Vistbakka J.,University of Tampere |
Elovaara I.,University of Tampere |
Lehtimaki T.,University of Tampere |
Lehtimaki T.,Fimlab Laboratories |
Hagman S.,University of Tampere
Multiple Sclerosis | Year: 2017
Background: In multiple sclerosis (MS), microRNA (miRNA) dysregulation is mostly reported in different immune cells, but less information is available on circulating miRNAs that exert strong biomarker potential due to their exceptional stability in body fluids. Objective: The aim of this study was to profile expression of circulating miRNAs in primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) and assess their association with neurological worsening. Methods: The expressions of 84 different miRNAs were profiled in serum of 83 subjects (62 MS and 21 controls) using miScript miRNA techniques. First, they were screened on 18 PPMS and 10 controls; thereafter, 10 most aberrantly expressed miRNAs were validated on a larger cohort. Results: In comparison with controls, upregulation of miR-191-5p was found in both progressive MS subtypes, while miR-376c-3p was overexpressed only in PPMS. Additionally, upregulation of miR-128-3p and miR-24-3p was detected in PPMS when compared to controls and SPMS. Progression index correlated with miR-128-3p in PPMS and miR-375 in SPMS. Conclusion: We detected overexpression of four miRNAs that have not been previously associated with progressive forms of MS. The increased expression of circulating miR-191-5p seems to be associated with progressive forms of MS, while miR-128-3p seems to be associated mostly with PPMS. © SAGE Publications.
Uusitalo-Seppala R.,Satakunta Central Hospital |
Huttunen R.,University of Tampere |
Aittoniemi J.,Fimlab Laboratories |
Koskinen P.,University of Turku |
And 3 more authors.
PLoS ONE | Year: 2013
Background: Early diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection. Methods: The study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA). Results: The median PTX3 levels in groups 1-5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (p<0.001). The median PTX3 concentration was higher in severe sepsis patients compared to others (16.7 vs. 4.9 ng/ml, p<0.001) and in non-survivors (day 28 case fatality) compared to survivors (14.1 vs. 5.1 ng/ml, p<0.001). A high PTX3 level predicted the need for ICU stay (p<0.001) and hypotension (p<0.001). AUCROC in the prediction of severe sepsis was 0.73 (95% CI 0.66-0.81, p<0.001) and 0.69 in case fatality (95% CI 0.58-0.79, p<0.001). PTX3 at a cut-off level for 14.1 ng/ml (optimal cut-off value for severe sepsis) showed 63% sensitivity and 80% specificity. At a cut-off level 7.7 ng/ml (optimal cut-off value for case fatality) showed 70% sensitivity and 63% specificity in predicting case fatality on day 28.In multivariate models, high PTX3 remained an independent predictor of severe sepsis and case fatality after adjusting for potential confounders. Conclusions: A high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection. © 2013 Uusitalo-Seppälä et al.
Alarmo E.-L.,University of Tampere |
Alarmo E.-L.,Fimlab Laboratories |
Huhtala H.,University of Tampere |
Korhonen T.,University of Tampere |
And 8 more authors.
Modern Pathology | Year: 2013
Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor β (TGFβ) superfamily and are known to regulate cell proliferation, differentiation and motility, especially during development. BMP4 has an indispensable role in vertebrate development while limited information on BMP4 expression and function exists in adult tissues. Nevertheless, its contribution to cancer development and progression has gained increasing interest in recent years. Functional studies, especially in breast cancer, have implicated BMP4 both in inhibition of cell proliferation and in promotion of cell migration and invasion. To gain an insight into the function of BMP4 in normal and cancer tissues, BMP4 protein expression levels were analyzed by immunohistochemistry in 34 different normal organs/tissues, 34 different tumor types and finally in 486 breast cancer samples where possible associations between BMP4 and clinicopathological parameters were statistically evaluated. In over 20% of normal and malignant tissues, BMP4 was expressed at high level. Strong expression was observed particularly in some normal epithelial cells, such as bladder and stomach, and in squamous cell carcinomas. In breast cancer, strong BMP4 expression was detected in 25% of patients, and was associated with low proliferation index and increased frequency of tumor recurrence. Taken together, BMP4 is expressed in a subset of normal adult tissues and is likely to contribute to tissue homeostasis. However, in tumors, BMP4 expression levels vary considerably, implying diverse roles in different tumor types. This role is biphasic in breast cancer as BMP4 expression is linked to reduced proliferation and increased recurrence, thus corroborating our previous in-vitro functional data. © 2013 USCAP, Inc.
Jylhava J.,University of Tampere |
Lehtimaki T.,University of Tampere |
Jula A.,Finnish National Institute for Health and Welfare |
Moilanen L.,Kuopio University Hospital |
And 5 more authors.
Atherosclerosis | Year: 2014
Cell-free circulating DNA (cf-DNA) has recently arisen as a promising biomarker in acute cardiovascular pathologies and as a mortality predictor in myocardial infarction. We wanted to investigate whether the baseline cf-DNA concentration could serve as an indicator of increased cardiovascular risk and early atherosclerosis. The study population consisted of 1337 participants (aged 46-77 years) in the Health 2000 Survey. cf-DNA was quantified directly in plasma using the fluorescence-based Quant-iT™ high-sensitivity DNA assay kit. Increased cf-DNA levels paralleled a cluster of cardiometabolic risk factors, such as high blood pressure, unfavorable lipid metabolism profile and systemic inflammation in both sexes. In addition, higher cf-DNA levels indicated decreased arterial elasticity and glucose intolerance in women not using hormonal replacement therapy (HRT). The cf-DNA level was also observed to be an independent determinant for Young's elastic modulus but not for carotid artery compliance or beta stiffness index in the women not using HRT. Hence, we conclude that cf-DNA could serve as an auxiliary biomarker in cardiometabolic risk assessment and as an indicator of arterial stiffness in women not using HRT. © 2014 Elsevier Ireland Ltd.
Hirvonen J.J.,Vaasa Central Hospital |
Hirvonen J.J.,Fimlab Laboratories |
Kaukoranta S.-S.,Vaasa Central Hospital
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2015
In this study, the usability and performance of GenomEra™ C. difficile and BD Max™ Cdiff nucleic acid amplification tests (NAATs) for the detection of toxigenic Clostridium difficile were investigated in comparison with toxigenic culture and C. difficile toxin A- and toxin B-detecting immunochromatographic antigen (IA) test, the Tox A/B QuikChek®. In total, 302 faecal specimens were collected, 113 of which were in parallel to conventional sample containers and FecalSwab liquid-based microbiology (LBM) tubes. Seventy-nine specimens were considered true-positives for toxigenic C. difficile. The sensitivity and specificity were 97.5 % and 99.6 % and 93.7 % and 98.7 % for the GenomEra and BD Max assays respectively. Toxigenic culture and Tox A/B QuikChek had sensitivity and specificity of 91.1 % and 100 % and 34.2 % and 100 % respectively. Hands-on time for analysing 1 to 24 specimens using NAATs was 1 to 15 min. The rate of PCR inhibition was 0 % for both NAATs with faeces in LBM tubes, while with faeces in conventional sample containers the respective inhibition rates were 5.3 % and 4.4 % for the GenomEra and the BD Max assays. The NAATs demonstrated an excellent analytical performance, reducing significantly the overall workload of laboratory personnel compared with culture and IA test. © 2015, Springer-Verlag Berlin Heidelberg.
Hytonen V.P.,Tampere University of Technology |
Hytonen V.P.,Fimlab Laboratories |
Wehrle-Haller B.,University of Geneva
Physical Chemistry Chemical Physics | Year: 2014
The dynamic regulation of cell-matrix adhesion is essential for tissue homeostasis and architecture, and thus numerous pathologies are linked to altered cell-extracellular matrix (ECM) interaction and ECM scaffold. The molecular machinery involved in cell-matrix adhesion is complex and involves both sensory and matrix-remodelling functions. In this review, we focus on how protein conformation controls the organization and dynamics of cell-matrix adhesion. The conformational changes in various adhesion machinery components are described, including examples from ECM as well as cytoplasmic proteins. The discussed mechanisms involved in the regulation of protein conformation include mechanical stress, post-translational modifications and allosteric ligand-binding. We emphasize the potential role of intrinsically disordered protein regions in these processes and discuss the role of protein networks and co-operative protein interactions in the formation and consolidation of cell-matrix adhesion and extracellular scaffolds. © 2014 the Partner Organisations.
Hytonen V.P.,University of Tampere |
Hytonen V.P.,Fimlab Laboratories |
Wehrle-Haller B.,University of Geneva
Experimental Cell Research | Year: 2016
Cell-matrix adhesions have since long been recognized to be critical for the survival and proliferation of cells. In fact, these adhesive structures do not only physically anchor cells, but they also induce vital intracellular signaling at cell-matrix adhesion sites. Recent progress in the cell adhesion field is now starting to provide data and ideas how this so far enigmatic signaling process is induced and regulated by intracellular acto-myosin tension, or stiffness of the extracellular matrix. Understanding how cells are using this mechanosignaling system will be key to control biological processes such as development, cancer growth, metastasis formation and tissue regeneration. In this review, we illustrate and discuss the mechanosignaling mechanisms important in the regulation of cell-matrix adhesions at the molecular level. © 2015 Elsevier Inc.
Laurila E.M.,University of Tampere |
Kallioniemi A.,University of Tampere |
Kallioniemi A.,Fimlab Laboratories
Genes Chromosomes and Cancer | Year: 2013
In the past 10 years research on miRNAs has demonstrated their central role in regulating gene expression both in normal and diseased tissue. The expression of miRNAs is widely altered in cancer, leading to abnormal expression of the genes regulated by these miRNAs, and subsequently alterations in entire molecular networks and pathways. One especially interesting cancer-related miRNA is miR-31 which is frequently altered in a large variety of cancers. The functional role of miR-31 is extremely complex and miR-31 can hold both tumor suppressive and oncogenic roles in different tumor types. The phenotype caused by aberrant miR-31 expression seems to be strongly dependent on the endogenous expression levels. For example, in breast cancer loss of miR-31 expression is associated with high risk of metastases, whereas in colorectal cancer high miR-31 expression correlates with advanced disease stage. This review summarizes the complex expression patterns of miR-31 in human cancers, describes the variable phenotypes caused by altered miR-31 expression, and highlights the current knowledge on the genes targeted by miR-31. © 2013 Wiley Periodicals, Inc.
Maatta K.M.,University of Tampere |
Nikkari S.T.,University of Tampere |
Nikkari S.T.,Fimlab Laboratories |
Kunnas T.A.,University of Tampere
Medicine (United States) | Year: 2015
Iron is essential for body homeostasis, but iron overload may lead to metabolic abnormalities and thus increase the risk for atherosclerosis and many other diseases. Major histocompatibility complex class I-like transmembrane protein (HFE) is involved in body iron metabolism. The gene coding for HFE has 3 well-known polymorphic sites of which H63D (rs1799945, C>G) has recently been associated with hypertension in a genome-wide association study (GWAS) study. In the present study, we wanted to clarify whether the genetic variant associates with hypertension in a Finnish cohort consisting of 50-year-old men and women. The study included 399 hypertensive cases and 751 controls from the Tampere adult population cardiovascular risk study (TAMRISK) cohort. Genotyping of polymorphisms was done by polymerase chain reaction using DNAs extracted from buccal swabs. We found that individuals with the mutated form of the H63D polymorphic site (G-allele) had a 1.4-fold risk (P = 0.037, 95% confidence interval [CI] 1.02-1.89) for hypertension at the age of 50 years compared with the CC genotype carriers. When obese subjects (body mass index>30kg/m2) were analyzed in their own group, the risk for hypertension was even stronger (odds ratio 4.15, P<0.001, 95% CI 1.98-8.68). We also noticed that the blood pressure (BP) readings were higher in those with the minor G-allele when compared to ones having a normal genotype already at the age of 35 years. Means of systolic/diastolic BPs were 127/81 mm Hg for CC and 131/83 mm Hg for CG+GG groups (P<0.001 for systolic and P = 0.005 for diastolic pressure). In conclusion, HFE genetic variant H63D was associated with essential hypertension in Finnish subjects from the TAMRISK cohort confirming a previous GWAS study. The effect of this SNP on BP was also confirmed from a longitudinal study. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Palazzo G.,University of Bari |
De Tullio D.,University of Bari |
Magliulo M.,University of Bari |
Mallardi A.,CNR Institute for Chemical and Physical Processes |
And 6 more authors.
Advanced Materials | Year: 2015
A systematic study of the sensor response as a function of the Debye's length, the receptor charge, and the distance at which the binding event occurred addressed the basic functional mechanisms of a bio-electrolyte-gated organic field-effect transistors (EGOFET). A bio-EGOFET sensing platform comprising a biological layer at the interface between the OSC and the electrolyte was used to conduct the investigations. The biological layer was composed of a phospholipid (PL) bilayer covalently anchored to the OSC surface through a plasma-deposited (?COOH)-functionalized thin coating. It was observed that some of the anchored PLs were endowed with a biotin moiety, having an incomparably high binding affinity for streptavidin (SA) or avidin (AV) proteins.