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  • 1. Al-Delaimy, W K
    et al.
    Slimani, N
    Ferrari, P
    Key, T
    Spencer, E
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Johansson, G
    Mattisson, I
    Wirfalt, E
    Sieri, S
    Agudo, A
    Celentano, E
    Palli, D
    Sacerdote, C
    Tumino, R
    Dorronsoro, M
    Ocké, M C
    Bueno-De-Mesquita, H B
    Overvad, K
    Chirlaque, Ma D
    Trichopoulou, A
    Naska, A
    Tjonneland, A
    Olsen, A
    Lund, E
    Skeie, G
    Ardanaz, E
    Kesse, E
    Boutron-Ruault, M-C
    Clavel-Chapelon, F
    Bingham, S
    Welch, A A
    Martinez-Garcia, C
    Nagel, G
    Linseisen, J
    Quirós, J R
    Peeters, P H M
    van Gils, C H
    Boeing, H
    van Kappel, A L
    Steghens, J-P
    Riboli, E
    Plasma carotenoids as biomarkers of intake of fruits and vegetables: ecological-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).2005In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 59, no 12, p. 1397-408Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to assess the ability of a single 24-h dietary recall (24HDR) and food questionnaires (FQ) to predict plasma carotenoid levels at the ecological level by assessing the relationship between mean plasma carotenoid levels and mean intake of fruit and vegetables measured by 24HDR and FQ across 16 European regions. DESIGN: A random subsample of 3089 subjects was included, stratified by age and gender. They provided blood samples and dietary information between 1992 and 2000 as part of the European Prospective Investigation into Cancer and Nutrition. RESULTS: Using Spearman's correlation coefficients, the correlations between mean regional 24HDR fruit and vegetable variables and corresponding mean plasma carotenoid levels were generally higher than the correlations using FQ means. The highest correlation was between the 24HDR citrus fruit variable and beta-cryptoxanthin (r = 0.90). For 24HDR, total fruits and vegetables were highly correlated with lutein, zeaxanthin, and beta-cryptoxanthin (r = 0.83-0.87), while vegetables were more closely related with lutein (r = 0.69) and zeaxanthin (r = 0.68), and fruits correlated with zeaxanthin (r = 0.87) and beta-cryptoxanthin (r = 0.84). Root vegetables (r = 0.81) and total carrots (r = 0.71) were well correlated with alpha-carotene. In the multivariate models adjusting for age, body mass index, and season, and using observations of means stratified by sex and region, the association was generally higher for 24HDR compared to FQ. CONCLUSION: Mean regional intakes of fruits and vegetables in several European countries were closely correlated with corresponding mean plasma levels of individual carotenoids. Fruits and vegetables measured by 24HDR were generally better able to predict plasma carotenoids at the ecological level.

  • 2. Al-Delaimy, WK
    et al.
    Ferrari, P
    Slimani, N
    Pala, V
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Nilsson, S
    Mattisson, I
    Wirfalt, E
    Galasso, R
    Palli, D
    Vineis, P
    Tumino, R
    Dorronsoro, M
    Pera, G
    Ocké, MC
    Bueno-de-Mesquita, HB
    Overvad, K
    Chirlaque, M
    Trichopoulou, A
    Naska, A
    Tjonneland, A
    Olsen, A
    Lund, E
    Alsaker, EH
    Barricarte, A
    Kesse, E
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Key, TJ
    Spencer, E
    Bingham, S
    Welch, AA
    Sanchez-Perez, MJ
    Nagel, G
    Linseisen, J
    Quirós, JR
    Peeters, PH
    van Gils, CH
    Boeing, H
    van Kappel, AL
    Steghens, JP
    Riboli, E
    Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).2005In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 59, no 12, p. 1387-1396Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. DESIGN: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. RESULTS: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R(partial)(2) = 17.2%) for beta-cryptoxanthin, total carrots ((partial)(2) = 13.4%) and root vegetables (R(partial)(2) = 13.3%) for alpha-carotene, and tomato products (R(partial)(2) = 13.8%) for lycopene. For 24HDR, the highest R(partial)(2) was for fruits in relation to beta-cryptoxanthin (7.9%). CONCLUSIONS: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.

  • 3. Al-Delaimy, WK
    et al.
    Van Kappel, AL
    Ferrari, P
    Slimani, N
    Steghens, JP
    Bingham, S
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Wallström, P
    Overvad, K
    Tjonneland, A
    Key, TJ
    Welch, AA
    Bas Bueno-De-Mesquita, H
    Peeters, PH
    Boeing, H
    Linseisen, J
    Clavel-Chapelon, F
    Guibout, C
    Navarro, C
    Quiros, JR
    Palli, D
    Celentano, E
    Trichopoulou, A
    Benetou, V
    Kaaks, R
    Riboli, E
    Plasma levels of six carotenoids in nine European countries: report from the European Prospective Investigation into Cancer and Nutrition (EPIC).2004In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 7, no 6, p. 713-722Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In addition to their possible direct biological effects, plasma carotenoids can be used as biochemical markers of fruit and vegetable consumption for identifying diet-disease associations in epidemiological studies. Few studies have compared levels of these carotenoids between countries in Europe. OBJECTIVE: Our aim was to assess the variability of plasma carotenoid levels within the cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Plasma levels of six carotenoids--alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein and zeaxanthin--were measured cross-sectionally in 3043 study subjects from 16 regions in nine European countries. We investigated the relative influence of gender, season, age, body mass index (BMI), alcohol intake and smoking status on plasma levels of the carotenoids. RESULTS: Mean plasma level of the sum of the six carotenoids varied twofold between regions (1.35 micromol l(-1) for men in Malmö, Sweden vs. 2.79 micromol l(-1) for men in Ragusa/Naples, Italy; 1.61 micromol l(-1) for women in The Netherlands vs. 3.52 micromol l(-1) in Ragusa/Naples, Italy). Mean levels of individual carotenoids varied up to fourfold (alpha-carotene: 0.06 micromol l(-1) for men in Murcia, Spain vs. 0.25 micromol l(-1) for vegetarian men living in the UK). In multivariate regression analyses, region was the most important predictor of total plasma carotenoid level (partial R(2)=27.3%), followed by BMI (partial R(2)=5.2%), gender (partial R(2)=2.7%) and smoking status (partial R(2)=2.8%). Females had higher total carotenoid levels than males across Europe. CONCLUSIONS: Plasma levels of carotenoids vary substantially between 16 different regions in Italy, Greece, Spain, France, Germany, the UK, Sweden, Denmark and The Netherlands. Compared with region of residence, the other demographic and lifestyle factors and laboratory measurements have limited predictive value for plasma carotenoid levels in Europe.

  • 4.
    Andersson-Wenckert, Ingrid
    et al.
    Umeå University, Faculty of Medicine, Odontology, Pediatric Dentistry.
    Sunnegårdh-Grönberg, Karin
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Flowable resin composite as a class II restorative in primary molars: A two-year clinical evaluation.2006In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 64, no 6, p. 334-340Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the clinical durability of flowable resin composite and resin-modified glass ionomer cement when used as class II restoratives in primary molars. MATERIAL AND METHODS: A total of 190 restorations were placed in 61 children, age in the range of 5-11 years. The restoratives, Tetric Flow, in combination with the adhesives, Excite or Prompt-L-Pop and Vitremer, were used in class II cavities in primary molars. An intra-individual study design was used and the restorations were evaluated by modified USPHS criteria over a 2-year period. RESULTS: 146 of the restorations could be evaluated at 2 years. The cumulative failure rate was 10.6% for Vitremer and 13.6% for Tetric Flow. No statistically significant differences were found in failure rates between different materials or between bonding systems. The main cause of failure for Tetric Flow was secondary caries and for Vitremer wear and dissolution. CONCLUSIONS: Vitremer and Tetric Flow showed no significant difference concerning clinical durability at 2 years when used as class II restoratives in primary molars. Both materials demonstrated acceptable clinical results.

  • 5. Bamia, C
    et al.
    Orfanos, P
    Ferrari, P
    Overvad, K
    Hundborg, HH
    Tjonneland, A
    Olsen, A
    Kesse, E
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Nagel, G
    Boffetta, P
    Boeing, H
    Hoffmann, K
    Trichopoulos, D
    Baibas, N
    Psaltopoulou, T
    Norat, T
    Slimani, N
    Palli, D
    Krogh, V
    Panico, S
    Tumino, R
    Sacerdote, C
    Bueno-de-Mesquita, HB
    Ocke, MC
    Peeters, PH
    van Rossum, CT
    Quiros, JR
    Sanchez, MJ
    Navarro, C
    Barricarte, A
    Dorronsoro, M
    Berglund, G
    Wirfalt, E
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Bingham, S
    Khaw, KT
    Spencer, EA
    Roddam, AW
    Riboli, E
    Trichopoulou, A
    Dietary patterns among older Europeans: the EPIC-Elderly study.2005In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 94, no 1, p. 100-13Article in journal (Refereed)
    Abstract [en]

    Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a 'vegetable-based' diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a 'sweet- and fat-dominated' diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. 'Vegetable-based' and a 'sweet- and fat-dominated' diets are prevalent among the elderly across Europe, and there is a north-south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival.

  • 6. Benetou, V
    et al.
    Orfanos, P
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Bergström, Ulrica
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Berrino, F
    Tumino, R
    Borch, K B
    Lund, E
    Peeters, P H M
    Grote, V
    Li, K
    Altzibar, J M
    Key, T
    Boeing, H
    von Ruesten, A
    Norat, T
    Wark, P A
    Riboli, E
    Trichopoulou, A
    Mediterranean diet and incidence of hip fractures in a European cohort2013In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, no 5, p. 1587-1598Article in journal (Refereed)
    Abstract [en]

    Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

  • 7. Benetou, V
    et al.
    Orfanos, P
    Zylis, D
    Sieri, S
    Contiero, P
    Tumino, R
    Giurdanella, M C
    Peeters, P H M
    Linseisen, J
    Nieters, A
    Boeing, H
    Weikert, C
    Pettersson, U
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Bueno-de-Mesquita, H B
    Dorronsoro, M
    Boffetta, P
    Trichopoulou, A
    Diet and hip fractures among elderly Europeans in the EPIC cohort2011In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 65, no 1, p. 132-139Article in journal (Refereed)
    Abstract [en]

    In a prospective study of the elderly, diet, including consumption of dairy products, alcohol and vitamin D, did not appear to play a major role in hip fracture incidence. There is however, weak and statistically non-significant evidence that vegetable and fish consumption and intake of polyunsaturated lipids may have a beneficial, whereas saturated lipid intake a detrimental effect.

  • 8. Bergdahl, M
    et al.
    Bergdahl, J
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Depressive symptoms in individuals with idiopathic subjective dry mouth1997In: Journal of Oral Pathology & Medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, Vol. 26, no 10, p. 448-450Article in journal (Refereed)
    Abstract [en]

    It has been known for many centuries that there is a relationship between saliva flow rate and emotional status. The significance of psychological processes in the subjective sensation of a dry mouth has been discussed earlier, and this study deals with the presence of depressive symptoms in individuals with idiopathic subjective sensation of a dry mouth. Depressive symptoms in 94 healthy subjects with normal flow rates for unstimulated and stimulated whole saliva but with a subjective sensation of a dry mouth were assessed by the Beck Depression Inventory (BDI) and compared with healthy age- and gender-matched controls. The subjects with a subjective dry mouth condition were significantly more depressive and also had a significantly higher frequency of depressive symptoms. Depression was found in 21.3% of the individuals with a subjective dry mouth sensation and in 3.2% of the controls. The results of this study indicate that, in some cases, subjective dry mouth may be of psychological origin.

  • 9. Boeing, H
    et al.
    Dietrich, T
    Hoffmann, K
    Pischon, T
    Ferrari, P
    Lahmann, PH
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Allen, N
    Key, T
    Skeie, G
    Lund, E
    Olsen, A
    Tjonneland, A
    Overvad, K
    Jensen, MK
    Rohrmann, S
    Linseisen, J
    Trichopoulou, A
    Bamia, C
    Psalttopoulou, T
    Weinehall, L
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Sanchez, MJ
    Jakszyn, P
    Ardanaz, E
    Amiano, P
    Chirlaque, MD
    Quiros, JR
    Wirfalt, E
    Berglund, G
    Peeters, PH
    van Gils, CH
    Bueno-de-Mesquita, HB
    Buchner, FL
    Berrino, F
    Palli, D
    Sacerdote, C
    Tumino, R
    Panico, S
    Bingham, S
    Khaw, KT
    Slimani, N
    Norat, T
    Jenab, M
    Riboli, E
    Intake of fruits and vegetables and risk of cancer of the upper aero-digestive tract: the prospective EPIC-study.2006In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 17, no 7, p. 957-969Article in journal (Refereed)
    Abstract [en]

    Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (<120 g/d) for fruits. Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract, particularly at low intake.

  • 10. Boffetta, Paolo
    et al.
    Couto, Elisabeth
    Wichmann, Janine
    Ferrari, Pietro
    Trichopoulos, Dimitrios
    Bueno-de-Mesquita, H Bas
    van Duijnhoven, Fränzel J B
    Büchner, Frederike L
    Key, Tim
    Boeing, Heiner
    Nöthlings, Ute
    Linseisen, Jakob
    Gonzalez, Carlos A
    Overvad, Kim
    Nielsen, Michael R S
    Tjønneland, Anne
    Olsen, Anja
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Lagiou, Pagona
    Naska, Androniki
    Benetou, Vassiliki
    Kaaks, Rudolf
    Rohrmann, Sabine
    Panico, Salvatore
    Sieri, Sabina
    Vineis, Paolo
    Palli, Domenico
    van Gils, Carla H
    Peeters, Petra H
    Lund, Eiliv
    Brustad, Magritt
    Engeset, Dagrun
    Huerta, José María
    Rodríguez, Laudina
    Sánchez, Maria-José
    Dorronsoro, Miren
    Barricarte, Aurelio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Manjer, Jonas
    Sonestedt, Emily
    Allen, Naomi E
    Bingham, Sheila
    Khaw, Kay-Tee
    Slimani, Nadia
    Jenab, Mazda
    Mouw, Traci
    Norat, Teresa
    Riboli, Elio
    Trichopoulou, Antonia
    Fruit and vegetable intake and overall cancer risk in the European prospective investigation into cancer and nutrition (EPIC)2010In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 102, no 8, p. 529-537Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is widely believed that cancer can be prevented by high intake of fruits and vegetables. However, inconsistent results from many studies have not been able to conclusively establish an inverse association between fruit and vegetable intake and overall cancer risk. METHODS: We conducted a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to assess relationships between intake of total fruits, total vegetables, and total fruits and vegetables combined and cancer risk during 1992-2000. Detailed information on the dietary habit and lifestyle variables of the cohort was obtained. Cancer incidence and mortality data were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models. Analyses were also conducted for cancers associated with tobacco and alcohol after stratification for tobacco smoking and alcohol drinking. RESULTS: Of the initial 142 605 men and 335 873 women included in the study, 9604 men and 21 000 women were identified with cancer after a median follow-up of 8.7 years. The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women. Associations between reduced cancer risk and increased intake of total fruits and vegetables combined and total vegetables for the entire cohort were similar (200 g/d increased intake of fruits and vegetables combined, HR = 0.97, 95% CI = 0.96 to 0.99; 100 g/d increased intake of total vegetables, HR = 0.98, 95% CI = 0.97 to 0.99); intake of fruits showed a weaker inverse association (100 g/d increased intake of total fruits, HR = 0.99, 95% CI = 0.98 to 1.00). The reduced risk of cancer associated with high vegetable intake was restricted to women (HR = 0.98, 95% CI = 0.97 to 0.99). Stratification by alcohol intake suggested a stronger reduction in risk in heavy drinkers and was confined to cancers caused by smoking and alcohol. CONCLUSIONS: A very small inverse association between intake of total fruits and vegetables and cancer risk was observed in this study. Given the small magnitude of the observed associations, caution should be applied in their interpretation.

  • 11.
    Brady, L. Jeannine
    et al.
    Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA.
    Maddocks, Sarah E.
    School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, UK.
    Larson, Matthew R.
    Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
    Forsgren, Nina
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Persson, Karina
    Umeå University, Faculty of Medicine, Department of Odontology.
    Deivanayagam, Champion C.
    Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
    Jenkinson, Howard F.
    School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, UK.
    The changing faces of Streptococcus antigen I/II polypeptide family adhesins2010In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 77, no 2, p. 276-286Article in journal (Refereed)
    Abstract [en]

    Streptococcus mutans antigen I/II (AgI/II) protein was one of the first cell wall-anchored adhesins identified in Gram-positive bacteria. It mediates attachment of S. mutans to tooth surfaces and has been a focus for immunization studies against dental caries. The AgI/II family polypeptides recognize salivary glycoproteins, and are also involved in biofilm formation, platelet aggregation, tissue invasion and immune modulation. The genes encoding AgI/II family polypeptides are found among Streptococcus species indigenous to the human mouth, as well as in Streptococcus pyogenes, S. agalactiae and S. suis. Evidence of functionalities for different regions of the AgI/II proteins has emerged. A sequence motif within the C-terminal portion of Streptococcus gordonii SspB (AgI/II) is bound by Porphyromonas gingivalis, thus promoting oral colonization by this anaerobic pathogen. The significance of other epitopes is now clearer following resolution of regional crystal structures. A new picture emerges of the central V (variable) region, predicted to contain a carbohydrate-binding trench, being projected from the cell surface by a stalk formed by an unusual association between an N-terminal α-helix and a C-terminal polyproline helix. This presentation mode might be important in determining functional conformations of other Gram-positive surface proteins that have adhesin domains flanked by α-helical and proline-rich regions.

    Ever since dental caries (tooth decay) was first shown to be caused by bacteria, there has been continued interest in developing vaccine or passive immunization protocols for its control or prevention (Lehner et al., 1980). Although dental caries is not fatal, and in developed countries caries is now considered to be largely avoidable through controlled diet and good oral hygiene, there remain significant problems with childhood disease, especially among indigent populations. Consequently, caries is one of the most common worldwide infectious diseases. Therefore, research continues towards employing vaccine formulations comprised of peptide components derived from surface proteins of Streptococcus mutans, a major agent associated with dental caries (Lehner et al., 1975). One of the most promising strategies seems to be delivery of peptides, derived from glucan-binding protein B (GbpB) and antigen I/II (AgI/II) protein, via a mucosal (nasal) route. The GbpB polypeptide binds extracellular glucans, thus promoting co-adhesion of S. mutans cells in the development of dental plaque (Taubman and Nash, 2006). The AgI/II protein (also named P1, SpaP, AgB or PAc) is a major surface protein that functions as an adhesin, attaching S. mutans to the saliva-coated tooth enamel surface (Koga et al., 1990; Kelly et al., 1995). Antibodies against SpaP and GbpB block adherence and co-adhesion, respectively, thus disrupting colonization of the oral cavity by S. mutans (Ma et al., 1990; 1998; Taubman and Nash, 2006).

    The terminology AgI/II derives from the identification of two major cell wall antigens I and II in S. mutans by Russell et al. (1980), and the subsequent recognition that AgII was a component of AgI. Following the discovery of AgI/II, it became apparent that genes encoding orthologous proteins were widely dispersed among the streptococci (Jenkinson and Demuth, 1997). The viridans Streptococcus AgI/II adhesins range in composition from 1310 to 1653 amino acid (aa) residues, while the Streptococcus agalactiae AgI/II proteins are smaller (826–932 aa residues) (Tettelin et al., 2005). The widespread distribution of these AgI/II protein genes across the streptococci is perhaps not surprising, given the complex streptococcal communities that exist on surfaces of the oro- and naso-pharynx and within the bacterial soup of saliva. It is interesting, though, that the AgI/II family polypeptide genes have not yet been discovered in Streptococcus pneumoniae, which might be by the fact that S. pneumoniae forms a distinct evolutionary cluster (Kilian et al., 2008).

  • 12. Bratt, P
    et al.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Linder, J
    Ericson, T
    Function of the rat salivary glands after exposure to inorganic mercury1995In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 172, no 1, p. 47-55Article in journal (Refereed)
    Abstract [en]

    In spite of many studies on the toxicity of mercury, very little is known about the effects of mercury on the function of exocrine glands. In the present paper selected functions of Sprague-Dawley rat salivary glands were studied after the exposure of the animals to inorganic mercury at two different doses; 3.25 mg/kg body weight given during 25 days and 7.0 mg/kg body weight given during 27 days. The function of the salivary glands was estimated by saliva secretion rate, secretion of electrolytes, proteins and biosynthesis of glycoproteins. The function was compared between mercury exposed rats and age and sex matched control rats that were given injections with equal volumes of 0.154 mol/l NaCl on the same time schedule. In the present study we report that no significant effect on saliva secretion rate, concentrations of salivary constituents or biosynthesis of glycoproteins in the salivary glands could be observed in rats as a result of mercury exposure at two levels that gave 30 or 60 times higher serum mercury concentrations than in the majority of the Swedish population.

  • 13. Bäckström, I
    et al.
    Funegård, Ulrika
    Andersson, I
    Franzén, L
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Dietary intake in head and neck irradiated patients with permanent dry mouth symptoms.1995In: European Journal of Cancer. Part B, Oral Oncology, ISSN 0964-1955, Vol. 31B, no 4, p. 253-257Article in journal (Refereed)
    Abstract [en]

    Radiotherapy of the head and neck region, which includes the major and minor salivary glands in the radiation field, usually leads to temporary or permanent xerostomia. This may affect eating and increase the risk of inadequate intake of energy and nutrients. The aim of the present study was to investigate the effects of radiotherapy-induced xerostomia on energy and nutrient intake in individuals treated for malignancies in the head and neck region. The dietary intake of 24 patients with a low chewing stimulated whole saliva flow rate (< 0.5 ml/min) and in age and sex matched controls with normal flow rate (> 1.0 ml/min) was recorded for 7 days. The average daily energy intake was nearly 300 kcal lower in the irradiated patients with dry mouth symptoms than in the control group. The mean intake in the former group was 1925 kcal per day whereas the control group had an intake of 2219 kcal per day. Irradiated patients with dry mouth symptoms had significantly lower mean intakes of vitamin A, beta-carotene, vitamin E, vitamin B6, folacine, iron and zinc than those in the control group. There was also a lower intake of vitamin C, but this was not statistically significant. The intake of vitamins A and C exceeded or reached the levels recommended in the Swedish Nutritional recommendations, but the average intakes of fibre, iron, beta-carotene, vitamin E, zinc, selenium, and iron did not reach recommended levels, in neither the experimental nor the control group. There was a slight positive correlation between energy intake and saliva secretion rate in the control group, but the energy intake was totally independent of variations in secretion rate in the irradiated patients with low secretion rate.

  • 14. Chuang, Shu-Chun
    et al.
    Norat, Teresa
    Murphy, Neil
    Olsen, Anja
    Tjonneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie Christine
    Perquier, Florence
    Dartois, Laureen
    Kaaks, Rudolf
    Teucher, Birgit
    Bergmann, Manuela M.
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Grioni, Sara
    Sacerdote, Carlotta
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Peeters, Petra H. M.
    Bueno-de-Mesquita, Bas
    Ros, Martine M.
    Brustad, Magritt
    Asli, Lene Angell
    Skeie, Guri
    Quiros, J. Ramon
    Gonzalez, Carlos A.
    Sanchez, Maria-Jose
    Navarro, Carmen
    Aicua, Eva Ardanaz
    Dorronsoro, Miren
    Drake, Isabel
    Sonestedt, Emily
    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.
    Key, Timothy
    Crowe, Francesca
    Khaw, Kay-Tee
    Wareham, Nicholas
    Ferrari, Pietro
    Slimani, Nadia
    Romieu, Isabelle
    Gallo, Valentina
    Riboli, Elio
    Vineis, Paolo
    Fiber intake and total and cause-specific mortality in the European Prospective Investigation into Cancer and Nutrition cohort2012In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 96, no 1, p. 164-174Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies have shown that high fiber intake is associated with lower mortality. However, little is known about the association of dietary fiber with specific causes of death other than cardiovascular disease (CVD). Objective: The aim of this study was to assess the relation between fiber intake, mortality, and cause-specific mortality in a large European prospective study of 452,7 I 7 men and women. Design: HRs and 95% CIs were estimated by using Cox proportional hazards models, stratified by age, sex, and center and adjusted for education, smoking, alcohol consumption, BMI, physical activity, total energy intake, and, in women, ever use of menopausal hormone therapy. Results: During a mean follow-up of 12.7 y, a total of 23,582 deaths were recorded. Fiber intake was inversely associated with total mortality (HRper (10-g/d) (increase): 0.90; 95% Cl: 0.88, 0.92); with mortality from circulatory (HRper (10-g/d increase): 0.90 and 0.88 for men and women, respectively), digestive (HR: 0.61 and 0.64), respiratory (HR: 0.77 and 0.62), and non-CVD noncancer inflammatory (HR: 0.85 and 0.80) diseases; and with smoking-related cancers (HR: 0.86 and 0.89) but not with non-smoking-related cancers (HR: 1.05 and 0.97). The associations were more evident for fiber from cereals and vegetables than from fruit. The associations were similar across BMI and physical activity categories but were stronger in smokers and participants who consumed >18 g alcohol/d. Conclusions: Higher fiber intake is associated with lower mortality, particularly from circulatory, digestive, and non-CVD noncancer inflammatory diseases. Our results support current recommendations of high dietary fiber intake for health maintenance. Am J Clin Nutr 2012;96:164-74.

  • 15. Couto, E
    et al.
    Boffetta, P
    Lagiou, P
    Ferrari, P
    Buckland, G
    Overvad, K
    Dahm, C C
    Tjønneland, A
    Olsen, A
    Clavel-Chapelon, F
    Boutron-Ruault, M-C
    Cottet, V
    Trichopoulos, D
    Naska, A
    Benetou, V
    Kaaks, R
    Rohrmann, S
    Boeing, H
    von Ruesten, A
    Panico, S
    Pala, V
    Vineis, P
    Palli, D
    Tumino, R
    May, A
    Peeters, P H
    Bueno-de-Mesquita, H B
    Büchner, F L
    Lund, E
    Skeie, G
    Engeset, D
    Gonzalez, C A
    Navarro, C
    Rodríguez, L
    Sánchez, M-J
    Amiano, P
    Barricarte, A
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Manjer, J
    Wirfärt, E
    Allen, N E
    Crowe, F
    Khaw, K-T
    Wareham, N
    Moskal, A
    Slimani, N
    Jenab, M
    Romaguera, D
    Mouw, T
    Norat, T
    Riboli, E
    Trichopoulou, A
    Mediterranean dietary pattern and cancer risk in the EPIC cohort.2011In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, no 9, p. 1493-1499Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse.

    METHODS: We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142,605 men and 335,873. Adherence to Mediterranean diet was examined using a score (range: 0-9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders.

    RESULTS: In all, 9669 incident cancers in men and 21,062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio=0.96, 95% CI 0.95-0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity)=0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern.

    CONCLUSION: Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk.

  • 16.
    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.

  • 17.
    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.

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  • 18.
    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.

  • 19.
    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.

  • 20.
    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.

  • 21.
    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.

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  • 22.
    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, 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.

  • 23.
    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.

  • 24.
    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.

  • 25.
    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.

  • 26.
    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.

  • 27.
    Ekblom, Kim
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wiklund, Per-Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Iron stores and HFE genotypes are not related to increased risk of ischemic stroke.: a prospective nested case-referent study2007In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 24, no 5, p. 405-411Article in journal (Refereed)
    Abstract [en]

    Background: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke.

    Methods: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting.

    Results: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke.

    Conclusions: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke. Copyright (c) 2007 S. Karger AG, Basel.

  • 28.
    Eriksson, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Frängsmyr, Lars
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Danielsson Niemi, Liza
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Loimaranta, Vuokko
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Holmskov, U
    Bergman, T
    Leffler, H
    Jenkinson, HF
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Variant size- and glycoforms of the scavenger receptor cysteine-rich protein gp-340 with differential bacterial aggregation2007In: Glycoconjugate Journal, ISSN 0282-0080, E-ISSN 1573-4986, Vol. 24, no 2-3, p. 131-142Article in journal (Refereed)
    Abstract [en]

    Glycoprotein gp-340 aggregates bacteria in saliva as part of innate defence at mucosal surfaces. We have detected size- and glycoforms of gp-340 between human saliva samples (n = 7) and lung gp-340 from a proteinosis patient using antibodies and lectins in Western blots and ELISA measurements. Western blots of saliva samples, and of gp-340 purified, from the seven donors using a gp-340 specific antibody distinguished four gp-340 size variants, designated I to IV (n = 2,2,2 and 1). While saliva gp-340 variants I to III had single bands of increasing sizes, variant IV and lung gp-340 had double bands. Purified I to IV proteins all revealed a N-terminal sequence TGGWIP upon Edman degradation. Moreover, purified gp-340 from the seven donors and lung gp-340 shared N-glycans, sialylated Galbeta1-3GalNAc and (poly)lactosamine structures. However, the larger size gp-340 grouping II/III (n = 4) and smaller size grouping I/IV correlated with a secretor, Se(+), and a non secretor, Se(-), dependent glycoform of gp-340, respectively (p = 0.03). The Se(+) glycoforms contained ABH, Le(b), Le(y) and polylactosamine structures, while the Se(-) glycoforms lacked ABH antigens but expressed Le(a), Le(x) and lactosamine structures. By contrast, lung gp-340 completely lacked ABH, Le(a/b), Le(x/y) or sLe(x) structures. Gp-340 and secretor typing of saliva from additional donors (n = 29) showed gp-340 glycoforms I to IV for 6, 16, 4 and 0 donors, respectively, and 3 non-typeable donors, and verified that gp-340 glycoforms I and II/III correlate with Se(-) and Se(+) phenotypes, respectively (p < 0.0001). The glycoforms of saliva and lung gp-340 mediated differential aggregation of Le(b)- (Helicobacter pylori), sialylpolylactosamine- (Streptococcus suis) or sialic acid- (Streptococcus mutans) binding bacteria. In conclusion, variant size- and glycoforms of gp-340 are expressed by different individuals and may modulate the biological properties of gp-340 pertinent to health and disease.

  • 29. Eriksson, Hanna M
    et al.
    Persson, Karina
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Zhang, Shuguang
    Wieslander, Åke
    High-yield expression and purification of a monotopic membrane glycosyltransferase2009In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 66, no 2, p. 143-148Article in journal (Refereed)
    Abstract [en]

    Membrane proteins are essential to many cellular processes. However, the systematic study of membrane protein structure has been hindered by the difficulty in obtaining large quantities of these proteins. Protein overexpression using Escherichia coli is commonly used to produce large quantities of protein, but usually yields very little membrane protein. Furthermore, optimization of the expressing conditions, as well as the choice of detergent and other buffer components, is thought to be crucial for increasing the yield of stable and homogeneous protein. Herein we report high-yield expression and purification of a membrane-associated monotopic protein, the glycosyltransferase monoglucosyldiacylglycerol synthase (alMGS), in E. coli. Systematic optimization of protein expression was achieved through controlling a few basic expression parameters, including temperature and growth media, and the purifications were monitored using a fast and efficient size-exclusion chromatography (SEC) screening method. The latter method was shown to be a powerful tool for fast screening and for finding the optimal protein-stabilizing conditions. For alMGS it was found that the concentration of detergent was just as important as the type of detergent, and a low concentration of n-dodecyl-beta-D-maltoside (DDM) (approximately 1x critical micelle concentration) was the best for keeping the protein stable and homogeneous. By using these simply methods to optimize the conditions for alMGS expression and purification, the final expression level increase by two orders of magnitude, reaching 170 mg of pure protein per litre culture.

  • 30.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Löfgren-Burström, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öhman, Ulla
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Host and bacterial phenotype variation in adhesion of streptococcus mutans to matched human hosts2012In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 80, no 11, p. 3869-3879Article in journal (Refereed)
    Abstract [en]

    The commensal pathogen Streptococcus mutans uses AgI/II adhesins to adhere to gp340 adsorbed on teeth. Here we analyzed isolates of S. mutans (n = 70 isolates) from caries and caries-free human extremes (n = 19 subjects) by multilocus sequence typing (MLST), AgI/II full-length gene sequencing, and adhesion to parotid saliva matched from the strain donors (nested from a case-control sample of defined gp340 and acidic proline-rich protein [PRP] profiles). The concatenated MLST as well as AgI/II gene sequences showed unique sequence types between, and identical types within, the subjects. The matched adhesion levels ranged widely (40% adhesion range), from low to moderate to high, between subjects but were similar within subjects (or sequence types). In contrast, the adhesion avidity of the strains was narrow, normally distributed for high, moderate, or low adhesion reference saliva or pure gp340 regardless of the sequence type. The adhesion of S. mutans Ingbritt and matched isolates and saliva samples correlated (r = 0.929), suggesting that the host specify about four-fifths (r(2) = 0.86) of the variation in matched adhesion. Half of the variation in S. mutans Ingbritt adhesion to saliva from the caries cases-controls (n = 218) was explained by the primary gp340 receptor and PRP coreceptor composition. The isolates also varied, although less so, in adhesion to standardized saliva (18% adhesion range) and clustered into three major AgI/II groups (groups A, B-1, and B-2) due to two variable V-region segments and diverse AgI/II sequence types due to a set of single-amino-acid substitutions. Isolates with AgI/II type A versus types B-1 and B-2 tended to differ in gp340 binding avidity and qualitative adhesion profiles for saliva gp340 phenotypes. In conclusion, the host saliva phenotype plays a more prominent role in S. mutans adhesion than anticipated previously.

  • 31.
    Forsgren, Nina
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Structural studies of the surface adhesin SspB from Streptococcus gordonii2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Surface proteins on microorganisms that build up the oral biofilm are key players in the formation of the biofilm. Antigen I/II proteins are surface adhesins found on virtually all oral streptococci and share a conserved multi-domain architecture. These adhesins bind surface components on other bacteria and on host cells. Thus, they are crucial for the development of the biofilm.    

    The objective of this thesis work is the structural characterization of the large multi-domain Antigen I/II protein SspB from the primary colonizing commensal bacterium Streptococcus gordonii.

    The crystal structure of the variable domain of SspB was determined to 2.3 Å resolution. The domain comprises a β-supersandwich and a putative binding cleft stabilized by a calcium ion. Despite high similarity in the overall structure, the cleft within SspB is significantly smaller than the cleft within the homologous protein from Streptococcus mutans, indicating that different substrates may bind in the clefts. A screen for carbohydrate binding resulted in no hits for interaction with the SspB variable domain suggesting that the cleft may not be suitable for binding sugars.

    This thesis also presents the high resolution 1.5 Å structure of a truncated C-terminal domain of SspB, the first of an Antigen I/II C-domain. The structure contains two structurally related domains, each containing one calcium ion and one intramolecular isopeptide bond. The SspB protein shares the feature of intramoleular isopeptide bonds with other surface proteins from Gram positive bacteria, such as pili from Streptococcus pyogenes and Corynebacterium diphtheriae. Intramolecular isopeptide bonds are suggested to be a common feature for retaining stability in a harsh environment. The SspB adherence region, shown to be the recognition motif for Porphyromonas gingivalis attachment to S. gordonii, protrudes from the core protein as a handle available for recognition.

    In conclusion, this thesis work has provided new knowledge about the SspB protein and increased the understanding of the common structure of AgI/II proteins.

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  • 32.
    Forsgren, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Lamont, Richard J
    Persson, Karina
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Crystal structure of the variable domain of the Streptococcus gordonii surface protein SspB2009In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 18, no 9, p. 1896-1905Article in journal (Refereed)
    Abstract [en]

    The Antigen I/II (AgI/II) family of proteins are cell wall anchored adhesins expressed on the surface of oral streptococci. The AgI/II proteins interact with molecules on other bacteria, on the surface of host cells, and with salivary proteins. Streptococcus gordonii is a commensal bacterium, and one of the primary colonizers that initiate the formation of the oral biofilm. S. gordonii expresses two AgI/II proteins, SspA and SspB that are closely related. One of the domains of SspB, called the variable (V-) domain, is significantly different from corresponding domains in SspA and all other AgI/II proteins. As a first step to elucidate the differences among these proteins, we have determined the crystal structure of the V-domain from S. gordonii SspB at 2.3 A resolution. The domain comprises a beta-supersandwich with a putative binding cleft stabilized by a metal ion. The overall structure of the SspB V-domain is similar to the previously reported V-domain of the Streptococcus mutans protein SpaP, despite their low sequence similarity. In spite of the conserved architecture of the binding cleft, the cavity is significantly smaller in SspB, which may provide clues about the difference in ligand specificity. We also verified that the metal in the binding cleft is a calcium ion, in concurrence with previous biological data. It was previously suggested that AgI/II V-domains are carbohydrate binding. However, we tested that hypothesis by screening the SspB V-domain for binding to over 400 glycoconjucates and found that the domain does not interact with any of the carbohydrates.

  • 33.
    Forsgren, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Lamont, Richard J
    Persson, Karina
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Two intramolecular isopeptide bonds are identified in the crystal structure of the Streptococcus gordonii SspB c-terminal domain2010In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 397, no 3, p. 740-751Article in journal (Refereed)
    Abstract [en]

    Streptococcus gordonii is a primary colonizer and is involved in the formation of dental plaque. This bacterium expresses several surface proteins. One of them is the adhesin SspB, which is a member of the Antigen I/II family of proteins. SspB is a large multi-domain protein that has interactions with surface molecules on other bacteria and on host cells, and is thus a key factor in the formation of biofilms. Here, we report the crystal structure of a truncated form of the SspB C-terminal domain, solved by single-wavelength anomalous dispersion to 1.5Å resolution. The structure represents the first of a C-terminal domain from a streptococcal Antigen I/II protein and is comprised of two structurally related β-sandwich domains, C2 and C3, both with a Ca2+ bound in equivalent positions. In each of the domains, a covalent isopeptide bond is observed between a lysine and an asparagine, a feature that is believed to be a common stabilization mechanism in Gram-positive surface proteins. S. gordonii biofilms contain attachment sites for the periodontal pathogen Porphyromonas gingivalis and the SspB C-terminal domain has been shown to have one such recognition motif, the SspB adherence region. The motif protrudes from the protein, and serves as a handle for attachment. The structure suggests several additional putative binding surfaces, and other binding clefts may be created when the fulllength protein is folded.

  • 34.
    Forsgren, Nina
    et al.
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Lamont, Richard
    Persson, Karina
    Umeå University, Faculty of Medicine, Odontology.
    A crystallizable form of the Streptococcus gordonii surface antigen SspB C-domain obtained by limited proteolysis2009In: Acta Crystallographica. Section F: Structural Biology and Crystallization Communications, ISSN 1744-3091, E-ISSN 1744-3091, Vol. 65, no 7, p. 712-714Article in journal (Refereed)
    Abstract [en]

    SspB is a 1500-residue adhesin expressed on the surface of the oral bacterium Streptococcus gordonii. Its interaction with other bacteria and host cells initiates the development of dental plaque. The full-length C-terminal domain of SspB was cloned, overexpressed in Escherichia coli and purified. However, the protein could not be crystallized. Limited proteolysis of the full-length C-domain identified a core fragment. The proteolysis product was cloned, expressed and purified. The protein was crystallized using the hanging-drop vapour-diffusion method. X-ray data were collected and processed to a maximum resolution of 2.1 A with 96.4% completeness. The crystals belonged to space group P2(1), with one molecule in the asymmetric unit, a solvent content of 33.7% and a corresponding Matthews coefficient of 1.85 A(3) Da(-1).

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  • 35. Funegård, Ulrika
    et al.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Franzén, L
    Ericson, T
    Nyström, H
    Henriksson, R
    Rat salivary gland function after fractionated irradiation.1997In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 36, no 2, p. 191-198Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate longitudinal effects of fractionated irradiation, with various total doses, on salivary gland function in the rat. Female Sprague-Dawley rats were irradiated with 4, 5, 6, 7 or 8 Gy per day on five consecutive days. Irradiation was given to the head and neck region. Whole saliva was collected before and 2, 15 and 26 weeks after irradiation. In general the effects of irradiation on salivary gland function were found to be related to dose and time after exposure. Secretion rates were significantly decreased two weeks after irradiation with doses of 30 Gy or higher, after 15 weeks with 25 Gy or higher, and after 26 weeks with 20 Gy or higher. Response patterns to irradiation differed between the salivary constituents. Thus, the conclusions from this study are that early and late effects display different patterns and that the model used to study variations in salivary gland function after fractionated irradiation must be adjusted to the question addressed.

  • 36. Funegård, Ulrika
    et al.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Malmer, B
    Henriksson, R
    Ericson, T
    Can alpha-tocopherol and beta-carotene supplementation reduce adverse radiation effects on salivary glands?1995In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 31A, no 13-14, p. 2347-2353Article in journal (Refereed)
    Abstract [en]

    In this study, we evaluated whether supplementation with antioxidant vitamins can reduce the adverse effects of irradiation on the salivary glands in the rat. Four groups of adult Sprague-Dawley rats were given a basic diet providing 0.6 mg alpha-tocopherol and no beta-carotene per day. In two groups the basic diet was supplemented with 3.4 mg alpha-tocopherol and 6 mg beta-carotene per day from 14 days before irradiation until 12 days after completed irradiation. One group of rats given basic diet and one group given supplemented diet were irradiated with 7 Gy daily for five consecutive days. Isoproterenol and pilocarpine-stimulated whole saliva was collected from all rats 2, 4 and 26 weeks after irradiation. Vitamin-supplemented irradiated rats had higher secretion rates on all three occasions compared with those of irradiated rats given basic diet. The changes in saliva composition seen in irradiated rats were less accentuated in vitamin-supplemented, irradiated rats. The proportions of acinar cells were significantly decreased both in parotid and submandibular glands 26 weeks after irradiation. Supplementation with alpha-tocopherol and beta-carotene did not alter the morphology of the glands.

  • 37. Gerdin, EW
    et al.
    Angbratt, M
    Aronsson, K
    Eriksson, E
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Dental caries and body mass index by socio-economic status in Swedish children2008In: Community Dentistry and Oral Epidemiology, ISSN 0301-5661, E-ISSN 1600-0528, Vol. 36, no 5, p. 459-465Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of the present study was to evaluate the association between dental caries, childhood body mass index (BMI), and socioeconomic status in Swedish children. Methods: The study cohort consisted of 2303 10-year-old children with data on socioeconomic status, BMI at 4, 5, 7 and 10 years of age, and caries at 6, 10 and 12 years of age. Anthropometric measures were carried out by trained nurses according to standardized routines. The occurrence of caries was registered from county records, and the children were classified into one of five socioeconomic clusters based on their census registration address. Results: Caries prevalence decreased with increasing socioeconomic status at all ages, whereas childhood BMI and proportion of overweight/obese children were unrelated to socioeconomic status. Obese, but not overweight, children had more caries affected teeth than non-obese, and BMI had an independent, though weak, effect on caries variation in multiple regression. Interestingly, overweight/obese 4-year-olds, who had normal body weight at 5, 7 and 10 years of age, had significantly less caries than children who had normal body weight from 4 to 10 years of age. Conclusions: Overweight and caries prevalence are significantly associated in Swedish children. However, the association is weak. Nevertheless, the concept that child dental services and child welfare services can benefit from joint programs is supported.

  • 38. Gerdin, EW
    et al.
    Einarson, S
    Jonsson, M
    Aronsson, K
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Impact of dry mouth conditions on oral health-related quality of life in older people.2005In: Gerodontology, ISSN 0734-0664, E-ISSN 1741-2358, Vol. 22, no 4, p. 219-226Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of the present study was to evaluate the impact of dry mouth conditions on oral health-related quality of life in frail old people, residents at community care centers. Further, reliability and validity of a visual analogue scale (VAS) for dry mouth symptoms were determined within the study cohort. BACKGROUND: In old people functional, social and psychological impacts of oral conditions are associated with an overall sense of well being and general health. Subjective dry mouth and reduced saliva flow are common disorders in old people caused by disease and medication. Thus, dry mouth conditions may be determinants for compromised oral health-related quality of life in old people. METHOD: In total, 50 old people living at service homes for the old people were asked to answer questionnaires on subjective dry mouth (VAS) and Oral Health Impact Profile (OHIP14) for oral health-related quality of life. Saliva flow was estimated by absorbing saliva into a pre-weighed cotton roll. RESULTS: The final study cohort comprised 41 old people (aged 83-91 years). Significant associations were identified between both objective and subjective dry mouth and overall or specific aspects of oral health-related quality of life. CONCLUSION: Dry mouth (objective and subjective) is significantly associated with oral health-related quality of life strengthening the value of monitoring dry mouth conditions in the care of frail old people.

  • 39. Hakkarainen, J
    et al.
    Toivanen, M
    Leinonen, A
    Frängsmyr, Lars
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Lapinjoki, S
    Nassif, X
    Tikkanen-Kaukanen, C
    Human and bovine milk oligosaccharides inhibit Neisseria meningitidis pili attachment in vitro.2005In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 135, no 10, p. 2445-2448Article in journal (Refereed)
    Abstract [en]

    Milk oligosaccharides have been shown to interfere with adhesion of many pathogens to host mucosal surfaces. Characterization of the adhesion mechanisms of the bacteria to host cell surface is needed to develop novel functional food, infant formulas, and anti-infective drugs. Adhesion of Neisseria meningitidis, a human specific pathogen causing meningitis and septicemia, is not completely understood but is mediated by type IV pili. Here, we developed a microtiter well pili binding assay to investigate the binding activities of N. meningitidis isolated type IV pili to different glycoproteins. Pili binding activities to bovine thyroglobulin and human salivary agglutinin but not to chicken ovalbumin were present. Inhibition of these binding activities was demonstrated by fractionated human or bovine milk oligosaccharides. The binding of neisserial pili to bovine thyroglobulin was most effective and was clearly inhibited by human milk neutral or bovine milk acidic oligosaccharides.

  • 40.
    Hallmans, Göran
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Agren, A
    Johansson, G
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Periodontology.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, JH
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindahl, B
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nilsson, M
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Cardiovascular disease and diabetes in the Northern Sweden Health and Disease Study Cohort: evaluation of risk factors and their interactions.2003In: Scandinavian Journal of Public Health. Supplement Links, ISSN 1403-4956, Vol. 61, p. 18-24Article in journal (Refereed)
    Abstract [en]

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

  • 41. Hansen, Louise
    et al.
    Skeie, Guri
    Landberg, Rikard
    Lund, Eiliv
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Dragsted, Lars O
    Egeberg, Rikke
    Johnsen, Nina F
    Christensen, Jane
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Intake of dietary fiber, especially from cereal foods, is associated with lower incidence of colon cancer in the HELGA cohort2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 131, no 2, p. 469-478Article in journal (Refereed)
    Abstract [en]

    The role of dietary fiber on the risk of colon and rectal cancer has been investigated in numerous studies, but findings have been inconsistent. The purpose of this study was to examine associations between intake of dietary fiber and risk of incident colon (including distal and proximal colon) and rectal cancer in the prospective Scandinavian HELGA cohort and to determine if fiber source (vegetables, fruits, potatoes, cereals) impacted the association. We included 1,168 incident cases (691 colon, 477 rectal cancer), diagnosed during a median of 11.3 years, among 108,081 cohort members. Sex-specific incidence rate ratios (IRRs) of colon and rectal cancer were related to intake of total or specific fiber source using Cox proportional hazards models. For men, an inverse association was observed between intake of total fiber and the risk of colon cancer per an incremental increase of 10 g day(-1) , IRR (95% CI): 0.74 (0.64-0.86). Intake of cereal fiber per 2 g day(-1) was associated with an IRR of 0.94 (0.91-0.98), which was also seen for intake of cereal fiber from foods with high fiber content (≥5 g per 100 g product), where the IRR per 2 g day(-1) was 0.94 (0.90-0.98). In women, intake of cereal fiber per 2 g day(-1) was also associated with lower risk of colon cancer, 0.97 (0.93-1.00). No clear associations were seen for rectal cancer. Our data indicate a protective role of total and cereal fiber intake, particularly from cereal foods with high fiber content, in the prevention of colon cancer.

  • 42. Hermann, Silke
    et al.
    Rohrmann, Sabine
    Linseisen, Jakob
    May, Anne M
    Kunst, Anton
    Besson, Herve
    Romaguera, Dora
    Travier, Noemie
    Tormo, Maria-Jose
    Molina, Esther
    Dorronsoro, Miren
    Barricarte, Aurelio
    Rodriguez, Laudina
    Crowe, Francesca L
    Khaw, Kay-Tee
    Wareham, Nicholas J
    van Boeckel, Petra Ga
    Bueno-de-Mesquita, H Bas
    Overvad, Kim
    Uhre Jakobsen, Marianne
    Tjonneland, Anne
    Halkjaer, Jytte
    Agnoli, Claudia
    Mattiello, Amalia
    Tumino, Rosario
    Masala, Giovanna
    Vineis, Paolo
    Naska, Androniki
    Orfanos, Philippos
    Trichopoulou, Antonia
    Kaaks, Rudolf
    Bergmann, Manuela M
    Steffen, Annika
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Borgquist, Signe
    Manjer, Jonas
    Braaten, Tonje
    Fagherazzi, Guy
    Clavel-Chapelon, Francoise
    Mouw, Traci
    Norat, Teresa
    Riboli, Elio
    Rinaldi, Sabina
    Slimani, Nadia
    Peeters, Petra Hm
    The association of education with body mass index and waist circumference in the EPIC-PANACEA study2011In: BMC Public Health, E-ISSN 1471-2458, Vol. 11, no 1, p. 169-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine the association of education with body mass index (BMI) and waist circumference (WC) in the European Prospective Investigation into Cancer and Nutrition (EPIC).

    METHOD: This study included 141,230 male and 336,637 female EPIC-participants, who were recruited between 1992 and 2000. Education, which was assessed by questionnaire, was classified into four categories; BMI and WC, measured by trained personnel in most participating centers, were modeled as continuous dependent variables. Associations were estimated using multilevel mixed effects linear regression models.

    RESULTS: Compared with the lowest education level, BMI and WC were significantly lower for all three higher education categories, which was consistent for all countries. Women with university degree had a 2.1 kg/m2 lower BMI compared with women with lowest education level. For men, a statistically significant, but less pronounced difference was observed (1.3 kg/m2). The association between WC and education level was also of greater magnitude for women: compared with the lowest education level, average WC of women was lower by 5.2 cm for women in the highest category. For men the difference was 2.9 cm.

    CONCLUSION: In this European cohort, there is an inverse association between higher BMI as well as higher WC and lower education level. Public Health Programs that aim to reduce overweight and obesity should primarily focus on the lower educated population.

  • 43.
    Hörnell, Agneta
    et al.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Winkvist, Anna
    Department of Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg .
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Mis-reporting, previous health status and health status of family may seriously bias the association between food patterns and disease2010In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 9, no 48Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Food pattern analyses are popular tools in the study of associations between diet and health. However, there is a need for further evaluation of this methodology. The aim of the present cross-sectional study was to evaluate the relationship between food pattern groups (FPG) and existing health, and to identify factors influencing this relationship.

    METHODS: The inhabitants of Västerbotten County in northern Sweden are invited to health check-ups when they turn 30, 40, 50, and 60 years of age. The present study includes data collected from almost 60,000 individuals between 1992 and 2005. Associations between FPG (established using K-means cluster analyses) and health were analyzed separately in men and women.

    RESULTS: The health status of the participants and their close family and reporting accuracy differed significantly between men and women and among FPG. Crude regression analyses, with the high fat FPG as reference, showed increased risks for several health outcomes for all other FPGs in both sexes. However, when limiting analysis to individuals without previous ill-health and with adequate energy intake reports, most of the risks instead showed a trend towards protective effects.

    CONCLUSIONS: Food pattern classifications reflect both eating habits and other own and family health related factors, a finding important to remember and to adjust for before singling out the diet as a primary cause for present and future health problems. Appropriate exclusions are suggested to avoid biases and attenuated associations in nutrition epidemiology.

  • 44. Jacobsson, B
    et al.
    Wendt, LK
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Dental caries and caries associated factors in Swedish 15-year-olds in relation to immigrant background.2005In: Swedish Dental Journal, ISSN 0347-9994, Vol. 29, no 2, p. 71-79Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the prevalence of caries and caries associated variables in 15-year-olds in relation to foreign background and to examine differences in the prevalence of caries in immigrant adolescents according to their length of residence in Sweden. All 15-year-old adolescents (n=143) at one public school in the city of Jönköping, Sweden were asked to participate in the study. The adolescents were divided into two groups according to their background: immigrants and non-immigrants. Data on caries prevalence were extracted from the dental records of the examination made when the participants were 15 years old. The proportions of immigrants and non-immigrants free from carious lesions were equal. Immigrant adolescents, however, had on average more enamel carious lesions. Adolescents born in Sweden of immigrant parents or who had arrived before 1 year of age had a caries prevalence similar to those of non-immigrant adolescents, whereas children who had immigrated to Sweden after 7 years of age had a caries prevalence that was 2-3 times higher. As the caries carious lesions in immigrant adolescents is mainly restricted to the enamel, and possibly reversible, early introduction of preventive programmes seems essential.

  • 45. Jakubovics, N.S.
    et al.
    Brittan , J.L.
    Kerrigan, S.
    Cox, D.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Odontology. Umeå University, Faculty of Medicine, Odontology, Cariology.
    Jenkinson, H.F.
    Interactions of mitis group streptococci with sialic acid receptors2006In: International Congress Series 1289, Elsevier B.V. , 2006, p. 275-278Chapter in book (Other academic)
    Abstract [en]

    The serine-rich repeat glycoprotein Hsa in Streptococcus gordonii Challis mediates bacterial cell interactions with fetuin, glycocalicin, fibronectin and human platelets. Different strains of S.gordonii vary markedly in their adhesion levels to sialylated proteins, while other mitis group streptococci have distinct patterns of recognition of sialylated or desialylated receptor oligosaccharides.  2005 Elsevier B.V. All rights reserved.

  • 46. Jakubovics, NS
    et al.
    Kerrigan, SW
    Nobbs, AH
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    van Dolleweerd, CJ
    Cox, DM
    Kelly, CG
    Jenkinson, HF
    Functions of cell surface-anchored antigen I/II family and Hsa polypeptides in interactions of Streptococcus gordonii with host receptors.2005In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 73, no 10, p. 6629-6638Article in journal (Refereed)
    Abstract [en]

    Streptococcus gordonii colonizes multiple sites within the human oral cavity. This colonization depends upon the initial interactions of streptococcal adhesins with host receptors. The adhesins that bind salivary agglutinin glycoprotein (gp340) and human cell surface receptors include the antigen I/II (AgI/II) family polypeptides SspA and SspB and a sialic acid-binding surface protein designated Hsa or GspB. In this study we determined the relative functions of the AgI/II polypeptides and Hsa in interactions of S. gordonii DL1 (Challis) with host receptors. For an isogenic mutant with the sspA and sspB genes deleted the levels of adhesion to surface-immobilized gp340 were reduced 40%, while deletion of the hsa gene alone resulted in >80% inhibition of bacterial cell adhesion to gp340. Adhesion of S. gordonii DL1 cells to gp340 was sialidase sensitive, verifying that Hsa has a major role in mediating sialic acid-specific adhesion to gp340. Conversely, aggregation of S. gordonii cells by fluid-phase gp340 was not affected by deletion of hsa but was eliminated by deletion of the sspA and sspB genes. Deletion of the AgI/II polypeptide genes had no measurable effect on hsa mRNA levels or Hsa surface protein expression, and deletion of hsa did not affect AgI/II polypeptide expression. Further analysis of mutant phenotypes showed that the Hsa and AgI/II proteins mediated adhesion of S. gordonii DL1 to human HEp-2 epithelial cells. Hsa was also a principal streptococcal cell surface component promoting adhesion of human platelets to immobilized streptococci, but Hsa and AgI/II polypeptides acted in concert in mediating streptococcal cell-platelet aggregation. The results suggest that Hsa directs primary adhesion events for S. gordonii DL1 (Challis) with immobilized gp340, epithelial cells, and platelets. AgI/II polypeptides direct gp340-mediated aggregation, facilitate multimodal interactions necessary for platelet aggregation, and modulate S. gordonii-host engagements into biologically productive phenomena.

  • 47. Jakubovics, NS
    et al.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    van Dolleweerd, CJ
    Kelly, CG
    Jenkinson, HF
    Differential binding specificities of oral streptococcal antigen I/II family adhesins for human or bacterial ligands.2005In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 55, no 5, p. 1591-1605Article in journal (Refereed)
    Abstract [en]

    The antigen I/II (AgI/II) family polypeptides, ranging from 1310 to 1653 amino acid (aa) residues, are cell wall anchored adhesins expressed by most indigenous species of oral streptococci. The polypeptides interact with a wide range of host molecules, in particular salivary agglutinin glycoprotein (SAG or gp340), and with ligands on other oral bacteria. To determine the receptor recognition properties of six different AgI/II family polypeptides from strains of Streptococcus gordonii, Streptococcus intermedius and Streptococcus mutans, the genes were cloned and expressed on the surface of the surrogate host Lactococcus lactis. The S. gordonii SspA and SspB polypeptides mediated higher binding levels of L. lactis cells to surface immobilized gp340 than did S. intermedius Pas protein, or S. mutans SpaP or PAc proteins. However, the AgI/II proteins were all similar in their abilities to mediate aggregation of lactococci by fluid phase gp340. The SpaP(I) polypeptide from S. mutans Ingbritt, which was C-terminally truncated by approximately 400 aa residues, did not bind gp340. Lactococci expressing AgI/II proteins, including SpaP(I), were aggregated by a synthetic 16 aa residue peptide SRCRP2 derived from the aa repeat block sequences within gp340. In coaggregation assays, SspB from S. gordonii was unique in mediating coaggregation with only group A and group E strains of Actinomyces naeslundii. All the other AgI/II polypeptides mediated coaggregation with group C and group D strains of A. naeslundii. Analysis of chimeric protein constructs revealed that coaggregation specificity was determined by sequences within the N-terminal half of AgI/II protein. A synthetic peptide (20 aa residues), which defines a putative adhesion epitope within the C-terminal region of polypeptide, inhibited AgI/II-mediated aggregation by gp340 but did not affect coaggregation with A. naeslundii. These results suggest that different mechanisms operate in interactions of AgI/II family polypeptides with native gp340, gp340 SRCR domain peptide, and A. naeslundii. Specificity of these interactions appears to be determined by discontinuous but interacting regions of the polypeptides, thus providing flexibility in receptor recognition for streptococcal colonization of the human host.

  • 48. Jenab, M
    et al.
    Riboli, E
    Ferrari, P
    Friesen, M
    Sabate, J
    Norat, T
    Slimani, N
    Tjonneland, A
    Olsen, A
    Overvad, K
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Boeing, H
    Schulz, M
    Linseisen, J
    Nagel, G
    Trichopoulou, A
    Naska, A
    Oikonomou, E
    Berrino, F
    Panico, S
    Palli, D
    Sacerdote, C
    Tumino, R
    Peeters, PH
    Numans, ME
    Bueno-de Mesquita, HB
    Buchner, FL
    Lund, E
    Pera, G
    Chirlaque, MD
    Sanchez, MJ
    Arriola, L
    Barricarte, A
    Quiros, JR
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Odontology, Periodontology.
    Berglund, G
    Bingham, S
    Khaw, KT
    Allen, N
    Key, T
    Carneiro, F
    Save, V
    Del Giudice, G
    Plebani, M
    Kaaks, R
    Gonzalez, CA
    Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition2006In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 95, no 3, p. 406-415Article in journal (Refereed)
    Abstract [en]

    Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and - and -tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and -tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma -cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30-0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22-0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33-0.93, Ptrend=0.005) and lipid-unadjusted -tocopherol (OR=0.59, 95% CI=0.37-0.94, Ptrend=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted -tocopherol (OR=0.26, 95% CI=0.11-0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and -tocopherol are associated with reduced risk of GC.

  • 49.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Åhren, Ann-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Prevalence of systemic immunoreactivity to Aggregatibacter actinomycetemcomitans leukotoxin in relation to the incidence of myocardial infarction2011In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 11, no 1, p. 55-Article in journal (Refereed)
    Abstract [en]

    Background: Chronic infections and associated inflammatory markers are suggested risk factors for cardiovascular disease (CVD). The proinflammatory cytokine, interleukin (IL)-1, is suggested to play a role in the regulation of local inflammatory responses in both CVD and periodontitis. The leukotoxin from the periodontal pathogen Aggregatibacter actinomycetemcomitans has recently been shown to cause abundant secretion of IL-1 from macrophages. The aim of the present study was to compare the prevalence of systemic immunoreactivity to A. actinomycetemcomitans leukotoxin in myocardial infarction (MI) cases (n=532) and matched controls (n=1000) in a population-based case and referents study in northern Sweden.

    Methods: Capacity to neutralize A. actinomycetemcomitans leukotoxin was analyzed in a bioassay with leukocytes, purified leukotoxin, and plasma. Plasma samples that inhibited lactate-dehydrogenase release from leukotoxin-lysed cells by 50 % were classified as positive.

    Results: Neutralizing capacity against A. actinomycetemcomitans leukotoxin was detected in 53.3% of the plasma samples. The ability to neutralize leukotoxin correlated to increasing age in men (n=1082) but not in women (n=450). There was no correlation between presence of systemic leukotoxin neutralization capacity and the incidence of MI, except for women (n=146). Women with a low neutralizing capacity had a significantly higher incidence of MI than those who had a high neutralizing capacity.

    Conclusions: Systemic immunoreactivity against A. actinomycetemcomitans leukotoxin was found at a high prevalence in the analyzed population of adults from northern Sweden. The results from the present study do not support the hypothesis that systemic leukotoxin-neutralizing capacity can decrease the risk for MI.

  • 50. Johansson, G
    et al.
    Wikman, Å
    Åhrén, Ann-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Underreporting of energy intake in repeated 24-hour recalls related to gender, age, weight status, day of interview, educational level, reported food intake, smoking habits and area of living.2001In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 4, no 4, p. 919-927Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aims of the present study were (1) to evaluate the degree to which underreporting of energy intake by repeated 24-hour recalls was related to gender, age, weight status, day of interview, educational level, smoking habits and area of living, and (2) to compare the dietary characteristics of underreporters with those of others. DESIGN: Cross-sectional study. Ten 24-hour recalls were performed during a one-year period. SETTING: The Västerbotten intervention programme of cardiovascular disease and diabetes in Northern Sweden. SUBJECTS: Ninety-four men and 99 women in four age groups: 30, 40, 50 and 60 years. RESULTS: The prevalence of men and women with a food intake level (FIL; reported energy intake divided by estimated basal metabolic rate) below 1.2 was 44% and 47%, respectively. The youngest age group had higher FIL values than the oldest age group for both men (1.5 versus 1.1) and women (1.4 versus 1.1). The prevalence and magnitude of underreporting were directly related to body mass index (BMI; correlation coefficient: -0.47 (men) and -0.55 (women)). Smokers had a lower FIL value (1.1) than non-smokers (1.3). The nutrient density was lower for the group with high FIL values for protein and calcium and higher for fat and sucrose. The upper FIL group often had higher intake frequencies and larger portion sizes than the lower FIL group. CONCLUSIONS: Underreporting of energy intake is prevalent when 24-hour recalls are used, but the prevalence differs between sub-groups in the population. BMI was the main predictor of underreporting but also old age and smoking seem to contribute in this aspect. Socially desirable food items were not underreported to the same extent as socially undesirable food items. The intake frequencies and portion sizes partly explained the differences in FIL.

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