| 1. |
- Koskinen, Walter J., et al.
(author)
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Alcohol, smoking and human papillomavirus in laryngeal carcinoma: a Nordic prospective multicenter study
- 2007
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In: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 1432-1335 .- 0171-5216. ; 133:9, s. 673-678
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Journal article (peer-reviewed)abstract
- Purpose Human papillomavirus (HPV) has been linked to oropharyngeal carcinomas, but its role in laryngeal squamous cell carcinoma (LSCC) is not clear. A prospective multicenter study based on known tumor-cell percentage of fresh frozen carcinoma biopsies was established to determine the HPV prevalence. Moreover risk factors such as smoking, alcohol abuse, chronic laryngitis and gastroesophageal reflux disease (GERD) were evaluated Methods Fresh-frozen laryngeal cancer biopsies from 108 patients in Finland, Norway, and Sweden were investigated. Patients whose biopsy samples contained at least 20% tumor tissue (N = 69) entered the study. HPV DNA was determined with MY09/11 and GP5+/6+ nested PCR and SPF10 PCR hybridization assay. Patients were examined by an ENT specialist and an extensive questionnaire concerning risk factors was filled in. Results Only three patients (4.4%) harbored HPV DNA in their carcinoma sample. Heavy alcohol drinking was associated with an increased risk of death, advanced-stage disease, and younger age at diagnosis. Chronic laryngitis, GERD, and orogenital sex contacts were rare. Poor oral hygiene was not associated with survival, although it correlated with heavy drinking. Conclusion In our series HPV was not important in LSCC. Heavy drinking led to major mortality in LSCC and promoted early carcinogenesis.
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| 2. |
- Antonen, Jaakko, et al.
(author)
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A severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant
- 2013
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 45:6, s. 494-496
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Journal article (peer-reviewed)abstract
- A patient with severe capillary leakage syndrome caused by a Puumala hantavirus infection was treated with a single dose of icatibant, a bradykinin receptor antagonist, with a dramatic positive response. We suggest that this drug should be tested in a larger number of patients with severe hantavirus infection.
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| 3. |
- Autero, Matti, et al.
(author)
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Ezrin is a substrate for Lck in T cells.
- 2003
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In: FEBS Lett. - 0014-5793. ; 535:1-3, s. 82-6
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Journal article (peer-reviewed)abstract
- We evaluated the role of Lck tyrosine kinase, an early effector of T cell activation, in regulation of the membrane-cytoskeleton linker protein ezrin. Ezrin was constitutively tyrosine phosphorylated in wild-type and CD45-deficient Jurkat T cells, but not in Lck-deficient cells. However, phosphorylation was evident in cells, in which Lck activity had been restored by transfection. Phosphorylation was reduced by the Src family kinase inhibitor PP2 and increased by the tyrosine phosphatase inhibitor pervanadate, implying continuous tyrosine phosphorylation and dephosphorylation. Lck phosphorylated ezrin in vitro, and the major phosphotyrosine was identified as Y145. These results identify ezrin as the first cytoskeletal substrate for Lck.
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| 4. |
- Hepojoki, Satu, et al.
(author)
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Competitive Homogeneous Immunoassay for Rapid Serodiagnosis of Hantavirus Disease
- 2015
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In: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 53:7, s. 2292-2297
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Journal article (peer-reviewed)abstract
- In this study, we describe a competitive homogeneous immunoassay that makes use of Forster resonance energy transfer (FRET) in rapid detection of pathogen-specific antibodies. The assay principle is based on competition between a monoclonal antibody (MAb) and serum antibodies to a given antigen. In the assay, named competitive FRET immunoassay (CFRET-IA), the FRET signal is induced if MAb carrying a donor label binds to an acceptor-labeled antigen. Specific antibodies in serum compete for antigen binding, resulting in reduced FRET signal. The proof-of-principle for the assay was obtained using donor-labeled Puumala virus nucleocapsid protein (PUUV-N) and acceptor-labeled anti-PUUV-N MAb. The assay was evaluated by analyzing 329 clinical samples comprising 101 from individuals with acute PUUV infection, 42 from individuals with past infection, and 186 from individuals with PUUV-seronegative sera, and the results were compared to those of reference tests. The rapid serodiagnostic test we introduced herein performed with 100% sensitivity and 99% specificity for diagnosing acute hantavirus disease.
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| 5. |
- Iheozor-Ejiofor, Rommel, et al.
(author)
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Neutralizing Antibody Titers in Hospitalized Patients with Acute Puumala Orthohantavirus Infection Do Not Associate with Disease Severity
- 2022
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In: Viruses. - : MDPI. - 1999-4915. ; 14:5
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Journal article (peer-reviewed)abstract
- Nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFRS), is an acute febrile illness caused by Puumala orthohantavirus (PUUV). NE manifests typically with acute kidney injury (AKI), with a case fatality rate of about 0.1%. The treatment and management of hantavirus infections are mainly supportive, although neutralizing monoclonal antibodies and immune sera therapeutics are under investigation. In order to assess the potential use of antibody therapeutics in NE, we sought to determine the relationship between circulating PUUV neutralizing antibodies, PUUV nucleocapsid protein (N) IgG antibodies, and viral loads with markers of disease severity. The study included serum samples of extensively characterized patient cohorts (n = 116) from Tampere University Hospital, Finland. The results showed that upon hospitalization, most patients already had considerable neutralizing and anti-PUUV-N IgG antibody levels. However, contrary to expectations, neutralizing antibody titers from the first day of hospitalization did not appear to protect from AKI or correlate with more favorable disease outcomes. This indicates that further studies are needed to investigate the applicability of neutralizing antibodies as a therapy for hospitalized NE patients.
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| 6. |
- Jaaskelainen, Anne J., et al.
(author)
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Development and Evaluation of a Real-Time RT-qPCR for Detection of Crimean-Congo Hemorrhagic Fever Virus Representing Different Genotypes
- 2014
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In: Vector Borne and Zoonotic Diseases. - : Mary Ann Liebert. - 1530-3667 .- 1557-7759. ; 14:12, s. 870-872
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Journal article (peer-reviewed)abstract
- Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease caused by a nairovirus belonging to family Bunyaviridae. The CCHF virus (CCHFV) can be transmitted to humans by Hyalomma ticks as well as by direct contact with infected body fluids or tissues from viremic livestock or humans. Our aim was to set up a fast RT-qPCR for detection of the different CCHFV genotypes in clinical samples, including an inactivation step to make the sample handling possible in lower biosafety levels (BSL) than BSL-4. This method was evaluated against commercial reference assays and international External Quality Assessment (EQA) samples. The analytical limit of detection for the developed CCHFV-S RT-qPCR was 11 CCHFV genomes per reaction. After exclusion of four dubious samples, we studied 38 CCHFV-positive samples (using reference tests) of which 38 were found positive by CCHFV-S RT-qPCR, suggesting a sensitivity of 100%. CCHFV-S RT q-PCR detected all eight different CCHFV strains representing five different CCHFV genotypes. In conclusion, the CCHFV-S RT-qPCR described in this study was evaluated using various sources of CCHFV samples and shown to be an accurate tool to detect human CCHFV infection caused by different genotypes of the virus.
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| 7. |
- Jääskeläinen, Anne J, et al.
(author)
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Evidence of ljungan virus specific antibodies in humans and rodents, Finland.
- 2013
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In: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 85:11, s. 2001-2008
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Journal article (peer-reviewed)abstract
- Ljungan virus (LV, genus Parechovirus, family Picornaviridae) is considered currently to be a rodent-borne virus. Despite suggested human disease associations, its zoonotic potential remains unclear. To date, LV antibody prevalence in both humans and rodents has not been studied. In this study, two different LV immunofluorescence assays (LV IFAs) were developed with LV genotypes 1 (LV strain 87-012G) and 2 (LV strain 145SLG), and cross-neutralization and -reaction studies were carried out with LV strain 145SLG. Finally, a panel of 37 Finnish sera was screened for anti-LV antibodies using two different LV IFAs (LV 145SLG and LV 87-012G) and a neutralization (NT) assay (LV 145SLG), and 50 samples from Myodes glareolus by LV IFA (LV 145SLG). The LV seroprevalence study showed 38% and 18% positivity in humans and M. glareolus, respectively. LV IFAs and NT assays were compared, and the results were in good agreement. The data are the first evidence of humans and rodents coming into contact with LV in Finland. Additional studies are required in order to acquire a better understanding of the prevalence, epidemiological patterns and possible disease association of LV infections.
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| 8. |
- Korhonen, Laura, Professor, 1974-, et al.
(author)
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Multivariate analyses of immune markers reveal increases in plasma EN-RAGE in first-episode psychosis patients
- 2023
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In: Translational Psychiatry. - : Springer. - 2158-3188. ; 13:1
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Journal article (peer-reviewed)abstract
- Immune cells and cytokines are largely recognized as significant factors in the pathophysiology of neuropsychiatric disorders. The possible role of other blood cells such as leukocytes in events of acute psychosis is in contrast only emerging. To study blood-born markers in acute psychosis we here evaluated plasma proteins in drug-naive first-episode psychosis (FEP) patients and healthy controls using a multiplex proximity extension assay technique. We analyzed a panel of 92 immune markers and plasma samples from 60 FEP patients and 50 controls and evaluated the changes obtained using multivariate statistical methods followed by protein pathway analyses. Data showed that 11 proteins are significantly different between FEP patients and healthy controls We observed increases in pro-inflammatory proteins such as interleukin-6, oncostatin-M, and transforming growth factor-alpha in FEP patients compared with controls. Likewise, the extracellular newly identified RAGE-binding protein (EN-RAGE) that regulates the expression of various cytokines was also elevated in the plasma of FEP patients. The results indicate that neutrophil-derived EN-RAGE could play an important role during the early phase of acute psychosis by stimulating cytokines and the immune response targeting thereby likely also the brain vasculature.
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| 9. |
- Ling, Jiaxin, et al.
(author)
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Evolution and postglacial colonization of Seewis hantavirus with Sorex araneus in Finland
- 2018
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In: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 57, s. 88-97
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Journal article (peer-reviewed)abstract
- Hantaviruses have co-existed with their hosts for millions of years. Seewis virus (SWSV), a soricomorph-borne hantavirus, is widespread in Eurasia, ranging from Central Siberia to Western Europe. To gain insight into the phylogeography and evolutionary history of SWSV in Finland, lung tissue samples of 225 common shrews (Sorex araneus) trapped from different parts of Finland were screened for the presence of SWSV RNA. Forty-two of the samples were positive. Partial small (S), medium (M) and large (L) segments of the virus were sequenced, and analyzed together with all SWSV sequences available in Genbank. The phylogenetic analysis of the partial S-segment sequences suggested that all Finnish SWSV strains shared their most recent common ancestor with the Eastern European strains, while the L-segment suggested multiple introductions. The difference between the Land S-segment phylogenies implied that reassortment events play a role in the evolution of SWSV. Of the Finnish strains, variants from Eastern Finland occupied the root position in the phylogeny, and had the highest genetic diversity, supporting the hypothesis that SWSV reached Finland first form the east. During the spread in Finland, the virus has formed three separate lineages, identified here by correlation analysis of genetic versus geographic distance combined with median-joining network analysis. These results support the hypothesis that Finnish SWSV recolonized Finland with its host, the common shrew, from east after the last ice age 12,000-8000 years ago, and then subsequently spread along emerging land bridges towards west or north with the migration and population expansion of its host.
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| 10. |
- Peteri, Ulla Kaisa, et al.
(author)
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Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome
- 2021
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In: GLIA. - : Wiley. - 0894-1491 .- 1098-1136. ; 69:12, s. 2947-2962
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Journal article (peer-reviewed)abstract
- The function of astrocytes intertwines with the extracellular matrix, whose neuron and glial cell-derived components shape neuronal plasticity. Astrocyte abnormalities have been reported in the brain of the mouse model for fragile X syndrome (FXS), the most common cause of inherited intellectual disability, and a monogenic cause of autism spectrum disorder. We compared human FXS and control astrocytes generated from human induced pluripotent stem cells and we found increased expression of urokinase plasminogen activator (uPA), which modulates degradation of extracellular matrix. Several pathways associated with uPA and its receptor function were activated in FXS astrocytes. Levels of uPA were also increased in conditioned medium collected from FXS hiPSC-derived astrocyte cultures and correlated inversely with intracellular Ca2+ responses to activation of L-type voltage-gated calcium channels in human astrocytes. Increased uPA augmented neuronal phosphorylation of TrkB within the docking site for the phospholipase-Cγ1 (PLCγ1), indicating effects of uPA on neuronal plasticity. Gene expression changes during neuronal differentiation preceding astrogenesis likely contributed to properties of astrocytes with FXS-specific alterations that showed specificity by not affecting differentiation of adenosine triphosphate (ATP)-responsive astrocyte population. To conclude, our studies identified uPA as an important regulator of astrocyte function and demonstrated that increased uPA in human FXS astrocytes modulated astrocytic responses and neuronal plasticity.
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