7.7.2008

Ahvenainen, T., Lehtonen, H. J., Lehtonen, R., Vahteristo, P., Aittomaki, K., Baynam, G., Dommering, C., Eng, C., Gruber, S. B., Gronberg, H., Harvima, R., Herva, R., Hietala, M., Kujala, M., Kaariainen, H., Sunde, L., Vierimaa, O., Pollard, P. J., Tomlinson, I. P. M., Bjorck, E., Aaltonen, L. A. and Launonen, V.

Cancer Genetics and Cytogenetics. 2008; 183(2): 83-88. Article. IF 1.559

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a syndrome predisposing to cutaneous and uterine leiomyomatosis as well as renal cell cancer and uterine leiomyosarcoma. Heterozygous germline mutations in the fumarate hydratase (FH, fumarase) gene are known to cause HLRCC. On occasion, no FH mutation is detected by direct sequencing, despite the evident HLRCC phenotype in a family. In the present study, to investigate whole gene or exonic deletions and amplifications in FH mutation-negative patients, we used multiplex ligation-dependent probe amplification technology. The study material comprised 7 FH mutation-negative HLRCC patients and 12 patients affected with HLRCC-associated phenotypes, including papillary RCC, early-onset RCC, uterine leiomyomas, or uterine leiomyosarcoma. A novel FH mutation, a deletion of FH exon 1 that encodes the mitochondrial signal peptide, was detected in one of the HLRCC patients (1/7). The patient with the FH mutation displayed numerous painful cutaneous leiomyomas and papillary type renal cell cancer.

Our finding, together with the two patients with whole FH gene deletion who had been detected previously, suggests that exonic or whole-gene FH deletions are not a frequent cause of HLRCC syndrome. (C) 2008 Elsevier Inc. All rights reserved.

Association of age and education with different types of leisure-time physical activity among 4437 Finnish adults

Borodulin, K., Laatikainen, T., Lahti-Koski, M., Jousilahti, P. and Lakka, T. A.

J Phys Act Health. 2008; 5(2): 242-51.

BACKGROUND: The aim of this study was to investigate the associations of age and education with types of leisure-time physical activity in a population sample of Finnish adults.

METHODS: The sample, part of the National FINRISK Study, comprised 1940 men and 2497 women age 25 to 64 years. Self-reported questionnaires were used to collect data on education and leisure-time physical activity. Overall leisure-time physical activity was further divided into conditioning and daily physical activity.

RESULTS: In men and women, age had an inverse association with conditioning physical activity but not with daily and overall leisure activity. Strong direct associations were found between education and conditioning and overall leisure activity.

CONCLUSIONS: All age groups report fairly similar levels of overall and daily levels of leisure-time physical activity, but the levels differ across educational groups. In health promotion, more emphasis should be targeted to the population groups with lower education.

Breast Cancer Onset in Twins and Women With Bilateral Disease

Hartman, M., Hall, P., Edgren, G., Reilly, M., Lindstrom, L., Lichtenstein, P., Kaprio, J., Skytthe, A., Peto, J. and Czene, K.

J Clin Oncol. 2008. IF 15.484

PURPOSE: Little is known of the onset of breast cancer in high-risk populations. We investigated the risk of breast cancer in twin sisters and in the contralateral breast taking family history into consideration.

PATIENTS AND METHODS: We analyzed a Scandinavian population-based cohort of 2,499 female twin pairs, in which at least one had a diagnosis of breast cancer and estimated the risk of breast cancer in the sister. Using a total of 11 million individuals in Sweden with complete family links, we identified 93,448 women with breast cancer and estimated the risk of a bilateral breast cancer.

RESULTS: The incidence of breast cancer in twin sisters of breast cancer patients was 0.64% per year and 0.42% per year in mono- and dizygotic twin sisters, respectively. In comparison, the risk of familial (affected first-degree relative) and nonfamilial bilateral breast cancer was 1.03% per year and 0.68% per year, respectively. Contrary to the risk of unilateral disease, the risk of cancer in the nonaffected twin and the opposite breast was not affected by age or time since first event. The relative risk of familial bilateral cancer was 52% higher (incidence rate ratio [IRR] = 1.52; 95% CI, 1.42 to 1.64) and the relative risk in the dizygotic twin sister was 25% lower (IRR = 0.75; 95% CI, 0.61 to 0.91) compared with the risk of nonfamilial bilateral cancer.

CONCLUSION: The elevated risk of breast cancer in high-risk groups is little affected by age and time since diagnosis. Our findings suggest that susceptible groups of women might have already aggregated genetic prerequisites for breast cancer.

Factors contributing to pertussis resurgence

He, Q. and Mertsola, J.

Future Microbiol. 2008; 3: 329-39. IF 0.645

Despite extensive immunization, the disease pertussis remains one of the world's leading causes of vaccine-preventable deaths. An estimated 50 million cases and 300,000 deaths occur every year. A resurgence of pertussis is observed in highly immunized populations. Increasing numbers of pertussis are reported in adolescents and adults who transmit bacteria to newborns and infants to whom pertussis may be a life-threatening disease. Many studies have shown that the causes for the resurgence are multiple, such as increased awareness of disease, use of better diagnostic tools, improved surveillance methods and waning vaccine-induced immunity. Recently, antigenic divergence has been found between vaccine strains and clinical isolates in many countries with high vaccination coverage.

Here, we summarize these findings and discuss the factors contributing to pertussis resurgence in immunized populations.

Total cholesterol and the risk of Parkinson disease

Hu, G., Antikainen, R., Jousilahti, P., Kivipelto, M. and Tuomilehto, J.

Neurology. 2008; 70(21): 1972-1979. Article. IF 6.014

Objective: To examine the association between serum total cholesterol at baseline and the risk of Parkinson disease (PD).

Methods: Study cohorts included 24,773 Finnish men and 26,153 women aged 25 to 74 years without a history of PD and stroke at baseline. Hazard ratios (HRs) of incident PD were estimated for different levels of total cholesterol.

Results: During a mean follow-up period of 18.1 years, 321 men and 304 women developed incident PD. After adjustment for confounding factors (age, study years, body mass index, systolic blood pressure, education, leisure-time physical activity, smoking, alcohol consumption, coffee and tea consumption, and history of diabetes), the HRs of PD at different levels of total cholesterol (< 5, 5-5.9, 6-6.9, and >= 7 mmol/L) were 1.00, 1.33, 1.53, and 1.84 ( p for trend = 0.035) in men; 1.00, 1.55, 1.57, and 1.86 (p for trend = 0.113) in women; and 1.00, 1.42, 1.56, and 1.86 (p for trend = 0.002) in men and women combined (adjusted also for sex). In both sexes combined, the increased risk of PD associated with increasing levels of serum total cholesterol was present both in subjects aged 25 - 44 years and in subjects aged 45 - 54 years at baseline, and in never smokers and smokers; however, no association was found among subjects aged 55 years or older at baseline.

Conclusion: This large prospective study suggests that high total cholesterol at baseline is associated with an increased risk of Parkinson disease.

Effects of solubility of urban air fine and coarse particles on cytotoxic and inflammatory responses in RAW 264.7 macrophage cell line

Jalava, P. I., Salonen, R. O., Pennanen, A. S., Happo, M. S., Penttinen, P., Halinen, A. I., Sillanpaa, M., Hillamo, R. and Hirvonen, M. R.

Toxicology and Applied Pharmacology. 2008; 229(2): 146-160. Article. IF 3.846

We investigated the inflammatory and cytotoxic activities of the water-soluble and -insoluble as well as organic-solvent-soluble and -insoluble fractions of urban air fine (PM2.5-0.2) and coarse (PM10-2.5) particulate samples. The samples were collected with a high volume cascade impactor (HVCI) in 7-week sampling campaigns of selected seasons in six European cities. Mouse macrophage cells (RAW 264.7) were exposed to the samples for 24 h. The production of nitric oxide (NO) and proinflammatory cytokines (TNF alpha, IL-6), and cytotoxicity (MTT-test, apoptosis, cell cycle) were measured. The inflammatory and cytotoxic responses in both size ranges were mostly associated with the insoluble particulate fractions. However, both the water- and organic-solvent-soluble particulate fractions induced TNF alpha production and apoptosis and had some other cytotoxic effects. Soil-derived water-soluble and -insoluble components of the chemical PM2.5-0.2 mass closure had consistent positive correlations with the responses, while the correlations were negative with the secondary inorganic anions (NO3-, NH4+, non-sea-salt SO42-) and particulate organic matter (POM). With the PM10-2.5 samples, sea salt and soluble soil components correlated positively with the induced toxic responses. In this size range, a possible underestimation of the insoluble, soil-related compounds containing Si and Ca, and biological components of POM, increased uncertainties in the evaluation of associations of the mass closure components with the responses.

It is concluded that insoluble components of the complex urban air particulate mixture exert the highest inflammatory and cytotoxic activities in the macrophage cell line but, at the same time, they may operate as carriers for active water- and lipid-soluble components. (C) 2008 Elsevier Inc. All rights reserved.

Young adults with very low birth weight: leaving the parental home and sexual relationships--Helsinki Study of Very Low Birth Weight Adults

Kajantie, E., Hovi, P., Raikkonen, K., Pesonen, A. K., Heinonen, K., Jarvenpaa, A. L., Eriksson, J. G., Strang-Karlsson, S. and Andersson, S.

Pediatrics. 2008; 122(1): e62-72. IF 4.473

OBJECTIVE: Although most children and adults who are born very preterm live healthy lives, they have, on average, lower cognitive scores, more internalizing behaviors, and deficits in social skills. This could well affect their transition to adulthood. We studied the tempo of first leaving the parental home and starting cohabitation with an intimate partner and sexual experience of young adults with very low birth weight (<1500 g).

METHODS: In conjunction with the Helsinki Study of Very Low Birth Weight Adults, 162 very low birth weight individuals and 188 individuals who were born at term (mean age: 22.3 years [range: 18.5-27.1]) and did not have any major disability filled out a questionnaire. For analysis of their ages at events which had not occurred in all subjects, we used survival analysis (Cox regression), adjusted for gender, current height, parents' ages at the birth, maternal smoking during pregnancy, parental educational attainment, number of siblings, and parental divorce/death.

RESULTS: During their late teens and early adulthood, these very low birth weight adults were less likely to leave the parental home and to start cohabiting with an intimate partner. In gender-stratified analyses, these hazard ratios were similar between genders, but the latter was statistically significant for women only. These very low birth weight adults were also less likely to experience sexual intercourse. This relationship was statistically significant for women but not for men; however, very low birth weight women and men both reported a smaller lifetime number of sex partners than did control subjects.

CONCLUSIONS: Healthy young adults with very low birth weight show a delay in leaving the parental home and starting sexual activity and partnerships.

The INDEX project: executive summary of a European Union project on indoor air pollutants

Koistinen, K., Kotzias, D., Kephalopoulos, S., Schlitt, C., Carrer, P., Jantunen, M., Kirchner, S., McLaughlin, J., Molhave, L., Fernandes, E. O. and Seifert, B.

Allergy. 2008; 63(7): 810-819. Article. IF 5.014

The prevalence of allergies, asthma and other respiratory diseases in large populations has increased in recent decades. Among other factors, this phenomenon has been connected to adverse health effects of air pollution. Although some causal links between occupational exposures and their health effects are shown, still little is known about the health risks of lifelong exposure to indoor air pollutants. To assess the health risks of indoor air pollutants at prevailing concentration levels in Europe, the Joint Research Centre of the European Commission carried out a project called "Critical Appraisal of the Setting and Implementation of Indoor Exposure Limits in the EU" (INDEX). The aims of the project were: (1) to assess health risks of indoor-originated chemical pollutants that might be regulated in the EU and (2) to provide suggestions and recommendations on potential exposure limits or other risk management measures.

The results of the INDEX project should contribute to the development of an EU strategy for the management of indoor air quality. The highest priority was given in this study to: formaldehyde, nitrogen dioxide, carbon monoxide, benzene and naphthalene. Exposure limits, recommendations and management options were also given to minimize the health risks for these compounds.

Sub-chronic nandrolone treatment modifies neurochemical and behavioral effects of amphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in rats

Kurling, S., Kankaanpaa, A. and Seppala, T.

Behav Brain Res. 2008; 189(1): 191-201. IF 2.626

Misuse of anabolic-androgenic steroids (AASs) is increasing, and appears to have much in common with the use of substances known to induce drug dependence. Moreover, persons who abuse AASs also tend to abuse other psychotropic drugs such as amphetamine or 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). The aim of this study was to investigate whether nandrolone (5 x 5 or 5 x 20 mg/kg) pre-exposure modulates the acute neurochemical and behavioral effects of amphetamine (1mg/kg) and MDMA (5 mg/kg) in rats. Dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites were measured from samples collected from the nucleus accumbens (NAc) by in vivo microdialysis. The behavior of the animals was recorded on videotapes, from which it was later rated. Our results demonstrate that sub-chronic treatments with supraphysiological doses of nandrolone attenuate dose-dependently the increase in extracellular DA concentration evoked by amphetamine or MDMA. The lower dose of nandrolone attenuated MDMA-induced increase in 5-HT-levels, while the higher dose potentiated it. Analysis of the behavioral data suggests that effects of the amphetamine and MDMA are dose-dependently attenuated by AAS-treatment, paralleling DA results.

In conclusion, the results of this study show that AAS-pre-treatment is able to modulate the reward-related neurochemical and behavioral effects of amphetamine and MDMA.

Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background

Loukola, A., Broms, U., Maunu, H., Widen, E., Heikkila, K., Siivola, M., Salo, A., Pergadia, M. L., Nyman, E., Sammalisto, S., Perola, M., Agrawal, A., Heath, A. C., Martin, N. G., Madden, P. A., Peltonen, L. and Kaprio, J.

Pharmacogenomics J. 2008; 8(3): 209-19. IF 4.968

The significant worldwide health burden introduced by tobacco smoking highlights the importance of studying the genetic determinants of smoking behavior and the key factor sustaining compulsive smoking, that is, nicotine dependence (ND).

We have here addressed the genetic background of smoking in a special study sample of twins, harmonized for early life events and specifically ascertained for smoking from the nationwide twin cohort of the genetically unique population of Finland. The twins and their families were carefully examined for extensive phenotype profiles and a genome-wide scan was performed to identify loci behind the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505 individuals from 153 families. We replicated previous linkage findings on 10q (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for ND also showed evidence for linkage for the comorbid phenotype.

Our study provides confirmatory evidence for the involvement of these genome regions in the genetic etiology of smoking behavior and ND and for the first time associates drinking and smoking to a shared locus on 10q.

The long-term trend of obesity in Finnish adults

Mannisto, S., Vartiainen, E., Lahti-Koski, M., Peltonen, M. and Jousilahti, P.

International Journal of Obesity. 2008; 32: S212-S212. Meeting Abstract. IF 3.560

Alexithymia and Somatization in General Population

Mattila, A. K., Kronholm, E., Jula, A., Salminen, J. K., Koivisto, A. M., Mielonen, R. L. and Joukamaa, M.

Psychosom Med. 2008. IF 3.109

Objective: Even though the association between alexithymia and somatization seems plausible according to several studies with selected populations, it has not been verified in carefully controlled and nationally representative population studies. We conducted such a study to find out whether alexithymia is associated with somatization at population level.

Methods: This study was a part of the Finnish Health 2000 Study. The nationally representative sample comprised 5129 subjects aged 30 to 97 years. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20) and somatic symptom reporting with the 12-item somatization scale derived from the Hopkins Symptom Checklist. Sociodemographic and health-related variables, including depressive and anxiety disorders, and physician verified somatic diagnoses, were treated as confounders in multivariate analyses.

Results: Alexithymia was associated with somatization independently of somatic diseases, depression and anxiety and confounding sociodemographic variables. The TAS-20 factor scale "Difficulties Identifying Feelings" was the strongest common denominator between alexithymia and somatization.

Conclusions: This was the first time the independent association between alexithymia and somatization was established in a large, nationally representative nonclinical sample of both young and old adults with and without mental disorders and somatic diseases.

Eating behavior in obesity - A study in monozygotic and dizygotic twins

Pietilainen, K. H., Korkeila, M., Yki-Jarvinen, H., Kaprio, J. and Rissanen, A.

International Journal of Obesity. 2008; 32: S203-S203. Meeting Abstract. IF 3.560

Labelling the salt content in foods: a useful tool in reducing sodium intake in Finland

Pietinen, P., Valsta, L. M., Hirvonen, T. and Sinkko, H.

Public Health Nutr. 2008; 11(4): 335-40. IF 1.858

OBJECTIVE: To estimate the impact of choosing food products labelled either as low or high in salt on salt intake in the Finnish adult population.

SETTING AND SUBJECTS: The National FINDIET 2002 survey with 48-hour recalls from 2007 subjects aged 25-64 years. Sodium intake was calculated based on the Fineli food composition database including the sodium content of natural and processed foods as well as the salt content of recipes. The distribution of salt intake was calculated in different ways: the present situation; assuming that all breads, cheeses, processed meat and fish, breakfast cereals and fat spreads consumed would be either 'lightly salted' or 'heavily salted' based on the current labelling practice; and, in addition, assuming that all foods would be prepared with 50% less or more salt.

RESULTS: Excluding underreporters, the mean salt intake would be reduced by 1.8 g in men and by 1.0 g in women if the entire population were to choose lightly salted products and further by 2.5 and 1.8 g, respectively, if also salt used in cooking were halved. Choosing heavily salted products would increase salt intake by 2.1 g in men and by 1.4 g in women. In the worst scenarios, salt intake would be further increased by 2.3 g in men and by 1.6 g in women.

CONCLUSIONS: These calculations show that the potential impact of labelling and giving consumers the possibility to choose products with less salt is of public health importance. In addition, strategies to reduce the salt content of all food groups are needed.

Critical immunological pathways are downregulated in APECED patient dendritic cells

Pöntynen, N., Strengell, M., Sillanpää, N., Saharinen, J., Ulmanen, I., Julkunen, I. and Peltonen, L.

J Mol Med. 2008. IF 4.820

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. AIRE functions as a transcriptional regulator, and it has a central role in the development of immunological tolerance. AIRE regulates the expression of ectopic antigens in epithelial cells of the thymic medulla and has been shown to participate in the development of peripheral tolerance. However, the mechanism of action of AIRE has remained elusive. To further investigate the role of AIRE in host immune functions, we studied the properties and transcript profiles in in vitro monocyte-differentiated dendritic cells (moDCs) obtained from APECED patients and healthy controls. AIRE-deficient monocytes showed typical DC morphology and expressed DC marker proteins cluster of differentiation 86 and human leukocyte antigen class II. APECED patient-derived moDCs were functionally impaired: the transcriptional response of cytokine genes to pathogens was drastically reduced. Interestingly, some changes were observable already at the immature DC stage. Pathway analyses of transcript profiles revealed that the expression of the components of the host cell signaling pathways involved in cell-cell signalling, innate immune responses, and cytokine activity were reduced in APECED moDCs.

Our observations support a role for AIRE in peripheral tolerance and are the first ones to show that AIRE has a critical role in DC responses to microbial stimuli in humans.

Lifetime anorexia nervosa in young men in the community: Five cases and their co-twins

Raevuori, A., Keski-Rahkonen, A., Hoek, H. W., Sihvola, E., Rissanen, A. and Kaprio, J.

International Journal of Eating Disorders. 2008; 41(5): 458-463. Article. IF 2.269

Objective: To describe patterns, comorbidity, and outcomes from a case series of anorexia nervosa (AN) among young men from the general population and their co-twins.

Method: Men (N = 2,122) born between 1975 and 1979 from Finnish twin cohorts were screened for lifetime eating disorders by questionnaire. The administration of the short version of the Structured Clinical Interview for DSM-IV for screen positives led to a lifetime AN diagnosis in five participants, described here with their co-twins.

Results: In males, overweight commonly predated AN, and symptoms of body dysmorphic disorder, particularly of muscle dysmorphia, were common among the anorexia-discordant co-twins. Affective and anxiety disorders were present in both the probands and their co-twins.

Conclusion: We found a strong familial clustering of AN, affective and anxiety disorders, and symptoms of muscle dysmorphia among men in the general population. In men, muscle dysmorphia may represent an alternative phenotype of AN. (C) 2008 by Wiley Periodicals, Inc.

Body composition in psychotic disorders - a general population survey

Saarni, S. E., Saarni, S. I., Fogelholm, M., Heliövaara, M., Perälä, J., Suvisaari, J. and Lönnqvist, J.

International Journal of Obesity. 2008; 32: S21-S21. Meeting Abstract. IF 3.560

Coronary Artery Disease-Associated Locus on Chromosome 9p21 and Early Markers of Atherosclerosis

Samani, N. J., Raitakari, O. T., Sipila, K., Tobin, M. D., Schunkert, H., Juonala, M., Braund, P. S., Erdmann, J., Viikari, J., Moilanen, L., Taittonen, L., Jula, A., Jokinen, E., Laitinen, T., Hutri-Kahonen, N., Nieminen, M. S., Kesaniemi, Y. A., Hall, A. S., Hulkkonen, J., Kahonen, M. and Lehtimaki, T.

Arterioscler Thromb Vasc Biol. 2008. IF 7.221

Background-Genome-wide association studies have recently identified a locus on chromosome 9p21 that influences risk of coronary artery disease (CAD). The effect of the locus on early markers of atherosclerosis is unknown. We examined its association with carotid intima-media thickness (CIMT) and brachial flow-mediated dilatation (FMD).

METHODS AND RESULTS: We genotyped 2277 individuals aged 24 to 39 years from the Cardiovascular Risk in Young Finns Study with CIMT and FMD measurements and 1295 individuals, aged 46 to 76 years from the Health 2000 Survey with CIMT for rs1333049, the chromosome 9p21 variant showing the strongest association with CAD. Both mean and maximum CIMT were significantly higher (P<0.001) in the older subjects of the Health 2000 Survey compared with the Young Finns Study. However, there was no association of the rs1333049 genotype with either mean or maximum CIMT at either age (P=0.959 and 0.977 for the 2 phenotypes in the Young Finns Study and P=0.714 and 0.725 in the Health 2000 Survey). Similarly, there was no association of the locus with variation in FMD in the Young Finns cohort (P=0.521).

CONCLUSIONS: The chromosome 9p21 locus does not influence CAD risk through a mechanism that also affects CIMT or induces early changes in FMD.

Effect of ageing and gender on naturally acquired antibodies to pneumococcal capsular polysaccharides and virulence-associated proteins

Simell, B., Lahdenkari, M., Reunanen, A., Käyhty, H. and Väkeväinen, M.

Clin Vaccine Immunol. 2008. IF 1.995

Aged individuals are susceptible to pneumococcal infections. Although factors contributing to the increased susceptibility of the elderly to bacterial infections may be several, compromised immune function, a consequence of normal human aging, is widely accepted to play a role. We evaluated the effect of ageing on the concentrations of naturally acquired antibodies to pneumococcal capsular polysaccharide (PPS) and protein antigens. The concentrations of IgG and IgM antibodies to PPSs of serotypes 3, 4, 6B, 9V, 14 and 23F, and IgG antibodies to pneumococcal virulence-associated proteins CbpA, LytC, PhtD and it's C-terminal fragment (PhtD C), NanA, PspA fam1 and PspA fam2 were measured by enzyme immunoassay in the sera of the younger (30 to 64 years of age) and elderly (65 to 97 years of age) adults. The concentrations of anti-PPS IgG against serotypes 3 and 6B, of anti-PPS IgM against serotypes 3, 4, 6B, 9V and 23F, and of anti-protein IgG against all tested antigens were significantly lower in the elderly compared to younger adults. Stronger decline in anti-PPS antibody concentrations was seen with age in women compared to men, while anti-protein antibody concentrations were mainly similar between the genders.

Age, gender and nature of the antigen have substantial and varying effects on the antibody concentrations in the sera of adults.

Obesity affects the regional distribution of bone density and mass - a monozygotic twin pair study

Sovijärvi, O., Kaprio, J., Rissanen, A., Yki-Järvinen, H. and Pietiläinen, K.

International Journal of Obesity. 2008; 32: S45-S45. Meeting Abstract. IF 3.560

Genetics of maximal walking speed and skeletal muscle characteristics in older women

Tiainen, K. M., Perola, M., Kovanen, V. M., Sipila, S., Tuononen, K. A., Rikalainen, K., Kauppinen, M. A., Widen, E. I. M., Kaprio, J., Rantanen, T. and Kujala, U. M.

Twin Research and Human Genetics. 2008; 11(3): 321-334. Article. IF 1.525

The aim of this study was to examine whether maximal walking speed, maximal isometric muscle strength, leg extensor power and lower leg muscle cross-sectional area (CSA) shared a genetic effect in common.

In addition, we wanted to identify the chromosomal areas linked to maximal walking speed and these muscle characteristics and also investigate whether maximal walking speed and these three skeletal muscle characteristics are regulated by the same chromosomal areas. We studied 217 monozygotic (MZ) and dizygotic (DZ) female twin pairs aged 66 to 75 years in the Finnish Twin Study on Aging study. The DZ pairs (94) were genotyped for 397 microsatellite markers in 22 autosomes and X-chromosome. Genetic modeling showed that, muscle CSA, strength, power and walking speed shared a genetic effect in common which accounted for 7% of the variation in CSA, 51% in strength, 37% in power and 35% in walking speed. The results of an explorative multipoint linkage analysis suggested that the highest LOD score found for each phenotype was 2.41 for walking speed on chromosome 13q22.1, 2.14 for strength on chromosome 15q14, 2.84 for power on chromosome 8q24.23, and 2.93 for muscle CSA on chromosome 20q13.31. Also a suggestive LOD score, 2.68, for muscle CSA was found on chromosome 9q34.3. The chromosomal areas of a suggestive linkage for strength and power partly overlapped LOD scores higher than 1.0 being seen for these phenotypes on chromosome 15.

The present study was the first genome-wide linkage analysis to be conducted for these multifactorial and clinically important phenotypes underlying functional independence in older women.

Use of mental health services and complementary and alternative medicine in persons with common mental disorders

Wahlström, M., Sihvo, S., Haukkala, A., Kiviruusu, O., Pirkola, S. and Isometsä, E.

Acta Psychiatrica Scandinavica. 2008; 118(1): 73-80. Article. IF 3.782

Objective: Few studies investigated the use of complementary and alternative medicine (CAM) by subjects with mental disorders. We examined the relationship between depressive, anxiety and alcohol-use disorders and their comorbidity, as well as the relationship between use of CAM and use of mental health services.

Method: The Finnish adult (>= 30 years) population-based Health 2000 Study (n = 5987) collected information on use of CAM plus health and mental health care services.

Results: Generalised anxiety disorder and panic disorder were positively associated and alcohol abuse was negatively associated with use of CAM. The prevalence was highest in persons with comorbidity of anxiety and depressive disorders. The use or perceived usefulness of mental health services did not differ between CAM users and other participants.

Conclusion: The relationship between the use of CAM and mental disorders appears to vary depending on the type of mental disorder. Use of CAM seems unrelated to the use and the perceived usefulness of mental health services.

Nucleotide- and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade

Yegutkin, G. G.

Biochim Biophys Acta. 2008; 1783(5): 673-94. IF 4.374

The involvement of extracellular nucleotides and adenosine in an array of cell-specific responses has long been known and appreciated, but the integrative view of purinergic signalling as a multistep coordinated cascade has emerged recently. Current models of nucleotide turnover include: (i) transient release of nanomolar concentrations of ATP and ADP; (ii) triggering of signalling events via a series of ligand-gated (P2X) and metabotropic (P2Y) receptors; (iii) nucleotide breakdown by membrane-bound and soluble nucleotidases, including the enzymes of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family, ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP) family, ecto-5'-nucleotidase/CD73, and alkaline phosphatases; (iv) interaction of the resulting adenosine with own nucleoside-selective receptors; and finally, (v) extracellular adenosine inactivation via adenosine deaminase and purine nucleoside phosphorylase reactions and/or nucleoside uptake by the cells. In contrast to traditional paradigms that focus on purine-inactivating mechanisms, it has now become clear that "classical" intracellular ATP-regenerating enzymes, adenylate kinase, nucleoside diphosphate (NDP) kinase and ATP synthase can also be co-expressed on the cell surface. Furthermore, data on the ability of various cells to retain micromolar ATP levels in their pericellular space, as well as to release other related compounds (adenosine, UTP, dinucleotide polyphosphates and nucleotide sugars) gain another important insight into our understanding of mechanisms regulating a signalling cascade.

This review summarizes recent advances in this rapidly evolving field, with particular emphasis on the nucleotide-releasing and purine-converting pathways in the vasculature.

Body mass index during childhood and adult body composition in men and women aged 56-70 y

Yliharsila, H., Kajantie, E., Osmond, C., Forsen, T., Barker, D. J. P. and Eriksson, J. G.

American Journal of Clinical Nutrition. 2008; 87(6): 1769-1775. Article. IF 6.603

Background: The relation between the change in body mass index (BMI) through childhood and body composition in adult life is important because body composition is known to affect adult health.

Objective: The objective was to examine how the change in BMI throughout childhood is related to adult lean and fat mass.

Design: We examined how the change in BMI in childhood was related to adult body composition in 885 men and 1032 women born during 1934-1944, whose weights and heights during childhood were recorded serially. Adult lean and fat mass were measured by bioelectrical impedance with an 8-polar tactile electrode system.

Results: In these 56-70-y-old men and women, adult lean body mass index (lean mass/height(2); in kg/m(2)) was positively associated with BMI at birth (0.24 and 0.20 higher for each 1-SD increase in BMI at birth, respectively) and with more rapid gain in BMI from birth to 1 y (0. 17 and 0.22), 1-2 y (0.21 and 0.20), 2-7 y (0.44 and 0.46), and 7-11 y (0.32 and 0.26) of age. Fat mass index (fat mass/ height(2)) was positively associated with more rapid increases in BMI between 2 and 11 y of age.

Conclusions: Rapid gain in BMI before the age of 2 y increased adult lean body mass without excess fat accumulation, whereas rapid gain in BMI in later childhood, despite the concurrent rise in lean mass, resulted in relatively larger increases in fat mass.