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  • 51.
    Asa, Sylvia
    et al.
    Department of Pathology, University Health Network, Toronto, Ontario, Canada.
    Bodén, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Treanor, Darren
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine.
    Lundström, Claes
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Pantatnowitz, Liron
    Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, USA.
    2020 vision of digital pathology in action2019In: Journal of Pathology Informatics, ISSN 2229-5089, E-ISSN 2153-3539, Vol. 10, no 27Article in journal (Refereed)
  • 52.
    Aslan, Cynthia
    et al.
    Tabriz Univ Med Sci, Iran.
    Maralbashi, Sepideh
    Kermanshah Univ Med Sci, Iran.
    Salari, Farhad
    Kermanshah Univ Med Sci, Iran.
    Kahroba, Houman
    Tabriz Univ Med Sci, Iran.
    Sigaroodi, Faraz
    Tabriz Univ Med Sci, Iran.
    Kazemi, Tohid
    Tabriz Univ Med Sci, Iran.
    Kharaziha, Pedram
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Tumor-derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy2019In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 234, no 10, p. 16885-16903Article, review/survey (Refereed)
    Abstract [en]

    Tumor cells utilize different strategies to communicate with neighboring tissues for facilitating tumor progression and invasion, one of these strategies has been shown to be the release of exosomes. Exosomes are small nanovesicles secreted by all kind of cells in the body, especially cancer cells, and mediate cell to cell communications. Exosomes play an important role in cancer invasiveness by harboring various cargoes that could accelerate angiogenesis. Here first, we will present an overview of exosomes, their biology, and their function in the body. Then, we will focus on exosomes derived from tumor cells as tumor angiogenesis mediators with a particular emphasis on the underlying mechanisms in various cancer origins. Also, exosomes derived from stem cells and tumor-associated macrophages will be discussed in this regard. Finally, we will discuss the novel therapeutic strategies of exosomes as drug delivery vehicles against angiogenesis.

  • 53.
    Banch Clausen, Frederik
    et al.
    Copenhagen Univ Hosp, Denmark; Natl Univ Singapore, Singapore.
    Barrett, Angela Natalie
    Copenhagen Univ Hosp, Denmark; Natl Univ Singapore, Singapore.
    Akkok, Cigdem Akalin
    Oslo Univ Hosp, Norway.
    Armstrong-Fisher, Sylvia
    Scottish Natl Blood Transfus Serv, Scotland.
    Danielsson Bergstrom, Karolina
    Orebro Univ Hosp, Sweden.
    Trucco Boggione, Carolina
    Univ Nacl Rosario, Argentina.
    Sillhagen Baevre, Mette
    Oslo Univ Hosp, Norway.
    Choolani, Mahesh
    Natl Univ Singapore City, Singapore.
    Christiansen, Mette
    Aarhus Univ, Denmark.
    Cotorruelo, Carlos
    Univ Nacl Rosario, Argentina.
    Drnovsek, Tadeja Dovc
    Blood Transfus Ctr Slovenia, Slovenia.
    Finning, Kirstin
    NHS Blood and Transplant, England.
    Guz, Katarzyna
    Inst Hematol and Transfus Med, Poland.
    de Haas, Masja
    Sanquin Blood Supply Fdn, Netherlands.
    Haimila, Katri
    Finnish Red Cross Blood Serv, Finland.
    Halldorsdottir, Anna Margret
    Landspitali Univ Hosp, Iceland.
    Hellberg, Asa
    Lund Univ, Sweden.
    Henny, Christine
    Interreg Blood Transfus SRC, Switzerland.
    Holmertz, Camilla
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Al Houghton, Jayne
    Royal Devon and Exeter NHS Fdn Trust, England.
    Hyland, Catherine
    Australian Red Cross Blood Serv, Australia.
    Jakobsen, Marianne Antonius
    Odense Univ Hosp, Denmark.
    Kvitland, Mona Andersen
    St Olavs Hosp, Norway.
    Lambert, Mark
    Natl Blood Ctr, Ireland.
    Legler, Tobias J.
    Georg August Univ, Germany.
    Liew, Yew-Wah
    Australian Red Cross Blood Serv, Australia.
    Muniz-Diaz, Eduardo
    Banc Sang and Teixits, Spain.
    Mortberg, Anette
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Niederhauser, Christoph
    Interreg Blood Transfus SRC, Switzerland.
    Nogues, Nuria
    Banc Sang and Teixits, Spain.
    Nyström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Olsson, Martin L.
    Lund Univ, Sweden; Lund Univ, Sweden.
    Orzinska, Agnieszka
    Inst Hematol and Transfus Med, Poland.
    Parks, Michael
    Nonacus Ltd, England.
    Rietkotter, Eva
    LADR GmbH MVZ Dr Kramer and Kollegen, Germany.
    Ryan, Helen
    Natl Blood Ctr, Ireland.
    Sachs, Ulrich J.
    Justus Liebig Univ, Germany.
    van der Schoot, Ellen
    Sanquin Res CLB, Netherlands.
    Silcock, Lee
    Nonacus Ltd, England.
    Steffensen, Rudi
    Aalborg Univ Hosp, Denmark.
    Sulin, Kati
    Finnish Red Cross Blood Serv, Finland.
    Sorensen, Anne Solling
    Naestved Hosp, Denmark.
    Tarrant, Sarah
    NHS Blood and Transplant, England.
    Thorlacius, Steinunn
    Landspitali Univ Hosp, Iceland.
    Wienzek-Lischka, Sandra
    Justus Liebig Univ, Germany.
    Wikman, Agneta
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Wulf-Johansson, Helle
    Naestved Hosp, Denmark.
    Zupan, Mojca
    Blood Transfus Ctr Slovenia, Slovenia.
    Dziegiel, Morten Hanefeld
    Copenhagen Univ Hosp, Denmark; Univ Copenhagen, Denmark.
    Noninvasive fetal RHD genotyping to guide targeted anti-D prophylaxis-an external quality assessment workshop2019In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 114, no 4, p. 386-393Article in journal (Refereed)
    Abstract [en]

    Background and Objectives Fetal RHD genotyping of cell-free fetal DNA from RhD-negative pregnant women can be used to guide targeted antenatal and postnatal anti-D prophylaxis for the prevention of RhD immunization. To assure the quality of clinical testing, we conducted an external quality assessment workshop with the participation of 28 laboratories. Materials and Methods Aliquots of pooled maternal plasma were sent to each laboratory. One sample was positive, and the second sample was negative for fetal RHD, verified by pre-workshop testing using quantitative real-time PCR (qPCR) analysis of RHD exons 4, 5, 7 and 10. Plasma samples were shipped at room temperature. A reporting scheme was supplied for data collection, including questions regarding the methodological setup, results and clinical recommendations. Different methodological approaches were used, all employing qPCR with a total of eight different combinations of RHD exon targets. The samples were tested blindly. Results Fetal RHD genotyping was performed with no false-negative and no false-positive results. One inconclusive result was reported for the RHD-positive sample, and four inconclusive results were reported for the RHD-negative sample. All clinical conclusions were satisfactory. Conclusion This external quality assessment workshop demonstrates that despite the different approaches taken to perform the clinical assays, fetal RHD genotyping is a reliable laboratory assay to guide targeted use of Rh prophylaxis in a clinical setting.

  • 54.
    Barcenilla, Hugo
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Pihl, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Mass Cytometry Identifies Distinct Subsets of Regulatory T Cells and Natural Killer Cells Associated With High Risk for Type 1 Diabetes2019In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 982Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin producing beta-cells. The time from onset of islet autoimmunity to manifest clinical disease can vary widely in length, and it is fairly uncharacterized both clinically and immunologically. In the current study, peripheral blood mononuclear cells from autoantibody-positive children with high risk for T1D, and from age-matched healthy individuals, were analyzed by mass cytometry using a panel of 32 antibodies. Surface markers were chosen to identify multiple cell types including T, B, NK, monocytes, and DC, and antibodies specific for identification of differentiation, activation and functional markers were also included in the panel. By applying dimensional reduction and computational unsupervised clustering approaches, we delineated in an unbiased fashion 132 phenotypically distinct subsets within the major immune cell populations. We were able to identify an effector memory Treg subset expressing HLA-DR, CCR4, CCR6, CXCR3, and GATA3 that was increased in the high-risk group. In addition, two subsets of NK cells defined by CD16(+) CD8(+) CXCR3(+) and CD16(+) CD8(+) CXCR3(+) CD11c(+) were also higher in the same subjects. High-risk individuals did not show impaired glucose tolerance at the time of sampling, suggesting that the changes observed were not the result of metabolic imbalance, and might be potential biomarkers predictive of T1D.

  • 55.
    Barde, Swapnali
    et al.
    Karolinska Institute, Sweden.
    Ruegg, Joelle
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden; Swedish Toxicol Science Research Centre Swetox, Sweden.
    Prudhomme, Jose
    Douglas Mental Health University of Institute, Canada.
    Ekström, Tomas J.
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Palkovits, Miklos
    Semmelweis University, Hungary.
    Turecki, Gustavo
    Douglas Mental Health University of Institute, Canada; McGill University, Canada.
    Bagdy, Gyorgy
    Semmelweis University, Hungary.
    Ihnatko, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Juhasz, Gabriella
    Semmelweis University, Hungary; University of Manchester, England.
    Diaz-Heijtz, Rochellys
    Karolinska Institute, Sweden.
    Mechawar, Naguib
    Douglas Mental Health University of Institute, Canada; McGill University, Canada.
    Hokfelt, Tomas G. M.
    Karolinska Institute, Sweden.
    Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide2016In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, ISSN 0027-8424, Vol. 113, no 52, p. E8472-E8481Article in journal (Refereed)
    Abstract [en]

    Major depressive disorder (MDD) is a substantial burden to patients, families, and society, but many patients cannot be treated adequately. Rodent experiments suggest that the neuropeptide galanin (GAL) and its three G protein-coupled receptors, GAL(1-3), are involved in mood regulation. To explore the translational potential of these results, we assessed the transcript levels (by quantitative PCR), DNA methylation status (by bisulfite pyrosequencing), and GAL peptide by RIA of the GAL system in postmortem brains from depressed persons who had committed suicide and controls. Transcripts for all four members were detected and showed marked regional variations, GAL and galanin receptor 1 (GALR1) being most abundant. Striking increases in GAL and GALR3 mRNA levels, especially in the noradrenergic locus coeruleus and the dorsal raphe nucleus, in parallel with decreased DNA methylation, were found in both male and female suicide subjects as compared with controls. In contrast, GAL and GALR3 transcript levels were decreased, GALR1 was increased, and DNA methylation was increased in the dorsolateral prefrontal cortex of male suicide subjects, however, there were no changes in the anterior cingulate cortex. Thus, GAL and its receptor GALR3 are differentially methylated and expressed in brains of MDD subjects in a region- and sex-specific manner. Such an epigenetic modification in GALR3, a hyperpolarizing receptor, might contribute to the dysregulation of noradrenergic and serotonergic neurons implicated in the pathogenesis of MDD. Thus, one may speculate that a GAL(3) antagonist could have antidepressant properties by disinhibiting the firing of these neurons, resulting in increased release of noradrenaline and serotonin in forebrain areas involved in mood regulation.

  • 56.
    Bar-Sever, Zvi
    et al.
    Tel Aviv Univ, Israel.
    Biassoni, Lorenzo
    Great Ormond St Hosp Children NHS Fdn Trust, England.
    Shulkin, Barry
    St Jude Childrens Res Hosp, TN 38105 USA.
    Kong, Grace
    Peter MacCallum Canc Ctr, Australia.
    Hofman, Michael S.
    Peter MacCallum Canc Ctr, Australia.
    Lopci, Egesta
    Humanitas Clin and Res Hosp, Italy.
    Manea, Irina
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Koziorowski, Jacek
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Castellani, Rita
    Ist Nazl Tumori, Italy.
    Boubaker, Ariane
    Clin Source, Switzerland.
    Lambert, Bieke
    Univ Ghent, Belgium.
    Pfluger, Thomas
    Ludwig Maximilian Univ Hosp, Germany.
    Nadel, Helen
    British Columbia Childrens Hosp, Canada.
    Sharp, Susan
    Cincinnati Childrens Hosp Med Ctr, OH 45229 USA.
    Giammarile, Francesco
    IAEA, Austria.
    Guidelines on nuclear medicine imaging in neuroblastoma2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no 11, p. 2009-2024Article in journal (Refereed)
    Abstract [en]

    Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on I-123-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with F-18-FDG, F-18-DOPA and Ga-68-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.

  • 57.
    Bausch, Birke
    et al.
    Albert Ludwigs University, Germany.
    Schiavi, Francesca
    Ist Ricovero and Cura Carattere Science, Italy.
    Ni, Ying
    Cleveland Clin, OH 44106 USA.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Patocs, Attila
    Semmelweis University, Hungary; Semmelweis University, Hungary.
    Ngeow, Joanne
    National Cancer Centre Singapore, Singapore; Nanyang Technology University, Singapore.
    Wellner, Ulrich
    University of Lubeck, Germany.
    Malinoc, Angelica
    Albert Ludwigs University, Germany.
    Taschin, Elisa
    Ist Ricovero and Cura Carattere Science, Italy.
    Barbon, Giovanni
    Ist Ricovero and Cura Carattere Science, Italy.
    Lanza, Virginia
    Ist Ricovero and Cura Carattere Science, Italy.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Stenman, Adam
    Karolinska Institute, Sweden.
    Larsson, Catharina
    Karolinska Institute, Sweden.
    Svahn, Fredrika
    Karolinska Institute, Sweden.
    Chen, Jin-Lian
    Cleveland Clin, OH 44106 USA.
    Marquard, Jessica
    Cleveland Clin, OH 44106 USA.
    Fraenkel, Merav
    Hadassah Hebrew University, Israel.
    Walter, Martin A.
    University Hospital, Switzerland.
    Peczkowska, Mariola
    Institute Cardiol, Poland.
    Prejbisz, Aleksander
    Institute Cardiol, Poland.
    Jarzab, Barbara
    Maria Sklodowska Curie Mem Cancer Centre and Institute Oncol, Poland.
    Hasse-Lazar, Kornelia
    Maria Sklodowska Curie Mem Cancer Centre and Institute Oncol, Poland.
    Petersenn, Stephan
    Centre Endocrine Tumors, Germany.
    Moeller, Lars C.
    University of Duisburg Essen, Germany.
    Meyer, Almuth
    HELIOS Klin, Germany.
    Reisch, Nicole
    Ludwigs Maximilians University of Munich, Germany.
    Trupka, Arnold
    City Hospital, Germany.
    Brase, Christoph
    University of Erlangen Nurnberg, Germany.
    Galiano, Matthias
    University Hospital Erlangen, Germany.
    Preuss, Simon F.
    University of Cologne, Germany.
    Kwok, Pingling
    University of Regensburg, Germany.
    Lendvai, Nikoletta
    Semmelweis University, Hungary.
    Berisha, Gani
    Albert Ludwigs University, Germany.
    Makay, Ozer
    Ege University, Turkey.
    Boedeker, Carsten C.
    HELIOS Hanseklinikum Stralsund, Germany.
    Weryha, Georges
    University of Nancy, France.
    Racz, Karoly
    Semmelweis University, Hungary.
    Januszewicz, Andrzej
    Institute Cardiol, Poland.
    Walz, Martin K.
    Kliniken Essen Mitte, Germany; Kliniken Essen Mitte, Germany.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Opocher, Giuseppe
    Ist Ricovero and Cura Carattere Science, Italy.
    Eng, Charis
    Cleveland Clin, OH 44106 USA; Cleveland Clin, OH 44106 USA.
    Neumann, Hartmut P. H.
    Albert Ludwigs University, Germany.
    Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention2017In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 3, no 9, p. 1204-1212Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P amp;lt; .001). CONCLUSIONS AND RELEVANCE The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.

  • 58.
    Bednarska, Olga
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Icenhour, Adriane
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne Tyson
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Elsenbruch, Sigrid
    Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome2019In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, no 9, p. 2004-2012Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstratealtered function in anterior insula (aINS), a key hub for integration of interoceptive, affective, and cognitive processes. However,alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changesremain elusive. Using quantitative magnetic resonance spectroscopy, we compared women with IBS and healthy women (healthycontrols [HC]) with respect to aINS glutamate 1 glutamine (Glx) and g-aminobutyric acid (GABA1) concentrations and addressedpossible associations with symptoms. Thirty-nine women with IBS and 21 HC underwent quantitative magnetic resonancespectroscopy of bilateral aINS to assess Glx and GABA1 concentrations. Questionnaire data from all participants and prospectivesymptom-diary data from patients were obtained for regression analyses of neurotransmitter concentrations with IBS-related andpsychological parameters. Concentrations of Glx were lower in IBS compared with HC (left aINS P , 0.05, right aINS P , 0.001),whereas no group differences were detected for GABA1concentrations. Lower right-lateralized Glx concentrations in patients weresubstantially predicted by longer pain duration, while less frequent use of adaptive pain‐coping predicted lower Glx in left aINS. Ourfindings provide first evidence for reduced excitatory but unaltered inhibitory neurotransmitter levels in aINS in IBS. The results alsoindicate a functional lateralization of aINS with a stronger involvement of the right hemisphere in perception of abdominal pain and ofthe left aINS in cognitive pain regulation. Our findings suggest that glutaminergic deficiency may play a role in pain processing in IBS.

  • 59.
    Bengtsson, Daniel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Joost, Patrick
    Lund University, Sweden.
    Aravidis, Christos
    Uppsala University, Sweden.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics. Off Medical Serv, Sweden; Lund University, Sweden.
    Backman, Ann-Sofie
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Melin, Beatrice
    Umeå University, Sweden.
    von Salome, Jenny
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Zagoras, Theofanis
    Sahlgrens University Hospital, Sweden.
    Gebre-Medhin, Samuel
    Lund University, Sweden; Karolinska University Hospital, Sweden.
    Burman, Pia
    Lund University, Sweden.
    Corticotroph Pituitary Carcinoma in a Patient With Lynch Syndrome (LS) and Pituitary Tumors in a Nationwide LS Cohort2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 11, p. 3928-3932Article in journal (Refereed)
    Abstract [en]

    Context: Lynch syndrome (LS) is a cancer-predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported. Case: A 51-year-old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patients germline mutation and displayed defect MMR function. Sixteen months later, the tumor had developed into a carcinoma with widespread liver metastases. The patient prompted us to perform a nationwide study in LS. Nationwide Study: A diagnosis consistent with a pituitary tumor was sought for in the Swedish National Patient Registry. In 910 patients with LS, representing all known cases in Sweden, another two clinically relevant pituitary tumors were found: an invasive nonsecreting macroadenoma and a microprolactinoma (i.e., in total three tumors vs. one expected). Conclusion: Germline mutations in MMR genes may contribute to the development and/or the clinical course of pituitary tumors. Because tumors with MMR mutations are susceptible to treatment with immune checkpoint inhibitors, we suggest to actively ask for a family history of LS in the workup of patients with aggressive pituitary tumors.

  • 60.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bich Hoang, Ngoc Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Kien Le, Ngai
    Vietnam Natl Childrens Hosp, Vietnam.
    Svartström, Olov
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Khanh Khu, Dung Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Thanh Le, Hai
    Vietnam Natl Childrens Hosp, Vietnam.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Olson, Linus
    TRAC, Sweden; TRAC, Vietnam; Karolinska Inst, Sweden.
    Larsson, Mattias
    TRAC, Sweden; TRAC, Vietnam; Karolinska Inst, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. TRAC, Sweden; TRAC, Vietnam.
    Insertion sequence transpositions and point mutations in mgrB causing colistin resistance in a clinical strain of carbapenem-resistant Klebsiella pneumoniae from Vietnam2018In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 51, no 5, p. 789-793Article in journal (Refereed)
    Abstract [en]

    Resistance among Klebsiella pneumoniae to the last-resort antibiotics carbapenems and colistin is increasing worldwide. In this study, whole-genome sequencing was used to determine the colistin resistance mechanisms in clinical isolates of carbapenem-and colistin-resistant K. pneumoniae from Vietnam. Alterations in the regulatory gene mgrB, via mutations and insertion sequence transpositions, were found in 30 of 31 isolates, emphasising the importance of this resistance mechanism in colistin-resistant K. pneumoniae. (c) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  • 61.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Chen, Baoli
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sun, Qiang
    Shandong Univ, Peoples R China.
    Xu, Liuchen
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Li, Yan
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Bi, Zhenwang
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Characterization of extended-spectrum -lactamase-producing Escherichia coli harboring mcr-1 and toxin genes from human fecal samples from China2018In: FUTURE COMPUTING ... the ... International Conference on Future Computational Technologies and Applications, ISSN 1746-0913, E-ISSN 1999-5903, Vol. 13, no 15, p. 1647-1656Article in journal (Refereed)
    Abstract [en]

    Aim: To characterize extended-spectrum -lactamase-producing Escherichia coli harboring the colistin resistance gene mcr-1 from human fecal samples collected in 2012 in a rural area of Shandong province, PR China. Materials amp; methods: Whole-genome sequencing and antimicrobial susceptibility testing was performed on 25 mcr-1-positive isolates to determine carriage of antibiotic resistance and virulence genes, diversity and antibiotic resistance profiles. Results: The isolates were highly genetically diverse and carried a large variety of different antibiotic resistance genes. The multidrug-resistance rate was high (96%). Virulence genes associated with intestinal pathogenic E. coli were carried by 32% of the isolates. Conclusion: Further monitoring of the epidemiological situation is necessary to ensure a preparedness for potential emergence of novel, difficult-to-treat strains and awareness of available treatment options.

  • 62.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hoang, Ngoc Thi Bich
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Le, Ngai Kien
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Khu, Dung Thi Khanh
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Olson, Linus
    The Karolinska Institute, Stockholm, Sweden.
    Le, Hai Thanh
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Larsson, Mattias
    The Karolinska Institute, Stockholm, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Colistin- and carbapenem-resistant Klebsiella pneumoniae carrying mcr-1 and bla(OXA-48) isolated at a paediatric hospital in Vietnam2018In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 4, p. 1100-1102Article in journal (Other academic)
    Abstract [en]

    n/a

  • 63.
    Bergström, G
    et al.
    University of Gothenburg / Sahlgrenska University Hospital.
    Berglund, G
    Lund University.
    Blomberg, A
    Umeå University.
    Brandberg, J
    Sahlgrenska University Hospital / University of Gothenburg.
    Engström, G
    Lund University.
    Engvall, Jan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Eriksson, M
    Karolinska University Hospital, Stockholm.
    de Faire, U
    Karolinska Institutet, Stockholm / Karolinska University Hospital, Stockholm.
    Flinck, A
    Sahlgrenska University Hospital, Stockholm / University of Gothenburg.
    Hansson, M G
    Uppsala University.
    Hedblad, B
    Lund University.
    Hjelmgren, O
    University of Gothenburg / Sahlgrenska University Hospital, Gothenburg.
    Janson, C
    Uppsala University.
    Jernberg, T
    Karolinska University Hospital, Stockholm / Karolinska Institutet, Stockholm.
    Johnsson, Å
    Sahlgrenska University Hospital, Gothenburg / University of Gothenburg.
    Johansson, L
    Unit of Radiology.
    Lind, L
    Uppsala University.
    Löfdahl, C-G
    Lund University / Lund University Hospital.
    Melander, O
    Lund University / Skåne University Hospital, Malmö.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Persson, M
    Lund University / Skåne University Hospital, Malmö.
    Sandström, A
    Umeå University.
    Schmidt, C
    University of Gothenburg.
    Söderberg, S
    Umeå University.
    Sundström, J
    Uppsala University / Uppsala Clinical Resarch Centre.
    Toren, K
    University of Gothenburg.
    Waldenström, A
    Umeå University Hospital.
    Wedel, H
    Nordic School of Public Health, Gothenburg.
    Vikgren, J
    Sahlgrenska University Hospital, Gothenburg / University of Gothenburg.
    Fagerberg, B
    University of Gothenburg.
    Rosengren, A
    University of Gothenburg.
    The Swedish CArdioPulmonary BioImage Study: objectives and design2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, no 6, p. 645-659Article in journal (Refereed)
    Abstract [en]

    Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

  • 64.
    Bergström, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jönsson, Simon
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sarndahl, Eva
    Örebro University, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Annexin A1 in blood mononuclear cells from patients with coronary artery disease: Its association with inflammatory status and glucocorticoid sensitivity2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174177Article in journal (Refereed)
    Abstract [en]

    Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.

  • 65.
    Berlin, Gösta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Cherif, Honar
    Akademiska sjukhuset - Hematologiska kliniken Uppsala, Sweden Akademiska sjukhuset - Hematologiska kliniken Uppsala, Sweden.
    Knutson, Folke
    Akademiska sjukhuset - Klinisk immunologi och transfusionsmedicin Uppsala, Sweden Akademiska sjukhuset - Klinisk immunologi och transfusionsmedicin Uppsala, Sweden.
    Mattsson, Jonas
    Karolinska Universitetssjukhuset - Centrum för allogen stamcellstransplantation Stockholm, Sweden .
    Axdorph Nygell, Ulla
    Karolinska Universitetssjukhuset - Klinisk immunologi och transfusionsmedicin Stockholm, Sweden .
    Granulocyttransfusion bör övervägas vid neutropeni och allvarlig infektion [Granulocyte transfusion – when and how should it be used?]2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, article id EXUUArticle, review/survey (Refereed)
    Abstract [en]

    There are no randomized controlled trials proving the clinical benefit of granulocyte transfusions. However, clinical experience and a number of case studies suggest that granulocyte transfusions may be life-saving in certain situations. In our opinion granulocyte transfusions should be considered for patients with profound neutropenia and severe, life-threatening infection not responding to antibiotic or antifungal therapy. Since the clinical effect seems to be dose-dependent, the granulocyte concentrate should contain a large number of cells, which usually means that the donor should be mobilized with steroids and G-CSF. Regular blood donors as well as relatives to the patient can be used for granulocyte donations with apheresis technique after information of the process. Granulocyte transfusion should be given daily as long as the indication remains. The clinical efficacy of the transfusions should be evaluated daily.

  • 66.
    Berlin, Gösta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Cherif, Honar
    Akademiska sjukhuset - Hematologiska kliniken Uppsala, Sweden Akademiska sjukhuset - Hematologiska kliniken Uppsala, Sweden.
    Knutson, Folke
    Akademiska sjukhuset - Klinisk immunologi och transfusionsmedicin Uppsala, Sweden Akademiska sjukhuset - Klinisk immunologi och transfusionsmedicin Uppsala, Sweden.
    Mattsson, Jonas
    Karolinska Universitetssjukhuset - Centrum för allogen stamcellstransplantation Stockholm, Sweden Karolinska Universitetssjukhuset - Centrum för allogen stamcellstransplantation Stockholm, Sweden.
    Axdorph Nygell, Ulla
    Karolinska Universitetssjukhuset - Klinisk immunologi och transfusionsmedicin Stockholm, Sweden Karolinska Universitetssjukhuset - Klinisk immunologi och transfusionsmedicin Stockholm, Sweden.
    Replik gällande granulocyttransfusion: Rekommendationerna är väl underbyggda2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article in journal (Refereed)
  • 67.
    Berlin, Gösta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Tapper, Linus
    Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Tynngård, Nahreen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Effects of age, gender and menstrual cycle on platelet function assessed by impedance aggregometry2019In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 30, no 4, p. 473-479Article in journal (Refereed)
    Abstract [en]

    Platelets are needed to prevent or arrest bleeding and aggregate at the site of injury upon vascular damage. Platelets express receptors for estrogens which might affect the function of the platelets and their hemostatic ability. The aim was to identify possible differences in platelet function related to age, gender, and phases of the menstrual cycle by use of impedance aggregometry with Multiplate. In the first part of the study, platelet function was assessed in 60 healthy individuals (30 men and 30 women) in each of three age groups (20-25, 40-45, and 60-65 years). In the second part of the study, the platelet function was analyzed on four occasions during the menstrual cycle in women without oral contraceptives (OCs) (n = 17) and compared to 19 women on OCs and 18 men of similar age (20-40 years). For the women on OCs, aggregation was analyzed once during the tablet-free week and once late during the period with OCs. The men were sampled once. Women of younger age (amp;lt;45 years) had significantly higher agonist-induced aggregation response than both men and post-menopausal women (60-65 years). The agonist-induced aggregation response did not differ between phases of the menstrual cycle or OC use. The results suggest that estradiol and/or progesterone affect spontaneous aggregation since it was found to be lowest in the mid-luteal phase. Spontaneous aggregation was significantly lower in women on OCs than in both men and women without OCs. Our findings indicate that fertile age is associated with higher aggregation response capacity of the platelets, possibly to prevent excessive bleeding during menstruation, but this response capacity is not altered during the menstrual cycle or by use of OCs.

  • 68.
    Bernard, Olivier
    et al.
    University of Lyon 1, France.
    Bosch, Johan G.
    Erasmus MC, Netherlands.
    Heyde, Brecht
    Katholieke University of Leuven, Belgium.
    Alessandrini, Martino
    Katholieke University of Leuven, Belgium.
    Barbosa, Daniel
    University of Minho, Portugal.
    Camarasu-Pop, Sorina
    University of Lyon 1, France.
    Cervenansky, Frederic
    University of Lyon 1, France.
    Valette, Sebastien
    University of Lyon 1, France.
    Mirea, Oana
    Katholieke University of Leuven, Belgium.
    Bernier, Michel
    University of Sherbrooke, Canada.
    Jodoin, Pierre-Marc
    University of Sherbrooke, Canada.
    Santo Domingos, Jaime
    University of Oxford, England.
    Stebbing, Richard V.
    University of Oxford, England.
    Keraudren, Kevin
    University of London Imperial Coll Science Technology and Med, England.
    Oktay, Ozan
    University of London Imperial Coll Science Technology and Med, England.
    Caballero, Jose
    University of London Imperial Coll Science Technology and Med, England.
    Shi, Wei
    University of London Imperial Coll Science Technology and Med, England.
    Rueckert, Daniel
    University of London Imperial Coll Science Technology and Med, England.
    Milletari, Fausto
    Technical University of Munich, Germany.
    Ahmadi, Seyed-Ahmad
    University of Munich, Germany.
    Smistad, Erik
    Norwegian University of Science and Technology, Norway.
    Lindseth, Frank
    Norwegian University of Science and Technology, Norway.
    van Stralen, Maartje
    University of Medical Centre Utrecht, Netherlands.
    Wang, Chen
    Not Found:Linkoping Univ, Dept Med and Hlth Sci IMH, Ctr Med Imaging Sci and Visualizat CMIV, SE-58185 Linkoping, Sweden.
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Donal, Erwan
    University of Rennes 1, France; University of Rennes 1, France; University of Rennes 1, France.
    Monaghan, Mark
    Kings Coll Hospital NHS Fdn Trust, England.
    Papachristidis, Alex
    Kings Coll Hospital NHS Fdn Trust, England.
    Geleijnse, Marcel L.
    Erasmus MC, Netherlands.
    Galli, Elena
    University of Rennes 1, France; University of Rennes 1, France; University of Rennes 1, France.
    Dhooge, Jan
    Katholieke University of Leuven, Belgium.
    Standardized Evaluation System for Left Ventricular Segmentation Algorithms in 3D Echocardiography2016In: IEEE Transactions on Medical Imaging, ISSN 0278-0062, E-ISSN 1558-254X, Vol. 35, no 4, p. 967-977Article in journal (Refereed)
    Abstract [en]

    Real-time 3D Echocardiography (RT3DE) has been proven to be an accurate tool for left ventricular (LV) volume assessment. However, identification of the LV endocardium remains a challenging task, mainly because of the low tissue/blood contrast of the images combined with typical artifacts. Several semi and fully automatic algorithms have been proposed for segmenting the endocardium in RT3DE data in order to extract relevant clinical indices, but a systematic and fair comparison between such methods has so far been impossible due to the lack of a publicly available common database. Here, we introduce a standardized evaluation framework to reliably evaluate and compare the performance of the algorithms developed to segment the LV border in RT3DE. A database consisting of 45 multivendor cardiac ultrasound recordings acquired at different centers with corresponding reference measurements from three experts are made available. The algorithms from nine research groups were quantitatively evaluated and compared using the proposed online platform. The results showed that the best methods produce promising results with respect to the experts measurements for the extraction of clinical indices, and that they offer good segmentation precision in terms of mean distance error in the context of the experts variability range. The platform remains open for new submissions.

  • 69.
    Bernhardsson, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sandberg, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Ressner, Marcus
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Koziorowski, Jacek
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Malmqvist, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Shining dead bone-cause for cautious interpretation of [F-18]NaF PET scans2018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 1, p. 124-127Article in journal (Refereed)
    Abstract [en]

    Background and purpose — [18F]Fluoride ([18F]NaF) PET scan is frequently used for estimation of bone healing rate and extent in cases of bone allografting and fracture healing. Some authors claim that [18F]NaF uptake is a measure of osteoblastic activity, calcium metabolism, or bone turnover. Based on the known affinity of fluoride to hydroxyapatite, we challenged this view.

    Methods — 10 male rats received crushed, frozen allogeneic cortical bone fragments in a pouch in the abdominal wall on the right side, and hydroxyapatite granules on left side. [18F]NaF was injected intravenously after 7 days. 60 minutes later, the rats were killed and [18F]NaF uptake was visualized in a PET/CT scanner. Specimens were retrieved for micro CT and histology.

    Results — MicroCT and histology showed no signs of new bone at the implant sites. Still, the implants showed a very high [18F]NaF uptake, on a par with the most actively growing and remodeling sites around the knee joint.

    Interpretation — [18F]NaF binds with high affinity to dead bone and calcium phosphate materials. Hence, an [18F]NaF PET/CT scan does not allow for sound conclusions about new bone ingrowth into bone allograft, healing activity in long bone shaft fractures with necrotic fragments, or remodeling around calcium phosphate coated prostheses

  • 70.
    Bettiga, Arianna
    et al.
    IRCCS Osped San Raffaele, Italy.
    Aureli, Massimo
    University of Milan, Italy.
    Colciago, Giorgia
    IRCCS Osped San Raffaele, Italy.
    Murdica, Valentina
    University of Milan, Italy.
    Moschini, Marco
    IRCCS Osped San Raffaele, Italy.
    Luciano, Roberta
    IRCCS Osped San Raffaele, Italy.
    Canals, Daniel
    SUNY Stony Brook, NY 11794 USA.
    Hannun, Yusuf
    SUNY Stony Brook, NY 11794 USA.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. IRCCS Osped San Raffaele, Italy.
    Lavorgna, Giovanni
    IRCCS Osped San Raffaele, Italy.
    Colombo, Renzo
    IRCCS Osped San Raffaele, Italy.
    Bassi, Rosaria
    University of Milan, Italy.
    Samarani, Maura
    University of Milan, Italy.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy; University of Vita Salute San Raffaele, Italy.
    Salonia, Andrea
    University of Vita Salute San Raffaele, Italy.
    Benigni, Fabio
    IRCCS Osped San Raffaele, Italy.
    Bladder cancer cell growth and motility implicate cannabinoid 2 receptor-mediated modifications of sphingolipids metabolism2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42157Article in journal (Refereed)
    Abstract [en]

    The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC). CB expression on human normal and BC specimens was tested by immunohistochemistry. Human BC cells RT4 and RT112 were challenged with CB agonists and assessed for proliferation, apoptosis, and motility. Cellular sphingolipids (SL) constitution and metabolism were evaluated after metabolic labelling. CB1-2 were detected in BC specimens, but only CB2 was more expressed in the tumour. Both cell lines expressed similar CB2. Exposure to CB2 agonists inhibited BC growth, down-modulated Akt, induced caspase 3-activation and modified SL metabolism. Baseline SL analysis in cell lines showed differences linked to unique migratory behaviours and cytoskeletal re-arrangements. CB2 activation changed the SL composition of more aggressive RT112 cells by reducing (p amp;lt; 0.01) Gb3 ganglioside (-50 +/- 3%) and sphingosine 1-phosphate (S1P, -40 +/- 4%), which ended up to reduction in cell motility (-46 +/- 5%) with inhibition of p-SRC. CB2-selective antagonists, gene silencing and an inhibitor of SL biosynthesis partially prevented CB2 agonist-induced effects on cell viability and motility. CB2 activation led to ceramide-mediated BC cell apoptosis independently of SL constitutive composition, which instead was modulated by CB2 agonists to reduce cell motility.

  • 71.
    Bivik Eding, Cecilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Domer, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wäster, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jerhammar, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases2015In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 7, p. 792-797Article in journal (Refereed)
    Abstract [en]

    Ultraviolet (UV) irradiation is a risk factor for development of malignant melanoma. UVA-induced lysosomal exocytosis and subsequent cell growth enhancement was studied in malignant melanoma cell lines and human skin melanocytes. UVA irradiation caused plasma membrane damage that was rapidly repaired by calcium-dependent lysosomal exocytosis. Lysosomal content was released into the culture medium directly after irradiation and such conditioned media stimulated the growth of non-irradiated cell cultures. By comparing melanocytes and melanoma cells, it was found that only the melanoma cells spontaneously secreted cathepsins into the surrounding medium. Melanoma cells from a primary tumour showed pronounced invasion ability, which was prevented by addition of inhibitors of cathepsins B, D and L. Proliferation was reduced by cathepsin L inhibition in all melanoma cell lines, but did not affect melanocyte growth. In conclusion, UVA-induced release of cathepsins outside cells may be an important factor that promotes melanoma growth and progression.

  • 72.
    Björnsson, Bergthor
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 6, p. 1775-1783Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate whether nitrite administered prior to ischemia/reperfusion (I/R) reduces liver injury.

    METHODS: Thirty-six male Sprague-Dawley rats were randomized to 3 groups, including sham operated (n = 8), 45-min segmental ischemia of the left liver lobe (IR, n = 14) and ischemia/reperfusion (I/R) preceded by the administration of 480 nmol of nitrite (n = 14). Serum transaminases were measured after 4 h of reperfusion. Liver microdialysate (MD) was sampled in 30-min intervals and analyzed for glucose, lactate, pyruvate and glycerol as well as the total nitrite and nitrate (NOx). The NOx was measured in serum.

    RESULTS: Aspartate aminotransferase (AST) at the end of reperfusion was higher in the IR group than in the nitrite group (40 ± 6.8 μkat/L vs 22 ± 2.6 μkat/L, P = 0.022). Similarly, alanine aminotransferase (ALT) was also higher in the I/R group than in the nitrite group (34 ± 6 μkat vs 14 ± 1.5 μkat, P = 0.0045). The NOx in MD was significantly higher in the nitrite group than in the I/R group (10.1 ± 2.9 μM vs 3.2 ± 0.9 μM, P = 0.031) after the administration of nitrite. During ischemia, the levels decreased in both groups and then increased again during reperfusion. At the end of reperfusion, there was a tendency towards a higher NOx in the I/R group than in the nitrite group (11.6 ± 0.7 μM vs 9.2 ± 1.1 μM, P = 0.067). Lactate in MD was significantly higher in the IR group than in the nitrite group (3.37 ± 0.18 mM vs 2.8 ± 0.12 mM, P = 0.01) during ischemia and the first 30 min of reperfusion. During the same period, glycerol was also higher in the IRI group than in the nitrite group (464 ± 38 μM vs 367 ± 31 μM, P = 0.049). With respect to histology, there were more signs of tissue damage in the I/R group than in the nitrite group, and 29% of the animals in the I/R group exhibited necrosis compared with none in the nitrite group. Inducible nitric oxide synthase (iNOS) transcription increased between early ischemia (t = 15) and the end of reperfusion in both groups.

    CONCLUSION: Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.

  • 73.
    Blanco, Ignacio
    et al.
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Kuchenbaecker, Karoline
    University of Cambridge, England.
    Cuadras, Daniel
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Wang, Xianshu
    Mayo Clin, MN USA.
    Barrowdale, Daniel
    University of Cambridge, England.
    Ruiz de Garibay, Gorka
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Librado, Pablo
    University of Barcelona, Spain.
    Sanchez-Gracia, Alejandro
    University of Barcelona, Spain.
    Rozas, Julio
    University of Barcelona, Spain.
    Bonifaci, Nuria
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    McGuffog, Lesley
    University of Cambridge, England.
    Pankratz, Vernon S.
    Mayo Clin, MN USA.
    Islam, Abul
    University of Dhaka, Bangladesh.
    Mateo, Francesca
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Berenguer, Antoni
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Petit, Anna
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Catala, Isabel
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Brunet, Joan
    Hospital Josep Trueta, Spain.
    Feliubadalo, Lidia
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Tornero, Eva
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Benitez, Javier
    Spanish National Cancer Centre CNIO, Spain; Biomed Network Rare Disease, Spain.
    Osorio, Ana
    Spanish National Cancer Centre CNIO, Spain; Biomed Network Rare Disease, Spain.
    Cajal, Teresa Ramon Y.
    Hospital Santa Creu and Sant Pau, Spain.
    Nevanlinna, Heli
    University of Helsinki, Finland; University of Helsinki, Finland.
    Aittomaki, Kristiina
    University of Helsinki, Finland.
    Arun, Banu K.
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Toland, Amanda E.
    Ohio State University, OH 43210 USA.
    Karlan, Beth Y.
    Cedars Sinai Medical Centre, CA 90048 USA.
    Walsh, Christine
    Cedars Sinai Medical Centre, CA 90048 USA.
    Lester, Jenny
    Cedars Sinai Medical Centre, CA 90048 USA.
    Greene, Mark H.
    National Cancer Institute, MD USA.
    Mai, Phuong L.
    National Cancer Institute, MD USA.
    Nussbaum, Robert L.
    University of Calif San Francisco, CA 94143 USA.
    Andrulis, Irene L.
    University of Toronto, Canada; University of Toronto, Canada; University of Toronto, Canada.
    Domchek, Susan M.
    University of Penn, PA 19104 USA; University of Penn, PA 19104 USA.
    Nathanson, Katherine L.
    University of Penn, PA 19104 USA; University of Penn, PA 19104 USA.
    Rebbeck, Timothy R.
    University of Penn Perelman, PA 19104 USA; University of Penn Perelman, PA 19104 USA.
    Barkardottir, Rosa B.
    University of Iceland, Iceland; University of Iceland, Iceland.
    Jakubowska, Anna
    Pomeranian Medical University, Poland.
    Lubinski, Jan
    Pomeranian Medical University, Poland.
    Durda, Katarzyna
    Pomeranian Medical University, Poland.
    Jaworska-Bieniek, Katarzyna
    Pomeranian Medical University, Poland.
    Claes, Kathleen
    University of Ghent, Belgium.
    Van Maerken, Tom
    University of Ghent, Belgium.
    Diez, Orland
    Vall Hebron Research Institute VHIR, Spain; University of Autonoma Barcelona, Spain.
    Hansen, Thomas V.
    Copenhagen University Hospital, Denmark.
    Jonson, Lars
    Copenhagen University Hospital, Denmark.
    Gerdes, Anne-Marie
    Copenhagen University Hospital, Denmark.
    Ejlertsen, Bent
    Copenhagen University Hospital, Denmark.
    de la Hoya, Miguel
    San Carlos Research Institute IdISSC, Spain.
    Caldes, Trinidad
    San Carlos Research Institute IdISSC, Spain.
    Dunning, Alison M.
    University of Cambridge, England.
    Oliver, Clare
    University of Cambridge, England.
    Fineberg, Elena
    University of Cambridge, England.
    Cook, Margaret
    University of Cambridge, England.
    Peock, Susan
    University of Cambridge, England.
    McCann, Emma
    Glan Clwyd Gen Hospital, Wales.
    Murray, Alex
    Singleton Hospital, Wales.
    Jacobs, Chris
    Guys and St Thomas National Health Serv NHS Fdn Trust, England.
    Pichert, Gabriella
    Guys and St Thomas National Health Serv NHS Fdn Trust, England.
    Lalloo, Fiona
    Central Manchester University Hospital National Health Serv NHS Fdn, England.
    Chu, Carol
    Yorkshire Regional Genet Serv, England.
    Dorkins, Huw
    Kennedy Galton Centre, England.
    Paterson, Joan
    Addenbrookes Hospital, England.
    Ong, Kai-Ren
    Birmingham Womens Hospital Healthcare National Health Serv, England.
    Teixeira, Manuel R.
    University of Porto, Portugal; University of Porto, Portugal.
    Teixeira,
    Netherlands Cancer Institute, The Netherlands.
    Hogervorst, Frans B. L.
    Netherlands Cancer Institute, The Netherlands.
    van der Hout, Annemarie H.
    University of Groningen, Netherlands.
    Seynaeve, Caroline
    Erasmus University, Netherlands.
    van der Luijt, Rob B.
    University of Medical Centre Utrecht, Netherlands.
    Ligtenberg, Marjolijn J. L.
    Radboud University of Nijmegen, Netherlands; Radboud University of Nijmegen, Netherlands; Leiden University, Netherlands.
    Devilee, Peter
    Leiden University, Netherlands; Leiden University, Netherlands.
    Wijnen, Juul T.
    Leiden University, Netherlands; Leiden University, Netherlands.
    Rookus, Matti A.
    Netherlands Cancer Institute, Netherlands.
    Meijers-Heijboer, Hanne E. J.
    Vrije University of VJ University of Medical Centre, Netherlands.
    Blok, Marinus J.
    Maastricht University, Netherlands.
    van den Ouweland, Ans M. W.
    Erasmus University, Netherlands.
    Aalfs, Cora M.
    University of Amsterdam, Netherlands.
    Rodriguez, Gustavo C.
    University of Chicago, IL 60637 USA.
    Phillips, Kelly-Anne A.
    Peter MacCallum Cancer Centre, Australia.
    Piedmonte, Marion
    Roswell Pk Cancer Institute, NY 14263 USA.
    Nerenstone, Stacy R.
    Hartford Hospital, CT USA.
    Bae-Jump, Victoria L.
    University of N Carolina, NC USA.
    OMalley, David M.
    Ohio State University, OH USA.
    Ratner, Elena S.
    Yale University, CT USA.
    Schmutzler, Rita K.
    University Hospital Cologne, Germany; University Hospital Cologne, Germany.
    Wappenschmidt, Barbara
    University Hospital Cologne, Germany; University Hospital Cologne, Germany.
    Rhiem, Kerstin
    University Hospital Cologne, Germany; University Hospital Cologne, Germany.
    Engel, Christoph
    University of Leipzig, Germany.
    Meindl, Alfons
    Technical University of Munich, Germany.
    Ditsch, Nina
    University of Munich, Germany.
    Arnold, Norbert
    University of Kiel, Germany.
    Plendl, Hansjoerg J.
    University of Kiel, Germany.
    Niederacher, Dieter
    University of Dusseldorf, Germany.
    Sutter, Christian
    University of Heidelberg Hospital, Germany.
    Wang-Gohrke, Shan
    University Hospital Ulm, Germany.
    Steinemann, Doris
    Hannover Medical Sch, Germany.
    Preisler-Adams, Sabine
    University of Munster, Germany.
    Kast, Karin
    Technical University of Dresden, Germany.
    Varon-Mateeva, Raymonda
    Charite, Germany.
    Gehrig, Andrea
    University of Wurzburg, Germany.
    Bojesen, Anders
    Vejle Hospital, Denmark.
    Sokilde Pedersen, Inge
    Aalborg University Hospital, Denmark.
    Sunde, Lone
    Aarhus University Hospital, Denmark.
    Birk Jensen, Uffe
    Aarhus University Hospital, Denmark.
    Thomassen, Mads
    Odense University Hospital, Denmark.
    Kruse, Torben A.
    Odense University Hospital, Denmark.
    Foretova, Lenka
    Masaryk Mem Cancer Institute, Czech Republic.
    Peterlongo, Paolo
    Fdn Italiana Ric Cancro, Italy.
    Bernard, Loris
    Cogentech Cancer Genet Test Lab, Italy.
    Peissel, Bernard
    Fdn Ist Nazl Tumori INT, Italy.
    Scuvera, Giulietta
    Fdn Ist Nazl Tumori INT, Italy.
    Manoukian, Siranoush
    Fdn Ist Nazl Tumori INT, Italy.
    Radice, Paolo
    Fdn Ist Nazl Tumori INT, Italy.
    Ottini, Laura
    University of Roma La Sapienza, Italy.
    Montagna, Marco
    IRCCS, Italy.
    Agata, Simona
    IRCCS, Italy.
    Maugard, Christine
    Hop University of Strasbourg, France.
    Simard, Jacques
    Centre Hospital University of Quebec, Canada; University of Laval, Canada.
    Soucy, Penny
    Centre Hospital University of Quebec, Canada; University of Laval, Canada.
    Berger, Andreas
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Fink-Retter, Anneliese
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Singer, Christian F.
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Rappaport, Christine
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Geschwantler-Kaulich, Daphne
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Tea, Muy-Kheng
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Pfeiler, Georg
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    John, Esther M.
    Cancer Prevent Institute Calif, CA USA.
    Miron, Alex
    Dana Farber Cancer Institute, MA 02115 USA.
    Neuhausen, Susan L.
    Beckman Research Institute City Hope, CA USA.
    Beth Terry, Mary
    Columbia University, NY USA.
    Chung, Wendy K.
    Columbia University, NY USA.
    Daly, Mary B.
    Fox Chase Cancer Centre, PA 19111 USA.
    Goldgar, David E.
    University of Utah, UT USA.
    Janavicius, Ramunas
    Vilnius University, Lithuania.
    Dorfling, Cecilia M.
    University of Pretoria, South Africa.
    van Rensburg, Elisabeth J.
    University of Pretoria, South Africa.
    Fostira, Florentia
    National Centre Science Research Demokritos, Greece.
    Konstantopoulou, Irene
    National Centre Science Research Demokritos, Greece.
    Garber, Judy
    Harvard University, MA USA.
    Godwin, Andrew K.
    University of Kansas, KS 66103 USA.
    Olah, Edith
    National Institute Oncol, Hungary.
    Narod, Steven A.
    University of Toronto, Canada.
    Rennert, Gad
    Clalit National Israeli Cancer Control Centre, Israel; Carmel Hospital, Israel; B Rappaport Fac Med, Israel.
    Shimon Paluch, Shani
    Chaim Sheba Medical Centre, Israel.
    Laitman, Yael
    Chaim Sheba Medical Centre, Israel.
    Friedman, Eitan
    Chaim Sheba Medical Centre, Israel; Tel Aviv University, Israel.
    Liljegren, Annelie
    Karolinska University Hospital, Sweden.
    Rantala, Johanna
    Karolinska University Hospital, Sweden.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Loman, Niklas
    University of Lund Hospital, Sweden.
    Imyanitov, Evgeny N.
    NN Petrov Institute Oncol, Russia.
    Hamann, Ute
    German Cancer Research Centre, Germany.
    Spurdle, Amanda B.
    Queensland Institute Medical Research, Australia.
    Healey, Sue
    Queensland Institute Medical Research, Australia.
    Weitzel, Jeffrey N.
    City Hope National Medical Centre, CA USA.
    Herzog, Josef
    City Hope National Medical Centre, CA USA.
    Margileth, David
    Care City Hope Clin Cancer Genet Commun Research Network, CA USA.
    Gorrini, Chiara
    University of Health Network, Canada.
    Esteller, Manel
    IDIBELL, Spain; University of Barcelona, Spain; Catalan Institute Research and Adv Studies ICREA, Spain.
    Gomez, Antonio
    IDIBELL, Spain.
    Sayols, Sergi
    IDIBELL, Spain.
    Vidal, Enrique
    IDIBELL, Spain.
    Heyn, Holger
    IDIBELL, Spain.
    Stoppa-Lyonnet, Dominique
    Institute Curie, France; Institute Curie, France; University of Paris 05, France.
    Leone, Melanie
    Hospital Civils Lyon, France.
    Barjhoux, Laure
    University of Lyon 1, France.
    Fassy-Colcombet, Marion
    Institute Curie, France.
    de Pauw, Antoine
    Institute Curie, France.
    Lasset, Christine
    University of Lyon 1, France; Centre Leon Berard, France.
    Fert Ferrer, Sandra
    Hop Hotel Dieu, France.
    Castera, Laurent
    Institute Curie, France.
    Berthet, Pascaline
    Centre Francois Baclesse, France.
    Cornelis, Francois
    Avicenne Hospital, France; Sud Francilien Hospital, France; University Hospital, France.
    Bignon, Yves-Jean
    University of Clermont Ferrand, France.
    Damiola, Francesca
    University of Lyon 1, France.
    Mazoyer, Sylvie
    University of Lyon 1, France.
    Sinilnikova, Olga M.
    Hospital Civils Lyon, France; University of Lyon 1, France.
    Maxwell, Christopher A.
    University of British Columbia, Canada.
    Vijai, Joseph
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Robson, Mark
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Kauff, Noah
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Corines, Marina J.
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Villano, Danylko
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Cunningham, Julie
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Lee, Adam
    Mayo Clin, MN USA.
    Lindor, Noralane
    Mayo Clin Scottsdale, AZ USA.
    Lazaro, Conxi
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Easton, Douglas F.
    University of Cambridge, England.
    Offit, Kenneth
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Chenevix-Trench, Georgia
    Queensland Institute Medical Research, Australia.
    Couch, Fergus J.
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Antoniou, Antonis C.
    University of Cambridge, England.
    Angel Pujana, Miguel
    Bellvitge Institute Biomed Research IDIBELL, Spain.
    Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0120020Article in journal (Refereed)
    Abstract [en]

    While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values greater than 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

  • 74.
    Blockhuys, S.
    et al.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Celauro, E.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Feizi, A.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fierro-González, J.C.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Wittung-Stafshede, P.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Defining the human copper proteome and analysis of its expression variation in cancers.2017In: Metallomics : integrated biometal science, ISSN 1756-591X, Vol. 9, no 2, p. 112-123Article in journal (Refereed)
    Abstract [en]

    Copper (Cu) is essential for living organisms, and acts as a cofactor in many metabolic enzymes. To avoid the toxicity of free Cu, organisms have specific transport systems that 'chaperone' the metal to targets. Cancer progression is associated with increased cellular Cu concentrations, whereby proliferative immortality, angiogenesis and metastasis are cancer hallmarks with defined requirements for Cu. The aim of this study is to gather all known Cu-binding proteins and reveal their putative involvement in cancers using the available database resources of RNA transcript levels. Using the database along with manual curation, we identified a total of 54 Cu-binding proteins (named the human Cu proteome). Next, we retrieved RNA expression levels in cancer versus normal tissues from the TCGA database for the human Cu proteome in 18 cancer types, and noted an intricate pattern of up- and downregulation of the genes in different cancers. Hierarchical clustering in combination with bioinformatics and functional genomics analyses allowed for the prediction of cancer-related Cu-binding proteins; these were specifically inspected for the breast cancer data. Finally, for the Cu chaperone ATOX1, which is the only Cu-binding protein proposed to have transcription factor activities, we validated its predicted over-expression in patient breast cancer tissue at the protein level. This collection of Cu-binding proteins, with RNA expression patterns in different cancers, will serve as an excellent resource for mechanistic-molecular studies of Cu-dependent processes in cancer.

  • 75.
    Blockhuys, Stephanie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Chalmers University of Technology, Sweden.
    Rani Agarwal, Nisha
    Chalmers University of Technology, Sweden; McMaster University, Canada; McMaster University, Canada.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Jarlsfelt, Ingvar
    Ryhov Hospital, Sweden.
    Wittung-Stafshede, Pernilla
    Chalmers University of Technology, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Second harmonic generation for collagen I characterization in rectal cancer patients with and without preoperative radiotherapy2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 10, article id 106006Article in journal (Refereed)
    Abstract [en]

    Rectal cancer is treated with preoperative radiotherapy (RT) to downstage the tumor, reduce local recurrence, and improve patient survival. Still, the treatment outcome varies significantly and new biomarkers are desired. Collagen I (Col-I) is a potential biomarker, which can be visualized label-free by second harmonic generation (SHG). Here, we used SHG to identify Col-I changes induced by RT in surgical tissue, with the aim to evaluate the clinical significance of RT-induced Col-I changes. First, we established a procedure for quantitative evaluation of Col-I by SHG in CDX2-stained tissue sections. Next, we evaluated Col-I properties in material from 31 non-RT and 29 RT rectal cancer patients. We discovered that the Col-I intensity and anisotropy were higher in the tumor invasive margin than in the inner tumor and normal mucosa, and RT increased and decreased the intensity in inner tumor and normal mucosa, respectively. Furthermore, higher Col-I intensity in the inner tumor was related to increased distant recurrence in the non-RT group but to longer survival in the RT group. In conclusion, we present a new application of SHG for quantitative analysis of Col-I in surgical material, and the first data suggest Col-I intensity as a putative prognostic biomarker in rectal cancer. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

  • 76.
    Blomgran, Parmis
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 29824Article in journal (Refereed)
    Abstract [en]

    Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected. 48 rats underwent Achilles tendon transection. Half of the rats received Botox injections into calf muscles to reduce mechanical loading. Cells from the regenerating tissue were analyzed by flow cytometry. In the loaded group, the regenerating tissue contained 83% leukocytes (CD45(+)) day 1, and 23% day 10. The M1/M2 macrophage ratio (CCR7/CD206) peaked at day 3, while T helper (CD3(+)CD4(+)) and T-reg cells (CD25(+) Foxp3(+)) increased over time. With Botox, markers associated with down-regulation of inflammation were more common day 5 (CD163, CD206, CD25, Foxp3), and M1 or M2 macrophages and T-reg cells were virtually absent day 10, while still present with full loading. The primary variable, CCR7/CD206 ratio day 5, was higher with full loading (p = 0.001) and the T-reg cell fraction was lower (p amp;lt; 0.001). Free cage activity loading is known to increase size and strength of the tendon in this model compared to Botox. Loading now appeared to delay the switch to an M2 type of inflammation with more T-reg cells. It seems a prolonged M1 phase due to loading might make the tendon regenerate bigger.

  • 77.
    Blomgran, Parmis
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Cox-2 inhibition and the composition of inflammatory cell populations during early and mid-time tendon healing2017In: Muscles, ligaments and Tendons journal, ISSN 2240-4554, Vol. 7, no 2, p. 223-229Article in journal (Refereed)
    Abstract [en]

    Background: During early tendon healing, the cells within the regenerating tissue are, to a large part, inflammatory leukocytes (CD45+). In a rat Achilles tendon healing model, the inflammation resolves between 5 and 10 days. In the same model, Cox inhibitors (NSAIDs) impair healing when given during the first 5 days, but have a positive effect if given later. We tested the hypothesis that a Cox inhibitor would exert these effects by influencing inflammation, and thereby the composition of the inflammatory cell subpopulations.Methods: Achilles tendon transection was performed in 44 animals. Animals were randomized to either parecoxib or saline injections. Healing was evaluated by mechanical testing day 7 after surgery and by flow cytometry day 3 and 10.Results: Cross-sectional area, peak force and stiffness were reduced by parecoxib 31, 33, and 25% respectively (p=0.005, p=0.002, and p=0.005). By flow cytometry, there was a strong effect of time (p<0.001) on virtually all inflammatory cell subpopulations (CD45, CD11b, CD68, CCR7, CD163, CD206, CD3, CD4), but no significant effect of parecoxib at any time point.Conclusion: The results suggest that the negative effects of Cox inhibitors on tendon healing might be exerted mainly via mechanisms not directly related to inflammatory cells.

  • 78.
    Blystad, Ida
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Håkansson, Irene
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Tisell, Anders
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Uppsala University, Sweden.
    Quantitative MRI for Analysis of Active Multiple Sclerosis Lesions without Gadolinium-Based Contrast Agent2016In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 37, no 1, p. 94-100Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Contrast-enhancing MS lesions are important markers of active inflammation in the diagnostic work-up of MS and in disease monitoring with MR imaging. Because intravenous contrast agents involve an expense and a potential risk of adverse events, it would be desirable to identify active lesions without using a contrast agent. The purpose of this study was to evaluate whether pre-contrast injection tissue-relaxation rates and proton density of MS lesions, by using a new quantitative MR imaging sequence, can identify active lesions. MATERIALS AND METHODS: Forty-four patients with a clinical suspicion of MS were studied. MR imaging with a standard clinical MS protocol and a quantitative MR imaging sequence was performed at inclusion (baseline) and after 1 year. ROIs were placed in MS lesions, classified as nonenhancing or enhancing. Longitudinal and transverse relaxation rates, as well as proton density were obtained from the quantitative MR imaging sequence. Statistical analyses of ROI values were performed by using a mixed linear model, logistic regression, and receiver operating characteristic analysis. RESULTS: Enhancing lesions had a significantly (P &lt; .001) higher mean longitudinal relaxation rate (1.22 0.36 versus 0.89 +/- 0.24), a higher mean transverse relaxation rate (9.8 +/- 2.6 versus 7.4 +/- 1.9), and a lower mean proton density (77 +/- 11.2 versus 90 +/- 8.4) than nonenhancing lesions. An area under the receiver operating characteristic curve value of 0.832 was obtained. CONCLUSIONS: Contrast-enhancing MS lesions often have proton density and relaxation times that differ from those in nonenhancing lesions, with lower proton density and shorter relaxation times in enhancing lesions compared with nonenhancing lesions.

  • 79.
    Blystad, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). KTH Royal Institute Technology, Sweden.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala University, Sweden.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Quantitative MRI for analysis of peritumoral edema in malignant gliomas2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0177135Article in journal (Refereed)
    Abstract [en]

    Background and purpose Damage to the blood-brain barrier with subsequent contrast enhancement is a hallmark of glioblastoma. Non-enhancing tumor invasion into the peritumoral edema is, however, not usually visible on conventional magnetic resonance imaging. New quantitative techniques using relaxometry offer additional information about tissue properties. The aim of this study was to evaluate longitudinal relaxation R-1, transverse relaxation R-2, and proton density in the peritumoral edema in a group of patients with malignant glioma before surgery to assess whether relaxometry can detect changes not visible on conventional images. Methods In a prospective study, 24 patients with suspected malignant glioma were examined before surgery. A standard MRI protocol was used with the addition of a quantitative MR method (MAGIC), which measured R-1, R-2, and proton density. The diagnosis of malignant glioma was confirmed after biopsy/surgery. In 19 patients synthetic MR images were then created from the MAGIC scan, and ROIs were placed in the peritumoral edema to obtain the quantitative values. Dynamic susceptibility contrast perfusion was used to obtain cerebral blood volume (rCBV) data of the peritumoral edema. Voxel-based statistical analysis was performed using a mixed linear model. Results R-1, R-2, and rCBV decrease with increasing distance from the contrast-enhancing part of the tumor. There is a significant increase in R1 gradient after contrast agent injection (Pamp;lt;.0001). There is a heterogeneous pattern of relaxation values in the peritumoral edema adjacent to the contrast-enhancing part of the tumor. Conclusion Quantitative analysis with relaxometry of peritumoral edema in malignant gliomas detects tissue changes not visualized on conventional MR images. The finding of decreasing R-1 and R-2 means shorter relaxation times closer to the tumor, which could reflect tumor invasion into the peritumoral edema. However, these findings need to be validated in the future.

  • 80.
    Boij, Roland
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Mjosberg, Jenny
    Karolinska Institute, Sweden.
    Svensson Arvelund, Judit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Hjorth, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Matthiesen, Leif
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Helsingborg Hospital, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia2015In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 74, no 4, p. 368-378Article in journal (Refereed)
    Abstract [en]

    Problem A deficiency in regulatory T (Treg) cells causing reduced immune regulatory capacity has been proposed in preeclampsia. Objective Utilizing recent advances in flow cytometry phenotyping, we aimed to assess whether a deficiency of Treg subpopulations occurs in preeclampsia. Method of study Six-color flow cytometry was used for Treg phenotyping in 18 preeclamptic women (one early-onset, one severe and 16 both), 20 women with normal pregnancy, and 20 non-pregnant controls. Results No differences were found in major Treg populations including CD127(low)CD25(+)/CD127(ow)FOXP3(+), resting (FOXP3(dim)CD45RA(+)), and activated (FOXP3(bright)CD45RA(-)) Treg cells, whereas preeclamptic women showed increased CTLA-4(+) and CCR4(+) proportions within resting/activated Treg populations. Corticosteroid treatment prior to blood sampling (n = 10) affected the distribution of Treg populations. Conclusions Although we found no major alterations in circulating Treg frequencies, differences in CTLA-4(+) and CCR4(+) frequencies suggest a migratory defect of Treg cells in preeclampsia. Corticosteroid treatment should be taken into account when evaluating Treg cells.

  • 81.
    Bojmar, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Zhang, Haiying
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Costa da Silva, Bruno
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Karlsson, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Vincent, Theresa
    Departments of Physiology and Biophysics and Cell and Developmental Biology, Weill Cornell Medical College, New York, USA / Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lyden, David
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome2015Manuscript (preprint) (Other academic)
    Abstract [en]

    The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast  tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.

  • 82.
    Boknäs, Niklas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Faxälv, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Flow cytometry-based platelet function testing is predictive of symptom burden in a cohort of bleeders2018In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 29, no 5, p. 512-519Article in journal (Refereed)
    Abstract [en]

    Platelet function disorders (PFDs) are common in patients with mild bleeding disorders (MBDs), yet the significance of laboratory findings suggestive of a PFD remain unclear due to the lack of evidence for a clinical correlation between the test results and the patient phenotype. Herein, we present the results from a study evaluating the potential utility of platelet function testing using whole-blood flow cytometry in a cohort of 105 patients undergoing investigation for MBD. Subjects were evaluated with a test panel comprising two different activation markers (fibrinogen binding and P-selectin exposure) and four physiologically relevant platelet agonists (ADP, PAR1-AP, PAR4-AP, and CRP-XL). Abnormal test results were identified by comparison with reference ranges constructed from 24 healthy controls or with the fifth percentile of the entire patient cohort. We found that the abnormal test results are predictive of bleeding symptom severity, and that the greatest predictive strength was achieved using a subset of the panel, comparing measurements of fibrinogen binding after activation with all four agonists with the fifth percentile of the patient cohort (p=0.00008, hazard ratio 8.7; 95% CI 2.5-40). Our results suggest that whole-blood flow cytometry-based platelet function testing could become a feasible alternative for the investigation of MBDs. We also show that platelet function testing using whole-blood flow cytometry could provide a clinically relevant quantitative assessment of platelet-related hemostasis.

  • 83.
    Bonzon, Jerome
    et al.
    University of Bern, Switzerland.
    Schoen, Corinna A.
    University of Bern, Switzerland.
    Schwendener, Nicole
    University of Bern, Switzerland.
    Zech, Wolf-Dieter
    University of Bern, Switzerland.
    Kara, Levent
    Triemli Hospital, Switzerland.
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jackowski, Christian
    University of Bern, Switzerland.
    Rigor mortis at the myocardium investigated by post-mortem magnetic resonance imaging2015In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 257, p. 93-97Article in journal (Refereed)
    Abstract [en]

    Introduction: Post-mortem cardiac MR exams present with different contraction appearances of the left ventricle in cardiac short axis images. It was hypothesized that the grade of post-mortem contraction may be related to the post-mortem interval (PMI) or cause of death and a phenomenon caused by internal rigor mortis that may give further insights in the circumstances of death. Method and materials: The cardiac contraction grade was investigated in 71 post-mortem cardiac MR exams (mean age at death 52 y, range 12-89 y; 48 males, 23 females). In cardiac short axis images the left ventricular lumen volume as well as the left ventricular myocardial volume were assessed by manual segmentation. The quotient of both (LVQ) represents the grade of myocardial contraction. LVQ was correlated to the PMI, sex, age, cardiac weight, body mass and height, cause of death and pericardial tamponade when present. In cardiac causes of death a separate correlation was investigated for acute myocardial infarction cases and arrhythmic deaths. Results: LVQ values ranged from 1.99 (maximum dilatation) to 42.91 (maximum contraction) with a mean of 15.13. LVQ decreased slightly with increasing PMI, however without significant correlation. Pericardial tamponade positively correlated with higher LVQ values. Variables such as sex, age, body mass and height, cardiac weight and cause of death did not correlate with LVQ values. There was no difference in LVQ values for myocardial infarction without tamponade and arrhythmic deaths. Conclusion: Based on the observation in our investigated cases, the phenomenon of post-mortem myocardial contraction cannot be explained by the influence of the investigated variables, except for pericardial tamponade cases. Further research addressing post-mortem myocardial contraction has to focus on other, less obvious factors, which may influence the early post-mortem phase too. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  • 84.
    Boud, David
    et al.
    Deakin University, Geelong, Australia / University of Technology, Sydney, Australia / Middlesex University, London, UK.
    Nyström, Sofia
    Linköping University, Department of Behavioural Sciences and Learning, Education and Adult Learning. Linköping University, Faculty of Educational Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Abrandt Dahlgren, Madeleine
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gustavsson, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Kelly, Michelle
    Curtin University, Perth, Australia.
    O’Keeffe, Dara
    Royal College of Surgeons in Ireland, Dublin, Ireland.
    Learning through observation2019In: Interprofessional Simulation in Health Care: Materiality, Embodiment, Interaction / [ed] Madeleine Abrandt Dahlgren, Hans Rystedt, Li Felländer-Tsai & Sofia Nyström, Cham: Springer, 2019, p. 115-137Chapter in book (Refereed)
    Abstract [en]

    This chapter has a particular focus on the observers’ role in simulation-based learning activities. Simulation-based learning is often organised so that participants rotates between active participation in the scenario and participation as observers. The research examples provided show that the conditions for learning are related to the locations where and the ways the observers are situated, and to how the instructions to the observers are formulated. Arguments are put forward that the observers’ role in simulation has unexploited potential for developing skills of noticing.

  • 85.
    Brinkman, D. J.
    et al.
    Vrije University of Amsterdam, Netherlands; Research and Expertise Centre Pharmacotherapy Educ RECIPE, Netherlands.
    Tichelaar, J.
    Vrije University of Amsterdam, Netherlands; Research and Expertise Centre Pharmacotherapy Educ RECIPE, Netherlands.
    Schutte, T.
    Vrije University of Amsterdam, Netherlands; Research and Expertise Centre Pharmacotherapy Educ RECIPE, Netherlands.
    Benemei, S.
    University of Florence, Italy.
    Böttiger, Ylva
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Chamontin, B.
    University of Toulouse, France.
    Christiaens, T.
    University of Ghent, Belgium.
    Likic, R.
    University of Zagreb, Croatia.
    Maciulaitis, R.
    Lithuanian University of Health Science, Lithuania.
    Marandi, T.
    University of Tartu, Estonia.
    Monteiro, E. C.
    NOVA Medical Sch, Portugal.
    Papaioannidou, P.
    Aristotle University of Thessaloniki, Greece.
    Pers, Y. M.
    University of Montpellier, France.
    Pontes, C.
    Autonomous University of Barcelona, Spain.
    Raskovic, A.
    University of Novi Sad, Serbia.
    Regenthal, R.
    University of Leipzig, Germany.
    Sanz, E. J.
    University of La Laguna, Spain.
    Tamba, B. I.
    Gr T Popa University of Medical and Pharm, Romania.
    Wilson, K.
    University of Manchester, England.
    de Vries, T. P.
    Vrije University of Amsterdam, Netherlands; Research and Expertise Centre Pharmacotherapy Educ RECIPE, Netherlands.
    Richir, M. C.
    Vrije University of Amsterdam, Netherlands; Research and Expertise Centre Pharmacotherapy Educ RECIPE, Netherlands.
    van Agtmael, M. A.
    Vrije University of Amsterdam, Netherlands; Research and Expertise Centre Pharmacotherapy Educ RECIPE, Netherlands.
    Essential Competencies in Prescribing: A First European Cross-Sectional Study Among 895 Final-Year Medical Students2017In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 101, no 2, p. 281-289Article in journal (Refereed)
    Abstract [en]

    European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.

  • 86.
    Bruhn, H.
    et al.
    Cty Hosp Ryhov, Sweden.
    Strandeus, M.
    Cty Hosp Ryhov, Sweden.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lind, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Improved survival of Swedish glioblastoma patients treated according to Stupp2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 332-337Article in journal (Refereed)
    Abstract [en]

    ObjectivesThe median survival in glioblastoma (GBM) patients used to be less than 1year. Surgical removal of the tumor with subsequent concomitant radiation/temozolomide (the Stupp regimen) has been shown to prolong survival. The Stupp protocol was implemented in the county of Jonkoping in 2006. The purpose of this study was to examine if the Stupp treatment has prolonged overall survival, in an unselected patient cohort with histologically verified GBM. Material and MethodThis study includes all patients from the county of Jonkoping, with a diagnosis of GBM from January 2001 to December 2012. Patients were divided into 2 cohorts, 2001-2005 and 2006-2012, that is before and after implementation of the Stupp regimen. By reviewing the medical case notes, the dates of the histological diagnosis and of death were identified. The median and mean overall survival and Kaplan-Meier survival analysis were calculated and compared between the 2 cohorts. ResultsThe mean survival was 110days longer in the cohort treated according to the Stupp regimen. Four patients in the 2006-2012 cohort and 1 patient in the 2001-2005 cohort are still alive. When comparing survival in patients with radical surgery vs biopsy, those that underwent radical surgery survived longer. The significance was slightly greater in the 2001-2005 cohort (mean 163 vs 344days, Pamp;lt;.001) than in the 2006-2012 cohort (mean 220 vs 397days, P=.02). ConclusionSurvival significantly improved after the implementation of the Stupp regimen in the study region of Sweden.

  • 87.
    Bruno, Valentina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Tor Vergata Univ Hosp, Italy.
    Svensson Arvelund, Judit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rubér, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Piccione, Emilio
    Tor Vergata Univ Hosp, Italy.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Effects of low molecular weight heparin on the polarization and cytokine profile of macrophages and T helper cells in vitro2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 4166Article in journal (Refereed)
    Abstract [en]

    Low molecular weight heparin (LMWH) is widely used in recurrent miscarriage treatment. The anticoagulant effects are established, while immunological effects are not fully known. Our aim was to assess LMWH effects on activation and polarization of central regulatory immune cells from healthy women, and on placenta tissues from women undergoing elective abortions. Isolated blood monocytes and T helper (Th) cells under different activation and polarizing conditions were cultured with or without LMWH. Flow cytometry showed that LMWH exposure induced increased expression of HLA-DR and CD206 in macrophages. This phenotype was associated with increased secretion of Th17-associated CCL20, and decreased secretion of CCL2 (M2-associated) and CCL22 (Th2), as measured by multiplex bead array. In accordance, LMWH exposure to Th cells reduced the proportion of CD25highFoxp3+ regulatory T-cells, intensified IFN-gamma secretion and showed a tendency to increase the lymphoblast proportions. Collectively, a mainly pro-inflammatory effect was noted on two essential tolerance-promoting cells. Although the biological significancies of these in vitro findings are uncertain and need to be confirmed in vivo, they suggest the possibility that immunological effects of LMWH may be beneficial mainly at an earlier gestational age to provide an appropriate implantation process in women with recurrent miscarriage.

  • 88.
    Bukmann Larsen, Pia
    et al.
    Slagelse Hospital, Denmark.
    Storjord, Elin
    Nordland Hospital, Norway; UiT, Norway.
    Bakke, Asne
    Stavanger University Hospital, Norway.
    Bukve, Tone
    Akershus University Hospital, Norway.
    Christensen, Mikael
    Aarhus University Hospital, Denmark.
    Eikeland, Joakim
    Oslo University Hospital, Norway.
    Engeland Haugen, Vegar
    Haukeland Hospital, Norway.
    Husby, Kristin
    Akershus University Hospital, Norway.
    McGrail, Rie
    Aarhus University Hospital, Denmark.
    Meier Mikaelsen, Solveig
    Sykehuset Innlandet, Norway.
    Monsen, Grete
    Noklus, Norway.
    Fogh Moller, Mette
    Herning Hospital, Denmark.
    Nybo, Jan
    Aalborg University Hospital, Denmark.
    Revsholm, Jesper
    Randers Regional Hospital, Denmark.
    Johanne Risoy, Aslaug
    Noklus, Norway; University of Bergen, Norway.
    Skalsvik, Unni Marie
    Nordland Hospital, Norway.
    Strand, Heidi
    Akershus University Hospital, Norway.
    Serrano Teruel, Reyes
    Noklus, Norway.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    The microINR portable coagulometer: analytical quality and user-friendliness of a PT (INR) point-of-care instrument2017In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 2, p. 115-121Article in journal (Refereed)
    Abstract [en]

    Regular measurement of prothrombin time as an international normalized ratio PT (INR) is mandatory for optimal and safe use of warfarin. Scandinavian evaluation of laboratory equipment for primary health care (SKUP) evaluated the microINR portable coagulometer (microINR((R))) (iLine Microsystems S.L., Spain) for measurement of PT (INR). Analytical quality and user-friendliness were evaluated under optimal conditions at an accredited hospital laboratory and at two primary health care centres (PHCCs). Patients were recruited at the outpatient clinic of the Laboratory of Medical Biochemistry, St Olavs University Hospital, Trondheim, Norway (n=98) and from two PHCCs (n=88). Venous blood samples were analyzed under optimal conditions on the STA-R((R))Evolution with STA-SPA+reagent (Stago, France) (Owren method), and the results were compared to capillary measurements on the microINR((R)). The imprecision of the microINR((R)) was 6% (90% CI: 5.3-7.0%) and 6.3% (90% CI: 5.1-8.3) in the outpatient clinic and PHCC2, respectively for INR 2.5. The microINR((R)) did not meet the SKUP quality requirement for imprecision 5.0%. For INR amp;lt;2.5 at PHCC2 and at both levels in PHCC1, CV% was 5.0. The accuracy fulfilled the SKUP quality goal in both outpatient clinic and PHCCs. User-friendliness of the operation manual was rated as intermediate, defined by SKUP as neutral ratings assessed as neither good nor bad. Operation facilities was rated unsatisfactory, and time factors satisfactory. In conclusion, quality requirements for imprecision were not met. The SKUP criteria for accuracy was fulfilled both at the hospital and at the PHCCs. The user-friendliness was rated intermediate.

  • 89.
    Böttiger, Ylva
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Laine, Kari
    Medbase Ltd, Finland; Univ Turku, Finland.
    Korhonen, Tuomas
    Medbase Ltd, Finland; Univ Turku, Finland.
    Lahdesmaki, Janne
    Medbase Ltd, Finland; Turku Univ Hosp, Finland; Univ Turku, Finland.
    Shemeikka, Tero
    Stockholm Cty Council, Sweden.
    Julander, Margaretha
    Stockholm Cty Council, Sweden.
    Edlert, Maria
    Stockholm Cty Council, Sweden.
    Andersson, Marine L.
    Karolinska Univ Hosp, Sweden.
    Development and pilot testing of PHARAO-a decision support system for pharmacological risk assessment in the elderly2018In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 74, no 3, p. 365-371Article in journal (Refereed)
    Abstract [en]

    The aims of this study are to describe the development of PHARAO (Pharmacological Risk Assessment Online), a decision support system providing a risk profile for adverse events, associated with combined effects of multiple medicines, and to present data from a pilot study, testing the use, functionality, and acceptance of the PHARAO system in a clinical setting. About 1400 substances were scored in relation to their risk to cause any of nine common and/or serious adverse effects. Algorithms for each adverse effect score were developed to create individual risk profiles from the patients list of medication. The system was tested and integrated to the electronic medical record, during a 4-month period in two geriatric wards and three primary healthcare centers, and a questionnaire was answered by the users before and after the test period. A total of 732 substances were tagged with one or more of the nine risks, most commonly with the risk of sedation or seizures. During the pilot, the system was used 933 times in 871 patients. The most common signals generated by PHARAO in these patients were related to the risks of constipation, sedation, and bleeding. A majority of responders considered PHARAO easy to use and that it gives useful support in performing medication reviews. The PHARAO decision support system, designed as a complement to a database on drug-drug interactions used nationally, worked as intended and was appreciated by the users during a 4-month test period. Integration aspects need to be improved to minimize unnecessary signaling.

  • 90.
    Capitanio, Arrigo
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Dina, R. E.
    Imperial Coll NHS Trust, England.
    Treanor, Darren
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology. Leeds Teaching Hosp NHS Trust, England.
    Digital cytology: A short review of technical and methodological approaches and applications2018In: Cytopathology, ISSN 0956-5507, E-ISSN 1365-2303, Vol. 29, no 4, p. 317-325Article, review/survey (Refereed)
    Abstract [en]

    The recent years have been characterised by a rapid development of whole slide imaging (WSI) especially in its applications to histology. The application of WSI technology to cytology is less common because of technological problems related to the three-dimensional nature of cytology preparations (which requires capturing of z-stack information, with an increase in file size and usability issues in viewing cytological preparations). The aim of this study is to provide a review of the literature on the use of digital cytology and provide an overview of cytological applications of WSI in current practice as well as identifying areas for future development.

  • 91.
    Capitanio, Arrigo
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Dina, Roberto E.
    Imperial Coll NHS Trust, England.
    Treanor, Darren
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology. Leeds Teaching Hosp NHS Trust, England.
    Reply to Van Es et al. Digital pathology: A constant evolution2019In: Cytopathology, ISSN 0956-5507, E-ISSN 1365-2303, Vol. 30, no 2, p. 264-264Article in journal (Other academic)
    Abstract [en]

    n/a

  • 92.
    Carlsson, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Robotassisterad kirurgi ökar – trots osäker kostnadseffektivitet2016In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, no 48, p. 1-5Article, review/survey (Refereed)
  • 93.
    Castiglione, Fabio
    et al.
    University of Leuven, Belgium; IRCCS Osped San Raffaele, Italy.
    Dewulf, Karel
    University of Leuven, Belgium.
    Hakim, Lukman
    University of Leuven, Belgium; Airlangga University, Indonesia.
    Weyne, Emmanuel
    University of Leuven, Belgium.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy.
    Russo, Andrea
    IRCCS Osped San Raffaele, Italy.
    Boeri, Luca
    IRCCS Osped San Raffaele, Italy.
    Bivalacqua, Trinity J.
    Johns Hopkins Medical Institute, MD 21205 USA.
    De Ridder, Dirk
    University of Leuven, Belgium.
    Joniau, Steven
    University of Leuven, Belgium.
    Albersen, Maarten
    University of Leuven, Belgium.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Lund University, Sweden.
    Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 6, p. 1032-1041Article in journal (Refereed)
    Abstract [en]

    Background: A medical treatment for urethral stricture (US) is not yet available. Objective: To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. Design, setting, and participants: Male rats were divided into three groups: sham, US, and hADSC (n = 12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-beta 1 in the urethral wall. Intervention: One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. Outcome measurements and statistical analysis: Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. Results and limitations: US rats exhibited 49-51% shorter micturition intervals, 35-51% smaller micturition volumes and bladder capacity, 33-62% higher threshold pressures and flow pressures, and 35-37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p amp;lt; 0.05). By ultrasound, US rats had hyperechogenic and thick urethral walls with narrowed lumen compared with sham rats, whereas hADSC rats displayed less extensive urethral changes. Isolated detrusor from US rats exhibited 34-55% smaller contractions than detrusor from sham rats (p amp;lt; 0.05). Corresponding values were 11-35% for isolated detrusors from hADSC rats. Collagen and elastin protein expression were increased in the penile urethras of US rats compared with sham and hADSC groups (p amp;lt; 0.05). Endothelial and inducible nitric oxide synthase expressions were higher (p amp;lt; 0.05) in the hADSC group. Compared with US rats, hADSC rats demonstrated decreased expression of several fibrosis-related genes. Administration of hADSCs was performed at an early stage of US development, which we consider a limitation of the study. Conclusions: Local injection of hADSCs prevents stricture formation and urodynamic complications in a new rat model for US. Patient summary: Stem cell therapy is effective for preventing urethral stricture in an experimental setting. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 94.
    Castiglione, Fabio
    et al.
    Univ Leuven, Belgium; Univ Coll London Hosp, England; IRCCS Osped San Raffaele, Italy.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Lund Univ, Sweden.
    Weyne, Emanuel
    Univ Leuven, Belgium.
    Hakim, Lukman
    Univ Leuven, Belgium; Airlangga Univ, Indonesia.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy.
    Bivalacqua, Trinity J.
    Johns Hopkins Med Inst, MD 21205 USA.
    De Ridder, Dirk
    Univ Leuven, Belgium.
    Milenkovic, Uros
    Univ Leuven, Belgium.
    Ralph, David
    Univ Coll London Hosp, England.
    Garaffa, Giulio
    Univ Coll London Hosp, England.
    Muneer, Asif
    Univ Coll London Hosp, England.
    Joniau, Steven
    Univ Leuven, Belgium.
    Intratunical Injection of Human Adipose Tissue-Derived Stem Cells Restores Collagen III/IRatio in a Rat Model of Chronic Peyronies Disease2019In: SEXUAL MEDICINE, ISSN 2050-1161, Vol. 7, no 1, p. 94-103Article in journal (Refereed)
    Abstract [en]

    Introduction: Previous studies have shown that the injection of adipose tissue-derived stem cells (ADSCs) into the tunica albuginea (TA) during the active phase of Peyronies disease (PD) prevents the development of fibrosis. Aim: To investigate, using an animal model, whether local injection of human ADSCs (hADSCs) can alter the degree of fibrosis in the chronic phase of PD. Methods: 27 male, 12-week-old rats were divided into 3 equal groups: sham, PD without treatment, and PD treated with hADSCs 1 month after disease induction. Sham rats underwent 2 injections of vehicle into the TA 1 month apart. PD rats underwent transforming growth factor beta 1 (TGF beta 1) injection and injection of vehicle 1 month later. PD-hADSC rats underwent TGF beta 1 injection followed by 1 million hADSCs 1 month later. 1 week after treatment, n = 3 animals/group were euthanized, and the penises were harvested for quantitative polymerase chain reaction. 1 month after treatment, the other animals, n = 6 per group, underwent measurement of intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrostimulation of the cavernous nerve. After euthanasia, penises were again harvested for histology and Western blot. Main Outcome Measure: The primary outcome measures included (a) gene expression at one week post-injection; (b) measurement of ICP/MAP upon cavernous nerve stimulation as a measure of erectile function; (c) elastin, collagen I and III protein expression; and (d) Histomorphometric analysis of the penis. Means where compared by analysis of variance (ANOVA) followed by a Student-Newman-Keuls test for post hoc comparisons or Mann-Whitney test when applicable. Results: No significant difference was noted in ICP or ICP/MAP in response to cavernous nerve electrostimulation between the 3 groups at 2.5, 5, and 7.5 V (Pamp;gt;.05 for all voltages). PD animals developed tunical and subtunical areas of fibrosis with a significant upregulation of collagen III protein. The collagen III/I ratio was higher in the PD (4.6 +/- 0.92) group compared with sham (0.66 +/- 0.18) and PD-hADSC (0.86 +/- 0.06) groups (Pamp;lt;.05) These fibrotic changes were prevented when treated with hADSCs. Compared with PD rats, PD-hADSC rats demonstrated a decreased expression of several fibrosis-related genes. Conclusion: Injection of hADSCs reduces collagen III expression in a rat model of chronic PD. Copyright (C) 2018, International Society for Sexual Medicine. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  • 95.
    Castiglione, Fabio
    et al.
    Univ Leuven, Belgium; Univ Coll London Hosp, England; IRCCS Osped San Raffaele, Italy.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Lund Univ, Sweden.
    Weyne, Emmanuel
    Univ Leuven, Belgium.
    Hakim, Lukman
    Univ Leuven, Belgium; Airlangga Univ, Indonesia.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy.
    Salonia, Andrea
    IRCCS Osped San Raffaele, Italy.
    Bivalacqua, Trinity J.
    Johns Hopkins Med Inst, MD 21205 USA.
    De Ridder, Dirk
    Univ Leuven, Belgium.
    Milenkovic, Uros
    Univ Leuven, Belgium.
    Ralph, David
    Univ Coll London Hosp, England.
    Garaffa, Giulio
    Univ Coll London Hosp, England.
    Muneer, Asif
    Univ Coll London Hosp, England.
    Joniau, Steven
    Univ Leuven, Belgium.
    Albersen, Maarten
    Univ Leuven, Belgium.
    Intratunical injection of stromal vascular fraction prevents fibrosis in a rat model of Peyronies disease2019In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 124, no 2, p. 342-348Article in journal (Refereed)
    Abstract [en]

    Objective To investigate whether local injection of autologous adipose stromal vascular fraction (SVF) can prevent the development of fibrosis and elastosis in the tunica albuginea (TA) using a rat model of the acute phase of Peyronies disease (PD). Methods A total of 24 male 12-week-old Sprague-Dawley rats were divided into three equal groups: sham; PD without treatment (transforming growth factor-beta [TGF -beta]); and PD treated with SVF 1 day after disease induction. Sham rats received two injections of vehicle into the TA 1 day apart. TGF -beta rats received TGF- beta 1 injection and injection of vehicle 1 day later. SVF rats received TGF-beta 1 injection, followed by SVF 1 day later. One month after treatment, all rats underwent measurement of intracavernosal pressure and mean arterial pressure during electrostimulation of the cavernous nerve. The rats were then killed and penises were harvested for histology and Western blot analysis. Results Erectile function was moderately reduced in the TGF-beta group and was significantly improved after SVF treatment (P amp;lt; 0.05). PD rats developed areas of fibrosis with a significant upregulation of collagen III, collagen I and elastin protein expression. These fibrotic changes were prevented when treated with SVF. Conclusions Local injection of SVF may represent treatment for the acute phase of PD.

  • 96.
    Cauvi, D.M.
    et al.
    University of California, San Diego, CA, USA.
    Hultman, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Pollard, K. Michael
    The Scripps Research Institute, La Jolla, CA, USA.
    Autoimmune models2015In: Reference module in biomedical sciences, Elsevier, 2015, p. 413-438Chapter in book (Refereed)
    Abstract [en]

    Models of autoimmunity fall into four categories: (a) those induced by immunization with self-antigen, (b) those induced by exogenous agents, (c) those which arise spontaneously, and (d) those which are produced by genetic manipulation. The autoimmunity exhibited by these models covers a spectrum of diseases which fall into the two broad categories, organ-specific and systemic autoimmunity. Animal models of autoimmune diseases have played an essential role in the discovery of many of mechanisms that result in the breaking of self-tolerance. This chapter describes a number of experimental animal models of autoimmunity and the underlying mechanisms that lead to disease.

  • 97.
    Chaireti, Roza
    et al.
    Karolinska Institute, Sweden.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Bystrom, Birgitta
    Karolinska Institute, Sweden.
    Bremme, Katarina
    Karolinska Institute, Sweden.
    Larsson, Anders
    Uppsala University, Sweden.
    Inflammatory and endothelial markers during the menstrual cycle2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 3, p. 190-194Article in journal (Refereed)
    Abstract [en]

    Background The menstrual cycle exhibits a pattern of repeated inflammatory activity. The present study aims to evaluate inflammatory and endothelial markers during the two phases of a menstrual cycle. Methods The study cohort consisted of 102 women with regular menstrual cycles. Inflammatory and endothelial markers (interleukin-6 [IL-6], pentraxin-3 [PTX-3], hs-C reactive protein [hs-CRP], sE-selectin, sP-selectin, intracellular and vascular cell adhesion molecules [ICAM-1 and VCAM-1] and cathepsins L, B and S) were measured during the early follicular and the late luteal phase of a normal menstrual cycle. Results Pentraxin-3 (PTX-3) and hs-CRP were significantly higher during the follicular phase compared to the luteal phase (p &lt; 0.001 respectively p = 0.025). The other inflammatory and endothelial markers, with the exception of cathepsin B, were higher, albeit not significantly, during the follicular phase. Conclusions Inflammatory activity, expressed mainly by members of the pentraxin family, is higher during the early follicular compared to the luteal phase. This could be associated to menstruation but the exact mechanisms behind this pattern are unclear and might involve the ovarian hormones or an effect on hepatocytes.

  • 98.
    Chalise, Jaya Prakash
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Pallotta, Maria Teresa
    Department of Experimental Medicine, University of Perugia, Perugia, Italy.
    Chenna Narendra, Sudeep
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Iacono, Alberta
    Department of Experimental Medicine, University of Perugia, Perugia, Italy.
    Boon, Louis
    EPIRUS Biopharmaceuticals, Utrecht, Netherlands.
    Grohmann, Ursula
    Department of Experimental Medicine, University of Perugia, Perugia, Italy.
    Magnusson, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    IDO1 and TGF- 1 β mediate protective effects of IFN-α in antigen-induced arthritisManuscript (preprint) (Other academic)
    Abstract [en]

    Interferon-α (IFN-α) prevents antigen-induced arthritis (AIA) in mice by an unknown mechanism. Indoleamine 2, 3 dioxygenase 1 (IDO1) is an immunoregulator via enzymatic as well as signalling activity, which can be activated by TGF-β and further mediated via non canonical NF-κB signalling. We here investigated whether IDO1 and TGF-β are involved in IFN-α protective effects in AIA. Arthritis was induced in wt, Ido1-/- or Ifnar-/- mice, treated or not with IFN-α or kynurenine, the main IDO1 product, and antibodies neutralizing TGF-β or 1-methyltryptophan (1-MT), an inhibitor of IDO1 catalytic activity. IDO1 expression and enzymatic activity were determined by RT-PCR and HPLC, respectively. Proliferation was measured by 3H-Thymidine incorporation. Non-canonical NF-κB signalling was evaluated by ELISA and Western blot in plasmacytoid DCs (pDCs) from treated mice. Protective effects of IFN-α in AIA were associated with increased IDO1 expression and kynurenine production in spleen cells, particularly at the time of mBSA sensitization. Lack of IDO1 ablated IFN-α protection and kynurenine prevented AIA in an IFNAR-independent manner. The IDO1 catalytic activity was crucial for IFN-α effects at the sensitization but not effector phase of AIA. The disease effector phase in mice treated with IFN-α was instead characterized by sustained IDO1 and TGF-β expression and activation of the noncanonical NF-κB pathway in pDCs. IFN-α protective effects in AIA involves IDO1 enzymatic and signalling activity in the disease sensitization and effector phase, respectively. Kynurenine, the main IDO1 metabolite, can be used as an alternative treatment to IFN-α in protecting mice from AIA.

  • 99.
    Chenna Narendra, Sudeep
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Prakash Chalise, Jaya
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Magnusson, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Local but Not Systemic Administration of Uridine Prevents Development of Antigen-Induced Arthritis2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, p. e0141863-Article in journal (Refereed)
    Abstract [en]

    Objective Uridine has earlier been show to down modulate inflammation in models of lung inflammation. The aim of this study was to evaluate the anti-inflammatory effect of uridine in arthritis. Methods Arthritis was induced by intra-articular injection of mBSA in the knee of NMRI mice preimmunized with mBSA. Uridine was either administered locally by direct injection into the knee joint or systemically. Systemic treatment included repeated injections or implantation of a pellet continuously releasing uridine during the entire experimental procedure. Anti-mBSA specific immune responses were determined by ELISA and cell proliferation and serum cytokine levels were determined by Luminex. Immunohistochemistry was used to identify cells, study expression of cytokines and adhesion molecules in the joint. Results Local administration of 25-100 mg/kg uridine at the time of arthritis onset clearly prevented development of joint inflammation. In contrast, systemic administration of uridine (max 1.5 mg uridine per day) did not prevent development of arthritis. Protection against arthritis by local administration of uridine did not affect the anti-mBSA specific immune response and did not prevent the rise in serum levels of pro-inflammatory cytokines associated with the triggering of arthritis. In contrast, local uridine treatment efficiently inhibited synovial expression of ICAM-1 and CD18, local cytokine production and recruitment of leukocytes to the synovium. Conclusion Local, but not systemic administration of uridine efficiently prevented development of antigen- induced arthritis. The protective effect did not involve alteration of systemic immunity to mBSA but clearly involved inhibition of synovial expression of adhesion molecules, decreased TNF and IL-6 production and prevention of leukocyte extravasation. Further, uridine is a small, inexpensive molecule and may thus be a new therapeutic option to treat joint inflammation in RA.

  • 100.
    Chermá, Maria D.
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Rydberg, Irene
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Woxler, Per
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Dependency in Linköping.
    Trygg, Tomas
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Dependency in Linköping.
    Hollertz, Olle
    Department of General Psychiatry, Västervik Hospital, Västervik, Sweden.
    Gustafsson, Per A.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Methylphenidate for Treating ADHD: A Naturalistic Clinical Study of Methylphenidate Blood Concentrations in Children and Adults With Optimized Dosage.2017In: European journal of drug metabolism and pharmacokinetics, ISSN 0378-7966, E-ISSN 2107-0180, Vol. 42, no 2, p. 295-307Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Methylphenidate (MPH), along with behavioral and psychosocial interventions, is the first-line medication to treat attention-deficit hyperactivity disorder (ADHD) in Sweden. The dose of MPH for good symptom control differs between patients. However, studies of MPH concentration measurement in ADHD treatment are limited.

    OBJECTIVE: To describe blood and oral fluid (OF) concentrations of MPH after administration of medication in patients with well-adjusted MPH treatment for ADHD, and to identify the most suitable matrix for accurate MPH concentration during treatment.

    METHODS: Patients were recruited from Child and Adolescent Psychiatry (CAP), General Psychiatry (GP), and the Department of Dependency (DD). Blood and OF samples were collected in the morning before MPH administration as well as 1 and 6 h after administration of the prescribed morning dose of MPH.

    RESULTS: Fifty-nine patients aged between 9 and 69 years, 76 % males. The daily dose of MPH varied from 18 to 180 mg, but the median daily dose per body weight was similar, approximately 1.0 mg/kg body weight. The median MPH concentration in blood 1 and 6 h after the morning dose was 5.4 and 9.3 ng/mL, respectively. Highly variable OF-to-blood ratios for MPH were found at all time points for all three groups.

    CONCLUSIONS: Weight is a reliable clinical parameter for optimal dose titration. Otherwise, MPH blood concentration might be used for individual dose optimization and for monitoring of the prescribed dose. Relying only on the outcome in OF cannot be recommended for evaluation of accurate MPH concentrations for treatment monitoring.

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