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Daniel A Patten, Garrick K Wilson, Dalan Bailey, Robert K Shaw, Sirpa Jalkanen, Marko Salmi, Antal Rot, Christopher J Weston, David H Adams, Shishir Shetty
: The recruitment of lymphocytes via the hepatic sinusoidal channels and positioning within liver tissue is a critical event in the development and persistence of chronic inflammatory liver diseases. The hepatic sinusoid is a unique vascular bed lined by hepatic sinusoidal endothelial cells (HSEC), a functionally and phenotypically distinct sub-population of endothelial cells. Using flow based adhesion assays to study the migration of lymphocytes across primary human HSEC, we found that lymphocytes enter into HSEC, confirmed by electron microscopy demonstrating clear intracellular localization of lymphocytes in vitro and by studies in human liver tissues...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Suvi T Vaara, Maija Hollmén, Anna-Maija Korhonen, Mikael Maksimow, Tero Ala-Kokko, Marko Salmi, Sirpa Jalkanen, Ville Pettilä
BACKGROUND: CD73 dephosphorylates adenosine monophosphate to adenosine that is an anti-inflammatory molecule inhibiting immune activation and vascular leakage. Therefore, CD73 could be an interesting mediator both in sepsis and acute kidney injury (AKI). We aimed to explore the soluble CD73 (sCD73) levels and their evolution in critically ill patients with severe sepsis and, second, to scrutinize the potential association of sCD73 levels with AKI and 90-day mortality. METHODS: This was a post-hoc laboratory analysis of the prospective, observational FINNAKI study conducted in 17 Finnish ICU during 5 months in 2011-2012...
2016: PloS One
Johanna M U Silvola, Helena Virtanen, Riikka Siitonen, Sanna Hellberg, Heidi Liljenbäck, Olli Metsälä, Mia Ståhle, Tiina Saanijoki, Meeri Käkelä, Harri Hakovirta, Seppo Ylä-Herttuala, Pekka Saukko, Matti Jauhiainen, Tibor Z Veres, Sirpa Jalkanen, Juhani Knuuti, Antti Saraste, Anne Roivainen
Given the important role of inflammation and the potential association of the leukocyte trafficking-associated adhesion molecule vascular adhesion protein 1 (VAP-1) with atherosclerosis, this study examined whether functional VAP-1 is expressed in atherosclerotic lesions and, if so, whether it could be targeted by positron emission tomography (PET). First, immunohistochemistry revealed that VAP-1 localized to endothelial cells of intra-plaque neovessels in human carotid endarterectomy samples from patients with recent ischemic symptoms...
October 12, 2016: Scientific Reports
Sirpa Kaunisto, Laura V Ferguson, Brent J Sinclair
The responses of insects to climate change will depend on their responses to abiotic and biotic stressors in combination. We surveyed the literature, and although synergistic stressor interactions appear common among insects, the thin taxonomic spread of existing data means that more multi-stressor studies and new approaches are needed. We need to move beyond descriptions of the effects of multiple stressors to a mechanistic, predictive understanding. Further, we must identify which stressor interactions, and species' responses to them, are sufficiently generalizable (i...
October 2016: Current Opinion in Insect Science
Sirpa Kaunisto, Ilkka Raunismaa, Raine Kortet, Hannu Ylönen
Predation can regulate populations and strongly affect invasion success of novel prey. The deer ked (Lipoptena cervi; Linnaeus 1758) is an invasive ectoparasite of cervids that spends a long period of its life cycle outside the host. Prior to this study, virtually nothing was known about natural summer time predation on the deer ked. We aimed to evaluate the magnitude of summer time predation on L. cervi pupae in different habitats and to identify potential predators. We conducted a set of field experiments, where we exposed L...
October 6, 2016: Parasitology
Antonella Muraro, Brecht Steelant, Sirpa Pietikainen, David Borrelli, Nessa Childers, Ina Callebaut, Inge Kortekaas Krohn, Katleen Martens, Benoit Pugin, Florin Dan-Popescu, Mariana Vieru, Marek Jutel, Ioana Agache, Peter W Hellings
From the 26th to the 28th of April 2016, an allergy awareness campaign was organized by the European Academy of Allergy and Clinical Immunology (EAACI) and the European Federation of Allergy and Airway Diseases Patients Associations (EFA) in the European Parliament in Brussels, with support of the European Parliament's Interest group on Allergy and Asthma and was co-hosted by the Members of the European Parliament (MEP) David Borrelli, Sirpa Pietikainen and Nessa Childers. Skin prick tests (SPT) were performed to gain attention for the increasing prevalence of allergic airways diseases in Europe...
October 3, 2016: Allergy
Sirpa Loukovaara, Jouko Sandholm, Kristiina Aalto, Janne Liukkonen, Sirpa Jalkanen, Gennady G Yegutkin
: Clear signaling roles for ATP and adenosine have been established in all tissues, including the eye. The magnitude of signaling responses is governed by networks of enzymes; however, little is known about the regulatory mechanisms of purinergic signaling in the eye. By employing thin-layer chromatographic assays with (3)H-labeled substrates, this study aimed to evaluate the role of nucleotide homeostasis in the pathogenesis of vitreoretinal diseases in humans. We have identified soluble enzymes ecto-5'-nucleotidase/CD73, adenylate kinase-1, and nucleoside diphosphate kinase in the vitreous fluid that control active cycling between pro-inflammatory ATP and anti-inflammatory adenosine...
September 16, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Juho Jalkanen, Mikael Maksimow, Maija Hollmén, Sirpa Jalkanen, Harri Hakovirta
Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease (PAD) and associated with an extremely poor clinical outcome. In order to understand the possible role of circulating cytokines and poor outcome associated with CLI we compared the circulating cytokine profile of patients with CLI against patients with intermittent claudication (IC). The levels of 48 circulating cytokines were examined in 226 consecutive patients with peripheral artery disease (PAD) admitted for elective, non-urgent, invasive treatment of IC or CLI...
2016: PloS One
Heidi Taipale, Marjaana Koponen, Antti Tanskanen, Anna-Maija Tolppanen, Jari Tiihonen, Sirpa Hartikainen
BACKGROUND: increasing number of persons reach very high age but few studies have investigated their drug use patterns. OBJECTIVE: to compare drug use among persons with Alzheimer's disease (AD) aged ≥90 years to persons without AD with similar age and to younger persons with AD. DESIGN: register-based data were from the MEDALZ cohort including all community-dwelling persons diagnosed with AD 2005-11 in Finland. They were identified from Special Reimbursement register...
September 8, 2016: Age and Ageing
Imtiaz Iftakhar-E-Khuda, Ruth Fair-Mäkelä, Anu Kukkonen-Macchi, Kati Elima, Marika Karikoski, Pia Rantakari, Masayuki Miyasaka, Marko Salmi, Sirpa Jalkanen
Afferent lymphatic vessels bring antigens and diverse populations of leukocytes to draining lymph nodes, whereas efferent lymphatics allow only lymphocytes and antigens to leave the nodes. Despite the fundamental importance of afferent vs. efferent lymphatics in immune response and cancer spread, the molecular characteristics of these different arms of the lymphatic vasculature are largely unknown. The objective of this work was to explore molecular differences behind the distinct functions of afferent and efferent lymphatic vessels, and find possible molecules mediating lymphocyte traffic...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
Mia Biström, Anna-Maria Moisander-Jylhä, Sirpa Heinikainen, Kirsti Pelkola, Mirja Raunio-Saarnisto
BACKGROUND: An outbreak of sudden death of pregnant farmed mink in Finland occurred during the busiest whelping period in the spring of 2013. The affected farms were all located in western Finland in a rather narrow geographic area, Ostrobothnia. Dead mink from 22 farms were submitted for laboratory diagnostics to the Finnish Food Safety Authority (Evira). The carcasses were necropsied and tissue specimens were prepared for histology. Samples of internal organs and peritoneal fluid were cultured bacteriologically...
2016: Acta Veterinaria Scandinavica
Qin Wang, Peter Würtz, Kirsi Auro, Laure Morin-Papunen, Antti J Kangas, Pasi Soininen, Mika Tiainen, Tuulia Tynkkynen, Anni Joensuu, Aki S Havulinna, Kristiina Aalto, Marko Salmi, Stefan Blankenberg, Tanja Zeller, Jorma Viikari, Mika Kähönen, Terho Lehtimäki, Veikko Salomaa, Sirpa Jalkanen, Marjo-Riitta Järvelin, Markus Perola, Olli T Raitakari, Debbie A Lawlor, Johannes Kettunen, Mika Ala-Korpela
BACKGROUND: Hormonal contraception is commonly used worldwide, but its systemic effects across lipoprotein subclasses, fatty acids, circulating metabolites and cytokines remain poorly understood. METHODS: A comprehensive molecular profile (75 metabolic measures and 37 cytokines) was measured for up to 5841 women (age range 24-49 years) from three population-based cohorts. Women using combined oral contraceptive pills (COCPs) or progestin-only contraceptives (POCs) were compared with those who did not use hormonal contraception...
August 18, 2016: International Journal of Epidemiology
Chris J Jung, Séverine Ménoret, Lucas Brusselle, Laurent Tesson, Claire Usal, Vanessa Chenouard, Séverine Remy, Laure-Hélène Ouisse, Nicolas Poirier, Bernard Vanhove, Pieter J de Jong, Ignacio Anegon
BAC transgenic mammalian systems offer an important platform for recapitulating human gene expression and disease modeling. While the larger body mass, and greater genetic and physiologic similarity to humans render rats well suited for reproducing human immune diseases and evaluating therapeutic strategies, difficulties of generating BAC transgenic rats have hindered progress. Thus, an efficient method for BAC transgenesis in rats would be valuable. Immunodeficient mice carrying a human SIRPA transgene have previously been shown to support improved human cell hematopoiesis...
2016: Scientific Reports
Anna Toljamo, Daniel Blande, Sirpa Kärenlampi, Harri Kokko
Crown rot (Phytophthora cactorum) causes significant economic losses in strawberry production. The best control strategy would be to use resistant cultivars, but polygenically inherited resistance makes the breeding of the garden strawberry (Fragaria × ananassa) challenging. The diploid wild strawberry Fragaria vesca Hawaii 4 genotype was shown previously to have resistance against crown rot. To explore the resistance mechanisms, we inoculated the roots of Hawaii 4 with P. cactorum in a novel in vitro hydroponic system to minimize interference caused by other microbes...
2016: PloS One
Manasi M Kamat, Sreelakshmi Vasudevan, Samar A Maalouf, David H Townson, Joy L Pate, Troy L Ott
Establishment of pregnancy requires interaction between the developing conceptus and the uterine mucosal immune system. Little is known regarding the role and distribution of myeloid lineage cells (macrophages and dendritic cells) during early pregnancy in ruminants. We tested the hypothesis that myeloid lineage cell number, distribution and function are altered during early pregnancy in dairy heifers. Dairy heifers were inseminated using sperm from a single bull (Day 0), and uteri and blood were collected at slaughter on Day 17 and 20 of pregnancy to investigate the response of uterine myeloid lineage cells to the presence of a conceptus...
August 10, 2016: Biology of Reproduction
Ayano Yurino, Katsuto Takenaka, Takuji Yamauchi, Takuya Nunomura, Yasufumi Uehara, Fumiaki Jinnouchi, Kohta Miyawaki, Yoshikane Kikushige, Koji Kato, Toshihiro Miyamoto, Hiromi Iwasaki, Yuya Kunisaki, Koichi Akashi
In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous Kit(Wv) mutations into C57BL/6.Rag2(null)Il2rg(null) mice with NOD-Sirpa (BRGS) strongly promoted human multi-lineage reconstitution. After xenotransplantation of human CD34(+)CD38(-) cord blood cells, these newly generated C57BL/6.Rag2(null)Il2rg(null)NOD-Sirpa Kit(Wv/Wv) (BRGSK(Wv/Wv)) mice showed significantly higher levels of human cell chimerism and long-term multi-lineage reconstitution compared with BRGS mice...
September 13, 2016: Stem Cell Reports
Lauri Lehtimäki, Péter Csonka, Eeva Mäkinen, Jaana Isojärvi, Sirpa-Liisa Hovi, Anneli Ahovuo-Saloranta
The clinical value of measuring fractional exhaled nitric oxide (FeNO) in asthma is not clear. We aimed to assess whether FeNO can reliably predict clinical outcomes in asthma treated with inhaled corticosteroids (ICS). We also evaluated whether its predictive role is influenced by different inflammatory phenotypes of asthma.We conducted a systematic review focusing on five clinically relevant questions. Two authors independently screened search results, extracted data and assessed quality of the included studies...
September 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Pranali Patel, Uros Kuzmanov, Seema Mital
BACKGROUND: Human tyrosine-protein phosphatase non-receptor type substrate 1α (SIRPA) is a surface marker identified in cardiomyocytes differentiated from human embryonic stem cells. Our objective was to determine if circulating SIRPA levels can serve as a biomarker of cardiac injury in children undergoing open heart surgery. RESULTS: Paired pre- and post-operative serum samples from 48 pediatric patients undergoing open heart surgery and from 6 pediatric patients undergoing non-cardiac surgery (controls) were tested for SIRPA protein levels using commercially available SIRPA ELISA kits from two manufacturers...
2016: BMC Biochemistry
Pia Rantakari, Daniel A Patten, Joona Valtonen, Marika Karikoski, Heidi Gerke, Harriet Dawes, Juha Laurila, Steffen Ohlmeier, Kati Elima, Stefan G Hübscher, Chris J Weston, Sirpa Jalkanen, David H Adams, Marko Salmi, Shishir Shetty
Macrophages are key regulators of fibrosis development and resolution. Elucidating the mechanisms by which they mediate this process is crucial for establishing their therapeutic potential. Here, we use experimental models of liver fibrosis to show that deficiency of the scavenger receptor, stabilin-1, exacerbates fibrosis and delays resolution during the recovery phase. We detected a subset of stabilin-1(+) macrophages that were induced at sites of cellular injury close to the hepatic scar in mouse models of liver fibrosis and in human liver disease...
August 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
Guihua Jiang, Todd J Herron, Julie Di Bernardo, Kendal A Walker, K Sue O'Shea, Shaun M Kunisaki
: : The establishment of an abundant source of autologous cardiac progenitor cells would represent a major advance toward eventual clinical translation of regenerative medicine strategies in children with prenatally diagnosed congenital heart disease. In support of this concept, we sought to examine whether functional, transgene-free human cardiomyocytes (CMs) with potential for patient-specific and autologous applications could be reliably generated following routine amniocentesis. Under institutional review board approval, amniotic fluid specimens (8-10 ml) at 20 weeks gestation were expanded and reprogrammed toward pluripotency using nonintegrating Sendai virus (SeV) expressing OCT4, SOX2, cMYC, and KLF4...
July 27, 2016: Stem Cells Translational Medicine
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