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  • 1.
    Anlauf, M
    et al.
    Department of Pathology, University of Kiel, Kiel, Germany.
    Perren, A
    Department of Pathology, University of Zürich, Zürich, Switzerland.
    Henopp, T
    Department of Pathology, University of Kiel, Kiel, Germany.
    Rudolf, T
    Department of Pathology, University of Zürich, Zürich, Switzerland.
    Garbrecht, N
    Department of Pathology, University of Kiel, Kiel, Germany.
    Schmitt, A
    Department of Pathology, University of Zürich, Zürich, Switzerland.
    Raffel, A
    Department of General, Visceral and Pediatric Surgery, University of Düsseldorf, North Rhine‐Westphalia, Germany.
    Gimm, O
    Department of General and Visceral Surgery, University of Halle, Halle, Germany.
    Weihe, E
    Department of Molecular Neuroscience, Department of Anatomy and Cell Biology, University of Marburg, Marburg, Germany.
    Knoefel, W T
    Department of General, Visceral and Pediatric Surgery, University of Düsseldorf, North Rhine‐Westphalia, Germany.
    Dralle, H
    Department of General and Visceral Surgery, University of Halle, Halle, Germany.
    Heitz, Ph U
    Department of Pathology, University of Zürich, Zürich, Switzerland.
    Komminoth, P
    Department of Pathology, Kantonsspital Baden, Baden, Switzerland.
    Klöppel, G
    Department of Pathology, University of Kiel, Kiel, Germany.
    Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions.2007In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 56, no 5, p. 637-44Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with a multiple endocrine neoplasia type 1 (MEN1)-associated Zollinger-Ellison syndrome (ZES) show multifocal duodenal gastrinomas and precursor lesions.

    AIMS: To test these lesions for loss of heterozygosity (LOH) of the MEN1 gene locus on chromosome 11q13, and to investigate whether the MEN1-related endocrine cell changes also involved somatostatin cells.

    MATERIAL AND METHODS: Tissue specimens from six patients with MEN1 and ZES were analysed by immunohistochemistry and immunofluorescence. LOH analysis was performed by fluorescence in situ hybridisation (FISH), using probes containing the MEN1 gene locus and the centromere 11 (C11) region. For simultaneous analysis of hormones and allelic deletions, a combined FISH/immunofluorescence protocol was established.

    RESULTS: 28 of a total of 33 duodenal neuroendocrine tumours (NETs) were gastrin-producing tumours; 13/28 (46.4%) revealed LOH on 11q13 and/or C11. Five of the NETs were somatostatin-expressing tumours, two revealing LOH. Allelic loss was detected in tumours as small as 300 microm (gastrin) and 400 microm (somatostatin) in diameter. The gastrin-producing tumours showed different deletion/retention patterns. Hyperplastic somatostatin cell lesions, similar to those of the gastrin cells, were present in all patients. The hyperplastic lesions of both cell lines consistently retained both 11q13 alleles.

    CONCLUSIONS: Allelic deletion of the MEN1 gene may reflect a pivotal event in the development of multifocal gastrin and somatostatin cell neoplasms in the duodenum of patients with MEN1. The observation of distinct deletion patterns in small synchronous tumours supports the concept that each gastrin-producing tumour in an individual MEN1 patient arises from an independent cell clone.

  • 2. Arber, N
    et al.
    Kuwada, S
    Leshno, M
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Hultcrantz, R
    Rex, D
    Sporadic adenomatous polyp regression with exisulind is effective but toxic: A randomised, double blind, placebo controlled, dose-response study2006In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, no 3, p. 367-373Article in journal (Refereed)
    Abstract [en]

    Background and aim: A 12 month, multicentre, randomised, double blind, placebo controlled, phase 3, dose-response study was carried out. Exisulind inhibits tumour growth by induction of apoptosis. The aim of our study was to investigate if exisulind induces regression of sporadic colonic adenomas. Patients and methods: A 12 month multicentre randomised double blind placebo controlled phase 3 dose response study was carried out. At baseline colonoscopy, left sided polyps (3-10 mm) were tattooed, measured, and left in place. Subjects received exisulind 200 or 400 mg, or placebo daily. Follow up sigmoidoscopy was performed after six months, and removal of any remaining polyps at the 12 month colonoscopy. The primary efficacy variable was change in polyp size from baseline. Results: A total of 281 patients were enrolled and randomised, 155 (55%) fulfilled the criteria for the intention to treat (ITT) analysis and 114 (41%) fulfilled the criteria for the efficacy evaluation analysis (patients who underwent the 12 month colonoscopy). The decrease in median polyp size was significantly greater (p = 0.03) in patients who received exisulind 400 mg (-10 mm2) compared with those who received placebo (-4 mm2). Complete or partial response was significantly higher in the exisulind 400 mg group (54.6%) compared with the placebo group (30.2%), and disease progression was significantly lower (6.1% v 27.9%) (p = 0.04 and 0.02, respectively). Increased liver enzymes (8.4%) and abdominal pain (14.7%) were also reported at a greater frequency in the exisulind 400 mg group. Conclusion: Exisulind caused significant regression of sporadic adenomatous polyps but was associated with more toxicity. This model of polyp regression, short in its term and involving a comparatively small patient sample size, may be the best available tool to assess a therapeutic regimen before launching into large preventive clinical studies.

  • 3.
    Bodger, K
    et al.
    University of Liverpool.
    Halfvarson, Jonas
    Örebro University Hospital.
    Dodson, AR
    Royal Liverpool University Hospital.
    Campbell, F
    Royal Liverpool University Hospital.
    Wilson, S
    University of Southampton.
    Lee, R
    University of Southampton.
    Lindberg, E
    Örebro University Hospital.
    Järnerot, Gunnar
    Örebro University Hospital.
    Tysk, Curt
    Örebro University Hospital.
    Rhodes, JM
    University of Liverpool.
    Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients.2006In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, no 7, p. 973-977Article in journal (Refereed)
    Abstract [en]

    Background and aims: Previous chromatographic analysis of colonic mucins from monozygotic twins with inflammatory bowel disease (IBD) suggested a genetic mucin alteration in ulcerative colitis (UC). This study explores this further by assessing mucosal expression of the oncofetal carbohydrate antigen TF (galactose β1, 3 N-acetylgalactosamine α-), among the same IBD twins.

    Materials and methods: Formalin fixed paraffin embedded rectal biopsies were studied from 22 monozygotic twin pairs with IBD. These included eight UC twin pairs and 14 Crohn’s disease (CD) twin pairs, with six pairs concordant for disease and 16 unaffected twin siblings. Closely adjacent sections were assessed by peanut lectin histochemistry for TF expression and immunohistochemically for nuclear factor κB (NFκB) activation with investigators blinded to the diagnosis.

    Results: Unaffected twins were almost all TF positive (15/16) compared with 5/29 histologically normal controls (p<0.0001). Unaffected UC (7/8) and CD twins (8/8) were similarly TF positive. TF positivity was confined mainly to the superficial epithelium and absent from the stem cell compartment of the lower crypts, suggesting that glycosylation changes are acquired rather than genetically determined. Activated NFκB was present in the surface epithelium of mucosal biopsies from 13/14 unaffected IBD twins but in only 6/22 histologically normal controls (p = 0.0004). All 22 affected IBD twins were TF positive and 18 were positive for activated NFκB.

    Conclusions: Altered mucosal glycosylation in unaffected identical twins of IBD patients was confirmed in this study. This occurred in both UC and CD twins. The changes are probably acquired rather than congenital and may reflect “preinflammatory” NFκB activation.

  • 4.
    Botella, S
    et al.
    Linkoping Univ Hosp, Div Gastroenterol & Hepatol, S-58185 Linkoping, Sweden Div Cell Biol, Dept Biomed & Surg, Linkoping, Sweden.
    Ericson, A
    Sjostrand, S
    Kechagias, Stergios
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    H-pylori infection is associated with increased expression of capsaicin receptors in gastric epithelial cells2002In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 51, p. 414-Conference paper (Other academic)
  • 5.
    Burisch, J.
    et al.
    Herlev University Hospital, Denmark .
    Pedersen, N.
    Herlev University Hospital, Denmark .
    Cukovic-Cavka, S.
    University of Zagreb, Croatia .
    Brinar, M.
    University of Zagreb, Croatia .
    Kaimakliotis, I.
    Nicosia Private Practice, Cyprus .
    Duricova, D.
    Charles University of Prague, Czech Republic .
    Shonova, O.
    Hospital Ceske Budejovice, Czech Republic .
    Vind, I.
    Amager Hospital, Denmark .
    Avnstrom, S.
    Amager Hospital, Denmark .
    Thorsgaard, N.
    Herning Central Hospital, Denmark .
    Andersen, V.
    Viborg Regional Hospital, Denmark Hospital Southern Jutland, Denmark University of Southern Denmark, Denmark .
    Krabbe, S.
    Viborg Regional Hospital, Viborg, Denmark.
    Dahlerup, J.F.
    Aarhus University Hospital, Denmark .
    Salupere, R.
    Tartu University Hospital, Estonia .
    Nielsen, K.R.
    National Hospital Faroe Isl, Denmark .
    Olsen, J.
    National Hospital Faroe Isl, Denmark .
    Manninen, P.
    Tampere University Hospital, Finland .
    Collin, P.
    Tampere University Hospital, Finland .
    Tsianos, E.V.
    University Hospital, Greece University Hospital, Greece .
    Katsanos, K.H.
    University Hospital, Greece University Hospital, Greece .
    Ladefoged, K.
    Dronning Ingrids Hospital, Greenland .
    Lakatos, L.
    Semmelweis University, Budapest, Hungary.
    Bjornsson, E.
    National University Hospital Reykjavik, Iceland .
    Ragnarsson, G.
    National University Hospital Reykjavik, Iceland .
    Bailey, Y.
    ACD, Ireland .
    Odes, S.
    Ben Gurion University of Negev, Israel Ben Gurion University of Negev, Israel .
    Schwartz, D.
    Ben Gurion University of Negev, Israel Ben Gurion University of Negev, Israel .
    Martinato, M.
    University of Padua, Italy .
    Lupinacci, G.
    UO Gastroenterol Endoscopia Digest, Italy .
    Milla, M.
    Careggi Hospital, Italy .
    De Padova, A.
    Osped Morgagni Pierantoni, Italy .
    D'lnca, R.
    Azienda Ospedaliera—Università di Padova, Padova, Italy.
    Beltrami, M.
    Azienda Osped Arcispedale S Maria Nuova, Italy .
    Kupcinskas, L.
    Az Osped Osped Cremona, Italy Lithuanian University of Health Science, Lithuania .
    Kiudelis, G.
    Lithuanian University of Health Science, Lithuania .
    Turcan, S.
    State University of Medicine and Pharmacy of the Republic of Moldova, Chisinau, Republic of Moldova.
    Tighineanu, O.
    Centre Mother and Child, Moldova .
    Mihu, I.
    Centre Mother and Child, Moldova .
    Magro, F.
    Hospital Sao Joao, Portugal Oporto Medical Sch, Portugal University of Porto, Portugal .
    Barros, L.F.
    Hospital Vale Sousa, Portugal .
    Goldis, A.
    University of Medical Victor Babes, Romania .
    Lazar, D.
    University of Medical Victor Babes, Romania .
    Belousova, E.
    Moscow Regional Research Clin Institute, Russia .
    Nikulina, I.
    Moscow Regional Research Clin Institute, Russia .
    Hernandez, V.
    Complexo Hospital University of Vigo, Spain .
    Martinez-Ares, D.
    Complexo Hospital University of Vigo, Spain .
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Zhulina, Y.
    Örebro University Hospital, Sweden .
    Halfvarson, J.
    Örebro University Hospital, Sweden Rebro University, Sweden .
    Arebi, N.
    University of London Imperial Coll Science Technology and Med, England .
    Sebastian, S.
    Hull and E Yorkshire NHS Trust and Hull and York, England .
    Lakatos, P.L.
    Semmelweis University, Budapest, Hungary.
    Langholz, E.
    Gentofte University Hospital, Denmark .
    Munkholm, P.
    Herlev University Hospital, Denmark .
    East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 4, p. 588-597Article in journal (Refereed)
    Abstract [en]

    Objective The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East–West gradient in the incidence of IBD in Europe exists.

    Design A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience.

    Results 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100 000 in 2010 for CD were 6.5 (range 0–10.7) in Western European centres and 3.1 (range 0.4–11.5) in Eastern European centres, for UC 10.8 (range 2.9–31.5) and 4.1 (range 2.4–10.3), respectively, and for IBDU 1.9 (range 0–39.4) and 0 (range 0–1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy.

    Conclusions An East–West gradient in IBD incidence exists in Europe. Among this inception cohort—including indolent and aggressive cases—international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

  • 6.
    Butwicka, Agnieszka
    et al.
    Karolinska Inst, Sweden; Med Univ Warsaw, Poland.
    Sariaslan, Amir
    Karolinska Inst, Sweden.
    Larsson, Henrik
    Karolinska Inst, Sweden.
    Halfvarson, Jonas
    Orebro Univ, Sweden.
    Myrelid, Pär
    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.
    Olen, Ola
    Stockholm South Gen Hosp, Sweden; Karolinska Inst, Sweden.
    Frisen, Louise
    Child and Adolescent Psychiat Res Ctr, Sweden; Karolinska Inst, Sweden.
    Lichtenstein, Paul
    Karolinska Inst, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ, Sweden.
    No association between urbanisation, neighbourhood deprivation and IBD: a population-based study of 4 million individuals2019In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 5, p. 947-+Article in journal (Other academic)
    Abstract [en]

    n/a

  • 7. Costa, M
    et al.
    Glise, H
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    The enteric nervous system in health and disease. Workshop.2000In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 47Article in journal (Other (popular science, discussion, etc.))
  • 8.
    Dimberg, J
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Samuelsson, A
    Hugander, A
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Differential expression of cyclooxygenase 2 in human colorectal cancer.1999In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 45, p. 730-732Article in journal (Refereed)
  • 9. Dimberg, Jan
    et al.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Letters to the Editor: Differential expression of cyclooxygenase 1 in human colorectal cancer. Reply.2000In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 47, p. 154-154Article in journal (Other (popular science, discussion, etc.))
  • 10.
    Ek, Weronica E
    et al.
    Karolinska Institutet, Stockholm .
    Reznichenko, Anna
    Karolinska Institutet, Stockholm.
    Ripke, Stephan
    Massachusetts General Hospital Boston, Cambridge Massachussetts, USA .
    Niesler, Beate
    University of Heidelberg, Germany .
    Zucchelli, Marco
    Karolinska Institutet, Stockholm.
    Rivera, Natalia V
    Karolinska Institutet, Stockholm.
    Schmidt, Peter T
    University Hospital, Karolinska institutet, Stockholm .
    Pedersen, Nancy L
    Karolinska Institutet, Stockholm.
    Magnusson, Patrik
    Karolinska Institutet, Stockholm.
    Talley, Nicholas J
    University of Newcastle, Australia .
    Holliday, Elizabeth G
    University of Newcastle, Australia .
    Houghton, Lesley
    University of Manchester UK and Mayo Clinic, Jacksonville USA.
    Gazouli, Maria
    University of Athens, Greece .
    Karamanolis, George
    University of Athens, Greece .
    Rappold, Gudrun
    University of Heidelberg, Germany.
    Burwinkel, Barbara
    University Women's Clinic, University of Heidelberg, Germany.
    Surowy, Harald
    University Women's Clinic, University of Heidelberg, Germany.
    Rafter, Joseph
    Karolinska Institutet, Stockholm .
    Assadi, Ghazaleh
    Karolinska Institutet, Stockholm .
    Li, Ling
    Karolinska Institutet, Stockholm .
    Papadaki, Evangelia
    Karolinska Institutet, Stockholm .
    Gambaccini, Dario
    University of Pisa, Pisa Italy .
    Marchi, Santino
    University of Pisa, Pisa Italy .
    Colucci, Rocchina
    Department of Clinical and Experimental Medicine University of Pisa, Italy .
    Blandizzi, Corrado
    Department of Clinical and Experimental Medicine University of Pisa, Italy .
    Barbaro, Raffaella
    University of Bologna, Italy .
    Karling, Pontus
    Umeå University .
    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.
    Ohlsson, Bodil
    Skånes University Hospital, Malmö .
    Tornblom, Hans
    Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Bresso, Francesca
    Karolinska University Hospital, Stockholm .
    Andreasson, Anna
    Sweden Stress Research Institute, Stockholm University.
    Dlugosz, Aldona
    Karolinska Instituet, Stockholm .
    Simren, Magnus
    Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Agreus, Lars
    Karolinska Institutet Stockholm .
    Lindberg, Greger
    Karolinska University Hospital, Karolinska Institutet, Stockholm.
    Boeckxstaens, Guy
    Leuven University, Leuven, Belgium .
    Bellini, Massimo
    University of Pisa, Italy .
    Stanghellini, Vincenzo
    University of Bologna, Italy .
    Barbara, Giovanni
    University of Bologna, Italy .
    Daly, Mark J
    Massachusetts General Hospital Boston, Cambridge Massachussetts, USA .
    Camilleri, Michael
    Mayo Clinic, Rochester, Minnesota, USA .
    Wouters, Mira M
    Leuven University, Belgium .
    D'Amato, Mauro
    Karolinska Institutet, Stockholm .
    Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts.2015In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 64, p. 1774-1782Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies.

    DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls.

    RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls.

    CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.

  • 11.
    Hadizadeh, Fatemeh
    et al.
    Karolinska Inst, Sweden; Isfahan Univ Med Sci, Iran.
    Bonfiglio, Ferdinando
    Karolinska Inst, Sweden; BioDonostia Hlth Res Inst, Spain.
    Belheouane, Meriem
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Vallier, Marie
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Sauer, Sascha
    Max Delbruck Ctr Mol Med BIMSB BIH, Germany.
    Bang, Corinna
    Christian Albrechts Univ Kiel, Germany.
    Bujanda, Luis
    BioDonostia Hlth Res Inst, Spain; Univ Pais Vasco UPV EHU, Spain.
    Andreasson, Anna
    Karolinska Inst, Sweden; Stockholm Univ, Sweden.
    Agreus, Lars
    Karolinska Inst, Sweden.
    Engstrand, Lars
    Karolinska Inst, Sweden; Sci Life Lab, Sweden.
    Talley, Nicholas J.
    Karolinska Inst, Sweden; Univ Newcastle, Australia; Mayo Clin, MN USA; AGIRA, Australia.
    Rafter, Joseph
    Karolinska Inst, Sweden.
    Baines, John F.
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    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.
    Franke, Andre
    Christian Albrechts Univ Kiel, Germany.
    DAmato, Mauro
    BioDonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden; Basque Sci Fdn, Spain.
    Faecal microbiota composition associates with abdominal pain in the general population2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 4, p. 778-+Article in journal (Other academic)
    Abstract [en]

    n/a

  • 12.
    Hadizadeh, Fatemeh
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; School of Nutrition, Isfahan University of Medical Sciences, Isfahan, Iran.
    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.
    Belheouane, Meriem
    Max Planck Institute for Evolutionary Biology, Plön, Germany; Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Heinsen, Femke-Anouska
    Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
    Andreasson, Anna
    Division for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Agreus, Lars
    Division for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Clinical Genomics Facility, Science for Life Laboratory, Stockholm, Sweden.
    Baines, John F
    Max Planck Institute for Evolutionary Biology, Plön, Germany; Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Rafter, Joseph
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Franke, Andre
    Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
    DAmato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
    Stool frequency is associated with gut microbiota composition2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 3, p. 559-560Article in journal (Other academic)
  • 13.
    Halfvarson, Jonas
    et al.
    Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden.
    Standaert-Vitse, A.
    Laboratoire de Mycologie Fondamentale and Appliquée, Inserm E360, Faculté de Médecine, CHU Lille, Lille, France .
    Järnerot, Gunnar
    Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden .
    Sendid, B.
    Laboratoire de Mycologie Fondamentale and Appliquée, Inserm E360, Faculté de Médecine, CHU Lille, Lille, France .
    Jouault, T.
    Laboratoire de Mycologie Fondamentale and Appliquée, Inserm E360, Faculté de Médecine, CHU Lille, Lille, France .
    Bodin, L.
    Statistical and Epidemiological Unit, Clinical Research Centre, Örebro University Hospital, Örebro, Sweden .
    Duhamel, A.
    Centre d’Etudes et de Recherche en Informatique Médicale, Faculté de Médecine, CHU Lille, Lille, France .
    Colombel, J F
    Department of Hepatogastroenterology, Hopital Huriez, CHU Lille, Lille, France .
    Tysk, Curt
    Division of Gastroenterology, Department of Internal Medicine, and Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden .
    Poulain, D.
    Laboratoire de Mycologie Fondamentale and Appliquée, Inserm E360, Faculté de Médecine, CHU Lille, Lille, France .
    Anti-Saccharomyces cerevisiae antibodies in twins with inflammatory bowel disease2005In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 54, no 9, p. 1237-1243Article in journal (Refereed)
    Abstract [en]

    Background and aims: An increased occurrence of anti-Saccharomyces cerevisiae antibodies (ASCA) is reported in unaffected members of families with Crohn’s disease. Whether ASCA is a familial trait due to genetic factors or is caused by exposure to environmental factors is unknown. To assess the genetic influence of ASCA we studied its occurrence in a twin population.

    Patients and methods: ASCA were analysed in 98 twin pairs with inflammatory bowel disease and were related to clinical phenotype and CARD15/NOD2 genotype.

    Results: ASCA were more common in Crohn’s disease than in ulcerative colitis (40/70 (57%) twins v 5/43 (12%) twins). Associations with ileal Crohn’s disease, stricturing/penetrating behaviour, and young age, but not CARD15/NOD2 were confirmed. ASCA were found in 1/20 (5%) healthy siblings in discordant monozygotic pairs with Crohn’s disease compared with 7/27 (26%) in discordant dizygotic pairs. Using the intraclass correlation coefficient (ICC), no agreement in ASCA titres was observed in discordant twin pairs with Crohn’s disease, in monozygotic (ICC = −0.02) or dizygotic (ICC = −0.26) pairs. In contrast, strong agreement was seen within concordant monozygotic twin pairs with Crohn’s disease (ICC = 0.76).

    Conclusions: These findings question the concept of ASCA as a marker of genetic susceptibility for Crohn’s disease. The agreement in ASCA titres within concordant monozygotic twin pairs with Crohn’s disease, suggests that the level of increase is genetically determined. We propose that ASCA are a marker of a response to an environmental antigen and that a specific gene(s) other than CARD15/NOD2 determines the level of response and perhaps also specific phenotypic characteristics.

  • 14.
    Henström, Maria
    et al.
    Karolinska Institute, Sweden.
    Diekmann, Lena
    University of Vet Medical Hannover, Germany.
    Bonfiglio, Ferdinando
    Karolinska Institute, Sweden.
    Hadizadeh, Fatemeh
    Karolinska Institute, Sweden.
    Kuech, Eva-Maria
    University of Vet Medical Hannover, Germany.
    von Koeckritz-Blickwede, Maren
    University of Vet Medical Hannover, Germany.
    Thingholm, Louise B.
    Christian Albrechts University of Kiel, Germany.
    Zheng, Tenghao
    Karolinska Institute, Sweden.
    Assadi, Ghazaleh
    Karolinska Institute, Sweden.
    Dierks, Claudia
    University of Vet Medical Hannover, Germany.
    Heine, Martin
    University of Vet Medical Hannover, Germany.
    Philipp, Ute
    University of Vet Medical Hannover, Germany.
    Distl, Ottmar
    University of Vet Medical Hannover, Germany.
    Money, Mary E.
    University of Maryland, MD 21201 USA; Meritus Medical Centre, MD USA.
    Belheouane, Meriem
    Max Planck Institute Evolutionary Biol, Germany; Christian Albrechts University of Kiel, Germany.
    Heinsen, Femke-Anouska
    Christian Albrechts University of Kiel, Germany.
    Rafter, Joseph
    Karolinska Institute, Sweden.
    Nardone, Gerardo
    Federico II University Hospital, Italy.
    Cuomo, Rosario
    Federico II University Hospital, Italy.
    Usai-Satta, Paolo
    Azienda Osped G Brotzu, Italy.
    Galeazzi, Francesca
    Padova University Hospital, Italy.
    Neri, Matteo
    GDAnnunzio University, Italy; University of GDAnnunzio, Italy.
    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).
    Simren, Magnus
    University of Gothenburg, Sweden; University of N Carolina, NC USA.
    Karling, Pontus
    Umeå University, Sweden.
    Ohlsson, Bodil
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Schmidt, Peter T.
    Karolinska University Hospital, Sweden.
    Lindberg, Greger
    Karolinska University Hospital, Sweden.
    Dlugosz, Aldona
    Karolinska University Hospital, Sweden.
    Agreus, Lars
    Karolinska Institute, Sweden.
    Andreasson, Anna
    Karolinska Institute, Sweden; Stockholm University, Sweden.
    Mayer, Emeran
    University of Calif Los Angeles, CA USA.
    Baines, John F.
    Max Planck Institute Evolutionary Biol, Germany; Christian Albrechts University of Kiel, Germany.
    Engstrand, Lars
    Karolinska Institute, Sweden.
    Portincasa, Piero
    University of Bari Aldo Moro, Italy.
    Bellini, Massimo
    University of Pisa, Italy.
    Stanghellini, Vincenzo
    University of Bologna, Italy.
    Barbara, Giovanni
    University of Bologna, Italy.
    Chang, Lin
    University of Calif Los Angeles, CA USA.
    Camilleri, Michael
    Mayo Clin, MN USA.
    Franke, Andre
    Christian Albrechts University of Kiel, Germany.
    Naim, Hassan Y.
    University of Vet Medical Hannover, Germany.
    DAmato, Mauro
    Karolinska Institute, Sweden; BioDonostia Health Research Institute, Spain; Basque Science Fdn, Spain; Karolinska Institute, Sweden.
    Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 2, p. 263-270Article in journal (Refereed)
    Abstract [en]

    Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucraseisomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p. Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (pamp;lt;0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.

  • 15.
    Henström, Maria
    et al.
    Karolinska Institute, Sweden.
    Hadizadeh, Fatemeh
    Karolinska Institute, Sweden; Isfahan University of Medical Science, Iran.
    Beyder, Arthur
    Mayo Clin, MN USA.
    Bonfiglio, Ferdinando
    Karolinska Institute, Sweden; BioDonostia Health Research Institute, Spain.
    Zheng, Tenghao
    Karolinska Institute, Sweden.
    Assadi, Ghazaleh
    Karolinska Institute, Sweden.
    Rafter, Joseph
    Karolinska Institute, Sweden.
    Bujanda, Luis
    BioDonostia Health Research Institute, Spain.
    Agreus, Lars
    Karolinska Institute, Sweden.
    Andreasson, Anna
    Karolinska Institute, Sweden; Stockholm University, Sweden.
    Dlugosz, Aldona
    Karolinska Institute, Sweden.
    Lindberg, Greger
    Karolinska Institute, Sweden.
    Schmidt, Peter T.
    Karolinska Institute, Sweden.
    Karling, Pontus
    Umeå University, Sweden.
    Ohlsson, Bodil
    Lund University, Sweden.
    Talley, Nicholas J.
    University of Newcastle, Australia.
    Simren, Magnus
    University of Gothenburg, Sweden.
    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).
    Wouters, Mira
    Leuven University, Belgium.
    Farrugia, Gianrico
    Mayo Clin, MN USA.
    DAmato, Mauro
    BioDonostia Health Research Institute, Spain; BioCruces Health Research Institute, Spain; Basque Fdn Science, Spain; Karolinska Institute, Sweden.
    TRPM8 polymorphisms associated with increased risk of IBS-C and IBS-M2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 9, p. 1725-+Article in journal (Other academic)
    Abstract [en]

    n/a

  • 16.
    Hindorf, Ulf
    et al.
    Lund .
    Lindqvist Appell, Malin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Pousette, A
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease2006In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, no 10, p. 1423-1431Article in journal (Refereed)
    Abstract [en]

    Background: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)), 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio, p = 0.02). Patients with meTIMP concentrations > 11 450 pmol/8 × 108 red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0, p = 0.015). Conclusions: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.

  • 17.
    Högberg, Lotta
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Laurin, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Grant, C.
    Laboratory Medicine Östergötland, Pathology, Norrköping Hospital, Sweden.
    Grodzinsky, Ewa
    Linköping University, Department of Department of Health and Society, General Practice. Linköping University, Faculty of Health Sciences.
    Jansson, Gunnar
    Department of Paediatrics, Motala Hospital, Sweden .
    Ascher, H.
    Department of Paediatrics, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden .
    Browaldh, L.
    Department of Paediatrics, Sachsska Hospital, Stockholm, Sweden .
    Hammersjö, Jan-Åke
    Department of Paediatrics, Västervik Hospital, Sweden .
    Lindberg, E.
    Department of Paediatrics, Örebro University Hospital, Sweden .
    Myrdal, U.
    Department of Paediatrics, Västerås Hospital, Sweden.
    Stenhammar, Lars
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Oats to children with newly diagnosed coeliac disease: a randomised double blind study2004In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 53, no 5, p. 649-654Article in journal (Refereed)
    Abstract [en]

    Background: Treatment of coeliac disease (CD) requires lifelong adherence to a strict gluten free diet (GFD) which hitherto has consisted of a diet free of wheat, rye, barley, and oats. Recent studies, mainly in adults, have shown that oats are non-toxic to CD patients. In children, only open studies comprising a small number of patients have been performed.

    Aim: To determine if children with CD tolerate oats in their GFD.

    Patients and methods: In this double blind multicentre study involving eight paediatric clinics, 116 children with newly diagnosed CD were randomised to one of two groups: one group was given a standard GFD (GFD-std) and one group was given a GFD with additional wheat free oat products (GFD-oats). The study period was one year. Small bowel biopsy was performed at the beginning and end of the study. Serum IgA antigliadin, antiendomysium, and antitissue transglutaminase antibodies were monitored at 0, 3, 6, and 12 months.

    Results: Ninety three patients completed the study. Median (range) daily oat intake in the GFD-oats group (n = 42) was 15 (5–40) g at the six month control and 15 (0–43) g at the end of the study. All patients were in clinical remission after the study period. The GFD-oats and GFD-std groups did not differ significantly at the end of the study regarding coeliac serology markers or small bowel mucosal architecture, including numbers of intraepithelial lymphocytes. Significantly more children in the youngest age group withdrew.

    Conclusions: This is the first randomised double blind study showing that the addition of moderate amounts of oats to a GFD does not prevent clinical or small bowel mucosal healing, or humoral immunological downregulation in coeliac children. This is in accordance with the findings of studies in adult coeliacs and indicates that oats, added to the otherwise GFD, can be accepted and tolerated by the majority of children with CD.

  • 18.
    Jakobsson, Hedvig E
    et al.
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Jenmalm, Maria C
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Harris, Keith
    School of Engineering, University of Glasgow, Glasgow, UK .
    Quince, Christopher
    School of Engineering, University of Glasgow, Glasgow, UK .
    Jernberg, Cecilia
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden .
    Björkstén, Bengt
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden .
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Anders F
    KTH Royal Institute of Technology, Science for Life Laboratory, School of Biotechnology, Division of Gene Technology, Solna, Sweden.
    Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 4, p. 559-566Article in journal (Refereed)
    Abstract [en]

    Objective The early intestinal microbiota exerts important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response.

    Design The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months.

    Results Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood.

    Conclusions CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.

  • 19.
    Jankipersadsing, Soesma A.
    et al.
    University of Groningen, Netherlands; University of Groningen, Netherlands.
    Hadizadeh, Fatemeh
    Karolinska Institute, Sweden; Isfahan University of Medical Science, Iran.
    Jan Bonder, Marc
    University of Groningen, Netherlands.
    Tigchelaar, Ettje F.
    University of Groningen, Netherlands; Top Institute Food and Nutr, Netherlands.
    Deelen, Patrick
    University of Groningen, Netherlands.
    Fu, Jingyuan
    University of Groningen, Netherlands.
    Andreasson, Anna
    Karolinska Institute, Sweden; Stockholm University, Sweden.
    Agreus, Lars
    Karolinska Institute, Sweden.
    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.
    Wijmenga, Cisca
    University of Groningen, Netherlands.
    Hysi, Pirro
    Kings Coll London, England.
    DAmato, Mauro
    Karolinska Institute, Sweden; BioDonostia Health Research Institute San Sebastian, Spain; Basque Fdn Science, Spain.
    Zhernakova, Alexandra
    University of Groningen, Netherlands.
    Letter: A GWAS meta-analysis suggests roles for xenobiotic metabolism and ion channel activity in the biology of stool frequency in GUT, vol 66, issue 4, pp 756-7582017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 4, p. 756-758Article in journal (Other academic)
    Abstract [en]

    n/a

  • 20.
    Kaplan, GG
    et al.
    Massachusetts General Hospital and Harvard University.
    Pedersen, BV
    Statens Serum Institut, Copenhagen.
    Andersson, Roland
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Sands, BE
    Massachusetts General Hospital and Harvard University.
    Korzenik, J
    Massachusetts General Hospital and Harvard University.
    Frisch, M
    Statens Serum Institut, Copenhagen.
    The risk of developing Crohn's disease after an appendectomy: A population-based cohort study in Sweden and Denmark2007In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 56, no 10, p. 1387-1392Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between appendectomy and Crohn's disease is controversial. A Swedish-Danish cohort study was conducted to assess the risk of developing Crohn's disease after an appendectomy. Methods: 709 353 appendectomy patients in Sweden (since 1964) and Denmark (since 1977) were followed for first hospitalisations for Crohn's disease to 2004. Standardised incidence ratios (SIR) served as relative risks. Results: Overall, 1655 Crohn's disease cases were observed during 11.1 million person-years of follow-up. Whereas appendectomy before the age of 10 years was not associated with the risk of Crohn's disease (SIR 1.00, 95% CI 0.80-1.25), the overall SIR of developing Crohn's disease was 1.52 (95% CI 1.45-1.59), being highest in the first 6 months (SIR 8.69, 95% CI 7.68-9.84). SIR diminished rapidly thereafter, with the risk of Crohn's disease reaching background levels after 5-10 years for Crohn's disease overall, as well as for Crohn's ileitis, ileocolonic Crohn's disease, Crohn's colitis and other/unspecified Crohn's disease. A long-term increased risk of Crohn's disease up to 20 years after the appendectomy was seen only in appendectomy patients without appendicitis or mesenteric lymphadenitis. Conclusion: The transient increased risk of Crohn's disease after an appendectomy is probably explained by diagnostic bias.

  • 21.
    Kechagias, Stergios
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ernersson, Åsa
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects2008In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, no 5, p. 649-654Article in journal (Refereed)
    Abstract [en]

     Objective: To study the effect of fast-food-based hyperalimentation on liver enzymes and hepatic triglyceride content (HTGC).

    Design: Prospective interventional study with parallel control group.

    Setting: University Hospital of Linko¨ping, Sweden.

    Participants: 12 healthy men and six healthy women with a mean (SD) age of 26 (6.6) years and a matched control group.

    Intervention: Subjects in the intervention group aimed for a body weight increase of 5–15% by eating at least two fast-food-based meals a day with the goal to double the regular caloric intake in combination with adoption of a sedentary lifestyle for 4 weeks.

    Main outcome measures: Weekly changes of serum aminotransferases and HTGC measured by proton nuclear magnetic resonance spectroscopy at baseline and after the intervention.

    Results: Subjects in the intervention group increased from 67.6 (9.1) kg to 74.0 (11) kg in weight (p,0.001). Serum ALT increased from 22.1 (11.4) U/l at study start to an individual mean maximum level of 97 (103) U/l (range 19.4–447 U/l). Eleven of the 18 subjectspersistently showed ALT above reference limits (women .19 U/l, men .30 U/l) during the intervention. Sugar (mono- and disaccharides) intake during week 3 correlated with the maximal ALT/baseline ALT ratio(r=0.62, p=0.006). HTGC increased from 1.1 (1.9)% to 2.8 (4.8)%, although this was not related to the increase in ALT levels. ALT levels were unchanged in controls.

    Conclusion: Hyper-alimentation per se can induce profound ALT elevations in less than 4 weeks. Our study clearly shows that in the evaluation of subjects with elevated ALT the medical history should include not only questions about alcohol intake but also explore whetherrecent excessive food intake has occurred.

  • 22. Kordasti, Shirin
    et al.
    Sjövall, Henrik
    Lundgren, Ove
    Svensson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology.
    Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea2004In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 53, no 7, p. 952-957Article in journal (Refereed)
    Abstract [en]

    Background and aims: The mechanisms underlying intestinal secretion in rotavirus diarrhoea remain to be established. We previously reported that rotavirus evokes intestinal fluid and electrolyte secretion by activation of the enteric nervous system. We now report that antagonists for the 5-hydroxytryptamine 3 receptor (5-HT3) and vasoactive intestinal peptide (VIP) receptor, but not antagonists for 5-hydroxytryptamine 4 receptor or the muscarinic receptor, attenuate rotavirus induced diarrhoea. Methods: Neurotransmitter antagonists were administered to wild-type or neurokinin 1 receptor knockout mice infected with homologous (EDIM) or heterologous (RRV) rotavirus. Results: While RRV infected mice had diarrhoea for 3.3 (0.2) days (95% confidence interval (CI) 3.04-3.56), the 5-HT3 receptor antagonist (granisetron) and the VIP receptor antagonist (4Cl-D-Phe 6,Leu17)-VIP both reduced the total number of days of RRV induced diarrhoea to 2.1 (0.3) (95% CI 1.31-2.9) (p<0.01). EDIM infected mice treated with granisetron had a significantly shorter duration of diarrhoea (5.6 (0.4) days) compared with untreated mice (8.0 (0.4) days, p<0.01). Experiments with neurokinin 1 receptor antagonists suggest that this receptor may possibly be involved in the secretory response to rotavirus. On the other hand, rotavirus diarrhoea was not attenuated in the neurokinin 1 receptor knockout mice. Conclusions: Our results suggest that the neurotransmitters serotonin and VIP are involved in rotavirus diarrhoea, observations that could imply new principles for treatment of this disease with significant global impact.

  • 23. Lesage, L
    et al.
    Zouali, H
    Colombel, J-F
    Belaiche, J
    C´zard, J-P
    Tysk, C
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Gassull, M
    Binder, V
    Chamaillard, M
    Le Gall, I
    Thomas, G
    Hugot, J-P
    Genetic analyses of chromosome 12 loci in Crohn's disease.2000In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 47, p. 787-791Article in journal (Refereed)
  • 24.
    Ludvigsson, Johnny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Coeliac disese in the father affects the newborn2001In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 49, p. 169-175Article in journal (Refereed)
  • 25.
    Ludvigsson, Jonas F.
    et al.
    Paediatric Department, Örebro Medical Centre Hospital, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Coeliac disease in the father affects the newborn2001In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 49, no 2, p. 169-175Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS Untreated coeliac disease in the mother is associated with lower birth weight. We examined the risk of adverse neonatal outcome when the infant's mother, father, or other relative suffered from known coeliac disease.

    METHODS Mothers answered a questionnaire a few days after the birth of their infant. Of a total of 10597 single birth infants from Southeast Sweden, 53 infants had a mother with coeliac disease (father 27, sibling 70, other close relative 442). Adjusted odds ratios and adjusted differences for neonatal outcome were calculated.

    RESULTS Infants whose father suffered from coeliac disease had a lower birth weight (95% adjusted confidence interval (CI) −459, −72 g), more often belonged to the low birth weight (LBW) category (LBW ⩽2499 g) (95% CI adjusted odds ratio (AOR) 1.48–17.18), and had a shorter pregnancy duration (95% adjusted CI −1.53, −0.08 weeks) than non-coeliac controls. They also weighed less than infants whose father suffered from other autoimmune diseases (95% CI −549, −93 g). Infants whose mother suffered from coeliac disease had a lower birth weight (95% adjusted CI −370, −74 g) and more often belonged to the LBW category (95% CI AOR 2.60–15.08) than non-coeliac controls. These infants were more often in the LBW category than infants whose mother suffered from non-diabetic autoimmune diseases (95% CI AOR 1.24–9.65). Coeliac disease in other relatives was not associated with any adverse effect on neonatal outcome.

    CONCLUSIONS This study suggests that even treated coeliac disease, in either of the parents, has a negative effect on pregnancy, resulting in lower birth weight and perhaps shorter duration of pregnancy.

  • 26.
    Münch, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Bohr, Johan
    Örebro University Hospital, and School of Health and Medical Sciences, Örebro University, Sweden .
    Miehlke, Stephan
    Centre for Digestive Disease, Hamburg, Germany .
    Benoni, Cecilia
    University Hospital, Malmö, Sweden .
    Olesen, Martin
    University Hospital, Malmö, Sweden .
    Ost, Ake
    Aleris Medilab, Täby, Sweden.
    Strandberg, Lars
    Region Hospital, Falun, Sweden.
    Hellström, Per M
    Uppsala University, Sweden.
    Hertervig, Erik
    University Hospital, Lund, Sweden.
    Armerding, Peter
    Gastroenterology, Private Practice, Berlin, Germany .
    Stehlik, Jiri
    Region Hospital, Usti nad Labem, Czech Repbulic.
    Lindberg, Greger
    Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Björk, Jan
    Karolinska University Hospital Solna, Stockholm, Sweden .
    Lapidus, Annika
    Ersta Hospital, Stockholm, Sweden .
    Löfberg, Robert
    Sophiahemmet, Stockholm, Sweden .
    Bonderup, Ole
    Regional Hospital, Silkeborg, Danmark .
    Avnström, Sören
    Amager Hospital, Copenhagen, Denmark .
    Rössle, Martin
    Gastroeneterology, Priva Practice, Freiburg, Germany.
    Dilger, Karin
    Dr Falk, Pharma GmBH, Freiburg, Germany.
    Mueller, Ralph
    Dr Falk, Pharma GmBH, Freiburg, Germany.
    Greinwald, Roland
    Dr Falk, Pharma GmBH, Freiburg, Germany.
    Tysk, Curt
    Örebro University Hospital, and School of Health and Medical Sciences, Örebro University, Sweden.
    Ström, Magnus
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial2016In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 65, no 1, p. 47-56Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis.

    DESIGN: A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase.

    RESULTS: Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious.

    CONCLUSIONS: Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation.

    TRIAL REGISTRATION NUMBERS: http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).

  • 27.
    Münch, Andreas
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology.
    Söderholm, Johan D
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Wallon, Conny
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Öst, Åke
    Medilab, Täby, Sweden.
    Olaison, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Ström, Magnus
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Dynamics of mucosal permeability and inflammation in collagenous colitis before, during, and after loop ileostomy2005In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 54, no 8, p. 1126-1128Article in journal (Refereed)
    Abstract [en]

    Collagenous colitis has become a more frequent diagnosis but the aetiology of this disease is still unknown. We describe a female patient with intractable collagenous colitis who was treated with a temporary loop ileostomy. She was followed clinically, histopathologically, and functionally by measuring mucosal permeability before surgery, after ileostomy, and after bowel reconstruction. In our case report, active collagenous colitis was combined with increased transcellular and paracellular mucosal permeability. Diversion of the faecal stream decreased inflammation of the mucosa and normalised epithelial degeneration and mucosal permeability. After restoration of bowel continuity, mucosal permeability was altered prior to the appearance of a collagenous layer.

  • 28.
    Nyström, Fredrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Fast-food hyper-alimentation and exercise restriction in healthy subjects Response2009In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 58, no 3, p. 470-470Article in journal (Other academic)
  • 29.
    Olesen, Martin
    et al.
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Eriksson, S.
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Bohr, J.
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Järnerot, Gunnar
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Tysk, Curt
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Lymphocytic colitis: a retrospective clinical study of 199 Swedish patients2004In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 53, no 4, p. 536-541Article in journal (Refereed)
    Abstract [en]

    Background: Lymphocytic colitis is characterised by chronic diarrhoea and specific microscopic changes in a macroscopically normal colonic mucosa. We report clinical features and treatment outcome in a large patient cohort.

    Methods: Patients were searched for in 24 Swedish gastroenterology clinics. The biopsy material was reassessed using strict histopathological criteria. Clinical data were obtained from medical notes.

    Results: Lymphocytic colitis was diagnosed in 199 cases. The female:male ratio was 2.4:1. Median age at diagnosis was 59 (48–70) years. The most frequent symptoms were diarrhoea (96%), abdominal pain (47%), and weight loss (41%). The course was chronic intermittent in 30% of patients, chronic continuous in 7%, and a single attack in 63%, and in these cases the disease duration was 6 (4–11) months. Seventy nine (40%) patients reported associated diseases, of which thyroid disorders, coeliac disease, and diabetes mellitus were the most common. In 34 first or second degree relatives of 24 (12%) patients, a family history of ulcerative colitis, Crohn’s disease, collagenous colitis, or coeliac disease was reported. Drug induced disease was suspected in 19 (10%) patients. A non-significant peak of disease onset was seen in December-January. More than 80% of treated patients improved on corticosteroids, including budesonide.

    Conclusions: A family history of other bowel disorders is a new finding. The sudden onset and single attack of limited duration may support a possible infectious cause in some cases. Drugs may cause lymphocytic colitis.

  • 30.
    Olesen, Martin
    et al.
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Eriksson, S.
    Department of Pathology, Örebro University Hospital, Örebro, Sweden .
    Bohr, J.
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Järnerot, Gunnar
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Tysk, Curt
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Microscopic colitis: a common diarrhoeal disease: an epidemiological study in Örebro, Sweden, 1993–19982004In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 53, no 3, p. 346-350Article in journal (Refereed)
    Abstract [en]

    Background: Microscopic colitis, including collagenous colitis and lymphocytic colitis, mainly affects middle aged and older subjects, with a female predominance in collagenous colitis. The diseases have previously been regarded as rare. We present an epidemiological study of microscopic colitis in a well defined Swedish population.

    Methods: Patients were retrospectively searched for in colonoscopy reports of those who had a colonoscopy in the period 1993–1998 for non-bloody diarrhoea. All colonic mucosal biopsies were reassessed using strict diagnostic criteria.

    Results: Biopsies from 1018 patients were reassessed. Fifty one (45 female) collagenous colitis patients and 46 (31 female) lymphocytic colitis patients were diagnosed. Median age at diagnosis was 64 years in collagenous colitis and 59 years in lymphocytic colitis. The mean annual incidence of collagenous colitis was 4.9/105 inhabitants (95% confidence interval (CI) 3.6–6.2/105) and of lymphocytic colitis 4.4/105 inhabitants (95% CI 3.1–5.7/105). The annual incidence of collagenous colitis increased from 3.7/105 in 1993–1995 to 6.1/105 in 1996–1998 (difference 2.4/105 (95% CI −0.3–5.1/105)) whereas the incidence of lymphocytic colitis increased from 3.1/105 to 5.7/105 (difference 2.6/105 (95% CI 0.1–5.2/105)).

    Conclusions: The annual incidences of collagenous colitis and lymphocytic colitis are higher than considered previously and are now equal to the incidence of Crohn’s disease in Sweden, and combined rates approach the incidence of ulcerative colitis. Microscopic colitis was diagnosed in 10% of all patients with non-bloody diarrhoea referred for colonoscopy and in almost 20% of those older than 70 years.

  • 31.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Letter: Incidence and prevalence rates in Budd-Chiari syndrome2009In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 58, no 6, p. 889-Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    [No abstract available]

  • 32.
    Romanos, J.
    et al.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, PO Box 30001, Groningen 9700 RB, Netherlands; School of Medicine, Lebanese American University, Beirut, Lebanon.
    Rosen, A.
    Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden; Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden.
    Kumar, V.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Trynka, G.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, PO Box 30001, Groningen 9700 RB, Netherlands; Division of Genetics and Division of Rheumatology, Harvard Medical School, Brigham and Womens Hospital, Boston, MA, United States.
    Franke, L.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Szperl, A.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Gutierrez-Achury, J.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Van, Diemen C.C.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Kanninga, R.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Jankipersadsing, S.A.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands.
    Steck, A.
    Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States.
    Eisenbarth, G.
    Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States.
    Van, Heel D.A.
    Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, United Kingdom.
    Cukrowska, B.
    Department of Pathology, Childrens Memorial Health Institute, Warsaw, Poland.
    Bruno, V.
    European Laboratory for Food-Induced Disease, University of of Naples Federico II, Naples, Italy.
    Mazzilli, M.C.
    Department of Molecular Medicine, Sapienza University of of Rome, Rome, Italy.
    Nunez, C.
    Clinical Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos IdISSC, Madrid, Spain.
    Bilbao, J.R.
    Immunogenetics Research Laboratory, Hospital de Cruces, Bizkaia, Spain.
    Mearin, M.L.
    Department of Paediatrics, Leiden University of Medical Centre, Leiden, Netherlands.
    Barisani, D.
    Department of Experimental Medicine, Faculty of Medicine, University of of Milano- Bicocca, Monza, Italy.
    Rewers, M.
    Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States.
    Norris, J.M.
    Epidemiology Department, Colorado School of Public Health, Aurora, United States.
    Ivarsson, A.
    Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden.
    Boezen, H.M.
    Department of Epidemiology, University of of Groningen, University of Medical Centre Groningen, Groningen, Netherlands.
    Liu, E.
    Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States.
    Wijmenga, C.
    Department of Genetics, University of of Groningen, University of Medical Centre Groningen, PO Box 30001, Groningen 9700 RB, Netherlands.
    Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 3, p. 415-422Article in journal (Refereed)
    Abstract [en]

    Background The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. Design We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case-control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. Results Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. Conclusions Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD.

  • 33. Santos, J
    et al.
    Yang, P-C
    Söderholm, Johan D
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Benjamin, M
    Perdue, MH
    Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat.2001In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 48, p. 630-636Article in journal (Refereed)
  • 34.
    Söderholm, Johan D
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Stress-related changes in oesophageal permeability: Filling the gaps of GORD?2007In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 56, no 9, p. 1177-1180Article, review/survey (Refereed)
    Abstract [en]

    Albeit remaining a controversial issue, it has become increasingly recognised that psychological stress has a major impact on gut mucosal function and affects the course of gastrointestinal disorders. Research during the last decade has shown that stress causes barrier dysfunction of the gastrointestinal mucosa by mechanisms that mainly involve neuropeptides and mast cells. Moreover, accumulating evidence implicates increased permeability as a pathogenic factor in gastroesophageal reflux disease (GORD). Recent data demonstrating that psychological stress may induce a permeability defect in stratified epithelia, including the oesophagus, shed new light on the pathophysiological events leading to heartburn and GORD.

  • 35.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Lindberg, E
    Hannestad, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Vindels, A
    Tysk, C
    Janerot, G
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Different intestinal permeability patterns in relative and spouses of patients with Crohn's disease: an inherited defect in mucosal defence?1999In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 44, p. 96-100Article in journal (Refereed)
  • 36.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Peterson, KH
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Franzén, LE
    Lindmark, T
    Wirén, Mikael
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of crohn's disease2002In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 50, no 3, p. 307-313Article in journal (Refereed)
    Abstract [en]

    Background: Crohn's disease is associated with deranged intestinal permeability in vivo, suggesting dysfunction of tight junctions. The luminal contents are important for development of neoinflammation following resection. Regulation of tight junctions by luminal factors has not previously been studied in Crohn's disease. Aims: The aim of the study was to investigate the effects of a luminal stimulus, known to affect tight junctions, on the distal ileum in patients with Crohn's disease. Patients: Surgical specimens from the distal ileum of patients with Crohn's disease (n=l 2) were studied, and ileal specimens from colon cancer patients (n=l 3) served as controls. Methods: Mucosal permeability to 51Cr-EDTA and electrical resistance were studied in Ussing chambers during luminal exposure to sodium caprate (a constituent of milk fat, affecting tight junctions) or to buffer only. The mechanisms involved were studied by mucosal ATP levels, and by electron and confocal microscopy. Results: Baseline permeability was the same in non-inflamed ileum of Crohn's disease and controls. Sodium caprate induced a rapid increase in paracellular permeability - that is, increased permeation of 51Cr-EDTA and decreased electrical resistance - which was more pronounced in non-inflamed ileum of Crohn's disease, and electron microscopy showed dilatations within the tight junctions. Moreover, sodium caprate induced disassembly of perijunctional filamentous actin was more pronounced in Crohn's disease mucosa. Mucosal permeability changes were accompanied by mitochondrial swelling and a fall in epithelial ATP content, suggesting uncoupling of oxidative phosphorylation. Conclusions: The tight junctions in the non-inflamed distal ileum of Crohn's disease were more reactive to luminal stimuli, possibly mediated via disturbed cytoskeletal contractility. This could contribute to the development of mucosal neoinflammation in Crohn's disease.

  • 37.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Streutker, C
    Yang, P-C
    Paterson, C
    Singh, PK
    McKay, DM
    Sherman, PM
    Croitoru, K
    Perdue, MH
    Increased epithelial uptake of protein antigens in the ileum of Crohn's disease mediated by tumour necrosis factor α2004In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 53, no 12, p. 1817-1824Article in journal (Refereed)
    Abstract [en]

    Background and aims: The exact nature of the epithelial barrier defect in Crohn's disease remains to be elucidated. Previously we showed increased permeability to proteins in ileal Crohn's disease. Our aims were to study if this barrier defect (a) involves endocytotic uptake of antigens and (b) is related to low grade inflammation not detectable by histology. Methods: Macroscopically normal segments of distal ileum of Crohn's disease patients (n = 10) were subgrouped into non-inflamed (histologically unaffected) and slightly inflamed tissues and studied in Ussing chambers, with normal ileal specimens from colon cancer patients (n = 9) as controls. Endocytotic uptake into enterocytes of the protein antigen horseradish peroxidase was assessed by measuring the area of horseradish peroxidase containing endosomes in electron photomicrographs. Mucosal tumour necrosis factor α (TNF-α) mRNA was quantified using real time polymerase chain reaction. For comparison, the effects of low doses of TNF-α on endosomal uptake of horseradish peroxidase were studied in cultured T84 cells grown on filter supports. Results: The area of horseradish peroxidase containing endosomes was increased (p<0.001) in enterocytes of non-inflamed ileum of Crohn's disease (2.8 (0.7) μm2/300 μm2) compared with control ileum (0.6 (0.06)). In non-inflamed mucosa, a significant association between endosomal uptake and mucosal expression of TNF-α mRNA (p = 0.03) was found. Low concentrations of TNF-α (0.25-1.0 ng/ml) enhanced the endosomal uptake of horseradish peroxidase in polarised T84 cells, without affecting transepithelial electrical resistance. Conclusions: Our findings suggest increased endosomal uptake of antigens in ileal Crohn's disease that may be mediated by TNF-α. These data highlight the transcellular route of antigen uptake in barrier dysfunction and implicate the interaction between epithelial cells and the innate immune system in the development of mucosal inflammation.

  • 38.
    Vanheel, Hanne
    et al.
    Katholieke University of Leuven, Belgium .
    Vicario, Maria
    University of Autonoma Barcelona, Spain Centre Invest Biomed Red Enfermedades Hepat and Digest, Spain .
    Vanuytsel, Tim
    Katholieke University of Leuven, Belgium .
    Van Oudenhove, Lukas
    Katholieke University of Leuven, Belgium .
    Martinez, Cristina
    University of Autonoma Barcelona, Spain .
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Pardon, Nicolas
    Katholieke University of Leuven, Belgium .
    Santos, Javier
    University of Autonoma Barcelona, Spain Centre Invest Biomed Red Enfermedades Hepat and Digest, Spain .
    Söderholm, Johan D
    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.
    Tack, Jan
    Katholieke University of Leuven, Belgium .
    Farre, Ricard
    Katholieke University of Leuven, Belgium Centre Invest Biomed Red Enfermedades Hepat and Digest, Spain .
    Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 2, p. 262-271Article in journal (Refereed)
    Abstract [en]

    Objective Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiology of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD. Design Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial electrical resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Numbers of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochemistry. Results Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addition, abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterised by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant association between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found. Conclusions These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiological mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.

  • 39.
    Vicario, Maria
    et al.
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain; Centre Invest Biomed Red Enfermedades Hepat and Digest, Spain.
    Gonzalez-Castro, Ana M.
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain.
    Martinez, Cristina
    Heidelberg University, Germany.
    Lobo, Beatriz
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain.
    Pigrau, Marc
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain.
    Guilarte, Mar
    University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain.
    de Torres, Ines
    University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain.
    Mosquera, Jose L.
    University of Barcelona, Spain.
    Fortea, Marina
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain.
    Sevillano-Aguilera, Cesar
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain.
    Salvo-Romero, Eloisa
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain.
    Alonso, Carmen
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain; Centre Invest Biomed Red Enfermedades Hepat and Digest, Spain.
    Rodino-Janeiro, Bruno K.
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain.
    Söderholm, Johan D.
    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.
    Azpiroz, Fernando
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain; Centre Invest Biomed Red Enfermedades Hepat and Digest, Spain.
    Santos, Javier
    Vall dHebron Institute Recerca, Spain; University of Autonoma Barcelona, Spain; University of Autonoma Barcelona, Spain; Centre Invest Biomed Red Enfermedades Hepat and Digest, Spain.
    Increased humoral immunity in the jejunum of diarrhoea-predominant irritable bowel syndrome associated with clinical manifestations2015In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 64, no 9, p. 1379-1388Article in journal (Refereed)
    Abstract [en]

    Background and aims Altered intestinal barrier is associated with immune activation and clinical symptoms in diarrhoea-predominant IBS (IBS-D). Increased mucosal antigen load may induce specific responses; however, local antibody production and its contribution to IBS aetiopathogenesis remain undefined. This study evaluated the role of humoral activity in IBS-D. Methods A single mucosal jejunal biopsy, luminal content and blood were obtained from healthy volunteers (H; n = 30) and IBS-D (n = 49; Rome III criteria) participants. Intraepithelial lymphocytes, mast cells, B lymphocytes and plasma cells were studied by imaging techniques. Differential gene expression and pathway analysis were assessed by microarray and PCR techniques. Blood and luminal immunoglobulins (Igs) were quantified. Gastrointestinal symptoms, respiratory atopy and stress and depression were also recorded. Results Patients with IBS-D showed a higher number and activation of mucosal B lymphocytes and plasma cells (p less than 0.05). Mast cell density was increased in patients with IBS-D (non-atopic) and in close proximity to plasma cells (p less than 0.05). Microarray profiling identified differential humoral activity in IBS-D, involving proliferation and activation of B lymphocytes and Igs production (p less than 0.001). Mucosal humoral activity was higher in IBS-D, with upregulation of germline transcripts and Ig genes (1.3-fold-1.7-fold increase; p less than 0.05), and increased IgG(+) cells and luminal IgG compared with H (p less than 0.05), with no differences in blood. Biological markers of humoral activity correlated positively with bowel movements, stool form and depression. Conclusions Enhanced small bowel humoral immunity is a distinctive feature of IBS-D. Mucosal Ig production contributes to local inflammation and clinical manifestations in IBS-D.

  • 40.
    Wallon, Conny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Yang, P.
    Intestinal Disease Research Programme, McMaster University, Hamilton, Canada.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    McKay, D. M.
    Department of Physiology and Biophysics, University of Calgary, Canada.
    Sherman, P. M.
    Departments of Paediatrics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
    Perdue, M. H.
    Intestinal Disease Research Programme, McMaster University, Hamilton, Canada.
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Corticotropin releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro2008In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, no 1, p. 50-58Article in journal (Refereed)
    Abstract [en]

    Objective: Persistent stress and life events affect the course of ulcerativecolitis and irritable bowel syndrome by largely unknown mechanisms.Corticotropin-releasing hormone (CRH) has been implicated asan important mediator of stress-induced abnormalities in intestinalmucosal function in animal models, but to date no studies inhuman colon have been reported. The aim was to examine the effectsof CRH on mucosal barrier function in the human colon and toelucidate the mechanisms involved in CRH-induced hyper-permeability.

    Design: Biopsies from 39 volunteers were assessed for macromolecularpermeability (horseradish peroxidise (HRP), 51Cr-EDTA), andelectrophysiology after CRH challenge in Ussing chambers. Thebiopsies were examined by electron and confocal microscopy forHRP and CRH receptor localisation, respectively. Moreover, CRHreceptor mRNA and protein expression were examined in the humanmast cell line, HMC-1.

    Results: Mucosal permeability to HRP was increased by CRH (2.8±0.5pmol/cm2/h) compared to vehicle exposure (1.5±0.4 pmol/cm2/h),p = 0.032, whereas permeability to 51Cr-EDTA and transmucosalelectrical resistance were unchanged. The increased permeabilityto HRP was abolished by -helical CRH (9-41) (1.3±0.6pmol/cm2/h) and the mast cell stabiliser, lodoxamide (1.6±0.6pmol/cm2/h). Electron microscopy showed transcellular passageof HRP through colonocytes. CRH receptor subtypes R1 and R2were detected in the HMC-1 cell line and in lamina propria mastcells in human colon.

    Conclusions: Our results suggest that CRH mediates transcellular uptake ofHRP in human colonic mucosa via CRH receptor subtypes R1 andR2 on subepithelial mast cells. CRH-induced macromolecular uptakein human colon mucosa may have implications for stress-relatedintestinal disorders.

  • 41.
    Westerlind, Helga
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Mellander, Marie-Rose
    Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Bresso, Francesca
    Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Munch, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences.
    Bonfiglio, Ferdinando
    Karolinska Institutet, Stockholm, Sweden.
    Assadi, Ghazaleh
    Karolinska Institutet, Stockholm, Sweden.
    Rafter, Joseph
    Karolinska Institutet, Stockholm, Sweden.
    Hübenthal, Matthias
    Christian-Albrechts-University of Kiel, Kiel, Germany.
    Lieb, Wolfgang
    Christian-Albrechts-University of Kiel, Kiel, Germany.
    Källberg, Henrik
    Karolinska Institutet, Stockholm, Sweden.
    Brynedal, Boel
    Karolinska Institutet, Stockholm, Sweden.
    Padyukov, Leonid
    Karolinska Institutet, Stockholm, Sweden.
    Halfvarson, Jonas
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Törkvist, Leif
    Karolinska University Hospital, Stockholm, Sweden.
    Bjork, Jan
    Karolinska University Hospital, Stockholm, Sweden.
    Andreasson, Anna
    Karolinska Institutet, Stockholm, Sweden.
    Agreus, Lars
    Karolinska Institutet, Stockholm, Sweden.
    Almer, Sven
    arolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Miehlke, Stephan
    Internal Medicine Center Eppendorf, Hamburg, Germany.
    Madisch, Ahmed
    Siloah Hospital, Hannover, Germany.
    Ohlsson, Bodil
    Skåne University Hospital, Lund University, Lund, Sweden.
    Löfberg, Robert
    Karolinska Institutet, Stockholm, Sweden Sophiahemmet Hospital, Stockholm, Sweden.
    Hultcrantz, Rolf
    Karolinska Institutet, Stockholm, Sweden.
    Franke, Andre
    D'Amato, Mauro
    Karolinska Institutet, Stockholm, Sweden BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain..
    Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis.2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 3, p. 421-428Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Collagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role.

    DESIGN: Three independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin.

    RESULTS: Forty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2×10(-10) for SNP rs4143332). Among the HLA variants, most pronounced risk effects were observed for 8.1 haplotype alleles including DQ2.5, which was targeted and confirmed in the replication data set (p=2.3×10(-11); OR=2.06; 95% CI (1.67 to 2.55) in the combined analysis).

    CONCLUSIONS: HLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.

  • 42. Zareie, M
    et al.
    Johnson-Henry, K
    Jury, J
    Yang, P-C
    Ngan, B-Y
    McKay, DM
    Söderholm, Johan D
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Perdue, MH
    Sherman, PM
    Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress2006In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, no 11, p. 1553-1560Article in journal (Refereed)
    Abstract [en]

    Background and aim: Chronic psychological stress, including water avoidance stress (WAS), induces intestinal mucosal barrier dysfunction and impairs mucosal defences against luminal bacteria. The aim of this study was to determine the ability of a defined probiotic regimen to prevent WAS induced intestinal pathophysiology. Methods: Male rats were subjected to either WAS or sham stress for one hour per day for 10 consecutive days. Additional animals received seven days of Lactobacillus helveticus and L. rhamnosus in the drinking water prior to stress and remained on these probiotics for the duration of the study. Rats were then sacrificed, intestinal segments assessed in Ussing chambers, and mesenteric lymph nodes cultured to determine bacterial translocation. Results: All animals remained healthy for the duration of the study. Chronic WAS induced excess ion secretion (elevated baseline short circuit current) and barrier dysfunction (increased conductance) in both the ileum and colon, associated with increased bacterial adhesion and penetration into surface epithelial cells. Approximately 70% of rats subjected to WAS had bacterial translocation to mesenteric lymph nodes while there was no bacterial translocation in controls. Probiotic pretreatment alone had no effect on intestinal barrier function. However, WAS induced increased ileal short circuit current was reduced with probiotics whereas there was no impact on altered conductance. Pretreatment of animals with probiotics also completely abrogated WAS induced bacterial adhesion and prevented translocation of bacteria to mesenteric lymph nodes. Conclusion: These findings indicate that probiotics can prevent chronic stress induced intestinal abnormalities and, thereby, exert beneficial effects in the intestinal tract.

  • 43. Zouali, H
    et al.
    Lesage, S
    Merlin, F
    Cezard, JP
    Colombel, JF
    Belaiche, J
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-magtarm.
    Tysk, C
    O'Morain, C
    Gassull, M
    Christensen, S
    Finkel, Y
    Modigliani, R
    Gower-Rousseau, C
    Macry, J
    Chamaillard, M
    Thomas, G
    Hugot, JP
    CARD4/NOD1 is not involved in inflammatory bowel disease2003In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 52, no 1, p. 71-74Article in journal (Refereed)
    Abstract [en]

    Background and aims: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic Factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD. Patients and methods: The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test. Results: Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence. Conclusion: Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD.

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