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Biomedical subjects

S Väisänen

Publications and source records attributed to S Väisänen.

At least 19 recordsLinked to original sources
PubMed2002

Coeliac disease in children and adolescents with type 1 diabetes: a study of growth, glycaemic control, and experiences of families.

UNLABELLED: The aim of this study was to evaluate whether coeliac disease affects growth, glycaemic control, and general well-being of children and adolescents with type I diabetes. Eighteen subjects were found to have coeliac disease by a screening program. Gastrointestinal symptoms, changes in growth and the levels of glycated haemoglobin (GHbA1) were analysed, as well as subjective well-being before and after diagnosis of coeliac disease. Overt gastrointestinal symptoms and deterioration of growth prior to disclosure of coeliac disease were seen only in one patient who had both of these conditions. Retrospectively, most subjects reported mild gastrointestinal complaints, which resolved on a gluten-free diet. Introduction of a gluten-free diet did not have any positive effect on glycaemic control, but was associated with an increase in weight-for-height (from 4.3+/-18.1 to 8.2+/-15.4% deviation from population median, p = 0.02). This increase in weight-for-height was inversely correlated with changes in GHbA1 (r = -0.574, p = 0.02). CONCLUSION: Coeliac disease is rarely associated with signs of malabsorption in children and adolescents with type I diabetes. Introduction of a gluten-free diet may be associated with excess weight gain. We recommend intensified follow-up for these subjects.

Adolescent↗
PubMed2000

Relationship between lipid peroxidation and plasma fibrinogen in middle-aged men.

The relationship between lipid peroxidation (plasma malondialdehyde [MDA] concentration) and plasma fibrinogen level was analyzed in 144 men, aged 53-62 years. MDA was measured colorimetrically and fibrinogen with the thrombin method. Mean plasma MDA concentration was 12.6 (SD 1.2) micromol/L, plasma fibrinogen level 2.91 (0.47) g/L, and body mass index 27.1 (3.5) kg/m(2). Prevalence of smoking was 17%. MDA correlated moderately with fibrinogen. Both MDA and fibrinogen correlated positively with waist hip ratio (WHR) and blood leukocyte count, but inversely with VO(2)max. Both MDA and fibrinogen levels were higher in smokers than in non-smokers (p<0. 01). In multiple stepwise regression analysis, plasma MDA, VO(2)max, smoking, and leukocyte count explained 38.1% of the variance in plasma fibrinogen level, with the individual contributions reaching 20.6%, 9.7%, 5.5%, and 2.3%, respectively. WHR, serum triglycerides, and age did not enter the model. These data suggest that increased lipid peroxidation is associated with elevated plasma fibrinogen level in middle-aged men.

Arteriosclerosis↗
PubMed1999

The importance of the putative helices 4 and 5 of human vitamin D(3) receptor for conformation and ligand binding.

The 3-D structure of the human vitamin D(3) receptor has not been solved to date. To study the conformation of the ligand binding pocket and the amino acid residues important for binding of calcitriol and its synthetic 20-epi analog MC1288, we have introduced several point mutations into putative helices 4 and 5 of human vitamin D(3) receptor by site-directed mutagenesis. The amino acid residues Ser256, Glu257, Asp258, Gln259, Lys264, Ser265, Ser266, Glu269, Arg274, Ser278, and Phe279 were substituted by alanine. Our results suggest that Arg274 is important for the binding of calcitriol and probably also for the binding of the synthetic vitamin D analog MC1288, whereas Asp258, Gln259, Glu269, and Phe279 may have an important role in stabilizing the conformation of hVDR after ligand binding.

Alanine↗
PubMed1999

Positive and negative life changes and LDL cholesterol.

Epidemiological studies have revealed that stressful changes in social environment increase the risk of cardiovascular mortality. In this study, the influence of major negative and positive life changes on serum cholesterol was examined in middle-aged men to determine a possible biochemical link between life changes and cardiovascular mortality. The results showed no influence of negative life changes on serum cholesterols. However, positive life changes significantly predicted a reduction in total and LDL (low-density lipoprotein) cholesterol levels after adjustment for the baseline cardiovascular health status, baseline cholesterol level, diet, body mass index, waist-to-hip ratio and cardiorespiratory fitness. The odds ratio for lowering LDL cholesterol was 5.2 in the men reporting positive events compared with those reporting none. The findings suggest a predictive value of positive life changes for atherogenic lipid profile in middle-aged men.

Cholesterol, LDL↗
PubMed1999

Structure-function studies of new C-20 epimer pairs of vitamin D3 analogs.

A growing number of calcitriol (1alpha,25-dihydroxyvitamin D3) analogs have become available in recent years. Many of these analogs exhibit lower calcemic effects than calcitriol and inhibit cell proliferation and enhance cell differentation more efficiently than calcitriol. We have compared structure-function relationships of a series of new C-20 epimer (20-epi) vitamin D3 analogs with their natural C-20 counterparts. In human MG-63 osteosarcoma cells, quantification of cellular osteocalcin mRNA levels by Northern blot analysis and osteocalcin biosynthesis by radioimmunoassay indicated that most studied analogs at a concentration of 10 nm induced osteocalcin gene expression more efficiently than the parent compound, calcitriol. Interestingly, when the biological responses were compared with the binding affinities of the analogs to in-vitro translated human vitamin D receptor and with their ability to protect the receptor against partial proteolytic digestion, significant correlations were not observed. Further, molecular modelling of the compounds by energy minimization did not reveal marked differences in the three-dimensional structures of the analogs. These results suggest that higher than normal ligand binding affinity or 'natural' conformation of the ligand-receptor complex are not necessarily required for the 'superagonist' transactivation activity. The mechanism of action of the efficient analogs may involve stabilization and/or differential binding of transcriptional coactivators or transcription intermediary factors to the hVDR during transactivation.

Cholecalciferol↗
PubMed1998

Putative helices 3 and 5 of the human vitamin D3 receptor are important for the binding of calcitriol.

We have introduced eleven point mutations into the human vitamin D receptor by site-directed mutagenesis in order to identify some of the amino acid residues that are important for ligand binding. The amino acid residues Ser225, His229, Asp232, Val234, Ser235, Tyr236, Ser237, Lys240, Ile242, Lys246 (helix 3), and Ser275 (helix 5) of the human vitamin D receptor were substituted by alanine. We report here that His229, Asp232, and Ser237 have an important role in the binding of calcitriol. In addition, the amino acid residues Tyr236 and Ser275 also seem to participate in the ligand binding process.

Amino Acid Sequence↗
PubMed1997

Conformational studies of human vitamin-D receptor by antipeptide antibodies, partial proteolytic digestion and ligand binding.

We have studied conformational changes of human vitamin-D receptor by using antipeptide antibodies, partial proteolytic digestion and binding of the natural ligand calcitriol or its synthetic analogs. Before exposing either [35S]methionine-labelled in vitro translated human vitamin-D receptor or a recombinant human vitamin-D receptor produced either in Escherichia coli or in Sf9 insect cells to limited proteolysis by trypsin or chymotrypsin, the proteins were treated with calcitriol or its synthetic analogs. The digestion products were analyzed by SDS/PAGE, immunoblotting with polyclonal antipeptide antibodies targeted against different domains of the receptor, and Edman N-terminal sequencing. After limited proteolysis with trypsin, two fragments of Mr 21,000 and Mr 34,000 could be localized into N-terminus and C-terminus of the receptor, respectively, by antipeptide antibodies. We found that treatment with calcitriol or its synthetic analogs leads to differential resistance of the ligand-binding domain of the recombinant receptor to partial proteolysis in vitro. We suggest that this is due to distinct conformational changes in the domain induced by the different ligands. The short N-terminal region and the Zn-finger domain form, however, a protease-resistant structure which is independent on the presence or absence of the ligand. When the C-terminal fragment of Mr 34,000 was further analyzed by Edman N-terminal sequencing, the major cleavage site in the receptor between amino acids Arg173 and His174 was revealed.

Amino Acid Sequence↗
PubMed1997

Relationship between changes in physical activity and plasma insulin during a 2.5-year follow-up study.

The association between changes in physical activity, body weight, and diet and fasting plasma insulin was analyzed in a 2.5-year follow-up study of 146 men aged 50 to 60 years. Physical activity was assessed by a 7-day physical activity recall interview, diet by a 4-day food record, and plasma insulin radioimmunologically. Total physical activity decreased from (mean +/- SD) 45.1 +/- 10.1 to 39.0 +/- 6.1 metabolic equivalent (MET) hours (METh).d-1 and conditioning physical activity (> 5.0 METs) from 8.0 +/- 11.2 to 2.7 +/- 5.0 METh.d-1, whereas plasma insulin increased from 8.2 +/- 5.8 to 9.2 +/- 6.7 mU.L-1 and body weight from 80.5 +/- 12.0 to 81.6 +/- 11.6 kg during the follow-up period (P < or = .001 for all). The change in conditioning physical activity correlated inversely (r = -.34, P < .001) and change in body weight positively (r = .42,P < .001) with the change in plasma insulin level. With data adjusted for the baseline insulin level, cardiovascular health status, alcohol intake, change in body weight, smoking, age, and follow-up time, the odds ratio for an increase in fasting plasma insulin was 8.9 (95% CI, 2.1 to 37.1; P = .003) for men with the greatest decrease in conditioning physical activity (< -7 METh) compared with men who reported an increase in conditioning physical activity. The same logistic regression model showed an odds ratio of 9.9 (95% CI, 2.1 to 45.4; P = .003) for the increase in plasma insulin for subjects who gained more than 3.3 kg body weight compared with subjects who lost at least 0.6 kg. Men who consumed at least 12 g.d-1 alcohol at both examinations had an odds ratio of 12.8 (95% CI, 1.7 to 94.5; P = .012) compared with nondrinkers. These data suggest that in middle-aged men, a reduction in physical activity increases the risk for increased plasma insulin independently of alcohol intake and changes in body weight.

Aging↗
PubMed1997

Hemostatic factors and platelet aggregation after a fish-enriched diet or fish oil or docosahexaenoic acid supplementation.

The effects of a fish-enriched diet or dietary supplements consisting of either fish oil or a docosahexaenoic acid-rich oil (DHA-oil) on platelet aggregation and hemostatic factors were studied in healthy male students. After an experimental period of 15 weeks, the levels of tissue factor pathway inhibitor, prothrombin fragment 1+2 and fibrinogen as well as factor VII activity were not changed. Factor X activity was slightly decreased by the fish diet (P < 0.05). Collagen but not ADP-induced maximum platelet aggregation decreased in the fish diet and the fish oil groups (P < 0.05 in both). In the DHA-oil group there was a slight, statistically insignificant, increase of platelet aggregation which correlated significantly with the decrease of plasma triglycerides. Platelet aggregation measured 4 h after a standardized fat meal was lower than in the fasting state and this decrease correlated with the increase of plasma triglycerides. These results show that a fish diet and fish oil, but not DHA-oil, inhibit in vitro platelet aggregation and that hemostatic factors are not affected by moderate n-3 fatty acid supplementation.

Adolescent↗
PubMed1997

Social network in relation to plasma fibrinogen.

Consistent findings about the inverse association of social network level with coronary heart disease mortality and morbidity suggest the importance of investigating biological pathways of association. Differences in plasma fibrinogen level were investigated among middle-aged men with weak and strong structural and functional social network ties. Men with low scores in the adequacy of social participation variable (structural) had higher mean values of plasma fibrinogen than those with high scores. The difference remained after adjustment for age, smoking and cardiovascular health status and after possible modifying factors were taken into account, but did not remain significant after allowing for physical fitness. Men with high scores in overall support (functional) had higher plasma fibrinogen levels compared to the men with low scores. This difference persisted after age and cardiovascular health status were taken into account but was explained by smoking. The data suggest that smoking and cardiorespiratory fitness are important mediating or modifying factors between structural and functional aspects of social network ties and plasma fibrinogen.

Cardiovascular Diseases↗
PubMed1997

Evaluation of occupational health service in the wood processing industry--determination of employee satisfaction.

In order to define priorities for improvement of the occupational health service (OHS) in one primary health care unit, employees' satisfaction was evaluated with a postal questionnaire. The questionnaire covered items on service reservation, personal health education received, quality of the OHS, and use of the OHS within six months by the employees. This evaluation was one step of the quality system that was planned in accordance with the ISO 9004-2 standard for continuous quality improvement of OHS. The study population was all of 1,050 employees working for five employers; 546 (52%) employees responded to the inquiry. However, only 377 of them had made use of the OHS within the last six months before the inquiry. The mean age of the responders was 42 years (SD = 9 years) and 76% of the respondents were men. The percentages of employees with a high degree of satisfaction with the quality of the OHS and personal health education in the OHS were 76% and 69%, respectively. However, concerning the quality of the OHS, the proportion of highly satisfied employees was 27% higher (95% CI = 19-35%) among those who had used OHS within six months compared to the others. Furthermore, when the oldest (> 48 years) and the youngest (< 35 years) age groups were compared, the difference between the proportions of highly satisfied employees was 21% (95% CI = 31%). In conclusion, the high differences suggest a close linkage between the employee's satisfaction with the OHS, the use of the OHS and ageing.

Adult↗
PubMed1997

Variation in plasma fibrinogen over one year: relationships with genetic polymorphisms and non-genetic factors.

We analyzed plasma fibrinogen level in relation to genetic polymorphisms in the alpha- and beta-fibrinogen gene loci. Furthermore, the association of other CVD risk markers with fibrinogen was studied twice, with a time interval of one year in 50 to 60 year old men (n = 183). DNA polymorphisms were detected by PCR and digestion with Taq I (alpha-fibrinogen), Hind III and Bcl I (beta-fibrinogen) restriction enzymes. The correlation coefficient between fibrinogen measurements was 0.48 (p < 0.001). Blood leucocytes and waist-to-hip circumference ratio were the strongest correlates of fibrinogen level in both examinations, and the changes in leucocyte count and plasma fibrinogen correlated positively (r = 0.40, p < 0.001). In Eastern Finnish men, the Taq I, Hind III or Bcl I restriction fragment length polymorphisms of the alpha- or beta-fibrinogen gene loci did not associate with fibrinogen level, either cross-sectionally or longitudinally.

Biomarkers↗
PubMed1997

Physical activity, fibrinogen plasma level and gene polymorphisms in postmenopausal women.

The relations between habitual physical activity (PA), fibrinogen gene polymorphisms and plasma fibrinogen were investigated in 191 postmenopausal women. Subjects who reported PA at least 4 times/week had lower fibrinogen level (3.19 g/l; 95% CI 3.10; 3.27) than women reporting PA 2-3 times/week (3.43 g/l; 3.29; 3.58) or sedentary subjects (3.64 g/l; 3.33; 3.94). There were no differences in plasma fibrinogen across the alpha-fibrinogen (RsaI, TaqI) or beta-fibrinogen (MnlI, BclI, HindIII) genotypes, the frequencies of which were in a Hardy-Weinberg equilibrium. An interaction between RsaI, which was in complete linkage disequilibrium with TaqI, and PA on plasma fibrinogen was observed, even after adjustments for BMI, smoking and medication (p = 0.024). Among women homozygous for the common RsaI allele, the physically most active had lower fibrinogen level (p <0.001) compared to the physically less active subjects. These results suggest that, in postmenopausal women, the relation between physical activity and plasma fibrinogen is modulated by genetic variation in the alpha-fibrinogen gene.

Aged↗
PubMed1997

Small, dense LDL particle concentration correlates with plasminogen activator inhibitor type-1 (PAI-1) activity.

The relation between LDL subfractions and fibrinolytic activity was studied in 150 men aged 53 to 63 years. Apolipoprotein B (apoB) concentration in the most dense LDL-5 (r = 0.39, p <0.001) and LDL-6 (r = 0.43, p <0.001) subfractions associated with plasminogen activator inhibitor type-1 (PAI-1) activity. Subjects in the highest LDL-6 apoB tertile had higher PAI-1 (24.7 vs. 13.1 AU/ml, p <0.001) and lower t-PA (0.26 vs. 0.54 IU/ml, p <0.001) activities than men in the lowest tertile. The difference in PAI-1 remained after adjusting for either triglycerides (p = 0.039) or insulin (p = 0.015) with cardiorespiratory fitness as an additional covariate, and history of cardiovascular disease and smoking as factors. In a regression analysis, plasma insulin and LDL-6 apoB, but not plasma triglycerides and body mass index, entered the model, and explained 30.6 and 3.9% of the variance in PAI-1 activity, respectively. The novel finding of the present study was the independent association between small, dense LDL particles and PAI-1 activity in middle-aged men.

Analysis of Variance↗
PubMed1996

Physical activity, fitness, and plasma fibrinogen with reference to fibrinogen genotypes.

The relation of daily energy expenditure (EE) and maximal oxygen uptake (VO2max) to plasma fibrinogen with reference to DNA polymorphism was analyzed in a random sample of men (N = 189), age 50-60. Fibrinogen polymorphism was detected using polymerase chain reaction (PCR) and digestion with HindIII and BclI (beta-fibrinogen), and TaqI (alpha-fibrinogen) restriction enzymes. Mean VO2max was 29.4 ml.kg-1.min-1 (95%CI 28.5; 30.2) and mean daily EE was 179 kJ.kg-1.d-1 (173; 186) and were similar in all fibrinogen genotypes. Plasma fibrinogen was 3.26 g.1-1 (3.18; 3.34) and did not associate with fibrinogen polymorphisms. Both EE and VO2max related inversely to fibrinogen level (r = -0.24, P < 0.001). Strongest predictors of plasma fibrinogen were VO2max in TaqI 800 bp homozygotes, and EE together with smoking in TaqI 900 bp homozygotes. The predictive role of VO2max was marginal in the common beta-fibrinogen genotypes, whereas physical activity level explained up to 9% of the variance in the less frequent genotypes. These data suggest that the association of VO2max and EE with plasma fibrinogen varies across the fibrinogen genotypes.

Cross-Sectional Studies↗
PubMed1996

Effects of moderate salt restriction alone and in combination with cilazapril on office and ambulatory blood pressure.

The purpose of the present study was to examine the effects of salt-restriction alone and in combination with an angiotensin-converting enzyme (ACE) inhibitor (cilazapril) on both office and ambulatory blood pressure (BP) levels in free living subjects with elevated BP. The study was carried out in an out-patient setting with subjects recruited from occupational health care system mainly. After exclusions, 39 subjects (24 men, 15 women, aged 28-65 years) with mildly to moderately elevated BP completed the study. After 3 months run-in period with placebo (first month on normal-salt and the next 2 months on sodium-restricted diet) the subjects were randomised into either salt-restriction placebo or salt-restriction cilazapril (2.5 mg daily) groups for 3 months. In the whole group, 24-h urinary sodium excretion decreased (mean +/- s.d.) from 198 +/- 60 to 112 +/- 59 mmol (4 weeks vs 24 weeks, P < 0.001). Systolic and diastolic office BP decreased during the placebo-sodium-restriction phase (-7.1 [95% Cl -11.2; -3.0] and -4.2 [95% Cl -6.6; -1.8] mm Hg for systolic and diastolic BP), and similarly the daytime ambulatory BP (ABP) was reduced during this period (-2.8 [95% Cl -5.2; -0.5] and -2.8 [95% Cl -4.5; -1.2] mm Hg, systolic (SBP) and diastolic blood pressure (DBP) respectively). No changes were observed in the night time ABP. Addition of cilazapril to sodium-restriction enhanced significantly the office BP (-13.2, [95% Cl -20.2; -6.2], and -9.1 [95% Cl -13.5; -4.7]) and daytime ABP (-5.9, [95% Cl -10.1; -1.8] and -5.3, [95% Cl -8.8; -1.9]) reduction. Blood glucose, plasma insulin or serum lipids did not change during the study. Moderate sodium restriction seems to lower the office and daytime ABP levels in subjects with mild-to-moderate hypertension. The antihypertensive effect of cilazapril could be enhanced by sodium restriction.

Adult↗
PubMed1995

Inverse relationship between cardiorespiratory fitness and carotid atherosclerosis.

The association between cardiorespiratory fitness (VO2max) and carotid atherosclerosis was analyzed in 163 men, aged 50 to 60 years. VO2max was assessed using breath-by-breath respiratory gas analyses during maximal exercise stress test. Atherosclerosis was evaluated quantitatively as intima-media thickness (IMT) of the right and left carotid arteries by high-resolution B-mode ultrasonography. Mean VO2max was 29.6 ml/kg per min (95%CI 28.7;30.5), common carotid IMT 1.04 mm (95%CI 1.01;1.07) and carotid bifurcation IMT 1.73 mm (95%CI 1.66;1.81). VO2max correlated inversely with carotid bifurcation IMT (r = -0.31, P < 0.001), but not with common carotid IMT (r = -0.13, P = 0.102). Men in the highest quartile of VO2max had lower (P < 0.001) bifurcation IMT 1.51 mm (95%CI 1.41;1.61) than men in the lowest (1.95 mm (95%CI 1.75;2.16)) and in the second lowest VO2max quartile (1.79 mm (1.63; 1.95)). The difference persisted (P = 0.014) after controlling for age, LDL-cholesterol, systolic blood pressure, saturated fat intake, current health status and exercise-induced ST-segment depression. These data suggest that cardiorespiratory fitness is an important independent predictor of carotid atherosclerosis in middle-aged men.

Arteriosclerosis↗