Eastern Finland Laboratory Center

Kuopio, Finland

Eastern Finland Laboratory Center

Kuopio, Finland
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Adem J.,University of Eastern Finland | Eray M.,University of Helsinki | Eeva J.,University of Tampere | Nuutinen U.,University of Eastern Finland | And 2 more authors.
Immunobiology | Year: 2017

CD40 is a cell surface receptor which belongs to tumor necrosis factor receptor (TNFR) family members. It transmits signals that regulate diverse cellular responses such as proliferation, differentiation, adhesion molecule expression and apoptosis. Unlike other TNFR family members (TRAIL-R, Fas-R and TNFR1), the CD40 cytoplasmic tail lacks death domain. However, CD40 is capable of inducing apoptosis in different types of cancer cells including lymphoma. The apoptotic effect of CD40 is linked to the involvement of Fas, TRAIL or receptor interacting protein 1 (RIP1) kinase. We have previously shown that CD40 activation has anti-apoptotic or apoptotic effect in follicular lymphoma (FL) cell lines. In this study, we investigated the mechanism by which CD40 mediates apoptosis in a follicular lymphoma cell line, HF4.9. We show here that CD40-induced apoptosis was dependent on caspase-8 activation because caspase-8 specific inhibitor, Z-IETD-FMK completely prevented apoptosis. Therefore, the involvement of TRAIL, Fas and RIP1 in caspase-8 activation was examined. The exogenous TRAIL-induced apoptosis was fully prevented by anti-TRAIL neutralizing antibody. However, the antibody had no effect on CD40-induced apoptosis indicating that CD40 did not induce the expression of endogenous TRAIL in HF4.9 cells. Moreover, the cells were not sensitive to Fas-mediated apoptosis. Interestingly, RIP1 specific inhibitor, necrostatin-1 decreased CD40-induced apoptosis, which showed that RIP1 has a role in caspase-8 activation. In conclusion, the survival or apoptotic effects of CD40-mediated signaling might be related to the differentiation stages of FL cells. © 2017 Elsevier GmbH.

Koskela H.O.,Kuopio University Hospital | Koskela H.O.,University of Eastern Finland | Salonen P.H.,Kuopio University Hospital | Romppanen J.,Eastern Finland Laboratory Center | And 2 more authors.
BMJ Open | Year: 2014

Objectives: Community-acquired pneumonia is associated with a significant long-term mortality after initial recovery. It has been acknowledged that additional research is urgently needed to examine the contributors to this long-term mortality. The objective of the present study was to assess whether diabetes or newly discovered hyperglycaemia during pneumonia affects long-term mortality. Design: A prospective, observational cohort study. Setting: A single secondary centre in eastern Finland. Participants: 153 consecutive hospitalised patients who survived at least 30 days after mild-to-moderate community-acquired pneumonia. Interventions: Plasma glucose levels were recorded seven times during the first day on the ward. Several possible confounders were also recorded. The surveillance status and causes of death were recorded after median of 5 years and 11 months. Results: In multivariate Cox regression analysis, a previous diagnosis of diabetes among the whole population (adjusted HR 2.84 (1.35-5.99)) and new postprandial hyperglycaemia among the non-diabetic population (adjusted HR 2.56 (1.04-6.32)) showed independent associations with late mortality. New fasting hyperglycaemia was not an independent predictor. The mortality rates at the end of follow-up were 54%, 37% and 10% among patients with diabetes, patients without diabetes with new postprandial hyperglycaemia and patients without diabetes without postprandial hyperglycaemia, respectively (p<0.001). The underlying causes of death roughly mirrored those in the Finnish general population with a slight excess in mortality due to chronic respiratory diseases. Pneumonia was the immediate cause of death in just 8% of all late deaths. Conclusions: A previous diagnosis of diabetes and newly discovered postprandial hyperglycaemia increase the risk of death for several years after community-acquired pneumonia. As the knowledge about patient subgroups with an increased late mortality risk is gradually gathering, more studies are needed to evaluate the possible postpneumonia interventions to reduce late mortality.

Nieminen P.,University of Eastern Finland | Kakela R.,University of Helsinki | Paakkonen T.,University of Eastern Finland | Halonen T.,Eastern Finland Laboratory Center | Mustonen A.-M.,University of Eastern Finland
Journal of Insect Physiology | Year: 2013

Poikilothermic organisms often modify their tissue fatty acids (FA) in response to cold exposure by increased unsaturation. In insects, this has been found to be accompanied by increases in the activities or mRNA expression of desaturase enzymes. In the present study, the FA composition of an obligatory ectoparasite, the deer ked (Lipoptena cervi), was analyzed in August-November. In addition to studying the general FA profile of the species, the possible contribution of FA to autumnal cold-hardening was examined. The FA composition of the deer ked imago was relatively similar to previously studied dipteran species, with high percentages of monounsaturated FA (especially 18:1n-9 and 16:1n-7) and 16:0. The individuals caught later in autumn had significantly higher values for the ratio of unsaturated to saturated FA and, regarding individual FA, the percentages of 18:1n-9, 18:2n-6, 18:3n-3, 20:4n-6 and 22:6n-3 were higher but those of 16:0 and 16:1n-7 lower than in August. Potential selective use of particular FA for energy could not account for the large increase in the levels of polyunsaturated FA (PUFA). The observed increased degree of FA unsaturation may have resulted from cold-induced desaturation, as observed previously in other species, or increased survival of the keds with relatively large PUFA contents. The PUFA with low melting points probably allow lipid membranes to maintain sufficient fluidity required to maintain protein functions at low ambient temperatures. © 2013 Elsevier Ltd.

Keikkala E.,University of Helsinki | Vuorela P.,Porvoo Hospital | Laivuori H.,University of Helsinki | Romppanen J.,Eastern Finland Laboratory Center | And 2 more authors.
Placenta | Year: 2013

Introduction Recent studies indicate that treatment with low-dose aspirin may reduce the risk of preeclampsia. Thus, early prediction of preeclampsia is needed. Low serum concentrations of hyperglycosylated human chorionic gonadotrophin (hCG-h) are associated with early pregnancy loss. We therefore studied whether it may serve as an early marker of preeclampsia. Methods A nested case-control study included 158 women with subsequent preeclampsia, 41 with gestational hypertension, 81 normotensive women giving birth to small-for-gestational-age (SGA) infants and 427 controls participating in first trimester screening for Down's syndrome between 8 and 13 weeks of gestation. Gestational-age-adjusted multiples of medians (MoMs) were calculated for serum concentrations of hCG-h, the free beta subunit of hCG (hCGβ) and pregnancy-associated plasma placental protein A (PAPP-A) and the proportion of hCG-h to hCG (%hCG-h). Clinical risk factors including mean arterial pressure (MAP) and parity were also included in the risk calculation. Results In women with subsequent preeclampsia %hCG-h was lower than in controls (median MoM 0.92, P < 0.001), especially in 29 cases with early-onset preeclampsia (0.86, P < 0.001), in which PAPP-A also was reduced (0.95, P = 0.001). At 90% specificity for prediction of early-onset preeclampsia, sensitivity was 56% (95% confidence interval, 52-61%) for %hCG-h, 33% (28-37%) for PAPP-A, and 69% (51-83%) for the combination of these with first trimester MAP and parity. The area under the receiver-operating characteristic (ROC) curve for the combination of all these was 0.863 (0.791-0.935). Conclusions hCG-h is a promising first trimester marker for early-onset preeclampsia. Addition of PAPP-A and maternal risk factors may improve the results. © 2013 Elsevier Ltd. All rights reserved.

Mustonen A.-M.,University of Eastern Finland | Kakela R.,University of Helsinki | Halonen T.,Eastern Finland Laboratory Center | Karja V.,Kuopio University Hospital | And 2 more authors.
Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology | Year: 2012

Factors regulating fatty acid (FA) composition of small herbivores are poorly known. Because of the fast response to food deprivation, the tissue FA profiles of voles could be rapidly modified. The selectivity of incorporating dietary FA into tissue total lipids and mobilizing tissue FA was examined in two Microtus vole species either fed or fasted for 12-18. h. The FA composition of the tissues reflected the dietary lipids, but FA were selectively incorporated depending on their structure. The FA profiles of white and brown adipose tissues were different and contained more saturated and monounsaturated FA and less polyunsaturated FA (PUFA) than the diet. The essential PUFA precursors with smaller tissue percentages were likely converted into longer-chain derivatives for structural lipids. The FA composition of the vole tissues was selectively modified by food deprivation. The preferences for retention or loss were tissue-specific and related to the FA structure. Livers displayed steatosis with characteristic accumulation of triacylglycerols, while FA prevalent in membrane phospholipids decreased in proportion. Hepatic FA could be partly derived from lipids hydrolyzed in fat depots. The FA profiles of the vole tissues reflect the dietary lipids and are rapidly and selectively modified by food deprivation. © 2012 Elsevier Inc.

Adem J.,University of Eastern Finland | Ropponen A.,University of Eastern Finland | Eeva J.,University of Eastern Finland | Eray M.,University of Tampere | And 3 more authors.
Leukemia and Lymphoma | Year: 2015

The addition of rituximab (RTX) to standard chemotherapy has improved the treatment of B-cell malignancies. We show here that RTX and dexamethasone (Dex) induced synergistic apoptosis in follicular lymphoma cell lines. However, apoptosis was delayed by RTX-induced early protective signaling. RTX-induced early signaling also decreased Dex-induced apoptosis and led to phosphorylation of ERK1/2, Bcl-2 (at serine 70) and phosphorylation/degradation of BimL/EL. All these events were prevented by the MEK inhibitor, UO126. Therefore, we suggest that RTX-induced ERK-mediated signaling events lead to protection from apoptosis during early signaling and that blocking of Bim and Bcl-2 phosphorylation might be used as a novel strategy for lymphoma treatment. © 2015 © 2015 Informa UK, Ltd.

Turtiainen J.,North Karelia Central Hospital | Hakala T.,North Karelia Central Hospital | Hakkarainen T.,North Karelia Central Hospital | Karhukorpi J.,Eastern Finland Laboratory Center
European Journal of Vascular and Endovascular Surgery | Year: 2014

Objective: To study the relationship between surgical wound bacterial colonization and the development of surgical site infection (SSI) after lower limb vascular surgery. SSI is a major problem after lower limb vascular surgery. Most SSIs in vascular surgery are caused by Staphylococcal species that are part of normal skin flora. A prospective observational investigator blind study to examine quantitative and qualitative analysis of surgical wound bacterial colonization and the correlation with the development of SSI has been conducted. Methods: The study cohort comprised 94 consecutive patients with 100 surgical procedures. Swabs for microbiological analyses were taken from surgical wounds at four different time intervals: before surgery, just before the surgical area had been scrubbed, at the end of surgery, and on the first and second postoperative days. Postoperative complications were recorded. Results: Three hundred and eighty-seven skin bacterial samples from 100 surgical wounds were analyzed. The most common bacteria isolated were coagulase-negative staphylococci (80%), Corynebacterium species (25%), and Propionibacterium species (15%). In 13 (62%) cases, the same bacterial isolates were found in the perioperative study samples as in the infected wounds. The incidence of SSI was 21%. Multivariate analysis revealed that high bacterial load on the second postoperative day and diabetes independently increased the risk of SSI. Elective redo surgery was protective against the development of SSI. Conclusions: A high bacterial load in the postoperative surgical wound independently increases the risk of the development of SSI after lower limb vascular surgery. © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Savolainen K.,University of Eastern Finland | Savolainen K.,Eastern Finland Laboratory Center | Kiimamaa R.,University of Eastern Finland | Kiimamaa R.,Eastern Finland Laboratory Center | And 2 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2011

Background: Liquid chromatography tandem-mass spectrometer (LC-MS/MS) techniques are more and more common in the measurement of testosterone concentrations in biological samples. However, LC-MS/MS methods are more laborious than streamlined automated immunochemistry methods because of the need for tedious pre-purification of the sample before the mass spectrometric analysis. We therefore developed a robust and rapid sample clean-up method to improve the throughput of the whole LC-MS/MS analysis procedure by applying an automated on-line solid-phase extraction (SPE) technique instead of the still widely used conventional liquid-liquid extraction. Methods: Testosterone was purified by the on-line SPE-column-switching technique after rapid precipitation of serum samples by zinc sulphate/internal standard solution before LC-MS/MS analysis. The results were compared with those of our previous routine LC-MS/MS method using liquid-liquid extraction with tert-butyl methyl ether for the pre-purification of the samples. Results: The tested on-line SPE-LC-MS/MS method reached the specifications of the previous method with liquid-liquid extraction. The precision of the new method was notably better, especially in the lower concentration range, than with the former method; the total variation was below 10% in the whole quantitation range of 0.25-35 nmol/L. The new method liberates more than 50% of hands-on time of laboratory technicians as well as expensive instrument time for other applications compared with the older method. Conclusions: The on-line SPE-pre-purification technique tested in long-term use offers a rapid and reliable technique in the LC-MS/MS analysis of serum testosterone and is a valuable tool in the improvement of efficiency in the laborious steroid analytics. © 2011 by Walter de Gruyter Berlin Boston 2011.

Dunder U.,Eastern Finland Laboratory Center | Dunder U.,University of Eastern Finland | Valtonen P.,University of Eastern Finland | Kelo E.,University of Eastern Finland
Journal of Inherited Metabolic Disease | Year: 2010

Aspartylglycosaminuria (AGU) is a lysosomal storage disease caused by deficient activity of glycosylasparaginase (AGA), and characterized by motor and mental retardation. Enzyme replacement therapy (ERT) in adult AGU mice with AGA removes the accumulating substance aspartylglucosamine from and reverses pathology in many somatic tissues, but has only limited efficacy in the brain tissue of the animals. In the current work, ERT of AGU mice was initiated at the age of 1 week with three different dosage schedules of recombinant glycosylasparaginase. The animals received either 3.4 U of AGA/kg every second day for 2 weeks (Group 1), 1.7 U/kg every second day for 9 days followed by an enzyme injection once a week for 4 weeks (Group 2) or 17 U/kg at the age of 7 and 9 days (Group 3). In the Group 1 and Group 3 mice, ERT reduced the amount of aspartylglucosamine by 34 and 41% in the brain tissue, respectively. No therapeutic effect was observed in the brain tissue of Group 2 mice. As in the case of adult AGU mice, the AGA therapy was much more effective in the somatic tissues than in the brain tissue of the newborn AGU mice. The combined evidence demonstrates that a high dose ERT with AGA in newborn AGU mice is up to twofold more effective in reducing the amount of the accumulated storage material from the brain tissue than ERT in adult AGU animals, indicating the importance of early detection and treatment of the disease. © 2010 SSIEM and Springer Reference:.

Koskela H.O.,Kuopio University Hospital | Purokivi M.K.,Kuopio University Hospital | Romppanen J.,Eastern Finland Laboratory Center
Clinical Respiratory Journal | Year: 2010

Background and Aims: Chronic cough is associated with an enhanced excitability of airway cough receptors, possibly due to action of neurotrophins. The present study aimed to compare the neurotrophin levels between healthy subjects and patients with chronic cough and to analyze the factors associated with these levels. Methods: Serum and sputum levels of nerve growth factor (NGF), serum levels of brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were analyzed by enzyme immunoassay in 19 healthy subjects and 47 patients with chronic cough. In addition, cough sensitivity to hypertonic saline was assessed, cough diary was kept, Leicester Cough Questionnaire was filled in, peak flow was monitored and spirometry, skin prick tests, exhaled nitric oxide measurement and histamine challenge were performed. Results: The NGF levels did not differ between the healthy subjects and the patients with chronic cough and were not associated with any index describing cough severity. However, these levels in both serum (P = 0.01) and sputum (P = 0.025) samples were associated with asthma. There was a statistically significant association between serum and sputum NGF levels (R = 0.45, P = 0.026). The serum BDNF levels did not differ between the groups and were not associated with any of the background characteristics. The serum NT-3 levels were below the detection limit in most subjects and therefore these data were not analyzed. Conclusions: Neither chronic cough nor its severity is associated with abnormal neurotrophin levels. High NGF levels among some patients with chronic cough may indicate a presence of asthma. © 2009 Blackwell Publishing Ltd.

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