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New articles - Uudet artikkelit 21.7.2008 - ISI Web of Knowledge & PubMed Search Alert
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An enterovirus strain isolated from diabetic child belongs to a genetic subcluster of echovirus 11, but is also neutralised with monotypic antisera to coxsackievirus A9
Al-Hello, H., Paananen, A., Eskelinen, M., Ylipaasto, P., Hovi, T., Salmela, K., Lukashev, A. N., Bobegamage, S. and Roivainen, M. J Gen Virol. 2008; 89(Pt 8): 1949-59. IF 3.120 An enterovirus strain (designated D207) isolated from a Slovakian diabetic child and originally serotyped as coxsackievirus A9 (CAV-9) was found to cause rapid cytolysis coinciding with severe functional damage of the surviving cells in primary cultures of human pancreatic islets. This finding prompted us to clone the isolate for full-length genome sequencing and molecular characterization as the prototype strain of CAV-9 is known to cause only minimal damage to insulin-producing beta-cells. Based on capsid-coding sequence comparisons, the isolate turned out to be echovirus 11 (E-11). Phylogenetic analyses demonstrated that E-11/D207 was closely related to a specific subgroup B of E-11 strains known to cause uveitis. To study further antigenic properties of isolate E-11/D207 and uveitis-causing E-11 strains, neutralization experiments were carried out with CAV-9- and E-11-specific antisera. Unlike the prototype strains, the isolate E-11/D207 and uveitis-causing E-11 strains were well neutralized with both CAV-9- and E-11-specific antisera. Attempts to identify recombination of the capsid coding sequences as a reason for double-reactivity using the Simplot analysis failed to reveal major transferred motifs. However, peptide scanning technique was able to identify antigenic regions of capsid proteins of E-11/D207 as well as regions cross-reacting with an antiserum raised to CAV-9. Thus, double specificity of E-11/D207 seems to be a real characteristic shared by the phylogenetically closely related virus strains in the genetic subgroup B of E-11. Collings, A., Hoyssa, S., Fan, M., Kahonen, M., Hutri-Kahonen, N., Marniemi, J., Juonala, M., Viikari, J. S. A., Raitakari, O. T. and Lehtimaki, T. J. Circulation Journal. 2008; 72(7): 1158-1164. Article. IF 2.373 Background Polymorphisms of the upstream transcription factor 1 (USF1) have been associated with familial combined hyperlipidemia and coronary heart disease. The impact of this gene on subclinical atherosclerosis is unknown. Associations of 3 allelic variants of the USF1 gene and their haplotypes with carotid artery intima-media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD) were studied in a population of Finnish healthy young adults. Methods and Results The study population comprised 2,281 individuals participating in the Cardiovascular Risk in Young Finns study. IMT, CAC and FMD values were measured by ultrasound examination. Genotypes were analysed using the 5' nuclease assay. A significant difference in IMT was found for usf1s1 (rs3737787) and usf1s8 (rs2516838) genotypes (p-values 0.046 and 0.021, respectively). Moreover, there was a significant difference between groups in haplotype 1 and haplotype 2 for IMT (p-values 0.011 and 0.028 respectively). In multivariate stepwise linear regression models adjusted by age, sex, body mass index, systolic and diastolic blood pressures, smoking, C-reactive protein, glucose, high- and low-density lipoprotein-cholesterols and triglycetides there were significant associations for the usf1s1 minor genotype AA to predict low IMT (p=0.038) and usf1s8 minor genotype GG to predict high IMT (p=0.003). There was also a significant association for haplotype 2 to predict low IMT in the otherwise similar multivariate model (p=0.006). No associations were found for polymorphisms and CAC, FMD or serum lipids. Conclusions The rs2516838 and rs3737787 polymorphisms of USF1 influence the carotid artery IMT, which is a new finding. Intragastric primary infection sensitizes to lung reinfection in a Chlamydia pneumoniae mouse model Erkkilä, L., Saario, E., Laitinen, K., Saikku, P. and Leinonen, M. Vaccine. 2008; 26(20): 2503-9. IF 3.377 The most frequently used infection route in Chlamydia pneumoniae animal models is intranasal (i.n.), while the intragastric (i.g.) infection route has not been studied previously. The aim of the present study was to examine the course of Chlamydia pneumoniae infection in mice infected via the i.g. route and to compare the outcome of i.n. reinfection in these mice to i.n. reinfection of primarily i.n. infected mice. C57BL/6JBom mice were used, and the infection was monitored using chlamydial culture, C. pneumoniae PCR and histological examination of several tissues, and antibody measurements. C. pneumoniae was able to disseminate from the gastrointestinal tract to other organs, and i.g. inoculation led to an immunological response. In addition, the primary i.g. challenge made mice more susceptible to i.n. reinfection. In conclusion, the results suggest that the nature of the immune response to a previous C. pneumoniae infection affects the outcome of reinfection. Haanperä, M., Forssten, S. D., Huovinen, P. and Jalava, J. Antimicrobial Agents and Chemotherapy. 2008; 52(7): 2632-2635. Article. IF 4.390 In Klebsiella pneumoniae, the cooccurrence of chromosomal and plasmid-mediated beta-lactamases can hinder their accurate molecular detection. We developed a fast and reliable method that allows the typing of isolates carrying more than one SHV gene. The method is based on pyrosequencing the DNA sequence corresponding to amino acid positions 35, 238, and 240. Heikkinen, H., Jallinoja, P., Saarni, S. I. and Patja, K. Nicotine Tob Res. 2008; 10(7): 1199-207. IF 2.129 The objective of the study was to examine the association between overall and health-related quality of life and smoking in men and women of discrete smoking groups in Finland. The design was a Health 2000 Survey, conducted in Finland 2000-2001. The setting and participants were a two-stage, stratified, nationally representative cluster sample that comprised 8,028 persons aged 30 or over living in mainland Finland. Health-related quality of life was measured by the 15D questionnaire; and overall quality of life was assessed by a single question measure capturing the respondent's own perception and estimation of his/her quality of life. The present study showed that daily smokers had both lower health-related and overall quality of life than never-smokers among the Finnish adult population. Health-related quality of life profiles showed that daily smokers did worse than never-smokers in a considerable number of the health dimensions. The effects of smoking were observed not only through health: the daily smokers registered significantly lower ratings of overall quality of life compared with never-smokers, too. Both the health-related and overall quality of life of ex-smokers approached those of never-smokers. The results of the present study suggest that improved health is not the only benefit of smoking cessation; better quality of life and more fulfilling everyday living can also be expected. As the major health consequences of smoking usually manifest themselves only after several years of smoking, both health-related and overall quality of life measurements could be used as an intervention tool for motivating people to quit. Joint effects of coffee consumption and serum gamma-glutamyltransferase on the risk of liver cancer Hu, G., Tuomilehto, J., Pukkala, E., Hakulinen, T., Antikainen, R., Vartiainen, E. and Jousilahti, P. Hepatology. 2008; 48(1): 129-136. Article. IF 10.734 Only three Japanese prospective studies have suggested an inverse association between coffee drinking and liver cancer risk. No prospective studies on the association between serum gamma-glutamyltransferase (GGT) and liver cancer risk have been reported. We aimed to determine the single and joint associations of coffee consumption and serum GGT with the risk of primary liver cancer. Study cohorts included 60,323 Finnish participants who were 25-74 years of age and free of any cancer at baseline. During a median follow-up period of 19.3 years (interquartile range: 9.3-29.2 years), 128 participants were diagnosed with an incident liver cancer. The multivariable-adjusted (age, sex, alcohol consumption, education, smoking, diabetes and chronic liver disease at baseline and during follow-up, and body mass index) hazards ratios of liver cancer in participants who drank 0-1, 2-3, 4-5, 6-7, and >= 8 cups of coffee daily were 1.00, 0.66, 0.44, 0.38, and 0.32 (P for trend = 0.003), respectively. Further adjustment for serum GGT in subgroup analysis affected the results only slightly. The multivariable-adjusted and coffee-adjusted hazard ratio of liver cancer for the highest versus the lowest quartile of serum GGT was 3.13 (95% confidence interval = 1.22-8.07). The multivariable-adjusted inverse association between coffee consumption and liver cancer risk persisted when stratified by baseline factors: age more/less than 50 years, current smoker/never smoked/ever smoked, alcohol drinker/never drinker, obese/nonobese, and the highest/lowest three quartiles; of serum GGT. A combination of very low coffee consumption and high level of serum GGT was associated with nearly nine-fold increased risk. Conclusion: Coffee drinking has an inverse and graded association with the risk of liver cancer. High serum GGT is associated with an increased risk of liver cancer. Jarvinen, T. M., Harjutsalo, V., Kinnunen, L., Miettinen, M. E., Tuomilehto-Wolf, E. and Tuomilehto, J. Genes Immun. 2008; 9(3): 207-13. IF 4.088 Children with type 1 diabetes (T1D) susceptibility HLA genotypes are shown to have an increased birthweight. We investigated to what extent T1D-predisposing HLA haplotypes were associated with increased birthweight. A total of 1255 Finnish children comprising those with T1D and their non-diabetic siblings were investigated. A total of 342 children and their non-diabetic parents were HLA genotyped. Birthweight data were obtained from the national Medical Birth Registry. The population-specific diabetogenic haplotype HLA-A2,Cw1,B56,DR4,DQ8 was associated with high birthweight (P=0.0280) in families with a diabetic offspring. Other T1D-predisposing HLA haplotypes showed nonsignificant tendency with high birthweight. More infants with a birthweight >or=4000 g were born in families with a T1D offspring than in the general Finnish population (P=0.0139). The previously observed direct association between birthweight and T1D risk may be mediated through the modulating effects that T1D susceptibility HLA genes have on weight. High birthweight and subsequent weight gain may accelerate the ongoing pancreatic autoimmune process in genetically susceptible individuals. The high proportion of infants having a birthweight >or=4000 g in families with a diabetic offspring raises a concern of potential adverse health outcomes that high birthweight can have. Karpanoja, P., Nyberg, S. T., Bergman, M., Voipio, T., Paakkari, P., Huovinen, P. and Sarkkinen, H. Antimicrobial Agents and Chemotherapy. 2008; 52(7): 2480-2485. Article. IF 4.390 The association between trimethoprim-sulfamethoxazole use and resistance among the major respiratory tract pathogens was investigated by comparing regional consumption of the drug to regional resistance in the following year in 21 central hospital districts in Finland. A total of 23,530 Streptococcus pneumoniae isolates, 28,320 Haemophilus influenzae isolates, and 14,138 Moraxella catarrhalis isolates were tested for trimethoprim-sulfamethoxazole susceptibility during the study period (1998-2004). Among the S. pneumoniae isolates, a statistically significant connection was found between regional consumption and resistance. No statistically significant connection was found between regional trimethoprim-sulfamethoxazole use and resistance among H. influenzae and M. catarrhalis isolates. According to our results, it seems that only in pneumococci can the development of trimethoprim-sulfamethoxazole resistance be influenced by restricting its use. However, trimethoprim-sulfamethoxazole remains an important antimicrobial agent because of its reasonable price. Hence, resistance to trimethoprim-sulfamethoxazole among these pathogens needs continuous monitoring. Childhood and current determinants of heavy drinking in early adulthood Kestilä, L., Martelin, T., Rahkonen, O., Joutsenniemi, K., Pirkola, S., Poikolainen, K. and Koskinen, S. Alcohol and Alcoholism. 2008; 43(4): 460-469. Article. IF 2.092 Aims: To explore the association of parental education, childhood living conditions and several adversities with heavy drinking in early adulthood, and to analyze the effect of the respondent's current circumstances on these associations. Method: The analyses were conducted in a sample of 1234 adults aged 18-29 years participating in the Finnish Health 2000 Survey (65% of the original representative two-stage cluster sample, N = 1894). The outcome measure was heavy drinking measured by g/week for pure alcohol (for men >= 280 g/week and for women >= 140 g/week). Results: 8% of young adult men and 5% of women were heavy drinkers. In both genders, parental alcohol problems and other childhood adversities, poor own education, and unemployment status increased the risk of heavy drinking. The impact of childhood on heavy drinking was partly independent and partly mediated by adult characteristics, in particular, for both genders, low level of education. Conclusions: Childhood adversities are associated with heavy drinking in early adulthood among both genders. Childhood social circumstances as well as low educational level and unemployment should be taken into account in planning preventive policies to tackle the harms caused by excessive alcohol use at the individual and population level. Lappalainen, M. H., Roponen, M., Hyvärinen, A., Nevalainen, A., Laine, O., Pekkanen, J. and Hirvonen, M. R. Clin Exp Allergy. 2008. IF 3.729 Background Our previous study showed an association between increased concentration of endotoxin in house dust and elevated IFN-gamma responses in neonates. The impact of other microbial agents on immune responses in infancy is poorly known. Objective To examine whether stimulated cytokine responses of mothers and their children are associated with concentrations of other microbial markers in addition to endotoxin in house dust samples. Methods Mitogen-stimulated production of IFN-gamma, IL-4, IL-6 and TNF-alpha was measured in cord blood and in peripheral blood of mothers (n=29) and their children (n=29) 3 months after birth. Gas chromatography mass spectrometric analysis was applied to measure the concentrations of ergosterol (marker of fungal biomass), muramic acid (indicating the presence of Gram-positive bacteria) and 3-hydroxy fatty acids (C(10:0)-C(14:0), indicating the presence of Gram-negative bacteria) in house dust. Endotoxin was determined with Limulus assay. Results Significant mother-to-child correlations were observed in stimulated production of TNF-alpha and IL-6 3 months after birth. 3-hydroxy fatty acid (C(10:0)-C(14:0)) levels in bed dust were inversely associated with the production of TNF-alpha and IL-6 in blood samples of mothers and their 3-month-old children. High concentrations of muramic acid in floor dust were related to increased production of TNF-alpha and IL-6 at the age of 3 months. In contrast to endotoxin, none of the other microbial markers were significantly associated with enhanced IFN-gamma-producing capacity from birth to 3 months. Conclusions Exposure to Gram-negative bacteria and their components may be associated with down-regulated immune responses in early infancy, indicated as an impaired production of pro-inflammatory cytokines following mitogen stimulation. Gram-positive bacteria and their constituents seem to have opposite effects. Of the measured markers, exposure to bioactive endotoxin appears to have the strongest impact on T-helper type 1 responses. Macrophage mannose receptor on lymphatics controls cell trafficking Marttila-Ichihara, F., Turja, R., Miiluniemi, M., Karikoski, M., Maksimow, M., Niemela, J., Martinez-Pomares, L., Salmi, M. and Jalkanen, S. Blood. 2008; 112(1): 64-72. IF 10.896 Macrophage mannose receptor (MR) participates in pathogen recognition, clearance of endogenous serum glycoproteins, and antigen presentation. MR is also present on lymphatic vessels, where its function is unknown. Here we show that migration of lymphocytes from the skin into the draining lymph nodes through the afferent lymphatics is reduced in MR-deficient mice, while the structure of lymphatic vasculature remains normal in these animals. Moreover, in a tumor model the primary tumors grow significantly bigger in MR(-/-) mice than in the wild-type (WT) controls, whereas the regional lymph node metastases are markedly smaller. Adhesion of both normal lymphocytes and tumor cells to lymphatic vessels is significantly decreased in MR-deficient mice. The ability of macrophages to present tumor antigens is indistinguishable between the 2 genotypes. Thus, MR on lymphatic endothelial cells is involved in leukocyte trafficking and contributes to the metastatic behavior of cancer cells. Blocking of MR may provide a new approach to controlling inflammation and cancer metastasis by targeting the lymphatic vasculature. Perinatal factors and the risk of asthma in childhood--a population-based register study in Finland Metsälä, J., Kilkkinen, A., Kaila, M., Tapanainen, H., Klaukka, T., Gissler, M. and Virtanen, S. M. Am J Epidemiol. 2008; 168(2): 170-8. IF 5.285 The aim of the study was to assess whether perinatal factors are associated with the risk of asthma in childhood in a register-based, nested case-control study in Finland. All children born between January 1, 1996, and April 30, 2004, who were entitled to a special reimbursement for antiasthmatic drugs (i.e., had diagnosed asthma by 2006 and had purchased inhaled corticosteroids or montelukast at least once), were identified (n = 21,038). For each case, one matched control child was selected. The associations between perinatal factors, derived from the Finnish Medical Birth Register, and the risk of asthma were analyzed by conditional logistic regression. In the final multivariate model, maternal asthma, young age, smoking, previous miscarriages, and a high number of previous deliveries, as well as cesarean section, low gestational age, and low ponderal index, were associated with an increased risk of asthma in children diagnosed before the age of 3 years. Among children diagnosed at the age of 3 years or later, maternal asthma, low gestational age, and low ponderal index were associated with an increased risk, and a high number of previous deliveries was associated with a decreased risk of asthma. In conclusion, perinatal factors play a role in the development of asthma in childhood, but the etiology may differ in early and late-onset asthma. Miettinen, M., Veckman, V., Latvala, S., Sareneva, T., Matikainen, S. and Julkunen, I. J Leukoc Biol. 2008. IF 4.128 Macrophages are phagocytes that recognize bacteria and subsequently activate appropriate innate and adaptive immune responses. TLRs are essential in identifying conserved bacterial structures and in initiating and mediating innate immune responses. In this work, we have characterized TLR gene expression in human monocyte-derived macrophages in response to stimulation with two live Gram-positive bacteria, a human commensal and probiotic Lactobacillus rhamnosus GG (LGG), and an important human pathogen Streptococcus pyogenes. LGG and S. pyogenes enhanced TLR2 expression in macrophages. LGG and S. pyogenes also required TLR2 for NF-kappaB activation. Only pathogenic S. pyogenes was able to up-regulate TLR3 and TLR7 gene expression. This up-regulation was dependent on IFN-alpha/beta, as neutralizing anti-IFN-alpha/beta antibodies reduced S. pyogenes-induced TLR3 and TLR7 mRNA expression. Our results show that despite similarities, TLR responses of macrophages differ for a Gram-positive probiotic and a pathogen. Our data suggest that macrophages can discriminate between probiotic and pathogenic bacteria by IFN-mediated TLR gene regulation. Niiranen, T., Jula, A. and Kantola, I. Journal of Hypertension. 2008; 26: S11-S11. Meeting Abstract. IF 4.364 Palmu, A., Jokinen, J. and Kilpi, T. Vaccine. 2008; 26(20): 2466-70. IF 3.377 Considerably higher vaccine efficacy estimate for clinical acute otitis media (AOM) has been obtained for the 11-valent pneumococcal conjugate vaccine with protein D of Haemophilus influenzae as a carrier (PncPD11) in the POET study than for the 7-valent pneumococcal conjugate vaccine (PncCRM7) in the Finnish Otitis Media (FinOM) Vaccine Trial. We recalculated PncCRM7 efficacy from the FinOM data using a case definition for AOM very close to the POET definition and a definition giving an incidence for AOM in the control group comparable to that obtained in the POET study. The different case definitions had only a slight impact on the vaccine efficacy estimates compared to the original case definitions. We were not able to show that the differences between the study results would be due to the case definitions used. Pointon, J. J., Chapman, K., Harvey, D., Sims, A. M., Bradbury, L., Laiho, K., Kauppi, M., Kaarela, K., Tuomilehto, J., Brown, M. A. and Wordsworth, B. P. J Rheumatol. 2008. IF 3.151 OBJECTIVE: To investigate the association of CD14 and Toll-like receptor (TLR4) with ankylosing spondylitis (AS). METHODS: A promoter variant in CD14 and 2 coding polymorphisms in TLR4 were investigated in UK and Finnish families with AS and in a UK case-control study. A metaanalysis of published TLR4 and CD14 studies was performed. RESULTS: In the Finnish study the CD14-260bp T variant showed an association (p = 0.006), and the common 2-marker TLR4 haplotype showed a weak association (global p = 0.03), with AS. No associations were seen in the UK based studies or in the metaanalyses. CONCLUSION: CD14 and TLR4 showed an association with AS in the Finns only. Skov, R., Gudlaugsson, O., Hardardottir, H., Harthug, S., Jakobsen, T., Kolmos, H. J., Olsson-Liljequist, B., Peltonen, R., Tveten, Y., Vuopio-Varkila, J. and Ahren, C. Scandinavian Journal of Infectious Diseases. 2008; 40(6-7): 495-502. Article. IF 1.209 The recent increase in the incidence of methicllin-resistant Staphylococcus aureus in all the Nordic countries prompted the Scandinavian Society for Antimicrobial Chemotherapy (SSAC) to create the 'SSAC Working Party on MRSA' with the objective to identify methods to keep the invasive MRSA infections in the Nordic countries below 1%. The lack of common definitions was recognized as a major obstacle for a joint Nordic effort to combat MRSA. The aim of this publication is to present proposals for epidemiological definitions of individual cases, for how to report MRSA frequency per country, and for communication of MRSA strain characteristics between the countries. Psychological distress and attitudes of emergency personnel towards suicide attempters Suokas, J., Suominen, K. and Lönnqvist, J. Nordic Journal of Psychiatry. 2008; 62(2): 144-146. Article. IF 0.752 Emergency personnel attitudes towards suicide attempters are important because they have a key role in the management of these patients. We examined the association between staff members' psychological distress and the attitudes towards suicide attempters. We also compared the attitudes towards suicide attempters among emergency personnel between a general and a psychiatric hospital. The Understanding Suicidal Patients (USP) Questionnaire and the 12-item version of General Health Questionnaire were given to all staff in the emergency rooms of a general hospital and a psychiatric hospital (n=151). There was a general tendency among emergency room staff to view attempted suicide patients positively and sympathetically. However, there were clear differences in staff attitudes between the two hospitals: those working in the general hospital expressed more negative attitudes than those in the psychiatric hospital. No evidence emerged of association between staff members' psychological distress and negative attitudes towards suicide attempters. There was no association between psychological distress and negative attitudes towards suicide attempters. Turpeinen, A. A., Ylonen, N., von Willebrand, E., Basu, S. and Aro, A. British Journal of Nutrition. 2008; 100(1): 112-119. Article. IF 2.339 Animal studies suggest that conjugated linoleic acid (CLA) may modulate the immune response, while studies in healthy human subjects have shown little effect and results are controversial. However, the effects of CLA may be more prominent in situations of immune imbalance, such as allergy. We studied the effects of the natural CLA isomer, cis-9, trans-11-CLA, on allergy symptoms and immunological parameters in subjects with birch pollen allergy. In a randomised, placebo-controlled study, forty subjects (20-46 years) with diagnosed birch pollen allergy received 2g CLA/d in capsules, which contained 65.3 % cis-9, trans-11-CLA and 8-5 % trans-10, cis-12-CLA (n 20), or placebo (high-oleic acid sunflower-seed oil) (n 20) for 12 weeks. The supplementation began 8 weeks before the birch pollen season and continued throughout the season. Allergy symptoms and use of medication were recorded daily. Lymphocyte subsets, cytokine production, immunoglobulins, C-reactive protein, lipid and glucose metabolism and lipid peroxidation were assessed before and after supplementation. The CLA group reported a better overall feeling of wellbeing (P<0.05) and less sneezing (P<0.05) during the pollen season. CLA supplementation decreased the in vitro production of TNF-alpha (P<0.01), interferon-gamma (P<0.05) and IL-5 (P<0.05). Total plasma IgE and birch-specific IgE concentrations did not differ between groups, whereas plasma IgA (P<0.05), granulocyte macrophage colony-stimulating factor (P<0.05) and eosinophil-derived neurotoxin (P<0.05) concentrations were lower after CLA supplementation. Urinary excretion of 8-iso-PGF(2 alpha), a major F-2-isoprostane (P<0.01), and 15-keto-dihydro-PGF(2 alpha), a primary PGF(2 alpha) metabolite (P< 0.05), increased in the CLA group. The results suggest that cis-9, trans-11-CLA has modest anti-inflammatory effects in allergic subjects. Uusi-Rauva, K., Luiro, K., Tanhuanpaa, K., Kopra, O., Martin-Vasallo, P., Kyttala, A. and Jalanko, A. Exp Cell Res. 2008. IF 3.695 Juvenile neuronal ceroid lipofuscinosis (JNCL, Batten disease) is the most common progressive neurodegenerative disorder of childhood. CLN3, the transmembrane protein underlying JNCL, is proposed to participate in multiple cellular events including membrane trafficking and cytoskeletal functions. We demonstrate here that CLN3 interacts with the plasma membrane-associated cytoskeletal and endocytic fodrin and the associated Na(+), K(+) ATPase. The ion pumping activity of Na(+), K(+) ATPase was unchanged in Cln3(-/-) mouse primary neurons. However, the immunostaining pattern of fodrin appeared abnormal in JNCL fibroblasts and Cln3(-/-) mouse brains suggesting disturbances in the fodrin cytoskeleton. Furthermore, the basal subcellular distribution as well as ouabain-induced endocytosis of neuron-specific Na(+), K(+) ATPase were remarkably affected in Cln3(-/-) mouse primary neurons. These data suggest that CLN3 is involved in the regulation of plasma membrane fodrin cytoskeleton and consequently, the plasma membrane association of Na(+), K(+) ATPase. Most of the processes regulated by multifunctional fodrin and Na(+), K(+) ATPase are also affected in JNCL and Cln3-deficiency implicating that dysregulation of fodrin cytoskeleton and non-pumping functions of Na(+), K(+) ATPase may play a role in the neuronal degeneration in JNCL. Genetic and environmental influences on pubertal timing assessed by height growth Wehkalampi, K., Silventoinen, K., Kaprio, J., Dick, D. M., Rose, R. J., Pulkkinen, L. and Dunkel, L. American Journal of Human Biology. 2008; 20(4): 417-423. Article. IF 1.805 Secular trends towards earlier puberty, possibly caused by new environmental triggers, provide a basis for periodic evaluation of the influence and interaction of genetic and environmental effects on pubertal timing. In such studies, a practical marker that reflects timing of puberty in both genders needs to be used. We investigated genetic and environmental influences on pubertal timing by using change in the relative height between early and late adolescence (HD:SDS, height difference in standard deviations) as a new marker of pubertal timing. HD:SDS correlated well with age at peak height velocity in a population of men and women with longitudinal growth data. In 2,309 twin girls and 1,828 twin boys, HD:SDS was calculated between height SDs at age 11.5 and 17.5, and 14.0 and 17.5 years, respectively. Quantitative genetic models for twin data were fitted to estimate the genetic contribution to HD:SDS. We also investigated whether the same genetic factors influenced individual differences between HD:SDS and development of secondary sex characteristics prospectively collected by pubertal development scale (PDS). Genetic effects contributed to 86 and 82% of the variance in HD:SDS in girls and boys, respectively, when using the same model including additive genetic and specific environmental factors. In girls, 30% and in boys, 49% of the genetic factors affecting PDS and HD:SDS were the same. Future comparison of the results of periodic evaluations allows estimation of possible changes in the effects of environment on timing of puberty. In such studies, HD:SDS can be used as a practical marker of pubertal timing. |