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  • 101.
    Palm, Eleonor
    et al.
    Örebro University, School of Medical Sciences.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Bengtsson, Torbjörn
    Örebro University, School of Medical Sciences.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    The role of toll-like and protease-activated receptors and associated intracellular signaling in Porphyromonas gingivalis-infected gingival fibroblasts2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 2, p. 157-169Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis, which is considered a keystone agent in periodontitis, has evolved elaborate mechanisms to grow and survive in a hostile milieu. The gingival fibroblast is the major cell type in the gingiva and is considered to be important in the periodontitis-associated inflammation. As a part of the innate immune response, they produce cytokines such as CXCL8 and interleukin (IL)-6 which are believed to contribute to the destruction of the tooth-supporting tissues. This study investigates how the expression of protease-activated receptors (PAR1, PAR2) and toll-like receptors (TLR2, TLR4) changes with P. gingivalis exposure and how silencing of one receptor affects the expression of the other receptors. The importance of protein kinase C (PKC) and p38 in the regulation of CXCL8 and IL-6 was also examined. Receptors were knockdown with small-interfering RNA. PKC or p38 was blocked prior to stimulation with P. gingivalis. Fibroblasts were able to compensate for PAR1 knockdown with increased expression of PAR2. PKC and p38 were involved in the regulation of P. gingivalis-induced CXCL8 and IL-6. Our results indicate that PAR1 and PAR2 could be implicated in periodontitis and that PKC and P38 play a role in the inflammatory response in P. gingivalis-infected gingival fibroblasts.

  • 102.
    Palm, Eleonor
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
    Demirel, Isak
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
    Bengtsson, Torbjörn
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
    Khalaf, Hazem
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
    The role of toll-like and protease-activated receptors in the expression of cytokines by gingival fibroblasts stimulated with the periodontal pathogen Porphyromonas gingivalis2015In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 76, no 2, p. 424-432Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis is a periodontitis-associated pathogen and interactions between the bacterium and gingival fibroblasts play an important role in development and progression of periodontitis, an inflammatory disease leading to degeneration of tooth-supporting structures. Gingival fibroblasts, which expresses protease activated receptors (PARs) as well as toll-like receptors (TLRs), produces inflammatory mediators upon bacterial challenges. In this study, we elucidated the importance of PAR1, PAR2, TLR2 and TLR4 for the expression and secretion of CXCL8, interleukin-6 (IL-6), transforming growth factor-beta 1 (TGF-beta 1) and secretory leukocyte inhibitor (SLPI). Human gingival fibroblasts were transfected with small-interfering RNA against the target genes, and then stimulated with P. gingivalis wild-type W50 and W50-derived double rgp mutant E8 and kgp mutant K1A. TLR2-silencing reduced P. gingivalis-induced CXCL8 and IL-6. IL-6 was also reduced after PAR1-silencing. No effects were observed for TGF-beta 1. SLPI was suppressed by P. gingivalis and silencing of PAR1 as well as TLR2, gave additional suppression at the mRNA level. TLR4 was not involved in the regulation of the investigated mediators. CXCL8 and IL-6 are important for progression and development of periodontitis, leading to a chronic inflammation that may contribute to the tissue destruction that follows an exacerbated host response. Therefore, regulating the expression of TLR2 and subsequent release of CXCL8 and IL-6 in periodontitis could attenuate the tissue destruction seen in periodontitis.

  • 103.
    Paramel, Geena
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Sirsjö, Allan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fransén, Karin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Role of genetic alterations in the NLRP3 and CARD8 genes in health and disease2015In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 846782Article in journal (Refereed)
    Abstract [en]

    The complexity of a common inflammatory disease is influenced by multiple genetic and environmental factors contributing to the susceptibility of disease. Studies have reported that these exogenous and endogenous components may perturb the balance of innate immune response by activating the NLRP3 inflammasome. The multimeric NLRP3 complex results in the caspase-1 activation and the release of potent inflammatory cytokines, like IL-1β. Several studies have been performed on the association of the genetic alterations in genes encoding NLRP3 and CARD8 with the complex diseases with inflammatory background, like inflammatory bowel disease, cardiovascular diseases, rheumatoid arthritis, and type 1 diabetes. The aim of the present review is therefore to summarize the literature regarding genetic alterations in these genes and their association with health and disease.

  • 104. Parmar, A S
    et al.
    Lappalainen, M
    Paavola-Sakki, P
    Halme, L
    Färkkilä, M
    Turunen, U
    Kontula, K
    Aromaa, A
    Salomaa, V
    Peltonen, L
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Törkvist, L
    D'Amato, M
    Saavalainen, P
    Einarsdottir, E
    Association of celiac disease genes with inflammatory bowel disease in Finnish and Swedish patients2012In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 13, no 6, p. 474-480Article in journal (Refereed)
    Abstract [en]

    Some genetic loci may affect susceptibility to multiple immune system-related diseases. In the current study, we investigated whether the known susceptibility loci for celiac disease (CelD) also associate with Crohn's disease (CD) and/or ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), in Finnish patients. A total of 45 genetic markers were genotyped in a Finnish data set comprising 699 IBD patients and 2482 controls. Single-marker association with IBD and its subphenotypes was tested. A meta-analysis with a Swedish UC data set was also performed. A total of 12 single-nucleotide polymorphisms associated with CD and/or UC (P<0.05). In the subphenotype analysis, rs6974491-ELMO1 (P=0.0002, odds ratio (OR): 2.20) and rs2298428-UBE2L3 (P=5.44 × 10(-5), OR: 2.59) associated with pediatric UC and CD, respectively. In the meta-analysis, rs4819388-ICOSLG (P=0.00042, OR: 0.79) associated with UC. In the subphenotype meta-analysis, rs1738074-TAGAP (P=7.40 × 10(-5), OR: 0.61), rs6974491-ELMO1 (P=0.00052, OR: 1.73) and rs4819388-ICOSLG (P=0.00019, OR: 0.75) associated with familial UC, pediatric UC and sporadic UC, respectively. Multiple CelD risk loci also confer susceptibility for CD and/or UC in the Finnish and Swedish populations. Certain genetic risk variants may furthermore predispose an individual for developing a particular disease phenotype.

  • 105.
    Persson, Alexander
    et al.
    Department of Molecular and Clinical Medicine, Linköping University, Sweden.
    Blomgran-Julinder, Robert
    Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Eklund, Daniel
    Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Lundström, Charlotte
    Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Stendahl, Olle
    Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Induction of apoptosis in human neutrophils by Mycobacterium tuberculosis is dependent on mature bacterial lipoproteins2009In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 47, no 3, p. 143-150Article in journal (Refereed)
    Abstract [en]

    Modulation of immune cell apoptosis is a key evasion strategy utilized by Mycobacterium tuberculosis (Mtb). To be able to multiply within macrophages, the bacterium delays apoptosis and down-regulates pro-inflammatory activation in these cells, whereas apoptosis is rapidly induced in the potently bactericidal neutrophils. Initial host-pathogen interactions between neutrophils and Mtb, subsequently leading to apoptosis, need to be investigated to understand the early features during Mtb infections. Opsonized Mtb were readily phagocytosed, and the immuno-mediated phagocytosis triggered early activation of anti-apoptotic Akt in the neutrophils but the bacteria still induced apoptosis to the same extent as non-phagocytosed Mtb. Mtb-induced apoptosis was strictly dependent on NADPH oxidase-generated reactive oxygen species, compounds shown to damage lysosomal granules. Despite this, we found no involvement of damaged azurophilic granules in Mtb-induced apoptosis in human neutrophils. Instead, the Mtb-induced apoptosis was p38 MAPK dependent and induced through the mitochondrial pathway. Moreover, Mtb deficient of mature lipoproteins lacked the determinants required for induction of neutrophil apoptosis. These results show that Mtb exert a strong intrinsic capacity to induce apoptosis in neutrophils that is capable of overcoming the anti-apoptotic signaling in the cell.

  • 106.
    Prag, Gustaf
    et al.
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Falk-Brynhildsen, Karin
    Department of Cardiothoracic and Vascular Surgery, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden; Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Decreased susceptibility to chlorhexidine and prevalence of disinfectant resistance genes among clinical isolates of Staphylococcus epidermidis2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 10, p. 961-967Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis, despite regarded as a commensal, is recognized as a nosocomial pathogen usually by acting as an opportunist, especially in infections associated with implanted foreign body materials. Pre-operative antiseptic preparation is an important strategy for reducing the risk of complications such as surgical site infection (SSI). The currently most widely used antiseptic compounds are alcohols and quaternary ammonium compounds (QACs), predominantly chlorhexidine.

    The aim of this study was to investigate if decreased susceptibility to chlorhexidine among S. epidermidis was present in our setting. S. epidermidis (n=143) were obtained from prosthetic joint infections (PJI) (n=61), commensals (n=24), post-operative infections after cardiothoracic surgery (n=31), and the skin of the chest after routine disinfection prior cardiothoracic surgery (n=27). Determination of MIC of chlorhexidine was performed on Müeller Hinton agar plates supplemented with serial dilutions of chlorhexidine. Five QAC resistance genes; qacA/B, smr, qacH, qacJ, and qacG, were detected using PCR.

    Decreased susceptibility to chlorhexidine was found in 54% of PJI isolates, 68% of cardiothoracic isolates, 21% of commensals, and 7% of isolates obtained from the skin of cardiothoracic patients, respectively.

    The qacA/B gene was present in 62/143 isolates (43%), smr in 8/143 (6%) and qacH in one isolate (0.7%). The qacA/B gene was found in 52% of PJI isolates, 61% of cardiothoracic isolates, 25% of commensals, and 19% of isolates obtained from the skin of cardiothoracic patients. In conclusion, decreased susceptibility to chlorhexidine as well as QAC resistance genes was highly prevalent among S. epidermidis causing deep SSIs.

  • 107. Rangel, I.
    et al.
    Ganda-Mall, J.-P.
    Elgbratt, K.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Development of colitis in Gai2-deficient mice is associated with profound changes in the microbiota2010Conference paper (Other academic)
  • 108.
    Rizzardi, Kristina
    et al.
    Public Health Agency of Sweden, Solna, Sweden .
    Norén, Torbjörn
    Örebro University, School of Medical Sciences.
    Aspevall, Olov
    Public Health Agency of Sweden, Solna, Sweden .
    Mäkitalo, Barbro
    Public Health Agency of Sweden, Solna, Sweden .
    Toepfer, Michael
    Unilabs Clinical Microbiology, Skövde, Sweden.
    Johansson, Åsa
    Växjö Hospital, Växjö, Sweden.
    Åkerlund, Thomas
    Public Health Agency of Sweden, Solna, Sweden .
    National Surveillance for Clostridioides difficile Infection, Sweden, 2009-20162018In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, no 9, p. 1617-1625Article in journal (Refereed)
    Abstract [en]

    We report results from a national surveillance program for Clostridioides difficile infection (CDI) in Sweden, where CDI incidence decreased by 22% and the proportion of multidrug-resistant isolates decreased by 80% during 2012-2016. Variation in incidence between counties also diminished during this period, which might be attributable to implementation of nucleic acid amplification testing as the primary diagnostic tool for most laboratories. In contrast to other studies, our study did not indicate increased CDI incidence attributable the introduction of nucleic acid amplification testing. Our results also suggest that successful implementation of hygiene measures is the major cause of the observed incidence decrease. Despite substantial reductions in CDI incidence and prevalence of multidrug-resistant isolates, Sweden still has one of the highest CDI incidence levels in Europe. This finding is unexpected and warrants further investigation, given that Sweden has among the lowest levels of antimicrobial drug use.

  • 109.
    Rumyantseva, Tatiana
    et al.
    Department of Molecular Diagnostics, Central Research Institute for Epidemiology, Moscow, Russian Federation.
    Golparian, Daniel
    WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, , Örebro University Hospital, Örebro, Sweden; Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Sweden.
    Nilsson, Christian S.
    Department of Dermatovenereology, Örebro University Hospital, Örebro, Sweden.
    Johansson, Emma
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Ctr Gonorrhoea & Other STIs, Natl Reference Lab Pathogen Neisseria, Dept Lab Med, Microbiol, Örebro University Hospital, Örebro, Sweden.
    Falk, My
    Department of Dermatovenereology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Ctr Gonorrhoea & Other STIs, Natl Reference Lab Pathogen Neisseria, Dept Lab Med, Microbiol, Örebro University Hospital, Örebro, Sweden.
    Van Dam, Alje
    Public Health Laboratory, Amsterdam Health Centre, Amsterdam, Netherlands; Department of Medical Microbiology, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, Netherlands.
    Guschin, Alexander
    Department of Molecular Diagnostics, Central Research Institute for Epidemiology, Moscow, Russian Federation.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Ctr Gonorrhoea & Other STIs, Natl Reference Lab Pathogen Neisseria, Dept Lab Med, Microbiol, Örebro University Hospital, Örebro, Sweden.
    Evaluation of the new AmpliSens multiplex real-time PCR assay for simultaneous detection of Neisseriagonorrhoeae, Chlamydiatrachomatis, Mycoplasmagenitalium, and Trichomonasvaginalis2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 10, p. 879-886Article in journal (Refereed)
    Abstract [en]

    In this study, we performed an evaluation of the new CE-marked multiplex real-time AmpliSens N.gonorrhoeae/C.trachomatis/M.genitalium/T.vaginalis-MULTIPRIME-FRT PCR assay compared to APTIMA tests, i.e., APTIMA COMBO 2assay, APTIMA Trichomonasvaginalis assay (FDA-approved), and two different APTIMA Mycoplasmagenitalium assays (research use only; one of them only used for discrepancy analysis). Vaginal swabs (n=209) and first-void urine (FVU) specimens from females (n=498) and males (n=554), consecutive attendees (n=1261) at a dermatovenerological clinic in Sweden, were examined. The sensitivity of the AmpliSens PCR assay for detection of C.trachomatis (6.3% prevalence), M.genitalium (5.7% prevalence), N.gonorrhoeae (0.3% prevalence), and T.vaginalis (0.08% prevalence) was 97.5% (95% confidence interval (CI): 91.2-99.6%), 81.9% (95% CI: 70.7-89.7%), 100% (95% CI: 40.2-100%) and 100% (95% CI: 16.5-100%), respectively. The specificity of the AmpliSens PCR assay was 100% (95% CI: 99.6-100%) for all agents. The analytical sensitivity and specificity for N.gonorrhoeae detection was excellent, i.e., 55 international gonococcal strains detected and 135 isolates of 13 non-gonococcal Neisseria species were negative. In conclusion, the multiplex real-time AmpliSens N.gonorrhoeae/C.trachomatis/M.genitalium/T.vaginalis-MULTIPRIME-FRT PCR assay demonstrated high sensitivity and excellent specificity for the detection of C.trachomatis, N.gonorrhoeae, and T.vaginalis, and excellent specificity but suboptimal sensitivity for M.genitalium detection.

  • 110.
    Rumyantseva, Tatiana
    et al.
    Central Research Institute for Epidemiology, Moscow, Russia.
    Shipitsyna, Elena
    Laboratory of Microbiology, D.O. Ott Research Institute of Obstetrics, Gynaecology and Reproductology, St. Petersburg, Russia; Department of Laboratory Medicine, Microbiology, WHO Collaborating Centre for Gonorrhoea and Other STIs, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Guschin, Alexander
    Central Research Institute for Epidemiology, Moscow, Russia.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Microbiology, WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University Hospital, Örebro, Sweden.
    Evaluation and subsequent optimizations of the quantitative AmpliSens Florocenosis/Bacterial vaginosis-FRT multiplex real-time PCR assay for diagnosis of bacterial vaginosis2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 12, p. 1099-1108Article in journal (Refereed)
    Abstract [en]

    Traditional microscopy-based methods for diagnosis of bacterial vaginosis (BV) are underutilized in many settings, and molecular techniques may provide opportunities for rapid, objective, and accurate BV diagnosis. This study evaluated the quantitative AmpliSens Florocenosis/Bacterial vaginosis-FRT multiplex real-time PCR (Florocenosis-BV) assay. Vaginal samples from a previous study including unselected female subjects (n = 163) and using Amsel criteria and 454 pyrosequencing for BV diagnosis were examined with the Florocenosis-BV test and additionally tested for the presence and quantity of Gardnerella vaginalis clades 3 and 4. The Florocenosis-BV assay demonstrated 100% and 98% sensitivity compared with the Amsel criteria and 454 pyrosequencing, respectively, with 91% specificity. The modified Florocenosis-BV assay (detecting also G. vaginalis clades 3 and 4) resulted in 100% sensitivity vs the Amsel criteria and 454 pyrosequencing with specificity of 86% and 88%, respectively. Further optimizations of thresholds for the quantitative parameters used in the kit resulted in 99-100% accuracy vs Amsel criteria and 454 pyrosequencing for selected parameters. The Florocenosis-BV assay is an objective, accurate, sensitive, and specific method for BV diagnosis; however, the performance of the test can be further improved with some minor optimizations.

  • 111.
    Salzer, Anna Thunström
    et al.
    Department of Radiation Sciences, University of Umeå, Umeå, Sweden; Department of Clinical Microbiology, Laboratory of Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
    Niemiec, Maria J.
    Department of Clinical Microbiology, Laboratory of Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden; Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Center for Sepsis Control and Care, Jena, Germany.
    Hosseinzadeh, Ave
    Department of Clinical Microbiology, Laboratory of Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
    Stylianou, Marios
    Örebro University, School of Science and Technology. Department of Clinical Microbiology, Laboratory of Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
    Åström, Fredrik
    Department of Radiation Sciences, University of Umeå, Umeå, Sweden.
    Röhm, Marc
    Department of Clinical Microbiology, Laboratory of Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
    Ahlm, Clas
    Department of Clinical Microbiology, Laboratory of Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
    Wahlin, Anders
    Department of Radiation Sciences, University of Umeå, Umeå, Sweden.
    Ermert, David
    Department of Clinical Microbiology, Laboratory of Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden; Department of Translational Medicine, Division of Medical Protein Chemistry, Lund University, Malmö, Sweden.
    Urban, Constantin F.
    Department of Clinical Microbiology, Laboratory of Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.
    Assessment of Neutrophil Chemotaxis Upon G-CSF Treatment of Healthy Stem Cell Donors and in Allogeneic Transplant Recipients2018In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 1968Article in journal (Refereed)
    Abstract [en]

    Neutrophils are crucial for the human innate immunity and constitute the majority of leukocytes in circulation. Thus, blood neutrophil counts serve as a measure for the immune system's functionality. Hematological patients often have low neutrophil counts due to disease or chemotherapy. To increase neutrophil counts and thereby preventing infections in high-risk patients, recombinant G-CSF is widely used as adjunct therapy to stimulate the maturation of neutrophils. In addition, G-CSF is utilized to recruit stem cells (SCs) into the peripheral blood of SC donors. Still, the actual functionality of neutrophils resulting from G-CSF treatment remains insufficiently understood. We tested the ex vivo functionality of neutrophils isolated from blood of G-CSF-treated healthy SC donors. We quantified chemotaxis, oxidative burst, and phagocytosis before and after treatment and detected significantly reduced chemotactic activity upon G-CSF treatment. Similarly, in vitro treatment of previously untreated neutrophils with G-CSF led to reduced chemotactic activity. In addition, we revealed that this effect persists in the allogeneic SC recipients up to 4 weeks after neutrophil engraftment. Our data indicates that neutrophil quantity, as a sole measure of immunocompetence in high-risk patients should be considered cautiously as neutrophil functionality might be affected by the primary treatment.

  • 112.
    Samuelsson, Malin
    et al.
    Department of Experimental Medical Science, Lund University, Lund, Sweden.
    Svensson, Lena
    Örebro University, School of Medical Sciences. Department of Experimental Medical Science, Lund University, Lund, Sweden;.
    Biotinylation Assay to Determine LFA-1 Recycling in Motile T-Lymphocytes2019In: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 1930, p. 115-122Article in journal (Refereed)
    Abstract [en]

    The cycles of internalization of the cell surface β2 integrin receptor lymphocyte function-associated antigen 1 (LFA-1) and its re-exposure on the plasma membrane are important for T-cell trafficking. Biotinylation of cells enables to measure surface expression of receptors, and after reducing surface biotin with reducing buffer, enables to measure the internalization of receptors. Here, by using biotin in combination with reducing buffer and recombinant intercellular adhesion molecule-1 (rICAM-1)-coated dishes and subsequent Western immunoblot analysis, we describe how to measure internalization of the LFA-1 receptor and its re-expression back to the cell surface in motile T-lymphocytes.

  • 113.
    Serwin, Agnieszka Beata
    et al.
    Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland.
    Bulhak-Koziol, Violetta
    Diagnostic and Research Centre for Sexually Transmitted Diseases, Bialystok, Poland.
    Sokolowska, Marianna
    Diagnostic and Research Centre for Sexually Transmitted Diseases, Bialystok, Poland.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Trichomonas vaginalis is very rare among women with vaginal discharge in Podlaskie province, Poland2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 9, p. 840-843Article in journal (Refereed)
    Abstract [en]

    Trichomonas vaginalis is the most common curable sexually transmitted pathogen globally. However, in the European Union (EU), trichomoniasis appears to be a rare condition. The aim of this study was to examine the prevalence of T. vaginalis among females attending an STI centre in Bialystok, Poland, using the highly sensitive and specific APTIMA T. vaginalis assay. Consecutive females, referred by gynaecologists mainly because of abnormal vaginal discharge, were diagnosed using wet mount microscopy, culture and APTIMA T. vaginalis assay. Among 272 women studied, 82% were pre- and 18% postmenopausal. The average age was 36.0 +/- 13.9 (range: 18-86) years. Abnormal discharge (alone or accompanied by itch or vulvovaginal burning) was the most frequent complain in both groups (66.2% and 48.0%). Erythema and discharge were the most frequent abnormal signs (58.6% and 56.0%). Not a single T. vaginalis-positive sample was detected using wet mount microscopy, culture or APTIMA T. vaginalis assay. Despite using the highly sensitive APTIMA T. vaginalis assay for detection, the pathogen could not be identified in females in the studied setting, similar to results from other EU settings. The need for general screening using NAAT for this pathogen while diagnosing vulvovaginal symptoms in females in Poland appears to be low.

  • 114. Silfverdal, S. A.
    et al.
    Ehlin, A.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Protection against clinical pertussis induced by whole-cell pertussis vaccination is related to primo-immunisation intervals2007In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 25, no 43, p. 7510-7515Article in journal (Refereed)
    Abstract [en]

    AIMS: Information on subjects who had at least three immunisations against pertussis was provided by longitudinal data from the 1970 British Cohort Study (BCS70) and used to assess whether three whole-cell pertussis (wP) immunisations given within less than 5 months confer less effective protection in childhood compared with a schedule with a longer interval.

    METHODS: Age at pertussis infection was the dependent variable in a Cox regression analysis, to investigate associations with duration between first and third pertussis immunisation; with third immunisation modelled as a time-dependent covariate. Adjustment was for number of pertussis immunisations (three or four), sex, social class and other potential confounding factors.

    RESULTS: A total of 8545 children were included in the analysis and 556 had a history of whooping cough. A duration of over 4 months between first and third pertussis immunisations is statistically significantly associated with a reduced risk of pertussis infection by age 10 years, compared with three immunisations given over a shorter period, producing a statistically significant adjusted hazard ratio of 0.74 (0.62-0.92). A fourth immunisation against pertussis further enhanced the protective effect with a hazard ratio of 0.59 (0.44-0.82).

    CONCLUSION: These results were based on a historical UK cohort using wP vaccine, and indicate that a vaccination schedule with an interval between the immunisations greater than 4 months, and also including a fourth immunisation, would be more effective in this population than a three dose schedule within a shorter interval without booster.

  • 115.
    Sjöberg, Lennart
    et al.
    Department of Clinical Microbiology, Örebro Medical Center Hospital, Örebro, Sweden.
    Fredlund, Hans
    Department of Clinical Microbiology, Örebro Medical Center Hospital, Örebro, Sweden.
    Duberg, Ann-Sofie
    Department of Clinical Microbiology, Örebro Medical Center Hospital, Örebro, Sweden.
    A comparison between Bactec aerobic resin and hypertonic blood culture media.1988In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 96, no 8, p. 720-722Article in journal (Refereed)
    Abstract [en]

    The presence of antimicrobial agents in patients' blood is thought to represent an important source of false-negative blood cultures. This has led to the incorporation of agents with inhibitory effects on antimicrobial drugs into culture medium. In the present study, Bactec aerobic resin-containing blood culture medium was compared with Bactec hypertonic blood culture medium. 504 patients receiving cytostatic and/or antibiotic treatment were studied. Sensitivity calculations on detection of bacteremia in these patients gave 0.91 for the resin medium and 0.79 for the hypertonic blood culture system and showed a significant difference (p = 0.016). In addition, the resin-containing system more rapidly detected positive cultures than the hypertonic system.

  • 116.
    Sjöberg, Maria
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Eriksson, Mats
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Centre for Health Care Sciences, Örebro University Hospital, Örebro, Sweden.
    Andersson, Josefin
    Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Norén, Torbjörn
    Örebro University Hospital. Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Transmission of Clostridium difficile spores in isolation room environments and through hospital beds2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 9, p. 800-803Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to determine the dissemination of Clostridium difficile (CD) spores in a hospital setting where the potassium monopersulfate-based disinfectant VirkonTM was used for cleaning. In the initial part of the study, we sampled 16 areas of frequent patient contact in 10 patient rooms where a patient with CD infection (CDI) had been accommodated. In the second part of the study, we obtained samples from 10 patient beds after discharge of CDI patients, both before and after the beds were cleaned. In the first part, CDspores were isolated in only 30% of the rooms. In the second part, which focused on transmission to hospital beds, C. difficile was found in four of 10 beds either before or after cleaning. In conclusion, in both parts of the study, we demonstrated a moderate spread of CD spores to the environment despite routine cleaning procedures involving VirkonTM. 

  • 117.
    Skoglund, Caroline
    et al.
    Department of Physics, Chemistry and Biology, Materials in Medicine, Division of Applied Physics, Linköping University, Linköping, Sweden; Department of Medical Sciences, Cardiovascular Inflammation Research Center, Linköping University, Linköping, Sweden; Department of Medical Sciences, Division of Pharmacology, Linköping University, Linköping, Sweden.
    Wetterö, Jonas
    Department of Clinical and Experimental Medicine, Division of Rheumatology/Autoimmunity and Immune Regulation Unit, Linköping University, Linköping, Sweden.
    Skogh, Thomas
    Department of Clinical and Experimental Medicine, Division of Rheumatology/Autoimmunity and Immune Regulation Unit, Linköping University, Linköping, Sweden.
    Sjöwall, Christopher
    Department of Clinical and Experimental Medicine, Division of Rheumatology/Autoimmunity and Immune Regulation Unit, Linköping University, Linköping, Sweden.
    Tengvall, Pentti
    Department of Physics, Chemistry and Biology, Materials in Medicine, Division of Applied Physics, Linköping University, Linköping, Sweden.
    Bengtsson, Torbjörn
    Department of Physics, Chemistry and Biology, Materials in Medicine, Division of Applied Physics, Linköping University, Linköping, Sweden; Department of Medical Sciences, Cardiovascular Inflammation Research Center, Linköping University, Linköping, Sweden.
    C-reactive protein and C1q regulate platelet adhesion and activation on adsorbed immunoglobulin G and albumin2008In: Immunology and Cell Biology, ISSN 0818-9641, E-ISSN 1440-1711, Vol. 86, no 5, p. 466-474Article in journal (Refereed)
    Abstract [en]

    Blood platelets and C-reactive protein (CRP) are both used clinically as markers of ongoing inflammation, and both participate actively in inflammatory responses, although the biological effects are still incompletely understood. Rapidly adhering platelets express receptors for complement factor 1q (C1q) and the Fc part of immunoglobulin G (IgG), and CRP is known to activate/regulate complement via C1q binding, and to ligate FcgammaRs. In the present study, we used normal human IgG pre-adsorbed to a well-characterized methylated surface as a model solid-phase immune complex when investigating the effects of CRP and C1q on platelet adhesion and activation. Protein adsorption was characterized using ellipsometry and polyclonal antibodies, and human serum albumin (HSA) and non-coated surfaces were used as reference surfaces. Platelet adhesion to IgG and HSA was inhibited by both C1q and CRP. Furthermore, CRP (moderately) and C1q (markedly) decreased the spreading of adhering platelets. The combination of C1q and CRP was slightly more potent in reducing cell adhesion to IgG, and also impaired the adhesion to HSA and non-coated surfaces. Platelet production of thromboxane B2 (TXB(2)) was also reduced by C1q both in the presence and absence of CRP, whereas CRP alone had no effect on TXB(2) production. We conclude that CRP and C1q regulate the behaviour of platelets, and that this may be an important immunoregulatory mechanism during inflammatory conditions.

  • 118.
    Squire, Michele M.
    et al.
    Univ Western Australia, Nedlands WA, Australia.
    Carter, Glen P.
    Monash Univ, Clayton Vic, Australia.
    Mackin, Kate E.
    Monash Univ, Clayton Vic, Australia.
    Chakravorty, Anjana
    Monash Univ, Clayton Vic, Australia.
    Norén, Torbjörn
    Örebro University Hospital.
    Elliott, Briony
    Univ Western Australia, Nedlands WA, Australia.
    Lyras, Dena
    Monash Univ, Clayton Vic, Australia.
    Riley, Thomas V.
    Univ Western Australia, Nedlands WA, Australia; PathWest Lab Med, Nedlands WA, Australia.
    Novel Molecular Type of Clostridium difficile in Neonatal Pigs, Western Australia2013In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 19, no 5, p. 790-792Article in journal (Refereed)
    Abstract [en]

    Clostridium difficile causes neonatal enteritis in piglets; strains of PCR ribotype 078 are most commonly identified. We investigated C. difficile prevalence in piglets in Australia and isolated a novel strain with a unique pathogenicity locus. In a mouse infection model, this strain produced more weight loss than did a ribotype 078 strain.

  • 119. Strid, H.
    et al.
    Kumawat, Ashok Kumar
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, J.
    Altered gene expression of IL-6 and rennin in colonic biopsies from collagenous colitis and ulcerative colitis compared to healthy controls2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no Suppl. 3, article id A317Article in journal (Refereed)
  • 120. Strid, Hilja
    et al.
    Kumawat, Ashok
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Medicine, Örebro University, Sweden.
    Bohr, Johan
    Genuttrycket för Renin och IL-6 i kolonmucosan är förändrad vid kollagen kolit2012Conference paper (Other academic)
  • 121. Sundin, Johanna
    et al.
    Kumawat, Ashok Kumar
    Rangel, I.
    Brummer, Robert
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Medicine, Örebro University, Sweden.
    Karakterisering av T-lymfocyter från tarmmukosan hos patienter med postinfektiös IBS2012Conference paper (Other academic)
  • 122.
    Svensson, Karolina
    et al.
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University, School of Medical Sciences.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Characterization of SCCmec elements in methicillin-resistant Staphylococcus epidermidis isolated from blood cultures from neonates during three decades2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 12, p. 885-893Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis is a major cause of nosocomial infections in immunocompromised patients and the predominant pathogen in catheter-related infections and bloodstream infections. Approximately 70-80% of S. epidermidis carry the mecA gene encoding methicillin resistance. The mecA gene is located on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec). The aim of this study was to characterize the SCCmec elements as well as the adjacent arginine catabolic mobile element (ACME) in 30 clinical blood isolates of mecA positive S. epidermidis obtained from neonates and collected over a period of three decades. The ccr and mec gene complexes were identified using PCR. The SCCmec elements were found among 29/30 isolates and 13 different combinations of ccr gene complexes and mec gene complexes were identified. Staphylococcus epidermidis regularly carried multiple copies of ccr gene complexes, but only one class of mec gene complex. Three isolates could be assigned the SCCmec type III (3A). The combinations of ccr gene complexes and the mec gene complexes differed among the three decades. The most frequent combination was class B mec in combination with ccr1 and ccr2. Staphylococcus epidermidis may constitute a large reservoir for SCCmec elements, and frequent exchange of mobile genetic elements between staphylococcal species may explain the emergence of new MRSA strains.

  • 123.
    Svärd, Jenny
    et al.
    Dept Med Huddinge, Unit Infect Dis & Dermatol, Karolinska Inst, Stockholm, Sweden.
    Sonnerborg, Anders
    Dept Med Huddinge, Unit Infect Dis & Dermatol, Karolinska Inst, Stockholm, Sweden; Dept Lab Med, Div Clin Microbiol, Karolinska Inst, Stockholm, Sweden.
    Vondracek, Martin
    Dept Clin Microbiol, Karolinska Univ Hosp, Stockholm, Sweden; Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Mölling, Paula
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Nowak, Piotr
    Dept Med Huddinge, Unit Infect Dis & Dermatol, Karolinska Inst, Stockholm, Sweden.
    On the Usefulness of Circulating Bacterial 16S rDNA as a Marker of Microbial Translocation in HIV-1-Infected Patients2014In: Journal of Acquired Immune Deficiency Syndromes, ISSN 1525-4135, E-ISSN 1944-7884, Vol. 66, no 4, p. E87-E89Article in journal (Refereed)
  • 124.
    Sysi-Aho, Marko
    et al.
    VTT Technical Research Centre of Finland, Espoo, Finland .
    Ermolov, Andrey
    Aalto University School of Science, Department of Information and Computer Science, Helsinki Institute for Information Technology HIIT, Espoo, Finland .
    Gopalacharyulu, Peddinti V.
    VTT Technical Research Centre of Finland, Espoo, Finland .
    Tripathi, Abhishek
    Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Finland .
    Seppänen-Laakso, Tuulikki
    VTT Technical Research Centre of Finland, Espoo, Finland .
    Maukonen, Johanna
    VTT Technical Research Centre of Finland, Espoo, Finland .
    Mattila, Ismo
    VTT Technical Research Centre of Finland, Espoo, Finland .
    Ruohonen, Suvi T.
    Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland .
    Vähätalo, Laura
    Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland .
    Yetukuri, Laxman
    VTT Technical Research Centre of Finland, Espoo, Finland .
    Härkönen, Taina
    Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland .
    Lindfors, Erno
    VTT Technical Research Centre of Finland, Espoo, Finland .
    Nikkilä, Janne
    Finnish Red Cross Blood Service, Helsinki, Finland .
    Ilonen, Jorma
    epartment of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland; Immunogenetics Laboratory, University of Turku, Turku, Finland.
    Simell, Olli
    Department of Pediatrics, University of Turku, Turku, Finland .
    Saarela, Maria
    VTT Technical Research Centre of Finland, Espoo, Finland .
    Knip, Mikael
    ospital for Children and Adolescents, University of Helsinki, Helsinki, Finland, Department of Pediatrics, Tampere University Hospital, Tampere, Finland; Folkhälsan Research Center, Helsinki, Finland.
    Kaski, Samuel
    Aalto University School of Science, Department of Information and Computer Science, Helsinki Institute for Information Technology HIIT, Espoo, Finland; Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Finland .
    Savontaus, Eriika
    Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland; Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland .
    Oresic, Matej
    VTT Technical Research Centre of Finland, Espoo, Finland; Institute of Molecular Medicine Finland FIMM, Helsinki, Finland .
    Metabolic regulation in progression to autoimmune diabetes2011In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 7, no 10, article id e1002257Article in journal (Refereed)
    Abstract [en]

    Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes.

  • 125.
    Säll, Olof
    et al.
    Örebro University, School of Medical Sciences. Faculty of Medicine and Health, Department of Infectious Diseases, Örebro University, Örebro, Sweden.
    Johansson, Karin
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden; , Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Norén, Torbjörn
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden; , Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Low colonization rates of Clostridium difficile among patients and healthcare workers at Örebro University Hospital in Sweden2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 3, p. 240-244Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the rate of asymptomatic colonization rate of Clostridium difficile among both healthcare workers (HCWs) and patients in a hospital ward in Sweden. In a prospective observational study, asymptomatic HCWs (n=22) (22/60; 37%) attending patients in an infectious disease ward in Sweden participated and were screened once for C. difficile. At the same time, 58 consecutive patients (58/227; 26%) admitted to the same ward were screened for C. difficile, first at admission and thereafter two times weekly. Fecal samples were obtained by rectal swabs and cultured anaerobically using both cycloserine-cefoxitin-fructose agar and enrichment (Cooked Meat broth). All samples were also tested by loop-mediated isothermal amplification and isolates were tested for the presence of toxin A or B by enzyme immunoassay. None of the analyzed fecal samples from HCWs contained C. difficile. Among the patients during a 2-month observational period, three of the 58 patients (5.2%) were culture positive regarding C. difficile on admission and one additional patient became asymptomatically colonized with C. difficile during the hospital stay. Thus, the colonization rates were 0% (0/22) (95% confidence interval (CI): 0-15.4%) among HCWs and 5.2% (3/58) (95% CI: 1.1-14.4%) among patients at admission. As the HCWs were screened only once, we have not studied transient colonization. In conclusion, with observed low colonization rates, we find no support that HCWs would be an important source for C. difficile transmission.

  • 126. Tangteerawatana, P.
    et al.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Perlmann, H.
    Looareesuwan, S.
    Troye-Blomberg, M.
    Khusmith, Srisin
    Differential regulation of IgG subclasses and IgE antimalarial antibody responses in complicated and uncomplicated Plasmodium falciparum malaria2007In: Parasite immunology (Print), ISSN 0141-9838, E-ISSN 1365-3024, Vol. 29, no 9, p. 475-483Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to assess the immunoglobulin (Ig)-subclass distribution of antimalarial antibody responses in 110 and 169 Thai patients with complicated and uncomplicated Plasmodium falciparum malaria, respectively. Antimalarial plasma IgG subclasses and IgE antibody levels against a crude malaria blood stages, and antigen preparation were determined using enzyme-linked immunosorbent assay (ELISA). On admission, the levels of anti-P. falciparum IgG1, IgG2 and IgG3 were significantly lower in patients with complicated malaria than uncomplicated malaria (IgG1, P < 0.0001; IgG2, P < 0.0001; IgG3, P < 0.0001). The levels of antimalarial IgE were slightly lower, but not statistically significant (P = 0.389) in the complicated malaria. After adjusting all antibody levels and age, anti-P. falciparum IgG3 levels remained significantly associated with complicated malaria. None of the other antibody concentrations showed statistically significant associations with complicated malaria. The anti-P. falciparum IgG3 levels were related to the IgG1 as well as IgG2 levels. A correlation between anti-P. falciparum IgG2 and IgE was observed in the complicated malaria group, and this may indicate their roles in the severity of disease. Our data suggest that anti-P. falciparum IgG3 is associated with a reduced risk of complicated malaria and that antimalarial Ig-subclasses are differently regulated in patients with complicated and uncomplicated malaria.

  • 127.
    Titov, Leonid P.
    et al.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Siniuk, Kanstantsin V.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Wollenberg, Kurt K.
    National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda MD, USA.
    Unemo, Magnus
    Örebro University Hospital. Dept Lab Med, Natl Reference Lab Pathogen Neisseria, Örebro University Hospital, Örebro, Sweden.
    Thulin Hedberg, Sara
    Örebro University Hospital. Dept Lab Med, Natl Reference Lab Pathogen Neisseria, Örebro University Hospital, Örebro, Sweden.
    Glazkova, Slavyana E.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Lebedzeu, Fiodar A.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Nosava, Alena S.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Yanovich, Volcha O.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Xirasagar, Sadhia
    National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda MD, USA.
    Hurt, Darrell
    National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda MD, USA.
    Huyen, Yentram
    National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda MD, USA.
    Evolutionary epidemiology of Neisseria meningitidis strains in Belarus compared to other European countries2013In: Acta Microbiologica et Immunologica Hungarica, ISSN 1217-8950, Vol. 60, no 4, p. 397-410Article in journal (Refereed)
    Abstract [en]

    Introduction. Meningococcal infections are major causes of death in children globally. In Belarus, the incidence of cases and fatality rate of meningococcal infections are low and comparable to the levels in other European countries. Aim. In the present study, the molecular and epidemiological traits of Neisseria meningitidis strains circulating in Belarus were characterized and compared to isolates from other European countries. Materials and Methods. Twenty N. meningitidis strains isolated from patients (n = 13) and healthy contacts (n = 7) during 2006-2012 in Belarus were selected for multilocus sequence typing (MLST), genosubtyping and FetA typing. The STs of the Belarusian strains were phylogenetically compared to the STs of 110 selected strains from 22 other European countries. Results. Overall, eleven different genosubtypes were observed, there were seven variants of variable region of the fetA gene detected. The majority of the STs (95%) found in Belarus were novel and all those were submitted to the Neisseria MLST database for assignment. Several newly discovered alleles of fumC (allele 451) and gdh (allele 560 and 621) appeared to be descendants of alleles which are widespread in Europe, and single aroE alleles (602 and 603) occurred as a result of separate evolution. Conclusions. N. meningitidis strains circulating in Belarus are heterogeneous and include sequence types, possibly, locally evolved in Belarus as well as representatives of widespread European hyperinvasive clonal complexes.

  • 128.
    Trøseid, Marius
    et al.
    Department of Clinical Virology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden; Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway .
    Nowak, Piotr
    Department of Clinical Virology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden; Department of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden .
    Nyström, Jessica
    Department of Clinical Virology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Lindkvist, Annica
    Department of Clinical Virology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Abdurahman, Samir
    Department of Clinical Virology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden; Department of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden .
    Sönnerborg, Anders
    Department of Clinical Virology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden; Department of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden .
    Elevated plasma levels of lipopolysaccharide and high mobility group box-1 protein are associated with high viral load in HIV-1 infection: reduction by 2-year antiretroviral therapy2010In: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 24, no 11, p. 1733-1737Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate plasma levels of high mobility group box-1 protein (HMGB1), a marker of tissue necrosis and immune activation, as well as lipopolysaccharide (LPS), a marker of bacterial translocation, in HIV-1-infected patients.

    DESIGN: We studied 32 HIV-1-positive patients who had responded to antiretroviral therapy with undetectable viremia after 2 years, 10 nonresponders and 19 healthy controls.

    METHODS: HMGB1 was analyzed by ELISA, and LPS by Lamilus colometric assay. Nonparametric statistics were applied.

    RESULTS: In naive HIV-1 patients, HMGB1 and LPS were elevated as compared with controls (P < 0.001). LPS levels were higher in African and Oriental patients compared with whites (P = 0.007). Notably, viral load was two-fold higher in patients with LPS, and HMGB1 was above median as compared with other patients (P = 0.005). This association was largely driven by African patients, who had a five-fold increased viral load in the presence of elevated LPS and HMGB1. After 2 years of effective antiretroviral therapy, LPS was reduced to the same median level as in the control group (P < 0.001), and HMGB1 was also reduced (P = 0.001), whereas no reductions were seen in nonresponders.

    CONCLUSION: The new findings are the association of elevated plasma levels of LPS and HMGB1 with high viral load, as well as the normalized levels of LPS, and the reduction of HMGB1 after 2 years of effective antiretroviral therapy. As LPS and HMGB1 tend to form immunologically active complexes in vitro, we propose that such complexes may be involved in the immune activation and pathogenesis of HIV-1 infection.

  • 129.
    Ugge, Henrik
    et al.
    Örebro University, School of Medical Sciences. Department of Urology.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Fall, Katja
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology.
    The influence of prostatic Cutibacterium acnes infection on serum levels of IL6 and CXCL8 in prostate cancer patients2018In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 13, article id 34Article in journal (Refereed)
    Abstract [en]

    Background: Chronic prostatic inflammation, caused by Cutibacterium acnes (C. acnes), has been proposed to influence the risk of prostate cancer development. In vitro studies have demonstrated the capacity of C. acnes to induce secretion of Interleukin 6 (IL6) and C-X-C motif chemokine ligand 8 (CXCL8) by prostate epithelial cells. Both these inflammatory mediators have been implicated in prostate cancer pathophysiology. In this cohort study, we aimed to investigate the influence of prostatic C. acnes on serum levels of IL6 and CXCL8.

    Methods: We recruited 99 prostate cancer patients who underwent radical prostatectomy at orebro University Hospital. The cultivation of pre-operatively obtained prostate biopsies identified C. acnes in 60 of the 99 patients. Levels of IL6 and CXCL8 in pre-operative serum samples were analyzed using ELISA, and concentrations were compared between prostate cancer patients with and without prostatic C. acnes infection using standard statistical methods.

    Results: No statistical differences were observed in serum levels of IL6 and CXCL8 between subjects with and without prostatic C. acnes infection.

    Conclusions: Our results indicate that prostatic C. acnes infection may give rise to low-grade inflammation with little effect on systemic levels of IL6 and CXCL8.

  • 130.
    Unemo, Magnus
    et al.
    Örebro University Hospital. World Hlth Org Collaborating Ctr Gonorrhoea & Other STIs, Örebro University Hospital, Örebro, Sweden.
    Brooks, B.
    Sch Med, Dept Genitourinary Med, Univ Southampton, Southampton, England.
    Cole, M.
    Sexually Transmitted Bacteria Reference Lab, Hlth Protect Agcy, London, England.
    Ross, J. D. C.
    Birmingham Univ Hosp, Birmingham, England.
    White, J. A.
    Guys & St Thomas NHS Fdn Trust, London, England.
    Patel, R.
    Sch Med, Dept Genitourinary Med, Univ Southampton, Southampton, England.
    Does the '2012 IUSTI ECCG report on the diagnosis and management of Neisseria gonorrhoeae infections in Europe' depict the situation in Europe?2013In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 24, no 6, p. 423-426Article in journal (Refereed)
    Abstract [en]

    Gonorrhoea is a major public health concern globally. Of particular grave concern is that resistance to the third generation cephalosporins has been identified during recent years. This paper summarises and discusses the results of the '2012 IUSTI European Collaborative Clinical Group (ECCG) report on the diagnosis and management of Neisseria gonorrhoeae infections in Europe'. Although high quality care was reported in many settings, in several other countries the testing, diagnostics, antimicrobial treatment and follow-up of gonorrhoea patients need to be optimized. This, together with increased access to and use of antimicrobial susceptibility testing, is crucial in controlling the emergent spread of cephalosporin-resistant and multidrug-resistant gonorrhoea.

  • 131.
    Vaht, Krista
    et al.
    Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Göransson, Magnus
    Department of Pediatrics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlson, Kristina
    Department of Hematology, Uppsala University Hospital, Uppsala, Sweden.
    Isaksson, Cecilia
    Department of Hematology, Cancer Centre, University Hospital, Umeå, Sweden.
    Lenhoff, Stig
    Department of Hematology, Skåne University Hospital, Lund University, Lund, Sweden.
    Sandstedt, Anna
    Department of Hematology, Linköping University Hospital, Linköping, Sweden.
    Uggla, Bertil
    Örebro University, School of Medical Sciences. Section of Hematology Department of Medicine.
    Winiarski, Jacek
    Astrid Lindgren Children's Hospital, Karolinska University Hospital, Huddinge and CLINTEC, Karolinska Institutet, Stockholm, Sweden.
    Ljungman, Per
    Centre of Allogeneic Stem Cell Transplantation Unit (CAST), Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Per-Ola
    Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden; Department of Medicine, Södra Älvsborg Hospital Borås, Borås, Sweden.
    Brune, Mats
    Section of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Medicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study2019In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 25, no 10, p. 1970-1974Article in journal (Refereed)
    Abstract [en]

    Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients. In total, 68 patients underwent SCT, and 63% of them had failed immunosuppressive therapy. We found that, with a median follow-up of 109 months (range, 35 to 192 months), 5-year overall survival (OS) for all patients was 86.8%, whereas graft-versus-host disease-free, relapse/rejection-free survival (GRFS) at 5 years was 69.1%. There was no survival impact regarding the donor type or stem cell source. Patients aged >= 40 years had a higher transplant-related mortality (29.4% versus 7.8%; P= .023), which translated into a lower 5-year OS: 70.6% versus 92.2% (A=.022) and a trend of lower GRFS (52.9% versus 74.5%; P = .069). In conclusion, we found in this real-world setting that both OS and GRFS were high, but SCT for patients with AA aged >= 40 years is problematic, and clinical trials addressing this issue are warranted. (C) 2019 American Society for Transplantation and Cellular Therapy.

  • 132.
    Vedin, Inger
    et al.
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Cederholm, Tommy
    Department of Public Health and Caring Sciences, Division of Clinical Nutrition and Metabolism Research, Uppsala University Hospital, Uppsala, Sweden.
    Freund-Levi, Yvonne
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Basun, Hans
    Department of Public Health and Caring Sciences, Division of Geriatrics, Uppsala University Hospital, Uppsala, Sweden.
    Garlind, Anita
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Faxén Irving, Gerd
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Jönhagen, Maria Eriksdotter
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Vessby, Bengt
    Department of Public Health and Caring Sciences, Division of Clinical Nutrition and Metabolism Research, Uppsala University Hospital, Uppsala, Sweden.
    Wahlund, Lars-Olof
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Palmblad, Jan
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Effects of docosahexaenoic acid-rich n-3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: the OmegAD study2008In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 87, no 6, p. 1616-1622Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Dietary fish or fish oil rich in n-3 fatty acids (n-3 FAs), eg, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), ameliorate inflammatory reactions by various mechanisms. Whereas most studies have explored the effects of predominantly EPA-based n-3 FAs preparations, few have addressed the effects of n-3 FAs preparations with DHA as the main FA.

    OBJECTIVE: The objective was to determine the effects of 6 mo of dietary supplementation with an n-3 FAs preparation rich in DHA on release of cytokines and growth factors from peripheral blood mononuclear cells (PBMCs).

    DESIGN: In a randomized, double-blind, placebo-controlled trial, 174 Alzheimer disease (AD) patients received daily either 1.7 g DHA and 0.6 g EPA (n-3 FAs group) or placebo for 6 mo. In the present study blood samples were obtained from the 23 first randomized patients, and PBMCs were isolated before and after 6 mo of treatment.

    RESULTS: Plasma concentrations of DHA and EPA were significantly increased at 6 mo in the n-3 FAs group. This group also showed significant decreases of interleukin (IL)-6, IL-1beta, and granulocyte colony-stimulating factor secretion after stimulation of PBMCs with lipopolysaccharide. Changes in the DHA and EPA concentrations were negatively associated with changes in IL-1beta and IL-6 release for all subjects. Reductions of IL-1beta and IL-6 were also significantly correlated with each other. In contrast, this n-3 FA treatment for 6 mo did not decrease tumor necrosis factor-alpha, IotaL-8, IL-10, and granulocyte-macrophage colony-stimulating factor secretion.

    CONCLUSION: AD patients treated with DHA-rich n-3 FAs supplementation increased their plasma concentrations of DHA (and EPA), which were associated with reduced release of IL-1beta, IL-6, and granulocyte colony-stimulating factor from PBMCs. This trial was registered at clinicaltrials.gov as NCT00211159.

  • 133.
    Verma, Deepti
    et al.
    Linköpings universitet.
    Lerm, Maria
    Linköpings universitet.
    Blomgran Julinder, Robert
    Linköpings universitet.
    Eriksson, Per
    Linköpings universitet.
    Söderkvist, Peter
    Linköpings universitet.
    Särndahl, Eva
    Örebro University, School of Health and Medical Sciences.
    Gene polymorphisms in the NALP3 inflammasome are associated with interleukin-1 production and severe inflammation: relation to common inflammatory diseases?2008In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 58, no 3, p. 888-894Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: NALP3, ASC, and TUCAN are components of the NALP3 inflammasome, which triggers caspase 1-mediated interleukin-1beta (IL-1beta) release. Activating mutations in the gene encoding NALP3 (NLRP3) have recently been linked to familial periodic fever syndromes. We undertook this study to determine whether a patient with arthritis and antibiotic-resistant fever carried mutations in the genes encoding the NALP3 inflammasome. METHODS: Genetic analysis of NLRP3 and the gene encoding TUCAN (CARD-8) was performed on genomic DNA from the patient and from a population-based collection of DNA (806 subjects). For in vitro studies of IL-1beta production and caspase 1 activity, blood was obtained from the patient at different time points after administration of anakinra, an IL-1 receptor antagonist, as well as from 5 healthy age- and sex-matched control subjects. RESULTS: Mutation analysis of the patient's genes encoding NALP3, ASC, and TUCAN revealed variations in the NLRP3 (Q705K) and CARD-8 (C10X) genes. The allele frequencies of these single-nucleotide polymorphisms (SNPs) in the population were 6.5% and 34%, respectively. The elevated activity of caspase 1 and the high levels of IL-1beta measured in samples from the patient returned to normal levels after treatment with anakinra. CONCLUSION: Our results indicate that the patient's symptoms were due to elevated levels of IL-1beta, since treatment with anakinra effectively abolished the symptoms. The compound SNPs may explain the increased IL-1beta levels and inflammatory symptoms observed, but further studies are needed to reveal a functional relationship. The prevalence of the polymorphisms (4% of the population carry both SNPs) in the general population may suggest a genetic predisposition for common inflammatory disorders.

  • 134.
    Viegas, Edna Omar
    et al.
    Instituto Nacional de Saúde, Maputo, Mozambique; Division of Clinical Microbiology, Department of Laboratory Medicine, Huddinge, Karolinska Institutet, Sweden; Universidade Eduardo Mondlane, Maputo, Mozambique.
    Tembe, Nelson
    Instituto Nacional de Saúde, Maputo, Mozambique; Division of Clinical Microbiology, Department of Laboratory Medicine, Huddinge, Karolinska Institutet, Sweden; Universidade Eduardo Mondlane, Maputo, Mozambique.
    Nilsson, Charlotta
    Division of Clinical Microbiology, Department of Laboratory Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Public Health Agency of Sweden (Folkhälsomyndigheten), Stockholm, Sweden.
    Meggi, Bindiya
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Maueia, Cremildo
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Augusto, Orvalho
    Universidade Eduardo Mondlane, Maputo, Mozambique.
    Stout, Richard
    Bioject Medical Technologies Inc, Tualatin OR, United States.
    Scarlatti, Gabriella
    Institute for Research and Health Care (IRCCS), San Raffaele Scientific Institute, Milan, Italy.
    Ferrari, Guido
    Department of Surgery and Molecular Genetics and Microbiology, Duke University Medical Center, Durham NC, United States.
    Earl, Patricia
    Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAD)/National Institutes of Health (NIH), Bethesda MD, United States.
    Wahren, Britta
    Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Robb, Merlin
    The Henry M. Jackson Foundation for the Advancement of Military Medicine, The Military HIV Research Program, Walter Reed Army Institute of Research, Bethesda MD, United States.
    Osman, Nafissa
    Universidade Eduardo Mondlane, Maputo, Mozambique.
    Biberfeld, Gunnel
    Microbiology,Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Jani, Ilesh
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Sandström, Eric
    Microbiology,Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Intradermal HIV-1 DNA immunization using needle-free ZetajetTM injection followed by HIV-modified vaccinia virus Ankara vaccination is safe and immunogenic in Mozambican young adults: a phase I randomized controlled trial2018In: AIDS Research and Human Retroviruses, ISSN 0889-2229, E-ISSN 1931-8405, Vol. 34, no 2, p. 193-205Article in journal (Refereed)
    Abstract [en]

    We assessed safety and immunogenicity of HIV-DNA priming using Zetajet<sup>TM</sup>, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 µg (n = 10; 2 x 0.1mL) or 1200 µg (n = 10; 2 x 0.2mL) of HIV-DNA (3 mg/mL), followed by two boosts of 10<sup>8</sup>pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups. After three HIV-DNA immunizations, IFN-γ ELISpot responses to Gag were detected in 9/17 (53%) vaccinees, while none responded to Env. After the first HIV-MVA, the overall response rate to Gag and/or Env increased to 14/15 (93%); 14/15 (93%) to Gag and 13/15 (87%) to Env. There were no significant differences between the immunization groups in frequency of response to Gag and Env or magnitude of Gag responses. Env responses were significantly higher in the higher-dose group (median 420 vs 157.5 SFC/million PBMC, p=0.014). HIV-specific antibodies to subtype C gp140 and subtype B gp160 were elicited in all vaccinees after the second HIV-MVA, without differences in titers between the groups. Neutralizing antibody responses were not detected. Two (13%) of 16 vaccinees, one in each of the priming groups, exhibited antibodies mediating antibody-dependent cellular cytotoxicity to CRF01_AE. In conclusion, HIV-DNA vaccine delivered intradermally in volumes of 0.1-0.2 mL using Zetajet<sup>TM</sup> was safe and well tolerated. Priming with the 1200 µg dose of HIV-DNA generated higher magnitudes of ELISpot responses to Env.

  • 135.
    Vumma, Ravi
    et al.
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Bang, Charlotte Sahlberg
    Örebro University, School of Health Sciences. iRiSC-Inflammatory Responses and Infection Susceptibility Centre, Örebro University, Örebro, Sweden.
    Kruse, Robert
    Örebro University, School of Medical Sciences. iRiSC-Inflammatory Responses and Infection Susceptibility Centre, Örebro University, Örebro, Sweden.
    Johansson, Kjell
    Örebro University, School of Medical Sciences.
    Persson, Katarina
    Örebro University, School of Medical Sciences. iRiSC-Inflammatory Responses and Infection Susceptibility Centre, Örebro University, Örebro, Sweden.
    Antibacterial effects of nitric oxide on uropathogenic Escherichia coli during bladder epithelial cell colonization-a comparison with nitrofurantoin2016In: Journal of antibiotics (Tokyo. 1968), ISSN 0021-8820, E-ISSN 1881-1469, Vol. 69, no 3, p. 183-186Article in journal (Refereed)
  • 136.
    Welin, Amanda
    et al.
    Linköping University, Linköping.
    Winberg, Martin E
    Linköping University, Linköping.
    Abdalla, Hana
    Linköping University, Linköping.
    Särndahl, Eva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Linköping University, Linköping.
    Rasmusson, Birgitta
    Linköping University, Linköping.
    Stendahl, Olle
    Linköping University, Linköping.
    Lerm, Maria
    Linköping University, Linköping.
    Incorporation of Mycobacterium tuberculosis lipoarabinomannan into macrophage membrane rafts is a prerequisite for the phagosomal maturation block2008In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 76, no 7, p. 2882-7Article in journal (Refereed)
    Abstract [en]

    Lipoarabinomannan (LAM) is one of the key virulence factors for Mycobacterium tuberculosis, the etiological agent of tuberculosis. During uptake of mycobacteria, LAM interacts with the cell membrane of the host macrophage and can be detected throughout the cell upon infection. LAM can inhibit phagosomal maturation as well as induce a proinflammatory response in bystander cells. The aim of this study was to investigate how LAM exerts its action on human macrophages. We show that LAM is incorporated into membrane rafts of the macrophage cell membrane via its glycosylphosphatidylinositol anchor and that incorporation of mannose-capped LAM from M. tuberculosis results in reduced phagosomal maturation. This is dependent on successful insertion of the glycosylphosphatidylinositol anchor. LAM does not, however, induce the phagosomal maturation block through activation of p38 mitogen-activated protein kinase, contradicting some previous suggestions.

  • 137.
    Werme, Karin
    et al.
    Södertörn University College, Huddinge, Sweden; Stockholm University, Stockholm, Sweden.
    Wigerius, Michael
    Södertörn University College, Huddinge, Sweden; Stockholm University, Stockholm, Sweden.
    Johansson, Magnus
    Södertörn University College, Huddinge, Sweden.
    Tick-borne encephalitis virus NS5 associates with membrane protein scribble and impairs interferon-stimulated JAK-STAT signalling.2008In: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 10, no 3, p. 696-712Article in journal (Refereed)
    Abstract [en]

    Tick-borne encephalitis virus (TBEV) NS5 protein is a multifunctional RNA-dependent RNA polymerase that is indispensable for viral replication. TBEV is considered to be highly neurovirulent and can cause lethal encephalitis. In this study, we demonstrate a novel interaction between TBEV NS5 and the PDZ protein scribble (hScrib) affecting interferon (IFN) type I and II mediated JAK-STAT signalling. The sequence of TBEV NS5 interacting with hScrib was identified using extensive site-directed mutagenesis analysis. Two consecutive mutations in the methyltransferase (MTase) domain of NS5 were found to disrupt binding to hScrib. Colocalization studies with hScrib demonstrated that TBEV NS5 was present at the plasma membrane of mammalian cells. To address the role of viral interference with the IFN response, NS5 proteins were expressed in IFN-stimulated cells. While TBEV NS5 substantially blocked phosphorylation of STAT1, a mutated NS5 protein defective in hScrib binding failed to inhibit JAK-STAT signalling correctly. Furthermore, hScrib knock-down resulted in re-localization of NS5 to intracellular locations and abrogated the impaired STAT1 phosphorylation. These results define the TBEV NS5 protein in concert with hScrib as an antagonist of the IFN response, by demonstrating a correlation between the association and JAK-STAT interference.

  • 138.
    Wi, Teodora E. C.
    et al.
    Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
    Ndowa, Francis J.
    Skin & Genito-Urinary Medicine Clinic, Harare, Zimbabwe.
    Ferreyra, Cecilia
    Department of Emerging Threat and AMR, FIND, Geneva, Switzerland.
    Kelly-Cirino, Cassandra
    Department of Emerging Threat and AMR, FIND, Geneva, Switzerland.
    Taylor, Melanie M.
    Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
    Toskin, Igor
    Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
    Kiarie, James
    Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
    Santesso, Nancy
    Department of Clinical Epidemiology and Biostatistics, McMaster University, Ontario, Canada.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    Diagnosing sexually transmitted infections in resource-constrained settings: challenges and ways forward2019In: Journal of the International AIDS Society, ISSN 1758-2652, E-ISSN 1758-2652, Vol. 22, no Suppl. 6, article id e25343Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Sexually transmitted infections (STIs) remain prevalent and are increasing in several populations. Appropriate STI diagnosis is crucial to prevent the transmission and sequelae of untreated infection. We reviewed the diagnostic accuracy of syndromic case management and existing point-of-care tests (POCTs), including those in the pipeline, to diagnose STIs in resource-constrained settings.

    Methods: We prioritized updating the systematic review and meta-analysis of the diagnostic accuracy of vaginal discharge from 2001 to 2015 to include studies until 2018. We calculated the absolute effects of different vaginal flowcharts and the diagnostic performance of POCTs on important outcomes. We searched the peer-reviewed literature for previously conducted systematic reviews and articles from 1990 to 2018 on the diagnostic accuracy of syndromic management of vaginal and urethral discharge, genital ulcer and anorectal infections. We conducted literature reviews from 2000 to 2018 on the existing POCTs and those in the pipeline.

    Results and discussions: The diagnostic accuracy of urethral discharge and genital ulcer disease syndromes is relatively adequate. Asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections limit the use of vaginal discharge and anorectal syndromes. The pooled diagnostic accuracy of vaginal syndromic case management for CT/NG is low, resulting in high numbers of overtreatment and missed treatment. The absolute effect of POCTs was reduced overtreatment and missed treatment. Findings of the reviews on syndromic case management underscored the need for low-cost and accurate POCTs for the identification, first, of CT/NG, and, second, of Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) and NG and MG resistance/susceptibility testing. Near-patient POCT molecular assays for CT/NG/TV are commercially available. The prices of these POCTs remain the barrier for uptake in resource-constrained settings. This is driving the development of lower cost solutions.

    Conclusions: The WHO syndromic case management guidelines should be updated to raise the quality of STI management through the integration of laboratory tests. STI screening strategies are needed to address asymptomatic STIs. POCTs that are accurate, rapid, simple and affordable are urgently needed in resource-constrained settings to support the uptake of aetiological diagnosis and treatment.

  • 139.
    Wind, Carolien M.
    et al.
    STI Outpatient Clinic, Department of Infectious Diseases Public Health Service Amsterdam, Amsterdam, The Netherlands; Department of Dermatology Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
    Schim van der Loeff, Maarten F.
    Department of Infectious Diseases Public Health Service Amsterdam, Amsterdam, The Netherlands; Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
    Unemo, Magnus
    Örebro University, School of Health Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Schuurman, Rob
    Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
    van Dam, Alje P.
    Public Health Laboratory, Public Health Service Amsterdam, Amsterdam, The Netherlands; Department of Medical Microbiology, Onze Lieve Vrouwe Gasthuis General Hospital, Amsterdam, The Netherlands.
    de Vries, Henry J. C.
    STI Outpatient Clinic, Department of Infectious Diseases Public Health Service Amsterdam, Amsterdam, The Netherlands; Department of Dermatology Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
    Test of cure for anogenital gonorrhoea using modern RNA-based and DNA-based nucleic acid amplification tests: a prospective cohort study2016In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 62, no 11, p. 1348-1355Article in journal (Refereed)
    Abstract [en]

    Background: The use of nucleic acid amplification tests (NAATs) to diagnose Neisseria gonorrhoeae infections complicates the performance of a test of cure (TOC) to monitor treatment failure, if this is indicated. As evidence for the timing of TOC using modern NAATs is limited, we performed a prospective cohort study to assess time to clearance when using modern RNA- and DNA-based NAATs.

    Methods: We included patients with anogenital gonorrhoea visiting the STI Clinic Amsterdam from March through October 2014. After treatment with ceftriaxone mono- or dual therapy (with azithromycin or doxycycline) anal, vaginal or urine samples were self-collected during 28 consecutive days, and analysed using an RNA-based NAAT (Aptima Combo 2) and a DNA-based NAAT (Cobas 4800). Clearance was defined as three consecutive negative results, and blips as isolated positive results following clearance.

    Results: We included 77 patients; five self-cleared gonorrhoea before treatment and ten were lost to follow-up. Clearance rate of the remaining 62 patients was 100%. Median time to clearance was two days, with a range of 1-7 days for RNA-based NAAT, and 1-15 days for DNA-based NAAT. The risk of finding a blip after clearance was 0.8% and 1.4%, respectively. One patient had a reinfection.

    Conclusions: If indicated, we recommend to perform a TOC for anogenital gonorrhoea at least 7 or 14 days after administering therapy, when using modern RNA- or DNA-based NAATs, respectively. When interpreting TOC results for possible treatment failure, both the occurrence of blips and a possible reinfection need to be taken into account.

  • 140.
    Zhang, Boxi
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Khalaf, Hazem
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Sirsjö, Allan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bengtsson, Torbjörn
    Örebro University, School of Medicine, Örebro University, Sweden.
    Gingipains from the Periodontal Pathogen Porphyromonas gingivalis Play a Significant Role in Regulation of Angiopoietin 1 and Angiopoietin 2 in Human Aortic Smooth Muscle Cells2015In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 83, no 11, p. 4256-4265Article in journal (Refereed)
    Abstract [en]

    Angiopoietin 1 (Angpt1) and angiopoietin 2 (Angpt2) are the ligands of tyrosine kinase (Tie) receptors, and they play important roles in vessel formation and the development of inflammatory diseases, such as atherosclerosis. Porphyromonas gingivalis is a Gram-negative periodontal bacterium that is thought to contribute to the progression of cardiovascular disease. The aim of this study was to investigate the role of P. gingivalis infection in the modulation of Angpt1 and Angpt2 in human aortic smooth muscle cells (AoSMCs). We exposed AoSMCs to wild-type (W50 and 381), gingipain mutant (E8 and K1A), and fimbrial mutant (DPG-3 and KRX-178) P. gingivalis strains and to different concentrations of tumor necrosis factor (TNF). The atherosclerosis risk factor TNF was used as a positive control in this study. We found that P. gingivalis (wild type, K1A, DPG3, and KRX178) and TNF upregulated the expression of Angpt2 and its transcription factor ETS1, respectively, in AoSMCs. In contrast, Angpt1 was inhibited by P. gingivalis and TNF. However, the RgpAB mutant E8 had no effect on the expression of Angpt1, Angpt2, or ETS1 in AoSMCs. The results also showed that ETS1 is critical for P. gingivalis induction of Angpt2. Exposure to Angpt2 protein enhanced the migration of AoSMCs but had no effect on proliferation. This study demonstrates that gingipains are crucial to the ability of P. gingivalis to markedly increase the expressed Angpt2/Angpt1 ratio in AoSMCs, which determines the regulatory role of angiopoietins in angiogenesis and their involvement in the development of atherosclerosis. These findings further support the association between periodontitis and cardiovascular disease.

  • 141.
    Åström, Maria
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden; Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tajeddinn, Walid
    iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Linder, Olle
    Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Palmblad, Jan
    Division of Hematology, Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Lindblad, Per
    Örebro University, School of Medical Sciences. Department of Urology.
    Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma2018In: Biomarker Insights, ISSN 1177-2719, E-ISSN 1177-2719, Vol. 13, article id UNSP 1177271918792246Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells.

    CASE PRESENTATIONS: A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-gamma) and IL-1 alpha, for the 3 renal cell carcinoma cases compared with healthy blood donors.

    CONCLUSIONS: In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma.

  • 142.
    Önnberg, Anna
    et al.
    Departments of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Departments of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Zimmermann, Johanna
    Departments of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Departments of Laboratory Medicine, Clinical Microbiology and Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Molecular and phenotypic characterization of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum β-lactamases with focus on CTX-M in a low-endemic area in Sweden2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 4-5, p. 287-295Article in journal (Refereed)
    Abstract [en]

    During the last decade increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has been detected worldwide, mainly due to dissemination of Escherichia coli and Klebsiella pneumoniae producing CTX-M-type ESBLs. CTX-M-15 is the most widespread CTX-M type, and the predominant type in various countries. Dissemination of ESBL-producing organisms is caused not only by horizontal transfer of plasmids, but also by clonal spread of ESBL-producing strains. In this study, the molecular epidemiology of class A ESBL (ESBL(A))-producing E. coli and K. pneumoniae isolated in Örebro County, Sweden, was investigated. Out of 200 ESBL(A) -producing E. coli and K. pneumoniae isolates, collected over a 10-year period, 87% were producing CTX-M, belonging to subgroup CTX-M-1 (64%), CTX-M-9 (34%), or CTX-M-2 (2%). The remaining isolates were producing variants of SHV and TEM. Sequencing of the bla(CTX-M) genes revealed 10 different CTX-M types, with a dominance of CTX-M-15 (E. coli 54%, K. pneumoniae 50%) followed by CTX-M-14 (E. coli 28%, K. pneumoniae 27%). Phenotypic characterization of the CTX-M-producing isolates was performed using the PhenePlate system. Although a few minor clusters of CTX-M-15 and CTX-M-14 producers were identified, the majority of the isolates did not appear to be clonally related.

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