| New articles - Uudet artikkelit
17.12.2007 - ISI Web of Knowledge & PubMed Search Alert |
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Palmitoyl protein thioesterase 1 (Ppt1)-deficient mouse neurons
show alterations in cholesterol metabolism and calcium homeostasis
prior to synaptic dysfunction
Ahtiainen, L., Kolikova, J., Mutka, A. L., Luiro, K., Gentile, M., Ikonen, E., Khiroug, L., Jalanko, A. and Kopra, O. Neurobiol Dis. 2007; 28(1): 52-64. IF 4.128 Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder of children, characterized by selective death of neocortical neurons. To understand early disease mechanisms in INCL, we have studied Ppt1(Deltaex4) knock-out mouse neurons in culture and acute brain slices. Global transcript profiling showed deregulation of key neuronal functions in knock-out mice including cholesterol metabolism, neuronal maturation, and calcium homeostasis. Cholesterol metabolism showed major changes; sterol biosynthesis was enhanced and steady-state amounts of sterols were altered at the cellular level. Changes were also present in early maturation of Ppt1(Deltaex4) neurons indicated by increased proliferative capacity of neuronal stem cells. Knock-out neurons presented unaltered electrophysiological properties suggesting uncompromised synaptic function in young animals. However, knock-out neurons exhibited more efficient recovery from glutamate-induced calcium transients, possibly indicating neuroprotective activation. This study established that the neuronal deregulation in INCL is linked to neuronal maturation, lipid metabolism and calcium homeostasis. Castro, F. A., Haimila, K., Pasanen, K., Kaasila, M., Patama, T., Partanen, J., Surcel, H. M., Pukkala, E. and Lehtinen, M. Int J STD AIDS. 2007; 18(10): 672-9. IF 1.274 Cervical cancer (CxCa) is a long-term sequelae caused by persistent human papillomavirus (HPV) infection. Genetic susceptibility to the persistent infection and CxCa is associated with certain human leucocyte antigen (HLA) types. The same susceptibility genes may also determine whether a woman will be protected against the persistent infection and against CxCa by HPV vaccination or not. A systematic review of literature identified following HLAs to be associated with CxCa: A11 (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.1-2.0); B7 (1.5, 1.1-2.0); B15 (0.6, 0.4-0.8); DR2 (1.2, 1.1-1.4) and DR6 (0.6, 0.5-0.8). In the Caucasian population, HLA-B7 and DR6, and DR2 and B15 antigens showed at least borderline associations. In view of a bone marrow donor registry at the Finnish Red Cross and the Finnish Cancer Registry, we created geographic distribution maps of index HLA frequencies and CxCa incidence in the fertile-aged Finnish population. Increased incidence of CxCa was found in a region of western coastal Finland, where frequency of two CxCa susceptibility genes (HLA-DR2 and B7) was increased, and frequency of one CxCa resistance gene (HLA-B15) was decreased. Whether or not HLA type determines also regional susceptibility to persistent HPV infection, and the success of HPV vaccination in preventing both the persistent infection and CxCa warrants further investigation. Heinikainen, S., Pohjanvirta, T., Eklund, M., Siitonen, A. and Pelkonen, S. Journal of Clinical Microbiology. 2007; 45(11): 3817-3820. Article. IF 3.445 Severe diarrheal infections caused by Shigatoxigenic Escherichia coli O103:H-2:stx(1):eae-epsilon:ehx, 0145:H28:stx(1): eae-gamma:ehx (two cases in a family), and O174:H21.stx(2c), in farm residents were traced to cattle. Molecular methods were applied to the isolation and characterization of the strains. The causative strains were also isolated from cattle samples 1 or 4 months later. The increasing prevalence of metabolic syndrome among Finnish men and women over a decade Hu, G., Lindstrom, J., Jousilahti, P., Peltonen, M., Sjoberg, L., Kaaja, R., Sundvall, J. and Tuomilehto, J. J Clin Endocrinol Metab. 2007. IF 5.799 Objective: To assess ten-year change in the prevalence of the metabolic syndrome defined by the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) among Finnish men and women. Design and Subjects: Two cross-sectional population surveys were carried out in Finland in 1992 and 2002. A total of 3495 participants aged 45-64 yr were included in the analysis. Result: In both years, the metabolic syndrome was more common among men than in women. In men, the prevalence of the metabolic syndrome tended to increase slightly between 1992 and 2002, from 48.8% to 52.6% (P = 0.139) based on the NCEP definition and from 51.4% to 55.6% based on the IDF definition (P = 0.102). In women, the prevalence of the metabolic syndrome increased significantly from 32.2% to 39.1% based on the NCEP definition (P = 0.003), and from 38.0% to 45.3% based on the IDF definition (P = 0.002). In both sexes, the prevalence of high blood pressure decreased, but the abnormalities in glucose metabolism increased between 1992 and 2002. The prevalence of central obesity increased in women between 1992 and 2002. Conclusion: In Finland, the prevalence of the metabolic syndrome, based both on the NCEP and IDF definitions, is higher in men than in women. However, the increase in the prevalence of the metabolic syndrome, from 1992 to 2002, was significant only among women. Chernobyl exposure as stressor during pregnancy and behaviour in adolescent offspring Huizink, A. C., Dick, D. M., Sihvola, E., Pulkkinen, L., Rose, R. J. and Kaprio, J. Acta Psychiatrica Scandinavica. 2007; 116(6): 438-446. Article. IF 3.857 Objective: Research in animals has shown that exposure to stressors during pregnancy is associated with offspring behavioural disorders. We aimed to study the effect of in utero exposure to the Chernobyl disaster in 1986, and maternal anxiety presumably associated with that exposure, on behaviour disorder observed at age 14. Method: Exposed (n = 232) and non-exposed Finnish twins (n = 572) were compared. A semi-structured interview was used to assess lifetime symptoms of depression, generalized anxiety disorder, attention deficit hyperactivity disorder, conduct disorder and oppositional defiant disorder symptoms. Results: Adolescents who were exposed from the second trimester in pregnancy onwards, had a 2.32-fold risk (95% CI: 1.13-4.72) of having lifetime depression symptoms, an increased risk of fulfilling DSM-III-R criteria of a major depressive disorder (OR = 2.48, 95% CI: 1.06-5.7), and a 2.01-fold risk (95% CI: 1.14-3.52) of having attention deficit hyperactivity disorder symptoms. Conclusion: Perturbations in fetal brain development during the second trimester may be associated with the increased prevalence of depressive and attention deficit hyperactivity disorder symptoms. Interpreting Trends in Prostate Cancer Incidence and Mortality in the Five Nordic Countries Kvale, R., Auvinen, A., Adami, H. O., Klint, A., Hernes, E., Moller, B., Pukkala, E., Storm, H. H., Tryggvadottir, L., Tretli, S., Wahlqvist, R., Weiderpass, E. and Bray, F. J Natl Cancer Inst. 2007. IF 15.271 Trends in incidence and mortality rates of prostate cancer were analyzed using data from the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden. Joinpoint regression models were used to quantify temporal trends for the period from 1980 to 2004. Incidence rates were increasing and similar in the Nordic countries during the 1980s. Around 1990, a more rapid incidence increase began in all Nordic countries except Denmark, where an increase was seen 5 years later. In 2001, incidence rates in Denmark were half of those seen in the other Nordic countries, but mortality rates varied only marginally among countries. Mean annual declines in prostate cancer mortality of 1.9% (95% CI = 0.4% to 3.3%) and 1.8% (95% CI = 0.5% to 3.0%) were observed from 1996 to 2004 in Finland and Norway, respectively. During the same period, mortality rates leveled off in Iceland and Sweden but continued to increase in Denmark. The rapid increase in incidence during the early 1990s coincided with the introduction of the prostate-specific antigen (PSA) test and conveys little information about the occurrence of potentially lethal disease. Mortality rates, however, have recently stabilized or declined in countries where PSA testing and curative treatment have been commonly practiced since the late 1980s. Although other explanatory factors may be in operation, these trends are consistent with a moderate effect of increased curative treatment of early diagnosed prostate cancer and improved treatment of more advanced disease. Lehtola, M. J., Torvinen, E., Kusnetsov, J., Pitkanen, T., Maunula, L., von Bonsdorff, C. H., Martikainen, P. J., Wilks, S. A., Keevil, C. W. and Miettinen, I. T. Appl Environ Microbiol. 2007; 73(9): 2854-9. IF 3.532 Most of the bacteria in drinking water distribution systems are associated with biofilms. In biofilms, their nutrient supply is better than in water, and biofilms can provide shelter against disinfection. We used a Propella biofilm reactor for studying the survival of Mycobacterium avium, Legionella pneumophila, Escherichia coli, and canine calicivirus (CaCV) (as a surrogate for human norovirus) in drinking water biofilms grown under high-shear turbulent-flow conditions. The numbers of M. avium and L. pneumophila were analyzed with both culture methods and with peptide nucleic acid fluorescence in situ hybridization (FISH) methods. Even though the numbers of pathogens in biofilms decreased during the experiments, M. avium and L. pneumophila survived in biofilms for more than 2 to 4 weeks in culturable forms. CaCV was detectable with a reverse transcription-PCR method in biofilms for more than 3 weeks. E. coli was detectable by culture for only 4 days in biofilms and 8 days in water, suggesting that it is a poor indicator of the presence of certain waterborne pathogens. With L. pneumophila and M. avium, culture methods underestimated the numbers of bacteria present compared to the FISH results. This study clearly proved that pathogenic bacteria entering water distribution systems can survive in biofilms for at least several weeks, even under conditions of high-shear turbulent flow, and may be a risk to water consumers. Also, considering the low number of virus particles needed to result in an infection, their extended survival in biofilms must be taken into account as a risk for the consumer. Menotti, A., Lanti, M., Kromhout, D., Blackburn, H., Nissinen, A., Dontas, A., Kafatos, A., Nedeljkovic, S. and Adachi, H. European Journal of Epidemiology. 2007; 22(11): 747-754. Article. IF 1.605 Time trends in coronary heart disease (CHD) mortality during a 40-year follow-up were studied in the Seven Countries Study. Thirteen cohorts of men aged 40-59 at entry were enrolled in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece and Japan) for a total of 10,628 subjects. Cardiovascular risk factors were measured at entry and at the 10-year follow-up examination and coronary heart disease mortality data collected during 40 years. During the 40-year follow-up, the hazard rate of the Weibull parametric distribution (annual conditional risk of death) for CHD mortality tended to slightly decline in the US, Finnish, Dutch and Japanese cohorts, moderately increased in Italy and exponentially increased in cohorts of Serbia and Greece. A strong positive association was found between the shape of the hazard curve, describing the acceleration of the hazard, and a score of population mean risk factor changes (serum cholesterol, systolic blood pressure and smoking prevalence) observed during the first 10 years of follow-up, with a correlation coefficient of 0.91 between the two indicators. The countries with a relative decline in the annual hazard function were the same where, during the same historical period, large decreases in official death rate from CHD were recorded, and viceversa. The acceleration in mortality risk for CHD mortality in different countries, described by the shape of the Weibull distribution, is related to changes in mean levels of major coronary risk factors. Pitkaniemi, J., Moltchanova, E., Haapala, L., Harjutsalo, V., Tuomilehto, J. and Hakulinen, T. Genetic Epidemiology. 2007; 31(7): 697-708. Article. IF 5.226 A shared and additive genetic variance component-long-term survivor (LTS) model for familial aggregation studies of complex diseases with variable age-at-onset phenotype and non-susceptible subjects in the study cohort is proposed. LTS has been used from the early 1970s, especially in epidemiological studies of cancer. The LTS model utilizes information on the age at onset (survival) distribution to make inference on partially latent susceptibility. Bayesian modeling with uninformative priors is used and estimates of the posterior distribution of age at onset and susceptibility parameters of interest have been obtained using Bayesian Markov chain Monte Carlo (MCMC) methods with OpenBugs program. A simulation study confirms that we obtain posterior estimates of the model parameters on shared and genetic variance components of age at onset and susceptibility with good coverage rates. Further, we analyze familial aggregation of diabetic nephropathy DN in large Finnish cohort of 528 sibships with type 1 diabetes (T1D). According to the variance components estimated a substantial familial variation in the susceptibility to DN exist among families, while time to DN is less influenced by shared familial factors. Raevuori, A., Dick, D. M., Keski-Rahkonen, A., Pulkkinen, L., Rose, R. J., Rissanen, A., Kaprio, J., Viken, R. J. and Silventoinen, K. Psychological Medicine. 2007; 37(11): 1625-1633. Article. IF 3.816 Background. We analysed genetic and environmental influences on self-esteem and its stability in adolescence. Method. Finnish twins born in 1983-1987 were assessed by questionnaire at ages 14 (n = 4132 twin individuals) and 17 years (n=3841 twin individuals). Self-esteem was measured using the Rosenberg global self-esteem scale and analyzed using quantitative genetic methods for twin data in the Mx statistical package. Results. The heritability of self-esteem was 0.62 [95% confidence interval (CI) 0.56-0.68] in 14-year-old boys and 0.40 (95% CI 0.26-0.54) in 14-year-old girls, while the corresponding estimates at age 17 were 0.48 (95% CI 0.39-0.56) and 0.29 (95% CI 0.11-0.45). Rosenberg self-esteem scores at ages 14 and 17 were modestly correlated (r = 0.44 in boys, r = 0.46 in girls). In boys, the correlation was mainly (82%) due to genetic factors, with residual co-variation due to unique environment. In girls, genetic (31%) and common environmental (61%) factors largely explained the correlation. Conclusions. In adolescence, self-esteem seems to be differently regulated in boys versus girls. A key challenge for future research is to identify environmental influences contributing to self-esteem during adolescence and determine how these factors interact with genetic influences. Sillanpaa, M. J. and Hoti, F. Genetics. 2007; 177(4): 2361-77. IF 4.242 A new effective Bayesian quantitative trait locus (QTL) mapping approach for the analysis of single-tail selected samples of the phenotype distribution is presented. The approach extends the affected-only tests to single-tail sampling with quantitative traits such as the log-normal survival time or censored/selected traits. A great benefit of the approach is that it enables the utilization of multiple-QTL models, is easy to incorporate into different data designs (experimental and outbred populations), and can potentially be extended to epistatic models. In inbred lines, the method exploits the fact that the parental mating type and the linkage phases (haplotypes) are known by definition. In outbred populations, two-generation data are needed, for example, selected offspring and one of the parents (the sires) in breeding material. The idea is to statistically (computationally) generate a fully complementary, maximally dissimilar, observation for each offspring in the sample. Bayesian data augmentation is then used to sample the space of possible trait values for the pseudoobservations. The benefits of the approach are illustrated using simulated data sets and a real data set on the survival of F(2) mice following infection with Listeria monocytogenes. Strang-Karlsson, S., Raikkonen, K., Kajantie, E., Andersson, S., Hovi, P., Heinonen, K., Pesonen, A. K., Jarvenpaa, A. L., Eriksson, J. G. and Paavonen, E. J. J Pediatr Psychol. 2007. IF 3.157 OBJECTIVE: To assess the relationship between very low birth weight (VLBW; <1,500 g) and quality and amount of sleep in young adults. METHODS: We compared 89 VLBW and 78 term-born 19- to 26-year-old adults, by actigraphy and the Basic Nordic Sleep Questionnaire. RESULTS: There were no group differences in sleep quality or amount (p's >.15), although VLBW adults went to bed on average 36 min earlier (95% confidence interval 6-66 min). Shorter gestational age was related to longer sleep latency both within VLBW (standardized regression coefficient beta = -.36, p =.040) and term-born adults (beta = -.25, p =.029). CONCLUSION: Adults with VLBW had similar quality and amount of sleep as those born at term, although VLBW adults went to bed earlier, suggesting an advanced sleep phase. Within each group, a lower gestational age was related to a longer sleep onset. Suna, T., Salminen, A., Soininen, P., Laatikainen, R., Ingman, P., Makela, S., Savolainen, M. J., Hannuksela, M. L., Jauhiainen, M., Taskinen, M. R., Kaski, K. and Ala-Korpela, M. NMR in Biomedicine. 2007; 20(7): 658-672. Article. IF 3.626 H-1 NMR spectra of plasma are known to provide specific information on lipoprotein subclasses in the form of complex overlapping resonances. A combination of H-1 NMR and self-organising map (SOM) analysis was applied to investigate if automated characterisation of subclass-related metabolic interactions can be achieved. To reliably assess the intrinsic capability of H-1 NMR for resolving lipoprotein subclass profiles, sum spectra representing the pure lipoprotein subclass part of actual plasma were simulated with the aid of experimentally derived model signals for 11 distinct lipoprotein subclasses. Two biochemically characteristic categories of spectra, representing normolipidaemic and metabolic syndrome status. were generated with corresponding lipoprotein subclass profiles. A set of spectra representing a metabolic pathway between the two categories was also generated. The SOM analysis, based solely on the aliphatic resonances of these simulated spectra, clearly revealed the lipoprotein subclass profiles and their changes. Comparable SOM analysis in a group of 69 experimental 'H NMR spectra of serum samples, which according to biochemical analyses represented a wide range of lipoprotein lipid concentrations, corroborated the findings based on the simulated data. Interestingly, the choline -N(C (H) under bar (3))(3) region seems to provide more resolved clustering of lipoprotein subclasses in the SOM analyses than the methyl -C (H) under bar (3) region commonly used for subclass quantification. The results illustrate the inherent suitability of H-1 NMR metabonomics for automated studies of lipoprotein subclass-related metabolism and demonstrate the power of SOM analysis in an extensive and representative case of H-1 NMR metabonomics. Copyright (c) 2007 John Wiley & Sons, Ltd. Tirkkonen, T., Pakarinen, J., Moisander, A. M., Maekinen, J., Soini, H. and Ali-Vehmas, T. Veterinary Microbiology. 2007; 125(1-2): 175-181. Article. IF 2.073 Members of the Mycobacterium avium complex cause pig mycobacteriosis and opportunistic human infections. Infections due to environmental mycobacteria are increasing in both industrial and developing countries. Mycobacterium-infected pig carcasses can pass for human consumption due to the poor specificity of meat control by visual detection at the slaughter houses. The genetic relatedness of porcine and human MAC isolates in Finland has been unknown. M. avium isolates isolated from pig organs (n = 16) and clinical samples (n = 13) were compared by IS/245 RFLP analysis to evaluate the similarity of the isolates obtained from human and porcine samples. Nearly identical multicopy M. avium subsp. hominissuis IS 1245 RFLP fingerprints were obtained for isolates of porcine and human origin. IS/245 RFLP patterns of 38% of the porcine and human M. a. hominissuis isolates were >90% similar. The RFLP patterns of two porcine and two human isolates showed >95% similarity. The high similarity of the IS1245 RFLP patterns of the human and porcine M. a. hominissuis isolates indicates close genetic relatedness, suggesting that M. a. hominissuis is transmitted between pigs and humans, or that pigs and humans share common environmental sources of infection. Porcine and human isolates with RFLP patterns differing by only one or two bands were found, which shows that the same M. a. hominissuis strains may infect both humans and pigs. (C) 2007 Elsevier B.V. All rights reserved. Genetic and environmental influences on hearing in older women Viljanen, A., Era, P., Kaprio, J., Pyykkö, M., Koskenvuo, M. and Rantanen, T. Journals of Gerontology Series a-Biological Sciences and Medical Sciences. 2007; 62(4): 447-452. Article. IF 2.861 Background. This study examined the relative contribution of genetic and environmental effects on the air-conducted hearing threshold level (0.5-4 kHz) and speech recognition threshold level of the better ear as well as self-reported hearing in older women. Methods. Hearing was measured as a part of the Finnish Twin Study on Aging in 103 monozygotic (MZ) and 114 dizygotic (DZ) female twin pairs aged 63-76 years. Audiometric measured hearing was tested using standardized methods in soundproof conditions. Self-reported hearing was assessed by a structured question. Quantitative genetic modeling was used for data analyses. Results. No significant differences in age, exposure to noise, hearing-aid use, auditory diseases or accidents, or number of self-reported chronic conditions or prescription medicines were observed between the MZ and DZ twins. A genetic component in common accounted for 75% (95% confidence interval [CI], 67%-81%) of the variance in the better ear's hearing threshold level and 54% (95% CI, 43%-64%) in the better ear's speech recognition threshold level, according to a bivariate genetic analysis. In addition, 10% (95% CI, 4%-15%) of the variance in the better ear's speech recognition threshold level was explained by its specific genetic component. Conclusion. Individual differences in audiometrically measured air-conducted hearing threshold level (0.5-4 kHz) and speech recognition threshold level in the better ear were largely accounted for by genetic differences between individuals. In contrast, self-reported hearing appears to be accounted for solely by environmental factors. |