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  • 1651. Wilhelmsson, Peter
    et al.
    Fryland, Linda
    Lindblom, Pontus
    Sjöwall, Johanna
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Berglund, Johan
    Haglund, Mats
    Henningsson, Anna J
    Nolskog, Peter
    Nordberg, Marika
    Nyberg, Clara
    Ornstein, Katharina
    Nyman, Dag
    Ekerfelt, Christina
    Forsberg, Pia
    Lindgren, Per-Eric
    A prospective study on the incidence of Borrelia burgdorferi sensu lato infection after a tick bite in Sweden and On the Åland Islands, Finland (2008-2009)2016In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 7, no 1, p. 71-79Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis (LB) is a common and increasing tick-borne disease in Europe. The risk of acquiring a Borrelia infection after a tick bite is not fully known. Therefore, we investigated the incidence of Borrelia infection after a bite by a Borrelia-infected tick and if the Borrelia load and/or the duration of tick-feeding influenced the risk of infection. During 2008-2009, ticks and blood samples were collected from 1546 tick-bitten persons from Sweden and the Åland Islands, Finland. Follow-up blood samples were taken 3 months after the tick bite. The duration of tick feeding was microscopically estimated and Borrelia was detected and quantified in ticks by real-time PCR. Anti-Borrelia antibodies were detected in sera using ELISA tests and immunoblot. Five percent (78/1546) of the study participants developed Borrelia infection (LB diagnosis and/or seroconversion) after a tick bite (45% bitten by Borrelia-infected ticks and 55% bitten by uninfected ticks). Of these, 33 developed LB (whereof 9 also seroconverted) while 45 participants seroconverted only. Experience of non-specific symptoms was more frequently reported by Borrelia-infected participants compared to uninfected participants. All who seroconverted removed "their" ticks significantly later than those who did not. The Borrelia load in the ticks did not explain the risk of seroconversion. Regional and sex differences in the Borrelia seroprevalence were found. The risk of developing a Borrelia infection after a bite by a Borrelia-infected tick is small but increases with the duration of tick feeding.

  • 1652.
    Williamson, Neil
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Phylogenetic Analysis of Rift Valley Fever using RT-PCR2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 1653.
    Winberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Lundell, Catarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Arencibia, Ignacio
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Mincheva Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dynamics of cytokine mRNA expression and fecal biomarkers in school-children undergoing a double-blind placebo-controlled food challenge series2016In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 88, p. 259-266Article in journal (Refereed)
    Abstract [en]

    Background: There is need for prognostic markers for symptomatic food allergy since current diagnostic methods are insufficient and/or time and labor consuming. Objective: To estimate the cytokine mRNA profiles in peripheral blood mononuclear cells (PBMC) before and after a double-blind placebo-controlled food challenge series in schoolchildren with suspected allergy to milk, egg or cod and in healthy controls. Analyses of fecal inflammatory biomarkers before and after the challenge were included. Methods: Twelve-year-old children from a population-based cohort reporting complete avoidance of milk, egg, cod or wheat due to perceived hypersensitivity were clinically examined and those with suspected food allergy were evaluated with a 3-session double-blind placebo-controlled food challenge (n = 18). Seven healthy controls participated in a double-blind challenge with egg. Before and after the challenge series, the cytokine mRNA expression was quantified for 13 cytokines discriminating between humoral Th2-, cytotoxic Thl-, regulatory Th3/Tr1- and inflammatory responses. Fecal calprotectin and eosinophil-derived neurotoxin (EDN) were also analyzed in children with suspected food allergy before and after the challenge series. Results: Pre challenge, children with suspected food allergy had higher IL-13 and TNF-alpha expression and lower IFN-gamma and IL-15 expression compared to healthy controls (all p < 0.05). Children with challenge proven food allergy had increased IL13 and IL-10 expression compared to the levels seen in negative challenges (p < 0.05). Post challenge, IL-1 beta and IL-6 mRNA levels were elevated in the food allergic children compared to controls (p < 0.05). Fecal calprotectin and EDN levels were higher in challenge-proven food allergy compared to a negative challenge although not statistically significantly. Conclusion & clinical relevance: Increased baseline mRNA levels of the Th2-related cytokine IL-13 and the regulatory cytokine IL-10 predicted a positive food challenge outcome. These cytokines in combination with fecal calprotectin and EDN might serve as future prognostic markers for symptomatic, IgEmediated food allergy but need further validation in a larger patient cohort.

  • 1654.
    Wirlander, Boris
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Makrofag migration inhibitorisk faktor (MIF) uttrycks i kolorektal cancervävnad2015Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 1655.
    Wiström, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Lundberg, Sonia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Settergren, Bo
    Tärnvik, Arne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Booster vaccination with recombinant hepatitis B vaccine four years after priming with one single dose1999In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 17, no 17, p. 2162-2165Article in journal (Refereed)
    Abstract [en]

    We here studied the antibody response to a booster dose four years after the administration of one single dose of recombinant HB vaccine. Before receiving the booster dose, levels of protective antibodies (anti-HBs) were generally low and 24/41 (59%) individuals lacked detectable antibodies (< 1 IU/L). Within 14 d of booster vaccination, 36/38 (95%) vaccinees showed levels of antibodies > 100 IU/L. Notably, these levels were at least as high as those of a reference group 12 months after initiation of vaccination according to the standard three-dose vaccination at intervals of 0, 1 and 6 months. In conclusion, one single dose of HB vaccine seemed to confer on young healthy individuals a well preserved B cell memory, disclosed as a rapid and strong antibody response to a second dose four years later.

  • 1656. Witt, Volker
    et al.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ptak, Jan
    Wikström, Björn
    Berlin, Gösta
    Axelsson, C G
    Griskevicius, A
    Centoni, Paolo Emilio
    Liumbruno, Giancarlo Maria
    Molfettini, Pietra
    Audzijoniene, Judita
    Mokvist, K
    Sojka, Birgitta Nilsson
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Norda, Rut
    Ramlow, W
    Blaha, Milan
    Evergren, M
    Tomaz, J
    World apheresis registry data from 2003 to 2007, the pediatric and adolescent side of the registry.2008In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 39, no 3, p. 255-60Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Paediatric patients are a special group in apheresis. It is general accepted to use adult indications in paediatric patients, but data in this age group are rare. In order to provide more information of apheresis practise in children and young adults (<21a) we will report of knowledge learnt by data from the registry from 2003 until 2007. METHODS: This is a web-based registry. A link is available from the WAA homepage (www.worldapheresis.org). So far data from 12,448 procedures have been included. Six hundred and twelve procedures were performed in 135 children and young adults (308 procedures<16a, 237 from 17 to 20a, and 67 with 21a) representing 5% of the total population. The median age was 14 years (range 1-21 years), 74 male and 61 female. These data were entered by 15 centres with a frequency of in median 18 aphereses in young patients per centre (range 1-287) from 2003 to 2007. RESULTS: Main indications: haematological diseases and also nephrological, and neurological. The type of aphereses was mainly Leukapheresis (196, 33%), plasma exchange (149, 25%), photopheresis (127, 21%), and lipid aphereses (79, 13%). Blood access: peripheral vessels in 305 procedures (50%, compared to 73% in adults), central venous catheter in 239 (38%), and AV-fistula in 2% and 0.3%, and in 8 (1.31%) procedures an arterial line was used. Anticoagulation was mostly by ACD (71%), heparin (18% or the combination of both (3%). 39 adverse events (AE) were registered in 22 (=3.59%) of the procedures, mostly graded as mild. Treatment was interrupted in 14 procedures (2.29%). AE's were abdominal pain, anaphylactic shock, flush, hyper- and hypotension, nausea, vertigo, cephalea and need for sedation and technical problems with the device and problems with the venous access. The rate of AE's was similar for stem cell harvesting and for plasma exchange (4% and 4.7%, respectively). CONCLUSION: The paediatric data compared to the whole registry data set are showing that aphereses are performed as safe in paediatrics as in adults. Centres are mostly handling only a few cases younger than 21. Therefore more exchange of information and experience in paediatric apheresis is warranted.

  • 1657.
    Wu, H. D.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Mei, Ya-Fang
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Replication-competent adenovirus 11p vector armed with ADP gene at E1 region significantly improved tumour-killing effect on metastatic prostate cells in vitro and in vivo2017In: Human Gene Therapy, ISSN 1043-0342, E-ISSN 1557-7422, Vol. 28, no 12, p. A29-A29Article in journal (Other academic)
  • 1658.
    Yanamandra, Kiran
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Alexeyev, Oleg
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zamotin, Vladimir
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Srivastava, Vaibhav
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Shchukarev, Andrey
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Brorsson, Ann-Christin
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Tartaglia, Gian Gaetano
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Vogl, Thomas
    Institute of Immunology, University of Münster, Münster, Germany.
    Kayed, Rakez
    Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America.
    Wingsle, Gunnar
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dobson, Christopher M
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Morozova-Roche, Ludmilla A
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate2009In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, no 5, p. e5562-Article in journal (Refereed)
    Abstract [en]

    Background The conversion of soluble peptides and proteins into polymeric amyloid structures is a hallmark of many age-related degenerative disorders, including Alzheimer's disease, type II diabetes and a variety of systemic amyloidoses. We report here that amyloid formation is linked to another major age-related phenomenon - prostate tissue remodelling in middle-aged and elderly men.

    Methodology/Principal Findings By using multidisciplinary analysis of corpora amylacea inclusions in prostate glands of patients diagnosed with prostate cancer we have revealed that their major components are the amyloid forms of S100A8 and S100A9 proteins associated with numerous inflammatory conditions and types of cancer. In prostate protease rich environment the amyloids are stabilized by dystrophic calcification and lateral thickening. We have demonstrated that material closely resembling CA can be produced from S100A8/A9 in vitro under native and acidic conditions and shows the characters of amyloids. This process is facilitated by calcium or zinc, both of which are abundant in ex vivo inclusions. These observations were supported by computational analysis of the S100A8/A9 calcium-dependent aggregation propensity profiles. We found DNA and proteins from Escherichia coli in CA bodies, suggesting that their formation is likely to be associated with bacterial infection. CA inclusions were also accompanied by the activation of macrophages and by an increase in the concentration of S100A8/A9 in the surrounding tissues, indicating inflammatory reactions.

    Conclusions/Significance These findings, taken together, suggest a link between bacterial infection, inflammation and amyloid deposition of pro-inflammatory proteins S100A8/A9 in the prostate gland, such that a self-perpetuating cycle can be triggered and may increase the risk of malignancy in the ageing prostate. The results provide strong support for the prediction that the generic ability of polypeptide chains to convert into amyloids could lead to their involvement in an increasing number of otherwise apparently unrelated diseases, particularly those associated with ageing.

  • 1659.
    Yau, Wai-Lok
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Nguyen-Dinh, Van
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Larsson, Elin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lindquist, Richard
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Lundmark, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Model System for the Formation of Tick-Borne Encephalitis Virus Replication Compartments without Viral RNA Replication2019In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 93, no 18, article id e00292-19Article in journal (Refereed)
    Abstract [en]

    Flavivirus is a positive-sense, single-stranded RNA viral genus, with members causing severe diseases in humans such as tick-borne encephalitis, yellow fever, and dengue fever. Flaviviruses are known to cause remodeling of intracellular membranes into small cavities, where replication of the viral RNA takes place. Nonstructural (NS) proteins are not part of the virus coat and are thought to participate in the formation of these viral replication compartments (RCs). Here, we used tick-borne encephalitis virus (TBEV) as a model for the flaviviruses and developed a stable human cell line in which the expression of NS proteins can be induced without viral RNA replication. The model system described provides a novel and benign tool for studies of the viral components under controlled expression levels. We show that the expression of six NS proteins is sufficient to induce infection-like dilation of the endoplasmic reticulum (ER) and the formation of RC-like membrane invaginations. The NS proteins form a membrane-associated complex in the ER, and electron tomography reveals that the dilated areas of the ER are closely associated with lipid droplets and mitochondria. We propose that the NS proteins drive the remodeling of ER membranes and that viral RNA, RNA replication, viral polymerase, and TBEV structural proteins are not required. IMPORTANCE TBEV infection causes a broad spectrum of symptoms, ranging from mild fever to severe encephalitis. Similar to other flaviviruses, TBEV exploits intracellular membranes to build RCs for viral replication. The viral NS proteins have been suggested to be involved in this process; however, the mechanism of RC formation and the roles of individual NS proteins remain unclear. To study how TBEV induces membrane remodeling, we developed an inducible stable cell system expressing the TBEV NS polyprotein in the absence of viral RNA replication. Using this system, we were able to reproduce RC-like vesicles that resembled the RCs formed in flavivirus-infected cells, in terms of morphology and size. This cell system is a robust tool to facilitate studies of flavivirus RC formation and is an ideal model for the screening of antiviral agents at a lower biosafety level.

  • 1660. Yeung, M M
    et al.
    Melgar, S
    Baranov, Vladimir
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Oberg, A
    Danielsson, A
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-gammadelta expression.2000In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 47, no 2, p. 215-27Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: A histopathological feature considered indicative of ulcerative colitis (UC) is the so-called basal lymphoid aggregates. Their relevance in the pathogenesis of UC is, however, unknown. We have performed a comprehensive analysis of the immune cells in these aggregates most likely corresponding to the lymphoid follicular hyperplasia also described in other colitides.

    METHODS: Resection specimens of UC and normal colon were analysed by immunomorphometry, immunoflow cytometry, and immunoelectron microscopy, using a large panel of monoclonal antibodies.

    RESULTS: (1) In all cases of UC, colonic lamina propria contained numerous basal aggregates composed of lymphocytes, follicular dendritic cells, and CD80/B7.1 positive dendritic cells. (2) CD4(+)CD28(-) alphabeta T cells and B cells were the dominant cell types in the aggregates. (3) The aggregates contained a large fraction of cells that are normally associated with the epithelium: that is, gammadelta T cells (11 (7)%) and alpha(E)beta(7)(+) cells (26 (13)%). The gammadelta T cells used Vdelta1 and were CD4(-)CD8(-). Immunoelectron microscopy analysis demonstrated TcR-gammadelta internalisation and surface downregulation, indicating that the gammadelta T cells were activated and engaged in the disease process. (4) One third of cells in the aggregates expressed the antiapoptotic protein bcl-2.

    CONCLUSIONS: Basal lymphoid aggregates in UC colon are a consequence of anomalous lymphoid follicular hyperplasia, characterised by abnormal follicular architecture and unusual cell immunophenotypes. The aggregates increase in size with severity of disease, and contain large numbers of apoptosis resistant cells and activated mucosal gammadelta T cells. The latter probably colonise the aggregates as an immunoregulatory response to stressed lymphocytes or as a substitute for defective T helper cells in B cell activation. gammadelta T cells in the aggregates may be characteristic of UC.

  • 1661.
    Yeung, Moorix Mo-Wai
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Specific and nonspecific immune mechanisms in human gut: a comparative study of normal and ulcerative colitis intestine1996Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The intestine, with its large mucosal surface area, digests and absorbs food nutrients and maintains a beneficial microbial flora in the colon. Local protective immune responses against intestinal pathogens ensure the survival of the individual. These immune reactions are both specific and non-specific in nature. The intestinal epithelium is single-layered and constantly renewed with differentiating epithelial cells moving from the crypt to the luminal surface. Intraepithelial lymphocytes (IEL) are interspersed between the epithelial cells. Ulcerative colitis (UC) is a life-threatening chronic inflammation affecting colon.

    In this study three molecules belonging to the carcinoembryonic antigen (CEA) family, namely CEA proper, nonspecific cross-reacting antigen 50/90 (NCA 50/90) and biliary glycoprotein (BGP), were found to be specifically localized to the apical surface of colonic epithelial cells. Full expression of these molecules occurs when the cells reach the upper 1/3 of the crypts and are maintained on the mature cells at the luminal surface. Ultrastructurally, CEA, NCA50/90 and BGP are localized to microvesicles and microfilaments of the fuzzy coat/glycocalyx as well as to the microvilli of the epithelial cells. Their unique localization and documented bacterial binding capacities suggest that they have a role in innate immunity.

    Functional analysis of IEL in normal jejunum, ileum and colon revealed that IEL are in vivo activated T-lymphocytes expressing mRNA for the cytokines IL-1β, IL-2, IL-8, IFNγ and TNFα and that jejunal IEL have T-cell receptor (TCR)/CD3 dependent cytolytic capacity. As many as 10% of IEL actively produce IFNγ. CD4+TCRαβ+IEL, CD8+TCRαβ+IEL and CD4-CD8-TCRαβ+IEL all had a TH1/cytotoxic cytokine profile. IEL could be further stimulated in vitro to express IL-10, TNFβ and TGFβ1, to proliferate and to secrete IFNγ. Thus, active protection and/or regulation of the epithelium via cell-mediated immune reactions are prominent in the gut.

    UC colon was characterized by a marked lymphocyte infiltration in the lamina propria, 10-50 times the normal level. Most lymphocytes were present in follicle-like cell aggregates containing both T- and B-cells. An unexpected finding was that γδT-cells constituted about 15% of the cells in the aggregates. Such cells are only found intraepithelially in normal gut. γδT-cells of both the intestinal- (TCR-Vδ1/Vγ8) and blood type (TCR-Vδ2/Vγ9) were seen. T-cells in UC colon were activated but nonproliferating and had a down-regulated TCR/CD3 complex. RT-PCR and quantitative immunohistochemistry for cytokine mRNA (n=11) and protein respectively, revealed that the T-cells in UC colon did not produce IL-2, in marked contrast to T-cells in normal colon and to ileal T-cells from UC patients. This was a selective defect since TNFα, IFNγ, IL-1β, IL-8 and TGFβ1 were similarly expressed in normal colon. No TH2 cytokines were seen. Lamina propria leukocytes in UC colon expressed IL-6, a cytokine not found in normal colon. The epithelial cells of UC colon were activated expressing MHC class II antigens, heat shock proteins and the co-stimulatory molecule B7.1/CD80.

    Our study demonstrates that UC is an immunological disease. The immunopathological picture seen in UC colon probably reflects an inappropriate down-regulation of local immune responses perhaps due to a selective loss of the key cytokine IL-2 in a situation of extreme antigenic stress.

  • 1662.
    Yeung, Moorix Mo-Wai
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Melgar, S
    Öberg, Å
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    A role for γδ T-cells in the pathogenesis of ulcerative colitis? Quantitative analysis of leukocytes in ulcerative colitis and normal colon.Manuscript (preprint) (Other academic)
  • 1663.
    Yeung, Moorix Mo-Wai
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Melgar, S
    Omholt, K
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Colonic T-lymphocytes in patients with ulcerative colitis do not produce IL-2Manuscript (preprint) (Other academic)
  • 1664.
    Yeung, Moorix Mo-Wai
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Melgar, S
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Phenotypic characterization of epithelial cells in ulcerative colitis colonManuscript (preprint) (Other academic)
  • 1665. Yeung, M-W
    et al.
    Melgar, S
    Baranov, Vladimir
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Öberg, Å
    Danielsson, Å
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Characterization of mucosal lymphoid aggregates in ulcerative colitis colon: Immune cell phenotypes and TcR-gammadelta expression.2000In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 47, p. 215-227Article in journal (Refereed)
  • 1666.
    Ylinenjärvi, Cecilia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Galleria mellonella som modellsystem för anrikning och identifiering av Francisella i miljöprover2017Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 1667.
    Zamannoun, Sarah
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Distensibilitet i karotisartären hos patienter med nydiagnostiserad rheumatoid artrit jämfört med patienter med längre sjukdomsduration: En klinisk och metodologisk studie2016Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 1668. Zapatero-Belinchon, Francisco J.
    et al.
    Dietzel, Erik
    Dolnik, Olga
    Doehner, Katinka
    Costa, Rui
    Hertel, Barbara
    Veselkova, Barbora
    Kirui, Jared
    Klintworth, Anneke
    Manns, Michael P.
    Poehlmann, Stefan
    Pietschmann, Thomas
    Krey, Thomas
    Ciesek, Sandra
    Gerold, Gisa
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology. TWINCORE, Center for Experimental and Clinical Infection Research, Institute for Experimental Virology, Hannover, Germany.
    Sodeik, Beate
    Becker, Stephan
    von Hahn, Thomas
    Characterization of the Filovirus-Resistant Cell Line SH-SY5Y Reveals Redundant Role of Cell Surface Entry Factors2019In: Viruses, ISSN 1999-4915, E-ISSN 1999-4915, Vol. 11, no 3, article id 275Article in journal (Refereed)
    Abstract [en]

    Filoviruses infect a wide range of cell types with the exception of lymphocytes. The intracellular proteins cathepsin B and L, two-pore channel 1 and 2, and bona fide receptor Niemann-Pick Disease C1 (NPC1) are essential for the endosomal phase of cell entry. However, earlier steps of filoviral infection remain poorly characterized. Numerous plasma membrane proteins have been implicated in attachment but it is still unclear which ones are sufficient for productive entry. To define a minimal set of host factors required for filoviral glycoprotein-driven cell entry, we screened twelve cell lines and identified the nonlymphocytic cell line SH-SY5Y to be specifically resistant to filovirus infection. Heterokaryons of SH-SY5Y cells fused to susceptible cells were susceptible to filoviruses, indicating that SH-SY5Y cells do not express a restriction factor but lack an enabling factor critical for filovirus entry. However, all tested cell lines expressed functional intracellular factors. Global gene expression profiling of known cell surface entry factors and protein expression levels of analyzed attachment factors did not reveal any correlation between susceptibility and expression of a specific host factor. Using binding assays with recombinant filovirus glycoprotein, we identified cell attachment as the step impaired in filovirus entry in SH-SY5Y cells. Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. Our study reveals that a lack of attachment factors limits filovirus entry and provides direct experimental support for a model of filoviral cell attachment where host factor usage at the cell surface is highly promiscuous.

  • 1669.
    Zarrinkoob, Laleh
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Quantification and mapping of cerebral hemodynamics before and after carotid endarterectomy: a 4D PCMRI studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background and purpose: A carotid stenosis can have a profound impact on the cerebral hemodynamics that cannot be inferred from the degree of stenosis by itself. We aimed to quantify and map the distribution of blood flow rate (BFR) in cerebral arteries before and after carotid endarterectomy (CEA), using four-dimensional phase-contrast magnetic resonance imaging (4D PCMRI).

    Methods: Nineteen patients (71±6 years, 2 women) with symptomatic carotid stenosis (≥50%)undergoing CEA were investigated using 4D PCMRI before and after surgery. BFR was measured in 17 cerebral arteries and in the ophthalmic arteries (OA). Collateral recruitment through the anterior and posterior communicating arteries, OA and the leptomeningeal arterial route was identified and quantified. BFR laterality was described as contralateral BFR minus ipsilateral BFR in paired arteries.

    Results: Total cerebral blood flow increased by 15% (p<0.01) after CEA. On the ipsilateral side, increased BFR was found after CEA in internal carotid artery (ICA) (246±62mL/min vs. 135±80mL/min; p<0.001), anterior cerebral artery (87±mL/min vs. 38±58mL/min; p<0.01) and middle cerebral artery (MCA) (149±43mL/min vs. 119±34mL/min; p<0.01), resulting in a postoperative BFR distribution without signs of laterality. In patients with preoperatively recruited collaterals (n=9), BFR laterality was found in MCA before, but not after, CEA (p<0.01). This laterality was not found in patients without collateral recruitment (n=10) (p=0.2). The degree of stenosis did not differ between the groups with vs. without collateral recruitment (p=0.85). 

    Conclusion: 4D PCMRI is a useful technique to quantify cerebral hemodynamic changes seen in patients with carotid stenosis before and after CEA. MCA laterality, seen in patients with collateral recruitment before CEA, pointed towards a hemodynamic disturbance in MCA territory for those patients. This study introduces a new and non-invasive way to evaluate cerebral hemodynamics due to carotid stenosis prior to and after CEA.

  • 1670. Zegenhagen, Loreen
    et al.
    Kurhade, Chaitanya
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Koniszewski, Nikolaus
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kroeger, Andrea
    Brain heterogeneity leads to differential innate immune responses and modulates pathogenesis of viral infections2016In: Cytokine & growth factor reviews, ISSN 1359-6101, E-ISSN 1879-0305, Vol. 30, p. 95-101Article, review/survey (Refereed)
    Abstract [en]

    The central nervous system (CNS) is a highly complex organ with highly specialized cell subtypes. Viral infections often target specific structures of the brain and replicate in certain regions. Studies in mice deficient in type I Interferon (IFN) receptor or IFN-I3 have highlighted the importance of the type I IFN system against viral infections and non-viral autoimmune disorders in the CNS. Direct antiviral effects of type I IFNs appear to be crucial in limiting early spread of a number of viruses in CNS tissues. Increased efforts have been made to characterize IFN expression and responses in the brain. In this context, it is important to identify cells that produce IFN, decipher pathways leading to type I IFN expression and to characterize responding cells. In this review we give an overview about region specific aspects that influence local innate immune responses. The route of entry is critical, but also the susceptibility of different cell types, heterogeneity in subpopulations and micro-environmental cues play an important role in antiviral responses. Recent work has outlined the tremendous importance of type I IFNs, particularly in the limitation of viral spread within the CNS. This review will address recent advances in understanding the mechanisms of local type I IFN production and response, in the particular context of the CNS. 

  • 1671. Zegenhagen, Loreen
    et al.
    Weber, Elvira
    Kurade, Chaitanya
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Nair, Sharmila
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kroeger, Andrea
    Differential innate immune responses in various brain regions regulate antiviral response in the CNS during Tick-borne encephalitis virus infection2015In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 76, no 1, p. 91-91Article in journal (Other academic)
  • 1672. Zeimes, Caroline B.
    et al.
    Olsson, Gert E.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Vanwambeke, Sophie O.
    Modelling zoonotic diseases in humans: comparison of methods for hantavirus in Sweden2012In: International Journal of Health Geographics, ISSN 1476-072X, E-ISSN 1476-072X, no 11, p. 39-Article in journal (Refereed)
    Abstract [en]

    Because their distribution usually depends on the presence of more than one species, modelling zoonotic diseases in humans differs from modelling individual species distribution even though the data are similar in nature. Three approaches can be used to model spatial distributions recorded by points: based on presence/absence, presence/available or presence data. Here, we compared one or two of several existing methods for each of these approaches. Human cases of hantavirus infection reported by place of infection between 1991 and 1998 in Sweden were used as a case study. Puumala virus (PUUV), the most common hantavirus in Europe, circulates among bank voles (Myodes glareolus). In northern Sweden, it causes nephropathia epidemica (NE) in humans, a mild form of hemorrhagic fever with renal syndrome. Logistic binomial regression and boosted regression trees were used to model presence and absence data. Presence and available sites (where the disease may occur) were modelled using cross-validated logistic regression. Finally, the ecological niche model MaxEnt, based on presence-only data, was used. In our study, logistic regression had the best predictive power, followed by boosted regression trees, MaxEnt and cross-validated logistic regression. It is also the most statistically reliable but requires absence data. The cross-validated method partly avoids the issue of absence data but requires fastidious calculations. MaxEnt accounts for non-linear responses but the estimators can be complex. The advantages and disadvantages of each method are reviewed.

  • 1673.
    Zetterström, Caroline E.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Hasselgren, Jenny
    Creative Antibiotics Sweden AB, Umeå, Sweden .
    Salin, Olli
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Davis, Rohan A.
    Eskitis Institute, Griffith University, Brisbane, Australia.
    Quinn, Ronald J.
    Eskitis Institute, Griffith University, Brisbane, Australia.
    Sundin, Charlotta
    Creative Antibiotics Sweden AB, Umeå, Sweden .
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    The Resveratrol Tetramer (-)-Hopeaphenol Inhibits Type III Secretion in the Gram-Negative Pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e81969Article in journal (Refereed)
    Abstract [en]

    Society faces huge challenges, as a large number of bacteria have developed resistance towards many or all of the antibiotics currently available. Novel strategies that can help solve this problem are urgently needed. One such strategy is to target bacterial virulence, the ability to cause disease e.g., by inhibition of type III secretion systems (T3SSs) utilized by many clinically relevant gram-negative pathogens. Many of the antibiotics used today originate from natural sources. In contrast, most virulence-blocking compounds towards the T3SS identified so far are small organic molecules. A recent high-throughput screening of a prefractionated natural product library identified the resveratrol tetramer (-)-hopeaphenol as an inhibitor of the T3SS in Yersinia pseudotuberculosis. In this study we have investigated the virulence blocking properties of (-)-hopeaphenol in three different gram-negative bacteria. (-)- Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In addition (-)-hopeaphenol reduced cell entry and subsequent intracellular growth of Chlamydia trachomatis.

  • 1674.
    Zhang, Lei-Qing
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Mei, Ya-Fang
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Human adenovirus serotypes 4 and 11 show higher binding affinity and infectivity for endothelial and carcinoma cell lines than serotype 52003In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 84, no 3, p. 687-695Article in journal (Refereed)
    Abstract [en]

    Adenoviruses are promising vectors for human cancer gene therapy. However, the extensively used adenoviruses serotypes 2 and 5 (Ad2 and Ad5) from species C have a major disadvantage in being highly prevalent; thus, most adults have an immunity against the two viruses. Furthermore, the expression of coxsackievirus and adenovirus receptors for Ad2 and Ad5 varies in different cells. This study aims to identify adenovirus serotypes with specific tropism for endothelial cells and epithelial tumour cells. Comparison of the binding affinities of Ad31, Ad11, Ad5, Ad37, Ad4 and Ad41, belonging to species A-F, respectively, to established cell lines of hepatoma (HepG2), breast cancer (CAMA and MG7), prostatic cancer (DU145 and LNCaP) and laryngeal cancer (Hep2), as well as to endothelial cells (HMEC), was carried out by flow cytometric analysis. Ad11 from species B showed markedly higher binding affinity than Ad5 for the endothelial cell line and all carcinoma cell lines studied. Ad4 showed a specific binding affinity for hepatoma cells and laryneal carcinoma cells. The ability of Ad11, Ad4 and Ad5 to be expressed in hepatoma, breast cancer and endothelial cell lines was studied by immunostaining and (35)S-labelling of viral proteins in infected cells. Ad11 and Ad4 manifested a higher proportion of infected cells and a higher degree of hexon expression than Ad5.

  • 1675. Zhou, G Q
    et al.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Pregnancy-specific glycoprotein (PSG) in baboon (Papio hamadryas): family size, domain structure, and prediction of a functional region in primate PSGs.2001In: Biology of Reproduction, ISSN 0006-3363, E-ISSN 1529-7268, Vol. 64, no 1, p. 90-9Article in journal (Refereed)
    Abstract [en]

    Pregnancy-specific glycoprotein (PSG) constitutes a major component of serum of pregnant women and appears to be essential for a successful pregnancy. Its function is, however, still unknown. Because of the evolutionary divergence between human and rodent PSG, functional studies may require a primate animal model. We have characterized PSG transcripts in a baboon placenta cDNA library and analyzed baboon genomic DNA. The main PSG isoform had the domain structure N-A1-B2-C similar to the human type IIa isoform. The type I isoform (N-A1-A2-B2-C) was also expressed. Fifteen similar PSG genes were identified of which at least nine were simultaneously expressed in third trimester baboon placenta. Thus, the baboon PSG family was as complex as that of humans. Recombinant baboon PSG (isoform IIa) had a molecular weight of 38 kDa and reacted with antibodies against human PSG. Comparative analysis of 43 N-domain amino acid sequences of PSG from four species and nine primate carcinoembryonic antigen subgroup N domain sequences identified a number of residues in the GFCC'C" ss-sheet and FG loop that are probable candidates for PSG binding to its putative ligand.

  • 1676. Zhou, G Q
    et al.
    Zhang, Y
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    The carcinoembryonic antigen (CEA) gene family in non-human primates.2001In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 264, no 1, p. 105-12Article in journal (Refereed)
    Abstract [en]

    Carcinoembryonic antigen (CEA) is a tumor marker of wide clinical use though its function remains unknown. The CEA counterpart and some related macromolecules cannot be demonstrated in mice, thus prohibiting studies of CEA function by gene disruption strategies. In an attempt to find a relevant animal model for functional studies of CEA we have investigated the occurrence of CEA subgroup members in baboon and African green monkey at the genomic and mRNA levels. The investigation was focused on the characteristic immunoglobulin-variable region-like (IgV-like) N-terminal domain of the family members. Based on N-domain sequences 3 and 4 different CEA subgroup genes, respectively, were identified. One sequence in each monkey species corresponded to human CEACAM8, while it was not possible to assign an obvious human counterpart for the other N-domain sequences. However, studies of cDNAs from African green monkey COS-1 cells identified one of the sequences as CEACAM1. Expression of CEACAM1 mRNA and protein was upregulated by IFNgamma as has previously been demonstrated for human CEACAM1. Presence of GPI-linked CEA subgroup members in African green monkey was suggested by sequencing. Both monkey species would thus seem suitable for functional studies of selected CEA subgroup members.

  • 1677. Zocher, Georg
    et al.
    Mistry, Nitesh
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Frank, Martin
    Hähnlein-Schick, Irmgard
    Ekström, Jens-Ola
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Stehle, Thilo
    A sialic acid binding site in a human picornavirus2014In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 10, no 10, p. e1004401-Article in journal (Refereed)
    Abstract [en]

    The picornaviruses coxsackievirus A24 variant (CVA24v) and enterovirus 70 (EV70) cause continued outbreaks and pandemics of acute hemorrhagic conjunctivitis (AHC), a highly contagious eye disease against which neither vaccines nor antiviral drugs are currently available. Moreover, these viruses can cause symptoms in the cornea, upper respiratory tract, and neurological impairments such as acute flaccid paralysis. EV70 and CVA24v are both known to use 5-N-acetylneuraminic acid (Neu5Ac) for cell attachment, thus providing a putative link between the glycan receptor specificity and cell tropism and disease. We report the structures of an intact human picornavirus in complex with a range of glycans terminating in Neu5Ac. We determined the structure of the CVA24v to 1.40 angstrom resolution, screened different glycans bearing Neu5Ac for CVA24v binding, and structurally characterized interactions with candidate glycan receptors. Biochemical studies verified the relevance of the binding site and demonstrated a preference of CVA24v for alpha 2,6-linked glycans. This preference can be rationalized by molecular dynamics simulations that show that alpha 2,6-linked glycans can establish more contacts with the viral capsid. Our results form an excellent platform for the design of antiviral compounds to prevent AHC.

  • 1678.
    Zygmuntowicz, Marcelina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Optimering vid detektion av anti-superoxiddismutas 1 (SOD1) med immunohistokemi: I transgena möss med användning av olika vävnadsförbehandlingsmetoder2016Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 1679.
    Ärlestig, Lisbeth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Einarsdottir, Elisabet
    Research Program Unit, Molecular Medicine, University of Helsinki, Finland.
    Holmberg, Dan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Novel risk locus on chromosome 14 in multi-case families with rheumatoid arthritis from northern SwedenManuscript (preprint) (Other academic)
  • 1680.
    Åberg, Anna-Maja
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Nilsson Sojka, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Larsson, Jan Erik
    Carbon monoxide concentration in donated blood: relation to cigarette smoking and other sources2009In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 49, no 2, p. 347-353Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Carbon monoxide (CO) is normally present in the human body due to endogenous production of CO. CO can also be inhaled by exposure to external sources such as cigarette smoke, car exhaust, and fire. The purpose of this study was to investigate CO concentrations in blood from 410 blood donors at the blood center in Umea, Sweden. To further evaluate the effects of cigarette smoking on CO concentrations, the elimination time for CO was examined in six volunteer smokers after a smoked cigarette. STUDY DESIGN AND METHODS: Blood samples from whole blood donors were obtained during the blood center's routine operation. In connection with blood donations, demographic and behavioral data were collected from the donors. The CO concentration was determined using gas chromatography. RESULTS: The majority of blood donors had approximately the same CO concentration (mean, 84.5 micromol/L). In 6 percent of the samples, the concentrations were higher than 130 micromol per L. The highest CO concentration was 561 micromol per L. The main source for these high CO concentrations appeared to be cigarette smoking. In the volunteer smokers, the elimination time after a smoked cigarette varied significantly, with elimination half-lives from 4.7 to 8.4 hours. CONCLUSION: These results show that blood bank red blood cell bags may have CO concentrations above the physiologic level. The time interval between cigarette smoking and blood donation seems to be a particularly important factor for elevated CO concentrations.

  • 1681. Åberg, Emma
    et al.
    Ottosson, Ann
    Granlund, Margareta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Saeedi, Baharak
    Stamm, Christina
    Brune, Thomas
    Tammelin, Ann
    Johansson, Stefan
    Harbouring group B streptococci in a neonatal intensive care unit led to an outbreak among preterm infants2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 1, p. 58-61Article in journal (Refereed)
    Abstract [en]

    We report a nosocomial outbreak with group B streptococci (GBS) in a level two neonatal intensive care unit (NICU) at Sachs' Children and Youth Hospital, Stockholm, Sweden, in 2014. There were five very preterm infants with severe late-onset septicaemia, and 10 further infants were colonised. Pulsed-field gel electrophoresis and multilocus sequence typing genetic characterisation showed that one GBS strain was the cause: serotype Ia, sequence type 23, clonal complex 23. The NICU environment cultures revealed GBS reservoirs on surfaces near sick and colonised patients. We identified workflows and guidelines that could increase the risks of nosocomial infections. Conclusion: This nosocomial GBS outbreak among preterm infants demonstrates that GBS can be harboured in the NICU environment.

  • 1682.
    Ådemo, Ida
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Tid- och temperaturoptimering av lipoproteinlipas-aktivitet: -   en studie på Soleus och Vastus lateralis hos möss2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 1683.
    Åhlund, Monika K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Stöven, Svenja
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster2010In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 78, no 7, p. 3118-3128Article in journal (Refereed)
    Abstract [en]

    Francisella tularensis is a highly virulent, facultative intracellular human pathogen whose virulence mechanisms are not well understood. Occasional outbreaks of tularemia and the potential use of F. tularensis as a bioterrorist agent warrant better knowledge about the pathogenicity of this bacterium. Thus far, genome-wide in vivo screens for virulence factors have been performed in mice, all however restricted by the necessity to apply competition-based, negative-selection assays. We wanted to individually evaluate putative virulence determinants suggested by such assays and performed directed screening of 249 F. novicida transposon insertion mutants by using survival of infected fruit flies as a measure of bacterial virulence. Some 20% of the genes tested were required for normal virulence in flies; most of these had not previously been investigated in detail in vitro or in vivo. We further characterized their involvement in bacterial proliferation and pathogenicity in flies and in mouse macrophages. Hierarchical cluster analysis of mutant phenotypes indicated a functional linkage between clustered genes. One cluster grouped all but four genes of the Francisella pathogenicity island and other loci required for intracellular survival. We also identified genes involved in adaptation to oxidative stress and genes which might induce host energy wasting. Several genes related to type IV pilus formation demonstrated hypervirulent mutant phenotypes. Collectively, the data demonstrate that the bacteria in part use similar virulence mechanisms in mammals as in Drosophila melanogaster but that a considerable proportion of the virulence factors active in mammals are dispensable for pathogenicity in the insect model.

  • 1684.
    Åström, Jeanette
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Att särskilja en stickblödning från subaraknoidal blödning vid likvoranalys: Ett underlag för en korrektionsformel som kan kompensera för bilirubinökning i likvor till följd av en stickblödning2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 1685.
    Öberg, Christopher T
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Strand, Mårten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Andersson, Emma K
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Edlund, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Tran, Nam Phuong Nguyen
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Mei, Ya-Fang
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Synthesis, biological evaluation, and structure-activity relationships of 2-[2-(benzoylamino)benzoylamino]benzoic acid analogues as inhibitors of adenovirus replication2012In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 55, no 7, p. 3170-3181Article in journal (Refereed)
    Abstract [en]

    2-[2-Benzoylamino)benzoylamino]benzoic acid (1) was previously identified as a potent and nontoxic antiadenoviral compound ( Antimicrob. Agents Chemother. 2010 , 54 , 3871 ). Here, the potency of 1 was improved over three generations of compounds. We found that the ortho, ortho substituent pattern and the presence of the carboxylic acid of 1 are favorable for this class of compounds and that the direction of the amide bonds (as in 1) is obligatory. Some variability in the N-terminal moiety was tolerated, but benzamides appear to be preferred. The substituents on the middle and C-terminal rings were varied, resulting in two potent inhibitors, 35g and 35j, with EC(50) = 0.6 μM and low cell toxicity.

  • 1686.
    Öberg, Elin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    EKG-avvikelser hos ungdomar i relation till kön, ålder och aktivitetsnivå2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 1687.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Prognostic factors in colorectal cancer: aspects of tumour dissemination2002Doctoral thesis, comprehensive summary (Other academic)
  • 1688.
    Öberg, Åke
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindmark, Gudrun
    Department of Surgery, Helsingborgs Lasarett, Lund University, Helsingborg, Sweden.
    Israelsson, Anne CE
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten G
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Marie-Louise KC
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR for CEA and CK20 mRNAS2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 111, no 1, p. 101-110Article in journal (Refereed)
    Abstract [en]

    The purpose of our study was to develop specific, sensitive, objective assays for early detection of disseminated tumour cells in patients with colorectal cancer (CRC). Carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) were chosen as markers because they are selectively expressed in epithelial cells with maintained expression in CRC. Real-time quantitative RT-PCR assays with RNA copy standards were constructed. Regional lymph nodes were collected from patients with CRC (n = 51) and benign intestinal disease (n = 10). Results were compared to routine histopathology and anti-CEA immunohistochemistry. Lymph node levels of CEA and CK20 mRNA correlated strongly (p < 0.0001, r = 0.8). Lymph nodes from non-CRC patients had <0.01 CEA and <0.001 CK20 mRNA copies/18S rRNA unit. Lymph nodes from 3/6 Dukes' A, 17/26 Dukes' B, 10/10 Dukes' C and 7/9 Dukes' D patients had CEA mRNA levels above cut-off. Corresponding figures for CK20 mRNA were 3/6, 10/26, 9/10 and 5/9, respectively. CEA mRNA levels varied from 0.001 to 100 copies/18S rRNA unit in Dukes' A and B, and 50% of the Dukes' B patients had CEA mRNA levels within the range of Dukes' C patients. Three Dukes' B patients have died from CRC or developed distant metastases. All 3 had high CEA and CK20 mRNA levels. Determination of mRNA was superior to immunohistochemistry in showing CEA expression in lymph nodes. The present qRT-PCR assay for CEA mRNA seems to be a superior tool to identify individuals with disseminated tumour cells. Future extended studies will establish the clinically most relevant cut-off level.

  • 1689.
    Ödin, Patrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Internalisering av yttermembranvesiklar från Aggregatibacter actinomycetemcomitans i humana celler2013Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 1690.
    Öhman, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    RNA uttryck av KIF23 i humana vävnader2013Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 1691.
    Ölvebo, Isabelle
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Leukotoxinproduktion i isolat från Aggregatibacter actinomycetemcomitans: En parodontitpatogen med stor genetisk variation2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 1692.
    Önskog, Jenny
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Freyhult, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Landfors, Mattias
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Hvidsten, Torgeir R
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Classification of microarrays: synergistic effects between normalization, gene selection and machine learning2011In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 12, no 1, article id 390Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Machine learning is a powerful approach for describing and predicting classes in microarray data. Although several comparative studies have investigated the relative performance of various machine learning methods, these often do not account for the fact that performance (e.g. error rate) is a result of a series of analysis steps of which the most important are data normalization, gene selection and machine learning.

    RESULTS: In this study, we used seven previously published cancer-related microarray data sets to compare the effects on classification performance of five normalization methods, three gene selection methods with 21 different numbers of selected genes and eight machine learning methods. Performance in term of error rate was rigorously estimated by repeatedly employing a double cross validation approach. Since performance varies greatly between data sets, we devised an analysis method that first compares methods within individual data sets and then visualizes the comparisons across data sets. We discovered both well performing individual methods and synergies between different methods.

    CONCLUSION: Support Vector Machines with a radial basis kernel, linear kernel or polynomial kernel of degree 2 all performed consistently well across data sets. We show that there is a synergistic relationship between these methods and gene selection based on the T-test and the selection of a relatively high number of genes. Also, we find that these methods benefit significantly from using normalized data, although it is hard to draw general conclusions about the relative performance of different normalization procedures.

  • 1693.
    Överby, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Nilsson, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Det tidiga immunförsvaret nyckel i kampen mot TBE-virus2014In: Neurologi i Sverige, ISSN 2000-8538, Vol. 2, no 14, p. 68-74Article in journal (Other academic)
  • 1694.
    Överby Wernstedt, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Weber, Friedemann
    Hiding from intracellular pattern recognition receptors, a passive strategy of flavivirus immune evasion2011In: Virulence, ISSN 2150-5594, E-ISSN 2150-5608, Vol. 2, no 3, p. 238-240Article in journal (Refereed)
    Abstract [en]

    Tick-borne encephalitis virus (TBEV) is a medically important flavivirus in Europe and Asia, causing meningitis and encephalitis in thousands of people annually. Despite its relevance for public health, the interaction of TBEV with the type I interferon (IFN) system is poorly characterized. Induction of these antiviral cytokines is normally triggered by cytoplasmic recognition of viral signature molecules such as double-stranded (ds) RNA. In a recent paper, we showed that TBEV infection leads to formation of intracellular membrane vesicles which protect the viral dsRNA from cellular recognition. This delays the onset of antiviral IFN production sufficiently enough for an unhindered release of progeny viruses over 24 h. Thus, TBEV has evolved a stealth strategy to outrun the antiviral IFN response.

  • 1695.
    Överby Wernstedt, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Weber, Friedemann
    Hiding from intracellular pattern recognition receptors, a passive strategy of flavivirus immune evasion2011Conference paper (Refereed)
  • 1696.
    Öystilä Sjödin, Madelen
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Kronisk behandling med allopregnanolon påverkar inte mängden beta-amyloida plack i AβPPSwePSEN1E9 AD-möss2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 1697. Łyszkiewicz, Marcin
    et al.
    Zietara, Natalia
    Rohde, Manfred
    Gekara, Nelson O
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Jabłońska, Jadwiga
    Dittmar, Kurt E
    Weiss, Siegfried
    SIGN-R1+MHC II+ cells of the splenic marginal zone: a novel type of resident dendritic cells2011In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 89, no 4, p. 607-615Article in journal (Refereed)
    Abstract [en]

    In the spleen, the MZ forms an interface between red and white pulp. Its major function is to trap blood-borne antigens and to reorient them to APCs and lymphocytes. SIGN-R1(+) cells are of the MZ inherent cell population, which for a long time, have been considered as macrophages. We now show that one subpopulation of SIGN-R1(+) cells that express MHC II molecules should be considered as a resident DC. Histological analysis indicated that SIGN-R1(+) cells have dendritic-like protrusions extending into T and B cell areas. Flow cytometry analysis revealed an expression profile of adhesion, costimulatory, and MHC molecules similar to cDCs but distinct from macrophages. Most importantly, SIGN-R1(+)MHC(+) cells were able to present antigen to naïve CD4 T cells, as well as to cross-present soluble, particulate antigens secreted by Listeria monocytogenes to CD8 T cells in vitro and in vivo. Our experiments identified SIGN-R1(+)MHC II(+) cells as professional APCs and indicate their nature as splenic resident DCs.

31323334 1651 - 1697 of 1697
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