umu.sePublications
Change search
Refine search result
12 1 - 50 of 65
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1.
    Alexeyev, Oleg A
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Aava, Birgitta
    Skoglig Zooekologi, SLU, Umeå.
    Palo, Thomas
    Skoglig Zooekologi, SLU, Umeå.
    Settergren, Bo
    Tärnvik, Arne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    A minority of seropositive wild bank voles (Clethrionomys glareolus) show evidence of current Puumala virus infection1998In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 121, no 2, p. 419-425Article in journal (Refereed)
    Abstract [en]

    Bank voles (Clethrionomys glareolus) serve as the reservoir for Puumala (PUU) virus, the aetiologic agent of nephropathia epidemica. The animals are believed to be persistently infected and the occurrence of serum antibodies is usually taken as an evidence of active infection. We found serum antibodies to PUU virus in 42 of 299 wild bank voles captured in a PUU virus endemic area. PUU virus RNA was demonstrated in lung specimens of 11 of these 42 animals and in 2 of them antigen was also found. Thus in the lungs of 31 of 42 seropositive animals neither PUU virus RNA nor antigen was detected. In 2 of 257 seronegative animals, lung specimens showed presence of PUU virus antigen and RNA. Isolation of PUU virus from lung tissue was successful in all 4 antigen-positive bank voles but in none of 16 tested antigen-negative animals. In conclusion, only a minority of bank voles with serum antibodies to PUU virus showed evidence of current infection.

  • 2.
    Allard, A
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Albinsson, B
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, G
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Rapid typing of human adenoviruses by a general PCR combined with restriction endonuclease analysis.2001In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 39, no 2, p. 498-505Article in journal (Refereed)
    Abstract [en]

    We have developed a system for rapid typing of adenoviruses (Ads) based on a combination of PCR and restriction endonuclease (RE) digestion (PCR-RE digestion). Degenerated consensus primers were designed, allowing amplification of DNA from all 51 human Ad prototype strains and altogether 44 different genome variants of Ad serotypes 1, 3, 4, 5, 7, 11, 19, 40, and 41. The 301-bp amplimer of 22 prototype strains representing all six subgenera and the genome variant was selected as a target for sequencing to look for subgenus and genome type variabilities. The sequences obtained were used to facilitate the selection of specific REs for discrimination purposes in a diagnostic assay by following the concept of cleavage or noncleavage of the 301-bp amplimer. On the basis of these results, a flowchart was constructed, allowing identification of subgenus B:2 and D serotypes and almost complete distinction of subgenus A, B:1, C, E, and F serotypes. Application of the PCR-RE digestion system to clinical samples allowed typing of 34 of 40 clinical samples positive for Ad. The genome type determined by this method was identical to that obtained by traditional RE typing of full-length Ad DNA. The remaining six samples were positive only after a nested PCR. Therefore, to reduce the risk of false-negative results, samples scored negative by the PCR-RE digestion system should be evaluated by the described nested PCR. Used in combination, the PCR-RE digestion method and the nested PCR provide a reliable and sensitive system that can easily be applied to all kinds of clinical samples when rapid identification of adenoviruses is needed.

  • 3.
    Andersson, Emma K
    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, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Adenovirus interactions with CD46 on transgenic mouse erythrocytes2010In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 402, no 1, p. 20-25Article in journal (Refereed)
    Abstract [en]

    Hemagglutination is an established method but has not been used previously to determine the efficacy of virus binding to a specific cellular receptor. Here we have utilized CD46-expressing erythrocytes from a transgenic mouse to establish whether and to what extent the species B adenoviruses (Ads) as well as Ad37 and Ad49 of species D can interact with CD46. A number of different agglutination patterns, and hence CD46 interactions, could be observed for the different adenovirus types. In this system Ad7p, Ad11a, and Ad14 did not agglutinate mouse erythrocytes at all. Hemagglutination of CD46 expressing erythrocytes with high efficiency was observed for the previously established CD46 users Ad11p and Ad35 as well as for the less investigated Ad34. Ad50 agglutinated with moderate efficiency. Ad16, Ad21 and Ad49 gave incomplete agglutination. Ad16 was the only adenovirus that could be eluted. No specific CD46 interaction could be observed for Ad3p or for Ad37.

  • 4.
    Andersson, Emma K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Strand, Mårten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Edlund, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lindman, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Enquist, Per-Anders
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Spjut, Sara
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Allard, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    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.
    Small molecule screening using a whole cell viral replication reporter gene assay identifies 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid as a novel anti-adenoviral compound2010In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 54, no 9, p. 3871-3877Article in journal (Refereed)
    Abstract [en]

    Adenovirus infections are widespread in society and are occasionally associated with severe, but rarely with life-threatening, disease in otherwise healthy individuals. In contrast, adenovirus infections present a real threat to immunocompromised individuals and can result in disseminated and fatal disease. The number of patients undergoing immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation is steadily increasing, as is the number of AIDS patients, and this makes the problem of adenovirus infections even more urgent to solve. There is no formally approved treatment of adenovirus infections today, and existing antiviral agents evaluated for their anti-adenoviral effect give inconsistent results. We have developed a whole cell-based assay for high-throughput screening of potential anti-adenoviral compounds. The assay is unique in that it is based on a replication competent adenovirus type 11p GFP-expressing vector (RCAd11pGFP). This allows measurement of fluorescence changes as a direct result of RCAd11pGFP genome expression. Using this assay, we have screened 9,800 commercially available small organic compounds. Initially, we observed approximately 400 compounds that inhibited adenovirus expression in vitro by >/= 80% but only 24 were later confirmed as dose-dependent inhibitors of adenovirus. One compound in particular, 2-[[2-(benzoylamino)benzoyl]amino]-benzoic acid, turned out to be a potent inhibitor of adenovirus replication.

  • 5. Aoki, Koki
    et al.
    Benkö, Mária
    Davison, Andrew J
    De Jong, Jan C
    Echavarria, Marcela
    Erdman, Dean D
    Harrach, Balázs
    Kajon, Adriana E
    Schnurr, David
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Towards an integrated human adenovirus designation system that utilizes molecular and serological data and serves both clinical and fundamental virology2011In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 85, no 11, p. 5703-5704Article in journal (Refereed)
  • 6.
    Arnberg, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Edlund, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kidd, Alistair H
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Adenovirus type 37 uses sialic acid as a cellular receptor2000In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 74, no 1, p. 42-48Article in journal (Refereed)
    Abstract [en]

    Two cellular receptors for adenovirus, coxsackievirus-adenovirus receptor (CAR) and major histocompatibility complex class I (MHC-I) alpha2, have recently been identified. In the absence of CAR, MHC-I alpha2 has been suggested to serve as a cellular attachment protein for subgenus C adenoviruses, while members from all subgenera except subgenus B have been shown to interact with CAR. We have found that adenovirus type 37 (Ad37) attachment to CAR-expressing CHO cells was no better than that to CHO cells lacking CAR expression, suggesting that CAR is not used by Ad37 during attachment. Instead, we have identified sialic acid as a third adenovirus receptor moiety. First, Ad37 attachment to both CAR-expressing CHO cells and MHC-I alpha2-expressing Daudi cells was sensitive to neuraminidase treatment, which eliminates sialic acid on the cell surface. Second, Ad37 attachment to sialic acid-expressing Pro-5 cells was more than 10-fold stronger than that to the Pro-5 subline Lec2, which is deficient in sialic acid expression. Third, neuraminidase treatment of A549 cells caused a 60% decrease in Ad37 replication in a fluorescent-focus assay. Moreover, the receptor sialoconjugate is most probably a glycoprotein rather than a ganglioside, since Ad37 attachment to sialic acid-expressing Pro-5 cells was sensitive to protease treatment. Ad37 attachment to Pro-5 cells occurs via alpha(2-->3)-linked sialic acid saccharides rather than alpha(2-->6)-linked ones, since (i) alpha(2-->3)-specific but not alpha(2-->6)-specific lectins blocked Ad37 attachment to Pro-5 cells and (ii) pretreatment of Pro-5 cells with alpha(2-->3)-specific neuraminidase resulted in decreased Ad37 binding. Taken together, these results suggest that, unlike Ad5, Ad37 makes use of alpha(2-->3)-linked sialic acid saccharides on glycoproteins for entry instead of using CAR or MHC-I alpha2.

  • 7.
    Arnberg, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kidd, Alistair H
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Edlund, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Pring-Åkerblom, Patricia
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Adenovirus type 37 binds to cell surface sialic acid through a charge-dependent interaction2002In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 302, no 1, p. 33-43Article in journal (Refereed)
    Abstract [en]

    Most adenoviruses use the coxsackie-adenovirus receptor (CAR) as a major cellular receptor. We have shown recently that adenovirus types 8, 19a, and 37, which are the major causes of epidemic keratoconjunctivitis, use sialic acid rather than CAR as a major cellular receptor. The predicted isoelectric point of the receptor-interacting knob domain in the adenovirus fiber protein is unusually high (9.0-9.1) in type 8, 19a, and 37. The pKa of sialic acid is low, 2.6, implying a possible involvement of charge in fiber knob-sialic acid interactions. Here we show that (i) positively charged adenovirus knobs require sialic acid for efficient cell membrane interactions; (ii) viral and knob interactions with immobilized sialic acid or cell-surface sialic acid are sensitive to increased ionic strength; (iii) negatively charged molecules such as sulfated glycosaminoglycans inhibit the binding of virions to target cells in a nonspecific, charge-dependent manner; and that (iv) the ability of adenovirus knobs to interact with sialic acid correlates with the overall charge on the top surface of the respective knobs as predicted by homology modeling. Taken together, the results presented provide strong evidence for a charge mechanism during the interaction between the Ad37 fiber knob and sialic acid.

  • 8.
    Arnberg, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kidd, Alistair H
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Edlund, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Olfat, Farzad
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Initial interactions of subgenus D adenoviruses with A549 cellular receptors: sialic acid versus alpha(v) integrins2000In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 74, no 16, p. 7691-3Article in journal (Refereed)
    Abstract [en]

    Selected members of the adenovirus family have been shown to interact with the coxsackie adenovirus receptor, alpha(v) integrins, and sialic acid on target cells. Initial interactions of subgenus D adenoviruses with target cells have until now been poorly characterized. Here, we demonstrate that adenovirus type 8 (Ad8), Ad19a, and Ad37 use sialic acid as a functional cellular receptor, whereas the Ad9 and Ad19 prototypes do not.

  • 9.
    Arnberg, Niklas
    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.
    Fiber genes of adenoviruses with tropism for the eye and the genital tract1997In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 227, no 1, p. 239-244Article in journal (Refereed)
    Abstract [en]

    We have characterized the fibergenes of adenovirus type 19p (Ad19p), Ad19a, and Ad37 by sequencing. The fiber genes of Ad19a and Ad37 are identical and only five amino acids differ comparing Ad19a/Ad37 with Ad19p. Based on the translated sequences we calculated the isoelectrical points (Ips) and found that the fiber knobs of Ad19p, Ad19a, and Ad37 together with Ad8 display the highest Ips of all so far characterized. Two regions within the fiber knob with unusually basic characteristics have been identified. Sequence alignments revealed that the corresponding regions in other fiber knobs are highly antigenic in pepscan analysis and of importance for hemagglutination. Only two positions differ in the knobs comparing Ad19a/Ad37 with Ad19p. Hence, either of these or both amino acid residues should be expected to be responsible for the observed differences in hemagglutination between Ad19p and Ad19a/Ad37. Moreover, we have found two amino acids (Ala227 and Lys252) that are unique in their respective position in Ad19p, Ad19a, Ad37, and Ad8. Three amino acids (Lys236, Lys240, and Asn251) are unique in their respective position in Ad19a and Ad37, that manifest a tropism for the genital tract. All five amino acids colocalize within one of the two basic regions.

  • 10.
    Arnberg, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Pring-Akerblom, Patricia
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Adenovirus type 37 uses sialic acid as a cellular receptor on Chang C cells2002In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 76, no 17, p. 8834-8841Article in journal (Refereed)
    Abstract [en]

    Epidemic keratoconjunctivitis (EKC) is a severe eye infection caused mainly by adenovirus type 8 (Ad8), Ad19, and Ad37. We have shown that the EKC-causing adenoviruses use sialic acid as a cellular receptor on A549 cells instead of the coxsackie-adenovirus receptor, which is used by most adenoviruses. Recently, Wu et al. (Virology 279:78-89, 2001) proposed that Ad37 uses a 50-kDa protein as a receptor on Chang C conjunctival cells and that this interaction is independent of sialic acid. According to the American Type Culture Collection, this cell line carries HeLa cell markers and should be considered to be a genital cell line. This prompted us to investigate the function of sialic acid as a cellular receptor for Ad37 in Chang C cells. In this study, we demonstrate that enzymatic removal or lectin-mediated blocking of cell surface sialic acid inhibits the binding of Ad37 virions to Chang C cells, as does soluble, virion-interacting sialic acid-containing substances. The binding was Ca2+ or Mg2+ ion independent and mediated by the knob domain of the trimeric viral fiber polypeptide. Moreover, Ad37 virions infected Chang C cells and two other genital cell lines (HeLa and SiHa) as well as a corneal cell line in a strictly sialic acid-dependent manner. From these results, we conclude that Ad37 uses sialic acid as a major receptor in cell lines derived from both genital and corneal tissues.

  • 11.
    Berglin, Ewa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Johansson, T
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sundin, U
    Jidell, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Hallmans, Göran
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset.2006In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 65, no 4, p. 453-458Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression. METHODS: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients) and were identified from among blood donors within the Medical Biobank of northern Sweden. Disease activity (erythrocyte sedimentation rate (ESR), C reactive protein, joint score, global visual analogue scale) and radiological destruction in hands and feet (Larsen score) were assessed at baseline and after two years. Anti-CCP antibodies and RFs were analysed using enzyme immunoassays. HLA shared epitope (SE) alleles (DRB1*0401/0404) were identified. RESULTS: Patients with anti-CCP antibodies before disease onset had significantly higher Larsen score at baseline and after two years. In multiple regression analyses baseline values of anti-CCP/IgA-RF/IgG-RF/IgM-RF, swollen joint count, and Larsen score significantly predicted radiological outcome at two years. In logistic regression analyses, baseline values of anti-CCP antibodies/IgA-RF, therapeutic response at six months, and swollen joint count/ESR significantly predicted radiological progression after two years. The baseline titre of anti-CCP antibodies was higher in patients with radiological progression and decreased significantly in those with response to therapy. SE allele carriage was associated with a positive test for anti-CCP antibodies in pre-patients and in early rheumatoid arthritis. CONCLUSIONS: Presence of anti-CCP antibodies before disease onset is associated with more severe radiological damage. The titre of anti-CCP antibodies is related to disease severity.

  • 12.
    Boman, Jens
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Gaydos, Charlotte
    Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Quinn, Thomas C
    Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
    Failure to detect Chlamydia trachomatis in cell culture by using a monoclonal antibody directed against the major outer membrane protein1997In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 35, no 10, p. 2679-2680Article in journal (Refereed)
    Abstract [en]

    Two commercially available monoclonal antibodies for cell culture confirmation of Chlamydia trachomatis were compared in two prospective studies and one large retrospective study. In total, more than 33,000 genital specimens were cultured in parallel and stained with both antibodies, one of which was directed against the major outer membrane protein (MOMP) and one uf which was directed against the lipopolysaccharide (LPS). We found the anti-LPS-based assay to be more sensitive and as specific as the anti-MOMP-based assay for C. trachomatis cell culture confirmation of genital specimens.

  • 13. Burmeister, Wim P
    et al.
    Guilligay, Delphine
    Cusack, Stephen
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Crystal structure of species D adenovirus fiber knobs and their sialic acid binding sites2004In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 78, no 14, p. 7727-7736Article in journal (Refereed)
    Abstract [en]

    Adenovirus serotype 37 (Ad37) belongs to species D and can cause epidemic keratoconjunctivitis, whereas the closely related Ad19p does not. Primary cell attachment by adenoviruses is mediated through receptor binding of the knob domain of the fiber protein. The knobs of Ad37 and Ad19p differ at only two positions, Lys240Glu and Asn340Asp. We report the high-resolution crystal structures of the Ad37 and Ad19p knobs, both native and in complex with sialic acid, which has been proposed as a receptor for Ad37. Overall, the Ad37 and Ad19p knobs are very similar to previously reported knob structures, especially to that of Ad5, which binds the coxsackievirus-adenovirus receptor (CAR). Ad37 and Ad19p knobs are structurally identical with the exception of the changed side chains and are structurally most similar to CAR-binding knobs (e.g., that of Ad5) rather than non-CAR-binding knobs (e.g., that of Ad3). The two mutations in Ad19p result in a partial loss of the exceptionally high positive surface charge of the Ad37 knob but do not affect sialic acid binding. This site is located on the top of the trimer and binds both alpha(2,3) and alpha(2,6)-linked sialyl-lactose, although only the sialic acid residue makes direct contact. Amino acid alignment suggests that the sialic acid binding site is conserved in several species D serotypes. Our results show that the altered viral tropism and cell binding of Ad19p relative to those of Ad37 are not explained by a different binding ability toward sialyl-lactose.

  • 14. Chen, Tianhui
    et al.
    Lukanova, Annekatrin
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Zeleniuch-Jacquotte, Anne
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schock, Helena
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Toniolo, Paolo
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    IGF-I during primiparous pregnancy and maternal risk of breast cancer2010In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 121, no 1, p. 169-175Article in journal (Refereed)
    Abstract [en]

    Previously, we reported that insulin-like growth factor (IGF)-I during early pregnancy is positively associated with maternal risk of breast cancer. To further explore this association, we designed a new study limited to women who donated a blood sample during their first pregnancy ending with childbirth. A case-control study was nested within the Northern Sweden Maternity Cohort in which repository since 1975, serum specimens remaining after early pregnancy screening for infectious diseases had been preserved. Study subjects were selected among women who donated a blood sample during the full-term pregnancy that led to the birth of their first child. Two hundred and forty-four women with invasive breast cancer were eligible. Two controls, matching the index case for age and date at blood donation were selected (n = 453). IGF-I was measured in serum samples on an Immulite 2000 analyzer. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. A significant positive association of breast cancer with IGF-I was observed, with OR of 1.73 (95% CI: 1.14-2.63) for the top tertile, P < 0.009. Subgroup analyses did not indicate statistical heterogeneity of the association by ages at sampling and diagnosis or by lag time to cancer diagnosis, although somewhat stronger associations with risk were observed in women < or = age 25 at index pregnancy and for cases diagnosed within 15 years of blood donation. The results of the study add further evidence for an adverse effect of elevated IGF-I concentrations during early reproductive life on risk of breast cancer.

  • 15. Chen, Tianhui
    et al.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Zeleniuch-Jacquotte, Anne
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Afanasyeva, Yelena
    Schock, Helena
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Toniolo, Paolo
    Lukanova, Annekatrin
    Maternal hormones during early pregnancy: a cross-sectional study2010In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 21, no 5, p. 719-727Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Little is known about correlates of first-trimester pregnancy hormones as in most studies maternal hormones have been measured later in gestation. We examined the associations of maternal characteristics and child sex with first-trimester maternal concentrations of four hormones implicated in breast cancer: human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), insulin-like growth factor (IGF)-I, and IGF-II. METHODS: About 338 serum samples donated to the Northern Sweden Maternity Cohort (NSMC), 1975-2001, during the first trimester of uncomplicated pregnancies, were analyzed for the hormones of interest as a part of a case-control study. The associations of maternal characteristics and child sex with hormone concentrations were investigated by correlation, general linear regression, and multivariate regression models. RESULTS: In the first trimester, greater maternal age was inversely correlated with IGF-I and IGF-II. In comparison with women carrying their first child, already parous women had higher IGF-I but lower hCG. Greater maternal weight and smoking were inversely correlated with hCG. No differences in hormone levels by child sex were observed. CONCLUSIONS: Our analyses indicated that potentially modifiable maternal characteristics (maternal weight and smoking) influence first-trimester pregnancy maternal hormone concentrations.

  • 16. Dahlström, Lisen Arnheim
    et al.
    Andersson, Kristin
    Luostarinen, Tapio
    Thoresen, Steinar
    Ögmundsdottir, Helga
    Tryggvadottir, Laufey
    Wiklund, Fredrik
    Skare, Gry B
    Eklund, Carina
    Sjölin, Kia
    Jellum, Egil
    Koskela, Pentti
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lehtinen, Matti
    Dillner, Joakim
    Prospective seroepidemiologic study of human papillomavirus and other risk factors in cervical cancer2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 12, p. 2541-2550Article in journal (Refereed)
    Abstract [en]

    Background: Several sexually transmitted infections (STI) have been reported to interact with human papillomavirus (HPV) in the etiology of cervical cancer. A large cohort study is required to obtain a both unbiased and stable estimate of their effects.

    Methods: Four major biobanks in the Nordic Countries containing samples from about 1,000,000 subjects were linked with nation-wide cancer registries. Serum samples from 604 women with invasive cervical cancer (ICC) diagnosed on average 10 years after sampling and 2,980 matched control women were retrieved and analyzed with serology for key STI.

    Results: Exposure to HPV16 was the strongest risk factor for cervical cancer [ OR = 2.4; 95% confidence interval (CI), 2.0-3.0], particularly for squamous cell carcinoma (OR = 2.9; 95% CI, 2.2-3.7). HPV18 was strongly associated with increased risk for adenocarcinoma (OR = 2.3; 95% CI, 1.3-4.1). Baseline seropositivity for HPV16 did not confer any increased risk for HPV18 DNA-positive cancer and conversely HPV18 seropositivity had no association with HPV16 DNA-positive cancers. HPV6 had no effect on its own (OR = 1.1; 95% CI, 0.9-1.3), but had an antagonistic effect on the risk conferred by HPV16 (P < 0.01). Herpes simplex virus 2 had little or no association (OR = 1.1; 95% CI, 0.8-1.4). Previous exposure to Chlamydia trachomatis, as indicated by serum antibodies, had a strongly increased risk for cervical cancer (OR = 1.9; 95% CI, 1.5-2.3).

    Conclusions: A large prospective study has assessed the role of different STIs in cervical cancer.

    Impact: Prospective evidence supports cofactor role of some STI in cervical cancer.

    Cancer Epidemiol Biomarkers Prev; 20(12); 2541-50. (C) 2011 AACR.

  • 17. Dicks, Matthew DJ
    et al.
    Spencer, Alexandra J
    Edwards, Nick J
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bojang, Kalifa
    Gilbert, Sarah C
    Hill, Adrian VS
    Cottingham, Matthew G
    A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, p. e40385-Article in journal (Refereed)
    Abstract [en]

    Recombinant adenoviruses are among the most promising tools for vaccine antigen delivery. Recently, the development of new vectors has focused on serotypes to which the human population is less exposed in order to circumvent preexisting anti vector immunity. This study describes the derivation of a new vaccine vector based on a chimpanzee adenovirus, Y25, together with a comparative assessment of its potential to elicit transgene product specific immune responses in mice. The vector was constructed in a bacterial artificial chromosome to facilitate genetic manipulation of genomic clones. In order to conduct a fair head-to-head immunological comparison of multiple adenoviral vectors, we optimised a method for accurate determination of infectious titre, since this parameter exhibits profound natural variability and can confound immunogenicity studies when doses are based on viral particle estimation. Cellular immunogenicity of recombinant E1 E3-deleted vector ChAdY25 was comparable to that of other species E derived chimpanzee adenovirus vectors including ChAd63, the first simian adenovirus vector to enter clinical trials in humans. Furthermore, the prevalence of virus neutralizing antibodies (titre >1:200) against ChAdY25 in serum samples collected from two human populations in the UK and Gambia was particularly low compared to published data for other chimpanzee adenoviruses. These findings support the continued development of new chimpanzee adenovirus vectors, including ChAdY25, for clinical use.

  • 18.
    Eriksson, Catharina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Kokkonen, Heidi
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Johansson, Martin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Autoantibodies predate the onset of Systemic Lupus Erythematosus in northern Sweden2011In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 13, no 1, p. R30-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Autoantibodies have a central role in systemic lupus erythematosus (SLE). The presence of autoantibodies preceding disease onset by years has been reported both in patients with SLE and those with rheumatoid arthritis, suggesting a gradual development of these diseases. To identify autoantibodies in a Northern European population predating the onset of symptoms of SLE and their relationship to presenting symptoms.

    METHODS: The register of patients fulfilling the American College of Rheumatology (ACR) criteria for SLE and with a given date for the onset of symptoms was co-analysed with the register of the Medical Biobank, Umea, Sweden. Thirty-eight patients were identified as having donated blood samples prior to symptom onset. A nested case-control study (1:4) was performed with 152 age- and sex-matched controls identified from within the Biobank register. Antibodies against anti- Sjogren's syndrome antigen A (Ro/SSA) (60 and 52 kDa), anti- Sjogren's syndrome antigen B (La/SSB), anti-Smith antibody (Sm), ribonucleoprotein (RNP), scleroderma-70 (Scl-70), anti- histidyl-tRNA synthetase antibody (Jo-1), double-stranded DNA (dsDNA); Centromere protein B and histones were analysed using the anti-nuclear antibody test II (ANA-II) Plus Test System (Athena Multi-Lyte(R)) on a Bio-Plex Array Reader (Luminex200). ANA were analysed using indirect immunofluorescence on Human Epidermal cells-2 (HEp2-cells) at a sample dilution of 1:100.

    RESULTS: Autoantibodies against nuclear antigens were detected 5.6 (+/- 4.7; mean +/- SD) years before the onset of symptoms and 8.7 (+/- 5.6) years before diagnosis in 63% of the individuals who subsequently developed SLE. The sensitivity (45.7%) was highest for ANA with a specificity of 95%, followed by anti-dsDNA and anti-Ro/SSA antibodies both with sensitivities of 20.0% at specificities of 98.7% and 97.4%, respectively. The odds ratio (OR) for anti-dsDNA predicting disease was 18.13 (CI 95%; 3.58-91.84), and for ANA 11.5 (CI 95%; 4.54-28.87). Anti-Ro/SSA antibodies appeared first, 6.6 (+/- 2.5) years prior to symptom onset. The mean number of autoantibodies in pre-diseased individuals was 1.4 and after disease onset 3.1 (P< 0.0005). The time predating disease was shorter, and the number of autoantibodies greater, in those individuals with serositis as a presenting symptom in comparison to those with arthritis and skin manifestations.

    CONCLUSIONS: Autoantibodies against nuclear antigens were detected in individuals developing SLE several years before the onset of symptoms and diagnosis. The most sensitive autoantibodies were ANA, Ro/SSA and dsDNA, with the highest predictive OR for anti-dsDNA antibodies. The first autoantibodies detected were anti-Ro/SSA.

  • 19. Forslund, Ola
    et al.
    Antonsson, Annika
    Edlund, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    van den Brule, Adrian J C
    Hansson, Bengt-Göran
    Meijer, Chris J L M
    Ryd, Walter
    Rylander, Eva
    Strand, Anders
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Dillner, Joakim
    Johansson, Bo
    Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish women.2002In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 66, no 4, p. 535-41Article in journal (Refereed)
    Abstract [en]

    Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5+/6+) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy.

  • 20. Greber, Urs F.
    et al.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Benko, Maria
    Kremer, Eric J.
    Adenoviruses: from pathogens to therapeutics: a report on the 10th International Adenovirus Meeting2013In: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 15, no 1, p. 16-23Article in journal (Refereed)
  • 21.
    Gustafsson, Dan J
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
    Segerman, Anna
    Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
    Lindman, Kristina
    Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
    Mei, Ya-Fang
    Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
    The Arg279Gln [corrected] substitution in the adenovirus type 11p (Ad11p) fiber knob abolishes EDTA-resistant binding to A549 and CHO-CD46 cells, converting the phenotype to that of Ad7p.2006In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 80, no 4, p. 1897-905Article in journal (Refereed)
    Abstract [en]

    The major determinant of adenovirus (Ad) attachment to host cells is the C-terminal knob domain of the trimeric fiber protein. Ad type 11p (Ad11p; species B2) in contrast to Ad7p (species B1) utilizes at least two different cellular attachment receptors, designated sBAR (species B adenovirus receptor) and sB2AR (species B2 adenovirus receptor). CD46 has recently been identified as one of the Ad11p attachment receptors. However, CD46 did not seem to constitute a functional receptor for Ad7p. Although Ad7p shares high knob amino acid identity with Ad11p, Ad7p is deficient in binding to both sB2AR and CD46. To determine what regions of the Ad11p fiber knob are necessary for sB2AR-CD46 interaction, we constructed recombinant fiber knobs (rFK) with Ad11p/Ad7p chimeras and Ad11p sequences having a single amino acid substitution from Ad7p. Binding of the constructs to A549 and CHO-CD46 BC1 isoform-expressing cells was analyzed by flow cytometry. Our results indicate that an Arg279Gln [corrected] substitution is sufficient to convert the Ad11p receptor-interaction phenotype to that of Ad7p and abolish sB2AR and CD46 interaction. Also a Glu279Arg substitution in Ad7p rFKs increases CD46 binding. Thus, the lateral HI loop of the Ad11p fiber knob seems to be the key determinant for Ad11p sB2AR-CD46 interaction. This result is comparable to another non-coxsackie-adenovirus receptor binding Ad (Ad37p), where substitution of one amino acid abolishes virus-cell interaction. In conjunction with previous results, our findings also strongly suggest that sB2AR is equivalent to CD46.

  • 22. Holl, Katsiaryna
    et al.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Surcel, Heljä-Marja
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Koskela, Pentti
    Dillner, Joakim
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Olafsdottir, Gudridur H
    Ogmundsdottir, Helga M
    Pukkala, Eero
    Lehtinen, Matti
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lukanova, Annekatrin
    Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: A nested case-referent study.2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 124, no 12, p. 2923-2928Article in journal (Refereed)
    Abstract [en]

    According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. (c) 2009 UICC.

  • 23. Holl, Katsiaryna
    et al.
    Surcel, Helja-Marja
    Koskela, Pentti
    Dillner, Joakim
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kaasila, Marjo
    Olafsdottir, Gudridur H
    Ogmundsdottir, Helga M
    Pukkala, Eero
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lehtinen, Matti
    Maternal Epstein-Barr virus and cytomegalovirus infections and risk of testicular cancer in the offspring: a nested case-control study2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 9, p. 816-822Article in journal (Refereed)
    Abstract [en]

    During recent decades the incidence of testicular cancer (TC) has increased rapidly around the world. Associated exogenous etiological factors might therefore be identifiable. We performed a case-control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of congenital or neonatal infections with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) as risk factors of TC in the offspring. For each case-index mother pair, three or four matched control-control mother pairs were identified using national population registries. First trimester sera were retrieved from the index mothers of 66 TC cases and 258 matched control mothers, and were tested for antibodies to EBV and CMV. High level of maternal EBV IgG antibodies was associated with significantly increased risk of TC in the offspring (odds ratio (OR), 2.50; 95% confidence interval (CI), 1.15, 5.40), especially with risk of non-seminoma TC (OR, 2.73; 950% CI, 1.25, 5.99) and non-seminoma TC diagnosed under 8 years of age (OR, 2.72; 95% CI, 1.05, 7.04). In contrast, offspring of CMV IgG-seropositive mothers had a decreased risk of TC diagnosed under 8 years of age (OR, 0.35; 95% CI, 0.14, 0.89). Our results suggest that EBV and CMV infections may be associated with TC.

  • 24.
    Jacobson, Sofie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Larsson, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Idrottsmedicin.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Leptin independently predicts development of future sepsis and determines survival in the acute phaseManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: To determine if levels of the adipocyte-derived hormones leptin and adiponectin (adipokines) predict sepsis development and if intra-individual changes in circulating levels from baseline to the acute phase affect outcome.

    Method: A nested case-referent study within the framework of the Northern Sweden Health and Disease Study (NSHDS) and the Northern Sweden Maternity Cohort (NSMC). Patients aged 18 years or more with documented sepsis within 24 hours after admission to the intensive care unit (ICU) were included if they had participated in a health survey and donated blood samples prior to the sepsis event, and if possible also had stored plasma from the acute phase. Two matched referents free of known sepsis were selected for each case. Baseline and acute phase plasma leptin and adiponectin levels were determined. The associations between adipokines and sepsis and its severity and outcome were determined.

    Results: We identified 57 men and 97 women with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in the health survey, and 83% of them had also samples from the acute septic phase. Hyperleptinemia associated with a future sepsis event (OR 1.77, 95% CI 1.04-3.00, P=0.03), with stronger associations with severe sepsis and septic shock than with sepsis. High leptin levels were also associated with hospital death in the fully adjusted model. Leptin remained associated with sepsis in men (P=0.02), but not in women (P=0.36), after stratification and adjustment for BMI. In the acute phase, leptin increased more in men than in women (P=0.001), and high leptin levels were associated with increased risk for in-hospital death in women (OR 4.18, 95%CI 1.17-15.00, P=0.03), while being protective in men (OR 0.05, 95% CI 0.01-0.48, P=0.01). Adiponectin did not associate with sepsis or outcome.

    Conclusions: Hyperleptinemia independently predicted the development of sepsis, and an unfavourable outcome in men. Adiponectin was not associated with sepsis development.

  • 25.
    Jacobson, Sofie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Åberg, Anna-Maja
    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.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Levels of mannose-binding lectin (MBL) predicts sepsis and associates with sepsis-related in-hospital mortality differentially in men and womenManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: To determine if levels of mannose-binding lectin (MBL) predict sepsis development and if intra-individual changes in circulating levels from baseline to the acute septic phase associate with in-hospital mortality.

    Method: A nested case-referent study within the framework of the Northern Sweden Health and Disease Study (NSHDS) and the Northern Sweden Maternity Cohort (NSMC). Patients aged 18 years or more with documented sepsis within 24 hours after admission to the intensive care unit were included if they had participated in a health survey and donated blood samples prior to the sepsis event. A subset of these patients had stored plasma also from the acute phase. Two matched referents free of known sepsis were selected for each case. Baseline and acute phase plasma MBL levels were determined. The association between MBL and sepsis, sepsis severity and in-hospital mortality were determined.

    Results: We identified 57 men and 95 women with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in a health survey, of which 127 also had samples from the acute septic phase. High baseline levels predicted future sepsis (OR 1.81, 95% CI 1.01-3.26), but were not associated with severity of sepsis or in-hospital fatality. Both high MBL levels in the acute phase (OR 4.94, 95% CI 1.44-16.89), and an increase from base line to the acute phase (OR 3.67, 95% CI 1.19-11.28) were associated with increased risk for in-hospital death in women, but not in men (OR 0.71, 95% CI 0.18-2.88). Low levels at baseline were not associated with future sepsis. Neither low levels at baseline, nor in the acute phase were associated with sepsis severity or in-hospital mortality.

    Conclusions: High pre-sepsis levels predicted a future sepsis event, and an increase from baseline to the acute phase as well as high levels in the acute phase associated with an unfavourable outcome in women.

  • 26.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Jonsson, Mari
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Marttila, Marko
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Persson, David
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Fan, Xiao-Long
    Skog, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Frängsmyr, Lars
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Adenoviruses use lactoferrin as a bridge for CAR-independent binding to and infection of epithelial cells2007In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 81, no 2, p. 954-963Article in journal (Refereed)
    Abstract [en]

    Most adenoviruses bind to the coxsackie- and adenovirus receptor (CAR). Surprisingly, CAR is not expressed apically on polarized cells and is thus not easily available to viruses. Consequently, alternative mechanisms for entry of coxsackievirus and adenovirus into cells have been suggested. We have found that tear fluid promotes adenovirus infection, and we have identified human lactoferrin (HLf) as the tear fluid component responsible for this effect. HLf alone was found to promote binding of adenovirus to epithelial cells in a dose-dependent manner and also infection of epithelial cells by adenovirus. HLf was also found to promote gene delivery from an adenovirus-based vector. The mechanism takes place at the binding stage and functions independently of CAR. Thus, we have identified a novel binding mechanism whereby adenovirus hijacks HLf, a component of the innate immune system, and uses it as a bridge for attachment to host cells.

  • 27.
    Johansson, Susanne M C
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kihlberg, Jan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Multivalent HSA conjugates of 3 '-siallyllactose are potent inhibitors of adenoviral cell attachment and infection2005In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 6, no 2, p. 358-364Article in journal (Refereed)
    Abstract [en]

    Adenoviruses of serotypes 8, 19 and 37 are the major cause of the severe eye infection EKC (epidemic keratoconjunctivitis). In general, all adenoviruses interact with their cellular receptors through the fibre proteins, which extend from the virus particle. Recently, adenovirus type 37 (Ad37) was found to bind and infect human corneal cells through attachment to carbohydrate structures that carry terminal alpha-(2-3)-linked sialic acids. Herein we present a synthetic route to a 3'-sialyllactose derivative and corresponding multivalent HSA conjugates with varying orders of valency. The potential of these compounds as inhibitors of EKC causing adenovirus of serotype Ad37, was studied with both binding assay and an infectivity assay. The results revealed that these compounds effectively prevent Ad37 from binding to and infecting human corneal epithelial (HCE) cells. Moreover, the inhibition is significantly increased with higher orders of multivalency.

  • 28. Kapeu, Aline Simen
    et al.
    Luostarinen, Tapio
    Jellum, Egil
    Dillner, Joakim
    Hakama, Matti
    Koskela, Pentti
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Löve, Arthur
    Mahlamaki, Eija
    Thoresen, Steinar
    Tryggvadóttir, Laufey
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Youngman, Linda
    Lehtinen, Matti
    Is smoking an independent risk factor for invasive cervical cancer?: A nested case-control study within Nordic biobanks2009In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 169, no 4, p. 480-488Article in journal (Refereed)
    Abstract [en]

    The strong correlation between smoking and exposure to oncogenic human papillomaviruses (HPVs) has made it difficult to verify the independent role of smoking in cervical carcinogenesis. Thus, the authors evaluated this role. Five large Nordic serum banks containing samples from more than 1,000,000 subjects were linked with nationwide cancer registries (1973-2003). Serum samples were retrieved from 588 women who developed invasive cervical cancer and 2,861 matched controls. The samples were analyzed for cotinine (a biomarker of tobacco exposure) and antibodies to HPV types 16 and 18, herpes simplex virus type 2, and Chlamydia trachomatis. Smoking was associated with the risk of squamous cell carcinoma (SCC) among HPV16- and/or HPV18-seropositive heavy smokers (odds ratio=2.7, 95% confidence interval: 1.7, 4.3). A similar risk of SCC (odds ratio=3.2, 95% confidence interval: 2.6, 4.0) was found in heavy smokers after adjustment for HPV16/18 antibodies. The point estimates increased with increasing age at diagnosis and increasing cotinine level. This study confirms that smoking is an independent risk factor for cervical cancer/SCC in women infected with oncogenic HPVs. These findings emphasize the importance of cervical cancer prevention among women exposed to tobacco smoke.

  • 29. Kjellberg, L
    et al.
    Hallmans, G
    Ahren, A M
    Johansson, R
    Bergman, F
    Wadell, G
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Angström, T
    Dillner, J
    Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection.2000In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 82, no 7, p. 1332-8Article in journal (Refereed)
    Abstract [en]

    Smoking, nutrition, parity and oral contraceptive use have been reported as major environmental risk factors for cervical cancer. After the discovery of the very strong link between human papillomavirus (HPV) infection and cervical cancer, it is unclear whether the association of these environmental factors with cervical cancer reflect secondary associations attributable to confounding by HPV, if they are independent risk factors or whether they may act as cofactors to HPV infection in cervical carcinogenesis. To investigate this issue, we performed a population-based case-control study in the Vasterbotten county of Northern Sweden of 137 women with high-grade cervical intra-epithelial neoplasia (CIN 2-3) and 253 healthy age-matched women. The women answered a 94-item questionnaire on diet, smoking, oral contraceptive use and sexual history and donated specimens for diagnosis of present HPV infection (nested polymerase chain reaction on cervical brush samples) and for past or present HPV infections (HPV seropositivity). The previously described protective effects of dietary micronutrients were not detected. Pregnancy appeared to be a risk factor in the multivariate analysis (P < 0.0001). Prolonged oral contraceptive use and sexual history were associated with CIN 2-3 in univariate analysis, but these associations lost significance after taking HPV into account. Smoking was associated with CIN 2-3 (odds ratio (OR) 2.6, 95% confidence interval (CI) 1.7-4.0), the effect was dose-dependent (P = 0.002) and the smoking-associated risk was not affected by adjusting for HPV, neither when adjusting for HPV DNA (OR 2.5, CI 1.3-4.9) nor when adjusting for HPV seropositivity (OR 3.0, CI 1.9-4.7). In conclusion, after taking HPV into account, smoking appeared to be the most significant environmental risk factor for cervical neoplasia.

  • 30. Kjellberg, L
    et al.
    Wadell, G
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergman, F
    Isaksson, M
    Angström, T
    Dillner, J
    Regular disappearance of the human papillomavirus genome after conization of cervical dysplasia by carbon dioxide laser.2000In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 183, no 5, p. 1238-42Article in journal (Refereed)
    Abstract [en]

    The human papillomavirus genome present before treatment was regularly cleared, and there was also no recurrence of dysplasia. The results suggest that human papillomavirus testing is useful for monitoring the efficacy of treatment and that treatment modalities resulting in clearance of human papillomavirus should be favored.

  • 31.
    Kokkonen, Heidi
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Mullazehi, Mohammed
    Division of Clinical Immunology, Uppsala University, 751 85 Uppsala, Sweden.
    Berglin, Ewa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Rönnelid, Johan
    Division of Clinical Immunology, Uppsala University, 751 85 Uppsala, Sweden.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis2011In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 13, no 1, p. R13-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We and others have previously shown that antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and in a more recent study we reported that individuals who subsequently developed RA had increased concentrations of several cytokines and chemokines years before the onset of symptoms of joint disease. Here we aimed to evaluate the prevalence and predictive values of anti-CCP antibodies of IgG, IgM and IgA isotype in individuals who subsequently developed RA and also to relate these to cytokines and chemokines, smoking, genetic factors and radiographic score.

    METHODS: A case-control study (1:4 ratio) was nested within the Medical Biobank and the Maternity cohorts of Northern Sweden. Patients with RA were identified from blood donors predating the onset of disease by years. Matched controls were selected randomly from the same registers. IgG, IgA and IgM anti-CCP2 antibodies were determined using EliA anti-CCP assay on ImmunoCAP 250 (Phadia AB, Uppsala, Sweden).

    RESULTS: Of 86 patients with RA identified as blood donors prior to the onset of symptoms, samples were available from 71 for analyses. The median (Q1 to Q3) predating time was 2.5 years (1.1 to 5.9 years). The sensitivity of anti-CCP antibodies in the pre-patient samples was 35.2% for IgG, 23.9% for IgA, and 11.8% for IgM. The presence of IgG and IgA anti-CCP antibodies was highly significant compared with controls. IgG and IgA anti-CCP2 predicted RA significantly in conditional logistic regression models odds ratio (OR) = 94.1, 95% confidence interval (CI) 12.7 to 695.4 and OR = 11.1, 95% CI 4.4 to 28.1, respectively, the IgM anti-CCP showed borderline significance OR = 2.5 95% CI 0.9 to 6.3. Concentrations of all anti-CCP isotypes increased the closer to the onset of symptoms the samples were collected with an earlier and higher increase for IgG and IgA compared with IgM anti-CCP. IgA and IgG anti-CCP positive individuals had different patterns of up-regulated chemokines and also, smoking brought forward the appearance of IgA anti-CCP antibodies in pre-RA individuals.

    CONCLUSIONS: Anti-CCP2 antibodies of both the IgG and IgA isotypes pre-dated the onset of RA by years; also, both IgG and IgA anti-CCP2 antibodies predicted the development of RA, with the highest predictive value for IgG anti-CCP2 antibodies.

  • 32.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Zeleniuch-Jacquotte, Anne
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Arslan, Alan A
    Afanasyeva, Yelena
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. null.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. null.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. null.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. null.
    Insulin-like growth factor I in pregnancy and maternal risk of breast cancer2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 12, p. 2489-2493Article in journal (Refereed)
    Abstract [en]

    Background: The role of insulin-like growth factor (IGF)-I in breast cancer remains controversial, despite numerous reports on the association of the hormone with breast cancer or high-risk mammographic densities. We hypothesized that exposure to elevated IGF-I during early pregnancy, a period characterized by intense cell proliferation in the breasts and in the presence of high concentrations of sex steroids, will be associated with increased maternal risk to develop a breast malignancy.

    Methods: The Northern Sweden Maternity Cohort is an ongoing prospective study, collecting blood samples from first-trimester-pregnant women since 1975 as part of screening for infectious diseases. A case-control study (212 cases and 369 controls) was nested among Northern Sweden Maternity Cohort members who delivered singleton babies. RIA was used to measure IGF-I and IGF-II levels. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).

    Results: Breast cancer risk increased with increasing IGF-I (top tertile OR, 1.7; 95% CI, 1.1-2.7). The association was stronger among the primiparous (OR, 2.2; 95% CI, 1.1-4.4) than in the nonprimiparous women (OR, 1.4; 95% CI, 0.7-2.8). Upper-tertile risks seemed to decrease within the <28-, 28 to 33, and >33-year groups of age at sampling, from 2.5 (0.9-7.6) to 2.1 (0.9-5.0) and 1.2 (0.5-2.5), respectively. There was no association of breast cancer with first-trimester-pregnancy IGF-II.

    Conclusions: The study offers further evidence that IGF-I is important in breast cancer. Our findings suggest that the adverse effect of IGF-I on the breast may be stronger before the remodeling of the gland induced by a first pregnancy.

  • 33.
    Luostarinen, T.
    et al.
    Finnish Cancer Registry, Helsinki, Finland.
    Dahlstrom, L. A.
    MEB, Karolinska Institutet, Stockholm, Sweden.
    Andersson, K.
    Department of Laboratory Medicine, Medical Microbiology, Lund University, Malmö, Sweden.
    Ogmundsdottir, H.
    Cancer Research Laboratory, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
    Jellum, E.
    Institute of Clinical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
    Koskela, P.
    National Institute for Health and Welfare, Oulu, Finland.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lehtinen, M.
    University of Tampere, Tampere, Finland.
    Dillner, J.
    Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Human papillomavirus, other sexually transmitted infections and risk of cervical cancer: A Nordic Joint Study2011In: IEA World Congress of Epidemiology, 7–11 August 2011, Edinburgh International Conference Centre, Edinburgh, Scotland: Programme and abstracts, 2011, Vol. 65, p. A266-Conference paper (Refereed)
    Abstract [en]

    Introduction: Human papillomavirus (HPV) is considered necessary cause of invasive cervical cancer (ICC), but relations between different HPV types and other sexually transmitted infections in cervical carcinogenesis are unresolved. The CCRPB-EU Network conducted a large study, aiming to assess how major high- and low-risk HPV types, 16, 18 and 6, and possible cofactors, Chlamydia trachomatis and herpes simplex virus type 2 (HSV-2), interact in the aetiology of cervical cancer.

    Methods: A case-control study was nested in four Nordic serum banks containing serum samples from approximately 1 000 000 women. Linkage to cancer registries resulted to 604 ICC cases diagnosed after serum sampling. Five controls were matched to bank, age at sampling and storage time. IgG antibodies specific for HPV types, C trachomatis and HSV-2 were determined, and tobacco smoke exposure measured by serum cotinine, and HPV DNA in cancer tissue PCR-tested. ORs were estimated by conditional logistic regression, and adjusted for cotinine and for HPV16, HPV18 and C trachomatis, when applicable.

    Results: Seropositivity for HPV16 did not confer any increased risk for HPV18 DNA positive cancer and HPV18 seropositivity had no association with HPV16 DNA positive cancer. HPV6 had no effect on its own but an antagonistic joint effect with HPV16. HSV-2 had little or no association. C trachomatis had a strongly increased risk for cervical cancer, which remained also among HPV18 seropositives.

    Conclusions: Type-specific HPV DNA persistence is important in cervical carcinogenesis. HSV-2 is possibly not a cofactor, but C trachomatis is probably a strong cofactor for ICC.

  • 34.
    Marttila, Marko
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Persson, David
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Gustafsson, Dan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Liszewski, M Kathryn
    Atkinson, John P
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    CD46 is a cellular receptor for all species B adenoviruses except types 3 and 72005In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 79, no 22, p. 14429-14436Article in journal (Refereed)
    Abstract [en]

    The 51 human adenovirus serotypes are divided into six species (A to F). Adenovirus serotypes from all species except species B utilize the coxsackie-adenovirus receptor for attachment to host cells in vitro. Species B adenoviruses primarily cause ocular and respiratory tract infections, but certain serotypes are also associated with renal disease. We have previously demonstrated that adenovirus type 11 (species B) uses CD46 (membrane cofactor protein) as a cellular receptor instead of the coxsackie-adenovirus receptor (A. Segerman et al., J. Virol. 77:9183-9191, 2003). In the present study, we found that transfection with human CD46 cDNA rendered poorly permissive Chinese hamster ovary cells more permissive to infection by all species B adenovirus serotypes except adenovirus types 3 and 7. Moreover, rabbit antiserum against human CD46 blocked or efficiently inhibited all species B serotypes except adenovirus types 3 and 7 from infecting human A549 cells. We also sequenced the gene encoding the fiber protein of adenovirus type 50 (species B) and compared it with the corresponding amino acid sequences from selected serotypes, including all other serotypes of species B. From the results obtained, we conclude that CD46 is a major cellular receptor on A549 cells for all species B adenoviruses except types 3 and 7.

  • 35.
    Mei, Ya-fang
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Harrach, Balzs
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Mastadenovirus: adenoviridae2012In: The Springer Index of Viruses / [ed] Christian Tidona, Gholamreza Darai, New York: Springer Science+Business Media B.V., 2012, p. 33-48Chapter in book (Refereed)
  • 36.
    Mei, Ya-Fang
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lindman, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Human adenoviruses of subgenera B, C, and E with various tropisms differ in both binding to and replication in the epithelial A549 and 293 cells2002In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 295, no 1, p. 30-43Article in journal (Refereed)
    Abstract [en]

    Adenoviruses of six subgenera, namely, adenovirus 31 (Ad31) (subgenus A), Ad3, Ad7, Ad11p, Ad11a, and Ad35 (subgenus B), Ad5v and Ad5p (subgenus C), Ad37 (subgenus D), Ad4 (subgenus E), and Ad41 (subgenus F), were studied. The relative binding properties of different adenoviruses to 293 (human kidney embryonic cells) and A549 (human lung carcinoma cells) cells were compared by flow cytometry. All analyzed adenoviruses bound to cells in a dose-dependent manner. The binding capacity showed that Ad11p, Ad35 (subgenus B:2) with kidney tropism, and Ad4 (subgenus E), which can cause adenopharyngoconjunctivitis, bound strongly to both A549 and 293 cells. The other members of subgenus B and Ad37 of subgenus D manifested an intermediate binding capacity. The analyzed adenoviruses of subgenera A, C, and F manifested a low affinity. Adenoviruses of subgenera B:2 and E manifested high binding affinity to preparations of cell membranes from the epithelial cell lines. Reciprocal competition experiments using Ad11p and Ad4 demonstrated that the two viruses did not block each other. Antibodies against alphavbeta3 and alphavbeta5 reduced the binding of Ad5v virions and slightly impaired the binding of Ad4 but did not affect Ad11p binding to the A549 cell surface. Recombinant fiber proteins of Ad11p and Ad35 reciprocally blocked the binding of both viruses to the epithelial cells but they could not block Ad4. The hexon protein expression of Ad11p and Ad4 was 100 times more efficient than that of the Ad5 vector (pFG140), whereas the infectivity of Ad11p and Ad4 was 40- to 200-fold that of the commonly used Ad5v vector. Taken together, our findings demonstrate that Ad11p and Ad4 bind different receptor molecules and that the fibers of these two viruses provide the predominant high degree of binding, which obviously is a requirement for subsequent internalization and efficacious expression.

  • 37.
    Mei, Ya-Fang
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Segerman, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lindman, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Hörnsten, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Human hematopoietic (CD34+) stem cells possess high-affinity receptors for adenovirus type 11p2004In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 328, no 2, p. 198-207Article in journal (Refereed)
    Abstract [en]

    Gene transfer into human hematopoietic stem cells using Ad5 is inefficient due to lack of the primary receptor CAR and the secondary receptors alphavbeta3 integrin and alphavbeta5 integrin, and due to the high seroprevalence of Ad5 antibodies in most adults, resulting in diminished gene transduction. In the present study, we screened six species (species A-F) of adenovirus, displaying different tropisms for interaction with CD34+ cells, at the level of virus attachment and expression. Virus particles were biotinylated and their binding capacity was determined by FACS analysis using streptavidin-FITC. Ad11p, Ad35, and Ad3 (species B) showed high binding affinity, while Ad7, Ad11a (species B), and Ad37 (species D) displayed intermediate affinity. Virions of Ad4 (species E), Ad5 (species C), Ad31 (species A), and Ad41 (species F) hardly bound to hematopoietic progenitor cells. Using a double-labeling system, we demonstrated that adenoviruses bind to quiescent CD34+ cells. Ad11p virions showed the highest affinity among the adenoviruses detected. We further confirmed that virus fiber-specific receptors were present on the hematopoietic progenitor cell surface, because both recombinant fiber of Ad11p and specific antiserum against rfiber could block virus attachment. The ability of the adenoviruses to infect hematopoietic cells was studied by immunofluorescence staining. The adenoviruses from species B and Ad37 showed higher infectivity than Ad31, Ad5, Ad4, and Ad41. Among the studied species B adenoviruses, Ad11p manifested a superior infectivity. Thus, we have confirmed that these cells have high-affinity receptors for species B:2 human adenovirus, Ad11p, and this virus may be used as candidate vector to target therapeutic genes to hematopoietic stem cells.

  • 38.
    Mei, Ya-Fang
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Skog, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lindman, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Comparative analysis of the genome organization of human adenovirus 11, a member of the human adenovirus species B, and the commonly used human adenovirus 5 vector, a member of species C2003In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 84, no 8, p. 2061-2071Article in journal (Refereed)
    Abstract [en]

    Adenovirus type 11 (Ad11), a member of the human adenovirus species B (HAdV-B), has a tropism for the urinary tract. The genome of Ad11 was found to comprise 34 794 bp and is 1141 bp shorter than the Ad5 genome of species HAdV-C. The G+C content of the Ad11 genome is 48.9 %, whereas that of Ad5 is 55.2 %. Ad11 and Ad5 share 57 % nucleotide identity and possess the same four early regions, but the E3 region of Ad11 could not be divided into E3A and E3B. The late genes of Ad11 and Ad5 are organized into six and five regions, respectively. Thirty-eight putative ORFs were identified in the Ad11 genome. The ORFs in the late regions, the E2B region and IVa2 show high amino acid identity between Ad11 and Ad5, whereas the ORFs in E1, E2A, E3 and E4, protein IX and the fibre protein show low amino acid identity. The highest and lowest identities were noted in the pre-terminal protein and fibre proteins: 85 % and 24.6 %, respectively. The E3 20.3K and 20.6K ORFs and the L6 agnoprotein were present in the Ad11 genome only, whereas the E3 11.6K cell death protein was identified only in Ad5. All ORFs but the E3 10.3K and L4 pVIII protein vary not only in composition but also in size. Ad11 may have a higher vector capacity than Ad5, since it has a shorter genome and a shorter fibre. Furthermore, in the E3 region, two additional ORFs can be deleted to give extra capacity for foreign DNA.

  • 39. Naucler, P
    et al.
    Ryd, W
    Törnberg, S
    Strand, A
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Hansson, B G
    Rylander, E
    Dillner, J
    HPV type-specific risks of high-grade CIN during 4 years of follow-up: a population-based prospective study.2007In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 97, no 1, p. 129-32Article in journal (Refereed)
    Abstract [en]

    We followed a population-based cohort of 5696 women, 32-38 years of age, by registry linkage with cytology and pathology registries during a mean follow-up time of 4.1 years to assess the importance for CIN2+ development of type-specific HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and were responsible for 33.1, 18.3 and 7.7% of CIN2+ cases, respectively. Women infected with HPV 18, 35, 39, 45, 51, 52, 56, 58, 59 and 66 had significantly lower risks of CIN2+ than women infected with HPV 16. After adjustment for infection with other HPV types, HPV types 35, 45, 59 and 66 had no detectable association with CIN2+. In summary, the different HPV types found in cervical cancer show distinctly different CIN2+ risks, with high risks being restricted to HPV 16 and its close relatives HPV 31 and HPV 33.

  • 40. Naucler, Pontus
    et al.
    Ryd, Walter
    Törnberg, Sven
    Strand, Anders
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elfgren, Kristina
    Rådberg, Thomas
    Strander, Björn
    Forslund, Ola
    Hansson, Bengt-Göran
    Hagmar, Björn
    Johansson, Bo
    Rylander, Eva
    Dillner, Joakim
    Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening.2009In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 101, no 2, p. 88-99Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective. METHODS: We used the database from the intervention arm (n = 6,257 women) of a population-based randomized trial of double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone, cytology alone, and HPV DNA testing combined with cytology among women aged 32-38 years. The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value (PPV) for each screening strategy. All statistical tests were two-sided. RESULTS: Compared with screening by cytology alone, double testing with cytology and for type-specific HPV persistence resulted in a 35% (95% confidence interval [CI] = 15% to 60%) increase in sensitivity to detect CIN3+, without a statistically significant reduction in the PPV (relative PPV = 0.76, 95% CI = 0.52 to 1.10), but with more than twice as many screening tests needed. Several strategies that incorporated screening for high-risk HPV subtypes were explored, but they resulted in reduced PPV compared with cytology. Compared with cytology, primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3+ sensitivity by 30% (95% CI = 9% to 54%), maintained a high PPV (relative PPV = 0.87, 95% CI = 0.60 to 1.26), and resulted in a mere 12% increase in the number of screening tests (from 6,257 to 7,019 tests). CONCLUSIONS: Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy.

  • 41. Naucler, Pontus
    et al.
    Ryd, Walter
    Törnberg, Sven
    Strand, Anders
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elfgren, Kristina
    Rådberg, Thomas
    Strander, Björn
    Johansson, Bo
    Forslund, Ola
    Hansson, Bengt-Göran
    Rylander, Eva
    Dillner, Joakim
    Human papillomavirus and Papanicolaou tests to screen for cervical cancer2007In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 357, no 16, p. 1589-1597Article in journal (Refereed)
    Abstract [en]

    Background: Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown.

    Methods: In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated.

    Results: At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy.

    Conclusions: The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.

  • 42. Nelson, J H
    et al.
    Hawkins, G A
    Edlund, K
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Evander, M
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kjellberg, L
    Wadell, G
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Dillner, J
    Gerasimova, T
    Coker, A L
    Pirisi, L
    Petereit, D
    Lambert, P F
    A novel and rapid PCR-based method for genotyping human papillomaviruses in clinical samples.2000In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 38, no 2, p. 688-95Article in journal (Refereed)
    Abstract [en]

    Many human papillomavirus (HPV) genotypes are associated with cervical carcinoma. We demonstrate the utility of an innovative technique for genotyping of HPV in cervical tissue samples. This method provides an accurate means of identification of the specific HPV genotypes present in clinical specimens. By using the MY09-MY11 and the GP5(+)-GP6(+) consensus primer pairs, HPV sequences were amplified by nested PCR from DNA isolated from cervical smear samples. This led to the production of an approximately 140-bp PCR product from the L1 (major capsid) gene of any of the HPVs present in the sample. PCR was performed with a deoxynucleoside triphosphate mixture which resulted in the incorporation of deoxyuridine into the amplified DNA product at positions where deoxythymidine would normally be incorporated at a frequency of about once or twice per strand. Following the PCR, the product was treated with an enzyme mix that contains uracil N-glycosylase (UNG) and endonuclease IV. UNG removes the uracil base from the nucleotide, and endonuclease IV cleaves the phosphodiester bond at this newly formed abasic site, producing fragments of various sizes. By having end labeled one of the amplification primers, a DNA ladder which is analogous to a "T-sequencing ladder" was produced upon electrophoresis of the products. By comparing this T-sequencing ladder to the known sequences of HPVs, the genotypes of unknown HPV isolates in samples were assigned. Data showing the utility of this technique for the rapid analysis of clinical samples are presented.

  • 43. Pukkala, Eero
    et al.
    Andersen, Aage
    Berglund, Göran
    Gislefoss, Randi
    Gudnason, Vilmundur
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jellum, Egil
    Jousilahti, Pekka
    Knekt, Paul
    Koskela, Pentti
    Kyyrönen, P Pentti
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Luostarinen, Tapio
    Löve, Arthur
    Ögmundsdóttir, Helga
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Tenkanen, Leena
    Tryggvadóttir, Laufey
    Virtamo, Jarmo
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Virologi.
    Widell, Anders
    Lehtinen, Matti
    Dillner, Joakim
    Nordic biological specimen banks as basis for studies of cancer causes and control - more than 2 million sample donors, 25 million person years and 100 000 prospective cancers.2007In: Acta Oncol, ISSN 0284-186X, Vol. 46, no 3, p. 286-307Article in journal (Refereed)
  • 44. Rantapää-Dahlqvist, Solbritt
    et al.
    de Jong, Ben AW
    Berglin, Ewa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Hallmans, Göran
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Stenlund, Hans
    Sundin, Ulf
    van Venrooij, Walther J
    Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis.2003In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 48, no 10, p. 2741-2749Article in journal (Refereed)
  • 45.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Smoking as a risk factor for multiple sclerosis2013In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 8, p. 1022-1027Article in journal (Refereed)
    Abstract [en]

    Background: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure.

    Objective: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples.

    Methods: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression.

    Results: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0–2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3–3.8).

    Conclusions: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.

  • 46.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vitamin A and systemic inflammation as protective factors in multiple sclerosis2013In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 8, p. 1046-1051Article in journal (Refereed)
    Abstract [en]

    Background: Vitamin A is important for the immune system, and might suppress inflammatory activity in multiple sclerosis (MS).

    Objectives: We aimed to examine if vitamin A levels were associated with MS risk in samples collected prospectively and during gestation.

    Methods: We measured Retinol Binding Protein (RBP – a surrogate marker for vitamin A) and high-sensitivity C-reactive protein (hs-CRP) levels, in (1) prospectively collected biobank blood samples from MS cases and controls, and (2) gestational samples where the offspring had later developed MS, and gestational control samples. The risk of MS was calculated using matched multivariable logistic regression adjusted for confounders.

    Results: In prospective samples, RBP levels within the second quintile (vs. the first) were associated with a lower MS risk (OR = 0.38, 95% CI 0.19–0.74). No effect on MS risk in the offspring by gestational RBP levels was found. In young subjects hs-CRP levels ≥10 mg/l in prospective samples were associated with a lower MS risk (OR = 0.36, 95% CI 0.14–0.95).

    Conclusions: Our results suggest that sub-optimal vitamin A levels may be associated with MS risk. The association between hs-CRP levels and MS risk in young subjects may support the role of the hygiene hypothesis in MS aetiology. 

  • 47.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vitamin D as a protective factor in multiple sclerosis2012In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, no 21, p. 2140-2145Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the association between 25-hydroxyvitamin D (25[OH]D) levels and the risk of multiple sclerosis (MS) in blood samples collected prospectively and during gestation.

    Methods: In this nested case-control study, 2 population-based biobanks with 291,500 samples from164,000 persons collected since 1975 in the northern half of Sweden were used. We identified prospectively collected blood samples from MS cases (n = 192, controls matched 2:1) and gestational samples from pregnant mothers where the offspring had later developed MS (n = 37, control mothers matched 5:1). 25(OH)D levels were measured using an ELISA, and the risk of MS was analyzed using matched logistic regression.

    Results: Levels of 25(OH)D ≥75 (vs <75) nmol/L in prospectively collected blood samples were associated with a decreased risk of MS (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.16- 0.98). No decrease in MS risk was found in the offspring exposed to gestational 25(OH)D levels ≥75 (vs <75) nmol/L (OR 1.8, 95%CI 0.53-5.8). The prevalence of 25(OH)D levels ≥75 nmol/L in female controls decreased gradually during 1976-2005 (p trend = 0.005).

    Conclusion: This study supports the presence of an association between high 25(OH)D levels during the years preceding disease onset and a decreased risk of MS. In the very limited material with samples drawn in early pregnancy, where month-of-birth effects were controlled for, we found no association between gestational 25(OH)D levels and MS risk in the offspring. Decreasing 25(OH) D levels in the population may contribute to explain the increasing MS incidence that is suggested from epidemiologic studies.

  • 48.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank sampels2013In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 12, p. 1587-1591Article in journal (Refereed)
    Abstract [en]

    Background: Increased antibody reactivity against Epstein-Barr Nuclear Antigen-1 (EBNA-1) has been associated with an increased risk for MS, and high levels of 25-Hydroxyvitamin D (25[OH]D) have been associated with a lower risk for MS. Interaction between these two factors has been proposed.

    Objectives: To examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk for multiple sclerosis (MS), and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.

    Methods: Antibody reactivity (as specified above) and 25(OH)D levels were measured using ELISAs in n=192 MS cases and n=384 matched controls. The risk for MS was analysed using matched logistic regression.

    Results: The risk for MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402–502, and domain EBNA-1385–420; p trend <0.001. The risk increase was most pronounced for EBNA-1385–420. In young individuals (below median age at sampling, <26.4 years) these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains.

    Conclusions: We confirm that increased antibody reactivity against EBNA-1 is a risk factor for MS. Our findings in young individuals suggest that 25(OH)D status might influence the immune response towards Epstein-Barr virus, and thereby modulate MS risk.

  • 49.
    Segerman, A
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Mei, Y F
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, G
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Adenovirus types 11p and 35p show high binding efficiencies for committed hematopoietic cell lines and are infective to these cell lines.2000In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 74, no 3, p. 1457-67Article in journal (Refereed)
    Abstract [en]

    Hematopoietic cells are attractive targets for gene therapy. However, no satisfactory vectors are currently available. A major problem with the most commonly used adenovirus vectors, based on adenovirus type 2 (Ad2) or Ad5, is their low binding efficiency for hematopoietic cells. In this study we identify two adenovirus serotypes with high affinity for hematopoietic cells. The binding efficiency of prototype serotypes Ad4p, Ad11p, and Ad35p for different committed hematopoietic cell lines representing T cells (Jurkat), B cells (DG75), monocytes (U937-2), myeloblasts (K562), and granulocytes (HL-60) was evaluated and compared to that of Ad5v, the commonly used adenovirus vector, using flow cytometry. In contrast to Ad5v, which bound to less than 10% of the cells in all experiments, Ad11p and Ad35p showed high binding efficiency for all of the different hematopoietic cell lines. Ad4p bound to the lymphocytic cell lines to some extent but less well to the myelomonocytic cell lines. The abilities of the different serotypes to infect, replicate, and form complete infectious particles in the hematopoietic cell lines were also investigated by immunostaining, (35)S labeling of viral proteins, and titrations of cell lysates. Ad11p and Ad35p infected the highest proportion of cells, and Ad11p infected all of the cell lines investigated. The Ad11p hexon was expressed equally well in K562 and A549 cells. Jurkat cells also showed high levels of expression of Ad11p hexons, but the production of infectious particles was low. The binding properties of virions were correlated to their ability to infect and be expressed.

  • 50.
    Segerman, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Erikson, Anders
    Lindman, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    There Are Two Different Species B Adenovirus Receptors: sBAR, Common to Species B1 and B2 Adenoviruses, and sB2AR, Exclusively Used by Species B2 Adenoviruses: THERE ARE TWO DIFFERENT SPECIES B ADENOVIRUS RECEPTORS2003In: Journal of Virology, ISSN 0022-538X, Vol. 77, no 2, p. 1157-1162Article in journal (Refereed)
12 1 - 50 of 65
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf