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Erika Gucciardo, Sirpa Loukovaara, Ani Korhonen, Pauliina Repo, Beatriz Martins, Helena Vihinen, Eija Jokitalo, Kaisa Lehti
Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication characterized by pathological angiogenesis. Several retinopathy animal models have been developed to study the disease mechanisms and putative targets. However, knowledge on the human proliferative disease remains incomplete, relying on steady-state results from thin histological neovascular tissue sections and vitreous samples. New translational models are thus required to comprehensively understand the disease pathophysiology and develop improved therapeutic interventions...
March 13, 2018: Journal of Pathology
Tommi Nora, Hanna Heinonen, Mirja Tenhunen, Sirpa Rainesalo, Soila Järvenpää, Kai Lehtimäki, Jukka Peltola
Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient's seizures in long-term follow-up...
2018: Frontiers in Neurology
Karolina Losenkova, Mariachiara Zuccarini, Mikko Helenius, Guillaume Jacquemet, Evgenia Gerasimovskaya, Camilla Tallgren, Sirpa Jalkanen, Gennady G Yegutkin
Intravascular ATP and adenosine have emerged as important regulators of endothelial barrier function, vascular remodeling and neovascularization at various pathological states, including hypoxia, inflammation and oxidative stress. By using human umbilical vein endothelial cells (HUVEC) and bovine vasa vasorum endothelial cells (VVEC) as representatives of macro- and microvessel phenotypes, this study was undertaken to evaluate cellular mechanisms contributing to physiological adaptation of vascular endothelium to hypoxia, with a particular emphasis on ectoenzymatic purine-converting activities and their link to intracellular ATP homeostasis and signaling pathways...
March 4, 2018: Biochimica et Biophysica Acta
Cecilia Hagert, Outi Sareila, Tiina Kelkka, Kutty Selva Nandakumar, Mattias Collin, Bingze Xu, Simon Guérard, Johan Bäcklund, Sirpa Jalkanen, Rikard Holmdahl
OBJECTIVE: To develop a new chronic RA model which is driven by the innate immune system. METHOD: The injection of a cocktail of four monoclonal antibodies against collagen type II followed by intra-peritoneal injections of mannan (from Saccharomyces cerevisiae) on days 5 and 60 led to the development of chronic arthritis in B10.Q mice. The role of the innate versus the adaptive immune system in this arthritis model was investigated using genetically modified mouse strains...
March 7, 2018: Arthritis & Rheumatology
Cecilia Hagert, Outi Sareila, Tiina Kelkka, Sirpa Jalkanen, Rikard Holmdahl
The injection of mannan into mice can result in the development of psoriasis (Ps) and psoriatic arthritis (PsA), whereas co-injection with antibodies toward collagen type II leads to a chronic rheumatoid-like arthritis. The critical event in all these diseases is mannan-mediated activation of macrophages, causing more severe disease if the macrophages are deficient in neutrophil cytosolic factor 1 (Ncf1), i.e., lack the capacity to make a reactive oxygen species (ROS) burst. In this study, we investigated the role of one of the receptors binding mannan; the macrophage mannose receptor (MR, CD206)...
2018: Frontiers in Immunology
Datu Respatika, Yasuyuki Saito, Ken Washio, Satomi Komori, Takenori Kotani, Hideki Okazawa, Yoji Murata, Takashi Matozaki
Signal regulatory protein α (SIRPα), is an immunoglobulin superfamily protein that is predominantly expressed in macrophages and dendritic cells (DCs), especially CD4+ conventional DCs (cDCs). In this study, we demonstrated that, in addition to the reduced number of CD4+ cDCs, the number of T cells was significantly decreased in the spleen of Sirpa-/- mice, in which full-length of SIRPα protein was systemically ablated. The size of the T cell zone was markedly reduced in the spleen of Sirpa-/- mice. In addition, Sirpa-/- mice revealed a marked reduction of CCL19, CCL21, and IL-7 expression, which are thought to be important for homeostasis of T cells in the spleen...
August 10, 2017: Kobe Journal of Medical Sciences
Sirpa Pirilä, Paula Pirilä, Terhi Ansamaa, Anneli Yliherva, Samuel Sonning, Leena Rantala
OBJECTIVE: Our interest was in how teachers' voices behave during the delivery of lessons in core subjects (e.g., mathematics, science, etc.). We sought to evaluate the relationship between voice sound pressure level (SPL), vocal fundamental frequency (F0), voice symptoms, activity noise, and differences therein during the first and the last lessons in core subjects of the day. PATIENTS AND METHODS: The participants were 24 female elementary school teachers. Voice symptoms were evaluated by questionnaire...
December 14, 2017: Folia Phoniatrica et Logopaedica
Leonor Lopes de Carvalho, Heli Elovaara, Jerôme de Ruyck, Gerard Vergoten, Sirpa Jalkanen, Gabriela Guédez, Tiina A Salminen
Human primary amine oxidase (hAOC3), also known as vascular adhesion protein 1, mediates leukocyte rolling and trafficking to sites of inflammation by a multistep adhesion cascade. hAOC3 is absent on the endothelium of normal tissues and is kept upregulated during inflammatory conditions, which is an applicable advantage for imaging inflammatory diseases. Sialic acid binding immunoglobulin like-lectin 9 (Siglec-9) is a leukocyte ligand for hAOC3. The peptide (CARLSLSWRGLTLCPSK) based on the region of Siglec-9 that interacts with hAOC3, can be used as a specific tracer for hAOC3-targeted imaging of inflammation using Positron Emission Tomography (PET)...
February 1, 2018: Scientific Reports
Olli Moisio, Riikka Siitonen, Heidi Liljenbäck, Elli Suomela, Sirpa Jalkanen, Xiang-Guo Li, Anne Roivainen
Amino acid residues 283-297 from sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) form a cyclic peptide ligand targeting vascular adhesion protein-1 (VAP-1). VAP-1 is associated with the transfer of leukocytes from blood to tissues upon inflammation. Therefore, analogs of Siglec-9 peptide are good candidates for visualizing inflammation non-invasively using positron emission tomography (PET). Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (DOTA)-conjugated Siglec-9 has been evaluated extensively for this purpose...
January 31, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Sirpa Loukovaara, Sari Sahanne, Annika Takala, Jari Haukka
PURPOSE: Vitreoretinal (VR) surgery is the third most common intraocular surgery after refractive and cataract surgery. The impact of statin therapy on VR surgery outcomes remains unclear, despite a potentially beneficial effect. We explored the association of preoperative statin therapy and the need for revitrectomy after primary vitrectomy. METHODS: Our historical, population-based, register-based, VR surgery cohort consisted of 5709 patients operated in a tertiary, academic referral hospital in Finland, during 2008-2014, covering 6...
January 16, 2018: Acta Ophthalmologica
Minna Brunfeldt, Harriet Teare, Sirpa Soini, Helena Kääriäinen
Biobanks accumulate huge amounts of research findings, including participants' genomic data. Increasingly this leads to biobanks receiving research results that could be of clinical significance to biobank participants. The EU Horizon 2020 Project 'Genetics Clinic of the Future' surveyed European biobanks' perceptions of the legal and regulatory requirements for communicating individual research results to donors. The goal was to gain background knowledge for possible future guidelines, especially relating to the consent process...
January 12, 2018: European Journal of Human Genetics: EJHG
Sirpa Soini, Pertti Mustajoki, Johan G Eriksson
OBJECTIVES: The main aims of this study were to assess motivational factors for weight loss, and support and difficulties during the weight loss and weight maintenance phase. METHODS: This study was based upon findings from the Finnish Weight Control Registry (FWCR), including 158 formerly obese persons, who lost at least 10% of their initial weight and maintained it for at least 2 years. Data have been collected through electronic forms. RESULTS: The 2 most commonly reported motivational factors for weight loss were health- and appearance-related factors...
January 1, 2018: American Journal of Health Behavior
Suvi-Katri Leivonen, Katherine Icay, Kirsi Jäntti, Ilari Siren, Chengyu Liu, Amjad Alkodsi, Alejandra Cervera, Maja Ludvigsen, Stephen Jacques Hamilton-Dutoit, Francesco d'Amore, Marja-Liisa Karjalainen-Lindsberg, Jan Delabie, Harald Holte, Rainer Lehtonen, Sampsa Hautaniemi, Sirpa Leppä
Despite better therapeutic options and improved survival of diffuse large B-cell lymphoma (DLBCL), 30-40% of the patients experience relapse or have primary refractory disease with a dismal prognosis. To identify biological correlates for treatment resistance, we profiled microRNAs (miRNAs) of matched primary and relapsed DLBCL by next-generation sequencing. Altogether 492 miRNAs were expressed in the DLBCL samples. Thirteen miRNAs showed significant differential expression between primary and relapse specimen pairs...
December 15, 2017: Blood Cancer Journal
Annika Pasanen, Leo Meriranta, Sirpa Leppä
Lymphomas are a heterogenous group of malignant diseases. Identification of sub-groups has created pressure for a more detailed diagnosis and individualized treatment. Although the underlying genetic and molecular pathologic factors of the most common B-cell derived lymphomas, i.e. diffuse large B-cell lymphoma and follicular lymphoma, have become more accurate, prognosis is evaluated and treatment options still selected mainly on the basis of clinical variables. In the future, new generation sequencing methods that are becoming more common in clinical practice will allow the assessment of prognosis and treatment on the basis of biologic and genetic risk factors...
2017: Duodecim; Lääketieteellinen Aikakauskirja
Jussi Haikarainen, Paula Rytilä, Sirkku Roos, Sirpa Metsärinne, Anita Happonen
Budesonide Easyhaler® multidose dry powder inhaler is approved for the treatment of asthma. Objectives were to determine the delivered dose (DD) uniformity of budesonide Easyhaler® in simulated real-world conditions and with different inspiration flow rates (IFRs). Three dose delivery studies were performed using 100, 200, and 400 µg/dose strengths of budesonide. Dose uniformity was assessed during in-use periods of 4-6 months after exposure to high temperature (30°C) and humidity (60% relative humidity) and after dropping and vibration testing...
January 1, 2017: Chronic Respiratory Disease
Sarah N Lauder, Keith Allen-Redpath, David A Slatter, Maceler Aldrovandi, Anne O'Connor, Daniel Farewell, Charles L Percy, Jessica E Molhoek, Sirpa Rannikko, Victoria J Tyrrell, Salvatore Ferla, Ginger L Milne, Alastair W Poole, Christopher P Thomas, Samya Obaji, Philip R Taylor, Simon A Jones, Phillip G de Groot, Rolf T Urbanus, Sohvi Hörkkö, Stefan Uderhardt, Jochen Ackermann, P Vince Jenkins, Andrea Brancale, Gerhard Krönke, Peter W Collins, Valerie B O'Donnell
Blood coagulation functions as part of the innate immune system by preventing bacterial invasion, and it is critical to stopping blood loss (hemostasis). Coagulation involves the external membrane surface of activated platelets and leukocytes. Using lipidomic, genetic, biochemical, and mathematical modeling approaches, we found that enzymatically oxidized phospholipids (eoxPLs) generated by the activity of leukocyte or platelet lipoxygenases (LOXs) were required for normal hemostasis and promoted coagulation factor activities in a Ca2+ - and phosphatidylserine (PS)-dependent manner...
November 28, 2017: Science Signaling
Juho-Antti Junno, Markku Niskanen, Heli Maijanen, Brigitte Holt, Vladimir Sladek, Sirpa Niinimäki, Margit Berner
The stature/bi-iliac breadth method provides reasonably precise, skeletal frame size (SFS) based body mass (BM) estimations across adults as a whole. In this study, we examine the potential effects of age changes in anthropometric dimensions on the estimation accuracy of SFS-based body mass estimation. We use anthropometric data from the literature and our own skeletal data from two osteological collections to study effects of age on stature, bi-iliac breadth, body mass, and body composition, as they are major components behind body size and body size estimations...
November 19, 2017: Journal of Human Evolution
Riikka Siitonen, Annukka Pietikäinen, Heidi Liljenbäck, Meeri Käkelä, Mirva Söderström, Sirpa Jalkanen, Jukka Hytönen, Anne Roivainen
BACKGROUND: In the present study, we sought to evaluate the feasibility of targeting vascular adhesion protein-1 (VAP-1) by positron emission tomography (PET) for the longitudinal quantitative assessment of Borrelia burgdorferi infection-induced inflammation in mice. METHODS: Mice with B. burgdorferi infection-induced arthritis were studied. During a 7-week follow-up period, the progression of arthritis was monitored weekly with68 Ga-DOTA-Siglec-9 PET/computed tomography (CT) and measurement of tibiotarsal joint swellings...
November 22, 2017: Arthritis Research & Therapy
Nan Guo Ring, Dietmar Herndler-Brandstetter, Kipp Weiskopf, Liang Shan, Jens-Peter Volkmer, Benson M George, Melanie Lietzenmayer, Kelly M McKenna, Tejaswitha J Naik, Aaron McCarty, Yunjiang Zheng, Aaron M Ring, Richard A Flavell, Irving L Weissman
Cancer immunotherapy has emerged as a promising therapeutic intervention. However, complete and durable responses are only seen in a fraction of patients who have cancer. A key factor that limits therapeutic success is the infiltration of tumors by cells of the myeloid lineage. The inhibitory receptor signal regulatory protein-α (SIRPα) is a myeloid-specific immune checkpoint that engages the "don't eat me" signal CD47 expressed on tumors and normal tissues. We therefore developed the monoclonal antibody KWAR23, which binds human SIRPα with high affinity and disrupts its binding to CD47...
December 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
Minna Miettinen, Miia Tiihonen, Sirpa Hartikainen, Irma Nykänen
BACKGROUND: Frailty is a common problem among older people and it is associated with an increased risk of death and long-term institutional care. Early identification of frailty is necessary to prevent a further decline in the health status of home care clients. The aims of the present study were to determine the prevalence of frailty and associated factors among 75-year-old or older home care clients. METHODS: The study participants were 75-year-old or older home care clients living in three cities in Eastern and Central Finland...
November 17, 2017: BMC Geriatrics
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