| New articles - Uudet artikkelit
23.10.2006 - ISI Web of Knowledge & PubMed Search Alert |
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Applying health psychology theories and models in disease
prevention: Two examples
Absetz, P., Valve, R. and Heinonen, H. Psychology & Health. 2006; 21: 9-10. Meeting Abstract. IF 1.796 A role for beta-arrestin 2 in mediating the rewarding properties of ethanol Bjork, K., Sommer, W. H., Rimondini, R., Hansson, A. C., Hyytia, P., Lefkowitz, R. J. and Heilig, M. Alcoholism-Clinical and Experimental Research. 2006; 30(6): 134A-134A. Meeting Abstract. IF 2.636 Genes and schizophrenia: beyond schizophrenia: the role of DISC1 in major mental illness Hennah, W., Thomson, P., Peltonen, L. and Porteous, D. Schizophr Bull. 2006; 32(3): 409-16. IF 2.871 Schizophrenia and related disorders have a major genetic component, but despite much effort and many claims, few genes have been consistently replicated and fewer have biological support. One recent exception is "Disrupted in Schizophrenia 1" (DISC1), which was identified at the breakpoint on chromosome 1 of the balanced translocation (1;11)(q42.1;q14.3) that co-segregated in a large Scottish family with a wide spectrum of major mental illnesses. Since then, genetic analysis has implicated DISC1 in schizophrenia, schizoaffective disorder, bipolar affective disorder, and major depression. Importantly, evidence is emerging from genetic studies for a causal relationship between DISC1 and directly measurable trait variables such as working memory, cognitive aging, and decreased gray matter volume in the prefrontal cortex, abnormalities in hippocampal structure and function, and reduction in the amplitude of the P300 event-related potential. Further, DISC1 binds a number of proteins known to be involved in essential processes of neuronal function, including neuronal migration, neurite outgrowth, cytoskeletal modulation, and signal transduction. Thus, both genetic and functional data provide evidence for a critical role for DISC1 in schizophrenia and related disorders, supporting the neurodevelopmental hypothesis for the molecular pathogenesis of these devastating illnesses. Brain dopamine D-1 receptors in twins discordant for schizophrenia Hirvonen, J., van Erp, T. G. M., Huttunen, J., Aalto, S., Nagren, K., Huttunen, M., Lönnqvist, J., Kaprio, J., Cannon, T. D. and Hietala, J. American Journal of Psychiatry. 2006; 163(10): 1747-1753. Article. IF 8.286 Objective: It has been suggested that deficits in higher-order cognitive functions serve as intermediate phenotypic indicators of genetic vulnerability to schizophrenia. The dopamine hypothesis of schizophrenia postulates that insufficiency of dopamine transmission in the prefrontal cortex contributes to the cognitive deficits observed in patients with the disease, and there is robust empirical evidence for a central role of prefrontal cortex dopamine D-1 receptors in working memory functions. Method: The authors examined the genetic and nongenetic effects on D1 receptor binding in schizophrenia by studying monozygotic and dizygotic twin pairs discordant for schizophrenia as well as healthy comparison twins using positron emission tomography ( PET) and the D-1 receptor antagonist ligand [C-11]SCH 23390. Performance on neuropsychological tests sensitive to frontal lobe functioning was evaluated. Results: High D-1 receptor density in the medial prefrontal cortex, superior temporal gyrus, and heteromodal association cortex (angular gyrus) was associated with increasing genetic risk for schizophrenia (comparison twins < unaffected dizygotic co-twins < unaffected monozygotic co-twins). Medicated schizophrenia patients demonstrated a widespread reduction in D-1 receptor binding when compared with the unaffected co-twin, and higher doses of antipsychotics were associated with lower D-1 receptor binding in the frontotemporal regions. Conclusions: This study demonstrated an association between genetic risk for schizophrenia and alterations in cortical D-1 receptor binding, an observation that has implications for future studies of the molecular genetics of schizophrenia. In addition, the data indicate a widespread reduction of D-1 receptor binding in medicated schizophrenia patients, supporting a link between antipsychotic drug action and dopamine D-1 receptor down-regulation. Huth, C., Heid, I. M., Vollmert, C., Gieger, C., Grallert, H., Wolford, J. K., Langer, B., Thorand, B., Klopp, N., Hamid, Y. H., Pedersen, O., Hansen, T., Lyssenko, V., Groop, L., Meisinger, C., Doring, A., Lowel, H., Lieb, W., Hengstenberg, C., Rathmann, W., Martin, S., Stephens, J. W., Ireland, H., Mather, H., Miller, G. J., Stringham, H. M., Boehnke, M., Tuomilehto, J., Boeing, H., Mohlig, M., Spranger, J., Pfeiffer, A., Wernstedt, I., Niklason, A., Lopez-Bermejo, A., Fernandez-Real, J. M., Hanson, R. L., Gallart, L., Vendrell, J., Tsiavou, A., Hatziagelaki, E., Humphries, S. E., Wichmann, H. E., Herder, C. and Illig, T. Diabetes. 2006; 55(10): 2915-2921. Article. IF 8.028 Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G > C (rs1800795) and -573G > C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on > 20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G > C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 -573G > C and type 2 diabetes. The observed association of the IL6 -174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding. From genes to systems: New global strategies for the characterization of NCL biology Jalanko, A., Tyynelä, J. and Peltonen, L. Biochim Biophys Acta. 2006. IF 2.506 Neuronal ceroid lipofuscinoses (NCL) are rare neurological disorders with a uniform phenotype, caused by mutations in seven known genes. NCL provide a unique model to characterize molecular pathways critical for normal neuronal development and pathological neuronal degeneration. Systems biology based approach utilizes the rapidly developing tools of genomics, proteomics, lipidomics and metabolomics and aims at thorough understanding of the functions of cells, tissues and whole organisms by molecular analysis and biocomputing-assisted modeling. The systems level understanding of NCL is now possible by utilizing different model organisms. Initial work has revealed disturbed metabolic pathways in several NCL disorders and most analyses have utilized the infantile (INCL/CLN1) and juvenile (JNCL/CLN3) disease modeling and utilized mainly human and mouse samples. To date, the data obtained from transcript and lipidomic profiling has pinpointed the role of lipid metabolism and synaptic function in the infantile NCL. Changes in glutamate utilization and amino acid metabolism have been a common theme emerging from the transcript and metabolite profiling of the juvenile NCL. Further experimental models are being developed and systematic sample collection as well as data integration projects are needed. The combined analyses of the global information should provide means to expose all the NCL-associated molecular pathways. Jalava, K., Häkkinen, M., Valkonen, M., Nakari, U. M., Palo, T., Hallanvuo, S., Ollgren, J., Siitonen, A. and Nuorti, J. P. J Infect Dis. 2006; 194(9): 1209-16. IF 4.953 Background. Outbreaks of Yersinia pseudotuberculosis infection have been epidemiologically linked to fresh produce, but the bacterium has not been recovered from the food items implicated. In May 2003, a cluster of gastrointestinal illness and erythema nodosum was detected among schoolchildren who had eaten lunches prepared by the same institutional kitchen. Methods. We conducted a case-control study and trace-back, environmental, and laboratory investigations. Case patients had culture-confirmed Y. pseudotuberculosis O:1 infection, erythema nodosum, or reactive arthritis. Bacterial isolates from clinical and environmental samples were compared using pulsed-field gel electrophoresis (PFGE).Results. Of 7392 persons at risk, 111 (1.5%) met the case definition; 76 case patients and 172 healthy control subjects were enrolled in the case-control study. Only raw grated carrots were significantly associated with illness in a logistic-regression model (multivariable odds ratio, 5.7 [95% confidence interval, 1.7-19.5]); a dose response was found for increasing amount of consumption. Y. pseudotuberculosis O:1 isolates from 39 stool specimens and from 5 (42%) of 12 soil samples that contained carrot residue and were obtained from peeling and washing equipment at the production farm were indistinguishable by PFGE. Conclusions. Carrots contaminated early in the production process caused a large point-source outbreak. Our findings enable the development of evidence-based strategies to prevent outbreaks of this emerging foodborne pathogen. Differences in the clinical characteristics of adolescent depressive disorders Karlsson, L., Pelkonen, M., Heila, H., Holi, M., Kiviruusu, O., Tuisku, V., Ruuttu, T. and Marttunen, M. Depress Anxiety. 2006. IF 1.975 Our objective was to analyze differences in clinical characteristics and comorbidity between different types of adolescent depressive disorders. A sample of 218 consecutive adolescent (ages 13-19 years) psychiatric outpatients with depressive disorders was interviewed for DSM-IV Axis I and Axis II diagnoses. We obtained data by interviewing the adolescents themselves and collecting additional background information from the clinical records. Lifetime age of onset for depression, current episode duration, frequency of suicidal behavior, psychosocial impairment, and the number of current comorbid psychiatric disorders varied between adolescent depressive disorder categories. The type of co-occurring disorder was mainly consistent across depressive disorders. Minor depression and dysthymia (DY) presented as milder depressions, whereas bipolar depression (BPD) and double depression [DD; i.e., DY with superimposed major depressive disorder (MDD)] appeared as especially severe conditions. Only earlier lifetime onset distinguished recurrent MDD from first-episode MDD, and newly emergent MDD appeared to be as impairing as recurrent MDD. Adolescent depressive disorder categories differ in many clinically relevant aspects, with most differences reflecting a continuum of depression severity. Identification of bipolarity and the subgroup with DD seems especially warranted. First episode MDD should be considered as severe a disorder as recurring MDD. Depression and Anxiety 0:1-12, 2006. (c) 2006 Wiley-Liss, Inc. Genome-wide scan for autism spectrum disorders in an extended pedigree from Finland Kilpinen, L. H., Ylisaukko-oja, T., Turunen, J. A., Alen, R., Vanhala, R., von Wendt, L., Varilo, T. and Peltonen, L. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2006; 141B(7): 703-703. Meeting Abstract. IF 3.521 Does parity affect mortality among parous women? Koski-Rahikkala, H., Pouta, A., Pietiläinen, K. and Hartikainen, A. L. J Epidemiol Community Health. 2006; 60(11): 968-73. IF 3.003 OBJECTIVE: To find out whether there is an association between parity and mortality. DESIGN: Prospective cohort study. SETTING: Northern Finland, 1966-2001. Participants and METHODS: 12 055 women in the two northernmost provinces of Finland were followed up from pregnancy in 1966-2001, the coverage percentage being 96%. The data on age, smoking, body mass index, socioeconomic position, age at menarche and age at first birth were collected during pregnancy, and data on deaths were obtained from the National Cause of Death Statistics, maintained by Statistics Finland. The Cox proportional hazard model was used to estimate relative mortality between parity groups. RESULTS: Total mortality was lowest among the women with 2-4 children (reference group). High parity was associated with an up to twofold risk of mortality from vascular complications, but after adjustment for all background factors, this significance disappeared. Mortality from haemorrhagic stroke was fourfold higher among the women with >/=10 births compared with those of the reference group. No differences in cerebral infarction or total cancer mortality were seen between the groups. Primiparity was associated with increased mortality from accidental death (relative risk 2.6, 95% confidence interval 1.6 to 4.4). CONCLUSIONS: High parity was associated with an increased risk of mortality from vascular complications, especially haemorrhagic stroke, and primiparity with an increased risk of accidental death. Lahti, T. A., Leppämäki, S., Lönnqvist, J. and Partonen, T. Neuroscience Letters. 2006; 406(3): 174-177. Article. IF 1.898 Daylight saving time (DST) is widely adopted. We explored the effects of transition to daylight saving time on sleep. With the use of wrist-worn accelerometers, we monitored the rest-activity cycles on a sample of 10 healthy adults for 10 days around the transition to summer time. Identical measurement protocols were carried out twice on the same individuals during the transitions in the years of 2003 and 2004, yielding data on 200 person-days for analysis. Both sleep duration and sleep efficiency were reduced after the transition both years. After the transition sleep time was shortened by 60.14 min (P < 0.01) and sleep efficiency was reduced by 10% (P < 0.01) on average. Transition to daylight saving time appears to compromise the process of sleep by decreasing both sleep duration and sleep efficiency. (c) 2006 Elsevier Ireland Ltd. All rights reserved. Mager, U., Kolehmainen, M., Lindström, J., Eriksson, J. G., Valle, T. T., Hämäläinen, H., Ilanne-Parikka, P., Keinanen-Kiukaanniemi, S., Tuomilehto, J. O., Pulkkinen, L. and Uusitupa, M. I. American Journal of Hypertension. 2006; 19(9): 920-926. Article. IF 3.496 Background: Ghrelin is a gut-brain hormone, which stimulates food intake and controls energy balance. Recently, it has been shown that ghrelin may also play a role in the regulation of blood pressure (BP) by acting at the sympathetic nervous system. In the present study we genotyped six variants of the ghrelin gene and its promoter, and tested whether these single nucleotide polymorphisms (SNPs) were associated with BP levels in participants of the Finnish Diabetes Prevention Study. Methods: The Finnish Diabetes Prevention Study was a longitudinal study where 522 subjects with impaired glucose tolerance were randomized into either an intervention or control group. DNA was available from 507 subjects (mean body mass index [BMI] 31.2 +/- 4.5 kg/m(2), age 55 +/- 7 years). All six SNPs were screened by the restriction fragment length polymorphism method. Results: Subjects with the most common genotype combination of the following four SNPs, -604G/A, -501A/C, Leu72Met, and G1n90Leu, had the lowest systolic (131 +/- 11 v 137 +/- 13 mm Hg, P = .003) and diastolic BP levels (79 7 v 83 +/- 7 mm Hg, P = .004) at the baseline of the study and during 3 years of follow-up compared to all other genotypes. Adjustments for age, gender, antihypertensive medication, BMI, waist circumference, and alcohol intake did not change this association. Conclusions: Several ghrelin gene variations were associated with BP levels in subjects with impaired glucose tolerance. Vascular amine oxidases are needed for leukocyte extravasation into inflamed joints in vivo Marttila-Ichihara, F., Smith, D. J., Stolen, C., Yegutkin, G. G., Elima, K., Mercier, N., Kiviranta, R., Pihlavisto, M., Alaranta, S., Pentikainen, U., Pentikainen, O., Fulop, F., Jalkanen, S. and Salmi, M. Arthritis and Rheumatism. 2006; 54(9): 2852-2862. Article. IF 7.421 Objective. Leukocyte traffic from the blood to the joints is crucial in the pathogenesis of arthritis. A bifunctional endothelial cell-surface glycoprotein, AOC3 (amine oxidase, copper-containing 3; also known as vascular adhesion protein 1), has both adhesive and enzymatic properties. We undertook this study to determine the contribution of AOC3 and its oxidase activity to leukocyte trafficking into inflamed joints in vivo. Methods. We used gene-modified animals, molecular modeling, an AOC3 enzyme inhibitor, oxidase assays, and arthritis models (adjuvant-induced arthritis [AIA] in rats and anti-type II collagen antibody-induced arthritis in mice) to dissect the importance of AOC3 in vivo. Results. The AOC3 inhibitor fitted well with a covalent binding mode into the active site of the AOC3 crystal structure. It selectively blocked the oxidase activity of AOC3 in enzyme assays. Intraperitoneal and oral administration of the AOC3 inhibitor significantly ameliorated rat AIA. In anti-type II collagen antibody- induced arthritis in mice, the AOC3 inhibitor also improved the outcome of the joint inflammation. The acute semicarbazide-sensitive amine oxidase blockade by the inhibitor had even more pronounced effects than genetic deletion of AOC3. Enzymatic analyses showed that the inhibitor also blocked 2 other structurally very closely related AOCs, but not any of more than 100 other enzymes tested. Conclusion. These are the first data to demonstrate that the enzymatic activity of the atypical endothelial adhesion molecule AOC3, and possibly that of other closely related ecto-oxidases, is crucial for leukocyte exit from the vessels in inflamed joints in vivo. Muller, H. P., Barrieshi-Nusair, K. M., Kononen, E. and Yang, M. Journal of Clinical Periodontology. 2006; 33(11): 811-818. Article. IF 2.225 Aim: To study longitudinal associations between plaque and gingival bleeding and multilevel variance/covariance structures after introducing triclosan-containing toothpaste. Material and Methods: A 10-week, randomized, two-arm, double-masked, controlled clinical trial was conducted in 34 healthy, non-smoking females with plaque-induced gingivitis. Clinical periodontal examinations were repeated every other week. At week 4, test toothpaste containing 0.24% sodium monofluorophosphate, 0.3% triclosan, and 2% polyvinyl-methyl ether maleic acid; or control toothpaste containing 0.76% sodium monofluorophosphate and 0.1% sodium fluoride, were randomly distributed. Results: Multivariate multilevel models indicated that, after introducing experimental toothpastes, subject random error was reduced from 0.6 to below 0.2. The odds ratio (OR) of bleeding on probing (BOP) was about 30% less in the test than in the control group (p < 0.01). At the end of the experiment, ORs for BOP and plaque index scores 1-3 (reference 0) were 2.1-2.4 in the control group, but 1.1-1.9 in the test group (p < 0.05). No effects on plaque levels and calculus were observed. Conclusions: Multivariate multilevel modelling allows the study of fixed and random effects of experimental toothpastes on gingival inflammation in small sample. Triclosan appears to attenuate the causal association between supragingival plaque and gingival bleeding in gingivitis. Nyman, E. S., Loukola, A., Varilo, T., Joukamaa, M., Moilanen, I., McGough, J., Järvelin, M. R., Smalley, S. and Peltonen, L. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2006; 141B(7): 759-760. Meeting Abstract. IF 3.521 Intestinal cytokine mRNA expression in delayed-type cow's milk allergy Paajanen, L., Kokkonen, J., Karttunen, T. J., Tuure, T., Korpela, R. and Vaarala, O. Journal of Pediatric Gastroenterology and Nutrition. 2006; 43(4): 470-476. Article. IF 2.077 Objectives: The aim of the study was to investigate the characteristics of intestinal immune activation (ie, a chemokine receptor and cytokine expression profile) in delayed-type cow's milk allergy (CMA) appearing in the form of gastrointestinal symptoms. Patients and Methods: In all biopsy samples taken from the duodenum and/or the terminal ileum, 30 were studied for the expression of interferon-gamma, transforming growth factor-beta, chemokine receptor (CCR)-4, CCR-5, IL-2, IL-6, IL-10, 1L-12p35, IL-12p40 and IL-18 specific mRNA by real-time quantitative reverse transcriptase-polymerase chain reaction in 26 children ages 3 to 15 years: 10 with untreated delayed-type CMA, 6 with celiac disease (CD) and 10 controls. Results: The children with delayed-type CMA showed lower IL-2 and IL-18 mRNA expression in the duodenum (both P = 0.055) and higher CCR-4 and IL-6 mRNA expression in the terminal ileum (P = 0.055, P = 0.016) compared with the controls. The children with CD exhibited slightly higher expression of interferon-gamma and CCR-4 mRNA (P 0.054, P = 0.053) and lower expression of IL-18 mRNA (P 0.004) in the duodenal samples compared with the controls. The mRNA expression levels of regulatory cytokines, transforming growth factor-beta and IL-10 remained similar in all 3 groups. Conclusions: The children with delayed-type gastrointestinal CMA showed a unique pattern of local intestinal hypersensitivity with Th2 response-related characteristics, a profile differing clearly from the children with CD. Pakkasjärvi, N., Ritvanen, A., Herva, R., Peltonen, L., Kestilä, M. and Ignatius, J. Am J Med Genet A. 2006; 140(17): 1834-9. IF 1.913 Arthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987-2002 including live born infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty-nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland. Haplotype association studies of the DISC1 gene in Finnish bipolar families Palo, O. M., Hennah, W., Kilpinen, H., Silander, K., Soronen, P., Antila, M., Tuulio-Henriksson, A., Kieseppa, T., Partonen, T., Lönnqvist, J., Peltonen, L. and Paunio, T. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2006; 141B(7): 696-696. Meeting Abstract. IF 3.521 Alleles of reelin gene show association with working memory in Finnish schizophrenia famillies Peltonen, J. O., Tuulio-Henriksson, A., Loukola, A., Ekelund, J., Paunio, T., Hennah, W., Varilo, T., Suvisaari, J., Partonen, T., Lönnqvist, J. and Peltonen, L. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2006; 141B(7): 705-705. Meeting Abstract. IF 3.521 Identification of complex disease genes in a genetic isolate: Example of Finland Peltonen, L. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2006; 141B(7): 691-691. Meeting Abstract. IF 3.521 Pesonen, S. A., Haavisto, T. E., Viluksela, M., Toppari, J. and Paranko, J. Reproductive Toxicology. 2006; 22(3): 521-528. Article. IF 1.636 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental pollutant and causes adverse effects on female reproduction when administered to rats. Our aims were to study effects of gestational and lactational exposure to TCDD on ovarian steroidogenesis and steroidogenic enzyme expression of offspring on postnatal day (PND) 14 in the rat and sensitivity of enzymatically isolated ovarian follicles to TCDD in vitro. Synthetic estrogen diethylstilbestrol (DES) was used as a treatment control. Serum progesterone (N) level in offspring increased significantly on PND 14 in the TCDD (1 mu g/kg)-exposed group while body weight, FSH and E2 levels were not changed. In ovarian follicles of offspring on PND 14 in the TCDD-exposed groups, protein expression of cytochrome P-450 aromatase, cytochrome P-450 cholesterol side-chain cleavage, steroidogenic acute regulatory protein, 3 beta-hydroxy-steroid-dehydrogenase/Delta(5)-Delta(4) isomerase type 1, or P4 receptor was not affected. TCDD decreased E2 and P4 production in ex vivo follicle culture. DES at a dose level of 0.1 mg/kg was dystocic while a dose 0.02 mg/kg increased ovarian ex vivo E2 and testosterone production without affecting P450arom activity indicating stimulation of early steps of steroidogenic pathway. Data suggests that TCDD has multiple targets in ovarian steroidogenesis, but the inhibitory action represented as decreased follicular steroid hormone production ex vivo is not apparent at the ovarian protein expression. Furthermore, TCDD had no direct effect on immature rat ovarian steroidogenesis in vitro suggesting that the follicle culture method is not a sensitive method to study the mechanisms of TCDD action. (c) 2006 Elsevier Inc. All rights reserved. Pietiläinen, O., Paunio, T., Loukola, A., Tuulio-Henriksson, A., Kieseppä, T., Soronen, P., Hennah, W., Turunen, J. A., Peltonen, J. O., Palo, O. M., Silander, K., Lönnqvist, J., Kaprio, J., Cannon, T. D. and Peltonen, L. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2006; 141B(7): 728-729. Meeting Abstract. IF 3.521 European population substructure: Clustering of northern and southern populations Seldin, M. F., Shigeta, R., Villoslada, P., Selmi, C., Tuomilehto, J., Silva, G., Belmont, J. W., Klareskog, L. and Gregersen, P. K. Plos Genetics. 2006; 2(9): 1339-1351. Article. IF Using a genome-wide single nucleotide polymorphism (SNP) panel, we observed population structure in a diverse group of Europeans and European Americans. Under a variety of conditions and tests, there is a consistent and reproducible distinction between "northern'' and "southern'' European population groups: most individual participants with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have > 85% membership in the "southern'' population; and most northern, western, eastern, and central Europeans have > 90% in the "northern'' population group. Ashkenazi Jewish as well as Sephardic Jewish origin also showed > 85% membership in the "southern'' population, consistent with a later Mediterranean origin of these ethnic groups. Based on this work, we have developed a core set of informative SNP markers that can control for this partition in European population structure in a variety of clinical and genetic studies. Family based study of 13 functional candidate genes and bipolar disorder Soronen, P., Palo, O. M., Silander, K., Antila, M., Tuulio-Henriksson, A., Kieseppä, T., Peltonen, L., Partonen, T., Lönnqvist, J. and Paunio, T. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2006; 141B(7): 760-760. Meeting Abstract. IF 3.521 Dietary insulin as an immunogen and tolerogen Tiittanen, M., Paronen, J., Savilahti, E., Virtanen, S. M., Ilonen, J., Knip, M., Åkerblom, H. K. and Vaarala, O. Pediatric Allergy and Immunology. 2006; 17(7): 538-543. Article. IF 2.126 We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin-specific immune response in infants. Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3-7 days and/or 3 months after delivery. After exclusive breast-feeding, the children received either CM formula or casein hydrolysate during the first 6-8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta-cell autoimmunity when compared with autoantibody-negative children (p = 0.030); this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast-fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI. However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance. Tomppo, L., Hennah, W., Lahermo, P., Loukola, A., Ekelund, J., Partonen, T., Palotie, A., Lönnqvist, J. and Peltonen, L. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2006; 141B(7): 717-717. Meeting Abstract. IF 3.521 Association analysis of SLC25A12 and EN2 in the Finnish families with autism-spectrum disorders Turunen, J., Ylisaukko-oja, T., Kilpinen, H., Rehnstrom, K., Kempas, E., Vanhala, R., Wendt, T. N. V., von Wendt, L. and Peltonen, L. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics. 2006; 141B(7): 766-766. Meeting Abstract. IF 3.521 Prospective study of risk factors for attempted suicide among patients with bipolar disorder Valtonen, H. M., Suominen, K., Mantere, O., Leppamäki, S., Arvilommi, P. and Isometsä, E. T. Bipolar Disord. 2006; 8(5 Pt 2): 576-85. IF 4.812 Objective: There are few prospective studies on risk factors for attempted suicide among representative samples of psychiatric patients with bipolar I and II disorders. We conducted a prospective study to investigate risk for suicide attempts among a secondary-level sample of psychiatric in- and outpatients with bipolar disorder (BD). Methods: In the Jorvi Bipolar Study (JoBS), 1,630 psychiatric in- and outpatients from three Finnish cities were screened for BDs with the Mood Disorder Questionnaire (MDQ). Using the Structured Clinical Interview for DSM-IV Disorders (SCID)-I and -II, 191 patients were diagnosed with BDs (90 bipolar I and 101 bipolar II). Information on suicide attempts during the follow-up was obtained for 176 patients (92%) at the 6-month follow-up and for 160 patients (84%) at the 18-month follow-up. Results: During the 18-month follow-up 20% of patients (35/176) attempted suicide. In a Cox regression model, baseline previous suicide attempts (OR 3.8, 95% CI 1.7-8.8; p = 0.001), hopelessness (OR 1.2, 95% CI 1.1-1.3; p < 0.001), depressive phase at index episode (OR 2.4, 95% CI 1.1-5.3; p = 0.03) and younger age at intake (OR 0.94, 95% CI 0.91-0.97; p < 0.001) were independent risk factors for suicide attempts during follow-up, whereas factors such as bipolar I or II, or comorbidity did not reach statistical significance. Conclusions: During a medium-term follow-up, as many as one-fifth of random psychiatric patients with BD attempted suicide, which highlights the public health importance of suicidal behavior in BD. Previous suicide attempts, hopelessness and depressive phase were the key indicators of risk. ATP-consuming and ATP-generating enzymes secreted by pancreas Yegutkin, G. G., Samburski, S. S., Jalkanen, S. and Novak, I. Journal of Biological Chemistry. 2006; 281(40): 29441-29447. Article. IF 5.854 Pancreatic acini release ATP in response to various stimuli, including cholecystokinin octapeptide (CCK-8), as we show in the present study. There were indications that pancreatic juice also contains enzymes that could hydrolyze ATP during its passage through the ductal system. The aim of this study was to determine which ATP-degrading and possibly ATP-generating enzymes were present in pancreatic secretion. For this purpose, pancreatic juice was collected from anesthetized rats stimulated with infusion of CCK-8. Purine-converting activities in juice samples were assayed by TLC using either [gamma-P-32] ATP or C-14/H-3-labeled and unlabeled nucleotides as appropriate substrates. Data show that the juice contains the enzyme ecto-nucleoside triphosphate diphosphohydrolase that can hydrolyze both [C-14]ATP and [H-3]ADP about equally well, i.e. CD39. Reverse-phase high-performance liquid chromatography analysis additionally shows that this enzyme has broad substrate specificity toward other nucleotides, UTP, UDP, ITP, and IDP. In addition, secretion contains ecto-5'-nucleotidase, CD73, further converting [H-3]AMP to adenosine. Along with highly active hydrolytic enzymes, there were also ATP-generating enzymes in pancreatic juice, adenylate kinase, and NDP kinase, capable of sequentially phosphorylating AMP via ADP to ATP. Activities of nonspecific phosphatases, nucleotide pyrophosphatase/phosphodiesterases, and adenosine deaminase were negligible. Taken together, CCK-8 stimulation of pancreas causes release of both ATP-consuming and ATP-generating enzymes into pancreatic juice. This newly discovered richness of secreted enzymes underscores the importance of purine signaling between acini and pancreatic ducts lumen and implies regulation of the purine-converting enzymes release. |