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Mette Vesterhus, Anders Holm, Johannes Roksund Hov, Ståle Nygård, Erik Schrumpf, Espen Melum, Liv Wenche Thorbjørnsen, Vemund Paulsen, Knut Lundin, Inge Dale, Odd Helge Gilja, Serge J L B Zweers, Morten Vatn, Frank G Schaap, Peter L M Jansen, Thor Ueland, Helge Røsjø, Bjørn Moum, Cyriel Y Ponsioen, Kirsten Muri Boberg, Martti Färkkilä, Tom H Karlsen, Fridtjof Lund-Johansen
BACKGROUND&AIMS: We aimed to identify novel protein biomarkers of disease severity and prognosis in primary sclerosing cholangitis (PSC). METHODS: Using a bead-based array targeting 63 proteins, we profiled a derivation panel of Norwegian endoscopic retrograde cholangiography-bile samples (55 PSC, 20 disease controls) and a Finnish validation panel (34 PSC, 10 disease controls). Selected identified proteins were measured in serum from two Norwegian PSC cohorts (n=167 [1992-2006] and n=138 [2008-2012]), inflammatory bowel disease (n=96) and healthy controls (n=100)...
February 1, 2017: Journal of Hepatology
Diem Nguyen, Johanna Boberg, Michelle Cleary, Helge Bruelheide, Lydia Hönig, Julia Koricheva, Jan Stenlid
Foliar fungi of silver birch (Betula pendula) in an experimental Finnish forest were investigated across a gradient of tree species richness using molecular high-throughput sequencing and visual macroscopic assessment. We hypothesized that the molecular approach detects more fungal taxa than visual assessment, and that there is a relationship among the most common fungal taxa detected by both techniques. Furthermore, we hypothesized that the fungal community composition, diversity, and distribution patterns are affected by changes in tree diversity...
February 2, 2017: Scientific Reports
Sun-Gou Ji, Brian D Juran, Sören Mucha, Trine Folseraas, Luke Jostins, Espen Melum, Natsuhiko Kumasaka, Elizabeth J Atkinson, Erik M Schlicht, Jimmy Z Liu, Tejas Shah, Javier Gutierrez-Achury, Kirsten M Boberg, Annika Bergquist, Severine Vermeire, Bertus Eksteen, Peter R Durie, Martti Farkkila, Tobias Müller, Christoph Schramm, Martina Sterneck, Tobias J Weismüller, Daniel N Gotthardt, David Ellinghaus, Felix Braun, Andreas Teufel, Mattias Laudes, Wolfgang Lieb, Gunnar Jacobs, Ulrich Beuers, Rinse K Weersma, Cisca Wijmenga, Hanns-Ulrich Marschall, Piotr Milkiewicz, Albert Pares, Kimmo Kontula, Olivier Chazouillères, Pietro Invernizzi, Elizabeth Goode, Kelly Spiess, Carmel Moore, Jennifer Sambrook, Willem H Ouwehand, David J Roberts, John Danesh, Annarosa Floreani, Aliya F Gulamhusein, John E Eaton, Stefan Schreiber, Catalina Coltescu, Christopher L Bowlus, Velimir A Luketic, Joseph A Odin, Kapil B Chopra, Kris V Kowdley, Naga Chalasani, Michael P Manns, Brijesh Srivastava, George Mells, Richard N Sandford, Graeme Alexander, Daniel J Gaffney, Roger W Chapman, Gideon M Hirschfield, Mariza de Andrade, Simon M Rushbrook, Andre Franke, Tom H Karlsen, Konstantinos N Lazaridis, Carl A Anderson
Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A...
February 2017: Nature Genetics
Mikael Boberg, Marc Vrana, Aanchal Mehrotra, Robin E Pearce, Andrea Gaedigk, Deepak Kumar Bhatt, J Steven Leeder, Bhagwat Prasad
The age-dependent absolute protein abundance of carboxylesterase 1 and 2 (CES1 and CES2) in human liver was investigated and applied to predict infant pharmacokinetics (PK) of oseltamivir. The CES absolute protein abundance was determined by LC-MS/MS proteomics in human liver microsomal and cytosolic fractions prepared from tissue samples obtained from 136 pediatric and 35 adult donors. Two surrogate peptides per protein were selected for the quantification of CES1 and CES2 protein abundance. Purified CES1 and CES2 protein standards were used as calibrators, and the heavy labeled peptides were used as the internal standards...
November 28, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Eva Kristine Klemsdal Henriksen, Kristin Kaasen Jørgensen, Fatemeh Kaveh, Kristian Holm, David Hamm, Johanna Olweus, Espen Melum, Brian K Chung, Tor J Eide, Knut E A Lundin, Kirsten Muri Boberg, Tom H Karlsen, Gideon M Hirschfield, Evaggelia Liaskou
BACKGROUND & AIMS: Recruitment of gut-derived memory T-cells to the liver is believed to drive hepatic inflammation in primary sclerosing cholangitis (PSC). However, whether gut-infiltrating and liver-infiltrating T-cells share T cell receptors (TCRs) and antigenic specificities is unknown. We used paired gut and liver samples from PSC patients with concurrent inflammatory bowel disease (PSC-IBD), and normal tissue samples from colon cancer controls, to assess potential T cell clonotype overlap between the two compartments...
January 2017: Journal of Hepatology
M H Lejonklou, S Christiansen, J Örberg, L Shen, S Larsson, J Boberg, U Hass, P M Lind
BACKGROUND: Bisphenol A (BPA) is a chemical produced in large volumes for use in manufacturing of consumer products and industrial applications, and an endocrine disruptor known to affect several hormonal systems. Bone produces hormones and is additionally a sensitive hormone target tissue, and is thus potentially sensitive to low doses of endocrine disruptors such as BPA, especially during development. METHODS: 110 pregnant Wistar rats were gavaged with 0; 25 μg; 250 μg; 5000 μg or 50,000 μg BPA/kg bodyweight (bw)/day from gestational day 7 until weaning at postnatal day 22...
December 2016: Chemosphere
Johannes R Hov, Kirsten M Boberg, Eli Taraldsrud, Mette Vesterhus, Maria Boyadzhieva, Inger Camilla Solberg, Erik Schrumpf, Morten H Vatn, Benedicte A Lie, Øyvind Molberg, Tom H Karlsen
BACKGROUND&AIMS: The strongest genetic risk factors in primary sclerosing cholangitis (PSC) are encoded in the HLA complex. Anti-neutrophil cytoplasmic antibodies (ANCA) have been reported in up to 94% of PSC patients, but their clinical significance and immunogenetic basis are ill-defined. We aimed to characterize clinical and genetic associations of ANCA in PSC. METHODS: ANCA were analyzed with indirect immunofluorescence in 241 Norwegian PSC patients. HLA-B and HLA-DRB1 genotyping was performed in the patients and in 368 healthy controls...
August 25, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Julie Boberg, Sofie Christiansen, Marta Axelstad, Thuri Seidler Kledal, Anne Marie Vinggaard, Majken Dalgaard, Christine Nellemann, Ulla Hass
No abstract text is available yet for this article.
August 2016: Reproductive Toxicology
Roman Zenouzi, Tobias J Weismüller, Kristin K Jørgensen, Michael Bubenheim, Henrike Lenzen, Peter Hübener, Kornelius Schulze, Christina Weiler-Normann, Marcial Sebode, Hanno Ehlken, Nadine Pannicke, Johannes Hartl, Moritz Peiseler, Sina Hübener, Tom H Karlsen, Kirsten M Boberg, Michael P Manns, Ansgar W Lohse, Christoph Schramm
BACKGROUND & AIMS: Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Patients with PSC also can have inflammatory bowel diseases (IBDs) or features of autoimmune hepatitis (AIH), and therefore are treated with azathioprine. Azathioprine has been associated with an increased risk for malignancy, therefore we investigated whether azathioprine use affects the risk of CCA in persons with PSC. METHODS: We performed a retrospective study of well-defined patients with PSC using data collected from 3 large-volume, tertiary care centers in Germany and Norway...
August 10, 2016: Clinical Gastroenterology and Hepatology
Ina M Andersen, Bjarte Fosby, Kirsten M Boberg, Ole P F Clausen, Peter Jebsen, Espen Melum, Pål D Line, Aksel Foss, Erik Schrumpf, Tom H Karlsen
BACKGROUND: Primary sclerosing cholangitis (PSC) is 1 of the leading causes of liver transplantation (LTX) in Scandinavia, and an increasing number of PSC patients have been transplanted in Norway during the last 2 decades. This trend is partly attributable to the recently established practice in Norway of offering LTX to PSC patients with cholangiocellular dysplasia. Based on the controversy associated with this practice, we herein aimed to report the main features and outcomes of our LTX program in PSC...
October 2015: Transplantation Direct
Lars C Boberg-Ans, Inger C Munch, Michael Larsen, Bamini Gopinath, Jie Jin Wang, Paul Mitchell
PURPOSE: To investigate the epidemiology of Gunn's dots and their associations in a population-based cohort of children. METHODS: Red-free fundus photographs from 2,286 children aged 11 years to 14 years from the Sydney Myopia Study were graded. Gunn's dots were manually marked and counted within a 6 mm grid centered on the optic disc. RESULTS: One or more Gunn's dots were seen in at least one eye in 82.6% of children. The median number of Gunn's dots per eye was 46 (range 0-482)...
February 2017: Retina
J Boberg, M Axelstad, T Svingen, K Mandrup, S Christiansen, A M Vinggaard, U Hass
Parabens comprise a group of preservatives commonly added to cosmetics, lotions, and other consumer products. Butylparaben has estrogenic and antiandrogenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine sensitive endpoints, however, remains largely unknown. In this study, time-mated Wistar rats (n = 18) were orally exposed to 0, 10, 100, or 500 mg/kg bw/d of butylparaben from gestation day 7 to pup day 22. Several endocrine-sensitive endpoints were adversely affected...
July 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Jesus M Banales, Vincenzo Cardinale, Guido Carpino, Marco Marzioni, Jesper B Andersen, Pietro Invernizzi, Guro E Lind, Trine Folseraas, Stuart J Forbes, Laura Fouassier, Andreas Geier, Diego F Calvisi, Joachim C Mertens, Michael Trauner, Antonio Benedetti, Luca Maroni, Javier Vaquero, Rocio I R Macias, Chiara Raggi, Maria J Perugorria, Eugenio Gaudio, Kirsten M Boberg, Jose J G Marin, Domenico Alvaro
Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: or was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level...
May 2016: Nature Reviews. Gastroenterology & Hepatology
U Hass, S Christiansen, J Boberg, M G Rasmussen, K Mandrup, M Axelstad
Bisphenol A is widely used in food contact materials and other products and is detected in human urine and blood. Bisphenol A may affect reproductive and neurological development; however, opinion of the European Food Safety Authority (EFSA) on bisphenol A (EFSA J, 13, 2015 and 3978) concluded that none of the available studies were robust enough to provide a point of departure for setting a tolerable daily intake for bisphenol A. In the present study, pregnant Wistar rats (n = 17-21) were gavaged from gestation day 7 to pup day 22 with bisphenol A doses of 0, 25 μg, 250 μg, 5 mg or 50 mg/kg bw/day...
July 2016: Andrology
K Mandrup, J Boberg, L K Isling, S Christiansen, U Hass
Bisphenol A (BPA) is widely used in food contact materials, toys, and other products. Several studies have indicated that effects observed at doses near human exposure levels may not be observed at higher doses. Many studies have shown effects on mammary glands at low doses of BPA, however, because of small number of animals or few doses investigated these data have not been used by EFSA as point of departure for the newly assessed tolerable daily intake (TDI). We performed a study with perinatal exposure to BPA (0, 0...
July 2016: Andrology
Diem Nguyen, Bastien Castagneyrol, Helge Bruelheide, Filippo Bussotti, Virginie Guyot, Hervé Jactel, Bogdan Jaroszewicz, Fernando Valladares, Jan Stenlid, Johanna Boberg
European forests host a diversity of tree species that are increasingly threatened by fungal pathogens, which may have cascading consequences for forest ecosystems and their functioning. Previous experimental studies suggest that foliar and root pathogen abundance and disease severity decrease with increasing tree species diversity, but evidences from natural forests are rare. Here, we tested whether foliar fungal disease incidence was negatively affected by tree species diversity in different forest types across Europe...
April 2016: Ecology and Evolution
Hanna Katarina Lilith Johansson, Pernille Rosenskjold Jacobsen, Ulla Hass, Terje Svingen, Anne Marie Vinggaard, Louise Krag Isling, Marta Axelstad, Sofie Christiansen, Julie Boberg
Exposure to endocrine disrupting chemicals (EDCs) during development can have negative consequences later in life. In this study we investigated the effect of perinatal exposure to mixtures of human relevant EDCs on the female reproductive system. Rat dams were exposed to a mixture of phthalates, pesticides, UV-filters, bisphenol A, butylparaben, as well as paracetamol. The compounds were tested together (Totalmix) or in subgroups with anti-androgenic (AAmix) or estrogenic (Emix) potentials. Paracetamol was tested separately...
June 2016: Reproductive Toxicology
F Bernuzzi, F Marabita, A Lleo, M Carbone, M Mirolo, M Marzioni, G Alpini, D Alvaro, K M Boberg, M Locati, G Torzilli, L Rimassa, F Piscaglia, X-S He, C L Bowlus, G-X Yang, M E Gershwin, P Invernizzi
The diagnosis of primary sclerosing cholangitis (PSC) is difficult due to the lack of sensitive and specific biomarkers, as is the early diagnosis of cholangiocarcinoma (CC), a complication of PSC. The aim of this study was to identify specific serum miRNAs as diagnostic biomarkers for PSC and CC. The levels of 667 miRNAs were evaluated in 90 human serum samples (30 PSC, 30 CC and 30 control subjects) to identify disease-associated candidate miRNAs (discovery phase). The deregulated miRNAs were validated in an independent cohort of 140 samples [40 PSC, 40 CC, 20 primary biliary cirrhosis (PBC) and 40 controls]...
July 2016: Clinical and Experimental Immunology
Adam Felton, Urban Nilsson, Johan Sonesson, Annika M Felton, Jean-Michel Roberge, Thomas Ranius, Martin Ahlström, Johan Bergh, Christer Björkman, Johanna Boberg, Lars Drössler, Nils Fahlvik, Peichen Gong, Emma Holmström, E Carina H Keskitalo, Maartje J Klapwijk, Hjalmar Laudon, Tomas Lundmark, Mats Niklasson, Annika Nordin, Maria Pettersson, Jan Stenlid, Anna Sténs, Kristina Wallertz
Whereas there is evidence that mixed-species approaches to production forestry in general can provide positive outcomes relative to monocultures, it is less clear to what extent multiple benefits can be derived from specific mixed-species alternatives. To provide such insights requires evaluations of an encompassing suite of ecosystem services, biodiversity, and forest management considerations provided by specific mixtures and monocultures within a region. Here, we conduct such an assessment in Sweden by contrasting even-aged Norway spruce (Picea abies)-dominated stands, with mixed-species stands of spruce and birch (Betula pendula or B...
February 2016: Ambio
Marcus Harbord, Vito Annese, Stephan R Vavricka, Matthieu Allez, Manuel Barreiro-de Acosta, Kirsten Muri Boberg, Johan Burisch, Martine De Vos, Anne-Marie De Vries, Andrew D Dick, Pascal Juillerat, Tom H Karlsen, Ioannis Koutroubakis, Peter L Lakatos, Tim Orchard, Pavol Papay, Tim Raine, Max Reinshagen, Diamant Thaci, Herbert Tilg, Franck Carbonnel
No abstract text is available yet for this article.
March 2016: Journal of Crohn's & Colitis
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