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  • 1.
    Crisci, Elisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ellegård, Rada
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Rondahl, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bergström, Tomas
    University of Gothenburg, Gothenburg, Sweden.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Eriksson, Kristina
    University of Gothenburg, Gothenburg, Sweden.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Complement opsonization promotes HSV-2 infection of human dendritic cells2016In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 90, no 10, p. 4939-4950Article in journal (Refereed)
    Abstract [en]

    Herpes virus type 2 (HSV2) is one of the most common sexually transmitted infections globally with a very high prevalence in many countries. During HSV2 infection viral particles become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. In genital mucosa, the primary target cells for HSV2 infection are epithelial cells, but resident immune cells such as dendritic cells (DCs) are also infected. The DCs are the activators of the ensuing immune responses directed against HSV2, and the aim of this study was to examine the effects opsonization of HSV2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV1 or HSV2 specific antibodies more or less abolished the HSV2 infection of DCs.Our results clearly demonstrate the importance of studying HSV2 infection under conditions that ensue in vivo, i.e. when the virions are covered in complement fragments and complement fragments and antibodies, as this will shape the infection and the subsequent immune response and needs to be further elucidated.

    IMPORTANCE: During HSV2 infection viral particles should become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. The dendritic cells are the activators of the immune responses directed against HSV2, and the aim of this study was to examine the effects of complement alone or complement and antibodies, on the HSV2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses.Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV2 pathogenesis.

  • 2.
    Jonsson, Nina
    et al.
    Linnaeus University, Sweden .
    Wahlström, Kristin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Lindberg, A. Michael
    Linnaeus University, Sweden .
    Aichi virus infection in elderly people in Sweden2012In: Archives of Virology, ISSN 0304-8608, E-ISSN 1432-8798, Vol. 157, no 7, p. 1365-1369Article in journal (Refereed)
    Abstract [en]

    Aichi virus (AiV), genus Kobuvirus, family Picornaviridae, is associated with gastroenteritis in humans. Previous studies have shown high seroprevalence but low incidence (0.9-4.1%) in clinical samples. We report here the first detection of AiV in Sweden. Two hundred twenty-one specimens from hospitalized patients with diarrhea, who were negative for other enteric viruses, were included in the study. AiV were detected in three specimens, all from elderly patients. Phylogenetic analysis revealed that the three Swedish isolates belonged to genotype A and were genetically closest to European and Asian strains of AiV.

  • 3.
    Larsson, Jenny
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Serrander, Lena
    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.
    Lundqvist-Gustafsson, Helen
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Involvement of the ß2-integrin CD18 in apoptosis signal transduction in human neutrophils2000In: Inflammation Research, ISSN 1023-3830, E-ISSN 1420-908X, Vol. 49, no 9, p. 452-459Article in journal (Refereed)
    Abstract [en]

    Objective and design: To examine the hypothesis that an accelerated rate of neutrophil apoptosis occurs following β2-integrin activation, and further investigate the signal transduction pathways involved.

    Material: Human polymorphonuclear neutrophils.

    Treatment: Neutrophils were challenged with pansorbins coated with antibodies towards the β2-integrin subunit CD18 in a proportion of 1:100 with or without the inhibitors diphenylene iodonium (10 M), cytochalasin B (5 μg/ml), genistein (10 nM), herbimycin A (10 M) and Z-VAD-FMK (10 μM).

    Methods: Measurement of phosphatidylserine exposure and DNA fragmentation in flow cytometry and assessment of H2O2-production through spectrofluorometry. The results were analysed using Mann Whitney U test and Kruskal Wallis.

    Results: Pansorbins coated with antibodies to CD18 induce apoptosis in neutrophils (p < 0.01), and activate the production of reactive oxygen species (p < 0.01). Pre-treatment with the inhibitors have no effect on anti-CD18 induced apoptosis.

    Conclusion: Anti-CD18 pansorbins induce apoptosis in neutrophils through an alternative pathway not involving reactive oxygen species and independent of tyrosine phosphorylation, cytoskeletal reorganisation and caspases.

  • 4.
    Larsson, Marie C.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Woksepp, Hanna
    Kalmar County Hospital, Sweden .
    Frolander, Kerstin
    Kalmar County Hospital, Sweden .
    Mårtensson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Rashed, Foad
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Annika, Wistedt
    Kalmar County Hospital, Sweden .
    Schön, Thomas
    Kalmar County Hospital, Sweden .
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Rapid identification of pneumococci, enterococci, beta-haemolytic streptococci and S. aureus from positive blood cultures enabling early reports2014In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 14, no 146Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The aim of this study was to evaluate diagnostic tests in order to introduce a diagnostic strategy to identify the most common gram-positive bacteria (pneumococci, enterococci, β-haemolytic streptococci and S. aureus) found in blood cultures within 6 hours after signalling growth.

    METHODS:

    The tube coagulase test was optimized and several latex agglutination tests were compared and evaluated before a validation period of 11 months was performed on consecutive positive blood culture patient samples from Kalmar County Hospital, Sweden.

    RESULTS:

    During the validation period 150 (91%) of a total of 166 gram-positive cocci (119 in clusters, 45 in chains or pairs and 2 undefined morphology) were correctly identified as S. aureus, CoNS, Pneumococci, Enterococci or group A streptococci (GAS), group B streptococci (GBS), group G streptococci (GGS) within 6 hours with a minimal increase in work-load and costs. The remaining samples (9%) were correctly identified during the next day. No samples were incorrectly grouped with this diagnostic strategy and no patient came to risk by early reporting.

    CONCLUSION:

    A simple strategy gives reliable and cost-effective reporting of >90% of the most common gram-positive cocci within 6 hours after a blood cultures become positive. The high specificity of the tests used makes preliminary reports reliable. The reports can be used to indicate the focus of infection and not the least, support faster administration of proper antimicrobial treatment for patients with serious bacterial infections.

  • 5.
    Lindmark, Maria
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Karlsson, Anna
    The Phagocyte Laboratory, Department of Medical Microbiology, Göteborg University, Göteborg, Sweden.
    Serrander, Lena
    Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland.
    Francois, Patrice
    Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland.
    Lew, Daniel
    Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland.
    Rasmusson, Birgitta
    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.
    Nüße, Oliver
    Immunology Group, Faculty of Science, Univ. Nancy, Vandoeuvre, France.
    Synaptotagmin II could confer Ca2+ sensitivity to phagocytosis in human neutrophils2002In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1590, no 1-3, p. 159-166Article in journal (Refereed)
    Abstract [en]

    Phagolysosome fusion and granule exocytosis in neutrophils are calcium-dependent processes. The calcium requirements vary between granule types, suggesting the presence of different calcium sensors. The synaptotagmins, a family of calcium-binding proteins, previously shown to participate in vesicle fusion and vesicle recycling in excitable cells, are putative calcium-sensors of exocytosis in excitable cells. In this study, we show that synaptotagmin II is present in human neutrophils and may participate in phagocytic and in exocytotic processes. In protein extracts from human neutrophils, we identified synaptotagmin II by Western blot as an 80 kDa protein. Subcellular fractionation revealed that synaptotagmin II was associated with the specific granules. In fMLP-stimulated cells, synaptotagmin II translocated to the plasma membrane. This correlated with the upregulation of complement receptor 3 (CR 3), reflecting the translocation of specific granules to the cell surface. Synaptotagmin II also translocated to the phagosome after complement-mediated phagocytosis in the presence of calcium. LAMP-1 translocated in parallel but probably was located to another subcellular compartment than synaptotagmin II. Under calcium-reduced conditions, neither synaptotagmin II nor LAMP-1 translocated to the phagosome. We therefore suggest a role for synaptotagmin II as calcium-sensor during phagocytosis and secretion in neutrophils.

  • 6.
    Löfgren, Ragnhild
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Serrander, Lena
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Forsberg, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Wilsson, Åsa
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Wasteson, Åke
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Stendahl, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    CR3, FcγRIIA and FcγRIIIB induce activation of the respiratory burst in human neutrophils: the role of intracellular Ca2+, phospholipase D and tyrosine phosphorylation1999In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1452, no 1, p. 46-59Article in journal (Refereed)
    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.

  • 7.
    Nguyen, Minh Vu Chuong
    et al.
    University of Grenoble 1, France .
    Lardy, Bernard
    University of Grenoble 1, France .
    Rousset, Francis
    University of Grenoble 1, France .
    Hazane-Puch, Florence
    University Hospital CHU Grenoble, France .
    Zhang, Leilei
    University of Grenoble 1, France .
    Trocme, Candice
    University Hospital CHU Grenoble, France .
    Serrander, Lena
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Krause, Karl-Heinz
    Medical Faculty and University Hospital, Geneva, Switzerland.
    Morel, Francoise
    University of Grenoble 1, France .
    Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox42013In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 85, no 11, p. 1644-1654Article in journal (Refereed)
    Abstract [en]

    NADPH oxidase Nox4 is expressed in a wide range of tissues and plays a role in cellular signaling by providing reactive oxygen species (ROS) as intracellular messengers. Nox4 oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific quinone derivatives could modulate this activity. In fact, we demonstrated a significant stimulation of Nox4 activity by 4 quinone derivatives (AA-861, tBuBHQ tBuBQ and duroquinone) observed in 3 different cellular models, HEK293E, T-REx (TM), and chondrocyte cell lines. Our results indicate that the effect is specific toward Nox4 versus Nox2. Furthermore, we showed that NAD(P)H:quinone oxidoreductase (NQO1) may participate in this stimulation. Interestingly, Nox4 activity is also stimulated by reducing agents that possibly act by reducing the disulfide bridge (Cys226, Cys270) located in the extracellular E-loop of Nox4. Such model of Nox4 activity regulation could provide new insight into the understanding of the molecular mechanism of the electron transfer through the enzyme, i.e., its potential redox regulation, and could also define new therapeutic targets in diseases in which quinones and Nox4 are implicated.

  • 8.
    Rondahl, Elin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Gruber, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Joelsson, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Sundqvist, Martin
    Örebro University, Sweden.
    Åkerlind, Britt
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Cardell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindh, Magnus
    Göteborg University .
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    The risk of HCV RNA contamination in serology screening instruments with a fixed needle for sample transfer.2014In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 60, no 2, p. 172-173Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hepatitis C diagnostics involve antibody screening and confirmation of current infection by detection of HCV RNA positivity. In screening instruments with fixed pipetting needle, there is a risk of sample carry-over contamination.

    OBJECTIVES: The aim of this study was to evaluate the risk of such contamination in a proposed clinical setting.

    STUDY DESIGN: In the present study, known HCV RNA positive (n=149) and negative (n=149) samples were analysed by anti-HCV Abbott in an Architect instrument in an alternating fashion in order to test for contamination.

    RESULTS: In subsequent retesting of the previously HCV RNA-negative samples, six samples (4%) were positive by the Cobas Taqman assay with a maximum level of 33IU/mL. The results show that there is a risk for transfer of HCV in the Architect instrument but they also show that the levels of HCV RNA observed are low.

    CONCLUSIONS: We conclude that complementary HCV RNA testing on samples identified as anti-HCV positive by screening can be recommended because the complementary results are reliable in the majority of cases when either HCV RNA is negative or HCV RNA is positive with a level >1000IU/mL. In a minority of cases, with low HCV RNA after anti-HCV antibody screening, cross-contamination should be suspected and a new sample requested for HCV RNA testing. This strategy would reduce the need for obtaining a new sample from the vast majority of patients with a newly discovered HCV antibody positivity.

  • 9.
    Serrander, Lena
    et al.
    Divison of Infectious Diseases, University of Geneva, Switzerland.
    Jerström Skarman, Petra
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Rasmusson, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Witke, Walter
    European Molecular Biology Laboratory Mouse Biology Program, Monterotondo, Italy.
    Lew, Daniel P.
    Divison of Infectious Diseases, University of Geneva, Switzerland.
    Krause, Karl-Heinz
    Divison of Infectious Diseases, University of Geneva, Switzerland.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nüße, Oliver
    Divison of Infectious Diseases, University of Geneva, Switzerland.
    Selective Inhibition of IgG-Mediated Phagocytosis in Gelsolin-Deficient Murine Neutrophils2000In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 165, no 5, p. 2451-2457Article in journal (Refereed)
    Abstract [en]

    Phagocytosis and the microbicidal functions of neutrophils require dynamic changes of the actin cytoskeleton. We have investigated the role of gelsolin, a calcium-dependent actin severing and capping protein, in peripheral blood neutrophils from gelsolin-null (Gsn) mice. The phagocytosis of complement opsonized yeast was only minimally affected. In contrast, phagocytosis of IgG-opsonized yeast was reduced close to background level in Gsn neutrophils. Thus, gelsolin is essential for efficient IgG- but not complement-mediated phagocytosis. Furthermore, attachment of IgG-opsonized yeast to Gsn neutrophils was reduced (∼50%) but not to the same extent as ingestion (∼73%). This was not due to reduced surface expression of the Fcγ-receptor or its lateral mobility. This suggests that attachment and ingestion of IgG-opsonized yeast by murine neutrophils are actin-dependent and gelsolin is important for both steps in phagocytosis. We also investigated granule exocytosis and several steps in phagosome processing, namely the formation of actin around the phagosome, translocation of granules, and activation of the NADPH-oxidase. All these functions were normal in Gsn neutrophils. Thus, the role of gelsolin is specific for IgG-mediated phagocytosis. Our data suggest that gelsolin is part of the molecular machinery that distinguishes complement and IgG-mediated phagocytosis. The latter requires a more dynamic reorganization of the cytoskeleton.

  • 10.
    Serrander, Lena
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Larsson, Jenny
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Lundqvist, Helen
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Lindmark, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Fällman, Maria
    Department of Medical Microbiology, University of Umeå, Umeå, Sweden.
    Dahlgren, Claes
    Department of Medical Microbiology, University of Göteborg, Göteborg, Sweden.
    Stendahl, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Particles binding β2-integrins mediate intracellular production of oxidative metabolites in human neutrophils independently of phagocytosis1999In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1452, no 2, p. 133-144Article in journal (Refereed)
    Abstract [en]

    Complement-opsonised particles are readily ingested by human neutrophils through a complement receptor-mediated process leading to phagolysosome fusion and production of oxidative metabolites. To investigate the complement receptor 3 (CR3)-associated signal system involved, cells were challenged with protein A-positive, heat-killed Staphylococcus aureus to which antibodies with specificity for the subunits of the β2-integrins, i.e. anti-CD11b (the α subunit of CR3) and anti-CD18 (the β subunit of CR3), were bound through their Fc moiety. Despite not being ingested by the neutrophils, the surface associated anti-CD18- and anti-CD11b-coated particles were able to activate the neutrophil NADPH-oxidase. Also anti-CD11a- (the α subunit of LFA-1) and to a lesser extent anti-CD11c- (the α subunit of CR4) coated particles were able to trigger the NADPH-oxidase. The NADPH-oxidase was activated without extracellular release of reactive oxygen species. The activity was inhibited by cytochalasin B, suggesting a necessary role for the cytoskeleton in the signalling pathway that activates the oxidase. We show that particle-mediated cross-linking of β2-integrins on the neutrophil surface initiates a signalling cascade, involving cytoskeletal rearrangements, leading to an activation of the NADPH-oxidase without phagosome formation or extracellular release of reactive oxygen species.

  • 11.
    Sundbom, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Hübbert, Laila
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Progressive multifocal leukoencephalopathy after heart transplantation: 4 years of clinically stable infection on low-dose immunosuppressive therapy2017In: Oxford Medical Case Reports, E-ISSN 2053-8855, Vol. 2017, no 2, p. 15-17Article in journal (Refereed)
    Abstract [en]

    Progressive multifocal leukoencephalopathy (PML), caused by reactivation of JC-virus is a relatively rare complication seen in patients with compromised immune system. There are no evidence-based treatment available and prognosis is poor. Withdrawal of immunosuppressant can result in further neurological deterioration and for patients with solid organ transplantations, fatal graft rejection. We report a 52-year-old women that presented with seizures within 1 month after heart transplantation. Initial diagnosis was vascular disease. After clinical deterioration 10 months after transplantation, further examinations led to the diagnosis. Minimizing tacrolimus, to a concentration of 2 ng/ml, and extensive physical therapy has improved the physical capacity of the patient. The patient has now been clinically stable for 4 years and extended survival for 5 years. This case adds to the limited adult cases of PML within the population of heart transplant recipients and the need for increased awareness to minimize diagnosis delay.

  • 12.
    Sundén, Birgitta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Falkeborn, Tina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Forsum, Urban
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Lindh, Magnus
    University of Gothenburg.
    Ydrenius, Liselotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Real-time PCR detection of Human Herpesvirus 1-5 in patients lacking clinical signs of a viral CNS infection2011In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 11, no 220Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Infections of the central nervous system (CNS) with herpes- or enterovirus can be self-limiting and benign, but occasionally result in severe and fatal disease. The polymerase chain reaction (PCR) has revolutionized the diagnostics of viral pathogens, and by multiple displacement amplification (MDA) prior to real-time PCR the sensitivity might be further enhanced. The aim of this study was to investigate if herpes- or enterovirus can be detected in cerebrospinal fluid (CSF) from patients without symptoms.

    METHODS:

    Cerebrospinal fluid (CSF) samples from 373 patients lacking typical symptoms of viral CNS infection were analysed by real-time PCR targeting herpesviruses or enteroviruses with or without prior MDA.

    RESULTS:

    In total, virus was detected in 17 patients (4%). Epstein-Barr virus (EBV) was most commonly detected, in general from patients with other conditions (e.g. infections, cerebral hemorrhage). MDA satisfactorily amplified viral DNA in the absence of human nucleic acids, but showed poor amplification capacity for viral DNA in CSF samples, and did not increase the sensitivity for herpes virus-detection with our methodology.

    CONCLUSIONS:

    Viral pathogens are rarely detected in CSF from patients without signs of CNS infection, supporting the view that real-time PCR is a highly specific method to detect symptomatic CNS-infection caused by these viruses. However, EBV may be subclinically reactivated due to other pathological conditions in the CNS.

  • 13.
    Åkerlund, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sundqvist, Martin
    Universitetssjukhuset, Örebro, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Åhrén, Christina
    regionala Strama, Västra Götalandsregionen, Göteborg, Sweden.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Giske, Christian G
    Karolinska universitetssjukhuset, Solna, Sweden.
    Svarstiderna kan kortas vid mikrobiologisk diagnostik av sepsis: Bättre öppettider på laboratorier och aktiv rådgivning ger snabbare terapi2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 7, article id C73SArticle in journal (Refereed)
    Abstract [sv]

    Snabbt insatt adekvat antibiotikabehandling är livräddande vid allvarliga bakteriella infektioner. 

    Snabb mikrobiologisk diagnostik krävs i och med ökande antibiotikaresistens och kommer att ge medicinska vinster.

    En enkät till landets mikrobiologiska laboratorier visar på stora skillnader avseende tillgänglighet, snabbhet och kommunikation med svarsmottagande enhet vad gäller positiva blododlingar.

    För snabbare svar krävs att mikrobiologiska laboratorier erbjuder mer generösa öppettider, effektivare transportsystem och patientnära blododlingsinkubatorer samt tidig och aktiv rådgivning till behandlande läkare.

    n/a

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