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  • 1.
    Bergkvist, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Zötterman, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tesselaar, Erik
    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 Radiation Physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Vascular Occlusion in a Porcine Flap Model: Effects on Blood Cell Concentration and Oxygenation.2017In: Plastic and reconstructive surgery. Global open, ISSN 2169-7574, Vol. 5, no 11, article id e1531Article in journal (Refereed)
    Abstract [en]

    Background: Venous congestion in skin flaps is difficult to detect. This study evaluated the ability of tissue viability imaging (TiVi) to measure changes in the concentration of red blood cells (CRBC), oxygenation, and heterogeneity during vascular provocations in a porcine fasciocutaneous flap model.

    Methods: In 5 pigs, cranial gluteal artery perforator flaps were raised (8 flaps in 5 pigs). The arterial and venous blood flow was monitored with ultrasonic flow probes. CRBC, tissue oxygenation, and heterogeneity in the skin were monitored with TiVi during baseline, 50% and 100% venous occlusion, recovery, 100% arterial occlusion and final recovery, thereby simulating venous and arterial occlusion of a free fasciocutaneous flap. A laser Doppler probe was used as a reference for microvascular perfusion in the flap.

    Results: During partial and complete venous occlusion, increases in CRBC were seen in different regions of the flap. They were more pronounced in the distal part. During complete arterial occlusion, CRBC decreased in all but the most distal parts of the flap. There were also increases in tissue oxygenation and heterogeneity during venous occlusion.

    Conclusions: TiVi measures regional changes in CRBC in the skin of the flap during arterial and venous occlusion, as well as an increase in oxygenated hemoglobin during venous occlusion that may be the result of reduced metabolism and impaired delivery of oxygen to the tissue. TiVi may provide a promising method for measuring flap viability because it is hand-held, easy to-use, and provides spatial information on venous congestion.

  • 2.
    Bivik Eding, Cecilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Domer, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wäster, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jerhammar, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases2015In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 7, p. 792-797Article in journal (Refereed)
    Abstract [en]

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

  • 3.
    Bivik Eding, Cecilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Involved and Uninvolved Psoriatic Keratinocytes Display a Resistance to Apoptosis that may Contribute to Epidermal Thickness2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 7, p. 788-796Article in journal (Refereed)
    Abstract [en]

    Psoriasis is a common autoimmune skin disease. The aim of this study was to investigate whether the apoptotic process is disturbed in psoriatic keratinocytes. In vitro culture of keratinocytes derived from both involved and uninvolved psoriatic skin, revealed higher viability and resistance to apoptosis following exposure to ultraviolet B, compared with cells from healthy controls. The position of apoptotic dysregulation was found to be upstream of cytochrome c release in the mitochondrial apoptotic pathway. Microarray transcriptome analysis revealed that 87 genes were differentially expressed in both involved and uninvolved psoriatic keratinocytes compared with controls. Among these, a general upregulation of anti-apoptotic genes and downregulation of pro-apoptotic genes were identified. This distinct apoptosis-resistant phenotype, unrelated to the inflammatory component of the disease, implies that intrinsic abnormalities in keratinocytes may contribute to the pathogenesis of psoriasis.

  • 4.
    Carlsson, Annica
    et al.
    Lund University, Sweden; Ängelholm Hospital, Sweden.
    Svensson, Åke
    Lund University, Sweden.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Baranovskaya, Irina
    Lund University, Sweden.
    Hindsen-Stenstrom, Monica
    Lund University, Sweden.
    Holt, Ingebjorg
    Angelholm Hospital, Sweden.
    Meding, Birgitta
    Karolinska Institute, Sweden.
    Stenberg, Berndt
    Umeå University, Sweden.
    Stenlund, Hans
    Umeå University, Sweden.
    Ganemo, Agneta
    Lund University, Sweden.
    Scoring of Hand Eczema: Good Reliability of the Hand Eczema Extent Score (HEES)2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 2, p. 193-197Article in journal (Refereed)
    Abstract [en]

    There is good agreement between dermatological staff and patients using the Hand Eczema Extent Score (HEES). The aim of this study was to assess inter-and intra-observer reliability of the HEES in dermatologists and intra-observer reliability of the HEES in patients with hand eczema. Six dermatologists assessed 18 patients twice. Only the hands of the patients were visible to the assessors. Patients performed a selfassessment twice. Inter-and intra-observer reliability was tested with intraclass correlation coefficient (ICC). The mean HEES score for all dermatologists assessments was 21.0 (range 3.6-46.3). The corresponding mean scores for all patients own assessments were 24.9 (range 4.0-54.0). Inter-observer reliability in the dermatologists observations ICC classification was very good, median value 0.82 (range 0.56-0.92). The overall intra-observer reliability for the 6 dermatologists ICC classification was very good (range 0.88-0.94). Intra-observer reliability in the patients 2 self-assessments ICC classification was very good (ICC 0.95). In conclusion, HEES is a reliable tool for both dermatologists and patients to grade the extent of hand eczema.

  • 5.
    Dahlen Gyllencreutz, J.
    et al.
    Skaraborg Hospital, Sweden.
    Paoli, J.
    University of Gothenburg, Sweden.
    Bjellerup, M.
    Lund University, Sweden.
    Bucharbajeva, Z.
    Umeå University, Sweden.
    Gonzalez, H.
    University of Gothenburg, Sweden.
    Nielsen, K.
    Lund University, Sweden.
    Sandberg, C.
    University of Gothenburg, Sweden.
    Synnerstad, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Faculty of Medicine and Health Sciences.
    Terstappen, K.
    Skaraborg Hospital, Sweden.
    Wennberg Larko, A. -M.
    University of Gothenburg, Sweden.
    Diagnostic agreement and interobserver concordance with teledermoscopy referrals2017In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 31, no 5, p. 898-903Article in journal (Refereed)
    Abstract [en]

    BackgroundMalignant melanoma and non-melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient. ObjectiveTo evaluate the diagnostic agreement and interobserver concordance achieved when assessing referrals sent through a mobile teledermoscopic referral system as compared to referrals sent via the current paper-based system without images. MethodsThe referral information from 80 teledermoscopy referrals and 77 paper referrals were evaluated by six Swedish dermatologists. They were asked to answer questions about the probable diagnosis, the priority, and a management decision. ResultsTeledermoscopy generally resulted in higher diagnostic agreement, better triaging and more malignant tumours being booked directly to surgery. The largest difference between the referral methods was seen for invasive melanomas. Referrals for benign lesions were significantly more often correctly resent to primary health care with teledermoscopy. However, referrals for cases of melanoma in situ were also incorrectly resent five times. The interobserver concordance was moderate with both methods. ConclusionBy adding clinical and dermoscopic images to referrals, the triage process for both benign and dangerous skin tumours can be improved. With teledermoscopy, patients with melanoma especially can receive treatment more swiftly.

  • 6.
    Dand, Nick
    et al.
    Kings Coll London, England.
    Mucha, Soeren
    Christian Albrechts University of Kiel, Germany.
    Tsoi, Lam C.
    University of Michigan, MI 48109 USA.
    Mahil, Satveer K.
    Kings Coll London, England.
    Stuart, Philip E.
    University of Michigan, MI USA.
    Arnold, Andreas
    University of Medical Greifswald, Germany.
    Baurecht, Hansjoerg
    University Hospital Schleswigholstein, Germany.
    David Burden, A.
    University of Glasgow, Scotland.
    Callis Duffin, Kristina
    University of Utah, UT USA.
    Chandran, Vinod
    University of Toronto, Canada; University of Health Network, Canada.
    Curtis, Charles J.
    NIHR, England; Maudsley NHS Fdn Trust, England; Kings Coll London, England; Kings Coll London, England.
    Das, Sayantan
    University of Michigan, MI 48109 USA.
    Ellinghaus, David
    Christian Albrechts University of Kiel, Germany.
    Ellinghaus, Eva
    Christian Albrechts University of Kiel, Germany.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Esko, Tonu
    University of Tartu, Estonia.
    Gladman, Dafna D.
    University of Toronto, Canada; University of Health Network, Canada.
    Griffiths, Christopher E. M.
    University of Manchester, England.
    Gudjonsson, Johann E.
    University of Michigan, MI USA.
    Hoffman, Per
    University of Basel, Switzerland; University of Bonn, Germany.
    Homuth, Georg
    University of Med, Germany; Ernst Moritz Arndt University of Greifswald, Germany.
    Hueffmeier, Ulrike
    University Hospital Schleswigholstein, Germany; Friedrich Alexander University of Erlangen Nurnberg, Germany.
    Krueger, Gerald G.
    University of Utah, UT USA.
    Laudes, Matthias
    Christian Albrechts University of Kiel, Germany.
    Hyuck Lee, Sang
    NIHR, England; Maudsley NHS Fdn Trust, England; Kings Coll London, England; Kings Coll London, England.
    Lieb, Wolfgang
    Christian Albrechts University of Kiel, Germany.
    Lim, Henry W.
    Henry Ford Hospital, MI 48202 USA.
    Loehr, Sabine
    Friedrich Alexander University of Erlangen Nurnberg, Germany.
    Mrowietz, Ulrich
    Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
    Mueller-Nurayid, Martina
    Helmholtz Zentrum Munich, Germany.
    Noethen, Markus
    University of Bonn, Germany.
    Peters, Annette
    Helmholtz Zentrum Munich, Germany.
    Rahman, Proton
    Mem University of Newfoundland, Canada.
    Reis, Andre
    Friedrich Alexander University of Erlangen Nurnberg, Germany.
    Reynolds, Nick J.
    Newcastle University, England; Newcastle Hospital NHS Fdn Trust, England.
    Rodriguez, Elke
    University Hospital Schleswigholstein, Germany.
    Schmidt, Carsten O.
    University of Medical Greifswald, Germany.
    Spain, Sarah L.
    Kings Coll London, England.
    Strauch, Konstantin
    Helmholtz Zentrum Munich, Germany.
    Tejasvi, Trilokraj
    University of Michigan, MI USA.
    Voorhees, John J.
    University of Michigan, MI USA.
    Warren, Richard B.
    University of Manchester, England.
    Weichenthal, Michael
    University of Medical Centre Schleswig Holstein, Germany.
    Weidinger, Stephan
    University Hospital Schleswigholstein, Germany.
    Zawistowski, Matthew
    University of Michigan, MI 48109 USA.
    Nair, Rajan P.
    University of Michigan, MI USA.
    Capon, Francesca
    Kings Coll London, England.
    Smith, Catherine H.
    Kings Coll London, England.
    Trembath, Richard C.
    Kings Coll London, England.
    Abecasis, Goncalo R.
    University of Michigan, MI 48109 USA.
    Elder, James T.
    University of Michigan, MI USA; Ann Arbor Vet Hospital, MI USA.
    Franke, Andre
    Christian Albrechts University of Kiel, Germany.
    Simpson, Michael A.
    Kings Coll London, England.
    Barker, Jonathan N.
    Kings Coll London, England.
    Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling2017In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 26, no 21, p. 4301-4313Article in journal (Refereed)
    Abstract [en]

    Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 x 10(-8), OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency amp;lt; 0.01) via gene-wide aggregation testing (IFIH1: p(burden) = 2.53 x 10(-7), OR = 0.707; TYK2: p(burden) = 6.17 x 10(-4), OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.

  • 7.
    Detert, H.
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Hedlund, S.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Rodvall, Y.
    Karolinska Institute, Sweden.
    Festin, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Whiteman, D. C.
    University of Queensland, Australia.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Validation of sun exposure and protection index (SEPI) for estimation of sun habits2015In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 39, no 6, p. 986-993Article in journal (Refereed)
    Abstract [en]

    Background: In both Sweden and Australia high incidence rates of skin cancer have become a major health problem. In prevention and risk communication, it is important to have reliable ways for identifying people with risky sun habits. In this study the validity and reliability of the questionnaire Sun Exposure Protection Index (SEPI), developed to assess individuals sun habits and their propensity to increase sun protection during routine, often brief, clinical encounters, has been evaluated. The aim of our study was to evaluate validity and reliability of the proposed SEPI scoring instrument, in two countries with markedly different ultraviolet radiation environments (Sweden and Australia). Method: Two subpopulations in Sweden and Australia respectively were asked to fill out the SEPI together with the previously evaluated Readiness to Alter Sun Protective Behaviour questionnaire (RASP-B) and the associated Sun-protective Behaviours Questionnaire. To test reliability, the SEPI was again filled out by the subjects one month later. Results: Comparison between SEPI and the questions in the Sun-protective Behaviours Questionnaire, analyzed with Spearmans Rho, showed good correlations regarding sun habits. Comparison between SEPI and RASP-B regarding propensity to increase sun protection showed concurrently lower SEPI mean scores for action stage, but no difference between precontemplation and contemplation stages. The SEPI test-retest analysis indicated stability over time. Internal consistency of the SEPI, assessed with Cronbachs alpha estimation showed values marginally lower than the desired >0.70 coefficient value generally recommended, and was somewhat negatively affected by the question on sunscreen use, likely related to the classic "sunscreen paradox". There were some differences in the performance of the SEPI between the Swedish and Australian samples, possibly due to the influence of "available" sunlight and differing attitudes to behaviour and protection "at home" and on vacation. Conclusions: SEPI appears to be a stable instrument with an overall acceptable validity and reliability, applicable for use in populations exposed to different UVR environments, in order to evaluate individual sun exposure and protection. (C) 2015 The Authors. Published by Elsevier Ltd.

  • 8.
    Ekman, Anna-Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Ingrid Asp Psoriasis Research Center.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Ingrid Asp Psoriasis Research Center.
    Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis.2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 2, p. 424-426Article in journal (Refereed)
  • 9.
    Ekman, Anna-Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Vegfors, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Overexpression of Psoriasin (S100A7) Contributes to Dysregulated Differentiation in Psoriasis.2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 4, p. 441-448Article in journal (Refereed)
    Abstract [en]

    Psoriasin, which is highly expressed in psoriasis, is encoded by a gene located within the epidermal differentiation complex. The aim of this study was to investigate the effect of endogenous psoriasin on disturbed keratinocyte differentiation in psoriasis. Immunohistochemical staining revealed a gradient of psoriasin expression in the psoriatic epidermis with highest expression in the suprabasal, differentiated layers. Induction of keratinocyte differentiation caused concurrent expression of psoriasin and the differentiation marker involucrin. The differentiation-induced psoriasin expression was found to be mediated by the protein kinase C pathway. The downregulation of psoriasin expression by small interfering RNA revealed that psoriasin mediates the expression of involucrin, desmoglein 1, transglutaminase 1 and CD24 in normal differentiation. The lentivirus-mediated overexpression of psoriasin, mimicking the psoriatic milieu, gave rise to an altered regulation of differentiation genes and an expression pattern reminiscent of that in psoriatic epidermis. These findings suggest that psoriasin contributes to the dysregulated differentiation process in the psoriasis epidermis.

  • 10.
    Enerbäck, Charlotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Univ Michigan, MI 48109 USA.
    Sandin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Lambert, S.
    Univ Michigan, MI 48109 USA.
    Zawistowski, M.
    Univ Michigan, MI 48109 USA.
    Stuart, P. E.
    Univ Michigan, MI 48109 USA.
    Verma, Deepti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Tsoi, L. C.
    Univ Michigan, MI 48109 USA.
    Nair, R. P.
    Univ Michigan, MI 48109 USA.
    Johnston, A.
    Univ Michigan, MI 48109 USA.
    Elder, J. T.
    Univ Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hlth Syst, MI USA.
    The psoriasis-protective TYK2 I684S variant impairs IL-12 stimulated pSTAT4 response in skin-homing CD4+and CD8+memory T-cells2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 7043Article in journal (Refereed)
    Abstract [en]

    Tyrosine kinase 2 (TYK2) belongs to the Janus kinase (JAK) family of tyrosine kinases, which transmit signals from activated cytokine receptors. GWAS have consistently implicated TYK2 in psoriasis susceptibility. We performed an in-depth association analysis of TYK2 using GWAS and resequencing data. Strong genetic association of three nonsynonymous variants in the exonic regions of the TYK2 gene (rs34536443, rs12720356, and rs2304256) were found. rs12720356 encoding I684S is predicted to be deleterious based on its location in the pseudokinase domain. We analyzed PBMCs from 29 individuals representing the haplotypes containing each of the significantly associated signals. STAT4 phosphorylation was evaluated by phospho-flow cytometry after CD3/CD28 activation of cells followed by IL-12 stimulation. Individuals carrying the protective I684S variant manifested significantly reduced p-STAT4 levels in CD4 + CD25 + CD45RO + (mean Stimulation Index (S.I.) 48.08, n = 10) and CD8 + CD25 + CD45RO + cells (S.I. 55.71, n = 10), compared to controls homozygous for the ancestral haplotype (S.I. 68.19, n = 10 (p = 0.002) and 76.76 n = 10 (p = 0.0008) respectively). Reduced p-STAT4 levels were also observed in skin-homing, cutaneous lymphocyte associated antigen (CLA)-positive CD4 and CD8 cells from I684S carriers. No significant changes in p-STAT4 for the psoriasis-associated variant rs34536443 was found. These data establish the functional significance of the TYK2 I684S variant in psoriasis susceptibility.

  • 11.
    Falk, Lars
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Skov Jensen, Jorgen
    Microbiology and Infection Control, Sexually Transmitted Infections, Research and Development, Statens Serum Institut, Copenhagen, Denmark.
    Successful outcome of macrolide-resistant Mycoplasma genitalium urethritis after spectinomycin treatment: a case report2017In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 72, no 2, p. 624-625Article in journal (Refereed)
  • 12.
    Fernando, Germain J. P.
    et al.
    Vaxxas Pty Ltd, Australia.
    Hickling, Julian
    Working Tandem Ltd, England.
    Flores, Cesar M. Jayashi
    Vaxxas Pty Ltd, Australia.
    Griffin, Paul
    QIMR Berghofer Med Res Inst, Australia; Q Pharm Pry Ltd, Australia; Mater Hosp, Australia; Mater Res Inst, Australia; Univ Queensland, Australia.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Heart and Med Ctr, Sweden.
    Skinner, S. Rachel
    Univ Sydney, Australia; Childrens Hosp Westmead, Australia.
    Davies, Cristyn
    Univ Sydney, Australia; Childrens Hosp Westmead, Australia.
    Witham, Katey
    Vaxxas Pty Ltd, Australia.
    Pryor, Melinda
    360Biolabs Pry Ltd, Australia.
    Bodle, Jesse
    Seqirus Pty Ltd, Australia.
    Rockman, Steve
    Seqirus Pty Ltd, Australia; Univ Melbourne, Australia.
    Frazer, Ian H.
    Not Found:[Fernando, Germain J. P.; Flores, Cesar M. Jayashi; Witham, Katey; Forster, Angus H.] Vaxxas Pty Ltd, Translat Res Inst, 37 Kent St, Brisbane, Qld 4102, Australia; [Hickling, Julian] Working Tandem Ltd, Cambridge, England; [Griffin, Paul] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia; [Griffin, Paul] Q Pharm Pry Ltd, Brisbane, Qld, Australia; [Griffin, Paul] Mater Hosp, Dept Med and Infect Dieases, Brisbane, Qld, Australia; [Griffin, Paul] Mater Res Inst, Brisbane, Qld, Australia; [Griffin, Paul] Univ Queensland, Brisbane, Qld, Australia; [Anderson, Christopher D.] Linkoping Univ, Dept Clin and Expt Med, Fac Hlth Sci, Linkoping, Sweden; [Anderson, Christopher D.] Heart and Med Ctr, Dept Dermatol and Venereol, Region Ostergotland, Sweden; [Skinner, S. Rachel; Davies, Cristyn] Univ Sydney, Sydney Med Sch, Discipline Child and Adolescent Hlth, Sydney, NSW, Australia; [Skinner, S. Rachel; Davies, Cristyn] Childrens Hosp Westmead, Sydney, NSW, Australia; [Pryor, Melinda] 360Biolabs Pry Ltd, Burnet Inst, Melbourne, Vic, Australia; [Bodle, Jesse; Rockman, Steve] Seqirus Pty Ltd, Melbourne, Vic, Australia; [Rockman, Steve] Univ Melbourne, Melbourne, Vic, Australia;.
    Forster, Angus H.
    Vaxxas Pty Ltd, Australia.
    Safety, tolerability, acceptability and immunogenicity of an influenza vaccine delivered to human skin by a novel high-density microprojection array patch (Nanopatch (TM))2018In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 36, no 26, p. 3779-3788Article in journal (Refereed)
    Abstract [en]

    Background: Injection using needle and syringe (Namp;S) is the most widely used method for vaccination, but requires trained healthcare workers. Fear of needles, risk of needle-stick injury, and the need to reconstitute lyophilised vaccines, are also drawbacks. The Nanopatch (NP) is a microarray skin patch comprised of a high-density array of microprojections dry-coated with vaccine that is being developed to address these shortcomings. Here we report a randomised, partly-blinded, placebo-controlled trial that represents the first use in humans of the NP to deliver a vaccine. Methods: Healthy volunteers were vaccinated once with one of the following: (1) NPs coated with split inactivated influenza virus (A/California/07/2009 [H1N1], 15 mu g haemagglutinin (HA) per dose), applied to the volar forearm (NP-HAIFA), n = 15; (2) NPs coated with split inactivated influenza virus (A/California/07/2009 11-11N1 I, 15 mu g HA per dose), applied to the upper arm (NP-HA/UA), n = 15; (3) Fluvaxe (R) 2016 containing 15 mu g of the same H1N1 HA antigen injected intramuscularly (IM) into the deltoid (IM-HA/D), n = 15; (4) NPs coated with excipients only, applied to the volar forearm (NP-placebo/FA), n = 5; (5) NPs coated with excipients only applied to the upper arm (NP-placebo/UA), n = 5; or (6) Saline injected IM into the deltoid (IM-placebo/D), n = 5. Antibody responses at days 0, 7, and 21 were measured by haemagglutination inhibition (HAI) and microneutralisation (MN) assays. Findings: NP vaccination was safe and acceptable; all adverse events were mild or moderate. Most subjects (55%) receiving patch vaccinations (HA or placebo) preferred the NP compared with their past experience of IM injection with Namp;S (preferred by 24%). The antigen-vaccinated groups had statistically higher HAI titres at day 7 and 21 compared with baseline (p amp;lt; 0.0001), with no statistical differences between the treatment groups (p amp;gt; 0.05), although the group sizes were small. The geometric mean HAI titres at day 21 for the NP-HA/FA, NP-HA/UA and IM-HA/D groups were: 335 (189-593 95% CI), 160 (74-345 95% CI), and 221 (129-380 95% CI) respectively. A similar pattern of responses was seen with the MN assays. Application site reactions were mild or moderate, and more marked with the influenza vaccine NPs than with the placebo or IM injection. Interpretation: Influenza vaccination using the NP appeared to be safe, and acceptable in this first time in humans study, and induced similar immune responses to vaccination by IM injection. (C) 2018 The Author(s). Published by Elsevier Ltd.

  • 13.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Microdialysis in Profiling Cytokines and Other Macromolecules in the Skin in Health and Disease: A Comment to Falcone et al.2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 10, p. 1269-1269Article in journal (Other academic)
    Abstract [en]

    n/a

  • 14.
    Griffin, Paul
    et al.
    QIMR Berghofer Medical Research Institute, Australia; Q Pharm Pty Ltd, Australia; Mater Hospital and Mater Research, Australia; University of Queensland, Australia.
    Elliott, Suzanne
    Q Pharm Pty Ltd, Australia.
    Krauer, Kenia
    Q Pharm Pty Ltd, Australia.
    Davies, Cristyn
    University of Sydney, Australia; Childrens Hospital Westmead, Australia.
    Rachel Skinner, S.
    University of Sydney, Australia; Childrens Hospital Westmead, Australia.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Heart and Medical Centre, Sweden.
    Forster, Angus
    Vaxxas Pty Ltd, Australia.
    Safety, acceptability and tolerability of uncoated and excipient-coated high density silicon micro-projection array patches in human subjects2017In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 35, no 48, p. 6676-6684Article in journal (Refereed)
    Abstract [en]

    Most vaccinations are performed by intramuscular injection with a needle and syringe. However, this method is not ideal due to limitations, such as the risk of needle-stick injury, the requirement for trained personnel to give injections and the need to reconstitute lyophilized vaccines. Therefore, we tested an alternative delivery technology that overcomes the problems with needle and syringe. The Nanopatch (TM) is an array of 10,000 silicon micro-projections per cm(2) that can be dry-coated with vaccine for skin delivery. The high number and density of micro-projections means that high velocity application is required to achieve consistent skin penetration. Before clinically testing a vaccine Nanopatch, this study tests the safety, tolerability and acceptability/utility of uncoated and excipient-coated Nanopatches in healthy adults. Nanopatches were applied to skin of the upper arm and volar forearm and left in contact with the skin for two minutes before removal. The application sites were assessed for local skin response over 28 days. Acceptability interviews were also performed. No unexpected adverse events directly related to the Nanopatch application were reported, All applications of the Nanopatch resulted in an expected erythema response which faded between days 3 and 7. In some subjects, some skin discolouration was visible for several days or up to 3 weeks after application. The majority (83%) of subjects reported a preference for the Nanopatch compared to the needle and syringe and found the application process to be simple and acceptable. On a pain scale from 0 to 10, 78% of applications were scored "0" (no pain) with the average scores for less than 1. The results from this study demonstrate the feasibility of the Nanopatch to improve vaccination by showing that application of the product without vaccine to human skin is safe, tolerable and preferred to needle and syringe administration. (C) 2017 The Authors. Published by Elsevier Ltd.

  • 15.
    Henricson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Toll John, Rani
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Diffuse Reflectance Spectroscopy: Getting the Capillary Refill Test Under Ones Thumb2017In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 130, article id e56737Article in journal (Refereed)
    Abstract [en]

    The capillary refill test was introduced in 1947 to help estimate circulatory status in critically ill patients. Guidelines commonly state that refill should occur within 2 s after releasing 5 s of firm pressure (e.g., by the physicians finger) in the normal healthy supine patient. A slower refill time indicates poor skin perfusion, which can be caused by conditions including sepsis, blood loss, hypoperfusion, and hypothermia. Since its introduction, the clinical usefulness of the test has been debated. Advocates point out its feasibility and simplicity and claim that it can indicate changes in vascular status earlier than changes in vital signs such as heart rate. Critics, on the other hand, stress that the lack of standardization in how the test is performed and the highly subjective nature of the naked eye assessment, as well as the tests susceptibility to ambient factors, markedly lowers the clinical value. The aim of the present work is to describe in detail the course of the refill event and to suggest potentially more objective and exact endpoint values for the capillary refill test using diffuse polarization spectroscopy.

    The full text will be freely available from 2019-12-02 09:45
  • 16.
    Iredahl, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Högstedt, Alexandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Henricson, Joakim
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    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 Radiation Physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load2016In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 23, no 7, p. 597-605Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load.

    METHODS: Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI).

    RESULTS: Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load.

    CONCLUSION: Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.

  • 17.
    Mernelius, S.
    et al.
    Ryhov County Hospital, Jönköping, Sweden.
    Carlsson, E.
    Ryhov County Hospital, Jönköping, Sweden.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Löfgren, S.
    Ryhov County Hospital, Jönköping, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Jönköping, Sweden.
    Ehricht, R.
    Alere Technology GmbH, Germany; InfectoGnostics, Germany.
    Monecke, S.
    Alere Technology GmbH, Germany; InfectoGnostics, Germany.
    Matussek, A.
    Ryhov County Hospital, Jönköping, Sweden.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Staphylococcus aureus colonization related to severity of hand eczema2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 8, p. 1355-1361Article in journal (Refereed)
    Abstract [en]

    Knowledge on Staphylococcus aureus colonization rates and epidemiology in hand eczema is limited. The aim of this study was to clarify some of these issues. Samples were collected by the "glove juice" method from the hands of 59 patients with chronic hand eczema and 24 healthy individuals. Swab samples were taken from anterior nares and throat from 43 of the 59 patients and all healthy individuals. S. aureus were spa typed and analysed by DNA-microarray-based genotyping. The extent of the eczema was evaluated by the hand eczema extent score (HEES). The colonization rate was higher on the hands of hand eczema patients (69 %) compared to healthy individuals (21 %, p amp;lt; 0.001). This was also seen for bacterial density (p = 0.002). Patients with severe hand eczema (HEES a parts per thousand yen 13) had a significantly higher S. aureus density on their hands compared to those with milder eczema (HEES = 1 to 12, p = 0.004). There was no difference between patients and healthy individuals regarding colonization rates in anterior nares or throat. spa typing and DNA-microarray-based genotyping indicated certain types more prone to colonize eczematous skin. Simultaneous colonization, in one individual, with S. aureus of different types, was identified in 60-85 % of the study subjects. The colonization rate and density indicate a need for effective treatment of eczema and may have an impact on infection control in healthcare.

  • 18.
    Nyman, Erika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Rakar, Jonathan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Kratz, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Exogenous hyaluronic acid induces accelerated re-epithelialization and altered protein expression in adult human skin wounds in vivoManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Hyaluronic acid, a large glycosaminoglycan involved in proliferation, migration, and tissue repair, is suggested to play an important role in ideal scarless fetal wound healing. This study aimed to investigate the effect of exogenous hyaluronic acid intradermal during deep dermal wound healing. Study parameters were erythema, re-epithelialization, and protein expression examined by using a previously described, minimally invasive in vivo human wound model in combination with tissue viability imaging, histology, and proteomics.

    Methods

    Standardized deep dermal wounds were created in the ventral forearm in ten healthy volunteers using blood collection lancets. The wound sites were injected with hyaluronic acid or saline solution, prior to wounding, or were left untreated. To quantify changes in red blood cell concentration as a measurement of inflammation, the study sites were photographed daily for two weeks using a tissue viability imaging system. At 24 hours and after 14 days, biopsy specimens were taken for histology and proteomics analysis.

    Results

    The inflammatory response was not affected by the injection of hyaluronic acid, as measured by tissue viability imaging. Hyaluronic acid significantly induced (p < 0.05) accelerated reepithelialization at 24 hours, and wounds treated with hyaluronic acid showed an altered protein expression.

    Conclusion

    The results from the present study are in concordance with  previous in vitro findings and suggest that exogenous hyaluronic acid has a  positive effect on the healing process of cutaneous wounds. We conclude that hyaluronic acid injected intradermally induces accelerated re-epithelialization and alters protein expression in vivo in human deep dermal skin wounds.

  • 19.
    Orfanidis, Kyriakos
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Wäster, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Lundmark, Katarzyna
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Evaluation of tubulin β-3 as a novel senescence-associated gene in melanocytic malignant transformation.2017In: Pigment Cell & Melanoma Research, ISSN 1755-1471, E-ISSN 1755-148X, Vol. 30, no 2, p. 243-254Article in journal (Refereed)
    Abstract [en]

    Malignant melanoma might develop from melanocytic nevi in which the growth-arrested state has been broken. We analyzed the gene expression of young and senescent human melanocytes in culture and compared the gene expression data with a dataset from nevi and melanomas. A concordant altered gene expression was identified in 84 genes when comparing the growth-arrested samples with proliferating samples. TUBB3, which encodes the microtubule protein tubulin β-3, showed a decreased expression in senescent melanocytes and nevi and was selected for further studies. Depletion of tubulin β-3 caused accumulation of cells in the G2/M phase and decreased proliferation and migration. Immunohistochemical assessment of tubulin β-3 in benign lesions revealed strong staining in the superficial part of the intradermal components, which faded with depth. In contrast, primary melanomas exhibited staining without gradient in a disordered pattern and strong staining of the invasive front. Our results describe an approach to find clinically useful diagnostic biomarkers to more precisely identify cutaneous malignant melanoma and present tubulin β-3 as a candidate marker. This article is protected by copyright. All rights reserved.

  • 20.
    Patrick, Matthew T.
    et al.
    Univ Michigan, MI 48109 USA.
    Stuart, Philip E.
    Univ Michigan, MI 48109 USA.
    Raja, Kalpana
    Univ Michigan, MI 48109 USA; Morgridge Inst Res, WI 53715 USA.
    Gudjonsson, Johann E.
    Univ Michigan, MI 48109 USA.
    Tejasvi, Trilokraj
    Univ Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hosp, MI 48105 USA.
    Yang, Jingjing
    Univ Michigan, MI 48109 USA; Emory Univ, GA 30322 USA.
    Chandran, Vinod
    Univ Toronto, Canada.
    Das, Sayantan
    Univ Michigan, MI 48109 USA.
    Callis-Duffin, Kristina
    Univ Utah, UT 84132 USA.
    Ellinghaus, Eva
    Christian Albrechts Univ Kiel, Germany.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Esko, Tonu
    Univ Tartu, Estonia; Broad Inst and Harvard, MA 02142 USA.
    Franke, Andre
    Christian Albrechts Univ Kiel, Germany.
    Kang, Hyun M.
    Univ Michigan, MI 48109 USA.
    Krueger, Gerald G.
    Univ Utah, UT 84132 USA.
    Lim, Henry W.
    Henry Ford Hosp, MI 48202 USA.
    Rahman, Proton
    Mem Univ, Canada.
    Rosen, Cheryl F.
    Univ Toronto, Canada.
    Weidinger, Stephan
    Univ Med Ctr Schleswig Holstein, Germany.
    Weichenthal, Michael
    Univ Med Ctr Schleswig Holstein, Germany.
    Wen, Xiaoquan
    Univ Michigan, MI 48109 USA.
    Voorhees, John J.
    Univ Michigan, MI 48109 USA.
    Abecasis, Goncalo R.
    Univ Michigan, MI 48109 USA.
    Gladman, Dafna D.
    Univ Toronto, Canada.
    Nair, Rajan P.
    Univ Michigan, MI 48109 USA.
    Elder, James T.
    Univ Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hosp, MI 48105 USA.
    Tsoi, Lam C.
    Univ Michigan, MI 48105 USA.
    Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients2018In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 4178Article in journal (Refereed)
    Abstract [en]

    Psoriatic arthritis (PsA) is a complex chronic musculoskeletal condition that occurs in similar to 30% of psoriasis patients. Currently, no systematic strategy is available that utilizes the differences in genetic architecture between PsA and cutaneous-only psoriasis (PsC) to assess PsA risk before symptoms appear. Here, we introduce a computational pipeline for predicting PsA among psoriasis patients using data from six cohorts with amp;gt;7000 genotyped PsA and PsC patients. We identify 9 new loci for psoriasis or its subtypes and achieve 0.82 area under the receiver operator curve in distinguishing PsA vs. PsC when using 200 genetic markers. Among the top 5% of our PsA prediction we achieve amp;gt;90% precision with 100% specificity and 16% recall for predicting PsA among psoriatic patients, using conditional inference forest or shrinkage discriminant analysis. Combining statistical and machine-learning techniques, we show that the underlying genetic differences between psoriasis subtypes can be used for individualized subtype risk assessment.

  • 21.
    Pettersson, Erik
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Henricsson, Joachim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Validation of phototesting for estimation of individual skin ultraviolet sensitivity based on a lengthwise attenuating ultraviolet B field.2015In: Journal of Medical Engineering & Technology, ISSN 0309-1902, E-ISSN 1464-522X, Vol. 39, no 2, p. 91-8Article in journal (Refereed)
    Abstract [en]

    Conventional skin UV-sensitivity phototesting is based on semi-quantitative assessment of minimal erythema dose (MED). This study demonstrates a method for quantitative MED determination, using a lengthwise attenuating UVB-field combined with tissue viability imaging (TiVi). The study aim was to investigate the agreement between MED acquired by traditional phototest and by the new method. Forty-seven voluntary subjects underwent phototesting with a traditional phototest and with the new technique. Test reading, carried out after 24 h, showed moderate agreement between the methods when assessed with TiVi (Kappa value=0.46) and visually (Kappa value=0.48). For the new method, no systematic differences were seen between outcomes assessed with TiVi or visually (95% CI for the mean difference=-1.6-2.0). In conclusion, the results give promising support for the concept of achieving a more precise MED estimation by combining continuous attenuating UV fields with new available bioengineering technology.

  • 22.
    Sandberg, Klas
    et al.
    Linköping University, Department of Medical and Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Rehabilitation in Norrköping. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Kleist, Marie
    Linköping University, Department of Medical and Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Rehabilitation in Norrköping. Linköping University, Faculty of Medicine and Health Sciences.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Enthoven, Paul
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Effects of Twice-Weekly Intense Aerobic Exercise inQ1 Early Subacute Stroke: A Randomized Controlled Trial2016In: Archives of Physical Medicine and Rehabilitation, ISSN 0003-9993, E-ISSN 1532-821X, Vol. 97, no 8, p. 1244-1253Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To examine the effects of 12 weeks of twice-weekly intensive aerobic exercise on physical function and quality of life after subacute stroke.

    DESIGN:

    Randomized controlled trial.

    SETTING:

    Ambulatory care.

    PARTICIPANTS:

    Patients (N=56; 28 women) aged ≥50 years who had a mild stroke (98% ischemic) and were discharged to independent living and enrolled 20 days (median) after stroke onset.

    INTERVENTIONS:

    Sixty minutes of group aerobic exercise, including 2 sets of 8 minutes of exercise with intensity up to exertion level 14 or 15 of 20 on the Borg rating of perceived exertion scale, twice weekly for 12 weeks (n=29). The nonintervention group (n=27) received no organized rehabilitation or scheduled physical exercise.

    MAIN OUTCOME MEASURES:

    Primary outcome measures included aerobic capacity on the standard ergometer exercise stress test (peak work rate) and walking distance on the 6-minute walk test (6MWT). Secondary outcome measures included maximum walking speed for 10m, balance on the timed Up and Go (TUG) test and single leg stance (SLS), health-related quality of life on the European Quality of Life Scale (EQ-5D), and participation and recovery after stroke on the Stroke Impact Scale (SIS) version 2.0 domains 8 and 9. Participants were evaluated pre- and postintervention. Patient-reported measures were also evaluated at 6-month follow-up.

    RESULTS:

    The following improved significantly more in the intervention group (pre- to postintervention): peak work rate (group × time interaction, P=.006), 6MWT (P=.011), maximum walking speed for 10m (P<.001), TUG test (P<.001), SLS right and left (eyes open) (P<.001 and P=.022, respectively), and SLS right (eyes closed) (P=.019). Aerobic exercise was associated with improved EQ-5D scores (visual analog scale, P=.008) and perceived recovery (SIS domain 9, P=.002). These patient-reported improvements persisted at 6-month follow-up.

    CONCLUSIONS:

    Intensive aerobic exercise twice weekly early in subacute mild stroke improved aerobic capacity, walking, balance, health-related quality of life, and patient-reported recovery.

  • 23.
    Shrestha, D.P.
    et al.
    Institute of Medicine, Kathmandu, Nepal.
    Suwash, B.
    Anandaban Hospital, Lalitpur, Nepal.
    Gurung, D.
    Silguri, India.
    Uprety, A.
    Khopasi Primary Health Care Centre Kavre, Nepal.
    Bhattarai, S.
    Kathmandu Medical College, Kathmandu, Nepal.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Mobile teledermatology for rural Nepal: Dermatologic care using mobile phone in a primary health care centre2016In: Journal of Institute of Medicine, ISSN ISSN: 1993-2979, Vol. 38, no 1, p. 7-10Article in journal (Refereed)
    Abstract [en]

    Introduction: Skin diseases are among the five most common health problems in Nepal. We have now tested the validity of mobile teledermatology with mobile phones to find a safe and easy way of diagnosis and treatment of skin diseases for the most vulnerable people in remote areas without access to derma­ tologists.

     

    Methods: A medical officer at a primary health care centre examined the patient, obtained information of the patient and the skin disease, took photographs of the skin lesions. Then  he transmitted  all these data  via Viber to a dermatologist in Kathmmandu, who in real time formulated diagnosis  and treatment  and  sent it via Viber to the medical officer. Subsequently the patient was examined face to face by a blinded dermatologist at the same primary health care centre. The time taken  for each modality  of consultation  was recorded .A third dermatologist analysed and compared the diagnoses formulated during telederma­ tology  and the face to face  consultations.

     

    Results: Altogether 107 skin diseases were diagnosed in 101 patients. There was an overall concordance  of 88% between the diagnoses of skin diseases by mobile teledermatology and face to face consultations (Cohen k coefficient 0.85). The average face to face consultation time was 5 minutes, while it was 7 min­ utes more for teleconsultation.  More than 75% of the photos  were of good   quality.

     

    Conclusions: Mobile teledermatology using smartphones is a reliable, useful, cost effective method to provide expertise for improving dermatologic care for the needy population in rural and remote parts of Nepal.

  • 24.
    Sigurdardottir, Gunnthorunn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ingrid Asp Psoriasis Research Center.
    Ekman, Anna-Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ingrid Asp Psoriasis Research Center.
    Verma, Deepti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ingrid Asp Psoriasis Research Center.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Ingrid Asp Psoriasis Research Center.
    Decreased Systemic Levels of Endocan-1 and CXCL16 in Psoriasis Are Restored following Narrowband UVB Treatment.2018In: Dermatology, ISSN 1018-8665, E-ISSN 1421-9832, Vol. 234, no 5-6, p. 173-179Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In psoriasis, a common immune-mediated disease affecting 2-3% of the population worldwide, there is an increased prevalence of extracutaneous diseases including obesity, the metabolic syndrome, and cardiovascular disease. This is believed to be linked to systemic inflammation. In previous studies, we have explored various markers in plasma and serum to characterize the ongoing systemic inflammation in psoriasis patients compared to controls. We have identified several markers that were altered in psoriasis patients, but which all were unresponsive to narrowband UVB (NB-UVB) treatment.

    OBJECTIVE: The objective of the study was to evaluate the effect of NB-UVB treatment on markers of cardiovascular risk and systemic inflammation in psoriasis.

    METHODS: The levels of 17 potential biomarkers with an association with cardiovascular risk were quantitated in plasma from 37 age- and gender-matched psoriasis patients and controls at baseline and in 21 psoriasis patients after 12 weeks of NB-UVB treatment to identify a systemic treatment response.

    RESULTS: We identified the mediators endocan-1, CXCL16, and sVEGFR1, which were systemically decreased in psoriasis at baseline, as well as FABP3, FABP4, and sIL-1R1, which showed normal baseline levels. After 10-12 weeks of NB-UVB treatment, endocan-1 and CXCL16 were restored to normal levels, while sVEGFR1, FABP3, FABP4, and sIL-1R1 showed a significant reduction.

    CONCLUSION: The current study expands the number of potential biomarkers in psoriasis by including a greater number and variety of mediators, approaching the systemic inflammation from additional vantage points, including soluble immune receptors and adipocyte contribution, to provide a more complete picture of the systemic inflammatory state in psoriasis.

  • 25.
    Stensson, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Nazdar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Träff, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Anderson, Chris D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Identification of Lipid Mediators in Peripheral Human Tissues Using an Integrative In Vivo Microdialysis Approach2016In: Journal of analytical and bioanalytical techniques, ISSN 2155-9872, Vol. 7, no 2, article id 1000306Article in journal (Refereed)
    Abstract [en]

    Endocannabinoids and related N-acylethanolamines (NAEs) are lipid mediators involved in a number of physiological and pathological mechanisms in peripheral tissues. Microdialysis (MD) technique allows continues sampling of endogenous substances in the interstitial fluids of the tissues. The main limitation of MD sampling of lipophilic compounds is low recovery due to adsorption to the MD system and particularly to the catheter membranes. In this in vivo study microdialysate samples were collected from human trapezius muscle and forearm skin. The levels of arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) were analyzed in both microdialysate and in catheter membrane samples using liquid chromatography tandem mass spectrometry.

    OEA, PEA and SEA were identified in all microdialysate and catheter membrane samples from trapezius and skin. 2-AG was found in all catheter membrane samples from both tissues but not in the actual microdialysate.

    In conclusion sampling of OEA, PEA and SEA was achievable from trapezius and skin with the presented MD set-up. 2-AG is present in both trapezius muscle and skin tissue but adsorbs to the membranes in a higher extent than the NAEs. Furthermore, consideration of data conserved in the membrane during an MD experiment could be a relevant and more broadly applicable extension of MD sampling methodology which could fill an "information gap" and enhance an adequate interpretation of microdialysate data outcomes.

  • 26.
    Strömfors, Lina
    et al.
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Child and Adult Habilitation in Norrköping. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelmsson, Susan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Höst, Gunnar E.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology.
    Experiences among children and adolescents of living with spina bifida and their visions of the future2017In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 39, no 3, p. 261-271Article in journal (Refereed)
    Abstract [en]

    Purpose: Transitioning to independence may be problematic for persons with spina bifida (SB). Experiences of young persons with SB may provide insights into this group's needs for support. Therefore, the aim of this study was to investigate children'€™s and adolescents' experiences of living with SB, their social and emotional adjustment, and their thoughts about becoming independent adults. Method: Semi-structured interviews were conducted with young persons with SB (N = 8, age range 10 - 17 years). Social and emotional problems were assessed using Beck Youth Inventories. The interview transcripts were analyzed using qualitative content analysis. Results: Three main themes were found: being a person with SB; everyday living as a person with SB; and preparing for life as an adult with SB. Indications of emotional and social problems were most prominent among participants with milder physical disability. Conclusions: The findings indicate that young persons with SB may overestimate their independence. Other potentially problematic areas were lack of motivation, planning and preparedness for becoming independent. Research on transition to independence in this group should consider assistance at an early age in planning and executing strategies for independence. In addition, the potentially difficult situation for young persons with mild SB should be investigated further.

  • 27.
    Stuart, Philip E.
    et al.
    University of Michigan, MI 48109 USA.
    Nair, Rajan P.
    University of Michigan, MI 48109 USA.
    Tsoi, Lam C.
    University of Michigan, MI 48109 USA; University of Michigan, MI 48109 USA; University of Michigan, MI 48109 USA.
    Tejasvi, Trilokraj
    University of Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hospital, MI 48105 USA.
    Das, Sayantan
    University of Michigan, MI 48109 USA.
    Min Kang, Hyun
    University of Michigan, MI 48109 USA.
    Ellinghaus, Eva
    University of Kiel, Germany.
    Chandran, Vinod
    University of Toronto, Canada; University of Toronto, Canada.
    Callis-Duffin, Kristina
    University of Utah, UT 84132 USA.
    Ike, Robert
    University of Michigan, MI 48109 USA.
    Li, Yanming
    University of Michigan, MI 48109 USA.
    Wen, Xiaoquan
    University of Michigan, MI 48109 USA.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Gudjonsson, Johann E.
    University of Michigan, MI 48109 USA.
    Koks, Sulev
    University of Tartu, Estonia; University of Tartu, Estonia; Estonian University of Life Science, Estonia.
    Kingo, Kuelli
    University of Tartu, Estonia.
    Esko, Tonu
    University of Tartu, Estonia.
    Mrowietz, Ulrich
    University of Medical Centre Schleswig Holstein, Germany.
    Reis, Andre
    University of Erlangen Nurnberg, Germany.
    Erich Wichmann, H.
    German Research Centre Environm Heatlh, Germany; University of Munich, Germany; Technical University of Munich, Germany.
    Gieger, Christian
    German Research Centre Environm Heatlh, Germany; German Research Centre Environm Heatlh, Germany.
    Hoffmann, Per
    University of Bonn, Germany; University of Bonn, Germany.
    Noethen, Markus M.
    University of Bonn, Germany; University of Bonn, Germany.
    Winkelmann, Juliane
    Technical University of Munich, Germany; German Research Centre Environm Heatlh, Germany.
    Kunz, Manfred
    University of Leipzig, Germany.
    Moreta, Elvia G.
    St Paul Rheumatol, MN 55121 USA.
    Mease, Philip J.
    Seattle Rheumatol Associates, WA 98122 USA.
    Ritchlin, Christopher T.
    University of Rochester, NY 14623 USA.
    Bowcock, Anne M.
    University of London Imperial Coll Science Technology and Med, England.
    Krueger, Gerald G.
    University of Utah, UT 84132 USA.
    Lim, Henry W.
    Henry Ford Hospital, MI 48202 USA.
    Weidinger, Stephan
    University of Medical Centre Schleswig Holstein, Germany.
    Weichenthal, Michael
    University of Medical Centre Schleswig Holstein, Germany.
    Voorhees, John J.
    University of Michigan, MI 48109 USA.
    Rahman, Proton
    Mem University, Canada.
    Gregersen, Peter K.
    North Shore Long Isl Jewish Health Syst, NY 11030 USA.
    Franke, Andre
    University of Kiel, Germany.
    Gladman, Dafna D.
    University of Toronto, Canada; University of Toronto, Canada.
    Abecasis, Goncalo R.
    University of Michigan, MI 48109 USA.
    Elder, James T.
    University of Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hospital, MI 48105 USA.
    Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture2015In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 97, no 6, p. 816-836Article in journal (Refereed)
    Abstract [en]

    Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 x 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 x 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA.

  • 28.
    Thomsen, S. F.
    et al.
    Bispebjerg Hospital, Denmark; University of Copenhagen, Denmark.
    Pritzier, E. C.
    Stavanger University Hospital, Norway.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Vaugelade-Baust, N.
    Novartis Norge, Norway.
    Dodge, R.
    Novartis Pharmaceut AS, Denmark.
    Dahlborn, A. -K.
    Novartis Sweden AB, Sweden.
    Vestergaard, C.
    Aarhus University Hospital, Denmark.
    Chronic urticaria in the real-life clinical practice setting in Sweden, Norway and Denmark: baseline results from the non-interventional multicentre AWARE study2017In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 31, no 6, p. 1048-1055Article in journal (Refereed)
    Abstract [en]

    BackgroundChronic urticaria (CU) is characterized by the recurrence of itchy hives and/or angioedema for more than 6 weeks. AWARE (A World-wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) is a multinational study designed to document the real-life treatment situation, burden of disease and clinical resource usage of H1-antihistamine-refractory CU patients. ObjectiveTo examine baseline data from Scandinavian AWARE patients. MethodsAWARE is a prospective, non-interventional, multinational, umbrella design study, which includes adults (18 years) with a confirmed CU diagnosis (amp;gt;2 months) that is refractory to H1-antihistamines. Baseline patient characteristics, disease activity (urticaria control test [UCT]), pharmacological treatment, comorbidities and healthcare usage were documented by the treating physician. Quality of life (QoL; dermatology life quality index [DLQI]; chronic urticaria quality of life questionnaire [CU-Q(2)oL; Danish patients only]) and work productivity and activity impairment (WPAI) scores were also assessed. ResultsOverall, 158 CU patients from seven centres in Denmark (n = 80), Norway (n = 50) and Sweden (n = 28) were included in this baseline analysis. Mean age and BMI were 40.3 years and 26.5 kg/m(2), respectively. The majority of patients were female (69.6%), had uncontrolled CU (75.6%; UCT score amp;lt;12) and had a spontaneous component to their CU (61.4% CSU; 20.3% both CSU and chronic inducible urticaria). Common comorbidities included asthma (19.6%), allergic rhinitis (16.5%) and food allergies (8.2%). Overall, 60.1% of patients reported using treatments for CU including non-sedative H1-antihistamines (40.5%), corticosteroids (19%), montelukast (14.6%) and omalizumab (8.2%). Pharmacological treatment rates increased to 96.2% during the baseline visit. On average, patient QoL was moderately affected (mean DLQI score 7.7) and healthcare resource usage was high. ConclusionAdult Scandinavian H1-antihistamine-refractory CU patients reported high rates of healthcare usage and QoL impairment. Rates of pharmacological treatment use were low before study enrolment but increased to almost 100% during the baseline visit.

  • 29.
    Toll John, Rani
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Junker, Johan
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Disaster Medicine and Traumatology.
    Jonson, Carl-Oscar
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Disaster Medicine and Traumatology.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. WheelsBridge AB, Linköping, Sweden.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    A cool response: the influence of ambient temperature on capillary refill time2018In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 11, no 6Article in journal (Refereed)
    Abstract [en]

    Objective

    To describe the effect of low ambient temperature on skin temperature and capillary refill (CR) time in forehead, sternum and finger pulp.

    Methods

    An observational, nonrandomized experimental study on 15 healthy subjects (6 females) in a cold room (8°C). Outcome measures were skin temperature and quantified CR test after application of a standardized blanching pressure (9 N/cm2) using digital photographic polarization spectroscopy to generate CR times.

    Results

    The finger pulp showed marked temperature fall and prolonged CR times (>10 seconds). The CR registrations of the forehead and sternum were more comparable to curves observed in a control material at room temperature, and skin temperature falls were less marked. CR times were not prolonged in forehead measurements. At the sternum, some individuals showed CR times beyond guideline recommendations despite only a marginal reduction in skin temperature.

    Conclusions

    Low ambient temperature is a strong independent factor for CR time at peripheral sites. Reservation about sternum as a site of measurement is warranted since cold provocation produced prolonged CR times in some individuals. We found that the forehead is the most thermostable of the 3 sites and thus the preferred site to avoid ambient temperature artifact in measuring CR time.

  • 30.
    Toll John, Rani
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Nilsson, Gert E.
    WheelsBridge AB, Linköping, Sweden.
    Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Reflectance spectroscopy: to shed new light on the capillary refill test2018In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 11, no 1, article id e201700043Article in journal (Refereed)
    Abstract [en]

    To use Bioengineering methodology is used to achieve, at five anatomical sites, a detailed, quantitative assessment of the return of blood content to the blanched area, during the Capillary Refill (CR) test. An observational, non-randomized, experimental study on 23 healthy subjects (14 females) was performed in our climate controlled skin physiology laboratory. Our main outcome measures were based on the chronological assessment and quantification of red blood cell concentration (RBC) after the release of blanching pressure in the CR test, using Tissue Viability Imaging (TiVi), a digital photographic technique based on polarisation spectroscopy. TiVi enabled collection of detailed data on skin RBC concentration during the CR test. The results were shown as curves with skin blood concentration (TiVi-value) on the y-axis and the time on the x-axis. Quantitative CR responses showed site and temperature variability. We also suggest possible objective endpoint values from the capillary refill curve. Detailed data on skin RBC concentration during the CR test is easily obtained and allows objective determination of end points not possible to achieve by naked eye assessment. These findings have the potential to place the utility of the CR test in a clinical setting in a new light. Picture: Regular photograph and TiVi Image showing CR test and corresponding graph for the CR response. [GRAPHICS] .

  • 31.
    Tsoi, Lam C.
    et al.
    University of Michigan, MI 48109 USA.
    Spain, Sarah L.
    Kings Coll London, England; Wellcome Trust Sanger Institute, England.
    Ellinghaus, Eva
    University of Kiel, Germany.
    Stuart, Philip E.
    University of Michigan, MI 48109 USA.
    Capon, Francesca
    Kings Coll London, England.
    Knight, Jo
    Centre Addict and Mental Heatlh, Canada; Guys and St Thomas NHS Fdn Trust, England.
    Tejasvi, Trilokraj
    University of Michigan, MI 48109 USA.
    Kang, Hyun M.
    University of Michigan, MI 48109 USA.
    Allen, Michael H.
    Kings Coll London, England.
    Lambert, Sylviane
    University of Michigan, MI 48109 USA.
    Stoll, Stefan W.
    University of Michigan, MI 48109 USA.
    Weidinger, Stephan
    University of Kiel, Germany.
    Gudjonsson, Johann E.
    University of Michigan, MI 48109 USA.
    Koks, Sulev
    University of Tartu, Estonia; University of Tartu, Estonia.
    Kingo, Kulli
    University of Tartu, Estonia.
    Esko, Tonu
    University of Tartu, Estonia.
    Das, Sayantan
    University of Michigan, MI 48109 USA.
    Metspalu, Andres
    University of Tartu, Estonia.
    Weichenthal, Michael
    University of Kiel, Germany.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Krueger, Gerald G.
    University of Utah, UT 84132 USA.
    Voorhees, John J.
    University of Michigan, MI 48109 USA.
    Chandran, Vinod
    University of Toronto, Canada.
    Rosen, Cheryl F.
    University of Toronto, Canada.
    Rahman, Proton
    Mem University, Canada.
    Gladman, Dafna D.
    University of Toronto, Canada.
    Reis, Andre
    University of Erlangen Nurnberg, Germany.
    Nair, Rajan P.
    University of Michigan, MI 48109 USA.
    Franke, Andre
    University of Kiel, Germany.
    Barker, Jonathan N. W. N.
    Kings Coll London, England.
    Abecasis, Goncalo R.
    University of Michigan, MI 48109 USA.
    Trembath, Richard C.
    Queen Mary University of London, England.
    Elder, James T.
    University of Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hospital, MI 48105 USA.
    Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci2015In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, no 7001Article in journal (Refereed)
    Abstract [en]

    Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genome-wide significance (Pless than5 x 10(-8)). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of IL-17 signalling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.

  • 32.
    Tsoi, Lam C.
    et al.
    University of Michigan, MI 48109 USA; University of Michigan, MI 48109 USA; University of Michigan, MI 48109 USA.
    Stuart, Philip E.
    University of Michigan, MI 48109 USA.
    Tian, Chao
    23andMe Inc, CA 94041 USA.
    Gudjonsson, Johann E.
    University of Michigan, MI 48109 USA.
    Das, Sayantan
    University of Michigan, MI 48109 USA.
    Zawistowski, Matthew
    University of Michigan, MI 48109 USA.
    Ellinghaus, Eva
    Christian Albrechts University of Kiel, Germany.
    Barker, Jonathan N.
    Kings Coll London, England.
    Chandran, Vinod
    University of Toronto, Canada; University of Toronto, Canada.
    Dand, Nick
    Kings Coll London, England.
    Callis Duffin, Kristina
    University of Utah, UT 84132 USA.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Esko, Tonu
    University of Tartu, Estonia; Broad Institute MIT and Harvard, MA 02142 USA.
    Franke, Andre
    Christian Albrechts University of Kiel, Germany.
    Gladman, Dafna D.
    University of Toronto, Canada; University of Toronto, Canada.
    Hoffmann, Per
    University of Bonn, Germany; University of Basel, Switzerland.
    Kingo, Kulli
    University of Tartu, Estonia.
    Koks, Sulev
    University of Tartu, Estonia; University of Tartu, Estonia; Estonian University of Life Science, Estonia.
    Krueger, Gerald G.
    University of Utah, UT 84132 USA.
    Lim, Henry W.
    Henry Ford Hospital, MI 48202 USA.
    Metspalu, Andres
    University of Tartu, Estonia.
    Mrowietz, Ulrich
    University of Medical Centre Schleswig Holstein, Germany.
    Mucha, Soren
    Christian Albrechts University of Kiel, Germany.
    Rahman, Proton
    Mem University, Canada.
    Reis, Andre
    FAU Erlangen Nurnberg, Germany.
    Tejasvi, Trilokraj
    University of Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hospital, MI 48105 USA.
    Trembath, Richard
    Kings Coll London, England.
    Voorhees, John J.
    University of Michigan, MI 48109 USA.
    Weidinger, Stephan
    University of Medical Centre Schleswig Holstein, Germany.
    Weichenthal, Michael
    University of Medical Centre Schleswig Holstein, Germany.
    Wen, Xiaoquan
    University of Michigan, MI 48109 USA.
    Eriksson, Nicholas
    23andMe Inc, CA 94041 USA.
    Kang, Hyun M.
    University of Michigan, MI 48109 USA.
    Hinds, David A.
    23andMe Inc, CA 94041 USA.
    Nair, Rajan P.
    University of Michigan, MI 48109 USA.
    Abecasis, Goncalo R.
    University of Michigan, MI 48109 USA.
    Elder, James T.
    University of Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hospital, MI 48105 USA.
    Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants2017In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 15382Article in journal (Refereed)
    Abstract [en]

    Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size amp;gt;39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFkB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8(+) T-cells and CD4(+) T-cells including T(H)0, T(H)1 and T(H)17). The identified loci explain similar to 28% of the genetic heritability and generate a discriminatory genetic risk score (AUC = 0.76 in our sample) that is significantly correlated with age at onset (p = 2 x 10(-89)). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

  • 33.
    Vegfors, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Ekman, Anna-Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Stoll, S W
    University of Michigan, Ann Arbor, MI, U.S.A.
    Bivik Eding, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Enerbäck, Charlotta
    Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Psoriasin (S100A7) promotes stress-induced angiogenesis.2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 175, no 6, p. 1263-1273Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Vascular modifications occur early in the development of psoriasis, and angiogenesis is one of the key features in the pathogenesis of the disease.

    OBJECTIVES: To identify the role of the S100 protein psoriasin in psoriasis-associated angiogenesis.

    METHODS: The role of psoriasin in mediating angiogenesis was investigated by silencing psoriasin with small interfering RNA (siRNA) and measuring psoriasis-associated angiogenic factors in human epidermal keratinocytes. The secretion of psoriasin and the effect of psoriasin on general regulators of angiogenesis in keratinocytes, and on endothelial cell migration, proliferation, tube formation and production of angiogenic mediators, was evaluated.

    RESULTS: Reactive oxygen species (ROS) and hypoxia induced the expression of psoriasin. Downregulation of psoriasin in keratinocytes using siRNA altered the ROS-induced expression of the psoriasis-associated angiogenic factors vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor, matrix metalloproteinase 1 and thrombospondin 1. Overexpression of psoriasin altered several regulators of angiogenesis and led to the secretion of psoriasin. Treatment with extracellular psoriasin induced proliferation, migration and tube formation in dermal-derived endothelial cells to a similar extent as VEGF and interleukin-17, and induced the expression and release of proangiogenic mediators. These effects were suggested to be mediated by the PI3K and nuclear factor kappa B pathways.

    CONCLUSIONS: These findings suggest that psoriasin expression is promoted by oxidative stress in keratinocytes and amplifies the ROS-induced expression of angiogenic factors relevant to psoriasis. Moreover, extracellularly secreted psoriasin may act on dermal endothelial cells to contribute to key features angiogenesis.

  • 34.
    Verma, Deepti
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ekman, Anna-Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Bivik Eding, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Genome-Wide DNA Methylation Profiling Identifies Differential Methylation in Uninvolved Psoriatic Epidermis2018In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 138, no 5, p. 1088-1093Article in journal (Refereed)
    Abstract [en]

    Psoriasis is a chronic inflammatory skin disease with both local and systemic components. Genome-wide approaches have identified more than 60 psoriasis-susceptibility loci, but genes are estimated to explain only one-third of the heritability in psoriasis, suggesting additional, yet unidentified, sources of heritability. Epigenetic modifications have been linked to psoriasis and altered DNA methylation patterns in psoriatic versus healthy skin have been reported in whole-skin biopsies. In this study, focusing on epigenetic modifications in the psoriatic uninvolved skin, we compared the lesional and non-lesional epidermis from psoriasis patients with epidermis from healthy controls. We performed an exhaustive genome-wide DNA methylation profiling using reduced representation bisulfite sequencing, which interrogates the methylation status of approximately 3-4 million CpG sites. More than 2,000 strongly differentially methylated sites were identified and a striking overrepresentation of the Wnt and cadherin pathways among the differentially methylated sites was found. In particular, we observe a strong differential methylation in several psoriasis candidate genes. A substantial number of differentially methylated sites present in the uninvolved versus healthy epidermis suggests the presence of a pre-psoriatic state in the clinically healthy skin type. Our exploratory study represents a starting point for identifying biomarkers for psoriasis-prone skin before disease onset.

  • 35.
    Wäster, Petra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Ida
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Vainikka, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 27890Article in journal (Refereed)
    Abstract [en]

    Ultraviolet (UV) irradiation induces skin pigmentation, which relies on the intercellular crosstalk of melanin between melanocytes to keratinocytes. However, studying the separate effects of UVA and UVB irradiation reveals differences in cellular response. Herein, we show an immediate shedding of extracellular vesicles (EVs) from the plasma membrane when exposing human melanocytes to UVA, but not UVB. The EV-shedding is preceded by UVA-induced plasma membrane damage, which is rapidly repaired by Ca2+-dependent lysosomal exocytosis. Using co-cultures of melanocytes and keratinocytes, we show that EVs are preferably endocytosed by keratinocytes. Importantly, EV-formation is prevented by the inhibition of exocytosis and increased lysosomal pH but is not affected by actin and microtubule inhibitors. Melanosome transfer from melanocytes to keratinocytes is equally stimulated by UVA and UVB and depends on a functional cytoskeleton. In conclusion, we show a novel cell response after UVA irradiation, resulting in transfer of lysosome-derived EVs from melanocytes to keratinocytes.

  • 36.
    Wäster, Petra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Orfanidis, Kyriakos
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Eriksson, Ida
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hospital, Sweden.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-beta 1-FAP-alpha2017In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 117, no 4, p. 535-544Article in journal (Refereed)
    Abstract [en]

    Background: Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-alpha is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-alpha is not yet completely revealed. Methods: Expression of FAP-alpha was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs. Cell migration and invasion was studied in relation to cathepsin activity and secretion of transforming growth factor (TGF)-beta 1. Results: Fibroblast activation protein-a expression was induced by UVR in melanocytes of human skin. The FAP-alpha expression was regulated by UVR-induced release of TGF-beta 1 and cathepsin inhibitors prevented such secretion. In melanoma cell culture models and in a xenograft tumour model of zebrafish embryos, FAP-alpha mediated ECM degradation and facilitated tumour cell dissemination. Conclusions: Our results provide evidence for a sequential reaction axis from UVR via cathepsins, TGF-beta 1 and FAP-alpha expression, promoting cancer cell dissemination and melanoma metastatic spread.

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