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  • 151.
    Hinz, Linnéa
    Örebro universitet, Institutionen för läkarutbildning.
    Cognitive ability and speech discrimination in adults with a unilateral cochlear implant2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 152.
    Hoglert, Malin
    Örebro universitet, Institutionen för läkarutbildning.
    Prevalence of sleep apnea in patients with transient ischemic attack or minor stroke2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 153.
    Holm, Ann-Charlotte B. Svensson
    et al.
    Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Grenegård, Magnus
    Örebro universitet, Institutionen för läkarutbildning. Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Pathology and Clinical Genetics, County Council of Östergötland, Linköping, Sweden.
    Ollinger, Karin
    Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Pathology and Clinical Genetics, County Council of Östergötland, Linköping, Sweden.
    Lindström, Eva G.
    Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Inhibition of 12-lipoxygenase reduces platelet activation and prevents their mitogenic function2014Ingår i: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 25, nr 2, s. 111-117Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of the present study was to investigate the role of 12-lipoxygenase (12-LOX) on platelet-induced airway smooth muscle cell (ASMC) proliferation. Co-incubation of platelets and ASMC caused platelet activation as determined by morphological changes. Simultaneously, reactive oxygen species (ROS)-generation was detected and ASMC proliferation (measured by using the MTS assay) increased significantly. Furthermore, we found that the 12-LOX inhibitors cinnamyl-3,4-dihydroxy-a-cyanocinnamate (CDC) and Baicalein prevented platelet activation in a co-cultures of platelets and ASMC. The inhibitory effect of CDC and Baicalein on platelets was also registered in a pure platelet preparation. Specifically, the 12-LOX inhibitors reduced collagen-induced platelet aggregation both in the presence and absence of external added fibrinogen. Importantly, platelet-induced ASMC proliferation and ROS production generated during the platelet/ASMC interaction was significantly inhibited in the presence of 12-LOX inhibitors. In conclusion, our findings reveal that 12-LOX is crucial for the observed enhancement of ASMC proliferation in co-cultures of platelets and ASMC. The present result suggests that 12-LOX activity is important in the initial step of platelet/ASMC interaction and platelet activation. Such action of 12-LOX represents a potential important mechanism that may contribute to platelet-induced airway remodelling.

  • 154.
    Holm, Jonas
    Örebro universitet, Institutionen för läkarutbildning.
    Högt BMI och fysisk kapacitet kopplat till hörselnedsättning hos unga män2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 155.
    Holmberg, Victor
    Örebro universitet, Institutionen för läkarutbildning.
    Exponering av Aflatoxin B1 i enhögriskpopulation för ventrikelcancer isydöstra Nicaragua2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 156.
    Hoof, Markus
    Örebro universitet, Institutionen för läkarutbildning.
    Quality assessment; adherence to Nordic guidelines for polycythemia vera2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 157.
    Hultgren Hörnquist, Elisabet
    Örebro universitet, Institutionen för läkarutbildning.
    The mucosal immune system in microscopic colitis2012Ingår i: Microscopic colitis / [ed] S. Miehlke, A. Münich, Basel: S. Karger, 2012, s. 33-39Konferensbidrag (Övrigt vetenskapligt)
  • 158.
    Hultgren, Tomas
    Örebro universitet, Institutionen för läkarutbildning.
    Blood pressure, BMI in late adolescence and the risk of Type 2 Diabetes : a Swedish prospective population-based study.2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 159.
    Hultén, Leif
    et al.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Angerås, U.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Scaglia, M.
    S. Luigi Gonzaga University Hospital, Orbassano, Turin, Italy.
    Delbro, Dick
    Örebro universitet, Institutionen för läkarutbildning.
    Sacral nerve stimulation (SNS), posterior tibial nerve stimulation (PTNS) or acupuncture for the treatment for fecal incontinence: a clinical commentary2013Ingår i: Techniques in Coloproctology, ISSN 1123-6337, E-ISSN 1128-045X, Vol. 17, nr 5, s. 589-592Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sacral nerve stimulation (SNS) has become an established therapy worldwide for the treatment for fecal incontinence. A large number of papers have been published over the years, and SNS is generally considered very effective with improved continence and quality of life for most patients. However, the results are mostly expressed in the semi-quantitative terms, that is, patients' diaries translated into score points. The clinical value of SNS is questionable, especially as the patient groups are usually small and/or etiologically heterogenic and the follow-up period mostly short. The Health Technology Assessment organization in the west region of Sweden has recently evaluated the SNS with regard to evidence, efficacy and risks. Economic and ethical aspects raise serious questions on this expensive and not entirely risk-free treatment in routine medical care. Similar criticism has also been raised by other reviewers proposing a more thorough scientific assessment with well-designed randomized trials and comparison with other similar methods of treatment.

  • 160.
    Hussain, Rashida
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Hugosson, Svante
    Örebro universitet, Institutionen för läkarutbildning. Department of Medical Education, Örebro University, Örebro, Sweden; Department of Otorhinolaryngology, Örebro University, Örebro, Sweden.
    Roomans, Godfried M.
    Örebro universitet, Institutionen för läkarutbildning. Department of Medical Education, Örebro University, Örebro, Sweden.
    Isolation and culture of primary human nasal epithelial cells from anesthetized nasal epithelia2014Ingår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, nr 3, s. 296-299Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Conclusion: Using a local anesthetic agent before obtaining nasal biopsies by nasal brushing makes the sampling procedure smooth, avoids lacrimation, nasal itching/irritation, and/or sneezing and provides enough viable cells to establish primary cultures.

    Objectives: To examine the use of local anesthesia to avoid the irritation experienced by the subject when nasal biopsies are obtained by nasal brushing in order to culture viable nasal epithelial cells.

    Methods: Nasal epithelial cells were collected from the mid-part of the inferior turbinate of healthy volunteers by brushing with interdental brushes, after spraying a topical anesthetic on the nasal mucosa. Immunocytochemistry was performed to assess the purity of epithelial cells.

    Results: Cell samples ranging from 1.16 x 10(5) to 3.06 x 10(5) cells/per sample were obtained. Of 11 samples, 7 formed confluent cultures, while the remaining 4 samples showed only patches of epithelial cells. Neither fungal nor bacterial contamination posed a problem. Immunocytochemistry of the cytospin slides confirmed the presence of epithelial cells in the cultures. No adverse effects were experienced by the volunteers.

  • 161.
    Hussain, Rashida
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Oliynyk, Igor
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Roomans, Godfried M.
    Örebro universitet, Institutionen för läkarutbildning.
    Björkqvist, Maria
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Department of Pediatrics, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Modulation of ENaC, CFTR, and iNOS expression in bronchial epithelial cells after stimulation with Staphylococcus epidermidis (94B080) and Staphylococcus aureus (90B083)2013Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, nr 9, s. 814-826Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bacteria affect the respiratory epithelium, which is covered by airway surface liquid (ASL) and mucus. Ion concentrations in the ASL are determined by the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na+ channel (ENaC). Neonatal sepsis is a major risk factor for subsequent pulmonary disease in preterm newborns. Predominating are coagulase-negative staphylococci (e.g., Staphylococccus epidermidis and Staphylococccus aureus). The aim of this study was to investigate modulation of CFTR, ENaC, mucins, proinflammatory cytokines, and inducible nitric oxide synthase (iNOS) in respiratory epithelial cells after S. epidermidis 94B080 and S. aureus 90B083 exposure. Bronchial epithelial cells were incubated with S. epidermidis 94B080 and S. aureus 90B083 (neonatal blood isolates) for 1-36h. Expression of CFTR, ENaC, iNOS, and mucins was analyzed by real-time PCR and Western blotting. Release of cytokines was analyzed by ELISA, and production of NO by the Griess assay. Expression of CFTR significantly decreased after 36h incubation with S. epidermidis and more prominently with S. aureus, whereas S. epidermidis caused a significant increase in the expression of - and -ENaC. Expression of iNOS increased, but NO was not detected. Both staphylococci caused a decrease in the intracellular Ca2+ concentration. S. aureus induced increased secretion of IL-6, IL-8, and transforming nuclear factor (TNF)- in a time-dependent manner as compared with S. epidermidis. In conclusion, expression of ENaC, CFTR, and iNOS is modulated by exposure to S. aureus 90B083 and S. epidermidis 94B080. S. aureus is more potent in causing release of IL-6, IL-8, and TNF- by bronchial epithelial cells as compared with S. epidermidis. The mRNA expression for the mucus proteins MUC2, MUC5AC, and MUC5B could not be measured, neither in the presence nor in the absence of bacteria.

  • 162.
    Hussain, Rashida
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Shahror, Rami
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Karpati, Ferenc
    3Stockholm CF-centre, Department of Pediatrics, Karolinska University Hospital, Huddinge, Stockholm.
    Roomans, Godfried M.
    Örebro universitet, Institutionen för läkarutbildning.
    Effect of IL-6, IL-8 and glucocorticoids on the internalization of Pseudomonas aeruginosa (ATCC 27853) in cystic fibrosis bronchial epithelial cellsManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Pseudomonas aeruginosa infection is common in cystic fibrosis (CF). Uptake of P. aeruginosa by the cell and the subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. CF airways have elevated levels of IL-6 and IL-8. Glucocorticoids (GCs) are anti-inflammatory but their use in CF is controversial. We studied the effect of IL- 6, IL-8 and GCs on bacterial internalization, apoptosis, and intracellular Ca2+concentration in CF bronchial epithelial (CFBE) cells and found that increased levels of IL-6 and IL-8 can increase the susceptibility of P. aeruginosa infected cells to apoptosis and/or internalization of these bacteria in CF cells. GCs decreased the extent of apoptosis in CFBE cells infected with P. aeruginosa, but may improve airway hydration by increasing the intracellular Ca2+ concentration. None of the GCs and cytokines affected apoptosis in cells not exposed to Pseudomonas. We conclude that increased levels of IL-6 and IL-8 may have important roles in the pathology of P. aeruginosa infection in CF airways. If internalization is beneficial for the host then GCs are not beneficial for the treatment of CF patients. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out. 

  • 163.
    Hussain, Shahida
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. IRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Varelogianni, Georgia
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Särndahl, Eva
    Örebro universitet, Institutionen för läkarutbildning. IRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Roomans, Godfried M
    Örebro universitet, Institutionen för läkarutbildning. IRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    N-acetylcysteine and azithromycin affect the innate immune response in cystic fibrosis bronchial epithelial cells in vitro2015Ingår i: Experimental Lung Research, ISSN 0190-2148, E-ISSN 1521-0499, Vol. 41, nr 5, s. 251-260Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective: We have previously reported that N-acetylcysteine (NAC), ambroxol and azithromycin (AZM) (partially) correct the chloride efflux dysfunction in cystic fibrosis bronchial epithelial (CFBE) cells with the ΔF508 homozygous mutation in vitro.

    Methods: In the present paper, we further investigated possible immunomodulatory effects of these drugs on the regulation of the innate immune system by studying the expression of the cytosolic NOD-like receptors NLRC1 and NLRC2, and interleukin (IL)-6 production in CFBE cells.

    Results: Under basal conditions, PCR and Western Blot data indicate that the NLRC2 receptor has a reduced expression in CF cells as compared to non-CF (16HBE) cells, but that the NLRC1 expression is the same in both cell lines. AZM significantly upregulated NLRC1 and NLRC2 while NAC upregulated only NLRC2 receptor expression in CF cells. Reduced basal IL-6 production was found in CF cells as compared to non-CF cells. MDP (an NLRC2 agonist), NAC and AZM, but not Tri-DAP (an NLRC1 agonist), increased IL-6 production in CF cells, indicating that in CF cells IL-6 upregulation is independent of NLRC1, but involves the activation of NLRC2.

    Conclusion: Overall, the results indicate that NAC and AZM not only can correct the chloride efflux dysfunction but also have a weakly strengthening effect on the innate immune system.

  • 164.
    Huttunen, Elina
    Örebro universitet, Institutionen för läkarutbildning.
    Hypertrophic Obstructive Cardiomyopathy – Symptoms, treatment and threats: A Systematic Review2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 165.
    Huzell, Christine
    Örebro universitet, Institutionen för läkarutbildning.
    Jämförelse av fotodynamisk terapi och imikvimod för behandling av multipla aktiniska keratoser: – En systematisk litteraturstudie2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 166.
    Ingberg, Edvin
    et al.
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Dock, Hua
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Theodorsson, Annette
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden; Division of Neuro and Inflammation Science, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Neurosurgery, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Linköping, Sweden.
    Ström, Jakob O.
    Örebro universitet, Institutionen för läkarutbildning. Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden; Vårdvetenskapligt Forskningscentrum/Centre for Health Sciences, Örebro University Hospital, County Council of Örebro, Örebro, Sweden.
    Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 21086Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specific pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters' impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models.

  • 167.
    Isaksson, Marlene
    Örebro universitet, Institutionen för läkarutbildning.
    A retrospective cohort study of symptoms described by patients with vitreous body detachment2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 168.
    Ito, Teruyo
    et al.
    Dept Bacteriol, Juntendo Univ, Tokyo, Japan .
    Hiramatsu, Keiichi
    Rockefeller University, New York NY, USA .
    Tomasz, Alexander
    Rockefeller University, New York NY, USA .
    de Lencastre, Herminia
    Rockefeller University, New York NY, USA; Inst Tecnol Quim & Biol, University Nova Lisboa, Oeiras, Portugal.
    Perreten, Vincent
    Inst Vet Bacteriol, University Bern, Bern, Switzerland.
    Holden, Matthew T. G.
    Wellcome Trust Sanger Inst, Hinxton, England.
    Coleman, David C.
    Dublin Dent University Hospital, Univ Dublin, Dublin, Ireland; Trinity College, Dublin, Ireland.
    Goering, Richard
    Medical Center, University of Nebraska, Omaha NE, USA.
    Giffard, Philip M.
    Menzies School of Heallth Research, Darwin NT, Australia.
    Skov, Robert L.
    Statens Serum Institut, Copenhagen, Denmark .
    Zhang, Kunyan
    Univ Calgary, Calgary AB, Canada.
    Westh, Henrik
    Faculty of Health, Copenhagen University, Copenhagen, Denmark; Hvidovre Hospital, Copenhagen University, Copenhagen, Denmark.
    O'Brien, Frances
    Curtin Univ Technol, Perth WA, Australia.
    Tenover, Fred C.
    Cepheid, Sunnyvale CA, USA.
    Oliveira, Duarte C.
    Inst Tecnol Quim & Biol, University Nova Lisboa, Oeiras, Portugal; Faculty of Ciencias & Tecnol, Dept Life Sciences, CREM, University Nova Lisboa, Caparica, Portugal .
    Boyle-Vavra, Susan
    Faculty of Ciencias & Tecnol, Dept Life Sciences, CREM, University Nova Lisboa, Caparica, Portugal .
    Laurent, Frederic
    French Natl Reference Ctr Staphylococci, Hosp Civils Lyon, Lyon, France.
    Kearns, Angela M.
    Staphylococcus Reference Unit, Heallth Protecttion Agency, London, England.
    Kreiswirth, Barry
    Pubicl Health Research Institute, New York NY, USA .
    Ko, Kwan Soo
    School of Medicine, Sungkyunkwan University, Seoul, South Korea .
    Grundmann, Hajo
    Nationall Insitute of Public Health & Environment, Utrecht, Netherlands .
    Sollid, Johanna E.
    Tromsø University, Tromsø, Norway .
    John, Joseph F. Jr.
    Ralph H Johnson VA Med Ctr, Charleston SC, USA.
    Daum, Robert
    University of Chicago, Chicago IL, USA.
    Söderquist, Bo
    Örebro universitet, Institutionen för läkarutbildning.
    Buist, Girbe
    Guidelines for Reporting Novel mecA Gene Homologues2012Ingår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 56, nr 10, s. 4997-4999Artikel i tidskrift (Övrigt vetenskapligt)
  • 169.
    Jalalvand, Farnaz
    Örebro universitet, Institutionen för läkarutbildning.
    Incidence of surgical site infections after dermatologic surgery at the Department of Dermatology, Örebro University Hospital2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 170.
    Jansson, A.
    et al.
    School of Life Sciences, Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
    Pernestig, A.-K.
    School of Life Sciences, Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
    Nilsson, P.
    School of Life Sciences, Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
    Jirstrand, M.
    Fraunhofer-Chalmers Research Centre for Industrial Mathematics, Gothenburg, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro universitet, Institutionen för läkarutbildning. Department of Biomedicine.
    Toward quantifying the thymic dysfunction state in mouse models of inflammatory bowel disease2013Ingår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 19, nr 4, s. 881-888Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Inflammatory bowel disease is characterized by a number of immunological alterations, not the least in the T-cell compartment. Numerous animal models of colitis have revealed aberrant thymocyte dynamics associated with skewed thymocyte development. The recent advancements in quantitative methods have proposed critical kinetic alterations in the thymocyte development during the progression of colitis. This review focuses on the aberrant thymocyte dynamics in Gαi2-deficient mice as this mouse model provides most quantitative data of the thymocyte development associated with colitis. Herein, we discuss several dynamic changes during the progression of colitis and propose a hypothesis for the underlying causes for the skewed proportions of the thymocyte populations seen in the Gαi2-deficient mice and in other mouse models of colitis.

  • 171.
    Jansson, Rebecca
    Örebro universitet, Institutionen för läkarutbildning.
    In-hospital patients with suspected heart failure: Is the prevalence of systolic and diastolic dysfunction high or low?2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 172.
    Jansson, Stefan P. O.
    et al.
    Örebro universitet, Institutionen för läkarutbildning. Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Family Medicine Research Centre, Örebro County Council, Örebro, Sweden.
    Andersson, D. K. G.
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Svärdsudd, K.
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Mortality and cardiovascular disease outcomes among 740 patients with new-onset Type 2 diabetes detected by screening or clinically diagnosed in general practice2016Ingår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 33, nr 3, s. 324-331Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: Screening for Type 2 diabetes among people at high risk is recommended by many organizations. The aim of this study was to analyse all-cause mortality and cardiovascular disease (CVD) outcomes in patients with Type 2 diabetes detected by screening or diagnosed clinically.

    Methods: A diabetes register was established at the primary healthcare centre in Laxa, Sweden beginning in 1972. The register was based on data from clinical records with information on medical treatment and laboratory data, as well as all-cause mortality, CVD, myocardial infarction and stroke events from national registers until 31 December 2013. A total of 740 patients with new-onset Type 2 diabetes were registered between 1972 and 2001. In addition, an opportunistic diabetes-screening programme involving people aged 35-79 years started in 1983 and was repeated onwards in 5-year cycles.

    Results: Baseline characteristics showed a significantly higher CVD risk, mainly depending on more prevalent CVD events in the screened compared with the clinically detected group (propensity score 0.59 vs. 0.46, P < 0.0001). After mean follow-up periods of 12.9 and 13.6 years for screening detected vs. clinically detected patients, respectively, hazard ratios were as follows: all-cause mortality, 0.99 (P = 0.89); CVD, 1.17 (P = 0.10); myocardial infarction, 1.08 (P = 0.49); and stroke, 1.03 (P = 0.83).

    Conclusions: No reduction in total mortality or CVD outcomes was found in patients with Type 2 diabetes that was detected by screening compared with those diagnosed clinically.

  • 173.
    Jayaprakash, Kartheyaene
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Demirel, Isak
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Khalaf, Hazem
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för läkarutbildning.
    The role of phagocytosis, oxidative burst and neutrophil extracellular traps in the interaction between neutrophils and the periodontal pathogen Porphyromonas gingivalis2015Ingår i: Molecular Oral Microbiology, ISSN 2041-1006, E-ISSN 2041-1014, Vol. 30, nr 5, s. 361-375Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neutrophils are regarded as the sentinel cells of innate immunity and are found in abundance within the gingival crevice. Discovery of neutrophil extracellular traps (NETs) within the gingival pockets prompted us to probe the nature of the interactions of neutrophils with the prominent periopathogen Porphyromonas gingivalis. Some of the noted virulence factors of this Gram-negative anaerobe are gingipains: arginine gingipains (RgpA/B) and lysine gingipain (Kgp). The aim of this study was to evaluate the role of gingipains in phagocytosis, formation of reactive oxygen species, NETs and CXCL8 modulation by using wild-type strains and isogenic gingipain mutants. Confocal imaging showed that gingipain mutants K1A (Kgp) and E8 (RgpA/B) induced extracellular traps in neutrophils, whereas ATCC33277 and W50 were phagocytosed. The viability of both ATCC33277 and W50 dwindled as the result of phagocytosis and could be salvaged by cytochalasin D, and the bacteria released high levels of lipopolysaccharide in the culture supernatant. Porphyromonas gingivalis induced reactive oxygen species and CXCL8 with the most prominent effect being that of the wild-type strain ATCC33277, whereas the other wild-type strain W50 was less effective. Quantitative real-time polymerase chain reaction revealed a significant CXCL8 expression by E8. All the tested P.gingivalis strains increased cytosolic free calcium. In conclusion, phagocytosis is the primary neutrophil response to P.gingivalis, although NETs could play an accessory role in infection control. Although gingipains do not seem to directly regulate phagocytosis, NETs or oxidative burst in neutrophils, their proteolytic properties could modulate the subsequent outcomes such as nutrition acquisition and survival by the bacteria.

  • 174.
    Jayaprakash, Kartheyaene
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Khalaf, Hazem
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för läkarutbildning.
    Gingipains from Porphyromonas gingivalis play a significant role in induction and regulation of CXCL8 in THP-1 cells2014Ingår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 14, artikel-id 193Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Porphyromonas gingivalis is an important bacterial etiological agent involved in periodontitis. The bacterium expresses two kinds of cysteine proteases called gingipains: arginine gingipains (RgpA/B) and lysine gingipain (Kgp). This study evaluated the interaction between P. gingivalis and THP-1 cells, a widely used monocytic cell line, in vitro with a focus on CXCL8 at the gene and protein levels and its fate thereafter in cell culture supernatants. THP-1 cells were stimulated with viable and heat-killed wild-type strains ATCC 33277 or W50 or viable isogenic gingipain mutants of W50, E8 (Rgp mutant) or K1A (Kgp mutant), for 24 hours.

    Results: ELISA and qPCR results show an elevated CXCL8 expression and secretion in THP-1 cells in response to P. gingivalis, where the heat-killed ATCC33277 and W50 induced higher levels of CXCL8 in comparison to their viable counterparts. Furthermore, the Kgp-deficient mutant K1A caused a higher CXCL8 response compared to the Rgp-deficient E8. Chromogenic quantification of lipopolysaccharide (LPS) in supernatant showed no significant differences between viable and heat killed bacteria except that W50 shed highest levels of LPS. The wild-type strains secreted relatively more Rgp during the co-culture with THP-1 cells. The CXCL8 degradation assay of filter-sterilized supernatant from heat-killed W50 treated cells showed that Rgp was most efficient at CXCL8 hydrolysis. Of all tested P. gingivalis strains, adhesion and internalization in THP-1 cells was least conspicuous by Rgp-deficient P. gingivalis (E8), as demonstrated by confocal imaging.

    Conclusions: W50 and its Kgp mutant K1A exhibit a higher immunogenic and proteolytic function in comparison to the Rgp mutant E8. Since K1A differs from E8 in the expression of Rgp, it is rational to conclude that Rgp contributes to immunomodulation in a more dynamic manner in comparison to Kgp. Also, W50 is a more virulent strain when compared to the laboratory strain ATCC33277.

  • 175.
    Johansson, Martina
    Örebro universitet, Institutionen för läkarutbildning.
    Amputation och Protesförsörjning av Nedre Extremitet: - en epidemiologisk studie genomförd på Universitetssjukhuset Örebro 2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 176.
    Johansson, Sanne
    Örebro universitet, Institutionen för läkarutbildning.
    Does activation of opioid receptors on tumor cells constitute a control mechanism for proliferation and/or metastasis?: A study undertaken with ovarian cancer cells.2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 177.
    Johnsson, Joakim
    Örebro universitet, Institutionen för läkarutbildning.
    Aldosteronblockad vid dialys. Effekter på blodtrycket.2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 178.
    Jones, Rupert
    et al.
    University of Plymouth, Plymouth, England.
    Price, David
    University of Aberdeen, Aberdeen, UK.
    Chavannes, Niels
    Leiden University, Leiden, Netherlands.
    Lee, Amanda
    University of Aberdeen, Aberdeen, UK.
    Gabe-Thomas, Elizabeth
    University of Plymouth, Plymouth, England.
    Ställberg, Björn
    Uppsala University, Uppsala, Sweden.
    Lisspers, Karin
    Uppsala University, Uppsala, Sweden.
    Sundh, Josefin
    Örebro universitet, Institutionen för läkarutbildning.
    A comparison of multi-component indices of COPD severity in primary care: An UNLOCK study from the IPCRG2013Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 42, nr 57, artikel-id 2831Artikel i tidskrift (Övrigt vetenskapligt)
  • 179.
    Jonsson, Sara
    Örebro universitet, Institutionen för läkarutbildning.
    A real life evaluation of hepatitis C treatment, with novel direct acting antivirals compared to older regimens2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 180.
    Jonsson, Thomas B.
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Larzon, Thomas
    Department of Surgery, University Hospital, Örebro, Sweden.
    Arfvidsson, B.
    Department of Surgery, University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro universitet, Institutionen för läkarutbildning. Department of Medicine, University Hospital, Örebro, Sweden.
    Axelsson, C.-G.
    Department of Transfusion Medicine, University Hospital, Örebro, Sweden.
    Jurstrand, M.
    Clinical Research Centre, University Hospital, Örebro, Sweden.
    Norgren, Lars
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Surgery, University Hospital, Örebro, Sweden.
    Adverse events during treatment limb ischemia with autologous peripheral blood mononuclear cell implant2012Ingår i: International Journal of Angiology, ISSN 0392-9590, E-ISSN 1827-1839, Vol. 31, nr 1, s. 77-84Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: Trials have reported clinical improvement and reduced need for amputation in critical limb ischemia (CLI) patients receiving therapeutic angiogenesis with stem cells. Our objective was to test peripheral stem cell therapy efficacy and safety to gain experiences for further work.

    Methods: We included nine CLI patients (mean age 76.7 ±9.7). Stem cells were mobilized to the peripheral blood by administration of G-CSF (Filgrastim) for 4 days, and were collected on day five, when 30 mL of a stem cell suspension was injected into 40 points of the limb. The clinical efficacy was evaluated by assessing pain relief, wound healing and changes in ankle-brachial pressure index (ABI). Local metabolic and inflammatory changes were measured with microdialysis, growth factors and cytokine level determination. Patients were followed for 24 weeks.

    Results: Four patients experienced some degree of improvement with pain relief and/or improved wound healing and ABI increase. One patient was lost to follow up due to chronic psychiatric illness; one was amputated after two weeks. Two patients had a myocardial infarction (MI), one died. One patient died from a massive mesenteric thrombosis after two weeks and one died from heart failure at week 11. Improved patients showed variable effects in cytokine-, growth factor- and local metabolic response.

    Conclusion: Even with some improvement in four patients, severe complications in four out of nine patients, and two in relation to the bone marrow stimulation, made us terminate the study prematurely. We conclude that with the increased risk and the reduced potential of the treatment, peripheral blood stem cell treatment in the older age group is less appropriate. Metabolic and inflammatory response may be of value to gain insight into mechanisms and possibly to evaluate effects of therapeutic angiogenesis.

  • 181. Joossens, S.
    et al.
    Halfvarson, Jonas
    Örebro universitet, Institutionen för läkarutbildning.
    Camps, M.
    Vermeire, S.
    Jarnerot, G.
    Stockbrugger, R.
    Bossuyt, X.
    Rutgeerts, P.
    Tysk, C.
    A panel of serologic markers in twins with inflammatory bowel disease2005Ingår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, nr Suppl.Artikel i tidskrift (Refereegranskat)
  • 182.
    Joussen, Antonia M
    et al.
    Department of Ophthalmology, Charité, University Medicine, Berlin, Germany.
    Rizzo, Stanislao
    U.O.Chirurgia Oftalmica, Azienda Ospedaliero, Universitaria Pisana, Pisa, Italy.
    Kirchhof, Bernd
    Department of Vitreoretinal Surgery, University of Cologne, Cologne, Germany.
    Schrage, Norbert
    Augenklinik Kön-Merheim, Cologne, Germany.
    Li, Xiaoxin
    Beijing University, Beijing, China.
    Lente, Christina
    Department of Medical Statistics, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
    Hilgers, Ralf-Dieter
    Department of Medical Statistics, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
    Crafoord, Sven
    Örebro universitet, Institutionen för läkarutbildning.
    Heavy silicone oil versus standard silicone oil in as vitreous tamponade in inferior PVR (HSO Study): interim analysis2011Ingår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 89, nr 6, s. e483-e489Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: The Heavy Silicone Oil versus Standard Silicone Oil Study (HSO study) is designed to answer the question whether a heavier-than-water tamponade improves the prognosis of eyes with proliferative vitreoretinopathy (PVR) of the lower retina.

    METHODS: The HSO Study is a multicentre, randomized, prospective, controlled clinical trial stratified by surgeon comparing two endotamponades within a two-arm parallel-group design. Patients with inferiorly and posteriorly located PVR grade C-A6 were randomized to either HSO or standard silicone oil as a tamponading agent. The main end-point criteria are complete retinal attachment at 12 months and change in visual acuity (VA) 12 months postoperatively compared to the preoperative VA.

    RESULTS: Forty-six patients treated with HSO were compared to 47 patients treated with standard silicone oil. There was no difference among the groups regarding baseline data. Three patients in the HSO and five patients in the standard silicone oil group fulfilled intraoperative exclusion criteria. There was no significant difference between both groups regarding anatomical success. Neither noninferiority nor superiority was shown with regard to final acuity.

    CONCLUSIONS: The HSO Study is the first randomized prospective clinical trial to compare heavy and standard silicone oil in patients with PVR of the lower retina. The intermediate results failed to demonstrate superiority of a heavy tamponade.

  • 183.
    Jönsson, Agnez
    Örebro universitet, Institutionen för läkarutbildning.
    High in vitro activity of the fluoroquinolone sitafloxacin against a global panel of antimicrobial resistant and multidrug-resistant Neisseria gonorrhoeae isolates2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 184.
    Kalla, R.
    et al.
    Gastrointestinal Unit, Univ Edinburgh, Edinburgh, UK.
    Kennedy, N.
    Gastrointestinal Unit, Univ Edinburgh, Edinburgh, UK.
    Hjelm, F.
    Olink Bioscience AB, Uppsala, Sweden.
    Modig, E.
    Olink Bioscience AB, Uppsala, Sweden.
    Sundell, M.
    Olink Bioscience AB, Uppsala, Sweden.
    Andreassen, B.
    Inst Clin Med, Univ Oslo, Oslo, Norway.
    Bergemalm, Daniel
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Ricanek, P.
    Dept Gastroenterol, Akershus Univ Hosp, Lorenskog, Norway.
    Söderholm, J.
    Gastroenterol, Linköping Univ, Linköping, Sweden.
    Vatn, M.
    Inst Clin Med, Univ Oslo, Oslo, Norway.
    Halfvarson, Jonas
    Örebro universitet, Institutionen för läkarutbildning.
    Gullberg, M.
    Olink, Biosci, Uppsala, Sweden.
    Satsangi, J.
    Gastrointestinal Unit, Univ Edinburgh, Edinburgh, UK.
    Proximity Extension Assay technology identifies novel serum biomarkers for predicting Inflammatory Bowel Disease: IBD Character Consortium2015Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 9, s. S146-S147Artikel i tidskrift (Övrigt vetenskapligt)
  • 185.
    Kallak, Theodora K.
    et al.
    Dept Womens & Childrens Health, Uppsala University, Uppsala, Sweden.
    Baumgart, Juliane
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Dept Obstetrics & Gynecology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Kerstin
    Örebro universitet, Institutionen för läkarutbildning. Dept Obstetrics & Gynecology, Örebro University Hospital, Örebro, Sweden.
    Poromaa, Inger Sundstrom
    Dept Womens & Childrens Health, Uppsala University, Uppsala, Sweden.
    Evers, Anneli Stavreus
    Dept Womens & Childrens Health, Uppsala University, Uppsala, Sweden.
    Treatment with aromatase inhibitor acts indirectly through the estrogen receptor pathway causing decreased junction plakoglobin mRNA expression and vaginal atrophy2013Ingår i: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 20, nr 12, s. 1328-1328Artikel i tidskrift (Övrigt vetenskapligt)
  • 186.
    Kallak, Theodora Kunovac
    et al.
    Dept Womens & Childrens Hlth, Uppsala Univ, Uppsala, Sweden.
    Baumgart, Juliane
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Dept Obstet & Gynecol, Örebro University Hospital, Örebro, Sweden.
    Göransson, Emma
    Dept Womens & Childrens Hlth, Uppsala Univ, Uppsala, Sweden..
    Nilsson, Kerstin
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Dept Obstet & Gynecol, Örebro University Hospital, Örebro, Sweden.
    Poromaa, Inger Sundström
    Dept Womens & Childrens Hlth, Uppsala Univ, Uppsala, Sweden..
    Stavreus-Evers, Anneli
    Dept Womens & Childrens Hlth, Uppsala Univ, Uppsala, Sweden..
    Aromatase inhibitors affect vaginal proliferation and steroid hormone receptors2014Ingår i: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 21, nr 4, s. 383-390Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Women with breast cancer who are treated with aromatase inhibitors often experience vaginal atrophy symptoms and sexual dysfunction. This work aims to study proliferation and the presence and distribution of steroid hormone receptors in vaginal biopsies in relation to vaginal atrophy and vaginal pH in women with breast cancer who are on adjuvant endocrine treatment and in healthy postmenopausal women.

    Methods: This is a cross-sectional study that compares postmenopausal aromatase inhibitor-treated women with breast cancer (n = 15) with tamoxifen-treated women with breast cancer (n = 16) and age-matched postmenopausal women without treatment (n = 19) or with vaginal estrogen therapy (n = 16). Immunohistochemistry was used to study proliferation and steroid hormone receptor staining intensity. Data was correlated with estrogen and androgen levels, vaginal atrophy scores, and vaginal pH.

    Results: Aromatase inhibitor-treated women had a lower grade of proliferation, weaker progesterone receptor staining, and stronger androgen receptor staining, which correlated with plasma estrone levels, vaginal atrophy scores, and vaginal pH.

    Conclusions: Women with aromatase inhibitor-treated breast cancer exhibit reduced proliferation and altered steroid hormone receptor staining intensity in the vagina, which are related to clinical signs of vaginal atrophy. Although these effects are most probably attributable to estrogen suppression, a possible local inhibition of aromatase cannot be ruled out.

  • 187.
    Kallak, Theodora Kunovac
    et al.
    Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
    Baumgart, Juliane
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Kerstin
    Örebro universitet, Institutionen för läkarutbildning. Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden.
    Åkerud, Helena
    Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
    Poromaa, Inger Sundström
    Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
    Stavreus-Evers, Anneli
    Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
    Vaginal Gene Expression During Treatment With Aromatase Inhibitors2015Ingår i: Clinical Breast Cancer, ISSN 1526-8209, E-ISSN 1938-0666, Vol. 15, nr 6, s. 527-535.e2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Vaginal gene expression in aromatase inhibitor-treated women was compared with postmenopausal control women treated with vaginal estrogen therapy. Vaginal tissue from aromatase inhibitor-treated women had low expression of genes involved in cell differentiation, proliferation, and cell adhesion, and associated with vaginal discomfort. The presence of vaginal aromatase suggests that this is the result of local and systemic aromatase inhibition.

    Background: Aromatase inhibitor (AI) treatment suppresses estrogen biosynthesis and causes genitourinary symptoms of menopause such as vaginal symptoms, ultimately affecting the quality of life for many postmenopausal women with breast cancer. Thus, the aim of this study was to examine vaginal gene expression in women during treatment with AIs compared with estrogen-treated women. The secondary aim was to study the presence and localization of vaginal aromatase.

    Patients and Methods: Vaginal biopsies were collected from postmenopausal women treated with AIs and from age-matched control women treated with vaginal estrogen therapy. Differential gene expression was studied with the Affymetrix Gene Chip Gene 1.0 ST Array (Affymetrix Inc, Santa Clara, CA) system, Ingenuity pathway analysis, quantitative real-time polymerase chain reaction, and immunohistochemistry.

    Results: The expression of 279 genes differed between the 2 groups; AI-treated women had low expression of genes involved in cell differentiation, proliferation, and cell adhesion. Some differentially expressed genes were found to interact indirectly with the estrogen receptor alpha. In addition, aromatase protein staining was evident in the basal and the intermediate vaginal epithelium layers, and also in stromal cells with a slightly stronger staining intensity found in AI-treated women.

    Conclusion: In this study, we demonstrated that genes involved in cell differentiation, proliferation, and cell adhesion are differentially expressed in AI-treated women. The expression of vaginal aromatase suggests that this could be the result of local and systemic inhibition of aromatase. Our results emphasize the role of estrogen for vaginal cell differentiation and proliferation and future drug candidates should be aimed at improving cell differentiation and proliferation.

  • 188.
    Karlsson, Christian
    Örebro universitet, Institutionen för läkarutbildning.
    Identifiering av specifka sekvenstyper av Staphylococcus epidermidis med mass-spektrometri2015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 189.
    Karlsson, Johanna
    Örebro universitet, Institutionen för läkarutbildning.
    Kunskapsläget om ebola bland Örebros läkarstudenter ht 20142015Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 190.
    Kasiga, Teresa
    Örebro universitet, Institutionen för läkarutbildning.
    Severe acne in late adolescence and risk of prostate cancer later in life: a nested case-control study2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 191.
    Keser, Toma
    et al.
    Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
    Akmacic, Irena Trbojevic
    Genos Glycoscience Research Laboratory, Zagreb, Croatia.
    Ventham, Nicholas T.
    Centre for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Theodoratou, Evropi
    Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
    Vuckovic, Frano
    Genos Glycoscience Research Laboratory, Zagreb, Croatia.
    Kennedy, Nicholas A.
    Centre for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Nimmo, Elaine R.
    Centre for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Kalla, Rahul
    Centre for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Drummond, Hazel
    Centre for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Stambuk, Jerko
    Genos Glycoscience Research Laboratory, Zagreb, Croatia.
    Campbell, Harry
    Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
    Hedin, Charlotte
    Diabetes and Nutritional Sciences Division, School of Medicine, King ’ s College London, London, UK; Centre for Digestive Diseases, Blizard Institute, Queen Mary University of London, London, UK.
    D'Amato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro universitet, Institutionen för läkarutbildning. Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Satsangi, Jack
    Centre for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
    Lauc, Gordan
    Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia; Genos Glycoscience Research Laboratory, Zagreb, Croatia.
    Changes in the immunoglobulin G glycome associated with inflammatory bowel disease2015Ingår i: Glycobiology, ISSN 0959-6658, E-ISSN 1460-2423, Vol. 25, nr 11, s. 1242-1242Artikel i tidskrift (Övrigt vetenskapligt)
  • 192.
    Khalaf, Hazem
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Division of Clinical Medicine,, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för läkarutbildning. Division of Clinical Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Altered T-cell responses by the periodontal pathogen Porphyromonas gingivalis2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 9, artikel-id e45192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several studies support an association between the chronic inflammatory diseases periodontitis and atherosclerosis with a crucial role for the periodontal pathogen Porphyromonas gingivalis. However, the interplay between this pathogen and the adaptive immune system, including T-cells, is sparsely investigated. Here we used Jurkat T-cells to determine the effects of P. gingivalis on T-cell-mediated adaptive immune responses. We show that viable P. gingivalis targets IL-2 expression at the protein level. Initial cellular events, including ROS production and [Ca2+]i, were elevated in response to P. gingivalis, but AP-1 and NF-κB activity dropped below basal levels and T-cells were unable to sustain stable IL-2 accumulation. IL-2 was partially restored by Leupeptin, but not by Cathepsin B Inhibitor, indicating an involvement of Rgp proteinases in the suppression of IL-2 accumulation. This was further confirmed by purified Rgp that caused a dose-dependent decrease in IL-2 levels. These results provide new insights of how this periodontal pathogen evades the host adaptive immune system by inhibiting IL-2 accumulation and thus attenuating T-cell proliferation and cellular communication.

  • 193.
    Khalaf, Hazem
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Demirel, Isak
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för läkarutbildning.
    Suppression of inflammatory gene expression in T cells by Porphyromonas gingivalis is mediated by targeting MAPK signaling2013Ingår i: Cellular & Molecular Immunology, ISSN 1672-7681, E-ISSN 2042-0226, Vol. 10, nr 5, s. 413-422Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is increasing awareness of the effects of Porphyromonas gingivalis on host immune responses. Degradation of cytokines and chemokines by cysteine proteinases has previously been reported. However, the precise mechanisms by which P. gingivalis is able to alter intracellular signaling, and thus proliferation and inflammation, have not been described. We have previously reported suppression of activator protein-1 (AP-1) and degradation of IL-2 by proteinases from P. gingivalis. In the present study, we have analyzed the effects of P. gingivalis on Jurkat T-cell signal transduction and subsequent IL-2 and CXCL8 expression. We found that CXCL8, but not IL-2, gene expression levels were significantly suppressed by viable P. gingivalis. Analysis of intracellular signaling revealed an inhibitory effect of P. gingivalis on c-Jun and c-Fos, but not NF kappa B (p50 and p65), NFAT or STAT5 expression. This inhibitory effect was not due to suppression of mitogen-activated protein kinase (MAPK) (p38, erk and JNK) gene expression, but was rather due to prevention of protein kinase C (PKC) and p38 phosphorylation, as demonstrated by western blot analysis. Furthermore, SOCS1 and SOCS3 expression levels decreased following treatment of Jurkat T cells with viable P. gingivalis. The results indicate that P. gingivalis is able to suppress inflammatory gene expression by targeting the activity of MAPK pathways in T cells, which was confirmed by using specific inhibitors of NF-kappa B, PKC, ERK, p38 and JNK.

  • 194.
    Khalaf, Hazem
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Lönn, Johanna
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för läkarutbildning.
    Cytokines and chemokines are differentially expressed in patients with periodontitis: Possible role for TGF-beta 1 as a marker for disease progression2014Ingår i: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 67, nr 1, s. 29-35Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Periodontitis is a chronic inflammatory disease characterized by destruction of periodontal tissue ultimately leading to bone destruction and has been associated with other inflammatory diseases, such as atherosclerosis. Attachment loss of periodontal tissue is primarily caused by host cell-derived immune responses against subgingival biofilm. The aim of the present study was to determine the cytokine profile in serum, saliva and gingival crevicular fluid (GCF) patients with periodontitis and healthy controls. We show that periodontitis patients exhibit higher numbers of periodontal pathogens and their immune responses are significantly altered. The levels of IL-6 in saliva and GCF were significantly suppressed, and while CXCL8 was not altered in serum, its expression levels were significantly suppressed in saliva and elevated in GCF. The T-cell-derived cytokine IL-2 did not differ between patients and controls in serum and saliva, but there was a significant suppression in GCF of patients. Interestingly, TGF-beta(1) levels were significantly elevated in serum, saliva and GCF in patients compared to controls. Furthermore, by using cultured gingival fibroblasts stimulated with wild type and proteinase mutant strains of Porphyromonas gingivalis, we show that the suppression of CXCL8 and IL-6, and the induction of TGF-beta(1) is primarily mediated by the proteolytic activity of lysine-specific proteinases. These results indicate that P. gingivalis is a major contributor to the altered immune responses and the pathology of periodontitis. Furthermore, the ease of sampling and analyzing cytokine expression profiles, including TGF-beta(1), in saliva and GCF may serve to predict the progression of periodontitis and associated systemic inflammatory diseases.

  • 195.
    Khalaf, Hazem
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Nakka, Sravya Sowdamini
    Örebro universitet, Institutionen för hälsovetenskap och medicin. PEAS Institut AB, Söderleden 1, Linköping.
    Sandén, Camilla
    Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Svärd, Anna
    Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Hultenby, Kjell
    Division of Clinical Research Centre, Department of Laboratory Medicine, Karolinska.
    Scherbak, Nikolai
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Aili, Daniel
    PEAS Institut AB, Söderleden 1, Linköping.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för läkarutbildning.
    Antibacterial effects of lactobacillus and bacteriocin NC8 αβ on the periodontal pathogen Porphyromonas gingivalisManuskript (preprint) (Övrigt vetenskapligt)
  • 196.
    Khan, Asif
    Örebro universitet, Institutionen för läkarutbildning.
    Optimizing a method to analysemetabolic markers in leucocytesusing Western Blot.2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 197.
    Khassebaf, Jasmin
    Örebro universitet, Institutionen för läkarutbildning.
    Antibiotic susceptibility patterns of Propionibacterium acnes isolated from prosthetic joint infections2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 198.
    Klarström-Engström, Kristin
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för läkarutbildning.
    Khalaf, Hazem
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    The platelet response to various strains of Porphyromonas gingivalisManuskript (preprint) (Övrigt vetenskapligt)
  • 199.
    Klarström-Engström, Kristin
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Brommesson, Caroline
    Department of Physics, Chemistry and Biology, Division of Molecular Surface Physics and Nanoscience, Linköping University, Linköping, Sweden.
    Kälvegren, Hanna
    Department of Clinical Pathology and Clinical Genetics, Linköping University Hospital, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden .
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för läkarutbildning.
    Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation2014Ingår i: Biointerphases, ISSN 1934-8630, E-ISSN 1559-4106, Vol. 9, nr 4, s. 041003-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Platelets are considered to have important functions in inflammatory processes as key players in innate immunity. Toll like receptors (TLRs), expressed on platelets, recognize pathogen associated molecular patterns and trigger immune responses. Pathogens are able to adhere to human tissues and form biofilms which cause a continuous activation of the immune system. The authors aimed to investigate how immobilized Pam(3)CSK(4) (a synthetic TLR2/1 agonist) and IgG, respectively, resembling a bacterial focus, affects adhesion and activation of platelets including release of two cytokines, regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF). The authors also aim to clarify the signaling downstream of TLR2/1 and Fc gamma RII (IgG receptor) and the role of adenine nucleotides in this process. Biolayers of Pam(3)CSK(4) and IgG, respectively, were confirmed by null-ellipsometry and contact angle measurements. Platelets were preincubated with signaling inhibitors for scr and Syk and antagonists for P2X1 or P2Y1 [adenosine triphosphate (ATP), adenosine diphosphate (ADP) receptors] prior to addition to the surfaces. The authors show that platelets adhere and spread on both Pam(3)CSK(4)- and IgG-coated surfaces and that this process is antagonized by scr and Syc inhibitors as well as P2X1 and P2Y antagonists. This suggests that Pam(3)CSK(4) activated platelets utilize the same pathway as Fc gamma RII. Moreover, the authors show that ATP-ligation of P2X1 is of importance for further platelet activation after TLR2/1-activation, and that P2Y12 is the prominent ADP-receptor involved in adhesion and spreading. RANTES and MIF were secreted over time from platelets adhering to the coated surfaces, but no MIF was released upon stimulation with soluble Pam(3)CSK(4). These results clarify the importance of TLR2/1 and Fc gamma RII in platelet adhesion and activation, and strengthen the role of platelets as an active player in sensing bacterial infections.

  • 200.
    Klarström-Engström, Kristin
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Khalaf, Hazem
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Kälvegren, H.
    Department of Clinical Pathology and Clinical Genetics, Linköping University Hospital, Linköping, Sweden.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för läkarutbildning.
    The role of Porphyromonas gingivalis gingipains in platelet activation and innate immune modulation2015Ingår i: Molecular Oral Microbiology, ISSN 2041-1006, E-ISSN 2041-1014, Vol. 30, nr 1, s. 62-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Platelets are considered to have important functions in inflammatory processes and as actors in the innate immunity. Several studies have shown associations between cardiovascular disease and periodontitis, where the oral anaerobic pathogen Porphyromonas gingivalis has a prominent role in modulating the immune response. Porphyromonas gingivalis has been found in atherosclerotic plaques, indicating spreading of the pathogen via the circulation, with an ability to interact with and activate platelets via e.g. Toll-like receptors (TLR) and protease-activated receptors. We aimed to evaluate how the cysteine proteases, gingipains, of P.gingivalis affect platelets in terms of activation and chemokine secretion, and to further investigate the mechanisms of platelet-bacteria interaction. This study shows that primary features of platelet activation, i.e. changes in intracellular free calcium and aggregation, are affected by P.gingivalis and that arg-gingipains are of great importance for the ability of the bacterium to activate platelets. The P.gingivalis induced a release of the chemokine RANTES, however, to a much lower extent compared with the TLR2/1-agonist Pam(3)CSK(4), which evoked a time-dependent release of the chemokine. Interestingly, the TLR2/1-evoked response was abolished by a following addition of viable P.gingivalis wild-types and gingipain mutants, showing that both Rgp and Kgp cleave the secreted chemokine. We also demonstrate that Pam(3)CSK(4)-stimulated platelets release migration inhibitory factor and plasminogen activator inhibitor-1, and that also these responses were antagonized by P.gingivalis. These results supports immune-modulatory activities of P.gingivalis and further clarify platelets as active players in innate immunity and in sensing bacterial infections, and as target cells in inflammatory reactions induced by P.gingivalis infection.

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