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  • 1. Bergman, Vivi
    et al.
    Leanderson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Starkhammar, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Urinary excretion of 8-hydroxydeoxyguanosine and malondialdehyde after high dose radiochemotherapy preceding stem cell transplantation2004In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 36, no 3, p. 300-306Article in journal (Refereed)
    Abstract [en]

    The urinary excretion of the hydroxylated DNA base 8-hydroxydeoxyguanosine (8-OHdG) and the lipid peroxidation product malondialdehyde (MDA) was monitored in 11 patients with hematological malignancies undergoing total body irradiation and high-dose chemotherapy preceding bone marrow transplantation. Nine patients showed a prompt increase in urinary 8-OHdG (8-25 times the initial baseline level) on days 0-7 after irradiation onset, the excretion then decreased during the aplastic period and increased again when engraftment took place (in 7 patients). A significant positive correlation was found between urinary 8-OHdG and whole blood leukocyte count, both on day 5 (p = .04, r = .72) and on day 22 (p = .009, r = .80) after irradiation onset. One patient who lacked the first peak of 8-OHdG excretion showed low blood leukocyte counts (less than 2×109/l) before therapy onset, this patient, however, later had a successful engraftment and then also showed considerable increases in both 8-OHdG excretion and leukocyte count. These observations suggest leukocytes play a part in the excretion of 8-OHdG after conditioning therapy preceding bone marrow transplantation. As opposed to the biphasic 8-OHdG excretion, the excretion of MDA showed a single peak appearing on days 11-19 after radiochemotherapy onset, i.e., during the period in which the patients suffered from cytopenia, mucositis, and other side effects of the treatment. It is suggested, therefore, that these clinical manifestations are associated with increased lipid peroxidation. Altogether, these findings illustrate the utility of serial urinary samples for monitoring oxidative stress due to conditioning therapy in clinical practice. They also demonstrate that different oxidative stress markers may behave quite differently regarding their appearance in the urine after whole-body oxidative stress.

  • 2. Carstensen, U
    et al.
    Hou, S
    Alexandrie, A-K
    Högstedt, B
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Warholm, M
    Rannung, A
    Lambert, B
    Axmon, A
    Hagmar, L
    Influence of genetic polymorphisms of biotransformation enzymes on gene mutations, strand breaks of deoxyribonucleic acid, and micronuclei in mononuclear blood cells and urinary 8-hydroxydeoxyguanosine in potroom workers exposed to polyaromatic hydrocarbons.1999In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 25, p. 351-360Article in journal (Refereed)
  • 3.
    Fornander, Louise
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science.
    Ghafouri, Bijar
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Kihlström, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Schön, Thomas
    Kalmar County Hospital.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science.
    Innate immunity proteins and a new truncated form of SPLUNC1 in nasopharyngeal aspirates from infants with respiratory syncytial virus infection2011In: PROTEOMICS CLINICAL APPLICATIONS, ISSN 1862-8346, Vol. 5, no 9-10, p. 513-522Article in journal (Refereed)
    Abstract [en]

    Purpose: Respiratory syncytial virus (RSV) is the most common cause of severe respiratory tract infection in infants. The aim was to identify host defence components in nasopharyngeal aspirate (NPA) from infants with RSV infection and to study the expression of the novel 25 kDa innate immunity protein SPLUNC1. less thanbrgreater than less thanbrgreater thanExperimental design: NPAs from infants were analyzed with 2-DE and MS in a pilot study. The levels of SPLUNC1 were analyzed with immunoblotting in 47 NPAs, admitted for RSV diagnosis. less thanbrgreater than less thanbrgreater thanResults: Totally, 35 proteins were identified in NPA, including several innate immunity proteins such as group X phospholipase A(2), different S100 proteins and SPLUNC1. In addition, a new truncated 15 kDa form of SPLUNC1 was identified that was detected in about 50% of the aspirates admitted for RSV diagnosis. RSV-positive boys had significantly less 25 kDa SPLUNC1 than RSV-negative boys while there were no significant differences among girls. less thanbrgreater than less thanbrgreater thanConclusions and clinical relevance: Several important innate immunity proteins were identified in NPA. Notably, a new truncated form of the newly suggested anti-bacterial protein SPLUNC1 was found. It is possible that a decrease in SPLUNC1 in the upper airways may increase the risk for severe pneumonia in boys.

  • 4.
    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.
    Carlsson, Anders
    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.
    Holmberg, Sara
    Department Research and Dev, Sweden.
    Thelin, Anders
    Uppsala University, Sweden.
    Tagesson, Christer
    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, Occupational and Environmental Medicine Center.
    Biomarkers of lsystemic inflammation in farmers with musculoskeletal disorders; a plasma proteomic study2016In: BMC Musculoskeletal Disorders, E-ISSN 1471-2474, Vol. 17, no 206Article in journal (Refereed)
    Abstract [en]

    Background: Farmers have an increased risk for musculoskeletal disorders (MSD) such as osteoarthritis of the hip, low back pain, and neck and upper limb complaints. The underlying mechanisms are not fully understood. Workrelated exposures and inflammatory responses might be involved. Our objective was to identify plasma proteins that differentiated farmers with MSD from rural referents. Methods: Plasma samples from 13 farmers with MSD and rural referents were included in the investigation. Gel based proteomics was used for protein analysis and proteins that differed significantly between the groups were identified by mass spectrometry. Results: In total, 15 proteins differed significantly between the groups. The levels of leucine-rich alpha-2-glycoprotein, haptoglobin, complement factor B, serotransferrin, one isoform of kininogen, one isoform of alpha-1-antitrypsin, and two isoforms of hemopexin were higher in farmers with MSD than in referents. On the other hand, the levels of alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, vitamin D-binding protein, apolipoprotein A1, antithrombin, one isoform of kininogen, and one isoform of alpha-1-antitrypsin were lower in farmers than in referents. Many of the identified proteins are known to be involved in inflammation. Conclusions: Farmers with MSD had altered plasma levels of protein biomarkers compared to the referents, indicating that farmers with MSD may be subject to a more systemic inflammation. It is possible that the identified differences of proteins may give clues to the biochemical changes occurring during the development and progression of MSD in farmers, and that one or several of these protein biomarkers might eventually be used to identify and prevent work-related MSD.

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  • 5.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Irander, Kristina
    Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Lindbom, John
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Comparative proteomics of nasal fluid in seasonal allergic rhinitis2006In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 5, no 2, p. 330-338Article in journal (Refereed)
    Abstract [en]

    A comparative proteomic approach was applied to examine nasal lavage fluid (NLF) from patients with seasonal allergic rhinitis (SAR, n = 6) and healthy subjects (controls, n = 5). NLF samples were taken both before allergy (pollen) season and during season, and proteins were analyzed by two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) after tryptic cleavage. Twenty proteins were selected and quantified. During allergy season, the levels of six sialylated isoforms of PLUNC (palate lung nasal epithelial clone) were lower in SAR patients than controls, as were the levels of six isoforms of von Ebner's gland protein (VEGP), including a previously undescribed form with N-linked glycosylation, and of cystatin S. PLUNC is a new innate immunity protein and VEGP and cystatin S are two endogenous proteinase inhibitors. By contrast, the levels of an acidic form of alpha-1-antitrypsin were higher in SAR patients than controls. One previously unidentified NLF protein was found in all samples from the SAR patients during allergy season but not in any sample before allergy season:  this protein was identified as eosinophil lysophospholipase (Charcot-Leyden crystal protein/galactin 10). MS/MS analysis of the N-terminus of the protein showed removal of Met and acetylation of Ser. Altogether, these findings illustrate the potential use of proteomics for identifying protein changes associated with allergic rhinitis and for revealing post-translational modifications of such new potential markers of allergic inflammation.

  • 6.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Lewander, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Peptide mass fingerprint data from silver stained proteins can be improved by using 2,5-dihydroxybenzoic acid instead of α-cyano-4-hydroxycinnamic acid as matrix in MALDI-TOF MS2007Article in journal (Refereed)
  • 7.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Mörtstedt, Harriet
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Lewander, Andreas
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Note: 2,5-Dihydroxybenzoic acid instead of α-cyano-4-hydroxycinnamic acid as matrix in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for analyses of in-gel digests of silver-stained proteins: in Analytical Biochemistry(ISSN 0003-2697), vol 371, issue 1, pp 121-1232007In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 371, no 1, p. 121-123Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 8.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Kihlström, Erik
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Ståhlbom, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid2003In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 31, no 4, p. 810-814Article in journal (Refereed)
    Abstract [en]

    PLUNC (palate, lung and nasal epithelial clone) is a newly discovered gene that is expressed in the upper respiratory tract and is suggested to be of importance in host defence against bacteria. We have identified two forms of the PLUNC protein in human nasal lavage fluid (NLF) using two-dimensional gel electrophoresis (2-DE) and MS. The apparent molecular masses and isoelectric points of these forms are 24.8 kDa/pI 5.4 and 25.1 kDa/pI 5.5. Notably, the 24.8 kDa/pI 5.4 form of PLUNC is an abundant protein in the 2-DE protein patterns of NLF from healthy subjects. Decreased levels of PLUNC were found in NLF from smokers and workers exposed to reactive epoxy chemicals, indicating that long-term exposure to airway irritants impairs the production of PLUNC in the upper respiratory tract. We have also investigated the presence of lipopolysaccharide (LPS)-binding proteins in NLF. Five proteins were found to adsorb to a LPS-coated surface; two of these proteins correspond to the two PLUNC forms, as judged by 2-DE pattern matching. For comparison, human saliva was found to contain a set of LPS-binding proteins with similar 2-DE spot positions (the same pIs but somewhat lower apparent molecular masses of 20 kDa). These results indicate that PLUNC may be a new marker of airway inflammation and may play a part in the innate immune response, and that human saliva contains yet other members of the family of LPS-binding proteins.

  • 9.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Kihlström, Erik
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    PLUNC in human nasal lavage fluid: multiple isoforms that bind to lipopolysaccharide2004In: Biochimica et Biophysica Acta - Proteins and Proteomics, ISSN 1570-9639, E-ISSN 1878-1454, Vol. 1699, no 1-2, p. 57-63Article in journal (Refereed)
    Abstract [en]

    Here, we demonstrate the presence of multiple isoforms of palate lung nasal epithelial clone (PLUNC) in human nasal lavage fluid (NLF). Eight isoforms were separated by two-dimensional gel electrophoresis (2-DE), and peptide mapping of the proteins was performed using MALDI-TOF MS (matrix assisted laser desorption/ionization time of flight mass spectrometry) of tryptic and asparginase cleavages. The identification was verified by amino acid sequencing after analysis of collision-induced dissociation (CID) fragmentation spectra with nanoelectrospray MS/MS. One isoform showed an electrophoretic mobility shift after N-glycosidase treatment, indicating that at least one of the PLUNC isoforms is glycosylated. We also demonstrate that PLUNC in NLF binds to lipopolysaccharide (LPS) in vitro; indeed, out of all proteins present in NLF only the PLUNC isoforms were found to adsorb to an LPS-coated surface. These results show that PLUNC is expressed as multiple LPS-binding isoforms in human NLF. The possibility that PLUNC may play a role in the innate immune response of the upper airways is inferred.

  • 10.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Persson, H Lennart
    Linköping University, Department of Medical and Health Sciences, Pulmonary Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Intriguing bronchoalveolar lavage proteome in a case of pulmonary langerhans cell histiocytosis2013In: The American journal of case reports, ISSN 1941-5923, Vol. 14, p. 129-133Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease associated with tobacco smoke exposure. New insights into its pathogenesis and how it differs from that of chronic obstructive pulmonary disease (COPD) may be provided by proteomic studies on bronchoalveolar lavage fluid (BALF).

    CASE REPORT: We present the BALF proteome in a biopsy-proven case of PLCH and compare it with typical proteomes of COPD and of the healthy lung. The BALF proteins were separated by two-dimensional gel electrophoresis (2-DE) and the protein patterns were analyzed with a computerized 2-DE imaging system. As compared to the healthy subject and the COPD case, the PLCH case showed a strikingly different 2-DE pattern. There was much more IgG (heavy chain) and orosomucoid, and less α1-antitrypsin, surfactant protein-A, haptoglobin, cystatin-S, Clara cell protein 10, transthyretin and gelsolin. Moreover, no apolipoprotein-A1, pro-apolipoprotein-A1, amyloid P, calgranulin A, or calgranulin B was detected at all.

    CONCLUSIONS: This case of PLCH presents with an extreme BALF proteome lacking significant amounts of protective and anti-inflammatory proteins. Thus, the intriguing BALF proteome opens up new lines of research into the pathophysiology of PLCH and how its pathogenesis differs from that in COPD.

  • 11.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ståhlbom, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Newly identified proteins in human nasal lavage fluid from non-smokers and smokers using two-dimensional gel electrophoresis and peptide mass fingerprinting2002In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 2, no 1, p. 112-120Article in journal (Refereed)
    Abstract [en]

    Human nasal lavage fluids (NLFs) were analyzed with two-dimensional gel electrophoresis (2-DE) and proteins were identified with peptide mass fingerprinting using matrix-assisted laser desoption/ionization time of flight mass spectrometry. In some cases, the identification was verified by analysis of post-source decay fragmentation spectra. Many of the identified proteins were new forms or fragments of previously found proteins (e.g. albumin, lactoferrin, cystatin, calgranulin, von Ebners gland protein and palate lung nasal epithelium clone), while others were proteins that have previously been indicated by 2-DE image matching or immunoblots (e.g. apolipoprotein AI, lysozyme C, and Clara cell secretory protein). Some new proteins, not shown before in 2-DE patterns of NLF were also found, e.g. mammaglobin B, 2-microglobulin and immunoglobulin J chain. Of the identified NLF proteins many appear to be involved in inflammatory and immune responses. A study was therefore conducted to investigate if the levels of these proteins were changed in smokers compared to nonsmokers. It was found that NLF from smokers contained decreased levels of Clara cell secretory protein, and increased proportions of a truncated variant of lipocortin-1, three acidic forms of α1-antitrypsin, and one phosphorylated form of cystatin S. Furthermore, NLF from smokers contained increased proportions of a new variant of palate lung nasal epithelium clone (PLUNC), a recently identified airway irritation marker. The results demonstrate that 2-DE of NLF may be used to assess alterations of proteins or post-translationally modified proteins in smokers. Clara cell secretory protein (CC 16, CC 10) and lipocortin-1 are two anti-inflammatory, phospholipase A2 inhibitory proteins, and α1-antitrypsin and cystatin S are two proteinase inhibitors. Changed levels of these proteins may therefore be of importance to the airway inflammation caused by smoking. The results also support the notion that PLUNC is involved in inflammatory responses in the upper airways.

  • 12.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Mapping of proteins in human saliva using two-dimensional gel electrophoresis and peptide mass fingerprinting2003In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 3, no 6, p. 1003-1015Article in journal (Refereed)
    Abstract [en]

    Human saliva contains a large number of proteins that can be used for diagnosis and are of great potential in clinical and epidemiological research. The aim of this work was to map the proteins in saliva by two-dimensional gel electrophoresis (2-DE), and to identify abundant proteins by peptide mass fingerprinting using trypsin cleavage and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry analysis. One hundred proteins were identified representing 20 different identities according to accession numbers. Abundant proteins expressed in different forms were: α-amylase, immunoglobulin A, prolactin-inducible protein, zinc-α2-glycoprotein and cystatins (S, SA, D and SN). Other proteins found were interleukin-1 receptor antagonist, von Ebner’s gland protein (lipocalin-1) and calgranulin A and B (S100A8 and A9). Furthermore, apolipoprotein A-I, β2-microglobulin, glutathione S-transferase P and fatty acid-binding protein were also identified. Our results show that human saliva contains a large number of proteins that are involved in inflammatory and immune responses. The 2-DE protein map constructed opens the possibility to investigate protein changes associated with disease processes.

  • 13.
    Hammar, Mats
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Strålning, cancer och forskarutbildning2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104Article in journal (Other academic)
  • 14.
    Jayawardena, Umesh
    et al.
    Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Tollemark, Linda
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Pyrogenic effect of respirable road dust particles2009In: Inhaled Particles X / [ed] Lee Kenny, Fintan Hurley, Institute of Physics Publishing (IOPP), 2009, Vol. 151, p. 012015-Conference paper (Refereed)
    Abstract [en]

    Because pyrogenic (fever-inducing) compounds on ambient particles may play an important role for particle toxicity, simple methods to measure pyrogens on particles are needed. Here we have used a modified in vitro pyrogen test (IPT) to study the release of interleukin 1β (IL-1β) in whole human blood exposed to respirable road-dust particles (RRDP). Road dusts were collected from the roadside at six different streets in three Swedish cities and particles with a diameter less than 10 μm (RRDP) were prepared by a water sedimentation procedure followed by lyophilisation. RRDP (200 μl of 1 - 106 ng/ml) were mixed with 50 μl whole blood and incubated at 37 °C overnight before IL-1β was analysed with chemiluminescence ELISA in 384-well plates. Endotoxin (lipopolysaccharide from Salmonella minnesota), zymosan B and Curdlan (P-1,3-glucan) were used as positive controls. All RRDP samples had a pyrogenic effect and the most active sample produced 1.6 times more IL-1β than the least active. This formation was of the same magnitude as in samples with 10 ng LPS/ml and was larger than that evoked by zymosan B and Curdlan (by mass basis). The method was sensitive enough to determine formation of IL-1β in mixtures with 10 ng RRDP/ml or 0.01 ng LPS/ml. The endotoxin inhibitor, polymyxin B (10 μg/ml), strongly reduced the RRDP-induced formation of IL-1β at 1μg RRDP/ml (around 80 % inhibition), but had only marginal or no effects at higher RRDP-concentrations (10 and 100 μg /ml). In summary, all RRDP tested had a clear pyrogen effect in this in vitro model. Endotoxin on the particles but also other factors contributed to the pyrogenic effect. As opposed to the limulus amebocyte lysate (LAL) assay (which measures endotoxin alone), IPT measures a broad range of pyrogens that may be present on particulate matter. The IPT method thus affords a simple, sensitive and quantitative determination of the total pyrogenic potential of ambient particles.

  • 15.
    Karlsson, Helen
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Ghafouri, Bijar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Leanderson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Kartläggning av proteiner i LDL och HDL med två-dimensionell gelelektrofores samt masspektrometri.2003In: Svenska Läkaresällskapets Handlingar,2003, 2003, p. 11-26Conference paper (Refereed)
  • 16.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lipoproteomics I: Mapping of proteins in low-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry2005In: Proteomics, ISSN 1615-9853, Vol. 5, no 2, p. 551-565Article in journal (Refereed)
    Abstract [en]

    The molecular mechanisms underlying the relationship between low-density lipoprotein (LDL) and the risk of atherosclerosis are not clear. Therefore, detailed information about the protein composition of LDL may contribute to reveal its role in atherogenesis and the mechanisms that lead to coronary disease in humans. Here, we sought to map the proteins in human LDL by a proteomic approach. LDL was isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix assisted laser desorption/ionization-time of flight-mass spectrometry and with amino acid sequencing using electrospray ionization tandem mass spectrometry. These procedures identified apo B-100, apo C-II, apo C-III (three isoforms), apo E (four isoforms), apo A-I (two isoforms), apo A-IV, apo J and apo M (three isoforms not previously described). In addition, three proteins that have not previously been identified in LDL were found: serum amyloid A-IV (two isoforms), calgranulin A, and lysozyme C. The identities of apo M, calgranulin A, and lysozyme C were confirmed by sequence information obtained after collision-induced dissociation fragmentation of peptides characteristic for these proteins. Moreover, the presence of lysozyme C was further corroborated by demonstrating enriched hydrolytic activity in LDL against Micrococcus lysodeikticus. These results indicate that in addition to the dominating apo B-100, LDL contains a number of other apolipoproteins, many of which occur in different isoforms. The demonstration, for the first time, that LDL contains calgranulin A and lysozyme C raises the possibility that LDL proteins may play hitherto unknown role(s) in immune and inflammatory reactions of the arterial wall.

  • 17.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lipoproteomics II: Mapping of proteins in high-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry2005In: Proteomics, ISSN 1615-9853, Vol. 5, no 5, p. 1431-1445Article in journal (Refereed)
    Abstract [en]

    High-density lipoprotein (HDL) is the most abundant lipoprotein particle in the plasma and a negative risk factor of atherosclerosis. By using a proteomic approach it is possible to obtain detailed information about its protein content and protein modifications that may give new information about the physiological roles of HDL. In this study the two subfractions; HDL2 and HDL3, were isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix-assisted laser desorption/ionisation time of flight mass spectrometry. Identified proteins in HDL were: the dominating apo A-I as six isoforms, four of them with a glycosylation pattern and one of them with retained propeptide, apolipoprotein (apo) A-II, apo A-IV, apo C-I, apo C-II, apo C-III (two isoforms), apo E (five isoforms), the recently discovered apo M (two isoforms), serum amyloid A (two isoforms) and serum amyloid A-IV (six isoforms). Furthermore, alpha-1-antitrypsin was identified in HDL for the first time. Additionally, salivary alpha-amylase was identified as two isoforms in HDL2, and apo L and a glycosylated apo A-II were identified in HDL3. Besides confirming the presence of different apolipoproteins, this study indicates new patterns of glycosylated apo A-I and apo A-II. Furthermore, the study reveals new proteins in HDL; alpha-1-antitrypsin and salivary alpha-amylase. Further investigations about these proteins may give new insight into the functional role of HDL in coronary artery diseases.

  • 18.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lindbom, John
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Gustafsson, Mats
    Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Ljungman, Anders G
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Wear Particles from Studded Tires and Granite Pavement Induce Pro-inflammatory Alterations in Human Monocyte-Derived Macrophages: A Proteomic Study.2011In: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 24, p. 45-53Article in journal (Refereed)
    Abstract [en]

    Airborne particulate matter is considered to be one of the environmental contributors to the mortality in cancer, respiratory, and cardiovascular diseases. For future preventive actions, it is of major concern to investigate the toxicity of defined groups of airborne particles and to clarify their pathways in biological tissues. To expand the knowledge beyond general inflammatory markers, this study examined the toxicoproteomic effects on human monocyte derived macrophages after exposure to wear particles generated from the interface of studded tires and a granite-containing pavement. As comparison, the effect of endotoxin was also investigated. The macrophage proteome was separated using two-dimensional gel electrophoresis. Detected proteins were quantified, and selected proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Among analyzed proteins, seven were significantly decreased and three were increased by exposure to wear particles as compared to unexposed control cells. Endotoxin exposure resulted in significant changes in the expression of six proteins: four decreased and two increased. For example, macrophage capping protein was significantly increased after wear particle exposure only, whereas calgizzarin and galectin-3 were increased by both wear particle and endotoxin exposure. Overall, proteins associated with inflammatory response were increased and proteins involved in cellular functions such as redox balance, anti-inflammatory response, and glycolysis were decreased. Investigating the effects of characterized wear particles on human macrophages with a toxicoproteomic approach has shown to be useful in the search for more detailed information about specific pathways and possible biological markers.

  • 19.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lindqvist, Helen
    Department of Chemistry and Bioscience/Food Science, Chalmers University of Technology, Göteborg, Sweden.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Characterization of apolipoprotein M isoforms in low-density lipoprotein2006In: Journal of proteome research, ISSN 1535-3893, Vol. 5, no 10, p. 2685-2690Article in journal (Refereed)
    Abstract [en]

    Apo M is a recently discovered human lipoprotein thought to be involved in the metabolism of lipids and lipoprotein particles. Here, a proteomic approach was applied to examine the glycosylation pattern of apo M in human LDL. We treated LDL proteins with N-glycosidase or neuraminidase, studied mobility shifts of Apo M by two-dimensional gel electrophoresis, and different isoforms were then identified with mass spectrometry. This way, we demonstrated the presence of five isoforms of apo M in LDL:  three that are both N-glycosylated and sialylated, one that is N-glycosylated but not sialylated, and one that is neither N-glycosylated nor sialylated. As judged from the examination of LDL from 20 healthy human subjects, the three N-glycosylated and sialylated forms are most abundant (80−100% of the total apo M in LDL) whereas the unsialylated and unglycosylated variants constitute at most 20%. Comparative analysis showed that the same five isoforms of apo M are also present in HDL. Further studies aiming at elucidating the role of apo M in health and disease will have to take this polymorphism of apo M proteins into account.

  • 20.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre. Östergötlands Läns Landsting, Centre for Medicine.
    Mortstedt, Harriet
    n/a.
    Lindqvist, Helen
    Chalmers.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Protein profiling of low-density lipoprotein from obese subjects2009In: PROTEOMICS CLINICAL APPLICATIONS, ISSN 1862-8346, Vol. 3, no 6, p. 663-671Article in journal (Refereed)
    Abstract [en]

    Although obesity and high levels of low-density lipoprotein (LDL) are well-known risk factors for cardiovascular disease, the precise role(s) of different LDL constituents in obesity has not been explored. In the present study, we compared the LDL proteome of healthy control adults (body mass index less than 25) and obese subjects (body mass index greater than 30). LDL was isolated by density-gradient ultracentrifugation and proteins were separated with 2-D PAGE, quantified, and identified by peptide mass fingerprinting using MALDI-TOF MS. A new LDL-associated protein was identified as transthyretin and found to be significantly more abundant in LDL from the obese subjects. In addition, LDL from the obese subjects contained relatively more alpha(1)-antitrypsin, apo J, apo C-II, than LDL from controls, and also more of an acidic isoform (pI/Mr; 5.2/23 100) of apo A-I. On the other hand, the relative amounts of apo A-IV and the major isoform of apo A-I (pI/Mr; 5.3/23 100) were significantly less in LDL from the obese subjects. Apo E was less and non-sialylated apo C-III more abundant in LDL from obese men than control men, while there were no such differences between LDL from obese and control women. These findings illustrate that obesity is not only associated with increased LDL-cholesterol levels but also with alterations in the LDL protein composition. The presence of transthyretin in LDL from obese subjects may reflect over-nutrition and affect the lipid metabolism in obesity.

  • 21.
    Kristenson, Margareta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Östergötlands Läns Landsting, FHVC - Folkhälsovetenskapligt centrum, Socialmed FHVC.
    Kucinskiené, Zita
    Schäfer-Elinder, Liselotte
    Leanderson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Lower serum levels of beta-carotene in Lithuanian men are accompanied by higher urinary excretion of the oxidative DNA adduct, 8-hydroxydeoxyguanosine: The LiVicordia study.2003In: Nutrition (Burbank, Los Angeles County, Calif.), ISSN 0899-9007, E-ISSN 1873-1244, Vol. 19, no 1, p. 11-15Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: In 1995, middle-aged Lithuanian men had a four-fold higher risk than Swedish men of dying from coronary heart disease. The cross-sectional LiVicordia study had reported significantly lower levels of the lipid-soluble antioxidants lycopene, ▀-carotene, and ?-tocopherol among Lithuanian men than among Swedish men. We examined whether there were differences in urinary 8-hydroxydeoxyguanosine (8OHdG), a marker of oxidative stress, between these groups of men. METHODS: Using automated coupled column high-performance liquid chromatography with electrochemical detection, we examined 50-y-old men randomly sampled from Link÷ping, Sweden (n = 99) and Vilnius, Lithuania (n = 109) with regard to urinary concentrations of 8-OHdG. RESULTS: Levels of 8-OHdG were higher in the Lithuanian men than in the Swedish men (20.9 ▒ 0.91 versus 14.9 ▒ 0.75 nM/L, P < 0.001), and this difference was evident in smokers (P < 0.01) and non-smokers (P < 0.001). Serum levels of a- and ▀-carotene were inversely correlated to urinary 8-OHdG levels (P < 0.05 in both cases). Habitual smoking and low levels of ▀-carotene contributed significantly to higher oxidative DNA damage expressed as urinary 8-OHdG. CONCLUSIONS: These findings indicate that increased urinary 8-OHdG levels accompany lower serum levels of antioxidants in Lithuanian men. They supported previous suggestions that increased oxidative stress may be one factor behind the higher mortality in Lithuanian men. ⌐ Elsevier Science Inc. 2003.

  • 22.
    Kristjansson, I
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice.
    Faresjö, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice.
    Lionis, C
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice.
    Nosratabadi, Ali Reza
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Gudmundsson, K
    Halling, A
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment. Östergötlands Läns Landsting, FHVC - Folkhälsovetenskapligt centrum, Förebygg.med.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Assessment of aluminium in human deciduous teeth2000In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 16, no 3, p. 231-233Article in journal (Refereed)
    Abstract [en]

    The possible role of environmental aluminium exposure in the pathogenesis of various diseases has highlighted the need for methods by which the long-term exposure to aluminium can be assessed. Therefore, we have further developed a method to determine aluminium in human deciduous teeth and applied this method for studying populations in Sweden, Crete and Iceland.

  • 23.
    Lagesson, Verner
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Nilsson, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Qualitative determination of compounds adsorbed on indoor dust particles using GC-UV and GC-MS after thermal desorption2000In: Chromatographia, ISSN 0009-5893, Vol. 52, no 9-10, p. 621-630Article in journal (Refereed)
    Abstract [en]

    Fifteen indoor dust samples were analysed qualitatively to determine the compounds adsorbed on the surfaces of the particles. The analyses were performed by GC-MS and GC-UV after thermal desorption at 150°C. A total of 192 different compounds with boiling points from about 50°C to 250°C were identified or classified. The results from the two methods, which were carried out under similar conditions of thermal desorption and gas chromatographic separation, were complementary. GC-MS clearly showed better results for non-aromatic compounds such as alkanes, chlorinated hydrocarbons, acids, esters and alcohols, but for aldehydes and compounds containing unconjugated double bonds the two methods were about equally successful. However, for aromatic or conjugated compounds, the GC-UV method had a clear advantage. Also two iodonated compounds were determined only by the GC-UV technique. These findings indicate that the combined use of GC-UV and GC-MS is appropiate for the analysis of chemical compounds adsorbed on indoor dust particles.

  • 24.
    Lindahl, Mats
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Irander, Kristina
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Ståhlbom, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Nasal lavage fluid and proteomics as means to identify the effects of the irritating epoxy chemical dimethylbenzylamine2004In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 9, no 1, p. 56-70Article in journal (Refereed)
    Abstract [en]

    The aims of this study were to describe the changes in the nasal lavage fluid (NLF) protein pattern after exposure to the irritating epoxy chemical dimethylbenzylamine (DMBA) and to identify the affected proteins using a proteomic approach. The protein patterns of NLF from six healthy subjects and eight epoxy workers with airway irritation were analysed using two-dimensional gel electrophoresis (2-DE) before and after exposure to 100 μg m-3 DMBA for 2 h in an exposure chamber. NLF proteins were identified by (i) comparison with a 2-DE NLF reference database, (ii) N-terminal amino acid sequencing, and (iii) mass spectrometry. In NLF from healthy subjects, the levels of immunoglobulin A increased and the levels of Clara cell protein 16 (CC16) decreased after chamber exposure, while in NLF from epoxy workers, α2-macroglobulin and caeruloplasmin increased. Two previously unidentified proteins decreased in NLF from epoxy workers after exposure, these were identified as statherin and calgranulin B. In addition, the subjects who developed high counts of eosinophils in their nasal mucosa after chamber exposure had significantly lower levels of immunoglobulin-binding factor (IgBF) before exposure than subjects with low eosinophil infiltration. These results show that short-term exposure to DMBA causes distinct changes in NLF proteins. Moreover, three proteins that have previously not been associated with upper airway irritation were identified: statherin, calgranulin B and IgBF. Further studies are needed to investigate whether these proteins may be used as biomarkers of airway irritation and to give new insight into the ways in which occupational exposure to irritants causes inflammation of the airways.

  • 25.
    Lindahl, Mats
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Ståhlbom, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Identification of a new potential airway irritation marker, palate lung nasal epithelial clone protein, in human nasal lavage fluid with two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time of flight.2001In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 22, p. 1795-1800Article in journal (Refereed)
  • 26.
    Lindahl, Mats
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Ståhlbom, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Newly identified proteins in human nasal and bronchoalveolar lavage fluids: Potential biomedical and clinical applications.1999In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 20, p. 3670-3676Article in journal (Refereed)
  • 27.
    Lindahl, Mats
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Svartz, Jesper
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Demonstration of different forms of the anti-inflammatory proteins lipocortin-1 and Clara cell protein-16 in human nasal and bronchoalveolar lavage fluids1999In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 20, no 4-5, p. 881-890Article in journal (Refereed)
    Abstract [en]

    The anti-inflammatory proteins lipocortin-1 and Clara cell protein-16 (CC-16) were studied in two-dimensional gel electrophoresis (2-DE) protein patterns of human nasal lavage fluids (NLFs) and bronchoalveolar lavage fluids (BALFs). Seven forms of lipocortin-1 were detected with Western immunoblots: three isoforms with an apparently normal Mr of 38 kDa and pI of 5.9, 6.0 and 6.1, and four truncated variants with pI/kDa 6.0/36, 6.4/36, 7.0/33, and 7.4/34. Four 6 kDa isoforms of CC-16 were found with pI 4.6, 4.8, 4.9, and 5.2. Lipocortin-1 and CC-16 were expressed in all individuals tested although not all variants were found in each individual. The overall levels of lipocortin-1 were higher in BALF than NLF and there were significant differences in the distribution of the different lipocortin-1 forms between BALFs and NLFs. One patient with occupational asthma and four children with rhinitis had increased levels of one of the truncated lipocortin-1 forms in NLF (pI/kDa: 7.4/34) and decreased levels of the major CC-16 form (pI/kDa: 4.8/6). The levels of CC-16 but not of lipocortin-1 were higher in BALF from smokers than from nonsmokers. These results indicate that the levels of lipocortin-1 and CC-16 in NLF and BALF may be altered in inflammatory airway disorders. Furthermore, the identification of different forms of the two proteins makes possible more detailed studies on the role of these proteins in inflammatory disease processes and anti-inflammatory therapies.

  • 28.
    Lindbom, John
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ljungman, Anders G.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lipopolysaccharide- and ß-glucan-stimulated macrophages upregulate cytolosic phospholipase A2 IVC in nasal epithelial cells: role of TNF-αManuscript (preprint) (Other academic)
    Abstract [en]

    Phospholipase A2 (PLA2) is a superfamily of enzymes that may play a major role in airways inflammation. We investigated the gene expression of 20 different PLA2 types in nasal epithelial cells (RPMI 2650) before and after incubation with cell growth medium from human monocyte-derived macrophages exposed to lipopolysaccharide (LPS) or ß-1,3-D-glucan (ßG). The macropbages were exposed to LPS (10 µ/ml) or ßG (500 µg/ml) for 48 hours and the mRNA levels of the different PLA2 types in RPMI 2650 cells were determined after incubation for 18 hours using reverse transcriptase-PCR (RT-PCR). It appeared that the mRNA levels of PLA2 type IVC were significantly increased after incubation, both with medium from LPS-exposed and ßG-exposed macrophages. In both cases, the increased PLA2 IVA mRNA expression was abolished by TNF-α antibodies and by the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). There were no significant alterations in the mRNA levels of the other PLA2 types, including PLA2 IVA. These findings indicate that both LPS- and ßG-activated macrophages can induce the gene expression of PLA2 IVC in nasal epithelial cells, and that this upregulation is mediated through TNF-α and under NF-κB control. Further studies are required to clarify whether these mechanisms may operate to cause inflammation in the nasal mucosa in vivo.

  • 29.
    Lindbom, John
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ljungman, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Irander, Kristina
    Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Phospholipase A2 mRNA expression in the nasal mucosa of healthy subjects and patients with seasonal allergic rhinitis2004In: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 42, no 2, p. 85-91Article in journal (Refereed)
    Abstract [en]

    Phospholipase A2 (PLA2) is a family of enzymes that play different role(s) in inflammation, but their importance in seasonal allergic rhinitis (SAR) has not been clarified. Here, we determined the levels of messenger ribonucleic acid (mRNA) for different PLA2 types in the nasal mucosa of SAR patients (n=6) and healthy controls (n=5). Nasal brush samples were taken both during pollen season, when the symptoms of the patients were severe, and off-season, when the patients were free of symptoms. We found that PLA2 IB, IIA, IID,IIE, IIF III, IVA, IVB, IVC, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII and XIII were all expressed in each subject at both occasions. The mRNA levels of PLA2 VIIA (platelet-activating factor (PAF) acetylhydrolase) were lower in SAR patients than controls, both during pollen season (p = 0.03) and off season (p = 0.03). These findings demonstrate that a large number of PLA2 types are expressed in the nasal mucosa, regardless of whether there is ongoing allergic inflammation or not. The observation that PAF acetylhydrolase mRNA expression in the nasal mucosa is lower in SAR patients than in healthy subjects suggests the possibility that impaired ability to inactivate PAF might be of importance in SAR. Further studies are required to clarify whether the decreased PAF acetylhydrolase mRNA expression in SAR is accompanied by decreased enzyme activity and whether aberrations in PAF acetylhydrolase are present in infectious rhinitis patients as well.

  • 30.
    Lindbom, John
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ljungman, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Expression of members of the phospholipase A2 family of enzymes in human nasal mucosa2001In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 18, no 1, p. 130-138Article in journal (Refereed)
    Abstract [en]

    Phospholipase A2 (PLA2) is a family of enzymes thought to play a key role in inflammation by releasing arachidonic acid for the synthesis of eicosanoids and lysophospholipid for the synthesis of platelet-activating factor. However, the precise contribution of different PLA2 types to the formation of inflammatory lipid mediators in the upper airways is not known and the expression of different PLA2 genes in the human nasal mucosa has not been examined.

    This study therefore investigated the occurrence of messenger ribonucleic acids (mRNAs) for different PLA2 forms (IB, IIA, IID, IIE, III, IVA, IVB, IVC, V, VI, VII, X, acid calcium-independent (aiPLA2), and calcium-independent membrane bound PLA2, (iPLA2-2)) in the nasal mucosa of five healthy human subjects.

    Using reversed transcription-polymerase chain reaction (RT-PCR) techniques it was found that all these PLA2 types except PLA2 V were expressed in all subjects, whereas PLA2 V was detected in only one individual on one single occasion. The relative abundance of the different PLA2 transcripts were aiPLA2>X≈IVA>IIA≈IIE≈IVB≈VI>IB≈IID≈III≈IVC≈VII≈iPLA2-2. To further quantify the mRNA-expression of PLA2 X, IVA and IIA, the samples were reanalysed with a quantitative PCR-technique utilizing competitive deoxyribonucleic acid (DNA) mimics as references. The amounts of PLA2 X, IVA and IIA mRNA were then estimated to 0.9±0.2, 1.1±0.7, and 0.0025±0.0021 amol (mean±se), respectively, confirming the relative abundance of these PLA2 transcripts and indicating that the recently described PLA2 X form is relatively strongly expressed.

    These findings demonstrate that a large number of PLA2 types are expressed in the normal human nasal mucosa. Moreover, this investigation demonstrates, for the first time, the presence of the newly discovered phospholipase A2 forms IID, IIE, III, IVB, IVC, X and calcium-independent membrane bound phospholipase A2 in the human nasal mucosa and raises the possibility that one or several of these may be involved in inflammatory reactions in the nose.

  • 31.
    Lindbom, John
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ljungman, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Increased gene expression of novel cytosolic and secretory phospholipase A2 types in human airway epithelial cells induced by tumor necrosis factor-α and IFN-γ2002In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 22, no 9, p. 947-955Article in journal (Refereed)
    Abstract [en]

    Phospholipase A2 (PLA2) is a growing family of enzymes that may play a major role in inflammation. We investigated the effect of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on the gene expression of 19 different PLA2 types (IB, IIA, IID, IIE, IIF, III, IVA, IVB, IVC, V, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII, and XIII) in human bronchoepithelial (BEAS-2B) and nasal epithelial (RPMI 2650) cells. The cells were stimulated with TNF-α or IFN-γ for different lengths of time (1, 4, 18, and 48 h), and the mRNA levels of the different PLA2 types were determined by reverse transcriptase-PCR (RT-PCR) and normalized to those of the housekeeping gene, GAPDH. In both cell lines, TNF-α increased the expression of PLA2 IVA and IVC, and IFN-γ increased the expression of PLA2 IIA and IID. No influence on the gene expression of PLA2-activating protein (PLAP) was noted on cytokine stimulation. These findings indicate that TNF-α and IFN-γ induce gene expression of two novel cytosolic and secretory PLA2 types (IVC and IID, respectively) in human airway epithelial cells. The possibility that these PLA2 types are involved in cytokine-mediated inflammation in the respiratory tract is inferred.

  • 32.
    Lindbom, John
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ljungman, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Interferon γ-induced gene expression of the novel secretory phospholipase A2 type IID in human monocyte-derived macrophages is inhibited by lipopolysaccharide2005In: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 29, no 2-3, p. 108-117Article in journal (Refereed)
    Abstract [en]

    Phospholipase A2 (PLA2) is a superfamily of enzymes that may play a major role in airways inflammation. We investigated the effect of interferon-γ (IFN-γ) on the gene expression of 19 different PLA2 types in human monocyte-derived macrophages and nasal epithelial cells (RPMI 2650). The cells were stimulated with IFN-γ for different lengths of time (up to 48 h), and the mRNA levels of the different PLA2 types were determined by reverse transcriptase–PCR (RT-PCR) and normalized to those of the house-keeping gene, GAPDH. It appeared that IFN-γ clearly increased the expression of secretory PLA2 IID (but not IIA) in macrophages, while both PLA2 IID and IIA were upregulated in RPMI 2650 cells. Moreover, after 18 h, the mRNA levels of cytosolic PLA2 IVA were 2–3 times higher in IFN-γ-stimulated macrophages than controls, while there was no such effect of IFN-γ in RPMI 2650 cells. Lipopolysaccharide (LPS) augmented the increased gene expression of PLA2 IVA but decreased both the basal and the IFN-γ-induced PLA2 IID mRNA expression in macrophages (but not in RPMI 2650 cells). The NF-κB inhibitor Pyrrolidine dithiocarbamate (PDTC) and the phoshatidylinositol 3-kinase (PI3K) inhibitor wortmannin were employed to get an insight into the mechanism behind these observations. Incubation of macrophages with PDTC had no effect on the LPS impairment of PLA2 IID gene expression, but inhibited the LPS mediated activation of PLA2 IVA. No significant effect was noted of PDTC on IFN-γ stimulation, while PI3K had no effect at all on any of the stimuli used. Furthermore, LPS (but not IFN-γ) increased the mRNA levels of the nuclear factor (NF)-κB inhibitors α and ξ in macrophages, but not in RPMI 2650 cells. These findings indicate that (a) the gene expression of secretory types PLA2 IID and IIA in response to IFN-γ is much dependent on cell type, and (b) the regulation of PLA2 type IID in human macrophages is clearly different from that of PLA2 type IVA. (c) PLA2 IVA is probably under control of both NF-κB and IFN-γ-responsive elements (GRE) or IFN-γ-activating sites (GAS). The possibility that PLA2 IID is involved in cytokine-mediated inflammation in the nasal mucosa is inferred, as is the potential role of PLA2 IID in the host defense against LPS-containing bacteria.

  • 33.
    Nilsson, Anders
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lagesson, Verner
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Bornehag, Carl-Gustaf
    Swedish National Testing and Research Institute.
    Sundell, Jan
    International Centre for Indoor Environment and Energy, Technical University of Denmark, Lyngby, Denmark.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Quantitative determination of volatile organic compounds in indoor dust using Gas Chromatography – UV spectrometry2005In: Environment International, ISSN 0160-4120, Vol. 31, no 8, p. 1141-1148Article in journal (Refereed)
    Abstract [en]

    A novel technique, gas chromatography-UV spectrometry (GC-UV), was used to quantify volatile organic compounds (VOCs) in settled dust from 389 residences in Sweden. The dust samples were thermally desorbed in an inert atmosphere and evaporated compounds were concentrated by solid phase micro extraction and separated by capillary GC. Eluting compounds were then detected, identified, and quantified using a diode array UV spectrophotometer. Altogether, 28 compounds were quantified in each sample; 24 of these were found in more than 50% of the samples. The compounds found in highest concentrations were saturated aldehydes (C5–C10), furfuryl alcohol, 2,6-di-tert-butyl-4-methylphenol (BHT), 2-furaldehyde, and benzaldehyde. Alkenals were also found, notably 2-butenal (crotonaldehyde), 2-methyl-propenal (methacrolein), hexenal, heptenal, octenal, and nonenal. The concentrations of each of the 28 compounds ranged between two to three orders of magnitude, or even more. These results demonstrate the presence of a number of VOCs in indoor dust, and provide, for the first time, a quantitative determination of these compounds in a larger number of dust samples from residents. The findings also illustrate the potential use of GC-UV for analysing volatile compounds in indoor dust, some of which are potential irritants (to the skin, eyes or respiratory system) if present at higher concentrations. The potential use of GC-UV for improving survey and control of the human exposure to particle-bound irritants and other chemicals is inferred.

  • 34.
    Nilsson, Anders
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Kihlström, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Lagesson, Verner
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Wessén, B.
    Pegasus Laboratory, Uppsala.
    Szponar, B.
    Department of Medical Microbiology, Dermatology and Infection, Lund University, Sweden.
    Larsson, L.
    Department of Medical Microbiology, Dermatology and Infection, Lund University, Sweden.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Microorganisms and volatile organic compounds in airborne dust from damp residences2004In: Indoor Air. International Journal of Indoor Environment and Health, ISSN 0905-6947, Vol. 14, no 2, p. 74-82Article in journal (Refereed)
    Abstract [en]

    Airborne dust samples from damp (n = 9) and control (n = 9) residences were analyzed for microorganisms (molds and bacteria), bacterial markers (3-hydroxy fatty acids and muramic acid), and adsorbed volatile organic compounds (VOCs). The number of mold species was greater in the damp residences than in the controls (23 vs.18) and nine mold species were found only in damp residences. The levels of 3-hydroxy fatty acids and muramic acid correlated better in damp residences than in controls, indicating that damp conditions affect the bacterial flora of airborne dust. Identifications made by culture and microscopy of the major molds found, i.e. Aspergillus, Cladosporium, and Penicillum, coincided with the identification of VOCs known to be produced by these species. A number of additional VOCs irritating to the skin, eyes, or respiratory tract were also found. The results from this pilot study illustrate the diversity of microorganisms and VOCs present in the indoor environment and suggest that analysis of airborne dust may help to assess human exposure to microorganisms and chemical compounds.

  • 35.
    Nilsson, Anders
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Nosratabadi, Ali Reza
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Lagesson, Verner
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Murgia, Nicola
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Novel technique for measuring low molecular weight chemicals in indoor dust2002In: Indoor and Built Environment, ISSN 1420-326X, Vol. 11, no 3, p. 153-161Article in journal (Refereed)
    Abstract [en]

    A new technique is described which can measure low molecular weight compounds adsorbed onto dust particles in a simple yet accurate way. The technique, gas chromatography-ultraviolet spectrometry (GC-UV), comprises a one-stage thermal desorption oven, a gas flow cell with a miniaturised GC column, and a nitrogen-flushed photo diode array (PDA) detector for fast UV spectra recording. The dust sample is thermally desorbed in the oven and the compounds released are flushed onto the GC column by means of a carrier gas stream. The separated compounds are then registered by the PDA detector and identified by their characteristic gas-phase UV spectra. This method enables the analysis of volatile organic as well as inorganic compounds adsorbed onto dust particles, many of which are difficult to analyse together in one single analysis using conventional methods. For example, both nitric oxide and ammonia can be analysed, as well as hydrogen sulphide, pyridine, 2-furaldehyde, 2-methylfuran, and isoprene. It is concluded that GC-UV may be used as an alternative or to complement other methods for measuring chemicals in indoor dusts, thus improving survey and control of the human exposure to particle-bound irritants and other chemicals.

  • 36. Nilsson, R
    et al.
    Norlinder, R
    Moen, BE
    Övrebö, S
    Bleie, K
    Skorve, AH
    Hollund, BE
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Increased urinary excretion of 8-hydroxydeoxyquanosine in engine room personnel exposed to polycyclic aromatic hydrocarbons2004In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 61, no 8, p. 692-696Article in journal (Refereed)
    Abstract [en]

    Background: Previous investigations indicate that engine room personnel on ships are exposed to polycyclic aromatic hydrocarbons (PAH) from oil and oil products, with dermal uptake as the major route of exposure. Several PAH are known carcinogens and mutagens. Aims: To investigate the urinary excretion of a marker for oxidative DNA damage, 8-hydroxydeoxyguanosine (8OHdG), in engine room personnel, and to study the association between 8OHdG and 1-hydroxypyrene (1OHP), a biological marker for PAH exposure. Methods: Urine samples were collected from engine room personnel (n = 36) on 10 Swedish and Norwegian ships and from unexposed controls (n = 34) with similar age and smoking habits. The exposure to oils, engine exhaust, and tobacco smoke 24 hours prior to sampling was estimated from questionnaires. The urinary samples were frozen for later analyses of 8OHdG and 1OHP by high performance liquid chromatography. Results: Excretion in urine of 8OHdG (adjusted to density 1.022) was similar for controls (mean 18.0 nmol/l, n = 33), and for those who had been in the engine room without skin contact with oils (mean 18.7 nmol/l, n = 15). Engine room personnel who reported skin contact with oil had increased excretion of 8OHdG (mean 23.2 nmol/l, n = 19). The difference between this group and the unexposed controls was significant. The urinary levels of ln 1OHP and ln 8OHdG were significantly correlated, and the association was still highly significant when the effects of smoking and age were accounted for in a multiple regression analysis. Conclusion: Results indicate that exposure to PAH or possibly other compounds from skin contact with oils in engine rooms may cause oxidative DNA damage.

  • 37.
    Nosratabadi, Ali Reza
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Ljungman, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Lindahl, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Welch, Richard
    Pilon, Aprile
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Clara cell 10-KDA protein inhibits endotoxin-induced airway contraction in isolated perfused rat lungs2003In: Experimental Lung Research, ISSN 0190-2148, E-ISSN 1521-0499, Vol. 29, no 7, p. 455-473Article in journal (Refereed)
    Abstract [en]

    Clara cell 10-kDa protein (CC10) is a major component of bronchoalveolar lavage fluid and is suggested to be a natural regulator of airway inflammation, possibly through its effects on theproin-flammatory enzyme(s), phospholipase A2. We examined the effect of recombinant human (rh) CC10 on endotoxin-induced airway contraction and cytokine release in isolated perfused rat lungs. We found that rhCC10 added to the lung perfusate abolished the endotoxin-induced airway contraction, and that it inhibited both the release of interleukin-1▀ and interleukin-6 into the lung perfusate and the release of tumor necrosis factors, into the pulmonary lavage fluid. By contrast, the levels of interferon-? were unaffected by CC10 administration. Rutin, a phospholipase A2 inhibitor, and N?-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, also attenuated the contraction induced by endotoxin. These findings demonstrate that rhCC10 inhibits endotoxin-induced airway contraction and the release of proinflammatory cytokines (interleukin-1▀, interleukin-6, and tumor necrosis factor-a) in isolated perfused rat lungs. The results also indicate that phospholipase A2 and nitric oxide are involved in the airway contraction in this model, possibly through their influence on the production of eicosanoids.

  • 38. Sperati, A
    et al.
    Abeni, D
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Forastiere, F
    Miceli, M
    Axelson, Olav
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Exposure to indoor background radiation and urinary concentrations of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage.1999In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 107, p. 213-215Article in journal (Refereed)
  • 39.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Peterson, KH
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Franzén, LE
    Lindmark, T
    Wirén, Mikael
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of crohn's disease2002In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 50, no 3, p. 307-313Article in journal (Refereed)
    Abstract [en]

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

  • 40.
    Tondel, Martin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Arynchyn, A.
    Research Clinical Institute of Radiation Medicine and Endocrinology, Minsk, Belarus.
    Jönsson, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Persson, Bodil
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Urinary 8-hydroxydeoxyguanosine in Belarussian children relates to urban living rather than radiation dose after the Chernobyl accident: A pilot study2005In: Archives of Environmental Contamination and Toxicology, ISSN 0090-4341, Vol. 48, no 4, p. 515-519Article in journal (Refereed)
    Abstract [en]

    As a result of the Chernobyl accident in 1986, exposure to radioactive cesium is still a concern in the contaminated regions of Belarus. We tested the hypothesis that long-term radiation exposure from the Chernobyl accident might increase the urinary excretion of the oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG), in Belarussian children. Urinary 8-OHdG was determined in two groups of children (—n = 31 and n = 46) —living in contaminated and uncontaminated areas of Belarus, respectively (the majority of the unexposed children lived in the capital Minsk). The children from the contaminated areas had a significantly higher annual summary effective dose but significantly lower urinary 8-OHdG levels than the children from the uncontaminated areas. Unexpectedly, children living in uncontaminated urban areas had significantly higher urinary 8-OHdG levels than children living in uncontaminated rural areas. There was no statistically significant effect of sex or body mass index on urinary 8-OHdG, but there was a weak significant inverse correlation to age as well as to the annual summary effective dose. These findings suggest that radiation from the Chernobyl accident is now a less important contributor to oxidative stress in Belarussian children than urban living.

  • 41.
    Wieslander, Gunilla
    et al.
    Uppsala University.
    Fabjan, Nina
    University of Ljubljana.
    Vogrincic, Maja
    University of Ljubljana.
    Kreft, Ivan
    University of Ljubljana.
    Janson, Christer
    Uppsala University.
    Spetz-Nystrom, Ulrike
    Uppsala University.
    Vombergar, Blanka
    Vocat College.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Norback, Dan
    Uppsala University.
    Eating Buckwheat Cookies Is Associated with the Reduction in Serum Levels of Myeloperoxidase and Cholesterol: A Double Blind Crossover Study in Day-Care Centre Staffs2011In: Tohoku journal of experimental medicine, ISSN 0040-8727, E-ISSN 1349-3329, Vol. 225, no 2, p. 123-130Article in journal (Refereed)
    Abstract [en]

    Buckwheat food is a good source of antioxidants, e.g. rutin, and other beneficial substances. Here we investigated the effects of the intake of common buckwheat (low rutin content) and tartary buckwheat cookies (high rutin content) on selected clinical markers. A double blind crossover study was performed among female day-care centre staffs (N = 62) from five day-care centres. Participants were randomly divided into two groups. The first group initially consumed four common buckwheat cookies per day (16.5 mg rutin equivalents/day) for two weeks, while the second group consumed four tartary buckwheat cookies per day (359.7 mg rutin equivalents/day). Then the groups switched their type of cookies and consumed them for another two weeks. We monitored selected clinical markers related to cardiovascular disease and lower airway inflammation, lung function, and subjective breathing difficulties in the staffs. Intake of tartary buckwheat cookies reduced the serum level of myeloperoxidase (MPO) by a factor 0.84 (p = 0.02). When grouping the two types of buckwheat cookies together, there was a reduction of total serum cholesterol (p andlt; 0.001) and HDL-cholesterol (p andlt; 0.001) during the study period, with improved lung vital capacity (p andlt; 0.001). The degree of reduction in total and HDL cholesterol levels was similar in staffs with low and high body mass index (cut off 25). In conclusion, intake of tartary buckwheat cookies with high level of the antioxidant rutin may reduce levels of MPO, an indicator of inflammation. Moreover, intake of both types of buckwheat cookies may lower cholesterol levels.

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