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  • 1.
    Aberg, Carola Höglund
    et al.
    Umeå University, Faculty of Medicine, Odontology. Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Sjödin, Bengt
    Lakio, Laura
    Pussinen, Pirkko J
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology. Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Odontology. Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Presence of Aggregatibacter actinomycetemcomitans in young individuals: a 16-year clinical and microbiological follow-up study.2009In: Journal of clinical periodontology, ISSN 1600-051X, Vol. 36, no 10, p. 815-22Article in journal (Refereed)
    Abstract [en]

    AIM: To look for clinical signs of periodontal disease in young adults who exhibited radiographic bone loss and detectable numbers of Aggregatibacter actinomycetemcomitans in their primary dentition. MATERIAL AND METHODS: Periodontal status and radiographic bone loss were examined in each of the subjects 16 years after the baseline observations. Techniques for anaerobic and selective culture, and checkerboard, were used to detect periodontitis-associated bacterial species. The isolated A. actinomycetemcomitans strains were characterized by polymerase chain reaction. RESULTS: Signs of localized attachment loss were found in three out of the 13 examined subjects. A. actinomycetemcomitans was recovered from six of these subjects and two of these samples were from sites with deepened probing depths and attachment loss. Among the isolated A. actinomycetemcomitans strains, serotypes a-c and e, but not d or f, were found. None of the isolated strains belonged to the highly leucotoxic JP2 clone, and one strain lacked genes for the cytolethal distending toxin. CONCLUSIONS: This study indicates that the presence of A. actinomycetemcomitans and early bone loss in the primary dentition does not necessarily predispose the individual to periodontal attachment loss in the permanent dentition.

  • 2. Akkaoui, Sanae
    et al.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Yagoubi, Maâmar
    Haubek, Dorte
    Aarhus University Denmark.
    El Hamidi, Adnane
    Mohammed V University in Rabat, Morocco.
    Rida, Sana
    Mohammed V University in Rabat, Morocco.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ennibi, OumKeltoum
    Mohammed V University in Rabat, Morocco.
    Chemical Composition, Antimicrobial activity, in Vitro Cytotoxicity and Leukotoxin Neutralization of Essential Oil from Origanum vulgare against Aggregatibacter actinomycetemcomitans2020In: Pathogens, E-ISSN 2076-0817, Vol. 9, no 3, article id 192Article in journal (Refereed)
    Abstract [en]

    In this study, the essential oil of Origanum vulgare was evaluated for putative antibacterial activity against six clinical strains and five reference strains of Aggregatibacter actinomycetemcomitans, in comparison with some antimicrobials. The chemical composition of the essential oil was analyzed, using chromatography (CG) and gas chromatography-mass spectrometry coupled (CG-MS). The major compounds in the oil were Carvacrol (32.36%), α-terpineol (16.70%), p-cymene (16.24%), and Thymol (12.05%). The antimicrobial activity was determined by an agar well diffusion test. A broth microdilution method was used to study the minimal inhibitory concentration (MIC). The minimal bactericidal concentration (MBC) was also determined. The cytotoxicity of the essential oil (IC50) was <125 µg/mL for THP-1 cells, which was high in comparison with different MIC values for the A. actinomycetemcomitans strains. O. vulgare essential oil did not interfere with the neutralizing capacity of Psidium guajava against the A. actinomycetemcomitans leukotoxin. In addition, it was shown that the O. vulgare EO had an antibacterial effect against A. actinomycetemcomitans on a similar level as some tested antimicrobials. In view of these findings, we suggest that O.vulgare EO may be used as an adjuvant for prevention and treatment of periodontal diseases associated to A. actinomycetemcomitans. In addition, it can be used together with the previously tested leukotoxin neutralizing Psidium guajava.

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  • 3. Aleksandrova, Krasimira
    et al.
    Boeing, Heiner
    Nöthlings, Ute
    Jenab, Mazda
    Fedirko, Veronika
    Kaaks, Rudolf
    Lukanova-McGregor, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Boffetta, Paolo
    Trepo, Elisabeth
    Westhpal, Sabine
    Duarte-Salles, Talita
    Stepien, Magdalena
    Overvad, Kim
    Tjønneland, Anne
    Halkjær, Jytte
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Lagiou, Pagona
    Bamia, Christina
    Benetou, Vassiliki
    Agnoli, Claudia
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, Bas
    Peeters, Petra H
    Gram, Inger Torhild
    Lund, Eiliv
    Weiderpass, Elisabete
    Quirós, J Ramón
    Agudo, Antonio
    Sánchez, María-José
    Gavrila, Diana
    Barricarte, Aurelio
    Dorronsoro, Miren
    Ohlsson, Bodil
    Lindkvist, Björn
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C
    Riboli, Elio
    Pischon, Tobias
    Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer2014In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 60, no 3, p. 858-871Article in journal (Refereed)
    Abstract [en]

    Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137) or IBD (n=34). Using risk set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total, high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured and incidence rate ratios (IRRs) and 95% confidence intervals (CI-s) estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection and adiposity measures, higher concentrations of CRP, IL-6, C-peptide and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95%CI = 1.02-1.46, P=0.03; 1.90; 95%CI = 1.30-2.77, P=0.001; 2.25; 95%CI = 1.43-3.54, P=0.0005 and 2.09; 95%CI = 1.19-3.67, P=0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95%CI = 1.05-1.42, P=0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95%CI = 1.25-2.11, P=0.0003) and IBD (IRR = 10.5; 95%CI = 2.20-50.90, P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide and non-HMW adiponectin, and 0.46 for GLDH indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.

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  • 4. Al-Otaibi, M
    et al.
    Al-Harthy, M
    Gustafsson, A
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Angmar-Månsson, B
    Subgingival plaque microbiota in Saudi Arabians after use of miswak chewing stick and toothbrush2004In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 31, no 12, p. 1048-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The chewing stick, the miswak, is used in many developing countries as the traditional means for oral hygiene. It is prepared from the roots, twigs and stem of Salvadora persica or other alternative local plants. OBJECTIVES: To compare the effects of the chewing stick miswak (from S. persica) and toothbrush on subgingival plaque microflora among Saudi Arabian individuals. Further, to investigate whether components extracted from S. persica may interfere with the subgingival plaque micro-organisms. MATERIAL AND METHODS: Fifteen healthy Saudi Arabian male volunteers aged 21-36 years were included in a single-blind, randomized cross-over study. The participants were taught how to use each device properly. Plaque sampling for DNA test was performed at the baseline, 1 week after professional tooth cleaning, and after 3 weeks of either miswak or toothbrush use. Identification and quantification of microbial species were performed by the checkerboard method, using whole genomic, digoxigenin-labelled DNA probes. Inhibition zones around miswak were examined on agar plates with Actinobacillus actinomycetemcomitans and the leukotoxicity of this bacterium was analyzed in a bioassay with macrophages+/-extracts of miswak. RESULTS: Miswak and toothbrushing had a similar influence on the levels of the subgingival microbiota. However, A. actinomycetemcomitans was significantly more reduced by miswak (p<0.05) than by toothbrushing. These results were supported by our in vitro results which, indicated that extracts from S. persica might interfere with the growth and leukotoxicity of A. actinomycetemcomitans. CONCLUSIONS: In contrast to toothbrush use, miswak use significantly reduced the amount of A. actinomycetemcomitans in the subgingival plaque.

  • 5.
    Behnam Motlagh, Parviz
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Tyler, Andreas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Brännstrom, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Co-expression of Globotriasosylceramide (Gb3) With MDR1 in Cisplatin-resistant Pleural Mesothelioma and Non-small Cell Lung Cancer Cell May Lead to a New Tumour Resistance Treatment Approach2011Conference paper (Refereed)
  • 6.
    Behnam-Mothlag, Parviz
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Tyler, Andreas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Karlsson, Terese
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Cisplatin Resistance in Malignant Pleural Mesothelioma2012In: Mesotheliomas: Synonyms and Definition, Epidemiology, Etiology, Pathogenesis, Cyto-Histopathological Features, Clinic, Diagnosis, Treatment, Prognosis / [ed] Alexander Zubritsky, Zagreb: InTech, 2012, Vol. 11, p. 169-186Chapter in book (Refereed)
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  • 7.
    Behnam-Motlagh, Parviz
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Tyler, Andreas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy2010In: Toxins, E-ISSN 2072-6651, Vol. 2, no 10, p. 2467-2477Article, review/survey (Refereed)
    Abstract [en]

    A major problem with anti-cancer drug treatment is the development of acquired multidrug resistance (MDR) of the tumor cells. Verotoxin-1 (VT-1) exerts its cytotoxicity by targeting the globotriaosylceramide membrane receptor (Gb3), a glycolipid associated with multidrug resistance. Gb3 is overexpressed in many human tumors and tumor cell lines with inherent or acquired MDR. Gb3 is co-expressed and interplays with the membrane efflux transporter P-gp encoded by the MDR1 gene. P-gp could act as a lipid flippase and stimulate Gb3 induction when tumor cells are exposed to cancer chemotherapy. Recent work has shown that apoptosis and inherent or acquired multidrug resistance in Gb3-expressing tumors could be affected by VT-1 holotoxin, a sub-toxic concentration of the holotoxin concomitant with chemotherapy or its Gb3-binding B-subunit coupled to cytotoxic or immunomodulatory drug, as well as chemical manipulation of Gb3 expression. The interplay between Gb3 and P-gp thus gives a possible physiological approach to augment the chemotherapeutic effect in multidrug resistant tumors.

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  • 8. Belibasakis, George
    et al.
    Brage, Monica
    Umeå University, Faculty of Medicine, Odontology, Periodontology. Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Lagergård, Teresa
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology.
    Cytolethal distending toxin upregulates RANKL expression in Jurkat T-cells: Cdt upregulates RANKL2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 6, p. 499-506Article in journal (Refereed)
    Abstract [en]

    Cytolethal distending toxin, a bacterial exotoxin produced by a number of Gram-negative species, causes growth arrest and morphological alterations in host cells. Among these species are Haemophilus ducreyi, the etiological agent of chancroid, and the periodontal pathogen Aggregatibacter actinomycetemcomitans, highly implicated in localized aggressive periodontitis. CDT induces receptor activator of NF-kappaB ligand (RANKL) expression in periodontal fibroblasts, the key bone-resorbing cytokine. T-cells are actively involved in localized inflammation-induced bone destruction, including periodontitis. The aim of this study was to investigate the effects of purified CDT on the expression of RANKL and its decoy receptor osteoprotegerin (OPG), in the Jurkat T-cell line. Quantitative real-time PCR indicated that 100 pg/ml of purified H. ducreyi CDT upregulated RANKL mRNA expression by 2.2-fold, after 24 h of exposure. This increase was corroborated by a 2.0-fold increase in RANKL protein release, as determined by ELISA. OPG was not detected in this experimental system. In conclusion, CDT enhances RANKL expression in T-cells, denoting that these cells are a potential target for the toxin and strengthening the potential link between this virulence factor and mechanisms associated with localized bone resorption.

  • 9.
    Belibasakis, Georgios N.
    et al.
    Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Belstrøm, Daniel
    Section for Clinical Oral Microbiology, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Eick, Sigrun
    Department of Periodontology, School of Dental Medicine, University of Bern, Bern, Switzerland.
    Gursoy, Ulvi K.
    Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Könönen, Eija
    Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland.
    Periodontal microbiology and microbial etiology of periodontal diseases: Historical concepts and contemporary perspectives2023In: Periodontology 2000, ISSN 0906-6713, E-ISSN 1600-0757Article in journal (Refereed)
    Abstract [en]

    This narrative review summarizes the collective knowledge on periodontal microbiology, through a historical timeline that highlights the European contribution in the global field. The etiological concepts on periodontal disease culminate to the ecological plaque hypothesis and its dysbiosis-centered interpretation. Reference is made to anerobic microbiology and to the discovery of select periodontal pathogens and their virulence factors, as well as to biofilms. The evolution of contemporary molecular methods and high-throughput platforms is highlighted in appreciating the breadth and depth of the periodontal microbiome. Finally clinical microbiology is brought into perspective with the contribution of different microbial species in periodontal diagnosis, the combination of microbial and host biomarkers for this purpose, and the use of antimicrobials in the treatment of the disease.

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  • 10. Belibasakis, Georgios N.
    et al.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology.
    Aggregatibacter actinomycetemcomitans targets NLRP3 and NLRP6 inflammasome expression in human mononuclear leukocytes2012In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 59, no 1, p. 124-130Article in journal (Refereed)
    Abstract [en]

    Periodontitis is an inflammatory condition that destroys the tooth-supporting tissues, as a result of local bacterial infection. Aggregatibacter actinomycetemcomitans is a Gram-negative facultative anaerobic species, highly associated with aggressive periodontitis. Periodontal inflammation is dominated by cytokines of the Interleukin (IL)-1 family. Prior to their secretion by mononuclear cells, IL-1 cytokines are processed by intracellular protein complexes, known as "inflammasomes", which can sense the bacterial challenge. The aim of this study was to investigate which inflammasomes are regulated in mononuclear cells in response to A. actinomycetemcomitans. The D7SS strain and its derivative leukotoxin and cytolethal distending toxin knock-out mutant strains were used to infect human mononuclear cells at a 1:10 cell: bacteria ratio, for 3h. The expression of various inflammasome components in the cells was investigated by TaqMan quantitative real-time polymerase chain reaction (qPCR). The expressions of NOD-like receptor protein (NLRP)1, NLRP2 and Absent In Melanoma (AIM)2 inflammasome sensors, as well as their effector Caspase-1 were not affected. However, NLRP3 was up-regulated, while NLRP6 was down-regulated. This effect was not dependent on the leukotoxin or the cytolethal distending toxin, as demonstrated by the use of specific gene knock-out mutant strains. IL-1β and IL-18 expressions were also up-regulated by the bacterial challenge. In conclusion, A. actinomycetemcomitans enhances NLRP3 and reduces NLRP6 inflammasome expression, irrespective of its major virulence factors, confirming the high pathogenic profile of this species, and providing further insights to the mechanisms of periodontal inflammation.

  • 11.
    Belibasakis, Georgios N
    et al.
    Umeå University, Faculty of Medicine, Odontology, Oral Cell Biology. Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Wang, Y
    Chen, C
    Kalfas, S
    Lerner, Ulf
    Umeå University, Faculty of Medicine, Odontology, Oral Cell Biology.
    The cytolethal distending toxin induces receptor activator of NF-κB ligand expression in human gingival fibroblasts and periodontal ligament cells2005In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 73, no 1, p. 342-351Article in journal (Refereed)
    Abstract [en]

    Actinobacillus actinomycetemcomitans is associated with localized aggressive periodontitis, a disease characterized by rapid loss of the alveolar bone surrounding the teeth. Receptor activator of NF-kappaB Ligand (RANKL) and osteoprotegerin (OPG) are two molecules that regulate osteoclast formation and bone resorption. RANKL induces osteoclast differentiation and activation, whereas OPG blocks this process by acting as a decoy receptor for RANKL. The purpose of this study was to investigate the effect of A. actinomycetemcomitans on the expression of RANKL and OPG in human gingival fibroblasts and periodontal ligament cells. RANKL mRNA expression was induced in both cell types challenged by A. actinomycetemcomitans extract, whereas OPG mRNA expression remained unaffected. Cell surface RANKL protein was also induced by A. actinomycetemcomitans, whereas there was no change in OPG protein secretion. A cytolethal distending toxin (Cdt) gene-knockout strain of A. actinomycetemcomitans did not induce RANKL expression, in contrast to its wild-type strain. Purified Cdt from Haemophilus ducreyi alone, or in combination with extract from the A. actinomycetemcomitans cdt mutant strain, induced RANKL expression. Pretreatment of A. actinomycetemcomitans wild-type extract with Cdt antiserum abolished RANKL expression. In conclusion, A. actinomycetemcomitans induces RANKL expression in periodontal connective tissue cells. Cdt is crucial for this induction and may therefore be involved in the pathological bone resorption during the process of localized aggressive periodontitis.

  • 12.
    Belibasakis, Georgios N
    et al.
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology. Umeå University, Faculty of Medicine, Odontology, Oral Cell Biology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Wang, Y
    Chen, C
    Lagergård, T
    Kalfas, S
    Lerner, Ulf
    Umeå University, Faculty of Medicine, Odontology, Oral Cell Biology.
    Cytokine responses of human gingival fibroblasts to Actinobacillus actinomycetemcomitans cytolethal distending toxin2005In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 30, no 2, p. 56-63Article in journal (Refereed)
    Abstract [en]

    Actinobacillus actinomycetemcomitans is implicated in the pathogenesis of localized aggressive periodontitis, and has the capacity to express a cytolethal distending toxin (Cdt). Gingival fibroblasts (GF) are resident cells of the periodontium, which can express several osteolytic cytokines. The aims of this study were a) to investigate the role of Cdt in A. actinomycetemcomitans-induced expression of osteolytic cytokines and their cognate receptors in GF and b) to determine if the previously demonstrated induction of receptor activator of NFkappaB ligand (RANKL) by A. actinomycetemcomitans is mediated by these pro-inflammatory cytokines or by prostaglandin E(2) (PGE(2)). A. actinomycetemcomitans clearly induced interleukin (IL)-6, IL-1beta, and to a minimal extent, tumor necrosis factor (TNF)-alpha mRNA expression. At the protein level, IL-6 but not IL-1beta or TNF-alpha expression was stimulated. The mRNA expression of the different receptor subtypes recognizing IL-6, IL-1beta and TNF-alpha was not affected. A cdt-knockout strain of A. actinomycetemcomitans had similar effects on cytokine and cytokine receptor mRNA expression, compared to its parental wild-type strain. Purified Cdt stimulated IL-6, but not IL-1beta or TNF-alpha protein biosynthesis. Antibodies neutralizing IL-6, IL-1 or TNF-alpha, and the PGE(2) synthesis inhibitor indomethacin, did not affect A. actinomycetemcomitans-induced RANKL expression. In conclusion, a) A. actinomycetemcomitans induces IL-6 production in GF by a mechanism largely independent of its Cdt and b) A. actinomycetemcomitans-induced RANKL expression in GF occurs independently of IL-1, IL-6, TNF-alpha, or PGE(2).

  • 13.
    Belibasakis, Georgios N
    et al.
    Umeå University, Faculty of Medicine, Odontology, Oral Cell Biology. Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Mattsson, Anna
    Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Wang, Ying
    Chen, Casey
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Cell cycle arrest of human gingival fibroblasts and periodontal ligament cells by Actinobacillus actinomycetemcomitans: involvement of the cytolethal distending toxin2004In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 112, no 10, p. 674-685Article in journal (Refereed)
    Abstract [en]

    The cytolethal distending toxin (Cdt) is produced by several Gram-negative bacterial species and causes growth arrest and morphological alterations in mammalian cells. Actinobacillus actinomycetemcomitans, which is involved in the pathogenesis of localized aggressive periodontitis, also produces a Cdt that affects periodontal connective tissue cells. The aim of this study was to investigate in which phase of the cell cycle these cells are arrested and enlarged when challenged with A. actinomycetemcomitans, and to evaluate the involvement of its Cdt. Human gingival fibroblasts and periodontal ligament cells were challenged with A. actinomycetemcomitans extract, or with purified Cdt, and cell cycle analysis was performed by propidium iodide staining and flow cytometry. Cells exposed to an A. actinomycetemcomitans wild-type strain, or to purified Cdt, were arrested in both G1 and G2/M phases, and appeared enlarged compared to the corresponding controls. The cellular enlargement occurred in both G1 and G2/M arrested cells. In contrast, cells exposed to an A. actinomycetemcomitans cdt-knockout mutant strain showed cell cycle phase distribution and size similar to the controls. In conclusion, A. actinomycetemcomitans causes a combined G1 and G2/M growth arrest and enlargement in periodontal connective tissue cells, which is attributed to its Cdt.

  • 14.
    Belibasakis, Georgios N
    et al.
    Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, S-141 04 Huddinge, Sweden.
    Maula, Terhi
    Department of Biochemistry, University of Turku, FI-20014 Turku, Finland.
    Bao, Kai
    Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, S-141 04 Huddinge, Sweden.
    Lindholm, Mark
    Umeå University, Faculty of Medicine, Department of Odontology.
    Bostanci, Nagihan
    Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, S-141 04 Huddinge, Sweden.
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ihalin, Riikka
    Department of Biochemistry, University of Turku, FI-20014 Turku, Finland.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Virulence and Pathogenicity Properties of Aggregatibacter actinomycetemcomitans2019In: Pathogens, E-ISSN 2076-0817, Vol. 8, no 4, article id E222Article in journal (Refereed)
    Abstract [en]

    Aggregatibacter actinomycetemcomitans is a periodontal pathogen colonizing the oral cavity of a large proportion of the human population. It is equipped with several potent virulence factors that can cause cell death and induce or evade inflammation. Because of the large genetic diversity within the species, both harmless and highly virulent genotypes of the bacterium have emerged. The oral condition and age, as well as the geographic origin of the individual, influence the risk to be colonized by a virulent genotype of the bacterium. In the present review, the virulence and pathogenicity properties of A. actinomycetemcomitans will be addressed.

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  • 15. Belibasakis, GN
    et al.
    Bostanci, N
    Hashim, A
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Aduse-Opoku, J
    Curtis, MA
    Hughes, FJ
    Regulation of RANKL and OPG gene expression in human gingival fibroblasts and periodontal ligament cells by Porphyromonas gingivalis: a putative role of the Arg-gingipains2007In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 43, no 1, p. 46-53Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis is highly implicated in the pathogenesis of periodontitis, which is characterized by the destruction of periodontal connective tissues and the supporting alveolar bone. Receptor Activator of NF-kappaB Ligand (RANKL) stimulates bone resorption, whereas osteoprotegerin (OPG) blocks its action, and this bi-molecular system is implicated in periodontitis. The aim of this work was (a) to investigate the regulation of RANKL and OPG gene expression in human periodontal ligament (PDL) cells and gingival fibroblasts (GF), in response to P. gingivalis culture supernatants, by quantitative real-time PCR and (b) to attempt to identify putative virulence factors involved in this process. The results indicated that P. gingivalis induced RANKL and reduced OPG mRNA expression by the studied cells, resulting in an increased RANKL/OPG expression ratio. Heat-inactivation of P. gingivalis resulted in significant reduction of RANKL mRNA expression. A Lys-gingipain mutant strain did not affect, whereas an Arg-gingipain mutant strain further enhanced RANKL mRNA expression, compared to their parental wild-type strain. In conclusion, P. gingivalis up-regulates the RANKL/OPG expression ratio in GF and PDL cells, denoting an enhanced osteoclastogenic potential by the cells. The component mainly responsible for RANKL induction appears to be proteinaceous, and it may be regulated by the Arg-gingipains.

  • 16.
    Birkeholm Jensen, Anne
    et al.
    Aarhus University, Denmark.
    Isidor, Flemming
    Aarhus University, Denmark.
    Lund, Marianne
    Aarhus University Denmark.
    Væth, Michael
    Aarhus University, Denmark.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lauritsen, Niels Nørskov
    Aarhus University, Denmark.
    Haubek, Dorte
    Aarhus University, Denmark.
    Prevalence of Aggregatibacter actinomycetemcomitans and Periodontal Findings among 14 to 15-Year Old Danish Adolescents: A Descriptive Cross-Sectional Study2020In: Pathogens, E-ISSN 2076-0817, Vol. 9, no 12, article id 1054Article in journal (Refereed)
    Abstract [en]

    Aggregatibacter actinomycetemcomitans (Aa) is a keystone pathogen associated with periodontitis in adolescents. The knowledge on the prevalence of Aa and periodontitis among adolescents in Northern Europe is sparse. A total of 525 14- to 15-year-old adolescents from the municipality of Aarhus, Denmark, underwent a full-mouth clinical examination. Plaque score (PS), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were recorded. Subgingival plaque samples (SPS) and stimulated saliva samples (SSS) were collected and analyzed for the presence of JP2 and non-JP2 genotypes of Aa using real-time PCR. A total of 70 (13.3%) individuals were positive for Aa, with 17 found in SPS, 19 in SSS, and 35 in both. The highly leukotoxic JP2 genotype of Aa was not detected. The individuals positive for Aa in both SPS and SSS had poorer periodontal outcomes (PPD and CAL) than individuals without Aa and individuals carrying Aa in either SPS or SSS only. In conclusion, 13% of 14- to 15-year-old Danish adolescents were positive for Aa, and the presence of Aa in both SPS and SSS was associated with poorer periodontal outcomes.

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  • 17.
    Boles, Usama
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Cardiology Department, Letterkenny University Hospital, Letterkenny, Co. Donegal, Ireland.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sharif, Zain
    David, Santhosh
    McGrory, Siobhan
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Molecular & Clinical Sciences Research Institute, St. George University, London, UK.
    Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis Pathogenesis2018In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 19, no 1, article id 260Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Coronary artery ectasia (CAE) is a rare disorder commonly associated with additional features of atherosclerosis. In the present study, we aimed to examine the systemic immune-inflammatory response that might associate CAE.

    METHODS: Plasma samples were obtained from 16 patients with coronary artery ectasia (mean age 64.9 ± 7.3 years, 6 female), 69 patients with coronary artery disease (CAD) and angiographic evidence for atherosclerosis (age 64.5 ± 8.7 years, 41 female), and 140 controls (mean age 58.6 ± 4.1 years, 40 female) with normal coronary arteries. Samples were analyzed at Umeå University Biochemistry Laboratory, Sweden, using the V-PLEX Pro-Inflammatory Panel 1 (human) Kit. Statistically significant differences (p < 0.05) between patient groups and controls were determined using Mann-Whitney U-tests.

    RESULTS: The CAE patients had significantly higher plasma levels of INF-γ, TNF-α, IL-1β, and IL-8 (p = 0.007, 0.01, 0.001, and 0.002, respectively), and lower levels of IL-2 and IL-4 (p < 0.001 for both) compared to CAD patients and controls. The plasma levels of IL-10, IL-12p, and IL-13 were not different between the three groups. None of these markers could differentiate between patients with pure (n = 6) and mixed with minimal atherosclerosis (n = 10) CAE.

    CONCLUSIONS: These results indicate an enhanced systemic pro-inflammatory response in CAE. The profile of this response indicates activation of macrophages through a pathway and trigger different from those of atherosclerosis immune inflammatory response.

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  • 18. Bougas, Kostas
    et al.
    Ransjö, Maria
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology.
    Effects of Porphyromonas gingivalis surface-associated material on osteoclast formation2013In: Odontology: official journal of The Society of the Nippon Dental University, ISSN 1618-1247, E-ISSN 1618-1255, Vol. 101, no 2, p. 141-149Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis strongly correlates with periodontitis, but the underlying mechanisms causing dentoalveolar bone resorption are not fully understood. As contradictory effects of P. gingivalis on osteoclastogenesis have been reported, this study investigates the effect of P. gingivalis extract on osteoclast formation. Osteoclast formation in mouse bone marrow (MBM) cell cultures and RAW 264.7 cells was stimulated by nuclear factor-κB ligand (RANKL) or parathyroid hormone (PTH). Cells were cultured with and without P. gingivalis surface-associated material and phenotypic characteristics were examined using microscopy, flow cytometry, and RT-PCR. P. gingivalis significantly decreased osteoclast formation and the expression of osteoclast phenotypic markers in PTH-stimulated MBM cultures. Additionally, P. gingivalis inhibited expression of osteoclast differentiation factors and stimulated expression of the mouse macrophage marker F4/80. The presence of P. gingivalis in RANKL-stimulated MBM cultures and RAW 264.7 cells inhibited osteoclastogenesis. Interestingly, a transient exposure with P. gingivalis before PTH stimulation increased osteoclastogenesis in MBM cultures. Flow cytometric analyses of cells transiently exposed to P. gingivalis demonstrated an increased proportion of potential osteoclast precursor cells. We conclude that a transient exposure of MBM cultures to P. gingivalis increases the number of osteoclast precursors and osteoclast formation, whereas a prolonged exposure completely abolishes osteoclastogenesis.

  • 19.
    Brage, Monica
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Holmlund, A
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Humoral immune response to Aggregatibacter actinomycetemcomitans leukotoxin2011In: Journal of Periodontal Research, ISSN 0022-3484, E-ISSN 1600-0765, Vol. 46, no 2, p. 170-175Article in journal (Refereed)
    Abstract [en]

    Background and Objective: Periodontal disease is an inflammatory condition caused by bacterial infections that result in loss of the tooth supporting tissue. The periodontal pathogens produce virulence factors with capacity to affect the host immune response. Aggregatibacter actinomycetemcomitans is a periodontal pathogen that produces a leukotoxin that specifically affects human leukocytes. The aims of the present study were to examine the presence and function of systemic antibodies to the leukotoxin. Material and Methods:  One hundred and ninety-seven middle-aged (57 ± 5 years) Swedes with well-documented periodontal status and medical factors related to cardiovascular diseases were studied. These data have been published previously. The serum samples were examined for the presence of leukotoxin antibodies by western blot and the capacity to neutralize leukotoxicity in an activity assay with leukotoxin and cultured leukemic cells. Results:  The results showed a high prevalence (57%) of antibodies against A. actinomycetemcomitans leukotoxin in the analyzed population. These antibodies were correlated with leukotoxin neutralizing capacity as well as with the ELISA titers of A. actinomycetemcomitans-specific IgA and IgG. In addition, high levels of leukotoxin antibodies were correlated with increasing age, but not with periodontal disease parameters or cardiovascular risk factors. Conclusion:  Systemic antibodies against A. actionmycetemcomitans leukotoxin were common in this adult Swedish population. These antibodies might contribute to limit the systemic effects of the infection.

  • 20.
    Brundin, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Figdor, David
    Department of Microbiology, Monash University, Melbourne, Australia.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sjögren, Ulf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Preservation of bacterial dna by human dentin2014In: Journal of Endodontics, ISSN 0099-2399, E-ISSN 1878-3554, Vol. 40, no 2, p. 241-245Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The capacity of dentin and collagen to bind DNA and protect against spontaneous and nuclease-induced degradation was evaluated individually and by the incubation of DNA with nuclease-producing bacteria in a mixed culture.

    METHODS: Extracted Fusobacterium nucleatum DNA was incubated with dentin shavings or collagen for 90 minutes. The DNA-bound substrates were incubated in different media (water, sera, and DNase I) for up to 3 months. Amplifiable DNA was released from dentin using EDTA,or from collagen using proteinase K, and evaluated by polymerase chain reaction (PCR). The stability of dentin-bound DNA was also assessed in a mixed culture (Parvimonas micra and Pseudoramibacter alactolyticus) containing a DNase-producing species, Prevotella intermedia. Samples were analyzed for amplifiable DNA.

    RESULTS: In water, dentin-bound DNA was recoverable by PCR at 3 months compared with no detectable DNA after 4 weeks in controls (no dentin). DNA bound to collagen was detectable by PCR after 3 months of incubation in water. In 10% human sera, amplifiable DNA was detectable at 3 months when dentin bound and in controls (no dentin). In mixed bacterial culture, dentin-bound DNA was recoverable throughout the experimental period (3 months), compared with no recoverable F. nucleatum DNA within 24 hours in controls (no dentin).

    CONCLUSIONS: There is a strong binding affinity between DNA and dentin, and between DNA and serum proteins or collagen. These substrates preserve DNA against natural decomposition and protect DNA from nuclease activity, factors that may confound molecular analysis of the endodontic microbiota yet favor paleomicrobiological studies of ancient DNA.

  • 21. Buhlin, Kare
    et al.
    Holmer, Jacob
    Gustafsson, Anders
    Hörkkö, Sohvi
    Pockley, Alan Graham
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Paju, Susanna
    Klinge, Björn
    Pussinen, Pirkko
    Association of periodontitis with persistent, pro-atherogenic antibody responses2015In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 42, no 11, p. 1006-1014Article in journal (Refereed)
    Abstract [en]

    AIM: To study antibody responses associated with molecular mimicry in periodontitis.

    MATERIAL AND METHODS: Fifty-four periodontitis cases (mean age 54.0 years) and 44 controls (53.6 years) were examined, after which cases received periodontal treatment. Established immunoassays were used to analyse levels of antibodies against two pathogens, Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg), heat shock proteins (Hsp), Hsp60, Hsp65, and Hsp70, and epitopes of oxidized low density lipoprotein (oxLDL) (CuOx-LDL and MDA-LDL) in plasma samples that were collected at baseline, after 3 (n=48) and 6 (n=30) months.

    RESULTS: When age, sex, smoking habit, and the number of teeth were considered in multivariate logistic regressions, Aa and Pg IgG, Hsp65-IgA, CuOx-LDL-IgG and -IgM and MDA-LDL-IgG antibody levels were associated with periodontitis, whereas Hsp60-IgG2 antibody levels were inversely associated. The Aa antibody levels significantly correlated with the levels of IgA antibodies to Hsp65 and Hsp70, and both OxLDL IgA-antibody levels. The levels of antibodies to Pg correlated with IgG antibodies to Hsp60, Hsp70 and both oxLDL antibody epitopes. None of the antibody levels changed significantly after treatment.

    CONCLUSIONS: Periodontitis is associated with persistently high levels of circulating antibodies that are reactive with pathogen- and host-derived antigens.

  • 22.
    Bylund, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Saarinen, Niina
    Zhang, Jie-Xian
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Periodontology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adlercreutz, Herman
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Mäkelä, Sari
    Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo.2005In: Experimental biology and medicine, ISSN 1535-3702, E-ISSN 1535-3699, Vol. 230, no 3, p. 217-223Article in journal (Refereed)
    Abstract [en]

    Clinical intervention studies and experimental studies with lignan-rich diets suggest that lignans may have inhibitory effects on prostate cancer, but no clinical or experimental studies with purified lignans have been published. The purpose of this study was to investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Athymic nude male mice were injected subcutaneously with LNCaP cells. Starting 3 days after tumor cell injections, a control diet or a control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of nongrowing tumors, and higher tumor cell apoptotic index compared with controls. Furthermore, the cell proliferation index was reduced in mice receiving the 0.30% HMR diet compared with mice receiving the control diet. Our results suggest that dietary HMR started at the early phase of the tumor development inhibits the growth of the LNCaP human prostate cancer xenografts in athymic male mice.

  • 23. Carlsson, G
    et al.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Odontology, Oral and Maxillofacial Radiology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Olsson, A
    Eriksson, T
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Odontology.
    Hänström, Lennart
    Umeå University, Faculty of Medicine, Odontology.
    Henter, JI
    Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia2006In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 77, no 4, p. 744-751Article in journal (Refereed)
    Abstract [en]

    Patients with Kostmann syndrome (severe congenital neutropenia [SCN]) typically normalize their absolute neutrophil count (ANC) upon granulocyte colony-stimulating factor (G-CSF) therapy. However, although they no longer experience life-threatening bacterial infections, they frequently still have recurrent gingivitis and even severe periodontitis, often starting in early childhood. METHODS: We studied the periodontal disease in the four surviving patients belonging to the family originally described by Kostmann. Their odontological records, x-rays, color photos, bacterial cultures, serum antibodies to oral bacteria, and histopathological examinations were reviewed. The data were also correlated to previous investigations on their antibacterial peptides and molecular biology. RESULTS: Three patients had periodontal disease, despite normal ANC and professional dental care, and had neutrophils deficient in antibacterial peptides. One of these patients also had a heterozygous mutation in the neutrophil elastase gene, had severe periodontal disease and overgrowth of the periodontal pathogen Actinobacillus actinomycetemcomitans in the dental flora, and 15 permanent teeth had been extracted by the age of 27. One bone marrow-transplanted patient had no periodontal disease. CONCLUSIONS: Normalized ANC levels are not sufficient to maintain normal oral health in SCN patients, and because neutrophils are important for first-line defense and innate immunity, the deficiency of the antibacterial peptide LL-37 probably explains their chronic periodontal disease. Professional dental care is still important for SCN patients, despite treatment with G-CSF and normal ANC levels. Whether antibacterial peptides play a role in the pathogenesis of periodontitis in other patients remains to be elucidated.

  • 24. Chatziioannou, Aristotelis
    et al.
    Georgiadis, Panagiotis
    Hebels, Dennie G
    Liampa, Irene
    Valavanis, Ioannis
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palli, Domenico
    Chadeau-Hyam, Marc
    Siskos, Alexandros P
    Keun, Hector
    Botsivali, Maria
    de Kok, Theo M C M
    Pérez, Almudena Espín
    Kleinjans, Jos C S
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 42870Article in journal (Refereed)
    Abstract [en]

    We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.

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  • 25.
    Claesson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Chiang, Huei-Min
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lindholm, Mark
    Umeå University, Faculty of Medicine, Department of Odontology.
    Höglund-Åberg, Carola
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haubek, Dorte
    Aarhus University, Denmark.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Characterization of Aggregatibacter actinomycetemcomitans Serotype b Strains with Five Different, Including Two Novel, Leukotoxin Promoter Structures2020In: Vaccines, E-ISSN 2076-393X, Vol. 8, no 3, article id 398Article in journal (Refereed)
    Abstract [en]

    The JP2 genotype of A. actinomycetemcomitans, serotype b has attracted much interest during the past three decades due to its close association with periodontitis in young individuals and the enhanced expression of a leukotoxin (LtxA). A typical feature of this genotype is a 530-base pair (bp) deletion in the ltxCABD promoter region controlling leukotoxin expression. In the present work, we have characterized serotype b strains with four additional promoter types. Two novel types have been recognized, that is, one with a 230-bp deletion and one with a 172-bp duplication. Moreover, a strain with a 640-bp deletion and three strains with a full-length promoter, including the type strain Y4, were included in the present study. The seven strains were characterized by multi locus sequence typing (MLST) and arbitrarily primed polymerase chain reaction (PCR) and assessed for LtxA production. MLST showed that the strains with the non-JP2-like deletions represented distinct monophyletic groups, whereas the JP2 strain, HK1651, represented a separate branch. LtxA production was high in all three strains with a promoter deletion, whereas the other four strains showed significantly lower levels. It can be concluded that the genetic characterization and determination of LtxA production of A. actinomycetemcomitans isolates from individuals with periodontitis can contribute to the identification of novel virulent genotypes of this bacterium.

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  • 26.
    Claesson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Gudmundson, Jan
    Östersund, Sweden.
    Höglund-Åberg, Carola
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haubek, Dorte
    Aarhus, Denmark.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Detection of a 640-bp deletion in the Aggregatibacter actinomycetemcomitans leukotoxin promoter region in isolates from an adolescent of Ethiopian origin2015In: Journal of Oral Microbiology, E-ISSN 2000-2297, Vol. 7, article id 26974Article in journal (Refereed)
    Abstract [en]

    The expression of the leukotoxin of Aggregatibacter actinomycetemcomitans is regulated by the leukotoxin promoter. A 530-bp deletion or an 886-bp insertion sequence (IS) element in this region has earlier been described in highly leukotoxic isolates. Here, we report on highly leukotoxic isolate with a 640-bp deletion, which was detected in an adolescent of Ethiopian origin.

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  • 27.
    Claesson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Höglund-Åberg, Carola
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haubek, Dorte
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Age-related prevalence and characteristics of Aggregatibacter actinomycetemcomitans in periodontitis patients living in Sweden2017In: Journal of Oral Microbiology, E-ISSN 2000-2297, Vol. 9, article id 1334504Article in journal (Refereed)
    Abstract [en]

    Background: The presence of Aggregatibacter actinomycetemcomitans in patients with periodontitis has been extensively studied for decades. Objective: To study the prevalence of A. actinomycetemcomitans in younger and older periodontitis patients and to genetically characterize isolates of this bacterium. Design: Data from microbiological analyses of 3459 subgingival plaque samples collected from 1445 patients, 337 'younger' patients (<= 35 yrs) and 1108 'older' patients (>35 yrs) during 15 years (2000-2014), has been summerized. Isolates of A. actinomycetemcomitans were serotyped, leukotoxin promoter typed (JP2 and non JP2) and arbitrarily primed PCR (APPCR) genotyped. The origin of the JP2 genotype detected in the study population was determined. Results: The prevalence of A. actinomycetemcomitans was higher among younger than older patients and samples from the younger patients contained higher proportions of the bacterium. Serotype b was more prevalent among younger patients and the majorty of these isolates was from the same AP-PCR genotype. The JP2 genotype was detected in 1.2% of the patients, and the majority of these carriers were of non-African origin. Conslusions: For presence and charcteristics of A. actinomycetemcomitans in clinical samples the age of the carriers were a discriminating factor. Additional, apparently non- African carriers of the JP2 genotype of A. actinomycetemcomitans were identified.

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  • 28.
    Claesson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Belibasakis, Georgios N.
    Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
    Age-related subgingival colonization of aggregatibacter actinomycetemcomitans, porphyromonas gingivalis and parvimonas micra: a pragmatic microbiological retrospective report2023In: Microorganisms, E-ISSN 2076-2607, Vol. 11, no 6, article id 1434Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare data about the prevalence and proportions of the bacterial species Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Parvimonas micra in periodontitis pocket samples collected from young, <35 years, and old, >35-year-old patients, YP and OP, respectively. The results from the analyses of a total of 3447 subgingival plaque samples analyzed for clinical diagnosis purposes by cultivation regarding the proportions of these species were collected from a database and elucidated. The prevalence of A. actinomycetemcomitans was found to be more than twice as high (OR = 2.96, 95% CI; 2.50–3.50) in samples from the younger (42.2%) than the older group (20.4%) (p < 0.001). The prevalence of P. micra was significantly lower in samples from the younger age group (OR = 0.43, 95%) (p < 0.001), whereas P. gingivalis was similarly distributed (OR = 0.78, 95%) in the two age groups (p = 0.006). A similar pattern was noticed for A. actinomycetemcomitans and P. gingivalis when high proportions (>50%) of the samples of these bacterial species were elucidated. In contrast, the proportion of samples containing >50% with P. micra was lower compared with the two other bacterial species. Furthermore, it was noted that the proportion of samples from old patients containing A. actinomycetemcomitans in combination with P. micra was almost three times higher than in samples when P. micra was replaced by P. gingivalis. In conclusion, A. actinomycetemcomitans showed an increased presence and proportion in samples from young patients compared with the old patients, while P. gingivalis was similarly distributed in the two age groups. P. micra showed an increased presence and proportion in samples from old patients compared with the young patients.

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  • 29.
    Claesson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Belibasakis, Georgios N.
    Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
    Clinical laboratory diagnostics in dentistry: application of microbiological methods2022In: Frontiers in Oral Health, E-ISSN 2673-4842, Vol. 3, article id 983991Article in journal (Refereed)
    Abstract [en]

    Diagnosis and treatment in dentistry are based on clinical examination of thepatients. Given that the major oral diseases are of microbial biofilm etiology,it can be expected that performing microbiological analysis on samplescollected from the patient could deliver supportive evidence to facilitate thedecision-making process by the clinician. Applicable microbiological methodsrange from microscopy, to culture, to molecular techniques, which can beperformed easily within dedicated laboratories proximal to the clinics, such asones in academic dental institutions. Periodontal and endodontic infections,along with odontogenic abscesses, have been identified as conditions in whichapplied clinical microbiology may be beneficial for the patient. Administrationof antimicrobial agents, backed by microbiological analysis, can yield morepredictable treatment outcomes in refractory or early-occurring forms ofperiodontitis. Confirming a sterile root canal using a culture-negative sampleduring endodontic treatment may ensure the longevity of its outcomeand prevent secondary infections. Susceptibility testing of samples obtainedfrom odontogenic abscesses may facilitate the selection of the appropriateantimicrobial treatment to prevent further spread of the infection.

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  • 30.
    Claesson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Höglund-Åberg, Carola
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haubek, Dorte
    Aarhus university, Denmark.
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Multilocus Sequence Typing of Non-JP2 Serotype b Aggregatibacter actinomycetemcomitans Strains of Ghanaian and Swedish Origin2021In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 11, article id 769671Article in journal (Refereed)
    Abstract [en]

    Objective and Methods: The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans is associated with periodontitis affecting young individuals. The geographic dissemination of the highly leukotoxic JP2 genotype of serotype b of this species was previously studied by multilocus sequence typing (MLST). Here, we have used MLST to genetically characterize non-JP2 genotype strains of serotype b, isolated from individuals living in Ghana (n=41), and in Sweden (n=13), respectively.

    Results: The MLST analysis revealed a total of nine sequence types (ST). Both Ghanaian and Swedish isolates were distributed in ST 1-3. ST 5 and 6 were only identified among the Ghanaian strains, whereas ST 4, 7, 8 and 9 were uniquely represented among the Swedish strains. Previously, we characterized these non-JP2 genotype strains of A. actinomycetemcomitans serotype b by arbitrarily-primed (AP)-PCR, which distributed them into three groups, AP-PCR type 1, 2, and 3, respectively. AP-PCR type 1 strains are generally highly leukotoxic, and are associated with progression of periodontal attachment loss. As AP-PCR type 1 includes both JP2 genotype strains and a proportion of non-JP2 genotype strains of serotype b, a straightforward diagnostic procedure has been sought. This has revealed a gene, cagE, which appears to be conserved only in this AP-PCR type. According to our results, MLST was not a highly discriminatory method to identify AP-PCR type 1, as strains of this AP-PCR type could be found within three different ST: ST 2, ST 3 and ST 8.

    Conclusion: According to MLST, a geographic dissemination of non-JP2 genotype A. actinomycetemcomitans serotype b appears to exist. However, aiming to identify carriers of AP-PCR type 1, non-JP2 genotype serotype b, PCR with cagE-specific primers is likely the most efficient diagnostic procedure known today.

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  • 31.
    Claesson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Kanasi, Eleni
    Umeå University, Faculty of Medicine, Department of Odontology.
    Anders, Johansson
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sotirios, Kalfas
    School of Dentistry, Aristotle University of Thessaloniki, Thessaloniki, Greece.
    A new cleavage site for elastase within the complement component 32010In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 118, no 10, p. 765-768Article in journal (Refereed)
    Abstract [en]

    The lysosomal enzyme elastase was earlier shown to cleave the complement molecule C3. During somepreliminary experiments on the interactions of certain pathogenic bacteria with the innate defencemechanisms, we observed C3 cleavage, in the presence of elastase, to fragments not previouslydescribed. To elucidate this proteolytic reaction, the present study was conducted. Degradation of C3in mixtures with elastase or cathepsin G was detected by an immunoblot procedure using anti-C3c andanti-C3d antibodies after separating the proteins by SDS-PAGE. Certain C3 fragments were analysedfor amino acid sequence. The results revealed the existence of a cleavage site for elastase at the positionalanine1350 ⁄ lysine1351 of the C3 molecule, which has not been previously described. The fragmentresulted from this cleavage has a size of about 39 kDa and it contains a part or the whole of C3d. Thiscleavage was distinct from the one previously described at position 987 ⁄ 988, which gives a 34 kDaC3d-containing fragment.

  • 32.
    Claesson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lagervall, Maria
    Department of Periodontology at Skanstull, Stockholm County Council, Stockholm, Sweden.
    Höglund-Åberg, Carola
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haubek, Dorte
    Department of Pediatric Dentistry, School of Dentistry, Aarhus, Denmark.
    Detection of the highly leucotoxic JP2 clone of Aggregatibacter actinomycetemcomitans in members of a Caucasian family living in Sweden2011In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 38, no 2, p. 115-121Article in journal (Refereed)
    Abstract [en]

    Background: Carriers of the JP2 clone of Aggregatibacter actinomycetemcomitans exhibit an enhanced risk for developing aggressive periodontitis compared with individuals carrying non-JP2 clones. While the JP2 clone is almost exclusively detected among adolescents of African descent, reports on Caucasians colonized with the JP2 clone are remarkably few.

    Objective: The aim of this paper is to report on the history of periodontal disease and microbiological findings in a Caucasian family.

    Material and Methods: A. actinomycetemcomitans and other periodontitis-associated bacterial species in subgingival plaque samples were quantified by conventional culture technique. Leucotoxin promoter typing, serotyping and further characterizations of A. actinomycetemcomitans isolates were performed by PCR. DNA sequencing of the pseudogene, hbpA was performed to determine the origin of the detected JP2 clones. Further, genetically ancestry testing of family members was carried out.

    Results: The JP2 clone was detected in samples from two of the family members, a 33-year-old daughter and her 62-year-old mother. Relationship of their JP2 clones with JP2 clone strains from the Mediterranean area of Africa was indicated. Genotyping confirmed the Caucasian origin of all family members.

    Conclusions: Caucasian JP2 carriers exist and older subjects can carry the JP2 clone of A. actinomycetemcomitans.

  • 33.
    Claesson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Carriage of the JP2 genotype of Aggregatibacter actinomycetemcomitans by periodontitis patients of various geographic origin, living in Sweden2022In: Pathogens, E-ISSN 2076-0817, Vol. 11, no 11, article id 1233Article in journal (Refereed)
    Abstract [en]

    The JP2 genotype of Aggregatibacter actinomycetemcomitans serotype b is associated with aggressive forms of periodontitis and was initially identified as affecting adolescents in North and West Africa. The dissemination of this genotype follows the migration routes and can today be detected in samples from periodontitis patients in a high number of countries. In the present study, we aim to describe findings of the JP2 genotype A. actinomycetemcomits in a clinical laboratory at the Dental School, Odontology, Umeå University, Sweden. The findings of JP2 carriers are documented during a 21-year period, and the age and geographic origin of the sampled individuals are described. In addition, the collected JP2 isolates were separated into North or West African origin by analyses of the presence of a point mutation in the hbpA2 pseudogene of the bacterium. In a total of 2296 sampled individuals during this period in this Swedish population of periodontitis patients, 32 JP2 carriers were detected by cultivation and PCR. The geographic background of these individuals was diverse, including sixteen with African origin, ten with a Swedish origin and six additional ones with a non-African origin. The JP2 genotypes of A. actinomycetemcomitans were mainly isolated from young individuals (<35 years of age), and seven out of the 32 isolates were of a West African origin based on the sequence of hbpA2. We conclude that the JP2 genotype of A. actinomycetemcomitans can be detected world-wide in subgingival plaque samples from adolescents affected by periodontitis.

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  • 34.
    Dahlén, Gunnar
    et al.
    Göteborgs Universitet.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Höglund Åberg, Carola
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Haubek, Dorte
    Aarhus University Denmark.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Kwamin, Francis
    Ghana University, Ghana.
    Subgingival bacteria in Ghanaian adolescents with or without progression of attachment loss2014In: Journal of Oral Microbiology, E-ISSN 2000-2297, Vol. 6, article id 23977Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study describes subgingival bacterial profiles associated with clinical periodontal status in Ghanaian adolescents with or without progression of attachment loss.

    MATERIALS AND METHODS: Among 500 adolescents included in a cohort study, 397 returned 2 years later for a periodontal re-examination, including full-mouth CAL measurements. At follow-up, a subgroup of 98 adolescents was also subjected to bacterial sampling with paper points at four periodontal sites (mesial aspect of 11, 26, 31, and 46) and analyzed with the checkerboard DNA-DNA hybridization technique against DNA-probes from nine periodontitis-associated bacterial species.

    RESULTS: The 98 Ghanaian adolescents examined in the present study were similar to the entire group examined at the 2-year follow-up with respect to age, gender, and CAL ≥3 mm. A high detection frequency of Fusobacterium nucleatum and Prevotella intermedia (>99%) using checkerboard analysis was found, while for Aggregatibacter actinomycetemcomitans the detection frequency was <50%. A strong correlation was found at the individual level between the presence of P. intermedia and the total CAL change, and P. intermedia and Porphyromonas gingivalis were strongly correlated with a change in CAL and probing pocket depth (PPD) at the sampled sites. In a linear regression model, a significant discriminating factor for the total CAL change in the dentition during the 2-year follow-up period was obtained for P. intermedia and public school.

    CONCLUSION: This study indicates that subgingival bacterial species other than A. actinomycetemcomitans, for example, P. intermedia, have a significant association with periodontal breakdown (change in CAL) in Ghanaian adolescents with progression of periodontal attachment loss.

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    Dahlén
  • 35.
    De Soet, Johannes J.
    et al.
    Department of Preventive Dentistry, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haubek, Dorte
    Section for Paediatric Dentistry, Department of Dentistry and Oral Health, Aarhus University, Aarhus, Denmark.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Buijs, Mark J.
    Department of Preventive Dentistry, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
    Volgenant, Catherine M. C.
    Department of Preventive Dentistry, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
    The Highly Leukotoxic JP2 Genotype of Aggregatibacter actinomycetemcomitans Is Present in the Population of the West African Island, Sal in Cape Verde: A Pilot Study2022In: Pathogens, E-ISSN 2076-0817, Vol. 11, no 5, article id 577Article in journal (Refereed)
    Abstract [en]

    Aggregatibacter actinomycetemcomitans is strongly associated with severe periodontitis, possibly due to its production of a potent leukotoxin. A genetic variant, the JP2 genotype, was found to produce more leukotoxin than the wild type because of a mutation in the leukotoxin gene, and this genotype is frequently found in African populations. The aim of this study was to investigate whether this JP2 genotype can be found in a randomly selected group of inhabitants of Sal, Cape Verde. Twenty-nine adults between 20 and 59 years of age (58.6% female) participated, and information on their oral health and living standards was collected. An oral examination was performed for each participant, including DMF-T and CPI scores. Plaque and saliva samples were collected and transported to Europe, where DNA was isolated, and the concentration of A. actinomycetemcomitans and its JP2 genotype was determined using dedicated PCR analyses. All 29 plaque and 31% of the saliva samples harboured A. actinomycetemcomitans, and two participants were positive for the JP2 genotype. The presence of this JP2 genotype was not associated with either CPI or DMF-T. This pilot study is the first to describe the presence of the A. actinomycetemcomitans JP2 genotype in a Cape Verdean population living in the Cape Verde Islands, and the findings warrant further research.

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  • 36. Engström, Marianne
    et al.
    Eriksson, Kaja
    Lee, Linkiat
    Hermansson, Monika
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nicholas, Anthony P.
    Gerasimcik, Natalija
    Lundberg, Karin
    Klareskog, Lars
    Catrina, Anca Irinel
    Yucel-Lindberg, Tülay
    Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis2018In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 16, article id 214Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A relationship between rheumatoid arthritis (RA) and periodontitis has been suggested from findings that individuals with RA are prone to have advanced periodontitis and vice versa. In search of possible common pathogenetic features of these two diseases, we investigated the presence of citrullinated proteins and expression of endogenous peptidylarginine deiminases (PAD2 and PAD4), in periodontal tissue of individuals with periodontitis and healthy controls, in relation to the periodontal pathogens Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), producing leukotoxin as virulence factor. These two oral bacteria have been suggested to be linked to anti-citrullinated protein antibodies in patients with RA.

    METHODS: Gingival tissue biopsies were obtained from 15 patients with periodontitis and 15 individuals without periodontal disease. Presence of CD3-positive lymphocytes, citrullinated proteins, PAD2, PAD4, P. gingivalis as well as A. actinomycetemcomitans and Mannheimia haemolytica produced leukotoxins were analysed by immunohistochemistry, followed by triple-blind semi-quantitative analysis. Mann-Whitney and Fisher's exact tests were used to analyse differences between groups. PADI2 and PADI4 mRNA levels were assessed by RT-qPCR and analysed using Wilcoxon signed rank test.

    RESULTS: Increased staining of citrullinated proteins was observed in gingival connective tissue from subjects with periodontitis (80%, 12/15) compared to healthy gingival tissue (27%, 4/15), whereas no differences were observed in gingival epithelium. There was also an increased staining of the citrullinating enzymes PAD2 and PAD4 in gingival connective tissue of patients with periodontitis whereas similar levels of PAD2 and PAD4 were observed in the gingival epithelium of the two groups. Similarly, the mRNA levels of PADI2 and PADI4 were also increased in the gingival tissue of patients with periodontitis compared to healthy controls. Furthermore, presence of P. gingivalis and leukotoxins was comparable in both epithelium and connective tissue, from the different investigated individuals with and without periodontitis, and there were no correlations between the presence of periodontal pathogens and the expression of citrullinated proteins or PAD enzymes.

    CONCLUSION: Chronic gingival inflammation is associated with increased local citrullination and PAD2 and PAD4 expression in periodontitis. The increased citrullination and PAD2 and PAD4 expression in periodontitis were, however, independent of the presence of periodontal pathogen P. gingivalis and A. actinomycetemcomitans leukotoxin.

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  • 37.
    Ennibi, Oum Keltoum
    et al.
    Department of Periodontology, School of Dentistry, Mohammed V University, Morocco.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Akkaoui, Sanae
    Laboratory of Oral Microbiology and Biotechnology, School of Dentistry, Mohammed V University in Rabat, Morocco.
    Reddahi, Sarah
    Department of Periodontology, School of Dentistry, Mohammed V University, Morocco.
    Kwamin, Francis
    Dental School University of Ghana, Ghana.
    Haubek, Dorte
    Section for Pediatric Dentistry, Department of Dentistry and Oral Health, Aarhus University, Denmark.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    High salivary levels of JP2 genotype of Aggregatibacter actinomycetemcomitans is associated with clinical attachment loss in Moroccan adolescents2019In: Clinical and Experimental Dental Research, E-ISSN 2057-4347, Vol. 5, no 1, p. 44-51Article in journal (Refereed)
    Abstract [en]

    It has previously been shown that the presence of Aggregatibacter actinomycetemcomitans in subgingival plaque is significantly associated with increased risk for clinical attachment loss. The highly leukotoxic JP2 genotype of this bacterium is frequently detected in adolescents with aggressive forms of periodontitis. The aims of the study were to quantify the levels of JP2 and non-JP2 genotypes of A. actinomycetemcomitans in saliva of Moroccan adolescents with the JP2 genotype earlier detected in the subgingival plaque. The salivary concentrations of inflammatory proteins were quantified and linked to the clinical parameters and microbial findings. Finally, a mouth rinse with leukotoxin-neutralizing effect was administrated and its effect on the levels the biomarkers and A. actinomycetemcomitans examined. The study population consisted of 22 adolescents that previously were found to be positive for the JP2 genotype in subgingival plaque. Periodontal registration and sampling of stimulated saliva was performed at baseline. A mouth rinse (active/placebo) was administrated, and saliva sampling repeated after 2 and 4 weeks rinse. The salivary levels of JP2 and non-JP2 were analyzed by quantitative PCR and inflammatory proteins by ELISA. Both the JP2 and the non-JP2 genotype were detected in all individuals with significantly higher levels of the non-JP2. Enhanced levels of the JP2 genotype of A. actinomycetemcomitans was significantly correlated to the presence of attachment loss (≥3 mm). Salivary concentrations of inflammatory biomarkers did not correlate to periodontal condition or levels of A. actinomycetemcomitans. The use of active or placebo leukotoxin-neutralizing mouth rinse did not significantly interfered with the levels of these biomarkers. Saliva is an excellent source for detection of A. actinomycetemcomitans on individual basis, and high levels of the JP2 genotype were significantly associated with the presence of clinical attachment loss.

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  • 38.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    43-Year Temporal Trends in Immune Response to Oral Bacteria in a Swedish Population2020In: Pathogens, E-ISSN 2076-0817, Vol. 9, no 7, article id 544Article in journal (Refereed)
    Abstract [en]

    Bacteria colonizing the mouth induce an adaptive immune response with the systemic and local presence of species or strain-specific immunoglobulins. Few studies have addressed global antibody patterns for oral bacteria or potential population time trends. We assessed these aspects in relation to a panel of oral bacteria. Using multiplex immunoblotting, IgG levels for 26 oral bacterial species (54 strains) were determined in 888 plasma samples from 30-year-old early pregnant women (n = 516) and 50-year-old men and women (n = 372) collected between 1976 and 2018. Inter-species correlations were found and age-dependent profiles and levels of immune responses to oral bacteria confirmed. We found temporal trends in the global and single-species antibody responses, but this was age-specific with both inclining and declining shifts. Prominent shifts in the younger group increased IgG towards health-associated Streptococcus salivarius and Streptococcus sanguinis, and in the older group towards disease-associated Aggregatibacter actinomycetemcomitans, Filifactor alocis, and Streptococcus mutans, among others. We concluded that temporal shifts occurred from 1976 to 2018, which may reflect improved oral health (more remaining teeth) and altered lifestyle habits, but this needs to be evaluated in observational studies considering more aspects.

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  • 39. Espín-Pérez, Almudena
    et al.
    Hebels, Dennie G. A. J.
    Kiviranta, Hannu
    Rantakokko, Panu
    Georgiadis, Panagiotis
    Botsivali, Maria
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Palli, Domenico
    Späth, Florentin
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Chadeau-Hyam, Marc
    Kyrtopoulos, Soterios A
    Kleinjans, Jos C. S.
    de Kok, Theo M. C. M.
    Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs)2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 746Article in journal (Refereed)
    Abstract [en]

    PCBs are classified as xenoestrogens and carcinogens and their health risks may be sex-specific. To identify potential sex-specific responses to PCB-exposure we established gene expression profiles in a population study subdivided into females and males. Gene expression profiles were determined in a study population consisting of 512 subjects from the EnviroGenomarkers project, 217 subjects who developed lymphoma and 295 controls were selected in later life. We ran linear mixed models in order to find associations between gene expression and exposure to PCBs, while correcting for confounders, in particular distribution of white blood cells (WBC), as well as random effects. The analysis was subdivided according to sex and development of lymphoma in later life. The changes in gene expression as a result of exposure to the six studied PCB congeners were sex- and WBC type specific. The relatively large number of genes that are significantly associated with PCB-exposure in the female subpopulation already indicates different biological response mechanisms to PCBs between the two sexes. The interaction analysis between different PCBs and WBCs provides only a small overlap between sexes. In males, cancer-related pathways and in females immune system-related pathways are identified in association with PCBs and WBCs. Future lymphoma cases and controls for both sexes show different responses to the interaction of PCBs with WBCs, suggesting a role of the immune system in PCB-related cancer development.

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  • 40. Fanidi, Anouar
    et al.
    Muller, David C
    Midttun, Øivind
    Ueland, Per Magne
    Vollset, Stein Emil
    Relton, Caroline
    Vineis, Paolo
    Weiderpass, Elisabete
    Skeie, Guri
    Brustad, Magritt
    Palli, Domenico
    Tumino, Rosario
    Grioni, Sara
    Sacerdote, Carlotta
    Bueno-de-Mesquita, H B As
    Peeters, Petra H
    Boutron-Ruault, Marie-Christine
    Kvaskoff, Marina
    Cadeau, Claire
    Huerta, José María
    Sánchez, Maria-José
    Agudo, Antonio
    Lasheras, Cristina
    Quirós, J Ramón
    Chamosa, Saioa
    Riboli, Elio
    Travis, Ruth C
    Ward, Heather
    Murphy, Neil
    Khaw, Kay-Tee
    Trichopoulou, Antonia
    Lagiou, Pagona
    Papatesta, Eleni-Maria
    Boeing, Heiner
    Kuehn, Tilman
    Katzke, Verena
    Steffen, Annika
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Brennan, Paul
    Johansson, Mattias
    Circulating vitamin D in relation to cancer incidence and survival of the head and neck and oesophagus in the EPIC cohort2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 36017Article in journal (Refereed)
    Abstract [en]

    Experimental and epidemiological data suggest that vitamin D play a role in pathogenesis and progression of cancer, but prospective data on head and neck cancer (HNC) and oesophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants with blood samples between 1992 and 2000. This analysis includes 497 case-control pairs of the head and neck and oesophagus, as well as 443 additional controls. Circulating 25(OH)D3 were measured in pre-diagnostic samples and evaluated in relation to HNC and oesophagus cancer risk and post-diagnosis all-cause mortality. After controlling for risk factors, a doubling of 25(OH)D3 was associated with 30% lower odds of HNC (OR 0.70, 95% confidence interval [95% CI] 0.56-0.88, Ptrend = 0.001). Subsequent analyses by anatomical sub-site indicated clear inverse associations with risk of larynx and hypopharynx cancer combined (OR 0.55, 95CI% 0.39-0.78) and oral cavity cancer (OR 0.60, 95CI% 0.42-0.87). Low 25(OH)D3 concentrations were also associated with higher risk of death from any cause among HNC cases. No clear association was seen with risk or survival for oesophageal cancer. Study participants with elevated circulating concentrations of 25(OH)D3 had decreased risk of HNC, as well as improved survival following diagnosis.

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  • 41. Georgiadis, Panagiotis
    et al.
    Hebels, Dennie G
    Valavanis, Ioannis
    Liampa, Irene
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palli, Domenico
    Chadeau-Hyam, Marc
    Chatziioannou, Aristotelis
    Jennen, Danyel G J
    Krauskopf, Julian
    Jetten, Marlon J
    Kleinjans, Jos C S
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    Omics for prediction of environmental health effects: Blood leukocyte-based cross-omic profiling reliably predicts diseases associated with tobacco smoking.2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 20544Article in journal (Refereed)
    Abstract [en]

    The utility of blood-based omic profiles for linking environmental exposures to their potential health effects was evaluated in 649 individuals, drawn from the general population, in relation to tobacco smoking, an exposure with well-characterised health effects. Using disease connectivity analysis, we found that the combination of smoking-modified, genome-wide gene (including miRNA) expression and DNA methylation profiles predicts with remarkable reliability most diseases and conditions independently known to be causally associated with smoking (indicative estimates of sensitivity and positive predictive value 94% and 84%, respectively). Bioinformatics analysis reveals the importance of a small number of smoking-modified, master-regulatory genes and suggest a central role for altered ubiquitination. The smoking-induced gene expression profiles overlap significantly with profiles present in blood cells of patients with lung cancer or coronary heart disease, diseases strongly associated with tobacco smoking. These results provide proof-of-principle support to the suggestion that omic profiling in peripheral blood has the potential of identifying early, disease-related perturbations caused by toxic exposures and may be a useful tool in hazard and risk assessment.

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  • 42.
    Golovliov, Igor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Bäckman, Stina
    Division of CBRN Defence and Security, Swedish Defence Research Agency FOI, Umeå, Sweden.
    Granberg, Malin
    Division of CBRN Defence and Security, Swedish Defence Research Agency FOI, Umeå, Sweden.
    Salomonsson, Emelie
    Division of CBRN Defence and Security, Swedish Defence Research Agency FOI, Umeå, Sweden.
    Lundmark, Eva
    Division of CBRN Defence and Security, Swedish Defence Research Agency FOI, Umeå, Sweden.
    Näslund, Jonas
    Division of CBRN Defence and Security, Swedish Defence Research Agency FOI, Umeå, Sweden.
    Busch, Joseph D.
    Pathogen and Microbiome Institute, Northern Arizona University, Arizona, Flagstaff, United States.
    Birdsell, Dawn
    Pathogen and Microbiome Institute, Northern Arizona University, Arizona, Flagstaff, United States.
    Sahl, Jason W.
    Pathogen and Microbiome Institute, Northern Arizona University, Arizona, Flagstaff, United States.
    Wagner, David M.
    Pathogen and Microbiome Institute, Northern Arizona University, Arizona, Flagstaff, United States.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Forsman, Mats
    Division of CBRN Defence and Security, Swedish Defence Research Agency FOI, Umeå, Sweden.
    Thelaus, Johanna
    Division of CBRN Defence and Security, Swedish Defence Research Agency FOI, Umeå, Sweden.
    Long-Term Survival of Virulent Tularemia Pathogens outside a Host in Conditions That Mimic Natural Aquatic Environments2021In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 87, no 6, p. 1-11, article id e02713-20Article in journal (Refereed)
    Abstract [en]

    Francisella tularensis, the causative agent of the zoonotic disease tularemia, can cause seasonal outbreaks of acute febrile illness in humans with disease peaks in late summer to autumn. Interestingly, its mechanisms for environmental persistence between outbreaks are poorly understood. One hypothesis is that F. tularensis forms biofilms in aquatic environments. We utilized two fully virulent wild-type strains: FSC200 (Francisella tularensis subsp. holarctica) and Schu S4 (Francisella tularensis subsp. tularensis) and three control strains, the attenuated live vaccine strain (LVS; F. tularensis subsp. holarctica), a Schu S4 DwbtI mutant that is documented to form biofilms, and the low-virulence strain U112 of the closely related species Francisella novicida. Strains were incubated in saline solution (0.9% NaCl) microcosms for 24 weeks at both 4°C and 20°C, whereupon viability and biofilm formation were measured. These temperatures were selected to approximate winter and summer temperatures of fresh water in Scandinavia, respectively. U112 and Schu S4 DwbtI formed biofilms, but F. tularensis strains FSC200 and Schu S4 and the LVS did not. All strains exhibited prolonged viability at 4°C compared to 20°C. U112 and FSC200 displayed remarkable long-term persistence at 4°C, with only 1- and 2-fold log reductions, respectively, of viable cells after 24weeks. Schu S4 exhibited lower survival, yielding no viable cells by week 20. At 24weeks, cells from FSC200, but not from Schu S4, were still fully virulent in mice. Taken together, these results demonstrate biofilm-independent, long-term survival of pathogenic F. tularensis subsp. holarctica in conditions that mimic overwinter survival in aquatic environments.

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  • 43.
    Gomez-Bañuelos, Eduardo
    et al.
    John Hopkins University, Baltimore United states.
    Johansson, Linda
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Konig, Maximilian F.
    John Hopkins University, Baltimore, United States.
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Paz, Merlin
    John Hopkins University, Baltimore, United States.
    Buhlin, Kåre
    Karolinska institutet, Stockholm, Sweden.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Andrade, Felipe
    John Hopkins University, Baltimore, United States.
    Exposure to Aggregatibacter Actinomycetemcomitans before Symptom Onset and the Risk of Evolving to Rheumatoid Arthritis2020In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, no 6, article id 1906Article in journal (Refereed)
    Abstract [en]

    Periodontal disease has been implicated in the pathogenesis of rheumatoid arthritis (RA), an autoimmune disease characterized by immune-mediated synovial damage, and antibodies to citrullinated antigens. Here, we investigate the association between exposure to the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) and the development of RA. IgM, IgG and IgA antibodies to Aa leukotoxin A (LtxA) were detected by ELISA in plasma from a cohort of Swedish adults at different stages of RA development, from before onset of symptoms to established disease. Patients with early and established RA had increased levels of anti-LtxA IgM compared with matched non-RA controls and periodontally healthy individuals. Logistic regression revealed that anti-LtxA IgM levels were associated with RA during early disease (OR 1.012, 95%CI 1.007, 1.017), which was maintained after adjustment for smoking, anti-CCP antibodies, rheumatoid factor, HLA-DRB1 shared epitope alleles and sex. We found no association between anti-LtxA IgG/IgA antibodies and RA at any stage of disease development. The data support a temporal association between anti-LtxA IgM antibodies and the development of RA, suggesting that a subset of RA patients may have been exposed to Aa around the time of transition from being asymptomatic to become a patient with RA.

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  • 44.
    Gonzales, Jose Roberto
    et al.
    Department of Periodontology, Justus-Liebig University of Giessen.
    Groeger, Sabine
    Department of Periodontology, Justus-Liebig University of Giessen.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Meyle, Jörg
    Department of Periodontology, Justus-Liebig University of Giessen.
    T helper cells from aggressive periodontitis patients produce higher levels of interleukin-1 beta and interleukin-6 in interaction with Porphyromonas gingivalis2014In: Clinical Oral Investigations, ISSN 1432-6981, E-ISSN 1436-3771, Vol. 18, no 7, p. 1835-1843Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: In this study, we analyzed the production of Interleukin-1 beta (IL-1β) and IL-6 by activated CD4+ cells obtained from aggressive periodontitis (AgP) patients in comparison with healthy subjects (HC).

    MATERIALS AND METHODS: CD4+ cells were automatically separated from lymphocytes obtained from peripheral blood of patients with AgP and healthy controls. Cells were activated for 4, 8, and 24 h with three different stimuli: anti-CD3/anti-CD28, phytohemagglutinin (PHA), and Porphyromonas gingivalis (P. gingivalis) outer membrane protein (OMP). Protein levels were measured in supernatants of activated CD4+ cells by a bead-based immunoassay (CBA). In addition, serum antibodies against P. gingivalis were determined. Data were analyzed using U test (p < 0.05).

    RESULTS: T helper cells of AgP patients activated with P. gingivalis OMP produced higher levels of IL-1β and IL-6 in comparison with healthy controls (p < 0.05). Neither the activation with anti-CD3/anti-CD28 nor the activation with PHA showed significantly different production of IL-1β and IL-6 by the cells 25 % of patients and 17 % of controls presented with high serum reactivity to P. gingivalis.

    CONCLUSION: In view of these results, it is possible to conclude that P. gingivalis contributes to the pathogenesis of AgP by inducing high levels of pro-inflammatory cytokines such as IL-1β and IL-6 by peripheral CD4+ T helper cells.

    CLINICAL RELEVANCE: In accordance with the clinical parameters and the immunological data, we suggest that full-mouth disinfection with adjunctive systemic antibiotics might be the anti-infectious non-surgical periodontal treatment of choice in this type of patients. Microbiological analyses at the beginning and at the end of the periodontal treatment are recommended. However, it is necessary to verify these data in longitudinal clinical studies.

  • 45.
    Granlund, Margareta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Höglund Åberg, Carola
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Discrepancies in Antimicrobial Susceptibility between the JP2 and the Non-JP2 Genotype of Aggregatibacter actinomycetemcomitans2022In: Antibiotics, ISSN 0066-4774, E-ISSN 2079-6382, Vol. 11, no 3, article id 317Article in journal (Refereed)
    Abstract [en]

    The Aggregatibacter actinomycetemcomitans JP2 genotype is associated with high leukotoxin production and severe (aggressive) periodontitis. The aim of this study was to compare the antimicrobial susceptibility of JP2 and non-JP2 genotype strains. Minimal inhibitory concentrations (MICs) of 11 antimicrobials were determined for 160 A. actinomycetemcomitans of serotype a, b, or c, mostly isolated in Sweden or Ghana. MIC distributions for benzylpenicillin and fusidic acid revealed a more susceptible subpopulation for 38 serotype b strains, including the 32 of the JP2 genotype, with a benzylpenicillin MIC range of 0.125–0.5 mg/L. In contrast, benzylpenicillin MIC ≤ 16 mg/L was the estimated 99.5% epidemiological cutoff (ECOFF) of all strains. Beta-lactamase production was not detected. The fusidic acid MIC distribution of 11 strains of Aggregatibacter aphrophilus agreed with that found in non-JP2 strains. Cefotaxime, meropenem, levofloxacin, and trimethoprim–sulfamethoxazole MICs were all ≤0.25 mg/L, while MIC90 values for amoxicillin, azithromycin and tetracycline were 1 mg/L. Metronidazole MICs varied between 0.5 and >256 mg/L. The discrepant findings indicate that A. actinomycetemcomitans may be divided into two separate wild types, with a suggested intrinsic reduced susceptibility for benzylpenicillin in the majority of non-JP2 genotype strains. Possible implications for the treatment of A. actinomycetemcomitans infections are discussed.

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  • 46.
    Hallmans, Göran
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Agren, A
    Johansson, G
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Periodontology.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, JH
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindahl, B
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nilsson, M
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Cardiovascular disease and diabetes in the Northern Sweden Health and Disease Study Cohort: evaluation of risk factors and their interactions.2003In: Scandinavian Journal of Public Health. Supplement Links, ISSN 1403-4956, Vol. 61, p. 18-24Article in journal (Refereed)
    Abstract [en]

    The purpose of this paper is, first, to describe the organization, sampling procedures, availability of samples/database, ethical considerations, and quality control program of the Northern Sweden Health and Disease Study Cohort. Secondly, some examples are given of studies on cardiovascular disease and diabetes with a focus on the biomarker programme. The cohort has been positioned as a national and international resource for scientific research.

  • 47.
    Hallmans, Göran
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Zhang, Jie-Xian
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Stattin, P
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Johansson, I
    Hultén, K
    Winkvist, A
    Aman, P
    Lenner, P
    Adlercreutz, H
    Rye, lignans and human health2003In: Proceedings of the Nutrition Society, ISSN 0029-6651, E-ISSN 1475-2719, Vol. 62, no 1, p. 193-9Article in journal (Refereed)
    Abstract [en]

    Rye bran contains a high content not only of dietary fibre, but also of plant lignans and other bioactive compounds in the so-called dietary fibre complex. Blood concentrations of lignans such as enterolactone have been used as biomarkers of intake of lignan-rich plant food. At present,evidence from studies in human subjects does not warrant the conclusion that rye, whole grains orphyto-oestrogens protect against cancer. Some studies, however, have pointed in that direction,especially in relation to cancers of the upper digestive tract. A number of prospective epidemiological studies have clearly shown a protective effect of wholegrain cereals against myocardial infarctions. A corresponding protective effect against diabetes and ischaemic stroke(brain infarct) has also been demonstrated. It seems reasonable to assume that these protective effects are associated with one or more factors in the dietary fibre complex.

  • 48.
    Haubek, Dorte
    et al.
    Århus universitet.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Pathogenicity of the highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans and its geographic dissemination and role in aggressive periodontitis2014In: Journal of Oral Microbiology, E-ISSN 2000-2297, Vol. 6, article id 23980Article in journal (Refereed)
    Abstract [en]

    For decades, Aggregatibacter actinomycetemcomitans has been associated with aggressive forms of periodontitis in adolescents. In the middle of the 1990s, a specific JP2 clone of A. actinomycetemcomitans, belonging to the cluster of serotype b strains of A. actinomycetemcomitans and having a number of other characteristics, was found to be strongly associated with aggressive forms of periodontitis, particularly in North Africa. Although several longitudinal studies still point to the bacterial species, A. actinomycetemcomitans as a risk factor of aggressive periodontitis, it is now also widely accepted that the highly leukotoxic JP2 clone of A. actinomycetemcomitans is implicated in rapidly progressing forms of aggressive periodontitis. The JP2 clone strains are highly prevalent in human populations living in Northern and Western parts of Africa. These strains are also prevalent in geographically widespread populations that have originated from the Northwest Africa. Only sporadic signs of a dissemination of the JP2 clone strains to non-African populations have been found despite Africans living geographically widespread for hundreds of years. It remains an unanswered question if a particular host tropism exists as a possible explanation for the frequent colonization of the Northwest African population with the JP2 clone. Two exotoxins of A. actinomycetemcomitans are known, leukotoxin (LtxA) and cytolethal distending toxin (Cdt). LtxA is able to kill human immune cells, and Cdt can block cell cycle progression in eukaryotic cells and thus induce cell cycle arrest. Whereas the leukotoxin production is enhanced in JP2 clone strains thus increasing the virulence potential of A. actinomycetemcomitans, it has not been possible so far to demonstrate such a role for Cdt. Lines of evidence have led to the understanding of the highly leukotoxic JP2 clone of A. actinomycetemcomitans as an aetiological factor of aggressive periodontitis. Patients, who are colonized with the JP2 clone, are likely to share this clone with several family members because the clone is transmitted through close contacts. This is a challenge to the clinicians. The patients need intense monitoring of their periodontal status as the risk for developing severely progressing periodontal lesions are relatively high. Furthermore, timely periodontal treatment, in some cases including periodontal surgery supplemented by the use of antibiotics, is warranted. Preferably, periodontal attachment loss should be prevented by early detection of the JP2 clone of A. actinomycetemcomitans by microbial diagnostic testing and/or by preventive means.

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  • 49.
    Haubek, Dorte
    et al.
    Aarhus university.
    Mulli, Tonnie
    University of Nairobi.
    Kemoli, Arthur
    University of Nairobi.
    Lindholm, Mark
    Umeå University, Faculty of Medicine, Department of Odontology.
    Gjørup, Hans
    Aarhus university.
    Nørregaard, Marie-Louise Milvang
    Aarhus university.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Prevalence of JP2 and Non-JP2 Genotypes of Aggregatibacter actinomycetemcomitans and Oral Hygiene Practice of Kenyan Adolescents in Maasai Mara2021In: Pathogens, E-ISSN 2076-0817, Vol. 10, no 4, article id 488Article in journal (Refereed)
    Abstract [en]

    Aggregatibacter actinomycetemcomitans is implicated in the etiology of periodontitis that affects adolescents. The monitoring and mapping of the geographic dissemination pattern of JP2 and non-JP2 genotypes of A. actinomycetemcomitans are of interest. In Africa, the highly leukotoxic JP2 genotype is known to be prevalent, particularly in north-west Africa. The aims of this study were to determine the prevalence of JP2 and non-JP2 genotypes and investigate the oral hygiene practices among adolescents living in Maasai Mara, Kenya. A total of 284 adolescents (mean age: 15.0 yrs; SD 1.1) were interviewed regarding their age, gender, medical history, and oral hygiene practice, and the number of teeth present was recorded. One subgingival pooled plaque sample from all the first molars of each participant was analyzed by conventional PCR. The mean number of permanent teeth present was 27.9 (SD: 2.0; range: 22-32; 95% CI: 27.7-28.1). Sixteen (5.6%) and two (0.7%) adolescents were positive for non-JP2 and JP2 genotypes, respectively. For the vast majority of the adolescents, the use of a toothbrush (99.3%) and toothpaste (80.1%), as well as some kind of toothpick (>60.2%), were part of their oral hygiene practice, with dental floss (0.4%) and/or mouth rinses (0.4%) rarely being used. We have, for the first time, identified Kenyan adolescents colonized with the JP2 genotype. The prevalence of the JP2 genotype of A. actinomycetemcomitans is low, a possible indicator that it spreading through human migration from North and West Africa to East Africa is a rare occasion.

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  • 50. Hirschfeld, Josefine
    et al.
    Roberts, Helen M
    Chapple, Iain L C
    Parčina, Marijo
    Jepsen, Søren
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Effects of Aggregatibacter actinomycetemcomitans leukotoxin on neutrophil migration and extracellular trap formation.2016In: Journal of Oral Microbiology, E-ISSN 2000-2297, Vol. 8, article id 33070Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Aggressive periodontitis is associated with the presence of Aggregatibacter actinomycetemcomitans, a leukotoxin (Ltx)-producing periodontal pathogen. Ltx has the ability to lyse white blood cells including neutrophils.

    OBJECTIVES: This study was aimed at investigating the interactions between neutrophils and Ltx with regard to the chemotactic properties of Ltx and the release of neutrophil extracellular traps (NETs).

    METHODS: Neutrophils from healthy blood donors were isolated and incubated for 30 min and 3 h with increasing concentrations of Ltx (1, 10, and 100 ng/mL) as well as with A. actinomycetemcomitans strains (NCTC 9710 and HK 1651) producing different levels of Ltx. Formation of NETs and cell lysis were assessed by microscopy, fluorescence-based assays, and measurement of released lactate dehydrogenase. Neutrophil migration in response to different Ltx gradients was monitored by real-time video microscopy, and image analysis was performed using ImageJ software.

    RESULTS: Although Ltx (10 and 100 ng/mL) and the leukotoxic A. actinomycetemcomitans strain HK 1651 lysed some neutrophils, other cells were still capable of performing NETosis in a concentration-dependent manner. Low doses of Ltx and the weakly leukotoxic strain NCTC 9710 did not lead to neutrophil lysis, but did induce some NETosis. Furthermore, all three concentrations of Ltx enhanced random neutrophil movement; however, low directional accuracy was observed compared with the positive control (fMLP).

    CONCLUSIONS: The results indicate that Ltx acts both as a neutrophil activator and also causes cell death. In addition, Ltx directly induces NETosis in neutrophils prior to cell lysis. In future studies, the underlying pathways involved in Ltx-meditated neutrophil activation and NETosis need to be investigated further.

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