Fimlab Laboratories Ltd.

Pirkanmaa, Finland

Fimlab Laboratories Ltd.

Pirkanmaa, Finland
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Parssinen J.,University of Tampere | Parssinen J.,Fimlab Laboratories Ltd. | Hammaren H.,University of Tampere | Rahikainen R.,University of Tampere | And 9 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2015

Poly(vinylidene fluoride) (PVDF) is a biocompatible material with excellent electroactive properties. Nonelec-troactive α-PVDF and electroactive β-PVDF were used to investigate the substrate polarization and polarity influence on the focal adhesion (FA) size and number as well as on human adipose stem cells (hASCs) differentiation. hASCs were cultured on different PVDF surfaces adsorbed with fibronectin and FA size and number, total adhesion area, cell size, cell aspect ratio and FA density were estimated using cells expressing vinculin fused to enhanced green fluorescent protein. Osteogenic differentiation was also determined using a quantitative alkaline phosphatase assay. The surface charge of the poled PVDF films (positive or negative) influenced the hydrophobicity of the samples, leading to variations in the conformation of adsorbed extracellular matrix proteins, which ultimately modulated the stem cell adhesion on the films and induced their osteogenic differentiation. © 2014 Wiley Periodicals, Inc.

Kovanen S.M.,University of Helsinki | Kivisto R.I.,University of Helsinki | Rossi M.,University of Helsinki | Schott T.,Leibniz Institute for Baltic Sea Research | And 8 more authors.
Journal of Clinical Microbiology | Year: 2014

A total of 95 human Campylobacter jejuni isolates acquired from domestic infections and collected from three districts in Finland during the seasonal peak (June to September) in 2012 were analyzed by PCR-based multilocus sequence typing (MLST) and by whole-genome sequencing (WGS). Four predominant sequence types (STs) were detected among the isolates: ST-45 (21%) and ST-230 (14%, ST-45 clonal complex [CC]), ST-267 (21%, ST-283 CC), and ST-677 (19%, ST-677 CC). In districts 1 and 3, most of the infections occurred from early July to the middle of August, with a peak at weeks 29 to 31, but in district 2, the infections were dispersed more evenly throughout 3 months (June to August). WGS data were used for further whole-genome MLST (wgMLST) analyses of the isolates representing the four common STs. Shared loci of the isolates within each ST were analyzed as distance matrices of allelic profiles by the neighbor-net algorithm. The highest allelic variations (>400 different alleles) were detected between different clusters of ST-45 isolates (1,121 shared loci), while ST-230 (1,264 shared loci), ST-677 (1,169 shared loci), and ST-267 isolates (1,217 shared loci) were less diverse with the clusters differing by<40 alleles. Closely related isolates showing no allelic variation (subclusters) were detected among all four major STs. In some cases, they originated from different districts, suggesting that isolates can be epidemiologically connected and may have the same infection source despite being originally identified as sporadic infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Saarelainen S.K.,University of Tampere | Peltonen N.,Fimlab Laboratories Ltd | Lehtimaki T.,Fimlab Laboratories Ltd | Lehtimaki T.,University of Tampere | And 3 more authors.
American Journal of Obstetrics and Gynecology | Year: 2013

Objective: The purpose of this study was to evaluate the performance of preoperative serum levels of human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) in the prediction of the presence of metastases in endometrial carcinoma. Study Design: Preoperative sera were collected from 98 women with a diagnosis of endometrial carcinoma. The concentrations of HE4 and CA125 were assessed by enzyme-linked immunosorbent assay and correlated with the results of the final histopathologic report. Results: Fourteen patients had metastases (≥stage IIIA, International Federation of Gynecology and Obstetrics 2009 classification). The serum concentrations of HE4 and CA125 were higher in the group with metastases than in the group without metastases (median [interquartile range], 148.6 pmol/L [71.6-219.1 pmol/L] vs 77.2 pmol/L [52.9-99.3 pmol/L]; P =.001; and 20.0 U/mL [10.1-70.8 U/mL] vs 4.3 U/mL [2.9-10.4 U/mL]; P <.001, respectively). By a multivariate analysis, the combination of HE4 and CA125 (a risk score algorithm) was the only predictive factor for the presence of metastases (odds ratio, 21.562; 95% confidence interval, 5.472-84.963; P <.001), and the grade was the predictor for a deep (≥50%) myometrial invasion by the tumor (odds ratio, 2.005; 95% confidence interval, 1.123-3.581; P =.019). The sensitivity, specificity, positive predictive value, and negative predictive value for the combination of the markers to predict the presence of metastases were 71.4%, 89.5%, 55.6%, and 94.4%, respectively. Conclusion: A combination of preoperative HE4 and CA125 seems to be a better predictor of metastatic disease than either 1 alone in endometrial carcinoma. © 2013 Mosby, Inc. All rights reserved.

Hirvonen J.J.,Vaasa Central Hospital | Hirvonen J.J.,Fimlab Laboratories Ltd. | Kaukoranta S.-S.,Vaasa Central Hospital
Journal of Clinical Microbiology | Year: 2014

Using a collection (n=12) of ATCC and known stock isolates, as well as 328 clinical stool specimens, we evaluated the ESwab and the new FecalSwab liquid-based microbiology (LBM) devices for storing and transporting diarrheagenic bacteria. The stock isolates were stored in these swab devices up to 48 h at refrigeration (4°C) or room (∼25°C) temperature and up to 3 months at -20°C or-70°C. With the clinical stool specimens, the performances of the ESwab and FecalSwab were compared to those of routinely used transport systems (Amies gel swabs and dry containers). At a refrigeration temperature, all isolates survived in FecalSwab up to 48 h, while in ESwab, only 10 isolates (83.3%) out of 12 survived. At-70°C, all isolates in FecalSwab were recovered after 3 months of storage, whereas in ESwab, none of the isolates were recovered. At-20°C, neither of the swab devices preserved the viability of stock isolates after 2 weeks of storage, and at room temperature, 7 (58.3%) of the stock isolates were recovered in both transport devices after 48 h. Of the 328 fecal specimens, 44 (13.4%) were positive for one of the common diarrheagenic bacterial species with all transport systems used. Thus, the suitability of the ESwab and FecalSwab devices for culturing fresh stools was at least equal to those of the Amies gel swabs and dry containers. Although the ESwab was shown to be an option for collecting and transporting fecal specimens, the FecalSwab device had clearly better preserving properties under different storage conditions. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Syrjanen L.,University of Tampere | Tolvanen M.E.E.,University of Tampere | Hilvo M.,VTT Technical Research Center of Finland | Vullo D.,University of Florence | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2013

Carbonic anhydrases (CAs) are essential and ubiquitous enzymes. Thus far, there are no articles on characterization of Drosophila melanogaster α-CAs. Data from invertebrate CA studies may provide opportunities for anti-parasitic drug development because α-CAs are found in many parasite or parasite vector invertebrates. We have expressed and purified D. melanogaster CAH1 and CAH2 as proteins of molecular weights 30 kDa and 28 kDa. CAH1 is cytoplasmic whereas CAH2 is a membrane-attached protein. Both are highly active enzymes for the CO2 hydration reaction, being efficiently inhibited by acetazolamide. CAH2 in the eye of D. melanogaster may provide a new animal model for CA-related eye diseases. A series of dithiocarbamates were also screened as inhibitors of these enzymes, with some representatives showing inhibition in the low nanomolar range. © 2012 Elsevier Ltd. All rights reserved.

Syrjanen L.,University of Tampere | Vermelho A.B.,Federal University of Rio de Janeiro | De Almeida Rodrigues I.,Federal University of Rio de Janeiro | Corte-Real S.,Oswaldo Cruz Institute OCI Platform | And 7 more authors.
Journal of Medicinal Chemistry | Year: 2013

Leishmaniasis is an infection provoked by protozoans belonging to the genus Leishmania. Among the many species and subsepecies of such protozoa, Leishmania donovani chagasi causes visceral leishmaniasis. A β-carbonic anhydrase (CA, EC was cloned and characterized from this organism, denominated here LdcCA. LdcCA possesses effective catalytic activity for the CO2 hydration reaction, with kcat of 9.35 × 105 s -1 and kcat/KM of 5.9 × 107 M-1 s-1. A large number of aromatic/heterocyclic sulfonamides and 5-mercapto-1,3,4-thiadiazoles were investigated as LdcCA inhibitors. The sulfonamides were medium potency to weak inhibitors (K I values of 50.2 nM-9.25 μM), whereas some heterocyclic thiols inhibited the enzyme with KIs in the range of 13.4-152 nM. Some of the investigated thiols efficiently inhibited the in vivo growth of Leishmania chagasi and Leishmania amazonensis promastigotes, by impairing the flagellar pocket and movement of the parasites and causing their death. The β-CA from Leishmania spp. is proposed here as a new antileishmanial drug target. © 2013 American Chemical Society.

Pohjoismaki J.L.O.,Max Planck Institute for Heart and Lung Research | Pohjoismaki J.L.O.,University of Eastern Finland | Kruger M.,Max Planck Institute for Heart and Lung Research | Al-Furoukh N.,Max Planck Institute for Heart and Lung Research | And 3 more authors.
Molecular BioSystems | Year: 2013

Fetal (fCM) and adult cardiomyocytes (aCM) significantly differ from each other both by structure and biochemical properties. aCM own a higher mitochondrial mass compared to fCM due to increased energy demand and show a greater density and higher degree of structural organization of myofibrils. The energy metabolism in aCM relies virtually completely on β-oxidation of fatty acids while fCM use carbohydrates. Rewinding of the aCM phenotype (de-differentiation) arises frequently in diseased hearts spurring questions about its functional relevance and the extent of de-differentiation. Yet, surprisingly little is known about the changes in the human proteome occurring during maturation of fCM to aCM. Here, we examined differences between human fetal and adult hearts resulting in the quantification of 3500 proteins. Moreover, we analyzed mitochondrial proteomes from both stages to obtain more detailed insight into underlying biochemical differences. We found that the majority of changes between fCM and aCM were attributed to growth and maturation of cardiomyocytes. As expected, adult hearts showed higher mitochondrial mass and expressed increased levels of proteins involved in energy metabolism but relatively lower copy numbers of mitochondrial DNA (mtDNA) per total cell volume. We uncovered that the TFAM/mtDNA ratio was kept constant during postnatal development despite a significant increase of mitochondrial protein per mtDNA in adult mitochondria, which revises previous concepts. © The Royal Society of Chemistry.

Rauhio A.,Fimlab Laboratories Ltd | Uusi-Rasi K.,UKK Institute for Health Promotion Research | Nikkari S.T.,Fimlab Laboratories Ltd | Nikkari S.T.,University of Tampere | And 4 more authors.
Maturitas | Year: 2013

Objective: The aim of this study was to investigate whether the polymorphisms of the fat mass and obesity-associated gene (FTO, rs9939609:T > A) and the 2-adrenergic receptor gene (ADRB2, rs1042714:Gln > Glu) are associated with weight loss in dieting obese premenopausal women and the association of these SNPs with body weight, body composition and distribution of fat mass. Methods: 75 obese (BMI > 30) premenopausal women participated in the intervention including a 3- month weight reduction period and a subsequent 9-month weight maintenance period. Weight and height were measured and BMI calculated. Body composition and fat mass distribution were assessed by dual energy X-ray absorptiometry. Results: At baseline, the AA homozygotes of the FTO gene were 10.1 kg heavier (p = 0.031), they had higher BMI (p = 0.038), and greater waist and greater hip circumference (p = 0.08 and p = 0.067, respectively) compared to the TT homozygotes. Gln/Gln carriers of the ADRB2 gene had smaller gynoid fat-% compared with both the Gln/Glu and Glu/Glu carriers (p = 0.050 and p = 0.009, respectively). The Gln homozygotes had also smaller total body fat-% and higher total body lean mass-% than that of the Glu homozygotes (p = 0.018 and p = 0.019, respectively). Conclusion: FTO genotype was associated with body weight in general, whereas ADRB2 genotype was associated with fat distribution. However, all women in the study group lost weight similarly independently of their genotypes. Neither the FTO nor ADRB2 genotype had statistically significant effect on weight reduction or weight maintenance. © 2013 Elsevier Ireland Ltd. All rights reserved.

Tolvanen M.E.E.,University of Tampere | Ortutay C.,University of Tampere | Barker H.R.,University of Tampere | Aspatwar A.,University of Tampere | And 5 more authors.
Bioorganic and Medicinal Chemistry | Year: 2013

Carbonic anhydrase (CA) isozymes CA IV and CA XV are anchored on the extracellular cell surface via glycosylphosphatidylinositol (GPI) linkage. Analysis of evolution of these isozymes in vertebrates reveals an additional group of GPI-linked CAs, CA XVII, which has been lost in mammals. Our work resolves nomenclature issues in GPI-linked fish CAs. Review of expression data brings forth previously unreported tissue and cancer types in which human CA IV is expressed. Analysis of collective glycosylation patterns of GPI-linked CAs suggests functionally important regions on the protein surface. © 2012 Elsevier Ltd. All rights reserved.

Hirvonen J.J.,Fimlab Laboratories Ltd.
Biomarkers in Medicine | Year: 2014

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in many hospitals and long-term care facilities as well as in the community. To limit the spread of MRSA, early detection and proper treatment are essential. Because conventional culture as gold standard is time consuming, new techniques such as PCR-based and hybridization assays have emerged for the rapid detection of MRSA. This review will focus on the currently available molecular-based assays and on their utility and performance for detection of S. aureus, of its virulence factors and of the markers for acquired resistance. © 2014 Future Medicine Ltd.

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