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  • 251.
    Dahlin, Anna M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Plasma vitamin B12 concentrations and the risk of colorectal cancer: a nested case-referent study2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 32, no 2, p. 304-314Article in journal (Refereed)
    Abstract [en]

    In this nested case-referent study, we related plasma concentrations of vitamin B12 to the risk of colorectal cancer, taking into consideration prediagnostic plasma folate and total homocysteine concentrations. Subjects were 226 cases and double matched referents from the population-based Northern Sweden Health and Disease Study. Follow-up times from recruitment to diagnosis ranged from 0.1 to 12.7 years, with a median of 4.2 years. Plasma vitamin B12 concentrations were inversely associated with the risk of rectal cancer: univariate odds ratio for the highest versus lowest quintile 0.34 (95% confidence interval (95% CI) 0.13-0.83), p(trend) = 0.004. Risk estimates were attenuated slightly but remained statistically significant after adjustment for body mass index, current smoking, recreational and occupational physical activity, alcohol intake and prediagnostic plasma folate and total homocysteine concentrations: OR 0.30 (95% CI 0.08-0.99), p(trend) = 0.025. The corresponding univariate and fully adjusted odds ratios for colon cancer were 1.25 (CI 0.66-2.36), p(trend) = 0.185 and 1.42 (CI 0.67-3.05), p(trend) = 0.113, respectively. The observed over-risk was attributable to left-sided colon cancer. Interaction analyses including vitamin B12, folate and homocysteine were in line with the results for vitamin B12 alone. In conclusion, these results suggest that increasing levels of plasma vitamin B12, alone or together with other factors involved in one-carbon metabolism, may reduce the risk of rectal cancer, whereas for colon cancer, the association appears to be less clear.

  • 252.
    Dahlqvist, Johanna
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Dahlqvist, Åke
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Marklund, Marie
    Umeå University, Faculty of Medicine, Odontology, Ortodontics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
    Physical findings in the upper airways related to obstructive sleep apnea in men and women2007In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 127, no 6, p. 623-630Article in journal (Refereed)
    Abstract [en]

    CONCLUSIONS:There are gender differences when it comes to the risk factors for sleep apnea. Large tonsils, a high tongue and a wide uvula are risk factors for sleep apnea in men, while large tonsils and a retrognathic mandible are risk factors in women. Upper airway abnormalities including mandibular retrognathia are, however, unable to predict sleep apnea among snorers being investigated for suspected sleep apnea.

    OBJECTIVES: To identify gender-specific risk factors for obstructive sleep apnea and the diagnostic performance from physical upper airway examinations among snoring men and women investigated because of suspected sleep apnea.

    PATIENTS AND METHODS: The dimensions of the uvula, tonsils, velopharynx and tongue, and nasal septal deviation, mandibular position, neck circumference, weight, and height were systematically scored in 801 consecutive snoring patients (596 men and 205 women), who had been referred for a primary sleep apnea recording.

    RESULTS: In men, large tonsils, a high tongue, and a wide uvula were independent factors associated with an apnea-hyopnea index of > 15. In women, large tonsils and mandibular retrognathia were independent factors associated with an apnea-hypopnea index of > 15. The positive predictive values for upper airway abnormalities ranged between 0.20 and 0.25 in men and between 0.09 and 0.15 in women.

  • 253.
    Dahlstrand Rudin, Arvid
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Burstedt, John
    Umeå University, Faculty of Medicine, Department of Odontology.
    The importance of OuterMembrane Protein A in SerumResistance in Aggregatibacteractinomycetemcomitans serotype astrain D7SS2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The Gram-negative bacterium Aggregatibacter actinomycetemcomitans is primarily associatedwith aggressive forms of periodontal disease. Additionally, it has occasionally been found to causemetastatic infections in non-oral sites. This requires the ability to evade the bactericidal activity ofthe complement system of the humoral immune system. Outer membrane proteins, namely,Omp100 and OmpA have been connected to normal human serum resistance for several bacteriaspecies. The objective of this study was to investigate if serum-resistant ompA mutants can beobtained, and to detect changes in OMP expression. We used A. actinomycetemcomitansserotype a strain D7SS and D7SS ompA knockouts. The strains were incubated in 50 % NHS.This resulted in a substantial decrease of survival among D7SS ompA knockouts. D7SS ompAknockouts were exposed to 50 % NHS once more to confirm stable serum resistance. 13 out of14 tested clones showed growth, indicating that serum resistant ompA mutants could begenerated. SDS-PAGE gel of extracted outer membrane vesicles revealed an additional proteinband of approximately 34 kDa in at least 4 of 5 tested serum resistant ompA mutants. This proteinband has been analyzed in the laboratory, and according to LC-MS/MS it contains an OmpAhomologue, which has been named OmpA2. We conclude that OmpA2 expression might be amajor mechanism for serum survival in A. actinomycetemcomitans serotype a strain D7SS ompAknockouts.

  • 254.
    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, ISSN 2000-2297, 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.

  • 255. Dalton Bittencourt, DD
    et al.
    Ezecelevski, IG
    Reis, A
    van Dijken, Jan
    Umeå University, Faculty of Medicine, Odontology, Dental Hygiene.
    Loguercio, AD
    An 18-months' evaluation of self-etch and etch & rinse adhesive in non-carious cervical lesions.2005In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 63, no 3, p. 173-178Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE. In this intra-individual comparison (an 18-months' randomized, controlled prospective study), we evaluated the clinical performance of one self-etch and one "etch & rinse" adhesive in non-carious cervical lesions. METHODS. Twenty-five patients with at least two pairs of similar-sized non-carious cervical lesions participated. Seventy-eight restorations were placed; 39 with etch & rinse (Single-Bond) and 39 with self-etch (Adper Prompt). Both adhesives were combined with the microfilled resin composite Filtek-A110. The restorations were evaluated at baseline, 6, 12, and 18 months according to slightly modified USPHS criteria. Statistical differences between the adhesives was tested with McNemar's test and clinical degradation over time for each material with the Fisher exact test (a=0.05). RESULTS. Thirty pairs were evaluated at 12 and 18 months. Two self-etch restorations were lost after 18 months. Nine Adper Prompt and four Single-Bond restorations scored bravo for marginal adaptation at 18 months (p<0.05). Nine Adper Prompt and three Single-Bond restorations scored bravo for marginal discoloration (p<0.05). CONCLUSIONS. Both adhesive systems showed acceptable clinical retention rates according to the ADA full acceptance criteria for enamel-bonding systems in class V non-carious lesions. The self-etch adhesive showed a faster progressive marginal degradation.

  • 256.
    Danielsson, Karin
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Oral lichen planus: studies of factors involved in differentiation, epithelial mesenchymal transition and inflammation2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Lichen planus is a chronic inflammation of skin and mucosa with unknown cause. Oral Lichen Planus, OLP, affects around 2% of the population. Autoimmunity has been suggested as a possible cause as the disease has autoimmune features such as female predominance, cyclic nature and cytotoxic T-cell infiltrate. It has been suggested that the intense inflammatory response seen in OLP is caused by factors on the keratinocyte surface triggering the immune system. Chronic inflammation is one of the hallmarks of oral lichen planus and chronic inflammation is connected to increased risk of tumor development. WHO classifies OLP as a potentially malignant condition with increased risk of developing Squamous cell carcinoma of head and neck, SCCHN, but malignant transformation of OLP is a matter of controversy. The aim of these studies was to further elucidate the autoimmune and premalignant character of OLP. Factors involved in malignant transformation, autoimmunity and inflammation were analyzed in normal oral mucosa, OLP and SCCHN. Factors studied were the signal transducers of Transforming growth factor-β the Smad proteins, microRNAs, COX-2, the receptor CXCR-3 and its ligands CXCL-10 and -11 and ELF-3.

    Material and methods: In the study on Smad protein expression formalin fixed and paraffin embedded biopsies from normal oral mucosa, OLP and SCCHN was used. For the remaining studies fresh frozen biopsies from OLP and normal controls was used. All of the fresh frozen OLP samples and their controls were micro dissected to be able to analyze the epithelial part only as well as sections of the whole biopsy. Methods used are immunohistochemistry, qRT-PCR and Western blot.

    Results: Analyses of smad proteins expression showed a clear increase of smad3 and smad7 in OLP compared to normal oral mucosa. The expressions of smad proteins in the tumors were more heterogeneous. Some of the SCCHN samples showed a similar expression as OLP while others did not. Micro RNA analyzes showed that miR-21 and miR-203 was significantly increased in OLP epithelium compared to normal oral epithelium while the expression of miR-125b and their potential targets p53 and p63 was decreased in OLP. The presence of COX-2 was significantly higher in OLP than normal controls. At the same time the expression of miR-26b, a suggested repressor of COX-2 was decreased in OLP compared to normal mucosa. The receptor CXCR-3 and its ligands CXCL-10 and -11 were increased in OLP. Expressions of the differentiation involved factor ELF-3 mRNA as well as protein were decreased in OLP.

    Conclusion: The factors studied are involved in differentiation, malignant transformation and inflammation. Some of the results in these studies indicate a similar expression pattern for OLP and SCCHN. Several of the factors studied are involved in differentiation and their deregulation suggests a disturbed differentiation pattern and this could indicate a premalignant character of OLP but malignant transformation of OLP lesions are relative rare. A lot of these factors are also involved in inflammatory processes and connected to autoimmune diseases and their deregulation in OLP could also support an autoimmune cause of the disease. Based on our studies a suggestion is that the disturbed differentiation pattern triggers the intense immune response directed against the epithelial cells seen in OLP.

  • 257.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Rentoft, Matilda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Coates, Philip
    Tayside Tissue Bank/Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wahlin, Ylva Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Autoantibodies and decreased expression of the transcription factor ELF-3 together with increased chemokine pathways support an autoimmune phenotype and altered differentiation in lichen planus located in oral mucosa2013In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 27, no 11, p. 1410-1416Article in journal (Refereed)
    Abstract [en]

    Background  The pathogenesis of oral lichen planus (OLP), a chronic inflammatory disease, is not fully understood. It is known that OLP has autoimmune features, and it is suggested to be an autoimmune disease. ELF-3 is involved in differentiation of keratinocytes and deregulated in different tumours and inflammatory diseases. CXCR-3 and its ligands CXCL-10 and CXCL-11 are increased in autoimmune diseases and linked to Th-1 immune response. Objectives  To analyse and compare expression of ELF-3, CXCR-3, CXCL-10 and CXCL-11 in OLP lesions and controls in whole and microdissected epithelium. Methods  Tissue biopsies from 20 patients clinically and histologically diagnosed with OLP and 20 healthy controls were studied using whole tissues or microdissected epithelium. By the use of qRT-PCR, mRNA levels of ELF-3, CXCR-3, CXCL-10 and CXCL-11 were studied. Western blot was used for analysis of ELF-3 protein expression. Sera from 19 OLP patients and 20 controls were analysed with ELISA in search for autoantibodies. Results  The upregulation of CXCR-3, CXCL-10 and CXCL-11 found in OLP is similar to previous findings showing an autoimmune phenotype in lichen planus (LP) and lichen sclerosus. Decreased expression of the differentiation-related transcription factor ELF-3 was also seen in OLP lesions, and we further demonstrate presence of circulating autoantibodies against the ELF-3 protein in sera from 3 of 19 (16%) LP patients tested. Conclusions  On the basis of these findings, we confirm that OLP shows features of an autoimmune disease and suggest deregulated differentiation of keratinocytes to be one of the causes of the disease phenotype.

  • 258.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Coates, Philip J
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Genes Involved in Epithelial Differentiation and Development are Differentially Expressed in Oral and Genital Lichen Planus Epithelium Compared to Normal Epithelium2014In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 94, no 5, p. 526-530Article in journal (Refereed)
    Abstract [en]

    Lichen planus (LP) is a chronic mucocutaneous disease with unknown cause. Patients with LP often have both oral and genital lesions, but these conditions are often considered as separate diseases and treated accordingly. To find out which genes are differently expressed in mucosal LP compared to normal mucosa and establish whether oral and genital LP are in fact the same disease, whole genome expression analysis was performed on epithelium from 13 patients diagnosed with oral and/or genital LP and normal controls. For confirmation of keratin 4 and corneodesmosin expression, quantitative reverse-transcription PCR and immunohistochemistry were used. Many genes involved in epithelial development and differentiation are differently expressed in epithelium from LP compared to normal epithelium. Several of the differentially expressed genes are common for oral and genital LP and the same biological processes are altered which supports the fact that oral and genital LP are manifestations of the same disease. The change in gene expression indicates that differentiation is altered leading to changes in the epithelial barrier.

  • 259.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ebrahimi, Maijd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Increased levels of COX-2 in oral lichen planus supports an autoimmune cause of the disease2012In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 26, no 11, p. 1415-1419Article in journal (Refereed)
    Abstract [en]

    Background: Oral lichen planus (OLP) is a chronic inflammatory disease for which the pathogenesis is not fully understood. OLP has autoimmune features and auto immunity has been suggested as a potential cause, whereas WHO has classified OLP as a premalignant condition. Association between chronic inflammation and cancer is known and chronic inflammation is one of the characteristics of OLP. A protein connected to inflammation and suggested to be involved in cancer development is cyclooxygenase-2 (COX-2) which can be inhibited by microRNA-26b (miR-26b).

    Objective: The aim was to map levels of COX-2 and miR-26b in OLP lesions to see if there was any correlation between expression of COX-2 and its regulator miR-26b in OLP.

    Methods: In biopsies from 20 OLP patients and 20 age and gender-matched controls laser- micro dissection of epithelium was performed. Quantitative RT-PCR, immunohistochemistry and Western blot were used in the analysis.

    Results: Levels of COX-2 mRNA were significantly higher while levels of miR-26b were significantly lower in OLP lesions compared to controls. Using immunohistochemistry normal oral mucosa samples did not show any expression of COX-2 while OLP samples expressed the protein. No COX-2 protein was detectable with Western blot.

    Conclusion: Increased expression of COX-2 and decreased expression of miR-26b in OLP suggests both to play a role in OLP. COX-2 has been connected to both malignant development and autoimmunity but as malignant development of OLP is quite rare we suggest that the increased levels of COX-2 seen here support an autoimmune cause of the disease.

  • 260.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wahlin, Ylva Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Alterations in factors involved in differentiation and barrier function in the epithelium in oral and genital lichen planus2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 2, p. 214-218Article in journal (Refereed)
    Abstract [en]

    Lichen planus is a chronic recurrent inflammatory disease affecting both skin and mucosa, mainly in oral and/or genital regions. Keratinocytes go through a well-regulated process of proliferation and differentiation, alterations in which may result in defects in the protective epithelial barrier. Long-term barrier impairment might lead to chronic inflammation. In order to broaden our understanding of the differentiation process in mucosal lichen planus, we mapped the expression of 4 factors known to be involved in differentiation. Biopsies were collected from oral and genital lichen planus lesions and normal controls. Altered expression of all 4 factors in epithelium from lichen planus lesions was found, clearly indicating disturbed epithelial differentiation in lichen planus lesions.

  • 261.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Diagnostics.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Diagnostics. Umeå University, Faculty of Medicine, Department of Odontology, Endodontics.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Diagnostics. Umeå University, Faculty of Medicine, Department of Odontology, Prosthetic Dentistry.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Reply to increased levels of COX-2 and oral lichen planus by P.D. Pigatto, F. Spaderi, G.P. Bombeccari, G. Guzzi by Danielsson et al2013In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 27, no 3, p. 395-396Article in journal (Refereed)
  • 262.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sjöström, Mats
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology.
    Epstein-Barr virus is not detected in mucosal lichen planus2018In: Medicina Oral, ISSN 1698-4447, E-ISSN 1698-6946, Vol. 23, no 5, p. e560-e563, article id 22617Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Lichen planus (LP) is a chronic inflammatory, immunological, mucocutaneous disease can affect skin, genital and oral mucosa. Oral lichen planus (OLP) is the most common noninfectious, chronic inflammatory oral disease affecting 1-2% of the general adult population. World Health Organization (WHO) classifies OLP as a potentially malignant disorder. Epstein Barr virus or human herpesvirus-4, is a member of the herpes virus family and one of the most ubiquitous viruses known to human, infecting approximately 90% of the world's adult population. The virus often infects B lymphocytes resulting in a wide spectrum of mucocutaneous and systemic diseases, ranging from mild lesions to aggressive malignancies. The aim of this study was to investigate expression of the EBV encoded RNAs EBER1 and EBER2 in oral and genital lichen planus and compare results with normal tissues in situ hybridization which is considered the golden standard for detection of EBER.

    MATERIAL AND METHODS: A total of 68 biopsies, 25 oral LP, 26 genital LP, 10 oral controls and finally 7 genital controls were analysed using situ hybridization.

    RESULT: All samples had RNA as shown by the control slide, whereas no case contained neither EBER1 nor EBER2.

    CONCLUSIONS: Based on results from our study EBV is not involved in aetiology of lichen planus.

  • 263.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Olah, Joakim
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Zohori-Zangeneh, Reza
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology.
    Increased expression of p16 in both oral and genital lichen planus2018In: Medicina Oral, ISSN 1698-4447, E-ISSN 1698-6946, Vol. 23, no 4, p. e449-e453Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Lichen Planus, LP, is an inflammatory disease of possible autoimmune origin affecting mainly oral and genital mucosa and skin. According to the WHO oral LP is considered a potentially malignant disorders. The p16 tumour suppressor protein can act as an inhibitor of cyclin dependent kinases 4 and 6 and thus down regulate cell cycle progression. Since the discovery of p16 several studies have evaluated its expression in various forms of human cancers. The aim of this study was to evaluate and compare the expression of p16 in oral and genital LP and corresponding healthy mucosa.

    MATERIAL AND METHODS: A total of 76 cases of oral LP (OLP), 34 cases of genital LP (GLP), 12 cases of healthy oral and 9 cases of healthy genital mucosa were analysed by the use of immunohistochemistry.

    RESULTS: Data showed p16 to be highly expressed in both oral and genital LP, higher than in oral (p=0.000), and genital controls (p=0.002).

    CONCLUSIONS: Results suggest that the over-expression of p16 seen in LP play a part in the histopathology of the disease.

  • 264.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wahlin, Ylva Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Coates, PJ
    Division of Medical Sciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Increased expression of Smad proteins, and in particular Smad3, in oral lichen planus compared to normal oral mucosa2010In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 39, no 9, p. 639-644Article in journal (Refereed)
    Abstract [en]

    Backgound: Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa which the World Health Organisation (WHO) considers a premalignant condition. One step in malignant development is so called epithelial mesenchymal transition (EMT), a process whereby epithelial cells acquire mesenchymal characteristics. EMT occurs during embryogenesis and wound healing but also in some human diseases such as cancer and fibrosis. A factor known to induce EMT is transforming growth factor-beta (TGF-beta), which uses the Smad proteins as mediators for its signalling. TGF-beta is also often over-expressed in squamous cell carcinoma of the head and neck (SCCHN).

    Methods: In the present study we mapped expression of Smad proteins in OLP lesions by immunohistochemistry, and compared to expression in normal and sensitive oral mucosa. The latter group of patients had developed SCCHN after shorter or longer periods of diffuse oral symptoms. The aim was to see if there were any signs of EMT related changes in the OLP lesions, as judged by changes in the TGF-beta pathway.

    Conclusion: Changes in the TGF-beta pathway related to EMT are seen in the very earliest stages of oral malignancy and become more severe as lesions progress.

  • 265.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Diagnostics.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Diagnostics. Umeå University, Faculty of Medicine, Department of Odontology, Prosthetic Dentistry.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Decreased expression of ELF-3 indicating disturbed differentiation in oral lichen planus2012In: Oral Diseases, ISSN 1354-523X, E-ISSN 1601-0825, Vol. 18, no Special Issue, Suppl. 1, p. 20-20Article in journal (Other academic)
  • 266.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Gu, Xiaolian
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Altered expression of miR-21, miR-125b, and miR-203 indicates a role for these microRNAs in oral lichen planus2012In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 41, no 1, p. 90-95Article in journal (Refereed)
    Abstract [en]

    Background: Oral lichen planus (OLP), which is a chronic inflammatory disease of the oral mucosa with unknown etiology, affects about 2% of the population. MicroRNAs are small non-coding RNAs involved in normal processes such as development and differentiation as well as progression of human diseases. The aim of this study was to investigate the expression of miR-21, miR-125b, and miR-203 and to compare RNA levels of their potential targets, the tumor suppressor p53 and its relative p63, both known to be deregulated in OLP.

    Methods: In biopsies from 20 patients with OLP and 20 age- and sex-matched healthy controls, epithelium was laser dissected and analyzed for the expression of miR-21, miR-125b, miR-203, p53, and p63 using qRT/PCR.

    Results: Increased expression of miR-21 and miR-203, decreased expression of miR-125, and down-regulation of p53 and ΔNp63 RNA were seen in OLP compared to normal oral mucosa. When comparing microRNA expression to levels of p53 and p63 RNA, a significant negative correlation was seen between ΔNp63 and miR-203 and between miR-21 and p53, respectively.

    Conclusion: Results indicate a role for the studied microRNAs in changes seen in OLP.

  • 267.
    Danielsson Niemi, Liza
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Host ligands and oral bacterial adhesion: studies on phosphorylated polypeptides and gp-340 in saliva and milk2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Infectious diseases e.g. gastric ulcer, caries and perodontitis, are caused by bacteria in a biofilm. Adhesion of bacteria to host ligands e.g. proteins, polypeptides and glycoproteins, is a key event in biofilm formation and colonization of surfaces such as mucosa and tooth tissues. Thus, host ligands could contribute to the susceptibility to infectious diseases. The general aim of this doctoral thesis was to study the effect of phosphorylated polypeptides and gp-340 in saliva and milk on oral bacterial adhesion and aggregation.

    Statherin is a non-glycosylated, phosphorylated polypeptide in saliva. The polypeptide inhibits precipitation and crystal growth of calcium phosphate and mediates adhesion of microorganisms. By using a hybrid peptide construct, the domain for adhesion of Actinomyces isolated from human infections and from rodents was found to reside in the C-terminal end, and the adhesion was inhibitable. With alanine substitution the peptide recognition epitope in the C-terminal end was delineated to Q and TF, where QAATF was an optimal inhibitory peptide. In contrast, human commensal Actinomyces bound to the middle region in a non-inhibitable fashion. Gp-340 is another protein in saliva, and it is a large, multifunctional glycoprotein. Four novel size variants (I-IV) of salivary gp-340 were distinguished within individuals, and their glycoforms were characterized. All four size variants were identical in the N-terminal amino acid sequence and shared core carbohydrates. Low-glyco lung gp-340, high-glyco saliva gp-340, and size variants I-III aggregated bacteria differently. Human milk, which shares many traits with saliva, could inhibit adhesion of Streptococcus mutans to saliva-coated hydroxyapatite (s-HA), a model for teeth, in an individually varying fashion. Human milk caseins, lactoferrin, secretory IgA, and IgG inhibited the binding avidly. By using synthetic peptides the inhibitory epitope in b-casein was mapped to a C-terminal stretch of 30 amino acids. Inhibition by human milk, secretory IgA and the b-casein-derived inhibitory peptide was universal among a panel of mutans streptococci.

    The main conclusions are: (i) statherin mediates differential binding of commensal versus infectious Actinomyces strains with small conformation-dependent binding epitopes, (ii) salivary gp-340 has individual polymorphisms that at least affect binding of bacteria, (iii) human milk inhibits S. mutans adhesion to s-HA in an individually varying fashion, and the C-terminal end of human milk β-casein is one inhibitory component. Together these results suggest that the studied host ligands can influence the composition of the oral biofilm. Statherin may protect the host from colonization of bacteria associated with infections. Gp-340 size variants may affect functions related to host innate immune defences such as interactions with a wide array of bacteria, and human milk may have a protective effect in infants from colonization of mutans streptococci.

  • 268.
    Danielsson Niemi, Liza
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Human milk compounds inhibiting adhesion of mutans streptococci to host ligand-coated hydroxyapatite in vitro2009In: Caries Research, ISSN 0008-6568, E-ISSN 1421-976X, Vol. 43, no 3, p. 171-178Article in journal (Refereed)
    Abstract [en]

    Acquisition of mutans streptococci at an early age is a risk factor for later caries development. Following our recent finding that human milk may inhibit adhesion of Streptococcus mutans the aim of the present study was to identify compounds in human milk preventing adhesion of mutans streptococci to saliva- or gp340-coated hydroxyapatite (s-HA and gp340-HA) using an in vitro model system. Superdex 200 fractions of human milk and purified proteins were screened for binding inhibition of the S. mutans strain Ingbritt. Avid inhibition was seen to both s-HA and gp340-HA for caseins, lactoferrin, IgA and IgG, and moderate inhibition for alpha-lactalbumin and bile salt-stimulated lipase, whereas albumin and lysozyme had no effect. The inhibitory epitope in beta-casein was delineated to its C-terminal LLNQELLNPTHQIYPVTQPLAPVHNPISV stretch by use of synthetic peptides. Similarly, a peptide (SCKFDEYFSQSCA) corresponding to the human lactoferrin stretch that is highly homologous to the previously shown inhibitory stretch of bovine lactoferrin was found to inhibit S. mutans Ingbritt binding. Inhibition by human milk, IgA, and the inhibitory beta-casein peptide was universal among 4 strains of S. mutans (Ingbritt, NG8, LT11, JBP) and 2 strains of S. sobrinus (6715 and OMZ176). IgG inhibited 4, alpha-lactalbumin 3 and lactoferrin 2 of these 6 strains. It was also confirmed that none of the milk components coated on HA mediated S. mutans Ingbritt adhesion, which was consistent with the finding that no milk protein was recognized on Western blots by gp340/DMBT1 monoclonal antibodies.

  • 269.
    Danielsson Niemi, Liza
    et al.
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Salivary statherin peptide-binding epitopes of commensal and potentially infectious Actinomyces spp. delineated by a hybrid peptide construct2004In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 72, no 2, p. 782-787Article, review/survey (Refereed)
    Abstract [en]

    Adhesion of microorganisms to host receptor molecules such as salivary statherin molecules is a common event in oral microbial colonization. Here we used a hybrid peptide construct (with both a hydroxyapatite-binding portion and a test peptide portion) to map the interaction of Actinomyces species (and Candida albicans) with statherin. Adhesion to hybrid peptides and truncated statherin variants revealed three binding types, types I to III. (i) Type I strains of rat, hamster, and human infection origins bound C-terminal-derived QQYTF and PYQPQY peptides. The QQYTF peptide inhibited statherin binding for some strains but not for others. (ii) Type II strains of human and monkey tooth origins bound middle-region-derived YQPVPE and QPLYPQ peptides. Neither strain was inhibited by soluble peptides. (iii) Type III strains of human infection origins (and C. albicans) did not bind to either statherin-derived peptides or truncated statherin. Moreover, the type I strains inhibited by QQYTF were also inhibited by TF and QAATF peptides and were detached from statherin by the same peptides. In conclusion, it is suggested that commensal and potentially infectious microorganisms bind middle or C-terminal statherin differently and that other microbes might require discontinuous epitopes.

  • 270. Davidson, Thomas
    et al.
    Rohlin, Madeleine
    Hultin, Margareta
    Jemt, Torsten
    Nilner, Krister
    Sunnegårdh Grönberg, Karin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Tranaeus, Sofia
    Nilsson, Mats
    Reimbursement systems influence prosthodontic treatment of adult patients2015In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 73, no 6, p. 414-420Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate the influence of reimbursement system and organizational structure on oral rehabilitation of adult patients with tooth loss. Materials and methods. Patient data were retrieved from the databases of the Swedish Social Insurance Agency. The data consisted of treatment records of patients aged 19 years and above claiming reimbursement for dental care from July 1, 2007 until June 30, 2009. Before July 1, 2008, a proportionately higher level of subsidy was available for dental care in patients 65 years and above, but thereafter the system was changed, so that the subsidy was the same, regardless of the patient's age. Prosthodontic treatment in patients 65 years and above was compared with that in younger patients before and after the change of the reimbursement system. Prosthodontic treatment carried out in the Public Dental Health Service and the private sector was also analyzed. Results. Data were retrieved for 722,842 adult patients, covering a total of 1,339,915 reimbursed treatment items. After the change of the reimbursement system, there was a decrease in the proportion of items in patients 65 years and above in relation to those under 65. Overall, there was a minimal change in the proportion of treatment items provided by the private sector compared to the public sector following the change of the reimbursement system. Conclusions. Irrespective of service provider, private or public, financial incentive such as the reimbursement system may influence the provision of prosthodontic treatment, in terms of volume of treatment.

  • 271. de Gee, Anton J
    et al.
    Kleverlaan, Cees J
    van Dijken, Jan
    Umeå University, Faculty of Medicine, Odontology, Dental Hygiene.
    Dentala kompositer: betydelsen av polymerisationskrympning och genererade spänningar2007In: Tandläkartidningen, ISSN 0039-6982, Vol. 99, no 3, p. 40-44Article in journal (Refereed)
    Abstract [en]

    During the curing shrinkage of adhesively bonded resin composites tensile stresses develop, which are exerted back onto the cavity walls. the extent of the stress determines whether part of the tooth structure will fracture. Unfortunately, shrinkage stress values are not available for the general practitioner. Recommendations are therefore made for the use of low shrinkage and/or low shrinkage stress resin ccomposites for different cavity types. In the current study, thirty resin composites were evaluated for shrinkage and shrinkage stress. The majorityof the composites compplied with the hypothesis that a low shrinkage is accompanied with a high shrinkage stress and visa-versa. Some composite materials showed both a low shrinkage and a low shrinkage stress and are thus proposed to give the least problems with respect to marginal seal and enamel fracture.

  • 272. de Oliveira Neto, Patricio José
    et al.
    Cricchio, Giovanni
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hawthorne, Ana Carolina
    Okamoto, Roberta
    Sennerby, Lars
    Lundgren, Stefan
    Umeå University, Faculty of Medicine, Department of Odontology, Oral and Maxillofacial Surgery.
    Salata, Luiz Antonio
    Tomographic, histological, and immunohistochemical evidences on the use of N-butyl-2-cyanoacrilate for onlay graft fixation in rabbits2012In: Clinical Implant Dentistry and Related Research, ISSN 1523-0899, E-ISSN 1708-8208, Vol. 14, no 6, p. 861-871Article in journal (Refereed)
    Abstract [en]

    Background: The bone tissue responses to Cyanoacrylate have been described in the literature, but none used N-butyl-2-cyanoacrilate (NB-Cn) for bone graft fixation.

    Purpose: The aims of the study were: (a) to analyze the bone grafts volume maintenance fixed either with NB-Cn or titanium screw; (b) to assess the incorporation of onlay grafts on perforated recipient bed; and (c) the differences of expression level of tartrate-resistant acid phosphatase (TRAP) protein involved in bone resorption.

    Materials and Methods: Eighteen New Zealand White rabbits were submitted to calvaria onlay grafting on both sides of the mandible. On one side, the graft was fixed with NB-Cn, while on the other hand the bone graft was secured with an osteosynthesis screw. The computed tomography (CT) was performed just after surgery and at animals sacrifice, after 1 (n = 9) and 6 weeks (n = 9), in order to estimate the bone grafts volume along the experiments. Histological sections of the grafted areas were prepared to evaluate the healing of bone grafts and to assess the expression of TRAP protein.

    Results: The CT scan showed better volume maintenance of bone grafts fixed with NB-Cn (p ≤ 0.05) compared with those fixed with screws, in both experimental times (analysis of variance). The immunohistochemical evaluation showed that the TRAP expression in a 6-week period was significantly higher compared with the 1-week period, without showing significant difference between the groups (Wilcoxon and Mann-Whitney). Histological analysis revealed that the NB-Cn caused periosteum damage, but provided bone graft stabilization and incorporation similar to the control group.

    Conclusion: The perforation provided by screw insertion into the graft during fixation may have triggered early revascularization and remodeling to render increased volume loss compared with the experimental group. These results indicate that the NB-Cn possesses equivalent properties to titanium screw to be used as bone fixation material in osteosynthesis.

  • 273. Del Gobbo, Liana C.
    et al.
    Imamura, Fumiaki
    Aslibekyan, Stella
    Marklund, Matti
    Virtanen, Jyrki K.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Yakoob, Mohammad Y.
    Chiuve, Stephanie E.
    dela Cruz, Luicito
    Frazier-Wood, Alexis C.
    Fretts, Amanda M.
    Guallar, Eliseo
    Matsumoto, Chisa
    Prem, Kiesha
    Tanaka, Tosh
    Wu, Jason H. Y.
    Zhou, Xia
    Helmer, Catherine
    Ingelsson, Erik
    Yuan, Jian-Min
    Barberger-Gateau, Pascale
    Campos, Hannia
    Chaves, Paulo H. M.
    Djousse, Luc
    Giles, Graham G.
    Gomez-Aracena, Jose
    Hodge, Allison M.
    Hu, Frank B.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Khaw, Kay-Tee
    Koh, Woon-Puay
    Lemaitre, Rozenn N.
    Lind, Lars
    Luben, Robert N.
    Rimm, Eric B.
    Riserus, Ulf
    Samieri, Cecilia
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Siscovick, David S.
    Stampfer, Meir
    Steffen, Lyn M.
    Steffen, Brian T.
    Tsai, Michael Y.
    van Dam, Rob M.
    Voutilainen, Sari
    Willett, Walter C.
    Woodward, Mark
    Mozaffarian, Dariush
    omega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease Pooling Project of 19 Cohort Studies2016In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, no 8, p. 1155-1166Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20: 5 omega-3), docosapentaenoic acid (DPA; 22: 5 omega-3), and docosahexaenoic acid (DHA; 22: 6 omega-3) and plant-derived alpha-linolenic acid (ALA; 18: 3 omega-3) for incident CHD. DATA SOURCES A global consortium of 19 studies identified by November 2014. STUDY SELECTION Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with omega-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the omega-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived omega-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

  • 274. Demirtas, Nihat
    et al.
    Barut, Oya
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ozcan, Ilknur
    Bayer, Suzan
    Kazancioglu, Hakki Oguz
    Recurrent cherubism in an adult patient2015In: The Journal of craniofacial surgery (Print), ISSN 1049-2275, E-ISSN 1536-3732, Vol. 26, no 3, p. E225-E227Article in journal (Refereed)
    Abstract [en]

    Cherubism is an uncommon, nonneoplastic, fibro-osseous disorder of the jaws in childhood and adolescence. It affects the jaw bones by deforming the cortical shell. Clinical features include progressive painless and mostly bilateral expansion of the mandible and/or maxilla. Because fibrous connective tissue replaces osseous tissue, radiographic features generally include expansile osteolytic lesions and a ground-glass appearance. Several treatment protocols for cherubism have been recommended in the literature; however, despite surgical curettage treatment, recurrences may occur. Our aim was to emphasize the high recurrence rate of cherubic lesions. In this article, we present cherubism in a young girl that relapsed after 5 surgical operations before her appearance to our clinic.

  • 275. Denolf, Petra L.
    et al.
    Vanderveken, Olivier M.
    Marklund, Marie E.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Braem, Marc J.
    The status of cephalometry in the prediction of non-CPAP treatment outcome in obstructive sleep apnea patients2016In: Sleep Medicine Reviews, ISSN 1087-0792, E-ISSN 1532-2955, Vol. 27, p. 56-73Article, review/survey (Refereed)
    Abstract [en]

    Obstructive sleep apnea syndrome (OSAS) is the most common sleep disordered breathing disorder (SDB) in adults and is characterized by a recurrent partial or complete collapse of the upper airway during sleep. This can be caused by many factors, sometimes interacting, such as skeletal malformations, soft tissue crowding, respiratory instability and the various effects of aging, obesity and gender that dictate craniofacial and upper airway anatomy. Research has demonstrated that the majority of patients exhibit at least one anatomical component such as retrognathia or a narrow posterior airway space that predisposes to the development of OSAS. Within the predisposing elements for OSAS many seem to point to anatomical characteristics. A standardized and relatively simple radiologic technique to evaluate anatomical craniofacial relationships is cephalometry. This has been used already for a long time in orthodontics, but is now gradually being introduced in OSAS treatment to envisage optimal treatment selection as well as to predict treatment outcomes. The purpose of the present review is to evaluate the contribution of cephalometry in the prediction of outcomes from OSAS treatments that depend on the upper airway morphology in their mechanisms of action such as oral appliances that advance the mandible as well as various surgical methods. In addition, an overview of imaging modalities and methods that currently are being used in cephalometric analysis in OSAS patients is provided. The findings indicate that isolated cephalometric parameters cannot be used to reliably predict treatment outcomes from mandibular advancement devices and surgical methods for OSAS. Extreme or outlying values of cephalometric parameters may rather be used as contra-indicators or 'red flags' instead of predictors.

  • 276. Derand, T
    et al.
    Molin, M
    Umeå University, Faculty of Medicine, Department of Odontology, Prosthetic Dentistry.
    Kleven, E
    Haag, P
    Karlsson, S
    Bond strength of luting materials to ceramic crowns after different surface treatments2008In: European Journal of Prosthodontics and Restorative Dentistry, ISSN 0965-7452, Vol. 16, no 1, p. 35-38Article in journal (Refereed)
    Abstract [en]

    The aim of present study was to evaluate the effect of different pre-treatments of alumina and zirconia copings on the bond strength of different luting materials. Pull out tests was performed on 60 alumina and 80 zirconia copings. Randomly selected, copings were divided in groups of; i) un-treated alumina and zirconia copings, (n=20) ii) alumina and zirconia copings sandblasted with 50 or 110 µm alumina particles respectively (n=20), iii) zirconia copings treated with monolayer of glass pearls fused to the inner surface (n=20) , iv) zirconia copings treated with silanized glass pearls (n=10). Zinc phosphate, Panavia 21 and VarioLink II were used for cementation. Pull out tests were done in an Instron universal testing machine with a speed of 0.5 mm/min and fracture loads was measured in N. Untreated zirconia copings cemented with zinc phosphate showed significantly higher bond strength values compared to those with sandblasted surfaces. No difference was seen between untreated alumina copings and those with sandblasted surfaces. Sandblasting decreased bond strength of zirconia and alumina copings. Glass pearls increased bond strength of zirconia copings, which was even better after silanization. Variolink II in combination with alumina gave significantly lower bond strength.

  • 277. Derand, Tore
    et al.
    Molin, Margareta
    Umeå University, Faculty of Medicine, Department of Odontology, Prosthetic Dentistry.
    Kvam, Ketil
    Bond strength of a composite luting agent to alumina ceramic surfaces.2006In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 64, no 4, p. 227-30Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The purpose of this study was to evaluate the shear bond strength (SBS) of a dental luting agent to alumina ceramics after different surface pretreatment. MATERIAL AND METHODS: Specimens (n=50) of pressed blocks (10 x 0 x 5 mm) of alumina ceramic (Procera AllCeram) were divided into untreated specimens (AF) as provided by the manufacturer and polished specimens (AP). Five groups of specimens (n=5 x 10) with different surface pretreatments were prepared. Groups 1 and 2: AF and AP without any pretreatment; Group 3: AF treated with silane, (AF-s); Group 4: AF treated with RF plasma spray (AF-RF); Group 5: AF treated with low fusing porcelain (AF-p) glass pearls. Composite cylinders (5 x 5 mm) were cemented to the test specimens with a resin luting agent. The specimens were loaded to failure in shear mode using a universal testing machine. Recorded loads were used to calculate SBS in MPa. The results were analyzed using one-way ANOVA and the Tukey HSD multiple comparison test at alpha = 0.05. Scanning electron microscopic micrographs (SEM) were used to characterize surfaces of interest. RESULTS: Polished surfaces had significantly lower SBS (p < 0.05) compared with untreated specimens (AP vs AF). Silanated, non-polished surfaces (AF-s) revealed lower SBS, even though the result was not significantly different from that of AF-s without silane treatment. Plasma treatment improved SBS by a factor of 2 (p<0.05) and treatment with low-fusing porcelain micro pearls increased SBS by a factor of 3 compared to untreated surfaces (p<0.05). The layer of glass pearls did not exceed 5 microm (SEM). CONCLUSIONS: Within the limitation of the conditions of this study, treatment of alumina oxide ceramic surfaces with a plasma spray coating or a low-fusing porcelain pearl layer significantly increased the SBS of a resin luting agent to the ceramic surface.

  • 278. Derand, Tore
    et al.
    Molin, Margareta
    Umeå University, Faculty of Medicine, Odontology, Prosthetic Dentistry.
    Kvam, Ketil
    Bond strength of composite luting cement to zirconia ceramic surfaces.2005In: Dental Materials, ISSN 0109-5641, E-ISSN 1879-0097, Vol. 21, no 12, p. 1158-62Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the bond strength of dental resin agent to zirconia ceramic after surface pre-treatment with different techniques. METHODS: Specimens of hot isostatic pressed yttrium-oxide-partially-stabilized zirconia blocks (ZF) were fabricated (Procera Zircon, Nobel Biocare, Sweden) and compared to glossy dense zirconia blocks (ZG). Four groups of specimens with different surface treatment were prepared. Group I: ZF (n = 5) and ZG (n = 5) without any pre-treatment, Group II: ZF-s (n = 5) and ZG-s (n = 5) treated with silane solution, Group III: ZF-P (n = 10) and ZG-P (n = 10) treated with RF plasma spraying (hexamethyldisiloxane) using a reactor (Plasma Electronic, Germany), Group IV: ZF-p (n = 10) and ZG-p (n = 10) treated with micro pearls of low fusing porcelain (720 degrees C) on the surfaces. Composite cylinders (Charisma, Hereus Kulzer, Dormagen, Germany) were luted with Variolink II (Ivoclar-Vivadent, Schaan, Liechtenstein) to the test specimens. The specimens were then stored in air for 1 h before shear loading in a universal testing machine (LRX, Lloyd Instruments, Farnham, England) until failure. RESULTS: No statistical difference was found between the untreated ZF and ZG specimens (Group I) neither between the specimens treated with silane (Group II). Plasma spraying treatment improved bond strength by a factor of three (p < 0.001). Treatment with low fusing porcelain micro pearls increased the bond strength by a factor of 10 compared to untreated surfaces (p < 0.001). No significant difference was seen between the surfaces treated ZF-p and ZG-p specimens. The thickness of the glass pearls layer did not exceed 5 microm. SEM showed dense grain borders of ZF and a flat glossy texture of ZG. SIGNIFICANCE: Treatment of zirconia ceramic surfaces with plasma spraying or a low fusing porcelain pearl layer significantly increased the bond strength of resin cement to the ceramic surface.

  • 279.
    Desai, Annika
    Umeå University, Faculty of Medicine, Department of Odontology.
    Changes in Binding Properties of  Helicobacter pylori Isolated over time from a Chronically Infected Patient2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Helicobacter pylori infects over 50 % of the world’s population, causing gastritis, and in some cases, peptic ulcer disease and gastric cancer. Adherence to the gastric surface occurs primarily through H. pylori outer membrane proteins (HOPs) and is essential for bacterial survival and establishment of infection. The Blood group Antigen-Binding Adhesin (BabA) is the best-characterized attachment protein, mediating adherence by binding to fucosylated carbohydrate structures on the surface of the gastric epithelium. H. pylori is highly adaptable to environmental changes that occur during stomach longterm infection, however little is known about the effect of such changes on the adaptability and functionality of BabA adherence properties. The aim of this study was to evaluate how BabA-mediated binding properties of H. pylori isolates were affected during 20 years of chronic infection. Two H. pylori clinical isolates collected from a single individual, 20 years apart were studied for their Leb-binding properties using a combination of radioimmunoassay (RIA) and in situ histo- and cytochemistry.

    Our results demonstrated that H. pylori isolated after 20 years of infection had lost its Lewis b binding ability due to a nucleotide deletion in the babA gene, resulting in a translational frame shift and hence, a non-functional BabA protein. We also showed that the non-adherent isolate contains sub-populations of bacteria that express BabA and have therefore maintained the ability to bind to Leb-conjugate and adhere to human gastric mucosa in vitro.  

    An additional adherence pattern was revealed when H. pylori bacterial cells were applied to human buccal epithelium cells (BEC), with all the isolates demonstrating attachment. These results suggest that H. pylori can express additional binding properties for adherence in the oral cavity which may contribute to re-infection as well as further transmission of the H. pylori infection.  

  • 280. Deschasaux, Melanie
    et al.
    Huybrechts, Inge
    Murphy, Neil
    Julia, Chantal
    Hercberg, Serge
    Srour, Bernard
    Kesse-Guyot, Emmanuelle
    Latino-Martel, Paule
    Biessy, Carine
    Casagrande, Corinne
    Jenab, Mazda
    Ward, Heather
    Weiderpass, Elisabete
    Dahm, Christina C.
    Overvad, Kim
    Kyro, Cecilie
    Olsen, Anja
    Affret, Aurelie
    Boutron-Ruault, Marie-Christine
    Mahamat-Saleh, Yahya
    Kaaks, Rudolf
    Kuehn, Tilman
    Boeing, Heiner
    Schwingshackl, Lukas
    Bamia, Christina
    Peppa, Eleni
    Trichopoulou, Antonia
    Masala, Giovanna
    Krogh, Vittorio
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Buen-de-Mesquita, Bas
    Peeters, Petra H.
    Hjartåker, Anette
    Rylander, Charlotta
    Skeie, Guri
    Ramon Quiros, J.
    Jakszyn, Paula
    Salamanca-Fernandez, Elena
    Maria Huerta, Jose
    Ardanaz, Eva
    Amiano, Pilar
    Ericson, Ulrika
    Sonestedt, Emily
    Huseinovic, Ena
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Khaw, Kay-Tee
    Wareham, Nick
    Bradbury, Kathryn E.
    Perez-Cornago, Aurora
    Tsilidis, Konstantinos K.
    Ferrari, Pietro
    Riboli, Elio
    Gunter, Marc J.
    Touvier, Mathilde
    Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: results from the EPIC prospective cohort study2018In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 15, no 9, article id e1002651Article in journal (Refereed)
    Abstract [en]

    Background

    Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations.

    Methods and findings

    This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus (Q1) = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out.

    Conclusions

    In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.

  • 281.
    Dijken, Jan W. V. van
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Dental Hygiene. Umeå University, Faculty of Medicine, Department of Odontology.
    Sunnegårdh-Grönberg, Karin
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology. Umeå University, Faculty of Medicine, Department of Odontology.
    A two-year clinical evaluation of a new calcium aluminate cement in Class II cavities2003In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 61, no 4, p. 235-40Article in journal (Refereed)
    Abstract [en]

    A calcium aluminate cement (Doxa Certex, Uppsala, Sweden) has recently been developed intended for use as direct restorative filling material for posterior restorations. The material is inorganic and non-metallic and the main components are CaO, Al2O3, SiO2, and water. The aim of this study was to evaluate intra-individually the experimental calcium aluminate cement (CAC) and a resin composite (RC) in Class II restorations. Each of 57 participants received at least one pair of restorations of the same size, one CAC and one RC (Tetric Ceram). Sixty-one pairs were performed. The restorations were evaluated clinically, according to slightly modified USPHS criteria, at baseline, after 6 months, 1, and 2 years. One-hundred-and-twenty restorations were evaluated at 2 years. Postoperative sensitivity was reported for 5 restorations (2 RC, 3 CAC). Significantly better clinical durability was shown for RC. Five non-acceptable CAC restorations (8.2%) were observed at 6 months, 10 CAC (16.7%) and 2 RC (3.3%) at 12 months, and 11 CAC (18.3%) at 24 months. This resulted in a cumulative failure frequency of 43.3% for the CAC material and 3.3% for the RC material. Main reasons for failure for the CAC were partial material fracture (7), cusp fracture (5), and proximal chip fracture (6). The CAC showed a non-acceptable clinical failure rate for Class II restorations, probably caused by its difficult handling and low mechanical properties.

  • 282.
    Dijken, Jan W.V. van
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ardlin, Berit
    Umeå University, Faculty of Medicine, Department of Odontology.
    Tillberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wahlin, Ylwa Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berglund, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sunnegårdh-Grönberg, Karin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lindberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Molin, Margareta
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sjögren, Göran
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hulterström, Anna Karin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Samarbete breddar forskning: Oral Biomaterialgruppen, Umeå2008In: Tandläkartidningen, Vol. 100, no 5, p. 74-79Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Vid institutionen för odontologi vid Umeå Universitet finns en lång tradition av biomaterialforskning. För drygt två år sedan samlades större delen av den forskningen i ett vetenskapligt nätverk. Här beskrivs ett axplock av det breda forskningsarbetet.

  • 283. Dinarello, Charles
    et al.
    Arend, William
    Sims, John
    Smith, Dirk
    Blumberg, Hal
    O'Neill, Luke
    Goldbach-Mansky, Raphaela
    Pizarro, Theresa
    Hoffman, H.
    Bufler, Philip
    Nold, Marcel
    Ghezzi, Pietro
    Mantovani, Alberto
    Garlanda, Cecilia
    Boraschi, Diana
    Rubartelli, Anna
    Netea, Mihai
    van der Meer, Jos
    Joosten, Leo
    Mandrup-Poulsen, Tom
    Donath, Marc
    Lewis, Eli
    Pfeilschifter, Josef
    Martin, Michael
    Kracht, Michael
    Muehl, H
    Novick, Daniela
    Lukic, Miodrag
    Conti, Bruno
    Solinger, Alan
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    van de Veerdonk, Frank
    Gabel, Chiristopher
    IL-1 family nomenclature2010In: Nature Immunology, ISSN 1529-2908, E-ISSN 1529-2916, Vol. 11, no 11, p. 973-973Article in journal (Refereed)
  • 284. Djais, A
    et al.
    Nakazawa, F
    Sato, M
    Sato, N
    Sunddqvist, G
    Umeå University, Faculty of Medicine, Odontology, Endodontics.
    Hoshino, E
    Asaccharolytic anaerobic gram-negative coccobacilli (AAGNC) isolated from infected root canals and periodontal pockets.2006In: Oral Microbiology and Immunology, Vol. 21, no 1, p. 28-31Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Culture-difficult bacteria, including asaccharolytic anaerobic gram-negative coccobacilli (AAGNC), may constitute a predominant group of organisms in oral sites. This study aimed to characterize phylogenetically 10 AAGNC isolated from endodontic lesions and periodontal pockets. METHODS: 16S rDNA sequence and G + C content were determined. Strains sharing more than 98% sequence similarities and similar G + C content were considered the same bacterial species. RESULTS: One isolate resembled Dialister pneumosintes (the type species of the genus Dialister) with 35 mol% G + C content and 97% sequence similarity. Of eight isolates having 45-47 mol% G + C content, seven were identified as D. invisus and one resembled Dialister invisus with 97% sequence similarity. However the 16S rDNA sequence similarities with D. pneumosintes were relatively low, indicating the strains may belong to a new genus. The last isolate revealed 35 mol% G + C content, but had higher 16S rDNA sequence similarity with D. invisus than with D. pneumosintes. CONCLUSION: The group of oral AAGNC isolates need to be reclassified

  • 285. Do, Ron
    et al.
    Willer, Cristen J.
    Schmidt, Ellen M.
    Sengupta, Sebanti
    Gao, Chi
    Peloso, Gina M.
    Gustafsson, Stefan
    Kanoni, Stavroula
    Ganna, Andrea
    Chen, Jin
    Buchkovich, Martin L.
    Mora, Samia
    Beckmann, Jacques S.
    Bragg-Gresham, Jennifer L.
    Chang, Hsing-Yi
    Demirkan, Ayse
    Den Hertog, Heleen M.
    Donnelly, Louise A.
    Ehret, Georg B.
    Esko, Tonu
    Feitosa, Mary F.
    Ferreira, Teresa
    Fischer, Krista
    Fontanillas, Pierre
    Fraser, Ross M.
    Freitag, Daniel F.
    Gurdasani, Deepti
    Heikkila, Kauko
    Hyppoenen, Elina
    Isaacs, Aaron
    Jackson, Anne U.
    Johansson, Asa
    Johnson, Toby
    Kaakinen, Marika
    Kettunen, Johannes
    Kleber, Marcus E.
    Li, Xiaohui
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Magnusson, Patrik K. E.
    Mangino, Massimo
    Mihailov, Evelin
    Montasser, May E.
    Mueller-Nurasyid, Martina
    Nolte, Ilja M.
    O'Connell, Jeffrey R.
    Palmer, Cameron D.
    Perola, Markus
    Petersen, Ann-Kristin
    Sanna, Serena
    Saxena, Richa
    Service, Susan K.
    Shah, Sonia
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology. Lunds universitet.
    Sidore, Carlo
    Song, Ci
    Strawbridge, Rona J.
    Surakka, Ida
    Tanaka, Toshiko
    Teslovich, Tanya M.
    Thorleifsson, Gudmar
    Van den Herik, Evita G.
    Voight, Benjamin F.
    Volcik, Kelly A.
    Waite, Lindsay L.
    Wong, Andrew
    Wu, Ying
    Zhang, Weihua
    Absher, Devin
    Asiki, Gershim
    Barroso, Ines
    Been, Latonya F.
    Bolton, Jennifer L.
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Burnett, Mary S.
    Cesana, Giancarlo
    Dimitriou, Maria
    Doney, Alex S. F.
    Doering, Angela
    Elliott, Paul
    Epstein, Stephen E.
    Eyjolfsson, Gudmundur Ingi
    Gigante, Bruna
    Goodarzi, Mark O.
    Grallert, Harald
    Gravito, Martha L.
    Groves, Christopher J.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Hernandez, Dena
    Hicks, Andrew A.
    Holm, Hilma
    Hung, Yi-Jen
    Illig, Thomas
    Jones, Michelle R.
    Kaleebu, Pontiano
    Kastelein, John J. P.
    Khaw, Kay-Tee
    Kim, Eric
    Klopp, Norman
    Komulainen, Pirjo
    Kumari, Meena
    Langenberg, Claudia
    Lehtimaki, Terho
    Lin, Shih-Yi
    Lindstrom, Jaana
    Loos, Ruth J. F.
    Mach, Francois
    McArdle, Wendy L.
    Meisinger, Christa
    Mitchell, Braxton D.
    Mueller, Gabrielle
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nieminen, Tuomo V. M.
    Nsubuga, Rebecca N.
    Olafsson, Isleifur
    Ong, Ken K.
    Palotie, Aarno
    Papamarkou, Theodore
    Pomilla, Cristina
    Pouta, Anneli
    Rader, Daniel J.
    Reilly, Muredach P.
    Ridker, Paul M.
    Rivadeneira, Fernando
    Rudan, Igor
    Ruokonen, Aimo
    Samani, Nilesh
    Scharnagl, Hubert
    Seeley, Janet
    Silander, Kaisa
    Stancakova, Alena
    Stirrups, Kathleen
    Swift, Amy J.
    Tiret, Laurence
    Uitterlinden, Andre G.
    van Pelt, L. Joost
    Vedantam, Sailaja
    Wainwright, Nicholas
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilsgaard, Tom
    Wilson, James F.
    Young, Elizabeth H.
    Zhao, Jing Hua
    Adair, Linda S.
    Arveiler, Dominique
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Bennett, Franklyn
    Bochud, Murielle
    Boehm, Bernhard O.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    Bornstein, Stefan R.
    Bovet, Pascal
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chambers, John C.
    Chen, Yii-Der Ida
    Collins, Francis S.
    Cooper, Richard S.
    Danesh, John
    Dedoussis, George
    de Faire, Ulf
    Feranil, Alan B.
    Ferrieres, Jean
    Ferrucci, Luigi
    Freimer, Nelson B.
    Gieger, Christian
    Groop, Leif C.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hamsten, Anders
    Harris, Tamara B.
    Hingorani, Aroon
    Hirschhorn, Joel N.
    Hofman, Albert
    Hovingh, G. Kees
    Hsiung, Chao Agnes
    Humphries, Steve E.
    Hunt, Steven C.
    Hveem, Kristian
    Iribarren, Carlos
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kaprio, Jaakko
    Kesaniemi, Antero
    Kivimaki, Mika
    Kooner, Jaspal S.
    Koudstaal, Peter J.
    Krauss, Ronald M.
    Kuh, Diana
    Kuusisto, Johanna
    Kyvik, Kirsten O.
    Laakso, Markku
    Lakka, Timo A.
    Lind, Lars
    Lindgren, Cecilia M.
    Martin, Nicholas G.
    Maerz, Winfried
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Metspalu, Andres
    Moilanen, Leena
    Morris, Andrew D.
    Munroe, Patricia B.
    Njolstad, Inger
    Pedersen, Nancy L.
    Power, Chris
    Pramstaller, Peter P.
    Price, Jackie F.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rauramaa, Rainer
    Saleheen, Danish
    Salomaa, Veikko
    Sanghera, Dharambir K.
    Saramies, Jouko
    Schwarz, Peter E. H.
    Sheu, Wayne H-H
    Shuldiner, Alan R.
    Siegbahn, Agneta
    Spector, Tim D.
    Stefansson, Kari
    Strachan, David P.
    Tayo, Bamidele O.
    Tremoli, Elena
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vollenweider, Peter
    Wallentin, Lars
    Wareham, Nicholas J.
    Whitfield, John B.
    Wolffenbuttel, Bruce H. R.
    Altshuler, David
    Ordovas, Jose M.
    Boerwinkle, Eric
    Palmer, Colin N. A.
    Thorsteinsdottir, Unnur
    Chasman, Daniel I.
    Rotter, Jerome I.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Lunds universitet, Harvard University.
    Ripatti, Samuli
    Cupples, L. Adrienne
    Sandhu, Manjinder S.
    Rich, Stephen S.
    Boehnke, Michael
    Deloukas, Panos
    Mohlke, Karen L.
    Ingelsson, Erik
    Abecasis, Goncalo R.
    Daly, Mark J.
    Neale, Benjamin M.
    Kathiresan, Sekar
    Common variants associated with plasma triglycerides and risk for coronary artery disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, p. 1345-+Article in journal (Refereed)
    Abstract [en]

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

  • 286. Dogan, B
    et al.
    Antinheimo, J
    Cetiner, D
    Bodur, A
    Emingil, G
    Buduneli, E
    Uygur, C
    Firatli, E
    Lakio, L
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Subgingival microflora in Turkish patients with periodontitis.2003In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 74, no 6, p. 803-814Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: No information exists on periodontitis-associated subgingival microbiota from Turkey. We determined the occurrence, interspecies relationships, and clonal characteristics for a group of periodontal bacteria in a Turkish study population. METHODS: Subgingival microbial samples were obtained from patients with localized (LAgP, N = 18) or generalized (GAgP, N = 17) types of aggressive periodontitis, generalized chronic periodontitis (GCP, N = 14), and non-periodontitis subjects (N = 20). Culture methods were used to recover 6 periodontal bacterial species and yeasts, and a polymerase chain reaction technique was used to detect Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Intraspecies characterization of A. actinomycetemcomitans was carried out by serotyping and genotyping. RESULTS: All species, except for Micromonas micros (formerly Peptostreptococcus micros) occurred more frequently (P < 0.05) in periodontitis than non-periodontitis subjects. Detection frequencies for Tannerella forsythensis (formerly Bacteroides forsythus) and Campylobacter rectus differed among the periodontitis subgroups; the lowest frequency occurred in LAgP. The mean proportions of A. actinomycetemcomitans, P. gingivalis, and C. rectus were higher (P < 0.008) in GAgP than in non-periodontitis subjects. Significant positive associations were seen between 7 of the 22 possible combinations (P < 0.05). A. actinomycetemcomitans serotype c (34%) and non-serotypeable isolates (34%) were the most common antigenic types among the 305 strains analyzed. Eleven arbitrarily primed (AP)-PCR genotypes were distinguished among 273 isolates from 29 subjects. Yeasts were found in 23% of the 69 subjects. CONCLUSIONS: The results on the Turkish study population were generally in line with earlier reports on the occurrence and interspecies relationships of certain bacteria in periodontitis. However, A. actinomycetemcomitans was not overrepresented in LAgP, and the serotype distribution resembled that reported from the East. The high frequency of non-serotypeable isolates suggests local characteristics of the species.

  • 287. Dogan, B
    et al.
    Buduneli, E
    Emingil, G
    Atilla, G
    Akilli, A
    Antinheimo, J
    Lakio, L
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Characteristics of periodontal microflora in acute myocardial infarction.2005In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 76, no 5, p. 740-748Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Periodontitis has been linked to increased risk of cardiovascular diseases. Systemic reactions associated with cardiovascular events may depend on characteristics of the subgingival microflora in periodontitis. Our objectives were to compare the numbers of cultivable bacteria, composition of subgingival microflora and clonal distribution of Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) in two groups of patients with generalized chronic periodontitis (GCP), one with an acute myocardial infarction (AMI-GCP) and the other one without AMI (non-AMI-GCP). METHODS: In all, 150 dentate individuals were screened for suitability to this study. Subgingival bacterial samples were collected from 11 AMI-GCP and 11 non-AMI-GCP patients who had been selected using strict inclusion criteria in an attempt to exclude confounding factors and to increase comparability of periodontal conditions by matching for periodontal probing depths and attachment levels. Culture methods were used to determine the total viable counts and occurrence and proportions of six periodontal bacterial species and yeasts. Polymerase chain reaction (PCR) technique was used to detect A. actinomycetemcomitans and Porphyromonas gingivalis (P. gingivalis). Intraspecies characterization of A. actinomycetemcomitans included serotyping and genotyping. RESULTS: The mean proportions of P. gingivalis (P = 0.05) and Tannerella forsythensis (T. forsythensis) (P = 0.01) were significantly lower, but the numbers of Micromonas micros (M. micros) and A. actinomycetemcomitans were up to nine times higher and the mean total number of cultivable bacteria per sample higher (P <0.01) in AMI-GCP than in non-AMI-GCP. CONCLUSION: The findings that no target subgingival species were overrepresented but the total bacterial number was higher in AMI-GCP than non-AMI-GCP patients may provide support to the hypothesis that elevated numbers of bacteria in close vicinity to sterile parenteral area present a risk for systemic health.

  • 288.
    Domäng, Markus
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Nasiri, Nargis
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Fluoride Levels in Saliva after Tea Intake2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Tea contains fluoride but its effect as a caries-preventive measure is not fully understood. The aim of this study was to evaluate the fluoride levels in saliva after tea-intake.

    Part one of the study analyzed the fluoride content of teas and one black and one green tea was thereafter selected for the clinical part of the study (part two). Ten healthy adults participated in part two which was designed as a prospective, crossover study where the salivary fluoride levels were analyzed after tea-intake at designated follow-ups.

    The fluoride level in saliva increased after tea-intake (0.04 ± 0.2 vs 0.97 ± 0.32 mg/L, (p < 0.01)). After intake of the black tea fluoride levels remained elevated compared to baseline at 5 minutes (0.04 ± 0.02 vs 0.12 ± 0.08 mg/L, ( p < 0.01)) and 10 minutes (0.04 ± 0.02 vs 0.09 ± 0.07 mg/L, (p < 0.05) but not at 20 minutes (0.04 ± 0.02 vs 0.05 ± 0.03 mg/L, (p = 0.056)). The green tea had elevated fluoride levels up to 5 minutes (0.05 ± 0.03 vs 0.14 ± 0.09 mg/L, (p < 0.01)) but not at 10 minutes (0.05 ± 0.03 vs 0.09 ± 0.08 mg/L, (p > 0.05)).

    The fluoride level in saliva is elevated after tea-intake which may suggest a caries-preventive effect, but not for a long period of time due to its rapid clearance in saliva.

  • 289. Doğan, B
    et al.
    Kipalev, AS
    Okte, E
    Sultan, N
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology. Umeå University, Faculty of Medicine, Odontology.
    Consistent intrafamilial transmission of Actinobacillus actinomycetemcomitans despite clonal diversity.2008In: Journal of periodontology, ISSN 0022-3492, Vol. 79, no 2, p. 307-15Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Actinobacillus actinomycetemcomitans is a major pathogen in aggressive periodontitis. Our objectives were to determine the periodontal status and occurrence of A. actinomycetemcomitans in family members of subjects with A. actinomycetemcomitans-positive aggressive periodontitis (AgP) and to evaluate the probability of its intrafamilial transmission. METHODS: Of the 300 subjects screened, 66 (22%) had AgP and A. actinomycetemcomitans. Eleven (probands) of these 66 subjects with AgP met the strict inclusion criteria for the study. The study population consisted of 55 subjects, including probands and their family members (N = 44). Two family groups were formed according to whether the proband was a child (N = 7) or a parent (N = 4). Subgingival samples from all subjects were cultured for A. actinomycetemcomitans, and its clonal types were determined by combining serotype and genotype data for each isolate. RESULTS: Among 42 dentate family members, 16 (38%) exhibited periodontitis and eight (50%) had AgP. Periodontitis was found in nine of 12 (75%) of the dentate parents and six of 17 (35%) siblings of the child probands. A. actinomycetemcomitans was detected in 16 of 31 (52%) family members, i.e., one parent and at least one sibling in six families. The child probands shared A. actinomycetemcomitans clonal types with their parents in five of six (83%) families and with their siblings in three of six (50%) families. In the four parent-proband families, A. actinomycetemcomitans occurred in two spouses and all nine children. The parent probands shared A. actinomycetemcomitans clonal types with their spouses in both families and with their children in three of four families. In all families, the likelihood of intrafamilial transmission of A. actinomycetemcomitans was statistically significant. Members of most families (eight of 11, 73%) also harbored additional clonal types of A. actinomycetemcomitans. CONCLUSION: Parents and siblings of an individual with A. actinomycetemcomitans-positive AgP may have an increased susceptibility to periodontitis and shared and/or other clonal types of oral A. actinomycetemcomitans.

  • 290.
    Drobni, Mirva
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Adhesion-related interactions of Actinomyces and Streptococcus biofilm bacteria2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Adhesion of bacteria is a key event in biofilm formation and is mediated by bacterial adhesins recognising host or bacterial partner receptors. In oral biofilm formation, primary Actinomyces and Streptococcus colonizers adhere to salivary pellicle proteins such as proline-rich proteins (PRPs) as well as to mucosal surfaces. Subsequently, Actinomyces and Streptococcus strains and other bacteria, such as Veillonella, Fusobacterium and Porphyromonas, adhere to each other. The nature of this community is highly important for the health or disease status, although specific pathogenic species may also have been implicated.

    The aim of this thesis was to study key players in early oral colonisation, Actinomyces and Streptococcus species, and more specifically the nature of their adhesins and ligands. A further aim was to study the function of the salivary PRP proteins and an innate peptide derived thereof on bacterial adhesion, proliferation and regulation of pH, i.e. key factors in biofilm formation.

    In paper I and II, adhesion, proliferation and pH affecting features of the RGRPQ (arginine-glycine-arginine-proline-glutamine) peptide, derived from PRP-1, were demonstrated. By use of an alanine-scan (I), motifs for adhesion inhibition and desorption of Actinomyces naeslundii, and proliferation stimulation, ammonia production and inhibition of sucrose induced pH drop by Streptococcus gordonii were indicated. The RGRPQ peptide also stimulated S. gordonii colonisation in vivo. In paper II, a more sophisticated quantitative structure-activity relationship (QSAR) study, using statistical molecular design (SMD) and multivariate modelling (partial least squares projections to latent structures, PLS), further narrowed down the RGRPQ peptide motifs. The R and Q amino acids were crucial for activity. For proliferation a hydrophobic and large size third position amino acid was crucial, while adhesion inhibition and desorption needed a small hydrophilic second position amino acid. All functions depended on a low polarity hydrophobic fourth position. Accordingly, activities could be optimized separately, with decreased function in the others.

    In paper III and IV, focus was on the bacterial adhesins and their binding epitopes. The genes for FimA major subunit proteins of type-2 fimbriae were sequenced from A. naeslundii genospecies 1 and 2 and Actinomyces odontolyticus, each with unique carbohydrate binding specificities (III). Three major subtypes of FimA proteins were found that correlated with binding specificity, including a novel fimA gene in A. odontolyticus. All subtypes contained a pilin, LPXTG and E box motif. In paper IV, multiple PRP binding patterns for Actinomyces and Streptococcus strains were mapped using a hybrid peptide construct. The two most deviating binding groups deviated in type-1 fimbriae mediated binding to milk and saliva protein ligands.

    In conclusion, differences in bacterial adhesins and their ability to utilise salivary proteins may render bacteria tropism for different niches. Peptides derived from protein receptors, such as RGRPQ, may be important modulators of biofilm formation, giving commensal bacteria a competitive edge in the bacterial community.

  • 291.
    Drobni, Mirva
    et al.
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Hallberg, K
    Öhman, Ulla
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Birve, Anna
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Persson, Karina
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Sequence analyses of fimbriae subunit FimA proteins on Actinomyces naeslundii genospecies 1 and 2 and Actinomyces odontolyticus with variant carbohydrate binding specificities.2006In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 43, no 6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Actinomyces naeslundii genospecies 1 and 2 express type-2 fimbriae (FimA subunit polymers) with variant Galbeta binding specificities and Actinomyces odontolyticus a sialic acid specificity to colonize different oral surfaces. However, the fimbrial nature of the sialic acid binding property and sequence information about FimA proteins from multiple strains are lacking. RESULTS: Here we have sequenced fimA genes from strains of A.naeslundii genospecies 1 (n = 4) and genospecies 2 (n = 4), both of which harboured variant Galbeta-dependent hemagglutination (HA) types, and from A.odontolyticus PK984 with a sialic acid-dependent HA pattern. Three unique subtypes of FimA proteins with 63.8-66.4% sequence identity were present in strains of A. naeslundii genospecies 1 and 2 and A. odontolyticus. The generally high FimA sequence identity (> 97.2%) within a genospecies revealed species specific sequences or segments that coincided with binding specificity. All three FimA protein variants contained a signal peptide, pilin motif, E box, proline-rich segment and an LPXTG sorting motif among other conserved segments for secretion, assembly and sorting of fimbrial proteins. The highly conserved pilin, E box and LPXTG motifs are present in fimbriae proteins from other Gram-positive bacteria. Moreover, only strains of genospecies 1 were agglutinated with type-2 fimbriae antisera derived from A. naeslundii genospecies 1 strain 12104, emphasizing that the overall folding of FimA may generate different functionalities. Western blot analyses with FimA antisera revealed monomers and oligomers of FimA in whole cell protein extracts and a purified recombinant FimA preparation, indicating a sortase-independent oligomerization of FimA. CONCLUSION: The genus Actinomyces involves a diversity of unique FimA proteins with conserved pilin, E box and LPXTG motifs, depending on subspecies and associated binding specificity. In addition, a sortase independent oligomerization of FimA subunit proteins in solution was indicated.

  • 292.
    Drobni, Mirva
    et al.
    Umeå University, Faculty of Medicine, Odontology.
    Jonasson, Anette
    Strömberg, Nicklas
    Johansson, Ingegerd
    Actinomyces and Streptococcus species display differential binding epitopes on acidic proline-rich protein PRP-1Manuscript (Other academic)
  • 293.
    Drobni, Mirva
    et al.
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Li, Tong
    Kruger, C
    Loimaranta, V
    Kilian, M
    Hammarström, L
    Jörnvall, H
    Bergman, T
    Strömberg, Nicklas
    A host-derived pentapeptide affecting adhesion, proliferation and local pH in Streptococcus-Actinomyces biofilm communities.2006In: Infection and immunityArticle, review/survey (Other (popular science, discussion, etc.))
    Abstract [en]

    Salivary proline-rich proteins (PRPs) attach commensal Actinomyces and Streptococcus species to teeth. Here, gel filtration, mass spectrometry and Edman degradation were applied to show the release of a pentapeptide, RGRPQ, from PRP-1 upon proteolysis by Streptococcus gordonii. Moreover, synthetic RGRPQ and derivatives were used to investigate associated innate properties and responsible motifs. The RGRPQ peptide increased 2.5-fold the growth rate of S. gordonii via a Q-dependent sequence motif, and selectively stimulated oral colonization of this organism in a rat model in vivo. By contrast, growth of Streptococcus mutans, implicated in caries, was unaffected. While the entire RGRPQ sequence was required to block sucrose-induced pH-decrease by S. gordonii and S. mutans, the N-terminal Arg residue mediated pH-increase (i.e. ammonia production) by S. gordonii alone (which exhibits Arg catabolism to ammonia). Strains of commensal viridans streptococci exhibited PRP degradation and Arg catabolism, while cariogenic species did not. The RGRPQ peptide mediated via a differential Q-dependent sequence motif, adhesion inhibition and desorption of PRP-1-binding strains of A. naeslundii genospecies 2 (5 out of 10 strains) but not of S. gordonii (n=5). The inhibitable A. naeslundii strains alone displayed the same binding profile as S. gordonii to hybrid peptides terminating in RGRPQ or GQSPQ, derived from the middle or C-terminal segments of PRP-1. The present findings indicate the presence of a host-bacteria interaction where a host peptide released by bacterial proteolysis affects key properties in biofilm formation.

  • 294.
    Drobni, Mirva
    et al.
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Li, Tong
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Krüger, Carina
    Loimaranta, Vuokko
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Kilian, Mogens
    Hammarström, Lennart
    Jörnvall, Hans
    Bergman, Tomas
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Host-derived pentapeptide affecting adhesion, proliferation, and local pH in biofilm communities composed of Streptococcus and Actinomyces species.2006In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 74, no 11, p. 6293-6299Article in journal (Refereed)
    Abstract [en]

    Salivary proline-rich proteins (PRPs) attach commensal Actinomyces and Streptococcus species to teeth. Here, gel filtration, mass spectrometry and Edman degradation were applied to show the release of a pentapeptide, RGRPQ, from PRP-1 upon proteolysis by Streptococcus gordonii. Moreover, synthetic RGRPQ and derivatives were used to investigate associated innate properties and responsible motifs. The RGRPQ peptide increased 2.5-fold the growth rate of S. gordonii via a Q-dependent sequence motif and selectively stimulated oral colonization of this organism in a rat model in vivo. In contrast, the growth of Streptococcus mutans, implicated in caries, was not affected. While the entire RGRPQ sequence was required to block sucrose-induced pH-decrease by S. gordonii and S. mutans, the N-terminal Arg residue mediated the pH increase (i.e., ammonia production) by S. gordonii alone (which exhibits Arg catabolism to ammonia). Strains of commensal viridans streptococci exhibited PRP degradation and Arg catabolism, whereas cariogenic species did not. The RGRPQ peptide mediated via a differential Q-dependent sequence motif, adhesion inhibition, and desorption of PRP-1-binding strains of A. naeslundii genospecies 2 (5 of 10 strains) but not of S. gordonii (n=5). The inhibitable A. naeslundii strains alone displayed the same binding profile as S. gordonii to hybrid peptides terminating in RGRPQ or GQSPQ, derived from the middle or C-terminal segments of PRP-1. The present findings indicate the presence of a host-bacterium interaction in which a host peptide released by bacterial proteolysis affects key properties in biofilm formation.

  • 295.
    Drobni, Mirva
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Li, Tong
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Krüger, Karina
    Loimaranta, Vuokko
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Kilian, Mogens
    Hammarström, Lennart
    Jörnvall, Hans
    Bergman, Tomas
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    A host-derived pentapeptide enhancing host-bacteria commensalisms and communication2006In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 74, no 11, p. 6293-6299Article in journal (Refereed)
    Abstract [en]

    Salivary proline-rich proteins (PRPs) attach commensal Actinomyces and Streptococcus species to teeth. Here, gel filtration, mass spectrometry and Edman degradation were applied to show the release of a pentapeptide, RGRPQ, from PRP-1 upon proteolysis by Streptococcus gordond. Moreover, synthetic RGRPQ and derivatives were used to investigate associated innate properties and responsible motifs. The RGRPQ peptide increased 2.5-fold the growth rate of S. gordonii via a Q-dependent sequence motif and selectively stimulated oral colonization of this organism in a rat model in vivo. In contrast, the growth of Streptococcus mutans, implicated in caries, was not affected. While the entire RGRPQ sequence was required to block sucrose-induced pH-decrease by S. gordonii and S. mutans, the N-terminal Arg residue mediated the pH increase (i.e., ammonia production) by S. gordonii alone (which exhibits Arg catabolism to ammonia). Strains of commensal viridans streptococci exhibited PR-P degradation and Arg catabolism, whereas cariogenic species did not. The RGRPQ peptide mediated via a differential Q-dependent sequence motif, adhesion inhibition, and desorption of PRP-1-binding strains of A. naeslundii genospecies 2 (5 of 10 strains) but not of S. gordonii (n = 5). The inhibitable A. naeslundii strains alone displayed the same binding profile as S. gordond to hybrid peptides terminating in RGRPQ or GQSPQ, derived from the middle or C-terminal segments of PRP-1. The present findings indicate the presence of a host-bacterium interaction in which a host peptide released by bacterial proteolysis affects key properties in biofilm formation.

  • 296.
    Drobni, Mirva
    et al.
    Umeå University, Faculty of Medicine, Odontology.
    Olsson, Ing-Marie
    Umeå University, Faculty of Science and Technology, Chemistry.
    Eriksson, Christer
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Almqvist, Fredrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Multivariate design and evaluation of a set of RGRPQ-derived innate immunity peptides2006In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 281, no 22, p. 15164-15171Article in journal (Refereed)
    Abstract [en]

    Oral commensal Streptococcus gordonii proteolytically cleave the salivary PRP-1 polypeptide into an RGRPQ innate peptide. The Arg and Gln termini are crucial for RGRPQ-mediated ammonia production and proliferation by S. gordonii SK12 and adhesion inhibition and desorption by Actinomyces naeslundii T14V, respectively. Here we have applied (i) a multivariate approach using RGRPQ-related peptides varied at amino acids 2, 3, and 4 simultaneously and (ii) size and N- and C-terminal modifications of RGRPQ to generate structure activity information. While the N-terminal arginine motif mediated ammonia production independent of peptide size, other responses required more or less full-length peptide motifs. The motifs for adhesion inhibition and desorption were the same. The adhesion and proliferation motifs required similarly a hydrophobic/low polarity amino acid 4 but differentially a hydrophilic or hydrophobic character of amino acids 2/3, respectively; polar peptides with small/hydrophilic and hydrophilic amino acids 2 and 3, respectively, had high adhesion inhibition/desorption activity, and lipophilic peptides with large/hydrophobic amino acids 2 and 3 had high proliferation activity. Accordingly, while RIWWQ had increased proliferation but abolished adhesion/desorption activity, peptides designed with hydrophilic amino acids 2 and 3 were predicted to behave in the opposite way. Moreover, a RGRPQ mimetic for all three responses should mimic small hydrophilic, large nitrogen-containing, and hydrophobic/low polarity amino acids 2, 3, and 4, respectively. Peptides fulfilling these criteria were 1-1.6-fold improved in all three responses. Thus, both mimetics and peptides with differential proliferation and adhesion activities may be generated for evaluation in biofilm models.

  • 297. Duarte-Salles, Talita
    et al.
    Fedirko, Veronika
    Stepien, Magdalena
    Aleksandrova, Krasimira
    Bamia, Christina
    Lagiou, Pagona
    Laursen, Anne Sofie Dam
    Hansen, Louise
    Overvad, Kim
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    His, Mathilde
    Boeing, Heiner
    Katzke, Verena
    Kühn, Tilman
    Trichopoulou, Antonia
    Valanou, Elissavet
    Kritikou, Maria
    Masala, Giovanna
    Panico, Salvatore
    Sieri, Sabina
    Ricceri, Fulvio
    Tumino, Rosario
    Bueno-de-Mesquita, H B As
    Peeters, Petra H
    Hjartåker, Anette
    Skeie, Guri
    Weiderpass, Elisabete
    Ardanaz, Eva
    Bonet, Catalina
    Chirlaque, Maria-Dolores
    Dorronsoro, Miren
    Quirós, J Ramón
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ohlsson, Bodil
    Sjöberg, Klas
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Travis, Ruth C
    Wareham, Nick
    Ferrari, Pietro
    Freisling, Heinz
    Romieu, Isabelle
    Cross, Amanda J
    Gunter, Marc
    Lu, Yunxia
    Jenab, Mazda
    Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 11, p. 2715-2728Article in journal (Refereed)
    Abstract [en]

    The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.

  • 298. Duarte-Salles, Talita
    et al.
    Fedirko, Veronika
    Stepien, Magdalena
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Trepo, Elisabeth
    Overvad, Kim
    Tjønneland, Anne
    Halkjaer, Jytte
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Cadeau, Claire
    Kühn, Tilman
    Aleksandrova, Krasimira
    Trichopoulos, Dimitrios
    Tsiotas, Konstantinos
    Boffetta, Paolo
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, H B as
    Dik, Vincent K
    Peeters, Petra H
    Weiderpass, Elisabete
    Torhild Gram, Inger
    Hjartåker, Anette
    Ramón Quirós, Jose
    Fonseca-Nunes, Ana
    Molina-Montes, Esther
    Dorronsoro, Miren
    Navarro Sanchez, Carmen
    Barricarte, Aurelio
    Lindkvist, Björn
    Sonestedt, Emily
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C
    Romieu, Isabelle
    Riboli, Elio
    Jenab, Mazda
    Dairy products and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 7, p. 1662-1672Article in journal (Refereed)
    Abstract [en]

    Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (N(cases) = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (N(cases) = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; p(trend) = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; p(trend) = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; p(trend) = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration.

  • 299. Duell, Eric J
    et al.
    Lujan-Barroso, Leila
    Llivina, Claudia
    Muñoz, Xavier
    Jenab, Mazda
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Racine, Antoine
    Boeing, Heiner
    Buijsse, Brian
    Canzian, Federico
    Johnson, Theron
    Dalgård, Christine
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Sánchez, Soledad C
    Sánchez-Cantalejo, Emilio
    Huerta, José-María
    Ardanaz, Eva
    Dorronsoro, Miren
    Khaw, Kay-Tee
    Travis, Ruth C
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Rafnsson, Snorri
    Palli, Domenico
    Sacerdote, Carlotta
    Tumino, Rosario
    Panico, Salvatore
    Grioni, Sara
    Bueno-de-Mesquita, H Bas
    Ros, Martine M
    Numans, Mattijs E
    Peeters, Petra H
    Johansen, Dorthe
    Lindkvist, Björn
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Biobank Research. Genetic Epidemiology Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Skeie, Guri
    Weiderpass, Elisabete
    Duarte-Salles, Talita
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Riboli, Elio
    Sala, Núria
    González, Carlos A
    Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort2013In: Genes & Nutrition, ISSN 1555-8932, E-ISSN 1865-3499, Vol. 8, no 6, p. 549-560Article in journal (Refereed)
    Abstract [en]

    Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 polymorphisms in vitamin C transporter genes SCL23A1 and SCL23A2 and GC risk in 365 cases and 1,284 controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. We also evaluated the association between these polymorphisms and baseline plasma vitamin C levels in a subset of participants. Four SNPs were predictors of plasma vitamin C levels (SLC23A1 rs11950646 and rs33972313; SLC23A2 rs6053005 and rs6133175) in multivariable linear regression models. One SNP (SLC23A2 rs6116569) was associated with GC risk, in particular non-cardia GC (OR = 1.63, 95 % CI = 1.11-2.39, based on 178 non-cardia cases), but this association was attenuated when plasma vitamin C was included in the logistic regression model. Haplotype analysis of SLC23A1 yielded no associations with GC. In SLC23A2, one haplotype was associated with both overall and non-cardia GC, another haplotype was associated with GC overall, and a third was associated with intestinal-type GC. Common variants in SLC23A1 and SLC23A2 may influence plasma vitamin C concentration independent of dietary intake, and variation in SLC23A2 may influence GC risk. Additional prospective studies in large populations and consortia are recommended. Investigation of variation in vitamin C transporter genes may shed light on the preventative properties of vitamin C in gastric carcinogenesis.

  • 300. Duell, Eric J
    et al.
    Travier, Noémie
    Lujan-Barroso, Leila
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Palli, Domenico
    Krogh, Vittorio
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Quirós, J Ramón
    Sánchez-Cantalejo, Emilio
    Navarro, Carmen
    Gurrea, Aurelio Barricarte
    Dorronsoro, Miren
    Khaw, Kay-Tee
    Allen, Naomi E
    Key, Timothy J
    Bueno-de-Mesquita, H Bas
    Ros, Martine M
    Numans, Mattijs E
    Peeters, Petra Hm
    Trichopoulou, Antonia
    Naska, Androniki
    Dilis, Vardis
    Teucher, Birgit
    Kaaks, Rudolf
    Boeing, Heiner
    Schütze, Madlen
    Regner, Sara
    Lindkvist, Björn
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Overvad, Kim
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Egeberg, Rikke
    Tjønneland, Anne
    Lund, Eiliv
    Weiderpass, Elisabete
    Braaten, Tonje
    Romieu, Isabelle
    Ferrari, Pietro
    Jenab, Mazda
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Aune, Dagfinn
    Norat, Teresa
    Riboli, Elio
    González, Carlos A
    Alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.2011In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 94, no 5, p. 1266-75Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer death worldwide. The association between alcohol consumption and GC has been investigated in numerous epidemiologic studies with inconsistent results.

    OBJECTIVE: We evaluated the association between alcohol consumption and GC risk.

    DESIGN: We conducted a prospective analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which included 444 cases of first primary gastric adenocarcinoma. HRs and 95% CIs for GC were estimated by using multivariable Cox proportional hazards regression for consumption of pure ethanol in grams per day, with stratification by smoking status, anatomic subsite (cardia, noncardia), and histologic subtype (diffuse, intestinal). In a subset of participants, results were further adjusted for baseline Helicobacter pylori serostatus.

    RESULTS: Heavy (compared with very light) alcohol consumption (≥60 compared with 0.1-4.9 g/d) at baseline was positively associated with GC risk (HR: 1.65; 95% CI: 1.06, 2.58), whereas lower consumption amounts (<60 g/d) were not. When we analyzed GC risk by type of alcoholic beverage, there was a positive association for beer (≥30 g/d; HR: 1.75; 95% CI: 1.13, 2.73) but not for wine or liquor. Associations were primarily observed at the highest amounts of drinking in men and limited to noncardia subsite and intestinal histology; no statistically significant linear dose-response trends with GC risk were observed.

    CONCLUSION: Heavy (but not light or moderate) consumption of alcohol at baseline (mainly from beer) is associated with intestinal-type noncardia GC risk in men from the EPIC cohort.

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