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  • 301.
    Faresjö, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Cytokine profile in children during the first 3 months after the diagnosis of type 1 diabetes2004In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 59, no 5, p. 517-526Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes is an autoimmune disease with an inflammatory process directed against the β cells in pancreas. This investigation aimed at studying the immune response during the first 3 months after the diagnosis of type 1 diabetes, with focus on the balance of T-helper 1 (Th1)- and Th2-like cytokines, produced spontaneously and in response to relevant autoantigens. Peripheral blood mononuclear cells (PBMCs) were collected from type 1 diabetic children (10-17 years) at 5, 20, 35 and 90 days after diagnosis. Expression of interferon-γ (IFN-γ) and interleukin-4 (IL-4) mRNA were detected by real-time reverse transcriptase polymerase chain reaction and IFN-γ, IL-10 and IL-13 by enzyme-linked immunosorbent assay in cell supernatant after stimulation with a glutamic acid decarboxylase 65 (GAD65)-peptide [amino acid (a.a.) 247-279], insulin, the ABBOS-peptide (a.a. 152-169), phytohaemagglutinin and keyhole limpet haemocyanin. Spontaneous and antigen-induced expression and secretion of cytokines were low at the diagnosis of type 1 diabetes. During the first month, after diagnosis, the GAD 65-peptide caused an increased ratio of IFN-γ/IL-4 mRNA expression (P < 0.05) and increased secretion of IFN-γ (P = 0.07). Expression of IFN-γ mRNA did also increase from stimulation with insulin (P < 0.05), even though cytokine secretion remained low. Thus, duration after diagnosis as well as metabolic state should be carefully considered both in studies of the pathogenesis of type 1 diabetes and in immune intervention studies at onset.

  • 302.
    Faresjö, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Diminished Th1-like response to autoantigens in children with a high risk of developing type 1 diabetes2005In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 61, no 2, p. 173-179Article in journal (Refereed)
    Abstract [en]

    The exact role of T-helper (Th) cells that precede the clinical manifestation of type 1 diabetes remains unclear. The aim of this investigation was to study the Th1- and Th2-like profile in children and adults with high risk of developing the disease. Peripheral blood mononuclear cells were collected from high-risk children and adults and from healthy individuals matched for age and gender. Using the sensitive enzyme-linked immunospot (ELISPOT) technique to divide Th1- from Th2-like lymphocytes, secretion of interferon-γ (IFN-γ) and interleukin-4 was analysed from lymphocytes spontaneously and after in vitro stimulation with different antigens, based on present paradigms regarding the pathogenesis of type 1 diabetes. Compared to the response observed in healthy individuals, we found that individuals with a high risk of developing type 1 diabetes, especially children, responded with less IFN-γ secretion to the three autoantigens glutamic acid decarboxylase 65 (GAD 65), insulin and tyrosinphosphatase (IA-2). Thus, a diminished Th1-like response by in vitro autoantigen stimulation was observed in especially children with a high risk of developing type 1 diabetes. Reduced Th1/Th2 response was related to signs of β cell exhaustion.

  • 303.
    Faresjö, Tomas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice.
    Roel, Eduardo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice.
    Olsen Faresjö, Å
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice.
    Kjellman, Max
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Astma hos barn blir allt vanligare. Journalstudie visar en fördubbling under en tioårsperiod. 1999In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 96, p. 5368-6369Article in journal (Other (popular science, discussion, etc.))
  • 304.
    Faresjö, Tomas
    et al.
    Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Söderquist, Johan
    Linköping University, Department of Social and Welfare Studies, Hälsa - utbildning - välfärdsinstitutioner (HUV) . Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Grodzinsky, Ewa
    Linköping University, Department of Department of Health and Society, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Nilsson, Hans
    Linköping University, Department for Studies of Social Change and Culture, Centre for Local History. Linköping University, Faculty of Arts and Sciences.
    Tvillingstäder med stora sociala skillnader i folkhälsa - ett samhällsmedicinskt experiment inleds i Norrköping och Linköping: [Twin cities with big social differences when it comes to public health. A sociomedical "experiment" introduced in Norrkoping and Linkoping]2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 23, p. 1788-1790Article in journal (Refereed)
    Abstract [en]

    An interdisciplinary research group entitled ”Twincities Research Group” has been initiated at Linköping University. The term twin cities refer to the Swedish cities Linköping and Norrköping, neighbours that are nearly equal in size. These two cities, located within a distance of only 40 km, are governed by the same county council and consequently have the same health care structure. However, health is remarkably different in these twin cities. The comparison of public health in these two cities during the development from the industrial to the post-industrial era has a design similar to classical experiments with a control and an experiment group, since the social history and the socio-economic structures of the cities are radically different. Through an interdisciplinary research design including historical, epidemiological and clinical competence we have a unique opportunity to increase our understanding of how social environment may affect public health.

  • 305.
    Faustini, Annunziata
    et al.
    Local Health Unit, Tarquinia (VT), Italy.
    Settimi, Laura
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Pacifici, Roberta
    Instituto Superiore di Sanita', Rome, Italy.
    Fano, Valeria
    Epidemiologic Unit, Lazio Regional Health Authority, Rome, Italy.
    Zuccaro, Piergiorgio
    Instituto Superiore di Sanita', Rome, Italy.
    Forastiere, Francesco
    Epidemiologic Unit, Lazio Regional Health Authority, Rome, Italy.
    Immunological changes among farmers exposed to phenoxy herbicides: preliminary observations1999In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 53, no 9, p. 583-589Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate short term immunological changes after agricultural exposure to commercial formulations of chlorophenoxy herbicides.

    METHODS: Blood samples were collected from 10 farmers within seven days before exposure, one to 12 days after exposure, and again 50 to 70 days after exposure. Whole blood was used to count lymphocyte subsets with monoclonal antibodies. Peripheral blood mononuclear (PBM) cells were used to measure natural killer (NK) cell activity and lymphocyte response to mitogenic stimulations. Values before exposure were used as reference.

    RESULTS: In comparison with concentrations before exposure, a significant reduction was found one to 12 days after exposure in the following variables (P < 0.05): circulating helper (CD4) and suppressor T cells (CD8), CD8 dim, cytotoxic T lymphocytes (CTL), natural killer cells (NK), and CD8 cells expressing the surface antigens HLA-DR (CD8-DR), and lymphoproliferative response to mitogen stimulations. All immunological values found 50-70 days after exposure were comparable with concentrations before exposure, but mitogenic proliferative responses of lymphocytes were still significantly decreased.

    CONCLUSIONS: According to our data agricultural exposure to commercial 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) formulations may exert short term immunosuppressive effects. Further studies should clarify whether the immunological changes found may have health implications and can specifically contribute to cancer aetiology.

  • 306.
    Favre, Cécile J.
    et al.
    Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
    Jerström, Petra
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Foti, Michelangelo
    Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
    Stendahl, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Huggler, Elzbieta
    Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
    Lew, Daniel P.
    Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
    Krause, Karl-Heinz
    Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
    Organization of Ca2+ stores in myeloid cells: association of SERCA2b and the type-1 inositol-1,4,5-trisphosphate receptor1996In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 316, no 1, p. 137-142Article in journal (Refereed)
    Abstract [en]

    In this study, we have analysed the relationship between Ca2+ pumps and Ins(1,4,5)P3-sensitive Ca2+ channels in myeloid cells. To study whether sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)-type Ca2+-ATPases are responsible for Ca2+ uptake into Ins(1,4,5)P3-sensitive Ca2+ stores, we used the three structurally unrelated inhibitors thapsigargin, 2,5-di-t-butylhydroquinone and cyclopiazonic acid. In HL-60 cells, all three compounds precluded formation of the phosphorylated intermediate of SERCA-type Ca2+-ATPases. They also decreased, in parallel, ATP-dependent Ca2+ accumulation and the amount of Ins(1,4,5)P3-releasable Ca2+. Immunoblotting with subtype-directed antibodies demonstrated that HL-60 cells contain the Ca2+ pump SERCA2 (subtype b), and the Ca2+-release-channel type-1 Ins(1,4,5)P3 receptor. In subcellular fractionation studies, SERCA2 and type-1 Ins(1,4,5)P3 receptor co-purified. Immunofluorescence studies demonstrated that both type-1 Ins(1,4,5)P3 receptor and SERCA2 were evenly distributed throughout the cell in moving neutrophils. During phagocytosis both proteins translocated to the periphagosomal space. Taken together, our results suggest that in myeloid cells (i) SERCA-type Ca2+-ATPases function as Ca2+ pumps of Ins(1,4,5)P3-sensitive Ca2+ stores, and (ii) SERCA2 and type-1 Ins(1,4,5)P3 receptor reside either in the same or two tightly associated subcellular compartments.

  • 307.
    Ferdousi, Hosne Ara
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Pollinosis in children with special reference to the development of asthma2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Children with rhinoconjunctivitis and increased bronchial hyperreactivity (BHR) are prone to develop asthma later in life. Eosinophil granule proteins in serum are indirect measures of eosinophil activity and regarded as markers of inflammation. Measurement of eosinophil cationic protein (ECP) has also been evaluated for prediction, diagnosis and monitoring of treatment in children with asthma. In 1992, a multicenter preventive allergy treatment study (PAT-study) was started in order to prevent the development of asthma in children with pollinosis using specific immunotherapy treatment (SIT). Sensitization to cat allergen is common in asthma and up to 50% of children with asthma are sensitized. Exposure to cat allergen can not be avoided because exposure occurs in schools and even in homes without a cat and is a major cause of persisting airway inflammation and asthma in cat sensitized schoolchildren. Data are needed to know the level of allergen maintaining BHR or asthma.

    The aims of the thesis were: 1) To assess the relationship between seasonal symptoms of allergy, BHR, PEP-variability and release of markers of inflammation. 2) To investigate the level of markers of inflammation, and PEF variability, in healthy school children. 3) To investigate the diagnostic value of the tests e.g. BHR and mediators of allergic inflammation for diagnosis of asthma in pollinosis. 4) To investigate the efficacy of SIT regarding prevention of asthma, BHR, and polysensitization. 5) To assess, the levels of cat allergens inhaled daily by asthmatic schoolchildren sensitized to cat and relate the levels of allergen to symptoms of asthma and BHR.

    The PAT study population comprised 205 birch and/or grass pollen allergic children with pollinosis, from 7 centres in 5 countries in Northern and Central Europe, 28 were enrolled in the Linköping. We recruited 56 healthy school children to study the normal level of inflammatory markers and PEFR variability and 10 asthmatic schoolchildren sensitized to cat to assess the allergen levels in their daily environment.

    In the pollinosis children, sensitization status was determined by skin and conjunctival provocation test and RAST. Mediators of allergic inflammation like ECP, EPX, and neutrophil mediators like MPO were measured by RIA methods, non-specific BHR by Methacholine and/or cold air challenge tests and bronchial lability by PEF variability using Mini Wrights Peak-Flow meters. The level of cat allergens in dust samples were measured by ELISA, and in air by amplified ELISA methods. SIT was given by birch and/or grass pollen allergen extracts (Alutard), during a period of 3 years.

    In pollinosis children in Linköping, there was no correlation between mediators of allergic inflammation in serum and symptoms and signs of clinical asthma. BHR and PEFR-variability persisted in the autumn, though s-ECP and s-EPX did not, indicating that mediators of inflammation do not reflect asthma. Positive MBPT and IHCA tests were more often found in the children with clinical asthma. The other investigated tests were not useful for screening of asthma in this group of children with pollinosis. In healthy schoolchildren, the mean daily PEF variations were 7.35 and 6.74%, and the 9Sth percentiles were 18 and 14% during the spring and autumn respectively. The 95th percentils for s-ECP were 41 and 38 µg/L, for s-EPX 74 and 62µg/L, for s-MPO 987 and 569 µg/L and for u-EPX tucreatinine 165 and 104 µg/mmol, during spring and autumn, respectively. Our findings for mediator levels in schoolchildren were higher than reported in adults. There was a significant decrease in the levels of the eosinophil and neutrophil mediators from May to November (p ≤ 0.001) and so did the PEF variability (p=0.037) in our healthy children. As normal reference values post seasonal data would be more appropriate. In the environment of cat sensitive children, exposure levels of cat allergen varied from 0.5 µg/g to 751 µg/g dust in homes (median, 36 µg/g) and from 17 µg/g to 378 µg/g in schools (median, 137 µg/g). Airborne allergen levels varied from 13 to 2184 pg/m3 (median, 43 pg/m3 ) in the homes and 68 to 7718 pg/m3 (median 352 pg/m3) in the schools. The inhaled dose was 8 pg to 2336 pg/min. A relation between BHR and exposure level was found. In the PAT-study, children actively treated with SIT had significantly fewer asthma symptoms after 3 years (odds ratio 2.52; p<0.05) and MBPT was improved (p<0.05) compare to the control group. Thus, SIT reduced the development of asthma in our children with pollinosis.

    We followed the pollinosis children in Linköping in our centre for 11 years. Our findings were: I) there was a trend of diminishing in sensitivity to MBPT and in PEF variation with age. 2) Pollen counts in different years influenced MBPT results in that particular year. 3) MBPT in 1992 could predict the development of asthma in 1994.

    List of papers
    1. Clinical characteristics of school children with birch and/or grass pollen hay-fever (The PAT-Study)
    Open this publication in new window or tab >>Clinical characteristics of school children with birch and/or grass pollen hay-fever (The PAT-Study)
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: To describe the clinical characteristics of school children with hay-fever based on baseline data from the PAT-Study.

    Material: Two hundred and five children, 6-15 years, mean 10.7 years, with birch and or grass pollen hay-fever, without known asthma were recruited by six pediatric allergy centers in Northern and Central Europe.

    Methods: Bronchial hyperresponsiveness (BHR) to methacholine tested by methacholine bronchial provocation test (MBPT) expressed in PC20 was registered during the birch and grass pollen seasons. During the winter symptoms of conjunctivitis, rhinitis and asthma were graded by visual analogue scale (VAS), conjunctival provocation test with birch and or timothy pollen extracts, skin tests with a panel of allergen extracts and MBPT were done and a questionnaire was filled in. Differences of p <0.01 level or less were considered significant.

    Results: Despite the children were included because of seasonal hay-fever without known asthma, 42/205 children (21 %) got doctor diagnosed asthma (DDA) after the first season. During the three seasons, between 60 and 73 % of the children had a PC20 to methacholine ≤ 8 mg/ml, about 30 % to ≤ 2 mg/ml and 7-10% even to ≤ 0.5 mg/ml. Most children had both rhinitis and conjunctivitis. Furthermore, 119/201 children (59%) were regularly exposed to furred animals.

    There was an association between DDA and the sum of VAS for asthma during the pollen seasons.

    The BHR was significantly more pronounced in those with than those without DDA during all three seasons: Using the three cut offs, the difference was most pronounced during the winter season but reached also significance using the cut off limit 0.5 mg/ml during the birch pollen season.

    Doctor diagnosed asthma correlated to PC20 during the seasons for most of the cut off limits for PC20 and in general there was an association in PC20 between the seasons independent of cut off limits.

    Furthermore, DDA, but not BHR, correlated to exposure to traffic and there was an association between exposure to traffic and industrial pollution, but not to ETS or duration of breastfeeding.

    Conclusion: The most striking feature of school children with uncomplicated hay-fever was the high frequency of DDA and BHR, most pronounced during the winter, the high frequency of exposure to living animals and sensitization to indoor allergens. Hay-fever is a generalized disease. Even without obvious asthma, BHR is common and most children have symptoms from both the eyes and the airways. Diagnosis of asthma in children with hay-fever and early anti-inflammatory treatment may improve the prognosis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85000 (URN)
    Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2012-10-30
    2. Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis: ECP and EPX levels are not related to bronchial hyperreactivity
    Open this publication in new window or tab >>Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis: ECP and EPX levels are not related to bronchial hyperreactivity
    1997 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 27, no 5, p. 530-539Article in journal (Refereed) Published
    Abstract [en]

    Background Symptoms of allergic asthma are triggered by allergen exposure inducing allergic inflammation and hyperreactivity of the bronchi.

    Objectives To investigate the possible relationship between clinical symptoms and signs of asthma, i.e. bronchial variability as measured by peak expiatory flow rate (PEFR). bronchial hyperreactivity (BHR) and mediators of allergic inflammation.

    Methods Twenty-eight children with pollinosis. but no obvious history of asthma, were studied at three occasions, i.e. before, during and after (autumn) the birch pollen season. Twelve children sensitive to birch pollen were considered as the case group. Sixteen children, who were only clinically sensitive to grass pollen, served as controls. Subjective symptoms of asthma were recorded by visual analogue scale, BHR was estimated by methacholine bronchial provocation tests, bronchial variability PEFR and circulating mediators of inflammation, i.e. eosinophil cationic protein, eosinophil protein X, myeloperoxidase and tryptase in serum.

    Results Bronchial hyperreactivity and by PEFR was more pronounced after than during the season (P < 0.01), whereas eosinophil mediators and the peak expiratory flow rate increased during the season (P < 0.05). Except for between PEFR variability and BHR in the autumn (r= 0.45; P= 0.014). no correlations were found. However, in the autumn, the majority of children were still hyperreactive in the bronchi and showed PEFR variability but the levels of eosinophil mediators in serum had returned to normal levels.

    Conclusion Signs and symptoms of asthma did not correlate with serum levels of mediators of allergic inflammation. Bronchial hyperreactivity and PEFR variability persisted after the pollen season when signs of bronchial inflammation had disappeared. We hypothesize that eosinophil mediators and other markers of allergic inflammation disappear after the late-phase reaction, whereas BHR persists. This would explain the lack of correlation between the levels of eosinophil mediators in serum and symptoms of asthma and BHR.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85002 (URN)10.1111/j.1365-2222.1997.tb00741.x (DOI)
    Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2017-12-07
    3. Seasonal differences of peak expiratory flow rate variability and mediators of allergic inflammation in non-atopic adolescents
    Open this publication in new window or tab >>Seasonal differences of peak expiratory flow rate variability and mediators of allergic inflammation in non-atopic adolescents
    2001 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 5, p. 238-246Article in journal (Refereed) Published
    Abstract [en]

    Variations in peak expiratory flow (PEF) and serum eosinophil mediators were studied in healthy adolescents. Twenty-five boys and 31 girls, 11–16 years of age (mean age 14.3 years), were selected and investigated during the birch pollen season of 1995; 45 were also investigated during the autumn of the same year. The PEF was measured twice daily and eosino-phil mediators in serum and in urine were measured by radioimmunoassay (RIA) once during the birch pollen season and once in autumn. The type values of the daily PEF variation, expressed in amplitude percentage mean, were 6.4 and 3.9%, mean values were 7.35 and 6.74%, and the 95th percentiles were 18 and 14%, during the birch pollen season and autumn, respectively. The 95th percentiles were 41 and 38 µg/l for serum eosinophil cationic protein (s-ECP), 74 and 62 µg/l for serum eosinophil protein X (s-EPX), 987 and 569 µg/l for serum myeloperoxidase (s-MPO), and 165 and 104 µg/mmol for urinary eosinophil protein X/urinary creatinine (u-EPX/u-creatinine), during the birch pollen season and autumn, respectively. The levels of the eosinophil mediators decreased significantly from May (n = 56) to November (n = 45), for s-ECP from a median value of 14 µg/l to 7 µg/l (p= 0.001), for s-EPX from a median value of 28 µg/l to 20 µg/l (p= 0.001), and for the neutrophil mediator, s-MPO, from a median value of 440 g/l to 292 g/l (p< 0.001). The PEF variability decreased significantly (p= 0.037), from spring (n = 55; median 8%, 95% confidence interval [CI] 7.8–10.19) to autumn (n = 44; median 6%, 95% CI 6.1–8.9). A significant correlation was found between the levels of s-ECP and s-EPX (rs = 0.7, p< 0.001), between s-ECP and s-MPO (rs = 0.6, p< 0.001), between s-EPX and s-MPO (rs = 0.4, p< 0.005), and between s-EPX and u-EPX/u-creatinine (rs = 0.6, p< 0.0001), in the birch pollen season (n = 56) and in the autumn (n = 45). There was a positive correlation found in PEF variability between the two seasons (n = 43; rs = 0.5, p= 0.0006). No other correlation was found between PEF variability and any other parameters. The difference in the levels of eosinophil mediators between seasons in non-atopic, healthy children is unexplained. Normal limits for mediators were higher and PEF variability was almost the same as has been reported in adults. When using normal values, seasonal influences should be considered.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25880 (URN)10.1034/j.1399-3038.2001.00024.x (DOI)10320 (Local ID)10320 (Archive number)10320 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
    4. Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever
    Open this publication in new window or tab >>Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever
    2005 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 16, no 6, p. 478-486Article in journal (Refereed) Published
    Abstract [en]

    In children with mild asthma, symptoms are not always apparent. Therefore, results of tests play an important role for the diagnosis. First, to investigate whether children with bronchial hyper-responsiveness (BHR) but no symptoms of asthma in 1992 had developed clinical asthma at follow up in 1994. The second aim was to find out the diagnostic properties of tests for asthma/allergic inflammation, using either doctor diagnosed asthma (DDA), self-assessed symptoms of asthma or iso-capnic hyperventilation of cold air (IHCA), as the standard, to diagnose asthma in a group of children with hay fever. Twenty-eight children with pollinosis, 12 of them with a history of asthma for the first time during the season 1992, were studied during the birch pollen season and in the autumn of 1994. During both periods, the bronchial hyper-reactivity was estimated by methacholine bronchial provocation tests (MBPT), bronchial variability by peak expiratory flow rate variability, subjective symptoms of asthma by visual analogue scale (VAS) and bronchial inflammation by serum and urine levels of inflammatory mediators. In 1994 IHCA was added during both seasons. Eight of 16 children with BHR but without clinical asthma in 1992 had developed asthma in 1994, 14 of 16 reacted to IHCA and 13 to MBPT. All 12 children with DDA in 1992 had still asthma in 1994 and 14 children with BHR in 1992 had persistent BHR in 1994. Of 23 children with BHR in 1992, 17 had DDA in 1994 and all maintained their BHR. Furthermore, 20 of them reacted to IHCA in 1994. In 1994, 24 of 28 hay-fever children had a positive IHCA tests and 24 had positive MBPT. In relation to VAS, the sensitivity of IHCA and MBPT to predict present asthma was high, but the specificity low, whereas the specificity of most other tests was high, but based on few individuals. In relation to DDA both the IHCA test (65–80%) and the MBPT test (79–85%) had a high sensitivity and it was three to six times more likely to find a positive test among asthmatics than in non-asthmatics. Children with hay fever without clinical asthma have a high risk of developing asthma within 2 yr. In relation to DDA, inhalation of cold air and the MBPT showed a high sensitivity.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-36346 (URN)10.1111/j.1399-3038.2005.00296.x (DOI)31085 (Local ID)31085 (Archive number)31085 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2018-03-21
    5. Cat allergen exposure in Swedish schools is high enough to maintain continuous bronchial hyperreactivity and to cause symptoms in children with asthma who are sensitized to cat
    Open this publication in new window or tab >>Cat allergen exposure in Swedish schools is high enough to maintain continuous bronchial hyperreactivity and to cause symptoms in children with asthma who are sensitized to cat
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Exposure to indoor allergens play a major role for development of sensitization and induction of allergic inflammation, bronchial hyperreactivity and symptoms in sensitized individual.

    Objective: fu this study, we investigated the individual exposure levels of cat allergen, Fel d1, among asthmatic schoolchildren sensitized to cats. We studied the exposure relationship with symptoms, medication, lung functions, bronchial hyperreactivity (BHR) and mediators of allergic inflallrmation.

    Methods: Ten school children with known allergy to cats were selected from 5 schools in Linköping, Sweden. All children had positive skin test to cats. We collected dust samples from homes and schools. All children carried a portable air-sampler in the schools during the period of 4-6 weeks. Air was also sampled fi·om the bedroom. The children performed lung function (PEF) twice daily using a digital Peak flow meter. They maintain symptom and medication chart once in a week. We performed methacholine bronchial provocation test (PD20) and analyzed mediators of allergic inflammation (s-ECP, EPX and MPO) iu blood and urine at the beginning and at the end of the study period. Dust and air samples were analyzed for major cat allergen (Fel d1) using ELISA.

    Results: Exposure levels of cat allergen varied from 0,5 µg/g to 751 µg/g dust in homes (median, 36 µg/g) and from 17 µg/g to 378 µg/g in schools (median, 137 µg/g). Airborne allergen levels varied from 13 to 2184 pg/m3 (median, 43 pg/m3) in the homes and 68 to 7718 pg/m3 (median 352 pg/m3) in the schools. The mediators of allergic inflammation ranged from 4 to 57 µg/L for ECP, from 12 to 73 µg/L for EPX and from 148 to 581 µg/L for MPO. All children had bronchial hyperreactivity and all but one child used asthma/allergy medicine during the entire study period. A significant relationship (p<0.05) was found between the peak allergen exposure and symptoms, airborne allergens and BHR of the children.

    Conclusions: Our study suggests, that school is an important source of cat allergen exposure, that cat sensitized asthmatic children inhale a substantial amount of cat allergen in the schools, that despite treatment of asthma including regular use of inhaled corticosteroids, 8 pg to 2336 pg of cat allergen inhaled per minute is sufficient enough to maintain a continuous airway hyper-responsiveness among this group of children.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85007 (URN)
    Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2012-10-30
    6. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)
    Open this publication in new window or tab >>Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)
    Show others...
    2002 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 109, no 2, p. 251-256Article in journal (Refereed) Published
    Abstract [en]

    Background: Children with allergic rhinitis are likely to develop asthma.

    Objective: The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis.

    Methods: From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean age, 10.7 years) with grass and/or birch pollen allergy but without any other clinically important allergy were randomized either to receive specific immunotherapy for 3 years or to an open control group. All subjects had moderate to severe hay fever symptoms, but at inclusion none reported asthma with need of daily treatment. Symptomatic treatment was limited to loratadine, levocabastine, sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by peak flow. Methacholine bronchial provocation tests were carried out during the season(s) and during the winter.

    Results: Before the start of immunotherapy, 20% of the children had mild asthma symptoms during the pollen season(s). Among those without asthma, the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P < .05). Methacholine bronchial provocation test results improved significant in the active group (P < .05).

    Conclusion: Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis.

    Keywords
    prevention, specific immunotherapy, bronchial hyperresponsiveness, asthma, rhinitis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-47894 (URN)10.1067/mai.2002.121317 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
    7. Asthma and allergy in pollinosis children: an 11-year follow-up of specific immunotherapy
    Open this publication in new window or tab >>Asthma and allergy in pollinosis children: an 11-year follow-up of specific immunotherapy
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Pollen immunotherapy is effective in hay fever and asthma in children, although there are few studies on the long-term benefit.

    Methods: We conducted a longitudinal follow up for 11 years of specific immunotherapy (SIT) for birch and or grass pollen allergy in children (n=28) who took part in the preventive allergic treatment (PAT) study. Bronchial hyperresponsiveness (BHR.) to methacholine, conjunctival provocation tests (CPT), and the skin sensitivity to common allergens-(SPT) were done. A matched group of patients who had not received immunotherapy served as controls.

    Results: Eight years after of discontinuation of IT, 11 children with and 11 children without IT could be investigated. In the SIT group 2 had asthma compared to 7 in the control group. The skin and conjunctival sensitivity in the SIT group decreased more (n.s.). Birch pollen counts were measured dming the pollen seasons in every year from 1992 to 1995 and in the year 1997. The years 1993 and 1995 had high levels of birch pollen counts compared to the other years.

    When all the children were considered, scores for asthma symptoms and BHR was higher in these years.

    PEF variation decreased with age in both groups.

    Conclusions: SIT for hay fever for three years induced a clinical remission 8 years after discontinuation of immunotherapy accompanied by a reduction in the degree of BHR, conjunctival sensitivity, number of allergen sensitizatlons, and occurrence of asthma symptoms.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85009 (URN)
    Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2012-10-30
  • 308.
    Ferdousi, Hosne Ara
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Dreborg, S.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis: ECP and EPX levels are not related to bronchial hyperreactivity1997In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 27, no 5, p. 530-539Article in journal (Refereed)
    Abstract [en]

    Background Symptoms of allergic asthma are triggered by allergen exposure inducing allergic inflammation and hyperreactivity of the bronchi.

    Objectives To investigate the possible relationship between clinical symptoms and signs of asthma, i.e. bronchial variability as measured by peak expiatory flow rate (PEFR). bronchial hyperreactivity (BHR) and mediators of allergic inflammation.

    Methods Twenty-eight children with pollinosis. but no obvious history of asthma, were studied at three occasions, i.e. before, during and after (autumn) the birch pollen season. Twelve children sensitive to birch pollen were considered as the case group. Sixteen children, who were only clinically sensitive to grass pollen, served as controls. Subjective symptoms of asthma were recorded by visual analogue scale, BHR was estimated by methacholine bronchial provocation tests, bronchial variability PEFR and circulating mediators of inflammation, i.e. eosinophil cationic protein, eosinophil protein X, myeloperoxidase and tryptase in serum.

    Results Bronchial hyperreactivity and by PEFR was more pronounced after than during the season (P < 0.01), whereas eosinophil mediators and the peak expiratory flow rate increased during the season (P < 0.05). Except for between PEFR variability and BHR in the autumn (r= 0.45; P= 0.014). no correlations were found. However, in the autumn, the majority of children were still hyperreactive in the bronchi and showed PEFR variability but the levels of eosinophil mediators in serum had returned to normal levels.

    Conclusion Signs and symptoms of asthma did not correlate with serum levels of mediators of allergic inflammation. Bronchial hyperreactivity and PEFR variability persisted after the pollen season when signs of bronchial inflammation had disappeared. We hypothesize that eosinophil mediators and other markers of allergic inflammation disappear after the late-phase reaction, whereas BHR persists. This would explain the lack of correlation between the levels of eosinophil mediators in serum and symptoms of asthma and BHR.

  • 309.
    Ferdousi, Hosne Ara
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Halken, Susanne
    Central Hospital, Sønderborg, Denmark.
    Høst, Arne
    University Hospital, Odense, Denmark.
    Jacobsen, Lars
    ALK-Albelló, Hørsholm, Denmark.
    Løwenstein, Henning
    ALK-Albelló, Hørsholm, Denmark.
    Koivikko, Antti
    University Hospital, Turku, Finland.
    Möller, Christian
    University Hospital, Umeå, Sweden.
    Niggemann, Bodo
    University Children's Hospital Charité of Humbolt-University, Berlin, Germany.
    Norberg, Lene Annette
    University Hospital, Odense, Denmark.
    Urbanek, Radvan
    University Hospital, Vienna, Austria.
    Koller, Dieter Y.
    University Hospital, Vienna, Austria.
    Wahn, Ulrich
    University Children's Hospital Charité of Humbolt-University, Berlin, Germany.
    Valovirta, Erkka
    University Hospital, Turku, Finland.
    Dreborg, Sten
    Linköping University, Faculty of Health Sciences.
    Clinical characteristics of school children with birch and/or grass pollen hay-fever (The PAT-Study)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: To describe the clinical characteristics of school children with hay-fever based on baseline data from the PAT-Study.

    Material: Two hundred and five children, 6-15 years, mean 10.7 years, with birch and or grass pollen hay-fever, without known asthma were recruited by six pediatric allergy centers in Northern and Central Europe.

    Methods: Bronchial hyperresponsiveness (BHR) to methacholine tested by methacholine bronchial provocation test (MBPT) expressed in PC20 was registered during the birch and grass pollen seasons. During the winter symptoms of conjunctivitis, rhinitis and asthma were graded by visual analogue scale (VAS), conjunctival provocation test with birch and or timothy pollen extracts, skin tests with a panel of allergen extracts and MBPT were done and a questionnaire was filled in. Differences of p <0.01 level or less were considered significant.

    Results: Despite the children were included because of seasonal hay-fever without known asthma, 42/205 children (21 %) got doctor diagnosed asthma (DDA) after the first season. During the three seasons, between 60 and 73 % of the children had a PC20 to methacholine ≤ 8 mg/ml, about 30 % to ≤ 2 mg/ml and 7-10% even to ≤ 0.5 mg/ml. Most children had both rhinitis and conjunctivitis. Furthermore, 119/201 children (59%) were regularly exposed to furred animals.

    There was an association between DDA and the sum of VAS for asthma during the pollen seasons.

    The BHR was significantly more pronounced in those with than those without DDA during all three seasons: Using the three cut offs, the difference was most pronounced during the winter season but reached also significance using the cut off limit 0.5 mg/ml during the birch pollen season.

    Doctor diagnosed asthma correlated to PC20 during the seasons for most of the cut off limits for PC20 and in general there was an association in PC20 between the seasons independent of cut off limits.

    Furthermore, DDA, but not BHR, correlated to exposure to traffic and there was an association between exposure to traffic and industrial pollution, but not to ETS or duration of breastfeeding.

    Conclusion: The most striking feature of school children with uncomplicated hay-fever was the high frequency of DDA and BHR, most pronounced during the winter, the high frequency of exposure to living animals and sensitization to indoor allergens. Hay-fever is a generalized disease. Even without obvious asthma, BHR is common and most children have symptoms from both the eyes and the airways. Diagnosis of asthma in children with hay-fever and early anti-inflammatory treatment may improve the prognosis.

  • 310.
    Ferdousi, Hosne Ara
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Munir, Abdul Kashem Mohamma
    Linköping University, Department of Medicine and Care, Pulmonary Medicine. Linköping University, Faculty of Health Sciences.
    Zetterström, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Dreborg, Sten
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Seasonal differences of peak expiratory flow rate variability and mediators of allergic inflammation in non-atopic adolescents2001In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 5, p. 238-246Article in journal (Refereed)
    Abstract [en]

    Variations in peak expiratory flow (PEF) and serum eosinophil mediators were studied in healthy adolescents. Twenty-five boys and 31 girls, 11–16 years of age (mean age 14.3 years), were selected and investigated during the birch pollen season of 1995; 45 were also investigated during the autumn of the same year. The PEF was measured twice daily and eosino-phil mediators in serum and in urine were measured by radioimmunoassay (RIA) once during the birch pollen season and once in autumn. The type values of the daily PEF variation, expressed in amplitude percentage mean, were 6.4 and 3.9%, mean values were 7.35 and 6.74%, and the 95th percentiles were 18 and 14%, during the birch pollen season and autumn, respectively. The 95th percentiles were 41 and 38 µg/l for serum eosinophil cationic protein (s-ECP), 74 and 62 µg/l for serum eosinophil protein X (s-EPX), 987 and 569 µg/l for serum myeloperoxidase (s-MPO), and 165 and 104 µg/mmol for urinary eosinophil protein X/urinary creatinine (u-EPX/u-creatinine), during the birch pollen season and autumn, respectively. The levels of the eosinophil mediators decreased significantly from May (n = 56) to November (n = 45), for s-ECP from a median value of 14 µg/l to 7 µg/l (p= 0.001), for s-EPX from a median value of 28 µg/l to 20 µg/l (p= 0.001), and for the neutrophil mediator, s-MPO, from a median value of 440 g/l to 292 g/l (p< 0.001). The PEF variability decreased significantly (p= 0.037), from spring (n = 55; median 8%, 95% confidence interval [CI] 7.8–10.19) to autumn (n = 44; median 6%, 95% CI 6.1–8.9). A significant correlation was found between the levels of s-ECP and s-EPX (rs = 0.7, p< 0.001), between s-ECP and s-MPO (rs = 0.6, p< 0.001), between s-EPX and s-MPO (rs = 0.4, p< 0.005), and between s-EPX and u-EPX/u-creatinine (rs = 0.6, p< 0.0001), in the birch pollen season (n = 56) and in the autumn (n = 45). There was a positive correlation found in PEF variability between the two seasons (n = 43; rs = 0.5, p= 0.0006). No other correlation was found between PEF variability and any other parameters. The difference in the levels of eosinophil mediators between seasons in non-atopic, healthy children is unexplained. Normal limits for mediators were higher and PEF variability was almost the same as has been reported in adults. When using normal values, seasonal influences should be considered.

  • 311.
    Ferdousi, Hosne Ara
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Zetterström, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences.
    Dreborg, Sten
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Asthma and allergy in pollinosis children: an 11-year follow-up of specific immunotherapyManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Pollen immunotherapy is effective in hay fever and asthma in children, although there are few studies on the long-term benefit.

    Methods: We conducted a longitudinal follow up for 11 years of specific immunotherapy (SIT) for birch and or grass pollen allergy in children (n=28) who took part in the preventive allergic treatment (PAT) study. Bronchial hyperresponsiveness (BHR.) to methacholine, conjunctival provocation tests (CPT), and the skin sensitivity to common allergens-(SPT) were done. A matched group of patients who had not received immunotherapy served as controls.

    Results: Eight years after of discontinuation of IT, 11 children with and 11 children without IT could be investigated. In the SIT group 2 had asthma compared to 7 in the control group. The skin and conjunctival sensitivity in the SIT group decreased more (n.s.). Birch pollen counts were measured dming the pollen seasons in every year from 1992 to 1995 and in the year 1997. The years 1993 and 1995 had high levels of birch pollen counts compared to the other years.

    When all the children were considered, scores for asthma symptoms and BHR was higher in these years.

    PEF variation decreased with age in both groups.

    Conclusions: SIT for hay fever for three years induced a clinical remission 8 years after discontinuation of immunotherapy accompanied by a reduction in the degree of BHR, conjunctival sensitivity, number of allergen sensitizatlons, and occurrence of asthma symptoms.

  • 312.
    Ferdousi, Hosne Ara
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Zetterström, Olle
    Linköping University, Department of Medicine and Care, Pulmonary Medicine. Linköping University, Faculty of Health Sciences.
    Dreborg, Sten
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever2005In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 16, no 6, p. 478-486Article in journal (Refereed)
    Abstract [en]

    In children with mild asthma, symptoms are not always apparent. Therefore, results of tests play an important role for the diagnosis. First, to investigate whether children with bronchial hyper-responsiveness (BHR) but no symptoms of asthma in 1992 had developed clinical asthma at follow up in 1994. The second aim was to find out the diagnostic properties of tests for asthma/allergic inflammation, using either doctor diagnosed asthma (DDA), self-assessed symptoms of asthma or iso-capnic hyperventilation of cold air (IHCA), as the standard, to diagnose asthma in a group of children with hay fever. Twenty-eight children with pollinosis, 12 of them with a history of asthma for the first time during the season 1992, were studied during the birch pollen season and in the autumn of 1994. During both periods, the bronchial hyper-reactivity was estimated by methacholine bronchial provocation tests (MBPT), bronchial variability by peak expiratory flow rate variability, subjective symptoms of asthma by visual analogue scale (VAS) and bronchial inflammation by serum and urine levels of inflammatory mediators. In 1994 IHCA was added during both seasons. Eight of 16 children with BHR but without clinical asthma in 1992 had developed asthma in 1994, 14 of 16 reacted to IHCA and 13 to MBPT. All 12 children with DDA in 1992 had still asthma in 1994 and 14 children with BHR in 1992 had persistent BHR in 1994. Of 23 children with BHR in 1992, 17 had DDA in 1994 and all maintained their BHR. Furthermore, 20 of them reacted to IHCA in 1994. In 1994, 24 of 28 hay-fever children had a positive IHCA tests and 24 had positive MBPT. In relation to VAS, the sensitivity of IHCA and MBPT to predict present asthma was high, but the specificity low, whereas the specificity of most other tests was high, but based on few individuals. In relation to DDA both the IHCA test (65–80%) and the MBPT test (79–85%) had a high sensitivity and it was three to six times more likely to find a positive test among asthmatics than in non-asthmatics. Children with hay fever without clinical asthma have a high risk of developing asthma within 2 yr. In relation to DDA, inhalation of cold air and the MBPT showed a high sensitivity.

  • 313.
    Ferdousi, Hosne Ara
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Zetterström, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences.
    Munir, Abdul Kashem Mohamma
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Respiratory Medicine. Linköping University, Faculty of Health Sciences.
    Cat allergen exposure in Swedish schools is high enough to maintain continuous bronchial hyperreactivity and to cause symptoms in children with asthma who are sensitized to catManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Exposure to indoor allergens play a major role for development of sensitization and induction of allergic inflammation, bronchial hyperreactivity and symptoms in sensitized individual.

    Objective: fu this study, we investigated the individual exposure levels of cat allergen, Fel d1, among asthmatic schoolchildren sensitized to cats. We studied the exposure relationship with symptoms, medication, lung functions, bronchial hyperreactivity (BHR) and mediators of allergic inflallrmation.

    Methods: Ten school children with known allergy to cats were selected from 5 schools in Linköping, Sweden. All children had positive skin test to cats. We collected dust samples from homes and schools. All children carried a portable air-sampler in the schools during the period of 4-6 weeks. Air was also sampled fi·om the bedroom. The children performed lung function (PEF) twice daily using a digital Peak flow meter. They maintain symptom and medication chart once in a week. We performed methacholine bronchial provocation test (PD20) and analyzed mediators of allergic inflammation (s-ECP, EPX and MPO) iu blood and urine at the beginning and at the end of the study period. Dust and air samples were analyzed for major cat allergen (Fel d1) using ELISA.

    Results: Exposure levels of cat allergen varied from 0,5 µg/g to 751 µg/g dust in homes (median, 36 µg/g) and from 17 µg/g to 378 µg/g in schools (median, 137 µg/g). Airborne allergen levels varied from 13 to 2184 pg/m3 (median, 43 pg/m3) in the homes and 68 to 7718 pg/m3 (median 352 pg/m3) in the schools. The mediators of allergic inflammation ranged from 4 to 57 µg/L for ECP, from 12 to 73 µg/L for EPX and from 148 to 581 µg/L for MPO. All children had bronchial hyperreactivity and all but one child used asthma/allergy medicine during the entire study period. A significant relationship (p<0.05) was found between the peak allergen exposure and symptoms, airborne allergens and BHR of the children.

    Conclusions: Our study suggests, that school is an important source of cat allergen exposure, that cat sensitized asthmatic children inhale a substantial amount of cat allergen in the schools, that despite treatment of asthma including regular use of inhaled corticosteroids, 8 pg to 2336 pg of cat allergen inhaled per minute is sufficient enough to maintain a continuous airway hyper-responsiveness among this group of children.

  • 314.
    Ferrándiz, Rafael
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Allergenic characterization of the domestic mite Dermatophagoides siboney1997Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Allergic reactions to Pyroglyphid mites of the genus Dennatophagoides play an important role in the pathogenesis of asthma and other atopic diseases. Dermatophagoides siboney was described in Cuba in 1982. D. pteronyssinus and D. siboney are the most frequent mites in house dust collected from the homes of Cuban asthmatics, i.e., 100 and 85%, respectively.

    The aims of the present studies were to investigate the prevalence of sensitization to D. siboney, Blomia tropicalis and other mite species in asthmatic patients from Cuba; to study the allergenic composition and to characterize the major allergens of D. siboney extracts; to investigate the crossreactivity between D. siboney and other mite allergens, and the relevance of patient selection for the determination of the biological activity of D. siboney and other domestic mites in the tropics.

    Dermatophagoides siboney was found to be an important sensitizing agent among asthmatics in Cuba. Sensitization to B. tropicalis, D. pteronyssinus, D. farinae and A. siro, was also common as studied by skin and specific IgE tests. A combination of SPT with D. siboney, D. pteronyssinus and B. tropicalis diagnosed sensitization to mites in almost all mite sensitive patients. Thirteen allergenic proteins were identified in D. siboney extracts. Three components, 25, 14 and 30 kD, which bound to specific IgE strongly and frequently, were purified by affinity chromatography using crossreacting monoclonal antibodies to group 1; 2 and 3 allergens and named Der s 1, Der s 2 and Der s 3, respectively. TheN-terminal sequences of these allergens showed higher homology with D. jarinae and D. microceras than with D. pteronyssinus. The homology between group 2 allergens was higher than that of group 1 and 3 allergens.

    A higher degree of crossreactivity was observed between allergens from D. siboney and D. farinae than betWeen D. siboney and D. pteronyssinus, B. tropicalis, A. siro, L. destructor or T. putrescentiae. Due to the crossreactivity, Cubans not exposed to D. farinae and Swedes not exposed to D. siboney and B. tropicalis, reacted to these mites. The individual allergens of D. siboney crossreacted more with those of D. farinae and D. microceras than with those of D. pteronyssinus. The 65, 62, 37 and 30 kD proteins, always inhibited by more than 50 % by the other mite species, were the main cause of the crossreactivity, The 80 kD protein was the less crossreactive allergen. Three MoAbs directed to Der s 1, one group crossreacting and two species specific, were produced. The crossreacting monoclonal antibody partly inhibited IgE binding to Der s 1 allergen. The results confmned the existence of crossreacting epitopes onDer s 1 but also indicate that this allergen has at least one species specific epitope.

    The degree of reactivity to different mites seemed to be more related to patient selection criteria and extract potency rather than to exposure to a specific species.

    Since D. siboney is common in dust from Cuban homes, it is probably present in other Caribbean countries and found to be an important sensitizer, it has been considered a potential candidate for the development of extracts for diagnosis and therapy of mite allergy. These studies contribute to the understanding of the characteristics of the allergens from this species and their relation to other mite allergens.

  • 315. Fierabracci, A
    et al.
    Biro, PA
    Yiangou, Y
    Mennuni, C
    Luzzago, A
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Cortese, R
    Bottazzo, GF
    Osteopontin is an autoantigen of the somatostatin cells in human islets: identification by screening random peptide libraries with sera of patients with insulin-dependent diabetes mellitus.1999In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 18, p. 342-354Article in journal (Refereed)
  • 316.
    Filbey, Derek
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Alloimmunization during pregnancy with special emphasis on anti-D: Laboratory and clinical management1995Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The laboratory and clinical management of alloimmunized in pregnancy has been investigated according to a protocol currently in use in Örebro region. A 12 year epidemiological study showed the prevalence of alloimmunization to be 0.57% in this Swedish populationwith a 0.24% incidence of clinically significant antibodies that can induce haemolytic disease of the newborn (HDN). Rh antibodies, predominantly anti-D, are still the causes of most cases of severe HDN in which 45/47 babies required exchange transfusion. During the studyperiod, 14 mothers were successfully treated with plasma exchange during pregnancy owing to high anti-D antibody concentrations. Only two other blood group syswms, Kell and Duffy, besides Rh affected newborns to alloimmunized mothers to such a grade that exchange transfusion of the newborns was necessary. All generally accepted for the fetus clinically nonsignificant antibodies were also followed and shown not to cause HDN. In 3 instances, anti-D was detected in partial RhO-positive mothers who were carrying normal RhO-positive fetuses,a study to identify these partial RhD individuals and to group them into D-categories was performed. The ability of the indirect antiglobulin titre (IAT), AutoAnalyzer (AA) quantitation and chemiluminescence l£st (CLT) performed on maternal anti-D serum during pregnancy to discriminal£ babies affected or unaffected by HDN has been studied. It was found that all methods had their weaknesses, but AA-quantitation and CLT improved speeifieity when compared to the IAT-titration method. However, a great improvement was achieved when the results of IAT-titration and AA-quantitation, as determined by the cut-offlimits applied to discriminate unaffected from affected newborns, were combined; specificity was then found to increase from 60-78% to 93% and was further increased with the addition of the CLT test to 95%. Finally, the detection of HLA class II monocyte-reactive antibodies and their potential protective role in ameliorating HDN has been viewed.

  • 317.
    Filippini, Daniel
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Tejle, Katarina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Lundström, Ingemar
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    ELISA test for anti-neutrophil cytoplasm antibodies detection evaluated by a computer screen photo-assisted technique2005In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 21, no 2, p. 266-272Article in journal (Refereed)
    Abstract [en]

    The computer screen photo-assisted technique (CSPT), a method for substance classification based on spectral fingerprinting, which involves just a computer screen and a web camera as measuring platform is used here for the evaluation of a prospective enzyme-linked immunosorbent assay (ELISA). A anti-neutrophil cytoplasm antibodies (ANCA-ELISA) test, typically used for diagnosing patients suffering from chronic inflammatory disorders in the skin, joints, blood vessels and other tissues is comparatively tested with a standard microplate reader and CSPT, yielding equivalent results at a fraction of the instrumental costs. The CSPT approach is discussed as a distributed measuring platform allowing decentralized measurements in routine applications, whereas keeping centralized information management due to its natural network embedded operation. © 2004 Elsevier B.V. All rights reserved.

  • 318.
    Finnström, Orvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    A genetic reason for male excess in infant respiratory mortality?2004In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 93, no 9, p. 1154-1155Article in journal (Refereed)
    Abstract [en]

    Male infants have a 50% higher risk of death from respiratory diseases and a number of congenital heart diseases that can lead to cerebral hypoxia. The most important of these diseases are infant respiratory distress syndrome and sudden infant death syndrome. Conclusion: The mechanism behind the excess peri-mortality rate in male infants is not known. A genetic factor leading to reduced tolerance to hypoxia is possible.

  • 319.
    Finnström, Orvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Mätfel i randomiserade kontrollerade studier i neonatala perioden- Kvalilteten brister rörande det informerade samtycket.2001In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, p. 2474-2475Article in journal (Other academic)
  • 320.
    Finnström, Orvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Berg, Göran
    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.
    Norman, Anna
    Centre for Epidemiology, National Board of Health and Welfare Stockholm.
    Otterblad Olausson, Petra
    Centre for Epidemiology, National Board of Health and Welfare Stockholm.
    Size of delivery unit and neonatal outcome in Sweden. A catchment area analysis2006In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 85, no 1, p. 63-67Article in journal (Refereed)
    Abstract [en]

    Background. Quality of perinatal care was evaluated in relation to size of delivery unit and size of catchment area for deliveries. Methods. Neonatal outcome, measured as neonatal mortality, low Apgar scores at 5 min, and the occurrence of respiratory disorders and cerebral palsy was analyzed during a 15-year period from 1985 to 1999 inclusive. Figures were derived from the Swedish Medical Birth Registry and the Hospital Discharge Registry. Odds ratios were estimated for the different outcomes in relation to size of delivery unit (actual and estimated number of births) and the provision of a pediatric department at the hospital. Seven possible confounders were considered: year of birth, maternal age, parity, smoking during pregnancy, gestational age, parental cohabitation, and maternal body mass index. Results. Neonatal mortality was significantly higher for infants in families living within the catchment area of the smallest units without a pediatric department. Small differences in the occurrence of respiratory disturbances and Apgar scores are probably due to diagnostic differences. There were no differences in the incidence of cerebral palsy. Neonatal mortality continued to decrease during the observation period. Conclusions. Differences were minor, pointing to a fairly homogeneous quality of perinatal care and an efficient referral system for risk pregnancies. Mortality continues to decrease in spite of a reduction in the number of units caring for deliveries. © 2006 Taylor & Francis.

  • 321.
    Finnström, Orvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Bylund, Bengt
    Västerviks sjukhus.
    Cervin, Torsten
    Centralsjukhuset i Kalmar.
    Gäddlin, Per-Olof
    Linköping University, Department of Molecular and Clinical Medicine.
    Leijon, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Mård, Selina
    Linköping University, Department of Behavioural Sciences.
    Samuelsson, Stefan
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Behavioural Sciences, Teaching and Learning in School, Teacher Education and other Educational Settings.
    Sandstedt, Per
    hälsouniversitetet i Linköping.
    Wärngård, Olof
    Norrköpings sjukhus.
    Mycket lågviktiga barn vid 9 års ålder. De flesta klarar sig bra men barn med skolsvårigheter är överrepresenterade2000In: Svenska läkartidningen, ISSN 0371-439X, Vol. 97, p. 3492-3498Article in journal (Refereed)
  • 322.
    Finnström, Orvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Giordano, Luisa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nelson, Nina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Jakobsson, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Komplikationer i nyföddhetsperioden kan ge synhandikapp senare i livet.2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 34, p. 2560-2562Article in journal (Other academic)
  • 323.
    Finnström, Orvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Gäddlin, Per-Olof
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Leijon, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Samuelsson, S
    Wadsby, Marie
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Child and Adolescent Psychiatry.
    Very-low-birth-weight children at school age: Academic achievement, behavior and self-esteem and relation to risk factors2003In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 14, no 2, p. 75-84Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate school performance, behavior and self-esteem of children with very low birth weight (VLBW). Methods: All children with birth weight below 1501 g (VLBW) and normal birth weight controls, born in the south-east region of Sweden during a 15-month period in 1987-88, were enrolled in a prospective follow-up study. At the age of 9 years, 81% and 82%, respectively, were re-examined regarding growth, neurofunctional classification, academic achievement tests, need for special education and behavioral problems. At 12 years, 89% and 76%, respectively, were re-examined regarding growth, neurofunctional classification, visual acuity and self-esteem. Results: VLBW children were shorter and lighter, and differed from the controls with regard to neurological functional classification. They produced poorer results in most academic achievement tests. When the comparison was restricted to children with normal intelligence, almost all the differences in other academic achievements disappeared. VLBW children had more reading difficulties but were less often than expected defined as dyslexics compared to control children. We did not find any major disparity in visual acuity and self-esteem between the groups. Low Apgar scores, intracranial hemorrhage and the need for mechanical ventilation neonatally were associated with poorer results in most outcome measures. Neurofunctional assessments in early childhood were associated with most outcome measures. The mother's education was related to delayed reading skills and need for special education. Conclusions: Although VLBW children performed less well in most academic achievement tests and on some behavioral subscales, those who had a normal intellectual capacity did not differ in any important aspects from the controls.

  • 324.
    Finnström, Orvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Leijon, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Samuelsson, S
    Bylund, B
    Cervin, T
    Gäddlin, PO
    Mård, S
    Wärngård, O
    Skolsvårigheter vanliga hos barn med mycket låg födelsevikt. Extra uppmärksamhet och stöd behövs vid skolstart.2000In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 97, p. 3492-3498Article in journal (Other academic)
  • 325.
    Finnström, Orvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nygren, KG
    IVF Clinic Sophiahemmet, Stockholm.
    Otterblad Olausson, P
    Centre for Epidemiology Stockholm.
    Strömberg, B
    Wennerholm, Ulla-Britt
    Kvinnokliniken Göteborg.
    Cerebral palsy in children born after IVF in Sweden 1982-1995: type of CP and maternal/obsterical characteristics are similar to those in non-IVF children with CP2005In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 84, no 12, p. 1215-1215Article in journal (Refereed)
  • 326.
    Finnström, Orvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nygren, K-G
    IVF och Fertilitetskliniken, Sophiahemmet, Stockholm.
    Otterblad Olausson, Petra
    Epidemiologiskt Centrum, Socialstyrelsen, Stockholm.
    IVF i Sverige - Fortsatt uppföljning av barn och mödrar2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, no 32-33, p. 2301-2305Article in journal (Refereed)
    Abstract [sv]

    This paper summarises six recently published studies which evaluate Swedish in vitro fertilization from 1982 to 2003 and is a register study, based on national registers linked through personal identification numbers. Data were available for all 12186 mothers and their 16280 children. Comparisons were made with the total delivering population. The number of children born after IVF increases steadily and amounts to 3% presently. The number of twins has decreased considerably. Some increased risks persist after IVF, a slightly higher perinatal death rate and an increased risk for congenital malformations. There were no differences between conventional IVF and ICSI. The risk for cancer was not increased with one possible exception, histiocytosis. Morbidity during childhood measured as hospital admissions, was increased due to more preterm births and multiple births in the IVF group. IVF mothers were older and smoked less than other mothers. Their medical drug use differed from that of other pregnant women. In general they had a decreased cancer risk, but probably an increased risk for ovarian cancer. Maternal mortality was not increased. Several obstetric complications were more common in IVF mothers: ovarial torsion, preeclampsia, premature rupture of membranes, bleeding at delivery and placental abruption. The deliveries were more often induced, and the frequency of caesarean section was increased.

  • 327.
    Finnström, Orvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Otterblad-Olausson, P
    Sedin, G
    Serenius, F
    Svenningsen, N
    Thiringer, K
    Tunell, R
    Wennergren, M
    Wesström, G
    Stor studie indikerar god prognos för barn med extremt låg födelsevikt. 1999In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 96, p. 1560-1567Article in journal (Other (popular science, discussion, etc.))
  • 328.
    Finnström, Orvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Persson, J
    Ethical aspects of decision-making at the limit of viability.1999In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 88, p. 708-709Article in journal (Other (popular science, discussion, etc.))
  • 329.
    Flodin, Ulf
    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.
    Jönsson, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Non-sensitising air pollution at workplaces and adult onset asthma2004In: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 77, no 1, p. 17-22Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to elucidate further whether occupational exposure to non-sensitising air pollution at workplaces increases the risk of adult onset asthma. Methods: One hundred and twenty persons with asthma diagnosed by general practitioners, aged 20-65 years, were compared with 446 referents matched for age and gender and living in the same community as the cases. Information about occupation, exposure to specific allergens, smoking habits, dwellings and atopy was obtained from a postal questionnaire. The subjects' occupations were categorised as clean or polluted, based on the judgement of the referents on their respective occupations. Results: Three years or more of work in air-polluted workplaces resulted in an odds ratio of 1.7 (95% confidence interval 1.0-2.7). Stratification of the material on smoking habits, gender or atopy did not alter the results, nor did exclusion of subjects exposed to specific allergens of statistical significance in this material, e.g. flour dust. Smoking per se did not bring any risk of asthma. Working in buildings affected by dampness and mould brought a fourfold significant risk. Conclusion: In this study occupational exposure to unspecific air pollution at workplaces was associated with an increased risk of adult-onset asthma.

  • 330.
    Flodin, Ulf
    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.
    Seneby, Agneta
    Tegenfeldt, Clas
    Provocation of electric hypersensitivity under everyday conditions2000In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 26, no 2, p. 93-98Article in journal (Refereed)
    Abstract [en]

    Objectives. In most previous provocation studies subjects suffering from ?electric hypersensitivity? have not been able to determine correctly whether or not they have been subjected to a sham or true provocation to magnetic or electric fields. However, an often-discussed weakness is that most of the earlier provocation studies have been performed in a laboratory situation, often with simulated fields, which may not be representative of conditions prevailing in the homes or workplaces of the patients. Criticism has also been put forth about neglect of the long latency period of symptoms. Therefore, a provocation study was performed in the homes or workplaces of the patients, where we also studied the symptoms and on-off answer 24 hours after the exposure. Methods. Fifteen subjects selected as having fast and distinct reactions from electric equipment were provoked on 4 occasions: mainly 2 true and 2 sham provocations. The intervals between exposure were a few or more days in order to provide the subjects with an opportunity to recover before the next provocation. A control group of healthy subjects with normal hearing and vision verified that the provocations were performed in a blind manner. Results. The patients suffering from ?electric hypersensitivity? were no better than the control group in deciding whether or not they were exposed to electric and magnetic fields. Conclusions. Exposure to electric and magnetic fields per se does not seem to be a sufficient cause of the symptoms experienced by this patient group.

  • 331. Foberg, U
    et al.
    Frydén, Aril
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Jahrling, P
    Johnson, A
    McKee, K
    Niklasson, B
    Normann, Bengt
    Linköping University, Department of Clinical and Experimental Medicine.
    Peters, C
    Bengtsson, M
    Viral haemorrhagic fever in Sweden: experiences from management of a case.1991In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 23, no 2, p. 143-151Article in journal (Refereed)
    Abstract [en]

    The first recognized case in Scandinavia with potential man to man transmission of viral haemorrhagic fever occurred in Linköping, Sweden, in January 1990. Following a visit to Kenya a 21-year-old male student suffered a very severe illness including extremely prolonged high grade fever, rash, disseminated intravascular coagulation with thrombocytopenia and severe bleedings. This necessitated one month of intensive care support including respirator treatment. The patient was discharged after 2 1/2 months in good condition, with a partial femoral nerve paresis. About 100 medical personnel were exposed to aerosol or blood before a strict containment regimen was established. No secondary cases occurred.

  • 332.
    Follin, Per
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    The primed neutrophil: a friend or a foe in inflammation1991Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Human neutrophils are the most abundant of the white blood cells in circulation and represent the first line of defense against invading microorganisms. With a membrane-bound enzyme system (the NADPH oxidase), these cells can generate reactive oxygen metabolites that serve efficiently in antimicrobial defense. Neutrophils are normally dormant in the circulation but may become primed; in that state they can produce an enhanced respiratory burst response upon activation and thereby strengthen the immune response.

    During bacterial infections, endogenous inflammatory mediators orbacterial products induce metabolic priming of neutrophils, which thenexpose an increased number of receptors to the peptide f-Meth-Leu-Phe(fMLP). There is, however, no correlation between the increased level ofrespiratory burst response and the level of receptor upregulation, indicating that post-receptor events in the activation sequence are also involved. Neutrophils isolated from an inflammatory focus were found tobe metabolically deactivated as far as the agonists NAP-1/IL 8 and C5awere concerned but primed in relation to tMLP. Further characterizationof exudated cells revealed that the mechanism of priming involves protein kinase C but not a rise in intracellular Ca2+ or a decreased inactivation rate of the oxidase. In primed cells most of the increased production of reactive oxygen species induced by fMLP is located intracellularly, whereas, an increased extracellular release of reactive oxygen species occurs during phagocytosis. The fact that primed cells can both produce and, under certain conditions, release increased amounts of hydrogen peroxide raises the question of whether the primed cell is a friend or a foe in the inflammatory reaction.

  • 333.
    Follin, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Frydén, Aril
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Tropiska virusinfektioner2004In: Infektionsmedicin: epidemiologi, klinik, terapi / [ed] Iwarson-Norrby, Säve Förlag , 2004, 3, p. 395-408Chapter in book (Other academic)
    Abstract [sv]

    Denna klassiska lärobok kom 2011 ut i sin 5:e, omarbetade upplaga. Boken innehåller 28 kapitel, vilka täcker hela infektionspanoramat, från influensa till AIDS. Samtliga författare är läkare och flertalet universitetslärare. Den innehåller även 16 sidor färgplanscher med fotoillustrationer av olika sjukdomar. Boken är avsedd att användas i undervisningen av blivande läkare och som uppslagsbok i sjukvården

  • 334.
    Fornell, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Urininkontinens vanligt hos nunnor2003In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, p. 2282-2282Article in journal (Other academic)
  • 335.
    Forsberg, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Signal transduction in human phagocytic cells during phagocytosis, oxidative activation and apoptosis2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Neutrophils and macrophages are professional phagocytic cells that play a crucial role in host defense against invading microorganisms. They bind to, internalize, and subsequently kill microbes with an arsenal of reactive oxygen metabolites and microbicidal agents. The microbes are recognized by cell surface receptors, mainly by the phagocytic receptors FcγR and complement receptor 3 (CR3) that recognize IgG and complement fragments C3b/C3bi, respectively. Microbial pathogens such as Salmonella typhimurium have developed sophisticated mechanisms to avoid the host defense system and enter the cells by invasion, mediated by a type III secretion system.

    The objective of this thesis was to investigate the signaling pathways during receptor-mediated phagocytosis by FcγRIIa, FcγRIIIb and complement receptor 3 (CR3), or during invasion by Salmonella typhimurium in human phagocytic cells. We have focused on the intracellular signaling pathways controlling phagocytosis, production of reactive oxygen metabolites, and apoptosis. Paper I-III focus on signal transduction events triggered after ligation of CR3, FcγRIIa, and FcγRIIIb in human neutrophils. Both activation of CR3 and FcγR induced production of reactive oxygen metabolites (ROM), where CR3 induced the most prominent response. The ROM production was dependent on intracellular Ca2+, tyrosine kinase activation, and phospholipase D (PLD) activity. FcγRIIa induced a strong phosphorylation Syk, which was less pronounced following FcγRIIIb ligation, and absent after CR3 activation. Our data indicate that CR3 and FcγR activate different signaling pathways. By exposing neutrophils to TNF-α prior to ligation of CR3, the oxidative response was strongly enhanced, whereas the response to FcγR-ligation was unaffected. This increase was in part due to a p38 MAPK-dependent upregulation of CR3 on the cell surface, but also due to modulation of intracellular signaling pathways since Syk was activated by CR3 as well as FcγR in TNF-α treated cells. In contrast to macrophages where only FcγR activates Rac, Cdc42, and the subsequent ROM production, we show that CR3 as well as FcγR activate the GTPases Rac2 and Cdc42 in human neutrophils. Their downstream target p21 activated kinase was also activated, and Rac2 translocated to the membrane fraction. Correct function of these small GTP-binding proteins was necessary for generating a proper signal for ROM production in these cells.

    One survival strategy exploited by microbial pathogens might be to induce apoptosis of tbe host. Invasive Salmonella typhimurium efficiently entered U937 cells and induced a pronounced degree of apoptosis in contrast to its opsonized mutants, which were internalized by receptor-mediated phagocytosis but failed to induce apoptosis. Invasion by Salmonella typhimurium activated Rac1 and Cdc42 independently of PI3 K and tyrosine kinase activation. Inhibition of Racl and Cdc42 inhibited both invasion and the induction of apoptosis. Receptor-mediated phagocytosis activated the survival signals Akt/PKB which protected the cells from apoptosis. Thus, control of apoptosis is a fine tuned balance between pro- and anti-apoptotic signaling proteins.

    List of papers
    1. CR3, FcγRIIA and FcγRIIIB induce activation of the respiratory burst in human neutrophils: the role of intracellular Ca2+, phospholipase D and tyrosine phosphorylation
    Open this publication in new window or tab >>CR3, FcγRIIA and FcγRIIIB induce activation of the respiratory burst in human neutrophils: the role of intracellular Ca2+, phospholipase D and tyrosine phosphorylation
    Show others...
    1999 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1452, no 1, p. 46-59Article in journal (Refereed) Published
    Abstract [en]

    Human neutrophils express two different types of phagocytic receptors, complement receptors (CR) and Fc receptors. In order to characterize the different signaling properties of each receptor we have used non-adherent human neutrophils and investigated CR3, FcγRIIA and FcγRIIIB for their signaling capacity. Selective activation of each receptor was achieved by coupling specific antibodies to heat-killed Staphylococcus aureus particles, Pansorbins, through their Fc moiety. Despite the fact that these particles are not phagocytosed, we show that addition of Pansorbins with anti-CD18 antibodies recognizing CR3 induced prominent signals leading to a respiratory burst. Stimulation with anti-FcγRIIIB Pansorbins induced about half of the response induced by anti-CR3 Pansorbins, whereas anti-FcγRIIA Pansorbins induced an even weaker signal. However, FcγRIIA induced strong phosphorylation of p72syk whereas FcγRIIIB induced only a very weak p72syk phosphorylation. During CR3 stimulation no tyrosine phosphorylation of p72syk was seen. Both phospholipase D and NADPH oxidase activities were dependent on intracellular calcium. This is in contrast to tyrosine phosphorylation of p72syk that occurred even in calcium-depleted cells, indicating that oxygen metabolism does not affect p72syk phosphorylation. Inhibitors of tyrosine phosphorylation blocked the respiratory burst induced by both FcγRIIA and FcγRIIIB as well as CR3. This shows that tyrosine phosphorylation of p72syk is an early signal in the cascade induced by FcγRIIA but not by CR3.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25448 (URN)10.1016/S0167-4889(99)00112-3 (DOI)9894 (Local ID)9894 (Archive number)9894 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Tumour necrosis factor-α potentiates CR3-induced respiratory burst by activating p38 MAP kinase in human neutrophils
    Open this publication in new window or tab >>Tumour necrosis factor-α potentiates CR3-induced respiratory burst by activating p38 MAP kinase in human neutrophils
    2001 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 103, no 4, p. 465-472Article in journal (Refereed) Published
    Abstract [en]

    CR3 and FcγRs are the main receptors involved in the phagocytic process leading to engulfment and killing of microbes by production of reactive oxygen intermediates (ROI) and degranulation. Various inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and lipopolysaccharide (LPS), are known to prime neutrophils leading to increased bactericidal responses, but the underlying mechanism of priming has only been partially elucidated. The purpose of this study was to investigate how TNF-α primes neutrophils for subsequent stimuli via either CR3 or FcγR. The receptors were specifically activated with pansorbins (protein-A-positive Staphylococcus aureus) coated with anti-CR3, anti-FcγRIIa, or anti-FcγRIIIb monoclonal antibody. Activation of neutrophils with these particles resulted in ROI production as measured by chemiluminescence. Anti-CR3 pansorbins induced the most prominent ROI production in neutrophils. TNF-α potentiated the CR3-mediated respiratory burst but had little effect on that mediated by FcγRs. The priming effect of TNF-α on CR3-mediated ROI production is associated with an increased activation of p38 MAPK as well as tyrosine phosphorylation of p72syk. Pretreatment of neutrophils with the inhibitors for p38 MAPK and p72syk markedly suppressed the respiratory burst induced by CR3. Furthermore, TNF-α induced about a three-fold increase in the expression of CR3 in neutrophils, an effect which is blocked by the p38 MAPK inhibitor. Taken together, these results showed that TNF-α potentiates the CR3-mediated respiratory burst in neutrophils not only by triggering a p38 MAPK-dependent up-regulation of CD11b/CD18 but also by modulating the signalling pathways.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25910 (URN)10.1046/j.1365-2567.2001.01270.x (DOI)10352 (Local ID)10352 (Archive number)10352 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils
    Open this publication in new window or tab >>Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils
    Show others...
    2003 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 74, no 4, p. 611-619Article in journal (Refereed) Published
    Abstract [en]

    Phagocytosis is a complex process engaging a concerted action of signal-transduction cascades that leads to ingestion, subsequent phagolysosome fusion, and oxidative activation. We have previously shown that in human neutrophils, C3bi-mediated phagocytosis elicits a significant oxidative response, suggesting that activation of the small GTPase Rac is involved in this process. This is contradictory to macrophages, where only Fc receptor for immunoglobulin G (FcγR)-mediated activation is Rac-dependent. The present study shows that engagement of the complement receptor 3 (CR3) and FcγR and CR3- and FcγR-mediated phagocytosis activates Rac, as well as Cdc42. Furthermore, following receptor-engagement of the CR3 or FcγRs, a downstream target of these small GTPases, p21-activated kinase, becomes phosphorylated, and Rac2 is translocated to the membrane fraction. Using the methyltransferase inhibitors N-acetyl-S-farnesyl-L-cysteine and N-acetyl-S-geranylgeranyl-L-cysteine, we found that the phagocytic uptake of bacteria was not Rac2- or Cdc42-dependent, whereas the oxidative activation was decreased. In conclusion, our results indicate that in neutrophils, Rac2 and Cdc42 are involved in FcR- and CR3-induced activation and for properly functioning signal transduction involved in the generation of oxygen radicals.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24991 (URN)10.1189/jlb.1102525 (DOI)9411 (Local ID)9411 (Archive number)9411 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Differential effects of invasion by and phagocytosis of Salmonella typhimurium on apoptosis in human macrophages: potential role of Rho–GTPases and Akt
    Open this publication in new window or tab >>Differential effects of invasion by and phagocytosis of Salmonella typhimurium on apoptosis in human macrophages: potential role of Rho–GTPases and Akt
    Show others...
    2003 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 74, no 4, p. 620-629Article in journal (Refereed) Published
    Abstract [en]

    In addition to direct activation of caspase-1 and induction of apoptosis by SipB, invasive Salmonella stimulates multiple signaling pathways that are key regulators of host cell survival. Nevertheless, little is known about the relative contributions of these pathways to Salmonella-mediated death of macrophages. We studied human monocytic U937 cells and found that apoptosis was induced by invading wild-type Salmonella typhimurium but not by phagocytosed, serum-opsonized, noninvasive Salmonella mutants. Pretreating U937 cells with inhibitors of tyrosine kinases or phosphatidylinositol-3 kinase (PI-3K) completely blocked phagocytosis of opsonized Salmonella mutants but did not affect invasion by wild-type Salmonella or the apoptosis caused by invasion. However, pretreatment with GGTI-298, a geranylgeranyltransferase-1 inhibitor that prevents prenylation of Cdc42 and Rac1, suppressed Salmonella-induced apoptosis by ∼70%. Transduction of Tat fusion constructs containing dominant-negative Cdc42 or Rac1 significantly inhibited Salmonella-induced cell death, indicating that the cytotoxicity of Salmonella requires activation of Cdc42 and Rac. In contrast to phagocytosis of opsonized bacteria, invasion by S. typhimurium stimulated Cdc42 and Rac1, regardless of the activities of tyrosine- or PI-3K. Moreover, Salmonella infection activated Akt protein in a tyrosine-kinase or PI-3K-dependent manner, and a reduced expression of Akt by antisense transfection rendered the cells more sensitive to apoptosis induced by opsonized Salmonella. These results indicate that direct activation of Cdc42 and Rac1 by invasive Salmonella is a prerequisite of Salmonella-mediated death of U937 cells, whereas the simultaneous activation of Akt by tyrosine kinase and PI-3K during receptor-mediated phagocytosis protects cells from apoptosis.

    Keywords
    macrophages, bacterial apoptosis, signal transduction
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14003 (URN)10.1189/jlb.1202586 (DOI)
    Available from: 2006-09-27 Created: 2006-09-27 Last updated: 2017-12-13Bibliographically approved
  • 336.
    Forsberg, Maria
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Lem, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Särndahl, Eva
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Sebti, Said M.
    Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, Department of Oncology, University of South Florida, Tampa.
    Hamilton, Andrew
    Department of Chemistry, Yale University, New Haven, Connecticut .
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Zheng, Limin
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Differential effects of invasion by and phagocytosis of Salmonella typhimurium on apoptosis in human macrophages: potential role of Rho–GTPases and Akt2003In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 74, no 4, p. 620-629Article in journal (Refereed)
    Abstract [en]

    In addition to direct activation of caspase-1 and induction of apoptosis by SipB, invasive Salmonella stimulates multiple signaling pathways that are key regulators of host cell survival. Nevertheless, little is known about the relative contributions of these pathways to Salmonella-mediated death of macrophages. We studied human monocytic U937 cells and found that apoptosis was induced by invading wild-type Salmonella typhimurium but not by phagocytosed, serum-opsonized, noninvasive Salmonella mutants. Pretreating U937 cells with inhibitors of tyrosine kinases or phosphatidylinositol-3 kinase (PI-3K) completely blocked phagocytosis of opsonized Salmonella mutants but did not affect invasion by wild-type Salmonella or the apoptosis caused by invasion. However, pretreatment with GGTI-298, a geranylgeranyltransferase-1 inhibitor that prevents prenylation of Cdc42 and Rac1, suppressed Salmonella-induced apoptosis by ∼70%. Transduction of Tat fusion constructs containing dominant-negative Cdc42 or Rac1 significantly inhibited Salmonella-induced cell death, indicating that the cytotoxicity of Salmonella requires activation of Cdc42 and Rac. In contrast to phagocytosis of opsonized bacteria, invasion by S. typhimurium stimulated Cdc42 and Rac1, regardless of the activities of tyrosine- or PI-3K. Moreover, Salmonella infection activated Akt protein in a tyrosine-kinase or PI-3K-dependent manner, and a reduced expression of Akt by antisense transfection rendered the cells more sensitive to apoptosis induced by opsonized Salmonella. These results indicate that direct activation of Cdc42 and Rac1 by invasive Salmonella is a prerequisite of Salmonella-mediated death of U937 cells, whereas the simultaneous activation of Akt by tyrosine kinase and PI-3K during receptor-mediated phagocytosis protects cells from apoptosis.

  • 337.
    Forsberg, Maria
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Druid, Pia
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Zheng, Limin
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Stendahl, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Särndahl, Eva
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils2003In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 74, no 4, p. 611-619Article in journal (Refereed)
    Abstract [en]

    Phagocytosis is a complex process engaging a concerted action of signal-transduction cascades that leads to ingestion, subsequent phagolysosome fusion, and oxidative activation. We have previously shown that in human neutrophils, C3bi-mediated phagocytosis elicits a significant oxidative response, suggesting that activation of the small GTPase Rac is involved in this process. This is contradictory to macrophages, where only Fc receptor for immunoglobulin G (FcγR)-mediated activation is Rac-dependent. The present study shows that engagement of the complement receptor 3 (CR3) and FcγR and CR3- and FcγR-mediated phagocytosis activates Rac, as well as Cdc42. Furthermore, following receptor-engagement of the CR3 or FcγRs, a downstream target of these small GTPases, p21-activated kinase, becomes phosphorylated, and Rac2 is translocated to the membrane fraction. Using the methyltransferase inhibitors N-acetyl-S-farnesyl-L-cysteine and N-acetyl-S-geranylgeranyl-L-cysteine, we found that the phagocytic uptake of bacteria was not Rac2- or Cdc42-dependent, whereas the oxidative activation was decreased. In conclusion, our results indicate that in neutrophils, Rac2 and Cdc42 are involved in FcR- and CR3-induced activation and for properly functioning signal transduction involved in the generation of oxygen radicals.

  • 338.
    Forsberg, Maria
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Löfgren, Ragnhild
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Zheng, Limin
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Stendahl, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Tumour necrosis factor-α potentiates CR3-induced respiratory burst by activating p38 MAP kinase in human neutrophils2001In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 103, no 4, p. 465-472Article in journal (Refereed)
    Abstract [en]

    CR3 and FcγRs are the main receptors involved in the phagocytic process leading to engulfment and killing of microbes by production of reactive oxygen intermediates (ROI) and degranulation. Various inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and lipopolysaccharide (LPS), are known to prime neutrophils leading to increased bactericidal responses, but the underlying mechanism of priming has only been partially elucidated. The purpose of this study was to investigate how TNF-α primes neutrophils for subsequent stimuli via either CR3 or FcγR. The receptors were specifically activated with pansorbins (protein-A-positive Staphylococcus aureus) coated with anti-CR3, anti-FcγRIIa, or anti-FcγRIIIb monoclonal antibody. Activation of neutrophils with these particles resulted in ROI production as measured by chemiluminescence. Anti-CR3 pansorbins induced the most prominent ROI production in neutrophils. TNF-α potentiated the CR3-mediated respiratory burst but had little effect on that mediated by FcγRs. The priming effect of TNF-α on CR3-mediated ROI production is associated with an increased activation of p38 MAPK as well as tyrosine phosphorylation of p72syk. Pretreatment of neutrophils with the inhibitors for p38 MAPK and p72syk markedly suppressed the respiratory burst induced by CR3. Furthermore, TNF-α induced about a three-fold increase in the expression of CR3 in neutrophils, an effect which is blocked by the p38 MAPK inhibitor. Taken together, these results showed that TNF-α potentiates the CR3-mediated respiratory burst in neutrophils not only by triggering a p38 MAPK-dependent up-regulation of CD11b/CD18 but also by modulating the signalling pathways.

  • 339.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Fästingöverförda infektioner i Sverige2004In: Infektionsmedicin: epidemiologi, klinik, terapi / [ed] Iwarson-Norrby och Iwarson, Sten, Säve Förlag , 2004, p. 378-382Chapter in book (Other academic)
    Abstract [sv]

    Denna klassiska lärobok kom 2011 ut i sin 5:e, omarbetade upplaga. Boken innehåller 28 kapitel, vilka täcker hela infektionspanoramat, från influensa till AIDS. Samtliga författare är läkare och flertalet universitetslärare. Den innehåller även 16 sidor färgplanscher med fotoillustrationer av olika sjukdomar. Boken är avsedd att användas i undervisningen av blivande läkare och som uppslagsbok i sjukvården.

  • 340. Forsey, RJ
    et al.
    Thompson, JM
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Hurst, TL
    Strindhall, J
    Johansson, B
    Nilsson, B-O
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases.
    Wikby, A
    Plasma cytokine profile in elderly humans.2003In: Mechanisms of Ageing and Development, ISSN 0047-6374, E-ISSN 1872-6216, Vol. 124, p. 487-493Article in journal (Refereed)
  • 341.
    Forslund, Tony
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nitric oxide modulates neutrophil function1997Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An important role of the neutrophils is to attack and destroy microbial intruders. In order to do so, these leukocytes must adhere to the blood vessel wall, pass through the endothelial cell layer, move through the tissues to the point of infection, ingest the intruder and destroy it.

    The aim of this thesis was to study the effects of nitric oxide (NO) on the different steps in the inflammatory response of the neutrophil.

    Adhesion to a collagen surface was decreased by pretreatment with a NO-releasing substance, and this was mimicked by pretreatment with a functional cGMP-analogue, indicating a role of the NO/cGMP pathway. Homotypic adhesion, aggregation, was not affected by external NO, but when the precursor of endogenous NO-production CLarginine) was added, the aggregation increased. Measurements of total F-actin content in cells showed that a NO-releasing substance decreased the total amount of F-actin, while cGMP increased it. Treatment with L-arginine had no effect.

    Phagocytosis was neither affected by endogenous NO, nor by a NO-releasing substance. However, if the prey itself released NO, both the adhesion to and phagocytosis of the target was decreased. This NO-particle also inhibited the production of oxygen metabolites, as measured using Luminal-dependent chemiluminescence. The inhibition was almost exclusively affecting the intracellular production of oxygen metabolites, as could be seen when neutrophils were stimulated with FMLP or PMA after an incubation with the NO-releasing particles.

    Treatment of neutrophils with the NO-releasing substance nitroprusside resulted in a decrease of the respiratory burst. It was primarily the extracellular release that was diminished. This effect can be explained by an inhibition of the enzyme producing oxygen metabolites. Endogenous NO-production increased the chemiluminescence whereas an inhibitor of the NO-synthase decreased it. A possible explanation for these effects is an NO-inhibition of the protection against hydrogen peroxide, i.e. catalase activity, resulting in an increased amount of oxygen metabolites.

    In conclusion, these results shows that NO has different effects depending on where it is produced and in what quantities. It modulates the different steps of the inflammatory response of neutrophils. Control of NO-formation could therefore be a way to control inflammation.

  • 342.
    Forslund, Tony
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Harriet
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nitric Oxide Regulates the Aggregation of Stimulated Human Neutrophils2000In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 274, no 2, p. 482-487Article in journal (Refereed)
    Abstract [en]

    Neutrophil aggregation is mediated by both CD18 integrin and L-selectin. Nitric oxide attenuates the integrin-mediated adhesion of neutrophils to collagen and to endothelium and may therefore affect aggregation as well. FMLP-stimulated neutrophils exposed to -arginine showed increased and prolonged aggregation, whereas cells pretreated with L-NAME did not differ from FMLP-stimulated controls. Nitric oxide is known to induce ADP ribosylation of G-actin, which inhibits polymerization. We detected equivalent levels of total F-actin in cells pretreated with -arginine or L-NAME and non-pretreated controls. However, neutrophils pretreated with -arginine and stimulated by CD18 integrin cross-linking exhibited a more limited increase in total F-actin, compared to control and L-NAME-pretreated cells. Thus at least two signaling pathways may be involved FMLP-stimulated aggregation, mediated by CD18 integrins. More specifically, it is plausible that FMLP-receptor signaling upregulates CD18 integrins and endogenous NO subsequently modulates CD18-mediated signaling to prolong aggregation, possibly through ADP-ribosylation of actin.

  • 343.
    Forsman, Lina
    et al.
    Department of Forensic Medicine, Umeå University, Umeå, Sweden.
    Edston, Erik
    Linköping University, Department of Molecular and Clinical Medicine, Forensic Medicine. Linköping University, Faculty of Health Sciences.
    Medicolegal certificates in investigations of asylum applications2000In: Journal of Medical Ethics, ISSN 0306-6800, E-ISSN 1473-4257, Vol. 26, no 4, p. 289-289Article in journal (Other academic)
    Abstract [en]

    No abstract available.

  • 344.
    Forsum, Elisabet
    et al.
    Linköping University, Department of Biomedicine and Surgery, Nutrition. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Biomedicine and Surgery, Nutrition. Linköping University, Faculty of Health Sciences.
    Olausson, Hanna
    Linköping University, Department of Biomedicine and Surgery, Nutrition. Linköping University, Faculty of Health Sciences.
    Olhager, Elisabeth
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Maternal body composition in relation to infant birth weight and subcutaneous adipose tissue2006In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 96, no 2, p. 408-414Article in journal (Refereed)
    Abstract [en]

    Infant birth weight has increased recently, representing an obstetric and potentially a public health problem since high birth weight involves a risk of obesity later in life. Maternal nutritional status is important for fetal growth and therefore relationships between maternal body weight and composition v. birth weight and infant subcutaneous adipose tissue were investigated in twenty-three healthy women and their newborn infants using multiple and simple linear regression analysis. Furthermore, using previously published data for nineteen infants, it was demonstrated that an anthropometric method could provide useful estimates of the amount of subcutaneous adipose tissue. Birth weight was correlated with the maternal content of total body fat (TBF) both before pregnancy and in gestational week 32 and, together with gestational age at birth, TBF (%) before pregnancy explained 45% of the variation in birth weight. This figure was not increased when gestational gains in weight or TBF were added to the model. Furthermore, in infants, birth weight correlated with the amount of their subcutaneous adipose tissue. Together maternal TBF (%) and amount of subcutaneous adipose tissue in infants explained 61–63% of the variation in birth weight while the amount of infant subcutaneous adipose tissue alone explained only 55%. The maternal TBF content is likely to be important for the recent increase in birth weight. This factor probably causes a general augmentation in fetal growth rather than a specific stimulation of adipose tissue growth.

  • 345.
    Forsum, Urban
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Referensmetodik för laboratoriediagnostik vid kliniskt mikrobiologiska laboratorier.: I, Infektionsdiagnostik, 11, Bakteriologisk diagnostik av infektioner i hud, mjukdelar, skelett och inre organ2003In: Smittskyddsinstitutet / [ed] Berndt Claesson, Linköping: Linköpings universitet , 2003, p. 89-117Chapter in book (Other academic)
  • 346.
    Forsum, Urban
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    The Swedish Society for Medical Microbiology, activities and scientific success during the first 100 years.2007Collection (editor) (Refereed)
  • 347.
    Forsum, Urban
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Varning för Ellen!2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 17, p. 1544-1544Article in journal (Other (popular science, discussion, etc.))
  • 348.
    Forsum, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Danielsson, Dan
    Uppsala.
    Developments in the recent past - Immunology2007In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 115, no 5, p. 406-408Article in journal (Other academic)
  • 349.
    Forsum, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Fyrenius, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Annorlunda kurslitteratur. Skönlitteratur en del av läkarutbildningen i Linköping.2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, no 35, p. 2483-2484Article in journal (Other academic)
  • 350.
    Forsum, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Fyrenius, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Literary fiction in the medical programme2006In: Celebrating the past by expanding the future.: the Faculty of Health Sciences, Linköping University 1986-2006 / [ed] Mats Hammar, Björn Bergdahl, Lena Öhman, Lecture Notes in Computer Science , 2006, p. 38-40Chapter in book (Other academic)
    Abstract [en]

    During the fall of 2006, the Faculty of Health Sciences (FHS) celebrates its 20th birthday. Linköping has a long tradition of health education; our nursing programme started already in 1895 and occupational therapy began in 1965. From the late 1960’s, medical students from Uppsala spent their last seven semesters in Linköping, mainly for clinical studies. After some years, academic and teachers from the young faculty, together with the county council, realized the enormous potential benefits of a complete undergraduate medical programme at Linköping University. Inspired by apparent innovations from McMaster University in Canada, Maastricht in Holland, Ben Gurion in Israel and Tromsø in Norway, these ideas and ideals were gradually turned into reality. In a complicated process, concerning the life or death of the medical faculty, a close co-operation between the University and the County Council of Östergötland was extremely fruitful. A proposal regarding a complete medical programme, and study periods integrated between the other health education programmes, was forwarded to the Swedish government in December 1982 and approved in 1984.

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