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  • 1.
    Alexeyev, Oleg
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Is there evidence for a role of Propionibacterium acnes in prostatic disease?2009In: Urology, ISSN 1527-9995, Vol. 73, no 2, p. 220-224Article in journal (Refereed)
  • 2.
    Bergh Drott, Johanna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Alexeyev, Oleg
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergström, Patrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Propionibacterium acnes infection induces upregulation of inflammatory genes and cytokine secretion in prostate epithelial cells2010In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 10, p. 126-Article in journal (Refereed)
    Abstract [en]

    Background: The immune stimulating bacterium Propionibacterium acnes is a frequent colonizer of benign and malignant prostate tissue. To understand the pathogenesis of the earliest phase of this infection, we examined the P. acnes triggered immune response in cultivated prostate epithelial cells.

    Results: Prostate epithelial cells are triggered to secrete IL-6, IL-8 and GM-CSF when infected with P. acnes. The secretion of cytokines is accompanied by NFκB related upregulation of the secreted cytokines as well as several components of the TLR2-NFκB signaling pathway.

    Conclusions: P. acnes has potential to trigger a strong immune reaction in the prostate glandular epithelium. Upon infection of prostate via the retrograde urethral route, the induced inflammatory reaction might facilitate bacterial colonization deeper in the prostate tissue where persistent inflammation may impact the development of prostate diseases as hyperplasia and/or malignancy.

  • 3.
    Bergh Drott, Johanna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Rudolfsson, Stina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Propionibacterium acnes induces chronic inflammation and precancerous epithelial lesions in the dorso-lateral prostate in ratsManuscript (preprint) (Other academic)
  • 4. Davidsson, Sabina
    et al.
    Söderquist, Bo
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Andrén, Ove
    Unemo, Magnus
    Mölling, Paula
    Multilocus sequence typing and repetitive-sequence-based PCR (DiversiLab) for molecular epidemiological characterization of Propionibacterium acnes isolates of heterogeneous origin2012In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 18, no 4, p. 392-399Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes is a gram-positive bacillus predominantly found on the skin. Although it is considered an opportunistic pathogen it is also been associated with severe infections. Some specific P. acnes subtypes are hypothesized to be more prone to cause infection than others. Thus, the aim of the present study was to investigate the ability to discriminate between P. acnes isolates of a refined multilocus sequence typing (MLST) method and a genotyping method, DiversiLab, based on repetitive-sequence-PCR technology. The MLST and DiversiLab analysis were performed on 29 P. acnes isolates of diverse origins; orthopedic implant infections, deep infections following cardiothoracic surgery, skin, and isolates from perioperative tissue samples from prostate cancer. Subtyping was based on recA, tly, and Tc12S sequences. The MLST analysis identified 23 sequence types and displayed a superior ability to discriminate P. acnes isolates compared to DiversiLab and the subtyping. The highest discriminatory index was found when using seven genes. DiversiLab was better able to differentiate the isolates compared to the MLST clonal complexes of sequence types. Our results suggest that DiversiLab can be useful as a rapid typing tool for initial discrimination of P. acnes isolates. When better discrimination is required, such as for investigations of the heterogeneity of P. acnes isolates and its involvement in different pathogenic processes, the present MLST protocol is valuable.

  • 5.
    Edqvist, Petra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Olsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Lavander, Moa
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Department of Microbiology, National Defense Research Agency, S-90182 Umeå.
    Sundberg, Lena
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Department of Microbiology, National Defense Research Agency, S-90182 Umeå.
    Forsberg, Åke
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Department of Microbiology, National Defense Research Agency, S-90182 Umeå.
    Wolf-Watz, Hans
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Lloyd, Scott
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    YscP and YscU Regulate Substrate Specificity of the Yersinia Type III Secretion System2003In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 185, no 7, p. 2259-2266Article in journal (Refereed)
    Abstract [en]

    Pathogenic Yersinia species use a type III secretion system to inhibit phagocytosis by eukaryotic cells. At 37 degrees C, the secretion system is assembled, forming a needle-like structure on the bacterial cell surface. Upon eukaryotic cell contact, six effector proteins, called Yops, are translocated into the eukaryotic cell cytosol. Here, we show that a yscP mutant exports an increased amount of the needle component YscF to the bacterial cell surface but is unable to efficiently secrete effector Yops. Mutations in the cytoplasmic domain of the inner membrane protein YscU suppress the yscP phenotype by reducing the level of YscF secretion and increasing the level of Yop secretion. These results suggest that YscP and YscU coordinately regulate the substrate specificity of the Yersinia type III secretion system. Furthermore, we show that YscP and YscU act upstream of the cell contact sensor YopN as well as the inner gatekeeper LcrG in the pathway of substrate export regulation. These results further strengthen the strong evolutionary link between flagellar biosynthesis and type III synthesis.

  • 6.
    Holmström, Anna
    et al.
    Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Cherepanov, Peter
    Maier, Elke
    Nordfelth, Roland
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Pettersson, Jonas
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Benz, Roland
    Wolf-Watz, Hans
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Forsberg, Åke
    LcrV is a channel size-determining component of the Yop effector translocon of Yersinia2001In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 39, no 3, p. 620-632Article in journal (Refereed)
    Abstract [en]

    Delivery of Yop effector proteins by pathogenic Yersinia across the eukaryotic cell membrane requires LcrV, YopB and YopD. These proteins were also required for channel formation in infected erythrocytes and, using different osmolytes, the contact‐dependent haemolysis assay was used to study channel size. Channels associated with LcrV were around 3 nm, whereas the homologous PcrV protein of Pseudomonas aeruginosa induced channels of around 2 nm in diameter. In lipid bilayer membranes, purified LcrV and PcrV induced a stepwise conductance increase of 3 nS and 1 nS, respectively, in 1 M KCl. The regions important for channel size were localized to amino acids 127–195 of LcrV and to amino acids 106–173 of PcrV. The size of the channel correlated with the ability to translocate Yop effectors into host cells. We suggest that LcrV is a size‐determining structural component of the Yop translocon.

  • 7.
    Jonsson, Sarah
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Oda, Husam
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Chlamydia trachomatis, Chlamydial Heat Shock Protein 60 and Anti-Chlamydial Antibodies in Women with Epithelial Ovarian Tumors2018In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 11, no 2, p. 546-551Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Chlamydia trachomatis (C. trachomatis) infection has been suggested to promote epithelial ovarian cancer (EOC) development. This study sought to explore the presence of C. trachomatis DNA and chlamydial heat shock protein 60 (chsp60) in ovarian tissue, as well as anti-chlamydial IgG antibodies in plasma, in relation to subtypes of EOC. METHODS: This cross-sectional cohort consisted of 69 women who underwent surgery due to suspected ovarian pathology. Ovarian tissue and corresponding blood samples were collected at the time of diagnosis. In ovarian tumor tissue, p53, p16, Ki67 and chsp60 were analyzed immunohistochemically, and PCR was used to detect C. trachomatis DNA. Plasma C. trachomatis IgG and cHSP60 IgG were analyzed with a commercial MIF-test and ELISA, respectively. RESULTS: Eight out of 69 women had C. trachomatis DNA in their ovarian tissue, all were invasive ovarian cancer cases (16.7% of invasive EOC). The prevalence of the chsp60 protein, C. trachomatis IgG and cHSP60 IgG in HGSC, compared to other ovarian tumors, was 56.0% vs. 37.2% P = .13, 15.4% vs. 9.3% P = .46 and 63.6% vs. 45.5% P = .33 respectively. None of the markers of C. trachomatis infection were associated with p53, p16 or Ki67. CONCLUSIONS: C. trachomatis was detected in invasive ovarian cancer, supporting a possible role in carcinogenesis of EOC. However, there were no statistically significant associations of chsp60 in ovarian tissue, or plasma anti-chlamydial IgG antibodies, with any of the subtypes of ovarian tumors.

  • 8.
    Lövheim, Hugo
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Norman, Tove
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study2019In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 1, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Background: Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer’s disease (AD) development.

    Objective: The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOE ɛ4) in a large population-based cohort with a long follow-up time.

    Methods: The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOE ɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared.

    Results: Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOE ɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOE ɛ4 for episodic memory decline (p < 0.001).

    Conclusion: In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOE ɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.

  • 9.
    Lövheim, Hugo
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Weidung, Bodil
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Interaction between Cytomegalovirus and Herpes Simplex Virus Type 1 Associated with the Risk of Alzheimer’s Disease Development2018In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 61, p. 939-945Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several environmental factors, including infectious agents, have been suggested to cause Alzheimer's disease (AD). Cytomegalovirus (CMV) has been associated with AD in several recent studies.

    OBJECTIVE: To investigate whether carriage of CMV, alone or in combination with Herpes simplex virus (HSV), increased the risk of developing AD.

    METHODS: Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years), taken an average of 9.6 years before AD diagnosis, and 360 age-, sex-, cohort-, and sampling date matched dementia-free controls were analyzed to detect anti-CMV (immunoglobulin [Ig] G and IgM), group-specific anti-HSV (IgG and IgM), and specific anti-HSV1 and HSV2 IgG antibodies by enzyme-linked immunosorbent assays. AD cases and dementia-free controls were compared using conditional logistic regression analyses.

    RESULTS: The presence of anti-CMV IgG antibodies did not increase the risk of AD (odds ratio [OR], 0.857; p = 0.497). Among AD cases, an association between CMV and HSV1 carriage was detected (OR 7.145, p < 0.001); in a conditional logistic regression model, the interaction between CMV and HSV1 was associated with AD development (OR 5.662; p = 0.007).

    CONCLUSION: The present findings do not support a direct relationship between CMV infection and the development of AD; however, an interaction between CMV and HSV1 was found to be associated significantly with AD development. These findings suggest that CMV infection facilitates the development of HSV1-associated AD, possibly via its effects on the immune system.

  • 10.
    Olsson, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergh Drott, Johanna
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Laurantzon, Lovisa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Laurantzon, Oscar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Chronic prostatic infection and inflammation by propionibacterium acnes in a rat prostate infection model2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e51434-Article in journal (Refereed)
    Abstract [en]

    Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the Gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic inflammation may be induced by P. acnes infection.

  • 11.
    Olsson, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Davidsson, Sabina
    Örebro Univ Hosp, Dept Urol, Örebro, Sweden.
    Unemo, Magnus
    Örebro Univ Hosp, Dept Lab Med, Örebro, Sweden.
    Mölling, Paula
    Örebro Univ Hosp, Dept Lab Med, Örebro, Sweden.
    Andersson, Swen-Olov
    Örebro Univ Hosp, Dept Urol, Örebro, Sweden.
    Andrén, Ove
    Örebro Univ Hosp, Dept Urol, Örebro, Sweden.
    Söderquist, Bo
    Örebro Univ Hosp, Dept Lab Med, Örebro, Sweden.
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Antibiotic susceptibility in prostate-derived Propionibacterium acnes isolates2012In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 120, no 10, p. 778-785Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to determine antibiotic susceptibility of Propionibacterium acnes isolates from prostate. Prostate-derived P. acnes isolates (n = 24, Umeå & Örebro, Sweden, 2007-2010) and a panel of control strains (n = 25, Sweden) collected from skin and deep infections were assessed for resistance to penicillin G, piperacillin-tazobactam, imipenem, gentamicin, azithromycin, erythromycin, vancomycin, ciprofloxacin, moxifloxacin, tetracycline, tigecycline, fusidic acid, clindamycin, rifampicin, linezolid, daptomycin, trimethoprim-sulfamethoxazole, and metronidazole. In addition, the isolates were tested for inducible clindamycin resistance. All prostate derived P. acnes isolates displayed wild-type distribution of MIC-values, without evidence of acquired resistance. In the reference panel, 5 of 25 isolates had acquired macrolide resistance with cross-resistance to azithromycin, clindamycin, and erythromycin. In addition, one of these isolates was resistant to tetracycline.

  • 12.
    Olsson, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Johansson, Jörgen
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Laboratory Medicine, Clinical Microbiology, Umeå University Hospital, Umeå, Sweden.
    Honkala, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Blomqvist, Bert
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Laboratory Medicine, Clinical Microbiology, Umeå University Hospital, Umeå, Sweden.
    Kok, Eloise
    Weidung, Bodil
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Urea dilution of serum for reproducible anti-HSV1 IgG avidity index2019In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 19, article id 164Article in journal (Refereed)
    Abstract [en]

    Herpes simplex virus type 1 (HSV1), establishes life-long latency and can cause symptoms during both first-time infection and later reactivation. The aim of the present study was to describe a protocol to generate a reliable and discriminative avidity index (AI) for anti-HSV1 IgG content in human sera. Human serum from two distinct cohorts; one a biobank collection (Betula) (n = 28), and one from a clinical diagnostics laboratory at Northern Sweden University Hospital (NUS) (n = 18), were assessed for presence of IgG antibodies against HSV1 by a commercially available ELISA-kit. Addition of urea at the incubation step reduces effective binding, and the ratio between urea treated sample and non-treated sample was used to express an avidity index (AI) for individual samples. AI score ranged between 43.2 and 73.4% among anti-HSV1 positive biobank sera. Clinical samples ranged between 36.3 and 74.9%. Reproducibility expressed as an intraclass correlation coefficient (ICC) was estimated at 0.948 (95% CI: 0.900-0.979) and 0.989 (95% CI 0.969-0.996) in the biobank and clinical samples, respectively. The method allows for AI scoring of anti-HSV1 IgG from individual human sera with a single measurement. The least significant change between two measurements at the p < 0.05 level was estimated at 5.4 and 3.2 points, respectively, for the two assessed cohorts.

  • 13.
    Olsson, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kok, Eloise
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Herpes virus seroepidemiology in the adult Swedish population2017In: Immunity & Ageing, ISSN 1742-4933, E-ISSN 1742-4933, Vol. 14, article id 10Article in journal (Refereed)
    Abstract [en]

    Background: Herpes viruses establish a life-long latency and can cause symptoms during both first-time infection and later reactivation. The aim of the present study was to describe the seroepidemiology of Herpes simplex type 1 (HSV1), Herpes simplex type 2 (HSV2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV) and Human herpes virus type 6 (HHV6) in an adult Swedish population (35-95 years of age). Methods: Presence of antibodies against the respective viruses in serum from individuals in the Betula study was determined with an enzyme-linked immunosorbent assay (ELISA). Singular samples from 535 persons (53.9% women, mean age at inclusion 62.7 +/- 14.4 years) collected 2003-2005 were analyzed for the five HHVs mentioned above. In addition, samples including follow-up samples collected 1988-2010 from 3,444 persons were analyzed for HSV. Results: Prevalence of HSV1 was 79.4%, HSV2 12.9%, CMV 83.2%, VZV 97.9%, and HHV6 97.5%. Herpes virus infections were more common among women (p = 0.010) and a lower age-adjusted HSV seroprevalence was found in later birth cohorts (p < 0.001). The yearly incidence of HSV infection was estimated at 14.0/1000. Conclusion: Women are more often seropositive for HHV, especially HSV2. Age-adjusted seroprevalence for HSV was lower in later birth cohorts indicating a decreasing childhood and adolescent risk of infection.

  • 14.
    Olsson, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Honkala, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Karhunen, Pekka J.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kok, Eloise H.
    HSV presence in brains of individuals without dementia: the TASTY brain series2016In: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 9, no 11, p. 1349-1355Article in journal (Refereed)
    Abstract [en]

    Herpes simplex virus (HSV) type 1 affects a majority of the population and recent evidence suggests involvement in Alzheimer's disease aetiology. We investigated the prevalence of HSV type 1 and 2 in the Tampere Autopsy Study (TASTY) brain samples using PCR and sero-positivity in plasma, and associations with Alzheimer's disease neuropathology. HSV was shown to be present in human brain tissue in 11/584 (1.9%) of samples in the TASTY cohort, of which six had Alzheimer's disease neuropathological amyloid beta (A beta) aggregations. Additionally, serological data revealed 86% of serum samples tested were IgG-positive for HSV. In conclusion, we report epidemiological evidence of the presence of HSV in brain tissue free from encephalitis symptoms in a cohort most closely representing the general population (a minimum prevalence of 1.9%). Whereas 6/11 samples with HSV DNA in the brain tissue had A beta aggregations, most of those with A beta aggregations did not have HSV present in the brain tissue.

  • 15.
    Yanamandra, Kiran
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Alexeyev, Oleg
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zamotin, Vladimir
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Srivastava, Vaibhav
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Shchukarev, Andrey
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Brorsson, Ann-Christin
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Tartaglia, Gian Gaetano
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Vogl, Thomas
    Institute of Immunology, University of Münster, Münster, Germany.
    Kayed, Rakez
    Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America.
    Wingsle, Gunnar
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dobson, Christopher M
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Morozova-Roche, Ludmilla A
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate2009In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, no 5, p. e5562-Article in journal (Refereed)
    Abstract [en]

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

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

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

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