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51.
  • Islander, Ulrika, 1975, et al. (författare)
  • Estren-mediated inhibition of T lymphopoiesis is estrogen receptor-independent whereas its suppression of T cell-mediated inflammation is estrogen receptor-dependent
  • 2005
  • Ingår i: Clin Exp Immunol. - 0009-9104. ; 139:2, s. 210-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogen has extensive effects on the immune system. The aim of the present experiments was to compare the effects of 17beta-estradiol (E2) and 4-estren-3alpha,17beta-diol (estren) on T lymphopoiesis and T cell-dependent inflammation. In order to investigate the role of estrogen receptors (ER) in the effects of E2 and estren on the immune system, ER knock-out mice lacking both ERalpha and ERbeta (DERKO) were used. T lymphopoiesis and T cell-dependent inflammation were studied by investigating thymus cellularity, the delayed-type hypersensitivity (DTH) reaction, CD4(+) T cells in spleen and serum levels of interleukin (IL)-6. As expected, the presence of ERs was mandatory for all the effects of E2. In contrast, treatment with estren reduced thymus cellularity in ER knock-out mice, indicating an effect through ER-independent pathways. Interestingly, estren suppressed only DTH, the frequency of CD4(+) T cells in spleen and serum levels of IL-6 in wild-type (WT) mice, but not in mice lacking ERs. Thus, our study is the first to show that estren inhibits T lymphopoiesis via ER-independent pathways, whereas its suppressive effects on inflammation are ER-dependent.
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52.
  • Janzi, Magdalena, et al. (författare)
  • Screening for C3 deficiency in newborns using microarrays.
  • 2009
  • Ingår i: PloS one. - 1932-6203. ; 4:4, s. e5321-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Dried blood spot samples (DBSS) from newborns are widely used in neonatal screening for selected metabolic diseases and diagnostic possibilities for additional disorders are continuously being evaluated. Primary immunodeficiency disorders comprise a group of more than one hundred diseases, several of which are fatal early in life. Yet, a majority of the patients are not diagnosed due to lack of high-throughput screening methods.METHODOLOGY/PRINCIPAL FINDINGS: We have previously developed a system using reverse phase protein microarrays for analysis of IgA levels in serum samples. In this study, we extended the applicability of the method to include determination of complement component C3 levels in eluates from DBSS collected at birth. Normal levels of C3 were readily detected in 269 DBSS from healthy newborns, while no C3 was detected in sera and DBSS from C3 deficient patients.CONCLUSIONS/SIGNIFICANCE: The findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.
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53.
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54.
  • Johansson, Ulrika, 1974-, et al. (författare)
  • Inflammatory mediators expressed in human islets of Langerhans : implications for islet transplantation
  • 2003
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - 0006-291X .- 1090-2104. ; 308:3, s. 474-479
  • Tidskriftsartikel (refereegranskat)abstract
    •   Expression of immune modulating mediators in human Islets of Langerhans could have important implications for development of autoimmunity in type 1 diabetes and influence the outcome of clinical islet transplantation. Islets obtained from five donors were analyzed at various times after isolation using cDNA array technology. The Atlas Human Cytokine/Receptor and Hematology/Immunology nylon membranes representing 268 genes and 406, respectively, were used and the relative expression of each gene analyzed. Of the 51 gene products identified, high mRNA expression of MCP-1, MIF, VEGF, and thymosin beta-10 was detected in all islet samples. IL-8, IL-1-beta, IL-5R, and INF-gamma antagonist were expressed in islets cultured for 2 days. IL-2R was expressed in islets cultured for more than 6 days. In conclusion, several inflammatory mediators were expressed in isolated islets, particularly at an early stage after isolation, indicating that a few days of culture could be beneficial for the outcome of islet transplantation.  
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55.
  • Karlsson, I., et al. (författare)
  • Peptide Reactivity of Isothiocyanates - Implications for Skin Allergy
  • 2016
  • Ingår i: Scientific Reports. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Skin allergy is a chronic condition that affects about 20% of the population of the western world. This disease is caused by small reactive compounds, haptens, able to penetrate into the epidermis and modify endogenous proteins, thereby triggering an immunogenic reaction. Phenyl isothiocyanate (PITC) and ethyl isothiocyanate (EITC) have been suggested to be responsible for allergic skin reactions to chloroprene rubber, the main constituent of wetsuits, orthopedic braces, and many types of sports gear. In the present work we have studied the reactivity of the isothiocyanates PITC, EITC, and tetramethylrhodamine-6-isothiocyanate (6-TRITC) toward peptides under aqueous conditions at physiological pH to gain information about the types of immunogenic complexes these compounds may form in the skin. We found that all three compounds reacted quickly with cysteine moieties. For PITC and 6-TRITC the cysteine adducts decomposed over time, while stable adducts with lysine were formed. These experimental findings were verified by DFT calculations. Our results may suggest that the latter are responsible for allergic reactions to isothiocyanates. The initial adduct formation with cysteine residues may still be of great importance as it prevents hydrolysis and facilitates the transport of isothiocyanates into epidermis where they can form stable immunogenic complexes with lysine-containing proteins.
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56.
  • Karlsson, I., et al. (författare)
  • The Fate of a Hapten - From the Skin to Modification of Macrophage Migration Inhibitory Factor (MIF) in Lymph Nodes
  • 2018
  • Ingår i: Scientific Reports. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Skin (contact) allergy, the most prevalent form of immunotoxicity in humans, is caused by low molecular weight chemicals (haptens) that penetrate stratum corneum and modify endogenous proteins. The fate of haptens after cutaneous absorption, especially what protein(s) they react with, is largely unknown. In this study the fluorescent hapten tetramethylrhodamine isothiocyanate (TRITC) was used to identify hapten-protein conjugates in the local lymph nodes after topical application, as they play a key role in activation of the adaptive immune system. TRITC interacted with dendritic cells but also with T and B cells in the lymph nodes as shown by flow cytometry. Identification of the most abundant TRITC-modified protein in lymph nodes by tandem mass spectrometry revealed TRITC-modification of the N-terminal proline of macrophage migration inhibitory factor (MIF) - an evolutionary well-conserved protein involved in cell-mediated immunity and inflammation. This is the first time a hapten-modified protein has been identified in lymph nodes after topical administration of the hapten. Most haptens are electrophiles and can therefore modify the N-terminal proline of MIF, which has an unusually reactive amino group under physiological conditions; thus, modification of MIF by haptens may have an immunomodulating role in contact allergy as well as in other immunotoxicity reactions.
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57.
  • Karlsson, Joakim, et al. (författare)
  • Molecular profiling of driver events in metastatic uveal melanoma
  • 2020
  • Ingår i: Nature Communications. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has a high mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genes associated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease. © 2020, The Author(s).
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58.
  • Knudsen, Kati, et al. (författare)
  • A nationwide postal questionnaire survey : the presence of airway guidelines in anaesthesia department in Sweden
  • 2014
  • Ingår i: BMC Anesthesiology. - London : BioMed Central. - 1471-2253 .- 1471-2253. ; 14:25
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In Sweden, airway guidelines aimed toward improving patient safety have been recommended by the Swedish Society of Anaesthesia and Intensive Care Medicine. Adherence to evidence-based airway guidelines is known to be generally poor in Sweden. The aim of this study was to determine whether airway guidelines are present in Swedish anaesthesia departments.Methods: A nationwide postal questionnaire inquiring about the presence of airway guidelines was sent out to directors of Swedish anaesthesia departments (n = 74). The structured questionnaire was based on a review of the Swedish Society of Anaesthesia and Intensive Care voluntary recommendations of guidelines for airway management. Mean, standard deviation, minimum/maximum, percentage (%) and number of general anaesthesia performed per year as frequency (n), were used to describe, each hospital type (university, county, private). For comparison between hospitals type and available written airway guidelines were cross tabulation used and analysed using Pearson’s Chi-Square tests. A p- value of less than 0 .05 was judged significant.Results: In total 68 directors who were responsible for the anaesthesia departments returned the questionnaire, which give a response rate of 92% (n 68 of 74). The presence of guidelines showing an airway algorithm was reported by 68% of the departments; 52% reported having a written patient information card in case of a difficult airway and guidelines for difficult airways, respectively; 43% reported the presence of guidelines for preoperative assessment; 31% had guidelines for Rapid Sequence Intubation; 26% reported criteria for performing an awake intubation; and 21% reported guidelines for awake fibre-optic intubation. A prescription for the registered nurse anaesthetist for performing tracheal intubation was reported by 24%. The most frequently pre-printed preoperative elements in the anaesthesiarecord form were dental status and head and neck mobility.Conclusions: Despite recommendations from the national anaesthesia society, the presence of airway guidelines in Swedish anaesthesia departments is low. From the perspective of safety for both patients and the anaesthesia staff, airway management guidelines should be considered a higher priority
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59.
  • Knudsen, Kati, et al. (författare)
  • A nationwide postal questionnaire survey: the presence of airway guidelines in anaesthesia department in Sweden
  • 2014
  • Ingår i: BMC Anesthesiology. - 1471-2253 .- 1471-2253. ; 14, s. 25-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIn Sweden, airway guidelines aimed toward improving patient safety have been recommended by the Swedish Society of Anaesthesia and Intensive Care Medicine. Adherence to evidence-based airway guidelines is known to be generally poor in Sweden. The aim of this study was to determine whether airway guidelines are present in Swedish anaesthesia departments.MethodsA nationwide postal questionnaire inquiring about the presence of airway guidelines was sent out to directors of Swedish anaesthesia departments (n = 74). The structured questionnaire was based on a review of the Swedish Society of Anaesthesia and Intensive Care voluntary recommendations of guidelines for airway management. Mean, standard deviation, minimum/maximum, percentage (%) and number of general anaesthesia performed per year as frequency (n), were used to describe, each hospital type (university, county, private). For comparison between hospitals type and available written airway guidelines were cross tabulation used and analysed using Pearson’s Chi-Square tests. A p- value of less than 0 .05 was judged significant.ResultsIn total 68 directors who were responsible for the anaesthesia departments returned the questionnaire, which give a response rate of 92% (n 68 of 74). The presence of guidelines showing an airway algorithm was reported by 68% of the departments; 52% reported having a written patient information card in case of a difficult airway and guidelines for difficult airways, respectively; 43% reported the presence of guidelines for preoperative assessment; 31% had guidelines for Rapid Sequence Intubation; 26% reported criteria for performing an awake intubation; and 21% reported guidelines for awake fibre-optic intubation. A prescription for the registered nurse anaesthetist for performing tracheal intubation was reported by 24%. The most frequently pre-printed preoperative elements in the anaesthesia record form were dental status and head and neck mobility.ConclusionsDespite recommendations from the national anaesthesia society, the presence of airway guidelines in Swedish anaesthesia departments is low. From the perspective of safety for both patients and the anaesthesia staff, airway management guidelines should be considered a higher priority.
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60.
  • Knudsen, Kati, et al. (författare)
  • Awake intubation creates feelings of being in a vulnerable situation but cared for in safe hands : a qualitative study
  • 2016
  • Ingår i: BMC Anesthesiology. - London, United Kingdom : BioMed Central. - 1471-2253 .- 1471-2253. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Awake fiberoptic intubation is an alternative procedure for securing the airway and is a recommended option when a difficult airway is expected. The aim of the present study was to describe patient experiences with this procedure.Methods: A qualitative, descriptive design was used and patients were recruited from three county hospitals and one university hospital in Sweden. Data was collected by semi-structured interviews with 13 patients who underwent awake fiberoptic intubation. A qualitative content analysis extracted theme, categories, and subcategories.Results: From the patient statements, one main theme emerged, feelings of being in a vulnerable situation but cared for in safe hands, which were described in five categories with 15 subcategories. The categories were: a need for tailored information, distress and fear of the intubation, acceptance and trust of the staff’s competence, professional caring and support, and no hesitation about new awake intubation. The patients felt they lacked information about what to expect and relied on the professionals’ expertise. Some patients felt overwhelmed by the information they were given and wanted less specific information about the equipment used but more information about how they would be cared for in the operating room. Undergoing awake intubation was an acceptable experience for most patients, whereas others experienced it as being painful and terrifying because they felt they could not breathe or communicate during the procedure itself.Conclusions: Tailored information about what to expect, ensuring eye contact and breathing instruction during the procedure seems to reduce patient distress when undergoing awake fiberoptic intubation. Most of the patients would not hesitate to undergo awake intubation again in the future if needed.
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