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1. Tributary-Specific Contribution to a Lacustrine Mixed-Stock Fishery of Brown Trout Salmo trutta (Salmonidae) in a Diverse Sub-Arctic Watershed.

Author

Mikheev, P. B., Prusov, S. V., Erkinaro, J., Samokhvalov, I. V., Dolotov, S. I., Potutkin, A. G., Orell, P., Seppänen, M., Kopylov, I. S., Puzik, A. Yu., Easton, R., Reid, M., and Closs, G.

Abstract

Mixed-stock fisheries which simultaneously cause mortality amongst several populations of a species of fish may occur where separate stocks partially or completely overlap in the geographic area of harvest. This study aims to analyze the population-of-origin of adult and subadult adfluvial lacustrine brown trout Salmo trutta, exploited in a mixed-stock fishery in Upper Tuloma Reservoir in Eastern Fennoscandia, using otolith microchemistry. To evaluate the origin of migratory brown trout captured in these mixed-stock harvest fisheries, we undertook otolith sampling of brown trout juveniles in fluvial spawning and rearing habitats in the reservoir watershed, including 13 natal tributaries across the catchment of the reservoir in both Russia and Finland. Harvested adult and subadult brown trout otoliths were sampled from the impoundment in the central area of the reservoir and we analyzed for stock-related character differences to compare with known populations, using trace element signatures, with fish from the mixed stock fishery. The assignments-of-origin in the mixed-stock fishery-harvest samples did not follow the known distribution of populations sampled from natal streams in the watershed. For example, brown trout from the largest tributary catchments of Lotta River and Nota River were less represented in the mixed-harvest sample, which was contradictory to their contribution to the overall spawning and rearing areas of the catchment. These results point towards the importance of maintaining the diversity of different spawning and rearing tributaries required for brown trout recruitment into mixed stock fisheries, and the potential of the existence of population structure of brown trout in the reservoir catchment. Our information suggests that it is important to develop conservation and management strategies for natal habitats in multiple streams utilized by adfluvial lacustrine brown trout populations inhabiting various catchments and that are harvested in mixed-stock fisheries. [ABSTRACT FROM AUTHOR]

Published
2023
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2. Symptoms and diagnostic delays in bladder cancer with high risk of recurrence:results from a prospective FinnBladder 9 trial

Author

Sell, V. (Ville), Ettala, O. (Otto), Perez, I. M. (Ileana Montoya), Järvinen, R. (Riikka), Pekkarinen, T. (Tarmo), Vaarala, M. (Markku), Seppänen, M. (Marjo), Liukkonen, T. (Tapani), Marttila, T. (Timo), Aaltomaa, S. (Sirpa), Kaasinen, E. (Eero), and Boström, P. J. (Peter J.)

Subjects
Diagnostic delay, Bladder cancer, Diagnosis, Symptoms, Hematuria
Abstract

Purpose: To investigate the symptoms and delays in the clinical pathway of bladder cancer (BC). Methods: This is a substudy of a prospective, randomized, multicenter phase III study (FinnBladder 9, NCT01675219) where the efficacy of photodynamic diagnosis and 6 weekly optimized mitomycin C instillations are studied in pTa bladder cancer with high risk for recurrence. The data of presenting symptoms and critical time points were prospectively collected, and the effect of factors on delays was analyzed. Results: At the time of analysis, 245 patients were randomized. Analysis included 131 patients with primary bladder cancer and their complete data. Sixty-nine percent had smoking history and 67% presented with macroscopic hematuria. Median patient delay (from symptoms to health-care contact) was 7 days. The median general practice delay (from health-care contact to urology referral) was 8 days. Median time from urology referral to cystoscopy was 23 days and from cystoscopy to TUR-BT 21 days. Total time used in the clinical pathway (from symptom to TUR-BT) was 78 days. Current and former smokers had non-significantly shorter patient-related and general practice delays compared to never smokers. TUR-BT delay was significantly shorter in patients with malignant cytology (16 days) compared to patients with benign cytology (21 days, p = 0.03). Conclusions: Patient-derived delay was short and most of the delay occurred in the referral centers. The majority had macroscopic hematuria as the initial symptom. Surprisingly, current and past smokers were more prone to contact the health-care system compared to never smokers.

Published
2020

3. Heterozygous TLR3 mutation in patients with hantavirus encephalitis

Author

Partanen, T. (Terhi), Chen, J. (Jie), Lehtonen, J. (Johanna), Kuismin, O. (Outi), Rusanen, H. (Harri), Vapalahti, O. (Olli), Vaheri, A. (Antti), Anttila, V.-J. (Veli-Jukka), Bode, M. (Michaela), Hautala, N. (Nina), Vuorinen, T. (Tytti), Glumoff, V. (Virpi), Kraatari, M. (Minna), Åström, P. (Pirjo), Saarela, J. (Janna), Kauma, H. (Heikki), Lorenzo, L. (Lazaro), Casanova, J.-L. (Jean-Laurent), Zhang, S.-Y. (Shen-Ying), Seppänen, M. (Mikko), Hautala, T. (Timo), Partanen, T. (Terhi), Chen, J. (Jie), Lehtonen, J. (Johanna), Kuismin, O. (Outi), Rusanen, H. (Harri), Vapalahti, O. (Olli), Vaheri, A. (Antti), Anttila, V.-J. (Veli-Jukka), Bode, M. (Michaela), Hautala, N. (Nina), Vuorinen, T. (Tytti), Glumoff, V. (Virpi), Kraatari, M. (Minna), Åström, P. (Pirjo), Saarela, J. (Janna), Kauma, H. (Heikki), Lorenzo, L. (Lazaro), Casanova, J.-L. (Jean-Laurent), Zhang, S.-Y. (Shen-Ying), Seppänen, M. (Mikko), and Hautala, T. (Timo)

Abstract

Puumala hantavirus (PUUV) hemorrhagic fever with renal syndrome (HFRS) is common in Northern Europe; this infection is usually self-limited and severe complications are uncommon. PUUV and other hantaviruses, however, can rarely cause encephalitis. The pathogenesis of these rare and severe events is unknown. In this study, we explored the possibility that genetic defects in innate anti-viral immunity, as analogous to Toll-like receptor 3 (TLR3) mutations seen in HSV-1 encephalitis, may explain PUUV encephalitis. We completed exome sequencing of seven adult patients with encephalitis or encephalomyelitis during acute PUUV infection. We found heterozygosity for the TLR3 p.L742F novel variant in two of the seven unrelated patients (29%, p = 0.0195). TLR3-deficient P2.1 fibrosarcoma cell line and SV40-immortalized fibroblasts (SV40-fibroblasts) from patient skin expressing mutant or wild-type TLR3 were tested functionally. The TLR3 p.L742F allele displayed low poly(I:C)-stimulated cytokine induction when expressed in P2.1 cells. SV40-fibroblasts from three healthy controls produced increasing levels of IFN-λ and IL-6 after 24 h of stimulation with increasing concentrations of poly(I:C), whereas the production of the cytokines was impaired in TLR3 L742F/WT patient SV40-fibroblasts. Heterozygous TLR3 mutation may underlie not only HSV-1 encephalitis but also PUUV hantavirus encephalitis. Such possibility should be further explored in encephalitis caused by these and other hantaviruses.

Published
2020

4. Tonsillar granuloma associated with hypogammaglobulinemia

Author

Laajala, A. (Aleksi), Kuismin, O. (Outi), Tastula, M. (Mikko), Tiitto, L. (Leena), Kauppila, S. (Saila), Salo, A. (Anna), Åström, P. (Pirjo), Nissinen, A. (Antti), Glumoff, V. (Virpi), Seppänen, M. R. (Mikko R. J.), Hautala, T. (Timo), Laajala, A. (Aleksi), Kuismin, O. (Outi), Tastula, M. (Mikko), Tiitto, L. (Leena), Kauppila, S. (Saila), Salo, A. (Anna), Åström, P. (Pirjo), Nissinen, A. (Antti), Glumoff, V. (Virpi), Seppänen, M. R. (Mikko R. J.), and Hautala, T. (Timo)

Abstract

Background: Rare tonsillar granulomas may be caused for example by infections, malignancies or sarcoidosis. Granulomas also occur in inborn errors of immunity (IEI) such as common variable immunodeficiency (CVID) with B cell maturation defects and hypogammaglobulinemia. CVID shares various features with sarcoidosis and drug-induced secondary hypogammaglobulinemia; careful consideration of differential diagnosis between these conditions is warranted. Case presentation: A 29-year-old female with epilepsy developed dysphagia, dyspnea and impaired exercise tolerance. Obstruction caused by swollen lingual tonsil and edema in the epiglottis and arytenoid mucosa were found. Lingual tonsil and epiglottis biopsies displayed non-necrotizing granulomas. There was no evidence of viral, bacterial, mycobacterial or fungal infections. Chest X-ray, computerized tomography of chest and ultrasound of neck and abdomen remained unremarkable. Positron emission tomography/computed tomography (PET/CT) showed laryngeal enhancement. Empiric antimicrobials combined with prednisolone were insufficient to control her disease. In immunological evaluation, the patient had normal counts of B and T cells. Proportions of CD27+ memory B cells (30.3%) and IgD−IgM−CD27+ switched memory B cells (7.2%; normal range 6.5–29.2%) were normal. Percentage of activated CD21low B cells was high (6.6%; normal range 0.6–3.5%). IgG (3.5 g/L; normal range 6.77–15.0 g/l) and all IgG subclass concentrations were low. Anti-polysaccharide responses were impaired, with 3/10 serotypes reaching a level of 0.35 µg/ml after immunization with Pneumovax®. The findings were consistent with hypogammaglobulinemia resembling CVID, possibly secondary to antiepileptic medication. Her dyspnea and dysphagia responded favorably to subcutaneous IgG and rituximab. Conclusions: Tonsillar granulomas can be the presenting and only clinical feature of B cell deficiency, highlighting the diversity of symptoms and findings in primary

Published
2020

5. Dominant TOM1 mutation associated with combined immunodeficiency and autoimmune disease

Author

Keskitalo, S. (Salla), Haapaniemi, E. M. (Emma M.), Glumoff, V. (Virpi), Liu, X. (Xiaonan), Lehtinen, V. (Ville), Fogarty, C. (Christopher), Rajala, H. (Hanna), Chiang, S. C. (Samuel C.), Mustjoki, S. (Satu), Kovanen, P. (Panu), Lohi, J. (Jouko), Bryceson, Y. T. (Yenan T.), Seppänen, M. (Mikko), Kere, J. (Juha), Heiskanen, K. (Kaarina), Varjosalo, M. (Markku), Keskitalo, S. (Salla), Haapaniemi, E. M. (Emma M.), Glumoff, V. (Virpi), Liu, X. (Xiaonan), Lehtinen, V. (Ville), Fogarty, C. (Christopher), Rajala, H. (Hanna), Chiang, S. C. (Samuel C.), Mustjoki, S. (Satu), Kovanen, P. (Panu), Lohi, J. (Jouko), Bryceson, Y. T. (Yenan T.), Seppänen, M. (Mikko), Kere, J. (Juha), Heiskanen, K. (Kaarina), and Varjosalo, M. (Markku)

Abstract

Mutations in several proteins functioning as endolysosomal components cause monogenic autoimmune diseases, of which pathogenesis is linked to increased endoplasmic reticulum stress, inefficient autophagy, and defective recycling of immune receptors. We report here a heterozygous TOM1 p.G307D missense mutation, detected by whole-exome sequencing, in two related patients presenting with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. The index patient suffered from recurrent respiratory tract infections and oligoarthritis since early teens, and later developed persistent low-copy EBV-viremia, as well as an antibody deficiency. Her infant son developed hypogammaglobulinemia, autoimmune enteropathy, interstitial lung disease, profound growth failure, and treatment-resistant psoriasis vulgaris. Consistent with previous knowledge on TOM1 protein function, we detected impaired autophagy and enhanced susceptibility to apoptosis in patient-derived cells. In addition, we noted diminished STAT and ERK1/2 signaling in patient fibroblasts, as well as poor IFN-γ and IL-17 secretion in T cells. The mutant TOM1 failed to interact with TOLLIP, a protein required for IL-1 recycling, PAMP signaling and autophagosome maturation, further strengthening the link between the candidate mutation and patient pathophysiology. In sum, we report here an identification of a novel gene, TOM1, associating with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. Other patient cases from unrelated families are needed to firmly establish a causal relationship between the genotype and the phenotype.

Published
2019

6. Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans

Author

Kaasinen, E. (Eevi), Kuismin, O. (Outi), Rajamäki, K. (Kristiina), Ristolainen, H. (Heikki), Aavikko, M. (Mervi), Kondelin, J. (Johanna), Saarinen, S. (Silva), Berta, D. G. (Davide G.), Katainen, R. (Riku), Hirvonen, E. A. (Elina A. M.), Karhu, A. (Auli), Taira, A. (Aurora), Tanskanen, T. (Tomas), Alkodsi, A. (Amjad), Taipale, M. (Minna), Morgunova, E. (Ekaterina), Franssila, K. (Kaarle), Lehtonen, R. (Rainer), Mäkinen, M. (Markus), Aittomäki, K. (Kristiina), Palotie, A. (Aarno), Kurki, M. I. (Mitja I.), Pietiläinen, O. (Olli), Hilpert, M. (Morgane), Saarentaus, E. (Elmo), Niinimäki, J. (Jaakko), Junttila, J. (Juhani), Kaikkonen, K. (Kari), Vahteristo, P. (Pia), Skoda, R. C. (Radek C.), Seppänen, M. R. (Mikko R. J.), Eklund, K. K. (Kari K.), Taipale, J. (Jussi), Kilpivaara, O. (Outi), Aaltonen, L. A. (Lauri A.), Kaasinen, E. (Eevi), Kuismin, O. (Outi), Rajamäki, K. (Kristiina), Ristolainen, H. (Heikki), Aavikko, M. (Mervi), Kondelin, J. (Johanna), Saarinen, S. (Silva), Berta, D. G. (Davide G.), Katainen, R. (Riku), Hirvonen, E. A. (Elina A. M.), Karhu, A. (Auli), Taira, A. (Aurora), Tanskanen, T. (Tomas), Alkodsi, A. (Amjad), Taipale, M. (Minna), Morgunova, E. (Ekaterina), Franssila, K. (Kaarle), Lehtonen, R. (Rainer), Mäkinen, M. (Markus), Aittomäki, K. (Kristiina), Palotie, A. (Aarno), Kurki, M. I. (Mitja I.), Pietiläinen, O. (Olli), Hilpert, M. (Morgane), Saarentaus, E. (Elmo), Niinimäki, J. (Jaakko), Junttila, J. (Juhani), Kaikkonen, K. (Kari), Vahteristo, P. (Pia), Skoda, R. C. (Radek C.), Seppänen, M. R. (Mikko R. J.), Eklund, K. K. (Kari K.), Taipale, J. (Jussi), Kilpivaara, O. (Outi), and Aaltonen, L. A. (Lauri A.)

Abstract

Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.

Published
2019

7. Hip arthroplasty after failed nailing of proximal femoral fractures.

Author

Mokka, J., Kirjasuo, K., Koivisto, M., Virolainen, P., Junnila, M., Seppänen, M., Äärimaa, V., Isotalo, K., and Mäkelä, K.

Abstract

Background and aims: Hip arthroplasty has been advocated as a salvage procedure after failed nailing of proximal femoral fractures. The aim of the current study was to evaluate chirurgical complications of hip arthroplasty after failed nailing of proximal femoral fractures. The second aim was to compare the complication profile of semiendoprosthesis (SEP) to that of total endoprosthesis (TEP). Materials and methods: There were 1,533 Gamma- or DHS-nailed proximal femoral fractures altogether at our institution during the study period 2000-2010. We reviewed the medical records of 51 hips in 50 patients with failed nailing of fracture followed by hip arthroplasty (3.3 % of all nailed proximal femoral fractures). The patients were identified retrospectively from a single academic institution's computerized database. Results: There was at least one re-operation after arthroplasty in ten patients (20 %). Dislocation was the most common reason of the re-operation (six patients). The SEP and TEP groups did not differ significantly from each other with regard the re-operation rate ( p = 0.72). Conclusions: Failed arthroplasty is common after failed nailing of proximal femoral fractures. [ABSTRACT FROM AUTHOR]

Published
2012
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8. Cerebral magnetic fields associated with voluntary limb movements in man.

Author

Hari, R., Antervo, A., Katila, T., Poutanen, T., Seppänen, M., Tuomisto, T., and Varpula, T.

Abstract

Copyright of Il Nuovo Cimento della Societa Italiana di Fisica: D is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
1983
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9. Comparison between measured and simulated magnetocardiograms in a case of anterolateral myocardial infarction.

Author

Siltanen, P., Poutanen, T., Katila, T., Seppänen, M., and Varpula, T.

Abstract

Copyright of Il Nuovo Cimento della Societa Italiana di Fisica: D is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
1983
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10. Measurement of biomagnetic fields using multichannel superconducting-magnetometer techniques.

Author

Seppänen, M., Katila, T., Tuomisto, T., Varpula, T., Duret, D., and Karp, P.

Abstract

Copyright of Il Nuovo Cimento della Societa Italiana di Fisica: D is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
1983
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11. Novel applications of myocardial perfusion imaging oral abstract session.

Author

Lautamäki, R., Airaksinen, K., Seppänen, M., Toikka, J., Luotolahti, M., Borra, R., Sundell, J., Knuuti, J., Nuutila, P., Hermann, S., Levkau, B., Theilmeier, G., Giet, M., Chun, J., Schober, O., Schäfers, M., Spadafora, M., Manganelli, F., Ferro, A., and Varrella, P.

Subjects
CARDIAC imaging, INSULIN, POSITRON emission tomography, SMOKING cessation
Abstract

The article presents abstracts on topics related to novel applications of myocardial perfusion imaging, including the effect of insulin on myocardial blood in patients with type 2 diabetes and coronary artery disease, the effect of high-density lipoproteins (HDL) on myocardial perfusion in vivo and the impact of smoking cessation on coronary vasomotor response assessed with O-15 labeled water and positron emission tomography (PET) in healthy young smokers.

Published
2005
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12. Young investigator award session oral abstract session.

Author

Tsukamoto, T., Morita, K., Naya, M., Katoh, C., Kuge, Y., Okamoto, H., Tsutsui, H., Tamaki, N., Namdar, M., Siegrist, P., Koepfli, P., Tschuetscher, P., Hany, T., Wyss, C., Kaufmann, P., Lautamäki, R., Airaksinen, K., Seppänen, M., Toikka, J., and Luotolahti, M.

Subjects
CARDIAC radionuclide imaging, POSITRON emission tomography, ROSIGLITAZONE, TYPE 2 diabetes
Abstract

The article presents abstracts on topics related to nuclear cardiology, including the impact of attenuation correction with computed tomography (CT) on myocardial perfusion imaging in a hybrid single photon emission computed tomography/computed tomography (SPECT/CT), the effect of rosiglitazone on myocardial glucose uptake in ischemic regions in patients with type 2 diabetes, as well as the relationship between plasma myeloperoxidase levels and ischemic response during stress nuclear perfusion imaging.

Published
2005
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15. Behavior of FDG-avid supradiaphragmatic lymph nodes in PET/CT throughout primary therapy in advanced serous epithelial ovarian cancer: a prospective study.

Author

Laasik M, Kemppainen J, Auranen A, Hietanen S, Grénman S, Seppänen M, and Hynninen J

Subjects
Adult, Aged, Carcinoma, Ovarian Epithelial pathology, Carcinoma, Ovarian Epithelial therapy, Female, Fluorodeoxyglucose F18 administration & dosage, Humans, Middle Aged, Ovarian Neoplasms pathology, Ovarian Neoplasms therapy, Radiopharmaceuticals, Carcinoma, Ovarian Epithelial diagnostic imaging, Lymphatic Metastasis diagnostic imaging, Ovarian Neoplasms diagnostic imaging, Positron Emission Tomography Computed Tomography
Abstract

Background: Epithelial ovarian cancer (EOC) typically spreads intra-abdominally, but preoperative evaluation with FDG PET/CT often reveals metabolically active supradiaphragmatic lymph nodes (sdLNs). Their clinical significance and behavior during treatment has not been established., Methods: EOC patients with PET positive sdLNs at diagnosis were prospectively followed with PET/CT after primary chemotherapy and at the first recurrence. In each patient, 2 most active LNs in 5 different supradiaphramatic regions were evaluated and the size and changes in FDG uptake (SUVmax) were recorded. The patients´ overall response to primary treatment was defined with RECIST criteria. The behavior of sdLNs during chemotherapy were compared in treatment responders and non-responders. Recurrence patterns were monitored., Results: Forty-one patients with 127 PET/CT scans were systematically evaluated. In pretreatment scan, 76% (31/41) of patients had FDG-avid sdLNs in multiple anatomical sites. Only a minority (22/136) of the sdLNs were enlarged in size, but their histopathologic confirmation by biopsy was not possible. Only 6/41 patients had FDG-avid sdLNs in a single surgically approachable site. The sdLNs became inactive during primary chemotherapy more often in the RECIST responders compared to the non-responders (HR 1.46 (95%CI: 1.09-1.96), p = 0.002). The size and SUVmax values did not predict treatment outcome. In 50% of the responders the same sdLNs reactivated when recurrence occurred. Persistent post-treatment metabolic activity did not predict earlier disease relapse (p = 0.59)., Conclusion: The behavior of metabolically active sdLNs during chemotherapy supports their metastatic nature. Due to their distribution to multiple regions, the benefit of removal of reachable sdLNS seems unlikely., Trial Registration: NCT, NCT01276574 . Registered 1 September 2010.

Published
2019
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