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Pirkanmaa, Finland

Fimlab Ltd

Pirkanmaa, Finland
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Hammerstad S.S.,University of Oslo | Jahnsen F.L.,University of Oslo | Tauriainen S.,University of Turku | Tauriainen S.,University of Tampere | And 5 more authors.
Thyroid | Year: 2014

Background: Few studies have systematically examined the immune cells that infiltrate thyroid tissue at the time of the onset of Graves' disease (GD). The role of viruses in the pathogenesis of autoimmune thyroid diseases is controversial. The present study analyzed inflammatory responses with respect to signs of virus infection. Methods: Thyroid tissue was obtained from 22 patients with newly diagnosed and untreated GD, 24 patients with chronic GD, and 24 controls. Inflammation was assessed by immunostaining for CD4+ and CD8+ T cells, plasma cells (CD138+), and plasmacytoid dendritic cells (PDCs). The production of interferon-inducible myxovirus resistance protein A (MxA) was analyzed as a sign of virus infection. Results: The degree of thyroid inflammation and fibrosis was significantly higher in both patient groups compared with that in controls. The number of CD4+ T cells and plasma cells (activated B cells) was significantly higher in both patient groups. CD8+ cells were only present in patients with chronic disease. MxA expression and the number of PDCs increased only in patients with newly diagnosed GD. There was a strong positive correlation between the number of PDCs and the number of MxA+ leucocytes. Conclusion: The increase in CD8+ T cells during the chronic stage of GD suggests that they may play a role in progression of the autoimmune process from early to chronic thyroiditis. Upregulation of MxA expression during the early stages of the disease, and the positive correlation between the number of PDCs and the number of MxA+ leucocytes, suggests that activated PDCs secrete type I IFNs at the lesion site, possibly in response to viral infection. © 2014, Mary Ann Liebert, Inc.

Anagandula M.,Uppsala University | Richardson S.J.,University of Exeter | Oberste M.S.,Centers for Disease Control and Prevention | Sioofy-Khojine A.-B.,University of Tampere | And 5 more authors.
Journal of Medical Virology | Year: 2014

Type 1 diabetes mellitus is believed to be triggered, in part, by one or more environmental factors and human enteroviruses (HEVs) are among the candidates. Therefore, this study has examined whether two strains of HEV may differentially affect the induction of genes involved in pathways leading to the synthesis of islet hormones, chemokines and cytokines in isolated, highly purified, human islets. Isolated, purified human pancreatic islets were infected with strains of Coxsackievirus B1.Viral replication and the degree of CPE/islet dissociation were monitored. The expression of insulin, glucagon, CXCL10, TLR3, IF1H1, CCL5, OAS-1, IFNβ, and DDX58 was analyzed. Both strains replicated in islets but only one of strain caused rapid islet dissociation/CPE. Expression of the insulin gene was reduced during infection of islets with either viral strain but the gene encoding glucagon was unaffected. All genes analyzed which are involved in viral sensing and the development of innate immunity were induced by Coxsackie B viruses, with the notable exception of TLR3. There was no qualitative difference in the expression pattern between each strain but the magnitude of the response varied between donors. The lack of virus induced expression of TLR3, together with the differential regulation of IF1H1, OAS1 and IFNβ, (each of which has polymorphic variants influence the predisposition to type 1 diabetes), that might result in defective clearance of virus from islet cells. The reduced expression of the insulin gene and the unaffected expression of the gene encoding glucagon by Coxsackie B1 infection is consistent with the preferential β-cell tropism of the virus. © 2013 Wiley Periodicals, Inc.

Kolehmainen P.,University of Tampere | Kolehmainen P.,University of Helsinki | Koskiniemi M.,University of Helsinki | Oikarinen S.,University of Tampere | And 11 more authors.
Journal of Medical Virology | Year: 2013

Human parechoviruses (HPeVs) are RNA viruses associated mainly with mild gastrointestinal and respiratory infections in children and also cause neonatal sepsis and CNS infections. Human enteroviruses, close relatives of HPeVs, associate with the development of type 1 diabetes. In this study, the potential role of HPeV infections in promoting beta cell autoimmunity was investigated by analyzing stool samples of 54 prediabetic case and 134 healthy control children for the presence of HPeV RNA and comparing the derived infection frequencies. All 188 children were participants of the Finnish prospective Diabetes Prediction and Prevention study. Viral RNA was screened for using an HPeV-specific RT-PCR method coupled to liquid hybridization of the PCR product. The overall HPeV infection frequency did not differ between prediabetic case and control children. However, case boys had more HPeV positive samples in the 6-month period before becoming autoantibody positive, when compared to the matching time-period in controls (P<0.01). HPeV infection at a young age does not appear to play a major role in the development of beta-cell autoimmunity. In boys, however, HPeVs showed time-dependent association with the first detection of diabetes-associated autoantibodies. Thus, in boys, HPeV infections cannot be excluded as a gender-specific risk factor which promotes the development of type 1 diabetes. © 2013 Wiley Periodicals, Inc.

Honkanen H.,University of Tampere | Oikarinen S.,University of Tampere | Pakkanen O.,Vactech Ltd. | Ruokoranta T.,Vactech Ltd. | And 16 more authors.
Journal of Clinical Virology | Year: 2013

Background: Human enterovirus 71 (HEV71) is a common cause of severe outbreaks of hand-foot- and mouth disease, aseptic meningitis and encephalitis in Asian populations but has not caused such epidemics in all populations. Objectives: To analyze the frequency of HEV71 in the background childhood population in Finland by screening in stool and serum samples and by measuring neutralizing antibodies against HEV71 in serum and to compare the genetic relationship of virus strains detected in asymptomatic children and those causing severe illness in Finland to the strains found in other countries. Study design: 4185 stool samples and 5686 serum samples were collected and clinical symptoms recorded from children who were observed from birth. Additional stool samples were available from four children hospitalized due to EV71 infection. Samples were screened for the presence of RNA of human enteroviruses using RT-PCR and HEV71 amplicons were identified by sequencing. Phylogenetic analyses were carried out to study genetic relationships between different virus strains. Neutralizing antibodies against HEV71 were screened from 522 children. Results: A total of 0.3% of stool samples and two serum samples from healthy children were positive for HEV71 genome. 1.6% of the children had neutralizing antibodies against HEV71. Most infections were asymptomatic or mild in contrast to the clear symptoms in the children hospitalized due to HEV71. All viruses were C strains. Conclusions: HEV71 is circulating in Finland but it is rare. No clear difference was seen between strains circulating in the Finnish background population and those found in hospitalized patients or those causing severe outbreaks worldwide. © 2012 Elsevier B.V.

Juonala M.,University of Turku | Jaaskelainen P.,University of Turku | Sabin M.A.,Murdoch Childrens Research Institute | Viikari J.S.A.,University of Turku | And 11 more authors.
Journal of Pediatrics | Year: 2013

Objectives: To investigate whether the body mass index (BMI) of a child's mother is associated with an increased future risk of type 2 diabetes, independent of genetic risk or childhood metabolic, behavioral, and environmental factors. Study design: The analyses were based on the Cardiovascular Risk in Young Finns Study including 1835 individuals aged 3-18 years at baseline with data on maternal BMI, childhood metabolic factors, as well as 34 newly identified type 2 diabetes susceptibility alleles. These subjects were then followed-up over 21-27 years. Results: Maternal BMI (OR for 1-SD increase 1.54 [95% CI 1.12-2.11], P = .008) and child's systolic blood pressure (1.54 [1.01-2.35], P = .04) were significantly associated with increased odds for later type 2 diabetes, in a multivariable analysis adjusted for age, sex, type 2 diabetes genetic risk score, childhood BMI, insulin, lipids, dietary factors, socioeconomic status, and mother's age, and history of type 2 diabetes. A risk prediction model, which included maternal BMI status outperformed one which utilized only child's BMI data (area under the receiver operating characteristic curve 0.720 vs 0.623, P = .02). The inclusion of genetic risk score and other baseline risk variables did not additionally improve prediction (area under the receiver operating characteristic curve 0.720 vs 0.745, P = .40). Conclusions: Maternal BMI is a useful variable in determining offspring risk of developing type 2 diabetes. © Copyright 2013 Mosby Inc. All rights reserved.

Taverniti V.,University of Milan | Minuzzo M.,University of Milan | Arioli S.,University of Milan | Junttila I.,University of Tampere | And 9 more authors.
Applied and Environmental Microbiology | Year: 2012

The use of proper bacterial strains as probiotics for the pharyngeal mucosa is a potential prophylactic strategy for upper respiratory tract infections. In this context, we characterized in vitro the functional and immunomodulatory properties of the strains Lactobacillus helveticus MIMLh5 and Streptococcus salivarius ST3 that were selected during previous investigations as promising pharyngeal probiotics. In this study, we demonstrated in vitro that strains MIMLh5 and ST3, alone and in combination, can efficiently adhere to pharyngeal epithelial cells, antagonize Streptococcus pyogenes, and modulate host innate immunity by inducing potentially protective effects. In particular, we found that the strains MIMLh5 and ST3 activate U937 human macrophages by significantly inducing the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). Nonetheless, the induction of the anti-inflammatory interleukin-10 (IL-10) by MIMLh5 or ST3 was never lower than that of TNF-α, suggesting that these bacteria can potentially exert a regulatory rather than a proinflammatory effect. We also found that the strains MIMLh5 and ST3 induce cyclooxygenase 2 (COX-2) expression and demonstrated that toll-like receptor 2 (TLR-2) participates in the recognition of the strains MIMLh5 and ST3 by U937 cells. Finally, we observed that these microorganisms grow efficiently when cocultured in milk, suggesting that the preparation of a milk-based fermented product containing both MIMLh5 and ST3 can be a practical solution for the administration of these bacteria. In conclusion, we propose the combined use of L. helveticus MIMLh5 and S. salivarius ST3 for the preparation of novel products that display probiotic properties for the pharyngeal mucosa. © 2012, American Society for Microbiology.

Tuomisto S.,University of Tampere | Tuomisto S.,Fimlab Ltd | Karhunen P.J.,University of Tampere | Karhunen P.J.,Fimlab Ltd | And 2 more authors.
Gut Pathogens | Year: 2013

Post mortem or even normal changes during life occurring in major gut bacterial populations are not known. We investigated Bacteroides sp., Bifidobacterium sp., Clostridium leptum, Clostridium coccoides, Streptococcus sp., Lactobacillus sp. and Enterobacteriacaea ratios in 7 fecal samples from healthy volunteers and in 61 autopsies rectum and cecum samples and studied the effect of post mortem time using quantitative real-time PCR. Bacterial ratios in stool samples from volunteers and rectum samples from autopsy cases were similar and did not change significantly up to 5 days post mortem. In cecum, significant post mortem time-dependent differences were observed in ratios of Bacteroides sp. (p = 0.014) and Lactobacillus sp. (p = 0.024). Our results showed that ratios of Bacteroides sp., Bifidobacterium sp., Clostridium leptum, Clostridium coccoides, Streptococcus sp., Lactobacillus sp. and Enterobacteriacaea can be investigated in autopsy rectum samples up to 5 days after death. © 2013 Tuomisto et al.; licensee BioMed Central Ltd.

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