|
New articles - Uudet artikkelit 6.10.2008 - ISI Web of Knowledge & PubMed Search Alert
|
|
Interaction of early cow's milk-based formula exposure and enterovirus infection in infancy in the development of type 1 diabetes-associated autoimmunity
Aarnisalo, J., Honkanen, H., Makela, M., Tauriainen, S., Marttila, J., Veijola, R., Knip, M., Simell, O., Hermann, R., Hyoty, H., Vaarala, O. and Ilonen, I Diabetologia. 2008; 51: S144-S144. Meeting Abstract. IF 5.822 Variation in KLK genes, prostate-specific antigen and risk of prostate cancer Ahn, J., Berndt, S. I., Wacholder, S., Kraft, P., Kibel, A. S., Yeager, M., Albanes, D., Giovannucci, E., Stampfer, M. J., Virtamo, J., Thun, M. J., Feigelson, H. S., Cancel-Tassin, G., Cussenot, O., Thomas, G., Hunter, D. J., Fraumeni, J. F., Hoover, R. N., Chanock, S. J. and Hayes, R. B. Nature Genetics. 2008; 40(9): 1032-1034. Letter. IF 25.556 Interleukin 17 activation in small intestine in rheumatoid arthritis and ankylosing spondylitis Aittomaki, S., Holtta, V., Salo, H. M., Paimela, L., Halme, L., Leirisalo-Repo, M. and Vaarala, O. Clinical and Experimental Rheumatology. 2008; 26(4): 727-727. Meeting Abstract. IF 2.270 Beldi, G., Wu, Y., Banz, Y., Nowak, M., Miller, L., Enjyoji, K., Haschemi, A., Yegutkin, G. G., Candinas, D., Exley, M. and Robson, S. C. Hepatology. 2008; 48(3): 841-852. Article. IF 10.734 Concanavalin A (Con A)-induced injury is an established natural killer T (NKT) cell-mediated model of inflammation that has been used in studies of immune liver disease. Extracellular nucleotides, such as adenosine triphosphate, are released by Con A-stimulated cells and bind to specific purinergic type 2 receptors to modulate immune activation responses. Levels of extracellular nucleotides are in turn closely regulated by ectonucleotidases, such as CD39/NTPDase1. Effects of extracellular nucleotides and CD39 on NKT cell activation and upon hepatic inflammation have been largely unexplored to date. Here, we show that NKT cells express both CD39 and CD73/ecto-5'-nucleotidase and can therefore generate adenosine from extracellular nucleotides, whereas natural killer cells do not express CD73. In vivo, mice null for CD39 are protected from Con A-induced liver injury and show substantively lower serum levels of interleukin-4 and interferon-gamma when compared with matched wild-type mice. Numbers of hepatic NKT cells are significantly decreased in CD39 null mice after Con A administration. Hepatic NKT cells express most P2X and P2Y receptors; exceptions include P2X3 and P2Y11. Heightened levels of apoptosis of CD39 null NKT cells in vivo and in vitro appear to be driven by unimpeded activation of the P2X7 receptor. CONCLUSION: CD39 and CD73 are novel phenotypic markers of NKT cells. Deletion of CD39 modulates nucleotide-mediated cytokine production by, and limits apoptosis of, hepatic NKT cells providing protection against Con A-induced hepatitis. This study illustrates a further role for purinergic signaling in NKT-mediated mechanisms that result in liver immune injury. Eight years of experience with molecular identification of human enteroviruses Blomqvist, S., Paananen, A., Savolainen-Kopra, C., Hovi, T. and Roivainen, M. Journal of Clinical Microbiology. 2008; 46(7): 2410-2413. Article. IF 3.708 We have successfully typed 1,121 human enterovirus (HEV) isolates during the last 8 years by adapting partial VP1 sequencing to routine identification of HEV isolated from diverse clinical and environmental specimens. The isolates include 48 of the 59 traditional nonpoliovirus HEV serotypes and members of 8 newly discovered types, which would have remained untypeable by neutralization using the conventional cross-sectional pools of antisera. Boyko, E. J., Shaw, J. E., Zimmet, P. Z., Chitson, P., Tuomilehto, J. and Alberti, K. Journal of Hypertension. 2008; 26(9): 1742-1749. Article. IF 4.364 OBJECTIVE: To estimate the associations between new-onset hypertension and glycemia, insulin resistance, and overall and regional adiposity in a prospective study conducted in Mauritius. RESEARCH DESIGN AND METHODS: Three thousand five hundred and eighty-one adults without hypertension, pregnancy, or known diabetes at baseline (1987) were followed for incident hypertension in 1992 and 1998, (systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg or antihypertensive medication treatment). Other measurements included fasting plasma glucose and 2-h plasma glucose after a 75-g oral glucose load, fasting insulin, BMI, waist circumference, smoking, alcohol use, exercise, and demographic information. Insulin sensitivity was estimated by the computerized homeostasis model assessment (HOMA2) program. RESULTS: In multivariable logistic models that included age, gender, ethnicity, alcohol use, exercise, education, systolic blood pressure, diastolic blood pressure, homeostasis model assessment, fasting plasma glucose, 2-h plasma glucose, BMI, and waist circumference, the independent predictors of incident hypertension by time of follow-up were (odds ratio for a 1 SD increase; 95% confidence interval): 1992 - age (1.73; 1.47-2.03), Creole ethnicity (1.42; 1.04-1.94), 2-h plasma glucose (1.26; 1.04-1.51); 1998 - age (1.60; 1.40-1.83) and BMI (1.33; 1.05-1.69). Also, systolic blood pressure and diastolic blood pressure significantly predicted hypertension at both time points. CONCLUSION: Risk factor patterns depended on duration of follow-up. Over 5 years, hypertension was related to 2-h plasma glucose but not to measures of body size or homeostasis model assessment, while over 11 years, incident hypertension was related to BMI but not waist circumference, 2-h plasma glucose, or homeostasis model assessment. These findings support a more important role for 2-h plasma glucose and overall adiposity than waist circumference, fasting plasma glucose, or insulin resistance in the development of hypertension in Mauritius. Castaneda, A. E., Suvisaari, J., Marttunen, M., Perala, J., Saarni, S. I., Aalto-Setala, T., Aro, H., Koskinen, S., Lonnqvist, J. and Tuuio-Henriksson, A. Journal of Affective Disorders. 2008; 110(1-2): 36-45. Article. IF 3.144 BACKGROUND: There is evidence for cognitive dysfunction in unipolar depression among middle-aged and elderly patients, but cognitive functioning among depressed young adults has scarcely been systematically investigated. The aims of the present study were to examine cognitive functioning among depressed young adults identified from the general population and to determine whether cognitive deficits vary as a function of different disorder characteristics, such as severity and age at onset. METHODS: Performance in verbal and visual short-term memory, verbal long-term memory and learning, attention, processing speed, and executive functioning was compared between a population-based sample of 21-35-year-olds with a lifetime history of non-psychotic unipolar depressive disorders without psychiatric comorbidity (n=68) and healthy controls derived from the same population (n=70). RESULTS: Depressed young adults were not found to be impaired in any of the assessed cognitive functions, except for some suggestion of mildly compromised verbal learning. Nevertheless, younger age at depression onset was associated with more impaired executive functioning. LIMITATIONS: The results may slightly underestimate of the true association between depression and cognitive impairments in the young adult population due to possible dropout of participants. Additionally, the problem of multiple testing was not entirely corrected. CONCLUSION: The findings from this study indicate that a lifetime history of non-psychotic unipolar depressive disorders among young adults without psychiatric comorbidity may be associated only with minimal cognitive deficits, even when some residual depressive symptoms are prevalent. However, early-onset depression may represent a more severe form of the disorder, associated with more cognitive dysfunction. Eerola, J. and Vakkari, P. Journal of Documentation. 2008; 64(1): 131-142. Article. IF 1.309 Purpose - This paper sets out to examine the degree to which General Finnish Thesaurus (GFT) and FinMeSh cover various semantic expressions of medical concepts in patients' questions and physicians' answers concerning cardiovascular diseases. The former represents arty persons' information needs. Design/methodology/approach - A total of 60 question-answer pairs were collected in a medical web site. Concepts and their expressions (terms) with their semantic relations were identified in questions and answers. Findings - FinMeSh covered 65 per cent and GFT 41 per cent of all medical terms in texts. The expressions of patients and physicians matched better with FinMeSh than GFT regardless of the type of expression. The difference in favour of FinMeSh was typically about 25 per cent-units. Originality/value - The low fit With users' vocabularies makes GFT a poor tool for supporting searching, whereas the relatively high fit of FinMeSH suggests that it is a reasonable tool in assisting searching. Conclusions concerning the bridging of these two thesauri sire discussed. Grimaldi, S., Partonen, T., Saarni, S. I., Aromaa, A. and Lonnqvist, J. Health and Quality of Life Outcomes. 2008; 6. Article. IF OBJECTIVE: Seasonal changes in mood and behavior are common in a general population, being of relevance to public health. We wanted to analyze whether the HRQoL is associated with the seasonal changes in mood and behavior. Because the shortage of exposure to daylight or artificial bright light has been linked to the occurrence of the seasonal changes, we wanted to know whether illumination indoors contributes to the HRQoL. METHODS: Of the sample of 7979 individuals, being representative of the Finnish general population aged 30 and over, 88% were interviewed face to face, and 84% participated in the health status examination after which the self-report assessment of the HRQoL and the seasonal changes in mood and behavior took place. The illumination levels experienced indoors were asked during the interview and the 12-item General Health Questionnaire (GHQ-12) was filled in before the health examination. RESULTS: The HRQoL was influenced by both the seasonal changes in mood and behavior (P < 0.001) and the illumination experienced indoors (P < 0.001). Greater seasonal changes (P < 0.001) and poor illumination indoors (P = 0.0035) were associated with more severe mental ill-being. CONCLUSION: The routinely emerging seasonal changes in mood and behavior are associated with the HRQoL and mental well-being. Better illumination indoors might alleviate the season-bound symptoms and thereby enhance the HRQoL and mental well-being. Clinical changes in periodontium during pregnancy and post-partum Gursoy, M., Pajukanta, R., Sorsa, T. and Kononen, E. J Clin Periodontol. 2008; 35(7): 576-83. IF 2.678 BACKGROUND AND AIM: Pregnancy has been presented to increase susceptibility to gingival inflammation. It is unclear whether pregnancy gingivitis exposes or proceeds to periodontitis. We examined longitudinally the severity of periodontal changes during pregnancy and post-partum, and compared the findings with an age-matched group of non-pregnant women. MATERIAL AND METHODS: Thirty generally healthy, non-smoking women at an early phase of their pregnancy and 24 non-pregnant women as controls were recruited. The pregnant group was examined three times during pregnancy and twice during post-partum, and the non-pregnant group three times, once per subsequent month. At each visit, visible plaque index (VPI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were measured from six sites per tooth. RESULTS: In the pregnant group, BOP and PPD increased simultaneously without relation to plaque between the first and second trimesters, and thereafter decreased during subsequent visits. No changes were detected in CAL during the study period. In the non-pregnant group, BOP stayed invariable during the follow-up and correlated with the amount of plaque. Neither periodontal pocket formation nor significant changes in attachment levels were observed. CONCLUSION: Based on this study, changes in clinical parameters during pregnancy are reversible, indicating that pregnancy gingivitis does not predispose or proceed to periodontitis. Haanpera, M., Forssten, S. D., Huovinen, P. and Jalava, J. Antimicrob Agents Chemother. 2008; 52(7): 2632-5. 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. Hazardous drinking: Prevalence and associations in the Finnish general population Halme, J. T., Seppa, K., Alho, H., Pirkola, S., Poikolainen, K., Lonnqvist, J. and Aalto, M. Alcoholism-Clinical and Experimental Research. 2008; 32(9): 1615-1622. Article. IF 3.175 BACKGROUND: Hazardous drinking, defined as consuming alcohol on a risky level and not meeting the diagnostic criteria of alcohol use disorders (AUDs), has been suggested for a new complementary nondependence diagnosis. This study aimed to investigate the prevalence and associations of hazardous drinking in comparison to AUDs, moderate drinking, and abstinence. METHODS: A national representative sample of Finns was examined in the Health 2000 Survey. For 4477 subjects aged 30 to 64 years (76%, 2341 females), both the quantity frequency data about alcohol consumption and Composite International Diagnostic Interview (CIDI) data concerning AUD diagnoses were available. The nationally recommended limits for hazardous dinking were used (males: 24 drinks, females: 16 drinks/wk). Logistic regression models were used to analyze associations. RESULTS: The prevalence of hazardous drinking was 5.8%. Hazardous drinking was more prevalent among males than females (8.5% vs. 3.1%). It was most prevalent among the subjects aged 40 to 49 years (7.3%), divorced or separated (8.3%), unemployed (8.2%) and subjects living in the southern (Helsinki) region (7.5%). AUDs versus hazardous drinking were more likely to be in males versus females and in the unemployed versus employed. Subjects aged 40 and over had higher odds for hazardous drinking versus AUDs. The odds for hazardous versus moderate drinking were higher for males versus females (adjusted odds ratio = 3.24), for subjects aged over 40 years, unemployed versus employed and cohabiting, divorced/separated or unmarried subjects versus married subjects. CONCLUSION: The high prevalence of hazardous drinking makes it an important public health concern. Hazardous drinkers have different sociodemographic characteristics as compared to people in other alcohol use categories. 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. Journal of Clinical Oncology. 2008; 26(25): 4086-4091. Article. 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. Circadian phenotype in patients with the co-morbid alcohol use and bipolar disorders Hatonen, T., Forsblom, S., Kieseppa, T., Lonnqvist, J. and Partonen, T. Alcohol and Alcoholism. 2008; 43(5): 564-568. Article. IF 2.061 AIMS: Alcohol misuse is associated with bipolar disorder. Abnormalities in the circadian clockwork play a role in the pathogenesis of bipolar disorder. Alcohol intake is likely to affect the circadian phenotype. We aimed at analysing the behavioural trait of the preference to morning or evening hours for the daily activities in bipolar disorder patients with or without the co-morbid alcohol use. METHODS: Our nationwide sample of families included patients with bipolar disorder born during 1940-1969 having at least one hospitalization due to bipolar disorder during 1969-1991 and their first-degree relatives. All the 148 participants were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders and assessed using the Morningness-Eveningness Questionnaire whose factor matrix applying for the maximum likelihood principle was calculated for the first time. RESULTS: Patients with the co-morbid alcohol use disorder were more of the morning type as compared with patients with bipolar disorder only. CONCLUSIONS: Co-morbid patients preferred more the morning hours for their daily activities, indicative of alcohol consumption having an effect on the circadian clock. Hattersley, A. T., Freathy, R. M., Bennett, A. I., Ring, S. M., Timpson, N. J., Pouta, A., Ruokonen, A., Hypponen, E., Power, C., Elliott, P., Strachan, D. P., Jarvelin, M. R., Smith, G. D., McCarthy, M. I. and Frayling, T. M. Diabetologia. 2008; 51: S127-S128. Meeting Abstract. IF 5.822 Helakorpi, S., Martelin, T., Torppa, J., Vartiainen, E., Uutela, A. and Patja, K. Prev Med. 2008; 46(4): 340-5. IF 2.314 OBJECTIVE: To assess the impact of the 1976 Tobacco Control Act (TCA) on smoking initiation across socioeconomic groups. METHODS: Nationwide data from independent annual cross-sectional postal surveys in 1978-2002 in Finland. Subjects were 25-64-year-old men and women born 1926-1975 (n=68 071). Socioeconomic status was derived individually from population census data. Logistic regression was applied to assess the impact of the 1976 TCA on the prevalence of ever daily smoking in birth cohorts and socioeconomic groups. RESULTS: Clear socioeconomic differences in ever daily smoking among men and women were found. In all socioeconomic groups a declining cohort trend was observed among men whereas women showed an increasing trend in early cohorts and a declining one thereafter. A statistically significant decline in the proportion of ever daily smokers compatible with the impact of the TCA was found in all socioeconomic groups except farmers. Among women the decline was roughly similar in each socioeconomic group, while among men it varied and was most pronounced among white collar employees. CONCLUSIONS: The impact of the 1976 TCA was less pronounced among male lower socioeconomic groups. In spite of the even impact of the TCA on female smoking across socioeconomic groups, large socioeconomic disparities remain. Tobacco control policy measures specifically directed at lower socioeconomic groups are needed. IL-23/IL-17 immunity as a hallmark of Crohn's disease. Holtta, V., Klemetti, P., Sipponen, T., Kociubinski, G., Westerholm-Ormio, M., Solo, H., Rasanen, L., Kolho, K. L., Farkkila, M., Savilahti, E. and Vaarala, O. Inflammatory Bowel Diseases. 2008; 14(9): 1175-1184. Article. IF 4.705 BACKGROUND: We studied the balance between ileal T-effector cells versus T-regulatory cells in active and inactive Crohn's disease (CD). METHODS: We compared effector and regulatory T-cell-related markers such as interleukin (IL)-17, interferon (IFN)-gamma, IL-4, and Foxp3 transforming growth factor (TGF)-beta CTLA-4 and markers for innate immune activation such as IL-6, IL-10, IL-18, IL-23, tumor necrosis factor (TNF)-alpha, and IL-12p70, studied with immunohistochemistry and RT-PCR in ileal biopsies from patients with active or inactive CD and from control subjects. IL-17 in fecal samples was detected by ELISA. The effect of IL-17 on IL-8 and TNF-alpha mRNA expression in epithelial cell line Caco-2 was studied. RESULTS: The numbers of IL-4-, IL-17-, and IL-23(p19)-positive cells in the lamina propria were higher in patients with CD, both active and inactive, than in the controls. mRNA expression of IL-17A, IL-6, and Foxp3 was increased in the biopsies both from patients with active disease and those in remission, whereas mRNA expression of IL-23 was increased only in active disease. Fecal IL-17 concentration was increased in patients with active disease. IL-17 enhanced the IL-8 and TNF-alpha response of the epithelial cell line to lipopolysaccharide (LPS) in vitro. CONCLUSIONS: Our findings suggest that activation of the IL-23/IL-17 axis is fundamentally connected to the etiology of CD and may represent the basis for the relapsing nature of the disease by increasing the sensitivity of epithelium to microbial LPS. New models and molecular markers in evaluation of developmental toxicity. Huuskonen, H. Toxicol Appl Pharmacol. 2005; 207(2 Suppl): 495-500. IF 3.846 Mammalian and non-mammalian embryos and embryonic stem cells may be used as models in mechanistic studies and in testing embryotoxicity of compounds. In addition to conventional culture methods, genetic modifications and use of molecular markers offer significant advantages in mechanistic studies as well as in developing new test methods for embryotoxicity. Zebrafish model has been used for a long time and at present several applications are available. It is an easy vertebral non-mammalian model, whose genome is largely known and several genetic modifications are easily constructed to study gene expression or knocked down genes. Fluorescent marker proteins can be used also in zebrafish to indicate gene activation in transgenic models. Chemical genetics approach has been developed using zebrafish model. This is a new approach to screen small molecules that regulate signaling pathways. Embryonic stem cells have been used in mechanistic studies and mouse embryonic stem cell test has been validated to study embryotoxicity in vitro. This method has been improved using quantitative measurements of molecular endpoints by real-time RT-PCR or fluorescent activated cell sorting methods (FACS). Methods facilitating differentiation to several different cell types are available. We have studied preimplantation mouse embryos as a possible model for in vitro testing. In this method, superovulated and in vivo fertilized preimplantation embryos were collected at morula stage and cultured up to blastocysts. The mouse preimplantation culture test was improved by quantitative gene expression measurement using two-step real-time RT-PCR methods. New endpoints improve the tests of in vitro embryotoxicity because subjective assessments are replaced by objective measurements. In addition, automation is possible and less time is needed for analysis. Thus, high throughput screening will come possible to test large numbers of compounds. Jacquemin, B., Antoniades, C., Nyberg, F., Plana, E., Muuller, M., Greven, S., Salomaa, V., Sunyer, J., Bellander, T., Chalamandaris, A. G., Pistelli, R., Koenig, W. and Peters, A. Journal of the American College of Cardiology. 2008; 52(11): 941-952. Article. IF 11.054 Objectives: This study was designed to investigate whether single nucleotide polymorphisms (SNPs) and haplotypes of the fibrinogen gene-cluster (fibrinogen chains alpha [FGA], beta [FGB], and gamma [FGG]) could explain the inter and intraindividual variability of fibrinogen levels in patients with atherosclerosis. We also searched for genetic determinants affecting the responses of fibrinogen genes to proinflammatory stimulation. Background: The mechanisms regulating fibrinogen levels are not fully understood, and they are likely to be regulated by complex gene-environment interactions. Methods: In the AIRGENE study, 895 survivors of myocardial infarction from 5 European cities were followed prospectively for 6 to 8 months, and plasma fibrinogen, interleukin (IL)-6, and C-reactive protein levels were determined monthly. We analyzed 21 SNPs and the corresponding haplotypes in the 3 fibrinogen genes. Results: Eight SNPs in FGA and FGB were significantly associated with fibrinogen levels. Similarly, 2 different haplotypes in FGA and 3 in FGB were also associated with mean fibrinogen levels. The IL-6 levels had a significant impact on the associations between SNPs/haplotypes in FGA/FGB and fibrinogen levels. We also identified SNPs and haplotypes in FGA and FGB with strong impact on the intraindividual variability of fibrinogen during the follow-up period. Conclusions: We identified common SNPs and haplotypes on FGA/FGB genes, explaining the interindividual and intraindividual variability of fibrinogen levels, in patients with a history of myocardial infarction. We have also identified for the first time, SNPs/haplotypes on FGA/FGB whose effects on fibrinogen expression are modified by the underlying IL-6 levels. These findings may have an impact on risk stratification and the design of genetically guided therapeutic approaches in patients with advanced atherosclerosis. Is migraine a lateralization defect? Kaaro, J., Partonen, T., Naik, P. and Hadjikhani, N. Neuroreport. 2008; 19(13): 1351-1353. Article. IF 2.163 Migraine often co-occurs with patent foramen ovale (PFO), and some people have suggested surgical closure as an efficient treatment for migraine. Prospective studies, however, do not report radical effect of PFO surgery on migraine. Here, we examined the hypothesis that PFO and migraine may cooccur as two independent manifestations of lateralization defect during embryonic development. We measured the absolute displacement of a midline structure, the pineal gland, on brain scans of 39 migraineurs and 26 controls. We found a significant asymmetry of the pineal gland in migraineurs compared with controls. Our data suggest that migraine's circadian component and its association with PFO may be linked to a lateralization defect during embryogenesis, which could be a result from abnormal serotonin regulation. Lipopolysaccharide associates with pro-atherogenic lipoproteins in periodontitis patients Kallio, K. A. E., Buhlin, K., Jauhiainen, M., Keva, R., Tuomainen, A. M., Klinge, B., Gustafsson, A. and Pussinen, P. J. Innate Immunity. 2008; 14(4): 247-253. Article. IF INTRODUCTION: Periodontitis patients are known to suffer from endotoxemia, which may be among the major risk factors for atherosclerosis. In health, lipopolysaccharide (LPS) is mainly carried with high density lipoprotein (HDL) particles. Shift of LPS toward lipoproteins with lower densities may result in less effective endotoxin scavenging. Our aim was to determine plasma LPS activity and lipoprotein-distribution before and after treatment in periodontitis patients. PATIENTS AND METHODS: Very low and intermediate density (VLDL-IDL), low density (LDL), HDL 2, HDL3, and lipoprotein-deficient plasma (LPDP) were isolated by sequential ultracentrifugation. Patients included 34 subjects aged 53.5 +/- 8.3 years, before and 6 months after periodontal treatment. RESULTS: The mean LPS distribution decreased among lipoprotein classes as follows: VLDL-IDL 41.3 +/- 12.1%, LPDP 25.0 +/- 7.0%, HDL3 13.1 +/- 5.2%, LDL 11.5 +/- 3.7%, and HDL2 9.2 +/- 2.8%. Plasma and VLDL-IDL-associated LPS correlated positively, and LDL- and HDL-associated LPS negatively with clinical periodontal parameters and plasma cytokine concentrations. Mean plasma LPS activity increased after periodontal treatment from 44.0 +/- 17.0 to 55.7 +/- 24.2 EU/ml (P = 0.006). No significant changes were found in LPS lipoprotein distribution and lipoprotein compositions after the treatment. CONCLUSIONS: Endotoxemia increases with severity of periodontitis. In periodontitis, LPS associates preferentially with the pro-atherogenic VLDL-IDL fraction. Periodontal treatment has only minor effects on plasma LPS activity or distribution, which reflects persistence of the disease. Kantele, A. M., Palkola, N. V., Arvilommi, H. S. and Kantele, J. M. Clinical Immunology. 2008; 128(3): 427-434. Article. IF 3.551 In contrast to other mucosal sites, information on migration/homing of lymphocytes activated in the human urinary tract is lacking. The expression of lymphocyte homing receptors (HR) on pathogen-specific antibody-secreting cells (ASC) originating from the urinary tract (patients with pyelonephritis, PN) was compared to that on antigen-specific ASC originating from the intestine (patients with gastroenteritis) or from a parenteral site (tetanus toxoid-immunized volunteers). In the PN group, 61% of ASC expressed the gut HR, alpha(4)beta(7,) 52% the peripheral lymph node HR, L-selectin, and 13% the skin HR, CLA. This homing profile of urinary tract-originating lymphocytes was found to differ from both of the two major vaccination routes, intestinal (less gut-targeting) or parenteral (more gut-targeting, less targeting to parenteral sites). This information on targeting of the immune response may prove useful when developing vaccines against urinary tract infection (UTI). Keskitalo, K., Tuorila, H., Spector, T. D., Cherkas, L. F., Knaapila, A., Kaprio, J., Silventoinen, K. and Perola, M. American Journal of Clinical Nutrition. 2008; 88(2): 263-271. Article. IF 6.603 BACKGROUND: The relation between body weight and energy-dense foods remains unclear. OBJECTIVE: We estimated the effects of genetic and environmental factors on cognitive and emotional aspects of dieting behavior, body mass index (BMI), and responses to fatty foods and on their relations. DESIGN: A total of 1326 adult twin persons (aged 17-82 y; 17% M and 83% F) from the United Kingdom and Finland completed the revised version of the Three-Factor Eating Questionnaire (TFEQ-R18) and reported the liking and use-frequency of 4 sweet-and-fatty and salty-and-fatty food items (6 items in the United Kingdom and 5 items in Finland). Genetic modeling was done by using linear structural equations. RESULTS: Heritability estimates were calculated separately for the countries and sexes; they were 26-63% for cognitive restraint, 45-69% for uncontrolled eating, and 9-45% for emotional eating, respectively. Of the variation in liking and use-frequency of fatty foods, 24-54% was attributed to interindividual genetic differences. No significant correlations were observed between BMI and fatty food use or liking. However, BMI was positively (mostly genetically) correlated (genetic r = 0.16-0.51) with all of the dieting behaviors, and they correlated with fatty food use and liking ratings. Uncontrolled eating was both genetically and environmentally associated with liking for salty-and-fatty foods (genetic and environmental r = 0.16), and emotional eating was genetically associated with liking for sweet-and-fatty foods (genetic r = 0.31). CONCLUSIONS: The relation between BMI and diet appears to be mediated through dieting behaviors. Dietary counseling should focus on unhealthy dieting behaviors rather than only on direct advice on food use. Antibiotic use predicts an increased risk of cancer Kilkkinen, A., Rissanen, H., Klaukka, T., Pukkala, E., Heliovaara, M., Huovinen, P., Mannisto, S., Aromaa, A. and Knekt, P. Int J Cancer. 2008; 123(9): 2152-5. IF 4.555 Antibiotic use has been hypothesized to be associated with the risk of cancer but the evidence is sparse and inconsistent. The aim of the present study was to determine whether antibiotic use predicts the development of various cancers. This nationwide cohort study included 3,112,624 individuals, aged 30-79 years, with no history of cancer. Information on their antibiotic use between 1995 and 1997 was obtained from the Drug Prescription Registry. During the period 1998-2004, 134,070 cancer cases were ascertained from the Finnish Cancer Registry. Cox proportional hazards regression was used to estimate the relative risks (RRs) with 95% confidence intervals (95% CIs). Antibiotic use was associated with an increased risk of cancer: for categories of increasing antibiotic use (0-1, 2-5 and >/=6 prescriptions), RRs (95% CIs) for cancer were 1.0 (reference), 1.27 (1.26-1.29) and 1.37 (1.34-1.40). RRs (for comparison of lowest and highest exposure group) for the most common primary sites i.e. prostate, breast, lung and colon were 1.39 (1.31-1.48), 1.14 (1.09-1.20), 1.79 (1.67-1.92), and 1.15 (1.04-1.26), respectively. RRs for other primary sites varied between 0.90 (0.76-1.05) for ovary to 2.60 (1.60-4.20) for endocrine gland (excluding thyroid). In conclusion, antibiotic use predicts an increased risk of cancer. Because of the design of our study the possibility of residual confounding cannot be excluded and further studies are required to confirm the results. Kiviranta, P. H., Salo, H. S., Leppanen, J., Rinne, V. M., Kyrylenko, S., Kuusisto, E., Suuronen, T., Salminen, A., Poso, A., Lahtela-Kakkonen, M. and Wallen, E. A. A. Bioorganic & Medicinal Chemistry. 2008; 16(17): 8054-8062. Article. IF 2.662 SIRT2 inhibitors with a N-(3-phenylpropenoyl)-glycine tryptamide backbone were studied. This backbone has been developed in our group, and it is derived from a compound originally found by virtual screening. In addition, compounds with a smaller 3-phenylpropenoic acid tryptamide backbone were also included in the study. Binding modes for the new compounds and the previously reported compounds were analyzed with molecular modelling methods. The approach, which included a combination of molecular dynamics, molecular docking and cluster analysis, showed that certain docking poses were favourable despite the conformational variation in the target protein. The N-(3-phenylpropenoyl)-glycine tryptamide backbone is also a good backbone for SIRT2 inhibitors, and the series of compounds includes several potent SIRT2 inhibitors. Klemets, P., Lyytikainen, O., Ruutu, P., Ollgren, J. and Pekka Nuorti, J. BMC Infect Dis. 2008; 8: 96. IF 2.021 BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for persons aged < 65 years with chronic medical conditions. We evaluated the risk and mortality from invasive pneumococcal disease (IPD) among persons with and without the underlying medical conditions which are considered PPV23 indications. METHODS: Population-based data on all episodes of IPD (positive blood or cerebrospinal fluid culture) reported by Finnish clinical microbiology laboratories during 1995-2002 were linked to data in national health care registries and vital statistics to obtain information on the patient's preceding hospitalisations, co-morbidities, and outcome of illness RESULTS: Overall, 4357 first episodes of IPD were identified in all age groups (average annual incidence, 10.6/100,000). Patients aged 18-49 and 50-64 years accounted for 1282 (29%) and 934 (21%) of IPD cases, of which 372 (29%) and 427 (46%) had a current PPV23 indication, respectively. Overall, 536 (12%) IPD patients died within one month of first positive culture. Persons aged 18-64 years accounted for 254 (47%) of all deaths (case-fatality proportion, 12%). Of those who died 117 (46%) did not have a vaccine indication. In a survival model, patients with alcohol-related diseases, non-haematological malignancies, and those aged 50-64 years were most likely to die. CONCLUSION: In the general population of non-elderly adults, almost two-thirds of IPD and half of fatal cases occurred in persons without a recognised PPV23 indication. Policymakers should consider additional prevention strategies such as lowering the age of universal PPV23 vaccination and introducing routine childhood pneumococcal conjugate immunisation which could provide substantial health benefits to this population through indirect vaccine effects. Serum vitamin D and subsequent occurrence of type 2 diabetes Knekt, P., Laaksonen, M., Mattila, C., Harkanen, T., Marniemi, J., Heliovaara, M., Rissanen, H., Montonen, J. and Reunanen, A. Epidemiology. 2008; 19(5): 666-671. Article. IF 5.283 BACKGROUND: Low vitamin D status has been suggested as a risk factor for type 2 diabetes. Although the epidemiologic evidence is scarce, 2 recent studies have suggested an association. The present study investigated the relation of serum vitamin D with type 2 diabetes incidence using pooled data from these 2 cohorts. METHODS: Two nested case-control studies, collected by the Finnish Mobile Clinic in 1973-1980, were pooled for analysis. The study populations consisted of men and women aged 40-74 years and free of diabetes at baseline. During a follow-up period of 22 years, 412 incident type 2 diabetes cases occurred, and 986 controls were selected by individual matching. Serum vitamin D (serum 25(OH)D) was determined from frozen samples, stored at baseline. Pooled estimates of the relationship between serum vitamin D concentration and type 2 diabetes incidence were calculated. RESULTS: Men had higher serum vitamin D concentrations than women and showed a reduced risk of type 2 diabetes in their highest vitamin D quartile. The relative odds between the highest and lowest quartiles was 0.28 (95% confidence interval = 0.10-0.81) in men and 1.14 (0.60-2.17) in women after adjustment for smoking, body mass index, physical activity, and education. CONCLUSIONS: The results support the hypothesis that high vitamin D status provides protection against type 2 diabetes. Residual confounding may contribute to this association. Koistinen, J., Kiviranta, H., Ruokojarvi, P., Parmanne, R., Verta, M., Hallikainen, A. and Vartiainen, T. Environ Pollut. 2008; 154(2): 172-83. IF 3.135 Organohalogen contaminants were investigated in Baltic herring caught from three catchment areas in the Baltic Sea, off the coasts of Finland. Pools of both small and large herring were analysed for polychlorinated biphenyls (PCB), dibenzo-p-dioxins, dibenzofurans, naphthalenes, camphenes (toxaphene), polybrominated diphenyl ethers and the pesticide DDT and its metabolites. PCB concentrations per fresh weight in small herring were at the same level in all catchment areas, i.e. the Bothnian Bay, the Bothnian Sea and the Gulf of Finland, revealing no hot spots and reflecting most likely long term emissions and atmospheric deposition. Differences in the levels and/or congener profiles of other contaminants between catchment areas may be explained by point sources. Similar concentrations in small and large herring in the Gulf of Finland were possibly due to their common nutrition. In the other areas, differences between small and large herring most likely reflected their different food sources. Koivunen, R., Pouta, A., Franks, S., Martikainen, H., Sovio, U., Hartikainen, A. L., McCarthy, M. I., Ruokonen, A., Bloigu, A., Jarvelin, M. R. and Morin-Papunen, L. Human Reproduction. 2008; 23(9): 2134-2139. Article. IF 3.543 BACKGROUND: Women with polycystic ovary syndrome (PCOS) suffer from anovulatory infertility and hospital-based studies suggest that they have an increased risk of spontaneous abortion. Our aim was to investigate the proportion of women, with self-reported oligo-amenorrhea and/or hirsutism in a general population, who had suffered from infertility, the percentage of them managing to conceive and their rate of spontaneous abortion. METHODS: At age 31, a postal questionnaire including questions about hirsutism and oligo-amenorrhea was sent to all women from the population-based Northern Finland Birth Cohort 1966 (total n = 5889). Of these, 4535 (79.5%) answered the questionnaire, 1103 reported hirsutism and/or oligo/amenorrhea (symptomatic women) and 3420 were non-symptomatic. The fecundability ratio (FR) was defined as the probability of conception of a clinically detectable pregnancy within 12 months. RESULTS: The overall pregnancy (77.7% versus 75.6%) and spontaneous abortion (19.3% versus 18.6%) rates did not differ between the two groups and the risk of spontaneous abortion was not associated with body mass index (BMI), waist-to-hip ratio (WHR) or waist circumference. Symptomatic women had suffered more often from infertility than non-symptomatic women (19.4% versus 11.1%, P < 0.01). Oligo-amenorrhea and/or hirsutism (FR = 0.74, P < 0.001) and obesity (FR = 0.68, P = 0.002) were both independently associated with decreased fecundability, but symptomatic women had become pregnant and had one or two successful deliveries as often as non-symptomatic women. CONCLUSIONS: Women with self-reported oligo-amenorrhea and/or hirsutism had lower fecundability and suffered more often from infertility, but had at least one delivery as often as non-symptomatic women, and did not exhibit an increased risk of spontaneous abortion. Koskela, A., Kauppinen, T., Keski-Rahkonen, A., Sihvola, E., Kaprio, J., Rissanen, A. and Ahonen, A. Chronobiology International. 2008; 25(5): 657-665. Article. IF 3.771 The neurotransmitter serotonin (5-HT) controls several physiological functions, and a disturbance of the 5-HT system is implicated in many psychiatric conditions. Seasonal variation has been suggested in the 5-HT system. We investigated within-subject seasonal variation in brain serotonin transporter (SERT) binding with the SERT-ligand [I-123]ADAM and single photon emission computed tomography (SPECT) in 12 healthy individuals. No systematic variation was found in the midbrain or thalamus areas between scans done in summer and winter. Our results suggest that factors other than season are more important in causing within-subject variation of brain SERT binding between summer and winter. Kroneman, A., Verhoef, L., Harris, J., Vennema, H., Duizer, E., van Duynhoven, Y., Gray, J., Iturriza, M., Bottiger, B., Falkenhorst, G., Johnsen, C., von Bonsdorff, C. H., Maunula, L., Kuusi, M., Pothier, P., Gallay, A., Schreier, E., Hohne, M., Koch, J., Szucs, G., Reuter, G., Krisztalovics, K., Lynch, M., McKeown, P., Foley, B., Coughlan, S., Ruggeri, F. M., Di Bartolo, I., Vainio, K., Isakbaeva, E., Poljsak-Prijatelj, M., Grom, A. H., Mijovski, J. Z., Bosch, A., Buesa, J., Fauquier, A. S., Hernandez-Pezzi, G., Hedlund, K. O. and Koopmans, M. Journal of Clinical Microbiology. 2008; 46(9): 2959-2965. Article. IF 3.708 The Foodborne Viruses in Europe network has developed integrated epidemiological and virological outbreak reporting with aggregation and sharing of data through a joint database. We analyzed data from reported outbreaks of norovirus (NoV)-caused gastroenteritis from 13 European countries (July 2001 to July 2006) for trends in time and indications of different epidemiology of genotypes and variants. Of the 13 countries participating in this surveillance network, 11 were capable of collecting integrated epidemiological and virological surveillance data and 10 countries reported outbreaks throughout the entire period. Large differences in the numbers and rates of reported outbreaks per country were observed, reflecting the differences in the focus and coverage of national surveillance systems. GII.4 strains predominated throughout the 5-year surveillance period, but the proportion of outbreaks associated with GII.4 rose remarkably during years in which NoV activity was particularly high. Spring and summer peaks indicated the emergence of genetically distinct variants within GII.4 across Europe and were followed by increased NoV activity during the 2002 - 2003 and 2004 - 2005 winter seasons. GII.4 viruses predominated in health care settings and in person-to-person transmission. The consecutive emergence of new GII.4 variants is highly indicative of immune-driven selection. Their predominance in health care settings suggests properties that facilitate transmission in settings with a high concentration of people such as higher virus loads in excreta or a higher incidence of vomiting. Understanding the mechanisms driving the changes in epidemiology and clinical impact of these rapidly evolving RNA viruses is essential to design effective intervention and prevention measures The unique toxic effect of acrebol, a novel peptide from Acremonium exuviarum Kruglov, A. G., Andersson, M. A., Mikkola, R., Kredics, L., Roivainen, M., Saris, N. E. L. and Salkinoja-Salonen, M. S. Journal of Peptide Science. 2008; 14(8): 103-104. Meeting Abstract. IF 1.768 Night-time work predisposes to non-Hodgkin lymphoma Lahti, T. A., Partonen, T., Kyyronen, P., Kauppinen, T. and Pukkala, E. Int J Cancer. 2008; 123(9): 2148-51. IF 4.555 Our aim was to find out whether non-Hodgkin lymphoma (NHL) was more common than expected among night-time shift workers. The Finnish job-exposure matrix (FINJEM) provided estimates of the proportion of exposed persons and the mean level of exposure among the exposed in each occupation. The probability of night-time work in each occupation was assessed, the observed and expected numbers of cancer cases in a cohort of persons born in 1906-1945 during the years of 1971-1995 were calculated, and the cumulative index of night-time work was scored. The cohort compromised of 1,669,272 persons of whom 6,307 (3,813 men and 2,494 women) had NHL during the follow-up. Night-time work increased significantly (p = 0.01) the risk of NHL in men, the overall relative risk being 1.10 (95% confidence interval of 1.03-1.19). Using the lag period of 10 years, the risk ratio was 1.28 (1.03-1.59) for men who worked in night-time shifts to a high degree as compared with those who had not been exposed to night-time work. Night-time workers are cancer prone and have a greater risk of NHL than population on average. (c) 2008 Wiley-Liss, Inc. Laiyemo, A., Kamangar, F., Marcus, P., Taylor, P., Virtamo, J., Albanes, D. and Stolzenberg-Solomon, R. American Journal of Gastroenterology. 2008; 103: S544-S545. Meeting Abstract. IF 6.101 |