical relevance of X-EDMD in heart conduction system disease is very low. It should, however, be included into the diagnostic work-up of young male individuals with idiopathic cardiac conduction disturbances.

Adolescent↗
PubMed2003

The incidence and persistence of the NCEP (National Cholesterol Education Program) metabolic syndrome. The French D.E.S.I.R. study.

CONTEXT: In 2001 the "National Cholesterol and Education Program Expert Panel" gave a clinical definition of the metabolic syndrome. The frequency of this syndrome at baseline and its incidence and persistence at three years is studied in a French population. SUBJECTS: 2109 men and 2184 women from the D.E.S.I.R. longitudinal cohort study (Data from an Epidemiological Study on the Insulin Resistance syndrome) in central-western France, aged 30 to 64 years, were examined at inclusion and three years later. METHODS: Evaluation of the frequencies, incidences and persistence of the metabolic syndrome and its abnormalities. This syndrome is defined by the presence of three or more of five abnormalities: waist circumference > 102/88 cm (men/women); triglycerides > o r=1.69 mmol/l, HDL-cholesterol<1.04/1.29 mmol/l (men/women); systolic/diastolic blood pressure > or =130 and/or 85 mmHg; fasting plasma glucose > or =6.1 mmol/l. RESULTS: At baseline, 10% of men and 7% of women had the metabolic syndrome. If the syndrome was defined to include a treatment in the abnormalities (for diabetes, hypertension, dyslipidemia), the syndrome frequencies increased to 16% and 11%. However only 12% and 8% respectively, had this syndrome both at inclusion and at three years. High blood pressure was the most frequent abnormality: 70% and 47% in men and women respectively, at inclusion. The most stable abnormality was high waist circumference (80% persisted), hyperglycaemia the least stable (60% persisted). Hyperinsulinaemia did not cluster closely with this syndrome. CONCLUSIONS: The age-specific frequency of the syndrome is more than 2.5 times higher in the US than in this French cohort and this ratio increased with age. The higher frequencies of abdominal obesity and low HDL-cholesterol in women than in men suggest that these gender-specific thresholds may need to be refined.

Abdomen↗
PubMed2002

Mapping the C terminal epitope of the Alzheimer's disease specific antibody MN423.

The mapping of monoclonal antibody epitopes is now predominantly carried out using molecular diversity techniques, phage display in particular. However, until very recently, phage display methods have been inappropriate for the analysis of epitopes that require a free carboxy terminus. Here we describe the use of two different techniques to analyze the known C terminal epitope specificity of MN423, a monoclonal antibody specifically staining truncated tau in Alzheimer's brain. Using a lambda phage based C-terminal random peptide library, and an intracellular expression library based on truncated tau, we show that this antibody has an absolute requirement for a glycine at position -3 with respect to the C terminus. Both methods give similar results, and identify other important residues in the binding site. However, affinity analysis of synthetic peptides revealed that the affinity of the antibody for identified tripeptides was far lower than the pentapeptide sequence in the native target, and that this in turn was considerably below the affinity for the native target itself. This suggests that molecular diversity methods may define minimum, but not necessarily complete epitopes. The methods described here have a general application to the analysis of antibody epitopes suspected to be found at the C terminus.

Aged↗
PubMed2002

Effect of Echinococcus multilocularis on the origin of acetyl-coA entering the tricarboxylic acid cycle in host liver.

Carbon-13 nuclear magnetic resonance (NMR) spectroscopy was employed to investigate alterations in hepatic carbohydrate metabolism in Meriones unguiculatus infected with Echinococcus multilocularis. Following portal vein injections of an equimolar mixture of [1,2-13C2]acetate and [3-13C]lactate, perchloric acid extracts of the livers were prepared and NMR spectra obtained. Isotopomer analysis using glutamate resonances in these spectra showed that the relative contributions of endogenous and exogenous substrates to the acetyl-CoA entering the tricarboxylic acid cycle differed significantly between infected and control groups. The mole fraction of acetyl-CoA that was derived from endogenous, unlabelled sources (F(U)) was 0.50 +/- 0.10 in controls compared to 0.34 +/- 0.04 in infected animals. However, the fraction of acetyl-CoA derived from [3-13C]lactate (FLL) was larger in livers of infected animals than those from controls with values of 0.27 +/- 0.04 and 0.18 +/- 0.04, respectively. Similarly, the fraction of acetyl-CoA derived from [1,2-13C2]acetate (FLA) was larger in livers of infected animals compared to those in controls; the fractions were 0.38 +/- 0.01 and 0.32 +/- 0.07, respectively. The ratio of FLA:FLL was significantly smaller in the infected group with a value of 1.42 +/- 0.18 compared to 1.74 +/- 0.09 for the controls. These results indicate that alveolar hydatid disease has a pronounced effect on the partitioning of substrates within the pathways of carbohydrate metabolism in the host liver.

Acetyl Coenzyme A↗
PubMed2001

Repetitive intrathecal injections of poliovirus replicons result in gene expression in neurons of the central nervous system without pathogenesis.

Poliovirus-based vectors (replicons) can be used for gene delivery to motor neurons of the CNS. In the current study, a replicon encoding green fluorescent protein (GFP) was encapsidated into authentic poliovirions, using established procedures. Intrathecal delivery of encapsidated replicons encoding GFP to the CNS of mice transgenic for the human poliovirus receptor did not result in any functional deficits as judged by behavioral testing. Histological analysis of the CNS of mice given a single intrathecal injection of poliovirus replicons encoding GFP revealed no obvious pathogenesis in neurons (or other cell types) within the CNS. The expression of GFP was confined to motor neurons throughout the neuroaxis; a time course of expression of GFP revealed that expression was detectable 24 hr postinoculation and returned to background levels by 120 hr postinoculation. A procedure was devised to allow repetitive inoculation of replicons within the same animal. Behavioral testing of animals that had received 6 to 13 independent inoculations of replicons revealed no functional deficits. Histological analysis of the CNS from animals that had received 6 to 13 sequential inoculations of replicons revealed no obvious abnormalities in neurons or other cell types in the CNS; expression of GFP was demonstrated in neurons 24 to 72 hr after the final inoculation of the replicon. Furthermore, there was no obvious inflammatory response in the CNS after the multiple inoculations. These studies establish the safety and efficacy of replicons for gene delivery to the CNS and are discussed with respect to use of replicons as new therapeutic strategies for spinal cord injuries and/or neurological diseases.

Animals↗
PubMed2001

Interaction of tau isoforms with Alzheimer's disease abnormally hyperphosphorylated tau and in vitro phosphorylation into the disease-like protein.

The microtubule-associated protein tau is a family of six isoforms that becomes abnormally hyperphosphorylated and accumulates in neurons undergoing neurodegeneration in the brains of patients with Alzheimer disease (AD). We investigated the isoform-specific interaction of normal tau with AD hyperphosphorylated tau (AD P-tau). We found that the binding of AD P-tau to normal human recombinant tau was tau4L > tau4S > tau4 and tau3L > tau3S > tau3, and that its binding to tau4L was greater than to tau3L. AD P-tau also inhibited the assembly of microtubules promoted by each tau isoform and caused disassembly when added to preassembled microtubules. This inhibition and depolymerization of microtubules by the AD P-tau corresponded directly to the degree of its interaction with the different tau isoforms. In vitro hyperphosphorylation of recombinant tau (P-tau) conferred AD P-tau-like characteristics. Like AD P-tau, P-tau interacted with and sequestered normal tau and inhibited microtubule assembly. These studies suggest that the AD P-tau interacts preferentially with the tau isoforms that have the amino-terminal inserts and four microtubule binding domain repeats and that hyperphosphorylation of tau appears to be sufficient to acquire AD P-tau characteristics. Thus, lack of amino-terminal inserts and extra microtubule binding domain repeat in fetal human brain might be protective from Alzheimer's neurofibrillary degeneration.

Alzheimer Disease↗
PubMed2001

Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments.

The microtubule-associated protein tau is a family of six isoforms that becomes abnormally hyperphosphorylated and accumulates in the form of paired helical filaments (PHF) in the brains of patients with Alzheimer's disease (AD) and patients with several other tauopathies. Here, we show that the abnormally hyperphosphorylated tau from AD brain cytosol (AD P-tau) self-aggregates into PHF-like structures on incubation at pH 6.9 under reducing conditions at 35 degrees C during 90 min. In vitro dephosphorylation, but not deglycosylation, of AD P-tau inhibits its self-association into PHF. Furthermore, hyperphosphorylation induces self-assembly of each of the six tau isoforms into tangles of PHF and straight filaments, and the microtubule binding domains/repeats region in the absence of the rest of the molecule can also self-assemble into PHF. Thus, it appears that tau self-assembles by association of the microtubule binding domains/repeats and that the abnormal hyperphosphorylation promotes the self-assembly of tau into tangles of PHF and straight filaments by neutralizing the inhibitory basic charges of the flanking regions.

Alzheimer Disease↗
PubMed2001

Microalbuminuria and markers of the atherosclerotic process: the D.E. S.I.R. study.

The relationship between microalbuminuria and tissue-type plasminogen activator antigen (tPA-ag) and fibrinogen was evaluated in non-diabetic subjects. Subjects were participants of the D.E.S.I. R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) Study. Analyses were carried out on 2248 women and 2402 men for fibrinogen and on 272 women and 284 men for tPA-ag. Microalbuminuria was defined as urinary albumin concentration greater than 20 mg/l. Men with microalbuminuria had a 6% higher fibrinogen concentration than those without (3.07 g/l (95% confidence interval: 2.99,3.15) vs. 2.89 g/l (2.87,2.91), adjusted for age and smoking). This relationship existed in hypertensive as well as non-hypertensive subjects. The association between microalbuminuria and tPA-ag existed only in hypertensive men, those with microalbuminuria having a 21% higher tPA-ag than those without (4.39 ng/ml (3.70,5.08) vs. 3.63 ng/ml (3.32,3.94), adjusted for age and smoking). Adjustment for other risk markers for cardiovascular disease did not change the results. There was no relationship between microalbuminuria and these haemostatic factors in women. The results of this study suggest that in non-diabetic men, microalbuminuria is associated with fibrinogen, but with tPA-ag only when concomitant with hypertension.

Adult↗
PubMed2001

Spotting zones of dissimilatory sulfate reduction in a forested catchment: the 34S-35S approach.

The localization of sulfate reducing sites in forested catchments is of major importance, because dissimilatory sulfate reduction can be a considerable sink for deposited sulfate. To localize dissimilatory sulfate reduction sites in a forested catchment (northeastern Bavaria, Germany), three sites within the catchment (upland site, intermittent seep, fen) were investigated for delta 34S depth profiles of soil sulfur and potential sulfate reduction rates were measured with 35S radiolabeling. Stable sulfur isotopes indicate that aerobic metabolism is the dominant process on the upland site and the intermittent seep (delta 34S of soil sulfur between +1.6 and +9.0@1000) and dissimilatory reduction is not a significant sink for sulfate. However, results of the 35S radiolabeling indicated for the upland site that the soil has potentially high sulfate reduction rates under laboratory conditions. Soil sulfur of the fen was markedly depleted in 34S (delta 34S between -6 and +2.6@1000). Both, 34S and 35S data indicated that dissimilatory sulfate reduction is an ongoing process on this site. The 34S and 35S approaches are complementary. While measurements using 35S can show momentary potential for dissimilatory bacterial sulfate reduction, delta 34S data reflect long-term predominance of either assimilatory or dissimilatory S metabolism at a particular site.

Germany↗
PubMed2001

Improvement of skin care during radiotherapy.

BACKGROUND: State-of-the-art radiotherapy, new insights into pharmacology and novel operating techniques require patient-oriented adaptation of care. PATIENTS AND METHOD: At the Radio-oncology Department of the Kaiser Franz Josef Spital, Vienna, a new skin care concept for patients undergoing radiotherapy was introduced in March 1999. This concept has subsequently been applied in all cases regardless of the diagnosis prompting referral (79 ENT, 305 breast, 134 prostate, 89 colorectal cancer and 751 other patients). Radiotherapy consisted of photon and/or electron radiation on the linear accelerator. The energy ranges were between 6 and 15 MV for photon therapy and between 6 and 12 MeV for electron radiation. Patients received an average total radiation dose of 50-66 Gy at single fractional doses of 1.8-2 Gy 5 times a week. Powdering of the skin was replaced by a moist skin care program. Patients were allowed to take cool whole-body showers without soap, including the irradiated skin areas, 3 times a week. RESULTS: With the new skin care program dryness of the skin and resultant allergic skin reactions became less common. Broken skin an epitheliolysis were clearly reduced and superinfections were prevented. CONCLUSION: Moist care of irradiated skin areas during radiotherapy thus improved radiation tolerance and patient acceptance.

Adult↗
PubMed2001

Is microalbuminuria an integrated risk marker for cardiovascular disease and insulin resistance in both men and women?

BACKGROUND: Microalbuminuria is associated with some cardiovascular risk factors. However, it is presently unclear whether microalbuminuria is associated with other cardiovascular risk factors and markers of insulin resistance in both men and women. DESIGN: The baseline parameters of the on-going prospective D.E.S.I.R. Study (Data from an Epidemiological Study on the Insulin Resistance syndrome) were analysed. METHODS: The subjects (n = 3878, age 30-64) had a medical and biological checkup including arterial pressure, ECG, lipids, haematocrit, leukocyte count, insulin and urinary albumin concentration. RESULTS: Arterial pressure was significantly higher in microalbuminuric than in normoalbuminuric men and women. The heart rate and the prevalence of smoking were higher in microalbuminuric than in normoalbuminuric men, but not in women. Total- and LDL-cholesterol, triglycerides, apolipoprotein-B, leukocyte count, uric acid, haematocrit, haemoglobin and red cell volume were greater in microalbuminuric than in normoalbuminuric men. Total- and HDL-cholesterol were lower whereas triglycerides and uric acid were significantly greater in microalbuminuric than in normoalbuminuric women. The 9-year calculated absolute cardiovascular risk was higher in microalbuminuric than in normoalbuminuric men (4.18% vs. 2.79%, respectively, P < 0.0001) but was similar in women (0.75% vs. 0.69%, respectively, NS). Fasting blood glucose and insulin were higher in microalbuminuric than in normoalbuminuric men, but not in women. A multiple regression showed that microalbuminuria was associated with systolic arterial pressure, fasting glucose, leukocyte count and haematocrit in men, and with systolic arterial pressure and triglycerides in women. CONCLUSIONS: Microalbuminuria is associated with most cardiovascular risk factors and markers of insulin resistance in men, but no consistent association is observed in women. The determinants of microalbuminuria appear different in men and women, suggesting a different pathophysiology and perhaps significance of microalbuminuria in men and women.

Adult↗
PubMed2001

Alzheimer's disease, inflammation and non-steroidal anti-inflammatory drugs.

Alzheimer's disease (AD) is a degenerative disease of the brain, which causes dementia. The disease is characterised by three main pathogenic factors: senile plaques, neurofibrillary tangles and inflammation. the participation of the local inflammatory reaction is confirmed especially by the results of studies dealing with activated microglia, reactive astrocytes, complement system, cytokines, reactive mediators of oxygen and nitrogen (free radicals), all of which participate significantly in inflammatory processes. These inflammatory markers are locally produced by brain cells, and occur in close proximity of beta-amyloid and tau protein deposits. Moreover, some epidemiologic and pilot clinical studies have proven that long-term administration of anti-inflammatory drugs have a protective effect on the onset of AD. Out of them, non-steroidal anti-inflammatory drugs (NSAIDs) are most extensively investigated medicaments. Despite some contradictory findings, the prevalent majority of these studies prove that long-term application of anti-inflammatory treatment can delay the onset, or at least slow down the progression of AD, namely in people between 65 and 75 years of age. The most appropriate prophylactic effect seems to be achieved by specific inhibitors of cyclooxygenase-2 (COX-2), namely celecoxib and rofecoxib. These preparations protect the gastrointestinal tract better than classical NSAIDs which inhibit both isoenzymes--COX-1 and COX-2. COX-2 is expressed in higher concentrations in the degenerating cells of the brain and this excessive expression can be decreased by selective inhibitors. The latter decrease also the excessive activation of some transcription factors (PPARgama and the nuclear factor kapa-B), which are responsible for the initiation of transcription of a number of pro-inflammatory genes. The selective inhibitors COX-2 can thereby have an anti-inflammatory effect operating on several levels. (Tab. 1, Fig. 1, Ref. 75.)

Alzheimer Disease↗
PubMed2000

The solution structure of the C-terminal segment of tau protein.

Pathological changes in the microtubule associated protein tau, leading to tau-containing filamentous lesions, are a major hallmark common to many types of human neurodegenerative diseases, including Alzheimer's disease (AD). No structural data are available which could rationalize the extensive conformational changes that occur when tau protein is converted to Alzheimer's paired helical filaments (PHF). The C-terminal portion of tau plays a crucial role in the aggregation of tau into PHF and in the truncation process that generates cytotoxic segments of tau. Therefore, we investigated the solution structure of the hydrophobic C-terminal segment 423-441 of tau protein (PQLATLADEVSASLAKQGL) by 1H 2D NMR spectroscopy. The peptide displays the typical NMR evidence consistent with a alpha-helix geometry with a stabilizing C-capping motif. The reported data represent the first piece of structural information on an important portion of the molecule and can have implications towards the understanding of its pathophysiology.

Amino Acid Sequence↗